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CIGARETTE SMOKING AND DISEASE, 1976 HEARINGS BEFORE THE SUBCOMMITTEE ON HEALTH OF THE COMMITTEE ON LABOR AND PUBLIC WELFARE UNITED STATES SENATE NINETY-FOURTH CONGRESS SECOND SESSION ON S. 2902 TO AMEND TITLE V OF THE PUBLIC HEALTH SERVICES ACT TO ESTABLISH A-NATIONAL HEALTH RESEARCH AND DEVELOPMENT ADVISORY COMMISSION, AND FOR OTHER PURPOSES FEBRUARY 19, MARCH 24, AND MAY 27, 1976 0 Printed for the use of the Committee on Labor and Public Welfare U.S. GOVERNMENT PRINTING OFFICE 70-057 0 WASHINGTON : 1976 f TIMN 450119

i CONTENTS COMMITTEE ON LABOR AND PUBLIC WELFARE HARRISON A. WILLIAMS, JR., New Jersey, Chairman JENNINGS RANDOLPH, West Virginia CLAIBORNE PELL, Rhode Island EDWARD :ii. KENNEDY, Massachusetts GAYLORD NELSON, Wisconsin WALTER F. MONDALE, Minnesota THOMAS F. EAGLETON, Missouri ALAN CRANSTON, California WILLIAM D. HATHAWAY, Maine JOHN A. DURKIN, New IIampshire JACOB K. JAVITS, New York RICHARD S. SCHWEIKER, Pennsylvania ROBERT TAFT, JR., Ohio J. GLENN BEALL, JR., Maryland ROBERT T. STAFFORD, Vermont PAUL LAXALT, Nevada DONALD FiLISBUR, General Counsel I•IARJORIF. 11I. WHITTAKEII, Chief Clerk JAY B. CUTLER, Minority Counsel SUBCOMMITTEE ON HEALTH EDWARD M. KENNEDY, Massachusetts, Chairman HARRISON A. WILLIAMS, JR., New Jersey GAYLORD NELSON, Wisconsin THOMAS F. EAGLFTON, 1•fis,rouri ALAN CRANSTON, California CLAIBORNE PELL, Rhode Island WALTER F. NIONDALP:, Minnesota WILLIAM 1). HATIIAWAY, Maine JOIIN A. DiJRKIN, New Ilampshire RICHARD S. SCIIWEIKER, Pennsylvania JACOB K. JAVITS, New York J. GLENN BEALL, JR., Maryland ROBERT TAFT, JR., Ohio ROBERT T. STAFFORD, Vermont PAUL LAXALT, Nevada LRRoY G. GOLDMAN, Professional Staff Member JAY B. CUTLER, Minority Counsel S. 2902, text of------------------------------------------------------ CHRONOLOGICAL LIST OF WITNESSES Page 4 THURSDAY, FEBRUARY 19, 1976 Hart, Hon. Gary, a U.a. aenator irom tine aiace ui voioiaLLr,-------------- ;^. Huddleaton, Hon. Walter D., a U.S. Senator from the State of Kentucky__ 26 Helms, Hon. Jesse, a U.S. Senator from the State of North Carolina-____- 72 Ford, Hon. Wendell H., a U.S. Senator from the State of Kentucky-------- 116 Perkins, Hon. Carl D., a Representative in Congress from the State of Kentucky --------------------------------------------------------- 168 Morgan, Hon. Robert, a U.S. Senator from the State of North Carolina__ 171 Cooper, Theodore, M.D., Assistant Secretary for Health, Department of Health, Education, and Welfare, accompanied by Dr. David Sencer, director, center for disease control ; Dr. Frank J. Rauscher, director, National Cancer Institute, National Institutes of Health ; Dr. Robert I. Levy, Director, National Heart and Lung Institute, National Institutes of Health ; and Mr. Gene R. Haislip, Deputy Assistant Secretary for Legislation (Health), Department of Health, Education, and Welfare, a panel------------------------------------------------------------ Dulbecco, Dr. Renato, Imperial Cancer Research Fund Laboratories, London, England-------------------------------------------------- Temin, Dr. Howard M., American Cancer Society, professor of viral on- cology and cell biology, McArdle Laboratory for Cancer Research, 175 239 Univexsity of Wisconsin, Madison__________________________________ 257 Sommers, Dr. Sheldon C., director, Laboratories at the Lenox Hill Hos- pital, New York, and professor of pathology, College of Physicians and Surgeons, Columbia University of New York, accompanied by Horace R. Kornegay, president, the Tobacco Institute, Washington, D.C., and Dr. Theodore D. Sterling, Director, Computer Science Program, Simon Fraser University, Canada_________________________________________ 268 Sterling, Theodore D., Ph. D., director, Computing Science Program, Simon Fraser University, Vancouver, Canada_______________________ 443 Byrd, Benjamin F., Jr., M.D., president, American Cancer Society, pro- fessor of clinical surgery, Vanderbilt University School of Medicine, Nashville, Tenn. ; Dr. Henry Blackburn, American Heart Association, professor and director, Laboratory of Physiological Hygiene, Univer- sity of Minnesota Schools of Medicine and Public Health, Minneapolis, Minn. ; and Dr. Stephen M. Ayres, board member, Americah Lung Asso- ciation, professor and chairman, Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, Mo., a panel______ 530 WEDNESDAY, MARCH 24, 1976 Moss, Hon. Frank E., a U.S. Senator from the State of Utah----------- 696 Hart, Hon. Gary, a U.S. Senator from the State of Colorado______________ 700 Brooke, Hon. Edward W., a U.S. Senator from the State of Massachusetts- 701 Jones, Hon. Walter B., a Representative in Congress from the State of North Carolina and chairman, Subcommittee on Tobacco of the House Agriculture Committee_____________________________________________ 703 712 721 the State of South Carolina________________________________________ 724 (IH) Mathis, Hon. Dawson, a Representative in Congress from the State of Georgia ---------------------------------------------------------- Fugua, Hon. Don, a Representative in Congress from the State of Florida_- Jenrette, Hon. John W. Jr., member of the House of Representatives from

CIGARETTE SMOKING AND DISEASE, 1976 THIIRBDAY, FEBRUARY 19, 1976 SUBCOMMPPI'EE ON IIEALTII OF TIiE COMMITrEE ON LABOR AND PUBLiC WELFARE, jVaBhinqt,on, D.C. The subconunittee nlet pursuant to notice, at cJ :36 a.m., in room 4232, Dirksen Senate Of6ce Building, Senator Edward Kennedy (chairman) presiding. Present : Senators Kennedy, Beall, and Schweiker. Senator KENNEDY. The suhcomllllttee will come to order. OPENINO STATEMENT BY SENATOR EDW.IRD M. KENNEDY Ladies and gentlemen, I welcome you here this morning to join the Subcommittee on Ilealtll in exploring a problem that is hecomii~s; increasingly important to us all : The relationship between cigarette siuoking and disease. This is not the first tiule that the ("culf;re5s has examined the question. 13ut, each time that a committee of the Senate or the. Ilouse of Itepre5entatives has held hearings on this subject, it seems to Ine that the weight. of scientific evicknce has become Inore convincing that there is, in fact, a direct relationship between cigarette smoking and certain types of disease. .IuSt yesterday, the subcotnmittee heard eviclence att a heat•ing on international health that. large -areas of the globe are still atllicted by a great, number of terrifying infectious di5easeti that exact a fearful toll in underdevelopecl countries. We are fortunate in thc United States that, we have successfully conquered most of the important infectious diseases, which once caused so much suffering and cleatfi. Iint. the problems of hneumonia, of tuLerculotii5, of holiowyelitis, ancl other diseases have given way to an even niore insiclions set of clisea5es «•hicll Ilow concerns its all. 'I'hese aree the more chronic cliyeaseti, and evidence is growing that. many of these are due to environinental fuctors. 'I'hese cliscascti are niore insidioii5 for two principle rcasons. Fir5t, many of thenc take an extreniely long ticue to develop, snul clepcncl upon the accnnnilation of snnall doses of the c:niFative agent over lonf; periocl5 of tillie. 'I'hus, while a canse/etCect relationshili can }m fairly easily establisllecl between tnlerc•ulosi5 and the tuhercle hacihis, or between poliomyelitis and the polio virus, it is far more clifficult to establish a direct. relationship lretween cancer of the liml-, or coronary heart clisease ancl any given environmental factor. 'More and molr, however, it is to the epidemiologist :uul Imhlic• health expert. that we inust turn for help with these 1>rohlenis, and (t)

4 n4•rll CONGRESS 2n GF.AAION S92902 5 2 1 (3) overwhelming scientific evidence exists that the 2 I N'I'll 1+.' SENATE Ole '1'III: i1NITEl) STATES V JANUARY 2!/,197(i Alr. (iARY W. IlAlrr (for hini,elf Rnd Mr. Kr;NNr:oY) introduced the following 4 hill; which N'R.9 read (Ile flrst tdnle 5 .IANIlARY :Ie,In7G Read (lie second l.ime aud by unanimons consent referred to the Committee 6 on Labor and Public Welfare, and if and w•hen reported to the Committee on Finance 7 8 A BILL 9 To amend title V of the Public Health F;ervices Act to establish 10 a National Health Research and I)evelopment Advisory 11 C'ommission, and for other purposes. 12 1 Be it enacted h!/ the ,4cnnle and Ilmcse of Representa- 13 2 tires of the United Stales of America in Congress assembled. 14 3 That, this Act may be cited as (he "National Health R.esearch 15 4 and Developwent Act of 1976". 16 5 P'IN1)IN(a AND DI f3LARA'PION Or PURI?OSI: 17 6 tftc. 2. (a )'1'he Congress finds that- 18 7 (1) preventable environmental factors pose serious 19 3 threats to the health of the American people; 20 9 (2) cigarette amoking is one of the principal con- 21 IO trihutors to the high incidence of cancer and diseases of 22 l l the heart, lungs, and other organs; 2:3 II `L4 harmful factors contained in cigarette sutoke are tars and nicotine; (4) current approaches to prevention of disease caused in whole. or in )art hv smokiuz have been in- adequate; and (5) progress in the prevention, alleviation, or cure of these and other diseases which afflict the American people must be based -both upon changes in personal habits with respect to smoking and upon a strong pro- gram of fundamental biomedical and behavioral research as well as upon effective meelutnisws for the translation and transfer of the benefits of this research into the health care delivery system. (b) The purpose of this Act is to- (1) establish a. National Health Research and I)e- velopment Advisory Commission to advise the President •and the Congress on the overall status of\ the national health research effort, and to make recommendations on the course and priorities of futcu•ce health research and develolnucnit in order to insure a comprehensive, hnl- anced, and etlicient, lrrogr;im for the prevention, t.reat. ment, and fure of disease. (2) establish a Nattional Ilealth Research and I)e- TIlVIN 450186

10 1 2 3 7 ter 53 of such title relating to classification and General Schedule pay rates; "(2) obtain the services of experts and consultants, 4 in accordance with the -provisions of section 3109 of title 5 5, ilnited States Code, at rates for individuals not to 6 exceed $100 per day; 7 "(3) enter into contracts for studies under subsec- 8 tion (e) above; and 9 "(4) publish and distribute reports and materials 10 to the scientific community and the public. 11 "(g) The Commission is authorized to request frorri any 12 department, agency, or independent instrumentality of the 13 (aovernment any inf(irmation and assistance it deems neces- 14 sary to carry out the purposes of this section and each such 15 department, agency, or instrumentality is authorized to co- 16 operate with the Commission and to the extent permitted by 17 law, to furnish such information and assistance to the Com- 18 mission upon request made by the Chairman or any other 19 member when acting as Chairman. 20 "NATIONAL III:ALT1f R1s5b3AR(ai ANI) nEVI:LOI'MF.NT b'liNl) 21 "Smi. 503. (a) There are hereby authorized to he 22 appropriated, in annual appropriations Acts, for fiscal years 23 1977, 1978, 1979, 1980, and 1981, those amount, deter- 24 winetl by the tiecret;lry of the Treasury to be equivalent to TITVTN 450189 11 8 1 the taxes received in the Treasury under section 5701 (b) (3) 2 of the Internal Revenue Code of 1954 (relating to a rate of 3 tax on cigarettes) for the following purposes- 4 "(i) fundamental laboratory and clinical research 5 in the biomedical and behavioral sciences; 6 "(ii) applied laboratory and clinical research in 7 the biomedical and behavioral sciences; 8 "(iii ) clinical trials, demonstration projects, ana 9 disease control programs, designed to test the efficacy and 10 practicability of new approaches to disease prevention, 11 therapies, and health technologies prior to their intro- 12 duction into the health care delivery system of the 13 Nation; 14 "(iv) research in the fields of preventive medicine 15 and public health, as well as development and imple- 16 mentation of health education programs designed to 17 furnish to the public the information necessary for main- 18 te.nance of their health•; 19 "(v) research on the e41'icient and econonlic integra- 20 tion and utilization of new technologies within the health 21 care delivery system; 22 "(vi) the operation and activities of the National 23 Health Research and Development Advisory Commis- 24 sion estttblished ttnder section 501 above-except that 25 no less than 50 per centunl of fund moneys appropriated

TIMN 450178

6 3 1 velopment Fund for the stable support of programs in 2 research, development, and the effective application of 3 knowledge in, the biomedical and behavioral sciences 4 aimed at the prevention, treatment, and cure of disease. 5 6 Si:c. 3. Title V of the Public Health Service Act is amended by inserting before section 501 the following new 7 part: 8 "PAR'L` A-NATIONAL IlEALTII I;.EsEARCII AND I)EVELOP- 9 MENT ADVISORY COMMISSION AND FUND 10 "NATIONAL IIEALTIi ItESL+'A1tCH AND DEVELOPMENT 11 ADVISORY COMMISSION 12 °`SEC. 501. (a) There is hereby established the Na- 13 tional IIealth Research and I)evelopment Advisory Commis- 14 sion (hereinafter referred to as the 'Commission') which 15 16 17 18 shall consist of fifteen Inelnbers of whom ten shall be ap- pointed by the President from persons who, by virtue of their training, experience, and background, are exceptionally qualifi9d to carry out the duties of the Commission, and five 19 shall be the chairmen of the expert panels authorized under 20 21 22 .33 subsection (e) (5) below. Appointment to the Commission shall be for a period of four years except that initial appoint- meut shall be for shorter periods staggered so as to insure that no more than four members of the Commission shall receive full-term appointlmnts in any year. No member of 7 5 s 8 9 18 I 19 20 21 22 23 24 25 4 1 the Commission shall serve more than two terms. No mem- 2 bcr of the Commission shall be an officer or employee of the 3 Federal qovernment. 4 " (b) The President shall appoint one of the members of 7 stitute a quorum and a vacancy shall not affect its powers. the Commission to serve as Chairman and one to serve as ,Y 1CH VLUIIlilAil. L` I~uW 1a~c1~SVOiJ v. vuv v+.,.,...,.:,'lr.'..... L 10 cies on the Commission shall be filled within three months. 11 "(d) Members of the Commission shall each be entitled 12 to receive the daily equivalent of the annual rate of basic 13 pay in effect for grade US~-18 of the Cieneral Schedule for 14 each day (including traveltime) during which they are 15 engaged in the actual performance of duties vested in the 16 COnllmsslon ; and while away from their homes or regular 17 places of business in the performance of services for the "(c) The Commissiori shall be appointed within six months following the date of enactment of this Act. Vacan- Commission, all members of the Commission shall be allowed travel expenses, including per diem in lieu of subsistence, in the same malmer as persons employed intermittently in the Qovernment service are allowed expenses under section 5703 (b) of title 5 of the ilnited States Code. " (e) The Comluission shall- " (1) Review and assess- "(i) the status of fundamental and applied TIMN 450187

2 witlc increasing clarity they tell us that environmental factors are the iuc~st iniportant. coutr1butors to t.he iuost serious preventa.ble diseases of t6e American people. In the face of a growing national conce.rn wit1L health problems, ancl with the rise in the cost of health care, I hc•sc• sauuc epicleiniolof;ist5, publie health experts, and ol her concerned in(livicluai5 arc demanding with increasing forcefichiess and justifica- f ion 111,11 the countr;y clevote 1uure of its attention to t.he prevention, as Acell as tlie c•in•e, of disease. It, was this approach to disease that first ailcrted t.hc+ world to the dangers of thalidomide, and more recently to the environmental hazards of such substances as kepone and articnic•. Now, these scientists tell us that foremost among the preventable c•n6runniental hazards which contribut.e to the ill health of the )eople and to the heavy burden of health care costs is the smoking of cif;arcttes. It is now over 11 years since the Surgeon General's report lirst clcclarecl that there was a firm link bet.ween cigarette smoking and canccr. Since then, eif;ht, suhsecluent official governmental reports on t he health consequences of smoking have presented mounting evidence thatt the tar and nicotine of cigarettes contributes not only to oral and pnlmonsu•y cancer, but also contributes significantly to increased morbidity and mortality from coronary heart disease, cerebral- vascnlar disease, pulmonary emphysema •and chronic bronchitis, and perhaps other conditions, as well. These :u•e nott the chance findings and reconnnendat.ions of some obscure scientist., published in some obscure journal. They are the finclinf;5 and recommendations of those leading physicians and scien- tists to whom we ultimately entrust the health of the American people; our Assistant Secretary for Health of Health, Education, and Wel- fare; the Surgeon General of the TTnited States; the Director of our National Cancer Institute; the Director of our National IIeart and Lung Institute; t.he I)irector of our Center for Disease Control; and man,y others. It is time that we started to listen io some of their advice. 11'hen onr personal doctor diagnoses a potential or actual disease in our body, and reconunends a course of action for our personal welfare, we generally take thatt advice seriously. Now, when our national doctor nc,cke5 a diagnosis and recommends a course of action in the national interest, itt is no less important that. we take that advice seriously and follow it. We must. recognize, however, t.he seriousness of the problem that we face. (ht the one hand are t.he health and scientific issues which I men- I innecl above. On the other hand are the potential economic and social t hiratti tu a 5ignificant. Sef*cnent. of our populat ion; the tobacco growers and t ho5e who work in the cigarette industry. We must, therefore, weigh the evidence again as fairly as possible, and hear from reputable sc•ient ists and phytiicians on bot.h sides. This we shall do during the c•oin•se of these hearings, because the problem demands it. But I must ,aV thatt the Scientific evidence at this point seems convincing to me and I think thatt the burden of proof has shifted in the past• few years froni those who claim that. cigarettes are dangerous to those who claim t hat t hey are not. ln the hearing today, ancl those to follow, we will attempt to ascer- tain to thc fullest extent possible, t.he current state of knowledge on tlie relation5hip between cigarette smoking and disease. While there is I , I 3 a bill before the subcommittee, S. 2902, entitled, the "National Health Research and I)evelopment Act of 1976," it is our hope to devote the initial hearings to the scientific aspects of cigarette smokin • and disease, and to postpone consideration of the details of the bill to a later date. We will at this time, however, include the text of S. 2902 in the record. [The text of S. 2902 follows :] TIMN 450185

~ 14 t 15 1 2 3 11 of this paragraph: Until such time as such reg- ulations are first issued, the conditions, methods, and procedures for conducting such tests shall 42 1 cigarettes which the manufacturer of such cigarettes removes 2 (within the meaning of section 5702 (k) of such Code) after 3 the date of enactment of this Act. 4 be those approved by the Commission for for- ,y mal testing which are in effect on the date of en- 6 actment of the National Health Research and 7 Development Advisory Act of 1976. 8 9 10 11 12 13 14 15 16 17 18 19 20 " (ii) CERTIFICATION TO SEC$ETARY.-At least once each calendar year, the Chairman of the Federal Trade Commission shall certify to the Secretary or his delegate, the tar and nico= tine content of each brand of cigarettes manu- factured in or Imported into the United States. The tar and nicotine content of a brand of cig= arettes as contained in such certification, for purposes of clause (i) shall be the tat and nico- tine content of cigarettes of such brand for the period beginning with the first day of the cal- endar quarter next beginning after such certifi= cation is made with respect to such brand and 21 ending with the last day of the calendar quarter 22 within which the next certification is made with 23 respect to such brand.". 2-1 (b) The amendments made by subsection (a) apply to 4 (c) The Federal Trade Commission and the Secretary of the Treasury or his delegate shall promulgate regulations for purposes of section 5701 (b) (3) of the Internal Revenue Code of 1954 within sixty days of the date of the enactment 8 of this Act. 9. SEC. 5. (a) The title of title V of the Public Health 10 Service Act is amended to read as follows : 11 "TITLE V-NATIONAL HEALTH, RESEACH, AND 12 DEVELOPMENT ADVISORY COMMISSION AND 13 FUND: GENERAL PROVISIONS". 14 (b) (1) Sections 501 through 513 of the Public Health 15 16 Service Act (as in effect prior this Act) are redesignated as 17 respectively. to the date of enactment of sections 521 through 533, 18 (2) Title V of the Public Health Service Act is 19 20 21 6 amended by inserting before section 521 (as redesignated by paragraph (1) ) the f ollowing • "PART B-G}ENERAL PROVISIONS". TIMM 450191

+ CONTENTS COMMITTEE ON LABOR AND PUBLIC WELFARE HARRISON A. WILLIAMS, JR., New Jersey, Chairman JM:NIVINl3B1 ICANUULPH, West Virginia CLAI I3ORNE' IiELL, Rhode Island EDWARD bt. KENNEDY, 111nN9achllsetts GAYLORD NELSON, Wisconsin WALTER F. MONDALF., Minnesota THOAIAS F. EAGLETON, Missouri ALAN CRANSTON, California WILLIAM D. HATHAWAY, Maine JOHN A. DURKIN, New Ilampshire JACOB K. JAVITS, New York ItIC1iARD S. SCHWEIKER, I'enusylvan4n ROBERT TAFT, JR., Ohio J. GLENN BEALL, JR., Maryland ROBERT T. STAFFORD, Vermont PAUL LAXALT, Nevada I/ONALD ELISBURU, General Counael MARJORIE 1(t. WHITTAKER, Chief Clerk JAY B. CUTL®R, MinoritV Counsel SUBCOMMITTEE ON HEALTII I EI)WARD AI. KENNI:1)Y, MassRel111sPtte, Chairman em n, r. owar ., merican Crulcer Society, professor of viral cology and cell biology, McArdle Laboratory for Cancer Resear University of Wisconsin Madison IIARItISON A. WILLIAMS, JR., New Jersey RICHARD S. SCIIWEIKI'sR, Pennsylvania , _______________________________ Sonuners, Dr. Sheldon C. director Laboratories at the Lenox Ilill H GAYLOItiF NELSON, Wisconsin JACOB K. JAVITS, New York , , pital, New York, and professor of pathology College of Physicians f TIIOMAS F. EAGI.ETON, Missouri ALAN (9tANS'I'ON, California J. GLENN BEALL, JR., Maryland .)R., Ohio ROBERT TAFT , Surgeons, Columbia University of New York, accompanied by Horace ('LA11tO1tNI: I'ELL, Rhode Island , itOR1:ItT T. STAFFORD Vermont Kornegay, president, the Tobacco Institute, Washington, D.C., and WALTIat F. MONDALE, Mlnnesotn , PAUL LAXALT Nevada Theodore I). Sterling, Director, Computer Science Program, Sini WILLIAM Ir. IIATIIAWAY. Maine , Fraser University, Canada______________________________________ JOHN A. I)I)RKIN New Ilampshlre Sterling, Theodore I)., Ph. D., director, Computing Science Progri , Simon Fraser University, Vancouver, Canada____________________ Lr.Ror (:. GoLOn1AN, I'roJeeaional Staff Member JAY B. CUTLER, Minority Counael S. 2902, text of--------------------------------------------------- CHRONOLOGICAL LIST OF WITNESSES THURSDAY, FEBRUARY 19, 1976 Hart, Hon. Gary, a U.S. Senator from the State of Colorado___-_______ rluliuiesl.0u, riutF. 'irall.er iJ., a'V.S. aenatur LPom cile ACHCe oi ~11ena7c~K, Heims, Hon. Jesse, a U.S. Senator from the State of North Carolina___ Ford, Hon. Wendell H., a U.S. Senator from the State of Kentttcky_____ I'erkins, Hon. Carl D., a Representative iII Congress from the State Kentucky ------------------------------------------------------ Morgan, Hon. Robert, a U.S. Senator from the State of North Carolinj Cooper. Theodore, M.D., Assistant Secretary for Health, Department Health, Education, and Welfare, accompanied by Dr. David Sen/ director, center for disease control; Dr. Frank J. Rauscher, direct National Cancer Institute, National Institutes of Health; Dr. Robert Levy, Director, National Heart and Lung Institute, National Institu of Health ; and Mr. Gene R. Haislip, Deputy Assistant Secretary . Legislation (Health), Department of Health, Education, and Welfe a panel --------------------------------------------------------- Dulbecco, Dr. Renato, Imperial Cancer Research Fund Laborator: London, England----------------------------------------------- 'I' i I) H d M A Byrd, Benjamin F., Jr., M.I)., president, American Cancer Society, p fessor of clinical surgery, Vanderbilt. iJniversity School of Medici Nashville, Tenn. ; Dr. Henry Blackburn, American Heart Associati professor and director, Laboratory of Physiological Hygiene, UniN sity of Minnesota Schools of Medicine and Public Health, Minneapo Minn.; and Dr. Stephen M. Ayres, board member, American Lung AF ciation, professor and chairman, Department of Internal Medici St. Louis University School of Medicine, St. Louis, Mo., a panel___ WEDNESDAY, MAR(:Ir 24, 1976 Moss, Hon. Frank F.., a U.S. Senator from the State of IJtah________ Hart, Hon. Gary, a U.S. Senator from the State of Colorado___________ Brooke, Hon. Edward W., a U.S. Senator from the State of Mnssachuset Jones, lion. Walter B., a Representative in Congress from the State North Carolina and chairman, Subcommittee on Tobacco of the Ho Aericttltttre Committee__________________________________________ Aiathis, Hon. Dawson, a Representative in Congress from the State Georgia ------------------------------------------------------- Fuqua, Hon. Don, a Representative in Congress from the State of Florid; Jenrette, Hon. John W. Jr., member of the House of Representatives fr the State of South Carolina_____________________________________ (III)

12 9 1 under this Act shall be used for the purposes described in subsections (iii) , (iv ), and (v) above. 2 2 "(b) The Secretary of Health, Education, and Welfare 3 3 4 shnll allocate these funds among those programs authorized 4 5 in the Public Hcalth Service Ac•t which are pursuant to tne 5 6 purposes defined in section (a) above. 6 7 "(c) Amounts provided in section 502 (a) herein shall 7 8 be in addition to, rather than in substitution for, appropria- 8 9 tions authorized by other Acts for those purposes stated in 9 10 section 502 (a) herein. 10 11 "(d) The programs funded by this section shall not 11 12 qualify as one of the exceptions provided in section 401(d) 12 13 of the Congressional Budget and Impoundment Control Act 13 14 of 1974: '. 14 1K SFC. 4. (a) Section 5701 (b) of the Internal Revenue 15 16 Code of 1954 (relating to the rate of tax on cigarettes) is 16 17 amended by adding the following new paragraph : 17 18 " (3) A1,L CIGARLTTE$.- 18 19 "(A) IMPOSITION OF TAx.-On every cigar. 19 20 rette, regardlm of weight, 20 21 "(i) in calendar year 1977, a health rL- 21 2L search and development tax of $0.0002 for each 22 23 milligram of tar and $0.002 for each milligram 23 24 of nicotine contained therein; 24 25 (ii) in calendar year 1978, a health re_ 13 10 search and development tax of $0.0003 for each milligram of tar and $0:003 for each milligram of nicotine contained therein; "(iii) in calendar ydar 1979, a health re- searcn ana deveiopmeni ulx vi W.ili,i,4 ;m Mwil milligram of tar and $0.004 for each milligram of nicotine contained therein; and "(iv) in calendar year 1980, and for each year thereafter, a health research and develop- ment tax of $0.0005 for eabh milligram of tar and $0.005 for e9ch milligram of nicotine con- tained,therein.' "(B) DE°1`ERMINATION OF TAR AND NICO- TINE C(dNT$NT.- "( i) TESTING BY FEDERAL TRADE COM- JVIIi;BION.-The Federal Trade Commission (hereinafter referred tb as- the 'Commission') shall from time to time (but at least once each calendar year) test for the tar and nicotine con- tent of each biand of cigarettes manufactured in or imported into the United States. The con- ditions, methods, and procedures for conducting such tests shall be promulgated by the Corn- mission in regulations issued by it for purpoqes TIIVIlN 450190

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 8 5 clinical nnd lahoratory research in the biomedical and behavioral sciences; (ii) thc scientific and socially significantt areas of health research aml development, and ways in which tiuc•h areas ma.y lie best developed; "(iii) the quality and efficacy of ongoing pro- grants in health demonstrations, clinical trials, and disease control programs, and make recornmenda- tlons for tlie timely initiation or modification of prograws as new opportunities arise from the re- search effort; "(iv) current activities in the fields of pre- ventive medicine and health education, and make recommendations on how such activities may be hest utilized; and "(v) the overall field of healt.h research and the application and dissemination of health tech- nology aucd knowledge to assure that a proper haLcnce of resource allocation and effort is wain- tained aniong the several components of the health re,warch, development, and applica.tion systeni, arnd tliat. the health care delivery system is receiving the henelils of the health research and development svmeul in a safc, t.irnel,y, and economieal tnanner. `= (2) ('ccnduct other studies relating to health re- I 9 I :3 4 6 search and development or the application and dissemi- nation of health technology as the President or the Con- gress may from time to time request or as the Commis- sion may deem necessary. , " ('i) lteport its conclusions concerning nctivities 6 7 8 9 10 11 12 13 mlder subsection (1) above, and make recommendations at least once every two years to tho President and the Congress. "(4) Make recommendations to the President and the Congress on the appropriate distribution of maneys in the National IIealth Research and Development Fund, established under section 502. "(5) Appoint five panels of qualified experts, one 14 for each of the areas defined in section 502 (a) (i), (ii), 15 (iii), (iv), and (v), to advise the Commission. Each 16 panel shall elect its own chairman, who shall serve as a 17 fnll member of the Commission as provided for in see- 18 tion (a) above. 19 "(f) 'I'he Commission is authorized to- , 20 4(0) appoint and fix the compensation of such per- 21 sonnel as may lie necessary, without regard to the pro- 22 visious of title 5, United States Code, governing arpoint- 23 rnents in tiie; cotrchetitive service, and withont regard to 24 thc lrrovisious of chapter :i 1 and suhchapter T1I of chap- TIMN 450188

W 48 for males, but remains stationary for females, which throws doubt on the theory that the increase in female incidence can be attri- buted to smoking." 2. This disease has a very clearly defined age-incidence. The peak occurs between 55-70 years of age in the general popu- lation. As will be seen later this age-incidence is an important item. 3. In spite of etatistical data to the contrary and arguments to support it, there is no clearly established dosage factor. The statistical associations generally point out that the more one smokes, or the longer that one has smoked, the grehter is the statistical chance of developing cancer of the lung. It has not been shown that increased smoking ie related to earlier onset. In fact, Profeseor'Passey clearly demonstrated that regard- less of the amount or duration of smoking the victims of this disease developed their tumors at approximately 60 years of age, as expected. The lack of a dosage factor emphasizes again the etrict age-i-ncidence distribution in the disease. 4. German pathologists, notably von Kikuth, showed this disease to be increasing in frequency in autopsy material beginning around 1890. was, u'.: .-- _. ~-- . rettea became popular. 49 5. Cancer is a rarity in the windpipe or trachea, even though all of the inhaled smoke passes through this tube, and the material deposited in the mucous lining of the air passages also exits through the trachea. 6. It is also rare to have a lung cancer appear on both sides of the lung and particularly on both sides simultaneously. if smoke is evenly distributed during smoking, why should this be so? 7. It is of further interest that people who have sur- vived the treatment of one lung cancer successfully do not appear to develop another in any significant proportion thereafter. 8. Cancer of the larynx or voice box is also a male disease and is conventionally related directly to smoking. eow- ever, this cancer has shown little increase in incidence despite the fact that the larynx is obviously much "closer to the fire." Certainly all inhaled "carcinogenic" material must enter and all material carried by the mucous must exit through this narrow portal between the vocal cords. Cancer of the larynx and cancer of the lung are supposedly caused by the same etiologic agent-- smoking. Yet, how could the same agent cause little change in the incidence in laryngeal cancer and simultaneously cause an "epidemic" incidence in luna aaneer7 TIMN 450208

64 ~ -5- 65 ~ -6- MAINE (23) (Cont.) PENNSYLVANIA (42) (Cont.) Death Rates A1f -Causes Death Rates ATFCauses Code Male Female Count Code Male Female Co unty_ 23021 138.2 Piscataquis _ 42045 194.1 139.0 Delaware 23023 181.2 145.6 Sagadahoc 42047 141.8 Elk 23025 141.9 Somerset 42049 190.8 140.5 Erie 23027 138.9 Waldo 42051 139.7 Fayette 23029 138.3 Washington 42053 153.8 Forest 23031 192.4 147.3 York 42069 195.4 152.6 Lacawanna 42073 137.0 Lawrence MINNESOTA (27) 42075 147.8 Lebanon 27075 143.0 Lake 42077 178.3 Lehigh 27123 186.0 Ramsey 42079 179.4 LuzeYne 27135 138.1 Roseau 42081 142.2 Lycoming 27137 181.4 137.2 St Louis 42089 157.4 Monroe 27139 140.7 Scott ?71.51 136.4 Swift 42095 187.5 Northampton 42097 138.7 Northumberland 42099 151.5 Perry • PENNSYLVANIA (42) 42101 i 221.1 155.6 Philadel hia 42003 202.1 143.1 _ p Allegheny --, 42103 184.1 149.2 Pike 42007 193.7 138.9 Beaver 42011 137.9 42107 150.0 Schuylkill Berks 42113 177.2 144.3 Sullivan 42023 197.7 Cameron 42117 136 1 Ti 42025 139.3 Carbon . oga TIMN 450216 42121 139.1 Venan o 42041 138.0 Cumberland g 42043 177.8 138.2 Dauphin 42125 182.3 Washington 4') 1 11 -~ ~ ....._ . -

Iv Dnncnn, lion. John J., a Representative in Congress from the State af Page p I'cnnc~scc ------------ 727 Soicriicld, Iion. I)avid E., a ItepreRentative in Congress from the State o l'irginin ------- ------------ Ncnt, lion. Stephen L., a Representative in ('onFreRR from the State of North ('aruliaa---------------------------------------------------- 729 733 TiiliRRnAY, MAY 27, 1976 iiaislip. (:ene R., Deputy Assistant Secretary for Legislation (Health) ; accompnnied by I)r. I)avid Senccr, director, ('enter for 1)isease Control l)r. Iinnald Lnmont-HaverR; and 1)r. (.ernld Rosenthal, director, National t'enter for Health Services Reccarch, Health Resourc•eR AdmiuiRtration_ 764 .Indt;e. 1'urtis II., president, 1'. Lorillard & Co., chalrman, Tobacco Institute H;sccniive (bmmitteer, accoiu17.7nnied by Arthur Stevens, vice president a+n nn~l general counsel------------------------------------------------ ivo STATEMENTS American Cancer Society, Inc., Benjamin F. Byrd, Jr., president, pre- pared statement-------------------- ---- American Lung Association, Stephen M. Ayers, M.I)., member, board of directors, prepared st.at.ement_____________________ Aviado, I)omingo M., M.D., professor of pharmacology, University of Penn- Rylvanin School of Medicine, prepared statement- Curricuhum vitae ------------------------------------------------ R liimorc• Dr Dnvid Nolx•l Prize winner, Massachusetts Institute of a 533 648 I , 2s _/(..1 , . . Technology, prepared statement.------------------------------------- 261 Blackburn, Itenry, ,M.D., representing the American Heart Association, director, Laboratory of PhysioloRical Hygiene, School of Public Health, ltniversity of Minnesota, prepared statement, with att.achments--___-__ 614 Rrooke, lion. Edward W., a 1T.S. Senator from the State of Massachusetts_ 701 Byrd, Benjamin F., M.D., president, American Cancer Society, professor of clinical surgery, Vanderbilt University School of Medicine, Nashville, 9'enn. ; Dr. llenry Blackburn, Anierican Heart Association, professor and director, Laboratory of Physiological Hygiene, University of Min- nesota Schools of Medicine and I'ublic• Health, Minneapolis, Minn. ; and 1)r. Stephen M. Ayers, board member, American Lung Association, pro- fessor and chairman, Department of Internal Medicine, St. i.ouis Uni- versit,v School of Medicine, St. ImuiR, Mo., a panel____________________ I'relm red stntement-------------- ('nrbnni;h S MnRon commissioner, Virginia l)epartment of Agriculture 530 533 antl ('nmmeree prepared statement---------------------------------- 688 ('nniti•r, Thecalore, MI)., Assistant Secretary for Ilealth, Department of licnlth, I4ducation, and Welfare, accompanied by Dr. David Sencer, Di- rector, Center for IlisenRe ('•ontrol ; Dr. Frank J. Rauscher, Di- rectnr, National Cancer Institute, National Institutes of Health; Dr. RnIK•rt 1. Levy, I)irector, Nntional Heart and Lung Institute, National InRtitntes of Iienlth; and ~.NIr. (;ene R. Haislip, Deputy Assistant Secre- tary for Legislation (Ilealth). Delmrtment of Health, Education, and Welfare, a panel--------------------------------------------------- Prepared statement---------------------------------------------- lianiel, Ilon. Dan, n ReprcRentatic•e in Congress from the Stat.e of Virginia, prepared sta(ement_----------------- I)ulherco. Dr. Renatn, Imix•rial Cancer Research Fund Lnboratories, Lon- dnn, England ------------------------------------------------------- Prplinrpd statement---------------------------------------------- I)micnn lton John J.. a Representative in Congress from the State of 175 187 683 239 244 TenneRsr _ 727 Forll, lion. Wendell Ii.. a TA.S. Senator from the State of Kentucky------- 116 Prepared Rtatement------------------------------- ------------- 123 Fnuntnin, i1on. L. ii.. a Representative in Congress from the State of North Carolina, prepared Rtatement--------------------------------------- 673 Fuqnn, lion. Don, a Representative in Congress from the State of F1orlda- 721 FarRt, Arthur, Ph. D., director, Institute of Chemical Biology, University of San Francisco, prepared statement-------------------------------- 100 V Haislip, Gene Il., Deputy Assistant Secretary for IAgislation (Health), ac- companied by Dr. David Sencer, Director, Center fqr DiAease Control ; Dr. Ronald Lamont-Havers ; and Dr. Gerald Rosenthal, Director, Na- tional Center for Health Services Research, Health Resources Adminis- Page tration ----------------------------------------------------------- 764 Prepared statement------------------------------- ~-------------- 769 Hart, Hon. Gary, a U.S. Senator from the State of Colorado------------- 17-700 Helms, Hon. Jesse, a U.S. Senator from the State of North Carolina__---- 72 Henderson, Hon. David N., a Representative In Congress from the State of North Carolina, prepared statement--------------------------------- 741 Hine, Charles H., M.D., Ph. D., clinical professor of pharmacology and pre- ventive medicine, School of Medicine, University of California, San Francisco, Medical Center, prepared statement----------------------- 127 Hockett, Robert C., Ph. D., research director, Council for Tobacco Research- U.S.A., Inc., prepared statement------------------------------------- 146 .... .... . I , r1VlLllls.~, 11V~~. u111COL 1., 6 V.U. AlCl12lLV1 11VW L/lC ,JLiILC Vl klV4Lll VULV- lIna, prepared statement------------------------------------------- 820 Hubbard, Hon. Carroll, Jr., a Representative In Congress from the State of _ Kentucky, prepared statement------------------------------------ -- 743 Huddleston, Hon. Walter D., a U.S. Senator from the State of Kentucky_- 26 Imperial Cancer Research Fund Laboratories, London, England, Dr. Renato Dulbecco, prepared statement--------------------------------------- 244 Jenrette, Hon. John W.,Jr., a Representative In Congress from the State of South Carolina-------------------------------------------------- 724 Jones, Hon. Walter B., a Representative In Congress from the State of North Carolina and chairman, Subcommittee on Tobacco of the House Agriculture Committee---------------------------------------------- 703 Prepared statement---------------------------------------------- 709 Judge, Curtis H., president, P. Lorillard & Co., chairman, Tobacco Institute Executive Committee, accompanied by Arthur Stevens, vice president and generalcounsel----------------------------------------------------- 796 Koch, Hon. Edward I., a Representative in Congress from the State of New York, prepared statement__________________________________________ 748 Kornegay, Horace R., president, the Tobacco Institute, Inc., prepared statement with attached exhibits____________________________________ 318 Laboratories at the Lenox Hill Hospital, New York, Dr. Sheldon C. Som- mers, director, preparecistatement----------------------------------- 280 Langston, Hiram Thomas, M.D., clinical professor of surgery, Abraham Lincoln College of Medicine, University of Illinois, prepared statement- 45 Biographical data------------------------------------------------ 53 Massachusetts Institute of Technology, Dr. David Baltimore, prepared statement --------------------------------------------------------- 267 1lfathiR, fion. I)awson, a Representative in Congress from the State of Georgia ----------------------------------------------------------- 712 Prepared statement---------------------------------------------- 717 McArdle Laboratory for Cancer Research, University of Wi§consin, Madi- son, l)r. Howard I1t. Temin, Americnn Cancer Society profes9or of viral oncology and cell bioloRy,prepared statement.------------------------- 262 Murgan, lion. Robert, a 11.S. Senator from the State of North Carolina____ 171 Moss, Hon. Frank E., a U.S. Senator from the State of Utah______________ &96 Neal, Iion. Stephen L., a Representative in ConRresR from he State of North ('nrolina---------------------------------------------------- 733 North Carolina Agribnsinc.eG Council, Frank Bryant, executive vice presi- dent, prepared stntement------------------------------------------- 760 North Carolina Farm Bureau Federation, John Sledge, president, prepared statement ---------- _- 757 Okun, Ronald, M.I)., M.S., associate professor of medicine and medical pharmacology an8 therapeutics, i'niversity of California, California Cal- lege of Medicine, Irvine. Calif., prepared Rtatement------------------ --- Perkins, lion. Carl I)., a Representative in Congress from the State of Kentucky --------------------------------------------------------- 168 Preyer, lion. Richardson, a Representative in Congress from the State of North Carolina, prepared stntement--------------------------------- 751 Satterfield, lion. David E., a Representative In Congress from the State of Virginia ---------------------------------------------------------- 729

democratic society, through its representatives, acts, it does so demo- cratically, equitably. ,"" I come from a major tobacco producing State-the income from which all aspects egceeds a billion dollars a year. We have taken it on the chin for many years--when others have sat back and watched us sweat-but the time has come for Congress, national organizations and research facilities to be honest enough to look at the entire picture, not one piece of the puzzle. I ask the following be made a part of the record : (1) Counties in the United States of subcommittee members plus Colorado, ranking above the national average for deaths from all forms of cancer. (2) An article from the Bergen County, N.J., paper dated Decem- ber 21, 1975, "N.J. : Cancer Capitol." (3) An article from the Washington Post, dated February 16,1976, entitled "Colorado Plutonium Safety Debate Rages." Senator KExxEnY. They will be made a part of the record. [The information referred to follows:] Counties in the United States with the Highest 1upper 10%) Age-Adjusted Death Rates for.Cancer from All Causes. ICD 140-205 TIMN 450213

60 61 COLORADO (08) WISCONSIN (55) Death Rates All Causes Death Rates A Caues Code Male Female County Code Hale Female County 08019 162.9 Clear Creek 55001 136.0 Adams 08033 139.5 Dolores 55003 141.4 Ashland 08047 194.0 Gilpin 55021 136.7 Columbia 08055 141.8 Huerfano 55031 148.9 Douglas 08057 163.5 Jackson 55037 186.6 Florence 08065 140.7 Lake 55051 192.2 Iron 08091 197.0 Ouray 55053 141.7 Jackson 08093 136.8 Park 55055 137.2 Jefferson 08119 187.6 Teller 55059 178.3 Kenosha 55063 137.0 La Crosse MASSACHUSETTS (25) 55071 136.2 Manitowoc 25001 142.0 Barnstable 55077 145.1 Marquette 25003 189.1 146.8 Berkshire 55079 203.2 144.0 Milwaukee 25005 199.1 143.7 Bristol 55085 192.1 139.1 Oneida 25007 190.0 Dukes ' 55101 180.1 Racine • 25009 192.6 138.4 Essex 55125 140.3 Vilas 25013 192.5 139.4 Har.ipden 55127 138.4 Walworth 25017 192.1 139.9 Middlesex 25019 181.8 129.5 Nantucket NEW JERSEY (34) 25021 181.8 136.4 Norfolk 34001 195.3 145.2 Atlantic 25023 179.3 136.5 ?1vr^outh 34003 202.1 148.1 Bergen 25025 223.3 ) l / 151.1 Suffol': 34005 188.5 139.9 Burlington

62 N - 3- NEW JERSEY (34) (Cont.) Death Rates All Causes Code Male 34007 204.7 . 34009 194.7 34011 181.4 34013 215.1 34015 191.1 34017 ~ 23~ 34019 175.7 34021 205.4 34023 220.8 34025 199.0 34027 179.2 34029 185.5 34031 209.5 34033 185.9 e~n~e 1 07. C 34037 180.8 34039 203.4 34041 189.3 Female Count 148.4 Camden 142.9 Cape May 140.0 Cumberland 154.5 Essex 141.8 Gloucester 153.5 Hudson 143.3 Hunterdon 145.2 Mercer 149.2 Middlesex 147.6 Monmouth Morris 137.2 Ocean 147.8 Passaic 146.4 . Salem Cnmcrc[?t 140.5 Sussex 151.6 Union 147.7 Warren CALIFORNIA (06) 63 Death Rates A-=Causes Code Male 06001 179.1 06003 191.3 06011 191.6 06023 06051 06067 186.2 06075 121.0 06115 182.3 Female County Alameda 373.4 Alpine Colusa 136.3 Humboldt 163.3 Mono Sacramento 149.6 San Francisco Yuba RHODE ISLAND (44) 44001 205.4 Bristol 44003 212.8 146.2 Rent 44005 199.3 145.6 Newport 44007 204.6 144.2 Providence • MAINE (23) 23001 194.8 148.6 Androscoggin 23005 187.1 139.8 Cumberland 23007 139.3 Franklin 23009 178.6 147.4 Hancock 23011 139.0 Kennebec 23013 192.6 143.1 Knox 23015 177.8 155.2 Lincoln TIMN 450215

46 I do, however, seriously object when such action is based upon the hypothesis that cigarette smoking is the cause of cancer of the lung. In addition to clinical observations refuting this hypothesis, there exists strong evidence that the incidence of lung cancer has crested and is turning down. Thus the rise and fall of the incidence of this disease is a biological phenomenon rather than a consequence of any action on our part. In this view I have the support of eminent physicians and statisticians. Thus I cannot agree with the hypothesis that ciga- rette smoking is the cause of cancer of the lung. The net result of the enormous volume of statistical data that has been amassed has merely been to establish an association between the consump-• tion of cigarettes and the development of lung cancer. I quite agree with Mr. Hart when he pointed out in the Congressional Record of January 29, 19T6, that "Determining that the association between smoking and excess death rates is causal was a judgement made by DHEW after a number of criteria fiad been met." I emphasize, however, that the establishment of HEW's criteria merely represents a refinement of statistical manipulation which attempts to change the data reviewed from a statistical association to one of cause and effect. 47 It is my purpose herewith to offer data in support of my judgement that the statistical associations, however strong and however voluminous, do not represent a causal relationship. I have not sought to alter the conclusions derived from these statistical associations by further statistical manipulations. Even if I succeeded, the end result would be inconclusive and would merely invalidate the method. I have consequently sought the basis for my opinion in the clinical area, observing the behavior of the disease in patients, rather than in statistical manipulations. There is an old adage, "It is the exception that proves (tests) the rule," that suggests to me that the clinical behavior of the disease offers sufficient exceptions to the ata- tistical association that we should pay them heed. The clincial behavior of this disease in my patients and as expressed in the literature from the experience of others can be clearly listed: 1. Lung cancer is predominately a disease of men. Although an increased incidence is reported in women, at least two studies from Iceland and England have shown that this increase is not due to the type of tumors usually associated with smokingt namely, the squamous cell and oat cell cancers (Rreyberg group I tumors). In fact, Dr. Jonas Hallgrimason in the Icelandic .«„a.. .F_«..~ " .,mw- _"- _~ ..___r-„-s ,,,,.r. - - : : aas , . . ., r. . .... , ... , ,.., .. .~.r .,ncreasec. TIMN 450207

I I ! 26 approaches to the alleviation or cure of disease. There are, however, other sig- niflcant steps in the translation of research progress into real benefits at the level of health care delivery system of the country. We have not paid enough attention to some of these critical steps. Thus, we must expand appreciaiN7 our efforts in the fields of preventive medicine, epidemiology, and public health. We must reinforce existing mechanisms, or develop new mechanisms to insure that the health care delivery system is receiving the benefits of health research and development in a safe, timely, and economical manner. Most important, there is an increasing need to assure that a proper balance of resource allocation and effort is maintained within the overall field of health research and the applica- tion and dissemination of health technology and knowledge, so that we may be sure that our -investment in these areas is appropriately serving Its desired pur- poses-Improvement of the •health of the people and Teduction of the costs of health care Mr. President, the bill introduced by Mr. HART and myself is inte.nded to: First, focus attention upon the increasingly important issues of environmental health hazards, and Second, stimulate consideration of underdeveloped areas In our health research and development activities. Initial hearings on the subject "Cigarette Smoking and Disease" will be held before the Subcommittee on Health of the Committee on Labor and Public Wel- fare on -February 19, 1976-as the first In a series of hearings on environmental health hazards. In addition, the Subcommittee on Health will be holding oversight hearings this spring on Federal support of biomedical research. We look forward to the report of the President's Biomedical Research Panel as a major input to these hearings. We also expect reports on more specific areas of medical research such as a review of the cost/benefit of high technologies being conducted by the Of- fice of Technology Assessment. The bill I join MT. HesT in introducing today will ultimately be considered in the light of this review of biomedical research-and the specific provisions of the bill, such as the new Commission It creates, will be integrated at the time with whatever structural changes result from this broad review. Mr. President, it is a great pleasure to join the Senator from Colorado in in- troducing this bill. Senator KENNEDY. We will hear from a number of my colleagues in the order of seniority which would be Senator Huddleston, Senator Ford, Senator Morgan, and Senator Helms who will follow Senator Huddleston. I notice the chairman of the House Committee, Congress- man Perkins is here. Well, we will take them and just proceed in the order listed. Senator Huddleston? e1.n ~ RITVTiTT nt.+ anW..TmL4 11. ... umnnr FQTnX- A 11.5. SENATOR I~IL.Ja...J.~.I.J.. .. u.. ..L1T. mI ..A.. .. FROM THE STATE OF KENTUCKY Senator Huani.ESTON. Thank you, Mr. Chairman. Senator KENNEUi. We want to welcome you, Senator. We know you are interested in this issue and welcome your testimony. Senator HUnni.E6TON. Thank you very much. I appreciate the opportunity to appear before the subcommittee and offer sonie thoughts relating to the legislation pending before this committee. Mr. Chairman, in preparing for this hearing, I reviewed a closing statement made by my former colleague, Senator Cook, at the con- clusion of hearings before the Consumer Subcommittee of the Senate ('ommittee on Conunet•ce on February 10, 1972. He said at that time the "question of smoking and health . . . is still a question." That, certainly, is where we commence in these hearings if we are talking 27 about the "tar" and nicotine content of cigarettes and their effect- if there isany effect--on human'health. Those 1972 hearings were held with regard to proposed legislation to require the Federal Trade Commission to set maxlmum levels of "tar" and nicotine content of cigarettes. And the result was that no one wanted to set any level of smoking as "safe." You may recall that-scientific witnesses who appeared, or submitted statements, did not believe that a cause-and-effect relationship had been established between cigarette smoking and disease. The arpv- ments were characterized by one doctor as a blend of logic, statistics, and emotion. Another-doctor found no convincing evidence that either (itar" or nicotine or, any other agent in cigarette smoke had been in- criminated in relation to any human disease. Statements were later- received from at least a half dozen scientists who: .. . (1) did not believe that tobacco smoke condensate had been' estab- lished as harmful or hazardous, (2) concluded that repotts of less disease in subjects switching to filter cigarettes were unconvincing, (3) questioned the data on heart disease and smoking and pointed out that much ocP the data failed to show any link, (4) disputed charges. that smoking causes injuries to pregnant women and their infants, (5) reviewed animal experimentation work and found it wanting with regard to its supporting any charge that tobacco smoke is car- cino ernc to`human beings, and (6) indicated that measures based on the amount of "tar" and nico- tine in the cigarettes were not scientifically based. Dr. Theodor Sterling, who I understand will be present to testify later today, has sent me a statement at my request for the hearing today. It is his concern that we will overlook, in the process of attempt- ing to solve all our disease problems by blaming smoking, the multi- tude of environmental hazards that may exist in our country today. An M.D. writing in the January 12, 1976, issue of the Journal of the American Medical Society took issue with a group he called medi- cal pests. He had this to say : When one considers the antismoking campaign, the seatbelt and seatbag - .__ _ ,.. . w..o ,.., ....t.... kt,., ....F1d, ..o.. .. to„ Ahn wntihorwrtPnslon _ ..,:,,.., ..,:• _.7 ... ,... •..,,,_.., ..,......... ,1,~.... .........._,. . campaign, the physical fitness camlpaign, the antidiabetic campaign, and the myriad of smaller paternalistic campaigns, one realizes that in no field of endeavor has the Big Brother concept been pushed further. than in preventive medicine. The doctor urges those who want the Federal Government to solve all our problems for us to-and I quote- recognize that they areitrodding on others freedom by some of their actions and by other actions are antagonizing the very Individuals they wish •to convert. Dr. I)omingo Aviado, a professor of pharmacology at the iTniver- sity of Pennsylvania, has submitted a statement to me in which he describes his experimentation work with the disease emphysema. IIe stated that in his laboratory experimental animals exposed to cigar- ette smoke have not developed functional or pathological signs of pulmonary emphysema. With regards to coronary heart disease he stated-

66 -7- NEW YORK (36) Death Rates A 1 Causes C d Male Female Count o e 36001 202.6 143.4 Albany 36015 191.5 136.7 Chemung 36021 180.8 Columbia 36029 207.0 142.3 Erie 36031 179.0 146.1 Essex 36035 187.9 137.5 Fulton 36039 191.5 147.6 Greene 36041 148.2 Hamilton 36043 180.1 138.7 Herkimer 36055 181.5 Monroe 36057 179.2 137.5 Montgomery 36059 212.3 155.1 Nassau 36061 215.6 159.8 New York City* 36063 184.2 Niagara 36067 189.9 Onondaga 36071 189.2 Orange 36077 137.9 Otsego 36079 195.6 156.2 Putnam 36083 198.4 147.4 Rensselaer 36087 180.6 Rockland 36091 184.2 Saratoga 36093 202.8 139.8 Scae:ectady 67 -e_ 4 NEW7 YORK (3A) (Cont. )_ \ Dea Rate~ !il .3 , ~:,fa "t~ d u .v . a seg . . ' ^.- ~ C, ode„ `; 4male Count ' .36105 188.4, .145..0 Sullivan 36111 193.4 144.3 Ulster 36113 191.8 1*43.1 Warren i 36115 142.7 iiashington 36119 :199..9 147.0 :iWestcYe4er • ' - .. . .' . . . Missouri (29) _ St.. Louis City St. Louis Jackson Jasper Laurehce Clinton Sullivan Male • , • Female .. 220.1 - , 145. 4 181.5 •182, 0' 180.5 A88. 3 144.9 a ' 140.4 * New York City is co-c=ised cf Bronx, Kings, New York, T'ITVIN 450217 Queens, and Ric::a:o: d Cc~-t~'s.

V0• 28 There are marked geographical differences in its incidence that cannot be explained by smoking patterns. For example, the .iapanese are among the heav- iest smokers but have a low coronarS heart disease rate. I ask that I)r. Aviado's statement, including his curriculum vitae and list of publications be made apart of the record. I)r. IIiram Langston, a thoracic surgeon in the Chicago area, also submitted to me, at my request, a statement. Ile states- I cannot agree with the hypothesis that cigarette smoking is the cause of cancer of the lung. I ask that Dr. Langston's statement also, including his curriculum vitae and bibliography be made a part. of the record. Mr. Chairman, I am aware that it. is a widely held belief that tar and nicotine in cigarette smoke cause lung cancer. This belief is based on what I and many others feel is questionable evidence. To inclicatu the lack of precise knowledge regarding cigarette smoke and health I would like to call to your attention an article that appeared in the Nocember 19, 1975, Wall Street Tournal. This article indicated that. one racliatinn expert says there is growin}g evidence that radioactive liarticle5 in cigarette smoke are the primary cause of lung cancer, not tars and nicotine. It. is reported that. the radioactivity gets into tobacco from ;;nperphoshhate fertilizers made from phosphate rock which na- turally contains uraniums. I ask that this article "Radioactive I'art.icles in Cigaret.te Smoke '1'ied to Lung Cancer" by Barry Kramer, which appeared in the November 19, 1975, Wall titreet Journal be included in the record. I The material referred to follows :] I 20 Statement of Domingo M. Aviado I am a medical doctor and professor of phaYffsacolo&ltt the University of Pennsylvania School of Medicine. A copy of 4ny curriculum vitae is attached for the record. - I have spent much of my time studying the•disease procesA called emphysema. Since the-dieeaee interferes sevtrrely with respiratory function, One ban detect emphysema in test anifnals by measuring changes in this capability after•eaporduie. Ih oKlr oivh' laboratory, rate and mice exposed to tigarttte smoke have not' .' developed functional or pathological signs of pulmonary eaiphyeeiaa. In emphysema, aa in many other diseasee, the role of genetics has been under investigation. For example, one genZtic defect, alpha-antitrypsin deficiency, has been identified, and, of course, there may be others. One cannot exclude the possibility that smokers who develop respiratory diseases have constitutional makeups or genetic characteristics that predispose them to acquire the smoking habit and at the same time develop respiratory disease. Other researchers have exposed dogs to cigarette smoke through a surgical opening in the trachea. They did not measure pulmonary function but instead examined the lungs histologically. The lesions that they have interpreted as•emphysema have been questioned. With regard to coronary heart disease, there are marked geographical differences in its incidence that cannot be explained by smoking patterns. For example, the Japanese are among the heaviest smokers but have a low coronary heart disease rate. "Tar" and nicotine in tobacco smoke have been singled out for special attention. In my native country, the Philippines, cigarettee are generally much higher in "tar" and nicotine than current U. S. brands. Yet the incidence of respiratory and heart disease is much lower than in the United States. I recognize that number comparisons TIMN 450198 . t

50 9. Finally, it would appear that the generation principally affected by this disease and whatever caused it is the one born between 1890 and 1900. Predictions are offered that when this generation passes into history the incidence of this dreadful disease can be expected to turn down. This welcome turn of events should occur for white males in the United States around 1980. I base my opinion in this area on a personal review of over 4,000 patients covering a period of thirty years in the Veterans Administration Hospital, Hines, Illinois. Broad spidemiological studies based on entire populations in the U.S., England, Wales, and Canada have confirmed the lowering rate of incidence of the disease in the younger age groups. The current wave of incidence is supplied by the older age groups primarily. It is of great comfort indeed to find that Sir Richard Doll, the Regius Professor of Medicine at Oxford University com- mented in the June 23, 1972, issue of World Medicine that "Dr. Langston's observations on the incidence of lung cancer in the United States follows similar observations on the incidence of lung cancer in Britain and lead to similar conclusions." More recently an eminent British thoracic surgeon, Mr. Be..c.ier o,. ,-m.,i.vwa the material available 51 to him from personal work, the national figures for England and Wales, and the HEW data in this country and clearly confirmed the preceding observations. I quote from Mr. Delcher's article: "It is interesting to speculate on the cause of these changes. Are they due to the discovery of the relationship of cigarette smoking to bron- chial carcinoma and the subsequent national campaign against the habit? This seem a likely suggestion until it is realised that the fall in the percentage increase in tha rate and eventually of the rate itself in the younger age groups was happening as long ago as 1950. It seews awre likely that the fall in the percentage rate of increase which dates back for at laast fifty years has eventually led to an actual -fall in the rate itself. This process has progressed steadily for many years and repre- sents the natural history of carcinoma of the bronchus." In conclusion, I point out that the conventional hypoths- sis of lung cancer causation is so familiar that it may be diffi- cult to accept the strong evidence to the contrary. I would like to call to your attention the fact that the incidence of cancer of the stomach in this country has exhibited a similar spontaneous decline. In 1949 the rate was 21 per 100,000 and by 1966 it had dropped to 10.7 per 100,000 for white males in the United States according to the Bureau of Vital Statistics. Just as in the case of lung cancer, there is no simple explanation of this phenomenon. In regard to the proposed bill, I cannot accept that such far- reaching legislation is based upon the easy answers of an unfounded hypothesis. TIMN 450209

54 17e1LN.1!'AL YRUFESSIONAL OR BUSIMPSS ACTIVITILS , Diplomate, American Board of Surgery, 1942 - Founder Mecnbber, Board of '1'horacic Surgery, 1948 - Member, The Board of Thoracic Surgery, 1956-1961 - Member of vari- ous co~mittees of national and local societies - Secretary, Aeoerican Association for Thoracic Surgery, 1956-1961 - Vice-President, American Association for Thoracic Surgery, 1968-1969 - President, American Association for Thoracic Surgery, 1969- 1970 - Chicago Surgical Society - Vice President 1971-1972. Member, Editorial Board of the John Alexander Series, Qurles C Thosus, Publisheri Member, Editorial Board, Journal of Thoracic and Cardiovascvlar Surgery; Meeiber, Residency Review Committee - Thoracic•Surgery - Representing American College Surgeons, 1967-72t Chairwan 1969-72. Vice President Staff Grant Hospital, 1972 and 1973; Mesber,Board of Directors Grant Hospital. 1973. Meaber, Advisory Editorial Board "Current Review of Thoracic Surgery" 1973s Thoracic Surgery Representative, Interspecialty Council AMA. 1972; National Thoracic Surgery. Manpower Study - Executive Cooittee, 1971. Membership in Medieal Societies 1lesrican 1lssociation for Thoracic Surgery American College of Chest Physicians (Fellow) American Medical Association American Surgical Association Chicago Medical Society Illinois Medical Society Illinois Surgical Society The Institute of Medicine of Chicago Pan-Pacific Surgical Association Society of Thoracic Surgeons Western Surgical Association Societe Internationale de Qiirurgie Asrrican TtwracJLc Soc:Lety Illinois Thoracic Society 55 Membership on Hospital Staffs Clinical Professor of Surgery, University of Illinois College of Medicine Chief of Surgery, Chicago State Tuberculosis Sanitariutm, Department of PuBlic Health, 1952- 1971, State of Illinois Consultant in Thoracic Surgery, Veterans adsministiation Hospital, Hines, Illinois Attending Physician in Thoracic Surgery, Cook County Hospital Grant Hospital Henrotin Hospital Augustana Hospital - Resigned 1971 Lake Forest Hospital St. Joseph Hospital Highland Park Hospital - Resigned 1971 Hosle Address: 952 Pine Tree Lane, Winnetka, Illinois 60093 Professional or Business Address: b913.ilortis Ckxm@mmsei1idt•.AVenue Chicago, Illinois 60667 TIMN 450211

irf 22 23 The National Health Research and Development Act also provides for amend- ment of the Internal Revenue Code in order to establish a new health tax on cigarettes. This new health tax will be in addition to the existing Federal ex- rise tax on cigarettes. The amount of the health tax for any given brand of clgar- ettes will be determined by the tar and nicotine content of the brand. °icc '1'he health tax will be phased in over a 4-year period. During 1977, the health lax will range from approximately 1 to 20 cents per pack-average. 12 cents per pnck. By 1980, the health tax will be completely phased in and wilt range from 2 14) 50 cents per pack-average, 30 cent.s per pack. At present consumption rates, tbis tax will generate approximately $3.7 billion In 1977 and up to $9.3 billion an- nunlly by 1990 in additional revenues. The health tax will be collected in the sarne manner as is the existing Federal excise tax on cigarettes. '1`his National Health Research and Development Act of 1976 authorizes the appropriation of sums equivalent to the amounts generated by the tax for the purposes and programs mentioned earlier. As with the expenditur+e of other general revenues, these funds will be subject to the regular annual appropriations process. It is expected that the health tax will not only provide necessary funding for those purposes and programs designated above, but will both encoul'age the con- sumer to further consider the significant health hazards of smoking and will provide an incentive for cigarette smokers ot reduce their consumption of tars and nicotine. Therefore, insofar as cigal'ette smoking Is the largest single un- necessary and preventable cause of Illness and early death In the United States, the health tax and revenues derived therefrom will not only contribute to the solution of existing health problems, but also will help reduce and minimize future threats to the public health. To help insure the effective and coordinated distribution of moneys generated by the health tax, this act also provides for amendment of the Public Health Service Act to establish a National Health Research and Development Advisory Commission. The Commission will have responsibility for the ongoing assess- ment of our national health research, development and implementatlons pro- Krnms. and will be charged with making recommendations to the President and the Congress regarding priorities for expansion and initiative within each area. In this fashion, the Commission will help insure the most efficient use of moneys and the balanced allocation of resources within and among the several com- ponents of the health research and development systems. Mr. President, these are only some of the things which the National Health Research and Develop- meat Act will do. Throughout history, America's greatest resource has been its people. However, •ax a Nation,•we have yet to dedicate ourselves to developing and delivering the best health care that medical science can provide. A gap has developed between the acquisition of knowledge and its useful application. In many instances, the msenrch hns been done and the conclusions have been drawn, but all too often we ignore the obvious solutions to problems when those solutions involve more- than-nominal short-term costs. As one result, we continue to allow many toxic substances to pollute our air, our water and our land. Mr. President, we are now confronted with the fact that cigarette smoking is ~ ... -` _ ,_~.. . ., -.. , Ihe largest unnecessary anc prevem ai'.~'i~, ~ i i.n, *hn l1nited States. What are the implications of this? What is the basis for this statement? For answers to these questions, I turn to the 197:'i U.S. Department of Health, F,ducation, and Welfare report entitled "The Health Consequences of Smoking." The i.ntroduction to this report summarizes the scientific basis which supports the conclusion that heart disease, lung cancer, chronic bronchitis and emphysema are not merely "associated with" or "linked to" smoking, but that they are in fact caused by cigarette smoking. Rather than paraphrase or take key sentences out of context, I ask unanimous consent that the pertinent section of this report be printed in the Record. 'P1lere being no objection, the material was ordered to be printed in the Record, as follows : OVERVIEw-HEALTH CONBEQIIENCEB OF SMOKING The statement, "Warning: The Surgeon General Has Determined That Ciga- rette Smoking Is Dangerous to Your Health," has been required by law on ciga- rette packaging since 1970 as a part of the I'ublic Health Cigarette Smoking Act of 1969. This Act was a response •by the U.S. Congress to the scientific infor7nation nn the health consequences of cigarette smoking summarized in reports then ,.., ,- -1- a,.....,..,., (1_-nPrnl'c Report of 1964 and the subsequent 1967, 1968, and 1969 PHS Health Consequences of Smoking). This Act was passed because a series of Important questions concerning cigarette smoking and health had been answered. The following discussion summarizes the basic questions, the methodology used to determine the answers, and the answers themselves. The initial question to be answered concerning the health consequences of smoking was ' Are there any harmful health effects of smoking cigarettes?" The answer to this question was provided in two ways. First, it was demonstrated that some diseases occurred more frequently in smokers than in nonsmokers. Sec- ond, a causal relationship was established between smoking and these diseases. A reasonable place to •begin to look at the health consequences of cigarette smoking was In the area of overall death rates. If cigarette smoking contributed substantially to the development of any major disease, this would be reflected in a higher overall death rate for smokers. Several large prospective studies have clearly shown that cigarette smokers have higher overall -death rates than non- smokers of the same age and sex. Demonstrating this association, however, was not enough to establish the causal nature of the relationship between smoking and excess death rates. The decision whether or not an association is causal is not merely a statement of statistical probability. Determining that the association between smoking and excess death rates is causal was a judgment made by DHI+3W after a number of criteria had been met, no one of which by itself was sufficient to make this judg- ment. These criteria include: a. The consistency of the association. b. The strength of the association. c. The specificity of the association. d. The temporal relationship of the association. e. The coherence of the association. The association between cigarette smoking and excess death rates has con- sistently been demonstrated in a large number of studies performed during the last 30 years. The few studies not showing this relationship had serious defects in their design or analysis which limited the iuterpretation of their results. The strength of the association has been firmly established by repeatedly show- ing that cigarette smokers have one and a half to two and a half times the overall death rates of nonsmokers. The specificity of the association was demonstrated by establishing that sub- stantial excess overall rates occurred in populations of smokers grouped by age, sex, race, socioeconomic class, occupation, place or residence, and many other variables. The temporal relationship of the association between cigarette smoking and overall death rates was clearly shown by the marked decrease in excess death rates that occurs after stopping smoking. The coherence of the association was established by showing that a dose- response relationship persisted when dosage was measured by number of ciga- rettes smoked per day, duration of smoking, age of initiation of smoking, depth of inhalation, or pack years of smoking. This relationship was also demonstrated in prospective as well as retrospective studies. .. ., ., . ... ..... , ,.,....,~.. ~ s... ...__ _ •_ ~ `:*F'- y many researchers and analy8eafor consiste u w - - gathered b ncy, strength, specificity, temporal relationship, and coherence has clearly established cigarette smoking as the cause of the excess mortality smoking cigarette smokers. The establishment of smoking as the cause of excess mortality brought up the additional question :'•How are the health consequences of smoking expressed as individual disease processes?" The most important specific health consequence of cigarette smoking in terms of the number of people affected Is the developnrent of premature coronary heart disease (CHD). Retrospective studies established that cigarette smokers have a greater risk of death due to CHD and have a higher prevalence of CHD than nonsmokers. Prospective studies confirmed that cigarette smokers have higher death rates from CHD and established that they have a higher incidence of CHD than nonsmokers. Long-term followup of healthy populations has confirmed that u cigarette smoker is more likely to have a rnyocardial infarction and to die from CHD than a nonsmoker. Cigarette s7noking has been shown to be one of •the major independent CHD risk factors and to act synergistically with tile other major alterable CHD risk factors (high blood pressure and elevated serum cholesterol). Autopsy studies have shown that persons who smoked cigarettes have more severe coronary atherosclerosis than persons who did not smoke.

32 33 Aviado - Page 2 Aviado - Page 3 Editorship: Section Editor of Chemical Abstracts 1952-1950 Societies (Continued) Society of Toxicology: Member 1971 . Associate Editor of Circulation Research 1958-1962 Drug Information-Association: Memb er 1973. Editorial Consultant of Dorlands' Illustrated Medical Dictionary 1963-1967 American Medical Association: Mem ber 1974; Special Session Chairman Editorial Consultant of Ste3man's Medical Dictionary, ZZnd Edition Member. Advisory Editorial Board of Archives Internationales de 1972-1975 College of Physicians of Philadelphia: Fellow 1975. Pharmacodynamle et de Theraple 1965-present Member, Editorial Board of Cardiology 1967-presant Editor, Scalpel and Tongs. Journal of Medical Philately 1971-1974 Member, Editorial Board of Drug Information Journal 1974-pres.nt tlonorc Alpba Omega Alpha Honorary Medical Society, Member ` Travel Award, Roekefaller Foundation Linnaeus Medal, First International Pharmacological Meeting, Stockholm Fellow of the Guglenbeim Foundation PnrkinJe Medal, Second international Pharmacological Meeting, Pratue ~ 1946 1961 1961 1962-1963 1963 Physician of the Year Award, Philippine Medical Association (Chicago)1969 University of Pennsyl.ania Undersrduate Teaching Award 1971 Univsrslty of Santo Tomas Luis, Guerrero Honorary Lecturer 1972 Lindback Award for'Distinguished Teaching 1974 Presidential Tropljy (Philippines) for Most Distinguished Filipino Abroad 1975 Societles: Physiologlcal Society of Philadelphia: Member, 1948, Secretary 1954-1958; President, 1959-1960; Councillor, 1960-1961. American Society for Pharmacolojy and Experimental Therapeutiee: Member 1950: Co-Chairman, 1965 Fall Meeting; Member Finance Committee, 1965-1970. American Physiological Society: Member, 1951. American Association for the Advancement of Science, 1951. The Society of Sigma XI: Member, 1952. John Morgan Society of the University of Pennsylvanfs. Member 1956. Life member, 1967. American Heart Association: Member 1957, Member Research Study Committee 1965-1967. Section on Phartriacology (SEPHAR); International Union of Physiological Sciences-Treasurer, 1959-1965. ,- .~.-i,,,,, (1UPHAR) Treasurer, 1965-1966. American Society of Tropical Medicine and Hygiene: Member, 19613. International Leprosy Association: Member, 1967. American College of Clinical Pharmacology: Charter Member, 1971. Biographical Data listed in: American Man of Science Leaders in American Science World Who's Who in Science (Marquis) Dlctiorrry of International Biography 195S 1961 1968 1970 1975. i TIMN 450200

30 -2- 31 CURRICULUM VITAE OF D') tI><:,O inL AVIADO Born August 28, 192d - vlani:a, Philipptnee; Ca?ze: c: the ?:?.ippines possessing cannot establieh whether or not a causal relationship exists, but I do a pertnanent visa to the U. S. since 1952. Married Ae-.;.-_c:3a P. Guevara August 15 :943; fc.-cr chi.dren: -' Maria. Cristita find it extremely interesting that while the average "tar" and nicotine , , borr. June 28, ic54; Ca=ios G. born Marci: 2, Do ='=go C. bornAugust l, content of Filipino cigarettes is 200 to 500% higher than U. S. cigarettes, 1959; Maria AsL:.-cion born June 11. 1962. ' - the incidence of lung cancer is only 6°0 of that in the U. S. and the College Education: Ur.iversity of the Phillppinu College of Liberal Arts I940-1942 University of the Philippinea College of Medicine 1942-1"5 incidence of heart disease is only 4°0 of that in the U. S. Universlty of Pennsylvania School of Med°.ctne , . 1946-19'N- I would like to comment on one of Senator Hart's remarks contained • Doctor of Mediclne, University of Penasylvan:a ' >t[arcti 19{0 . in the Congressional Record regarding tobacco smoke and addiction. As a pharmacologist, I am concerned that there seems to be a growing popular belief that smoking is literally addictive. Even the 1964 Advisory Committee's report to the Surgeon General concluded that this was not correct. Further, from my review of the literature, it is apparent neither nicotine nor tobacco smoke should properly be con- sidered addictive. . Also, I am familiar with the book upon which Senator Hart evidently based his remarks, and in my opinion, anyone reviewing the book completely would conclude that few scientists believe nicotine or tobacco to be addictive. While I agree that good basic research is needed in many disease areas, for the several reasons which I have stated, I disagree with the implications and direction of the legislation here proposed. mingo M. Aviado, M.D. Professor of Pharmacology _ Audemic Positions at the University of Peer..y:vaLla: - . Assistant Instructor in Pharmacology , Instructor in Pharraacology Assocfate ir. Pharmacology - . Aul3tant Professor of Pharmacology Associate Professor of Pharmacology - Pro-'eseor of Pharmacology Member, Parasitology Graduate Group • Acting Chairman of Pharmacology Miscellaneons Positions: National Ihstitctes of Health Post-Doctorate Research Fellow Assistant Attendin* Physician of Cardiology, Phi'.adelphla Genaral Hospital Visiting Lecturerin Aneethesiology, Albert Etnsteiq Medlnl Canter '1945-1949 1949-19f0 ~ 1950-1953 1953-1960 1960-1965 ,, t965-presee} 1967-preseet _ 1969-I970 1948-1960 1955-1972 . 1955-ptesent Visitin` Professor of Pharmacoloiy, University of the East 1[dial: Center (Philippines)' 1959-preeeet Visiting Lecturer in Physiology, Women's Medical College - 1961-1962 Consultant, Poison Control Program of Philadelphia 1964-1970 Visiting Lecturer in Physiology, Rutgers Universlty .1966-1967 Member, Ad Hoc Committee on Air Pollution and Air Hygian., ' ' Philadelphia, Medical Society 1967-1969 Member, Bronchopulmonary Panel of National Clearinghouse for Smoking and Health t969-1970 Chairman, Medical Advisory Committee„ to the Clinical Research • Center, Graduate Hospital of University of Peansylvania 1969-1970 Member, American Heart Association Ad Hoc Coc:mittee on Cigarette Smoking 1969-1970 Consultant, Council for Tobacco Research 1972-1973 Deiegate, Unlted;States Pharmacopelal Conver.tior. 1975 ' i TIMN 450199

52 Bibliography ®elcher, J. R., "The Changing Pattern of Bronchial Carcinoma, British Journal Diaeaeea of the Cheet 69: 247, 1975. Doll, Sir Richard, Commentary on "Cancer Clues from the Decadent Nineties?" World Medicine, June 23, 1972. eallgrimason, J., "Lung Tumors in Iceland," Acta Path. Microbiol. Scand. 81(Section A): 813-823, 19 . Kennedy, A.. "Relationship Between Cigarette smoking and Nistologic Typs of Lung Cancer in Women," Thorax 28: 204, 1973. Langston, H. T., "Etiology by Edict,' Editorial, Journal of Thoracic and Cardiovascular Surgery 51: 459, Marc , 066. Langaton, ~_ oracicLand CardiovascularsSurgeryt63:~,"4Jouznaa~cof 1972. Passey, R. D., 'Some Problems of Lung Cancer," The Lancet II, July 21, 1972. p. 107. Vital Stetistic• of ths United States, Volume 2, tables 1-22, 1968. 53 BIOGRAPBICAL DATAt HIRAM TMOM/1.S LaNGSTOM, M.D. Place of 6irth: Rio ds Janeiro, Brazil Date of Eirth: January 12, 1912 (U.S.A. Citizen by Derivative Citizenship) Father's Naset Alva E. Langston Mother' Mas+e: Lvuise Foe Diuguid sducations Collegio Batista, Rio de Janeiro, Brazil, to 1928 Georgetown College, Kentucky, 1929 C University of Louisville, Kentucky,1929-30, A.S. University of Louisville, Kentucky, 1930-34, M.D. University of Michigan, Graduate School, 1939-41, M.S. Married: Helen M. Orth Date of Marriage: June 22, 1941 Childrent Paula F. Langston, born June 15, 1946 Thosus 0. Langston, born Sept. 5, 1949 Carol E. Langston, born Sept. 4, 1953 ERIE! CAREER SIliMARY (Surgery) Eorn of U.S. parents engaged in educational missions under the Southern Baptist Convention. Educated through sophos,ore year of college in Rio de Janeiro, sub- sequent education as outlined above. Elected to Theta Kappa Psi medical fraternity and Alpha Omega Alpha honorary medical fraternity. Internship: Garfield Memorial Eospital, Washington, D.C., 1934-35s Resident in Pathology, Garfield Memorial Mospital, 1935-37t Assistant Resident in Surgery, University Hospital, Ann Arbor, Michigan, 1937-38r Resident in Surgery, University Hospital, Ann Arbor, Michigan, 1938-40t instructor in Thoracic Surq.ry, University Nospital, Ann Arbor, Michigan, 1940-41r Private Practice and Associate in Surgery, Northwestern University, Chicago, Illinois. 1941-42t February 1942 to February, 1946, Military Service, Northwestern University sponaored hospital (12-th General.) Served in North Africa and Italy as Chief of Thoracic Surgery. Rose to rank of sujor, AIS, ultis+ately awarded Army Ccaftendation Ribbon, Bronze Star Medal and Ordew do Merito Aeronautico (Officer Grade) (Brazilian Air Force.) Returned to Morthwesterri University with rank of Assistant Professor of Surgery. In 1948 entered private practice of Thoracic Surgery in Detroit, Michigan, and served as Associate Professor of Surgery at Wayne University. Returned to Chicago in 1952 with Appointments as follows: 1. Associate Professor of Surgery at University of Illinois College of Medicine. 2. Chief Surgeon. Chicago State Tuberculosis Sanitarium, Department of Public Health, State of Illinois, 1952-71. 3. Consultant in Thoracic Surgery to the Veterans Administration Hospital, Hines, Illinois. r.:.: o,:~wgus'tana to 1971; Gottliebs Grantt Henrotin and St. Joseph Mospi- tal, Chicago. Appointed Clinical Professor of Surgery at University of Illinois College of Medicine, 1962. Appointed Attending Physician in Thoracic Surgery at Cook County Hospital, 1966. Professor of Surgery, Abrahas Lincoln School of Medi- eine. University of Illinois - Cliief of r...r.:-:- M ora,ie Surgery, 1973: %y TIMN 450210

J VI VII RvItzer. ('arI C., Ph. D., senior research associate, Harvard University Pa90 Srhool of I'uhlic Iiealth, February 15, 1976, prcpared statement-___-_ 77 tininmers• IrrI tiheiclon C., director, laboratories at ihe Lcnox Ilill Ilospital, New S'ork. and professor of pntholugy. ('nllege of I'hy'sicians and tiur- gc•sins., ('ulutubia llniversity of New York, accompnnied by Ilorace R. ICnrucgay. president, The 'i'obacc•o Institute, Wachington, I).('., and Dr. '1'hc4Hlorc 1). Sterling, dir(4•tor, (•ompater Science program, Siman Fraser 1'nii•crcity. ('anadn------------------------------------------------- 68 1'rcpa rcd st n t ement----- ----------------------------------------- 280 SIeriint;.'1'heodore I)., I'h. 11., direc•lor, ('ompnting Science I'rograun, Simon 1erascr liniversity. Vancouver, ('anada------------------------------- 443 1'repa red cta tement-------- --------------------------------------- 446 'i'emin, I)r. Howard Dt., American Cancer Society, professor of viral on- coingy and cell biology, DicArdle Laboratory for (•ancer Research, Uni- versity of Wisconsin, Madison--------------------------------------- I'repa red statement----------------------------------------------- 9'obacc•o Institute, Inc., Horace R. Kornegay, president, prepared state- ment ------------------------------------------------------------- 257 262 318 Virginia Agrtnllsiness ('onncil, .1. 1'alll Williams, executive citrector, prepared statement------------------------------------------------ 690 Wauupler, Ilon. William C., a Representative In Congress from the Rtate of Virginia, prepared statement ---------------------------------------- 736 ADi)ITIONAI. INFORMATION Articles, publications, etc.: Cancer and the Environment : Ten Top Suspects, excerpt from News- week, January 26, 197(',----------------------------------------- 125 Cigarette Smoking Among Teen-age Girls and Young Women, sum- wary of the tindings, by Y ankelovich, Skelly, and White, Inc., February 1976------------------------------------------------- Cigarette Smoking/Lung Cancer Hypothesis, by 1lfichel A. Ibrahim, 111.I)., Ph. D---------------------------------------------------- Colorado Plutonium Safety Debate Rages, by Steve Wynkoop, from 595 212 the Washington Post, February 16, 197fi_________________________ 70 Council for Tobacco Research-U.S.A., Inc., report of, submitted by Curtis 11. Judge, president, I'. Lorillard & Co., chairman, Tobacco Institute Executive Committee, 1975----------------------------- 8(Yr Counties in the United States With the Highest (upper 10 percent) Age-Adjusted I)eath Rates for Cancer from All Causes__________ 59 Critical Reassessment of the Evidence Bearing on Smoking as the ('ause (If Lung Cancer, by Theodor Il. Sterling, Ph. D., from AJPH, Vol. (tiro, No. 1), September 1975---------------------------------- 216 i)isease's Trail Leads to the Factory, by John Walcott, from the Sun- (lay Record, December 21, 1975________________________________ 68 Fighting the First Cause of Lung Disease, annual report. of the Ameri- can Lung Association, 1974-1975-------------------------------- 653 ~ ~ I~1 ~ ~ ~ 0 ~ ~ Introductory remarks including text of S. 2902, by Senator Gary Hart, from the Congressional Record, January 29, 197('i_______________ Lung Cancer and Smoking, by Theodor I). Sterling, Ph. D., Febru- ary 1976------------------------------------------------------ Male Lung Cancer Soars iu Factory Area, by B. D. Colen, from 21 479 the Washington I'ost, February 15, 197Ci_______________________ 126 New Jersey : Cancer Capital. Bergen in Top 10 percent 9n Nine Types, from the Sunday Record, December 21, 1975______________ 68 Overview-Health Consequences of Smoking, excerpt from The Ilealt.h Consequences of Smoking, 1975 reportt from the U.S. I)e- partment of Health, Education, and Welfare___________________ 22 • Procedure for C•ollecting and Revising Scientific Data for Report to ('ongress ----------------------------------------------------- Puhlic Health Cigarette Amendments of 1971, excerptt from hearings before the Consumer Sulx'omniittee of the Committee on Commerce, 214 Articles, publications, etc.-Continued Reviewing Progress Made Toward the Development and Marketing uf a Less HaTardous Cigarette, excerpt from hearings before the Consumer Subcommittee of the Committee on Commerce, August 23, Page 24, and 25, 1967------------------------------------------------ 427 Smoking and Cancer, a rebuttal, by William Weiss, M.D., from AJPH, Vol. 65, No. 9, September 1975___________________________________ 231 Smoking and Cardiovascular Health, by Henry Blackburn, M.D., rep- resenting the American IIeart Association, professor and director, Lalroratory of Physiological Hygiene School of Public Health, Univ- versity of Minnesota and profesgor of Medicine, Medical School, lTniversity of Minnesota________________________________________ 14 Statement on Cigarette Smoking by the American Cancer Society, Inc., a 13-point program to reduce cigarette smoking, 1974________ 541 Statistician vis-a-vis Issues of Public Health, by Theodor D. Sterling, Ph. D., from the American Statistician, December 1978, Vol. 27, No. 5--------------------------------------------------------- 519 Smoking Patterns by Type and Place of Ilmployment, by Theodor D. ~'.~Leriing, i'n. L., P'eoruary 18((i--------------------------------- 4t>ri Trends in Mortality Among British Doctors in Relation to Their Smok- ing Habits, by Sir Richard I)oll, DM, DSc, FRCP, FRS, Regius, professor of medicine, University of Oxford, and M. C. Pike, Ph. D., first assistant, Department of the Regius, professor, Radcliffe Infirmary, Oxford, from J. Roy. Coll. Phyens, Lond., vol. 6, No. 2, January 1972-------------------------------------------------- 250 Communications to : Kennedy, Hon. Edward Ai., Chairman, Subcommittee on Health, from : Cooper, Theodore, DLD., Assistant Secretary for Health, Depart- ment of Health, Education, and Welfare, April 6, 1976______-_ 209 Datt, John C., director, Washington office, American Farm Bu- reau Federation, March 23, 1976____________________________ 759 Helms, Hon. Jesse, a U.S. Senator from the State of North Caro- lina, February 19. 1976------------------------------------- 76 Sonuners, Sheldon C., M.D., director, Lenox Hill Hospital, New York, N.Y., March 1), 1976 (with enclosures)__________________ 289 . February 1, 3, and 10. 1972-------------------------------------- 430 Radioactive Particles in Cigarette Smoke Tied to Lung Cancer, by Barry Kramer, from t.he Wall Street Journal, November 19, 1975___ 56

I .)Eea {Uet.Mf Na+nN eawauN. 76 'WstifeD .Sfat¢s ,$enaf¢ MA~IMNITO4 D.G a/NI February 19, 1976 The Honorable Edward H. Kennedy Chairmn Subcom®ittee on Health Senate Committee on Labor and Public Welfare Washington, D.C. 20510 Dear Senator Kennedy: This morning, while speaking on the Senate floor, I received word that the Subcommittee on Health hed agreed to receive the testimony of several Senators from tobacco- producing etatee as a part of this morning's hearings. I further understand that several very able Senators of like persuasion with me did, in fact, testify. Of course, I am pleased that the Subcommittee agreed to the request contained in my letter of February 12, asking that Senators from tobacco states be allowed to testify. I regret that my request met with such confusion and indeci- siveness which I am confident was the result of inadvertence and was wholly unintended. Attached is a copy of testimony related to the subject matter of today's hearings which I hope can be included in the hearing record for this date together with a copy of this letter of transmittal. . Again, I appreciate the decision of the Subcommittee to include this testimony respecting a matter that is vital to the economy of my State and to hundreds of thousands of working people all across the country. Thank you for your consideration. Kindest regards. Sincerely, JESSE HELMS:pd 77 ,n. (al„ 7,.-„oe (./f1 7,A-„n (A.wl w.,) C.A.[ A-... NUtNANV, as.1r» Honorable Jesse He1Ds United States Senate Washington, D. C. 20510 Dear Senator Hel®s: HARVARD UNIVERSITY SCHOOL OF PUBLIC HEALTH CVAn1NeNT eI NUINITICN .,a NUNnN~rpN AY[NUa awroN. NAaewcMUU1T. P,ne February 15. 1976 I have received your letter of February 6 requesting a statemant of my current views relative to a bill proposed by Senators 1{art and Kennedy to amend Title V of the Public Health Service Act. I have read the copy of the proposed bill which you sent r and can conment on that portion of the FINDINGS AND DECLHRATION OF PURPOSE which concerns itself with the proble. of smoking and heart disease. As you say knov, sinca I was asked by the Surgeon General to participate in the work of the Advisory Committee on Smoking and Health in 1964, I have devoted a major part of my energies to the problem of smoking and heart disease as well as the influence of the human constitution on disease. Over the years, I have probably published as much as any othar single person on the subject of rmoking and heart disease, and have restricted my efforts to this disease since the major cause of death in this country is attributed to heart disease. Enclosed you will find my curriculum vitae together with a statement of my views with reference to the bill'• "findings" that "cigarette smoking !s one of the principle contributors to the high incidence of ...diseases of the heart... and that "overwhelming evidence exiets that the harmful factor. contained iD cigarette smoke are tar and nicotine." Sincerely yours, CCS:rf Enclosures Carl C: Seltzer, Ph.D. Senior Research Associate TIMN 450222

90 Ciaph E Age-standardized Relative Risk Ratios, Ages 35-64 at Exam I Framoingham Heart Study - Men M.R. 16-Years Follov-up 180 Death From Coronary Heart Disease 169 160 " 140 .J 120 Z ~ 21 108 0 20 100 All Frasdngham Men O ~ 19 r.r.j ~ 18 80 ~ ~~ 17 60 ~ h 16 ~ 15 40 20 N oar.rr.. ..r A•+ 91 Granh F (Legend for FiLure) '51 '52 '53 '54 '55 '56 '57 '58 '59 '60 '61 '62 '63 '64 '65 '52 '53 '54 '55 '56 '57 '58 '59 '60 '61 '62 '63 '64 '65 '66 42 38 R 18 SECULAR TRENDS XN -0EATH RATES AND PERCENTAGE CIGARETTE SMOKERS FOR BRITISH DOCTORS AGES 35 to 84 FROM 1951 to 1966 iCi:aei ::or age)it ' * Death rates taken from Table 1 and percentage cigarette smokers from Table 4 of Doll and Pike.l0 The dashed lines (semi-bar graphs) show average death rate values for the periods 1953-57, 1957-61, 1961-65 as given in Table 2 of Doll and Pike,10 TyMN 450229

I l80 160 140 120 100 go 60 40 88 Craph C Age-standardirrd Rolntive Risk R1t(ns, Ag, s 35 64 at Esun I MYOCAROIAL INFARCTION Framingham Ilrart Study - 21rn 16-Years Follou-up 123 102 110 .. All Framingham men <20 20 >20 Cigarettes per day H.R. 200 .1 180 J 160 a 140 ,J 120 100 80 J 60 40 89 Graph D Age-Standardizcd Relative Rfsk Ratios, Ages 35-64 at Exam I Framinghnm Heart Study - Hen 16 Yeara Follow-up . SDDDEN DFATH FROH CORONARY-NFART DISEASE 173 152 All Framingham Men 85 <20 20 >20 Cigarettes per day TIAIN 450228

N.R. 160 ,J 140 ,~ 120 100 so .a 60 40 ~ 86 Crnph A Age-standardlzed Relative Risk Ratios, Ages 35-64 at Exae. I Framinghan Heart Study - Men 16-Years Follow-up TOTAL CORONARY HEART DISEASE <20 m 12e >20 C1garettes par day M.R. 200 1g0 .J 160 j 140 .i 120 ~ 100 80 .; 40 a 76 Crnph D Agc-standardized Relative Risk Ratios, Ages 35-64 at Exam I Framingham Heart Study - Men 16-Years Follow-up ANGINA PECTORIS, UNCOMPLICATED 129 110 All Framinghac. Men r..-• <4D m >20 Cigarettes per day 87 TIMN 450227

18 As many in attendance here this morning are aware, Senator Ken- nedy and I havee sponsored S. 2902, the National Health Research and I)evelopment Act of 1976, wwhich is presently being considered by this subconunittee. Today, however, rather than speaking specifically 4q]}t ihc, details of tile bill, I would like to address the more general issue of the relationship between cigarette smoking and disease. As the clistinglushed chairman has already noted, this is not the first. time that a congressional commit.tee has held hearings on tllis sullject. But the problems caused by cigarette smoking are perhaps luore in evidence now than ever before. The 1975 Health, Education, aucl Welfare repolt on the health consequences of smoking clearly slates that "Cigarette smoking remains the single largest preventable c1nlse of illness and early death" in the United States. Yet, as a nation, we have been unable and unwilling to come to grips with the problem. Let, us stop for a moment. and consider the magnitude of the prob- lelu. Approximately one out. of every three Americans smoke. Ameri- call adults have a per capita consumption of more than 4,000 ciga- rettes per year. Cigarette smokers have 70 percent more heart attacks than non- snlokers. Eighty percent of all lung cancers are caused by cigarette smoking. Cigarette smokers are 10 times more likely to die from lung cancer than nonsmokers. Cigarette smokers are 6 to 15 times more likely to die from chronic bronchitis and emphysema, and much more likely to develop many other malignant and nonmalignant diseases than are nonsmokers. And in 1976, anywhere from one-fourth to one- half million Americans will die of these diseases. This means that un- less something is done, and done soon, more Americans will die from these diseases within the next year than have been killed in action in all the wars of our historv. In addition, life expectancy has been increasing steadily since the nlicldle of the 19th century. The longer average life span today is a result, mainly of improvements in public health coupled with the discovery and use of vaccines, antibiotics and other technological achievements. Today, for tile most. part, death has been confined to old a-ae and c'an therefore be attributed to diseases that are either specifically pe- cnliar or lethal only to older people. The two particular conditions ii•hicll commonly arise in old age and are often a dlrect cause of death _ ~.;..:,.. . are arteria c'Asease anr cancer. Ar'_r ' a. I'ects the arteries supplyins-r the heartt or the brain, and it now accounts I'or about 50 percent of all deaths in the ZTnited States. Cancers now account for almost 20 tercent of all jT.S. deaths. It is becominir obvious that people have develoned verv different .lttitucles toward these two diseases. It is not just that death from ar- terial clisease is often rapid. whereas death from cancer c•an be pain- fully drawn out. For some reason, heart attacks and strokes tend to be thought of as natural hazards of age. They are considered as either a ilornlal end to a satisfactorilv lon-- life, or. when they occur in middle aged ulen, the wages of overeating and lack of exercise. Cancer is popularly viewed as an mluredictahle disease that strikes incliscrimi- natelv att rich and poor. fat. ancl thin. old and middle aged. Iloth of these percel)tions are sii-nificantly in error. Arterial disease is not necessarily a natural bazard of old a!re. ancl cancer is not leces- c~timate s:u•ilv related to imcc» lh•ollable causes. In fact, scientists now 19 that 70 to 90 percent of all cancers are the result of environmental factors. Hundreds of billions of pognds of synthetic organic chemicals are now produced annually in the•United States. Many of these chemicals are harmless. But more and more we are finding others that are deadly. While our economic dependence on complex chemical substances such as plastics and pesticides has become so great that our survival as a modern society may depend on their continued use, our inability to distinguish between those which are dangerous and those which are not is increasingly placing us in the position of having to choose be- tween alternatives which either put the health of a substantiall portion of the population at risk or involve severe economic dislocation. What few people fully grasp is that there is no full scale testing taking place on most chemicals being put on the market to determine whether or not they cause diseases such as cancer. Unfortunately, for many health problems which are caused by chemical exposure there are no simple predictive tests in existence. But this is not the case with tobacco and cigarettes, for in many instances, the health consequences of smoking have been clearly de- fined-and they are obviously serious. The HEW report which I re- ferred to earlier summarizes the scientific basis for concluding that heart disease, lung cancer, chronic bronchitis and emphysema are not merely "associated with" or "linked to" smoking but that they, in fact, can be caused by cigarette smoking. Mr. Chairman, this is a very important conclusion and it represents the consensus of most medical scientists in the United States. For this reason, rather than paraphrasing or reading exerpts from it, I would ask that tile entire section of this report which deals directly with the causation of disease be appended in my remarks in today's hearing. Senator KFxxF.nr. We will include the relevant sections of this HEW report in the record. Senator HART. As I indicated I do not intend to go into detail about the provisions of this bill. I would only say that, it provides for a dif- ferential tax, not on cigarettes themselves, but on the tar and nico- tine contained in cigarettes. The tax during the first. year of operation, would range from ap- proximately 1 cent per pack on low tar and nicotine cigarettes up to 50 cents per pack on hiah tar and nicotine brands. By the fourth 'i.`,':7.7 ~-_ y ;./.'.11s6seC. in 11-. \1'ou'.6. range from approximtaely 2 cents per pack up to 50 cents per pack. I have brought three packages of cigarettes with me to give a fac- t llal indication of how this tax would opPrate. The first is a Carlton cigarette which contains 5 milligrams of tar and 0.5 milligram of nicotine. The firstt year of tax on this package would be 4 cents and by the fourth year 10 cents. The seconcl brand, Winston, has a content of 19.f3 milligrams of tar and 1.39 millizrfuns nicotine. Tile first year this package would be taxed un aclclitional 13 cents, increasing to 3:3 cents by the fourth year. The third brand, Chesterfield, has a conteut- of tar ancl nicotine which would lie taxed an additional 18 cents during the first year, and 40 cents by the time the tax is com- pletely phasecl in. Mr. (,'hairman, as was indicatecl in the luaterial we circulated to our colleagues the differential tax proc•idee by S. 'L90•2 wolllcl generate al>proxinlately $3.7 billion in revenue for health research and cure

16 Senator KFNNFns-. This is an issue which is not a new one to the ('„l,~rlc•ss nf the lTnitecl States. The.re have been extensive hearings =t I,eriocl of Years and there has been some action taken by the ('ongress of the tcnitecl States as related to smoking in the labeling ;,,'V;,. No Senate health committee could function responsibly without et ccmtiniling oversight on this particular issue and addressing this issnc in the most, responsible way, to provide protection for the .\luerican people and to bring tl)ls issne to the attention of our ,•cllleagnes in the Senate of the TTnitecl States. Ihlrmg the c•ocn•se of this morning's hearin- we will hear from clis- ~ ,;Qr z 1,, o ' luany instances have spent a lifetime on ..;:,...: .: ~.. Ihi~ pat•ticnl,tt is5ue. ti\'e will listen to thc)se people who are c•hargecl Avithin the Federal („overnnlcnt to protect the Ilclaltll of the American peclple: the i)epart- nicnt of Ile:llth, tlle ("ancer Institutc, the Ileart and Lling Institute. ,~n~l the ('entc•r for I)isease ('ontrol.'They will present te5tintony N;•hich I hclieve i5 vet~v clear :tncl convincing abont tlle callsal rclationship Irotwcen t:lr ancl nicutine and sericmti he:llth hazards in the forn) of :•anrer:ulcl Ilmg:lncl heart cliscasc. .\t e;u•lien cearing5 helcl by different conlmittee5, the pre5tlmption fell npon tile 5cientists to pro~•e this can5al relationship. It appears to mm ncnN• that this ln•csnnlption must he rehnttcd by those «•ho support f lie cclnt inuccl use of high lucot ine anci high tar c•igalrttes. Now, there are al)llroxin)ately lO(l,tllNl workers, as I understand, who au•e ilnpactccl l)v anv nse of tobacco in a nlnnber of oar States in tliis ccluntrv. '1'hc Wbacco inclnstry has Leen an itnhortant inclustrv in ilw comnlerccl of onr Nation. It seems to tile that the apln•oach taken in S. •")0'3, introclucecl hv Senattor llart of ('oloraclo ancl sprnlsorecl as «oll I/y nlcself, rec•ogni•r.cs that the .\mcrican people alr going to ,•nntinno snlokin'. . 'I'hee conlllelliing thrust of this legislation is to tie tlic, tax nlecllanislu to tile t:tr and nlcotine content of cigarettes. (h) the cme hand, «•e want to preserve tile Option :lnd freedom of incliviclnals tn sclcct whatever Ilranc) of c•igarettc the}' want. lint we also want to proviclc aul inlportant incentivc to the inclnstrv itself to comm lip with lower tar ancl lower nic•otine cigarettes. I milst sav I have been im- I,rossmI by tile efforts tllat have been maclc by thc~ tobacco indnstry ancl tl niitnhc~r of di(Tetc~nt conll)alUC's, «ho ha~•e hecn atten)pt.ing to dc:ll witll this, and have been proposing new l/rands in thcir efforts to conccrn themsc•lves with tllis, llealth ltazqrcl. So Ncc look forward to tllis hearing this morning. I nnlst say that this itisne is not unrelated to a nnnllx•r of tile other issnc". which tllis c•omnlittee is c•clncernccl ahont, that is, the extraor- clin;lrilv hi-(rh cost-of he:tltll c•;u•c in ont-Gociety. I mn hopefnl that. dm•- ing tlie cxchangc• witll those in tile I)epartn)ent of ilealth, we will be able to /intl out what aclditionatl cost burdens we are placing on the wIlole Anrcrican system by tile utilization of health se rvices and health personnel due to tile ccmtinuecl incidence of heart and lung disease Vsliitiecl !~v tile excessive use of nicotinc and tar. We «•elconle the witnesses that we have this morning. Thev include nulny clistinguisllecl 'Melnhers of the Senate as well as the IIouse and :llso :1 verv considerable nwnber of distint,rttished scientists who have sIrenta a. gr~•at deal of time rn) t his partic'ltlal• issue. 17 T«•ill say at t.he otrtset that when we scheduled these hearings we invited a number of scientists, since this particular issue is realjy a scientific question. Some have come from as far away as Great Britain. In recent days, there have been a number of Members of Congress (which I think in the, last count included some 23 Members), who not only wanted to testify on the first day of hearings but also wanted to testify first. So we will deal with this issue as best we can. I will ask if Senator Be,a.ll would like to make any comment? Senator BEM,r.. Thank you, Mr. Chairman. Just a brief comment. I do not have any pre ared testimony but I think it is very much in the interest of the _~u~lic ne;,,,- !,~ ~ e ~:- - "J ' ~ ~l-a/41.1VlWlll~l between smoking of cigarettes and the effect it has on our health. Some of us have gotten the message previously. I used to smoke three packs of cigarettes a day. But I got the message and I would recommend that otherc (10 likewise. I do, however, think that we have some very important questions to answer as we go about with this kind of leg islative effort. First of all, I think we have to determine if in fact we do want to do basic research on these dedicated funds. I think that has to be answered during the course of hearings today. I think we made sub- stantial progress recently getting additional research funds for NIH. As the chairman well 'knows, we went through a period of drought for a while. But, we have been having some greater success lately. We want to determine who sets the priorities and the extent to w hich the research will be done as I said on the basis of need rather than the basis of income available. Second, I happen to come from a State that produces-tobacco. We have five counties in Maryland where tobacco is the main agricultural product of those counties and it hasn't affected anything on t•he eco- nomics in those areas. Particularly, I think in looking at the tax on tobacco, we might be able to see how we are preempting the States. So «•e are not just talking about the connection between cigarette smoking and hea.lth, but larger questions as to t•he. role of the Federal taxation policy on research generally and the role the Federal Govern- ment itself is going to play with the State government. I hope as these hearings proceed we can be enlightened on those subjects as well as tile health aspects of the subject matter in consideration today. Thank you, Mr. Chairman. Senator Ki')NNEpT. Thank you very much. Senator Gary I-Tart? .5enator, we are glad to have you here. We recognize you are the prin)e mover in this area. and I am delil,rhted to have t.he chance to join you in the introduction of this legislation. I just want. to commend you for doing this. STATEMENT OF HON. GARY HART, A U.S. SENATOR FROM THE STATE OF COLORADO Senator HART. Thank you very much, Mr. Chairman. Mr. (`hairman and members of the committee, I want to begin by expressing my appreciation for the opportunity to testify at this ini- tial hearing on cigarette smoking and disease.

70 TIMN 450219 71 Senator KENNEDY. The only point I make, Senator, is there are unquestionably a varjet.y of causes of cancer. This Health Committee tried to act in the areas where we can show the causal relationship between cancer and health problems, and that is why we passed the DES bill. We have been absolutely convinced on the basis of doctors' letters about the causal relationship between I)ES and cancer in the children of women who had taken it. We had testimony here about dis- ease. caused by the constant use of premarin, which had been on the market actually since 1940, initially approved by the Food and Drug Administration. It is still being overtitilized. I think it still poses some very serious health hazards. You obviously get into the drug dose-effect in any of these areas. Senator IIUDDLESTON. In these cases, Senator, you move to where you found a direct and provable link. Senator KENNEDY. That is right. Senator HUnDLESTON. And rather than to impose a tax to take it out of the hands of those that could not, afford it presumably for the purpose of financing a research progranl which seems to be counter- productive from the outset. Senator Kr•,NNE DY. Well, you say that. only if we can show an •absolute link between cigarette smoking and disease and denionstrate it, only then should we ban it completely. I suppose there are those that be- lieve that.. However, there are those t.hatt believe that action should lxt taken. It. seems to nte that this is just. a ruininltun kind of a step. If the scient.ific information is overwhelming ;uul con>pelling, then an effort. should be luade to deal witlt the problen> in line with human uat.ure. It, is a reasonable response ]lott to ball smoking, but to encotu'- at;e the tobacco industry to nlove toward lower levels of nicotine and tar. Now, the point that I really wanted to make in response to your ob- s;ervatious about. fhe (litl'erenc'e in perc'entages of Statepopulations affected by cancer is that• this is absolutely t rne. I coul(1 give you more examples of it. in ternls of world probletus.'I'here are a vtu'lety of dif- ferent causal factors in those ar'eas, and I believe to a very substaltial degree those are basically ev>virotnuental. I think we will hear later ft'onl our distiuguished witnesses t•hat. approxituately 80 percent of all htuuat> caalcels :u'e basically environn>ental. They are food, food ad- tliti.- . .t,... , face is~what can/1we possll>ly (loytotllllnlnl Lejthose tl> ~1tts,Iand that is tvhat we are attempt.ing to (jo. As we find clear anci convincing evidence relating a givott environnlental factot' to the ine.iclence of hunlan cancer, trce should act. I 1111 hopeful that tve c'an get a reac'tion front the Food and I)rug Adminlstt'atlon so that we c.an legislate in t•hese areas. Senator IIUDDr.ESTON. Our suggestirn> would be to get the total pic- t.tu'e and attack tlte entire problenl rather tltaul zeroing in on one- prob- lem., rather than with a tax that woulcl prove hau'mfnl eronornically to very many peol>le; in the country. Senator KFrvxr•,DY. We want to thank you. I think you have presented your case very effectively and I think ~ou have given us a nltutber of points that ought. to be addressed 1>.y the scientists and we appreciatee your appearance here. I want to thank you. At this point we will include in the record the statementt of Senator Helms along with other m9teri:,l cnhntitted by him.

i.: 110 111 -4- Arthur Furst proposal appears to accept theories based on outmoded mouse skin painting techniques.'As for nicotine, even the 1964 report of the Advisory Committee to the Surgeon General virtually exonerated it as a health hazard. New techniques present a better, although not perfect, method of evaluating possible effects of smoke. These techniques use whole smoke rather than the topical application of materials to the shaved skin on the back.of the mouse. Senate Bill l" 2902 would ignore the acknowledgement by.many scientists that mouse skin paining is not an adequate base for action and that further work is necessary in light of newer and more applicable techniques. Arthur Furst What effect will there be if we legislate excessive reductions in "tar" and nicotine? Would an increase of nicotine content be better? Would people smoke less and thus inhale less "tar"? How can be make simple guesses to complex problems? There is insuffient knowledge to predict the effects on animals or humans if the quality of the smoke is altered. I have suggested time and time again that more research must be conducted on effects of low level doses on physiological and biological responses. Experiments must also be conducted to see what takes place in the intact animal when low doses of the substances under investigation are administered at a regular schedule. Not only should pure materials be investigated but combinations must also After many years of experimentation conducted by various laboratories throughout the world it has not been possible to date to induce squamous cell carcinoma in the lungs of animals by the inhalation of tobacco smoke. Tests are being conducted still. I continue to urge that we must simulate the human experience when smoking experiments are conducted. The parameters have been suggested by me at the A.E.C. symposium held as far back as 1970. be studied. It is well known that some chemicals which have similar biological activity can nullify the reaction effect when given together. On the other hand, the effects may be additive, they may even enhance each other, but without the experiments which can Qive unequiur,rai. we just do not know. I cannot draw conclusions without actual valid data. TIMN 450239

102 rn ny lectures I detail the fantastic a>loounts of hydrocarbons over a metropolitan area; soot is also a problem as will be the fa ash as a result of burning coal. All of these can be in some way iavplicated in the etiology of cancer. People have interal detoxification mechanisms which can be protectives yet in many cities metallic compounds are inhaled. These particulates can inhibit the protective enzymes. 103 1GB UNIVERSITY OF SAIN FRANCISCO INSTr(CTE OF CHEMICAL [\IOLOGY Dr. Arthur Furst - Arthur Furst,Ph.D. Institute of Chewical Biology University of San Francisco San Francisco, California 94117 In 1972, I testified before the Consumer Subcommittee of the Committee on Commerce in the United States Senate con- cerning Senate Bill 1454. For reference, I have fncluded a copy of that 1972 statement which contains a listing of both my educational background and scientific experience. I have maintained my interest in the area•of smoking and health and devote a good portion of my research in this field. I still continue to monitor the world scientific lit- erature, maintain current bibliographies and I keep a reprint and duplicate file of pertinent articles. All this, I feel, is necessary in an area as prolific as smoking and health. Recently, my attention has been called to the minutes / of meetings of the National Cancer Advisory Board (NCAB) and subsequent recommendations in relation to the regulation of "tar" and nicotine content of cigarettes. I am amazed that the NCAB has made no recommendations for further research in a number of areas where we have no up-to-date knowledge. In suggesting the regulation of what is known as "tar", the NCAB must still equate the skin painting of mice with "carcinog:.necity". I, and othcrs, have developed tech- niqucs fcr plocing pirt:iculates ilirectly on the lung surface of Iaice. 7hcse nnirlals were cilosrn as th^ biolor,ical r..odcl 11nH\VY tit,11SNt:l: .^.V V'1'ial SA N i .\1.1i UI:NV.'/1G7 al./:,',..:1.^.~~ 1 •:1 `+a TIlMN 450235

•sr 92 INCIDENCE OF CHD IN FRAMINGIIAM MEN (Other than Angina Pectoris ) Ages 45-74, Over 12yr Period a(ler Expm 4 (Age-Adusled) 16 4 SMOKERS SMOKERS SMOKERS NEVER EX- CIGARETTE 93 CURRICULU?1VI7AE Name. Carl Coleman Seltzer ACADEMIC TRAINIHC tes 1L Institution DeRree ^ Jons 1929 Harvard University A. R. pebrwry 1933 Harvard University Ph. D. POSITIONS HELD Dates Position Institution 1933-1935 Research Fellow Harvard University RioloRical Science 1936-1956 Anthropologist Harvard University 1937-1938 Research Assistant Harvard University Fatigue Laboratory 1937-1942 Consultant ' Otfice of Indian Affalrs Anthropologist U.S. Department of the Interior 1938-1941 Ressarch Associate Harvard Univeraity Anthropology 193E-1942 Research Associate Harvard University Physical Anthropology 1942-1947 Anthropologist to Harvard University Grant Study Dsparteent of Hyaiene 1940-present Consultant Robert B. Brigham Hospital Anthropologist Boston. Massachusetts 1947-1946 Associate Editor American Journal of Physical Anthropology 1929-preeent Member American Association of Physical Anthropology 1942-present Research pellov in Peabody MUseu. Physical Anthropology Harvard University TIMN 450230

1W 100 101 Dear Sirs: UNIVr RSITY OF SAN F'RANCI SCO I have read with interest the proposed ammendment to Title V of the Public Health Service Act to establish a National Health Research and Development Advisory.Conmaission - S 2902. Your first statement: "(1) Preventable environmental factors pose serious threats to the health of the American People" is an admirable one. Following that I am amazed that you only concern yourself with cigarette smoking. Non. Jesse Ne1 ms United States Senator North Carolina United States Senate Washington, D.C. 20510 Dear Senator Helms: INSTITUTE OF CHEMICAL BIOLOGY February 12, 1976 Thank you for your letter of February 6, 1976 informing me of the hearings scheduled for February 19, 1976. It will not be possible for me to attend these hearings on such short notice, but I am enclosing a statement for the SubCommittee. As a working scientist, I am disturbed by the fact that years are going by and so few questions regarding smok- ing and health are being answered. Sincerely yours, AF: amb Arthur Furst, Ph.D. Director HARNEY SCIENCE CENTER SAN FRhNCISCO. CALIFORNIA 94117 415/666•6415 That the need for more fundamental research in all areas of environmental contaminents, and their adverse effect on the American people is self evident. That taxing cigarettes for their "tar" and nico- tine content to establish the National Health Research and Development Advisory Commission does not seem logical. Z am afraid that the Conmfssion will just be another means of using tax money for more talk. The implication of a new Commission is that the various Institutes of the National Institutes of Health are not fulfilling their mandates. My reaction as a scientist is that the entire Commission will serve only to distract us from our fundamental task; that is to get good, hard data to answer the questions raised concerning the effects of cigarette smoking on health. I am sure you must be aware that many questions continue to be raised; I can list many for you i.e. smoking impairs hearing, smoking lowers sex life, smoking is the cause of about every type of cancer. In a series of lectures given by me at a number of Calif- ornia State Colleges and Universities, I discuss Environmental Carcinogenesis. In many cases of environmental contaminants we have some related animal models. In these cases, we can induce in rodents cancers of similar histo- logical types to those found in workers exposed to the same chemicals. For other chemicals, using arsenic as an example, the epidemiologists relate cancer in m3n to arsenic exposure, no valid animal model exists. What then will the Commission tell us that we do not know. In my appearances before the Consumer SubCommittee of the Committee on Coamlerce, and in my further statements I stated "I am amazed that the NCAB ~.'or ruruler researcl in a num.)er a. areas waere we have no up to date knowledge". Also I stated that "Nothing has been said about the fact that after many years of experimentation it has not been possible to date to induce lung cancer (and by this I mean the so called oat cell, s_quamous cell carcinoma)in animals by the inhalation of tobacco smoke". No valid experiment has yet been published in the scientific literature to date February 1976. ' TIMN 450234

106 The NCqB al;o notes that other factors have shown to increase the susceptibility of cigarette smokers to lung cancer. lti'hat are these factors? Are they referring to mesotheliolaas which is associated with asbestos? Can this really be demon- strated in clean cut experiments? What about other factors like the state of nutrition and health of the smoker? What about the drinking habits; alcohol and coffee? Are these related? I had hoped that the NCAB would take a stand concerning the need for further knowledge on how experiments could be designed so as to be more applicable to man. Good research should be encouraged to help resolve the many questions in this area. On the contrary_ the NCAB has not acted to add to our scientific knowledge but may have discouraged research by its apparej denial of any need for it. Arthur Furst, Fh.D. • Director AF :amb 107 UNIVGRSITY OF SAN FRANCISCO INSTITUTE OF CHEMICAL BIOLOGY February 12, 1976 Hon. Jesse Helms United States Senator North Carolina United States Senate. Washington, D. C. 20510 Dear Senator Helms: Thank you for your letter of February 6, 1976 informing me of the hearings scheduled for February 19, 1976. It will not be possible for me to attend these hearings on such short notice, but I appreciate the opportunity to enclose a statement for the subcommittee. For your information I am enclosing a copy of my curriculum vitae. Si rely/your , rt ar'FuiIst, Ph.~~ Director HnRNEY SCIENCE CENTER SAN FRANCISCO, CALIFORNIA 94117 415 . _ 1000 -. , G 4C4 - 4-1/.J 'I'IIVIN 450237

. 44 pa{e ll Vilt prl{Inal Investlptlons on ToxicitY of Aero.ob l9{. Cardiopul.nonary effects of fluorocarbon compounds. D. M. Aviado. In: Proceedinas of the 2nd Annual Conference on Environmental Toxtcolory. Aerompaee Medical lteaearch Laboratory, Wri{ht-Patterson Air Force Base, Ohlo, pp. 31-39. 197L 195. Krstachmer reflex induced by Inhalation of aerosol propellants. D. M. Avtada !n: Conf.renco on Toxic Hazards of Halocarbon Proprllanb• Edited by G. E. Thompson, DepL of Health• Education, and Welfare. Public Hralth Service, Food and Drug Administratton, Washin{ton. DC, pp. 63-77, 1972. 196. Toxicity of propallanta. D. M. Aviado. In: Proceedings of the 4th Annual Conference on Environmental Toxicolo{y. Aerospace Medical aesearch Laboratory. Wri{ht- Patterson Air Force Base, Ohio, pp. 291-32A 1973. 197. Toxicity of propolants, D. M. Avlado. In: Pro{reaa in Drw{ ttesearch. Idlted by L Jocker. nirkbaosor Verla{ . BassL 10: 365-398. 1974. , 19s. Toslclty of aoroaol propellants on the respiratory and clrculatory ayatema; L Cardiac arrhytkmia 1a tho mooae. D. M. Avlado and M. A. Delej. Toxicolo{x 2: 31-42, 1974. 199. Toxicity of aerosol propellants on the respiratory and circulatory systemst [4 Respiratory and broachapulmonary eff.cta In the rat. S. A. Friedman, M. Camrearato and D. M. A.Iado• Tnxlcoloeu . 1: 34S-YSS, 1973. .200 Toxicity of aerosol propellants on the respiratory and circulatory systamr 111. Innuenca of broachopulmonary lesion on cardlo-pulmonary toxicity in the mouao. A. S. Drody. T. 9/at.nabe and D. lA. Aelado. Toxicolo{y.2:173-LfN, 1974. 201 Toxicity of aerosol propellants in the respiratory and circulatory systems; IV. Cat•dlo- y tosdcity ta the monkey. M. A. Helaj, D. G. Smith and D. M. A.lado• ToxicololY_• 2: 391-395, 1974. 7 202 Toxicity of aerosol propellants In t'ha respiratory and circulatory syst.nu; V. Vonteleular EIE fsettott In the dog. D. :1. A.lado and M. A. Do1aj. Toxlcelo{Y. 3: 79-1i6, 1975. Toxicity of aerosol propellants in the respiratory and circulatory systerns; Vt. Influence af cardlac and palmonary saacalar lesions in the nt A. S Doherty and D. M. A.lado. Toxieolo{Y. 3: 213-224. 1975. 204 Toxicity of aerosol propellants in the respiratory and circulatory systems; Vn. Influence _ - of pyletoaary etnphys.tem and anesthesia in the rat T. llabnabe and D. M. Aotado. Tosicnlo{y . 3: 22 5-240.. 205 Toxicity of aerosol propellants in the respiratory and circulatory syatams. V(IL Reaf+iritien and circulatiea in pritrtataa. D. M. Aelado and D. G. Smith. Toxicololx 3: 24i-262. L97S. 206 Toxicity of aorosel propellants in the respiratory aad circulatory systema. [X. Summary of the tnoot toxic: trtchlorefluoromethans IFC tl). D, M. Aviado. Toxicolo0y . 3: 311-319, 1973. L_._ T,.':,:--'--°_a ln the reapiratoryand circulatory syatema: X. Proposed claoaincatlon. D. M. Avlado. Toxlcolo[Y.3: 321-332, 1975. 20t! Toxicity of aarosols. n M. Aviado. The Journal of Clinical Pharmacolo{y. 1S: e6-10a. 1975. 209 Cardiopulmonary toxicity of propellants for aerosoht. M. A. Be1e) and D. M. Aviado. The Journal of Clinical Pharmacolorr• IS: 105-1IS, 1975. 210 Flre nuorocarbons for administration of aerosol bronchodilators. D. M. Avlado and J. Drlraal. Tho Journal of Clinical Pharmacolo{y. LS: 116-t2[r, 197y. . 45 STATEMERT OF HIRAM THGMAS LANGSTON, M.D., CLINICAL PROFESSOR OF SURGERY, ABRAftAM LINCOLN COLLEGE OF MEDICINE, UNIVERSITY OF ILLINOIS I am Hiram Thomas Langatonr a thoracic surgeon in private practice of this Specialty since 1941 and in the Chicago area con- tinuously since 1952. Prior to that, my practice was interrupted by service in World War II with the Northwestern University affili- ated unit, the 12th General Hospital. I am currently a clinical professor of surgery at the Abraham Lincoln College of Medicine of the University of Illinois. I am grateful for this opportunity to present my views on Senate Bill 2902 and certain issues that relate to questions concerning smoking and health. I am fully aware of the enormous . t volume of statistical data that would link the consumption of tobacco with disease in hmaans. Out of this material I have been particularly interested in the statistical association of ciga- rette smoking to lung cancer because this is directly within my field of clinical interest. Tha acquisition of such a large sum of money as specified by the proposed act devotsd to health research would be most wel- come, I am sure, and I can only hops that it would ba appropriately directed. I do not feel myself qualified to cofmalent upon the propriety of acquiring this funding through the taxation proposed. SDecificaliv. since I do not sNwkee this tax would be one that I personally need not bear. TIMN 450206

84 Scltzer-Appendix Page 5 APPF.NDI% 9 There are two hypotheses relative to smoking and heart disease, (a) smoking has a causal effect an the development of heart dtaease, and (b) the constitutional hypothesis which states that the predisposition to certain smoking habits is associated with a predisposition to certain diseases, such as CHD. Minimal recognition and attention bas been given to the constitutional hypothesis. The potential importance of this alternate hypothesis was stressed by the Surgeon General's Advisory Coimnittee on Smoking and Health in 1964 (46): "If it could be shown that cigarette smokers and nonsmokers had significant constitutional differences apart from differences that might be caused by smoking Itself, then a possibility would exist that some predisposition of smokers to a particular disease might also be of constitutional origin and not caused by smoking (46)." This constitutional hypothesis has been supported by a number of Investigators including R.A. Fisher (28), Eerkson (29), Seltzer (30), Burch (31). Hickey et a1 (32). Many items of evidence have been accumulated In support of the constitutional hypothesis. Seymour Kety (33) has confirmed the presence of a genetic component in the tendency to smoke, and smokers have been shown to differ from nonaoeokers ilf personality, body structure, physiology, biochemistry, socio-phyeiologic features, and life styles (34,35,36,37). These basic differences have been repeatedly ignored in the epidemiologic assumptions that cohorts of smokers and nonsmokers differ only In their smoking habits. The best method of distinguishing between the smoking and the constitutional hypothesis ts from twin studies. Twin studies have supported the influence of constitutional factors, rather than smoking, in the etiology of CND. In a large scala investigation of Swedish twin, Cederlof et al (38) emphasized the importance of the genetic influence on CHD. A similar result was obtained by Lundnun (39) In a detailed study of identical and non-identical twin pairs. Lundman noted that overt or silent CBD has essentially the same occurrence rate In the smoking and nonsmoking member of twin pairs. He interpreted his findings as being inconsistent with the causal smoking hypothesis, but consistent with the constitutional hypothesis; and concluded that "Cigarette smoking ie probably not associated with coronary heart disease." De Faire (40) in a study of heart disease In death dieaordant twins, found that the smoking habits failed to distinguish between deceased and surviving co-twins. tiiJefors (41), In a study of hereditary and environmental factors as related to heart disease smoking concordant and discordant twin pairs, reported that cigarette smoking did not discriminate twins that probably had CHD from those that probably had not had CND. In the large scale Swedish twin study, Friberg and Cederlof (4l) found no relationship between smoking and angina pectoris among their identical twin pairs discordant for smoking - a result inconsistent with the causal hypothesis but consistent with the constitutional hypothesis. Cederlof viewed the evidence "as strongly supporting the hypothesis that tobacco smoking does not cause coronary heart disease (43)." Analogous results were obtained in a similar study of U.S, veteran twins by the National Research Council (44), It is of great significance that published follow-up studies of the Swedish twins by Friberg et al (45) show no mortality differences between identical twins discordant for cigarette smoking. As Burch (22) has pointed out, "The equality of death-rates among the 'low' and 'high' smoking members of discordant 12 pairs agrees with the expectations of the constitutional hypothesis and conflicts with the causal hypothesis." This array of evidence provides positive support for the constitutional theory of Tmoking and heart disease, thereby exonerating smoking. It is clearly a source of bias that proponents of the causal theory of smoking and heart disease ignore or deprecate this evidence. The continued neglect or disregard of alternative evtdence and hypotheses by the proponents of the causal theory of smoking is a serious misapplication of orderly scientific procedure. 85 Table I Age-standardized relative sisk ratios for Fra:ninghas Study male cigarette smokers, age 35-64 at Exatm 1, according to Amount of Cigarettes smoked - 16 years follow-up Relative Risk Ratiose CND eventa 4moant of cigarettea smoked under 20/dav 20/day over 20/da Total coronary heart disease . di l i f Ill 103 128 a Nyocar n arction i t i 102 123 110 na pec or Ang s, uncomplicated d ath f dd 110 76 129 e en Su rom coronary heart disease th from c D 152 85 173 ea oronary heart disease 108 e6 169 R Relativa risk ratios and age-standardisation calculated fro. data given in A-tables of Section 26 In referenea ~, The-Framingha. Study. Age-standardised by indirect method with total Pramingha4 nale population (relative risk - 100) as standard. TIMN 450226

74 Mr. Chairtuan, I feel that it is important to re,tilize that the bill language is not limited to tobacco products. Indeed, the (,'on>n>ission would ho vested with broad discretlon as to the subjec•t matter of its reviews and assessments. I respectfully suggest that-tl>e Anlerican peo- ple are growing increasingly weary of having t.heir 1>ersomal prefer- enc'es rev>ewecl l>y instrumentalities of the Federal Government, and they au•o growing increasingly weary of paying tax tnoney to finance a host of bureaucr•at-,to ccasses5" what t.ltey are doing. Indee.cl, I seriously question the deslrability of creating another Federal agr,ency to tell Congress how to spend n>oney. What is desper- atcly needed, is some additional voices telling Congress how to save t.ho ta xpayers' money. It, gives tile no pleasure, Mr. Chairman, to be a pessimist. But, over tile ycars, we have seen the Congress create one new Federal agency ufter auother. And, wa have read in our newspapers the regular in- clictutents that these anonymous bureaucrats distribute against vir- tually every institution of our Nation. What will be the pernnetets of I ho reviews and assessu)ent5 of the new Coutmission ? Will it become ;~. self-appointed oracle to invade the daily habits of private citizens aml various industries, telling them what is good and what is bad, what, is in the public interest and what is not? Will it needlessly malign health care procedures on the basis of inadequatc research or simple error, as we have seen other Federal agencies do with respect to some consumer products? If so, will it claim an exenll>t.ion from any civil responsibility for its actions under the antiquated doctrine of sover- eign ilumtmity accorded the Federal Government? ANTIC(1N6U11fERISAi ANI) EXORBI'rANT TAXATION Atr. Chairman, I reiterate that• the proposed legislation is, frankly, an assault. on the 60 million consumers of tobacco products all across the country. More than a century ago, Chief .lustice John Marshall warned Americans that• the power to tax is the power to destroy-tl>e proponents of Senate bill 2902 know that t•he discriminatory tax it would create, is intended to effectively destroy the freedom of choice of tenti of millions of American consumers as they enter the nlarket- placc. .AW. 011 y ~~ui _~.. A li„ r.~ ...iU terrific burden of the excessive, new taxation, but our cities, counties, :uld titatcr, would find that the hederal Governmentt h:ul effectively precullctcd a.nother large portion of income resonrces, and had un- dcrniinccl thc+ cconrnllic stability of olu• local units of government.; t-1>e rncs vlccsctit to the lieol>le. 'I'o gral>hically illuntrate the 'b>u•den of the 1>rol>osed new tax, let ns:ICCe.tct 1 he reasonahle asscuuption that. the consumers of thew affected tohac•co pt•od>u•ts are. fairly evenly dish•ihuted across tile Nat.ion. In ihat event, by simply applying census figures to tile $9 billion revenue iig,u•e tile proponents of the legislation say it will generate, we can have a good estuuate of what. that, tax will cost the various States and their citizens. For cxalnple, the consumers in the State of Massachusetts would, uncler tile new tax, pay an additional $300 million in taxes; consumers 75 in Pennsylvania would send another $550 million to Washington; in New Jersey the proposed tax would cost the consumers $310 million. Of course, the list goes on for each State, but let nle mention just a few more. The cost of that new tax to consumers in Missouri would be $210 million; in New York and California, consumers would pay about $900 million each; and in my own State of North Carolina, the increased tax burden would be to the tune of another $225 million. And, Mr. Chairman, the fact is that this enormous additional tax burden cannot be justified; it tivill be highly discriminatory; it will increase unemployment; and it will adversely impact upon millions of American consumers all across the Nation. It is no secret that the tax burden on Americans is so excessive now that it serves to further undermine our citizens' faith in government. And, we are being told at every turn that the consumers are bein "ripped off." I respectively submit that Senate bill 2902 is an example of the problem-not the solution. Thank you. [The material referred to follows :] TIMN 450221

108 UNIVERSITY OF SAN FRANCISCO INSTITUTE OF CHEMICAL BIOLOGY February 12, 1976 STATEMENT OF DR. ARTHUR FURST In 1972, I testified before the Consumer Sub- committee of the Committee on Commerce in the United State Senate concerning Senate Bill 1454. I have attached a copy of the 1972 statement and my current curriculum vitae. I have maintained my interest in smoking and health and devote a good portion of my research activity to this area. I continue to monitor the world scientific literature, maintain current bibliographies and keep a reprint file of pertinent articles. All this, I feel, is necessary in an area as prolific as smoking and health. I have consulted with the Envimmental Protection Agency, and serve as a consultant (temporary) to the World Ilealth Organization committee on envir64ncntal carcinogens. I am currently lecturing to a number of California Units of the American Cancer Society on frequently ignored environmental hazards. HARNEY SCIENCE CENTER SAN FRANCISCO, CnLIFORNIn 94117 41si75a-00--F4t_~s L• L6 G9i~ 109 -2- Arthur Furst Because of my background in Chemical Biology, and my long-standing interest in the smoking and health issue, and because I have conducted extensive research in this field, I welcome the oppor tunity to present my views on Senate Bill 02902. Senators Kennedy and Hart have asserted that of the more than 90,000 new cases of lung cancer which will be diagnosed in 1976, "more than 85 percent of these will have been caused by cigarette smoking." The minimizing of the environmental factors is astounding."And the bill claims that "overwhelming scientific evidence exists that the harmful factors contained in cigarette smoke are "tars" and nicotine Such certainty, in the face of a vast mass of contradictory scientific material, must be comforting. I am unable, I fear, to join them in that certainty, nor do I share their views minimizing the environmental aspects. The proposed differential tax on "tar" and nicotine is an attempt, by financial means, to regulate the "tar" and nicotine content of cigarettes. The rationale for such regulation is not substantiated by current scientific knoalcdge. Int i suggesting "tar" as a basis, for example, the TIMN 450238

72 STATEMENT OF HON. JESSE HELMS, A U.S. SENATOR FROM THE THE STATE OF NORTH CAROLINA Sellator IIF.LMS. Mr. Chairman, I appreciat.e the opportunity to pre- sent this testimony to t.he distinguished subcommit.tee ats it, begins its he:rrint,rs respecting a matter t.hat. encompasses 5enat.e bill 2902, en- titled ihe "National llealth Research and I)evelopment Act." lTlnloubtedly these hearingsare very important.. They are important because that( bill wonld allversely impact upon nlany rnilllons, of Arner- icans--including those thousands of farmers who grow tobacco, and the acltlitional hundreds of thousands who are employed in the man- ufartnre and merchandising of tobacco products. These are citizens who are striving in the face of continued inflation to provide a liveli- hood for their families and educate their children so that the next gen- erat ion can have a better life. IM1'ORF.fi IIF.AVIF.RT RURDF.N ON TIIF. LERR AFFLUENT In addition to threatening the livelihood of those employed in the tohaeco indnstr.v, that proposed let;i5lation would also impose a heavy burden on the (iO million Americans who are consumers of tobacco pro- cluc.ts.'1'Ire bill proposes a new regressive tax that. discriminates against tho less privileged-those in lower income brackets. Of course, that regressive tax seriously burdens the minorities and the disadvantaged of our land. And, hecause the tax would Ix.~ gradua.ted according to the so-called tar content of the tobacco ln•oducts, thee less aFlluent Americans will not have the sanre level of freedom in the marketplace that will, under that lef!islation, bo afforded to thc «•ealthy of our Nation. Senators, highly paid professionals, and others who enjo•y a substantial income will not he denied t•he freedom of individual selection that. is now available to all consumers. For example, if a consumer with an annual inconre of $5,000 paid $100 in tax under this legislation, the tax would equal 2 percent, of tha.tt consnmer's income. ]int, for a consumer with an annual income of l tn-nnn- c,trrrll:lRlnSr the s:rnte tobacco tlrocllrctt and paying t'he S~Ime aunotmt of tax, that, new, regressive tax would equal only one-haJt' o1: 1 l)ercent of his income. ,1 cit izen earning only one-folu•th as much as his neighbor would be lnaying four times as rmlch tax as his neighbor in tertns of their re- SPect ir•p annual incnnles. I.ong ago, we amended the ('onstitution with reslrect. to the. Federal income tax to avoid that. kind of discrimination :It;ainst, the less fortunate of rnn• society. Yet., now, many years later, we tind legislat ion being 1)rol)o5ecl that. would perpetuate that. eco- nomic bias. LR(11t;LATI(1N RASr•.I) ON UNPROVEN EVIDENCE Fnrther, Mr. Chairman. I arn al>1)alled that, the proponents of that. hill have obvionsly based i heir claim that, it. is needed upon such state- ntents as "cit;arette smoking is the largcst single unnece5sar,y and pre- %•rntable cnnse of illness :uul ear•lv death in the United States." With respect, I am comhellecl to suggest. that t.he statement is a gross exaggeration support able by no more than inferenc,e and speculation. 73 Indeed, despite continuing research, no one has been able to assign any creditable validity to any such proposition. And, while I would not wish to debate or seek to resolve that question at this time, I do feel that, it. is important. to note that. a considerable body of medical opinion strongly disagrees with that contention. It shollld 'be recognized that there are wide ranges of opinion among those who are engaged in med- ical research on this subject. In fact, I have written to several eminent and highly respected rnem- bers of the scientific community to solicit their assessments of the most current research respecting the question of supposed harmful effects of tar and nicotine found in tobacco smoke. One of these gentle- men, I)r. Carl Seltzer of the Harvard University School of Public Health, has told me that such statements as quoted a.bove are "un- proven, incompatible with much available scientific information, and in flat contradiction with a number of important studies." Dr. Seltzer, and the others with whom I have corresponded, list many other conclusions and offer other evidence which strongly indi- cat.es that the fundamental assumptions of that legislation are faulty and based upon wholly inconclusive medical evidence. Mr. Chairman, I would like to share with the members of the sub- committee copies of letters from Dr. Seltzer, and from Dr. Sheldon C. Sommers, director of laboratories at the Lenox fiill Hospital, New York, N.Y., and from I)r. Arthur Furst of the Institute of Chemical Biology, University of San Francisco, together with the related reports that were enclosed with them. This material, in my view, substantiates the fact that a wide diversity of opinion exists among informed, and highly respecttd professionals. Further, the ma- terial substantiates that such charges as previously quoted respecting tobacco products and health care are clearly not, supportable. I cannot believe that this Congress would consent to such an. exten- sive proposal as the one before us when its fundamental premises are still a rnatter of considerable controversy. Indeed, Mr. Chairman, the Congress has repeatedly reject.ed such contentions. The bill before us proposes to discourage higher levels of tar and nicotine in cigarette smoke by imposing progressively higher taxes upon those substances. As the Senators know. hearinxrG werp. hPlrl ;,, 1079. fo le~g sl f io l ;tlu nll lo cannot ~~uld l not establ h a proper predicate , a so now. ADDITIONAL EXPENSIVE ANI) niTRDF.NSOMR BUREAUCRACY Thatt bill wo„ld, among other things, create a new National Re- search trncl I)evelopment Advisory ('•olnnlission. The bill language pro- vides t.hat, the proposed ("onuuission will cc('onchlct. * * * studies rela.tiug to health reselnrh and development or the application and di55eulinat.ion of health technology *** as the Commission ma,y cleem neces5al.y." Its conclusion5 are to be reported to the President and tile (bnt,~rr5s together with recolnulenciations "on the appropriate clistrihution of moneys in the health research and development. fund," also create(l under the bill and financed by the discriminatory new taxation the bill would impose.

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82 Seltzer-ApPendiX Page 3 A_PPF.NDIX 6 Proponents of the causal theory of cigarette smoking and CHD lay emphasis on the contention that the risk of developing smoking-associated diseases decreases after smoking cessation. However, inconsistencies in the atop smoking data are not taken into account, nor is the fact that data on ex-smokers contain so many contradictory findings that they can be used to support of refute alawst any argua+ent (20). The basic difficulty is that people who decide to stop smoking are a self-selected rather than a randomly assigned group. Since one of the reasons for the decision to stop smoking auy be ill health, this tends to introduce a bias which "dirties-up" the data on ex-saxrkers and thereby creates problems in establishing clear-cut trends and effects. Furthermore, a large segment of ex-smokers are not "confirmed" cigarette smokers and they are able to discontinue the smoking habit quite readily. There are published data from the 2ecumaeh, Michigan Study (21), from Reid and co-workers' study of migrants (9), and from the U.S. National Survey (11), that men who stopped smoking cigarettes had higher CHD rates than nonsmokers or those who continued to smoke cigarettes. On the other hand. the Fra.inghan Heart Study has published data showing ex-saawkers with lwer CHD rates than even nonsmokers (17). In an examination of the Doll and Hill data for British doctors it was bhown that the overall mortality rates showed no relationship to the simultaneous downward trend in cigarette smoking between 1951 and 1965. British doctors aged 35-84, had a 50; decline in cigarette smoking from 1951 to 1966 while CHD mortality was increasing by 8% between 1953-57 and 1961-65. The Framingham 8eart Study reported recently that men who had stopped smoking after entry into the tudy had subsequent CHD rates that were half those experienced by those who continue to smoke (17). These data, on the surface, would sees to support the value of giving-up cigarettes. However, this report has been criticized by Burch (22) on the grounds that the mett who gave up smoking were self-selected and not randomly selected from the population of smokers, and hence the results obtained "vitiates the conclusions regarding causality." In addition, a further examination of the report poses additional problems in the interpretation of these data. To begin with, the Fraoinghan Study reports an 11% excess risk of C8D for cigarette smokers as compared with never smokers over an 18-year study period. It le therefore difficult to see how one can obtain a 50% absolute reduction in CHD rates for those who stop smoking when the risk attributable to smoking is but llx. But even more curious, !e the fact that when appropriate CBD rates for never smokers were examined, they were found to be considerably hi er than the rates for thoae who topped smoking (See Graph G). This anoaaloua finding would suggest that it is better (as regards C110) to begin sawking cigarettes and then to give them up than never to have smoked cigarettes at all. In summary, the use of ex-smoker data is unreliable since the people who quit cmoking are not random samples of continuing smokers; there 'are inconsistencies !n the results using ex-smoker data in comparison with continuing cigarette smokers and non- smokers. Accordingly, the evidence does not allow for confidence in the view that the risk of developing CHD decreases after smoking cessation. 83 ' Seltzer-Appendix Page 4 APPENDIX 7 Proof of the alleged mechanisms or agents by which cigarette smoking causes s CHD he not been established. None of the suggested agents, running the gasrut from nicotine to carbon monoxide, has yet been proved (23). In the Surgeon General's Report of 1964, the posalble cauael role of nicotine was rejected with the statement that "No additional or unique cardiovascular effects have been demonstrated..,to account for the observed association of cigarette smoking with an increased lncidence of coronary disease." The recent emphasis on the role of carbon monoxide is unproven, still in the hypothetical stage, and discounted by Hickey et al (24). Hill and Wynder (25) favor nicotine rather than carbon monoxide as an effective agent and state "nicotine rather than carbon monoxide enhances the risk of a coronary event." Yet the clinical and experimental evidence for chronic vascular effects of smoking is unclear and lnconsistent with other information (23). Chronic effects of smoking have been alleged to increase atherosclerosis, yet io the age category with greatest amounts of atherosclerosis (in the elderly), we find no association between cigarette smoking and CHD. For the acute physiologic effects of cigarette saioking, the reviewed evidencehis been found to be tenuous, hypothetiFal, and replete with unproven hypotheses (23), an precipitating acutesryocardial infaret onseare2unknovnc"~Ahsimilarrconclusionswas expressed by the World Health Organization: "11te mechanism by•vhich smoking leads to (coronary heart disease) is not yet known.,,° (27). Thus, it can hardly be claimed by the BILL without qualification that cigarette moking is one of the principle contributors to diseases of the heart. APPENDIX 8 It has been repeatedly asserted by the Fraoingham Heart Study that angina pectoris, ' as a manifestation of CHD, is probably unrelated to cigarette smoking. This view has been reinforced in the latest Framingham Heart Study of smoking and CHD (17), wherein consideration of angina pectoris has been omitted from their presentation as a manifestation of CHD. This latest study now considers in their main tables "Incidence of C.H.D. Other Than Angina Pectoris." If angina pectoris is considered as unrelated to cigarette smoking, this would eliminate a large segment of CHD eutnifestations from active coneideration, TIMN 450225

131 -4- provide a basis for concluding that cigarette smoking causes various diseases and do not iustify the proposed arbitrary taxation On "tar" and nicotine levela. The results of animal experimentation cannot serve as a basis for determining which ingredient or ingrediente might be carcinogenic for humans. Scientific doubt arises not only from the unrealistic dosages involved in these animal experiments, but also from the failure to duplicate the reaults in other test animals. There are numerous reasons why a tax levied on the basis of "tar" and nicotine levels is undesirable. For example, econo- mic pressure created by the graduated tax omight well cause many people to switch to low "tar" and nicotine cigarettes. But in the final analysis, the individual smoker will ultimately decide the amount of "tar" and nicotine he inhales. Therefore, the pro- posed legislation might force an individual to unconsciously increase his consumption of cigarettes. From the preceding, one ie aware of the lack of cer- tainty concerning "tar" and nicotine. So.e scientists view any lowering of these substances as dangerous because of the possible removal of anti-carcinogens. Others reco®moend the lowering of "tar" levels, but the raising of nicotine levels. -s- In short, there is anything but unanimity in the scientific community concerning "tar" and nicotina. I have attempted to outline some of the problems con- nected with the proposed lav. My purpoae has been threefold: (1) to discourage any sort of decision which is not supportad by sufficient scientific evidence; (2) to e>tphasize the unex- plored repercuasiona which ay result fro any "tinkering" activity; and (3) to question the effects of forcing individuals to consume cigarettes with lower levela of "tar" and nicotine. Quite frankly, this 1e not the time for Congress to use scientific blinders and unwittingly plunge into an area as complex ae this. Respectfully submitted, .Ni dt .... Charles H. 8ine, M.D., Ph.D. TIMN 450249

78 STA:EIIEMT ON SMOKING AND HFAItT DISEASE Dr. Carl C. Seltzer 2/11/76 The BILL h.s made the folloving statement relative to heart disease: "clgarette smoking is one of the principle contributors to the high incidence of... diseases of the heart..."' The above statement is unproven inco®patible with much of the availabl• scientific inforesation and 1n flat contradiction vith the results of num_erous important studles. The reasons are given below: The proponents of the causal theory of cigarette smoking and coronary heart disease (CHD) have rested their conclasions on the following types df evidence: a statistical association between cigarette smoking and excess rates of CHD mortality and morbidity; a consistently rising gradient of CHD rates with increases In amount and duration of cigarette smoking; secular (calendrical) changes in CHD rates associated with secular changes in cigarette consumption; and reduction of CND rates with reduction or stopping of cigarette smoking. I shall point out below that in each Instance the proponents of the cause-effect theory of smoking and CHD have given an unbalanced presentation of the evidence, with almost no reference to inconsietent or contradictory data, and with inadequate consideration of an alternative hypothesis. ' 1. There are considerable geographic lnconsistencils In the data on cigarette smoking and coronary heart disease (CHD). Statistically significant associations between cigarette smoking and heart disease do not occur consistently in all populations'and in all countries. (aee Appendix 1). 2. There are inconsistenoies in the alleged dose-response relationship of increased rates of CHD with increased amounts of cigarette smoking. The evidence shovs no consistent positive gradient of CHD with amount of cigarettes am<eked In a number of atudies, and lnversions or inconsistencies in'the alleged gradient In other I studies. This is particularly evident In the data from the praninghan Neart Study of the U.S. Public Health Service. (see Appendix 2). " 3. There Is an absence of consistency with regard to the data concerning duration of cigarette smoking. The alleged association between CHD rates and duration of cigarette smoking 1 unsupported in several important epidemiological Investlgations. (see Appendix 3). 4. There is an absence of risk in elderly people. A number of important studies show that continued cigarette smoking In the elderly (ages 65 and over) ahow essentially no different risk of developing CHD than elderly who quit smoking. (see Appendix 4) This view has been accepted editorially by the British Medical Journal. 5. There are secular (calendrical) inconsistencies. Theallegation that secular rates of CHD have risen concomitantly with Increased cigarette consumption ie not supported by some studies. (see Appendix 5) 6. There are inconsistencies in the stop smoking data. A number of studies considered ukuoesnu.n~{ stopping ant uceliabi e scientifi c pro edure for estimating the purported benefits of sto smnking. (see Appendix 6) 79 Statement - 2 7 There !s an absence of definitive proof of cigarette smoking as an active agent in the development of CHD. The mechanism or oechanisma by which smoking is alleged to lead to heart disease have been stated by the World Health organization to be "as yet unknown". (see Appendix 7) B. Angina pectoris,a major manifestation of heart disease, is regarded by the Praminghaa Heart Study as unrelated to cigarsltte smoking. (see Appendix g) 9. The alternate "constitutional'4typothesis relative to smoking and heart disease has been nini®ized or ignored. Yet, there is compelling evidence from twin studies that the predisposition to certain smoking habits is associated with the predisposition to heart disease, and not caused by snoking. (see Appendix 4) The BILL makes the statement that "overvheluing evidence exists that the harmful factors contained In cigarette smoke are tar and nicotineJ' In this connection it has never been argued by tha proponents of the cause-effect tfieory of ssa~king and heart dlaca.e that tar"' has • har.ful effect on CHD. Micotlne hu been suggested, but it should be pointed out that after the Surgeon Qeneral's Advfsory Co.aittee on Smoking and Health In 1964 had reviewed all the evidence, rejected the possible role of nicotine with the statement that "Mo additional or unique cardiovascular effects r ,nicotine? have been deoonstrated...to account for the observed assoclation of ctgarette smoking with an increased incidence of coronary dlsease." In summ.ry, the above statements illustrate inconsistencies In geographic rates,• dose-response relationships, duration of cigarette smoking, risk for the elderly people, secular trends, stop smoking data, and proof for a specific causal mechanism. Scientific truth has never been attained by regarding this scientific problem as a political issue to be settled by a democratic process of majority vote or opinion. Unless these lnconsistencies and conflicts in the data are satisfactorily disproved or reconciled, and until the constitutional hypothesis has been fully considered, the currqnt dogaa that cigarette smoking is a.aJor risk factor in coronary heart disease.may become an outstanding fallacy of our era. TIMN 450223

128 -2- 2. "It would, therefore, seem most unscientific to lower arbitrarily the 'tar' content of cigarettes. l+e simply not know whether cigarette 'tar' has any relationship to human disease." I have reviewed my previous statement in view of current scientific data and find that the opinions expressed therein are certainly applicable to the present inquiry. I have examined approximately 700 scientific papers dealing with tobacco smoke and its constituents since 1972. The continuous review of current literature by my group has enabled me to keep informed of the developments concerning "tar" and nicotine and the relationship of these materials to human disease. My earlier opinion has been reinforced by these subsequent publications. do In my 1972 statement, I discussed specifically Chapter Nine of the 1972 Report of the Surgeon General, "Harmful Constituents of Cigarette Smoke." I noted with interest (1) the avoidance of the term "known contributors" i., tti-, , uni. (2) the reliance upon uncertain descriptors such as "probable" end "suspected.° This confirmed to me that current research hes failed to show any compound in cigarette smoke to be an established health hazard in the quantites which are apt to be absorbed by the average cigarette smoker. Since 1972, I have had an opportunity to read the transcript of the one-day conference in 1970 which formed the basis for Chapter Nine. The discussion of tobacco smoke con- stituents greatly disappoints me. Instead of offering an informed inquiry on the subject, the conference evidenced with its indecision and disagreement the lack of data dealing with the effects of cigarette smoke on human health. As a result, Chapter Nine of the 1972 Report represents an attempt to cate- gorize various poorly defined materials and chemical conatituenta into levels of supposed harmfulness to health, despite an absence of scientific evidence. It is hoped that government publications in the future will adequately set forth a scientific data base from which critical evaluation would implicate or exonerate materials as potentially harmful or free from effect at the concentrations at which they appear in tobacco smoke. Due to the scarcity of new developments in the cigarette smoke controversy, I question the baeie for this new attempt at government Involvement. Events subsequent to 1972 have failed to TIIVIN 450248

i 104 for we know More about the genetics, viral profilcs, and bio- chemical responses of this species than any other. We now have a better, but not perfect, method to evaluate "tars", and com- poncnts of smoke on the lungs of mice, not on the shaved skin of theirbacks. Nevertheless, no acknowledgement has been made that further work is necessary in light of the newer and more applicable techniques. While I realize the difficulty of test- inj smokeand its condensate, the fact is that tests in animals to date are inadequate. Nothing has been said about the fact that after many years of experimentation it has not been possible to date to in- ducelun cancer in animals by the inhalation of tobacco smoke. Tests are still being conducted. In the A.E.C. symposium held inGatlinburg in 1970 I made the suggestion that we must simulate thehumaq experience when smoking experiments are conducted. Nowhere in the subsequent Surgeon General's reports, or in NCAB recommendations are these criteria mentioned. These are, after ~ all,minimum requirements for acceptable experimentation. We are all aware that smoke is a complex mixture; what effect will there be if we reduce only one ingredient? We cannot assume without experimentation what this effect will be. For that matter would an increase of nicotine conteht be better? Would people smoke less and thus inhale less tar? How can we make simple guesses on complex problems? There is no knowledge about ie e"Lec`:s on ._s.. altered. I have suggested time and time again that more research be conducted on effects of low level doses on physiological and biological responses. Expc rinicnts must be conducted to see what 105 tal.es place in the intact aniiNal uhen low doses of the substance under investigation are administered at a regular schedule. Not only must pure materials be investigated, but combinations must also be studied. It is well known that some chemicals which have simi- lar biological activity can nullify each other when given together. This phenomenon of antagonism can be relevant to the lowering of only one substance in cigarettes. On the other hand the effects may be additive, they may even enhance each other, but without the experiments which can give unequivocal results, we just do not know. I cannot draw conclusions without real data. I am still concerned about the comprehensive list of harmful constituents given in the 1972 Surgeon General's report. In Chapter 9-there is no documentation. This has not been ampli- J fied as yet. It is essential that this information be made avail- able to scientists so that they can evaluate the claims.made about these listed constituents. In paragraph 4 of the NCAB recommendations the term toxic components is used. What does this mean? Toxicity is a relative term; everything including water, is toxic if given at a high enough dose level. This term really requires medification and amplification. In reference to my comments given previously, what are the experimental results when animals have been continu- ously exposed to low levels of hydrogen cyanide in the presence -f -i*- a*+A what are the results if the hydrogen cyanide is given intermittently, again in air? What happens when a mixture off carbon mono::ide and hydrogen cyanic'.e are administered to mice in ~ pulsed amounts? These are the types of experiments which eiust be done. • TIMN 450236

I 126 I have seen the letter of January 26, 1976, written by Senators Kennedy and Hart to their fellow Senators asking CHARLES H. HINE, M.D., Ph.D. I support for Senate Bill /2902. biased conclusions with respect 127 This letter contains extremely to the role of cigarette awoking in health. It should be noted that the claims stated the scientific evidence and that many etiological queations remain unanswered. so dogwatically as fact are not aupported by On two previous occasions. I have presented y vievs to Congress. Most recently, in 1972, 1 prepared a state.ent in relation to Senate Bill /1454 and the 1972 report of the Department of Health, Education and Welfare entitled The Health Conseguences of Smoking. A copy of this statement, which includes a list of my professional qualifications, is attached. Since the Kennedy-Hart Bill stresses the "harmful" effect of "tar" and nicotine, I would like to quote briefly from y earlier statement: 1. "All the pharmacologic effects from smoking are due to an active alkaloid, nicotine. Due to the rapidity of absorption, metabolism and excretion, these effects are transitory and can be repeated without cumulative effects. Tolerance to these effects develops rapidly on repeated expo- sures. Nicotine exerts a number of beneficial effects." TININ 450247

123 Statement by Senator Wendell H. Ford Subcomaittee on Health Cosssittee on Labor and Public Welfare February 19, 1976 Mr. Chairman, I am extremely pleased to have the opportunity to testify on S. 2902 and to state to the members of the Subcosmittee on Health the detrimental effects that this bill will have in Kentucky. Mr. Chairman, Kentucky has 164,161 farms involved in the growing of tobacco. You could take that number of farms and easily multiply by four and arrive at a figure of those involved in planting, harvesting and marketing--better than 650,000 aentuckians--whoae livelihood depends on tobacco. That crop is worth $t'YO million to the farm economy of my state. State, Federal and local taxes are paid on farm income from that amount plus the fact that on the sale of the finished product, Rentuckians pay another $22,457,000,000 to the State plus a 5 percent tax on the end sale price of the amount, and Federal tax yields $59,888,000 more. Rentuckians have spent millions of dollars on health research. They are concerned about the health of people and they are spending millions of their hard earned dollars to determine any elements in tobacco products that are detrimental to health and to find ways to remove them. This approach is positive and it is fair. I recently received a letter from one of my constituents stressing the adverse effect that S. 2902 would have and I quote a portion of that letter, •With taxes this high cigarette consumption would decline extremely and the end result would mean less tobacco needed which would mean less money for the tobacco farmers in Kentucky. Tobacco ie a major cash crop to your Kentucky farmers and we feel this bill would be very detrimental to the farmers, dealers and manufacturers of tobacco products.• I agree with that statement. Under this bill we would be requiring one product to defray a major cost of health research. No other industry has been so severely penalized. I remind the Committee that the power to tax is the power to destroy. The imposition of a tax as proposed in this legis- lation is so great that it will destroy the tobacco industry in Kentucky and the other tobacco growing states. It will destroy the small farrrs and place an economic hardship on millions. Are we taxing to regulatet taxing for revenue; or taxing in an attempt to kill the tobacco industry? Regardless of the intent, the effect will be to drive.domestic tobacco producers out of business. We will drive more and more small farmers in Kentucky, North Carolina, South Carolina, Tennessee and other tobacco producing states out of business by imposing an unreasonable tax burden on the products they produce. The tax will not only affect the farmers, but it will also have a.ajor effect on state and federal revenue and even an overall econo0ic impact because of exports. The tobacco industry already bears a heavy tax burden at both the federal and state levels. In 1975, $2,261,100,000 in Federal taxes and $3,284,660,000 in state taxes were collected from cigarette taxes. Further, the export value of unmanufactured tobacco and tobacco products in Fiscal Year 1974-75 was $1,234,000,000. This volume makes tobacco an economic asset both to farmers specifically and to the public in general because of its impact on the balance of trade. (The import value of these products for 1974- 75 was $209,200,000 leaving a surplus from tobacco in excess of $1 billion.) .n.i.iiiR:inyl a:a:e revenue by ancrear%ng cigarette taxes. This bill would pre-empt an increase in state taxes planned for cigarettes because up to 50 cents per package of federal taxes would reduce consumption to the point that it would reduce state revenues. This bill would have an extremely detrimental effect on the tobacco farmers and it would also be a regressive tax of $180 a year on the 50 million Americans using these products. We would be aaking them to pay the coat of research that may or may not affect them. Are we establishing a precedent by taxing consumers to correct presumed health ailments? Where would this precedent lead us? A sugar or starch tax? A non-exercising tax? A tax on people living in urban areas because they have poor health rather than the affluent? An increased tax on people who live in highly industrialized neighborhoods? The precedent is there in this bill. TITVIN 450245

114 -2- 115 -3- .. -•i1R FL'.4ST ?F!'iS55TON1iL EYPE?lE"~CS: II puring sabbatical leaves of absence: . . 7•''•7R FUPST LFSSED ZN (Co!:=.): 1946 Visiting Scientist Radium Znstituce, Paris 'rlho's or. the Pacific Coast ifio's :3c in the West 1969 Clir•ical Professor , Pathology College of Physicians and Surgeo^s, Colurbia Cn?versity, 1%ew York Worlds f:Ro's Who in Sclence 1974 Visiting Scholar Interrr3tlonal Bibliogr ,+hy - Men of Achicz•er-rct fCr.ob ritiJo, Frglanr,)• . University of Washington, Seattle, Washington 1974 Visiting Fellov, Battelle Seattle Research Center S National Register of Prominent Aurricans PGSLICATIO.WS: eattle, Washington See Attached List. pROFESSIONAL EXPERIENCE: III As of ~ > this date: J Guest Lecturer at rany Universities throughout the World Speaker at a number of Symposia, and at Gordon Conferences Papers in Print Papers accepted and.in Press Consultant to various industries and Laboratories Papers subraitted 1!E?73ER OF: American Association for the Advancement of Science (Fellow 1956) American Association for Cancer Research 0 In Fields of:. 1) Organic Synthesis 2) Cancer.Research a) Carcinogenesis b) Cheeotherapy American Chemical Society (Member, Executive Board, Three Years) 3) CNS: Amsrican Society of Pharmacology and Experimental Therape~tics California Association Chemistry Teachers (Organizer, First President) New York Academy of Science (Fellow 1966) a) Psychopharnacology b) diochemistry Phi Lambda Upsilon (Honorary Scholastic Society) ' Society Sigea Xi (Life Member) Society of Toxicology Western Pharmacology Society (Charter Member) NISCELLAPJEOUS: 1970- Consultant (TeTporary) World Health Organization 1973 Seventh Distinguished Teaching Aaard - University of San Francisco i.:= nD SN: . Who's Who in America - i- .w~ n...t tmA states Aurerican Nen of Science international Biogrr.phy R^:o's N'n-n in F^:•rican Educrt?o~ • .+':c's '•'YI :.^ Co)teyo a.,d.Unlvcrsi^7 R!'minis!ra_`•oc TIMN 450241

98 Dr. Carl Seltzer "Twin Registrie in the Study of Chronic Disease", Report of an International Sy.posfut in San Juan, Puerto Rico, 1-4 December 1969. Acta Mad. Scandinavian Supplementum 523 "Critical Appraisal Of the Royal College of Phyiiclana' Report on S.okin8 and Health", Tha Lancet, January 29, 1972, pp. 243-248 "S+.oking and Health", The Lancet, March 11, 1972, pp. 586-588 11 "Aja and Physiqua in Healthy White Veterans at Boaton"; (Damon, Seltzer, Stoudt and ea11). J_ of GarontoloBY 27:202-208, 1972 "Anthropometry in the Normative Aging Study of Veterans: Physique and Aga, Seru. Choleatarol, Uric Acid, and Personalfty", (Damon and Seltzer) Aging and Human Developernt, 3:71-76, 1972 "'Saoking Among Whita, Bl.ek, and Yellow Men and Woarna (iried.an, Seltzer, Siegelaub; Pelds7an and Coll.n), A., J. Epid. 96:23-35, 1972 ' "Differences Between Cigar end Pipe Smokere in Healthy White Veterans", Arch. Environ. Health 25:187-191, 1972 "Smoking Habits and the Iwukocyte Count" (Pried.en, 81e8elaub, Seltzer, Peldean, Collen) Archivee of Environrntal Nealth, 26:137-143, 1973 "S.oking and Coronary Heart Disease", N. i<. J. M.d. (letter) 288:1186, 1973 "Obesity: how it 1e aeeasurad, what causee it, how to traat Lt." (Seltzer and Stara) Medical Insight, 5:10-22, 1973 "Mail Survay Response by Haalth Statua of Smokers, Monsaokers, and Ez-S.nkers". (Oakea, P'riedaun, Seltser), A.. J. Epidemiology (98:50-55, 1973) "Cigarette Smoking and Exposur to Occupational Hasarde, (Friedrn, SfeBelaub, Seltzer) A.. J. Epide.iology 98~175-183, 1973 "Relationship Between E®otional Stability and Phyaiqw". JANk 226:86-87, 1973 "ibta on Smoking and Heart Disease". Nw England J. N.d. 289:1200-1201, 1973 "Cl{erettas, Alcohol, Coffee and Peptic Ulcer" (Friedman, Bfeplaub, Seltzer) New Eng. J. Ned. 290:469-473, 1974 "Clprette Smoking and Longevity in the tlderly" MMedical Counterpoint, 6:29-33, 1974 "Amkin6 and Drug Consumption in White. Black, and Oriental M.n and Women. (Seltzer, Priedman, Stegelaub) Am. J. Public Nealth, 64:466:473, 1974 "Ieoting and Cancer". Naw Scientist (letter) 62:195-196, 1974 99 Page 6 Dr. Carl C. Seltzer Page 7 "Effect of Smoking on Blood Pressure" American Heart Journal 87:558-564, 1974 "Racial Differences in Serum and Urine Glucose pfter Glucose Challenge". Diabetes 23:327-332, 1974 (Dales, Siegelaub, Feldman, Friedman. Seltzer, Collen) "Smoking, Weight Change, and Age" (Carvey, Boese, Seltzer) Archives of Environmental Health 28:327-329, 1974 "Hearing Loss 1n Adults" (Slegelaub, Friedman, Adour, Seltzer) Archives of Environmental Health 29:107-109, 1974 "Smoking Habits and Pain Tolerance" (Seltzer, Friedman, Slegelaub, Collen) Archives of Environmental Health, 29:170-172, 1974 "Cigarette Smoking and Serum Chemistry Tests" (Dales, Friedman, Sfegelaub, Seltzer) J. Chronic Dieeaaes 27-293-307, 1974 "Differencee in Pulmonary Function Related to Smoking Habits and Race". (Seltzer, Siegelaub, Friedman, Collen) Am. Review of Respiratory Disease 110:598-608, 1974 "Health Service Utilization by Smokers and Nonsmokers" Medical Care 12:958-966, 1974 "Effente of Selection on Mortality". (Seltzer, Jablon) Am. J. Epidemiology 100:367-372, 1974 "Smoking and Cardiovascular Dlsease" American Heart Journal 90:125-126, 1975 "Smoking and Coronary Heart Dieeaee in the Elderly" Am. J. of MediCal Sciences 269:309-315, 1975 "Meil Survey Response by Smoking Status" (Seltzer, Boeae, Carvey) Am. J. Epidemiology 100:453-457, 1975. TIMN 450233

112 ~ 113 t -1- Arthur Furst CURFICJLUM VIT11E OF ARTNUF FU'ST - Discussions of tobacco smoke carcinogenicity frequently use the term toxic components. What does Borr. flinr-eapolis, Xinnesota, Decenber 25, 1914. Hovcd to C'alifornia, 1919 N.arried, four children. this mean ? Toxicity is a relative term; everything, ':f.:'CFTIOel: including watef is toxic if given at high enough dose level. This term really requires modification and amplification. Los J.ngeles City College 1932-35 Psychology, C1•cnistry A.A. University of Califo-nia Chenistry, Psycholoyy, At Los Angeles (UCLa) 1935-37 Physics, Educetion A.a_ UCLA 1940 Chemistry N.A. Stanford University 1945 Chemistry Ph.D. Further, the method by which a substance is administered PROr^ESSIO.\'AL EJfPERIENCE= Z may certainly influence its effects on an animal. For 1937-39 Teaching Assistant example: what are the experimental results when animals 1939-40 University of CaIifornia at Los Angeles a Sci nce and Mathematics T h have been continuousl~lcxposed to low levels of any e c er, e •Pacific Military Academy, Culver City, California 1940-47 Chemistry Department Z structor gas in the presence of air, and what are the results if , n San,Francisco City College that agent is given intermittently, again in air? What happens when a mixture of only some of the materials in 947-49 During War, part time atr University of California Nar Trainingt San Francisco State Colleget University of San Francisco Assistant Professor of Chemistry tobacco smoke are administed to mice in pulsed amounts ? University of San Francisco 1949-52 Associate Professor of Chemistry These are but a few of the types of experiments which University of San Francisco still must be done. 1949- Research Associate Mount Zion.Eospital, San Francisco 1952-61 Lecturer, Chemistry Department The idea of treating "tar" and nicotine content University of San Francisco as a valid basis for a graduated tax is not, in my 1952-57 Associate Professor of Pharmacology (Medicina2 Chemistry) Stanford University ,. - rt.?b?.P ~r,ientific proposition. Further, 1957-62 Professor of Kedicinal Cheir-istry, Phar.racology Dc-partrnent I fear that Senate Bill 12902 may well discourage ' 1961- . :.m,-uJ.u ~....rrc.... , Director, Znstitute of Chemical Diology research in some of the most basic areas ofthe smoking health controversy by its apparent denial of any need for further knowledge in these areas. University of San Francisco Professor of Cheraistry TIMN 450240

36 for the Iherapy of pulmonary disordere- T. P. Pruas~and D. M. Avlado, In: Annual u D 42. p r Reporta in Medicinal Chemtatry, Academic Press Inc., New York, pp. 55-62, 1970. i3. $ympathomlmetic bronchoditator preparationa avaliable in the United Statee. D. M. Arlado and H. Salem. Rev, Allerr. 25: 441-450. 1970. 44 Xanthine broochodilator preparations available in the United States. H. Salem and D. M. . Aviado. Rev. Alle f. 24: 624-630. 1970. ' 45. Antiaathmatic preparations containing corticasteroids available in the United States. and D. M. Aviado. Rev. Allert. 24: 819-822, 1970. H. Salem 46. Topical nasal decongestant preparations available In the United States, H. Salem and Aviado. Rev. Altera. 25: 271-277, 1971. D. M. Aviado. In: Drill'a Pharmacology in M D etimulant and blockin drugs G li i M .dicin._. 47. . . g . ang on c Edited by J. DiPalma, 4th Edition. McGraw-Hill, New York, pp. 708-734, 1971. 48. Requlation ot bronchomotor tone during anesthesia. D.M. Aviado. Aneathutology. 42(j): 68-80, 1975. 49. Drug action, reaction and interaction (DARI): I. Cardiac arrhythmlaa. D.M. Avlado and H. Salem. J. Clin. Pharmacol. 15(7): 477-485. 1975. 50. Drug action, reaction and interaction (DARI). II.Iatrr.aic cardlopathlaa. J. ClW.~P __harmacol. (In praaa). D.M. Aviado. DL Original Inveatlaationa on Phyatoloay apd Pharmacology of Respiratory and Cardiovascular Systems SI. 52. SS. The reflex reapiratory and circulatory actione of veratAdin. on pulmonary, cardiac r and carotid receptors. D. M. Aviado, R. G. Pontius and C. F. Schmidt. J. Pharmacol. tY. Thar. 97: 420-431, 1949. The mechanism of apnea following intravenoua Injection of varioua antihbstaminic compounda; Ita relation to their chemical atructure. D. M. Aviado. R. G. Ponttus and T. H. Li. J lfiarmacol, Exp. Ther. 99: 425-431, 1950. Respiratory and circulatory reHaxea from the perfuaed heart and pulmonary circulatlon of dhe dog. D. M. Aviado, T. H. Li, W. Kalow. C. F. Schmidt. G. L Turnbull, G. W. Peskin, M. I He.. aad A. J. Netaa. Amer. J. Phyalol. 165: 261-277, 1951. 54. Early respiratory depraaaion by curare and curare-potaaatum antagoniam. T. H. Lt, B. R. Jacoba, D. M. Aviado and C. F. Schmidt. J. Pharmacol. Exy. Ther. 104: 149-161, 1952. SS. Effects of anoaia on preaaure, resistance and blood (P32) volume of pulmonary veaae9a. D. M. Aviado, A. CarletH, J. Alania, P. H. Bulla and C. F. Schmidt. Amer. J. Physiol. 169:460-470, 1952. 56. Respiratory burne with special reference to pulmonary edema and congestion. D. M. Aviado and C. F. Schmidt. Circulation 6: 666-680, 1952. . 57. The activation of carotid ainua preasoreceptors and intracranial receptora by veratridina and potaaatum. D. M. Avtado, A. Cerletti. T, H. L1 and C. F. Schmidt. Js,Pharmacol. Exp. Thar. 115: 329-338, 1955. 58. Effects of pulmonary embolism on the pulmonary dreulaHa+:witn apecia. ra,.erence i:o arterlovenoua ahunta In the lunj. A. H. Niden and D. M. Aviado. Ciic. Rea. 4: 67-73, 1956. 59. >Cffecta of aympathomimetic drup on pulmonary ctrculatlon.ith special reference to a ne, palmonary vaaodilator. D. M. Aviado and C. F. Schmidt. J. Pharmacol. Exp. Thar. 120: S12-S27, 1957. 60,1 Pathogenesia of pulmonary edema by alloxan. . D. M. Aviado and C. F. ~Schmidt, Circ. R:a. S: 100-186, 1957. 37 61. 62. 63. 64. 65. 66. 67. Patie , Effects of anoxia on pulmonary circulation: reflex pulmonary vaaoconatrtction. D. M. Aviada J, S. Linj and C. F. Schrr.idt. Amer. J. PhvaloL I89: 253-262, 1957. Mechaniama for cardiac alowing'by metboxamine. D, M. Aviado and A. I.. lrnuck. Ji lrl+armacol, Exp. Ther. 119: 99-106, 1957. The aflecta of molar aodlum lactate on cardiac (uactlon: an experimantal study In dogs. S. B.lleq S. V. Cuamaq, J. W. West and D, M. Aviado. Amer, J. Med. Sei. 233: 206-295, 1957. The effects of am{nophylline and other :unthlnaa on the pulmonary dreulatton. C. W. Quinby, Jr., D. M, Anado and C. F. Schmidt. J. Pha:macol. Fxo. Ther. 122: 3%-405, 1958. Cardiovaacolar dfeda of aympathdmimetic bronchodilatora: eptnaphrlna, phadHne,, peaudoepb.drina, faoproterennl, methortyphamamtaa aad iaoprophenamtna. D. M. Avlado, A.L.M.uck and E. J. D.Beer. J. Pharmacol, Exa. Thor. 122: 406-417, 1958. The effeda of aympathondmatlc drnp on renal vessels. D. M. Aviado, A. L ttftmck and E, J. D.Beer. 3. Pharrnaeol. t:m. Thar. 124: 238-244, 1958. A comparative study of nasal decongestion by aympatbomlmetie druita. D.ld.'Avlado. A. 1. 1lnuckand E.J_D.Beer. Arch. Otolarvna.-69: 598-605, 1939. _ 60, Therapy of aap.rimentd palaoonary ederer tn the do0: with apodal r.fsra0eo_toaburu of the 69, 70. 'roiptratory trad. D.M, Arlado. Qrc. R.oe. 7: 1010-1030, 1959. Cardiorascotlar and reapiratory raAexea frdrn tha Idt a4do of rAa hrrt. D.14. Artado aad C. F, tteltmidR Araer. J. Pkwtol. 1%: 726-730, 1959. lYfecta of anaaia on the vascular r.atatanca of tha dog'a kind limb. J. L1tw1a, A. H. Dil and D. M. Ariade. Qre. Raa. Ile 605-593, 1960. TI. 1YHcta of acate ateloctaala oa lobar blood Dow, D.64 A.dado. Amar. J. Pkn1oL 198: 349-333, 1%0. 92, Pthneeary.onular reaponaea to ano:ta, S.bydroxytryptamtne and hiataminq D. M. Avtado. Ataer. 3. Pbratol. 190: 1032a1036, 1960. - 11 Effects of a aaw aympath.Nc blocking drug (Bretyltum) on nrdlevaacvlar centroL D. M. Avlado and A. H. DLL J. Pharmacol. Eso. They, 129: 330-337, 1960. i 74. Digitalis and the pulmonary circolatlon. Y. J. Kim and D. M. Avlado. Amer. Hurt J. 62: 680-686, 1961. 73, DlHerentW roaponae of-ranal anditmtoral:bload Dowanattd+nacotar realataneaiirr'pypotenatve and kypartanaive procedarea. J. C. Me6H! an0 D. M. Aviado. Clrc, Raa. 9: 1J27-1335, 1961. 76. Reflex attmulatloa of hwrt lnduc:d by partial oeclualon nf pulmonary artery. A. C. Taqolnl aod D. M. A.tado. Amer. J. Pbyalol. 200: N7-6S0, 1961. 77. Nervous Influencea on the pulmonary dreulaNOn. D. M. Av/ade. lfamyn Scbrnledebart •- Arch. Pharnt. 240: 446-452, 1961. - . T0. Contribution of the bronchial circulation to the venoua adnrlxdnre In aulrnnnarr veawa blood. D. M, Avtado, M. den. Dely, C. Y. Laa and C. F. Schmidt. J. Physiol. aSS: 602- 622, 1961. 79. Iahalation of sulfur dioaide. Comparative bekaaoi of bro3dtiolai and pulmonary vascular amoot' a5uaclea. --.. H. Salem and D. M, Avlado. Areh. F]avlron. Health 2: 656-662, 1961. 80,. Local and reflex effecta of bronchial arterial iq/ecHow uf drop, J, MarNnea L. da L.lona, R. Castro de la Mata and D. M. Avlado. J. Pharmacol. Exc. Ther, 133: 295-303, 1961. Q: Effects of nerve stimulation and druga on the axtrapulmonary portion of the pulmoaary vato. M. Ellaklm and D. M. Aviado. .[, Pfiarmacol- Exo. Ther. 133: 304-312, 1961. 112,. Role of carotid and aortie bodies 1o mediating the Increaae in cardiac output during anoxemla. ht. Penna, I. Some and D- M. Avlado. Amer. J. Phyalol. 203: 133-136; 1962. TIMN 450202

i 20 of awide variety of diseases. By the fourth year of operation, the tax revenues.rollld amount to somc' ~+9.:1 billion which similarly would be ma(le avaliable for health-1•elated research and development ef- fol•ts. In closing, Mr. Chairman, I would again like to expre.ss my appre- ciation for the invitation to appear here this morning. In addition, I wottld like to take this oplmrtunity to con-mmend the subcommittee and its clistingllislle(l chairman for provicling outstanclint; leadership in both scientific and medic.al affairs. In this forum, I feel confident. that the issue under discussion here today will be fully explored and that appropriate action will be taken in order to protect. and enhance the quality of life for all Americans. Thank you, Mr. Chairman. Senator KFNNFnY. Thank you very much, Senator Hart.. You and I are not scientists and I think t.here may only be a few in tlle Ilouse. So we really have to rely upon those that have the scientific expertise and are (•hart;e(1 by the Congress to protect, the health of the Anlerica.n people, such as the. l)epartmeutt of Health, with its war on cancer, to .vhich we have allocated hundreds of millions of dollars. So we will have to listen to the scientists. I am sure there will also be other sc•ientists who may reach a differe'nt decision or conclusion with regard to the whole question of nicot ine and tar. Iint it ahva,ys interests me that on the one hand individual Ameri- (•ans are prepared to obey the admonitions of their own individual doctor, and most. of them cio .chat the doctor says. On the other hand, while onr national cloctclrs are uniformly agreeing on the health dan- ger5 on cigarette smeking, we find that. Americans ,just' do not, seem to bc willing to listen to them. I am wondering if you would share wit 1) us what. ,your o.vn i-mpressions are abont. t.his -phenomenon, because tha1. is an t'ssential aspect. of the problem. tienator iIART. Mr. Chairman, in thatt regard I have received many inquiries fronl individuals on this bill since. its introclnction. Almost llniversally, people say they tllink that a gradual tax based on tar and nicol ine is a good idea. However, when I have been criticized, it has heen primarily by those who think the Government. should do more an(1 )lot. less. flriven the predominance of the evidence which links l'I~!711'('I~li(' SIIIO~dII)~~~ il) 11..1'.'~,1-..:7-~~°`"•~ FI19'fl'este,d that. thls bil) is inst. a halfway measmr. 'I'he situation is really as serious as tlle.body of medical knoWleclge.indicates. I was particularly interested in the comments of one woman I mett m•er the last .+•eekencl. She was very (•ritical of this bill. She said it is tax on addiction. Slle said that she is addicted to cigarettes, and she tllinks it is Imfair to tax peehle for substance when they have no c•clntr(ll over their neecl for it. \vell, if that 1)oint of view is repl•esentative, then I think the situa- ticm mav be even more serious than «•e a5 sponsors of this measure nritrinally thought. If we are talking a1)ollt• a situation that really is c•cmunensltl•ate willl c1r11„r a(I(lictien, then perhaps the incentivee pro- vi(le(I l)v a tax isn't ellOI1!Lh. '1'hat is inst my thought on the matter. 1(hl not lhatlln'n to lx' a(•igarettc smeker, ancl sci I cannot si)Pak from. • lx r~nnal c'.perienc•c. I nlusl rely on thc opinions and exheriences of (it hel•s. I TIMN 450194 21 Senator KExNF•nY. You are, I am sure, aware of what we have found in this committee's review of a variety of health legislation. The area where we can do the most in terms of cost is in preventive medicine, both in terms of savings for individuals, as well as in terms of life and longevity. And that relates primarily to exercise, eating, and smoking. It seems to me that as a country, a great deal more has to be done in these areas: we are obviously not doing enough. The at- tempt you •made here is an effo'rt to deal with one of those major areas, that has a very direct relationship to the qitestion of total health care, and in a way which preserves some degree of choice. You are aware of the efl'orts made a few years ago to ban particular brands of cigarettes with high nicotine and tar content. It seems to me we have to address that particular problem while preserving the free choice of individuals, but also providing the resources to deal with the cancer and heart and lung diseases that affect so many people in our society. I have no further questions. Senator Bea114 Senator Bi';ALL. No questions. Senator IIART. I would like to make one final point. It has been sug- gested that creating this health research fund might shortcircuit the established congressional budgetary procedures. It should be em- phasized, and the bill itsel f specifically states, that all of the revenues collected will be directed t.o expand healt.h research effort.s. Those tax revenues are all subject to the normal and constitutional provisions and authorization mechanisms t.hat we use with all of our other revenues. Senator KENNFnY. There was not any reluctance to set up a high- way trust fund. I want to thank you very much. If you feel you can join us here on the panel we will welcome you. Senator HART. Thank you very much. [Senator Hart joined Uhe panel.] [Introductory remarks on S. 29'02 and the article referred to fol lows :] [From the Congrenefonal Record, Jan. 20, 19761 By 11ir. Gary Hart (for himself and Mr. Kennedy) • S. 2902. A bill to amend title V of the Public Health Services Actt to estahliRh a National Health Research and Development Adviaol'y Commission, and for other purposes. Mr. GARY HART. 111r. President, the distinguished Senater from Massachusetts (ilir. Kennedy) and I today are introduc[nt; the National Health Research I)evelopment Act of 1976. This aet will help extend the promise of good health to every American by insuring continued advances In the diagnosis, treatment, and prevention of d[sease. Mr. I'resident, the Nntional IIealth Research and I)evelopment Act will im- prove the public health and strengthen the foundations of health care delivery here in the United State.-t. The National Henlth Research and I)evelopment Act is a commitment to the future of America, for it makes an im•ectment in the health of our IK'ople.. The return on this investment will be realized not only by ourselves and our children• but also by generations yet to come. In urder to realize th[5 goal, the National Health Research and Development Act provides for substantial increases in the support of biomedical research and development programs, clinical trials. demonstration projects and disease control programs as well as a research and development efforts in the fields of public health and preventive medicine. In addition, innovat[ve pt'ograms of henlth edu- cation designed to provide the public with the information necessary for the maintenance of good health and programs relating to the efficient and timely application of new technologies will be emphasized.

80 Seltzer REFERENCE APPENDIX APPENDIX 1 There are geographic inconsistencies in the-data on cigarette smoking and coronary heart disease. A statistical association between cigarette smoking and coronary heart disease does not occur in all populations or in all countries. Ancel-Res, et al (1) found no ignificant statistical associations between cigarette emoking and CHD In Finland, the Netherlands, Yugoslavia, Italy, Greece, and Japan. The U.S. Public Health Service's own study (2) in Yugoslavia also found no statistically significant association between cigarette smoking and CHD. Recently, the National Heart and Lung Institute (3) reported that cigarette smoking In Puerto Rico Is unrelated to the incidence of eqocardial infaretion and CHD death, This lack of association between cigarette smoking and CHD in so many countries cannot be ascribed to low CHD rates in these countries, since Finland has one of the highest rates of CHD recorded. The fact that there are associations between cigarette snwking and CHD in some countries and some populations but not in others, does not lend support to the charge that smoking is one of the principle contributors to heart disease. APPENDIX 2 Proponents of the causal theory of cigarette smoking and CHD have laid great stress on alleged "dose-response" relationships (that CHD rates shov a consistent rising Bradient In relation to increased amount of cigarette smoking). However, an examination of the evidence frous a number of epidemiological tudies shows that no consistent positive gradient of CHD srortality with amounts of cigarettes was found in the Dall and Hill study of British doctors (4) in the Canadian Veterans Study (5), In the Negro and White men of lower social class in the Evan. County Georgia study (6). Inversions or inconsistencies in the gradient of CND mortality and morbidity with average number of cigarettes smoked were found in the combined Albany and Framingham study (7), the Hammond Study of American men (8), in Reid and co-vorkers' migrant study (9), in the H.I.P. investigation (10), and in the U.S. National Health Survey (11). The 16-year follow-up data from the Framinghas Heart Study (12) is a very good example of this inconsistency in "dose-response" relationship. The accompanying Table 1 and Graphs A-E show that the gradient of CHD risk does not consistently rise with increased amounts of cigarette smoking. None of the five types of CHD events show a monotonic (consistent rieing)gradient, With respect to myocardial tnfarction, the pattern of trend is convex. With respect to total CHD events, angina pectoris, sudden death from CHD, and CND deaths, the patterns are concave. Furthermore, in a recent paper from the Framinghaa Study (13), it has been confirmed that there in no distinct dose-response relation with lnereasing amounts of cigarette smoking over an 1S-vear surveillance period. This evidence from "dose-response" relationships raises serious questions as to any causal relationship between cigarette smoking and heart disease. 81 Seltzer-Appendix Page 2 APPENDIX 3 Proponents of the causal theory of cigarette smoking and CHD have laid stress on ofof cigarette snoking. thevever allegeno d associ association betweas enndb CHD ratesetweenanddurationdurationcigarette Ho , ation v fou amoking and risk of ayocardial infarctioo in the U.S. Public Health Service's combined Albany and Framinghaa Heart studies (7). In the Canadian veteran study (5), no consistent gradient occurred for rise In CUD mortality with increasing years of cigarette smoking. In Kahn's analysis of data for porn's U.S, veterans (14) there was also no significant relationship between duration of cigarette smoking and risk of death from CHD. The absence of association between duration of cigaretta smoking and increased CHD rate, in these studies, raises serious questions as to the role of cigarette smaking and heart disease. APPENDIx.4_ No acknowledgement is made by the HCAg of the evidsnce that continued cigaretta smoking In the elderly (ages 65 and over) shows essentially no greater risk developing CHD than elderly vho quit smoking. Yet, a secular analysis of trends for elderly gritish doctor. (15) showed that despite a 33Z decline in elderly cigarette smokers froo 1953 to 1966, the CHD rates for these doctors increased by 19% over the sa.e period. Furthermore, in a cohort investigation of cigarette smoking and CHD In the elderly (ages 65-84), (based on the data from Doll and Hill's British doctors, Haaasond's etudy of American men and women, Kahn's analysis of the Dorn U.S. Veterans data, and that of the Framinghao Heart Study), the results showed the risks of CHD death and disability were essentially similar in elderly people regardless of whether they ~ continued to smoke cigarettes or stopped smoking cigarettes (16). This finding is very important since CHD In the elderly comprise fully two-thirds of the CHD deaths in the general population. , In a recent publication, the Pra.inghaa Heart Study (17) concurs with ap conclusion in the following statement: "., those aged over 65 derived no benefit from giving up emoking. The latter finding, while based on limited experience, is consistent with the previous Framingham observation that the impact of cigarette smoking on C,H.D. incidence diminishes progressively with advancing age and becooues virtually non-existent beyond 65." (17) Recently, the British Medical Journal acknowledged the absence of risk in the elderly. (47). The above information, by eliminating from risk the major eegaent of the population who develop CHD, does not tend support to tha claim that smoking has a severe lmpact on cardiovascular dieease. APPiNDIX 5 Mother type of evidence coazoonly cited in support of the causal theory of cigaretrisente smoking andconcoaitantlyCHDwiisththeseculallaegationreases have CHD ino thatinsecularciga(rettecalendrical)ptconsunm ion. rates of However, r an examination of pertinent data from the World Health Oraanizaci,,,, r.... .~- -- --- 955 to 1967 s,,. .....--_, _ -,,eu. showei'c no consistent parallel secular changes In cigarette consumption with coronary heart diaeaee mortality (18). The converse, reduction of cigarette consumption with parallel reduction In CHD was not found in Doll and Hill's British doctors, either In the elderly or for all ages. A 50% reduction in cigarette consumption by Rritieh doctors, ages 35-84, from 1951 to 1966 (a 15 year period), shoved no change In yearly death rates for these sa®e British doctors over the same period (19). (See Graph F.) TIMN 450224

94 Dr. Carl C. seltsar 1950-19K 1957-1971 Board of Freshman Advisors Research Associata page 2 Harvard University Adolescent Unit Children's Hospital Boston, Massachusetts Jan. 1963-196g Research Associate physical Anthropology pallov, Counctl of Epidemiology Consultant Department of Nutrition Harvard School of Public Health American Heart Aasociation Veterans Administration, Boston outpatient Cllnic Senior Research Associate Department of Nutrition in giological Anthropology Harvard School of Public Health "phydcal Characteriattcs of the Yaqui Indians", Texas technoloStcal Collep gullatle, Vol. XII, No. 1, January, 1936 "A Critique of the Coefficient of Racial Likenaes", Ms. J. Phys. Anthropology, 23:July-Sept., t937, p. 101 "The Anthropoestry of the Western and Copper Eski.os, Based on Data of VilhJal.ur Stefan,son", Human Bio1., 5:S.pt. 1933, p. 313 "7ha Jw - Wis Racial Status" - "An Anthropological Appraiaal", Harvard Medical Alusnt gulletin, April 1939, p. 1 "The Racial Charactaristics of Syrians and Arncnians", Papers of the Peabody Nuaeum of Asrican Archeology and Ethnology. Harvard University, XLI, 1936. 77 "Contributtons to the Racial Anthropology of the Near Eaat", Papers of the Peabody Museu., XVI, 1940, 39 "The 'Masculine' Co.poaent and Physical Fitnass", AM. J. of Physical Anthropology, N.g. 1: March 1943, p. 95 "Anthroportry and Arthritia: I. Differences between Rheumatoid and Degenerative Joint Diseasn: iWlu" Medicine, 22: May 1943, p. 163 II. Differences Betwen Rheumatoid and Degenerative Joint Diseues: Fwlee, Medicine 22: N.y 1943, 189 "fhe Value of the SFwuldar-Htp Ratio as an Index of Masculintty and its Relation to Dynamic Physicd pitneu", Revue Canadianne de Biologie, 2: August, 1943, 329 95 Dr. Carl C. Seltzer "Selection of Officer Candidate: , Harvard University Press, 1943 "Anthropometric Characteristics and Physical Fitnesa", Research Quarterly, March, 1946 ' "Racial Prehistory in the Southwest and the Hawikuh Zunis", Papers of the Peabody Museum, XXIII, 1944, 33 "The Relationship Between the Masculine Component and Personality", American J. Phys. Anthropology, N.S. 3:ltrcch 1945, p. 33 "Body Disproportion and DominAnt Personality Traits", Phychomattc Medicine, VIII, March-April 1946, p. 75 "Somatotypes of an Adolescent Group", Am. J. Phys. Anthropology, N.S. 4:June 1946, 153 "Academic Success in College and Public and Private School Students: Freshaun Year at Harvard", The Journal of Psychology, 25:1948, p. 419 "Phenotype Patterns of Racial Reference and Outstanding Personality 7raits", J. Genetic Psychology, 72:1948, p. 221 "A Comparative Study of the Morphological Characteristics of Deliquents and Non-Deliquenta", Unraveling Juvenile Ileltquency, Clueck and Glueck, 1950 "A Relationship Between Sheldonian Somatotype and Psychotype", J. Personality, 16:1948 Page 3 "Constltutional Aspects of Juvenile Deliquency", Cold Spring Harbor Symposia on Quantitative Biology, XV: 1951, 361 "Body Disproportions and Personality Ratings in a Croup of Adoleacent Males", Growth, XXIII, 1959, p. I "Maturlty Ratings and the Prediction of Height of Short 14-year old Boys", Pediatrlcs, 1961 (Gallagher, Roswell, and Seltzer) "Skeletal Age, Chronological Age and Maturity Ratings in a Group of Adolescents", 1961 (Gallagher, Roswell and Seltzer) "Masculinity and Smoking", Science, 130: No. 3390, 1959, p. 1706 "Some Harvard Men and the Smoking Habit", Harvard Alumni Bulletin, February 4, 1961 "Why People Smoke", Atlantic Monthly, July 1962 "Morphological Constitution and Smoking", J. Am. Medical Assoc., 183:639-645, 1963 "Changes in Specific Gravity and Body Fat in Overveight Female Adolescents as a Result of Weight Reduction", Ann. N.Y. Acad. Sci. 110:913, 1963 (Coldman, Bullen and Seltzer) TIM-N 450231

132 S'I'Al l:' --'I• UI' UIL C. 11. ll l ta: 1.11 -,. U.. IS;n: , 1 n•n ("I inic.:l I'iof: ssor cy; I7:. •o: ralogY •''nd 1'revcntivo I9ccliciuc• in Lhr :chool o[ P':.dicinc, U,lic..lr•;t,• of California, San Fr.oncisco Mcclical Cenl,er. I have bcc•:I a staff mcl.^.bcr at thaL ins!n i Luti-on for the past ti-•cnty years, during which time I have engaged in teaching and research in my area!l of specialty. I am Doard-yualificd in Preventive Medicine and Toxicology. I am the Program Director of a training grant in Toxicology sponsored by the U. S. Public Health Service and have predoctorate and post-doctorate students under my direction. I teach in the Schools of Medicine and Pharmacy. In addition, I am Consultant in the areas of Pharmacology, Toxicology, Occupational Medicine and Environmental Health to a number of industrial concerns and to several State and Federal agencies. I have published over 150 papers in the fields of pharmacology, toxicology and environmental health, and have been a member of the various scientific societies organized for the promotion of scientific endeavors in the fields of pharmacology, toxicology and environmental health. I am a Fellow of the American Academy of Occupational Medicine and of the Industrial Medical Association, as well as holding membership in 15 olh^r scientific and professional societies, and an Consultant to the California State Department of Public Health in the area of Tnxicology. I am a former member of the National Research Cocuicil's Cotvnittce on Toxicoloyy. 133 J n 1969 1)n':l:.r_ nL: d:I : C•1•raaLLcc oa )n[er:;t;lt<• ond Forr_icln Co:t:n;:rc•:: of Llr• Ihu::•: af lbt•: ::~utati~cs i.n clarificaLion of the bacl-yround for proposcd lcgiclaL-ion on Cigarette 1.abe.ling and Advertising. I should .lilcc to repeat two brief portions of that statement at this time: 1. "it has not been established that the tar and nicotine yield of cigarettes is related to human health. No safe level has even been claimed to be established by those who say there is a relationship."• 2. "The majority of the publications on smoking and health have failed to indicate the extent to which smoking is beneficial. There is no question but that a great deal of pleasure, and certainly much tranquility, is obtained from the smoking of tobacco." At this time I should like to present a further sta4- ment addressed to Senate Bill 1454 and com-nent on the 1972 report of the Department of Health, Education and Welfare entitled "The Hr•alth Consequences of Smoking". in reviewing portions of the Report, one•must conclude iliat ccrt.iin vlisconceptions or unproven th3ories are presented ati f,^,clu 11 data. These bi.ases niight lend support to Senate Bill wiiic, •, ca f:.o elmene. L,le F'cr:ara: C'.garettc L.;b ling and P.dvcrtiFtin? Act Lo require thc Federal Trr.ae ComTis.^.ien to T'ITVIN 450250

96 Dr. Carl C. Seltzer Page 4 "Serm Iron and Iron-Binding Capacity in Adolescents. I. Standard Values", Aa. j. Clin. Nutr. 13:343, 1963, (Seltzer, Wenzel and Mayer) "Serm Iron and Iron-Binding Capacity in Adolescents, II. Comparison of Obese and Non-Obese Subjects, Am. J. Clin. Nutr. 13:354, 1963, (Seltzer and Mayer) "Occupation and Smoking in College Graduates", J. Appl. Psychol. 48:1-6, 1964 "Morphological Constitution of Smokers", Special Report prepared by the Surgeon General's Advisory Comnittee on Smoking and Health. U.S. Dept. Health, Educ. and Welfare. Public Health Service Publication No. 1103, 1964 "Rody Build and Obesity - Who are the Obese", J.A.M.A., 189,677, 1964, (Seltzer and Mayer) "Tha Importance of Body Characteristics in the Excretion of 17 Ketosteroids and 17 Ketogenic Steroids in Obeaity", N. E. J. Med., 271:651-656, 1964, (Jacobson, Seltzer, Bondy and Mayer) "The Triceps Skinfold a a Predictive Measure of Body Density and Body Fat in Obese Adolescent Girls". Pediatrics, 36:212-218, 1965, (Seltzer, Coldnan and Mayer) "Constitutional Aspects of Smoking and Lung Cancer". "Psychosomatic Aspects of Neoplastic Disease". Pitman Medical Publishing Co., Ltd. 1964. (The Proceedings of the Third International Conference of the International Psychosomatic Cancer Study Group held at Nevnhao College, Cambridge, England.) pp. 138-151 "Standards of Obesity". Section for Obesity Manual. Division of Chronic Diseases, Bureau of State Services, U. S. Public Health Service, Washington, D. C. (1965) "Hunger and Satiety Sensations in Men, Women, Boys and Girls: A Preliminary Report." Annals of the New York Academy of Sciences. (Monello, Seltzer and Mayer), 131:593, 1965 "A Review of„Cenetic and Constitutional Factors in Human Obesity." Annals of the New York Aced. Scl., 134:688-695, 1966 "Hunger and Satiety Sensations in Man", Postgraduate Medicine, 37, A-96-100, 1965 (Mayer, Monello and Seltzer) "A Simple Criterion of Obesity Based on Triceps Skinfold Thickness", Postgraduate Medicine, 38:A-101-107, 1965 (Seltzer and Mayer) "Limitations of Height-Wetght Standards", New Eng. J. Med., 272:1132, 1965 "Appraisal of Nutrition" (Editorial), The New Eng. J. Med., 272:1129, 1965 "Some Re-evaluations of Build and Blood Pressure Study, 1959 - Ponderal Index, Somatotype, and Mortality", Nev F.ng. J. Ned., 274:254-259, 1966 97 Dr. Carl Seltzer Page 5 "Constitution and Heredity in Relation to Tobacco Smoking", Ann. N. Y. Acad. Science, 142:322-330, 1967 "Standards of Obesity", Section for Obesity Manual, Division of Chronic Diseases, Bureau of State Services, U. S. Public Health Service, Pub. Health Service Publication No. 1485, 1966 "Tobacco Smoke as a Possible Mutagen Affecting the X-Chrosaososr: Parental Smoking and Sex of Children", Am. J. Epidemiology 83:530-536, 1966 "Body Measurements in Relation to Diseasa•", Part I and Part II. Postgraduate Medicine 40:A107-A111, A145-A151, 1966 "Now Representative Are the Weights of Insured Men and Wonien7:. JAM 201:221-224, 1967 "Genetic and Anthropological Factors in Obesity", Modern Treatment, pp. 16-30, Vol. 4, No. 6, Hoebner & Co. 1967 ' "Greater Reliability of the Triceps, Skinfold over the Subscapulsr Skinfold as an Index of Obesity'", Am. J. Clinical Nutrition. 20:950-953, 1967 "An Evaluation of the Effect of Smoking on Coronary Heart Disease", JAMA 203:193-200, 1968 "Morphological Constitution and Smoking. A Further Validation", Archives of Environmental Health, 17:143-147, 1968 "Genetics and Obesity'", In Physiopathology of Adipose Tissue. Edited by J. Vague. Excerpts Medica Foundation, Amsterdam 1969, pp. 325-336, "Thromboembolic Disorders and Oral Contraceptives - An Editorial Viewpoint", JAM 207:1152 (Beb 10) 1969 "Adolescent Attitudes Toward Weight and Appearance", (Dvyer, Feldemen, Seltzer and Mayer) J. Nutritional Education 1:14-19, 1969 "Overweight and Obesity - The Associated Cardiovascular Risk", Minnesota Medicine 52:1265-1270, (Aug) 1969 "Body Build (Somatotype) Distinctiveness in Obese Women", J. Am. Dietetic Asa. 55:454-458 (Nov) 1969 "The Effect of Cigarette Smoking on Coronary Heart Disease - W'here Do We Nov Stand?", Arch. Environmental Health, 20:418-423, 1970 "An Effective Weight-Control Program in a Public School System", Am. J. Pub. Hlth. 60:679-689, 1970 "Reliability of Relative 8ody Weight as a Criterion of Obesity", Am. J. Epid. 92:339-350, 1970 "Cigarettes and Heart Disease", N. E. J. Med. (letter) 284:557-558, 1971 TIIVIN 450232

0 134 :ldlol'y •....... 1.:- 5lr1 lr.. Ic. c• Lu-" :utd nic:oL'inc, qhc 1972 Report spnaks of three caLegori.es of compounds in cig.rrettc suoke, those "judged rost likely to contribute to ih~ hcalth hazards of smoking," those "judged as probable con- triLutors to the health hazards of smoking" and those "judged as suspected contributors to the health hazards of srnoking." The descriptions quoted avoid characterizing any compounds as "known contributors". This confirms that even after years and years of intensive research, no co:apound, as found in cigarette smoke, has been established as a health hazard. Tar, nicotine and carbon monoxide are the compounds "judged most likely to contribute to the health hazard of smoking." If the evidence for such a "judgment" is inadequate with ~ respect to these three compounds, then the judgments on compounds / in the other two categories are obviously unjustified. NICOTIi:1; The Surgeon General's Report of 1964 on Smoking and Health nnI nnl~ ;;+.led to conEi rn older sucpicions that nicotine m:g!-.t be "I i" fcw a s:~o):nr httC c-;;presrly exonerated it as any significant 135 KicoLino. wr•u; firsL iu ]tt3ii aw] hi:: buen a eubjecL of much ruz;earch saur.: thcn_ ]t:a: biological action is ::Cill be,ing invcsl i.g:cted in a ncc-bcr of laboratories throug?:out- the world. Nicotine possesses an unusual biphasic capacity having both stimwl.ating and tranquilizing characteristics dc•panding on the site of action and the amount administered and the psychic state of the subject at the time. As regards the central nervous system, nicotine acts as a stimulant, particularly on the respiratory centers, the vasomotor centers, and the central chemoreceptor site. Under certain conditions it has the ability to sedate the reaction of these centers. The cardiovascular responses to nicotine can be characterized as mildly $timulating resulting in a modest pulse pressure elevation, a slight.increase in coronary arterial flow, and a somewhat decreased akin vascular flow. These responses are of limited duration in time and to the extent that they can be activated by the nicotine in cigarette rmoke, last only for a moment. The action on the gastrointestinal system of a novice smoker.may be such as to result.in temporary nausea. The fact that this reaction is encountered only in the novice smoker shows how quickly the body adjusts'to nicotine. The absorption of nicotine is excellent over a number of routes, such as the skin, respiratory system and the qastrointcst;r,a1 trc•ct. It is rapidly degradod'i.n the liver, kidnr--y and lungs and c>:creted in the urine as cotinine. Its removal from the body i.s TIMN 450251 1

+ 136 v,. ; far•t v!.1 l: :cca iil:we at nn rat.c a•lr:u larger zu,,: nnts nle ubnorbad. A11 of the pharmacologic effects from smolcing are due to the active alkaloid, nicotine. Due to the rapidity of ahsorption, metabolism and excretion th=se effects are transitory and can be repeated without cumu)ative effects. Tolerance to these effects develop rapidly on repeated exposures. Nicotine exerts a number of beneficial effects. Suppression of appetite gives positive effect on weight control. it may exert on one occasion a tranquilizing effect and on another a stimulating effect occurs. This transient period during which nicotine remains active in the body, coupled with its ability to be absorbed through the mucous mefibranes of the oral cavity makes it possible for a smoker . ._.I rto regulate his intake with ease. The frequency of puffs and the i duration of the period during which the smoke is retained in the oral cavity can be varied to produce a greater or lesser intake. !'h: nicotine content of a cigarette, therefore, is unlikely to prbr+e eifective as a regulator of such intake. The smoker may ci,gare'.'.es, sr:oke more of each cigarette he uses, or vaty his technique of smoking to produce whatever level he prefers. T:•3 setting of mandat.ory limits on nicotina coutc•nt based on ),!»rn[ory tests of thr~ cigarcite is likely, therefore, to be ' 1!r_t n v.in and inc•ffrctive effort. If smoko from.cigarettes is arti.ficialJ.y cbndonsed at~ extrem3ly lam temperatures under~labbratory co1iditibnd!)'the; result is doscribed as "tar"„ Occasionally polycyc2ic hydrocarbons, w*hich"dn+their pure •~ form can,be demonstrated in laboratory animals to produce cancer, 1~ can be identified in these"tars." This is not surprising„hovrover; -, since these materials can be produced by combustion of as sitople a substance as methane gas, are found in the•senoke of barbecues, and are adherent to both roasted and barbecued meats•. In fact there has been noted only a weak co-carcinogenic effect in mice which has previously been painted with the highly carcinogenic material, 3,4 beneypyrene. These reports confirmed the findings of•Passey in Great BrS.tain.:. Wynder:,found a marked . .. / difference in the percentage of animals affected by experimental cancer tests, depending on the strain used, when he tested"tara" in cigarettes from American manufacture. It is possible to pro- duce cancer of the skin in some animals with smoke condensate; however, the amount of uiLrec'', are and not comparable to whole smoke. enormous Hammond and Selilcoff recently.deQonstrated in a study oP roofers e::po;:ed on a daily basis to benzpyr.ene contents in asphalt equivalent ta that found in more than 750 cigarettes, that 1,-) increa:cd incidence of lung cancer occurred. This would seem to TIMN 450252

140 Ca1b3n mouo irlc is P-cr.cnt in :r7.1 ucb:m nLcronl,Ircres and is a no=m51 excretory product of n:;m. ','he effect of carbon monoxide arises from its property of con:bining with hemoglobin to displace oxygen and by its action on the dissociation curve of oxyhemoglobin. There are acceptable air levels of carbon monoxide recognized as being safe for continuous exposure in environmental air and for repeated interrupted exposures in the work environment. Repeated exposures to low levels of carbon monoxide have little or no effect and the physiologic changes accompanying high exposures do not occur. Any discussion involving man and carbon monoxide must consider the findings of Sievers et al. This study includes n great number of persons repeatedly exposed over a consideyable length of time to relatively high concentrations of carbon monoxide. The subjects were a group of 156 Holland Tunnel traffic officers. Over the 13 years in this en,,ironrer•.t, the average carbon monoxide level was 70 ppm giving rise to levels of carboxyhemoglobin of as great as 10% with an occasional peak to 200 and 300 ppm. These men shomed no evidence of injury to their health as monitored by bloa9 a.nd urine studics. EIiG recordings. blond prr,-:„ro n~nts and neurological exa^rinatior.s. Using pistol marksmanship r,^ a means Lo determine neurolo.ryical integrity, a high degree of p-•t'ormance was maintaincd by thcaa mcn. 141 O:.i:: cn11_:e ~~[x•uliun to tbc ace:.I±•: which oc•curo; in Im::nns, sho::i.nj that n•crr vor.S-i.ng iu for r.xaeu:,tc, expcricuce no discomfort from levclo of carbon monoxido which will cause in a visito'r unaccustomed to the::e levcl•^., dizziness ar•d headache. In addition, Dinman has shown the presence of higher levels of 2,3,Diphosphoglycerate in smokers. He has suggested that this substance reverses the inhibitory effect of carbon monoxide on the ability of the.blood to release oxygen to the tissues. Whether 2,3,Diphosphoglycerate establishes a complete I reversal of the inhibition of oxygen release by the cells is not known at this time. The mechanism is established, and effects of its operation are known. the beneficial The carbon monoxide content of cigarette smoke has been .. d expressed by some authorities as equalling 475 parts per million by volume. Any contrast with the Maximum Allowable Concentration of 50 ppm for industrial exposure is, of course, inapplicable. t_,C's are established on the basis of every inhalation during an eight-hour period. The cigarette smoker does not begin to ::ens::cr :~as po:.n+:ec. out, the puff from a cic;arcLt.e (35 r:a) is greatly di.lutcd in inhalation. One puff . i ;:a r: is rer3: rcicd ,•:: st.•nd¢u:d sma7:ing pre_cr';are, leaving th_ re- r-;i.;ir.g inhal.aLio!es fren of smokir;g. There t!re substantial pz.riods TIMN 450254

38 pap 5 83. N. ® Stimulatton of aortlc body chsmorscsptors by pnallon stimulsnts. M. Patma and D. M. Avtado. Arch. Int. Pharmacodvo. 140: 269-2m0. 1962. Phartcacolojlc.l studies of hoam.thylono-bis-urbaminoyicholioa (imbratil) on the cardiovascular and rospiratory systems in dog.. S. Saito and D. M. Avisdo. Sap. Circ, J. 27:791-796, 1962.. lmflusnco of brotylium oa sasponsas of the h.art-lung proparatton: DMPP and partial occluslon of tha pulmonary artary. ft. Castro da In Mata, P. Aramandia, J. Martlnas do Lstoaa and D. ai. A-do. J. Pharvwcol. Exp. Th.r. 135: 156-163. 1962. pan 6 10). Cardiopulenooary alTocts of Slycsryl trlnitrat* and tso.orbtds dtoltrat.. D. M. Avlado, L. B. Folls, aad S. Ballet. Cardloloria 52: 2A7-303, 1968. 102. 103. 104. f6. $ovorsal of aympatbomimatic broachodllatation by dtchlorotaoprotaranol. &. Gstro ds 14 Mat., M. Poaaa aod D. M. Avlado. J. Pharmacol. ESm. Thar. 135: 197-203, 1962. {7. Aospoaaaa of tho bronchlal veins ia a hsart-lung bronchisl praparatton. P. Aramsadta, J. tdartiasa 1. da Iwtoaa aod D. M. Avlado. pra Ros. 10: 3-10, 196Z. t<I. Factora tatlusocl®j pulmonary bypsrtanslva rosponso to S-hydrosytryptamisa. J. DotaD - aM D.16. A.fado. . Aas.. 1Ir.466-473, .1962. W~ Lsehanp of blood batwaoo the pulmooary and sy.tamic circulattoas via braacloptdmemary assstomosas: pulmooary arterial llptlon, ambollsattos aad tnbalation of bst. P. Aramsadia, . J..idsttiJs L. d.'l..tootaod D.M. Avtado. Circ.-Aos;:lt-y,}7Q~079. 1962....~ 90, EIlacts of byparcapols on the vascular rasistance of tbo dod'a hiad limb. J. Ltwitb A. H. DIl and D, M. Adado. Pflucar Arch. 277: 3t7-396, 1963. 1V, o.i.f t t.sstl[sttooa aw Carttoactlva Dru[s - 91, Machantsm (os bradycardta aristnd from stlmulatlon ot carotid bodiaa.-.IC 6alqm, 14. P.noa a.d IL M. Avlada. Arcb. Int. Pharmacodrn. 150: 249-25t, 1964. 02, MacLalsm for cardiac stlmulatloo dnrins anozamla In the modiBlad h.art-luas proparattona. L. IL Doms, M. Psaaa and D. M, Aviado. PAurar Arch. 282: 209-224, 1965. 93. Cardlovascular sllada of anosia and the tnflwnco ot a sar bata adronordle racsptor blookim0 drug. L. 8 FoDa and D. M. Av/ado. J. Pharrttacol. lS.p. TMs. 149: 79-90, 1965. !4. Myocardlal mWbollc changes during acute hemorrhage. T. W. tbo, D. M. A.fado and 6. Dallat Am[toleay 16: SSi-537, 1965. - 95. 96. 97. q{. 99. 105. 39 Coroaary vasodilators oa myocardial oxyssn con.umptlon and ammonla productioa. D. M. Avladc, Ii. Ito, Y. W. tho and S. IIaDot. Cardtoloala 53: 27-46, 1960. Dronchopukopaary a/tscta of psntasrythrityl tatramitrate and isoprot.rsnol. D. M. Aviado, T. tllshimoto, and H.J. blosid(n,2ar, J. Pharmacol. Fom. Thsr. 165: 274-2d5, 1969. Stitnulattoa oI adrsaar{ic beta receptors by halothan* and Its antagonism by two now drugs. A. M. tCltd6 ld. Ponoa. and D. M. Aviado. Aaosth. Anala. 48: 5tf-65, 1949. CComparative aftacta of di4ortm and proscillartdia la.tba hMrt.lmy propaat)oia, lt. Pto, ' Y.M. Cho, ad D.al. Aviado. D1s. Choat. 56: 37-42, 1969. ' - 106. • Pharmacology of a s.o antiardln.l drud: pazk.alDna. 1. Coronary clrcclqtlam aad myourdfal 107. mofabolism. Y, 7I. Cho, 1& DolaJ and D. M. AMado. Cbast. 58: 577-5t/1, 1970. Pbarmacoloqy od a aow aallau{Wi dru4: pack.allln.. II. ~C:at Fat~ aad traa.m.mbz.a.`. ppt.aWl of mtdlac tLaaa. f. 11at.vo. Y, 71, Cho aad D, N: Avlalo. Chaat St: 6t1-SIS,•' 1970. Fttasaaoology a/ a aaw aatlaa,{frl drug: psrhadllaa. lII. Eroachopulnsoaary syatsm in tha dos aad bum.a.. O. Faiaa/lv.r, Y.O. t'aw sad D. M. Adado. Gtast, S0: S5/-561, 1970. 7Ytacts of ospradlol os coroaary dreulatton.ad eardtac mataboltsm. J. Drlmal tod D.at. Avlado. JT,a,PharmacoL D®. Thsr. 176: 312-319, 1Y/1. Cardiac afGcts o! sodlum sal.nlta. D. M. Aviado, J. Drlawl, T. Matanabs and P. M. Llsb. Grdiologll' (In proa). ~ ' Pharmacology of aaw .asoduator drugs. D.M. Avlado. Procaodlnp of Phrstolottcal Eoclaty of PhDaddphfa. (ia praas). Comparatlva hs_modyoamlc sffocts of papavarlns and catlodll. J. Slmaaa and D.M. Avlsdo. Pharenacol. F.xp. Thar. (3ubmittad). Csrdtotosictty ot sol..ats. D. ).t. Aviado. To:icoloay. (Submittad). V. Origlad lavsstlaaticos oa Droochodtlators and Aatlastbnutico Qtudtaa o/ myacardlal oaidativa .oaymss during hiatamfalc shock. Y. W. fh., J. ThsopraJ, M. Avlado.ad S. D.Dat. Arch. lat. Ptrarmacod.nt. 1S.: 314-323, 1965. D 114. . Tha myoeardial aucclao-mddaso ani myoslo adonosina trlphoapbatass actlvlts after coro.ary . arterial tnAtsloo of hlstamina (n doss. Y. W. Gho, L. Dpast sad D. M. Av4do. Arch Ist. 115, • Pharmacodra. 161: 167-173. 1966. ' The cpFdlopulmomr7 affscts of qsdaldlaa amd psocqlnamido. 1. E. Follo a.A D. M. A.isdo.. L Phasmaeolh..+ 116: Tha wrdlopnl.nonary dtacts ol a quin.aollns (MJ 191+0): Cardlac stimulamt, pulmorry vaaodWto aad bsoachodtlator. D. M. Aviado, I. 8. Follo and J. Plsaoty. J Pharrnacol. Eav. Thsr. 117r 1SS: 76-63, 1967. - , The lafla.mca of a nosr adronsrgle bota receptor (MJ 1999) blocldng drug on tAa pulmoasry dreulation. D.14 Adado, 1. 1` Folis and J. Plsaaty. Arcl. Int. Pharrnacod9n. 160: 323- lU: $38, 1967. Droochopulmoaary effects of dtgitalis in the anesthetized dog. V. Marco, C. D. Park aat 119. D. M. Aviado. Dls. Chsst 54: 437-444, 19611. 120. lil. Sroadtodllatatioa by a watsr-solubla dorivNlvs of thsobromLts administratlom by various rout.a. D.t1. A.LdaandV.A. Patd. Arch, tat. Pharmaoodraa lSO: 336-347, 1964. Iatorralationshtps bshraan pulmoaary blood flow and broochanotor tooa: PDa aad PCpr a[. damaaak aad D. M. Avtads. J Appi. Physlol, 22: 719-730, 1967. . Macbanism for the raductlon In pulntonary rosisdnca inducad by halotbaaa. A. M. lUida 1 and D.T,1. Avlado. J. Phataucol. Exp. Thor. 158: 2ta-35, 1967. Pharaucolo{ta potsney aaid s..lsctlMity ol1 a aav broocho4'i4'rtor a Jant: sotorsno , i,. N:. Y. w. Daapa, Y. M. cko, A. W. Gomoll, D. M. Aaado and P. M. Idsb. J. Ph.roucol. t 7Sm. Thsr. 144: 290-301, 1968. . . ' ttlfucy of a naw bronchodWtor, sotsronol, aa ospsrimmtal lockod-luns syodroms In dogs. Y.7l. Qo, D.M. Adado and P.M. Lish. J. All.ry. 42: 36-45, 1965. . DronchadRator actlon of p.ataorythrltyl tatranltrata in o:parintontal pulmonary omboltsm, D. M. Avlado, M. Saaasnak, F. Palscak aod S. Hdlot. Cardtolorta 52: 340 -361, 19611. Mechanisms for the bronchodtlator .ffocts of corticostorotds In ths ssa.tti.ad rabbit. 1. R Clrrlllo, and D. M. Aviado. J. Pharmacol. Esp. Thor. 164: 30Z-311, 1968. - D.onchopulmooary and cardiac effects of hydrocort(sona. M. Oskoui and D, M. Adado. Arch. Int. Pharmacodyn. 179: 314-325, 1969. TIMN 450203

154 155 i I -3- 5. How accustomed the person is to smoking. 6. The chemical content of the tobacco smoke. 7. The moisture content of the tobacco smoke. 8. The characteristics of the tobacco. 9. The use of a filter. 10. The acidity of the tobacco smoke. 11. The agglomeration of smoke particles. 12. The amount of moisture over which the smoke travels. All these variables must be carefully studied and held constant before a scientist can accurately predict absorption. No one has ldentified disease-producing components in tobacco smoke In significant amounts or forms available to the human body. "Tar" is something produced in a laboratory and not something In cigarette amoke to which humans are exposed. Human beings do not smoke "tai"and laboratory reports on "tar" yields have not been established as significant to human health. A great deal of data Is available concerning the acute cardiovascular ef- fects of nicotine In man. For example, nicotine can cause liberation of catecholamines from the adrenal gland. There are many other actions known, which I need not detail here. However, the net results are transient, non-cumulative and reversible increases in heart rate, cardiac output, etc. The Surgeon General's Advisory Committee, in its 1964 report, reviewed and analyzed the large body of data then ava.ilable on nicotine and concluded that nicotine did not represent a significant health hazard. Since this report, there are still no data which would allow a person to draw any other conclusion regard- Ing the health effects of nicotine on smokers. - Some people assume that any dose of nicotine is bad--this is scien- tifically not true. Many common household materials are harmful in large doses but quite acceptable and perhaps even necessary in small doses; for example, table salt in large amounts can be harmful but in small amounts is acceptable by almost every person. However, ordinary doses of salt may be harmful to certain people, such as those with heart failure of hypertension. But this is a problem of an (ndividual patient which must be determined by the physician for each patient and no general rules can be made. Although there have been many reports dealing with cigarette "tar" and nicotine since 1972, there are no new data which would justify a change in my then stated conclusion that no ingredient or group of ingredients as found in tobacco smoke have been established as disease producing in smokers. In fact, one such report showed that nicotine failed to influence the severity, histopatholgic, ultra- i:'.,r:c'ni.s:oc"iem.ca:. or ang.ograp:'I lc :~ea:ures o:: aorCas anc coronary arteries or serum lipids of otherwise untreated rabbits, as well as rabbits subjected to such derterminanls of atherosclerosis as hypercholesterolemia or hypertension or both. Accordingly, as I stated in 1972 and continue to believe, I cannot tell the signiH- rTWlN' 450261

120 kind of testing that. is necessar;y in ternrs of a wide variety of clifferent inclustries on occupational ancl health safety. So I want you to know we are taking that responsibility serirnrsly as we1l. tienator Fcncn. I have a copy of that-article and would ask it be made ir part of the record. Senator Kr:NN>:uY. Fine. It will hc so done. tienator Fcruu. In the January 26 issue of Newsweek on page 6:i, we find an interesting chart entitled "('ancer and the Environment: 'Ten Top Suspects." I sulrmit. a copy for the record and ask that. it- he made a part of my renrark5. Amon~ the suspects IiGtecl are arsenic, found in mining ancl smelting industries; asbestos, fronr hreaklinings, construc- t ion sites, and insrilatron ; and other snhstances- from almost every type of industry and segment of our environment. Senator Kz;NNr;nt. It will be made a part of the record. Senator Fortu. The Newsweek extract lists the 10 top suspected sources of cancer and I see no effort to require the other 9 t.o share in the cost, of health researrh. This bill has singled out the tobacco indus- t ry as t hongh it. is the only one suspect. and proposes to impose punitive taxes to cover research on all suspected causes. I am extremely concerned about. the health hazards and the need for research to find ways to prevent. ca,ncer, and in fact, all dreadful clisease. I am concerned about. the effects that tobacco may have on hea.)th. I support. t.he est.ablishment. of the Tobacco and Il[ealt.h Re- search Institute at. the. TTniversit.y of Kea~t.ucky to shudy the effects tobac.co has on health to det.errnine the. impurities and to find ways to remove t hem. I recognize and support this effort, and I find no justifi'ca- t ion to support. a tax based upon tat• and nicotine content in cigarettes. AIr. ('hairman, I recof;nize that I do not have a scientific back- ground. I posed this question to three imminent scientists and asked thenr their opinion abontt it. The scientists are: I)r. Charles II. Iiine, Ilro Iline Laboratories, Inc., San Francisco, ('alif.; I)r. Robert C. l Iockett, re5e:irch director, the Council for Tobacco Research-i?.S.A., Inc•., New York; and I)r. Ronald Ukun, director of clinical pharma- c•crlogy, Cedars-Sinai Medical (.'enter,l.)s Angeles, Calif. Senator Kr:NNr;uY.'I'hey will be made a part. of the record. Senator Fcnrn. I will nol bother the members by reading their st.ate- ments, bnt. each of them indicates that in his opinion, no scientific basis exists to levy a tax based on tar ancL nrcotine in cigarecires. _ wi-~~. as ~c permission to I>lace their responses, qualifications, and list of publica- tions in the record. None of them support. such an approach. I have tried to he objective in my evaluat.ion and I find no justification from eit her an economic or scient.ific standpoint. Senator KF.\iNF,n}-, Fine. They will be made a partt of this record. Senator Fot;u. Mr. Chairman, I ask the members in their delibera- tions to consider the many dollars thatt are now spent on research, the precedent. that, this bill sets, and the detrimental effect that a tax of this ma-nitude will have on millions of small farmers whose liveli- hoods clepend on tobacco. A1r. Chairman, I thank you for the opportunity t.o speak here and i f you have any questions I will try to answer them. Senator KENNEDY. You c.an help us in these areas, where serious efforts are being nunde in the universtties and centers of research. I for one would welcome any kind of proposal that you could make or others 121 would make to see if we can allocate some of t.hese resources back into t.hose arras, as a source of funding. There may be some efforts that can be made in t.hose areas. I certainly would welcome it. Maybe it is pos- sible and ma,ybe it i, not.. It is just off the top of my head. As I said we wonld be glacl to work with you. Senator FoRD. Senator, if you want to eliminate tar and nicotine and if you want to really find impurities, be positive. There is a prob- lem and right now we have many varying views as to tobacco. We need the research centers to deal directly with the plant. and its genetics and pesticides, insecticides, plant hormone, and even housing of tobacco and curing of tobacco. We are in need of research in that area. So, Mr. Chairman, I feel strongly about it because the people who are trying their best to make a living stay on small farms, are willing to spend millions of their own money in order to define the impurities and find ways to remove them (stay in business) and we seem to be here today directing ourselves toward the elimination of small farmers. Senator KFN*rr:nY. As I understand fi•om the Department of Agri- culture there are a number of farms producing tobacco in Kentucky, 135,000. Senator FoRn. It is 164,000 farms plus. And I think you take a figure of four times t.hat gives approximately 654,000 people alone involved in tobacco for making a living. Senator Kr:NNruv. The fignre of 100,0~00 I used was industry work- ers. I was not clear on that. The 1t>O,000 figure as I understand was industry workers approximately 100,000. Senator Forcn. If there is fir0,t)0t) people involved in Kentucky I woulcl believe that, 1Ot),I)00 figure would be somewhat low and I woulcl like to have an opportrurity to clo some research. Senator Kr1NNEm-. Ia'ine.We can ameml it. rThe prepared statenrent, of Senator Ford and other material referred to follows:] TIMN 450244

152 W , CEDARS-SINAI MEDICAL CENTER t"jV w. Ya.w J1nr Nnu++r DMI+leA L .M..+a. crifo.M. ~r February 17, 1974 SSenator Wendell H. Ford Room 2104 Dirksen Senate Office Building Waehln`ton, D. C., 20510 STATEMENT OF DR. RONALD OKUN Dear Senator Ford, I am Ronald Okun, M, D., Aesociate Professor of Medicine and Medical Pharma- , colop and Therapeutica at the Unlverslqy of California, California College of Medlcine In Irvine. California. I am a`raduate of the University of Calitarnia where I received degrees of M.D., and M.B., in Pharmacology and Toxlcolop. After having completed a Fellowshtp tn Clinical Pharmacology at John Hopkins School of Medicine, I became Assistant Profeesor of Medicine and Pharmacology at University of Californfa, Loa Angeles, School of Medicine and am now Director of Clinical Pharmacology at Cedars- 61n.t Medical Center, Los An,yelee, California. I am also Past-Preeident of the American Academy of Clinical Toxicology. ..se vlLewe I express are mine derived from over 16 years of research and training H4r medical echool. Including research on effects of environmental etreae in toxi- 70-087 181 •Y\0 0\Y\OlY ,OYt\VA110 . LOO ANOfL[G. GALIFOONIA 000.0 . i[L[f-NONt f1/7/ Ott•0000 153 U -2- cology, which have convinced me that scientific research and not guess work should settle questions of physiological and medical effects of various pharmacologic agents. I am famlliar with the bill sponeored by Senators Hart and Kennedy and called the National Ilealth Research and Development Act.of 1976. This bill iadteates that "over- whelming scientific evidence exists that the harmful factors contained In cigaretts, smoke are tars and nicotine" and lt is to this statement In particular that I address the following remarks: I had the privilege of presenting my views on smoking and health to the Commerce Committee of the U.S. House of Representatives in 1969 and to the Con- sumer Subcommittee, Committee on Commerce of the U.S. Senate In 1972. On those occasions, I noted that research had not succeeded In establishing a causal relation- ship between smoking and disease. Let me again state that since 1972 no research has established a causal role for smoking In the production of disease. In 1972, I pointed out that: The rate and amount of absorption of cigarette smoke constituents from smoke probably depends unnn tho 1. The number, size and frequency of puffs. u 2. The length and time the smoke remains in contact with the mueou® membranes. 3. The acidity of the body fluids with which the smoke comes In contact. 4. The depth and degree of inhalation. TIMN 450260

146 STATS+lENT CF DR. RCBFRT C. ROCKETT I aa Robert Cased Rockett, a Ph.D. in the fields of organie chemistry and biochemistry and Research Director of The Council for Tobacoo Research-U.S.A., Inc. I have reviewed the Hart-Kennedy billl regarding the National Research and Development Act of 19'/6 and would like to offer the following comnents regarding the unfounded claims that cigarette smoking is one of the principle contributors to the high incidence of cancer and other disease; and that "overwhelming scientific evidence exists that the harmful factors contained in cigarette smoke are 'tars' and nicotine": In 1965, 1969 and 1972, I had the privilege of presenting to various Conmdtteee of Congress reviews of tobacco and health research sponeored by The Council. My statements setting forth my background and views are attached. In 1972, when the regulation of "tar" anfl nicotine levels was being proposed, I stated that I could find no convincing evidence that "tar,"* nicotine or any specific ingredient as found in cigarette smoke had been shown to play a role in producing any human disease. Consequently, there was no scientific basis upon which to establish maximua acceptable levels of "tar" or nicotine. My remarks to Congress in 1972 may be briefly aummarized as follows: The 1964 Report to the Surgeon General of the U.S. Public Health Service concluded with respect to nicotine: "The rapidity of degradation -- W.~ ~.,..~- ~....... : .,~. .._.. ,, .. -- •_ , , *The so-called "tars" are camplex mixturea of condensed smoke ingredients. "Tars" vary in composition with tobacco types and treatmente and with conditions of cambustion, ;ooli.ection and storage. Equal amounts of two different "tars" can have vastly different biological effects in animal experiments. 147 and the low mortality ratios of pipe and cigar smokers when compared with non-smokers indicate that the chronic toxicity of nicotine in quantities absorbed from smoking and other methods of tobacco use is very low and probably does not represent a significant health problem." Since 1964, no data have been published which would require a change in that position. On the contrary, studies have confiraed the conclusion that nicotine in the body ia rapidly converted into other substances of much lower pharmacological activity. It has never been scientifically established that nicotine causes or contributes to atherosclerosis or -- for that matter -- any other cardiovascular disease. Rather it ia generally recognized that many factors must be involved in determining the rate at which atherosclerosis develops and also in influencing the precipitation of acute disease evente. At least twenty such factors have been reported and same are clearl,jy of a genetic nature, while others are environmental. To date no one has been able to define scientifically the predaminant causal factors or how they interact in the production of this disease. In general, human studies on atherosclerosis still.frequentl,}• appear confusing, inconsistent and contradictory. Recently it has become possible to design more systematic and better controlled animal studies to investigate what role, if any, nicotine could play in the complex etiology of athero'sclerosis. So far, such studies have not established that nicotine can be implicated in the production of this disease. The pharmacological effects of nicotine in humans have been shown to be very transient and some are probabl,jy beneficial. While many studies have been done in this field, none have established nicotine as contributing to the causation, aggravation or precipitation of any cardiovascular disease. TIMN 450257

156 I 157 ~ -5- CURRICULUM VITAE Ronald Okun, M.D. Date of Birth : August 7, 1932 Marital Status : Wife, Katherine G. Okun - 3 children Social Security: 556-34-3175 EDUCATION cance of nlooth+e or "tar" derived from cigarette smoke on human health and cer- tenly ihero la sn ecientific basis for the claim that "tar" and nicotine have been ehown te be harmful to human smokers. University of California, Los Angeles, California University of California, San Francisco, California School of Medicine Pharmacology TRAINING 1950-1954 B. A. 1954-1958 1958 M. D. 1958 M. S. la conciuelon, although I favor financial support from the government for medi- Teaching Asslstant, University of California San Francisco, Cal(fornia Feb 1958-June 1958 cal research, in my opin(on, the discrfminatory tax by the Hart Kennedy bill is un- falr and has no scientific basis. Intern, General Medical & Surgical Hospital Veterans Administration Hospital Los Angeles, California 1958-1959 Resident, Veterans Administration Hospital Los Angeles, California 1959-1961 4 Fellow, Clinical Pharmacology, Johns Hopkins Hospital Baltimore, Maryland PRESENT APPOINTMENTS 1961-1963 Ronald Okun, M.D. Director, Clinical Pharmacology, Cedars-Sinai Medical Center Los Angeles, California Assistant Professor of Pharmacology (in Residence) University of California, Los Angeles, California July 1963-Present Sept 1963- Present Assistant Professor of Medicine University of California, Los Angeles, California Associate Professor Medicine & Medical Pharmacology & Therapeutlcs University of California, Irvine-California College of Medicine Sept 1963-June 1970 July 1970-Present Research Pharmacologist, Veterans Administration Hospital Sepulveda, Califo rnia 1964-1971 Consultant In Pharmacology State of California, Department of Public Health 1969-1971 Attending Physician In Cardiology, Veterans Administration Hospital Los Angeles, California 1969-Present TIMN 450262

40 122.• pale 7 CardtopuLrtonary affect. of noreplorpbrina snd propranolol. M- tMkoul and D.M. Avtado. Daiop. J. Pturmacol. 5: 321-327. 1969. 123. Monocrotsllne-tnduced pulmonary hypertenslon and p-cbloropbenylaLrdna (PCPA). I.. It. ~ Carrtllo,and D. M. Arlado. L.b. Ioveet. 20: 243-24m, 1969. 124. The naeal sod broachopulmonary effects of oxymstasoline and KB 227. T. Ktebtmoto and D. M. A.iado. Ann. Otot. 76: 1-10, 1969. I. Garrfllo, 125.. Eronehopulmomry and pstrolntestinal effects of lobdlne. P. J- Cambar, S. L Skare and D,M. Avtado. Arch. 1M. Pharmscodym, 177: 1-27, 1969. - . 126. Droachopulmonary effects of a reduction in oxygen cootaat of blood porfaelag the Pulntenary artery. V. Marce, C. D. Park, and D.M. A.iado. l,tSrclraNon. 26: 313-326. 1969. 127. >lroaehopulmooar7 effeets of paraqwt and sxpectorant.. P.J. Camber and D. )d. Aviada ' ' . Arch, 17t.torn. Health. 20: 4t0-494, 1970. 12s. mronrbopulmenary stfsets of eaffelne fa tbe aneetheHssd di0. N. Oskeai, 0. M. A.Gdo sad D. Dalld. Roeparattua 27: 63-73, 1970. 129. Perrmacotopy of anttaethrnatac drugs. D. M. Avfade. AtN. Aeed. Eelanae Medlelno s Chirurnte. 127: ISS-173, 1973. 130. Pharmacologle principles ln tM trsatmont of acuto reaplratory tesuffietsncy. L. V, Dalcaso, Jr. and D.M. Aviado. Semirura In Dru{ Treatment S(3): 241-24l, 1973. 131. Preclintcal and cllnlcal Inveetlptlon of drug.. I. Droncbodllaters and antlaetbmatic .., dru0s. H. Salom and D. M. Avtado. Drug Infotmation EmHet4t m: 14-19, 1974. 132. Prewatlon of acot. polmonary ioeafficisney by srlodletyol. D.M.Aviado tad 1«V. Ealeaeo, Jr. 1. Pharmscol. Exp: Thor. 1l9t 157-166, 1974. 13). Pharmacology of mobsearbe: a ae.r drug for treabnent of aeote pulmonary WufQeioney. D.M. Aviade. Circulatortri Shock. (dubmlttsd.) .. •- i InvssHnttons on Pulmonary Emoh.sema Pro[ostatlonal Steroids and Tobacco .134. Droorhopulmopary e!leets of tobacco and related eubstaneea. L Eronehoeenatrletlon and ."' broachodllatsHon: influence of lung dsner.+tton. D. M. A.lado and IH. Eamasek. Ar _ P~a.tora Hsalth al: 141-151. 1965. 135.. Dronehopulmoerry effeets of tobacco and rsLted subet.nees, D. Bronchial artsrfal tnJactleea of nicottns and hlst.ratne. M. Samanek aad D. M. A.3ado. Arc• Eavtren, Health, 11: VI. 136. .» 132. 139: 1406. 192-159. 1965. , , - .. . '` -;e Droachopulmonary ofteets of tabaeco and retatsd substances. DL Axon reDates olldtod frotn„ tho visceral pleura. M. 3amanek. D. M. A.lado and C. W. P.ektn. Arc nf.iron, Haalth, 11: 160-166. 1963. f tobacco aod rslated substanees. IV. EroncStal vaseular sod •~ t H e o ee nary e wraeckeenlmo • /a - . ....• . . . broachomotor responses: their eu{pstsd t el.enee :.uncr.or6 Arch. Eoviron. Hoalth, 11: 167-176. 1966. Cardiopulmonary effects of tobacco snd related subshncos. L The relsase of hlstamimo dnrfa{ inhalatian of d6areNe smoke and anoxemla In tha h.art-lua2 and intact dog Prsparatlon. D,ht, A.lado, M. Samsoek and L. E. Folle. Arch. L]+rlron. Hwlth. 12: 705-711, 1966. Oard(opqdmonary effscte of tobacco and related aubstancos. D. Coronary sascvlar effecN of cigarette smoka and nicotine. 1. E. Fa11o, 1.(. 3amanak and D.M. Aviado. Areh. Envlron. Heslth, 12: 712-716, 1966. Cardlopulmonary sffscts ottobacco and related subetances. DI. Pulmoaaryvascular sffecte of cigarette smoke and nicotine. M. Satnanek and D. M. Avlado. Arch. Environ. Health, l2: 717-1124. 1966. -. 41 I 141. flolaaonary effects of totrceo and reLted sub.tancas. L Pulma.oary compltamce and resistance Ix the tn the ane.thetiaed dog. D. M. Avlado and F. Palscsk. Arch. Envlrot Health. IS: 107- 193, 1967. 142. . Pnlmmaary affeets of tobacco and related anbstancos. IL Conpatatlvo sftects of el0aratte smoke. nicotine and histamine om the anesth.tlaod cat. F. Palecek aad D. M, A.fade. Arck. Eaviroe. Hsaltk, 1S: 194-203, 1967. 143. Pulmoaary effects of tobacco and relatad substaxces. ID. IabtbtRloa o[ syntkasia al ki.famta. is various spscloa. F. P.lecek, M. Oskoui aod D. M. Aviade. Arch. Env(roe. Hwlth. IS: 204-213, 1967. 144. >-/yyssma in lmmaturs rits maditloa produced by tracheal eostrletfoa-and-Mpaala, F. P.loeek, 11, Paleceko.a and D.Id. A.Iado. Arch, Envlron, HeaHh. 1S: 332-342, 1967. 145. Prosale of lnslmoaary smpkysetn, in rate by *rofeetoroao. H. Ito d D.ld, Avfada. ' J. Fbarmaest Exo. Tk.r. 161: 197-204, 1968. ., -- 146. Palntorry orettkyss®a aad d0arstta srn.*s. LSqarlmonl.l iadueqon awk ass e[ bronehodllators la rato. H. tto aad D.Id. ANado. A:ak. Ea.iroa. NooHk, 16: a6S-t70t 196tt. • • .- 147. DHfsroacos is the aKacts of tnb1ailoft of sa1Gt: diexido and cfpratto etnoka. Y. W. Cho. M. tlana.xoh aad D. M. A.4ado. A.q%,. 10a.lrea Hsalth. 16: 6l1-6Sl, t160. 140. drotfd raosptora asd bronchomator respoosos. Effects of dsarette smoko, labellns. a:d cvaaldo. A.M. Klkte and D,M. A.tade. Arch. LLvtre.. Hea1tY. 17:65-70, 1968. 149. Oral Propsta{a.a ad oxPorlmonW Palmtoeary empkyoeraa. D. M. A.Iado atid O. L MeKlanqr. PYSrmacot Rso. Covanux(catlons. l: 2/3-2tt7, 1969. 100. Hermoaea add Palmoxary effects e[ tobaeem: L C.rtlt:estoratde aad their arNaetLtrtlc aetiw, , D, M, A.1ado aad I., L Carrlllo. Arch. Endron. Hsalth. 182 925-933, 1969. 151. Horttwus sad Palntonary eff.cts of tobacco. D. Prososteroas. a. L 1+koro tad D. M. A.tado. '. /trcb. En.drot Health. 19: 09-69, 1969. 152. Hernooss and qrlemonary.tlads of tobacco. DL CortlcxietsrNds Ia unstbatlxod de2s. - 1. L.OarsilloanQD.M. A.lade, Areh. Es.iron, Hwlth. 21:149-163, 1970., 181 CfOarette smeke and *almonary smnphyseeta. faDoeneo of brenelodlLtoro aaidblo{wic amiaos in axperlmsntal Induction in rats. D. M. Asado, C. dada.oapivad and L. L Carr111s. Arch. En.lrot Hrlth. 20:487-4H, 1970. • 164. Pharmacolo0ical slgal9canco of bto`edc aotlnes Is the lays: btstamtns. 'D.1(. Adado and C. lTada.oay.l.ad, Drtt. J. Pharmacet 3t+: 366-373, 1970. . 1!!. PharmaeoloZlcal .lptlfcsaee of biopalo anSnao in the luags: soradreaolfas and dopamiao. D,M, A.ladosad C, dada.e"'E.had. DrH, J. Pbarttnaot 30: 374-3t!S, 1970. , 166'. . drdlopnltnoaary eHscts of }rosostatieoal apats In empby.amatons rats. T. laisb and D,/1. A.lado. es S9: 659-666, 1971. . IS7.. Ixootlmenbl aalmonarr omnkrsaena ted aro...t.r.,.,._ n_u_ a.t.w.- a.. , Impk7soma and Protsol7sts. Academic Pross. lnp., New York, pp. 419-42i,/, ' ITIU..-. IBO. Tke cass aplnst tobacco 1o not closed. D.M. A.lado. Execatir. Health 10 (llh 1-S , 1974. 159. Fonctlonal and biochemical efMcts on the lon{ following inhalstion of cipratte smoks and eoast[tuontr.. 1, Hlgh- and low.nleottns el/arsttos in mlw. D. M. Aviado and . T. Matanabo. Toxicol. Appl. Pharmacel. 30 (t)t lOS-200, 1974. ,. Functlonal and biocbsmlcal effects on the long follo.lng Intulatlon of clgaretts-smoks and constltuents, D. Mutols. acroleln, and acetaldshyde. T: Matandbo and D.M. Avlado.- Toxteol. and Appl. Phartnacol. 30(2): 201-209, 1974. 161. Functional and biochemical sffeete on the lung follo.rlng Inh.lation of elxaretts smoks I and constltuents. IH. Role of blog.nlc amines. D. M. Avlade. Toxicol, Appl. Pharmicol. (Submttted). TIMN 450204

4* 162 BIBLIOGRAPHY Ronald Okun 39. 40. Okun, R. , Maibach, H., and Gates, T. : Acute Acneiform.Eruption Secondary to MK-672. Arch. Derm. 104:563, Nov. 1971 Karpman, H. L., and Okun, R.: The Place of Vasodilator Drugs in Peripheral Vascular Disease. Geriatrics 27:109, September 1972 41. Champion, G. D. , Paulus, H. E. , Mongan, E., Okun, R., Pearson, C. M. : The Effect of Aspirin on Serum Indomethacin. Clin. Pharm & Therap. 13:239- 244, March-Apri11972. 42. Okun, R.: Treatment of Sedative Drug Overdose. Clin. Tox 6(2): 13-21, 1973 43. Okun, R.: Drugs for the Patient as well as the Disease. Emergency Medicine. pgs141-151, January 1972 44. Paulus, H.E., Okun,R., and Calabro, J.J.: Guidelines for Drug Dosage: Depression In Bone Marrow Granulocyte Reserves In Systemic Lupus Erthyema- tosus. Arthritis & Rheumatism 15:29-35, 1972 45. Kert, M. J. , Tarr, L. W. , Franklin, S., Gold, E., Okun, R., and Maxwell, M. : Experience with the Use of an Aldosterone Antagonist in Selected Hypertensive Patients. Angiology 23(10):617-627, November 1972 46. Bleifer, D.J., Bleifer, S. B., and Okun, R.: Perhexiline Maleate in Angina Pectoris: A Controlled Double-B1ind Clinical Trial. Geriatrics 29:109-115, September 1972. 4;. Silverman, A.G., and Okun, R. : Depressant Drug Overdose-method of. - Current Therapy 1973. Edited Howard F. Conn, M. D. W. B. Saunders Company Philadelphia, Pennsylvania pg. 861 48. Lubitz, J. A. , Freeman, L., and Okun, R. : Mitotane Use in Inoperable Adrenal Cortical Carminoma. JAMA 223(10): 1109-1112, March 5, 1973. 49. Plotkin, D. A. , Plotkin, D., and Okun, R. : Haloperidol in the Treatment of Nausea and Vomiting Due to Cytoloxic Drug Administration. Current Therapeutic Research.15(9): 599-602, September 1973. 50. 51. 52. 163 BIBLIOGRAPHY Ronald Okun Okun, R.: Treatment of Claudication in Obliterative Arterial Disease Drug TheraPy:Pp24-29, January 1974 Okun, R.: On the Other Hand. hrfedical World News 9/20/1974, pg 68. Weldmann, P., Hirsch, D., Maxwell, M. H., Okun, R. and Schroth, P. • Plasma Renin and Blood Pressure During Treatment with Methyldopa. Am. J. Cardiology 34:671-676, November 1974. TIMN 450265

148 Kith regard to to'bacco smoke, over the years numerous animal inhalation experiments have been conducted. Wevertheless, all such studies have failed e of lung cancer that in humans has been statistically t yp e the to produc associated with smoking. One experimental method that produced observable results was the painting of smoke condensates (generally but erroneously called "tare") on the skins of mice• 1'b/ skepticism about the relevance of such experiments to humans is based upon the following considerations: 1. Relatively enormous doses of "tar" were used in the animal skin experiments. 2. Creat differences exist between mice and primates, including man, in susceptibility to cancer-inducing chemicals. 3. There are marw important differences between skin and lung tissues, including various cleansing mechanisms. 4. There are both chemical and physical differences between smoke condensate or "tar" and whole, fresh, normal smoke. 5. The role, if any, of viral agents in the skin painting experiments is unknown. As to carbon monoxide, it is a normal constituent of human blood produced by metabolism and can be destroyed by the body, though slowly. Without arV exposure at all to carbon monoxide in the air, the blood contains from 0.2% to 1.0% of cesboxyhenoglobin (the combination formed by this gas with the red blood pigment). This level is equivalent b that produced by constant breathing of air containing seven parts per million of the gas. Long ago it was found that smokers, after smoking and inhaling from l0 to 15 cigarettes within a period of two hour®, showed a rise in percentage saturation of carboxyhemoglobin from 3.1% to 6.7% (average 4.3'f,). None of them experienced any symptoms attributable to carbon monoxide, which 149 acceptable in prolonged industrial exposures. Further, cigarette exposure is generally intermittent as compared to the day-long exposure often encountered in industries. As to long term exposure to carbon monoxide, studies of men chronically exposed (10 to 18 years) in their work to relatively high carbon monoxide levels show no earlier or more substantial circulatory abnormalities attributable to atherosclerosis than the general population. In short, no one has ever scientifically shown carbon monoxide exposures from ordinary smoking to be hazardous to humans. Since 1972, I have followed the pertinent scientific literattire but have not seen any data which would change my opinion that smoking has not been scientifically established as a "major health hazard" to humans. Nor have I seen any studies in the medical literature which establish "tar," nicotine or any other constituent of tobacco smoke as disease producing in human smokers. This is especially true with regard to the so-called epidemiological or statistical studies. It is generally conceded that the cause or causes of disease cannot be determined by epidemiological studies alone. Such studies merely point to areas in which laboratory experiments with animals, integrated with human clinical observations, are needed to explain and interpret the real meaning of statistical relationships gleaned from human population studies. Experts in the field have pointed out many unsolved problems relating to the epidemiologicall approach. Perhaps the most disturbing criticism of existing studies is that in human populations, the smoker and the non-smoker groups are self-selected to begin with instead of being assigned at random as would be the case in any competent animal experiment. At present, we do not know enough about the conscious or unconscious motivations involved in the adoption or maintenance of cigarette smoking to judge fully the nature TIAIN 450258

I 142 It:'- ,-! .• I . .: tn,: • t•". •1 1 0 ...•n!.• tI. rt'ct• a11 •'tla• c-.,, I., t•. I,:v, 1 f.,l l. to L1h.a! t •i•u t:h.:i _ thi:: level oi our ritics h-t.:: hi,thcr luvvis by r.tiny r:ulliplcs iu the ambient air. Drivers in ordinary traffic far e'•_: -•ed thc: e levels, and tl:o:;e who delayed i n tunnels, coverod bridges, or garages expericnce substant-ially greater lcvels than drivers in ordinary traffic, it should be noted, too, that the effects from different sources of carbon monoxide are not additive. If one source provides an exposure of 5 ppm and simultaneously another source provides an exposure of only 3 ppm, the carboxyheatoglobin level of the individual is not based on a level of 8 ppm, the total of the two, but only on 4 ppm, the average of the t%''o exposures. In demonstrating an acclimitization to carbon monoxide in animals, Nasmith and Graham, Campbell and Barbatow et al exposed animals to ever~ increasing levels of carbon monoxide eventually deve1ol,ing a tolerance to levels unacceptable to the control Inimals. 4'he work of Clark shows the similar physiologic response between carbon.monoxide and high altitude acclimitization. Animals subjected tn cquivalent to 18,000 feet t•ould accept an atmosphere of 2,500 l,•:•t carbon rrono>:ide withouL ill effects e:hile another group raised on 1,200 ppm carbon monoxide was able to live in an c:cp-v.,l at::~::,tterc equivalar.t to 34,000 feet while showing 143 l.!. •. L,:- •- tile Vrt,'y 1.• "1, 1Ct- 1:. 0, t•.. 1:.•u an l:._ :miwj c:. .. :yh,:r:rnllc!•in .•.ct'-t-1.o~i tlut bo:it n~::l c:n:i .er.it-:as ho.•u suacre.ta-ully tolet.,l~•. , ou•• c.•:,not I,cr impressed c:ilh effocts from fleetinca exposures of 40 to 60 pp:m carhon t:onoxi8a. Purthe,r, exposures to peal: carboai t:onoxide con- centrations in this range and higher are a common occurrence in today's heavily mechanized world. The t-laxinwa Allowable Concen- trations for industrial exposure are-50 ppm, and it must be recalled that. this allowance is based upon a forty-hour per week exposure. Transient exposure to the levels found in cigarette smoke cannot begin to equal these levels. . The section of the 1972 Report dealing with possible effects on non-smokers is, in my opinion, so speculative that little more need be said. Until we have settled the questions „ which abound concerning possible effects on the smoker, it seems premature to consider the charges seriously. - In closing, it t•:ould be regrettable to ban certain tob3cco products when our knowledge of any effect they may have is incom- plete and when the effect of such a ban on smokers' pleasures, or desires is too little ur.Ac•rstood. J TIMN 450255

24 A cecond major health consequence of smoking is the development of cancer In smoker::. ('igarette smoking was firmly established as the major cause nf lung cancPr b}• several large retrospective and prospective shrdies. 'I9iP risk of devel- opinK lung cancer was found to be 10 times greater for cigarette smokers than for ncinsmc:kers. The risk of developing lung cancer increases with the number (if cia;nrettes smoked per dny and is greater in cigarPtie smrckers who report inhaling, who ctarteti stnoking att an early age, or who have smoked for a greater nutnl:Pr of years. Smokers of filter cigarettes have hePn shown to have a lower risk of developing lung cancer than smokers of non(ltter cigarettes, but the risk rcmnins well above that for tionstnukerv. 'I'hP risk of developing cancer of the larynx. pharynx, oral cavity, esophagus, nud urinnry bladder was also found to be significantly higher in cigarette Gmnkers than in nonsmokers. Pipe and cigar srunkers were found to have elevated risks for IhP clevelopment of cancer of the oral cavity, pliar;vnx, larynx, aud esophagus when cumpared to nonsmokers. I'ipe and cigar smokers rcpnrtt that they inhale mncli lec!: frequently than cigarette smokers. As a result their hmgs receive much IPss smoke exposure than cigarette srnoker,v'. This is felt to be the reason for the Ionver incidence of cancer uf the lung for pipe and cigar smokers compared to rigarci(c smokerr. \\'mnen have hati far lower ratev of lung cancer than men. This has been nitributed to women:s tenden(;v to smoke fewer cigarettes per (lay, the fac•tt that. fewer women than uten .<tnuke, and the fact that wonien snmkers generally select filter and low tar nnd nicotine cigarettes. llnwever, the percentage of women sninkerti in the 1lnited Stalex hais increased rlramatit•ally in the last.:10 years, and cincP 1955 Ithe dea(th riNP~ front Ituig eancer in womPn have increased prnlxtrtion- ntely more rapidly than Ilie rates for men, reflec•ting ihis inc•reased propnrtinn of women smokers. 'l'he lar fruni c•igaretle uuinke has hPen found to induce rnalignantt changes in the skin and respiratory tractt of experimental aninialv, and a number of specific chemicnl compounds ecmtained in cigarette smoke were ectahlished as potent carcinngens or co-carcincigenc. Malignant changes includiug c•arcinoma iTi sitit were fom:d in tLP Iarynx ancl the sputum cxfoliative cytology of t•xperimental animnis exposed to cigarette cmcike. Nommalignant re.yiirat(rry disease is a third area of smcrking-induc•ed morbidity and mortality. ('igarettP smokers have beeu shown to have more freqnent minor respiratory infections, nli." niore days from work due to resldratury illnes.s, antl repnrt, symptoms of cough nnd sputnm prnduclinn tnore freryueutly tlian non- smokers. Retrospective :tnd prospective sludies with loug-term followup have found that cigarette smoking i:; the primnry cansP of Phrnnic• hronchitis :vtd emphycornn in the linited titates. ('ignrette smnkers have also heen found to be more likely to have abnormalities of their pnlinonary function tests and have higher denth rates from respiratory diseases than nonsmokers. 1)ata frorn autopsy studies have shown that cigarette ms-cikers were more likely to have the macro- sr•opic changes of empliysema, and that these changes are closely related to the rrnmher of cigarettes smoked per day. Mucous cell hyperid:isia has been found mc:re often in cigarette sntokers. ('ignrette smnke also inhibits the ciliary motion rP-1mmAhle for cleansing the respiralory trac•t. 11Aic•r- Mr. 1'resiclent• tlris report goes on to spell out in even grealer l(ehnic:il detail what hy nuw shnultl 'x• o )v;iouc `i,i , i'', „- ,r•,y -win,ue discv:sPC are caused 'b}• cig:iretle smoking. The cvidence supporting tliis concln- ,imn is overwhebning. 1'et. Ainc•ricans contiunP Ic: smoke. Nmv, 12 years after ll:P ti:n•t;PC:n (1enPral's iuiti:cl \carning, cigiirettc cvinsnmpticin ls agnin at or nrnr i:n r:ll-tinie high. Ilnring 1975, uover (i(111 billion cigarettes were sold in ihe i'::itm~l SIaIP., for ::n adnlt I:Pr capila consumpiinn in excess of 2(H) packs--more th::n 1.(NN) cigarclles. Iwr yearr•. Althnugh some uiay not lrP aware of thP fac•ts an:l la•rhalis a few may %vi'h lo deny reality, many lrouple cleariy have 'beeu ceillinr In aPCPId sig::ilir:int l::ng-tcrm risks to their lieatlth rather than forgo ihe tlsr of Iolmccn. \\•hy is this? ilrcw can this. be exl:i:iined? Whiit is it in tobacco that prodnce.c Ii:c vrnvinl:? In :m cinryuent an~wer tcc this questinn, llr. Dt. A. Ilamilton Russell rcxl:nnQcd : "If it .vPre not for thP nirotine in tobacco smoke. people would be little more inclinPCl to smoke cig:irott:w than they are to blow bubbles or light sparklers." It iv im intervestint: Ihcmghl. 'I•he first tnc:dorn ~cienlific Pviclence suggesting that nicotine is an addicf- ing clrng altpearetl mnre 'Ihan :10 }•ear.,t ago in the English Medical Journal Lancet. 25 Dr. Lennox Johnston there reported that he had given small Injections of nico• tine solution to 35 volunteers, including himself. "Smokers almost invariabl,v thought the sensation pleasant." I )r. .f ohnston declared, "and. given an adequate dose, were disinclined to smoke for a time there- after. • . . After a course of 80 Injections of nicotine, an injection was preferred to a cigarette." If the nicotine injections were abruptly discontinued, craving arose. Dr. Jolm- ston tound that in satisfying this craving, 1 milligram of injected nicotine was roughly the equivalent of smoking one cigarette. He concluded that • "Smoking tobacco i.s essentially a means of administering nicotine, just as smoking opium is a means of administering morphine." On the basis of this atnd other Information, it Is obvious that we should make every effort to insure that our children receive all the facts regarding smoking and health. To do anything less clearly would be irresponsible. Mr. I'resklent, the National Health Research and Development Act. of 1976, through support of extensive public health educatiRa pcograms, offers the ounce of prevention which previously has been rationed all too sparingly. Perhaps mainly as a resultt of such efforts, the promise of good health may be realized by all Americans in the not: too-distant future. Mr. President, I ask unanimous-consent that the bill be printed in the record. There being no objection, the bill was ordered to be printed in the record, as follows: - [For t.ext of S. 2902, see p. 4.1 * * * * * * * Mr. RFNNenY. Mr. I'resident, I am mostt pleased to join the Senator from Colo- rado (Mr. IIAar) In introducing legislation which addresses two important and interrelated issues affecting the health of the American people. It has become increasingly c•lear iu recent years t.hatt environmental factors are the utost imlwrtant contribtttors to prevent.able diseases of the American peopie, In the face of growing concern with health problems and the rise In cost of health care, public henlth experts and other concernetld individuals are • demanding with ever-increasing furcefulness and justiflcatiott that the Nation devote iuore of its attention to the prevention as well as the cure of disease. Foremost among the preventahle environment.al hazards which contribute to the ill health of the people and to the heavy burden of healtli care costs Is the smoking of cigarettes• It is now over 25 years since the first preliminary data were published suggesting thatt cigarette smoking Increases the incidence of lung cancer, and 11 years since the Surgeon General's report established an incon- trovertible relationship between cigarette smoking and cancer. Since then, evi- tit•ncP has uiounted that the tar and nicotine of cigarettes contributes not only to oral and pulmonary cancer, but also contributes significantly to increased uiorhidity and mortality from coronary heart disease, ceretrrovascalar disease, pnlmonary emphysenta, and chronic bronchitis, and perhaps many other disease conditions as well. ti cile ihP m intlatc: r 1, ,. ~, .t .~o_ •t rry waruing labei \vhich all cigarette iackages now contain abnut the dangers to health of cigarette smoking, we find that the smoking of cigarPltPs is uuce again on the increase. Mr. l'resident, it is clear that. one cannot legislate a total ban upou cigarette srnuking, bnt it is also clear that alternative courses of ac•tion to ineet this chal- ~ IcngP atre no only available to nv, bnt in fact required of us. Simply raising the ~ price uf all cigarettea by impotaitinu of an acrcss-the-board tax is inadequate, as was well illustrntcd by the failure of :t sharp rise in the price of gasoline to ~ sPrimrsly afTect tlie driving habits uf the Auieric•an people. The presentt bill tJierefrrre propnsex to denl with this problem in the most etfect.ive way known to an opPn and democ•ratic society-the iniposition of a differential tax on the tar aind uicotine enutont of cigarettes sucli that a flnruicial incentive will be pro- vided to cnusmuers to reduce their consnniption uf high tar aud nicotine prtxl- ncts, while a financ•ial incentive will bP provicled to indtistry to develop less hazardous t•igarettes for a public which stvtus unwilling at this point to give trp stnoking c'ompletely. °t r-1 ~ The second ntajor issue addressed by this bill relates to the preventive medi- i ~ c ne aspects mentionecl above. We have in this country a biomedical research establishment of which we can be justifiably proud, engaged in important lab- oratory nn(1 , ime(I at understanding the hasis of disease and

56 Rarlioactiwe Particles In Cigaret Smoke Tied to Lung Cancer " a . Radiation Expert Savs Tars, Nicotine May Not Be T1ailt Caiises, as No.d Believed By BARR) KRAMt7t Staff Xcporlcra oJ Taa Nt'am. Staaer Joca,:A t. CHICAGO=A radiation expert says there s fs growing evidence that radioactive partl- cles in cJgaret smoke are the primary cause of lung cancer, rather than currenUy sus- pect compounds such as tars and-nlcotine.=- Althougti It 1s atill only i< theory. Edward A. Martell, i radlochemiat on the staff of the National Center for 'Atmospheric Re- search 1n Boulder, Colo., told the meeting here of the American Public Health Associa- Uon thtt new human evidence supports It. The atmospherie research'center 1s part of the National Science Foundatlon.- Mr. Mirtell's theory Is that smaD amowlte of radioactive lead in the tiny hairs on the surface Of tobacco leaves becoine concentrated In fnsoluable•smoke particles wben the tobacco fa burned. These parUcles are then Inhaled into the lungs, where the radioactive lead "decays" Into radioactive polonium, a substance that emits destruc- Uve rays called alpha particles. The -alpha rays can either destroy lung cells or dam- age them so that some become malgnant.. Mr. Martell said that recent autopsies of human lung tissue from smokers and non- smokers have. disclosed that radioacUve-i are two to three times higher in smokers than in nonsmokers. But the lnaoluble radioactive particles are con- centraled at the blfurcaUona, or forks, In the branching tunnels of smokers' lungs, where tumors most often occur. In young smokers, he sald, the concentra- Uon of particles at the brancldng-off places fs hundreds of times hlgher thart In non- smokers, wblle In long-tlme smokers It is thousands of times greater. ltesolls Are PreIDnL+iry only eight lungs were examined, four from smokers and tour from nonsmoker., a physician and professor at the Johns Hop- klns University School of Hygiene and Pulr llc Health In Baltimore. Because of the sma11 number of lunga actopsied, Mr. Mar- nary. Prevlous'work by otner rv.arcners at " Johr.s Hopkins has shown that comparable doses of radioAClive polonium are capable of producinglung tumors in hamsters. Dtr. Tfartell said that the radioacttvuy gets into the tobacco because tobacco fields are hcavily fertilized with ao-called super- phosphate feritlizers made from mined phosphate rock. Phosphate rock, espec'us]ly that from Florida, naturally contains urat nium. The uranium decays and givee off ra- don gas, which llselt becays Into radioactive lead, the substmnce collected by the tobacco- leaf hairs. The Colorado scientist sald one way of at- tacking the smoking-cancer problem, if his theory proves cbrrect, would be to stop using superphosphate fertilizer of tobacco. Another would be to usi only newly har- vested tobacco in clgarets, as storing to- bacco In closed easks a_pparetitly allows the spreading of sadtoactivlty'tnto all parts odf the tobaccco leaf and thus iesufts in higher concentrattons in the smoke, he said. FoUow-Up Exper/uienb Mr. Martell said that researchers at the General Electric Oo. laboratortEs at Schs- nectady, N.Y., weie starting follow-up ex- periments to measure lung-ttssue radioactlv- fty. But he said few other researchers, In- cluding those of the federal government, were doing studies that could confirm or re- fute the radioactlvity theory, a fact that Mr. Martell said was a"traglc overslght." That there 1s a small amount of iadfoac- Uvity In cigaret smoke has -been known for many yeirs. But, because it Is In such small quantities, radloacUvity had been discarded as a possible cause of lung cancer. Mr: Mar tell said the new finding that radloat:Uve lead ls concentrated in Insoluble partlcteslbn cigaret smoke "changes the whole complex- lon of the problem." He explained that radioactive lead pro- duces radioactive polonium for decides, and thft the buildup of the fnsoluble particles ta ,the lungs challenges.the surrounding :issue with alpha radiation ,over many years, as long as smoking continues. ' Mr. Marten said his theory may atao ex- plain the high rate of cancer among asbea- tos worken, especially among those who also smoke. 4he abestos particles, he said, may Impede the lung's ability to sweep out the radioaAUvlty lead parUc1es, thus in= creaaing the lung expoaure to radiatfoei. That radiation can cause cancer In bu- mans Is known. Uranium miners, for tn- stance, have a slgnificanqy higher rate of lung cancer. The cumulative levels of alpha radiation fwnd In the lungs of clgaret amok- era is comparable to that which gives rise to lung tumors in uranhtpi miners, Mr. Martell said. TIMN 450212 57 Senator HUDDLESTON.- But even if we were to assume strong evidence--convincing evidence-that cigarette smoking is related to disease and that tar and nicotine are the culprits-vlwould we wantt the bill passed that is to be considered by this committee in connection with these hearings? Do we want to -tax out of existence products which we would not directly prohibit? The very purpose of the bill is to decrease smoking. There will not be an increased Federal tax on all cigarettes-it will simply be much higher on some. We will be saying to the public that while we al'e'not willing to take direct steps to ban certain products we are willing to keep them out of the hands of thosl, people who cannot afford them. What do we want to call this bill? If wee want it to produce revenue, then we want it to fail in all its so-called tar and' nicoti>}e reducing function. Because t.he higlferbhe tar and nicoti"ot/hetll'dre,the tax. On the other hand, if the splhnebrs want it to sttoceed'4ts a public health measure, then its revenue producing potential wottld be-considerably less. t ' . - - , ' Mr. Chairman, my staff has dolte some reseterch and found thttt in your State, 11 counties rank far above tlle average for deaths per 100,000 as a result of cancer from all causes. So high in fact that your State ranks among the top 10 percent in the Nation. Senator KENNEDY. That is a good reason to try and do something to pass this bill. Senator HUDDLESTON. Right. But let's find out the cause. The average deaths per 100,000 in the United States of all cancer mortalities is 174.04 for males and 130.10 for females. Your Suffolk County rates 223.3 for males and 151.1 for females. In fact, Senator, 11 counties out of your 14 total are far above the nationftl-average. The only member of this subcommittee with a higher rate per 100,0IH> is Senator Williams. His Hudson County, N.J., with a figure of 231.8 for males and 153.5 for females leads all others. In fact, taking all oE the members of this subcommittee plus tlle State of Colorado (the home State of Senator Hart who introduced this bill), you all have 157 counties out of the 303 in the entire United States ranked highest for cancer from all causes as a percentage of deaths. These figures were computed from the "Atlas of Cancer Mortality for U.S. Counties" published by the U.S. Department of Health, Edu- cation, cation, anc. u u e:.i:are, u ~-~ic Serv'ice, 'i,:,',' , . ,:, . . .:, ,,.. , . Health. Its compilation was done by a staff of doctors and statisti- cians from the Epidemology Branch, National Cancer Institute. Now, Senator, this was not done to embarrass anyone-only to en- lighten the subcommittee and staff that there exists a myriad of aretl.s to be studied-a multitude of suspected causes to be analyzed. But to impose a prohibitory tax on one suspected cause-ignoring all the others-ignoring area significance as I have pointed out-in no way promotes what the Senator said in his remarks on the floor, and I quot,e-- The present bill therefore proposes to deal with this problem In the most effec- tive way known to an open and democratic society ... And so forth. If that democratic society is blind, his remarks could well be cor- rect. My purpose in being here is to open those eyes so that when a

138 ')'alc tl.r h. A, ug Lo Lh':: }•aint bcen unaer tlle grcatcut sur;picir+n. OCL'c:r :+;lent.s have •becn ic1L.;a-ified in "tar" which might in thcory have er carcinogcni.c off.oct, but the qualil-ative identification of a particular agent in a complex mir.L-uro does not mean that it is present in sufficient quantities to proeuce a biological effect; neither does the effect in a par- ticulnr species mean that it may occur either quantitatively or qualitatively in man. it has been suggested that tobacco smoke may serve'as a co- carcinogen to carcihogens from other sources such as those occur- ring in the general atmosphere. Experimental evidence for this hypothesis is lacking. Steiner and Falk have reviewed the literature concerning data elicited from experinients involving various combinations of chemical carcinogens, tumor-producing vituses, radiant energy, and trauma. Some of these experiments showed summation.of•efffects,. others did not, and a third group showed inhibition. Simultaneous administration of two potent carcinogens, when injected together, • sometimes were inhibitory. These equivocal effects suggest the desirability of reviewing the problem of anti-carcinogenesis and compounds tested in combination. Inhibition of the action of potent carcinogens has been roported by a number of investigators. F.n*_ardnti.on of the rate of tumor induction has resulted follcr.•ling application of non-carcinogenic e]v:;.=Jy ro]..H..i ,cu:npo+nI.1: fcon+l ill tohcr.•r:. • ~. slno::c. fallc h:rs deluono-:tratc:d thu iuhibu.t•ion uL c. cc:.nogenic activity by .-dministration of cxudc sa:np]cs'of cigarelte slmn).re extracts. It is apparent from thc er.parimental worY, of many investigators that the carcinogenic potency of crude mixturos is less than the sum total of anticipated carcinogens;* imti- carcinogenicity as well as co-carcinogenicity must be recognized as an ubiquitous phenomenon. Inhibition of experimental carcin- ogenicity is related to a number of factors, including th. vehicli used, the ratio of the anticarcinogen to the carcinogen, t'he relative structural relationship of these two substances, and the time of administration. It must be kept firmly in mind that in speaking of carcinogens, we are speaking of the effect upon the skins of mice. The above is cited to emphasize that though carcinogenic ' substanees may be identified iti tobacco"tars,"the presence: of' other constituents may themselves be strongly inhibitory of damaging effect. It would therefore seem most unscientific to lower ' arbitrarily the"tar"content of cigarettes. We simply do not know whether cigarette "tar" has any relationship to human disease. A loaer"tar"content may differ qualitatively as well as quantita- tively from a higher"tar"content, and whether this differencc would be disproportionatcly lower in anti-carcinogens or carcinogen inl!i;.iL•ors is unknot•:n. Tinl:erir•.g with .•rhat we do not compreh2nd can l:e r• ::af.o::lun~te results, pnrtic;:], rl}- in an arcr as complex as this . ~I TIMN 450253

W 164 BIBLIOGRAPHY Ronald Okun Charlers in a Book OkMm, R.:Development of New Drugs. Chapter in Essentials of Pharmacology Editor: John A. Bevan. Publisher Hoeber Medical Division, Harper & Row, 1969 , pp. 29-35. Okum, R.: Pharmacology of Placebos. Chapter in Essentials of Pharmacology _ Editor: John A. Bevan. Publisher lioeber Medical Division, Harper & Row 1969 pp 36-42. Okun, R.: Drug Dependence. Chapter in Essentials of Pharmacology. Editor: John A. Bevan. Publisher Hoeber Medical Division, Harper & Row 1969, pp 59-68. Okiui, R.: Acute Drug Poisoning. Chapter In Essentials of Pharmacol2m. Editor: John A. Bevan. Publisher Hoeber Medical Division, Harper & Row, 1969 pp 75-84. Okau+, R.: Psychopharmacologic Agents. Chapter in Essentials of Pharmacology Editor: John A. Bevan. Publisher Hoeber Medical Division, Harper & Row, 1969, pp 187-212. Okun, R.: Alcohol (Ethanol) and Tetraethylthiuram Disulfide. Chapter in Essentials of Pharmacology. Editor: John A. Bevan. Publisher Hoeber Medical Division, Ilarper & Row, 1969, pp 597-599. Okun, R.: Antilipid Agents. Chopter in Essentials of Pharmacology. Editor: John A. Bevan. Publisher Iloeber Medical Division, Harper & Row, 1969, pp 600-603. Okum, R.: General Principles of Clinical Pharmacology and Psychopharmacology and Early Clinical Drug Evaluations. Chapter in Principles of Psychopharmacology Editors: W. G. Clark and J. del Giudice. Publisher Academic Press, New York, New York, 1970 pp 381-390. Okun, R.: Use of Diuretics in the Management of Hypertension. Chapter in Diuretics in the Management of Fluid Retention, Editor Ilenry O. Iieincmann, M.D., in Modern Treatment, Volume 7, Number 2, March 1970, Publisher Hoeber Medical Division, Ilarper and Row, New York, New York. Si'lverman, A. G., and Okun, R.: Depressant Drug Overdose. Chapter in Current Therapy, 1971 Section 15, pages 772-774. Publisher W. B. Saunders Company, Philadelphia, Pennsylvania. 165 BIBLIOGRAPHY Ronald Okun Chapters In a Book Silverman, A. G. , and Okun, R.: Depressant Drug Overdose. Chapter ln Current Therap; 1972, Section 15, pages 835-836, Publisher W. B. Saunders Company, Philadelphia, Pennsylvania TIMN 450266

/ 188 Mr. Chairman and Members of the Subcommittee: We welcome this opportunity to discuss with your committee the health consequences of smoking and the policy of the Department of Health, Education, and Welfare with regard to preventable health problems in general and to smoking in particular. HEALTH CONSEQUENCES OF SMOKING The relationship between cigarette smoking and excess disease morbidity and mortality has been thoroughly documented, most recently in the June 1975 Public Health Service report on The Health Consequences of Smoking. The most important specific health consequence of cigarette smoking in terms of the number of people affected is the development of premature coronary heart disease (CHD). Both prospective and retrospective studies clearly established that cigarette smokers have a greater risk of death due to CHD and have a higher prevalence of CHD than nonsmokers. Long-term follow-up of health populations~has confirmed that a cigarette smoker is more likely to have myocardial infarction and to die from CHD than a nonsmoker. Cigarette one o:= tae major lLndePendent ;- ...-. c...i . ux,n .o .:)e 189 - 2 - CHD risk factors and also to act in combination with other alterable CHD risk factors (high bl,pod pressure and,y elevated serum cholesterol). Autopsy studies have shown that persons who smoked cigarettes have more severe coronary atherosclerosis than persons who did not smoke. Physiologic studies and animal experiments have indicated several mechanisms whereby these effects can take place. A second major health consequence of smoking is the develop- ment of cancer in smokers. Cigarette smoking is firmly established as the major risk factor in lung cancer. The risk of developing lung cancer was found to be 10 times greater for cigarette smokers than for nonsmokers. The risk of developing lung cancer increases with the number of cigarettes smoked per day and is greater in cigarette smokers who report inhaling, who started smoking at an early age, or who have smoked for a greater number of years. Smokers of filter cigarettes have been shown to have lower risk of develon;.,R ~ _ .....,. _.- ..'-,..... •:......,'._--_~ of nonfilter cigarettes, but the risk remains well above that for nonsmokers. TIMN 450278

- 3 - Women have had far lower rates of lung cancer than men. This has been attributed to the fact that fewer women than men smoke and the fact that women smokers generally select filter and low tar and nicotine cigarettes. However, the percentage of women smokers in the United States has increased steadily in the last 30 years, and since 1955 the death rates from lung cancer in women have increased proportionately more rapidly than the rates for men, reflecting this increased proportion of women smokers. The tar from cigarette smoke has been found to induce malignant changes in the skin and respiratory tract of experimental animals, and a number of specific chemical compounds contained in cigarette smoke were established as potent carcinogens or co- carcinogens. Malignant changes including carcinoma in situ were found in the larynx and in the sputum exfoliative cytology of experimental animals exposed to cigarette smoke. c.isease is a t..Urcl area of smok- ing-induced morbidity and mortality. Cigarette smokers have been shoFn to have more frequent minor respiratory 191 - 4 - infections, miss more days from work due to respiratory illness, and report symptoms of cough and sputum pro- duction more frequently than nonsmokers. Retrospective and prospective studies with long-term follow-up have found that cigarette smoking is the primary factor in the development of chronic bronchitis and emphysema in the United States. Cigarette smokers have also been found to be more likely to have abonormalities of pul- monary function and have higher death rates from respiratory diseases than nonsmokers. Data from autopsy studies have shown that cigarette smokers were more likely to have the macroscopic changes of emphysema, and that these changes are closely related to the number of cigarettes smoked per day. Mucous cell hyperplasia has been found more often in cigarette smokers. Cigarette smoke also inhibits the ciliary motion responsible for cleansing the respiratory tract. An additional area of health concern has been the effect of c.uring pregnancy. Mothers who smoke cigarettes during the last two trimesters of their preg- nancy have been found to have babies with a lower average TIMN 450279

166 BIBLIOGRAPHY Ronald Okun A I351•RACTS 1. Siegel, M., Mongan, E., Okun, R., Calabro, J. J. and Paulus, H. E. : The Self-Sustaining Survival of High Serum Salicylate Levels in Patients with Rheumatoid Arthritis. Arthritis and Rheumatism. pg 697, Dec. 1969 2. Paulus, H. E., and Okun, R., and Calabro, J. J.: Granulocyte Response to Prednisone and Etiocholanolone. Clin. Res. 18:132, 1970. 3. Paulus, H.E., Okun,R., and Calabro, J.J.: Depression of Bone Marrow Granulocyte Reserves In Systemic Lupus Erythematosus (SLE). Arthritis and Rheumatism. 13(3):344, May 1970 4. Paulus, H. E., Mongan, E. S. , Siegel, M. , Okun, R., and Pearson, C. M: Persistence of Serum Salicylate Levels in Patients with Chronic Rheumatoid Arthritis. The Pharmacologist 12:(2): 293, Fall 1970. .5. Champion, D., Mongan, E., Paulus, H. Sarkissian, E., Okun, R., and Pearson, C. : Effect of Concurrent Aspirin (ASA) Administration on Serum Concentrations of Indomethacin (1). Arthritis . Arthritis & Rheumatism. 14:375, 1971 6. Karpman, H. L., and Okun, R. : Vasodilating Agents in the Prevention of Acute Myocardial Infarctions. Cardlo-Vascular Research. 4.: 182, Sept.1970 7.' Silverman, M., and Okun, R.: The Use of an Appetite Suppressant (Diethyl- proplon Hydrochloride) During Pregnancy. Ob/Gyn Digest, 1971 8. Weidmann, P, Hirsch, D., Okun, R., and Maxwell, M. H.: Renin-Blood P2~4e5s8ure~7During Sympathetic Inhibition with Methyldopa. Clinical Research 9. Lubitz, J. , Freeman, I,. , and Okun, R.: Mitotane in.Inoperable Adrenal Cortical Carinoma. The Hebrew Pharmacists (Harokeah Haivrlt) 17(1):92,1973 Treatment of Inoperable Adrenal Cortical Carcinoma with Mitotane (o,p'DDD) in Advances in Antimicrobial and Antineoplaslic Chemotherapy. Progress in Research and Clinical Application. Pro. of the VII International Congress of Chemo-Therapy, Prague 1971 Editor Munchen, Urban & Schwarzenberg, 1972. 2'ol. 11 pp 563-565. 10. Marks,J.,Bonorris, G., Chung, A., Coyne, M., Goldstein, L., Okun, R., and Schoenfield, L.: Feasibility of Low Dose and Intermittent Chenodeoxycholic Acid Therapy of Gallstones. Gastroenterology 68:946, 1975 167 BIBLIOGRAPHY Ronald Okun ABSTRACTS 11, Okun, R.: Drug Interactions. Clinical Toxicology 7(2):215, 1974 12. Levy, R., Sellers, A., Mandel, W.J. and Okun, R.: Quinidine Pharmacoki in Anephric and Normal Subjects. Clinical Research TIMN 450267

186 Dr. COOPER. We would be pleased to comment on it. Senator KENNEDY. If y0U could, we would appreciate having you and those others whose work is qnestioned, to comment on it, if they «•ant to, and to make any rebuttal. We will make that a part of the recorcl as well. I think itt would be useful to have your comments on ihat particnlar data. 1'Vo want. to t.hank you very much. I h. CoorER. '1'h ank you, si r. [Tlie prepared statement of Mr. Cooper and other material referred lo follows:] 187 FOR RELEASE ONLY UPON DELIVER DEPARTMENT OF HEALTH. EDUCATION. AND WELFARE APPENDIX A STATEMENT BY THEODORE COOPER, M.D. ASSISTANT SECRETARY FOR HEALTH BEFORE THE SUBCOMMITTEE ON HEALTH COMMITTEE ON LABOR AND PUBLIC WELFARE UNITED STATES SENATE THURSDAY, FEBRUARY 19, 1976 TIlVIN 450277

W,. 160 14. 15. 16. 17. BIBLIOGRAPHY Ronald Okun Sokoi, A., Rashner, M. H., Okun,R.: Nephrotic Syndrome Caused by probenecid. JAMA 199:43-44, 1967 paltes, B., Ellison, T., Levy, L., and Okun, R.: The Metabolic Fate of d-Amphetamine-H Sulfate. The pharmacologist 8:220, 1966 Okun, R.: Diuretics-Use and Abuse. The Medical Television Network, U( LA, Center for the Health Scicnces. 1967 okun, R. and Kleeman, C. R.: Renal Disease Secondary to Metabolio f)isorders or Physiological Deficiency States. Calif. Med 107:8-10, 1967 18. (',erstein, A. R. , Okun, R., Gonick, H. C. , Wilner, H.I., Kleeman, C. R. and Maxwell, M.H.: Prolonged Use of Methenamine Ilippurate in Treatment of Itrinary Tract Infection. J. Ilrol 100:767, 1968 19. Siegel~ M., F.llison, T., Silverman, A.G., and Okun,R.: Tissue Distribution of dl- `Il-Amphetamine HCI in Tolerant and Nontolerant Cats. Proc. West. Pharmacol. Soc. 11:90-94, 1968 20. Ellison, T., Siegel, M., Silverman, A.G., and Okun, R.: Comparative Metabolism of dl- 311-Amphetamine Ilydrochloride in Tolerant and Nontolerant Cats. Proc. West. Pharmacol Soc. 11:75-77, 1968 21 Silverman, A. G. , and Okun, R. ,:]soproternol and Dopamine in the Treatment of Meprobamate Overdosage in Cats. Proc. West. Pharmacol Soc. 11:94-98,1968 22. Okun, R.: Medical Pain Relief. J. liosp. Dental Practice 11:32-36, 1968 23. Okun, R.: Use and Abuse of Antibiotics. J. Ilosp. Dental Practice 11:58-62, 1968 24. Silverman, A. G. , Wilner, H. I., and Okun, R. : A Case Report of Gastro- intestinal Bleeding Following the Use of Tolazoline. Tox and Appl. Pharm. 16:318-320, 1970 25. Silverman, A.G., Wilner, H.I., and Okun, R.,: A Case-of Accidental Parenteral Injection of Povan. Tax and Appl. Pharm. 16:740-742, 1970. 26. Silverman, A.G., and Okun, R.: A Look at Some of the Common Adverse Drug Reactions. J1. Hospital Dental Practice . April 1970, pgs-50-56. 27. Rllison, T., Levy, L., Bolger,.J. and Okun, R.: The Metabolic Fate of 311-Fenetylline In Man. European J{. Pharmacology 13 :123-128, 1970._ 161 BIBLIOGRAPHY Ronald Okun 28. Ellison,T., Snyder, A.; Bolger, J., and Okun, R.: Metabolism of Orphenadrine Citrate in Man. J. Pharm & Exp. Therap. 176 (2):284- 295, 1971 29. Ellison, T., Okun, R., Silverman, A., and Siegel, M.: Metabolic Fate of Amphetamine in the Cat During Development of Tolerance: Arch. Int. Pharmacodyn 190:135-149, 1971 30. Silverman, A. G. and Okun, R.: A Double Blind Evaluation of Capuride in Treating Hospitalized Patients Suffering from Lose of Sleep. J. Clin. Pharm. 11 (3):215-219, 1971 31. Okun, R. : Therapy of Barbiturate Overdose. Geriatrics 26:113, 1971. 32. Silverman, M. and Okun, R.: The Use of an Appetite Suppressant (Diethylproprlon Hydorchlorlde) During Pregnancy. Curr. Therap. Res. 13: 648-653, October 1971 33. Silverman, M. and Okun,R.: Oxytetracycline-Nystatin in the Prevention of Candidal Vaginitis. Am. J. OB GYN 111:398, October 1971 34. Okun, R.: Clinical Studies in Adrenal Cortical Carcinoma: Current Studies. Proceedings of the Chemotherapy Conference on Ortho Para'DDD. Ed. Broder, L. E. and Carter S. K.- NatlonalCancer Institute. Pgs70-79, Nov.1970. 35. Ross, J.F., Hewit, W.L., Wahl, C.W., Okun,R., Shapiro, B.J., Slawson, P. F., and Shneidman, E. S.: The Management of the Presuicidal, Suicidal and Post suicidal Patient. UCLA Conference. Annals of bit. Med. 75:441, September 1971 36. Paulus, H. E. , Siegel, M. ,• Mongan, E., Okun, R., and Calabro, J. J. : Variations of-Serum Concentrations and Half-Life of Salicylate In Patients with Rheumatoid Arthritis. Arthritis & Rheumatism 14:527, 1971 . 37. Okun, R. : Principles of Treatment: Metabolism and Excretion of Toxic substances. Clin. Toxicology Bulletin 2(5):9-14, 1971 38. Kaufman, 'J. J., Maxwell, M.H., Craven, J. D., and Okun, R. : UCLA Conference. Hypertension- Primary and Secondary. Ann. Int. Med. 75:761- 776, 1971. TIMN 450264

158 I 159 CURRICULUM VITAE Ronald Okun, M.D. BIBLIOGRAPHY Ronald Okun ESENT APPOINTMENTS (continuedl /'1f 1. Okun,R., and Elliott, H. W.: Acute Pharmacological Studies of Some New M hi _ Svienlific Advisor to the Board of Directors,Cedars-Sinai Medical Center 1969 - Present orp ne Derivatives. J. Pharmcol Exp. & Ther. 124:225-259, 1958. Associate Editor of Annual Review of Pharmacology 1970 2. Okun,R., Liddon, S.C., and Lasagna, L: The Effects of Aggregation, Attending Staff in Internal Medicine (Nephrology) County of Los Angeles/Harbor General Hospital, Los Angeles, Calif. 1970 Electric Shock and Adrenerglc Blocking Drugs on Inhibition of the Writhing Syndrome. J. Pharmacol. Exp. & Ther 193 (1):107-109, 1963 American College of Clinical Pharmacology Foltnw 1971 , Chief, Scientific Advisory Board, Committee to Combat Huntington's Disease 1971-Present 3. Wilson, R., Okun, R.: The Acute Hemodynamic Effects of Diazoxide In Chairman, Committee on Pharmacy & Therapeutics, California Medical Assn.1973- 1974 Man. Circulation 28:89-93, 1963 Pharmacist Advisory Commission to Assembly California Legislature 1973- 1975 President, American Academy Clinical Toxicology May 1973 4. Wolff, F. W. , Parmley, W. W. , White, K. and Okun, R. : Drug Induced Diabetes. JAMA 185:568-574, 1963 PROFESSIONAL SOCIETY MEMBERSHIPS 5. Wilson, W.R., Okun, R., Tetreault, L., and Fallis, N.: Methlydopaand, Hydrochlorothiazide In Primary Hypertension: Controlled Clinical Trial of D rugs , Singly and In Combination. JAMA 185:819-825, 1963 Sigma Xi 1958 American Federation for Clinical Research 1961 6. Wennberg, J. E. , Okun, R. , Hirman, E. J. , Northcutt, R. C. Griep, R. J. , A merican Assn. for Advancement of Science 1961 and Walker, W. G.: Renal Toxicity of Oral Cholecyetographic Media. JAMA. New York Academy of Sciences 1961 186:461-467, 1963 Amer. Soc. for Pharmacology & Experimental Therapeutics 1968 Am• r. Academy of Clinical Toxicology 1968 7. Okun, R., Russell, R. P_ and Wilson, W. R. : Use of Diazoxide with Trichlor- Amer. Snc. for Clinical Pharmacology & Therapeutics 1971 methiazide for Hypertension. Arch Intern. Med 112:882-888, 1963 SPECIAL AWARDS & HONORS 8. 9 Okun, R. , Wilson, W. R., and Gelfand, M.D.: The Hyperglycemic Effect of Hypotensive Drugs J. Chron. Dis. 17:31-39, 1964 C li i.egge Preventive Medicine Award, University of California Med Cntr. Feb - June 1958 . ar ner, N. H., Schelling, J., Russell, R. P., Okun, R. , and Davis, M.: Thiazide and Phtalimidine Induced Hyperglycemia in Hypertensive Patients. Fellow, American College of Physicians Apri115, 1972 JAMA 191:535, 1965 10. Okun, R.: Principles of Clinical Drug Evaluation. Proc West. Pharm. Soc. 8:23-32, 1965 11. Winters, R. H., Levy, L., Thurman, W., and Okun, R.: Studies on the Metabolism and Distribution of Radioactive Amphetamine. Proc. of West. Pharm. Soc. 9:1-3, 1966 12. Okun, R., Roth, S. E., Gordon, A., and Maxwell. M. H. : The Long Term Effectiveness of Methykiopa in Hypertension. Calif. Med. 104:46-50, 1966 13. Kleeman, C. R. , and Okun, R., and lfelle r, R. J. : The Renal Regulation of Sodium and Potassium in Patients with Chronic Renal Failure and the Effect of Diuretics on the Excretion of these Ions. Ann. New York _Academy Scl. 1391.520-529, 1966 TIMN 450263

U 192 -5- birth weight than nonsmoking mothers. In addition cigarette smoking mothers had a higher risk of having a stillborn child, and their infants had higher late fetal and neonatal death rates. There are some data to show that these risks due to cigarette smoking are even greater in women who have a high risk pregnancy. for other reasons. These effects may occur because carbon monoxide passes freely across the placenta and is readily bound by fetal hemoglobin, thereby de- creasing the oxygen carrying capacity of fetal blood. Having established that cigarette smoking is a signifi- cant causal factor in a number of serious disease processes, two additional questions become important. They are "Can the health consequences to the individua 1 be averted by stopping smoking or by changing the cigarette?" and "What are the overall public health consequences of cessation and of the changes made in cigarettes?" The first question is the simpler of the two to answer. in the individual, cessation of ciaarPrtP Gmoki_rn .~,... i.n a rapid decline of the carbon monoxide level in the 193 - 6 - blood over the first 12 hours. Symptoms of cough, sputum production, and shortness of breath usually improve over the next few weeks. A women who stops smoking by the fourth month of her pregnancy has'no increased risk of stillbirth or perinatal death in her infant related to smoking. The deterioration in pulmonary function tests that occurs in some sinbkers becomes less rapid than that of continuing smokers. The death rates from ischemic heart disease, chronic bronchitis, and emphysema also become less than those of the continuing smoker. The risk of developing cancer of the lung, larynx, and oral cavity declines in the first few years after cessation and 10 to 15 years after stopping smoking approximates that of nonsmokers. A smoker who switches to filter cigarettes and has smoked them for 10 years or longer has a lower risk of develop- ing lung cancer than a smoker whocontinues to smoke non- filter cigarettes. The risk to a filter cigarette smoker, however, still remains well above that c,f ?.,r,,,,,,,, The public health benefits of cessation are more diffi- cult to determine than the effeats of cessation on the TIMN 450280

194 - 7 - individual. Just as cause-specific death rates have reflected the effect of cigarette smoking on certain diseases, they should also reflect any substantial benefits to be gained by cessation or reduction- in cigarette smoking. Several factors combined to produce a reduction in per capita dosage of tobacco exposure in the United States for the years 1966-1970. ~First, per capita consumption of cigarettes declined from 4,287 cigarettes per person in 1966 to 3,985 in 1970. Second, during this period there was a slow but signifi- cant decrease in the average tar and nicotine content of cigarettes as well as a decrease in the amount of tobacco contained in the average cigarette. The decline in per capita consumption during those years occurred in the face of a substantial increase in the proportion of young women becoming smokers as compared to women of previous generations and so reflected predominately a decrease in cigarette consumption by men. Since 1970, although the per capita consumption of cigarettes has increa"sed, the average levels of tar and nicotine have continued to decline making it more difficult to determine what has happened to per capita dosage. 195 - 8 - Examination of cause-specific death rates for the period ; of this declining per capita consumption reveals that there was a downturn in the male death rate from is- ~ chemic heart disease beginning in 1966 which reversed the upward trend that had occurred over the previous two decades. This dealine in the death rate from ischemic heart disease has not occurred in!womgn. The male death rate from chronic bronchitis has also been declining since 1967, and the male death rate for emphysema has declined since 1968 when it was first recorded as a separate category. Female-death rates for these two diseases have not shown these trends. Despite the impressive coincidences of the decline in death rates among males occurring at the same time that there was a decline in per capita cigarette,con- sumption, it is impossible to be certain of,the exact cause of the decline in the death rates. These diseases are influenced hv a ,,,,,':, t-.Lon -:o TITdIN 450281

144 GHAnLea H. HINr. M. D., FH D PROFESSIONAL QUALIFICATIONS EDUCATION 1 St. Norbert College Che.istzy E.A. 1937 . 2. University of wisconsin Gradua te Sc hool Chemistry M.A. 1936 3. University of Uisconsin Gradua te Sc hool Pharmacology and Toxicology Ph.D. 1942 4 University of wisconsin Medica l Sch ool Medicine M.D. 1943 . 5. Internship (Rotating) U.S. Nav y 1943- San Diego Naval Hospital 1944 ACADEMIC AND RESEARCH POSITIONS HELD 1. Nisconsin Alu.ni Research Fellow 1930-42 2. Maad of Toxicoloqy Activity, National Naval Rssearch Institute 1946 3 Chief Toxicologist and Acting Head of Radiological Defense Laboratory, U.S. Naval Shipyards, San Francisco 1947 4. School of Medicine, University of California, San yrancisco • M.dical Center Lecturar in Phar.acology . 1947-48 Assistant Professor of Pharmacolog y 1946-52 Associate Clinical Professor of Pharmacology and Toxicology 1952-64 Associate Clinical Professor of Preventive (Occupational) 1957-64 Medicine Clinical Professor of Preventivs (Occupational) Medicine and 1964- Toxicology and Environmental Medicine present S. University of California, School of Public Health _ Assistant Professor 1948-52 Associate Clinical Professor 1953-62 Lecturer 1963-66 BORRD CERTIFICATION 1. Industrial Hygiene (Toxicology) 1962 2. Preventive (Occupational) Medicine 1956 MILITARy EERVICE U.S. Navy Medical Corps: Ensign (MCVP) 1942-43 Lieut+nant (J.g.) 1944-45 Lieutenant (e.g.) 1946-47 NEMNERSHIP IN PROFESSIONAL SOCIETIES 1. 1Naerican Academy of Forensic Science (Fellow 1957) 1950 2. American Academy of Occupational Medicine (Fellov 1960) 1957 3. American Chemical Society 1950 4. American oard of Industrial Hygiana - 1962 S. American Board of Praventive Medicine 1956 6. American Indu.crl.l n....4 -.+- . 7. American Medical Association 1946 r. American Society for Pharmacology and Experimental Therapeutics 1947 145 CMARLEf H. MINE• M. 0. M. D. pROliSSIONAL QOALIPICATIONS (Continuad) !. American Therapeutic Society 1965' 10. California Academy of Preventive Medicine 1957 11. California Medical Association 1!1• 12. American Oocupational Medical Association (fellov 1950) . 1951 13. International Association of Forensic Toxicologists 1963 14. San Francisco County Medical Society 1l4i 1S. sig.a xi 1942 lb. society for ixpariuantal Biology and Medicine 1947 17. Society of Toxicololy (Founding Ne.bar) 1961 ls. Mestarn OeaDpational Medieal Association 1952 pROPi6RIOMAL RCliVITlti 1. Iwdependent Nedioai sxa.iner for State of California lierh.an-e Compensation Appeals soard 2. Practicing Physician, licwnsad 1944, DSNr 1946 itita of Califernia 3. Toxioololist to the Coroner, City and County of san praneisoe 4. Consultant in Oooupational Ilaalth and toxioology S,. Consultant to California state Department of publie saalth ~in toxicololy "V iI)1L MOMOR6 A,ND NLlCTION TO iptCIRL MlRNtRtNip{ 10 ! 11~'11sN ~~_ . .. 1. Certified by the American soard of pre.entiil•M.di61*4"Yw the i ~~. ~~. field of Ocoupational Nsdioine (toundor•s Oteap) ;+ slevated to Fellov in the American Co11ele Af fir~ ~rb Medicine +~ ` ". Elevated to iollov ~n the American Academy et OA lesa Net7icin. ' •. ele.ata4 to lrllow in the American Ooo.patie.al Medlea )les'n. S. soard of In4ustri.l•syliene, eertified in•Toxieelegy.' 6. Appointed to ser..,on inter.ational Advisory Coll.ltt6i of National In~titMt.a of soalth TIMN 450256

® 199 centered around two basic methods: the first measures levels of specific substances found in involuntary smoking situations and then establishes the effects of the levels found of a given substance on persons with pre-existing disease; the second evaluates healthy populations of nonsmokers to discover health consequences. Several minor symptoms (conjunctival irritation, dry throat, etc) are caused by levels of cigarette smoking encountered in everyday life, and serious allergic-like reactions to cigarette smoke may occur in some sensitive individuals. Of particular concern, however, relative to atmospheric contamination by cigarette smoke has been the production of significant levels of sub- stances such as carbon monoxide, nicotine, benzo(a)pyrene, acrolein, and acetaldehyde. The amount of carbon monoxide (CO) in involuntary smoking situations has been measured and the effects to persons 'aeen we-._. C.ocumen-lec.. Levels found in small, poorly ventilated spaces for ex- ample, automobiles and conference rooms, are well above the current ambient air standard for carbon monoxide (CO), 9 ppm. The higher levels recorded for CO represent con- ditions of heavy smoking and poor ventilation and so probably represent the upper limit of exposure conditions. Data indicate that exposure to CO at levels found i1i some involuntary smoking situations may well have a significant impact on the functional capacity of persons with angina pectoris. Carbon monoxide has also been shown to decrease cardiac contractility in persons with coronary heart disease at levels similar to those produced due to involuntary smoking situations. it is reasonable to assume that any significant CO exposure to the diseased heart reduces itsfunctional reserve. Persons with chronic bonchitis and emphysema have con- siderable excess mortality under conditions of severe air pollution. In smoke-filled environments levels of CO and several other pollutants may be as high or higher than occur during air pollution emergencies. Because people with pre-exist;ng i,.)_]^.-^ .,,i..e susceptJ.,O.Le to the harmful effects of adverse environmental conditions than healthy populations, it is worthwhile to examine the effects of involuntary smoking on healthy populations. TIIVIINR 450283

.r 116 Senator KENNEDti-. I do not. know whether Senators Schweiker or 13eall have, any questions. tienatOr SC11wEIKER. No. Senator BEnt,l.. No questions. tienator KENNEDV. Senator Ford ? STATEMENT OF HON. WENDELL H. FORD, A U.S. SENATOR FROM THE STATE OF KENTUCKY Sennt.or KENNEny. I want to welcome you here before the committee. «'e look forward to your test.inlony. tienat.or Fonn. Mr. Chairman, I am extremely pleased to have the ol/portimity to testify on S. 2902 and to state to the. members of the tiubnonunitte.e on Health the detrimental effects that t,his bill will have on mnny in Kentucky. I believe the chairlnan made a statement in his ohening remarks t.hat. sonlc 100,000 workers would be involved and I want, to correct, him on that if I may. Kentucky has 164,161 farms involved in the growing of tobacco. You could take the number of farnis and easily multiply by four and arrive at a figure of those in- volved in planting, harvestm and marketing better than 650,000 Kentuckians-whose livelihoo~de.pends on tobacco. That crop is worth $470 million to the farm economy of my State. Stat,e, Federal, and local taxes are paid on farm income from that amount plus t91e fact t.hat, on the sale of t.he finished product., Kent.uckians pay another $22,457,000 to the Stnte plus a 5-percent tax on t.he end sale price of t.he amount and Federal tax yields $59,888,000 more. Kentuckians have spent millions of dollars on health research. They are concerned about the health of the pe,ople and they are spending millions of their hard-earned dollars to determine any elements of tobacco products that. a.re detrimental to health and to find ways to remove them. This approach is l)ositive and it. is fair. I recently received a letter froln one of my constituents stressing the adverse effect of S. 2902 and I quot,e a portion of that. letter: With taxes this high cigarette consumption would decline extremely and the end result would mean less tobacco needed which would mean less money for the tobacco farmers in Kentiuky. Tobacco ia a major cagh crop to your Kentucky farmere and we feel this bill would be very detrimental to the farmers, dealers and nlnmlfnchlTPra n4 tnhnnnn nrnr711ntC Mr. Chairman, I agree. with that. stateluent. Under this bill we wonicl be requiring one hroduc.t to defray a Imljor cnst, of health re- 5carch. No other indushy has been so severely p<'nalized. I remind the "rnmilittee that the power to tax is the llower to clest.roy. The imposi- I icnl of a. tax as proposed in this legislation is so great, that. it, will de- stroy thP tobacco industl;y in Kentucky and other tobacco growing Nt.ates. Senator KF.NNEDI". would your position be the samP if it. was found t hat, cigarette smoking was thee same. kind of health hazarcl that doctors from IiF.W and CDC have testified to? Senator FORD. Mr. C1hai17nan, you can takc harm elements otlt. If vou put this kind of money in t.ha tobacco industry, within two grow- ing seasons you find the impurities and they can lie grown otlt or take tobacco to a climate where it gets 12 months of growth you can grow it out in 1 year. 117 Senator KENNEDy. That is not my question, Senator. I asked whether if you were convinced that the tar and nicotine that is in the tobacco is a cancer-causing agent and is a serious health hazard to the people, would your answer be the same g Senator FORD. I believe the people are trying to make a correction. We are trying to do it in this State and you are asking a hypothetical case. What about asbestos and brake linings Y Senator KENNEDY. It is not a hypothetical case. I am asking for the third time if you believe it? You can say they have not made the case, but if you were personally convinced that it was a health hazard would your,position be the same Y Senator t~ ORD. Senator, I would have to represent my peaple and I have to represent their voice. Whatever I beheve personally, I think the decision and the desires of the people of the State must be over- ridden. If-I cannot do that I should get out of the Senate and then take a personal vendetta against any of these various things that I disagree with. Senator KENNEDY. I want to make it clear that we are not inter- ested in personal vendetta. We are trying to find out, as far as this hearing goes, what the facts are in terms of the causal relationship between tar and nicotine and the health of the American people, and then try to impose ways and means to effectively deal with the health hazard of smoking. Ways and means have been proposed and I am sure it is not strong enough for some. The only point that I am asking you, is, if you were convinced that those scientists who are charged and approved by the Congress to study all the best scientific information relating to the war on cancer- and who were able to reach this deci- sion-lf you were convinced of it, would your positiori be the same Y But I tihulk .you have answered that. If you would like to make any additional comment. Senator FORD. Senator, you asked if I was convinced or if the case has been made. But I want to say to you, sir, that I have sonie testi- mony today from reliable scientists that will refute that statement. So I cannot say that I am convinced or not convinced. I am trying to make a point as related to the tax and what, it would do to my State. I am not a scientist. I will present, if you will allow it Senator KENNEDY. Sure. T T- ~.u .;s.~.. .. t.l~~,.r. .. ~~.L... f11CeSPri; Sr,a',enlenl;S :"rOm CtUa1hP.C. 1nC.1V1C.i1&5 that will refute some of the statements that will be made here today. Senator KENNEDY. I want to make it very clear, I want to make it very, very clear that we are not interested in putting those farmers out of business. What we are interested in is having them grow safer tobacco. That is what we are attempting to do. Now that may be pos- sible, it may not be. I have been impressed that those in the tobacco industry are. making a very dramatic effort in trying to reduce the tar and nicotine in cigarettes and then promoting them. We saw sonle cigarette advertisements in the Washington Post this morning showing the nicotine and tar content. I would just be hopeful that those farmers would be out there growing the lower tar and nicotine and safe tobacco. So I want you to understand at least what my position is as co- sponsor of that bill. Senator FoRn. Senator, I would he very sure you are well versed in the area in which you are endeavoring to enter here. But I have to re-

196 - 9 - cigarettc smoking such as blood pressure and air pollution. Some of these factors have also been subject to major control efforts which may have contributed to the decline in the death rates. In addition, there have been therapeutic advances in the treatment of these problems which may also have helped lower the death rates. A decline in male death rates from lung cancer should also follow the decline in per capita consumption. This rate would not be influenced as much by changes in other etiologic factors or changes in therapy because cigarette smoking causes from 85 to 90 percent of all lung cancer and there have been no major improvements in survival due to changes in therapy. With lung cancer, however, two additional considerations must be kept in mind. A decline in death rates from lung cancer would be ex- pected to lag several years behind a decline in per capita consumption. In addition, the decline in consumption and switch to low tar and nicotine cigarettes occurred predominately in the younger age groups where death rates from lung cancer are low. For these reasons, it is necessary to look at lung cancer death rates by age group rather than total lung cancer death rates. The lung cancer rates by age groups for 1971 s,ug%est that there may be a decline in the lung cancer rates for the younger males (under 45), buk the,confiderice I , limits on these trends at presentn remain wide enough that it is impossible to say whether this is a real decline or merely a leveling off. _The.•data by age group from a few more years will be necessary to dtermine whether the changes in smoking behavior which have taken place have reveised the tz`end of the pr`dced- ing 40 years of continually increating lung canceY`rates in men. The trends of the 9.ast few+ years "offer soine * hope that the peak of the "lung cancer epideltifc," as some have termed this ph2nomenon, imay haVe been reached and that future years will show a slow but consistent decline. Another area of concern is exposure to atomospherio e• pollution from cigarette smoke which has been referred to as passive smoking or "involuntary smokin'g." The exposure~ can be called "smoking"'because many of"the same constituents of cigarette smoke that cause health problems for the smoker sre inhaled: Work on•this problem has TIMN 450282

200 The first of these effects is the annoyance that non- smokers experience when exposed to secondhand smoke. This annoyance is often due to minor symptoms such as eye and throat irritation. The prevalence of this irritation among air travelers was studied in a survey of the attitudes of the passengers on 20 military and 8 domestic flights where smoking was unrestricted. Despite very low levels of measurable tobacco combustion products in the atmosphere of these'airplanes over 60 percent of the nonsmoking passengers stated that they were annoyed by tobacco smoke during the flight. This annoyance was even more common among those passengers who gave a history of having a respiratory condition. An additional effect on a healthy population is respira- tory infection in children during the first year of life. In a controlled prospective study a relationship between the incidence of pneumonia and bronchitis in the first year of life and the smoking habits of the pare.n -_s was snown. :-zis r2=_a-_ions-n:ip persis:_-ec. w-aen controlled for presence of respiratory symptoms in the parents, social class, and birth weight of the infants, 201 but was no longer present after the first birthday. The study was also able to establish a dose-response curve that showed an increasing incidence of infant infection with greater numbers of cigarettes smoked in the home. The data suggest that the cause of the increased incidence of respiratory infections in the children may well be exposure to smoke in the home environment. This and other evidence supports the conclusions that involuntary smoking causes minor symptomatic•irritation in a majority of nonsmokers, bronchitis and pneumonia in the first year of life, and a reduced cardiac reserve in some persons with coronary heart diseases. Additional information on such topics as tobacco allergy and the psychomotor effects of CO also suggest health effects. These effects are dependent on the degree of. individual exposure to cigarette smoke which is determined by• proximity to the source of the tobacco smoke, the type and amount of tobacco product smoked, conditions of _.a,. • . . room size and ventilation as well as the amount of time the individual spends in the smoke-filled environment, and his physiologic condition at the time of exposure. ,rIMN 450284

204 effect of the 1971 ban on electronic media advertising for cigarettes, which resulted in greatly reducing the frequency and visibility of anti-smoking messages because the "fairness doctrine" was no longer applicable. We have been failing where we had hoped for success-- with our children. Much more effective programs must be developed and conducted to reverse the trends toward increasingly younger children taking up cigarette smoking. As we stated in the Forward Plan for Health, it is not realistic to view `smok"ing primarily as a medical problem. 'it is a major social, economic, cultural,'and psychological phenomenon that has profound health implications. We believe it is more productive to focus our attention on the underlying conditions or antecedent causes of preventable diseases than to concentrate on the diseases themselves. For examp°le, by reviewing the dimension of a problem such as cigarette smoking, we'can fashion program goals and initiatives more,carefully aimed at basic causes.- In ca . . . - . 205 this case, an important prevention objective depends in part on individuals deciding to change their style of living, to stop smoking, reduce consumption, or smoke cigarettes with less hazardous contents. The question then is how to accomplish this objective. A key prevention technique is health education of the public, for much of the health risks which the individual faces today he has imposed on himself. This is patently the case with smoking. This is not, of course to say that reduction of smoking is a simple matter of more health education. Decisions by individuals to change their behavior are complex events, deeply influenced by the knowledge, values, and social ecology of each person. There is no one approach which can be set forth as a solution to the health problems brought on by smoking. We must continue to increase our understanding of underlying causes and factors, and, as a society, promote approaches which are appropriate and effective, whether they be aimed at behavioral change which leads to smoking cessation (for example, anti-smoking campaigns) or at environmental change which protects the individual from the deleterious effects (for example, less harmful cigarettes). TIMN 450286

118 rnind ti,ou that private enterprise is doing an excellent job as you have just statc'd, in reducing tar ancl nicotine. We have one brand of cigarettes on the market now that is 2, which is prohably the lowest urr the Iuarket, and this was even lower I believe than the one, the lowest pack of cigarettes that Senator I Iart presented this morning. And I wonder what kind of tax that would produce. liut if it is your intention not to put tobacco farmers out of busi- ness, if that is not your interrt then I think you ought to reconsider yunr position as to the tax on one productt rather than going through general taxes. You cannot zero in on one product and ask them to carr,y the load. Senator KENNEnt. We heard that from the catt.lemen about 3 months agCi R•hen talking about DES : Why are you singling in on this? Why ,h,n't you leave us alone and go after somebody else? 11'hat we are trying to do is look out after the health of the Ameri- Pall IK•ople. I would make it very clear that we are going to make every effort in a numbe r of different. ot.her areas to move ahead on it if we can. Ilut I want you to understand. Although I am sure it. will be difficult to convince you that we are not trying to single out the tobacco indus- try. We are trying to look at. No. 1 issues in terms of the protettion of the American people's health and if we can move in a more responsible wa~y to try and protect itr- henator FoRn. Senator, is it not true that the money you receive or exeept to receive from tax on tar and nicotine will go to research in all fields9 Senator KENNEDY. Yes. Biomedical research in cancer, heart, and luag. I think it is to be very, very useful. Senator FoRO. It is apparent that you are zeroing in on the tobacco industry. Senator KENNEDY. I.am sure you feel the importance of biomedical research. Senator FORD. I understand that. liut rather than zeroing in on one product continuously, when t.he industry itself is doing a wonderful job, even the people in the State that is the backbone of the farm econotuy which helped this country get $22 billion in balance of pay- ments last year. We just keep zeroing in on the little fellow and keel) ~ud.ting him out. of business. I am here fighting for that. individual. ~ want to lw fair_ I iun interested in research. We Kentuckipng h.nvr. IMPn willing to pay millions af dollars for tobacco research. 1'Ve are building a $4 uullion-pluti laboratory at the University of Kentuck,y. It is not sonlething new to us. Senator. We have been working at it a long tiine and have not asked the Federal Government to help find an answer. We are going out• lx•st ancl I ain trying to defend what we have la•en trying to do and rrraking improvements. Senator KENsF:ny. Senator, I think that is conunendable and I think solue uf the Iuajor tohacco producers an~l iuanufac•turers and distribu- t~~I:~ ~~f the cigarettes have (lone nn outstanding joti, but st.ill there is a ver. %•, very substantial problenc we are facinfi. Perhaps we differ in t4•rnis (If our interpretations of scientific inforuiation. tienut~~r FnRU. I think the tobacco in(lush•ies are carrying their fair slinr~•, Senator, and I just ~~•oncl~•r. a, I~aY, the ability to tax is the t,o%••et• to destroy--the power to tax is the power to destroy and I hate t„ see the small fariuc•r in my State iuid other titates Iming destroyed. 119 It will destroy the small farmers and place an economic hardship on millions. Are we taxing to regulate; taxing for revenue; or taxing in an attempt to kill the tobacco industry? Regardless of the intent, the effect. will be to drive domestic tobacco producers out of business. We will clrive more and more snrall farmers in Kentucky,Nortlr Carolina, South Carolina, Tennessee, and Maryland and other tobacco-produc- ing States out of business by imposing an unreasonable tax burden on the products they produce. The tax will not only affect the farmers, but it will also have a major effect on State and Federal revenues and even an overall economic impact at both the Federal and State levels. In 1975, $2,261,100,000 in Federal taxes and $3,284,660,000 in State taxes were collected from cigarettes alone. Further, the export valuo of unmanufactured tobacco and tobacco products in fiscal year 1974-75 was $1,234 million. This volume of tobacco is an economic asset both to farmers specifically and to the public in general because of its impact on the balance of trade. Senator KENNEDY. I want to recognize our chairman of the House Labor Conunittee and a good friend, Congressman Perkins, who is here. But I know lie has been in and left. Senator FORD. I was going to defer to the chairman, Senator, and lle told me to proceed. Senator KENNEnY. Yes. Af r. PERKINS. Yes. Senator KENNEDY. I just wanted to recognize him. You can sit up here, Air. Chairman. Senator FORD. The import value of these products for 1974-75 was $209,200,000 leaving a surplus from tobacco in excess of $1 billion. Soule States are considering raising additional State revenue by increasing cigarette taxes. This bill would preenipt an increase in State taxes planned for cigarettes because up to 50 cents per package of Federal taxes would reduce consumption to the point that it would reduce State revenues. This bill would have an extremely detrimental effect on the tobacco farmers and it would also be regressive tax of $180 a year on the 50 million Americans using these products. We would be asking them to pay the cost of research that. may or may not affect them. Are we establishing a precedent by taxing consumers to correct pre- sumed health ailments? 1Vhere would this precedent. lead us? A sugar fo.r 2fw,.r, nn iinnnln l.ivino in urha.n areas becausc: they have poor health rather than t:le afltuent? An in- creased tax on people who live in highly industrialized neighborhoods? The prrc•eclent is here in this bill. Mr. C'hairman, in Sunday's Washington Post on page B-10 a head- line stated "Male Lung C'ancer fioars ln Factory Area." The article then proceeds to state from the results of a Johns Ilopkins University study, and I quote- ' ... men living iu a certain highly industrialized area of the city. I have a copy of the article and ask that it be made a part of the record. Senator KENNEDY. I would point out, Senator. that this committee was the author of the Occupational Iiealth and Safety Act that has been in effect., and we are pressing hard on the Department to do the

206 207 - 20 - Obviously, much of the responsibility for implementing these approaches rests outside the Federal government. The institutions of society in addition to government are responsible for articulating, affirming, and conveying the human values which utlimately are expressed in the individual's lifestyles. We must, however, assure that scientific knowledge is acquired and widely made known, and that mechanisms exist for protecting and reinforcing Consumer health education is a primary vehicle for presenting and interpreting the facts about smoking, and their implications, to the public. While the Department has made a substantial commitment to health education directly, it is evident that much of the educational effort should flow from non=Federal sources through• the multiple channels available to the many persons our social concerns. Thus, the Department's prevention strategy emphasizes those areas in which Federal leader- ship is appropriate: Research efforts include biomedical investigations into disease causation; expanded efforts to find a safer cigarette; study of effective techniques to assist people to stop smoking; and evaluation of health education approaches which help the individual to make informed decisions about his own health. Research carries with it the obligation to assure wide distribution of pertinent findinas_ Th»a; not only vther researchers, but also the medical community, the public health community, voluntary societies, and the general public need to be made aware of findings on the health consequences of smoking. and groups involved in this endeavor. Regulatory programs in this area are the responsibility of the independent Federal regulatory agencies and the States. We stay aware of and cooperate in developing the labeling regulations of the Federal Trade Commission and the advertising policies of the Federal Communications Commission. State legislatures have become active in a variety of areas relating to smoking in public places, taxation, and tobacco sales. In pursuit of preventive impact, one orientation of our ec.uca':5_on strategy is to target groups. Children are the logical beneficiaries of health education, for they are not yet smokers, and they are still forming their values. The Department has made a major commitment TIMN 450287

42 VIL Orlttmal Investlntlons on Naw Antinularial Dru[• 162. 163. pa{. 9 Patholoftc physiolofy and chemotherapy of Plasmodtum herRhet. 1. Supprassion of paradtemia by sullonas and solfooarnldes in mice. D. M. Aviado. E:m. Parasitol. 20: 88-97, 1967. Patholofic physiology aod chemotherapy of Plasmodium berrh.tt lI. Ouyhamoslobin dissociation curve in mice infact.d with chloroquino-seositlva and resistant atrain.. F. Palecek, M. Pal.cekova and D.M. Aviado. F.Lm. Parasitol,21: 16-30, 1967. 164. Patholo4ic physiolo{y and chemotherapy of Plasmodium berahei. Ili. Reoal function in rats infected with Plasmodium b.rah.i. T. Kis6imoto, M. Oskoui and D. M. Aviado. Exp. Parasitol, 22: 160-177, 1968. 165. 166. 167. Patholofic physiology and chemotherapy of Plasmodiutn berthei. IV. Influence of cbloroquine oa oxygen uptake of red blood calla infected with sensitive or resistant strains. Y. W. Cho and D.M. ANado. FScp. Parasitol. 23: 143-150, 1968. Pathologic pmysiolop and chemotherapy of Plasmodium barZiheL V. Suppresston of paradtomi., diurastrd amd cardiac depression by ptsridines. D. M. Aviado, 8. Hru8ler ard J. Dall.t. Lltn. Parasttoj 23: 294-302, 1968. Patholotie physiology and chemotherapy of Plasmodtum berthoi. VL Mechanical properties and histological features of the lung. C. Sadavontvivad aod D. M. Aviado. Srm. Parasitol. 24: 313-326, 1969 ' 160. Patholo flc physioloty and ch.motherapy of Plasmodtum b.rrhel. VII. Electrocardio fram In d 169. 170. 171. 172. 173. '174. 176. • 177. 178. 179 mice treated wltk quinldina and tuantdins (ICi 3349 and WR 81, f44). M. A. Silver an D. M. A.fado. E'an. ParasitoL 24: 152-162, 1969. Pathologic physiology and rAe+aotherapy of Piasmodtum barahd. VIII. Li.or enaymes and the influence of boachloropara:ylsne (WR 17, 206). D. M. Aylado, Y. W. Cho and J. M. Smith. t~+. Pansitel. 25:2t3-290, 1969. Pathologic physiology and chemotherapy of Plasmodium berthat. IX. Gastric secretioo and the intluenco of 1-uninocyclopeotane carbosylic acid (WR 14. 997) or Cyoleuclne). D. hL Aslado and IL~. Renttor, Jr. Exp. Paraettol. 26: 314-322, 1969. , Patholofic physiology and chemotherapy of Plasmodium bar[he1 X. Pulmonary edama and saplttkoqutnones (WR 26.041 and WR 49.808). D. M. Aviado and P. J. (Ymber. Esv. Paraeitol. 26: 354-368, 196t. Antiotalar4l and anttarrhythmlc activity of plant e:3racta. 1. Cinchona and quinine in Plasmodium batthei in tmnuture rata. D. M. Avlado, R. Rosen. H. Dacanay and S. Platktn. Mod. £so. 19:79-96, 1969. Antimalarial a.d aMiarrbytbmic activity oi plant e:tracts. 2. Acid e:dracta oI plants. D. M. Avlado and H. Reuttor. MW. I5t0. 19: 9'5-100, 1969. - Chemotherapy of Plasmodium barthol. Including bibllofraphy of Plasmodturn barthei. Parasitoloftal Itadew . D. M. A.iado, San. Para.itol. 25: 399-482, 1969. . -a.,.. nf new antimalartal drugs. L SuHones. D. M. Aviado. In: Mode of Action of a_ ~... Anti-Parasitic Druts (Proceedin8s of the 3rd Tnterna.t.ona., °•_ 30, 1966). V.L 1, 1?ar{amon Praas, New York, pp. 51-67. 1968. . Pharmacolop of naw antimatarlal dru{a. IL RC 12, sodium antimony salt of aittban and kathoal-bia-thiosomlcarbaaone. D. M. Avtado, V. Marco and D. W.ad. Chemotharapy, 13: 339-355, 1968. pharmacolofy of naw antimalarial drugs. W. Sullonanddea and trimathoprtm. D. t.l. Aviado, G. Sinfh and R. 8.rkley. Chemotherapy. 14: 37-53, 1969. Pharmacology of naw anttmalarial dru8s. IV. A pipsraatna whtch exerts an unusual type of adr.ner8tc blockade. P. J. Camber and D. )d. Aviado. Arch. Int. Pharmacodyo. 183: 107- I26. 1970. Pharmacology of n.w antimalarial dru8s. Two qulnolinemathaaols. D. M. Avtado and M. Selej. Pharmacoloty. 3: 257-272, 1970. 43 page 10 180. Pharmacology of n.w antimalarial dru8s: three tuanylhydrasones. R. Rula and D. M. Aviado. Plurmacoloty, 4:45-62, 1970. 181. '. Pharmacodynamtc effects of the diformyl derlvativo of diaminodiphsnyl sullose (DDS). D.M. Aviado, 0. Marroquin and S.R. Shore. Int. J. Leorosy. 36: 432-441, 1962. 192. . Pharmacology of m.tacblorldino; with special refarenca to ita antlmalarial activity. D.M. A.i.do amd A. If.. Chemotharaoy. 13: 289-302, 1968. 183." P6armacalofy of napbthoquinones; .iith special reference to the antimalarial activity of lapinon. (WR 26.041). D.Id. A.iado and D. H. WiIL Amor. J. Trop, Mod. H.[. If: itt-198, 1969. - 1t6. Comparative toxicity of delorofuantda and nitrofuaniL D. M. A.lado, T. t.oh aad Y. W. do. TosicoL Anvl. PharmacoL l3: 22t-241, 1968. ~ 185. Compar.ti.o toxicity of ckloroqntas aY ht. //rbloro.7o-qnt.olyl-4~,).amlood~propyl/-1,4. : ptparaais. (lyR 3863). D. M. Avfado aad S. Ddlet. 7odc.1. A..L Phareaaeo~l t8t 331- 344, 1969. - - Ita.' I.Daeaeo'm! clioroquimo and pheaaatbrans methanola (WR 33.063) oa cp.toat of klopMc ~A ' anoL.a tm tIIo mou.o lua2. C. Sada.onfyi.ad aad D. M. A.iado. Mlltt....b.d. 134: 1106-1118, 1969. 187. Cardiopulmonary offects of aetlmslartal drufs. L 4-aatl.oqulnollnos: chloroqutno qalaatkoLt D.tt. Avtado, Cq Sadavorg.irad ard P. Camber. To:dcoL A~L PhartoacoL 17: 107-117. 197 Ift. . C.rdlopulaionary ogocta od.ntlmaLrfal d -t - A(. Eo1o sad D. M. Aslado. ~a• D' R. Ruts, - f TotdeoL Am1 pkarrsaeo~l 17: llt-t29, 1970. . ~ Cardlopulmoa.ry effects ot anHmalartal dru8s. III. Dl.mtmopyrlaShcaas: Trlmettw rlm ' (yIR 5949) and 5-ptparonyl-2 4.dt.mi p ~ 190. no Oe (~ 40, 070). S, ktat..o, R. Ruta, J. fmlth, Jr, and D.Id. Aytado. T p~ 9alcoL Aonl. Pharrnacol. 17: 130-150, 1970. Grdl°Pol~ry •Docts otantlmalartal drufs. IV. Toreplrthaltc acid aad Ita dl4ydroamine dorhativo (wR 74, 106). L-O. Grlps, P. Ruia and D. M. Avtado. ToaicoL AppL PharteacoL 18: 469-4t6. 1911. - 191. . Cardtopulmnnary dlacts ot antivtaarlal druss. V. GyclopsanD and a m.w trladno onmpo0d - 1wR 99, 662). R: Ru1a.. B. 0. Grips and D. M. A.fado. Toxieol AooL Pharmaco~l lt: 487-497, 1971. Card(opalmooary Kfocta of antimalarial drofs. VI. Adanoalno t a:1' t:" . , qu erlao and n, a prlmaqsine. 8. Das. end D.M.A.lado. Teodcol. Aonl. ptat'maco1.21: 464.4t1, 1972, 197. Cardtopnlmonary oK.cts o! antimalarlal drofa. V D. Coronary wscolar .Hoeta of -. ,.. .. p rldo utnolln. MAR y q .. amlraa Jd D ..,. Drimal at.M. Ayledo. Tosacol. Aool. . Pbarmacol. 21t 4t2.494r 1972. TIMN 450205

202 - 15 - DEPARTMENTAL POLICY It has•been over eleven years since the report of the Advisory Committee to the Surgeon General in 1964 noted the relationship between cigarette smoking and excess disease morbidity and mortality. This relationship has been further reviewed in nine PHS reports on the Health Consequences of Smoking. The statement--"Warning: the Surgeon General Has Determined That Cigarette Smoking Is Dangerous to Your Health"--has been required by law on cigarette packaging since 1970. Yet today smoking remains'the largest single urmecessary and preventable cause of illness and early death. Cigarette smoking by adults has changed markedly since 1963, when our highest per capita consumption rate was reached. Since the release of the Report of the Advisory Committee to the Surgeon General in 1964, per capita consumption has dipped to below 4,000, and has not returned to the 1963 level. Moreover, current ciqarettes contain much less "tar" and nicotine (and less tobacco) than they contained a decade ago. Eighty-six percent of the cigarettes sold in 1974 were filter tipped. At the same time, because of our expanding population base, 203 the total sales of cigarettes has been growing slowly but steadily. Although still not a satisfactory situation, this reflects real progress in the face of tremendous advertising pressures, cultural factors, peer influences, loss of respect for authority, and many other important influences. The merchandising of cigarettes has exploited the interest inriev lifestyles.equating smoking with independent, secure, self- confident, sexually adequate images. Also, youth's concern for ecology is manipulated by advertisements showing clear blue mountain sky, the Grand Canyon, leaping wild trout, yet at the same time, rarely showing a puff of cigarette smoke with the product. This year, the dollar volume of cigarette advertising will probably exceed the pre- television ban expenditures of $300 million. The American Cancer Society has released (February 1976) a study on the smoking behavior and attitudes of teenage girls and young women which indicated that 87 percent reported in ~ oGO Fw~, ~s - '-~ - ...... _.••.._ _.,....r .,.•~::~• or ..iearcc an antismoking television commercial in the past month; currently, only 48 percent have been exposed. This shows the TIMN 450285

W 8tst.e.ent by Senator ifindsll H. Ford lebruary 19, 1976 lags 2 124 Nr. Chairwan, in Sunday's "Washington Post•on Page B-10 a headline atstad. 'Nale Lung Cancaz Soars in Factory Area.• The article then proceeds to stsN from the results of a Johns Hopkins University tudy, and I quote: ..rn living in a certain highly induatrialized neighborhood of Baltimore had a lung cancer rate four times that of a demographically similar group of rn living in a non-industrialized area of the city.' I have a copy of the article and ask that it be made a part of the record. In the January 26 issue of "Nsvsreek" on Page 65, we find an interesting chart entitled, 'Cancer and the Envirorumente Ten Top Susp.cts.• I sttb•it a copy for the record and ask that it be made a part of my rerarks. Among the suspects listed are Arsenic, found in mining and etaelting industries; Asbsstos, fros breaklinings, construction sites and insulation; and other substance fros alsoat every type of industry and segment of our environment. The "Newsveek" extract lists the Ten Top Suspects of Cancer and I saa no effort to require the other nine to share in the cost of health research. This bill has ingled out the tobacco industry as though it in the only suspect and proposes to impose punitive taxes to cover research on all suspected causes. I as extremely concerned about the health hazards and the need for research to find ways to prevent cancer, and in fact, all dreadful saladies. I am concefned about the effects that tobacco may have on health. I supported the establishment of the Tobacco and Health Research Institute at the Univer- sity of Rentucky to study the effects tobacco has on health to determine the iwpurities and to find ways to remove them. I recognize and support this effort, but I find no justification to support a tax based upon tar and nicotine content in cigarettee. Recognizing that I do not have a scientific background, I posed this question to three iszninent scientists and asked them their opinion about it. The scientists ares Dr. Charles H. Hine, The Hine Laboratories, Inc, San Francisco, Californiat Dr. Pnber~t C. Hocket Research Director, The Council for Tobacco Research--U.S.A., Inc., New YorkT and Dr. Ronald Okun, Dirsctor of Clinical Pharmacology, Cedars-Sinai Xedical Center, Loe Angeies, California. I ron't bother the members by reading their statements, but each of thea indicate/that in his opinion, no scientific basis exists to levy a tax based on tar and nicotine in cigarettes. I will ask permission to place their responses, qualifications, and list of publications in the record. None of thesl support such an approach. I have tried to be objective in my evaluation and I find no justification from either an economic or scientific standpoint. Mr. Chairman, I ask the members in their deliberations to consider the aany dollars that are now spent on research, the precedent that this bill aet and the detrimental effect that a tax of this magnitude will have on illions of small fars+ara whose livelihoods depend on tobacco. 125 Ibxuvnn•< um 4xlon w play :1 I+art in hra•nrl r•4uarr w+d lhr ulrn•ut ,u.pl. inu i, th.41 f b nwy u.•a•r.tnu4J:ala• I"uuxm.' ' xhn~u,rn r.r 4liauld n..n+cll lu•rnxn.r '',7:.+ xh l+~tunl n rLm•d h. dn• J.•v.'Inlxn.•nt ul a•.nw,n ui thr 4 n.ll+,. rhn>:d. r.:•pllapn,• 1:4n n< and 11.'•~r Itnt lhr, i.t: i>>;rrut••.t:wwn, In'•IVV dl inl.,'r. hu a1.n,lmukr• Itialn _ ri•.• a• llu' L-h•d lh.d nk +hnt 6. praarau,+crn.:h~liuK in xiJnw1ir/11 wldl lnlah•n lnlain•'/4n,. A14x•nt( nn'll n'Ixl (16,4. r)wr/r rhall .4 ulax'r Inul a Iclll ul li.yulr4l tia), IIu~ nlo/blily Innw n1.J aancrr i> hcu U. <i< tinun ~ul.•r Il>.+u il i. inr ta•a•tnWh drp•Ix1:nC• in di1rN pl ,~.rtim41 dw• unNn1111thcy+rv4udr• iLrhl'.IV)'llri~l.•r• ,nIJ mlwdcrn, Ihe ri,k I. up In Rfta.•n tin+e<hfxlwr lFwn fur rh•••r ulul rn•idn•r 1 ..,•,.nr,:._nul.a•iRhaJin. dlinkn.rcsuu.kr. ~'«~.. ~ . It.,l.n ••.. •n•L,prtnll..,nnwayr'pu..din.un.rr MLWC/'NR 2. DRUGS nx+n- ~~~III VVV-+UU1 4.•rl Jlxw4l Uw r:nn.~r Ix.~ 1.-nv.d l1-A b)• Jlu- tlwu Ih.y :ur wlxxu 1+.x11nhliliv•a, Iw•aau..- Ih+n^• Iw rrtun•rly Imlµ drw•, A arll.+iu.:uwrr rl.k.imaxlwa:nrs,nl.r>~L• bt 111•. w•rk+uau•„ of Un• J-.+naL-I IIn (Irlll i, lL'.i;n~µYl W 4rJt,>.r IJn, nln,t L.+iJna• 1ha• Ix•nrhr ucalu.l ll,~ 1 i<l. f hn• nl dn• nlnd di.huh- u411 liwl. IN•tWrul, a aI(4/~ a1nl fana••r n A. Ilu• Iliacv.'.•a) rn 1971 IhJ Uu• alwwalrlrra ul au' < I t/x•k IIM a)Idhrln ealrn- p.•n d'u'th)istillu••trul (UI•a) in e.nk Imwrre slnlwplihla• tn An uhrw f UI rJCillal aanc.•r Ilx/<. Rlgc 66). Uliti u a. xiven lu Ilxwl<.wds ul wouwn u01~1 11S+rIJ \Yur 1t ml Ox• Ibrnry tl-.lt it oldd n •nt mia,uriayt<•. \lurh IJlrr, Ih. Au~lnr 1.. lfed•.t and hi. a<dl.•agw•< u1 ~IJ.,.x•hu,r.•tts Crm•ml Ifn<pWal rn. an+lu4~ra~.l w•crn )+.uuR wmin•n uilh a r,1y~11rJI .ah•IIM'Mrt'In:m+n•:1 Jial'J,.• Ih.41 i< ma•nllyr ur,buth:uLdnnl,tu.•rcrim~f•nr Ix'•~u Mm+d in u uo~n,u. ulnk•r thr.4C.• •d 50. Cimr li.y; thr uwdir:d hi.tnric,• tla dlxp•I,hN111fI11n11Jllllh•IrpJIN'lllj ehNa- lN• ILnI 41<.VI UI'.S in Ixly;Iwllq'. ShMr tl.d iniliul n•p.n, uxxe llulu c250.hnilar aJ•<Il.mc Ix•ru akx unwmrd. lhnr rl •a•nlly, ,rvrml xhulin hlvr ,nlq' •.Irvl t1 ul thr u>r uf e.tmxras by uli4kllr..y,rJ avnlu•n an idlrvide aynqr tom, nf Ib,r uwlwpauxr hn'rcaeet Ilwir tirlelull•ILwacunrr Nnr.•ara•henatlba• U ivrr.ky af \Vnahinpun4 mpurtal thn lM• dak uf r.uurr w.n nrad,r fivr Ilnrl•< hiKl.•r urnlmx c•nnwn ..hn twlk the lnmww4r> 16.u1 amunx Ih:.a• wllu rlid+i t. .1 nwJ..r u nrrul.,•d qnr>tf.m i, whrllr a•r Ih.• hidllraulrnl piil-t.d.•u b) lo nlilliml V 4 n--:dv.l +arsueaura-r Ii l In••.p-iuu•n•.danim:Ja,rrlrnArn<, c.ili, h m•• ...... wlwnt nf the pTll,, lco.• 4i i:;AfvC_fi AND THE ENVIRONMENT: TEN TOP SUSPECTS i SUD5''AYCES I WHER FOUND • CANCERS THEY MAY CAUSE ADSEqIC aSDESTOS .n•EN2ENE flENZ10)NE- _ O'ri r'Id^IISlI1qIPNODUCTS X ., :-I LUtarf.ONO$ RADIAnnN t.hn,w•,.+ndsm nng,ndusn,er l4•,•w,•hnl p!, ')IruCliDnfilH. niwlalwnr_pGr.•erhCUfas -Solranl :, tn7 relmenn• in•xel.rr:ff iWbbe. mxltln!7. dy.+tults---'-' Slr•./ m•II<, p• IruChamical indur:.ry, a<n11n11• rnnl lnt Ut6"-del tay, 1rom Ih" >un. mtr~lirallh.raUr _ Skm• wnp li..r _^ Eung.oteure.pe•nw1- eCMmMrmv _.•- - BlatklMr - -- tun4,l+lidJe.- s:rnlnim lun 1. n n.+l >im.<+s aUnr mJatMV, aMin Ihyrda . I:+D IIr, EStt10CEN5 I Pu•1••/.'1 SraORE I p.pa.. eqau- - -- l o bl,dn•,, mu •h. r.uphJnu<. p+aryn.. l.uyn. LIpI101DE ......... .. 1 .o. •••1.1t •:Il..lp -i61••..m•mr._h.n••Ix Ili•1••n+in•.I..p+rn.ntnh,IJne.rnu. 9.5 TIMN 450246 I

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151 populations. 11ar can we determine whether these differences are thenselves assoeiated with disease predispoaitions apart tYm sesoking. 1Fleverthelese, wherever such differences have been explored at the levels of pereonality, body bvild, electroencephalography, style of life, vocationa7.interests, or psychological make-up, they have been found to be real. It is important to look for sti11 other differences acd especielly, in each case, to find out what, if any, relationship the differences th®selves or any associated differences in heslth may have to the C[irEtICUW1 VITAZ OF lEt. ROMT C. R9CEUT Dr. Robert C. Hockett, Research Dixecter of Tha Council for Tobacco Research - U.B.A., Ino., 110 East 59th Street, Nev York, Rev York 10022, xas born in Fayette, Missouri on Jhily 1, A graduata of the Ohio State University, Dr. Hockett pursaeQ graduate study In the sasos institution and receivedtha Ph.D. degree In chemistry there in 1929. As a Aatiopal Research Couneil ?ellow ia Chemistry, he eas*a guest scientist at the National Institutes of Health, U. 8. Public Health Service iro. 1929 to 1931 and then Associata Chemist on the Institute staff 1~ 1931 to 1935. 'In 1935 he Joined the faculty of the Massachfuetts Institutr of practice of smoking. In view of these unresolved probleas, it is obvious that epideslological studies have not, and cannot incriminate specific components of cigarette smalce in the causation of husen disease. Neither these epideai.ological studies, nor animal and clinical studies, have identified any ingredient or group of ingredients as found In smoke as disease producing in humans. In conclusion, it is mpr opinion that there ie no scientific basis for selective taxation of cigarettes, based upon their yields of "tars" and nicotine. ~-..~-- ~•13,1976 Technology as Assistant Professor of Cheaistr,r, becoming Associate Professor in 1941. . i . In 1943 be was granted a leave of abience from 11.I.t. to serre as Scientific Director of the Sugar Research Foundation, Ina., r6ieA position he occupied until 1952. Re,haa also beea Visiting Professor at the Universities of I113nois and North Carolina. From 1952 until 19% be served as a consultant to indostrial firms on problems relating to foods, saitrition, pharmacauticals, fermentations and sponsored research. In 1954 he Joined the present Couneil*fer Tobacco Researcb's predecessor organization - the Tobacco Industry Research Cesetittea - as an Associate Scientific director. Dr. Hockett Is a Fellok of the American Acadeq of Arts and Sciences, the Aer York AcadenV of Sciences, the American Public Health Association, the Royal Society of Arts, and the American Institute of Chemists. He holds nenbership In the Fsiericen Chemical Society, In which he has served as aa l+ltercate Cot ncilor, cs.r.:ber of the ::oxen- clature Ccr:?ttee, Vice-C'r.airnan of the Division of Carbohydrata Cl:er.+istry in 1944, Chairman in 1945 and 1946, and Secretary-Treasnrer from 1956 to 1960. He also holds meebership in the American Society of Biological Chemists, American Association for the advancement of Science, Friends of the World Health Organization, Royal Society of Health, and the Phi Beta Kappa Associates. ?, t '.u u : i arrn-. as a:.ec :urer :.n hwiNtserland for the American- Swiss fioundation for Scientific Exchange, member of the Food Industries' Advisory Cmittee to the Nutrition Foundation, Inc., Collaborator to the United States Department of Agriculture, member of the Advisory Comittee for Advances in Carbohydrate Chemistry, as Associate to the State Department's Ces®ittee for Interamerican Scientific Publication and member of the Sugar Advisory Ccsiaittee to the Administrator of the Production and Marketing Act, U. 8. Department of Agriculture. He is author of numerous research papers on cheniistry of the carbobydrates, of articles and lectures on nutrition and public health, of many revies+a and sumoaries on tobacco and health research and contributor to a book, Beet Sugar Beoanos+ics. TIMN 450259

208 I to improve the health of the nation's children. We believe that, if they acquire, through school health curricula and other information sources, an under- standing of their own bodies and the influence they can have on their own health, and adopt positive concepts of self-dignity, self-appreciation, and self-help, the probability they may not elect to smoke will be greatly enhanced. Achieving all these results will take time and diligent effort, but if we succeed they will be well worth it, in human as well as economic terms. . Thank you, Mr. Chairman. My colleagues and I will be happy to answer any questions you and other members of the Subcommittee may have. 209 DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE OFFICE OF THE ASSISTANT SECRETARY FOR HEALTH WASHINGTON, D.C 20201 APR 0 E L976 The Honorable Edward M. Kennedy Chairnan, Subcommittee on Health Committee on Labor and Public Welfare United States Senate Washington, D. C. 20510 Dear Mr. Chaireoan: Thank you for the opportunity to review the testimony presented by rapreaentatives of the Tobacco Institute at hearings held on Cigarette Smoking and Disease on February 19. Staff of the Center for Disease Control and the National Inetitutes of Health have reviewed the testimony. A protocol deacribing the procedures employed by the National Clearinghouse for Smoking and Health (NCSH) in collecting, analyzing, and disseminating acientific information on smoking and health is enclosed. Every effort is made to obtain copies of published results of all research conducted in the United States and other countries, and to interpret the results cited in the articles as objectively and accurately as possible. The allegation that the Clearinghouee has omitted approximately 1,790 articles is erroneous. The list was presented in t1Hearings Before the Consumer Subcommittee of the Committee on Commerce, United States Senate, 92nd Congress, Second Session, on S. 1454; February 1, 3, and 10, 1972; Serial No. 92-A2; Pages 483-592, 729-776. The facts are that many of the 1,790 articles are among the nearly 24,000 articles assessed by the Clearinghouse's Technical Infomation Center since its establishment in 1965; many were reviewed but not deemed adequate for citing in the Reports; others were not included in the collection because they were not concerned with smoking and health. As you know, the Advisory Coaaittee to the Surgeon General, appointed by the President in 1962, conducted an intensive and extensive review of the wrld' scientific information on smoking and health as the +-.__'._ ..- `.t~. ... . _ _-._._,,. ..~....... .~.7 a 11M..L~..,~ .,~A ..lth . Rannrt ., .. •._,. • . ,. „ ..., .......f... ... q... of the Advisory Committee to the Surgeon General of the Public Health Service.tl The Tobacco Institute, Inc., participated in preplanning of the report and was provided a veto of any of the scientists recoe,- manded for membership on the advisory committee. Particular care was taken to eliminate the names of any persons who had taken a public position on the questions at issue. i1e have conscien- tiously attempted to maintain the integrity and scientific approach TIMN 450288

4 246 -3- induce increases markedly as the period of exposure to a chemical getslonger. Cigarette smoke acts in exactly the same way. It contains mutation-inducing chemicals, and can be shown to cause cancer in experimental animals; in man the lag between beginning of smoking and the appearance of cancer can be thirty, forty years. The action of smoking is cumulative: doubling the number of years one smokes increases about sixteen fold the risk of lung cancer. The evidence unambiguously shows that lung cancer is a prime example of a preventable cancer, caused by a clear:y identified and unessential agent, cigarette smoke. Why is it then that US governments have done so little to discourage smoking although they have very actively fought other dangerous drugs? Is it because key people in government have doubts about the evidence on the hazards of cigarettes? Certainly interested parties make every possible effort to create such doubts. But surely the government has means for getting to the truth, thus fh,n rr~~.to.l tobacco brings in revenue? But it is a gruesome revenue, based on the disease, death and great suffering of many people, and, anyway, probably outweighed by the costs of lost productivity and medical care. Or is it because powerful interests have their way, irrespective of the consequences? No matter what the cause is, it is a great failing of our society that so little has been done to control tobacco smoking. TIMN 450307 247 -4- Considering what the government might do to alleviate lung cancer, one must keep in mind the consequences of the cumulative effect of smoking. One consequence is that the long lag between beginning of smoking and the appearance of lung cancer gives a false sense of safety to those who begin smoking; a second consequence is that the reduction.of lcancer incidence in those who give up smoking is slow, producing values close to that of non-smokers in not less than ten years. Another consequence is that the age at which people begin to smoke has a dramatic effect on the later incidence of lung cancer. 1:'or instance, those beginning at 15 have a five fold higher incidence than those beginning at 25. All these facts show that cutting down the number of years one smokes is, next to not smoking at all, the most effective way to alleviate lung cancer. In my view legislation is needed to alleviate the health dangers of tobacco smoke, and should be based on the following concepts•- 1) The main thrust should be to convince young people .:uii`.a'J".e program o,: ec.uca.'ci.on directed at breaking the chain of events which give a status value to cigarette smoking. At the same time there should be a complete ban on any kind of cigarette advertisement or promotion, otherwise the truth about smoking would be submerged by the clever propaganda glamorising this dangerous habit in the eyes of the youth. 2) Since any shortening of the time one smokes will be very beneficial, efforts should be made at inducing people to quit smoking, even though they hxve already smoked for a long time. That quitting is possible has been shown by 30 million

244 Statement on the health hazard of cigarette smoking to the US Senate Health Subcommittee R. Dulbecco I am glad to have the opportunity to appear in front of this subcommittee to discuss the health hazards of cigarette smoking, because this is an issue requiring both scientific knowledge and governmental action. I think that in the past there has been too little cooperation between scientists and government on issues which, like this one, can improve the welfare of society; but I hope that this attitude is changing on both sides, and that my presence here reflects such a change. Among the health hazards of cigarette smoke, I will concentrate on lung cancer, which is within my field of competence. The disease is essentially incurable and can only be alleviated through prevention. Prevention has great value in most cancers, because it is now clear that 80% of all human cancers are due to environmental causes, such as what we eat, what we drink, and the air we breathe. The case for prevention rests on the public health experience with infectious diseases during the last century. ' In fact these diseases have been controlled mostly by preventive measures, such as hygiene and vaccination, and very little by therapy. Preventive measures are aPAica e to all env:rn,,,-,o..F.i Ue most effective for those cancers whose agents are known and are not essential. The cancer of the lung is by far the most com:non cancer of the latter type; the agent, cigarette smoking, is known and is not essential to life. Hence this cancer should be completely preventable. The fact that it has not been prevented, and that 245 -2- sixty thousand Americans are killed by it every year must be squarely attributed to lack of adequate action by the government, and its failure to heed the many calls made by responsible scientists, over the last two decades. As a cancer researcher and as a medical man I am shocked by this lack of action, and I question the credibility of the government as a promoter of health. However, I hope that the government will now take a firm stand, implementing measures suitable for stamping out lung cancer and other diseases caused by cigarettes. The world is looking to this country to lead the way by adopting strong and effeCtive measures. In order to understand how cancer prevention can be mounted, it is important to understand that cancer is a disease of the hereditary material of the cells of our body, which determines all the properties of the cells. Cancer-inducing chemicals cause damages of the hereditary material, called mutations, which in turn change the cells. However the change to cancer requires several mutations and other events in the same cell; therefore in the early period of exposure to a,cancer-inducing chemical, mutations occur but remain silent, i. e. the cells stay normal. In experimental animals cancers begin to arise inna after exposure to a chemical has begun; in industrial cancers in man the lag can be twenty to forty years. Silent mutations persist in the cells and can cause cancer at a later time, even after the cancer- inducing chemical is withdrawn from the environment. Accumulation of mutations in cells of the body explains the cumulative action of cancer-inducing chemicals, i. e. that the number of cancers they TIMN 450306

248 Americans who have done so in the last twenty years, since the dangers of smoking became known. However, many more still smoke. Further progress requires more education, suitable facilities, such as specialised clinics, and possibly compensation for lost income during the treatment. 3) Since, in spite of all efforts, many people will still smoke, it will be imperative to promote the adoption of less harmful cigarettes. This requires in the first place a determination of the hazard value of a given type of cigarette, on the basis.of the properties of the smoke. A recognised measure of the cancer hazard is the amount of tar in the smoke. However, reduction of tar must be accompanied by direct evidence that the mutation- inducing activity of the smoke and its cancer-inducing activity in animals are also reduced. The tar content if backed by the biological tests, could be used to determine the cancer hazard value of each type of cigarette, taking something like 30 mg as 100%. It may be useful to prominently display the hazard value on cigarette,packets. Of course, other hazards of the smoke, such as chronic bronchitis or heart disease, which derive from other constituents of the smoke, must be alsb evaluated. Cigarettes with reduced tar have been on the market for almost 20 years. Smokers who adopted them have suffered fewer lung cancers but still four times more than non smokers. Therefore a further reduction of the cancer-inducing activity o:: ciigare::es musl> >e attained. Considerable pressure must be exerted in order to ~ promote the development and sale of the least harm.ful cigarette, 249 -6- for instance by imposing a new heavy tax on cigarettes, proportional to the hazard value. The usefulness of this approach is indicated by several studies showing that increasing the cost of cigarettes decreases for a while their consumption. In order to sustain this reduction the tax should be increased gradually by a certain amount every year. Moreover once cigarettes of low hazard values have been successfully marketed, those of higher hazard may be banned altogether. The new tax would yield new revenue, very large at first, but subsequently declining, which could be used to support the proposed program and the necessary research, and if• necessary, to subsidise the necessary changes in agriculture and industry. The program I have outlined would require the formation of a special agency to implement it, to determine standards and to monitor its effects on the basis of the results of epidemiological studies. TIMN 450308 70-087 0 - 76 - 17

262 Statement for Hearing on the subject of "Cigarette Smoking and Disease", February 19, 1976, of the Subcommittee on Health of the U. S. Senate Committee on Labor and Public Welfare. Howard M. Temin American Cancer Society Professor of Viral Oncology and Cell Biology McArdle Laboratory for Cancer Research The Medical School University of Wisconsin - Madison Thank you for giving me the opportunity to speak with you on this topic. My point of view is that of a cancer researcher who has been working for the last 20 years with RNA viruses that cause cancer in chickens. Since the early years of this century, it has been known that viruses cause cancer in chickens. In more recent years viruses have been shown to cause cancer not only in chickens, but also in mice, cats, and even in some primates. Therefore, it was a reasonable hypothesis that viruses might cause cancer in humans and that, if a human cancer virus existed, it could be prevented by a vaccine as so many other virus diseases have been prevented. ... .,t :?rc hwo lnd tn an iindprstandina of much of the genetic basis of how viruses cause cancer in animals, namely, by adding their qenetic information to the DNA, that is, the genetic material, of the cell. With this understanding and the tools of molecular biology, it has been possible to look for viruses potentially 263 2 preventable by vaccines that might cause human cancer. Unfortunately, I think we can now conclude that most human cancer is not caused by such viruses. Scientifically this conclusion Is an advance, for science progresses by disproving hypotheses. But, in terms of preventive medicine, I believe this conclusion ends the hope for a vaccine that would prevent cancer caused by viruses. Must we, therefore, give up hope of preventing cancer? No. For in recent years, the hypothesis that chemicals and radiation probably cause cancer by mutation of the cell genome has been strongly supported. Furthermore, epidemiological evidence has shown that the incidence of human cancer is not the same In all parts of the world and in all population groups, but that the incidence of human cancer varies from countr~ to country, region to region, and population group to population group depending on the nature of the environment. Therefore, there must be environmental features that play a determining role In the formation of human cancer. One of the most clearly established of these environmental features Is smoking, especially cigarette smoking. Cigarette smokers not only have a much greater probability of developing lung cancer than do otherwise similar nonsmokers, but the smokers have a greater probability of dying from a number of other diseases. Therefore, our best present hope of preventing cancer does not appear to lie in a vaccine against viruses, but in removing or reducing the levels of chemical carcinogens from the environment. The single most important source of these carcinogens and the one which should be most easily removable is tobacco, probably especially TIMN 450315

264 3 the tars from tobacco. The American Cancer Society estimates that the life expectancy of a man of 25 who continually smokes 2 packs of cigarettes a day is 8 years less than that of a 25-year-old nonsmoker. Stopping cigarette smoking would have the greatest effect on increasing life expectancy, but, if that is not possible, reducing the level of tar from tobacco would at least serve to reduce the cancer risk of smokers. Therefore, if a tax based on the level of tar and nicotine in cigarettes decreased the amount of exposure to tar, it would help to prevent some of the cancers which otherwise would be caused by smoking. However, further research is still needed on cancer and other diseases both to help prevent those diseases that are not caused by smoking and to help cure those diseases that cannot be prevented. For example, we need to develop better therapies for cancer based upon an understanding of the differences in biochemistry and control of cell multiplication between cancer cells and normal cells. Comparison of virus-transformed cells and normal cells is one of the best systems to find such differences. However, we must try even harder to prevent cancer before it starts, since so far it has been difficult to find many biochemical differences between cancer cells and normal cells that can be exploited in therapy. For prevention, we must devise better methods of testing for factors in the environment, including chemicals from industrial processes and possibly food additives, that can cause cancer, and after we find these factors we must try to remove them. In addition, we must try to understand more of the mechanisms by which chemicals and radiation cause cancer in the hope that such knowledge will make it easier for us to recognize these carcinogens and perhaps to devise means to prevent their 265 action. However, when, as in the case of smoking, we find that a carcinogen exists, we must act to prevent it from entering the environment. From the point of view of a scientist engaged in cancer research, it is paradoxical that the U.S. people, through Congress spend hundreds of millions of dollars a year for research to prevent and cure human cancer. But when we can say how to prevent much human cancer, namely, stop cigarette smoking, little or nothing is done to prevent this cancer. In fact, I believe the U. S. government even subsidizes the growing of tobacco. As I said at the Nobel Festival banquet in Stockholm, I am outraged that this one major method available to prevent much human cancer, namely the cessation of cigarette smoking, is not more widely adopted. I should also like to comment on a possible large increase in funding for biomedical and other health-related research. At preserit the U. S. system of support of biomedical research and the results of this biomedical research are the best in the world. Therefore, we must be careful before undertaking drastic changes in the way we fund biomedical research, and we should especially be careful to ensure that quality is stressed in all biomedical research. An excellent way to insure this quality Is the system of peer review of grants used at NIH. Furthermore, although at a particular time we might wish to work on a particular problem in biomedical research or solve some health-related problems•, if techniques and theoretical knowledge are not advanced enough to supply a proper foundation for the research, it may not be possible to approach such problems. Nature yields her secrets slowly, and only when a proper foundation of previous knowledge exists. Therefore, I wonder about the 7U_U97 0 - 76 - 18 TIMN 450316

170 Ilo ran»('t P'tt anythint* else on tllat. little toLac•co patc•h, or find ;cnc~lhcr crc~P fO1' hi5 farm, that will give llirn the inc•oule llc rul get f1,011i I,iil•l(.y tobacco. '1'o be realistic, we must accept tile fact that, lle c•ithcr r,(ises hiu'Ic;y, or he goes out, of farming anc] onto welfare. tic) sniuc thongllt onghtt to ]x' given to these people also-the families who hoii'c' raisecl this crop since before we ever becanle a nat iou. We aI,;,, „iit.htt to give some thought. to their c•ormnlmities, and what. hap- I,c.iis to those coiunlunities when the economicc base disappears. I have not. heard any supporter•s of legislation which would (lrive these fclrwer;5 ont" of business offer to ]lelp get. factories transferred out, of Iheir titates, and down into the tobacco areas, so that tile people can hrcve jobs. Senator Kr:NNF.nI". We have. not got many lc•ft, Congressman. All'. PF'.RKINS. Well, you have considerably more than we have, tienator, lett tile put, it that way. We should also look at. the entire conc.eptt of taxing a specific produce hecanse of the uresunlption of its effect on health. I)oes this nlean that ('onf;ress will be studying bills which put a tax on bacon, based on the amount of nitrite. it. contains, or that. we should put. a tax on other meats which contain nitrites? All of rts have • heard of tile danger to health creatcd by nitrite, and I have to wonder if aucyone has t.hought, about. the relationship between c•onsnnption of nitrite l~y the public, an(1 the nleat. industry. All of us are also aware of the terrible damage done to health by luollnl ion which is in tile environmentt of all of the cities of the country, created by auto exhausts, or by factory emissions. Uranium debris is a lcrions problcm and t.housan(ls of acres of the 1Vest are polllrte(1 by it.. N'orkers in specific industries arestricken hec•anse of c•er•taln chenlic•als. Shonlcl therc be a special, extra heavy tax on asbestos because it has Imcil shown to cause can(•er amon,- people who are unfortunate as to liax•e to work with it.? Should tlleree he an extra-heavy tax on copper prucluctti because c•olllrer smclter workers get severe lung illnesses at nrlnV t icnes the nornlal rate? '1'll,ctt is tlle direction this legislation heads ns, and it is the wrong (I i roct ion. I woiil(1 like to say to tlue c•omulittee that, ('ar•1 Perkins will support ex•(•ry progranl you pro(lnc•e that is ccstt;nec to improve : le lea°,t.l o-' IIu, :\nierican people, but. I cannot. suppor't. au,y legislation which singles out sul incliviclnal t;roup-such as srrlall farmer•s in Kentucky- to bcar a hnrclen which all taxtrayer•s shonld share. 'I'hiti couiinittce ought to stop right now, ancl rethink what it is dccing. I ani afrai(1 tllat if yon (-ontinne in t.he clirection of this let;isla- t i(» c)•cui will set hcaltll care hack, not advance it. Aiiother exanl]>lc. As I lrointcd out, c•opper snlelter workers who hreath cu•scnic get Inng cancer at two to eight times the normal rate. .\gain, the frequency of lnng c•ancer aniong coke oven workers has incrcas(•cl as muc•h as 15 tirues, more than 30 percent as nmch as the ashestos workers. In this regard medical tmrioclicals in 1975 quoted several doctors from leading hospitals in the country reporting that asbestos workers sccm to pass the risk of lung cancer to their families who do not work in the factory. 171 Senator Kennecly, I appreciate the opportunity of being here. I just left ('ont;res.5man I)ent., and he asked me to put in an appearance likewise for him because of tile tobacco growing in his State. I just feel that, it. is not. fair to take this approach. As long as it is legal tc smoke it. is the duty of all of ns to try tA) find out and do something abont, the causal connection, if it exists, and nlake a determination where that cause is, if it. is in the growing, or if it is in the manufactur- ing, or wherever in t.he prcx ess. I think that. is the way that we shuuld proceecl. Then we Should accept these research findings and legislatc orl tlle research findiuf,•s and not take an arbitrary approach. I thank you very much. Senator Kr:NNFns-. I want to thank you, (Iongressman Perkins, fot ,yonr statement and comments. We are always glad to have thenl. We appreciate your being here. tienator SrrrwFIxt:R. I want to say, too, ('•ongressnlan, we are glad tc have you with us. 11'e enjoyed working with you in the past an(1 will in the futcu•e.'1'hlulk,you very much forc•ominh over]lere. Ai r. PraexlNS. Thank you very much. Senator KN NNr:rn-. Senator Morf;an ? STATEMENT OF HON. ROBERT MORGAN, A U.S. SENATOR FROIti9 THE STATE OF NORTH CAROLINA Seala.tor Moec;AN. Mr. Chairman and gentlemen of tile committee. I is really not, possihle for me to express to you the def,re,e of concerr t.hat, I experienced when I read of tile introduct.ion of this bill, S. 2902 1 think my real shock came. when I saw that S. 2902 attempts to dc something over and above what. C,ont;ress has previously aut.horized ir t.he <u•ea, of bionmclical and behaviora.l research programs and that, th- hill at.tempts to do it t.hr•ough t.hc imposition of an additional tax o $9.3 hillion which would 91e levied only on one segment of our societ• and this is the (it) million users of t.ohacco prorlucts. Now tho total health research and development commitment in th- iTnitc(1 titates lxrth in tile pu'blic•:uc(1 llrivatc sector was about.$-1.5 mil lion in 1974. And health is import;lnt and I am willing to do whateve is nec•essary to carry on all of t.hc research that c,an be effectively car riea. on. IVell, here., gentlemen, we+ are talking about. t.he tripling o spen(lint; in reseatrch. Now i f the pu rlrotie of t.his tax is, in fact., for the purpose of creatinl moro research then I feel an nnfair burden is being or will be plac(N on one segucc.ntf of t he cconom,y to its detriment.. For insta.ncc, if you ar going to do nie(lical research let, us 1>lace thc burden either• on tile gen cral taxpayer or lct us place it, on all of those items or cxlrnmodit.ies tha wo know contribute to pcx>r health. Why, for instance., should $9.3 bi] lion tax be plac•ed upon t.he nscr•s of to1racco hec,anse we expect that i may ha.ve+ can(•er causing etfec•ts aulcl not. place any additional tax o liquor, a, c•onlmodit.•y that. we know as a fact is detrimental to the he;llt and not only is it de.t.rimental to the health of the person drinking i hnt it is detrimental to t.he hcalth of everyone else that comes in con tact with it.. And I must. confess, Mr. Chairman, that I get a little con cerned when I find people expressing concern for t,obac.c,o and neve mention liquor.

266 5 advisability of trying to spend rapidly much larger sums of money in this area. I suggest that a large and rapid increase in money is not warranted. More important is a mechanism for assurance of continuing support of good basic biomedical research and a good peer review system. In conclusion, I feel that the support previously extended to cancer research by the U. S. people through the Congress indicates a concern with preventing this disease. Research indicates that the best present method available to prevent much cancer is to decrease smoking. I, therefore, support Congressional action to decrease smoking. I 267 Statement by Dr. David Baltimore For 19 February 1976 Hearing on "Cigarette Smoking and Disease" The causation of cancer is a complicated process involving. interactions at.many levels. Chemidals, radiation and viruses coupled with dietary factors, hereditary factors and other influences, cause cancer by interacting with each other and with the myriad of cell types in the body. Evi- dence from studies on populationsin various parts of the world strongly suggests that 80% or more of cancer has as one necessary component of its causation some factor that is not hereditary. Such factors come to the people from outside of themselves and are taken in either voluntarily or not. As another way of saying this, 80% or more of can- cer is a result of our lifestyle and not either a conse- quence of our genes or a natural consequence of the process of aging. In the light of this understanding of cancer causation, it is certainly a necessary and appropriate action for the government to try to ascertain exactly what aspects of our lifestyle are responsible for cancer. Increased research activity in the areas of epidemiology and chemical carcino- genesis are one important way to fulfill this responsibility. Another way to meet the responsibility would be for the gov- ernment to develop mechanisms for helping people to avoid exposure to carcinogenic substances. Such mechanisms might be pollution taxes, strict regulation of pollution emission, taxes on carcinogenic substances, rapid dissemination of new information as it becomes available, and training of pro- fessionals who could assist individuals in making decisions about how to avoid the carcinogenic influences in their lifestyles. The best-documented, wide-spread cause of cancer in the American population is certainly the smoking of cigarettes. Although the link between cigarette cmoking and cancer was made _vears aQO. tha rnnctimntinn nf n -os-a--.. = y horror, young people continueVtoVtake~ ~ and, to m up the habit. I personally doubt that advertising is a major factor in the undiminished rate of cigarette smoking. I think we are seeing a self-propagating, cultural pattern that could only be broken by a very strong incentive. In that regard, S.2902 seems to me a move in the right direction because it would provide an incentive for people to lower their intake of the tars that cause cancer and the nicotine that has other detrimental effects. TIMN 450317

, 168 Serl:1to1• RF.NNI:DY. ~qell:ltor Sc}lweiker? ticn:llor 5rnw>:Ixr.rr. No clnestions. Senrlf0r Iir:nra,. No yuesf ions. tirualur i(r;NNl:m-. 11'e wantto thank yon. I sc•r Senator Dlorgan. I f ycln would yield, IAconlcl like to hear frcml onr c•halil•man, if that is agreeable, ticn:rtor. 1Cc melconle ('cmf;ressrnan 1'erkins, c•ll:rirman of tile Lahor ("•om- lllillcc. «ith Whom alll of ns on Illis Ilc:11t11 Snbconllnittee, enjo}• ver;y gIrvcng :1n:1 warrn Acorkina relalticmGhills. «'e alllrreciate yotu• presence hcrc :rrl:l «•ill Ix• glad to he,lr• yom• st atement. STATEMENT OF HON. CARL D. PERRINS, A REPRESENTATIVE IN CONGRESS FROM THE STATE OF KENTUCKY 111r. I'r•.rcrtl>`s. 1ir. ('llalirnlan, I wslnt to thank you for the opllortnn- itc to I/c llere ancl testifv c,n S. 2!tO2, the bill which would set nl> n. Na- li;)nal Ilexltll Resenr•c•I1 :lncl 1)evclolnm•nt. Advisory ('cmlmis5ion, and cc lli:•h Nc•nilIcl :llsn I>nt :1 nc•w, aclclit ion:ll 1ax cln cigarettes. I Illinlc ;lnyc~no f:unilinr witll Ille recclrcl I ltxve built since i c:lnlc to ("cm~ros~ Icno%c•ti nllont 1111, lont^;l:rncling a11d clecll c•ornrnifnlcnt to im- luvocin~r Iltv Ilealtll of olir• Imcll/le. I have joinecl in the sllolscll•sllip nn(I Ilrc snlllx/rl of nlc/st, if not nll, of tile I/rvlhranl5 passed cllu•ing thc Iris1 26 t•eul;s, A%•Ilicll wc•re wr•itlen 1c/ inlprove the. hc•allh of oln lmople. 11v intcrest. ill 'henlf Il crnneti al/clllt lx•cansee nl•y :r.rex of Eastern Ken- Inl•k•v for vc:rr's ancl ycars, vcrv sllort. of healltll lx•rsonnel and Ilralill f:lcilitic5. Inll/rovenlcnls have lmen rnmle--we llnve n1:uty nlcxl- c4rn facililics ancl get nlclre exllert pcrsonnel all of tLe tilne, th;lnks tuairaly to llro;grnrm5 p:lssecl l/y tlle ('ongres,5. NIc :lrc•u lulti also Il:lcl :r long hislclry of being short of jo1/5- of lulv- ing luanA• In•ol/le u•Ilcl Avenlt lo worlc. :lncl neccl tcl Nvork, Inlt wllo have bc•c•n i1nalllc tc/ tincl :1 •jclll. 'I'he 1incn111li)ynlcnl problem is still .vitll n5, hcncc•ver, ancl «•ith. us ~~crv nlnrll. I nu•nlicln tllesc I.vo sltl/jecl5. ItealIh cnre alrlil lnlcnll/lcrvmeni, be- c:lnsc I~~•:rnt to pc/irlt cnrt that the,y are clirectly rrl:ltecl to thc issues inc-cclc•c•ct in the le5,i;l;lt ion wc :Ilr cliticllssing. ln nlv clitilric•1 tllcrc :lrc• :llxmt 2(1,(1O0 smslll farnlers wllo have a. ticn.lfclr Kcnneclv .lncl nlenlllcrs of the committee, I have said clver ;ln(l c,x•cr agnlin that tlle 1c11rlcco f,rowel•s crf Kentnck,r• llave longasked ccll:ll in,rcclicntS in tcclr,lcccl can5c Ilnnlnn clise:lse sc/ tlltlt it_ mav Ue relnnvc•cl, :lncl 5o h:lvc•l. No comllelent nns«•er hn5 ever lleen for•th- rcnui'1'lle fact, Illiti falct shcllrlcl Ilc eminl;h for nnyone, I ihink, to scrinnsly ccrosiclcr t lu con~c clncnc eti clf t llis nlca~ln c. We h:rvc mGe:rrc•11 cc•nfcls 1c/ tr;y tcl cleternlinc wlu•ther the Ilroblem is in tllc• growing llroccs", t}lc cln•in" I1rc1cc5G, or ihc mnnnfactnrinf; pro- ross• :lncl Ihe tlccll/le n5 nAcholc tihonlcl sllare this Lln•clen. As long als it is lcgml to slnoke. to manlifactln•e cigarettes, people are going to •.luokc, nntNA•ithsi:rnclingr .carningn, frclnt tile (":lnc•er 4ociety or 1lnycnle vIsc•. Bnt I 111ink ( lult «•c shrnllcl clcl ;lll in orn• lmwer to nlnlce ilu• doter- iuin;ltion if therc• is :1 calls:ll cclnnec•tion between smoking nnd ctulcel', ;ln1l fin:l out t}lrongh cnrl• 11rc:5cnf rese:u•ch centers instead of putting n:liI it icmn 1 I/u rclens on t h(, farmers. 169 Now tllese farmers thrrt. I represent-nnd I said 20,000 smal filrnlers-may llave an allocation which allows them to procince 1,501 rn• 2,04H), or mx.ybe. 2,500 in tobacco. I f a. grower raised or solci 2,001 porulcls of tobacco during the season jnstt ended and if lie got, na gooc price for it, say, about $1.20 a pouncl-lle dichl't, get that-at most }l, prot/Rbly got ~1.15-but. le.t us say $1.20, Il(,. l;rossecl $•L,400. Now thc agricultural economics experts say it. costs abont• 90 cents a ponncl tc 1)roclacc bnrley so if we snbtract what. lle paid for seed, fertilizer, fuel anct t he. otller things. lle, needed to produce tlle crop lie has spent $1,80C leaving Ilim a profit of $600, and I arn tallcing;lbont tlle srn:rll growelY Achlally tlle srnnll mountain farmer does not. inchlcle the cost of Ili; own Rnci his family's labor in thc figln•es on gross nncl net profit. so Il/ is nlore likely to feel as thongh Ile mncle something like $1,2010 to $1,5011 on hiti crol>. By a.nyone's reckoning that is not enough to live one. h wcrlllcl have•e to Ire clonblecl or tripled to get rlp c•ven with the povertj level. lint. thc srnall mountain farmer is also raising a. garden and it if ususllly a big gnrden. lie raises some chickens, a few hogs, maybe i conlllc~ of cows and out. of it all lie feeds hi5 family and clothes thent :unl f,rcts tile c•hilclren to school. Ile does it. wi111ontt food starnlls anl withont welfare checks. Ancl he helps to snllport the econonly of thi; comrnlnlily Lccanse that is where he 5pcnc15 his tol/acco checl{. Now ti. 2902 contrnlpl:rtes singling ont his product for n new tm llasecl n;>on tile nnlormt of tlu• anci nicotine in each hrancl of cigarette The tax wrnllcl rnnf;e from I ccnt to 50 cents per pac•l: next ye:rr, aver al;ingr al/rnif 12 cents a pack. Ill 1980 it wonlcl rslnge froln 2 to 50 cent: •1 I/nckaf e, :Incl averxge :lhont aO cents. The bill ccmtemplntes cl0ll:li for clcc)l:lr In:ltcllinf; the revenne rai5ecl throli".ll what we mif*llt as wel c:lll a sln•fsrs, Lecarlse it is a tax on toll of n t,ls.'1'he luoney wrnllcl lx n"ecl to incrc•nse Snpl,or•t- for health rrse:lrch, health eclncation, }lealtl Irrogr:crus f,mnernlly. Ncnv, ar(-orcling to the Staternent of the sllon5ors in tile Recorcl cl' .I lmrarv 21), fhe,y hope aml expec•t. that the high llri(-e they wonlcl lmt cln al 1>ali•k of cigarettes will rnflke people stop tinloking cigarettc5, or at least nl,lke tllenl Smoke low nicotinc cigarettes. The latter expectation anncmncecl on pnge S. 77:1, is connterecl 1>.y the sponsors' own eviclenc•c on page ti. 774, where they qnote I)r. 11f. A. II:Inlilton Rnssell a: 0 °.!le nicot:ine in iLo /ncco srno te, people wolllci Ix~ lltt.le nlore inclinecl fo smoke cignrettes than they :u•e to blow bclbhle~ rn• light 5parklers•" Scl what. tile sllonscns are reall,y saying is that throngll this lef;isla ticln they llope thut ciprette smokiri~,r will greally clecrea5e. If we c•:u•r1• their hotle one s1c•p along tile wsly, tve c•an see t}lc Ixlss ihilitv tllat thousands of sm:lll falrnl f:rnlilies ~cill I/e out of hnsi• ness. At tllis point I wnnt to c•l;u•ify a nlistxken impression which arises allrolrt tile nat ln•e of tile Snlall toll;lcco far•nl• Often, sc/nleclne will ask why the tollncco farrrner cannot. merely Snh- stitnlc+ Rnof)ler croll, ancl c•ontinne to nlake a livinf;. Perhaps lle cnn if lle i5 a I/ig farnler, wlu/ al5o h:r5 n lar•ge livestock operation, or other nlajor crotn. 'I'h;lt is not so for the snl;ill, burley rxiser in the mormt:lins. Iie mRy hslve 40, nr 50, or 60 ;lcres, Lut. lie will have <r5 little as hnlf-acre tohaccc allotment. C)nt. of that. half acre will come the $1,500 or so that is lli< caGh crop, the c•rol, tl,c,t -1rT•ics his family thrvmgh the year.

238 COMrvAENFARY 7. W.goner.J..Talkpresemedtn ~ D.C.~Septc h mberlO511975'- fornnnnn Aaoota~mn. Wad"inF . ., R~ E W.. Gammon• F.. 11 .0 unn, W., Huphc•s. 4 G Ikdl O, R Tyrer. F Flcher. H.and Wi4ron, W-. Mnrlality of Gas \Vmken with Sprcial Rcfnence to Cancer of the Lung and Bl:alder, CMrpP1,K ®ronchilif. and Pncumoconiosis• Hr. J. Ind. .Nrd.. 22.1-12• 1965. Canar Mortality in AI'Icgheny County 5 Iloyd. J. W- Lu~ toml Dissenatinn, Univcrsily of Piltv- CokrPlanl WurkenD~ hurgh, 1(W+ me,did standard _ .... Occupalional Ex- 6. Crieda for a reewn pmute 1oCokeO~cm F.missions, U.S. National lnaitute for Oc- eupahonJ Safety and Henlth, 1973. 7. Woiss. Wm. and Boucot. K. rrsen ed alRlhe Internal onal Coo-o ('hLxanrtMl M Dh` I r• p frrmceon Lung Montreal. Canada, May IS-21. 1975. R Schur, C. C., Ctitical APt~~ of the Royal College of Physi- ci.ns Repon un Smoking and Health, fwtncet 1:243-248. 1972. Q Corbelt. T., Cancer and Congenital Anomalies Associated with Anaesthedrs. Preseated to the Meeting on Oceupational Car- einnpcnesn.Ma+rb• 1975,AnnnlsnJN.Y. Aend. Scf. (in Preae) 10 SctikoR, I L and Ham^mnd, C. E.. AsbecMS es in The New Ynrk Ci1y Pnpulaloon in Two Periods af'fime, in Shapiro. II A(edt. pmteedings of The International Conference on Pneunwconions. New York, Orford UniversRy Prese. 99-I05. wm II. C<derluLR.FtiherB.L..Hmbcc.7..•andLorich•U.•l'heRda- tiunalnp of Smoking and Sume Soeial Covariables to Mortality and Morhidity. A Ten Year Follow-Up in a Protwtbility Sample of 95•1'NNI Swedish Suhjectr Age 18 to 69. nqtattmenl nf F.nvi- ronmenl:d Hygiene• Kxrotinska Institute. S-IiIi-OI Stockholm. Sweden. 1975. 12. National Center for Health Slatistics, Tape Release Package of The 1970 Health Interview Survey. 13. Wagoncr. J. ap- cit. 14. Newhouse. M. 1... Berry, G., Wagoner. J. C. and Turok. M. E., A Study of the Mortality of Female Asbestos Workerx. Rnt.l. lndurtr. Afcd. 29: 134-141. 1972. 15. Hammond. E. C. and Horn, D.. Smoking and Death Rates- Report on Fruty-Four Months of Follow-Up of 187,783 Men. I. Total Mortality-J.A.M.A. 166:1159-1172. 1958. 16. National Academy of Sciences. Biologic Effects of Atmospheric Pollutants: Particulate Polycyclic Organic Matter. Report of the Committee on Biologic Effects of Atmospheric Pollutants. Na- tional Academy of Sciences, Washington, D.C.. 1973. 17. NCHS Personal Communication. 19. Fraumeni, 1. F.. Atlas of Cancer Mortality for U.S. Coun- Iies:195(-1969. Governmenl Printing Office, Washington. D.C.. 1975- 19. President's Report of Studies and Surveys of the Hazards to Human Health and Safety from Common Environmental Pollu- lion: prepared by HEW and EPA, 92nd. Congress, 2nd Session. Houseof Representatives. Document No.92-241,Jan.31, 1972, pp. 13, 17, 19. 164 AJPH February.1976, Vol.66• No. 2 TIMN 450303 239 Senator KENNEDY. Our next witnesses are among the most dis- tinguished scientists in the world. Last year they shared the Nobel Prize in medicine. As you all know, the Nobel Prize is the highest recognition that a scientist can receive. Dr. Renato Dulbecco, Nobel Laureate, Imperial Cancer Research Fund Laboratories, London, England and Dr. Howard Temin, Nobel Laureate, McArdle Labora- tories, University of Wisconsin, Madison, Wisconsin. We extend an apology to you for the delay of getting started. Dr. Dulbecco, you get the award for coming the longest dist ance to come and testify here. We are deeply concerned in this matter, and look forward to your comments. STATEMENT OF DR. RENATO DULBECCO, IMPERIAL CANCER RESEARCH FUND LABORATORIES, LONDON, ENGLAND Dr. DULBECCO. Senator Kennedy and members of the subcommittee, I am glad t.o have the opportunity t.o appear in front of this subconi- mittee to discuss the health hazards of cigarette smoking because this is an issire requiring both scientific knowledge and. governmental action. I think that in the past there has been too little cooperation bebiveen scientists and governments. I will mention a number of these issues such as disposal of nuclear wastes, which is very important in these days and the procedures for solving these problems are of great, inter- est, to many scientists. I am glad to be here because I feel indebted to t.he American People who accepted me as an equal when I came here many years ago and who provided t1Je means for my work. Among the health hazards of cigarette smoke, I will concentrate on lung cancer, which is within my field of competence. The disease is essentially incurable, it, can only be alleviated through prevention. Prevention has great value in most other cancers as well. Tt is now clear that 80 percent of all human cancers are due to environmental causes. This includes the things we eat., what. we drink, and the air we breathe. Senator KENNEDY. That is an enormous figlll•e, I)octor, and one I do not think we as a societ.y have been dealing with very effectively, ancl something we in this committee, also are interested in. I3utt it is inter- ""+;.. `7 '--, I_;:; u.~ o.n i'-. ,'. i-.'lin'. «re are in c anger oi: causing so....., - rne sort of epidemic, in terms of cancer:5, with insecticides, pesticides and drugs and many other things. But we are just. beginning to feel our way, and I do appreciate your comments. Dr. I)ur.BFrco. I fully al;ree with you. The case for prevention rests on the public health experience with infectious diseases clurint; the last century. In fact t.hese diseases have been controlled mostly by preventive mctasm'es, such as h,ygienc and vaccination, and very litt,le. by therapy. I'reventive measnres arr, ap- plicable to all environmental cancers but. will be most eflective for those cancers «•hose agents are known and are not essential. The cancer of the lung is by far the most common cancer of the lat.t( P type; the agent, cigarette smckingr, is known and is not essential to life. Hence this cancer should be completely preventable. Tlre fact, that it has not. been prevented, and that 60,000 Americans are killecl by it every year must be squarely attributed to lack of adequate action by the Government, and its failure to heed the many calls made by re-

240 sponsible scientists over the last. two decades. Tlle main question in m,y, mind is how the Cxovermnent can perfornl this rolee in a democratic society. I consider that is not my job and that I will stick to the scien- tific side by indicating what should be done. As a cancer researcher and as a medical nzan I am shocked by this lack of action, and I queStion the credibility of the Government as a promoter of health. However, I hope that tlle Goverlunentt will now take a firm stand, implementing measures suitable for stanlpinn out lung cancer and other diseases caused by cigarettes.'I'he.vorld is look- ing to this country to lead the way by adopting strong and effective measures. i In order to understand how cancer prevention can be molulted, it. is important to understand that cancer is a disease of the hereclit:u;y material of the cells of our body, which determines all the propert.ies of the cells. Cancer-inducing chemicals causedamages of the hereditary material, called m>.itations, which in turn change tile cells. Ilowever, the change to cancer requires several mutations and other events in the same cell; therefore, in the early period of expostn•e to a cancer-induc- ing chemical, mutations occur butt remain silent, that is, the cells stay normal. In experimental animals cancers begin to arise lout; after exposure to a chemical has begun; in industrial cancers in ruan the lag can be 20 to 40 years. Silent mutations persistt in the cells and can cause cancer at a later time, even after the cancer-inducing chemical is with- drawn from the environment. Accumulation of mutat.ions in cells of the body explains the cumulative action of cancer-inducing chemicals, that is, that the number of cancers they induce increases luarlcecily as the period of exposure to a chemical t;ets longer. Cigarette smoke acts in exactly the same way. It contains muta- tion-mducing chemicals, and can be shown to cause cancer in experi- mental animals; in man the lag between beginninf; of smoking and the appearance of cancer can be 30,40 years. The action of smoking is clun- ulative : Doubling the number of years one smokes increases about six- teenfold the risk of lung cancer. The evidence unambiguously shows t.hatt lung cancer is a prilm example of a preventable cancer, caused by a clearly identified and unessential agent, cigarette smoke.'VPhy is it then that the U.S. Govel•n- ment has done so little to discourage smoking although they have very actively fought other dangerous drugs? Is it because key people in Government have doubts about the evidence on the hazards of cigar- ettes ? Senator KENNEDY. This appears to be so. But there is no question in your mind ? Dr. DULBECCO. If there is such a doubt I wish to make a strong state- ment here. I have carefully reviewed all of the available evidence and am fully convinced that the evidence is conclusive that cigarette smok- ing is the cause of 90 percent of lung cancer. Doubts have been raised from time to time but have no scientific validity in my opinion. Senator KENNEDY. You have reviewed all of the scientific informa- tion that has been available to you ? Dr. DULBECCO. Yes. Senator KENNEDY. From govermnental sources, the Surgeon Gen- eral, the Center for Disease Control, the Cancer Institute, as well as those documents which challenged that information? 241 Dr. DuLBECCCI. That is right. Senator KENNEDY. And you are sat.isfiecl ? Dr. DULnECCO. I have stuclied every iloculnent I coulcl put my lland~ on. I made a special etl'ortt to read the statements made by soule of the people who were major opponents over the connection between lulr; cancer and cigarettes. Senator KENNEDY. And you :u•e satitifiecl to a sc•ientific c•ertainty about the causal relationship between t:u• and nic•otine and cancer of the lungs and other health complications, is that col•rect? Dr. DUl.nr:Cc;o. '1'bis goes a, little bitt further. I aln c•onvinc•ed :lhout t.he fact that. clgill•ette Slllolie causes :)'t) pl'rCPntt of liing cancer, and th:11, the tar is the mo5t elanl;erous ingreclie•nt. in slnoke for tllis partic•nlar clisease. Senator KEzvrEnr_ All right. Dr. Dtn.Br:cco. Certainly interested par•t ies lnake every possible ettorl. to createe such doubts. Iluty sw•el•y t.he (iovernule~nt ha51m•ans for t;c~t i ing to the truth, thus elinlinatint; the artificially created doubts. nr is itt because tobacco brings in revenue? Rut. it is ag.ruesouiv rerenue basecl on tile disease, death, ancl great suffering of nlany pc.ollle, ancl, anv- way, probably outweighed by the costs of lost llroduetlvlty and ulecli- cal care. Or is it. becau5e powerful interest5 have their way irresllective of the consequences? No matter what the c•ause is, it. is agreata failing of our society that so litt.le has been done to control tobacco smoking. C'onsidca•inl; what. the Goveruuentt mit;•ht, do to alleviate lung cancer, one must keep ;in mind the consequences of the cumulative effect of srnoking. One consecluence is that the lonl; lag between beginning of smoking and the appearallcC of lung cancer gives a false sense of safety to those who begin smoking; a second conse,quence is t11att the reduc- tion of cancer incxlence in t.hose who give up snlokint; is slow, produc- int; values close to thatt of nonsmokers in not less than 10 years. Another consequence is that. the age at. which people begin to smoke has a drarnatre effect on the later rncidenoe of llmg canc•er. For instauc•e, those beginning at 15 ha.ve a fivefold hig'her ineiclence than those beginning at 25. All these facts show thatt cutting down the number of years one snlokes is, next, to not smokint; at all, tile most effective way to allevi- ate lung cancer. Senator KENNEDY. Of course you must be aware, Doctor, of the in- creasing incidence of t.he use of tobacco'by teenagers? Dr. DULBECCO. Yes. .... LL....v ____.---__„.rr ~: .~ ~ ii Sel lat.or KENNEDY. This is an additional problem and I think youl' warning on this is terribly important. Dr. Dur.BECCo. Now, I will briefly consider some possible legislation which of course is based only orl health, not. because I wish to le;;lslate. That is not, my job. Tt is simply for the sake of discussion. Clearly it, nmst be in thh fraauework of our societ,y but it is a fact. that. Govern- ment is called to more and ruore take action on difficultt issues. So I would consider now three points in this respect. , One is that. the. main thrust should be to convince ,yolult; people mrt, to begin to smoke, through a suitable progranl of education cllre.ctecl at breaking the chain of events which give a status value to cigarette smoking. At t.he same time there should'be a complete ban on any kind of cigarette advertisement or promotion, otherwise the truth about TIMN 450304

182 :.rr:rc. "I'r>ial umclic•al c•ost5, tienator. ifor Ihr•r.'1'c>tal nrccl'tc•:cI costs. j)r. Sr•:xc•r•:rt. l"cs. ti,~n:ctor ll.~trr. Ol~l>c>rrcr>ts of tl,iti legislation fron> the tobacco I~rn:luc•ing :u•ca5 I,:rvc' nrainlainccl 1>efc>rc tlris ,n1,c•nnnnittce that thc c•II'cc•t c,f S. 2ittr•? wr>ulcl IK• to run a luf of sn>all fat•n>ersont of lnrsiness. 'I'lu• fol,:rc•rc, indntitr;v invc>lve,, al)1>c•oxirnatcly i.i ruillic>n fiu•mers in II,c tc>f:rl inclusfr•}• itself. ''I,c ret-enncs ;~encratc•cl by those farmers Icat•in" aside the Ferleral and State tax-lmt cleclncted from the $11. 5 hillion leaves a net social cost of :hR.f{ I,illic>n. If it has the effect op- l,cn:c•ufs Irsrt'e clainrecl, therc wonicl still lK, a. probable net social sav- irrrS„r net meclicatl savingGOf $3 to:E;-f l,illion. 1«':rntI to 1>in clown til>cc•ific•o-tlly oil the 5cicnt-i(ic 1>art Of )'om state- nrc•nf. I,)• arsking Il>rcc clrreslic>ns: Is Il>crc any (Irnrl)t rn vorn• mincl flrat c•igarctte snrokin~,r c•anses :Ii"c•uu•5? I)r. ("cx,rrac. \r>, srnnc, not all ciiseases. tienn I c>r• I hrt•r. 11'eI I, tionre rl iseases. I )r. ('c:c,r•r•:rc. Yc5, sir. Scnalor Ihrc•r. Iti tlrerc arrv clcnrl>t. irr }•o:n nrind tlrat tire tar content in c•it'arcftc•SC•c>ntrilnricti to thc>tic sl>ec•ific cliscotscs? I)r. ('ni,rr•.rt. 1:uu :rl,le to I,e les" In•ecitic nr)•tielf about the shecific• an.,4wcr fo Ilr:rt rlnestirm. M }• pncss is frrnn tlre cxlmrin>cntal c•vulenc•e tl:ad it 1>rc,llr.rl>I)• clc,es. I3crf Imrl,:cl>s IsI,c>nl:l ask nr)• colleagueti Th•. li:rrrsrrlrcr:rncl 1)r. I.cl•}• Irerc to con>nrcnt on that. I)r. I6t'sc'nr;rc. Senator, Ilrerc is no clnesfion ill onr mind that the f:u• cuntcnt is a rmtjc>r• inclncer of canccr. We rcrr>.-rizc sc>me •3/1 ditl'cr- (•nt rcwrl,r,rmcls. Imn•r,c,-2-1)yrene a5 an exanrl,lc, «'Iric•Ir ar•c Icno«'n to be I,:vtr•nt. lit•c,:1nc•er:s of tlrc c•ancer in aniruals, ancl we fecl str•ongly that f:rr iti:r slrun" c•.rnsc• c,f the lr,rtlru"enic e/l'ec•ts of c•i"aurttes. tion:rlc,r Ilnrrr. 11'rnrl(l tlrc ti:rme lmtruc of nicotinc as.vell? I)r. tic•n:rtor. nra.% • IS:ty tb:tt Iwonlcl cxtencl the comments and ,:rv Ilrat I'm• lrnr;, disease and :•:rrcliot•asc•rrlau• disease there is no donbt. I l::rf (•ir:u•cttc srur,kint, is a rnajr>r cansat ivc factor, st risk factnr in its c,wn ri~Irl ancl as I)r. ('onl)cr sard, an exacerhating factor for al1 other I;inclti c,l' risl;. In c.rrclirnasrnlar cli5easc~e it al>1>ears tlrat botl> the niruline rrmtent in cif;:rrettcti :unl tbe. carhon monoxicle that, is taken in ~t•In n c•i;,rarettcti are snrc>Icccl are the ('nll>rits.'I'Iris al,lmars to bc h•ue. fnr Irnr;e tlisc:t:;c as «•ell. )r. ('c,:,rr:rr. You sc•c• f Irc cli::t inction. Scnatrn•? I thinlc I)r. Hanscher I'rcrr>, his vantage 1>oint. points ont what lre views as the weight of thee rcidenc•o :rnd frorn tlre c•atrcliovascnlar Statndl>oint tlre qnestion of the ,•c,rnl,nncnt is constrn:•tit•c srn(l I)r. LprV hi;rhlights carhon oronoridc. ,1S 1)r. I e•Vv s:ticl, t hrre is nr> clnest ion in nrl' nrind that it 1>recil>itates c•erf:rin Icincls of el,isc,cle;; srncl exstcer•bafey tbc disease. Nic•ofinr 1r.r5 nraru* v l,:ult• etl'ccts that express themselves in a variety c,f At'u%•ti wlrirlr cour exacc:rl>attc disease. Tlr>w nicotine, however, conlcl n0n:rllv csrnse anY of tlresc cliscases is tlrc kind of researcl> that is ctu'- rcnt Iy trc>ing on. ~enattn• I IART. It ls nol t IH''`how" so rmrcb as "tbat"? 1)r. ('cH,rr.rc. 'flue relationshil> is :t very 1>o«•erfrrl encc. 'I'he actnal '4l,rc•iti:• stcl,G, linlc:tmcs, c•crt:rin of tlrc•se elcnrents and c•ertatin of the ,litica"c wifh which Ihcy arc 1>owcrfnlly as:;(x•iatccl remain to be clclinc;rfecl. 183 TWIN 450275 tic'nator Ii.trrr: 11'ell, Iwonld refer to the rel>ort .vbic•h you signc irr .lnne the Ilcalth ('onscqnenccs of Srnokinf;, ancl slmci(ical t Im I)otttrrrr of Ir,tge 4 wlrcre it is stated that c•i;raret te snroking has bec shown to I,c one of the major C71II)-cot•onar;y heart clisease-ri: factors auul-cxist5 with other alterable CIII) risk factor. I won nrcr•cly aslc if citrarette smoking causes Ireart disease? 1)r. ('oorrrt. No. tienatot• IIArcT. It does not? I ) r. ( `cx>rr;n. No. I think to be al>solntely candid with you, the risk factor does nc n>can c•anso; it r>reans tlre prol>abilit.y of you having the disease if you inclnlgence is ver;y lrigh. liut t•Ire nse of thc% word "risk" factor in tlri context. is a ver;y pr•ecrsely selected I>hrase and I used the same pbras in my forn>al testrmony today, lifted out, of t•bat report that. I signed That does not nreatn that. I personally clo not feel that. it is an importan as,srx•iat.c(1 carrsc for the expression of cliscase. Scnattc,r IiArrr. On the previous pages you (lid not. use the term "rish fac•tor. }"on s>ticl it was the major cause of lung cancer by several larg: ret r•oslmctit•ed ancl I)r9spective 1)r. ('cH,rr.rr. 1«•as talking about. coronat•y Lc:tirt. disease on the firs rlnc>te tlrat. Yorr raisccl, and I tbink you heard froin I)r. Ransc•beron tIu 20 (ler•ivaiit•es tlrat, firmly link in our• view the clnestion of c•ansc tc c•anc.cr. Senaior IIAs•r. :1Ir. (`hairrmin, I have no further questions. tienator Srrrn•r;n:r:rt. I)oc•tor, a nnmber of people challenge. the va liditv of the animal experiments to tcstt the cigarette tars. As a scien tist, how confidentt su•e yon of the resnlts? 1)r. ('cmrr:u. I anr lmrsc>nally conficlcnt. Perhxl>s Ih•. Hanscher «•bf- clirecl Iy m•ersees that I)rogt•arn conlrl esl>ress Iris clegree of c•onficlence, I)r. Kst'sr.rrr•:a. Based on animal tests, we recognizc 1,OO(1 or so to cansc, rancer. 13etween 25 ancl :3/) ar•e l:nown to 1e indacers of tire rancer in people, and everyone of t.bose were, with the I>ossible exc•cl>- tion of one, inorgautic arsenic which are also inclnc•er•s of canccr in aninrals. So onr ability to extrapolate is based on confidence in abont. lrercent. As a scientist., I am confident, thatt tbesc systems have a, ver,y good 1)recl ict.i ~•o ctiect. Senator Sc•rr.vRIKF.2 In .•01.,.. ;,*v,._. ,>ecrei ary, you referred i-o t-m excess mot•tality and morbidity dire to cigarette smoking. Ilow is this formed, on the basis of lung cancer. enrl>hysenra, or coronar,y lreat•t clisease? I)r. ~r:xr iac. 'I'his is :lerit•ecl front clcter•ruining the expected occ•rn•- rcnce ot' earclr of those 1>articnl:u• rliseaties by a-e sutcl Ix>pulation auni 11ren conrl>arin~ flrc ol>sert•ecl ocrrn•rcnc•eti in 'Zinrilar no»ulaNons «'ho smoke. I?zccsti rnorl)iclity or nwrtalit Y fm• srnokers is that whiclr occrn•s ot•er :rnrl alx>t•e tlre amcrmrt exlmctccl in the nonsmoking 1>ol>ulatimt. 1)r•. ('cwrr;rc. .1ti it r•eflec•tion, Senator, n-e believe tb:tt other fhin~,rs Imsicles smoking c;trr5e dcatlr ancl discawe obt•ionsl}•, tbese cbronic clise:cties. tienatrn• tic•rnvr.umr:. I)octor, yorr referrecl ln•iefly in vnnr fornral sf:tfcnrcnt to c-,l>anciccl efl'ortti to fincl a safer c•i;,•arctte. What I wunlcl likee tc, sk )•rnr not~• is shrnrlcl a safcr ri~arette-n•ell. in t•rnn• vie~c of tlre oh~•i;rr>rrs (litlic•rrltv r>f c•Iran;rin;o lror,l>les lifesh•It:S ancl' l>articrrlarl)• as fat• :rs ~nrokin« ~: jn~l as warning I:rl,rls :rn,l ,rcxul illn~-

176 \ Ilr:tltlt, Eehtralfioll, and 11'elf:trc wiflt regarrNo~eVentahle health I~r~rlrlr Ins in ~cnc'ral ancl sntokin" in lrurticnl:tt•. I hacr' asf:tfcutcnl wIiiclt I wr/ttlrl rcrltte5l Irr' pl'lrc•d ill tllc reeorcl. ,41•n:ltr/r tic ItxvF:rl{Fat. .~ffer klrlkin;~ at tlte lcn;rt hth Of onr witness list I cc rlrrriue f Ilat 5tt;rt,•c5l iort :trlrl :tc•c•olrt t he iole:t. 1)1•. ('rrnrl;tt. In tlte intet•etit of titue anrl flle witnesses that I know t•rru •canf tr, Iletlr front, I«•rlttlrl snggcsf Ihal i sunutlatrize briefly our ~ it•tv;;. tienafor tic•11wFI1KRIt. That wil1 Ile fint•. ( in a}teacl. I)r. ('t,urF;lt.11'c «'ill Ire av:til:tlllr• fclr rlucsti(lm at any tinte. In hiscrllelting renl:trks I nnrlr'rsictucl tltc clruirnl:tn was interestecl ill rrur contutenf in;r on lhe heall It cuntierlncnces (lf srrtoking. I Imgin lly sstying tltsrf cltn• eslint:ttcs of tltc' nterlic•al costs of snlok- irll; rlnl ~+111, l/illion. 11'e :tltio cst itutttc' f hat 10 ~•eat•s st,~o there were 77 ntllli(lrl w(lrkda}•s lost flt:tt could lle :ttlriLtited to con(litions related fu cir:u'ettc stltokinirand :3O(i luillicln rl:tvs of rest ricted :tctivities. Fr(nn lltat sIarting point, Nvr' helicvc tltat llrospcr•tive anrl retrospec- live Slndies clearly e5tail,li511 that cignrette smoket:5lt:tve :t grrenter risk uf clr•uth c1nco trl crlronar}• Iteart ditie:tse :tnd a Iliglter prevalence of cor- rtnary heart disease th:tn nonsrltolcerti. IVe recogrnizc Illat the risk fac- Iors act in coutbinntion xvith ollter f:tctcn:s, like hi~h blo()cl 1)ressure or rlov:tletl 5erunt cholesterol. :tnd do not. nec•css:trily reflect these fi;ntres :tlone: All fivturs SFtot%• tltatt llersons who sruoke ciL,r:tt'ettcs have ntore `r'te.rr• crlron:tr;y rtther(tsc•lerosts that ller5om who do not smoke. Ancl Ilir'rr• :uvc :tninl:tl cxllerituents that have been done anrl are going on slntlying fhe set•cra) ntec•hnnisluti «•herelly these cfTects tllif;llt take I,latrr•. 11'c he:trd aa grentt cle:tl earlier about :ulother t•cr}• iluportant, ver}' t-isil/lt• heall It conswlncnce of sntrllcingof great itd ere5t to f he Amer•ican penl/Ie :tnrl tlte crlttttuittee and that is tlte ckereloplurolt of cancer in sinokr•rs.We find il sil-rnili(:utt that sntrcl:iny is lirntl}• estal)liS}lecl :ls Ihr' ntu jr>r ritzl: f:tctcrr in 1tung r anr cr. '1'hc ri~k of dr~ rlollin~ ltnlg c:ulccr cc:ts 11)Iinu'~:~rc:ttcr frtr•ct~:trellr'Srtl()lcerstltull n(mtintr~kcr5. 11rotucn ill tlle Ir:lst liavc lt:td :l. fat• lower r:tlr• r,f ltlrlr c:tnc•er th:tn tur'n, :uul fltiti is gr'ncr:tll)• :ltirillnferl to tltc fact tlult fewer wonlen Ilt:ut nicn sntrrko :lnrl Ilt:tf «•rrntcn stnrlkc't:5 gencr:tll)• Sclcr•t ftller :tntl Imt• I:n• :tnrl nicotinc riqr:u•ctt(>s. Itcm•et•cr, fltc Ilrrcent:l(re of «•(lnlen sInrrki•rs in Illr' [Tnited Sl:ties It:ts inrrr•aticd stcadil)' in tlle last :3O }•eat•s. ctn4l• sinre l!)!'r:'i, ihe deatlt r:tic frrnu Ittll1"canr•cr ill trotnon has inctr:tsecl propurlirm:tfel}• lu(lrc rallicllY iltatrl tlle ritfes for nu•tl. reflecting, this itrrrr•nsod lrrrrllortiott rrf tt•clnlen 51u(llcerti. ;~ciw tt•c rec(l;~nttiic st'tirr~'t:l' 'S ur' 11, 1 0 i' ~ ic, r•:tn"atit'e factor ill 1n11 r c:tnoer, and we do reco--nize that there :ur oilit•t•:;nttl•r•r's in inltal:tlictn of r:ur ino; clls Iltat c(l~tlrl crnttrihntc tohof Il tlu• incidtvl(•ee gener,tllY :lnd tltt' incirlcnc•c in tuen anrl «rltnen sel,:t r:ticl}•. Nrrtuu:tligrnatnt rr'.,;pir:licrrV rli,~r'a5e is:t tltircl :tre:t of sntrll:in-'r-indlrcerl tn0rlriclit)• :tn(l nlrn•tallit)•. ('i,r:lrefte stnrlkers have lreen shmwn to have lurltv• frcrlur•nt resllir:ttrlr)' infcrf irlns arld tuiss turlrc clsl}'s frcnn u•ot•l: drtc to msIliralor* A• inft'cf irln.11 lnore frerlnenllY tltan n(lnsmclkers. There li:tt•(' Iu•en trtrrl5lmdit•c alntl Ilrrr,.,lrcr•tit•e ~tnrlic~ t'rl:ltinu trr c•i(rm•c,tte !Ntlir& inr a', :t priut:tr, V f:tctrrr ill fllo dcvclrllnuoni of vht•cmic llrclrlchitis and r'tuplt}'sr'tna ill thc I"nifc•d tit:ties. 177 There h:tt•o heen studies point.ing ont, the factotss tllat afl'ect pnlmo ary function :ulc( special strnctures in the lung wllic•11 are resl)onsll; for cle.ulsin,-, t lle respiratory tract. .1n additional area that merits special comment at t}lis llearing ihink is the concet•n that. has been voiced abottt the efl'ects of cigare.t snlrlkinl; dtn•ing pre;gnancy. Mothers wllo smoke ci~:trcttes dtn•ing tl last two trintesters of tlleir pregnancy have been found to Ita• l/nl; es with a lower average birth weight tltan nonsmoking mothei 'I'he}• ltave a hil;ller risk of having a stillborn child, and their infan have higher late fetal and neonatal death rates. There :u•e Sotne rlat to show that. these risks dne to cigarette smoking are even greater : AVc/nlen who have a high risk premlancy for othe>; reasons. This poini (,tlt• a fille(•ific, Ilrinciple that I tltink is important, and that is wit respect to all of these considerations as associ.itive factors that ace erate the expression of disease or symptomatology, I think that ~ donllt• the evidence wotild show t.llat the incidence of chronic dizcal front otlter canses would be accentuated or accelerated by cimtrett smoking. I think we need to address hvo general questions: What are the col se(3nenc~s to individuals observed 11>> st(lhping smoking or changin t}le cigarette? What. are the overall public health consequences of ce snti(ln of cigarette smoking or changre5 nlade in cigarettes? The fir: conse(lttence is sonleR•llat easier to allswet•: In the individual the cessl tion of cigarette smoking is followed l~y reduc'tion of the carbon m(11 oxide level of the blood and the symptoms of c(lngh, spntnnt prodn, tirln, :lnrl sllortnetis of ltre:lth nsuall,y Intprove rlver ( lte next few week 'I'Ite' rlata is showing tllat risk for v:u'irnts crmclitiolls tltat I have on• linerl Imfore over varying periods of time is rerlltced over time nftt wif Itdr:ttvnl frrlm cigarettc sln(1lclnf,•• 11'(, :tro also :ttt•nre Ih:tt over the past caet•er:t1 years tllere Ilave Ilee prlirtterl out t•:trintirlns in tlle ller cnl/ita crntsttntl/tion «•itlt ciY:lreftr tt•itlt scmte imllact dnl•ing 1960 to 1r.)71)-ati Senator Iiart has Il(linte (lttt, with srtnte ret•crtiiolt, perlutlls dnc• at that f itne as lte Il(linterl ottt t tluc clt:lnm, in acc•css to television and t)te radio. But also rltn•in(~ tlla period of titue there was ;la c•h:tnge ill tlle r•ir:trettc :tnd tLe c•i,r:trett tltatf is Ilcing snlolcerl now is not• tlte s:tnlc :ts tlte c•itr:u•cite snt(lkecl i t Ile lr:tst. I f hink cln tllee c•onst rrtct-ivc side tlle lm(ltlncet:s of the ci;r:t retit's. as AVell :ts Ille rese:trchers in the fielrl, all have c•rnltinnonsl At-clrkecl icltt•urd tr;ving to trrince the t:lr and nicotine nnd any othe noxi(lns sttlrsi:tnccs ihey can identify as a h:lz:trd. 'I'herefor~, sin( 1ua11}• of tltese efTerts tlt:tt Il:tve been described :t5 ltealth cfl'ects:u•e dos I `'tc per c:thii,a consnntl/tirln r'ontinncti to incre:lsc• tt•rc r•:trlnctt crrnclttrle fltere h:t5 Ireen a Irrowre,~,,it•e inct•ease in exposnrc We Avolllrl 1)rcfcr to :;ce th:tt Ilotlt fatct(lt•5 :u•e in the 5ante clirection Itott•el•er a1tt1 e tir'natrn• I I.Att•1: ,1fay I intet•rnpt yon I'or u question? tit'll:tt(11• St•II\1•P.11cER. Sure fr(1 :tllc'ad. Senat(n• ILv:•r. .Inst.:t factnnl qttcstion, I)r. ("clopet•. lron have per ll:tlls alre:trl}• st:ttecl thi5. Il:ts the Iler c:tllita crlnstnnptirln rll' cigstrettc: inr•re:tscrl 5inco 1')71 ? i)r. ('rlorF:it. l'eti. 'Thcre was somc incre;t5e in the per capita. L:tst, }•eai tt•e lle-:ul f(r see sorllc let'elint; oft•. Whether this is a. new trend towar( leveling ofl' I:ttn not. sure. I'erhaps I)t: Sencer or Dr•. Levy- TIMN 450272

250 J. Roy. Coll. I'h)•cns Lond. °fi`evads in M®rtalAty among SMUsh Doctors mn 1"2keAaae091 to "i"heir S" moking Flabit5 Sir RICHARD DOLL, DM, DSc, FRCP, FRS, Regius Professor of Medicine, University of Oxford, and M. C. PII{c, Ph D, First Assistant, Department of the Regius Professor, Radcliffe Infirmary, Oxford Ou 31 October 1951, Doll and Hill sent a questionary to all members of the rnedical profcssirnt in tlic United Kingdom enquiriog about their smoking hatrits. On thc basis of their replies 9(1,637 doctors (3-1,1•15 men and 6,192 Xc'om(u) could thcu be classified in a few broad groups according to thcir age, the an,onnt of tobacco they smoked, their method of smoking, and whether smoking had been continued or abandoned. Further duestiouarics were seul to thc malc survivors at the end of 1957 and again at tht• bc•r;innir~g of 1966, and to the female survivors in 1961. Infbrmation ahout tlie cl~ate and cause of dcath of'tltc men and women who died was obtained Nvith the assistance of thc he;isU•ai;t General in the United Kingdom, the General \Icdical Council, and the British Medical Association. When necessary, information was also sought from the recorrls of tile rghtinl,• Services and from other sources at homc and abroad. A few deaths camc• to light only as a result of tile response to the second and third questionaries. Doctors who did not reply to tile third qnc•,tionary and who were not known to havc died or to havc been struck ofh tlic• ;ncdical register were followed up indivichially. All but 21 of the 39,41`'i men (tl•U6 pc•r cent) were eventually shown to be alive ou 1November 1965 or to have died belbre that date, so that the mortality rates calculated from the data can be only very slightly in error. ]letailed accounts of the stttdy have been given in previous publications (T1oll and Hill, 1954, 1956, 1964). In thesc reports it was noted that the doctors who chose to answer the initial qucstions cannot have bc•cn altoVcthcr rc•prc- sentati\ c of the total. The seriously ill would have been unable to respond, so tllat thr mortality of tho;e who clid would have been, at Ieast for a time, ab- nrnmally low. In fact, using a I in 10 randoni samplc of those who wc•re initially written to as a basis, Doll and Hill (1964) calculated that thc stand<u-dised death rate of those who (lid reply was only 63 pc•r cent of fhe de<<tli rate for all doctors in the second year of the inquiry and 85 per cent in tile third year. In the fotrrth to tenth )'e•ars the proportion varied about an avcrane of 93 per cent and there was no cvidc•ncc• of any regular change 11 251 J. Roy. Coll. Pllycns Lond. with the fitrther passage of time. Evidently the effect of selection did not wear off entirely, but after the third year it had become slight. TRENDS IN MORTALITY In this report, we present the trends in mortality fi•om diRcrent diseases and groups of diseases observed in male doctors during the first fifteen years of the study, and we compare them with the trends recorded for the whole popula- tion of England and Wales. We have limited the comparison to ages 35 to 84 years as (i) none of the doctors under observation was less than 35 years old at the end of the period of study, and (ii) age-spccific death rates for the general population arc not published for men more than 84 years old. A1- togethcr, 6,321 deaths occurred among 34,203 men in this age group. The total mortality observed in each of the fifteen years is shown in Table 1. TABLE 1. Observed mortality in doctors, by year of observation ( Year of observation I 1951-52 14•3 2 1952-53 15•2 3 1953-•54 17•4 4 19'54-55 17•9 5 1955-56 17•0 6 1956-57 17•3 7 1957-58 19•9 8 1958-59 17•2 9 1959-t'i0 17•4 !0 1960-61 17•6 11 1961-62 16•3 12 1962-63 18•5 13 1963-64 17•7 /r 15 ;, -,a 1965-66 ., j, 16•4 Calendar year (I November to 31 October) Death rate per 1,000 men fn this and subsequent tables the death rates have been standardised for age, using the population of England and 1Nales as recorded in 5-year age groups at the 1961 census as the standard. For the purpose of comparison with the national data we have omitted the experience of the first and second years, since the mortality rates in these years are obviously biased by tile selection of relatively fit men at the start of the enquiry. We have also omitted the fifteenth year as the last intensive follow-up was conducted in 1966 and wc cannot be as certain that all deaths that occurred in that year have been recorded as for other years. The data for the remaining twelve ycars have TIMN 450309 217

256 ,J. Roy. C:oll. Phycns Lond. S-1tOKING HABITS '1'hc snwkint; habits of doctors were, in all probability, never identical with ti wse uf thc general population and the habits of those who responded to the initial clnt•stionary were certainly different from those who did not (1)oll and liill, 1964 ). The habits of those who replied to the three questionarics are stu)Imariscd in Table 4, standardised for age within the broad age groups of 35 to 8-1 years and 35 to 64 years respectively. Over the period of observation, the pruportion of doctors of comparable ages who were ex-smokets increased progressively at ages 35 to 84 years from 20 per cent to 32 per cent, while the proportiou who smoked only cigarettes fell from 41 per cent to 21 per cent. Lt ages 35 to 6-1 years the corresponding proportions were 18, 29, 44 and 2'2 per cent. l:stinlatcs of the smoking habits of all men in Britain of the san)e ::ges are not avail,tble to enable au exact comparison to be made between tile smoking habits of doctors and other men. The results of surveys undertaken L•etweerl 1956 and 1968 have been published by the Tobacco Research Council (1969) autd some of the most relevant results were cited in the College's report oII x•moking (Royal College of Physicians, 1971). Some data relating to tlic ycars 19-18-50 were obtained by Research Services Limited and have been reported by Todd and Laws (1959). Estimates of the average number of cigarettes smoked by an adult male in the United Kingdom in the same years in which inlormation was obtained for the British doctors have been extracted lrom the report of the Tobacco Research Council (1969) and are shown in Table 5. From these data it seems unlikely that any major change in smoking habits can have taken place that was at all comparable with the change in the habits of the doctors that were under observation. It should be noted, however, that the sale of cigarettes with filter tips increased greatly and the proportion of all manufactured cigarettes that were tipped (and consequently contained less tobacco) increased from 1 per cent in 1951 to 61 per cent in 1966. We have no data for the use of filter-tipped cigarettes by doctors, but it is unlikely that t11CV can have avnirlrrl hrina ~,fi•~rtP`l 1,.. References Doll, R. and Hill, A. B. (1954) British rbfedicalJournal, 1, 1451. Dull, R. and Hill, A.11. (1936) British .lfedicalJounoal, 2, 1071. Doll, R. and Hill, A. B. (1964) British dqedicalgounml, 1, 1399, 1460. Royal Collcgc of Physicians (11)'1) Smoking and Health Abw. London: Pitinan 1ledical. Tobacco Research Council (!' •°'r) Statistics ojSmoR-ing i„ tlu United Kingrlont. Research Pnper \o. 1, Fifth Edition. London: To':.: o Research CounciL Todd, G. F. and Iaws, J. •r. ;,;y) The Reliability of Stutemerds about Sntoh,ing Nabits. Rese;u ch Paper No. 2, Second Edition. Lon,lvu: Tobacco Research Council. 222 257 Senator KENNEDY. Very good. We will conle back with sonle que5- tions but I will hear fronl Dr. Temin now. STATEMENT OF DR. HOWARD M. TEMIN, AMERICAN CANCER SO- CIETY PROFESSOR OF VIRAL ONCOLO(IY AND CELL BIOLOGY, McARDLE LABORATORY FOR CANCER RESEARCH, UNIVERSITY OF WISCONSIN-MADISON Dr. TEMIN. Thank you, Mr. Chairman, for givinl;• tile tile opportu- nity to speak with you on this topic. My point of view is thatt of a cancer researcher who has been working for the past •?0 years with RNA viruses that cause cancer in chickens. In spite of the fact that my work is performed in the State of lVis- consin, I felt it more important today to coDte here tutd speak with you oll this topic than to continue my own work today becatlsc' elhtll'ette smoking is quantitatively t1le most important factor that we c•an do something about as far as human cancer is concerned. Since the early years of this century it has lwen known that viruses cause cancer in chickens. Iu more recent. years viruses have been shown to cause cancer not only in chickens, but. also ili Iuice, cats, and evc:u in solue primates. Therefore, it was a reasonable hypothesis that. vir- uses might cause cancer in humans and that, if a human cancer virns existed, it could be prevented by a vaccine as so ntany other virus diseases have been prevented. Experiments performed in 1•ecentt years have led to an understand- ing of Iuuc1l of the genetic basis of how viruses cause cancer in anitual5, namely, by adding their genetic information to the I)NA, that is, the genetic material, of the cell. With this untlelst.antling:unl tlle tools of molecular biology, it has been possihle to look for vtruses potentiall,y preventable by vaccines that might cause human cancer. t7nfol•t.unatel,y, I think we can now conclude that most hutuan cancer is not caused by such viruses. Scientifically this conclusion is an advance, for science progresses by disproving hypotheses. But in ternls of preventive ntetlicine. I be- lieve that this conclusion ends tile hope for a vaccine that would lire- vent cancer caused by viruses. Senator KENNEDY. Can I make an observation? Usually when we have scientists who are talking about their specialties they are pre- nn,rnrl fn rlnfanO thp.ir n..•n ci>rrisiltv_ in t~rni~ nf tlinir n.uit nnrtir•ttlttt• researcl), particularly in thc. area of cancer. It. seeul5 to me thatt tile most extraordinary and gravest c•outulent that you have made, is that your research forces you to eonclude that there Is no hope for .I. vaccine to /)revellt cancer caused by viruses. Dr. Tl•.11IIN. I think thtit. Iuost virologists now would ap;ree witll this assessment of the role of infectious viruses in human caucer. That is not t,o say there are no more iutpolttu)t roles for virologists ill ctulcer 1'eSea1'ch, bllt as fal' tls the causes of hlllllan cancer tll'e concerned, cigar- ette smoking rather than viruses is one thatt wc* (-till put otu• hands on. So if we no lonl;c~r have holle for a va(•t'ine at;ainst viru:;es that wonltl pt•event lnuuan cancer, must we give ul) all hope of preventing ltntuan cancer? TIMN 450312

242 srnokinl; would be submerged by thc: clever propaganda glamorizing this dangerous babit. in the eyes of the youth. Since an,y shortening of the time one smokes will be very beneficYal, efforts should be made at inducing people to quit smoking, even though they have already smoked for a long time. That quitting is possible has been shown by 30 million Americans who have done so in the 20 years, since t.he dangers of smoking became known. However, many moro still smoke. Fiu•ther progress requires more. education, suitable facilities, such as specialized clinics, and possibly compensation for lost income during the treatment. And No. 3 Senator KENNEDY. I1rell, the point you gave there is that it is never t(H) late. to stnp smoking. Would you agreo with that? I)r•. Dur.r;FOco. Yes. 5enat-ot• Kr;n Nra>v. I suppose there .nre a lot of people, who have'been sn)oking 15 or 20 years, who wonder whether it makes any difference il' they stop or not. I think your point here is that it is never too late t+) st op. I)r. Ut~r,rtr,cc o. Actually t.here is a good British study on that, the strtcl)• of British c3ortors. tienator KrNNran-. I[a.N-e yori got a cop,y of that? I)r. I)tTiasnx•co. I do not. have a copy with me. tie.nator Kr•;NNr:n~-. ("an •yon supply that? I)r. l)tTt,ru,rc;r). I can send it, to you. Seriat.or KENNEDY. We. woulcl appre.ciateat. I)r. I)cTr,n>•;cco. Then the third point is that it seems in spite of all o(1'orts many people.vill still smoke, it will beimperativetopromote t he+ adoption of less harmful cigarettes. This requires in the first, place ) cleternrination of tlre hazarcl value of a given type of cigarette, on the basis of t lro properties in the. smoke. A recomiized measure of the cancer hazard is the, amo)u)t of tar in the. smoke. However, reduction of tar mu:;t, he accompanied by direct evidence that, t.he mutation-inducing .)ctivity of the snroke a.nd its cancer-inducing act:ivity in animals are also reciric•ecl. Tlre tar content if backed by the biological tests eotild be nsc~d to t.hen cleiermine the c;incer hazard value of each type of cigar- ette, htking 5ometlrinr;• like 30 milligrams as 100 percent. It may be ,r+ Of cotu Seother haaarcls~of thel.smoke, such'a~J as chronic bronchrtzs or heart clisease which clerive. from other constit.uents of the smoke, must. altio b, evaluated. Filter cigarettes have been on the market for almost 20 years. Smok- cr•s who adopted them have suffered fewer lung cancers but still four tinres more th;u) non5mokers. Therefore, a. further reduction of the c•a.ncer•-inclucing act.iv itv of cigarettes must be attained. Now I miisty ta•y to lvarn yott at this point that there are ot.her diseases (•rr.nsecl'I) y)y smoking in acldition to cancer, as we heard, and we are not clear on whether t.he reduction of tar alleviates the problem. A cert-ai) 0nrotintt of research tvill he reqnired. I think considerable pressure may lia NT to be exert ed to prompt. the development and qale df-less harmful cigotretles and this might be done for example by iml)osing a, new heav* V ta.x on cigarett.es, proportionally to the haztird value. The use- frilness of t.his approach is indicated by several studies showing that inwreasing the cost of cigarettes decreases for awhile their ronsump- 243 tion. In order to sustain this reduction the tax should be increased gradually by a certain amount every year. Moreover, once cigarettes of low hazard values have been successfully marketed those of higher hazard may be banned althogether. The new tax would yield new rev- enue, very large at first., but subsequently declining, which could'be used to support the proposed program and the necessary research and if necessary to subsidize the necessary changes in agriculture and in- clustry. The program I have outlined would require the formation of a special agency to implement it, to determine standards and to monitor its effects on the basis of the results of epidemiological studies. If there is a program of this kind epidemiological studies should be set up ] n a very competent way from the very beginning of the program. [The prepared statement of Dr. Dulbecco and the British study referred to follows:] TIlVIN 450305

212 The Cigarette SmokingJLung Cancer Hypdthesis The persistent controversy regarding the role of smok- ing in iung cancer cannot be resolved merely by escalating the force of arguments pro and con. That these arguments are becoming increasingly sophisticated and more vigorous serves to demonstrate that the issue is hardly trivial. Let us, therefore, carefully examine the nature of the problems we confront and seek to identify means of approaching them in the best interests of both the scientific community and the general population. In a recent issue of this Journal. Sterling's critique of Aamrican Cancer Society and other studies challenged the apparent association between cigarette smoking and lung cancer•t In addition to insisting that uncontrolled selective factors bias the ACS findings. Sterling cited a number of epi- dcmiulogic observations which presumably cast doubt on the importance of smoking in the etiology of lung cancer. He emphasized that these observations demand further apprais- al,of current evidence about environmental and industrial fuctors in the complex causal web of cancer. Only by the most careful reading of Sterling's article can one nvuid the imprccsion that cigarette smoking should be diwnunted as a conlribuiting cause in lung cancer. In the snme issue of the Journal, however, Weiss states that .. the evidence in favor of the smokingduug cancer hy- polhesis is overwhelming."s With reference to studies not in- cluded in Sterling's survey, Weiss cites further support for the smoking-lung cancer hypothesis: "No matter where we look, the association is consistent, strong, and specific. .:- In this month's issue of the Journal two commtmications constitute additional rebuttals to Slerling s charges of spu- rioasness?•' Sterling's reply to these communications also appears.s Clearly, there is substantial interest in this debate, and the publication of this series of papersis interrsely pro- vocative-although more of heat than light! Study of the arguments from all sides rev4als some com- mon ground upon which we might proceed more dis- passionately. While debating the relative importance of smoking, we, can, nevertheless, agree that cigarette smoking is at least included in the array of causal factors. A concern for appropriate public health policies and activities relevant to smoking and cancer follows from this agreement. t\ Continued divisiveness around lhe precise contribution of smoking hat potentially two tragic consequences for poli- cy. On the one hand, to insist that smoking independently accounts for lung cancer is to construct an obstacle to future investigations and reappraisals of environmental carcino• gens. On the other hand, there can be no question that wide- spread cessation of smoking would result in rnore good than hartn. To dilute the importance.of smoking is to foolishly di= vert us from an important goal. ff The precise degree to which smoking may be indicted in occurrences of lung cancercannot be determined at present. In his discussion of the difficulties frt}rerent in estimating the magnitude of a causal relationship. Greenberg• shows that in simply choosing relative otattributable risk, on; tlistorts tJte measurement of ef!'ect. Surely we have a professional and hu- manitarian responsibility to cease bickering in an area where currently available investigative strategies ind analytic tech- niques preclude any precise determination. " Why must this paralyze policy planning? Can we not concede that experimental proof wiB not be forthcoming, that new observational studies cannot greatly enlighten us? Since we do not expect to know the exact position which smoking occupies in the causal network of cancer, how much longer can we posipone action! . Weighing thdconsequences ofaction choias, wecan re" fer to Greenberg's rlecision modeP in which the degree of proof needed to recommend an action increases with the se- verity of consequences following a wrong decision. This kind ofanalysis leads us to accept present evidence for pro- moting campaigns to disGourage smoking. It also emphasiiss predictable requirements for more stringent evidence about the merits of more potent policies. To act now at the first level of intervention can simulm- neously clarify our subsequent interventive policy goals. Our wisest course, then, is to move simultaneously in three directions: - 1. The promotion of antiarnoking campaigns; 213 EDIiOR1ALS 2. The conduct of carefully designed community-based intervention trials to estimate_ the_ impact of cessation of . 5mokiitg on health stades; and 3. The conduct of carefully designed studies, and per- haps reartalysis of existing one9, in order to eiucidate accu- mtelyihe role of environmental and industrial factors. In shtxt, we must not conthnre evading action in favor of ar- gument. We possess both sufficient empiric grounds and a strong moral obligation tq proceed from where we are, through conscientious intervention programs and creative environmental studies, toward refining our understanding of lung cancer etiology. MICHEL A. IBRAHIM, IViD, PHD Dr. fbralvm, Chairmman of the Joamd's Editaial Board, is pnofessor of Epidenouoloey. Uttiversity of NotM Caaolina, ChapetHil127311. REFEaEIWbES 1. Steding. T. I). A Ctitital Reassessment of the Evidance Bearing on Smokieg as the Cause of Um8 Caneer. Am. J. Public Healrh 65(9):939-955, 19T5. 2. Weiss, W. Smoking and Caneer. A Rebuttal. Am. J. Public . Health 6$9):951-955, 1975. 3. Bross.I.D.J.Commentary,Am.J.PublkHeahh,66a6t,1976. 4. Higgins. 1. T. T. Commentary, Am. J. Pub)ic Health, 66:159- 16t,1976. 5. Sterling. T. D. Commentary. Am. J. Pub1k Hsalrh, 66: t61-16t, 1976. 6. Crrtenberg, B. G. Problems of Statistical Inference in Health with Special Reference to the Cigarette Smoking and Lung Gncer Controversy. J. American Statistical Assaciafion 65:739-758, 1969. 1 TIlVIlV 450290

260 you can give us to effectively utilize it, you might give some thought to that. I really have just one more question. Here we have two scientists who have conunitted themselves to very excellent research, which has been justifiably recognized in the world community. They have exam- ined the data that has been developed and reached a very conclusive opinion about the dangers of smoking and the clanl;er of tar and nico- tlno in terms of disease of the heart ancl lungs and cancer. Why does tl- e other side not see it as rlearly as you two do? I)r. TE.rIN. I think that most scientists involved in cancer research accept the relationship between cigarette smoking and disease. For illstance-you must realize, Senator, there are thousands and thou- sands of scientists and even if 90 percent of them agree, it does not mean that one cannot find a scientist who may have some special point of view. But the great majority of scientists involved in these areas feel that cigarette smoking is deleterious to health. So much so that at, a recent. meeting on persons with a high risk of cancer, sup- ported by t1le American Cancer Society and the National Cancer Insti- tute, the relationship of smokinl; to lung cancer was so completely accepted that it was not even discussed. Most of the people involved in cancer research certainly feel the same way. If there is something that might be questioned, it might be worthwhile, as Dr. Dulbecco 5ugqsted earlier, that. you have a National Academy of Sciences study to give another authoritative statement by scientists about this. But there is no question about the opinion of most of the scientists who have looked at the data on cigarette smoking and disease. Senator KENNEDY. Would you say it is 95 percent? Dr. TEMIN. I would say in this area, yes, 95 percent of the scientists in the area of cancer research agree that cigarette smoking causes lung cancer. Senator KENNEDY. What about Dr. Dulbecco? Dr. Dur.nECCO. I would say probably more even. Senator KENNEDY. Is it about as clear and convincing as scientific information can be? Dr. DuLI3ECao. Sure. Actually if you look at the dissident voices you can pick up flaws in their armour. Senator KENNEDY. Pick up what? Dr. DULBECCO. Flaws. Senator KENNEDY. Flaws? Dr. Dul,nECCO. Yes. In their arInour. They pick out certain data and forget the other. They make up arbitrary remarks. Sn vo,,. Qpa u. !:Ie cas;,.e in 1.iIs area. Dr. TEMIN. And the reason scientists who look at this data on ciga- rette smoking and lung cancer find it so convincing is because it is from a number of different types of evidence. People can criticize, at times, certain studies and certain types of evidence, but in a case like the relationship of cigarette smoking, and lung cancer where there are many different t.ypes of evidence supporting each other, I think the general conclusion is extremely strong. Senator KENNEDY. Well, I want to thank you. The point has been made here that the scientists understand this kind of evidence. Per- haps the public may be somewhat confused. I really do not think so, quite frankly. For example, if they hear scientists on one side, even 261 representing less than G percent, and you have other scientists saying something else, you know, they are somewhat confused. Dr. TEniiN. Another group you niil;htt approach is the American Association for Cancer Research, which is an organization of the people in this country working in cancer research. They might give you an authoritative statement from the body of people who have spent their whole professional life working in this area. I am sure they would be pleased to supply such a statement. Senator KENNEDY. I think these are good suggestions. I and some of my colleagues who testified this morning, who are all well inten tioned and honorable inclividuals of integrity, Avill just have to keep in mind this kind of evidence presented by you. The thing that bothers and troubles me, in the coru•se: of the debate on other caucrr- causing agents, is that the consumer heai:5 the risk and the danger, and this in Intolerable. You have to prove that I)E'S caused the rincer. Until you are able to prove something, absolutely, and just have almost a who7esale epidemic, they refuse to relieve the consuiuer of that par- tieular burden. It seems to me you have developed such overwhelming evidence in this area that we should not 1esitatee to move into it in a way that is responsible. I want to thank you very, very much for your presence here this morning and perhaps as we go through these liearings we can stay in touch wit1l you and call on you for your scientific information. These are scientific comments and statements and thatt is the value of this testimony. Thank you very much. We have also received written testimony from the third of last year's Nobel Prize winners, I)r. David lialtimore of the Massachusetts Insti- tut.e of Technology. We will include his testimony in the record here. [The prepared statements of I)r.'1'emin and I)r. Baltimore follow:] TIMN 450314

J• Ruy-. Corl. rllyt:ns Lond. stllnkin; par7tllc•Icd tlle trend in the mortality froni related diseascs in doctors, but dt'crcasc•d progressively in the general population. 'I'II/• trt•ntls in ntnrtality at ages 35 to 84 years arc influenced to a large extent b%• the rt•Ial.ivcly high mortality recorded at the oldest ages. In these age ~,tppl7s tlltlgnosls is least certain and the effect of changes ill smoking hal)Its is lt;ta likely to be able to make itself felt. We have, therefore, t•\atllined sipatatrly thc trends in mortality at ages 35 to 64 years and thcse are shown in 1`.rblc3.'I•hc resultsshowthatatthcscagcsthcmortalityfi•om`rclateddiseases' 254 •I•Am.r• 3. Al;es 35 to 6•1 years. Dcath rate in doctors and in population of I;ngland ,n(I 11'alcs, by cause and date of obzervation: standardised for age I Clausc of clrath - I( 1953 --57 Standarclised dcath rate per 1,000 nlen per year in 1)octors 1957 -61 I•ung ranc• r othcr canl, rs of uppcr respiratory and cligc•,tivc tracts C:hronic Ilrnnc hitis and cmphyselua rlrterilrsrlrrutic heart disease 1'Cptic nICCr (lirrho.ais uf lit•cr and atc:nlwlism 1'ulmon:u y t ubctr uLnis 1ielAtlVl causes 0•60 0-1-1 0•18 2-94 0•04 0•Iti 0-16 4•22 0-56 0-20 0-12 2-73 0•05 0•1•1 0•1 1 3-90 1961 -65 0-37 0• 13 0•14 2-77 0•05 0• 13 0-03 3•li1 England and \1:IIcs 1954 -57 1958 -61 1962 -65 1-13 0-14 0-74 2•19 0•19 0.05 0-29 4•72 1•19 0•13 0-73 2•:i2 0•l3 0-05 0-17 1-20 0-12 0-71 2•90 0•10 0-05 Cl• 10 4•91 :i•19 Othcrcanrcr 1•1ti 1•03 0-86 1-39 1-36 1-33 OtLcr rrslniratut y disease 0.18 0-22 0• 16 0•55 0•52 042 t:n•rbr:n•ascular disease 0•56 0•96 0•50 0•80 0•75 0•70 (lthrr cardioxasctdar disease 1•11 1•01 1-07 l•05 0•92 ll 82 \'inlrnrc 0•53 0•84 0•68 0-60 0•61 0•61) Oth'rr rausrs 0-77 tl.q0 n.5n •,... .„ Unnlatrll causcs- `~ 4•30 ' 4-64 3-86 I 5•21 1 80 t 47- _ _ :1II causcs 8•52 8•54 7•47 I 9•93 9•71 9•(i6 ---'' -- ., J ~ fr • 11 pro.~tcssiw•lr in doctors and increased progressively in thc countty as a 10101e. Again tltc contrast was most marked for cancer of the lung (-•3B per cent and -{7 pcr cent). For diseases that were unrelated to smoking the trend in mortality in doctors was irregular, while in thc country as avvholc tllc tnortality steadily decreased. For all canscs taken togcthcr the mortality in (l(clots decreased by 12 per cent, while in the country as a whole it decreased by 3 per cent. NC)O T G ~ c ~ °c ~ ~ r. CJ G) NM ~.o MQIM CJM1- -c7o -~• LV 6 ^ C) O) NC.1 J rz C ?M?• ciCO ~ -•CC d CM ^I U J L N V 1 C)1~ID M O CC N tO N C ~ 1 a2 tr ~ a 0 .n'T o C) s cl •-•^IM CZ4 4 d 5 ~ nc~ COC~ C 0 -3•t~•7 CJMO ~ „ ^I_1N C`I:V:1 o : W U 255 U ~ V V ~ rr. ~ . c _y.?. L u ~ i ~~cb C) M M TIMN 450311 220

214 Prnced::rr for Cnilectir~ :r,t•i Revtewinz.S._icntific D_It n for Rc•pprl- tu Con~ess .~-__._._._. . . . _ _ _ _ Acc~uisition The Technical Informatior_ C•enter of the National Clearinghouse for Smoking and Health, BuLCau of Ilealth Education, Center for Diseaue Control., Pqhli'c Health Service, has on contract ast intormation science'corporation to scan .,and abstract from•the world's literat:ure all articles on smo'Ring and h+Pdlth. -These articles artO sent to the NCSH for review. At p'resent, tha coneracto* retains, on a hub-contract, the Library otr the College of Physician5 ,iri,.ld; ,/ Philudelphia. Thi•s library scans all incoming journals, monographs,,e>;td .. , other titles, as received, and acquires smoking and,health articles accocd'-, ing to instructions provided by the NCSH contractor. In addition, the Clearinghouse has several in-house niechdd•!sm§ fvf.acY(tiiridg:, aiticle's. (1) a monthly print-out is received from the National Library,.of Medicine (NLtI) from its MEULARS .>y:,tam on smoking. Arti.cles not acqnired-by&-the contractor are t}ten enlered from thc+ NL4[n (2) The NCSH receives many high yield journal titles in-house. ArticJles from these titles are sent to the contractor for, pr•ocessing into the -. NCSH collection. (3)' Journals received in the CDC library are also scanned,'dnd those' ..,selected are sent to the contractor for processing. (4) The Clearinghouse receives several bibliographic items each month from various sources. These are al:>o scanned and articles not identi- fied and collected from any of the above procedures are acquired. The titles and originating organizations srnding these bibliographies are ' as follows: Current Contents - Life Sciences, published by ISI In Philadelphia and published every 2 weeks. Tobacco and Health Information Service (THIS) - monthly citation listinx of the University of Kentucky. Tobacco Bibliography - issued by Imperial Tobacco of the United Kingdom includes citations from many areas related to tobacco including agriculture, biochemistry, health, and processing methods. Tobacco Abstracts - published mn„rh1.. >.. «, .. "-_----- u.`. taor--1 Carolina; lists many items but most are related to agronomy. CORESTA Information Bulletin, issued quarterly by the CORESTA organization listin; foreign articles on tobacco including many health related items. Tobacco Research Council Library Checklist, monthly listing of this European organization reviewing many European and English items on smoking and health acquired by the Tobacco Research Council. NTIS Weekly Government Abstracts, published by the National Technical Information Service listing many unpublished papers which received Federal funding for project. 215 -G- If.••I,t1Yp~1J~MMbL>•n•,nmhsril.~~••'+:^tl«~ (5) The Ctearinghouse receiv_c from indivi8uai r,esP r~c~~rs many published aIS~ :tj#"Ses. Aay items of sidii.Y1c3tid;3W.%ed n are>3:ianslated for staff rev.(e All items,P,~oces•ed into the NC,~H col tion havR, English language.~i~s~A~~d'oir+y.tl «°.~J 6`xXA'V $li11M GM19 , Frocesp 1~j _ „r .. - . ., tt , ,. . . . , The Clearinghouse, after•reyietrt4g .art#cle~•jfpqq+yaboxe,sourres,• ends .thetst. Co the Contractor. The Contractor then prepares an abst,ract for'oeach•.•Ltem.;:• according to staff instructions.' An averag6'of fi•ve1ihd&y(nteY>iftt ilre°' applied to each. -°'34ftdr the-it¢ms 4are prepai•eiT; 'the ;'ftikris"t6g'fttt'et~wft'h camera-ready copy of all items prepared are sent back to NCSH for publish- ing in the foxm of "Smoking and Health Bulletin.,',',~,.,A4 14 >pppearing in: Bulletin then become part of the permanent colle~tion of't~TeLhi41ca1 •t . , ,t•-,.,s,., . . I f i C r n ormat on ente . In addition, all items in Bulletin are prepared for compat•t:er in-put.add • thN Clearinghouse updates its computer files• twice-each yedtr-•-t4aterials••=•+• 1970 to date are stored in an automated data base. The artiCles acqaii•ed by the Technical Information Center are the nucleus of eac)% ~eporG to Con„ies,s: There hav'LV befLn_eighCreports to Congress sinSe the••,origia~l•''•i'A~ • Su;geon Ceneral`Fs iepo,la bf'1964 ,(%967,''1968; 19b9; 1911'1';X1'`2;"1l~7$;'1934, For each repArt, Yeach'-year's 'collettion of articles isa 3n1tia11y:revie.wed •,p; by the moFtfcal and technical staff of the NCSH:"a•Nent 3~ifiorwattiwon''thic 'r1y taealth consequences of smoking af¢ summarize'd And' o-qaciiAd" ixt~' ch8pters' in the catagorips of':cardioviscular, cancA;',ifrtlttahOgUlttFofia7C~'c~igtas~,' ' and other topics by the etedical agd scie tffic, s,~af£'.,, Drjfts o~. P~ch, ,„ chapter are submitted to experts in the ~ieldl,tel•epsure an.accufiate rep sentation of data for the'yehi`: • A discusstone of~ this protedure 'as ve11' tLS •'t a lisf of reviewers arcW incluiled in each annua~- report. ;E~c~} reviewe;F commeit_s freeJ.y on',the ieport,and i_ndicat;es,.d,~iletions,,A$.at¢~l a§:~d~ to the information. The Clearinghouse staff incorpdrates these changes into the repo¢0.•fThis.a+ reoort draft is theh subYbitted• to several ovPr:i7l'..,:.{,~••~ a".urs oL tie 1FIat'.Lonal Institutes of Health for their commenta;•their . rlames are also listed. The final versioti,.of,the rejibrt.is EKransmitteQ frdtn the Director, Center for Disease Control,.:.through clearance channels in Department of Health, Education; ad d We~-14re to the Secretary who transmits ~...• the annual report to Congress. TIMN 450291

280 JitF.'NT OF SHELDON C. SOJ&ERS, M.D. My purpose, in response to the invitation to present my personal view of the status of knowledge of smoking and health, is to review the newer scientific data. This material is not included in the quotations from the 1975 version of the USPHS Smoking and Health report cited by Senator Hart as justifying Bill Nq. S 2902. Cognizance of the present day knowledge by fairminded individuals casts grave doubt on the existence of any such 'overwhelming evidence' as claimed by the dis- tinguished Senator. I am Sheldon C'. Sommers, M.D., Director of Laboratories, Lenox Hill Hospital, New York; Clinical Professor of Pathology, Columbia Univ. College of Physicians & Surgeons, New York, and Univ. of Southern California, Los Angeles; editor of the Pathology Annual and Pathology Decennial series; Chairman of the Scientific Advisory Board, Council for Tobacco Research, U.S.A., Inc; with about 260 publications. curriculum vitae and publication list are available. My First, in respect to the reported overall higher death rates of smokers than non-smokers, the results were obtained• by statistical epidemiologic methods now recognized as erroneous and use of which is no longer regarded as justified. One to one comparisons of smokers and non-smokers ignored many confounding variables. As Berkson pre- dicted the result proved to be a statistical artefact. This resulted from ignoring three serious sources of error: (1) Nonrandom comparisons, meaning that smokers and non-smokers are 281 -2- , not random subsets of the population being tested. Smokers choose to smoke and others choose not to smoke, and both groups are self- selected, apparently by complex processes not presently understood. The crucial error is the use of statistical methods to test non- random groups, designed for and applicable only to comparing random groups. Rolling the loaded dice statistically gives an invalid answer. (2) Dependence on limited statistical tests for proof. When Rose and Bell wrote their monograph on predicting longevity, they tested factors that might be associated with early death among a group of Boston WW II veterans, followed carefully for 30 years. A one-to- one comparison of cigarette smokers and non-smokers gave smoking the number one place as a predictor, like in many other studies. However, when multiple factors were included statistically, cigarette smoking dropped to somewhere beyond the 30th most significant pre- dictor of early death. Dissatisfaction with job became the number one predictor. (3) Secularity, meaning the change in habit patterns of the population from about 1910 to 1960, with increased proportions of cigarette smokers in Paeh decade. A model population (not a real population) with such changes over equal time will show a statistically signif- icant increase in total death rate as a minority changes toward a majority. This secularity factor or change in population patterns has no health implication. For example, in the original Surgeon General's Report a table showed pipe smokers to have a lower death rate (0.8) than non-smokers. While encouraging a belief that pipe TIMN 450324 Y

184 1 185 TIMN 450276 h•ation have not had mrrch imhact on lifest,yles, how rnnch suc•cess coulcl we expect. frorn fincling a safer cil;arette and how much of our ubje cti.•essLouldLeplacrd in that direct.ion? Dr. ('•oc>rH:rt. I think Dr. Hauscher could conlmentt at some lenJ,rtll on tliis, but I think a great deal of progress has been made on achievinn a less lurr.:u•clous cigarette. I think it is tecllnically l>ossible ancl I tllink tic•nator Ilurt nsed the conuuent carlicr: if itt is a dose-relatecl addic- I irnl, does it really N+•ork. I3ut I think I here are ruauy enconral;ing sit,ms liore. I )r. K;luscller? Dr. Hnttsc•nh:u. We 1>ave a hrol;ram llere cm tlrc order of $G or $7 niillion for 11>e development of .t les.5 hazardous cigarette. We prefer (luit Imc;ln5c onr view is that tl>cre is uo coull>Ietely safe cigsu•ette. tien:rtor Scrtwrarcr:rr. A c•rnul>letcly safe cil;;urtte would be witllout, I;u• ;rncl nicot ine? I)r. ItAtiScrrrx.'1'I>at. is about it. I3nI tlu•n you have to worry about otl>et•t.hinf;s. tienoltor ~qr.nwEncr•al. 1 was going to say, llo1V aboutt lettucc? Dr. KntIscI rH:rt. I tllink any organic ulatericil you burn at, tl>att tem- Imrut in c is J oinJ,r to cansc sornc ln•obleuls. Senator Srnrwi•.rrcr:x. So the report. about a safe cigarette was not. I r•uc+? Dr. RAuScur:rt. Well, it ~nrells bad, too. It. is not safe. Iu fact, we uiaclr great. progress and together I u>ust point. alrt with sonle very good cooperation fronl tlleo tobacc•o inclnstr;y. We now have cigarettes on the market. ou tlle order of, at least, less than 10 milligrams of tar. '1'here is now one wit.h 2 milligrams of tar. I3ecause we feel strongly aUOllt. Olly data, if tllese cit;aretleti are accel>table to the lml>lic tnst.e- Wise, we s'llould see a dimulintttion of the lncrc'a8111g Cn1•ve of lung c,tncer irtcitlence in the next, years. :+enator SrrrwtaxN;R. Psu•t of rn,y question was when we knock down tl>e, t;us and nicotinc~ Would cigarettes lle acccptal>le tastewise? Dr. Knusrur:u. 1'1'e now haA•e the technolory developed by our own Institute;uld tobacco conll>anieti wl>ercl>,y tatite and srncll c•on>l>oltcnts c;rn bo reinscrted into tohacco whicll 1>;ts been extrac•tecl for sonlc of these chenticalti. 11'e tllink tlult wonlcl 1>e n>ore ;lc•ccl>tal>le to tlle 1>ublic t han I>rc vious less 1>arsu <lons ci~:u cttcti. Sonsltor ILAtrr. A'Ir. CIrairrn.u>, Iwould likc to ask I)r. R;wscLcr, as a resnll of tlre infortuation that. 1las; Lc•cn av;lil;lLle, there has heen this cinc', 01! l,yi>rici sn>o{rn, ( , r nratc•rial, i', >at is not qrute a cigr;u•ctte anc noi, ctiiile ;r ci:,rar. I tliink Nvc• worrlcl 1>c inlcre:;tecl in •yolu• views on Wlren a cig:urttc I>ecomes n c•iJ;;u• or lu•con>cs :1 c•ig;rrcttc aaul so forth. l'uu %•on con>n>cnt on tl>at ? 1)r. ItAUSc•rrr:n. AIy n>aljor concern is tllc t;u•, in «•hatever you c;lll it, cigr;ir, cigarette, or ci•arillo. Ancl ati to legalities, wllen sornetlling I>o~ c>iurs tion>ctliin~~ clsc, I arn not verscd orn that. tienatc>r Ihrrr.11'I>, t about inhulation? Dr. H6t1sc•nr.rc. Wc•I1, inlral;rtion is ln• far tl>e key to onc's habit. 'I•liorc• is thc key to tl>e factv of tolrlcco. I 1>at•e been tolcl that thc smoko Of sc>nic of the newer snlall cig;u:v is n>ore ;>1>l>c;lling- and the smoker hat>l>en nuiv inh;lle it ; anci if that cloes liul>1>cu-- and ISay if it does il %coulcl 1>ut 11>at )mr:son in tnnch greater risk than if hc sn>okecl ;1 real viv;rr ancl did not inliale. Senator ScilwFixFn. I would like to clarify that for monitoring. you inLale tlle consequences are greater t.han Dr. Rnuscn>;>t. If you inhale the cigar, there is more smoke and per unit. 5enator Sctrwr:ncr;e, tio the WIlole matter is whetlrcr you inllale I)r. Rnusrrtr,u. OIl, absolutely. h)xcept lerluil>s for cancer of lip and moutll, where tlle risk is enhanced reJ;arelless of inhalation. Senator 5c:irwr:rxFar. So the litt.lee cil,rars or big cigarettes, it. is rea WLether or not you inhale? I )r. KAUSrr tr;rt. Right. Senator Sctrw>•;lxr:rr. Senator Kcrulcdy has been trying to get. ba froni tl>e Judic•iau•y (`omulittee ~~•he~re they are embroiled in so r-oting secluence and lulfortrnlately I am not%• going to have to lea •ltt tllrs point but I lu>derst,and Senator Ilsu•t will carry on becat Senator Kennedy does «•ant to sliencl a few minutes Witll this pan So if it. is agreeable I uul going to turn the gavel over to Svnal I Iart to cont inuc nntil Scnator Iic nnccly J;ets bac k. IScnator Kennedy jnst retarned j Seuator Kr:NNra»•.11•'c Will conle to ot•der. I rel;ret, my absence very runc•11, Dr. ('ool>er. The firll ,Judicia (•orunlittce «•as on a very iurl>or•tant rnsttter ;tncl I 1>ad to excl m ysel f. I am informed that rt good m:ulv of thc questions have been cc ered. One point. wlrich I n>enl ionecl irn nly earlier ol>scrvat ions is nbo tllee total cost of ciJ;arette sn>ol:inJ; to Ihe I>eallI> c;ue systeni. I nnclc st;u>d you have mentionecl ;t figurn of ;tl>rnrt :J;11.5 I>ill'ion. I)r. ('cx>rt.rc. Yes, medical costs. Selltltor KP:NNI:ns•. In tcrn>s of n>edic•al c•ost. Dr. ('cx>rr;tc. Ancl we;rlsomeutionccl- i)r. SrNrt:R. Abont. 77 nlillion workdays lost. and :308 million da of resh•icled tinte. Scn;rtor KN1NNFni•. And yorr spoke abontt the causal relationsh Ilerc, I>;tve yoir not? I)r. ('cHirt:u. We 1>ave talked a>Lont thc risk factor, whalt tile ri: factor is, t 1>c quest ion of al l lcrgy ;r ucl t li,rt srn•t o f t hint;. Senator Kr:NNr:uY. Well, IWilI rct•iew tlie tcstimoriy and if we ha• sonre other 1>alrt ictilar ure.rs I will sulnuit tlicnl. '? "uc>rrat. ~4~e Woni u' m 1> c;csecl to rel>1 y. Serliltol• KENNPan•. ''Iier•c~ is no doul>t ill yuin• o%vn rnincl, as I ru derst;lncl I>oth `'ocn• testiu>ony wliic•I> I rc~ icwcyl prior to the ruectir ancl also Ir,csl testin>rn>y, ;cbon/ tlic seriouti Iie;tllh risks that are sup -ested by thee use of t:u• uncl nirut inc :rti f:>r :rs 1>e;trt uncl lcn>~• clise;lsc Dr. ("cx>rr:r:. Right. ~' Scnator KENNEDY. Is tlifit h•ne ;clso M•itli yon, Dr. Ranschcr? Dr. H6usc•rrH:rt. 1"es, it is, sir. Senator KH:NNr•,rn-. Ancl I Icno1%• yc,ii 51>ellecl tl>,rt out in great clet,l hnt I tl>inlc it is tcrril>ly incl>orl:u>t. In contiiclering tliis scienlitic ir 1•cn•nurtion, Nve 1>at•c to c1CI>rncl ul,on tliosc AN•ho have the retil>onsihilit •rncl 7bility to have sc•ientific iuforrusltion, from those Wliose lives 11,11 been decllt•atccl in thesv areas, to help us and coimscl Ivith us. ZVc hat•e h:ui tiiil>n>ittccl to us otlicr ~:>•icnt lic inforrnlat ion ;lncl I thin We «•ill have thart referred to yoi>, Dr. Cooper.

TIMN 450271 174 I liacc not icecf in (•onnection Avitli tliis ilncl other lerislati(m in whicl) I have Lcen involvccl, that llicre is an irr•gnnlcnt iu'onncl tlu, 1}ill tu lhe ell'cct Iliat,yon shoulcl not enilc•t legi5liltion in illly (me inclttstry until yun solve all the 1)roblerus tllatA relate to all olher in(in5t1•ies. I inn in- vulccd, as the Senator frorn Nor•Ili {'al•olt»a knows, in lcgislation that. sccks to inc•reaso c•ompetition in tlic oil industry. Argnnlelit is rmLde thiit tv(+at'c I>icking on tllc+ oil cornpanies ancl that we onght to intro- clin•c it liill lo increa5e (livcstitiu'e 1>rovisions nn otLer in(luslries.'I'he tieuiitor• well kno.vs that. is not. the way •yotl legislate. If yott wait to scciu•(, itll the 1)robleius witll one bill or solve all tlle soc•ial ills with one bill, it will not. 1)e done. So I mnst say obvionsl,y, Congr('sslnarl, froin ii I)iitse(1 1>ointt of view, I(lo not. fincl tlle ar~lnncntI tllat. tliis 1>ill singles (>nt tobitcco iul(1(loes not. solve tlle 1>rol>lelns of alcoliolisln in our society or (liilhctes or I>olio or irnyl liinr else has been very per'sliasive. 'I'he fact. is 1 hcrc iire (it) million snlokers ln onr society and 10 million alcoLolics. 1/'tliis I)ill is foinlcl effective in solvina the 1>roblen)s of lnnt* an(1 heart uncl rclale(1 ills, whicll arc tlie dominant. ills, then I think we look to legisliit ion to solve the 1>rolrlenis of alcoholisni. Iwonlcl 1>e willing to cosl)onsor lerislation witll the Senator towar(1 lliat, encl. Ilnt yoti clo not ulix al>lrle5 and oranges. tienator MoitanN. I think tlierce is a real clifference. You are talkting aboul. busting up tlle oil cartels. )"c» 1 ar•e talking about. here taxing a given indnstr,y and llutting tlle taxes into general health research which is going to lrenefit all others. '1'Irere is ii very real distinction in lily inind. Of colll•sc•, I ilssunie that both of us have, a prejuclicecl point of' view. Ilere you are going to, break ttI> the oil companies to restore conil>etition for all of the people. But. going into a I)rot;rirru to estab- lish research, t.he money should conie froin the general revennes of tlle 'I'reasul;y unless we are. going to try to levy revenues on all clisease calises, lll llly OI)lllroll. Senator IIArr•r. The Senator treats Leartt and lung (lisc*ases as though they were a minor problem, bnt. look at. the statistres on deaths that. occur from these kinds of tLinf!s. Arterial diseases are accounting for 50 )ercent. of the deaths in the TTnited States. Aenator Molzr.AN. Rnt. the fiunl is not, going to be liinit.eil to t.hat.. As I unclerstand section 5 or section 2, itt is t;oint; irlt.o fundamental bio- ntediral an(11>nhavioral reseitr•cL. Senator IIAUT. We are taking a procluc•t. whi(•lr causes two of the rm)stt serious kinds of diseases in onr society, and that is Iny 1)oint. l3nt. I want, to move on to a c•oul>le of other things. 'I'lie Senator says in his Stateruent. that the warning on cit;aretle 1>ackat;eti (loes not in(•rease consnnil>tion. I think there was a sharp (lec•rease in conswnl)tion cl(le to the Intense eclncational antisnlokinf; ciinipaign. I think the facts sho«' tliere was a 5nl>titanlial clecrea5c•, soniclliing in the iu•ea of f:3 1>erecnt in tlre aclult I>ol>ulation to aG 1)cr•- ceni--- tiena l or 111'oxc.AN. I I ils it Ilot g1one back Itl> ? ti(•nator ITArrr. Yes. 1"es. «'licn the restrlction was lntt on this calu- lc,iign. l~articularly the t>ttLlic• air~~•avs. I woulcl likc~ to niovc~ on iincl ii4 S(•verilJ questions regiu•cling 1lic "Dear Colleague" letter which you circillalc•cl not too long a"o.'1'hal letter does not accnrately reflect the inlent,l>in•pose, ancl the fact5of tllisl>ill. Nmv it. sa1's first of all that tlie 11ar1-Kenne(I,y bill if;nores the r•e- srarch on cilusiction of disease. Otm Stnclies have revealed that, tlle 175 domrnance of researi cievelolnne.rlts over recent. morrths and y( tnotr, solidify the fact, that smoking causes these diseases. We, coltr:Se, would be more than lial)py to hear any resnlt.s that Senator has. Senator MortoAN. We will have sonle, and there is an area in wl tliere is a very decicle cl clifl'ereneee of Opinion. Senator IIw1T. I lwi sitre tlicr e i5 a(li ffercnce of opinion. ~r,nator Mor((:AN. Ancl I think I ('an sul>lror•t it, Senator, wit}r s( meclic,ll research and we will have sonie iLvailirble if t.llis cornlni• wil l allow us to prnsent it. Senal.or IlAlrr. Ver'y briefly, yotit' "I)ear Colleague" letter of J tiiiry 2f) says t11e llat•t-Kc~nncdy bill shorlt circtlits c•ongrestiionitl a siclerat.ion for funcling in biorne.dical research. 'I'he fact. is tllis exl>licity provides lllat. Conhress will 1mLintain (•ontrol over tlle ftl~ ing of sucll researcli. Seuator• DtoluiAN. Wliell I say shorl, cir(•nits con~ressional consich tion I aiil talking about, 511or•t. circuitinl; in proc•ednres by wllichl 1(x•at ions Itave been rnadc+ for iuedieal researcL on tlre basis of need q cal>al)ilit;y. As I recall f-r•oni last. year we were trying to force tiornc I (lit.ional nioney on sonte of the intititutes tliat. they did not. feRl t1 coulci use at, tlletirne. SPnator• SciiwrllKPar. WeII, I have sonie (lnestions lnlt. I think we c };et into tlient in later le.gislation since I anl tlle only one arouncl. 'I'Itank •you ver .y ,mlclt. I have been infor•wecl that. tlie chairulan of tlie snl)contuiittee had rmke iL (fllor'11111 1)Ilt. lrl the Ilieinttirue I wonlcl like to welconie Cont,n•c nian Fountain who is here froni North Carolina to testif,y. IIe is t her•e? '191en I think tlie subconiuiit.tee will stand in recess until I C11aItYililll Ir.turns wlliclt will be ver,y, very shorily. IBrief re.ces,s.] Senator 5c;rrwi•:rxr:rt. The snbconunittee will please reconvene a we are goint; to contintle. I clo not believe there ar•c+ any other (Iont,n•essrnen I>lrsent so we i going to contiuue, with I)r.'I'lieoilor•e Co(>1>cr, ASsistirut. Secretary - Itealth, I)epartulentof Ilealth. I+klnc:ctint, .,,,.1 STATEMENT OF THEODORE COOPER, M.D., ASSISTANT SECRETA] FOR HEALTH, DEPARTMENT OF HEALTH, EDUCATION, AND WI FARE, ACCOMPANIED BY DR. DAVID SENCER, DIRECTOR, CENT] FOR DISEASE CONTROL; DR. FRANK 7. RAUSCHER, DIRECTC NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES ' HEALTH; DR. ROBERT I. LEVY, DIRECTOR, NATIONAL HEAJ AND LUNG INSTITUTE, NATIONAL INSTITUTES OF HEALT AND MR. GENE R. HAISLIP, DEPUTY ASSISTANT SECRETARY FI LEGISLATION (HEALTH), DEPARTMENT OF HEALTH, EDUC TION, AND WELFARE, A PANEL 1)r•. Coorr•.ir. Wc liave, in aclclition to I)r. tiencer, I)r. liails(•licr•. I Lev)•, ancl AIi•. Iliiisliu iiti availal>Ic resonmcs. We 14elc•onie tliiS ol)fwt•tiinity to (liticnSs n•itli }'oin• corurnitict' I Iieilltli consc(laencc:5 of sniolcinf; ancl the iolicl; of tli(- ); ,

282 -3- smokers were the sturdiest humans, a better explanation would be the secularity effect. There were fewer pipe smokers in each decade, the converse of cigarette smokers. These data are published and available for all to read. Why have the proposers of the bill not heard of them? It is because the annual supplements to the Surgeon General's Report on Smoking and Health are limited reviews and interpretations of the medical and scientific literature, from which are screened out articles that do not agree with, call into question, or destroy arguments and conclusions supportive of the official government position. As an example, in a presentation prepared for hearings on a proposal by Sen. Moss (Utah) to limit by law the amounts of nicotine and con- densate (so-called tar) in cigarettes, I pointed out in 1972 that ap- proximately 1790 articles published since 1960 were not cited. Lists of these were supplied. On occasion, publications not supporting the official position have been suppressed. The epidemiologic problems, shortcomings and errors were aired at a nane1 mantino nP +S+e eenc t_ , rI. ; .., ,. '.. e a :)ove _Ls no ~ secret information. One regrets that the proposers of the bill have not been made aware of the serious defects, obsolescence, bias and incompleteness of the information on which they appear to base the current proposed bill. Now as to lung cancer, there is a statistical association between cig- arette smoking and lung cancer. But at present the natupe of the 283 -4- association or whether it is causal are not•known. The text of tlie original Surgeon General's report deals with the difficulties of assigning causality, but the summary and conclusions brush these aside, and assign a causality not demonstrably evident in the text. It is widely known that a statistical association is not by itself proof of causation. A statistical association may point to experiments that will help to determine whether there is cause involved. Animal experiments to my knowledge have not succeeded in the production of so-called human type lung cancers (pathologically termed squamous cell carcinomas) in a significant, percentage of any species tested. This includes inbred mice exposed to heavy cigarette smoke inhalation over practically their entire life span. Certain false alarms like the Auerbach beagle dogs, and other studies of rats -and mice, have stirred hope that a model had been achieved, but no cancers that grew, spread and-led to death like human squamous cell lung carcinomas have been reported. After 45 years of inhalation research, and although expensive efforts continue, no success has been achieved in producing experimental lung cancers in any reasonable or even small numbers of experimental animals. Skin painting is cited in the bill proposal as part of the evidence of carcinogenicity of tobacco smoke condensates. Suffice to say that in the past 5 years, skin painting of animals with tobacco condensate has yielded so few tumors, either benign or malignant, that the practice has practically been given up. Only a few governmental agency experiments continue. Why tumors were produced years ago following skin painting TIMN 450325

278 Senator KANNEDY. Would you say those are the leading three, or do you want to add a couple more, just so we got the last couple, and we have your prime references ? Dr. SOMMERS. Well, sir, there are a large nunrber. Senator KENNEDY. No; just the top couple, that come to mind, within the last 5 years; studies that you are relying on. Dr. SOMMERS. In relation to the cigarette as a Senator KENNEDY. Exactly. That is right. Dr. SoMMERS. There has been very recent interest in this. In terms of the pathological literature, and the epidemological literature, is re- viewed and summarized hy Professor Iiurch. Senator KENNEDY. Well, that is the problem, you see, it see-ms that you are referring to the old studies. We asked you what the new studies that support your position- you seem to have some difficulty in finding them, or naming them. I)r. SOMDiERR, There are a number, sir. Senator KFNNEDY. (xive me the last two or three that you think are the leading ones, in the leading medical journals in the country, that support your position. Dr. SontMERS. In my position, there is not enough that is known about lung cancer. Senator Kl:-, Nr:DY. Well, that supports your position that it has not been proved about the relationship between smoking and lung cancer. Let me state that• very definitively, very precisely. You say you have not. done t.he research ,yourself in this area. You are relying on other testirnony, and other puhlications. Now, name them. I)r. SomMERS. Sir, the basis of my understanding is reading in the field for 40 years, and investigations in the field, and most difficult thing to provee in science is a negative. Birtt the fact that no articles producing conclusive proof of a positive, causative effect year after year, indicates it perhaps does not even exist. So you areaskina me to prove the negative. Senator IinRT. Will the chairman yield? Senator KFN NEDY. Yes. Senator HnR•r. I think the chairman is asking the same question I am. The first sentence in your prepared remarks says you are going to re1lie«• t.le newer scienhhc c: ata, no1; ana yze f ie ac.~c or a3sence. Y ou state you will discuss newer scientific data. Now, I look over the references in your statement, there are 3 (locmnents out of 1:3 that are dated 1975. AMy position, franklv, and I think to a certain degree, the chairman's is based on the 1975 IIh:W reports, Senator Morgan said there was more information than that. We want to he provided with tha.tt newer information. We are not talkinr aheut provinn the negative. We are talking about this new scientific data that you refer to, and some people this morning referred to in their testimony. We have threP articleG here that have 1975 data on it. Now, we are at a loss here, because there are no footnotes. You make some categorical assertions abrnit the state of the informa- tion and the evidence, and list 13 articles. We do not know -which ar- ticle5-which one refers to which statement. That would be helpful. TIMN 450323 279 if you would provide them. Three are dated 1955, an en you go to the 1960's. - I am talking about the HEW report, "Health Consequenses of Smoking," where on page 15 it says- Coronary heart disease is the major cause of death In the United States, and is the most Important single cause of excess mortality among cigarette smokers. I am referring to page 65, which says- Cigarette smoking Is the most Important cause of chronic obstructive pulmonary disease, emphysema, and bronchitis. I think it is, in a sense, with regard to this report, that we want the newer scientific data which you have promised. Dr. SOMMERS. In addition to what was already cited there are three papers by the Leuchtenbergers, who work in Switzerland, they point out that if you use condensates, so-called tar, in their model system, it has no relationship to the development of abnormal changes, which they regard as possibly cancerous, and if there is any part of the ciga- rette that might be held responsible, it is not the condensate. Those are the three papers in 1974. Senator HART. But those are newer than the HEW report? Dr. SOMMERS. Yes. Senator HART. June 1975 ? Dr. SOMMER6. Yes. If you will look at the reference in the HEW report, in certain sections, about a third of them were within 2 years of the report, in others, about half of them within 2 years of the report.. So the references used in that report a•lso go back quite a number of years. Senator HnRT. But the Assistant Secretary for Health signed this in .Iune 1975, and I presume he agreed with the conclusions then. He would have had the benefit of the Leuchtenbergers, or whoever. Dr. SOMMERS. No, sir, you do not realize there is a little lag involved between publication and receipt of a journal in the 1;Tnited States, that in abstracting, and the use of it by the Government. Senator KENNEDY. In fairness, just-your point just does not hold up. They have list after list of pages of recent studies, a•nd I will just read the year. Starting-I mean just at random, on page 62, this is one o;" i.'nem, :.,lecemijer ::' 'i 2, Sepv:em ier :,1;i`i 2-going (.ow n, ecem )er again, 1972. American Medical Association, November of 1972. Most of these ref- erences-March of 1973. March of 1973. May of 1973. Iust• taking one pa•Ire. And this is 1974 report. There is nott one that is before 1971. Dr. SoMMERS. Yes, sir, but I referred to the 1975 report. Senator KENNEDY. Who does I)r. Burch work for? Dr. SoMMERS. He is at the University of Leeds. Senator KENNEDY. Is he a consultant over there for any organiza- t.ion? Dr. SoMMFRS. He stat.es, in one of his articles, to answer obvious questions, he is, No. 1, not a smoker; and No. 2, not. in the pay of the tobacco industry. Senator KF.NNF,DY. OK. FThe prepared statement of Dr. Sommers and supplemental letter follow :] I

Garfinkel, L. Effects of Cigarette Smoking on Dogs. I. Design of Experiment, Mortality, and Findings in Lung Parenchyma. Arch. Environ- Health 21:740-753,1970, 93, Editorial. Nature 230:547-548, 1971. 94. New York Timee, May 9, 1970; June 11, 1971. 95. Wall Street Journal, July 8, 1970. 96. Letter to the Editor- Nature 231:643, 1971- 230 105. Magee, P. N., and Barnes, J. M. Carcinogenic Nitroso Compounds. Adv. Cancer Res, 10:163-246, 1967. lO6a. Proceedings of The Conference on OecapaHoaa/ ,,,--,Carcinogeneses. Trans. N.Y. Acad. Sci., in preas, 197ti! 106 ev e mo , k 97. Andena~nt, H. B. L The Susceptibility of the Lunga of `~ J- Am- Stat- Aseoc- 60:722 w - o 739, 1965. Ing and Health Albino Mice to the Carcinogenic Action of 108. einstain, A. Neoplaams of the Lung. In Cecil-Loeb 1:2:5:6-Dibenzanthncene. Public Health Rep. Textbook of Medicine, edited by Beeson, P- and 92r419-991 1039 98. Andervont, H. B. Pulmonary Tumors In Mice. IV. Lung Tumors Induced by Subcutaneous Injection of 1:2:6:6-Dibenzanthracene in Different Media and by McDermott, W. W. B. Saunders Company, Philadel- phia, 1971- Fisher, R. A. Letters to the Editor. Nature 136:474, 1936 Br Med 1 2 297- 98 ; : ,. -,, 2 1957; Nature 182:696 Its Direct Contact with Lung Ti®uee. Public Health 958. Rep. 62:1684-1689, 1937. 110- nher, R. A. Cigarettsa, Cancer and Statistics. In 99. Campbell, J. A. Cancer of Skin and Increase in Centennial Review of Arts and Sciences, Vol. 2, p. Incidence of Prima T f ry umourn o Lung in Mice Exposed to Dust Obtained from Tarred Roads. Br. J. E:p.Patho1.16:287-294,1934. 100, Campbell, J. A. The Effects of Road Dust °Freed^ from Tar Products upon the Incidence of Primary Lung-Tumoure of Mice. Br. J. Exp. Pathol. 18:216-223,1937. 101, Kotin, P., and Falk, H. L. 1. The Role and Action of Environmental Agents in the Pathogeneais of Lung Cancer. Cancer 12:147-163,1969. 102. Kotin, P., Courington, D., and Falk, H. L. Pathogene- sia of Cancer in a C'iliated Mucous-Secreting Epithe- - lium. Am. Rev. Reapu, Db. 93:115-133, 1966. 103.' Feinetein, A. Clinical Bioetatistics. XIX. Ambiguity " and Abuse in the Twelve Different Concepts of 'Control'. Clin. Pharmacol. Ther. 14:112-122, 1973. 104. Lijinaky. W., .nd Epstein, S. S. Nitrosamines ne Environmental Carcinogens. Nature 225:21-23, 1970. 161-Mrdopn State University, Ann Arbor, 1958. 11 Mainland, D, and Herreraa, L. The Risk of Biased Se~lwctinn in Fn..c.l.r2..i„ A,. :{. N... .-.L.. 1 3. Berkaon, J. The Statistical Study of Associatiom between Smokin~g and Lung Cancer. Proc. Staff Meetings Mayo Ctin-30:319-348,1966- Browntee R A A R i f"S ' iond Interviewers. J. Chronic Dis. 4:240-244, 1956. eruahalmy, J., and Palmer, C. B. On the Methodd- ogy of Inveatigationa of Etiologic Factors in Chronic Diseases. J. Chronic Di.- 10:27-40, 1969. - hd J Si eruamy,.tatstical Considerations and Evalua- tion of Epidemiological Evidence. In Tobacco and Health, edited by James, O., and Rosenthd, T., pp. 208-230. Charlea C Thomas, Springfield, IL, 1962. 114. Egner, R., and Denonn, L. (ed.). The Basic Writings of Bertrand Russell. Allen and Unwin London, 1961, 116. Sterling, T. D. Difficulty of Evwduating the Toxicity and Teratogenicity of 2, 4, 5-T from Existing Animal Experiments.scienee 174:1368-1369,1971. (100 Sterling, T. D. The Statistician Vi.-a-Via Issues of Public Health. Am. Stat. 27:212-217, 1973. 231 Smoking and Cancer A Rebuttal WILLIAM WEISS. MD The views expressed by Dr. Sterling in the preceding article are rebutted. 11 In his paper entitled "A Critical Reassessment of the Evidence Bearing on Smoking as the Cause of Lung Cancer," Dr. Theodor D. Sterling has reiterated his stand against a generally accepted hypothesis which is the basis for one of the moat important advances in preventive medicine during the past two decades- The evidence underlying the hypothesis has been thoroughly surveyed by the United States Public Health Service In a series of seven published reports from 1964 to 1973 so there is no need to review It In detail. Suffice it to say that the Public Health Service has concluded that cigarette smoking Is the major cause of lung cancer in the United States as a result of detailed epidemiological, clinical, autopsy, and experi- mental data. While it is true that an association between smoking and lung cancer does not constitute proof that the association is one of cause and effect, the judgment that the association is causal is bued on the criteria of consistency, strength, specificity, temporal relationship, and coherence. The data fulfiliing, these criteria were covered adequately in Smoking and Health, the initial report of the Advisory Committee to the Surgeon General of the Public Health Service in 1964 (pp. 179-189). The Iater reports have summarized newer data which continue to support the validity of the hypothesis. Dr. Sterling has chosen to ignore most of the clinical, autopsy, and experimental data and concentrate his criticism on the epidemiological evidence. His dissertation is characterized by the sins of omission, misinterpretation, overgeneralizatlon, Inconsistency, and innuendo. Without baina exhaueUvn I wnuld like tn diecua enm. .v.rnnlee nf these sins in Dr. Sterling's paper. Dr. Sterling's major contention is that the prospective epidemiological studies are biased by selection of the I ~ Dr. Weiss is Professor of Medicine, Hahnemann Medical College, Philadelphia, Pennsylvania 19102, ( 954 AJPH SEPTEMBER, 1975, Vol- 65, No.9 SMOKING AND I.UNG CANCER 953 populations surveyed and he singles out the American Cancer Society investigation of more than one milllonrf people for deta8ed criticism. He asks us to consider the possibility that the several deficiencies In method operate insuch a way that the population was loaded with smoken:m who developed lung cancer and nonsmokers who did no" This presumes remarkable penpicacity among the vulunteeri workers who recruited the population. He then generalizes i and assumes that the same deficiencies characterize other prospective studies despite the lack of documentation. H omits reference to the several prospectlve studies, such the Philadelphia Pulmonary Neoplaam Research Projeck which screened populations with periodic chest roentgen grams so that the prevalence cases were readily separated from the Incidence eases without altering the strong association between cigarette smoking and lung cancer ris While on the one hand it suits Dr. Sterling to invalidate the prospective studies on the grounds of populutlo selection, he uses the immigration studies as an argumen against the hypothesis. Certainly immigrants are SN selected. - Dr. Sterling's use of the Japanese study by Hlrayama of a quarter million people Is a flagrant distortion. He chooses to ignore the 5-year results of this prospective study which duplicate those of all of the other prospective Investigattons (see The Health Consequences of Smoking, pp. 68-69: Public Health Service, U-S. Department of Health, Educa- tion, and Welfare, Washington, DC, 1973), in favor of a preliminary 15-month report by Hirayama and contends ~ that the mortality rates of smokers and nonsmokers were a "lar.niv fhn com. " Thn .imh rin nnt rt.nRcn. hic int.m..ts. . tion- Indeed, the ratio of observed deaths In smokers to 1 deaths expected from the rates in nonsmokers was 1.06 for ~ males and 1.17 for females even in the short period of 15 ~ ~ months. The ratio for lung cancer was 2.92- This was exceeded only by the ratios for cancer of the pancreas and -~ cancer of the bladder but these were based on smaller ~ TIMN 450299

~ 284 -5- but are now rarely produced is unknown. An English book review of a work on tobacco and carcinogenesis stated that if in the 1950's the author had not reported 44% skin tumors when other laboratories were finding 3 to 5%, this field of research might have developed in a more orderly way. On what basis is the claim made of 90,000 lung cancer cases per year? It is based on death certificates, which are not scientific documents, alqd in general are not corrected by findings if an autopsy is performed. When analysis has been undertaken of the accuracy of a death certificate diagnosis of lung, cancer, when compared with autopsy findings, slightly less than 50 percent were found to be accurate. Pneumonia and tumors spreading to the lungs from other parts of the body, so-called metastases, are most often mistaken for lung cancer. Regrettably we lack a sound data base by which to establish the true incidence of lung cancer. The figures appear exaggerated two-fold at least. Lung cancer is not an entity either pathologically or etiologically. There are some 10 different varieties of lung cancer, each of which is likely a different disease with a different causation. One type called oat-cell carcinoma recentlv was renorted in a wrcmm of r.hamina1 wnrkers most of whom were non-smokers, and it appeared that smokers in the same plant were in some way protected. Time, scholarship, and money are needed to work out these difficult problems. Chronic pulmonary disease, also called bronchitis-emphysema or chronic obstructive pulmonary disc:ase, is a serious public health problem. When k -(r 285 a disease has several names, it is an indication that not very much is known about it. Emphysema of the lungs is difficult to diagnose clinically. Also pathologically it is difficult to establish its presence, type and extent, even when lung sections. These large sections a panel of experts examines whole are only available in a few re- search centers. Experts examining such sections, it was reported, could reach no agreement on whether, how much and what type of emphy- sema was present. In the current limited state of knowledge, blaming cigarettes as a cause is premature. Note that emphysema is largely a disease of white men. Blcak men exposed to the same environment including cigarette smoking, scarcely ever develop emphysema. Women likewise are uncommonly affected. Much investigation, including animal models, is needed. A claim that the cause of emphysema is lmown, if anything, tends to in- hibit research. Coronary heart disease is considered the most common cause of death in the U.S., affecting particularly males, the overweight, the diabetic, and individuals with certain inherited lipid diseases. The Framingham data originally publicized do not withstand critical evaluation. Studies of twins discordant for smoking have indicated that the strongest factor is evidently genetic or constitutional. A certain personality type has been discovered with a striving, time and pressure life style, evidently particularly predisposed to coronary disease. Today active researchers look elsewhere than cigarettes for the causes of coronary heart disease. TIMN 450326

Gl1 , YaQe 2 - The 13onorable Edward *:. FCennedy inherent in the original report. Scientists througaout the world have examined the original report and its elgnt successors and have had ample opportunity to examine tl:e lite;ature cited and conclusions drawn in ttae report9. T::e technical and scientific merit of the reports 1uve stood tae test of timie and scrutiny of the scientific body at large.. The other issue raised by the testimony is one w?-,ic.i questions the conclusiveness of the health evidonct. Rather than respond on a point-by-point baais to the testimony of :)ra. aommers, 1lockett„ Sterling, and others, I am enclosing.copies of an article by Theodore ll. Sterling; Ph.ll., entitled, "A Critical :teasnessmcnt of the Fvidence 8earing on SmokinF as the Cause of LunK Cancer," which appeared in the" Journal of the American Public Healtl: Aisso- ci;ation, Vol. 65, Np. 9, pages 935-952. 'ChiF article addFeseeF many 61 the 811eRed wea[cnessen or $apc 'i.n t~iL 'stientific evidence in the smoking-lung cancer hynottiesis, and the~e, sai~ne criticisms appeat' in the papers of the other authors. 4~iliiam'Wei'ss, '{.u., from Sa?rneman 'iedical College, Pai.ladelp`tia, Pennsylvania, authored a rebuttal of Ur. Sterltng'e article in the'nqme issue (pages 954-' 955)'. :'he,rebuttal is brief, Ia)t 'conci.se, and `refeYs to lmicl, of Stprling's argu®ents as "simpXe diversionary obfuscatiou.` 'S`L:e" ?'ebiuar: is'sue of JAFtIM continued'the diycussion, vith comments by Arq. tiiQg I ins, P.rosn, and Sterling (pages 15l-164). Bross and 1lipp,.ins tatze issue with Sterlins;-•-liigkins for the i.>•.iplication that :)e agreed •rftn 'Sterlinn's article. 'iic'nael A. Ibrahin, :'.:?., Ph.D., !:artirman of tlie Journal's I:ditorial Board, coxment3 on the discuesion with arn a, pronriute editorial (pages 132-134) , concluding t:uzt: "'Yhe persist@nt tontro+ie•ray''reg'3rdinfi the roj.a of'sil.-oling in lun}~'cadc3r c.atillot ~+e Xe'sol`v ed`ved merply by escaiating tht! `force of atEigaentVnrim and toa; 't`hat tliesc argulncnt's' ake t.ecominK ircireasl;ngly epph'is'ti"t'ed and rr.or'e'viRotous srives' to deason- eE`r*6 thaE tha' i's"i 1.011u#01~'Crlyiai.' "Let uo, taerefoi`e, Ca°rPfuiYy'oxath~{~e nature of the ti'ioi"hinss we cor[ftont hnd io'`iden~Ifv,mi,laGS~o`f a'c,ofoacfiatz them !.n `tae be3E"'int-ures"ts ti~' L~oth t~te `~ teilt~I'EiC~' Cp1V'CiiG~t;! 9nd thb' `~eneY3ly p~}iiiiation: r' " Continued div:isiveness around tho nrecise contribution of sdtd![~rr='~~`s'j~ot~n$ia'i'!v `~~o'`traFtt ddtisei•~rthot`es Fbit7polia8." s~r. ,. ._.. ......~,.; - ..,.,. ... . . . . . . ... . . . ~'Vinw"carittt is'~o=c5naruct aii' cybstacl6 "to '.Eutu'iM, ihdest{paWna •drid.rFat,~ia~a5l+i e`f; anvir•otuqenia`1'•cart.tnWhens: '4fi- the'ot•t.cr a,d'hd, ` lttia.re`can no yt*ktioti V.1ht e+tdeayreind"'hei9yKfion.af `aRroKi`h''k ~r,•'oulu result' ire mre=*aod ttin harm. To dilute thcAi4oorfance of smot•.ing tb''fo6As!'tlt div@rt'ua frefm an iis+ortAn`t IL•$a`• " " ".9.It'r+thott; F~a'mEr!st• not Cortti=1.ue'evtidi~ +ction it favor of argu rient§n He ~oi,8ti: both ~1,ffici?ht' eai+iric grouttds and a ntrong ~.<. . . . t „ ,,. .. , , . . .. " ~• , ~, ,.. Page 3-'t'he tlonorable Fdward M. Tennedy moral oblip,ation to oroceod from where we are, throuFth consci- entious interventioa programs and creative environmental stndies, tovard refining our understandint of 1nnp, cancer etioloray." In our view, Dt. Ibrahia's summar7 draws an appropriate bottom line to the current status of the scientific debate. i'?'~•j lvis submitted Us teeti+eony on this issue, apd the oriv,inal report and eirrht •subsequent reports to Congress are available. 4*e have purposefully not prepared analytical com+eentaries on the papers you enclosed with your letter since most of theat are not documented by references. Copies of e11 of the above mentioned references are enclosed., as well as a copy of a technical report issued by the World Health Organization in 1975, entitled "Smoking and Its Effect on nealth." I hope this adequately responds to your request. Any elaboration or additional infore.ation you desire will be prorided promptly. Gincerely youra, Theodore Cooper. *i.P. Assistant Secretary for Nealth Enclosures I i TIMN 450289 ~

252 J. Roy. Coll. Phycns Lond. been groupcd in three four-year periods to reduce the effect of randont varia- tion of small numbers which, while not important in relation to all deaths, could be important for deaths due to individual diseases. By grouping (he observations in this way, it will be noted that we have included out- year of observation in the first period for whiclr I)oll and 1-Iill (196•1-) had evidence that the initial self=selcction of respondents might still be af3ecting the treud in mortality. By so doing we may have slightly underestimated the mortality in the first four-year period and, consequently, underestimated the extent to which mortality subsequcntly fell, and overestimated the extent to which it rose. '1'ntn.r. 2. Ages 35 to 84 years. Death rate iu doctors and in population of England and Walcs, by cause and date of observation: standardised for age ~ r, CI L Standardised death ratc per 1 000 •~ i, , men per year in Doctors England and 11'ales Causcofdeath 15 -J7 1957 -61 1961 -65 1954 -57 19;i8 -61 1962 -65 Lung canccr I•10 0•85 0•83 1••19 1•71 1.88 Other c:utcers of uppcr respiratory and digcstive tracts 0•28 0-30 0-17 0•32 0•28 0-27 CBrunicbronchitisandcmphyseuia 0•44 0••19 0•54 1•GO 1-70 1•84 •\rteriosclerotic heart disease 5.19 5•64 5•59 425 4-91 5•64 Peptic ulcer 0•09 0•16 0•08 0-36 0•28 0-23 Cirrhosis of liver and alcoholism 0• 14 0• 17 0• 17 0•01i 0•06 0•0G t 1'ulmon;u•y tuberculosis 0•16 0•17 0-03 0-35 0-23 0-16 Related causes 7-40 7•77 7•4'2 8-43 9-17 10-08 Other cancer Other respiratory disease 2-25 0-49 2-06 0•62~ 2•07- 0-65 2•75 2-73 2-67 Cercbrovascular disease 2-06 2-41 1 2-03 ._ 1•36 2•69 1••16 2•57 1••t2 2-48 Other cardiovascular disease 3-01 2-93 3•03 4-13 3-16 2-93 Violence Other causes 0-74 1• F5 0•8G 0•79 0-81 0•79 0•77 • 1•36 1•30 1•89 1•56 1••t2 Unrelated causes 10•00 10•l4 ' 9•88 1 13 G2 12 57 11•69 N.,causcs 17-40 22•05 l8•01 '.17•3 ~ 21•74 21•77 I - - I I i ~~?u ~ We have compared these rates with tlre rat s for Lngland and Wales, as the great majority of thc doctors were resident in these countries. The inclusion of data for Scotland, Northern Ireland, and tlre Republic of Ireland would have improved the comparison, hut would have made little difference to the results. IIad we done this, the comparison would still not have bccn perfect as some of the doctors were nationals of other Comntonwealth cotu1trie, and returned home during the period of observation, while othcrs emigrated. 218 253 ,J. Roy. C:oll. I'hycns Loud. Rates for the doctors observed ovcr periods beginning on 1 Novemht•r and ending on 31 October have been compared with national rates ahscrvt•d uco months later (that is, from I January to 31 December). llortality rates observed in the three four-year perio, re shown at•I,,u;ttrly in Table 2 for 13 causes of death or groups of causes a for all rtu,cs. 'I'he causes of death have been shown in two classes according to tvhclher the conditions causing death were or were- not thought to be related to sntt,hit;g. For this purpuse, we used the classification suggested by the results oftht• lir,t tcn years' observations (Doll and Hill, 196•1). 1•Ve, therefore, cht„ilied as 'related causes': cancer of the lut,g (ICD number 162-163), otltrr cancers of tht: upper respiratory and di~estive tracts (ICD numbers I IQ--14f1, '150, 160-161), chronic bronchitis and entphyscma (ICD numbers 502, 527), arteriosclerotic heart disease with certain caclusions (ICD number •1?Q), peptic ulcer (ICl) numbers 540-542), cirrhosis of the liver and alcuhuliwT (ICD numbers 322, 581), and pulrnonary tuberculosis (ICD numbers 001-008). Since we had obtained detailed evidence of the causes of death for all patients who were certified as dying of cancer of the lung, we limited this category to deaths in which lung cancer was the most probable diagnosis. Fourteen out of 280 deaths were couse(luetrtly attributed to other causes; 3 in the lirst period, 6 in tlte sccond, and 5 in the third. Deaths attribtrtcd to arteriosclerotic heart disease with mention of cltronic bronchitis or cor pulmonale were excluded, as these would he associated with snjokin, for other reasons*, and deaths attributed to curonary disease with mention of hypertension were classified with deaths due to hypcrtension, as the carlier data had shown that these deaths were unrelated to smoking (Doll and Ilill) 1964). `I'Ite mortality attributable to lung cancer and arteriosclerotic (1ke2Ut: in doctors is, thercfin•e, not strictly comparable with the correspondin}; ratrs in the population of England and Wales as a whole. Thcre is, howevt r, tto reason to suppose that these modifications have affected the relative mortality rates in difTert:ut periods. "'.ie resu'r.s s'tow ~.'uar, e'ie morca'.ii.y o° c.oc, :ors :roui a''a ciseases werc `related to smoking' increased from the first to the second period an(1 tht:it fell to its initial '.••vel, while the corresponding mol•tality rate of all mcn iu England and XV;..: s increased steadily throughotrt. Of the individual disea,es, the most striking difference is observed for lung cancer, the mortality of,hielr fell by 25 per cent in doctors ;urd incrr:,,ed by 26 per cent in the ;;eucral population. ".fhe trend in mortality from diseases that were unrclatt•(I to *'1'hi. cxclusion Mas tuade fot- the ptu'p(ue ofcsainining coronary disease un(.uutplic.tteLl b) athcr faclurs, but tl csr dctths should have bec•u inrludai ;uuung 'rrlatcct diseases'. The numbcr (-ti), however, is tuo s,nalt to have matcrinlly alrectcd the result. 219 TIMN 450310

TIMN 450313 • 258 259 \Fo. For in recent years ihe hyllothesis tllat• chcmicals ancl racliation Ilroltal/lt' csmql (.:lnrcr lty iniitatlon of the e ell -enolue Ilas heell strongly sul)llol•ted. Fin•therntore, I he epidenliolctiric•al evidence ltas sho«'n t11at tha inc iclenr( of hrlulan ('a11(•er is nott the salnc: in all parts of tlle world ancl in all pol>iil:ction gronlls, bi;t that. the incidenc•ek of lnlnlan cancer vsuies front conntl;ti' to c•ountry, revion to rel;ion, alul llopnlation ,!rroup to poln:lation group clellencling on the natln•e of the ellvlron- ntenl. 'I'herefore, there nlnst be envir•onnlental features that play a deternlining role in the fornlation of lulnlan cancer. One of the most clearl}• established of these environnlental features is snloking, espe- cially c•ig arctte. snlokinl;. ('ilal.rette snloker5 not only have a nluch grc;lter probahility of develol)ing lung cancer than do otherwise sinli.- lau• Ilollslllokel:v, hnt. the smoker•s'have a greater probahility of dying froul a mlrlllrer of other cliseases. Therefore, our best present hope of proventin;,r canc•er doe5 not appear to lie in a vac•cinc against. viruses, lnitt in reuloving or reducing the levels of chenlical carcinogens fronl thr cnvironrnent. '1'fle single most intltortant• Source of these carcinogens and the one n•hich should be nlotit casil- v rentovahle is tollac•co, probably especiall,y thr t;il:ti fronl toltacco.'I'he. kInerican Cancer Soc•iety has etitilnatecl that lhe life cxllectancy of a man of 25 who continuall,y 5rnol:es two packs of cit;aurttes a day is 8 yeall•s less than that of a 25-year-old nonsmoker. .1n(l since witnesses at this hearing have previously raised the qnes- tion of wllY tobacccl h:ls heen singled out, I would like to refer to proh- altilit•`• tahles of death within the next. 1/) years for specific cause.s, which look at all cleaths. Taking the age range of a.70-ycal•-old nlan, the ntost prominentt c•ause of death is arteriosclerotic heart disease; thc• sec•oncl is lculg c•':ulccr; ;lnd the third is stroke. So the three rltajor categorical causes of death in this age gronp alro those where the risk factor is much higher in snlokers. Thc other itlajor c•ate."'rn•ical c•ause5 of cleat-17 inc•lncle enll)hysenta, where snlol:ing V. a canse, ancl lmenntonia, where it is prol/•<rbl•y a c•ontribnting factor. So it. is Ohvi(,us that. we 5ingle out snloking Imca118(: of its (hlantdt.ative iniltor'tance in causing death. titolll/in,_r cigarette snlolcing wollld have the greatest effect on in- c•reasino. life cxilc(•tan( Y, lnlt, if that is not Ilossiltle, re(lticing the level III! 1or 4 ,u +..1......... ..1.7 ..11....,.4 ......._ ~ ..7. 7~_-(i__- .• i r - .,.. ~,.. Sntolccl:s. I'hcref(/re. 1 f a tax based on the level of tar and nicotine in vi.-;n•(•ttc5 clec•reased tlte ;uuonntt of expo5ure to tar, it Woldd help to llrovent sonic of the caul(•cr:s which otherwitie wotd(1 be cansed lty sntolcing. Iiowever. f(u•tller research is still lleecled on cancer and otller clis- e:l,~eti l:oth to lielll ]ncvcnt• those di5ea5es tllat are not. c•arlsecl by slnok- inqr und to hell) cln•e those cliseases that cannot be plrvented. For ex- alnllle. Ive need to develoll better therapies for cancer l/ased nl)rnl an tutcleishlncling of the diil'erences in'hiochelui5try and (•ontl•ol of cell rltt;llilllicatien between cancer cellti ancl normal'cells. Colnparison of vil'tis-tr:nl::fonnecl cells ancl nol•lual cells is one of the ]mstt systeln5 to tind 5iu•h ditlerences. I lmcevel: «•e n7u5t tr~' evcn harcler tYl llrevent cancer before it starts, sincee so far it ha" llc~cn (liflicnlt to finel Inanv Liochenlical ciifferenc•es lnItWeen c'all(•er cclls and nornlal cells tltat can he exploited in therapy. i'or prevention, «•e mnst devise hetter nlethocls of testing for factors in the environment., including chemicals from industrial processes and possibly food additives, that can cause cancer, and after we find these factors we must try to remove them. In addition, we must try to under- stand more of the mechanisms by which chemicals and radiation cause cancer in the hope that such knowledge will make it easier for us to recognize these carcinogens and perhaps to devise means to prevent their action. Ilowever, when as in the case of smoking we find that a carcinogen exists we must act to prevent it from entering the environnlent. From the point of view of a scientist engaged in cancer research, it is .paradoxlcal that t.he U.S. people, through Congress, spend hun- dreds of millions of dollars a year for research to prevent and cure human cancer. But when we can say ]low to prevent much human cancer; nanlely, stop cigarette sluoking, litt.le or nothing is done to pre- vent this cancer. In fact, I believe the U.S. Government even subsidizes the grOwlng of tobacco. As I said at the Nobel Festival banquet in titockhohn, I am personally outraged that this one major method avail- ablo to prevent much human cancer; namely, the cessation of cigar- ette smoking, is not nlore widely adopted. Finally, I should also like to conwlentt on a possible large increase in fundiilg for biomedical and other health-related research. At present the U.S. system of snpport of biomedical research and the results of this I/iomedicall research are the best. in the world. Therefore, we must be carefn] before undertaking drastic changes in the way we fund bio- medical research, and we should especially be careful to ensure that quality is stressed in all bionledical research. An excellent way to insure ihls quality is the s,ystenm of peer review of grants used at NIH. Fnr- ther•llore, although at a particular time we might wish to work on a particular problem in biomedical research or solve some health-related problems, if techniques and theoretical knowledge are not advanced enongll to supply a proper foundation for the research, it may not be possible to approach such problems. Nature yields her secrets slowly and only when a proper foundation of previous knowledge exists. 'I'herefore, I.vonder about the advisability of trying to spend rapidly much larger suuls of money in this area. I suggest. that a large and rapicl inclrase in ruoney is not warranted. ATore lmportantt is a mechan- r.. 1Snl for .7tiRttranrn nf seareh and a<roocl ~eer review c,inec, ea. re . „, 1 e.~ system. In concluslon, I feel t.hat, the snpport previonsly extended to can- ccr research by the .Nr7Mr']l'an 1)eople. through this Congress indicates a c'oncern with lweventingr this disease. Research indicates that. the best present. luethod available to ln•event nnlch cancer is to clecrease smok- in;,r. I. therefore, snpport congressional action to decrease smoking. Thank yon. Senator KF:vrrFnr. I want, to thank you very much for ,your com- ments. Tt. will be a wonderful lnxur~• to find 'ways of spendlllg the money, if we get• this bill passed. We will take notice of your com- ments al/ontt the real potential for the elimination of cancer in terrns of being able to exlmnd resources in these areas. Of course, we do have enornlous flexiLility bnilt in. It can be spent on health education or ))re- vention in the cancer provram. There is now fronl $40 to $60 million being spentt on this which I think is inadequate. But any comments

290 Hon. Senator Edward M. Kennedy page 2. I request that this letter and its attachments be made a part of the hearing record by insertion at the close of my testimony. 291 Enclosure #1 References To Additional Personal Publications On Lung Cancer And Its Origin 1 1. Williaems, M.J. and S.C. Somers. Cancer, 1962, 15, 109. Respectfully submitted, 2. Willi:ms, M.J., R.N. Barnes and-S.C. Sommere. Dim. Chest, 1963, 44, 95. 3.- Williams, M.J. and Sommere. Aa. J. Mad. Sci., 1964, 247, 422. Sheldon C. Sommera, M.D. Director of Laboratories 4. Rennedy; J.H., M.J. Williams and S.C. Somers. Ann.,Sutg.;, 1964, 160, 90. 5. Ober, W.B. and S.C. Son®er.. N.T.S: J. Med. 1970 70 869. SCS:nee , , , Enc:(1)pereonal lung publication (2)publication list s 6. Gould, V.E.,,R. Wenk and S.C. Soc®era. Cancer, 1971, 28, 426. (3)additional references (4)correctione of transcript 7. Terzakis, J.A., S.C. So®ere and B. Andereeon. Lab. Inve.t.,'1972 26 127. cc:Mr. Horace Kornegay, Pres., Tobacco Institute , , 8. 5oc®ere,-S.C. Pathobiology Annual, 1973, Appleton, N:I., p:309. 9. Sammers,. S.C..Proc. IX World Assoc. Soc: Path., in press, 1976. TIMN 450329

I 286 -7- A decision to_tax cigarettes in proportion to nicotine and 'tar' would be based on doubtful, specious or mistaken information. The original Surgeon General's report, for example stated that nicotine is probably not a significant health hazard. No new persuasive studies contradict this generally held opinion. Etiologic conclusions based upon ciga- rette condensate (so-called 'tar') suffer from the demonstration that . fresh condensate free of artefacts of storage has virtually no tumor producing quality. In summary, I wish for better health for Americans, and have worked hard•in the field for 35 years. In my considered opinion the bill pro- posed is scientifically unjustified, and if passed would generate such huge sums of money as would be likely to coopt and to corrupt most of our medical and scientific research effort. C..~.___... 287 References \ 1. Berkson, J. Proc. Staff Meetin s Mayo Clin. 30 (15): 319-348 2. (27 July 1955 "Statistical Study of Association between Smoking and Lung Cancer." DeFaire, U., Friberg, L. and Lundman, T. Prevent. Med. 4 (4): 509-17 (Dec. 1975). "Concordance for Mortal t~ y rwith Special Reference to Ischemic Heart Disease and Cerebrovascular Disease." 3. DeFaire, U. Acta. Med. Scand. Suppl. 568. Stockholm 1975. 109 pp. "Ischemic Heart Disease in Death Discordant Twins." 4. Friedman, M. and Rosenman, R.H. Type A Behavior and Your Heart. A.A. Knopf, Inc. New York 1974, 2 pp. 5. Hammond, E.C., Auerbach, 0., Kirman, D. and Garfinkel, L. Arch Environ. Health 21 (6); 740-68 (Dec. 1970). "Effects of 6. Cigarette Smoking on Uogs." Kreyberg, L. Histological Typing of Lung Tumors. International Histological Classification of Tumors, No. 1. Wor Organization, Geneva, 1967. 28 pp. ld Health 7. Passey, R.D. Nature 219: 98-99 (6 July 1968) "Tobacco and Tobacco Smoke Studies in Experimental Carcinogenesis." 8. Rose, C.L. and Bell, B. Predictin Lon gevit . D.C. Heath & Co. Lexington, Mas s. 1971. 2 5 pp. 9. Rosenblatt, M.B., Lisa, J.R., Teng, P. and Beck, I. Bull. N.Y. Acad Med. 45 (6): 519-527 (June 1969) "Validity of Lung Cancer Mortality Dta." 10. Rosenblatt, M.B.. Teng, P.K. and Kerpe, S. Prog."in Clin Cancer Vol. 5, pp 71-80. I.M. Ariel Ed. Grune & Stratton, Inc. 1973 "Diagnostic Accuracy in Cancer as Determined by Post Mortem Exam- ination." 11. Rn ent,l~++ v n m...... n ..._S_............ ..:... . ._:..a~f ...,.v_,~~V~ ~ __~ n_~.y t ..__ ..e. . . 3(10): 53-59 (Oct 1971) "Prevalence of Lung Cancer.`" 12. Thurlbeck, W.M., Anderson, A.E., Janis, M., Mitchell, R.S., Pratt, P., Restrepo, G., Ryan, S.F. and Vincent, T. Am. Rev. Re.^,p. Dis. 98: 217-228 (1968) "A Cooperative Study of Certain hleasurements of Emphysema." - 13. Weiss, W. and Boucot, K.R. J. Am. Med Assoc. 234 (1.1): 1139-1142 (15 Dec. 1975). "The Respiratory Effects of Cholormethyl Methyl Ether." T'IFMN 450327

Ilrr ci I, I:w 1 fl . ,;t 11'r• tirllwl•arcr:r;. l"on arc saevl'n though lhl' person hchind nrrissluolcin, r Irecause thatt is where IIu• lr:u•rier is, tllat.llte c•irc•ulat.ion issut'll that- Iltis lx>Ilufion prnl)le'ut would not iulpac't on tlte seat in tbl fronl ? Ih'. tir.nl'I'his is a restllt of a stndy by the F:1:1; yes. tirnaior ti/ rnt i:nct:rt. Go uhc'ad. I1r. ('cu,rrar. Iwoulll likc' to conc•ludc' nty initial con'ntents, Senator, «-ith just a view of how we see the p1•obleut. 11"1• Ito think thal cigar•ette sntoktnt; is huz:u•dous to,yoln• heabtli and rr I:u•re prolrtblli cause of illnes.ti anlt pr/rbably 1)rcm:lfure death. We fl•1•I that Ive Itavc' nlade sonte progrl'ss in oltr• bealth e(ucation effort, and wl' are ulakin". sonle prol;rl:s.5 overall ill the c•onlrol of disease, rec- n"nizing tlutt, ntsut}• ot' these cllronic• ltealtlt prol)lcrns probabl,y have nnllt il)le c•auses. .1lthonrh t her•e. is st ill not a sat isfactlx;y situation, we Ihinlc Illere is prol re'ss bc'ing rmt.dc' in thee face of many pressures, 4•nllural factors, loss of resl)e/•I for authority, and urany other iml)or- I;Int illtlul'nc•c's. I thinlc Illat the su•ea. which I:un ntost concerned about relates to Ihe f;u•t that we- have apparently Ireen failing where we. had hopecl for srll•cl'ss ;tnd tltats is with ottr 1•Itildren and the youn~(r.11'e need ntuch lnore 1•ITective prlif;rarns to revl'1•sc' tlte+ trenels ill the inl•reasingly yunn.g/•r l•Itilll lalcin~ up ci~are.lle snlol.inf . So ;ts ~t•l' titalell ill our Forward I'lan for IIc'altlt, it is not realistic tn rie%A• this priruarily as a ntedical prohlent. It is :t major slx'ial, eco- noolic, rultlu•al, Irtiycholohical pllernorucnon tI)at indl'ed has profound lumllh iluplicationti. We lx'lievee it. is nrore produc•tivc' to focus otu• altenliun on ihc' umlerlyin" conclitions .utll antecedent causes of pre- vent;tl,le disl'asc' ill this respect 11t:ur to concentrate only on the treat- nlont of clisl'ase itsc'lf. For exautl,le, by reviewin". the dirnension of a I)rol,lenl slu•h as 1•igsu•etle snloking, %%-e Nv:tnl to fasllion I)rogrra.m goals :ul/l initiutives ainted at wlty pl'opll'. «•ant to snloke au)d ellruurate tltat p;u•t il•nlar f.u•lor ill t hc' prevent ive roll' t hat Wl' have to achieve. No%%• :t key prevc'ntion locltnillne is t.hl' lu'alf h cclncat iuu of the pul.)lic. 11'r llisrlissell this with tlle conum(tl'e l,reviously ancl yoll ha~•c' pcnding II'gislatiun in this regard. liut %%-e have lo llo a nnlch ruore creative and innovat ivh ~ol) in t ltese arc'as. I do nol. want. to impl•y f hat a sucl'essful I,ro~rnnt of prevc'ntion will l't•entually lx' jnsl as a sinll>lee ruatter of rnurl' pnl,lil+ elluc•ation or healtb edncation. I)cl isions b~y individllals C' 'l•_1,S, C~,ePp y 111','„Ilelll'eh, ')y ln tn) valul ti and t he social l'rolol;y of c au•h pc'I on, and no one :tl)proac~t r:ut lx' set forth as a solution to the healtlt prol)lents brouhht ou by sruolcingr . 11'e rultst continne to incrcasc o1n• underst:ut/ling of the Inuler•lying , ans/'s suul factors, incluliing our rescarrh I)ro~ rants. As a scx irty we lullst al)lu•oac~h this ell•l't•tively to Ix' aintet'1 .u In ita~'ior :utli rit:ull;e WhieIl lealls to srnokinf; cessation; antisntolcinr rarrnpail;ns or even ,•In•irunntenhtl chan~cti Whil•It In•otc'rt tlre inllivrdnal frout the efl'ec•ts „f 1•iYarl'ite smol:ing or an}' Icincl of sutolcinf; itself, for exaunl)le the II'ss Il;u•luful cil;:u•c'tte. As you kno~~•, sonte outstandinl; progress has I,ren ln;ule in reduc•tion ill the t:tr ancl nic•ot.ine l•ontentand thcexpostu•e 180 inn it,;e'If is Ilp and oul rathl'r thnn II'n,rtltwi5e throu- lr t.lte llere' is ltuife a separalion of nonsmakcls froln tlte smoke rated ill Iheslnokin);au•ea. 181 V X\ l to substances like c•aa•Ix>n ntonoxide by improverrrent in the lrtur ing, growinl;, ln•ocessinl;, and mauufacture of c'if;arcttes. '1'hus our overall sf rate.gy emphasizes those areas we think is a.ppropriate and does include biomcdic•al research. We think thatt we have tlte oblit-lation to as•5ure. wide, dist.ribu,t.ion of the findings so that people nnderstand the iruportance of tlre labeling, whether it be t.he Sur~emi General's label or the tar-rtrc.'otlne label that has been r•eeommended in the past. 11'e think we should nrake sure t.hat this health education awareness and irnpact on all of the progranrs reach the> special target populations inclucling the chilllren and par•ticularly the youug women. Now, t•et,rulator;y programs in this area ar•e. the responsibility of industry, I{'ederal regulatory agencies, and the States to stay aware of ttnd coope'r:ttc' in cleveloping regulations for the Federal Trade Cout- ruissiorr :raut the advertising policies for the Federal (bmmtutic'ations Colnlnlssroll. 11nd we are aware that the State lel;islatures have be- corne'e act ive in a variety of areas such as snrokinl; in public places, taxa- tion, and sales re;;nlat•ions. In lnlr'suit• of the preventive rmpact, one factor is or•ientation of our health education strategy; the childr'en ar•e, for the most, par't•, t1Le logical kmneficiaries of whatever we. are ~,*Orn~,• to try •to do now in health education. They are not. yet. smokers in larhe propor•t.ion and they are•still forining their behavioral patterns anct their values. The Depal't•nlellt. has a Illajor responsibility and comnritntentt to try to work particularly with this target group and the Nation's children. We believe if they acquire throuf,rlr school healtlt cln•r•icultun a new t,ype of infornrat.ion source and wtder•standing of their own bodies and t.he influence they can have on their own healtlt wit.h the proper lutllerstanlling of disease, if the'y adopt the positive conc•ept of their self-dignity, self-confidence, self-help, tLe probabilit,y is t.hey may not elect, to bel•ome chronic srnokers or sntoke at all, and we think that we can enhanc.e that• prospect. Itt will cost nroney and we have no instant solution but we are l•om- mitted to working ful•t.her in this area. Dly collea(rues and I will be. pleased to r•espond. Senator SlIrrwrrxFrt. Senator Iiart? Senat or 1 i.vtT. Thank you, Mr. Chairman. '1'he tirst. question is, do you know, since presumably thc recom- menclation will corne from your collective offices, whether and if so when the administration will take a lwsitiort on this piece of leglslatron ? Mr. ILVs1.IP. \Ve_ of r•nttrgn fov.,n 41+ 7. °t'" i`td 1l'IC. nicotine content. of cigarettes, l~ttt. to focus on lllis patrticular piece of legislation, I thinl:, is probably not the desirable vehicle for suppot•t- iul,r research, bel'.ause of the uncerta.inty of the kind of fundinr and t.he onus of wheree those. clollars for research would have been der•ived. 11'e have not, hlrwever, taken a formal po,ition on tlte lel;islation. I)r. ('oorr':rl. I have no timetable for you, Senator. If you wish, we will get that information t.o yon. Senator ILtur•. Th:urk you vcry much. Now, I believe in your irttroductory remarks, I)r. Cooper, you men- tion that. total social costs-I'm not. sure of the phrase you used-of ril;arette Smokinf,r relating to disease was in the neighborhood of $11.ri billion. TIMN 450274

xrt 222 TABLE a-SmokkN ard Total lls.thr. 15 Month's Fo10ow-up RsarFt of Prospectire Study for 265,118 Advlts A0e over 40 in 29 Hwlta Cenur Districts in Jepan (January. 1966-March, 1967)' Jan.-June, 1966 (First 8 Months) July, 1966-March,1967 (Next 9 months) Jae., 1966-March,1967 (Total of 15 Months) M F Total M F Total M F Total Actueldrethsimon0srnok.rs 426 4 80 486 792 104 896 1,218 164 1.382 Expscoeddwrhet 44 52 496 704 88 792 1,148 140 1,288 Ratio MwuExPxtb 096 1,15 0.98 1.12 1.18 1.13 1.06 1.17 1.07 • Soums- Hhayane.' ~ TebOe 4. t 0oni.d by spWYine epe-specific deaeh nte lor nonsmokers to smokeri populanon by age groups. And, Indeed, tkb is exactly what was found. Smoking and ffeelth reports that of 26 diseases, 25 had mortality ratios of I or larger and only one had a mortality ratio of smaller than 1(p. 1g2 in Reference 9). However, proponents of smokingidllease links have refused to accept Berkson's arguments. Instead, they have claimed either that specific- ity don exist, nevertheless, by pointing to the very large mortality ratio for lung cancer9 and to the tact that a very small numlxr of diseases did not show a higher incidence of morta8ty for amokers than for nonsmokers 3 z or they have lended to daim that the overall increase In mortality of smokers h due to the ubiquitous effect of smoking 3 3 But fhr Ja,panne daU, which appear to be free from at least one major source of selection bias, fa8 to find an overall diffeyence in morttlity between smokers and nonsmokers ("1'able 9). 0f 37 diseases analyzed, smokers have a higher mortality ntio for 21 and a lower mortality ratio for 16 nuses of death. Also, the largest smoker mortality ratios aee for eanar of the pancreas and cancer of the bladder and not torlungrancer. The lung cancer rate is about 3 times as great for aeokers than for nonsmokers, but so are the rates of canarof the esophagus and of the cervix. On the other hand, chronic rheumatic heart disease, anemia, and cancer of the nrtum are reported much less frequently among mloken. In general, a distribution of 16 mortality ratios below anity and 21 above unity out of 37 could easily ocrurby chance if It were true that smoking has no effect at am on aay of the diseases. It mssl be emphasized again, however, that the data ptvssakd by Dr. Hirayama are In need of careful elaiaaBan. Of the number of problems raised by that dudf, two are especially vexing. Ffnt, the pattern of high incidence of cancer of the paaneas, bladder, lung, and esophagus raises the suspicion tlat members of the population have a high incidence of oecupational exposure to irritant air pollutants and ,' u.uc":nu~i~,ens. -nieeC, -~r. -=:rayamas popu:r:.on sppeats to have been gathered in districts with a high density of Industrial workers. But It is becoming increas- EdY apparent that the ocupational background of anokers and nonsmokers in of paramount importance in determining the incidence from lung cancer. It is not at all dear what accounts for thi® Interaction between occupa- ttonal exposure to irritating dusts and fumes and smoking. Selikoff has suggested that there exists a special synergism between smoking and some pollutants.3a A simpler explanation may be that constant exposure to lung irritants contributes to the cigarette habit so that the more a worker is exposed to irritating pollutants, the more he may smoke. The second factor Impeding critical evaluation of the Japanese data is the dearth of detailed information available about it. We have presented here the most detailed report of results made available by Dr. Hirayama In 1968. Two other reports were made public since then, one in a newsletter published by Seventh-Day Adventists35 and the other In a news release through the American Cancer Society.sa Neither one of these two reports offers a detailed picture of the Japanese data. Rather, they report only those diseases for which smokers have a higher incidence that nonsmokers and even here fall to provide the detailed analysis that Is required for proper dissemination of results of scientific investigations. Nevertheless, the results as reported37 were used by the National Clearing- house for Smoking and Health to prepare follow-up reports to Smoking and Health.ss Since the incomplete results of these later releases are In line with the eadier and much fuller reports In 1968 by Dr. Hirayama to HEW, we have presented those data, even though they are from an older summary of his results.* If we pull together the information which has become available in the last few years about the prospective studies, we find substantial support for the possibility that the findings linking smoking to lung cancer, and perhaps also to * It is disturbing to have to evaluate the results of a possibly important inveatigation from whatever fragments are made available to the public process. Ordinarily little merit would be placed on ecientific reports that remain hidden in the files of an agency (as waa the case with Dr. in the filea of NCSA until this author presented them in 1971 as part of a symposium during the 138th meeting of AAAS in 1971) or are related in newaletten or presented as news releases. Science ought not be conducted behind closed doors and it is to be hoped that a full report of Dr. Hirayama'e work will be prepared and properly refereed before publication. Meantime, all attempts by this author have failed to obtain additional information about this important study. SMOKING AND LUNG CANCER 945 other diseases, were due to a faulty selection process that introduced a large number of biases. A serious disagreement may well exist between a statistical viewpoint-maintaining that if N studies commit the same selection bias, they ail may end up with the same erroneous results-and the not Insubstantial reasoning that data collected under so many different conditions and yet showing the same results need to be taken seriously. Perhaps it La for this reason that a number of macrostatiatical studies (using population aggre- gates) become increasingly important. Results of Macrostatistical Population Studies Tkat Conflict with the Relationship between Smoking and Lung Cancer Contrary to the belief that a large number of observations on populations tend to support the findings that smokers have a higher incidence of lung cancer and other diseases than do nonsmokers, there are nlany studies using population groupings and aggregates that raise serious questions about that hypothesis. There Is no question that the most important of the macrostatistical observations concerns the leveling off of lung cancer mortality, which appears to have started sometime between 1950 and 1960. Lung Cancer Mortality Appears to Have Leveled Off Starting in 1954 It was suspected in the early 1960s that the prevalence of lung cancer was beginning to level off.36 Recent findings have verified that lung cancer mortality rates, both in this country and In England and Wales, have stabilized and begun to decline for younger and middle-age population groups. This decline appears to date from 1955 in the United Statess and from 1954 in England and Wales.J9 The decline in England and Wales is much more marked than that for the United States and apparently started in 1954 for age groups up to 44 years, in 1957 for age groups up to 54 years, and in 1964 for age groups up to 64 years (Figure 3). Clearly, it would be unreasonable to observe a decline in lung cancer rates at a time when the consumption of cigarettes is increasing if it were true that cigarettes are a major cause of lung cancer. The parallel observation of the leveling off and decline of lung cancer In this country and In England ought to have far-reaching negative implica- tions.* a The harm that may be caused in this entire area by press releases is well demonstrated by the release by Dr. Horn that "it may be three yeus before final mortality Ggures for 1970-71 are compiled, but early indications clearly show a lessening of the lung cancer death toll."'" Dr. Horn then goes on to ascribe the decline in cancer rates to the decline in smoking since 1964. However, the decline in lung cancer rates may date to 15 years earlier. 946 AJPH SEPTEMBER, 1975, Vo1.85, No.9 223 TABLE 9-Snwktrq and Eaeh Cauw of Deaths, Japsneae Data• Aduad Deaths urqng Smokers Expectad Deathst Ratio of Actual tn Expepcted Deaths Ca.pencraas 14 0.9 15.56 Ca. bladder 6 0.6 10.00 Ca.lung 40 13.7 2.92 Ca. nophagus 21 8.5 2.47 Ca.cervix 10 4.2 2.38 Other Mart diseaae 22 102 2.04 Stomach ulcer 37 21.2 1.74 Rheumatic fever 1 0.6 1.67 Ineectiousd'neases 7 42 1.67 Bronchitis 7 4.3 1.63 Ca. breest 3 2.1 1.43 Ca. liver 45 31.9 1.41 Othercencer 39 29.7 1.31 Other hypertensive d'qeese 17 13.5 1.26 Ileus 5 4.2 1.19 Hypertenirve heart dkaesa 18 13.8 1.18 Ca. stomach 176 150.6 1.17 Liver cirrhosis 35 31.0 1.13 Other disease 125 110.3 1.13 Otheraccklent 28 26.0 1.08 Arteriosclarotic heart disease 82 76.8 1.07 Ca.tongue 4 4.2 0.95 Senility 37 39.4 0.94 Nephritis and naphrosis 23 28.4 0.87 Diabetes 12 14.3 0.84 Daaenerative heart disease 26 34.5 0.75 Syphilis 3 4.2 Respiratory tubercuksis 38 55.4 0.69 Gastritis, enteritis 9 13.2 0.68 Vascular lesions for cwstral " nervous system 387 573.4 0.67 Benign neoplasms 14 21.6 0.65 Pneurnonia 23 35.3 0.65 Suicide 20 32.0 0.63 Automobile accident 29 47.5 0.61 Appendicitis 5 8.6 0.58 Ca.rectum 11 269 0.41 Anemia 2 4.9 0.41 Chronic rhaumetic heart disease 1 5.5 0.18 • Sourp; Hireyama,r s Table 5. 1 Obtained by applyina death rate among nonsmokan far each aex to smokers' population for sach sex. Other Macrostatistical Eoirlnnro Thof Th,- Doubt on the Relationship between Smoking and Lung Cancer There are many much-neglected findings of other tlfacrostatlstical studues that conflict with present beliefs about smoking and lung cancer, Briefly, the most striking of these are: TIMN 450295

r It 270 Senator KFNNFnY. Doctor, I ain going to have to go. I only have 4 Ininutes to get. dver there. 11'e will recess to 2:15. AFTERNOON SESSION Senator KENNEDY. We will come to order. 1)r. Somnlers, woiild,yon continue? Dr. SorrrrEas. In the interest of saving time, before the lunch break, I d id not iclent.ify myself. I am Sheldon C. Sommers, M.D., director of laboratories, Lenox Ili1l Iiaspitktil, New York; clinical professor of Pathology, Columbia University College of Physicians and Surgeons, New York, and Uni- versit,y of Southern Callfo1911a, Los Angeles; editor of the Pathology Annual and Pathology 1)ecennial Series; chairman of the Scient.ific Alvisory 13oard, Council for Tobacco Research, U.S.A., Inc.; with about 260 publications. My curriculum vitae auid publication list are available. I would like to briefly recapitulat.e the points made already, if you would like, Mr. (~hairn~an. My purpose, in response to the invitation to present. m,y personal view of the status of knowledge of smoking and health, is to review t.lle newer scientific data. This material is not included in the quota- tions from the 19 75 version of the USPIIS smoking and health report cited by Senator Ilart as justifying bill S. 2902. First, in respect to t.he reported overall higher death rates of smok- ers t.han nonsmokers, the results were obtained by statistical epide- miologic methods now recognized as erroneous and use of which is no longer regarded as justified. Nonrandom colnparlSolls, meaning that. smokers and nonsmokers a re nott random subsets of the population being tested. Number two, dependence on limited statistical tests for proof. 1`'hen Rose and Bell wrote their monograph on predictimr longevity, they tested factors that might be associated with early death among aa group of Boston World War 11 veterans, followed carefully for 30 yea rs. A one-to-one comparison of cigarette smokers and nonsmokers gave smoking the number one place as a predictor, like in many other studies. Ilowever, .vhen rmrltinle factors were included statistically. ci;raurtte smoking dropped to sotnewhere beyond the 30th most silg- nificant rurdictor of early death. Third, secularit;y, meaninu the change in habit. patterns of the poj-)u- Lltion from about 1910 to 1960, with increased proportions of cigarette snioken5 in each decade. A model ponulation, not. a real population, with such changes over equal tinle will show a statistichilly significant incrrase in total death rate as a minority changes toward a majorit,y. This secularity factor or change in population patterns has no health imrllication. For example, in the original Surgeon General's report a table showed pipe snml:ers to have a lower death rate, 0.8, t.han nonsmokers. 11'hile encouraging a belief that pipe smokers were the stltrdiestt hmnans, a better explanation would be tl,e secularity effect. Now, as to lung cancer, tllere is a statistical association between cigarette smoking ancl lung cancer. Rutt at the present the nature of i lie association, or whether it- is causal are not known. TIMN 450319 271 The text of the original Surgeon General's repq%aeals with the difficulties of assigning causality, but the summary, and conclusions brnsll thesc aside, and assign a causality not demonstrably evident in the text. One wonders about the Surgeon General's report, because it turns out to be a limited review. Articles are screened out that do not sup- port the official Government position. Senator KENNEDY. That is a very serious charge, Doctor, as you well know. What you are accusing is the Surgeon General, and Dr. Cooper and others; you are accusing them of lying, and fraud, and deceiving the public. That is the way I read that language. Dr. Sorrasslzs. No, sir. Senator KENNEDY. Well, what do you call the selective choice? I)r. Soaratlazs. Sir? Senator KENNEDY. That do not agree with. Dr. Sonzrrri;s. Sir, if you read the entire scientific literature- Senator KPNNRDY. I am not a scientist.. I am talking about your ac- cusation here, and that you might have a different interpretation of the English language, but I would interpret what you were stating here about the selective use of fact and figures that only agree with and support a position, as accusing them of misleading, misrepresent- ing, and committing a fraud in terms of their responsibility. I)r. SoMarFRS. No, sir, that is not true. Their responsibility is to inform the public, as I understand it, of the dangers of cigarettes with respect to health. My interest is in disease, and the causes, and pat.hogenesis of disease. We evidently read differentt literature. Senator Kr•,NNr:n1. Well, is that not what you are saying here? I)r. SmNrnrN:RS. Sir, if I may cont.inue Senator KENNEDY. That is, there is no question about what the subst.ance of the representation that they are making, and that is the cause and relationship between cigarette smoking and cancer, heart disease, and other lung diseases. Now. tlrat has been niade by the Surgeon General, Dr. Rauscher of the National Cancer Institute, the two outstanding Nobel Prize win- ners, and the CI)C. Now, if the substance and thrust of your testimony is to dot I's, and cross 'I"s, talk abont different aspects and say that there can be dtfferltlg interpretations, that. is one t.hing. If you are trying, by yotu• test.imonv, to impeach the overwhelming substance of their conclu- sion, that is sometlting else. No«-,.vl,ich is it.? Are you challenging their basic and fundamental conclusions, and t.hatt is about, the cause ancl relationship between smoking and cancer? That. is what vou are attacking. Dr. Sc):1rMFRS. My pet•sonal belief, sir•, is that the causative relation ship of cigarette smoking to lung cancer is not proved. Senator K1;-,NxnY. Not proof to what.? To an absolute infinite certainty ? I mean, does anything get. proven, any more than this particular factor, in terms of medical conclusion? I)r. Sonrarl:r.s. Sir, the data available do not. support the conclusions.

228 15. U.S. Bureau of the Census. U.S. Census of Popula- tion: 1960. Genrveral Population Characteristics, United States Summary. Final Report PC(1}1D. U.S. Government Printing Office, Washington, DC, 1963. 16. Hammond, E. C. Tables on the ACS Samples Prepared for the Executive Council of the American Cancer Society, 1962-(On request from ACS.) 17. National Center for Health Statistics- Weight by Height and Age of Adulita, United States, 1960-62, by Roberta, J. In Vital and Health Statistics, P.H.S. Publication No. 1000 S.rin 11 No. 14. Public Health Service. U.S. Government Printing Office, Washing- ton, DC, 1966. 18. U.S. Bureau of the Census. Current Population Reports: Population Chancteristica. Series P-20. U.S. Government Printing Office, Washington, DC, 1958. 19. Hammond, E. C. A Multiple Factor Analysis of the " Association between Cigarette Smoking and Mortality. Presented at the meeting ofAe American Association for the Advancement of Science, Philadelphia, December 28, 1971. 20. Hammond, E. C., and Horn, D. Smoking and Death Rates-Report on Forty-Four Months of Follow-Up of 187,783 Men. I. Total Mortality. J. A. M. A. 166:1169-1172,1968. 21. U.S. Public Health Service. Vital Statistics of the United Statea, 1960, Vol. II, Part A. U.S. Department of Health, Education, and Welfare. U.S. Government ' Printing Office, Washington, DC, 1963. 22. Dunn, J. E., Linden, G., and Brealow, L. Lung Cancer Mortality Experience of Men in Certain Occupations in California, Am. J. Public Health 60:1475-1487, 1960. 23. Dorn, H. F. Tobaccb Consumption and Mortality from Cancer and Other Diseases. Public Health Rep. 74:681-593,1989. - 24. Best, E. W. R. A Canadian Study of Smoking and Health. Department of National Health and Welfare, Ottawa, 1966. 25. Buell, P. E., Dunn, J. E., and Breslow, L. Cancer of the Lung and Los Angeles-Type Air Pollution. Prospective Study. Cancer 20:2139-2147, 1967. 26. Weir, J. M., and Dunn, J. E., Jr. Smoking and Mortality: A Prospective Study. Cancer 25:105-112, 1970. 27. Doll, R., and Hill, A. B. Mortality in Relation to Smoking: Tan Years' Obaervations of British Doctors (Part 1). Br. Med. J. 1:1399-1410, 1964. 28. H81, A. B. Principles of Medical Statistics. Oxford University Press, New York, 1971. 29. Hir.yama, T. Smoking in Relation to the Death Rates of 266,118 Man and Women in Japan. National Cancer Center Research Institute, Epidemiology Divi- .ioa, Tokyo, 1967. ~ 8f1. Berkson, J., Smoking and Lung Cancer: Some ' Observations on Two Recent Reports. J. Am. Stat. c. fi3:28 38,1958- ~ 31. kson, J., Smoking and Cancer of the Lung. Proc. ` Staff Meetings Mayo Clin. 36:367 386, 1960. 32. Kahn, H. A. The Dorn Study of Smoking and Mortality among U.S. Veterana: Report on Eight and One-Half Years of Observation. In Epidemiological Approachea to the Study of Cancer and Other Chronic Diseases, edited by Haenszel. W., pp. 1-125. National Cancer Institute Monograph No. 19. Na- tional Cancer Institute, Bethesda, MD, 1966. 33. U.S. Public Health Service-'llre Health Consequencas of Smoking. Supplement to the 1967 Public Health Sarvice Review. U.S. Department of Health, Educa- `iun, ant; 7TeF..re. ~-- :, ijoveramrnt 4iinting Office, Washington, DC, 1968, 1971, 1972, 1973. 34. Selikoff, I., and Hammond, E. C. Relation of Cigarette Smoking to Risk of Death of Asbestos- Associated Disease among Insulation workers in the United States. Presented at the meeting of the Working Group to Aaseas Biological Effects of Asbestos, October, 1972. 35. Hirayama, T. A Prospective Study on the Influence of Cigarette Smoking and Alcohol Drinking on the Death Rates for Total and Selected Causea of Death in Japan. Smoke Signala, July, 1970. 36. Hirayama, T. Smoking in Relation to the Death Ratea of 265,118 Men and Women in Japan. Presented at the American Caacer Society's Fourteenth Science Writers' Seminar, March 27, 1972. 37. National Clearinghouse for Smoking and Health. Directory of On-Going Research in Smoking and Health. U.S. Department of Health, Education, and Welfare, Public Health Service. U.S. Government Printing Office, Washington, DC, 1970. 38- GBliun, A. G., Miiomore, B. K., and Lloyd, J. W. Trends of Mortality Attributed to Carcinoma of the Lung. The Declining Rate of Increase. Cancer 14:622-628,19,61. 39. Doll, R. Practical Steps toward the Prevention of Bronchial Carcinoma. Scott. Med. J. 16:433-447, 1970, 40. Horn, D. Comment. Made at a Science Writers' Seminar Sponsored by the American Cancer Society, April, 1971. Chicago Sun-T'mtes, Chicago, April 8, 1971. 41. Segi. M., Kurihara, M., and Matsuyama, T. Cancer Mortality for Selected Sites in 24 Countries, No. 4 (1962-1963). Department of Public Health, Tohoku University School of Medicine, Tohoku, Sendai, Japan,1966. 42. Segi, M., Kurihara, M.; and Matsuyama, T. Cancer Mortality for Selected Sites in 24 Countries, No. 6 (1964-1965). Department of Public Health, Tohoku University School of Medicine, Tohoku, Sendai, Japan, 1969. 43, Beeae, D. H. (ed.). Tobacco Consumption in Various Countries. Research Paper 6. Tobacco Research Council, London, 1968. 44. Buechley, R., Dunn, J. E., Jr., Linden, G., and Brealow, L. Excas Lung-Cancer-Mortality Rates among Mexican Women in California. Cancer 10:63-66,1957. 45. Dean, G. Lung Cancer among White South Africans. Br. Med. J. 2:852-887, 1969. 46. Dean, G. Lung Cancer in Australia. Med. J. Aust. 1:1003-1006,1962. 47. Eastcotl, D. F. Epidemiology of Lung Cancer in New Zealand. Lancet, 1:37-39, 1956. 48. Haenuel, W. Cancer Mortality among the Foreign- Born in the United States. J. Natl. Cancer Inst. 26:37-132,1961. 49. McCall, M. G., and Stenhouse, N. S. Death from Lung Cancer in Australia. Mrd. J. Aust. 1:524-525, 1971. 60- Mancuso, T. F., and Coulter, E. J. Cancer Mortality among Native White, Foreign-Bom White and Non- white Male Residdents of Ohio: Cancer of the Lung, Larynx, Bladder, and Central Nervous System. J. Natl. Cancer Iust. 20:79-10fi, 1958. 61. Rakover, J., and Kallner, G. Cancer Mortality and Morbidity in Israel. World Health Organization, Geneva, 1967. 52. Mancuso. T. F., and Coulter, E. J. Methodology in Industrial Health Studies. Arch. Environ. Health 6:515-624,1963. 63. Horowitz. I.. and Entedt„. P tr, 1,,.,. c.,.,..........; __ the Jews. Am. J. Public Has Itb 60:276-282, 1970. 63a. Mancuso, T. F., and Sterling, T. D. Relation of Place of Birth and Migration in Cancer Mortality. J. Chronic SMOKING AND LUNG CANCER 951 229 Dis. 27:469-474, 1974. H. Mortality in Smoking Discordant Monozygotic and 63b. Mancuso, T. F., and Sterling, T. D. Lung Cancer J NatL Med among Black and White Migrants Dirygotic Twina. Arch. Environ. Health 21 :508-613, 1970 . . . Aasoc., in press, 1975. . 73: Hickey, R. J. Environment-Re.ourea., Pollution & 64. Stocks, P. Recent Epidemiological Studies of Lung Society. Sinauer Associates, Inc., Stamford, CT, Cancer Mortality, Cigarette Smoking and Air Pollu- 1971. tion, with Discussion of a New Hypothesis of 74. Haenszel, W., 9himkin, M. B., and MlDler, H. P. C.uution. Br. J. Cancer 20:696-623, 1966. Tobacco Smoking Patterns in the United States. 66. Stocks, P. Lung Cancer and Bronchitis in Relation to Public Health Monograph No. 45. U.S. Government Cigarette Smoking and Fuel Consumption in 20 Printing Office, Washington, DC, 1956. Countries. Br. J. Prev. Soc. Med. 21:181-186, 1967. 75. Doll, R. The Age Distribution of Cancer: Implications 66. Dijkatra, B. K. S. Carcinoma of the Bronchus. A for Models of Carcinogenesis. J. R. Stat. Arsoc. Survey of 278 Cases. Pract. Otorhinolaryngol. 134:133-166,1971. 23:146-166,1961. 67. Hueper, W. C. A Quest into the Environmental Cauaes 76. Seltzer, C. C. Critical Appraisal of the Royal College of Physicians' Report on Smoking and Health. Lancet of Cancer of the Lung. Public Health Monograph No. 1:243-248,1972. 36. U.S. Government Printing Office, Washington, 77. Royal College of Physicians. Smoking and Health DC, 1955. Now. A Report. London, 1971. 58. Hueper, W. C., and Conway, W. D. Chemical 78. National Center for Health Statistics. Health Inter• Carcinogeneais and Cancers. Charles C Thomas, view Responses Compared with Medical Records. Springfield, IL, 1964. Vital and Health Statistics. P.H.S. Publication No. 59. Long, C. F. Tobacco Dust d Stud f Pulmo ar C t ll and Human Lung; s in Indust Findin 1000-Series 2-No. 7. Public Health Service. U.S. Washington Government Printing Office DC 1965 ry y o n y g on ro e Where Silica Hazard is Absent, aa is True of Majority , , , . 79. Health, C. W. Differences between Smokere and of American Industries. btd. Med. Surg. 8:365-368, Non-Smokers. A. M. A. Arch. Intern. Med. 1939. 60, Mancuso, T. F., and Brennan, M. J. Epidemiologicd Considerations of Cancer of the Gallbladder, Bile Ducts, and Salivary Glands in the Rubber Industry. J. Occup. Med. 12:333-341, 1970. 61. Manoe, N. E. Comparative Mortality among Metro- politan Areas of U.S., 1949-51, 102 Causes of Death. ' U.S. Public Health Service Publication No. 562. U.S. 101:377-388,1968. 80 Yeruahalmy, J. The Relationship of Parents' Cigarelte Smoking to Outcome of Pregnancy-Implicatiom a to the Problem of Inferring Causation from Observed Associations. Am. J. Epidemiol. 93:443-466, 1971. 81. Bronte-Stewart, B. Cigarette Smoking and Lduemic Heart Disease. Br. Med. J. 1:379-384, 1961. 82, Damon, A. Constitution and Smoking. Science Government Printing Office, Washington, DC, 1967. 62. Phair, J., and Sterling, T. Report on the Survival of , 134:339-341,1961. 83~. Karvonen, M., Keys, A., Omu, E., Fidanra, F., and Steel Workers. Kettering Report, Univereity of Cin- ti 1961 i Brozek, J. Cigarette Smoking, Serum-Choleaterol, Blood-Preraure and Body Fatness Observations in . nna , c 63. Sterling, T. D., Phair, J. J., and Rtutagi, J. New , , Finland. Lancet 1:492-494, 1959. Developments in Chronic Diseaae Epidemiology: 84, Miller, D. C., Trulaon, M. F., McCann, M. B., White, P. , Competing Risks and Eligibility. Am. Ind. Hyg. D., and Stare, F. J. Diet, Blood Lipids and Health of Aasoc. J. 23:433-446, 1962. Italian Men in Boston. Ann. Intern. Med. 64. Anderson, R. J. Epidemiologic Studies of Air Pollu- tion. ffu. Chest 42:474-481, 1962. 49:1178-1200,1958. 85. Thomaa, C. B. Familial and Epidemiologic Aspects of 65o Curwen, M. P., Kennaway, E. L., and Kennawey, N. M. The Incidence of Cancer of the Lung and Larynx Coronery Disease and Hypertension. J. Chronic Dia. 7:198-208,1958. in Urban and Rural Districts. Br. J. Cancer 86, Sterling, T. D. A Review of the Claim That Excear 8:181-198, 1954. Morbidity and Disability Can Be Ascribed to Smok- 66: Haenszel, W., Marcue, S. C., and Zimmerer, E. Cancer Morbidity in Urban and Rural Iowa. Public Health 87. ing. J. Am. Stet. Aaaoc. 66:261-257, 1971. National Center for Health Statistics. Cigarette Smok- Monograph No. 37. U.S. Government Printing Off ce, ing and Health Characteristics, United Statee--July Washington, DC, 1966. 67. Haemzel, W. Quantitative Evaluation of the Etiologic Factors in Lung Cancer. In Tobacco and Health, 264-290 and Rosenthal Jamee G T pp dited b 1964-June 1966. Vital and Health Statistics. P.H.S. Publication No. 1000-Series 10-No. 34. Public Health Service. U.S. Government Printing OfOce, Waahington DC 1967 . , , ., ., . e y Charles C Thomaa, Springfield, IL, 1962. 88~ , , . Kuachner, M., Laskin, S., Criatofano, E., and Nelson, 68. Berkaon, J., and Elveback, L. Competing Exponential N. Experimental Carcinoma of the Lung. In Proceed- Risks, with Particular Reference to the Study of ings of the Third National Cancer Conference, pp. Smoking and Lung Cancer. J. Am. Stat. Assoc. 56:415-4 28, 1960. 485-496. J. B. Lippincott Company, Philadelphia, 1967. J. First Course in Probability and Statiatics. Neyman 89. Leuchtenberger, C., Leuchtenberger, R., Zebrun, W., , New York, 1960. Henry Holt and Company and Shaffer, P. A Correlated Histological, Cytological, 70. , Barnes, B. O. Susceptibility to Tuberculosis and the and Cytochemical Study of the Tracheobronchial Rising Incidence of Lung Cancer. Presented at the meeting of the Federation of American Societies of Tree and Lungs of Mice Exposed to Cigarette Smoke. Cancer 13:721-732, 1960. Experimental Biology, Atlantic City, NJ, April -20 1968 1f 90. Shabad, L. M. Review of Attempts to Induce Lung Cancer in Experimental Animals by Tobacco Smoke. 71, , . r Ipsen, J. The Epidemiology of Lung Cancer in Cancer 27:61-56, 1971. Relation to Pulmonary Tuberculosis. Presented at the Seventeenth General Assembly of the Japan Medical 91. Stewart, H. L. Committee on Interstate and Foreian Commerce, House of Representatives, Washington, 72. Congress, Nagoya, Japan, April 2, 1967. Friberg, L., Cederlof, R., Lundman, T., and Odason, DC, April 6, 1960. 92. Hammond, E. C., Auerbach, 0., Kirman, D., and 952 AJPH SEPI'EMBER,1976, Vo1.6B, No.9 TIMN 450298

276 Dr. SOMMERS. Y~ that is given-those are references number 10 and 11, and they are cited more recently in other publications. Senator KENNEnY. We hope you send us a copy of your paper. Dr. SOMMERS. I will be glad to sir. Senator KENNEnY. Why do we not continue ? Dr. SOMMERS. May I continue? Senator KENNEnY. Please. Dr. SOMMERS. In t1le current limited state of knowledge, blaming cigarettes as a cause is prermlture. Note that emphysema is largely a disease of white men. Black rnen exposed to the sanle environment, in- cluding cigarette smoking, scarcely ever develop emplrysenra. jhomen likewise are uncommonly affected. A clairn that the cause of emphysema is known, if anytlring, tends to inhibit researclr. Coronary heart disease is consider•ed the most common cause of death in the United States, affecting particularly males, the overweight, the diabetic, and individuals with certain inherited lipid diseases. The b'ramingham data originally publicized do not withstand critical evaluation. Studies of twins discordant for smoking have indicated that the strongest factor is evidently genetic or constitutional. A certain per- sonality type has been discovered with a strivin r life style, evidently particularly predisposed to c i~o;la1 time adr; a,as sS Toe day active researchers look elsewlrere than cigarettes for the causes of coronary heart disease. A decision to tax cigarettes in proportion to nicotine and 41tar" would be based on doubtful, specious or mistaken information. The original "Surgeon General's report, for example, stated that nicotine is probably not a significant health hazard. No new persuasive studies contradict this generally held opinion. Etiologic conclusions based upon cigarette condensate (so-called tar) suffer from the demonstration that fresh condensate free of arti- facts of storage has virtually no tumor producing qrrality. In summary, I wish for better health for Americans, and have worked hard in the field for 35 years. In my considered opinion, the bill propqsed is scientifically unjustified, and if passed, would gener- ate such huge sums of money as would be likely to co-opt and to corrupt most of our medical and scientific research effort. Thank you. Senator KENNEDY. Corrupt and co-opt - and corrupt our medical scientists. e~^Well, I think every scientifir. ,P~pfl» r, _____ , ,aswel;s vou~ua ,je interested in that Let me ask you, what scientific study, what publications in the last. five years, support Your position ? Dr. SOMMERS. There are a large number of them, sir and I woulri refer you to the work of Dr. Philip Burch of England. In England there is a somewhat more open medicall>ress and sense of fair play, and his controversy with Sir Ricliard Doll which is going on, including 1975, I think you will find very interesting. Senator KENNEnY. Dr. Birch, and what is his - what is the thrust of his work ? Dr. SoMMERS. I will give you the references. Professor 277 Senator KENNEDY. Give me the name of the article. Dr. SOMMERS. Oh, well, I can give you some references, sir. That is New Scientist, 1974. February 2,1 issue, and February 28 issue. The 1975 is in various issues of Lancet and British Medical Journal. Senator KENNEDY. Give rue the name of the article. Dr. SOMMERS. The name of the article is "Snroking as a Cause of Lung Cancer." Senator KENNEDY. All right. Now, that is one. What are the others ? Dr. SOMMERS. In respect to emphysema, in addition to the articles I cited, there are a number of papers by Russell P. Sherwin. They ap- peared in the Pathology Annual, about 19tit3, and again Senator KENNEDY. I am not asking you for 1968, but the last five years. Dr. SOMMERS. Oh, in the pulmonary pathology seminar, published in 1975, there were articles by I)r. 'i'hurlbeck and 1)r•. Sherwin, reviewing the subject, and with respect to coronary disease, there are a nunllber ol' articles. Senator KENNEDY. Is this on emphysema and smoking? Dr. SOMMERs. Yes, srr•. - Senator IiENNEni. The causal relationship between smoking and Dr. SOMMERS. No, it discusses emphysema as a disease in relation to its development, and the possible causative factor. Senator KENNEDY. And it has discussed smoking in that, too? Dr. SoMMERS. Smoking is included in the discussion. Senator KENNEDY. And what conclusion did they reach? Dr. SOMMERS. That since it is so hard to define the disease by present methods, it. is hard to implicate any factors causing it. Senator KENNEDY. That is tlre conclusion of the Thurlbeck ar•t.icle'? Dr. SOMMERS. Of that particular article, yes. Also, the article cited in the references here. Senator KENNEDY. That is two. What other ones? Dr. SOMMERS. On emphysema, sir? Senator KENNEDY. No; on lungs and cancer, and cancer of the lung. Dr. SOMMERS. I have a pack of reference cards this thick in uiy bag. Senator KENNEDY. No; you are here as an expert. I am just asking the last 5 years. I would exnect that vou could be able to kickoff at least half a dozen pretty quickly. You are here as an expert witness, and you ought to be able to, since you have not done any researrh directly but are relying on other peoples' work. I)r. SOMMERS. Yes, article by Weir and Mitchell iu ('ancer 1970. In respect to carcinoma Senator KENNEDY. What is Weir and Mitchell's article on? Dr. SoMMERS. The Weir and Mitchell article dealt with lung cancer, and tlre difficulties in diagnosis and classification. It•drew the conclusion that with the little we know it would be pre- mat.ure to draw an etiologic conclusion, including cigarette smoking. Senator KENNEDY. Thatt is excuse me ? Dr. SOMMERS. It would be premature to draw an etiologic condlusion from cigarette smoking. TIMN 450322

I ( I .+..U TABLE 7-Parantqa of Deaths for Moe of Causes for the ACS MaJa Population and US, yr"hit., MaW Popwdatwn (1960) by Raa and Sex, for Aaes 35-84• Underlyina Caur of Dpth Intnnationad List Nos. ACS Populauon Males Comparable U.S. White Mades Comparable U.S. All Males Lrmy /arcf4 trachu, Pf-l 162 5111 2.49 2.44 Butal avity, phryn 140-148 0.51 0.69 0.67 Larynx 161 0.25 0.33 0.33 Esophaaus 150 0.26 0.52 0.57 Bdaddsr and other wioary 181 0.73 0.81 0.78 Kidney 1811 0.54 0.47 oA5 Prostate 177 1.94 1.91 1.97 Pantreas 157 1.45 1.18 1.17 Liwr, beiary passaan 155 0.54 0.39 0.39 Stomach 151 1.50 1.83 1.88 Colon, rectum 153,154 3.22 2.84 2.74 Leukemia 204 1.15 0.86 0.81 Lynrphoma, Hodakin's diteasa 200-203, 205 1.27 1.02 0.99 Breast 170 0.03 0.03 0.03 Uterus 171-174 - - - Ovary, Fallopdan tubas 175 - - - Coronary heart dAea.ra 420 49.94 45.21 43.20 Rheumstic heart disease 400-402, 410-416 1.33 1.24 1.19 Hypertensive hean disease 440-443 250 3.32 3.93 Other heart disease 421, 422, 430-434 3.63 5.22 5.42 AorticaneurYsm (ransyphihtic) 451 1.63 0.93 0.89 C.retralvascutarlesions 330-334 9.62 11.57 12.00 Other circulatory diseases 444-447.450, 452-468 2.46 3.35 3.93 Emphyssma 627.1 1.84 1.27 1.20 Gastric uk.rr 641 0.50 0.67 0.64 Cirrhais of liver 581 1.20 2.03 1.99 Dlabetes 260 1.22 1.68 1.70 III defined diseases 780-795 0.47 1.02 1.30 Violence,accidents,suicide E800-E965, E970-E999 5.36 7.12 7.39 Total 100.00 100.00 100.00 ' In order to construct this table, only thosa auses of death were used for which deaths in the U.S. poPulation were availabla for comparable aaes. The Hamrnand data ame from Appendix, Table 13 of Rrference 12, and the U.S. date from pp. 48-97 in Refevena 21. Conparisons were not possible for the following ausa of death from Hammond's table: other speciPed sites, ancer-site not specified, pneumonia, influenza, other pulmonary diseases, duodenel ulcxs, nephritis and other kidney diseases, and other specified diseasq, invotvinq a tonl of 2,754 or 10.4% of all deaths reported by Hammond. Hammond's fiaures for 4una cancer exclude involwmant of trachea or pleura. Hoywver, the fiyures for the U.S. include it. For 1960 there were only 93 lurp cancer deaths with involvement of trachea and pleura for aaes 35-84. This not only leaves open the question of just how many wch cases were not eliminated in the first study because no notea were made on the margin of the questionnaire but alao how many cases of lung cancer were included by volunteers in the second and cmcial study of over a million men and wornen to "vote," so to apeak, their confidence that smoking cauaed lung eancer. (The sstne may be true for heart disease and emphysema.) Data released by Dr. Hammond in 1966" is of utmost significance since It offers considerable support for this posdbi8ty. In Tables 6 and 7 we compare the distribution of duses of death for most deaths in the ACS population with the distribution of deaths for the same causes that would be expected from a aegment of the U.S. nnnulattn.n' ih.. ...• ~,-; u;- slm0ariy, by age, sex, and race, to the ACS population. We find that the ACS males die from lung cancer proportion- ately twice as frequently as do U.S. males, and the ACS females die propottionately 3 times as frequently from this disease as do U.S. females. Twice as many females also die from breast cancer, and for males approximately 10 per cent more deaths for coronary heart disease are reported in the ACS than in the U.S. population. Also, ACS males and females die at an -Increasing rate from emphysema (50 and 40 per cent more, respectively). Note that (with the exception of breast cancer) these are a8 diseases popularly associated with smoking. (Yet, it Is not true that the ACS population died at an overall faster rate than did the U.S. population. The overall mortality in these populations is Cl ,,..u, "u.r auen ant somewlat Iless for ACS women.) It is difficult to explain such startlingly peculiar results. SMOKING AND LUNG CANCER 943 J 221 How could one intentionally design a selection procedure that would ensure that individuals prone to eventla8y, die from lung cancer somehow are induded at twice or 3 times the rate typical for the U.S. population, or which would include 10 per cent more heart disease, or twice as many breast cancer, or 40 or 60 per cent more future emphysema caseSt Smoking Is ruled out iminediately as a possible condition here. The number of smokers in the ACS population is probably smaller than would be true for a representative sample of the US. population.; One reasonable expdanation for this peculiar finding is that some of the volunteers selected households with sick individuals, especially those suffering from cancer, heart disease, and emphysema. Such an argument gains special weight If we consider the doubled prevalence of breast cancen among the ACS women. If the volunteers selected women smokers who were already suffering from cancer, such a result as we observe may have easily come about aince the number of lung cancers among ACS women is extremely small and that of breast cancers quite large. It Is also possible that the ASC population was assembled by a selection process that may have preferred persons who were In a high respiratory disease or cancer risk group. There are such groups among some occupations, and it is not Impossible that selection could have operated In that direction. There is yet one other explanation, at least for the lung cancer deaths, namely, that more than half of the primary lung cancers really were secondary metastases. But this explanation has been ruled out by Dr. Hammond, who is quite spedfic in reporting his lung cancers as primary and Insists that most of the 1,159 male deaths in the second study had specific reports from physicians and that while "it may be that a few of the 1,159 deaths attributed to lung cancer were due to cancer of some other primary site ... Even so, the evidence would indicate that most of these men (probably needy all) actually died of cancer originating in the lungs" (p. 150 of Reference 12).f Were Similar Elements of Bias Present in Other Prospective Studies? In many ways, the other studies suffered from many of the same multiple selection factors of the ACS study because infottllation about a subject depended primarily upon his willingness to participate In the study or on the Investigator's ability to locate individuals who were ill with the same facility as individuals who were not, and so on. It • Comparison groups are not easy to find beceuse of the unusual d'utribution of the ACS population. The ACS population ia nearest in composition to that of employed adWt.. For a group of employed adults, Dunn found that the percentage of nonsmokers among'men in 10 occupa- tions varied from 17 to 28 percent' On the other hand, approximately 33 percent of the ACS males were non- aaokeis. ' " t Nevertheless, it would be interestina to aee how wbjects classifted originally as not speci6ed were appor- tiosted among smokers and nonsmokers. , B/I A,MH SEPTEMBER,1975, Vo1.66, No.9 is true that the results of all of these studies are uniformly alike and that is impressive. Whenever snloken and nonsmokers are compared, smokers die with increased incidence from most diseases but especia0y from lung cancer. But to what extent are these sbnilar results due to sunilar selection biases? It is difficult to get answers to this question without making the same detailed comparisons to reference populations as we have done with the ACS study and which the authors of other prospective studles have neglected. It would be valuable to know to what extent the veterans in Dom's7 3 or Best's2a studies are different from the veterans in the U.S. or Canada or to what extent the various workers in the Califomia studyls'1s are different from all workers in the same profession. Addit)onal evidence that study populations are highly selected comes from Dolt and Hill 17 who Indicate that physicians in the United Kingdom who volunteered to become part of theh study differ from the population of British physicians. The very fact that 30 per cent of the British physicians did not respond to the questionnaire ought to have raised serious concern about the results of Doll and Htll's study. Studies based on the follow-up of individuals who respond to solicitation via questionnaires are very sensitive to biases and for that reason every effort ought to be made In such investigattons to intensively study a subwnple of the nonresponding popula0on.aa Doll and Hil1 never reported the results of such a follow-up attempt nor any other information that would jusUfy the conclusion that the 70 per cent of physicians who responded to their original inquiry do not constitute a highly selected study popula- tion. Because of these shortcomings common to all Ameri- can, British, and Canadian prospective studies, one new investigation looms with special importance. This Japanese study avoided the dangers of self-selection bias by attempting to obtain informaUon on all individualsover 40 yean of age living in particular districts 19 All adults over the age of 40 In a number of districts were interviewed by trained public health nursee at the time that the National Census took place. The actual number interviewed was very large, 265,118, and is reported to range from 91 to 99 per cent of the reference population in different districb. While caution needs to be exercised in accepting findings in a population so different in race and culture from the white, Western, European citizens of the other studies, the results reported by Hirayama form an interest- ing contrast. Table 8 shows that the mortality among Japanese smokers and nonsmokers was largely the same. In fact, during part of the study, smokers died at a lesser rate than did nonsmokers. If we inspect the Japanese data for all diseases in Table 8, the difference in overall mortality be- tween smokers and nonsmokers is far from Impressive. The Japanese study offers substantial support for the suspicion that selection bias affected the seven retrospective studies on which Smoking and Health bases Its major conclusions. It has been pointed out by Berksonso's t and also by many otler leading statisticians that one Indication of biased population selection would be an all-pervasive increased prevalence of smokers' mortality for all disease categories. TITVIN 450294 ,41

288 Sheldon C. Soasaers, M. D. CORRICIILUPS VITAE Born: July 7, 1916, Indianapolis, Indiana Married: November 9, 1943, Edith, Briggs, No children Harvard College, 1937, eum laude. M. D., Harvard Medical School, 1941, cum laude. Intern: Chicago University Clinics, 1941-1942 Assistant Resident and Resident in Pathology, New England Deaconess Hospital, Boston, 1946-48 Assistant Resident in Pathology, Free Hospital for Bomen, Brookline, Mass, 1948 Assistant Resident in Pathology, Boston Lying-In Hospital, Boston, 1948-49 Reaident in Pathology, Henry Ford Hospital, Detroit, 1949-50 American Board Certificate in Pathology (Clinical Pathology - Pathologic Anatomy), 1950 Associate Pathologist, New England Deaconess Hospital, Boston, 1950-53 Assistant Pathologist, Harvard Cancer Commission, Boston, 1950-53 Pathologist, Massachusetts Memorial Hospitals, Boston, 1953-61 Pathologist, Scripps Memorial Hospital, La Jolla, California, 1961-63 Associate Director of Laboratories, Francis Dalafield Hospital, New York, 19~63-67; Director, 1967-68 ' Director of Laboratories, Lenox Hill Hospital, New York, 1968 - . Assistant in Pathology, Harvard Medical School, 1948-49, Instructor in Pathology, 1950-52, Associate in Pathology, 1952-53, Lecturer in Pathology, 1954-61. Associate Professor of Pathology, Boston UaiverBity School of Medicine, Boston 1953-61 Clinical Professor of Pathology. University of Southern California School of Medicine, Los Angeles, 1962- Associate Professor of Pathology, Columbia University, College of Physicians & Surgeons, R. 1 1963-1965, Professor of Pathology, 1965-68, Clinical Professor of Pathology, 1968 - Captain, Medical Corp, United States Army, 1943-1946 • Silver Star, Bronze Star, Croix de Guerre and Presidential Unit Citation New York County Medical Society, N.Y. . American Association of Pathologists and Bacteriologists College of American Pathologists American Society of Clinical Pathology ' The Uistochcmical Society American Society of Experimental Pathology _Ncv England Cancer Society - New England Society of Pathologista; President, 1959-60 Intcrnational Academy of Pathology Federated Societies for Esperimental Biology and Medicine New York Academy of Medicine . New York Academy of Science Nev York Patllological Society: Secretary 1969- 1972 Editor, Pathology Annual, 1966 - t.,,(:/" , Pniik.i;lacScJ 1~••~c+•~1isLQ Sdt;r, Editorial Boards: American J. of lficrapeutics and Clinical Reports - ~yt& .?t ' Scientific Advisory Board: Council for Tobacco Rdsearch 1967- : ResenrSh Director 1969-: Droast Cancer Task Force (Pathology Rorking Group), NCI, 1968-1974 Clinical Laboratory Advisory Committee, N.Y. State Departncnt of Health, 1975. /o.nM1119 289 LENOX HILL HOSPITAL 100 EAST 77TH STREET / NEW YOaK, N. Y. 10021 March 9, 1976 Ron. Senator Edward M. Kennedy, Chairman, Subcommittee on Public Health Committee on Labor & Public Welfare U.S. Senate Washington, D.C. Dear Senator Kennedy: In respect to the hearing on S 2902, on February 19, 1976, I would respectfully request to make some additions to and corrections of my testimony. Regarding the evident misunderstanding about whether or not I had published on the causation of lung cancer recently, may I note 8 additional personal publications in the years 1962-1973 and one now in press that deal in part or wholly with the cells of origin, the growth, the special hormonal activities and other features of lung cancer that may aid in its diagnosis, management and thus a better basic understanding of the disease processes. References are appended, including 4 papers written with Dr. Marjorie J. Williams, present chief of pathology, VA Central Office, Washington. Also appended is my publication list. If it seemed to appear from my testimony that I had contributed little to discovering the cause of lung cancer, perhaps that may be explained by the difficulty of understanding this mysterious disease. Dr. Alexander Haddow, a famous British cancer researcher, was quoted as saying he would not choose lung cancer as a research topic because it was too complicated. Human endometrial carcinoma, breast cancer and renovascular hypertension are some other diseases to the knowledge of which I believe I have made significant contribution. In regard to the inquiry concerning new publications that tend to o e.,aed- T annend a list of over 70 such scient- rr rh.. o ..+o o T ,..,,- scient- A,,.,,. . . , .. . . ific and medical publications in 1975. Some corrections to the transcript of my testimony are also submitted. TIMN 450328

172 1 r•c•:ul ihc• uthet• clav rvherc 5nmeortt• wonlcl irnl>o,c a han ou smoking in lrul,lia hrriklint*s. ''hatt might he agcxxl ich•a. I;ut- then «'e shonlcl not clrinli in Irrrblic hailclint*s lxcan5c lhatt canscti c•ir•rhesis of the liver. ~1ncl I have not. known of an,yono gettinf; in a car ~.'ith a c•igat•ette and IciIliu~ ~,nrcone else. So if t•he pnrlrclsC is for rcac•arrc•h an(1 to 90, it, from Ihost~ iteru5 or c'onrnrcxlit-ics t.hat. ean5e illnes5cs then lett tts put. it on ~:rncl~..InSf. «•itlrin the last.2 or a.vc•eks I read wher•c in England they ::rr I i;r•inY ncnc to place a«•arrrin;g on all csrncly b;us, flrat c•onsrrnrption of r:r n6, tilay Ime danger••on5 to a per•son's hcalt.h. Nccw we know t-hatt cancly can c•an5c-swe.et snt;ars can canse disek•lse. 11'Iry nc,1. lrlacr it. otl vcrft.clr•inlcti? l1'Iy c•oncern is if you a.rc goingto place it on cma rtcm thcm let n5 hc fair and place itt on all items. On the other hand, Alr. (lrairtmul ancl t;ent.lemen, if the pnrpose of ihw Irill is tu (10 ;rwar.,y with the nu+of iobacco thc~n did ~~•e not learn our Ic•"scrn in the lrt•uhibition clays? Wc- t lrunglrt. we conlcl clo :rwa,y with the riSr of :clc'oholic• lmverages ancl we c•onlchr't. 13nt if tlrat is the Inu•1>ose ll:c•n Ic•t n5 s:ry so. I will he willing to live with that if that is thc will of tlre Imople. lint• yon are just. not t;oingr to stop lmollle from uxing cit!arl•cttcs 1>y adding an aclciii ional 1ax. l'on are going to, when yun Irut tlre Warninr on the c•igarcltc pac•ks the c•onsumlrlrnn of ciga- rettes; continucks: to rise. So it seems to me there is an unfair efI'ortt to tiin~le out one iteru tlrat is used bv the Anrerican consnmcr to say we ;ur- t;oing to tax ,you but lett the liqnor drinkers and tho5e who clrink Iro)r rn•cloall thc+otherthint*sgo free. If yon Illac.c it. on all of them then I have no c•omplaint• and find no fanltt with this corntnittce. But. I am slrocked also, gentlemen, to realize or to tiee ilow or even envision how our Government can spend an addi- tional $6).:'i billion in more, hearlth re;5e,u'ch and get. the clesnr.cl resnlts. A ln»blern would he created for the. private sector and research nevcltiW1'rear om' manpower tools and seient.ists arr, alreacly clraine.cl; 17; (4(1O sc•ientitits aree already committed to tlre National C;incer Inst•itute progr:rm and they estimate that nncler trrrsent, pl;uls itl will ner.d 28,000 sc'•ic•ntistti by 1982. 1 f we add this acklitional $!).Ci billion to it how many morn ~~•nnlcl they need? ln Short, I Ix•lieve that this bill would snhcrimllose on the I)cpart: ux•nt of I Iralt-h, F.clnc•at ion, and Welfarr. other'Inn•ealuc.rae,y of a pork Irurrc Ivariety.'1'ripling spcncling is no Ilanac•ea, for health. Creating a rx•N% Inn•caucr;r.cy is not the an5wcr. What. «•e have got to clo is spencl NA•Irnt. cc•ealrcacly havc c•onrnrittc•cl ancl nscite wisely ancl usethe valnaltlc~ m:rnt:owcr judicially. '1'lris bill may intc•ncl to nse the tltYx•e,ecls of a ,inglc, inclnxtr,y to financc+ thiti, nrt• rt may vcry se c.csi.toy 1;. . re in- rlnstry. It. will not. destroy the nse of tohac•co. Even if you clest.roy the in:ln,try. Somehow, u)me«•ay people will find, tlroscwho nse it, lnst ;rs I Irc•v fcmncl «•ay5 to fincl licfncn• (lrrrintr the lrrc>h'ihition clayti. 'I'hiy initial proposal is clisarmin;~ly snnple, basecl on the nesd which fmv v.-nnlcl nuestion for grcatcr lhcaltlr research aml hvalth care. Fed- eral frmcls for thc>Se prrr•Iro5e5 would ho greatly angmentecl. Incleed, fcrck"c•nt. tit•ovisions would hc clwarfc•cl with the t•e:rliz.rtlon of $9 hillion. 'I'Iris t:rx wonlcl be Ilaicl presnnralrly 1>.v the marnnfac•tnr•ers of cigarettes ;:ncl rc•c'ovc•recl at• earh stagct of the Irrolnc•tion clist-r•ilmtion system down to :rncl inchrclintg the rcUtail stxmsor5 of thc+ propoG;rl as a jnGt• contri- Lnt icrn of t hc* soc••ial cost. whic•h t hc•y hc•licvco to 1e clerivcd if thc' choice is n::ulc, by incliviclnals to engagc• in a hazarclons practicc: the Smoking crf c•it.rarc•ttc•s. 173 The-rc+ is lit.t•le, cloubt t.his proposal will find acr.eptabilit•y in a very lxrge lxxly of authoritative opinion. In fact, it. embodies a principlc which may prolx'rl}, become the event.na-l standards for virtually al of t.lre. re.venne rcqiurements of the Federal Government. A few ex• amplcs of thci possibility would serve to underscore the rationality oi tax on ta.r ancl nicot•ine. It is well known t•hatt statistical assoctatlon: have lxT.n reporte<l in the scientific literature over the years betweer eit,•aretio smoking and healtll problenrs, inclncling heart drsease, homi cide, and so on. What has been less publicized which is less obvious i~ thcro arc+ man,y other such correlat ion5 involved in activities selected b3 IT.S. citizens for which research and health care needs are far-reach. ing, indcrcl. No one need to be told for instance that airline passengert are at. a spec•ial risk with annually observed c•orrelations llet.ween deathl cnd injrn•ies on passenger miles flown. Thus, every air carrier shoula he obligccl to make, to pay taxes on this basis, recovering the amolmt,~ from the passengers themselves. 'I'he consequences of automobile riders and the factor of automobili cnlis5ions. It, would appear to be+ relatively Simple to t.ax aut.omobi ell accorclint; to t.lre make a.nd niodel certi ficat.ions from t.he Environmental Protection Agency with an increment depending upon the numbei of seats per car and coordinated to the miles driven which could b det.crnlnlecl'by the several States at, the time of annual automobile in spect.ion. I conlcl f;o on and listt others. Iiut, of course, serious conse.quences o cxposnre to the various risks t.hat come from many, many differen sabstances c.onld open the door to all kinds of taxes. If the recent. pas is agnicle, perhaps the only elemcntt of our society which will remair relatively aloof will be the citizens themselves, if llill takers, drinkers ca.nd,y va.tcrs, bacon lovers, and conntless other•s who have forced sucl •twesomo responsibility upon the Fe.cleral (xoverrnnent and I believe Mr. Chairman and gentlemen, there is a better way to approach thi; In my 5ta.te of North Carolina I think we have more than 400,0011 indiviclna.l tobacco farmers. I am not snre of the exact• figure. And know we have in excess of 100,000 workers in tobacco and it. will have : substantial impac•t although I-Ariously que5t.ion how mucyh taxatior will ha tnper the nse of it. I;ut. I clo nots be-lieve t-hat. tiris is t.he right. wa; loloat•il.. lint, if you think it. is, if yon will add aa tRx orl llquor erynal t.ot.hesam amonnt-becan5e God only knows, a.nd everybody knows that liquo t•anSC;4 as mndt ntiSvrv Sinrl cnfl•arincr in thic wnrtd nc nnv, n+.hnr cinffl conrnuHlity then I think my people in North Carolina. n•oulcl not.lxa a lilcc*ly to complain. l;nt• do not• sint;lee ont. one indust.ry'by it.self anr say wo are gomt,~ to pnt- t•he bnrclen of tax to this industry. 'I'hank yon very much, Mr. (".hairman. (Scktnator Sc.lrwcikcr assnmcd the Chairl. Senatnr :;c'rrwr;rxr:a. 'I'hank you very tmtch, Senator Morgan. Senator tiart? Senator Ilnr;•r. Thank yon very rmrch,Mr. Chairman. Fir51. of all, Srnator A'[organ knows T have greatt respect. for hin I thinlc he spoke well and strongly on hehalf of his constituency her t.his rnorning and that is what all of its arc clc•c•tecl to do. I conr ratn l:cte hinr on his statcment. Ilnt IAvonlcl lil:e to pnrtine a couple of tlr argrrments arlcl u>mc rclatccl issucks if I may, Mr. Chairnlan, ver hrrcfl•y. TIMN 450270

I 272 . ~ Senator KENNpDY. Well, how are we supposed to understand all this? The best scientists that are available, in terms of responsibilities to the public, all agree. What do you know that the Nobel Prize winners do not know? Dr. SOMMERS. Sir Senator KENNEDY. Or what information do you have that the De- ~Iartment of Health does not have, or the CDC has not got, or the Surgeon General has not. l;ot ? Dr. SOMMERS. Sir, I cannot answer that question, because I do not know what information these different individuals have. All I can say to you is, sir, that I have been in cancer research for 40 years. Senator KENNEDY. I do nott know why you make a statement you do not know. They are all published reports. Dr. SOMMERS. From their published reports, sir, I conclude that the data are insufficient to support the conclusions, that is, for example, cigarette smoking is the major cause or a major cause of lung cancei Senator KENNEDY. Do you think it has any relationship ? Dr. SOMMER$. I think it has an association, sir. It is in my statement, if I may continue. Senator KENNEDY. To what extent? Dr. SOMMERS. If I may continue, it will be in my statement. In respect to the 1972 hearing by Senator Moss of Utah, it was pointed out that approximately 1,790 articles publislled since 1960 were not cited. Lists of these were supplied. We will be glad to update that list to this year. Now, as to lung cancer, there is a statistical association between cigarette smoking and lung cancer. But. at present the nature of asso- ciation, or whether it is causal are not known. The text of the original Surgeon General's report deals with the difficulties of assigning causality, but the summary and conclusions brush these aside, and assign a causality not demonstrably evident in the text. It is widely known that a statistical association is not by itself proof of causation. A statistical association may point to experiments that will help to determine whether there is cause involved. Animal experiments, to my knowledge, have not succeeded in the production Senator KENNEDY. Before we leave, is that all you are going to say about the associations of cigarette smoking and cancer ? .. . - , Tomnn.nrr+r..+....rl.+......, tionh over cl ractiabredce exposed to heavy cigarette smoke inllala- p y their entire lifespan. Certain false alarms like the Auerbach beagle dogs, and other studies of rats and mice, have stirred hope that a model had been achieved, but no cancers that grew, spread, and led to death like human squamous cell lung carcinomas have been reported in animals. After 45 years of inhalation research, and although expensive efforts continue, no success has been achieved in producing experimental lung cancers in any reasonable, or even small numbers of experimental animals. Skin painting is cited in the bill proposal as part of the evidence of carcinogenicity of tobacco smoke condensates. Suffice to say that in the past 5 years, skin painting of animals with t.obacco condensate has 273 mlded so few tumors, either benign or malil,rJlilllt, lI t the practice s practically been given up. Only a few t;o~•erlunen ageney expcri- ments continue. Why tnlnoIS were produced years ago following skin painting but are now rarely produced is unknown. Au Lnt;lish book review of a work on tobacco and carcinogenesis stated thatt if in the 1950's the author had not reported 44 percent skin ttuuors when other labol'ilt orles were finding 3 to 5 percent, this field of research niit;ht have develol,ul in a more orderly way. On what. basis is the claim made of 90,000 lulll; cancer cases ller ,)'car? It is based on death certificates, which are not scientific docwnvnts, ancl in qeneral are not corrected by findings if in autopsy is herforiuc+cl. Senator KENNEDY. What percent do you think? I)r. Sorlnlrals. Sir, I come to that-I think t.lle Senat.or KENNEDY. If you can answer my questions, because we are discussing this point now. You keel) saying we are coming to it, and tben we are beyond the fact. I)r. SOMMERS. I believe the excess factor at least is two-fold in- volved Senator KENNEDY. I)o you think there are 45,000 lung cancer cases? I)r. SoMNIE Rs. I doubt it, sir. Senator KENNEnY. YOU Sald twofold fac(Or. I)r. SOMMIaRs. At least twofold. Senator Kr:NNra>Y. Well, is it 30,00.0'? Dr. SOMMERS. Sir, there is no way of detrrminint; it. Senator KENNEDY. Do you think it is more t.han 10,000? Dr. SoMn1r•.RS. I iniat;ine. Senator KENNEDY. It is more than 10,000. If it is more than 10,000, t.hen why does not this approacll make sense, that we are talking about here? Dr. SOMMERS. The approach to tax Senator KENNEDY. Yes.111ore than 10,000 people. Why does this not make sense, then ? I)r. SOMMr:as. Sir, because there is no animal, or other experimental proof, that cigarette condensate, which you call tar, is a 1)rodu(•er of cancer. Senator KENNEDY. Well, I thought y0u just said that it was. I)r. SOMMERS. No, sir. There has been no success in animal experi- ments to proc[uce hmg cancers , i;{e t,: Iose in Iunian mings. Senator KENNEDY. Well, I have difficulty following your line of reasoning there. You are prepared to say there is a given percentage of cancer because of tobacco, ancl you are prepared to say it is att least twofold, and then when we give you onealinth of that, and then yon move off that figure. I)r. SomIVIERs. Well, sir, if I may explain, the 10,000, or whatever number of lunl; cancer cases, like many other types of cancer, are in my opinion, of unknown cause. You have accepted cigarette smoking as a cause. The evidence, in my opinion, does not support that. Senator KENNEDY. Do you think it is a cause? One of the causes? Dr. SoMMERS. I think it might be a cause, but I do not think it has ever been proved. TIMN 450320

178 1)r. tirxhr•at. 'I'Ite incrralse in 1973 :and 1974 was slow hut. there has Irren aSte:td}' inc•reastj since 1971. tic.n:ttor Ihtrt•.'1'Irere is an arl;ttruent tu:tcle• tltat Ati•heu you clecre~.se tluv Inr atncl nicoline content in a c•il;au'ctle. yott siuutllaneously cle- rrc•:r~r fhr t:tstee anci tltereforr. ihem hross c•onsnntlttiort of tar and nico- I inc~ iti I Ite sanie. Itr. Si:xc'rat. 'I'his is :11 resltee taltle :u•gnnx•nt thal.t. lle•oltle stcit•atnc'e.1VP Iisrro no c•unrlrrsiVe eV iclence one way or t he utltet•. tic'n:tlor 1l.ut•r.'1'lutnk yon. I)r. ('ocrrtat. Iwould catrtion you, Semttor, in acc•el>(ing that. I think I hcre is unue re:tson to Lc•licVe lx•c•ause of the exllerience in health e.du- caticrn nncl cessation, tlu•re is mot•e to it thsut just reduce the (lose of nic•ol ino suul t:tr itself. I would also want. to ccmtntent in view of the statistics, and Iwi1l notI go oVer :t l I of theru i n I l tee i nte•re5t. of t i ntc•, as I s:t id. We hamto l ook :rI age tilmc•ific•, sex specific, statistics and tlte impact on difl'etrttt age rronlrs. It. is oln•iously (lifi'erent. 1'luerc+ are interestinf; data abont ntothers of new lrabies «•ho sntoke• for exaurl>le, :uul the correlation with the inciclenc'e• of respiratory in- fect.ions---rf tlte people itt the Ironseholcl timoke cirn•inl; the first ve:u• of the halry•5 life, there is inc•re:tse•d syrnlrtontatolol;y and respiratory infection dtn•inf; tltat. period of tinu•.'I'hat is age-specific, and after 1 %•ear one does not see it. If )•on look at. this, you are going to have to look at. age sllc•cific and other factors contributing to these health slatislic':; trend in c'arclioVasrnl,u• clise:tse, c•anc•er, c'hronic ltutg clisease, :tncl respiratory infection. Now, there is one point that. wc• shoulcl also tnake and that is durinh Ihe last s(•t•eral yc•:lrti we h:tve seen a rc'duction in coronar;y disease which AVe. It;tVe reltorte•cl to this contntittee under other circuntstances :rnd to the Altltrolrriations ('ornutittee. This is :tn itltpot'lant clt:ut;~t• in c~iu' I~rc•~-ion-l~' oltserwed elriclenric• of c•uron:u;v he:trt cliseuse. It slrows tlratt. ;;otnelltinur trood is happening to effect this. 1Ve are also seeing ticrtue reclurt ion in I Ire fi~in•e, on enrltlt)•setuu :tncl lrronrhit is :tncl I tlrinlc Ilriv is also attrilnttaltle, in fact, to some of the health eclucation c;lnt- Irtimn, lterhttlts sonte of the clitl'erent. products, some of the other con- Irilrnlin;r t'uctors, as Well :ts the socioeconontic fn(ttors that. c'ontrihute lirrt a slrec•ial conrnrent is warranted for c:ulcer of the lnngfor whicll cc•r. c:rtutot say tlte s:tnte trencl is t:tking place, at least in the am;regate. I'~ rlurlr~ I)r•. Katlsc•hc•r rtrn help Itc're and wonlcl want to c•ounnent in 101110 :Ic•I:ril. I think we It:tVc• to look at a difl'erent tiuu• fraune antl we li:rVc• In Iocrlc Itere ut a clill'erent :t!-e gronlt intltact. wlterc• we c:ltl cxpect dill'erc'nt Irrllet•us stncl ciill'c'r'enI closc+exlxlsnt•es and the like. So we are :rn:u•r, I li:tt. I lw Irroblerus c:urnot lm lutnl>ecl together :ts if tltey respond villu•r rlira'tIV to the c:u•c•inogens or the lnrltltc health measnres in the s:uuc, ~~ :r ~• I~rrc•isel ~' for• one a~ for 1 he ot lu•r. 1 n onr tetif intony we hac•c~ I«•o contnrenis on that :tgee groult :lnd th(•. inlrrrelal ion51rip to that. 'I'Ire urst, point. lhatt tuerits speciul corntnent is the question of inlllact. (,I' I rassi t•e sntolcing. Sc'n:rtor Srrrwa.n(r;tt. I tltinl: this is Vel•y itnllortatut because one of Ilw witnesties e:trlier saicl tlreree was a llroltos:tl to I,:ul cigrareite srnok- ing iu ]ntltlic places. I f we did that. why did we nott ban drinkinl; in TIMN 450273 179 I ltublic buildings. Ithink the anstrer• is fairly dln•ions, V. is, i someone takes a drink it (loes not. afl'ectt his neif;lthor and his smok tuight. Iwonder if you would elalxlratc+on t-hat.? I)r. ('.cxlt>r•.iz. j'hell, I think in some Itul,lic Luildinf,'s, at least by regu- lation, drinking is Ilannecl.Whether it is Itonot•cd ornot, I could not say with any authorit.y. I sullllose if we wantecl to be glib and sav, yes, et•en drinking could h:lt•e uu ell'rct ill tlte Sc•ntie of nu~blir lx•havior, if it is out of h:uul in a llul,lia place or other unl,leasantness lrerhaps even including bad breath. Iton•ever, it. is not quite the satne kind of problem generally lrer<eived. What. we are talkingallontt is Ilassive srnokinh or involuntary smok- in1; and that, is f,rener.tilly called ihatt because the constituents of solne of tlle cigarette smoke are in a confined place where the person who is a nonsmoker• tlten inhales tlte sante 1>su•t icnlatte nr:tttcr in the s:tute other a irlx>rne substances that. the smoker woul(l, :tlLeit. in rt different concen- tration. And there hstvee been studies meatsnt•ing the specific amounts of 5nhstance and dift'erent conditions for ventilation for involuntary smoking, and there have heen many studies cione, partic•ularly stu•c•eys to asscss the impact, on nonsntoket•s of tltis type of esllerience. Peolile (10 report. several symptonts: conjunctival irrittttion, u•ritattiotl of thc throat, some ]leolllc• have nller•I;ic'-like symlltoms, autd even, indeed, sonte dedir:ltecl sntokel:5 h:tVe:lllerric• rcatc•tious therusclves. I'hc•re• are other ronse(]nences of the smokc•-c:trhon ntonoxide-th:tt this nonsntoker• is exposed to, and these have been doctunent.ccl; the atctn:tI lcx•els with clifl'erent t ylte•s of ventil:tl ion have lx•en shuliecl. Ancl, again, herc the rrrost inthort:urt cornsecluence• of iltis is not the imrue•cliate disease lmt ]trrcillit:ttion of'tuttow:u'd extrrestiion of disease or:u'celera- tion of symlttottu:tlolol;y or ac•ute eltisoclc• on tolt ot' tlrtt. unclerl}•ing cl isease. 'I'Itc•re is sl lril;lt clegrc•e of anno,y:utc•e rellortecl Ity nonsruokers tc•lriclt is I)ecunlin,r sontell•hat. more comnlon. I tltink this is a vet.y imlrorlant. In•inciltle for the strccess of any heultlt ecluc:ttiott c,tmll:tihn related to t.he Itroltleru of srnoking, becanse I thiuk one of tlte grc•attest forces tllat. cottl(1 lr,tVe• an lrnll:tet on tltis is tlu• nuestion of social accent:uue. Senator ...... rT'.-r T , "11111f i l(•t'e ~ I sc~c~ in your detailecl st:tternent. you s;ty t hc•t•e was a c•ont rollecl stnci•y (lone of the relationsltilr of inc'idenc'es oi' ]meuntonia and bronchitis in the first year of life to the smoking halrits of the• p:trents. i)r. ('ctort•:rt. Yes, sir. I c•onrruented on tlt:tt e:trlic•r in sunte cletstil. 1 mmlll ionecl th:rf in respolnc lo Senatnr II:u•1..1ritit to r(•iterate th:tt, with reslec•t. to the environrucml in the lirst ye:tr of lifc•, tlu• c•ltilclren seeru to clo ntore lworl}• if there is't Iti-lt snroking ent•ironnu•nt in tc•rntti of irritattion, Irronclritis, :tnci Itrterrntoni:tj tir•nutor tic•rrn•i:rtn,. 11'lutt c•un ~•ou Iell rtti :rltotrf. the c•onclitions orr :tirltlancs wIrerc• ttl:tt•Ile It:rlt' of' tire a tlrirrl of' tlte area is h:urnecl front swolcin", :tncl I lue ot luer Iral f is nol ? 11'Itat Icincl of intc•r:tc•l iotr iti Ihc•re fortlroscsittin~; in tlro nonsntulcing:u•e:r in Ierntsof rec•irc•tul:llion or ]tol l trt ion ?('u rl :utylrocly retiltoncl t~t t lurt ? Ucx~s t Irut. t ukc c:u e of t l ie c.irc•rrlation ]troblc•nt say Ix:twc'en Ilu•srnukirtg:u•e:t:tnrl (he nonsnroking strca ? I)r. ~e.c r.tt. 'I'he Federal .1viation ldminislr;tlion in 1l171 r•ctn- dnc•tecl a stncl), of the air c•ircitlation Itetween llle dill'c•rent au•eas.'1'lue

300 114: Sanchez, G.C. and Sommera, S.C.: Peptic ulcer diathesia with a mixed adenocarcinoma of the pancreas: Case report. Gastroenterology, 38: 467-470, 1960. 115. Somers, S.C.: Renal and adrenal pathology in hypertension. Conn. 116. Med., 24: 240-244, 1960. Kelly, J.W.H., Parsons, L., Friedell, G.H. and Soamers, S.C.: A pathologic study in 55 autopsies after radical surgery for cancer of the cervix. Swrg., Gynec. and Obst., 110:423-432, 1960. 117. Hollander, A. and Sommers, S.C.: A histochemical study of mucopoly- saccharides of leprosy of the skin. Acta. Dermat. Venereol. Proc. 11th Internat. Congr. Dermat. 3: 407-411, 1957.....1960. 118. Buckingham, S., and Sommers, S.C.:Pulmonary hyaline membranes. J. Dis. Child, 99: 216-227, 1960. 119. Patton, R.B' and Sommers, S.C.: The histopathology of infarction and - other ulcerative disease of the esophagus. Am. J. Clin. Path., 33: 516-524, 1960. 120. Hollander, A. and S oamers, S.C.: Histochemical comparison of Boeck's Sarcoid with-other cutaneous granulomas. Arch. Dermat. 81: 944-946, 1960. 121. Friedell, G.H., Sherman, J.D. and Sommers, S.C.: Spleen and liver in the anemia of the tumor-bearing hamster. Arch. Path., 70: 863-871, 1960. 122. Grassi, J.E. and Sommere, S.C.: A case of carcinoma of the breast in a young woman srith hamartomatous hypothalamic malformation. Am. J. Surg., 100: 606-612, 1960. 123. Celoria, G.C., Friedell, G.H. and Sommers, S.C.: Raynaud's disease and primary pulmonary hypertension.Circulation. 22: 1055-1059, 1960. 124. Turgeon, C. and Soamiers, S.C.: Juxtaglomerular cell counts and human hypertension. Am. J. Path., 38: 227-241, 1961. 125. Sommers, S. . and Turgeon, C.: Morphologic studies on relationship of pyelonep~iritis to hypertension in: "Biology of pyelonephritis" Little Brown and Company, Boston, 1960. 126. McAuley, R.L. and Sosmnera, S.C.: Mast cells in nonspecific ulcerative colitis. Am. J. Digest. Dis., 6: 233-236, 1961. 127. Sommera, S.C. and Verendia, J.B.: An appraisal of laboratory determinations of estrogena, Am. J. Clin. Path., 35: 319-327, 1961. E 301 128. 129. 130. 131. Yin, P-H and Sommers, S.C.: Some pathologic correlations of ovarian stromal hyperplasia. J. C1in.Endocrinol. & Metab. 21: 472-477, 1961. Patalano, V.J. and Soamers, S.C.: Biopsy diagnosis of periarteritis nodosa. Arch. Path., 72: 1-7, 1961. Tedeschi, L.G. and Sommers, S.C.: Oxytalan fibers in sclerosing hemangiomas. Arch. Dermatol., 84: 128-130, 1961. Sommers, S.C.: Some pathologic conditions associated with renal and adrenal hypettension. J.A.M.A. 178: 715-717, 1961. 132. Friedell, G.R., Sherman, J.D. and Sammers, S.C.: Growth curves of human cancer transplants during experimental chemotherapy. 14: 1117-1121, 1961. 133. Sherwin, R.P., Grassi, J.E. and Sommers, S.C.: Hamartomatous malformation of the postlateral hypothalamus. Lab. Invest., 11: 89-97, 1962. 134. Williams, M.J. and Sommera, S.C.: Endocrine and certain other changes in men with carcinoma of the lung. Cancer, 15: 109-117, 1962. 135. Ganem, K, Friedell, G.H. and Sommers, S.C.: A study of ovarian thecomatosis. California Medicine, 96: 254-256, 1962. 136. Tedeschi, L.G. and Sommers, S.C.: Oxytalan fibers - dermal fibromas and giant cell tendon sheath tumors. Arch. Derm., 85: 527-529, 1962. 137. Soergel, K.H., and Sommers, S.C.: The alveolar epithelial lesion of idiopathic pulmonary hemosiderosis. Am. Rev. of Reap. Dis., 85: 540- 552, 1962. 138. Soergel, K.H. and Somaers, S.C.c Idiopathic pulmonary hemosiderosis and related syndromes. Am. J. Med., 32: 499-511, 1962. 139. Soamers, S.C., McLaughlin, R.J. and McAuley,R.L.: Pathology of diastolic hypertension as a generlized vascular disease. Am. J. Cardiol. May, 1962, 653-658. TIMN 450334

218 include all segments of the population except illiterate and migrant workers" (p. 4 in Reference 14). But years later the claim is made that "The study population was not intended to he a probability sample of the total population of the United States. Instead, we attempted to enroll a dispropor- ti°nate number of peopte from certain selected groups so as 35-JV 4044 45aV 50-54 SS-SV 6064 65-69 7074 /S7V 8085 ALE FIGURE 2 Comparison of the ACS and U.S. populations: perantaae distribution by spa. The aqe distribution of ACS females in 1960 comes from Hemmondl° Comparabia fiaures for a population of U.S. fematas between the a9es of 35 erd 85 were cornputed from tables aiven in the 1960 U.S. ansus report!' TABLE 1-Comprison of the ACS and U.S. Populations: P.rant- aqe Distribmbn by Educational Analnmem No Some High High High School Some College Population School School Graduate Collrpe Graduate ACS' meles, ages 45-79 24.30 20.97 17.85 18.10 18.78 U.S.t white ma4n, 54.67 16.78 14.43 7.07 7.05 eans 45-79 ' Fiaures for the ACS Population were derived from Hanr mond,'r Table 2. t Fiaures for the U.S. Population were derived from U.S. Bureau of the Cansus,' s p. 406. TABLE 2-CompeAson of the ACS and U.S. Populatiom: Parcant. .qa Disbibrrtbn by Height Population Under 66 Inches 66-67 68-69 70-71 Ovar72 ACS' males, 8.57 18.89 26.37 29.30 16.87 eqes 45-79 U.S.tmalef, 27.57 28.67 26.29 ®ges 45-79 13.74 5.75 • Fieures for the ACS population were derived from Hem- mond " t Fieures for the U.S. population were derived from National Centerfor Health Statistics," p. 14. TABLE 3-Comparisoas of ACS Mata Smokers ard the U.S. Male Population (1960) by Raa and PM1aa of Bleth' % of ACS %of U.S. Race and Country Smoken' Populetiont of Birth (Me4e) (Mate) Native-bom 94.89 78.80 whita Faei®nborn 4.20 12.67 whita Black 0.91 8.33 ' Source: Hammond.' • 1 Source: U.S. Bureau of the Censas," p.369. organize the extensive effort needed to collect the subjects and follow them through time; • 1}le access volunteers had to friends and others for recruits (rrtany of the ACS volunteer researchets reputedly were doctors' wives with a possible access to patients); • The feelings, opinions, and motives of the individual volunteer in selecting her subjects; . 7fie agreement of smokers and nonsmokers, or sick and healthy individuals, to cooperate with the study; • The ability of the volunteer or the staft member to locate healthy Individuals with the same facility as he or she could locate sick persons; and • The constant publicity concerning cigarette smoking that may have had any number of subtle psychologi- 219 cal and sociologirxl effects on selecting out the final group of subjects (or, for that matter, affecting Interpretation of the data obtained). Just how did these se1ection processes operate with respect to disease and smoking? For instance, did some volunteen of the American Cancer Society, in their zeal and perhaps without being aware of doing so, favoralnong potential recruits those who sttwked and were tB (perhapa even from cancer) and those who did not smoke and wete free of diseaae? Dr. Hammond himself reports that the number of questionnaires In the tirst prospective study (1952) had to be eliminated because volunteers had noted on the margin that the 11un selected for atudy had been already diagnosed with lung (or swne other) cancer, despite instructi°ns that such subjects were not to be recruited.2 ° TABLE 4-Comparison of ACS Mata Smoke.a to the U.S. MaN (AII Reas) Population of 1967 by Retiaton for Ages 45-79 TABLE 6-Perantpe of D..ths for Most of Ceusn for the ACS Femete Population and U.S. White, Population Protestant Catholic Je.vish Total Fewrle Population (1980) by Raa and S.x, for Aan 36-&P ACS' smoken, a9es 79.55 17.33 3.12 100.00 Internatione! ACS Population Comprable U.S.white Compambla U.S.AII 45-79 Undxlyina Cause of Death List Nos. Fernales FemNaa Females U.S.t man, ell races, 70.80 24.95 4.25 100.00 o9es 45-79 Lung (excl. trecMa, plaura) 162 1.47 0.47 0.45 8uccal cavity, pherynx 140-148 0.30 0.30 0 30 ' Source: Hemmond.' e Larynx 161 0.01 0.04 . 0.04 t Soume: U.S. Bureeu of the Census," p. B. U.S. data for Esophaqus 150 0 12 0 20 0 21 1957 were compiled from e9e 9roupinqs 45-64 and 85 years end Bladder and other urinary 181 . 0.47 . 0.45 . 0.45 over. Kidney P 190 OAB 0.36 0.33 TABLE 5-Compedson of the ACS and U.S. Populatiuns (1980) of rostete Panaeas 177 157 - 1.63 - 1.17 - 1.13 Comparable Aaes, by Sex and Plaa of Reddence Liver, biliery passa9ea Stomach 155 151 1.08 1 63 0.76 0.70 %of %of Coton, rectum 153,154 . 513 1.52 4.16 1.51 3.94 % of U.S. All Leukemie 204 1.32 0.88 0.83 ACS Whita U.S. Lymphoma, Hodykin's disaosa 200-203, 205 1.85 1.07 1.01 Type of Aree Men' Ment Ment Breast 170 9.20 4.98 4.77 Uterus 171-174 2.80 2.70 . 2.87 Metropolitan (more then 50,000 61.64 63.22 53.93 Ovary, Fallopren tubes 175 2.76 1.75 1.85 populntion) Coronary heart disease ' 420 32.48 34.13 32.74 Nonmetropolitan (2,500-50,000 17.79 16.12 15.84 Rheumatic heart disease 400-402, 410-416 2.17 1.91 1.80 populntion) a Hypnrtemive heart disease 440-443 4.31 6.90 6.71 Rural 20.57 30.66 30.23 Other heart disease 421, 422, 430-434 4.21 6.92 6.05 Total 100.00 100.00 100.00 Aortic eneurysm (nonsyphilitic) Cerebral vascular lesions 451 330 334 0.60 0.42 '0.41 • Source: Hammond." (The 2,093 men reported as "Not Other circu4tory diteasea - 444-447, 450, 452-468 14.03 3.11 16.56 4.31 16.90 4.80 Ctassified" are not used here to compute peranta9es.) fmphysema 627.1 0.34 0.23 0.21 1 Source: U.S. Bureau of the Census," pp. 148-151. Gastric ukxr 541 0.25 0.23 0.22 Cirrhosis of liver 581 0 96 1 37 1 35 Diebetes 260 . 2.61 . 3 16 . 3 28 o have sufficient numbers for analysis of death rates " within III defined diseaua 780-795 0.38 . 0 65 . 0 97 ach such group (p. 2 in Reference 19). But, what ever the Viotence,accidents,suicide E800-E965, E970-E999 4.42 . 4.41 . 4 37 reasons, to a statistician. such differencee between t he 11.5_ Total . nd the largely self-selected population are alarmi n The e a g. objection is not that the study population was not drawn at random but that self-selection processes may have spuri- ously created (or at least substantially contributed to) differences between categories of the study population that are not present in the population at large or, vice versa, may hide true differences. After all, the factors determining whether a subject was followed included; • The zeal of the chapters and of the volunteers to SMOKING AND LUNG CANCER 941 • In order to construct this teble, only those wusea of death were used for which deatM in the U.S. popula0on were available for conparable apa. The Hammond dete canr from Appendix, Table 13 of Referena 12, and the U.S. d®te from pp. 48-87 Fn Referena 21. Conparisona wasa not possdb6a for the lollowing uuees of death from Henenond's table: other specified sites, ancer-sita not pecified, pneumonie, influenza, other pulmonary diteaaes, duodanel uteers, nephritis and other kidney diseeses, and other specified diseeses, involvinp e total of 2,005 or 12.0% of oil deaths reported by Hammmnd. Hammond's fiaures for lung cancer exclude invotvement of trachea or pleura. However, the fiprres for the U.S. include it. For 1960 there were only 29 lunq cancer deaths with involvement of trachee and plaura for age, 35-84. 942 AJPH SEPTEMBER,1975, Vo1.65, No.9 TIMN 450293

11 274 Senator KJNEDY. Do you, or do you not think that it is a cause? sir, that I do not be- I ha`•e expressed nlyself clearly aF , ' Soht~fF I>r.lierc that itI 1Go al ea dausc. torFENNEnY Sena T>r. So~cMFRS• When analysis has been undertaken of the accuracy of a cler~t), certificate diagnosis of lung cancer, when compared with autop'~r 5ndings, slighily less than 50 percent were found to be accuratc. I)11eilmonia and tnnlors spreading to the lungs from other parts of the bn(J~he~t blllcd ir 1 i kta s~uadd~t~tbtise b rr~ 1tcll to establi~l the ccr. Rel, ' y~ Y t1.iu, incidencc of Iunf; cancer.'Che figures appear exaggerated twofold at leqst. l,1ing cancer is not an entity either pathologically or etiologicallT. I'here are some 10 diflerent varieties of lung cancer, each of which is likel,)'a different clisease witb a difCercnt causation. t)nc type called oat-ee•lI c•arc•inonia recently was re.ported in a group of cheiuical workers, nlostt of «•honr 13•ercv nonsmokers, and it appeared tliet smolcers in the same Irizurt were in sonre way protected. Time, scholarsbil),:urd nroney are needed to work out. these difficult problems. Chronic piilnronar;y disease, also called brcmchitis-emphysema, or chrouic obstructive pulnionary cliseaGe, is a serious public health prob- leni.11'hen a disease has several names, it, is an indication that not very much is known about it. Fmphyserna of the lrurgs is difficult. to diagnose clinically. Also pathologically it. is difficult. to establish its presence, type and extent, even when a pane.l of expertsexamines whole lung sections. These large sections are only at'allable in a few research centers. Experts examining such sections, it was reported, could reach no agreement, on whether, how much and what. type of emphysema was present. Senator HART. i)octor, excuse me just. a, second. The first page of your statement, you talk about the Berkson study. Dr. SOMMERS. Yes, si r. Senator IInR•r. Now, «•ha.t was t.he date of that? Dr. 8011IIVLF',RS. It is gl \'e n in the references on the last page. Senator HnRT.1 955 ? I)r. fioMrsERs.1.955. _ TF .",LDI11C~,1 Oi~ w 1a1; you t:.a..{ aJollt, thereafter, is based upon thatt study, is that. correct? I)r. S(1llr11rF.Rs. No, nothing thereafter is based on that study. Scnator HART. Page 2, paragraph 3, refers to data collected from 1919 to 1960. You ta.lk a.bout the Berkson predictions, and so on. 1 jnst, wonder how r-alid tllat would be. 20 years ago? I)r. SoIArnrFns. Sonic very «•ise thinf,•s were said about smoking and he'llth 2(1 years ago. Rerkson simpl,y predicted that when the fa.cts were out, or the scrence was improved, the relations}rip would be a ver;r spm•ions artifact. I simpl,ystatethat.I feel he hasbeen supported. Senator HnR•r. Thank you very mucll. Senator KENNEDY. Have you done any research in this area yourself recently? Dr. SoMMEns. Yes, sir, the• day before yesterday. 275 ~ Senator KENNEDY. Could you submit the reports ? Co4ld you file the reports ? Dr. SOMMERS. They are also published in the medical hiterature. Senator KENNEDY. When is the last one, and what medical litera- ture ? Dr. SOMMERS. The last one that dealt with lung cancer specifically? Senator KENNEDY. Yes, all right. Dr. SOMMERS. The last one? Senator KENNEDY. That is right. I)r. SOMMERS. In the neighborhood of 1958, I believe. Senator KENNEDY. 1958? I)r. SOMMERS. I believe. Senator KENNEDY. Why have you not published in that area since then ? Dr. SOMMERS. Sir, I have not had the material available. Senator KENNEDY. What do you mean by that? Dr. SOMMERS. I am a pathologist, working with human autopsy, and surgical specimens, and the hospital where I have worked since that time did not havo enough cases on which to base a good study. Senator KENNEDY. What is the basis of your testimony here today? I)r. SOMMF,RI+i. My continuing interest, and study in the field, and a paper on which I am now working. Senator KENNEDY. On what, on the lung ? Dr. SOMMERS. On the lung, sir. Senator KENNEDY. When will it be published ? Dr. SoMrrERS. Sir, I anticipate within a year. Senator KENNEDY. But you have done no original research that has been the basis of publication in 18 years? Dr. SOMMERS. It may be true, sir. Senator KENNEDY. And you are the best fellow that the industry could come up with ? Dr. SoMMERs. Sir, knowledge in the field involves reading as well as research, and I am active]y interested in the field. As one gets older, sir, one leaves research somewhat to younger people. Senator HART. Or Nobel prize winners? Senator KENNEDY. I do not know how old they are. T)r C., ~ Tt r J 'c. .responc i,;.'lat. Those gentlemen were virologists, and so far as I know, they never worked on lung cancer, and the last Nobel prize given for lung cancer was to Fibiger for producing it in rats with worms-it is one of the blots on the. Nobel prize history Senator KENNEDY. Well, I am sure they will be interested in your medical evaluation of their scientific contribution. Ih•. Scrnrnrr:ns. I know the.y arewonderful vir•ologists. Senator KENNFDY. Of course, the. Armed Forces Institute of Pathol- ogy which is probably the outstanding center of the world, quite frankly, complet.ely agrees and supports t.he Surgeon General's posi- tion, and does nott support yours. So I think when we are talking about biology, and pathology, that tlratt ought t.o be noted for the record as well. Senator HART. Could I ask for a reference on a previous page, page 5, of your prepared statement, where you discussed the analysis of the accuracy of death certificates?

lu I 292 11 293 PUBLISHED ARTICLES Sheldon C. Sommers, M.D. 1. Jacobs, J.L, and Sommers, S.C.: The specificity of for®olized proteins. J. Ismunol. 36: 531-541, 1937. 2. Menkin, V., Kadish, M.A. and So®mera, S.C.: Leukocytosis promoting factor in inflammatory exudates of man. Arch. Path., 33: 188-192, 1942. 3. LeCompte, P.14., Soa®ers, S.C. and Lathrop, F.D.: Tumor of carotid body type arising in the middle ear. Arch. Path., 44: 78-81, 1947. 4. Warren, S. and S osmers, S.C.: Cicatrizing enteritis (regional ileitis) as a pathologic entity. Am. J. Path., 24: 475-501, 1948. 5. Warren, S. and Sommers, S.C.: Giant cell inclusions in cicatrizing enteritis. Proc. Soc. Exper. Biol. & Med., 8: 461-463, 1948. 6. Warren,'S. and Sommers, S.C.: Pathogenesis of ulcerative colitis. Am. J. Path., 25: 657-659, 1949. 7. Hertig, A.T. and Son.mers, S.C.: Genesis of endometrial carcinoma. I. Study of prior biopsies. Cancer, 2: 946-956, 1949. 8. Sommers, S.C., Hertig, A.T. and Bengloff, H.: Genesis of endometrial carcinoma. II. Cases 19 to 35 years old. Cancer, 2: 957-963, 1949. 9. Hertig, A.T., Sommers, S.C. and Bengloff, H.: Genesis of endometrial carcinoma. III. Carcinoma in situ. Cancer, 2: 964-971, 1949. 10. Sommers, S.C., Lawley, T.B. and Hertig, A.T.: A study of the placenta in pregnancy treated by stilbestrol. Am. J. Obat. & Gynec., 58: 1010, 1949. 11. Warren, S. and Sommers, S.C.: Proteolysia in intestinal disease. 12. Gastroenterology, 14: 522-526, 1950. Wyatt, J.P. and Sommers, S.C.: Chronic marrow fiilure, myelosclerosis and extramedullary hematopoiesis. Blood. 5:'329-347, 1950. 13. Meissner, W,A, and Sommers, S.C.: Postpartum endometrial hyperplasia in diabetics treated with stilbestrol and progesterone. J. Clin. Endocrinol., 10: 603-609, 1950. 14. Sommers, S.C. and Johnson, J.M.: Congenital tricuspid atresia. Am. Heart J., 41: 130-143, 1951. 15. 16. 17. 18. 19. 20. Sommers, S.C., Wilson, J.C. and Hartman, F.W.: l.ysephoid lesions in poliomyelitis. J. Exper. Med., 93: 505-512, 1951. Warren, S., Holt, M.W. and Sommers, S.C.: Some early nuclear effects of ionizing radiation. Proc. Soc. Exper. Biol. & Med., 77: 288-291, 1951. Holt, M.W., Sommers, S.C. and Warren, S.: Preparation of tissue sections for quantitative histochemical studies. Anat. Rec., 112: 177-186, 1952. So®ers, S.C. and Teloh, H.: Ovarian stromal hyperplasia in breast cancer. Arch. Path., 53: 160-166, 1952. Warren, S., Holt, M.W. and Sommers, S.C.: Some cytologic and histochemical studies of radiation reaction. Am. J. C1in.- Path., 22: 411-417, 1952. McManus, R.G. and Sommers, S.C.: Breast cancer prognosis and ovarian cortical stromal hyperplaaia. New Eng. J. Med, 246: 890-892, 1952. 21. Sommers, S.C. and Young, T.L.: Oxyphil parathyroid adenomas. Am. J. Path., 28: 673-689, 1952. 22. Edwards, J.L. and Sommers, S.C.: Radiation reactions in parabiotic rats. J. Lab. and Clin. Med., 40: 342-354, 1952. 23. Chute, R.N. and Sommers, S.C.: Hemolytic disease and polycythemia in parabiosis intoxication. Blood. 7: 1005-1016, 1952. 24. Hollander, A. and Sommers, S.C.: Lepromatous leprosy. New Eng. J. Med., 247: 634, 1952. 25. Christensen, W.R., Sommers, S.C. and Spaulding, C.K.: Effect of soft roentgen rays on the rabbit skin. Am. J. Roentgenol., 63: 801-808, 1952. 26. S ommers, S.C., Chute, R.N. and Warren, S.: Heterotranaplantation of human cancer. I. Irradiated rats. Cancer Ree., 12: 909-911, 1952. 26A. Chute, R.N. and Sommers, S.C. and Warren, S: Heterotransplantation of human cancer. II: Hamster cheek pouch. Cancer. Ree., 12: 912-914, 1952. 26B. Sommers, S.C., Sullivan, B.A. and Warren, S.: Heterotransplantation of human cancer. III. Chorioallantoic membranes of embryonated eggs. Cancer Res., 12: 915-917, 1952. I TIMN 450330 k

328 Mr. Chairman, the cause or causes of cancer are unknown. And in the face of the unknown, Pasteur also provided this wise guidance on the conduct of research: "Preconceived ideas are like searchlights which illumine the path of the experimenter and serve him as a guide to interrogate nature. They become a danger only if he transforms them into fixed ideas.. " Is it too much to suggest, Mr. Chairman, that preconceptions about the over-riding nature of the health hazard of smoking have become transformed into fixed ideas? A recent study by the prestigious National Academy of Sciences also sounds a note of caution. °Ffhe enormity of our ignorance about cancer receives less emphasis than it merits. Much Is said about the lines of research that appear promising today -virology, cellular immunology, and genetics, for example - but too little is made of the genuine possibility that any or all of today's ieads...couid turn out to be the wrong leads." Is it too much to suggest, Mr. Chairman, that this observation has relevance to these deliberations? 329 EXHIBIT A TOBACCO INDUSTRY RESEARCH ON SMOKING AND HEALTfI TIMN 450348

322 It is instructive that in Dr. Hueper's view the disproportionate attention to cigarettes has produced a distorted assessment of the relative significance of the various factors that may be involved and has interfered with an effective approach to preventive n7easures. In support of the charge that cigarette smoking is "the largest single unnecessary and preventable cause of illness and early death in the United States," the bill before the committee relies primarily on statistical evidence cited in the 1975 H.E.W. report entitled "The Health Consequences of Smoking." Senator Hart, in a statement appearing on page S773 of the Congressional Record incorporates an "Overview" from this Report. I would, therefore, like to attach to my statement for the record a review of the 1975 Health Consequences of Smoking (Exhibit C) which summarizes some of the contradictory evidence omitted from this Report. I believe anyone reading the attached review will, in all fairness, have to conclude that the question of smoking and health is still an open one. I will briefly provide a few "highlights" and some of the questions raised by our Review: (1) The 1975 Report ignores a crucial fact which has been conceded by even an outspoken critic of tobacco smoking: "in spite of 20 years work on tobacco smoking," he admitted, "we cannot identify...nobody has been able to identify a carcinogen to explain the incidence of lung cancer in man." (2) The 1975 Report fails to state the basic caveat made by other government reports that "statistical methods cannot establish proof of a causal relationship in an association." 323 (3) The 1975 Report ignores a well-known Harvard researcher's study which finds that the cessation of smoking among men over sixty-five appears to have no effect on their heart disease rates, while in women over sixty-five, the risk of cardio- vascular disease increased upon the cessation of smoking. (4) The 1975 Report acknowledges that smokers on the average have lower blood pressure than nonsmokers, yet suggests that cigarette smoking acts, together with high blood pressure, to somehow cause coronary heart disease. (5) Why does the 1975 Report and all previous reports fail to explain that the Advisory Committee to the Surgeon General in 1964 was wrong, if such was the case, when it concluded that nicotine does not present a significant health hazard to smokers? (6) Where is the explanation-if there is one-for the studies showing that the age at which lung cancer occurs does not depend upon the age at which one starts to smoke, or how long one smokes, or even whether or not one smokes? (7) Why does the 1975 Report ignore the lack of correlation between cigarette consumption data and lung cancer death rates in various countries? For example, the United States and Canada have the two highest per capita consumptions of cigarettes in the world, yet they rank 10th and 16th respectively with regard to white male death rates from lung cancer. Conversely, England, Finland and the Netherlands, with lower per capita cigarette consumption, all have. substantially higher lung cancer death rates than the United States. Please bear in mind that the 1975 Report on the Health Consequences of Smoking was prepared by the National Clearinghouse for Smoking and Health, which is the arm of vaau a..a:__._a . ' . iip on . .. . „ . TIMN 450345 ~

320 I recognize that S2902 does not call for absolute prohibition. But I submit that it calls for creeping prohibition through taxation. As in the Limbo dance, the "tar" and nicotine content could then be progressively lowered to zero through fiscal controls. Throughout the United States today, low "tar" and nicotine cigarettes are available to every smoker. Information concerning "tar" and nicotine content is available to every smoker from a variety of sources including cigarette advertising and periodic reports by the FTC. This availability of a broad range of brands together with information about their "tar" and nicotine content affords every smoker an opportunity to freely express his preference in the marketplace. As the free market mechanism works out, more than 80 percent of all cigarettes purchased in the U.S. are 19 mg. of "tar" or below. The sales weighted average "tar" level of U.S. cigarettes has dropped over 50 percent in the past 20 years to a present level of 18.5 mgs. In 1974, the most recent figures, cigarette advertising expenditures were weighted overwhelmingly (over 95%) in favor of brands containing 19 mg. or less. S2902 proposes to intervene in the marketplace, in what we are told is "the most effective way known to an open and democratic society." This most effective way turns out to be a "differential tax" on cigarettes, which it is said-and I quote-"will both encourage the consumer to further consider the significant health hazards of smoking and will provide an incentive for cigarette smokers to reduce their consumption of tars and nicotine." I have some doubts that this proposal will be recognized as democracy in action by the people. It would not only discriminate against tobacco consumers in general but it is also clearly regressive, hitting hardest at those least able to pay. Blue collar workers, service industry workers, clerks, typists, and others would have higher sa7called "Incentives" than executives, managers and proprietors. I 321 What is the scientific basis for such action? A letter which accompanied the bill asserts that "It is now clear that heart disease, lung cancer, chronic bronchitis and emphysema are but a few of the diseases caused by cigarette smoking." However, as one scientist has recently observed "The readiness with which the existing evidence has been accepted as demonstrating causality for cigarette smoking perhaps is the best measure for the desire to keep our world simple and orderly." Recent research into environmental and occupational factors is developing new data indicating that chronic disease may no longer be so readily and simply attributed to tobacco smoke as some have claimed. Some of this new evidence has been summarized by the CBS program "The American Way of Cancer" and in a lengthy article in Newsweek magazine. Moreover, a recent report to the Ford Foundation says: "Occupational factors may very well play a far more significant role than is presently realized in the causation of the major diseases and health problems that confront us." The report to the Ford Foundation goes on to say that of the two million people who die every year in the United States, heart disease, the leading cause of death, which accounts for 38.7% or about 750,000 deaths,-and I quote-"is only 25% 'explained' by known physiological and environmental factors, such as excess weight, hypertension, serum cholesterol, and cigarette smoking." Last April, the Society of Occupational and Environmental Health gave its first annual award to Dr. W. C. Hueper "for his role in pioneering and fostering the study of occupational and environmental cancer and in establishing the scientific and public awareness that most human cancers are caused by environmental factors and can be prevented." Most of the oresent interest here and abroad in the environmental e®uses of human cancer can be traced to Dr. Hueper who headed the environmental cancer section oftNational Cancer Institute. . TIMN 450344

E 310 311 ~ 255. Fisher, E.R., Gregorgio, R., Redmond, C., Vellios, F., Sommers, S.C. and nt breast d l Enclosure #3 i juva a Fisher, B. Pathologic findings from the national surgica project - (Protocol No. 4). "1. Observations concerning the multicentric- 1975 ity of Mammary cancer.,Cancer, 35:247-254, 1975. Additi l R f 56 Sommers, S.C. and Korelitz, B.I.: Mucosal-cell counts in ulcerative and ona erences e . 2 granulomatous colitis. Amer. J. Clin. Path., 63:359-365, #3, March, 1975. 1. R.E. Albert, N.T. Peterson, Jr. and D.E. Bohning. Arch. Environ. Hl.th., 257 Waller,J. & Sommers,S.C.: Fulminant Fatal•Sclerodercna. Amer. J. of 1975, 30, 361-367. . Yherap. & Clin. Reports, 1:51-54 1975. 2. E.L. Babbott, R.C. Hall, D.N. Gump and D.L. Sylvester. APHA, Health & 25g. Fiaher, E.R., Gregorio, R.M., Fisher, B., Sommers, S.C.: The pathology Work in America meeting, November 16-20, 1975, Abstract, 210B. of invasive breast cancer, Cancer 36:1-85, Vol. 36, #1 for July, 1975. 3. J. Bednarzewaki, A. Jach, S. Rywik and W. Milolajczyk. Polaki Tygod. Lek., Adrenocortical Postirradiation Fibrosis, Arch. M E 1975, 30,1737-1738. 259. . . Sommsers,S.C., Carter, Aug. 1975. 99:421-423 Path , ., 4. J.R. Belcher. Brit. J. Die. Chest, 1975, 69, 247-258. 260. Terzakis, J.A., Sommers, S.C., Snyder, R.W. & Sabbath, M.: X-ray micro- 5 T Ber e and N G Toremalm Scand J Dia Rea 1975 56 109-119 analysis of Hepatic thorium depositions, Arch. Path., 98:241-242, Oct.1974. . . g . . . . . ., p. , , . 6. T. Berge and N.G. Toremalm. Scand. J. Reap. Dis. 1975, 56, 120-126. 261. Barber, R.K., Sommers, S.C., Snyder, R. and Kwon, T.H.: Histologic and , nuclear grading and stromal reactions as indices for prognosis in ovarian 7. G. Berglund and L. Wilhelmsen, Acta Med. Scand., 1975, 198, 291-298. cancer, Amer. J. of OBS/GYN., 121:795-807, #6, March, 1975. Korelitz B.I. & Sommers S.C.: Responses to drug therapy in ulcerative 8. W.J. Blot and J.F. Fraumeni, Jr. Lancet, 1975, 2, 142-144. 262 ical changes atholo d histo t l bi b l . , g p opsy an a uation y rec colitis - Eva Amer. J. Gaatroenterol., 8 pages, November 1975. 9. S.M. Brown, M.G. Marmot, S.T. Sacks and L.W. Kwok. Nature, 1975, 257, 263. pathology Decennials (7 volumes), Appleton-Century-Crofts, N.Y.C., 306-307. Edited by S.C. Sommers, 1975. 10. S.M. Brown, S. Selvin and W. Winkelatein, Jr. Cancer, 1975, 36, 1903-1911. 11. P.R.J. Burch. Lancet, 1975, 1, 797. 12. P.R.J. Burch. J. Soc. Occup. Med., 1975, 25, 2-10. 13. S. Burrows. JAMA, 1975, 233, 441-443. 14. M. Caplin and F. Festenstein. Brit. Med. J.,.1975, 2,*348., J.B. Macdonald, 15. ibid (Letters to Editor). R. Cooke and I. Toogood, Aust, N.Z. J. Med., 1975, 5, 147-154. 16. E. Corday and S.R. Corday. Am. J. Cardiol., 1975, 35, 330 (Editorial). 17. De F. Ulf. J. Paychoaom. Res., 1975, 19, 273-278. 18. I. Doniach, K.V. Swettenham and M.K.S. Hathorn. Brit. J. Indust. Med., 1975, 32, 16-30. 19. P. Phelan. "The Beginnings of B." Aust. N.Z. J. Med., 1975, 5, 281, 20. (Abstract). J.I. Raft and Y. Sarkel. Clin. Res., 1975, p.186A, (Abstract). 21. N.-P. Uarke. Preventive Med., 1975, 4, 373-374. 22. R.J. Hickey, R.C. Clelland, D.E. Boyce and E.J. Bowers. JAMA, 1975, 232, (Letter to Editor). TIMN 450339

302 140. Reeves, G. and Sommers, S.C.: Endometrial hemosiderin as evidence 151. of inetrorrhagia. OBS. and GYN., 19: 790-792, 1962. 141. Reynolds, C.T. and Smithwick, R.H. and Sommers, S.C.: Excision 152 of adrenal adenoma and sympathectomy in the therapy of hypertension. . Am. J'. Surgery, 103: 696-701, 1962. 142. More, B.M. and Sommers, S.C.: Status of the myocardial arterioles 153. in angina pectoris. Amer. Heart J., 64: 323-393, 1962. 143 Reynolds, C.T. and Sommers, S.C,: Sympathectomy for glomerulo- . nephritis with hypertension. Arch. Surg., 85: 390-393, 1962. 154. G.B., Babin, D.S. and Knaack, C.T.: Chronic Robbina S C Sommers 144. , . ., , pyelonephritis, renal tubular atrophy and hypertension. Arch. Int. 155 Med., 110: 505-510, 1962. . 145 Whisenand, J.M., Kostas, D. and Sommers, S.C.: Some host factors . in the development of renal cell carcinoma. West. J. Surg., Oba. 156. & Gynec., 70i 284-285, 1962. 146. .Boughton, R.M. andSommers, S.C.: A new concept of renal hypertension. 89: 113-136, 1963. Urology j , . 157. 147. Reeves,. G., Lowenstein, L. and Sommers, S.C,: A suggested mechanism of erythropoietic control of juxtaglomerular cells. Am. J. Med. Sci., 1963. 245: 134-187 , 158. 148. Hark, B. and Sommers, S.C.: Endometrial curettage in,diagnoais and therapy. Obat, & Gynec.,.21: 636-638, 1963. 149. Sommers, S.C., Weber, C.E. and Reeves, E.: A hemagglutination reaction of mothers and infants of different ABO and Rh groups. Am. J. Clin. 159. 39: 482-484, 1963. Path. , 160. 150. Russfield, A.B. and Sommers, S.C.: The effect of malnutrition on tropic hormone storage in the human hypophysis. Arch. Path., 75: 564 1963. , 161. 162. 163. 164. 165. 303 Beaser, S,B., Sak, M. and S oaaDera, S.C.: Influence of insulin therapy and pyelonephritis upon diabetic glomerulosclerosis in hamsters. Metab. 12: 704-709, 1963. Sommers, S.C.: Some endocrine and imcunologic aspects of prognosis in breast carcinoma. Acta Union Int. Contre Cancer 16: 959-960, 1962. Reeves, G., Figueredo, A. and Somers, S.C.: A case of breast carcinoma with hypothalamic malformation. West. J. Surg. Oba. & Gyn. 71: 184-186, 1963. Hutt, M.S.R. and Sommers, S.C.: A clinicopathologic analysis of biopsy specimens in persistent glomerulonephritie. Am. J. Path., 43: 459-475, 1963. Bowden, D.H., Danis, P.G. and Sommers, S.C.: Ataxia-Telangiectasia. J. Neuropath. & Exp. Neur. 22: 549-553, 1963. Beaaer, S.B., Sak, M.D., Donaldson, G.W., McLaughlin, R.J. and Sommers, S.C.: Alloxan diabetes in the golden hamster, Mesocricetus Auratus II. Glomeruloaclerosis and its relation to diabetic regulation. Diabetee; 13: 49-53, 1964. Williame, M., Barnes, M.D, and Sommers, S.C.: Hyponatremia, anti- diuretic hormone secretion and oat cell carcinoma of the lung. Dia. of Cheat, 44: 95-99, 1963. Monroe, L,S „ Boughton, G,A. and Sommers, S.C.: The association of gastric epithelial hyperplasia and cancer. Gaetroenterology 46: 267-272, 1964. Teel, P, and Somers, S,C,: Vascular invasion as a prognostic factor in breast carcinoma. Surg. Gynec. and Obstet. 118: 1006-1008, 1964. Reeves, G., Lowenatein, L. and Sommers, S.C.: The renal macula densa and juxtaglomerular body in cirrhosis. Arch. Int. Med. 112: 708-715, 1963. Williams, M.J. and Sommers, S.C.: Fmphysema, peptic ulcer'and lung carcinoma with pituitary Crooke's cells. Am. J. Med. Sci., 247: 422-426, 1964. Sommers, S.C. and Dixon, F,J.: Seminar on untoward reactions to treatment. Am. Society of Clinical Pathologists, Chicago, 1964, 67 pp. Breslau. A.M.. Conick_ H.C __ s-- s e -.,a Pathogene6is of chronic pyelonephritia. Am. J. Path. 44~:~679-705, 1964. Wright, C.F„ Medenilla, G.A. and Sommers, S.C.: Perinatal death: A clinicopathological analysis of 99 cases. Calif. Med. 100: 336-339, 1964. Soasaers,S.C.: Abnormalities accompanying carcinomas of the large intestine. Die. Colon and Rectum 7: 262-269, 1964. TIMN 450335

, 3 334 TOBACCO INDUSTRY RECORD OF SELF-REGULATION AND VOLUNTARY ACTION In 1963, the industry stopped all promotion on college cainpuses. In 1964, it established an advertising code to limit its message from reaching youth audiences. Although the code has been technically terminated, its principles are still adhered to. In 1967, the industry began a continuing program of technical assistance to the FTC, related to the Commission's "tar" and nicotine testing period. in 1968, research directors employed by various tobacco companies began serving in individual capacities as advisors to the Tobacco Working Group of the Lung Cancer Task Force, National Cancer Institute. In 1969., the industry volunteered to stop all advertising on radio and television. Today, cigarette advertising is off the air waves as a result of statutory implementation of the self-regula- tory initiative by the industry. In 1970, cigarette companies voluntarily began to include FTC "tar" and nicotine ratings in advertising. - Page 2 Attachment A 335 In 1971, all of the member companies of the Tobacco Institute began voluntarily to depict in advertising the side of the package carrying the Surgeon General's warning. In 1972, the industry consented to the order by the FTC which requires a disclosure of the Surgeon General's warning in newspapers, magazines, billboards, and other advertising. TIMN 450351 • i

29'6 297 57. Sommers, S.C.: Some applications of ultraviolet mieroseopq to pathology. 71. Sommers, S.C. and Chute, R,H,: Carcinogenesis and altered host reactions BHQ, 5: 105-108, 1954. in paral:iotic rats. Arch. Path., 61: 295-304, 1956. 58. Lemon, H,M, aud Sommers, S.C.: Clinicopathologic conference. AM. J. Clin. 72. Sommers, S.C.: Introduction to pathology of neoplastic diseases. J, Path., 24: 1402-1407, 1954. Student A.M.A„ 21-25, April, 1956. 59. Sommers, S,C„ Crozier, R, and Warreu, S+: A study of the ultraviolet 77. Shakhashir, T. and Sommers, S.C.: Chronic men&trual endometrium. Obst. & microscopy of renal vascular diseases. Circulatio:., 11: 38-43, 1955. Gynec., 8:112-115, 1956. 60. Wood, J,S „ Jr., Holyoke, E,D„ Somsrers, S.C, and Warren, S.: L.fluence 74. Sot+mera, S.C.: Basement membranes, ground substances and lymphocytic of pituitary growth hormone on growth and metastasia.formatio n of a aggregates in aging organs. J. Gerontol., 11: 251-260, 1956. transplantable mouse sarcoma. Bull, John Hopkins Hosp., 96: 93-100, 1955. 5 : A "blighted" ascites tumor. Transplant. Bull., n cnd Sommers S C Bric 61. Som:cuers, S,C, and Warren, S.: Ulcerative colitis lesions in irradiated . 7 , , . ., 3: iC2-103, 1956. rats. Am. J, Digest. Dis., 22: 111, 1955. : Pathogenesis of polycystic ovaries. Am. and Wodman P J S C 62,' Sommers, S.C.: Endocrine abnormalities in women with breast cancer4 Lab. 764 , , . Sommers, , , J. Obst. & Gynec., 72:160-169, 1956. Invest., 4: 160-174, 1955. 77. Boughton, G,A, and Sommers, S.C.: Runal changes in shock treated with 63. Haley, H.L., Dews, G,H, and Sommers, S,C.S A histochemical comparison levarterenol (Levophed). Am. J. Clin. Path., 27:29-34, 1957. of primary thyroid hypirplasia and adenomatous goiter. Arch. Path., 59: 635-640, 1955. 78, Br.rr, R. and Sommers, S.C.: Unusual causes of death after cardiac 64. Keefer, C,S,, and Sommers , S.C.: Clinicopathologic Conference. Am. J, su:gcr , Am. Heart J, 53: 232-239, 1957. Clin. Path „ 25: 1053-1057, 1955. 79. M^r`,1., l:. and Sommers, S.C.: Endocrine correlations in mammary adeno- 65. Soauners, S.C., Gatea, 0. and Goodof, I,I,: Late recurrence of granulosa fih=jsis and chronic cystic mastitis. Ann. Surg., 145: 326-333, 1957. cell tumors. Obst. & Gynec., 6: 395-398, 1955. 80. Scm,mers, S.C.: Endocrine changes with prostatic carcinoma. Cnncer, 10: 345-358, 1957. 66. Sommers, S,C,: Development of research at Massachusetts Memorial Hospitals. BMQ, 6: 113-115, 1955. 81. Lambie, A,T, Burrows, B.A. and Sommers, S,C,: Clinicopathologic 67. Handler, A,H;, Davis, S, and Sasmers, S,C,: Heterotransplantation C=:nference. Refractory anemia, agammaglobulinemia, and mediastinal tumor. Am. J. Clin. Path., 27: 444-452, 1957. experiments with human cancers, Cancer Res., 16; 32-36, 1956. 82. McHulty, J,R, and Somers, S.C.: Kcratoncanthoma as a surgical pathologic 68. Parker, T,G; and Sommers, S.C.: Adrenal cortical hyperplasia accompanying entity. Surg., Gynec. & Obst., 104: 663-668. 1957. cancer. Arch. Surg., 72: 495-499, 1956. 83. Janes, R,G, and Somers, S,C,: Glomerular alterations in kidneys of 69. Sommera, S,C;: Testicular spermatogenic cell hypertrophy accampanying rats treated with desoxycorticosterone. Arch. Peth., 64: 58-62, 1957. prqstatic hypertrophy and cancer. Am. J, Path., 32: 185-199, 1956. 84. Saltz, M, Sommers, S,C, and Smithwick, R.H.: Clinicopathologic 70. Sommers, S,C. and Haley, K,H,:. Similarity of glomerular ultraviolet correlations of renal biopsies from essential hypertensive patients. absorptions in diabetes mellitus and after cortisone therapy. Proc. Circulation, 16: 207-212, 1957. $ocr, E._per,, Biol, & 1ied,, 91: 262-265, 1956. 85. Merriam, J,C „ Jr. and Sommers, S.C.: Mammary periductal hyalin in diabetic women. Lnb. invest. 6: 412-420, 1957. TIMN 450332

332 1 333 -3- what t,hey found The findings of research studies funded•*in whole or in part by the industry have already resulted in publication of more than 2,000 scientific papers in the professional literature. Through this work much valuable data have been produced about lung cancer, heart disease, chronic respiratory ailments and other diseases. However, there's still a lot more to be learned. The findings are not secret All the above reports have been published in medical and scien- tific journals in the United States and other parts of the world. These documents are available to scientists and doctors interested in pursuing the scientific truths on the smoking and health issue. The work should c .Lo forward There are eminent scientists who believe that the question of smoking and health is an open one and that research in this area must go forward. From the beginning, the tobacco industry has believed that the American people deserve objective, scientific answers. With this same credo in mind, the tobacco industry stands ready today to make new commitments for additional valid scientific research that offers to shed light on the question of smoking and health. THE TOBACCO INSTITUTE February, 1976 EXHIBIT B CHRONOLOGY OF TOBACCO INDUSTRY RECORD OF SELF-REGULATION AND VOLUNTARY ACTION TIMN 450350

to :318 STATEMENT OF HORACE R. KORNEGAY PRESIDENT, THE TOBACCO INSTITUTE, INC. Before the Subcommittee on Health Senate Committee on Labor and Public Welfare February 19, 1976 My name is Horace R. Kornegay. Since June 1970, I have served as President of the Tobacco Institute, an association of tobacco manufacturers in the United States. I appreciate your invitation, Mr. Chairman, to testify before this distinguished subcommittee at what you called an initial hearing to "explore the possible relationship between smoking and disease." I thank you for this opportunity to express views on behalf of the Tobacco Institute, in what you also said will be a series of hearings on "environmental health hazards." Congressional hearings can be very helpfuL As the New York Times said in an editorial last week, there is a "need for accompanying all national health statistics with more illuminating commentary and explanation than are now provided." Hopefully, as a result of these hearings such "illuminating commentary and explanation" will be extended to the controversial and emotional subject of smoking and health. In February 1972 1 had the honor of testifying before the Consumer Subcommittee of the Senate Committee on Commerce. At that time I expressed the tobacco industry's vital concern in determining whether cigarette smoking causes human disease, whether there is some ingredient as found in cigarette smoke that can be demonstrated to be responsible, and if so, what it is. At this time, the tobacco industry is still vitally concerned about these critical questions concerning smoking and health. For the past 20 years, the tobacco industry has supported independent scientific research with comoletelv nonrestrictive fundina_ Thn totw] hpn nnw ronnhor9 S57 millinn dollars, including 742 grants to scientists in 317 medical schools, hospitals and institutions. The industry has funded multi-million dollar projects at Washington University in St. Louis, the Harvard Medical School and the UCLA School of Medicine. I would like to submit for the record at this point a brief report_ on tobacco industry research on smoking and health (Exhibit A). 319 In addition to its research commitment, the conduct of the tobacco industry in re1®tion to the marketing of tobacco products has been both responsive and responsible to mn extent which might be considered unparallelled. I would like to submit for the record a br{ef chronology of some of our initiatives toward self-regulation and other voluntary ections (Exhibit B). This Committee's inquiry is of deep and direct concern to the tobacco industry- msnufacturers, distributors, suppliers, workers and farmers, in fact millions of people in this country. In a larger sense, it should be of concern to the management, labor and agricultural segments of other industries. In the broadest sense, It is of legitimate concern to all Americans. For the proposed legislation raises a fundamental question: How protective should the government be of its citizens and how much responsibility should reside in the individual? The question assumes even larger magnitude as the definition of "environmental health factors" is broadened beyond the toxic substances to which mankind is exposed In the general environment or in the specific work environments, and is extended to the kind and amount of foods we eat, the beverages we drink, and the personal style of life we follow. If the Government's proper role with reference to legal products is to inform the people, to give them the facts, to see that advertising gives them the facts, and. then to leave the exercise of free choice to the individual, then there may be no place for government intervention and manipulation to restrict such products. To give further meaning and support to this proposition, last June, Dr. Theodore 3ecre:ary cor ,eaJ.th, said that in his judgment, "we will achieve the greatest good not through absolute bans, but by giving our people the knowledge necessary to make rational and informed personal decisions." TIMN 450343 I I

298 t 86. Meissner, W.A., Sommers, S.C. and Sherman, G.: Endometrial hyperplasia, endometrial carcinoma and endo metr iosis produced experimentally by estrogen. Cancer, 10: 500-509, 1957. 87. Smmners, S.C. and Meissner, W.A.: Host relationships in experimental endometrial carcinoma. Cancer, 10: 510-515, 1957. 88. Sommers, S.C. and Meissner, W.A.: Endocrine abnormalities accompanying human endometrial cancer. Cancer, 10: 516-52 1, 1957. 89. Soutter, L., Sommers, S.C., Relman, A.S. and Emerson, C.P.: Problems in the surgical management of thymic tumors. Ann. Surg. 146: 424- 438, 1957, 90. Barr, R.W. and Sommers, S.C.: Endocrine abnormalities accompanying hepatic cirrhosis and hepatoma. J. Clin. Endocrinol, 17: 1017-1029, 1957. 91. Ullrick, W.C., Lentini, E.A. and Sommers, S.C.: Excitability and contractility of postmortem human heart muscle. Lab. Invest., 6: 528-535, 1957. 92. Sommers, S.C.: Host factors in fatal human lung cancer. Arch. Path., 65: 104-111, 1958. 93. Merriam, J.C., Sommers, S.C. and Smithwick, R.H.: Clinicopathologic correlations of renal biopsies in hypertension with pyelonephritis. Circulation, 17: 243-248, 1958. 94. Koefer, E.D., Swinton, N.W., Atkinson, R.P. and Sommers, S.C.: Panel discussion on chronic ulcerative colitis. Am. J. Gastroenterol., 29: 359-373, 1958. 95. Azar, H.A. and Sommers, S.C.: Retroperitoneal ectopic seminal 96. vesicle communicating with a contralateral solitary kidney. Report of a case. J. Urol., 79: 94-98, 1958. Sommers, S.C., Relman, A.S. and Smithwick, R.H.: Histologic studies of kidney biopsy specimens from patients with hypertension. Am. J. Path., 34: 685-715, 1958. 97. Sommers, S.C.: Constitutional aspects of gastric carcinoma. Arch. Path., 66: 487-493, 1958. 98. Ullrick, W.C., Lentini, E.A. and Sommers, S.C.: Oxyge n consumption of postmo rtem h uman hea rt mus cle. Proc. Soc. Exper. B iol. & Med., 99: e:46-i:4,', ..;/:8. 99. Shamma, A.H., Goddard, J.W. and Sommers, S.C.: A study of the adrenal status in hypertension. J. Chronic Dis., 8: 587-595, 1958. 299 100. Silva,%F, and Sommers, S,C,: Renal biopsy changes with pheochromocytoma. Am.J. Med. Sci., 236:700-704, 1958. 101. Keffler, R., Lenson, N, and Sommers, S.C.: Carcinama arising in minor salivary gland ducts of the lower lip. Am. J, Surg., 97: 79-82, 1959. 102. Strong, S,M, and Sommers, S.C.: Bronchbgenic carcinoma. Arch. Otolaryng. 68: 764-769, 1958. 103. Wilkins, R,W, and Sommers, S.C.: Clinicopathologic Conference. Enlargement of the heart,-cardiac failure and loose, dry scaly skin. Am. J, Clin. Path., 31: 66-72, 1959. 104. Sommers, S.C.: Pituitary cell relations to body states. Lab. Invest., 8: 588-621, 1959. 105. Coffman, J.D, and Sommers, S,C,d Familial pseudoxanthoma elasticum and valvular heart disease. Circulation, 19:242-250, 1959. 106. Sommers, S.C.: Pathology of the Kidney and adrenal gland in relationship to hypertension. In: "Hypertension" W,B. Saunders Co., 23, 1950. 107. Andriteakia, G,D, and Sommers, S,C,t Criteria of thymic cancer and clinical correlations of thymic tumors. J. Thoracic Surg., 37: 273-290, 1959. 108. Androutsopoulos, N.A, and Sommers, S.C.: Postmenopausal endometriosis. Obstet. & Gynec., 14: 245-248, 1959. 109. Ullrick, W,C., Lentini, E,A, and Sommers, S.C.: Summation and tetanas in postmortem human heart muscle. J. Appl. Phygiol., 14: 567-560, 1959. 110. Hollander, A, and Sommers, S.C.: Current case of lepromatous leprosy, acid-fast bacilli in epidermis. Conn. Med., 23: 650-654, 1959. 111. Thayer, C,L, and Sommers, S.C.: Hoet factors in carcinoma of the uterine cervix. Am. J, Obstet. & G ynec., 78: 386-392, 1959. 112. Bloodworth, J,M,B. and Sommers, S.C.: "Cirrhotic glomerulosclerosis", A renal lesion associated with helatic cirrhosis. Lab. Invest., 8:962- 978, 1959. 113. Fuller, C,N, and Sommers, S,C,: The thyroid status in relation to arteriosclerotic disease. B,Mq, 10: 1-2, 1959. TIMN 450333

312 Enclosure #3 Continued. 23. R.J. Hickey, R.C. Clelland, D.E. Boyce and E.J. Bowers. Lancet, 1975, 1, 40-41, (Letter to Editor). 24. T.D. Sterling. Amer. J. Publ. Hlth., 1976, 66, 161. (cf also I.T.T. Higgins, ibid, 159-161; I.D.J. Bross, ibid, 161 vs. Sterling). 25. W.C. Hinds and M.W. First. N. Eng. J. Med., 1975, 292, 844-845. 26. G.L. Huber. N. Eng. J. Med., 1975, 293, 48-49, (Letter to Editor), (also letters by N.T. Iverson and G.R. Williams, A.K. Friemanis, S. Foster, W.C. Hinds and M.W. First). 27. R. Hoover, T.J. Mason, F.W. McKay and J.F. Fraumeni, Jr. Science, 1975, 1005-1007. 28. R. Hoover and J.F. Fraumeni, Jr., Environ. Res., 1975, 9, 196-207. 29. Z. Hrubec, R. Cederlof and L. Friberg. Am. J. Epidermiol., 1976, 103, 16-29. 30. 0. Hrustic and M. Saric. Arhiv. Za Higijenu Rada I Tok., 1975, 26, 15-22. 31. G.L. Huber. N. Eng. J. Med., 1975, 292, 858-859. 32. F.J. Ingelfinger. N. Eng. J. Med., 1975, 293, 1319-1320. 33. C.D. Jenkins, G. Thomas, d. Olewine, S.J. Zyzanski, M.T. Simpson and C.G. Hames. J. Human Stress, 1975, 1, 34-46. 34. F. Jimenez, P. Teng and M.B. Rosenblatt. Bull. N.Y. Acad. Med., 1975, 51, 432-438. 35. H.D. Kerr, T.J. Kulle, M.L. Mcllhany and P. Swidersky. Am. Rev. Resp. Dis., 1975, 3, 763-773. 36. W. Kloeterkoffer and E. Gono. Arbeitsmed., Sozialmed., Praventivmed., 1975, 12, 233. 37. B. Lavergne, L. Frappier-Davignon and J. St-Pierre. Union Medicale du Canada, 1975, 104, 1397-1406. 38. B. Lebovits, E. Lichter and V.K. Moses. Soc. Sci. & Med., 1975, 9, 207-219. 39. M.D. Lebowitz and B. Burrows. Chest, 1976, 69, 48-50. 40. V.L. Levendel, A. Mezei, E. Erdely and G. Litvai. Zeitschrift fuer Psycho- soma'.. .!.f!t.. ~Y .[t;{.IL:., .../'_, , .,. .... 41. U. Lundberg, T. Theorell and E. Lind. J. Psychosomat. Res., 1975, 19, 27-32. 42. T.F. Mancuso and C.K. Redmond. Am. Heart J., 1975, 90, 380-388. 43. R.R. Martin, D. Lindsay, P. Despas, D. Bruce, M. Lerouz, N.R. Anthonisen and P.T. Macklem. Am. Rev. Resp. Dis., 1975, 3, 119-125. 44. S.F. McCullagh and L.N. Balsam. Med. J. Aust., 1975, 2, 173-175. 313 Enclosure #3 Continued. 45. M.L. Mcllhany, J.W. Shaffer and E.A. Hines, Jr. The Johns Hopkins Hed. J., 1975, 136, 57-64. 46. H.J. Morowitz. Hosp. Pract., 1975, (August), pp.35 & 39. 47. R.S. Paffenbarger, Jr. and W.E. Hale. N. Eng. J. Med., 1975, 292, 545-550. 48. A.J. Palmer. Med. 3. Aust., 1975, 1,539-543. 49. E. Pesonen, R. Norio and S. Sarna. Circulation, 1975, 51, 218-225. 50. S. Punsar, 0. Erametsa, M.J. Karvonen, A. Ryhanen, P. Hilska and H. Vornamo. J. Chron. Dis., 1975., 28, 259-287. 51. G. Reckzeh, W. Dontenwill and F. Leuschner. Toxicol., 1975, 3, 289-295. 52. L.B. Reichman, B.M. Cooper, S. Blumenthal, G. Block, D. O'Hare, A.D. Chaves, M.H. Alderman, Q.B. Deming, S.J. Farber and G.E. Thomson, J. Chron. Dis., 1975, 28, 161-171. 53. R.H. Rosenman, R.J. Brand, C.D. Jenkins, M. Friedman, R. Straus and M. Wurm. JAMA, 1975, 233, 872-877. 54. H.G. Schrott, R.M. Lauer, W.E. Connor, K. Schreiber and W.R. Clarke. 1975, Supp. II to vols. 51 and 52, 43. 55. C.C. Seltzer. Am. Heart J., 1975, 90, 125-126. 56. C.C. Seltzer, Am. J. Med. Sci., 1975, 269, 309-315. 57. R.I. Sholtz, R.H. Rosenman and R.J. Brand. Am. J. Epidermiol., 1975, 102, 350-356. 58. V.K. Smith. J. Am. Stat. Assoc., 1975, 70, 341-343. 59. F.E. Speizer, (Am. Public Hlth. Assoc.), Nov. 16-20, 1975, Chicago. 447-A. 60. J. Stamler, P. Rhomberg, J.A. Schoenberger, R.B. Shekelle, A. Dyer, S. Shekelle, R. Stamler and J. Wannamaker. J. Chron. Dis., 1975, 28, 527-548. 61. M. Steinbach, P. Harnagea, M. Constantineanu, S. Theodorini, R. Cretescu, R. Voiosu, A. Suciu and H. Bujar. Rev. Roum. Med. - Med. Int., 1975, 13, 13-18. Atnn 1o'lS 65 010-OS'3 63. T.D. Sterling and D. Kobayashi. J. of Sex Res., 1975, 2, 201-217. 64. S.L. Syme, M.G. Marmot, A. Kagan, H. Kato and G. Rhoads. Am. J. Epidermiol., 1975, 102, 477-480. 65. C.B. Thomas, D.C. Ross and K.R. Duszynaki. The Johns Hopkins Med. J., 1975, 136, 193-208. 66. C. Velican and D. Velican. Rev. Roum. Med. - Med. Int., 1975, 13, 19-24. TIMN 450340

314 Enclosure #3 Continued. 67. 68. 69. 70. 71. J.A. Wagner, S.M. Horvath and T.E. Dahms. Fed. Proc., 1975, 34, 443. R,E, Waller and P.J. Lawther. Nature, 1976, 259, 559-560, and M.G. Marmot, S.M. Brown, S.T. Sacks and L.W. Kvok. pp.560-561. S,B, Webb. JAMA, 1975, 234, 380 (Letter to the Editor). and D.K. Craig. Am. Indust. Hyg. A.P. Wehner, R.H. Busch, R•J8011810, Assoc. J., 1975 (November), W. Weiss and K.R. Boucot. JAMA, 1975, 234, 1139-1142. TIMN 450341 315 Mr. KORNE(3AY. May I proceed, Senator? Senator KENNEDY. Yes. Mr. KORNEGAY. My name is Horace R. Kornegay. Since June 1970 I have served e,s president of the Tobacco Institute, an association of tobacco manufacturers in the United States. I appreciate your invitation, Mr. Chairman, to testify before this distinguished subcommittee at what you called an initial hearing to explore the possible relationship between smoking and disease. I thank you for this opportunity to express views on behalf of the Tobacco Institute in what you also said will be a series of hearings on "environmental health hazards." Congressional hearings can be very helpful. As the New York Times said in an editorial last week, there is a "need for accompanying all national health statistics with more illuminating commentary and ex- planation than are now provided." Hopefully, as a result of these hearings such "illuminating com- mentary and explanation" will be extended to the controversial and emotional subject of smoking and health. In February 1972 I had the honor of testifying before the Consumer Subcommittee of the Senate Committee on Commerce. At that time I expressed the tobacco industry's vital concern in det.ermining' whether cigarette smoking causes human disease, whether there is some ingre- dient as found in cigarette smoke that can be demonstrated to be responsible, and if so, what it is. At this time, the tobacco industry is still vitally concerned about these critical questions concerning smoking and health. For the past 20 years, the tobacco industry has supported independ- ent scientific research with completely nonrestrictive funding. The total has now reached $57 million, including 742 grants to scientists in 317 medical schools, hospitals and institutions. The industry has funded multimillion dollar projects at.Washington University in St. Louis, the Harvard Medical School, and the UCLA School of Medicine. I would like to submit for the record at this point a brief report on tobacco industry research on smoking and health (exhibit A). Mr. Chairman, I have others, some-other exhibits, and I would like tn oev ,~n,. i...,.,.. Senator KENNEDY. `Ve will have them included. If they are lengthy, we will work that out. But we will include them. Mr. KORNEGAY. Yes. I do not think you will find them too lengthy, hopefully not. In addition to its research commitment., the conduct of the tobacco industry in relation to the marketing of tobacco products has been both responsive and responsible to an extent which might be considered un- paralleled. I would like to submit for the record a brief chronology of some of our initiatives toward self-regulation and other voluntary actions (exhibit B). This committee's inquiry is of deep and direct, concern to the tobacco industry-manufacturers, distributors, suppliers, workers and farm- ers, in fact, millions of people in this country. In a larger sense, it should be of concern to the management, labor, and agricultural seg-

I l 338 Nor have there been any developments since 1964 to per- mit the conclusion that there is a 20-year latent period for the development of lung cancer. To the contrary, there is wide disagreement among prominent cancer researchers as to how long it takes for lung cancer to develop. Ac- cording to Hammond, it takes 10 to 20 years, while Kreyberg's position is that it takes 30 to 50 years. Doll's view covers both extremes and then some. He indicates that "In fact, the period must vary widely in individuals over a range of at least 5 to 80 years, and a better estimate of the mean 'induc- tion period' under current conditions of mortality would probably be nearer 40 years than 20." Likewise, the Overview's treatment of carcino- genesis conflicts with the 1964 Report. That Report dis- cussed tobacco carcinogenesis at length and concluded that the "carcinogenicity of tobacco smoke tars present a puz- zling anomaly." Elsewhere, the 1964 Report acknowledged the complex nature of carcinogenesis, stating "Carcinogenesis is a complex process. Many factors are involved. Some are related to the host, others to the agents. The host factors include genetic, strain, and organ differences in sensitivity to given agents; hormonal and other factors which modify sensitivity of cells; and nutritional state." The 1964 Report even admitted that "the amount of known carcinogens in cigarette smoke is too small to account for their carcinogenic activity" and labeled this area a"gi- gantic problem for exploration." I 339 The 1975 Report avoids this topic by noting that "a number of specific chemical compounds contained in cigarette smoke were established as potent carcinogens or co-carcinogens." Thus, the Report passes over the "gigantic area for exploration." Nowhere is the "puzzling anomaly" ever referred to, much less resolved. The lack of progress in this field, despite all of the research that has been done, is well known. Dr. Lijinsky of the Oak Ridge National Laboratories, a critic of tobacco smoking, told Congress in 1971 that "in spite of 20 year's work on tobacco smoking we cannot identify or nobody has been able to identify a carcinogen to.explain the incidence of lung cancer in man." He further stated that, while smoke is carcinogenic in test animals, it is not sufficiently carcinogenic by itself to account for the high incidence of lung cancer in humans. This matter, however, is simply ignored by the 1975 Report. Another example of this Report's conflict with past reports is its treatment of the study by Harris. Here the 1975 Report analyzes the purported increase of lung cancer in women in terms of histological types. Thus, it simply ignores the conclusion of the 1964 Report that the use of histological types "as an index of the magni- tude of increase in lung cancer is of limited value." TIMN 450353 .1

( 336 11. 337 1975 Health Consequences of Smoking The 1975 Report on the Health Consequences of Smoking has been written without regard for contradictory material in the scientific literature and even without regard for what has been stated in past reports or supple- ments on this topic. This is particularly true in the introductory section entitled "Overview - The Health Consequences of Smoking." Further, the Overview makes statements which are contradicted by the studies reported EXHIBIT C I in the various chapters on disease.. Moreover, the 1975 Report is highly selective REVIEW OF THE 1975 in its review of the scientific literature, emphasizing HEALTH CONSEQUENCES OF SMOKING only those studies which seemingly support its position. F I F On its face, the 1975 Report's bibliography indicates that available articles have not been discussed or men- tioned. As an example of the 1975 Report's disregard for scientific fact, as well as for what has been stated in previous reports, it asserts that there is a "long latent period (about 20 years)" for the development of lung cancer. In contrast, the 1964 Report of the Advisory Committee to the Surgeon General ("1964 Report") could not determine the.latent period for chronic diseases such as lung cancer on the basis of the then existing data. TIMN 450352

340 The 1964 Report reached this conclusion pri- marily because of the study by Herman, et al., also ignored by the 1975 Report. Dr. Herman and her co-workers examined the histology of lung tumors at Los Angeles County General Hospital. They reported that, while the incidence of lung cancer had increased over time, the ratio between Group I and Group II tumors had not changed perceptibly. A later study by Dr. Herman of lung cancer cases at the Francis Delafield Hospital in New York City resulted in similar findings. Since then her results have been confirmed by the study of Berge, et al. Yet, these studies are not mentioned either in the Overview or in the Cancer Chapter. The biased nature of the 1975 Report is clearly shown by its analysis of the Harris study. The Report claims that "adenocarcinoma is by far the most common type of lung cancer in nonsmokers while squamous cell is by far the most common when smokers are included." However, the 1975 Report ignores the finding by Harris that among all women lung cancer patients - smokers, as well as non-smokers - the most common histological type (23%) was bronchiolar. This type has not even been statistically associated with smoking. These findings by Harris are supported by the recently reported study from the Lahey Clinic in Boston 341 of lung cancer in women between 1957 and 1975. There the researchers found a marked increase in the total num- ber of women with lung cancer, but they did not find a significant change in the proportion of Group I to Group II tumors during this period. However, these findings are not unexpected in view of the 1964 Report's indication that several studies had found that "adenocarcinoma is also contributing to the increment of lung cancer in women." The Overview states that a causal relationship exists between smoking and "excess death" and bases this conclusion solely upon statistical or epidemiological studies. Thus, the Overview ignores the caveat of the 1964 Report that "statistical methods cannot establish proof of a causal relationship in an association." The Overview also ignores the observation in the 1964 Report that epidemiological studies must be "coupled with the other data" in order to provide the basis for causal con- clusions. The Overview concludes that smoking is the cause of excess death, even though the 1964 Report could not reach this conclusion arrive at this conclusion on the same data. In order to on causation, the Overview ap- plies certain "criteria" of .iudgment - which criteria were used by the 1964 Report in its analysis of lung cancer among smokers - to statistical studies, instead of TIMN 450354

3;30 Tobacco Industry Research on Smoking and Health For the past two decades, hundreds of scientists have per- formed thousands of experiments and written millions of words in a dedicated effort to explore the question of smoking and health. Result: So far, in spite of this massive effort, there are eminent scientists who question whether any causal relation- ship has been proved between cigarette smoking and human disease--including lung cancer, coronary heart disease, or emphysema. They believe that years more of exhaustive in- vestigation will be required to clear up what is indeed now a muddy picture. What has been learned is this: Establishing cause-and-effect relationships, which have been claimed to exist by goverr,ment agencie5 and other groups, is much more complex than originally thought. In fact, even those who claim a cause-and-effect re- lationship has been proved admit that no particular ingredient, as it occurs in cigarette smoke, has been demonstrated as the cause of any particular disease. Who sponsored the research There are those who believe that voluntary health associations have provided the money for most of this research. Others think it was strictly a project of the various U.S. Government departments. It is true that both have been--and continue to be--active in this field. But, a major portion of this scientific inquiry has been financed by the people who know the most about ciga- rettes and have a great desire to learn the truth...the tobacco industry. And the industry has committed itself to this task in the most objective and scientific way possible. A $57,000,000 2Eogram In the interest of absolute objectivity, the tobacco industry has supported totally independent research efforts with com- pletely non-restrictive funding. In 1954, the industry established what is now known as CTR, the Council for Tobacco Research-USA, to provide financial support for research by independent scientists into all phases of tobacco 331 -2- use and health. Completely autonomous, CTR's research activity is directed by a board of ten scientists and physicians who re- tain their affiliations with their respective universities and institutions. This board has full authority and responsibility for policy, development and direction of the research effort. Each researcher receiving a grant has complete freedom to pub- lish the results of his work, whatever the results may be. As of this year, CTR has made grants totaling more than 35 millicn dollars. In 1964, the tobacco industry made a commitment for additional independent research that amounted, during a ten-year program, to 15 million dollars. This commitment was made to AMA-ERF, the Education and Research Foundation, an arm of the American Medical Association. Under this program the ERF, like the CTR, made grants for scientific research with complete freedom and autonomy. What they did As of January 1976, the Council for Tobacco Research alone has awarded 520 separate grants to scientists in 230 medical schools, hospitals and institutions in this country and five other coun- tries. During the ten years of the Education and Research Foundation program 222 grants were awarded to scientists in 87 medical and research institutions. 4 While the projects of these researchers may be considered rela- tively narrow in individual scope, the industry has not over- looked its research responsibilities in broader areas. In 1970, Washington University in St. Louis announced two million dollars in tobacco industry funding for study of immunologic factors in cancer. The grant has since,been increased to 2.8 million dol- lars. In 1972, Harvard Medical School announced receipt of a 2.8-million-dollar tobacco industry grant for a five-year investi- gation into pulmonary and cardiovascular diseases. And in 1974 _ „ . the UCLA School of Medicine announced a t_7-m4,i,~4-.- ~ - .-°., .. ~..,....,:.,. , :Ln- u~~..._G'.-,a,.,. er., :cive- ear mechanisms and early detectiongand treatmentcof cancer,defense The combined commitment by the tobacco industry for all these projects amounts to more than 57 million dollars. In many years, the tobacco industry's commitment in this area has exceeded that of any government department...and has come to millions more than the research expenditure on smoking 2nd health reported by all the voluntary health associations combined. TIMN 450349

324 If we look at research produced by government researchers who are free of this possible conflict of interest we find a different picture. I would commend a copy of the recently published H.E.W. Atlas of Cancer Mortality for U.S. Counties to every member of the Committee. Based on a massive study by the National Cancer Institute, its effect on some preconceived ideas concerning associations between various factors and cancer mortality has been unprecedented. With regard to lung cancer, the Atlas states: "The maps for lung cancer indicate that excessive mortality is not limited to highly populated urban areas where cigarette smoking and air pollution are most prominent. In fact, the rates are highest along the coast of the Gulf of Mexico, particularly in Louisiana...Further studies are needed to identify the environ- mental and demographic factors contributing to the increased risk of lung cancer in these predominantly rural and port areas." Two authors of the cancer Atlas also announced in Lancet, a prestigious English medical journal, significantly increased lung cancer mortality in counties where certain industries were located, compared to the rest of the United States. In fact, the three counties with the highest proportion of their population employed in these industries had "an average increased lung-cancer mortality of 92% in males and 36% in females." The researchers specifically discounted the role of workers' smoking habits. Similarly, the Washington Post of Sunday, February 15, reports that men living near a particular plant in Baltimore had a lung cancer rate four times that of a similar group of men living in a non-industrial area of the city. Similar reports come out of Texas. Eleanor Macdonald, an epidemiologist, commented at the Forum on Science and Society held in 1974, that based on data which she had developed, there was a great difference in lung cancer mortality among various census tracts in Houston. "The regions with low rates are out of the path of the usual q, iC~ iC1 curry,ing po:.:.u-:iion ancc save .la.l: Le or no i',ndustry within their borders. Atmospheric pollution or lack of it seems to be the major difference between regions of high and regions of low lung cancer mortality." 325 An article in the September 1975 issue of Nature, a respected scientific journal, reported on the effect on mortality of the 1974 fuel crisis, which the authors said provided a natural experiment. In San Francisco and Alameda Counties, California, they reported "dramatic decreases" in death rates from cardiovascular disease, asthma, chronic bronchitis and emphysema, with the greatest drop of 38 percent in chronic lung disease, all following a 9.5 percent reduction in gasoline sales. Recently the public was reminded by the London Times in Great Britain and by Medical World News in this country, that the theory connecting lung cancer and smok ing continues to evoke considerable scientific discussion. The views of Philip Burch, Professor in the department of Medical Physics at the University of Leeds, England, have been presented in a series of letters and articles in Lancet, New Scientist, and the Journal of the Society of Occupational Medicine as well as the lay press. A nonsmoker who once believed that cigarette smoking causes lung cancer, Professor Burch found after his own investigation, that such a conclusion is simply "not warranted by the evidence." For this reason Professor Burch has stated that he and some of his colleagues are - and I quote- "disturbed that Government policy and so much propaganda should rest on such weak and unscientific foundations." A detailed presentation of Professor Burch's views on smoking and health appears in Chapter 10 of his new book, Biology of Cancer: A New A roach which was published in January of this year. The constitutional hypothesis stated by Burch was first advanced by the internationally-renowned biostatistician Sir Ronald Fisher. Fisher predicted the smoking- lung cancer hypothesis might prove to be a "catastrophic and conspicuous howler," a view Professor Burch endorses. TIMN 450346

I 224 Tha~n Are Larga Differanas in the Geographial Dis'tribution of Both Smoking and Lung Cancer Patterns That Are Completely Unrelated to Each Other For instance, the highest known lung cancer rates occur In England, Austria, Belgium, and Finland. The United St.tes, Canada, Australla, and New Zealand report a mach smaller rate of lung cancer deaths. The lowest lung cancer rates are In such countries as Norway and Italy.e1'41 Yet, per capita smoking rates are, by far, the greatest in Canada, the United States, and New Zealand, considerably lower in England, and lowest In Finland and AnStI1L4 J Lung Cancer Mortality for Migrant Populations F.Bs batwan the Rata in Country of Origin and N.w Host Country This observation has been establiahed predominantly for English immigranta to the U.S., C.nada, South Africa, Australia, and New Zealand. It haa also been observed for Jewish populations in Israel, the United States, and Canada FIGURE 3 Trends in lung cancer mortality, rreported by Doll for man In England and Waia, 1950 to 1968, by a9e: Adaptad from DoUls' Fi9ure 6. and for Italian immigrants to the United States.44-s t For an example of the consistency of the migration effects, see Tables 10 and 11. The observed changes in lung cancer rates of immigrants is of great importance, especially for the U.S., Australia, Canada, and Isnel. These are countries with extremely high consumption of cigarettes while England and Italy have a lower per capita consumption. The smoking rates and prevalence of lung cancers among hnmignnts, when compared to each other and to native- bom, often make up a puzzling mixture. For instance, some groups who are the lightest smokers may also report the largest death rate, and vice versa 53 One recent study by Mancuso may be of special relevance. He compared the lung cancer death rates of native Americans who were born and died in Ohio with those of native Americans who were born in a southem st.te and migrated to Ohio. While the death rates from lung cancer among native Ohio males were somewhat smaller than among U.S. males, the death rates among migrants from the South were considerably higher for white males and approximately double for black males born in the South when compared to black males born In Ohio. Mancuso pointed out that, on one hand, smoking was less frequent among southern males than among northemetss, espeeially for blacka, and on the other hand, that migrants, especially blacks, tended to be employed In the "dirtier" jobs, where they would tend to be exposed to high concentrations of irritants.sae,sab . The shift in lung cancer deaths from origin to host rates in the immigrating population suggests the importance of environmental factors in the etiology of this disease. Both Sterlings and Stockss4,ss have suggested that this factor might be the aolount of soot-earrying benzpyrene in the atmosphere. There Are Pronounced Occupational Differences in the Incidence of Lung Cancer The heaviest incidence is among steel, coke oven, and asbestos workers and most individuals who are exposed to dust or Irritating fumea.s4'sa"*3 Smoking is also very heavy in these groups. It is tantalizing to know what the lung cancer rates in the ACS or US. veteran studies would be if these occupational groups were eliminated from an analysis. There Are Large Numbers of Differences in Lung Cancer Rates for a Variety of Population Parameters •'Ihese differences are consistent and occur almost wherever comparisons are made. This is true especially for urban/rural differences 6 t•64-a ° The constant difference between men and women in the Incidence of lung cancer has persisted although the frequency of smoking among women has Increased more rapidly than among men. (For instance, in 1950 the male/female mortality ratio was 4.7 to 1, and in 1965 the ratio had increased to 6.1 to 1.' `' A sex differential persists also among nonsmokers.33 SMOKING AND LUNG CANCER 947 225 TABLE 10-As*arNdan Luna Camar Dath Ratea (19a2-196a) with ComperatMa Ra1.s for Enalad, WWas, roe Scrosland (19631' Ma1a Raves/100,000 of Popudation Far6as 40-49 Sf)-59 60-69 70-79 40-49 50 59 60-69 70-79 Country of Birth and Rasidenca Yaus Yeau Yean Years Yar. Ysars Yars Years Nativaborn Australiain 16 60 Enaiish and Wslsh-bom ummiarants 28 125 to Auatralia Nativ.born English and Welsh 38 • 173 Scotiborn immi{Pants to Aunralia 44 167 Natrva-bomScota 41 208 iS6 239 4 11 16 26 301 388 7 15 24 45 435 482 10 26 46 51 39~6 363 5 19 21 65 489 535 34 28 50 86 ' Source: C.tcCall and Stenhousa,'s Tabla 1. There Is a Constantly Changing Constellation of Factors Affecting the Lung Cancer Death Rate One example of such factors is furnished by the interrelated fate of all diseases. Decreases in some must be compensated by concurrent or subsequent increases in others, or vice versa, since the probability of death, unfortunately, remains unity under all conditions.B3•bs•s9 That a definite relationship exists between the decline in mortality due to respiratory diseases and an increase in lung cancer is only now beginning to be undetsstood.7o•91 It is also interesting to note that wherever attempts are made to simultaneously evaluate the effect of smoking and such other factors as levels of pollution or familial backgrounds, the co-variables have tended to account for much larger portions of the observed variance t11an has the smoking habit s4•7=•77 TABLE 11-Avupa Annual Adfuared Dalh Rata Due tu Lurr Cancer par 100,000 White Ohio Ma1as' Ara Death Rata (Ae*a 26-84 and Population Group Years 1947-1961) Nativeborn white males raidinq in Ohio 2095 Immiarants from all foreign countria Rasidin9 in Ohio 38.67 Residinp in Cuyahoga County 38.11 Cuyahoaa County raidents who immiprated from Enaland and Wala 31.76 Iu1y 18.61 Resident populations of England and Walq (1950) 55.48 Italy (1951) 16.28 ' Sowce: atancuso and Coultar,'s Table 4. How About the Observation That the Incidence of Lung Cancer Decrusa Rapidly for Those Who Stop Smoking? On close scrutiny, this observation ought to raise serious questions. Individuals who have been exposed to a known carcinogenic agent incur a risk in some relation to the amount of their exposure. Why should the probability of incurring a consequence associated with this risk diminish when an individual is removed from further exposure to a carcinogen? Although it is possible that cessation of smoking calis forth a unique and little understood repair process, a more likely explanation is that the decline In the incidence of lung cancer after'4emoval'• from the smoking habit Is yet another manifestation of self-selection.* It is not unlikely that many individuals cease smoking because they are concerned with their health and not necessarily because they are ill. This possibility has been advanced by Doll and Hill (p. 1408 In Reference 27). It is also known that a laroe eon,h.r ..f t,,,a;..a ..~I. ...r... ...._ * Removal from smoking habit may be of degree only, aa for individuals who had switched to filter or low tar cigarettes. 948 AJPH SEPTEMBER, 1876, Vo1.65, No.9 smoking are actually the light smokers.04 (To Increase the confusion on this Issue, doubt has lately been expressed by Doll that the incidence of lung cancer decreases for former smokers when compared to the Incidence of the disease in nonsmokers (pp. 152-153 In Reference 75). This conclu- sion is In line with a recent analysis by Seltzer06 of mortality data assembled by the Royal Commission." Seltzer points out that the apparent decline in mortality for men who stop smoking may be due to deletlon of some of the age groups and follow-up periods from the analysis.) How About the Dose-Response Curve That Is Often Eteport.d Which Relates the Mortality of Smokers to the Rate of Smoking? One problem with any dose-response curve is the reliability of the measurements used. Information obtained beset with extremely large errors.'e Differences In the Incidence of smoking reported In various studies Indicate that such errors exist and that they must be large. But these erron may have disproportionately large effects TIMN 450296

348 al. of rats exposed to carbon monoxide, found that the exposed rats had lower cholesterol and triglyceride levels than the unexposed animals. Most notably absent is reference to or discussion of the study by Fisher, et al. These researchers exposed rabbits on an atherogenic diet to cigarette smoke (which the Report claims is a source of carbon monoxide), but did not find 'any increase in atherosclerotic lesions in the exposed group. The 1975 Report states that the Coronary Drug Project found smoking to have an effect on mortality after myocardial infarction. The Report fails to mention that on univariate analysis smoking was ranked 16th in a list of 40 factors. And, more importantly, the 1975 Report omits the fact that, after multivariate analysis, smoking dropped out entirely as an independent risk factor. The Overview indicates that cigarette smoking acts synergistically with high blood pressure in the caus- ation of coronary heart disease. Yet, the Cardiovascular Disease Chapter acknowledges that smokers on the average have lower blood pressure than non-smokers, citing three that the cessation of smoking was followed by an increase in blood'Fressure and concluded therefrom that cigarette 349 smoking tends to inhibit blood pressure increases. Studies which report data contrary to the 1975 Report's position are criticized as unsound, while studies which support its theories about smoking are reported without editorial comment. This biased approach to the scientific literature is illustrated by the Report's attempt to explain away the Boston Collaborative Drug Study's finding of a correlation between heavy coffee drinking and myocardial infarction. In this case, the Report sug- gests that the correlation is specious and that smoking might be the compounding factor. However, the 1975 Re- port ignores a later Boston Collaborative Drug Study report - published in 1973 - which confirmed the positive as- sociation between heavy coffee drinking and myocardial infarction and found that this association could not be attributed to smoking. As to nicotine, the 1964 Report concluded that it does not present a significant health hazard to smokers. Now, after ten years of intensive research, there is no data which would warrant a change in that conclusion. Nevertheless, all of the subsequent PHS Reports and Supplements have sought - in speculative fashion and without demonstrating any mechanism - to implicate nic- otine as having some role in various cardiovascular diseases. The 1975 Report is no exception. It discusses a single TIMN 450358 ;~,~.

COMM'ENTARY r- Deomh ,Wes Irem nsctipnoM nucplmvn ot,he rm:reta+y. {~- systtm (l[5 p60-1641 Non-while mcNs eqrd 25-74M nS 1940-1970 C 180 •5-e. ss-4. 234 ts•1~ TABLE 1-C4gaqtte Smoking Habits 4n US Woman'ktt~ PreseM Cg.wene 9moken Percenl Age-yny - : 1955 1954-19a5 4970 17-24I 28.4 33.9 '3g.2 25-44 32.5 43.6 38.6 45•64 18.9 31.9 32.8 65+ 3.4 9.5 10.9 17 yr. andover 23.6 33.2 . 30.9 TABLE 2-MOrtNky Rlak RaMoa for Lung Canar Aeoordkny to Smoking Habha Among Men and Wornan In Sare- derN January 1, 1963 to Daoamber 31, 1972 6mokkq Catsgory Msn Ylomws Non smokers 1.0 1.0 Cigarenes only: 1-7/day 2.3 1.8 8-15/day 8.8 11.3 18 end ovb4day 13.9 - Pipe (no dgarettes atter 1953) 7.1 - Doll (1966)r that lung cancer death rAtes tuud dectitted amdng physicians who had as a group reduced their smoking, but had increased in other men in England and Wales who.had increased their smoking. provides the nearest approach to an experimental test of the hypothesis in man is is either prao-~ " ticableorethicat. .- 9. The greater importance ojotherjactors. - Dr. Sterling would have us believe that some other occu- pational or environmental factor is really more important than smoking. The evidence from the British physicinns, not many of whom-t imagine moonlight in steel, coke oven, or asbestos work, is against this. Careful analysis has shown that environmental air (3ollutioti can only play a very'-minoi role compared with smoking in the etiology of this disease. It is good that generally held lleliefs should be rpap- praised; but it is important that such a reappraisal shall be ' complete and accurate. That ihere are factors other than smoking in the etiology of lung cancer has been well known for many years. Further investigation of them is clearly in- dicated. But that smoking is not the major factor in this dis- ....._...:u--_''_••-`---------' . .. -' - - .. ,...._-.. ... ,. --. ,.. ,: , .,uin.~:.:.oain:.r.e:er- ling presents. LuvT. T. Hrcctxs, MD Dr. Higgins is Professor. Dept. of Epidemiology. School of Public Health. University of Michigan. Ann Arbor, Mi 49104 REFERENCES I. Vital Slatictics of the U.S.. 1940 to 1967, Vol. 11 part A. U.S. De- AJPH Feluuary,1976, Vol. 66, No. 2 COi.M,tENTARY padment of H.E. W., U.S. Governenent Printing G'like, Washing- ton, D.C. 2. Todd, G. F. Statistics of Smoking in the United Kingdom. To- bacco Manufacturers Standing Committee. London. 1962. 3. Hirayama. T. Smoking in Relation to the Death Rates of 265.118 ' Men and Women in Japan. A Report of 5 Yean„Foltowup. PACsented at the American Cancer Socitty's Foarteptth Science •Writer's SeddnaF, Cleatwathr BeaeB, FMrida, Merch 27: 1972, upp. ,..,~. A, Cederiaf, R., L. Friberg„Z. Hr.u6eo, and U. Lorict~. The Rela. ~, tiansh6y of Smoking and Some Sociaul Co~ariabks tq 34qpaldty "' ~hod Mmhtdhy. A Ten Year FoBo" w-Up in a Ivr6babilny Sample ot A1.d00 SwwbHisbSubjects Age 19 to 69. flephrtnirint ot Elrvitods saenut Hygiene, Karolinska Institute; S•104-0I. Stockholm, Sac- i . .. a{:r~ta~tL'`7:-FF:5~1'hS't1~f~'f$.'¢Itl'J/h11:"i1'VJx°!±,{'?'r3tVo • ,.. -,,.rr :ir`..ar,Ww'rL•donv!.}rt(M . .. .. .... _., " :"CtimmoiCation fi6m-gr_oajs: M.= ,; s i,yt d~ nn ta?zdit;c (ad ~d iax:m ta -: - ~ . _ OneofthegfaphsshownbySterlingl(Figure3)as"con- nnrmtierariig~etibK~l~ ttadicting'• the cigarette•canceK Jtilatiot'ts}up really serves to nicotine actftel1y deereYSed In tbp q96ds. rw$I Gb~hd Bevd suo@est an interesting point aliout this relationship. What the more iiupaet in the yomtNlr:tlan fl1lP81d6y edity. Stl•4raTiltY graph shows is tha4,in England tl'le lung cancer mortality in thegrJ,ph really suggtktt i6thGt t1Nl9~Hhg 011 ai4d'itid011Me•Ilki- the older age group (such as age, 65-7A) continued to rise, eld'oart have sdnhe ilPtytact>eMa pUJotlWttibif MHH`Ytrfri:'#it7ji164 whik the rpottality in thq youngett age gpoup stayed level or fully; this thay, beaott~ tnat~e fi~tkt, th'U! 9: fi+d $te~19311 even declined between 1950 and 1968. Sterling comments death rates in the next few years. that "it would be unreasonable to observe a declipe in lung cattcec rates at atipte wbenthe eonsiMption qf ciganetles is :{R(Y{R(D I:,8RO3~'1rA!D :r. .. increasinq if it.were true that cit;arettes ate,a ma9or;iuse of ,~~, Dr. Bross ii i%i•ectq~ or bidfiU'lt'sci. R~wetl>~k~ llteoi6ttal ivrtgcancer•" ' ' ' Institute.ButTatd,NY1I267 However, a; I have previously pointed out tb Stetling, : 1, there was an important change in the eature of the cigarettes , .,, ~FE~~ i+ ihemselv,es.during the ppriod 1950 to 1968 shown on this I. Steding,T.D.Acrit'rea{rcasse#rmentoftheevFdoncebeari.gili '. graph. Filter cigarettes won a large share of the market, par- smoking as the cause ofkmgcancar, Am.J. PWbOclteahh.650), ticularly among the younger smokers. Although the total 939-953. Septemlxr 1975. I Additional Comments on the Critical A>SlsetSatiYent of th8 Ev(denCe ' Bearing on Smoking as the Cause of Lung Cancer". ;;ommunccon rom :_-r cer r ng Disagreements about scientific evidence usually are clar- ified by discussion. This exchange is no exception. As is common, it also may focus on heretofore neglected evi- dence. i The points raised by Bross. Higgins, and Weiss' touch on a number of major issues in my revicw. -. •See Weiss. W. Smoking and cancer: A rebuttal. AmJ. Public Heehh.65:954-955, 1975. • AIPH February, 1976. VW.66, No.2 5. Haenszel:W.iP• B. luvdaedJaRdl.f. Gc$frkcal:Waag•GaosetT Mortality as Relatell lo PAItidenceaadSmoking•Historles. White Males. J. Nat. Gruer Inst:21, 947-1b01. 1962. 6.' Haensul, W. end K. E. Teeubei. Lung-Cancer Moriallty a6 Re- lated to Residence and Sdroking Historier, White Females, 7. Doi1, R. C..mcer Braochklola:at Tatao ka Brmsches, 16. 3131, 1966;., . , r*tl btd~~"'nr 6:a:nr.i .. ..•f , 4. Heensiel; 'W fd..h- Sb6cJc~p1, . 7ob+(crn $tDMSkini Paitem5.fntfuetleiltei3'$Si(e~. r 1 nyS~WDI*ea•o,tirJq463. Fublfe Het~f 5drv~;"19BI~' ~ ' . 9..DfoomthlY'vV1a13tsdisip4Af10if -- sioal Datt~ypln thqaNada>tat.~6btgtar tfWilr3Whtks: Nr „ tiousl ~t~lp,r;,},lcarisA:r~'a10'.aU?!h972~,.N:2).~p,7~•'~1~axk ~ _ ::~.a xwirN ~~n91i.~ .q •tobslxa.qvtufr}us,ant:ru~:. '?xi'Mt ~ni~tss 4i an9 ' V• + ; ~ , i a ' t + ~ rr . , ' „ r }, ~5l 6F. a•h ,y a wlu , a r. gs [F ~'.i: 1a TIMN 450301 t„ompehnon jorCauses oj Lung L.ancer Higgins is correct. I did infer that "occupational and en- vironmental factors are more important than smoking.••" To Higgins, the evidence from the British physicians' study, "Qot many of whom (he imagines) moonlight in steel, coke oven, or asbestos work, is against this." But direct com- 'See Sterling, T. D. A critical reusessment of the ecidence bcaring on smoking as the cause of tung cancer. Am. J. Public Health. 65:939-953,1975. 161 !

, L 342 examining "the other data." The claimed statistical association between smoking and overall mortality is better explained by a constitutional or genetic hypothesis (i.e., the smoker and not the smoking is responsible for the association) than by the smoking-causation hypothesis. It is highly unlikely that the smoking of a very small number of cig- arettes (one to nine per day) could account for the reported large differences in life expectancy between such smokers and non-smokers. A genetic explanation for this statistical association is supported by twin studies which indicate that, in monozygotic twins with discordant smoking habits, smoking has no effect upon overall mortal- ity. The Overview also ignores other data which are inconsistent with its theory of smoking as a cause of "excess death," even though these data were mentioned in the 1964 Report. For example, in Doll and Hill's study of British doctors, current smokers of cigarettes and tobacco in other forms had lower mortality ratios than the ex-smokers. Likewise, in the five prospective studies plus tobacco in other forms had mortality ratios lower than persons who smoked cigarettes only. Moreover, in several of these studies, pipe and cigar smokers had lower 343 mortality ratios than'~the non-smokers. And, in the U. S. f Veterans study, persdns whb;^had smoked cigarettes for 25- 34 years had lower mortality ratios than persons smoking 15-24 years; while in the Canadibn Veterans study, smokers of 15-29 years had lower mortalitys.ratios than 'persons who had smoked for less than 15 years. A11 .trhese observa- tions are ignored by the 1975 Report. The Overview indicates that "the most important specific health consequence of cigarette smoking . . . is the development of premature coronary heart disease." It goes on to state that cigarette smoking is a"ma,ior inde- pendent" CHD risk factor and that it acts synergistically with other CHD risk factors. Thus, the Overview gives,the impression that smoking has been established as a cause of CHD. Of course, the causes and pathogenesis of car- diovascular disease remain unestablished. Scientists generally agree that cardiovascular disease is statistically associated with many factors other than smoking. Which, if any, play a causal role is as yet unclear. It may well be that some are not causes but instead reflect one or more underlying causes, such as a particular genetic type. The genetic hypothesis is.supported by the recent twin study of Friberg, et al., discussed in the Cardiovas- cular Disease Chapter but not mentioned in the Overview. TIMN 450355

268 Senator KENNEDY. Our next panel is Mr. IIorace Kol•negay, presi- dent., Tlle Tobacco Institute, acconlpanied hy I)1•. Sheldon C. Sommers and Dr. T'heodore 1). Sterling, director of computinl; science pro- graln, Simon Fraser University of Canada. There is a vote now. I can probabl,y go over this this afternoon. I want to give you a chauce and I will stay with you until the 5 minute bell rings and then come back at 2:15 or •2::30. If you have got a hard hitting comment or state.melrt you better niake it now because, with all. due respect to the press, the afternoon hearings are not as well attended. You can make whatever colulnent you want. to make now ancl then come back this afternoon. So if you would like, to use tlle. 5 or 6 minutes to make whatever comment you would and we will have you back at 2 :15. Mr. Konrri•x1Ar. I anl not a scientist, Mr. Chairman, so I am going to ask Dr. Sominers if he would go ahead with his statemcntt first. STATEMENT OF SHELDON C. SOMMERS, M.D., DIRECTOR, LABORA- TORIES AT THE LENOX HILL HOSPITAL, NEW YORK, AND PRO- FESSOR OF PATHOLOGY, COLLEGE OF PHYSICIANS AND SURGEONS, COLUMBIA UNIVERSITY OF NEW YORK, ACCOMPA- NIED BY HORACE R. KORNEGAY, PRESIDENT, THE TOBACCO IN= STITUTE, WASHINGTON, D.C., AND THEODORE D. STERLING, Ph.D., DIRECTOR, COMPUTER SCIENCE PROGRAM, SIMON FRASER UNIVERSITY, CANADA Dr. SCMMERB. Mr. Chairman and members of the committee. My purpose, in response to the invitation to present my personal view of the status of knowledge of smolcinl; and health Senator KENNEDY. You may summarize if you wish and then Dr. SoMaiFRS My statement is a summary. Senator KENNEDY. OK. Dr. SoMt,cFxs. My purpose, in response to the invitation to present my personal view of the status of knowledge of smoking and healtll, is to review the'newer scientific data. This material is not included in the quotations from the 1975 version of tlle USPIIS snoking and health report cited b,y Seuator IIaI•t, as justifying bill No. S. 2902. Cognizance of the present da,y knowledl;e by fairminded individuals casts grave doubt on the existence of fuiy such "overwhelming evi- dence" as claimed by the distinguished Senator. ~ ~. . . ._ _ ,.... ~. ~. ~ ~ .,i, 'r'g..ier ralR oir a.ear.i o smokers than nonsmokers, tlie results were obtained by statistical epidemiologic methods now recognized as erroneous and use of which is no longer regarded as justified. One to one comparisons of smokers and nonsmokers ignored many confounding variables. As I3erkson predicted the result proved to be a statistical artifact. This resulted from ignoring three serious sources of error : (1) Nonrandom comparisons, meaning thatt smokers' and non- smokers are not. random subsets of the population being tested. Snlok- ers choose to smoke. and others choose not. to smoke, and both t;roul>s are self-selected, anparently by complex processes not presently under- stood. The crucial error is tlle use of statistical methods to test non- random groups, designed for and applicable only to comparing 269 random groups. Rolling the loaded dice statistically gives an invalid answer. (2) I)ependence on limited statistical tests for proof. When fiose and Bell wrote their lnouol;rallh oil preclivting lonl;evity, they tested factors that mightt be a55ociatecl with early death among a group of Boston I1'orld 11'ar I I veterans, followed carefully for 30 years. A one- to-one colnpal•ison of cigarette smokers alld nollsnlokei:s gave smoking t}le llunlller one 1>lace as a predictor, like ill lu;uly other studies. IIow- ever, when multiple factors were inclndecl statistically cigarette snloking dropped to somewhere beyond the :3nt11 most sil;nitic•alit. predictor of earl•y death. llissatisfaction with job lmc•alue the nunll,er one predictor. (3) Secularity, nleauinr;• the c•hant;e ill habit p;ltterns of the Ilol,u- latioll from about 1!)1U to 1960, wwith increased proportions of ette '4mokel;s in each decade. A rnocle.l llopulation (not a real polnila- tion) with such c•hanges over equal tiuie will show a statistie,ill,y sil;nllic•ant, increase ill total deatll rate ;is a luinority cllault;es towurci •i luajority. ''his secularity factor or c•haull;e in populatiou Incttc~rus ~has no health iluplic•aticln. I+'or cx:uulllc, in the ori,rin;l) Surheon G'reneral's report a table showed pipe siuol:ers to have a lower clcatll rate than nonsnlokel:5. While encouragin;,• a belief that pipe sinokwrs were the sturdiest hwuans, a better exlllanation would be the secularit.y etl'eet. There were fewer pipe sulokwr5 in each decaclc, the c•ollvel:5e of cigarette smokers. These data:u•e published and available for all to reud. Why have the proposers of the bill not hearcl of thenl? It is because the aliunal supplements to the 51ugeon Gerlcral'S report on snolciu" llnd health are limited reviews 1u1d interpretations of the. nledical ancl 5rientilic• literature, from which ve screened out articles that do not ;c~rec• N~~ith, call into question, or destrcl.y :u•guulents :uld conclusions sallportive of the official Govermnent position. As au exalnhle, in a presentation ln•eparecl for hearinl;s on a pro- posal by Senator Moss of ITtah to liullt. by law tlle alllollnts of 111(•otinc and condensate, so called tar, in cigarettes, I poiuted out in 1972 thatt approximately 1,790 articles published since 1960 were not cited. Lists of thesc: «•ere suhplied. On occasion, public•ations not snpportinp,• the official position have been suppl•essed. The el/ideluiolo;~ic llrobleuis, shorh•omiul;s:nld errors were aired at-a panel meeting at, tlle AAAS in 1971, so the above is not secret. infol•luatlon. Ole regrets thatt the proposers of the bill have not beell illacle. SI.R•AI•e. of tlin. -rinng clnfPr•tc n}i~n}ncrynn,nn }iipic onr~ incompleteness of the inforulation on which they appear to base the current. proposed bill. Now, as to lungr caneer, tliere is a statistical association I/etweerl cigarette snlolcint; 4uld l1111f,r cancer. l3ut at present. the natlll•e of the association or .~•hether it. is causal are not. kno~~•n. Thc test of thc original s111•t;POn Gellel•al's report deals with the. difficulties of assitn- ing causality, but the suulmary and c•onclusions brush thesc sl5ide, ancl •ls.5i~n a c~ausality not denlonstrably evident in thc+ text. It is witiQlv known that a statistical assoc•iation is not by itself 11rooF of c•ausation. A statistical assoc•iatloll lllay I , loint to expc1riulVnts tllat Will help to deterlniue whether there iti cauye involved. Animal experiments to lny knon•led,Ye havr not surc•eedel ill tli0 proclnetion of so-called hunlan type 111119 c•anCers in a signifie:ult Iler- centage of any speeies tested. TIMN 450318 v

344 There the researchers found an excess of CHD mortality among dizygotic twins with discordant smoking habits, but no similar excess in the monozygotic twins. They reported their data as supporting the theory that smoking does not cause CHD but rather that both smoking and CHD are con- stitutionally determined. Also supportive of the constitutional or genetic hypothesis are the studies indicating that cessation of smoking does not result in a decreased risk for cardio- vascular disease among ex-smokers. For example, in Doll and Hill's study of British doctors, the incidence of CHD among ex-smokers did not decrease. More recently, Dr. Carl Seltzer of the Harvard School of Public Health found that in several other prospective studies (i.e., Hammond, Kahn - Dorn and Framingham) the cessation of smoking among males over 65 did not result in a decreased risk for cardiovascular disease. And, in women over 65, the risk of cardiovascular disease increased upon their cessation of smoking. These data, inconsistent with the smoking- causation hypothesis, are ignored in the 1975 Report. The Overview states that the cessation of smok- ing results in a rapid decline of carbon monoxide in the ."~ .. Disease Chapter, the Report characterizes carbon monoxide as a "dangerous gas," noting that the amount of carbon 345 monoxide in the blood is related to cigarette smoking. Nowhere does the 1975 Report mention the facts necessary to put this observation in its proper perspective: (i) Carbon monoxide is a natural body constituent, created by metabolism, so that with- out any exposure at all to external carbon monoxide in air, the blood contains from 0.2% to 1.0% carboxyhemoglobin (the combination formed by this gas with the red blood pigment). (ii) It has never been shown that the re- ported small increases in COHb levels in smokers are harmful to health. [And, of course, smoking is only an intermittent activity, so that these levels are reduced when not smoking.] There are many other distortions in the'1975 Report's treat- ment of carbon monoxide: (i) The Cardiovascular Disease Chapter claims that the carboxyhemoglobin levels of smokers vary from 2% to 15% depending upon the amount smoked, etc. However, the data then referred to demonstrate that the carboxyhemoglobin levels of smokers rarely reach 10%. In fact, the 1975 Report notes that the carboxvhemoglobin levels of smoking workers in high exposure occupations (e.g., London taxi drivers and service station operators) reached only TIAIN 450356 RLl,

326 Thus, based upon the opinion of these scientists it is not "clear" that smoking e,uses disease. What is clear is that a number of respected scientists continue to believe thet the preoccupation with cigarette smoking as "one of the principal contributors" to the ineidenee of certain diseases may be ill-founded and dangerous-ill-founded because the acientific evidence on many critical points is conflicting, and dangerous because attention has been diverted from such suspected hazards as occupational exposure, environmental pollution, diet, heredity, life-style and the like. As with the presently proposed legislation, much of the controversy surrounding smoking and health has centered on "tar" and nicotine. Despite much repetition of the claim that "tar" and nicotine (or any other agent) in cigarettes are harmful to smokers, there is little scientific evidence to support such a position. A technical paper discussing the pertinent scientific literature is provided for the record (Exhibit D). Government interest in "tar" and nicotine dates back to the 1950s. A detailed chronicle of this interest is attached (Exhibit E). Most notable of the recent Government actions concerning "tar" and nicotine were the 1972 Senate Commerce Subcommittee Hearings. Let me summarize some points that are as cogent today as they were when I made them at those Senate Hearings. (1) Information concerning "tar" and nicotine content is available to every smoker from a variety of sources including cigarette advertising and periodic reports by the FTC. (2) A wide range of tobacco products with varying levels of "tar" and nicotine is available to consumers. (3) Neither "tar", nicotine nor any other ingredlient or nngrec;ieni:s concentrations as found in cigarette smoke, has been established as causing disease in humans. 1 (4) No one has established that any particular level of "tar" and nicotine is significant. 327 (5) Reduction of nicotine content may cause an increase in smoking. (6) Confronted with a dramatic increase In the price of cigarettes, the individual may adjust his "tar" and nicotine intake by smoking more cigarettes, by smoking them down to a shorter length, by puffing more frequently and by inhaling more deeply. Aside from the lack of scientific basis for the action called for in S2902, other problems and questions are apparent on examination of this measure. It imposes upon only one segment of our society the burden of the biomedical research and health education costs necessary to remedy all the diseases which afflict all segments of our society, smokers and nonsmokers. It also imposes on only one segment of our society the cost of development, improvement and utilization of the health care delivery system-all the defects of which can hardly be the responsibility of this one segment of society. The record should show that 60 million consumers of tobacco products already pay about $6 billion more a year in taxes than other citizens. This bill would increase that tax burden by an additional $9 billion a year, to a total of $15 billion a year. Why should 60 million consumers of a legal product bear this burden? In conclusion, it is obvious that many scientific as well as practical problems and questions remain unanswered in this continuing controversy. In the considered view of the tobacco industry S2902 does little to resolve the problems or answer the questions. It would in its single-minded focus on tobacco, serve to deter and delay, rather than to encourage and enhance, the search for scientific truth into the causation of disease. Louis Pasteur put his finger on the problem almost a century ago when he said, "All thinos are hidden. obscure and debatable if the cause of the phenomena be unknown but everything is clear if this cause be known." TIMN 450347

346 10.8%. (ii) The 1975 Report also notes that New York City tunnel workers who smoke have higher carboxyhemoglobin levels (5.01x)than the non- smokers (2.93%). It fails to note, however, that several studies of tunnel workers and factory workers exposed for many years (10-18) in their work to high carbon monoxide levels, have not shown any earlier or more substantial circulatory abnormalities attributable to atherosclerosis than the general population. (iii) The 1975 Report notes that patients suffering angina pectoris have a decrease in the mean duration of exercise before the onset of pain when they are exposed to pure carbon monoxide. The 1975 Report ignores the fact that many studies (including the Bengtsson study cited in the Car- diovascular Disease Chapter) indicate angina pectoris not to be statistically correlated with smoking. The 1975 Report also ignores the fact that CO, as found in smoke, is reported to have different biological consequences from similar amounts of CO from other sources. Aronow, et al. found no changes in left ventricular contractility 347 (dp/dt) or in cardiac index following smoking but did note changes in these parameters after the inhalation of "pure" CO. While the reason for these findings is as yet unknown, Aronow suggests that it might be due.to "nicotine, which antagonizes the negative inotropic effect of carbon monoxide." In any event, whatever is the reason, the fact remains that the 1975 Report has chosen to bury this important observation. (iv) The human studies have failed to impli- cate low levels of CO in the causation of cardio- vascular disease. Possibly for this reason the Report stresses the studies by Astrup and Kjeldsen. These researchers exposed 'rabbits on an atherogenic diet to various levels of carbon monoxide. Ac- cording to the Report, they found that the exposed rabbits had a higher cholesterol content than the nonexposed group. The exposed rabbits were also reported to have arterial changes "indistinguish- able from early atherosclerosis." But the Report fails to discuss, or even mention, the numerous studies :Ln o't.zer an:.ma:. moc,e:.., (monkeys, dogs, etc.), which have not found in- creased arterial changes as a result of carbon monoxide exposure. One recent study by Finelli, .et TITVIN 450357

350 study [Hill and Wynder], which reports that nicotine is related to increased levels of serum epinephrine and corticoids, and later speculates that increased epinephrine levels might be involved in thrombogenesis. But this has not been shown and the fact remains that, even if serum epinephrine and corticoid levels are increased as a result of nicotine exposure, such increases have never been shown to cause disease in humans. As to the finding in the Levine study that smok- ing a single cigarette increased the platelet response to a standard aggregating stimulus, several studies have shown that smoking does not affect blood coaguability or plate- let adhesiveness. (Jenkins & Rosenman, et al.) While the Cardiovascular Disease Chapter makes a passing reference to "psychological Type A behavior" as a risk factor for coronary heart disease, there is no mention of the recently published work of Jenkins & Rosen- man on this topic. They found that a person's personality type - particularly Type A as opposed to Type B - is the most important determinant in whether or not a person develops coronary heart disease. For example, one study by these authors found that the coronary heart disease rates in heavy smokers of personality Type B were similar to or lower than those of the non-smokers and ex-smokers of personality Type A. 351 The Cardiovascular Disease Chapter notes-a statistical association in the Bengtsson study between smoking and myocardial infarction in women but omits reference to the author§ statement that risk factors are Mnot necessarily" causes of disease. It also fails to note the finding of no correlation between smoking and angina pectoris or electrocardiogram changes suggestive of myocardial infarction. Nor does the Report mention the significant correlation between heart disease and women with personality Type A - a type the author also found more common among smokers than non-smokers. As to lung cancer, the Overview states that cigarette smoking was firmly established as the major cause of this disease by several large retrospective and pro- spective studies. Absent entirely from the Report, however, is any mention of the views recently expressed by Profes- sor Philip Burch of England regarding cigarette smoking as a claimed cause of lung cancer. According to Profes- sor Burch, the smoking and lung cancer mortality data in Britain are more consistent with the constitutional hy- pothesis first postulated by Sir Ronald Fisher in the 1950's than with the smoking-causation hypothesis. These views have provoked considerable discussion and controversy in the scientific literature, but there is not a single aeference to the matter in this Report. TIMN 450359

294 27:- Brqrsa, W1,7S, Winston, Ri and Soasrs,. s1'Cii lSa:sbtsgous tltaphylococcal enteritis after antibiotic therapy. kbport of two- casea,.Am. JDigast.• DisR, 20: 73-75, 1953. 28. Sos®ers, S,C.- and McManus, R,G,:. _Multiple stseqieal bancats of skin and internal organs. Cancer, 6: 347•359, 1953. 29. Sommers, S.C„ Anderson, L,M, and Warren, S.: Basesent membranee in chronic intestinal diseases. Lab. Invest., 2:. 223-226, 1953. 30. Wakefield, R,D, and Sommers, S.C.: Fatal membranous staphylocoecal enteritis in surgical patients. Ann. Surg., 138: 249-252, 1953. 31. McManus, R,G, and Sommers, S,C.e Significance of gastric polyps accompanying cancer.. Am. J, Clin. Path., 23: 746-757, 1953. 32. Sommers, S.C,s Ovarian Rete Cysts. Am. J, Path., 29: 853-859, 1953. 33. Somers, S,C,: Endocrine changes after hemiadranalectomy and total body irradiation in parabiotic rats. J. Lab. & Clin. Med., 24: 396-407, 1953. 34. Holt, M,W„ Sommers, S,C, and Warren, S.: Intranuclear changes resulting from exposure to ionizing radiation as detected in frozen-dried preparations. Lab. Invest., 2: 408-418, 1953._ 35. Sommers, S,C„ Geyer, B,S, and Chute, R,N,: Autoradiographic arsenic localization in adult and embryonic epithelium and connective tissue. Proc. Soc. E.per. Biol. & Med., 84; 234-239, 1953. 36. Sotmeers, S.C., Teloh, H,A, and Goldman, C,: Ovarian influence upon survival in breast cancer. Arch. Surg., 67: 916-919, 1953. 37. Sommers, S,C, and Lombard, O,M,: Cancer associated with ovarian atromal hyperplaeia. Arch. Path., 56: 462-465, 1953. 38. Warren, S, and Sowmers, S,C,: Pathology of regional ileitis and ulcerative colitis, J, Am. Med. Assoc., 154: 189-193, 1954. 39. Adamaon, N,E„ Jr: and Somers, S.C.: Endometrial ossification. Amt'J. Obst. and Gynec., 67: 187-190, 1954. 40. Chute, R,N,;, Renton, H,B, and Somers, S,C,: A laboratory epidemic of human-type tuberculoeie in hamsters. Am. J, Clin. Path., 24: 223-226, 1954. 41. Marcial-Rojaa, R.A, and Sommera, S,C,: Differentiated mucoepidermoid tumors of saliyary glands. Arch. 0tolaryng„ 59; 135-140, 1954. 295 42. Hollander, A., Sommers, S,C, and Grimraade, A;E,: Histochamical and ultraviolet microscopic studies of chronic dermatoses and the corium membrane. J. Invest. Dermat., 22: 335-348, 1954. 43. Strande, A., Somers, S,C, and Petrak, M,2 Regional enterocolitis in cocker spaniel dogs. Arch. Path., 57: 357-362, 1~54._ 44. Sommers, S,C, and Heissner, W,A,: Basement membrane changes in chronic thyroiditis and other thyroid diseases. Am. J, Clin. Path., 24: 434-440, 1954. 45. Wood, J,Si, Jr., Holyoke, E,D6, Clason, W,P,C„ Sommers, S,C, and Warren, S.: An experimental study of the relationship between tumor size and number of lung metastasee. Cancer, 7: 437-443, 1954. 46. Goddard, J,,W,- and Sommers, S.C. Method for thyroid cell mapping. Lab. Invest., 3: 197-210, 1954. 47.. Colcock, B,P. and Somers, S.C.: Prognosis in Paget's disease of the breast. Surg. Clin. N, Am., 34: 773-783, 1954. 48. Burt, A,S „ Landing, B,H, and Sommers, S,C,: Aacphophil tumors of the hypophysia induced in mice by 1131, Cancer Rea., 14: 497-502, 1954. 49. Sommers, S,C, and Meissner, W,A,: Unusual carcinomas of the pancreas. Arch. Path., 58: 101-111, 1954. 50. Sommers, S.C., Edwards, J,L, and Chute, R,N.: Increase in hyper- sensitivity lesions of parabiosis intoxication after adrenalectomy. JA Lab, and Clin. Med., 44:. 531-543, 1954. 51. Sommers, S.C., Crozier, R, and Warren, S.: Ultraviolet microscopy of glomerular diseases. Am. J, Path., 30: 919-939, 1954. 52, Turner, D,D, and Sommers, S.C.: Medical intelligence. New. Eng. J, Med., 251: 744-745, 1954. 53. Patterson, W,B„ Chute, R,N, and Somers, S.C.: Tranplantation of human tumors into cortisone-treated hamsters. Cancer Res., 14: 656-659, 1954. 54. Goddard, J,W, and Soaceers, S,C,: Thyroid etimulation in diabetes mellitus. Diabetes„ 3: 383-388, 1954. 55. Somners, S.C„ Murphy, S,A, and Warren, S;: Pancreatic duct hyperplasia and cancer. GastroenteroloAV. 27: 629-640. 1954.. 56. Rohman, M, and Somers, S.C.: A double primary carcinoma of the urinary bladder. J. Urol., 72: 1174-1177, 1954, TIMN 450331

308 309 /1235. Lang, M. E. and Sosners, S.C.: Staging, Grading and Hiatocheeiatry of Ovarian Epithelial Tumors: Clinical Obstetrics and Gynecology: 12: 937-954, 1969. 226. Claps F. X. and 8omzsers, S.C. (CPC): Back Pain, Renal Failure and Abnormal Infusion Pyelogram: N.Y- State . Mad., Vol. 70, 869-879, April, 1970 227. Buda, J. A , McAllister, F F. and Soa~era, S. C-: Surgical Treatment of Renovapcular Hypertension: The American J. of Surg.: 119• 574-578, 1970 228. Baer, L., Sosmers, S.C., Krafoff, L. R. et al: Aldosteroniam Pseudo-primary Circulation Research: 27: 1-203, 1970 (Supplement #1) 229. Sorera, S. C.: The significance af Endo®etrial•Hyperplasia and Its Early Diagnosis: Gynecological Oncology: Pages 129-140, May 1969. 230. Soamers, S. C., and Terzakis, .Y. A.: Ultrastructural Study of Aldosterone- secreting Cells of the Adrenal"Cortax: Amer. J. Clin. Path.: 54: 303-310, Sept. 1970. 231. Obar, W. B. and Sosazer•s, S. C.: (CPC) Backachtand Abnormal Findings on Chest Filsss: N. Y. State J. Mad. Vol. 70, 2692-2702,=Nov.-1970. 232. So®ers, S. C.: "Effects of Ionizing Radiation Upon Endocrine Glands," In Pathology of Irradiation, edited by C.C. Berjis, Williams and Wilkins Co., Chap. 18, page 408, 1970. 233. Gould, V. E., Wank, R., and Sonmers, S. C.: Ultraatructural Observations on Bronchial Epithelial Hyperplasia and Snuamous Metaplasia: Cancer, Vol. 28, No. 2 August 1971 by the American Cancer Society, Inc. J. B Lippincott Company. Pages 426-436. 234. Terzakis, J.A., Soomners, S. C. and Andersson, B.: Neuroaecretory appearing cells of human segmental bronchi: Laboratory Investigation 26: #1, 127-132. 1972. 235. Mattern, R. D., Soe:mers, S. C., and Kaasirer. Z: P.: Oliguric acute renal failure in li a 236. m gnant hypertension: The Am. J. of Med. 52: 187-197, 1972. Soamrs,-Sheldon C., "Adrenal Glands" in Path___ olo:tv, W. A. D. Anderaon, ed., Sixth Edition, C. V. Mosby Company, St. Lous,-i~"71. Vol 2, ch. 36, pp. 1464-1487 237. Soaasers, Sheldon C., "Thyroid Gland", in PatholoQV, W. A. D. Anderson, ed., Sixth Edition, C. V. Mosby Co., St. Louis, 1971. VOL 2, Ch. 34, pp. 1431-1451 238. Falls, William F. Jr., Randall, Russell E. Jr., Sommere, Sheldon C., Stacy, Williaas K., Larkin, Ernest G., Still, W.J.S. Nonhypercalcemic Sarcoid Mepbropathy.. Archives of Ipternal Medicine, 130, August 1972, p. 285. 239. Mehta, B., Brigg., D, K., Soamers, S.C., Karpatkin, Margaret. Disseminated intravascular coagulation following cardiac arreat: a study of 15 patients. An. J. of the Medical aci.,,.... 240. Nadji, Pouran and Soammers, Sheldon C. Lesions of toxead.a in first trimester pregnancies. Amer J of Clin Path. 59:344, 1973 241. Bercovitz, Z.T., Kirsner, Joseph B., Lindner, Arthur E., Msrshak, Richard'H., Menguy, Rene B., Soasers, Sheldon C. "Ulcerative and Granulo®atous Colitis". Charles C. Thomas, Springfield, Illinois, 1973. 242. Koralitz, Burton I., and Somers, Sheldon C. Perforated nongranulosatous appen- dicitis in the course of regional ileitis. Gastroenterology 64:1020-1025, 1973. 243. Somers, Sheldon C. Growth Rates, Cell Kinetics, and Matheaatical Models of Human Cancers. Pathobiology Annual, 1973, 3:309-340. 244. Somers, Sheldon C. Carcinoma of Endo.etrium. International Academy of Path- ology Monograph - THE UTERUS., Williams & Wilkins, Waverly Press, In Maryland, Chapter: 14, pp. 276-297. 245. Sonaers, Sheldon C. & Long, Margaret E., Ovarian Carcinoma: Pathology, Staging, Grading, and Prognosis. Bulletin of the N.Y. Academy of Medicine, vol.49, #10, pp.858-869, October, 1973, 246. So®ere, S.l:z Mrlesaaen,B. Vascular morphologic changes in essential hyper- tension. Hypertension: Mechanisms and Management, Grune & Stratton, Inc. New York, pp. 165-173, 1973. 247. Cannon, P.J., Mohamed, H., Case, D.B., Casarella, W.J., So®ers, S.C. & LeRoy, E.C. The relationship of hypertension and renal failure in scleroderme (progressive system sclerosis) to structural and functional abnormalities of the renal cortical circulation. Med., 53:1-46, #1, 1974. 248. Barber, H.R.K., Sommers, S.C., Vaginal adenosis, dysplasia, and clear cell adenocarcinoma after diethylstilbestrol treatment in pregnancy. Obstetrics a:d Gynecology, 43:645-652, #5, May 1974. 249. Chabon, A.B., S:dnji Takeuchi and Sommers, S.C. Histologic differences in breast carcinoma of Japanese and American women. Cancer, 33:1577-1579, #6, June 1974. 250. Hartmann, W.H., Sommers, S.C., Taylor, H.B., Friedell, G.H., Gallager, H.S., Hutter, R.V.P. & Ozzello, L.: T1u Pathology Working Group. Standardized Management of Breast Specimens. Aa. J. of Clin. Path., 60:789-798, #6, Dec.1973. 251. Barber, R.I., Reisman, B, Soamers, S.C. & Grabar, E.A. Cancer of the andometriun. Tex. Med., 70:41-56, July 1974. 252. T•orelitz, B.I. & Sosvers, S.C. Differential Diagnosis of Ulcerative and Granuloaiatous Colitis by Sige:oidoacopy, Rectal Biopsy and Cell Counts of Rectal Mucosa. Amer. J. Gastroenterol., 61:460-469, June. 1974 253. Free.an, B.C., xreps, B.M., Ronshei.. N.J., Re.edios, F.L. & Sos.ers, S.C. Poststaphylococcal Gloaerulonepbritis in Heroin Addicts. N.Y.S.J.of Med., 74:2241-2243, November 1974. 6.1//. eeithelial-Nerve Intermingling in Benign Breast Lesions. Arch, Path..q 99;596-598, #11, November 1975. TITVIN 450338

1 354 "approximmates that of non-smokers" 10 to 15 years after the cessation of smoking. However, as early as 1966, Doll stated that his study of British doctors "suggested that the risk for acquiring the disease (lung cancer) remains almost the same as it was when smoking was dis- continued and that the risk decreases in comparison with the risk of smokers only because the latter's risk con- tinues to increase." With the exception of a brief period in early 1974, Doll has consistently maintained the view, based upon his data, that cessation does not result in a decreased risk. He confirmed this in October, 1974 at the llth International Cancer Conference in Florence, Italy. The Overview's suggestion that any decrease in the male death rate from lung cancer is the result of a decline in per capita consumption of cigarettes, as well as a switch to low "tar" cigarettes, ignores the work of Gilliam, et al. in the early 1960's. They examined the lung cancer death rates from the 1930's through the 1950's and found them to be increasing, but at a decreasing rate. 4 As a result of their analysis, they predicted in 1961 that the male death rate from lung cancer would level off in the next decade or so, and ihey reached their con- clusion without regard to smoking habits in the population. Later studies by Springett, by Langston and by Belcher (1975) 355 have supported their prediction. The Overview, however, does not even mention, let alone discuss, the Gilliam thesis as a possible explanation for the apparent peaking and decline of the male incidence of lung cancer. The 1975 Report's treatment of other cancers (larynx, oral cavity, etc.) is Just as superficial as its treatment of lung cancer. For example, it does not ex- plain the various statistical anomalies relating to these diseases. In all these:sites, there has been little, ifi any, increase in cancer.s.among white males and females during the last 20 to 30 years. Even the Public Health Service recognizes that both. the incidence of and mor- tality from oral cancer has remained steady over this period. Yet, the overall consumption of tobacco has in- creased dramatically during this same period. The 1975 Report exhibits a lack of understand- ing of epithelial changes such as a squamous metaplasia . and carcinoma in situ. The Overview discusses carcinoma in situ as if it were a "malignant change," which it is not. The Cancer Chapter, on the other hand, categorizes _ carcinoma in situ and squamous metaplasia as "premalignant changes." It fails to note, however, that-these so-called pre- malignant changes do not inevitably and Invariably develop into cancer. The Report's claim that these changes are TIMN 450361

352 Nor is there any reference in the 1975 Report to the recent migrant studies in this country by Mancuso, et al., which support the constitutional hypothesis. These researchers studied lung cancer mortality in white and black migrants in Ohio and found that the white migrants from the South had a 50% excess risk of lung cancer com- pared with the native-born white population, while the black migrants had a 100% excess risk compared with native- born- black population. No difference was found in the lung cancer incidence of the native-born black and white populations. Mancuso's study lends further weight to the earlier migrant studies by Dean and by Eastcott, both of which also support the constitutional hypothesis and both of which are ignored by the 1975 Report. The Dean study found that the British living in South Africa, with ap- parently identical smoking habits and living in the same areas as their southern contemporaries, still had a higher death rate from lung cancer than the native-born white population. The Eastcott study, which dealt with British immigrants to New Zealand, found that the incidence of lung cancer among the imniigrants was considerably higher than the native-born population regardless of the age at w.,i:.ca they jLmmigrated. The Overview, as well as the Chapter on Cancer, 353 indicates that the risk of developing lung cancer is related to the age at which smoking commenced and the number of cigarettes smoked. But, the 1975 Report ignores the studies by recently - by of lung cancer Passey, by Pike and Doll and - more Herrold showing that the age of incidence does not depend either upon the age at which smoking commenced or the duration of smoking or even whether or not one smokes. Also ignored is the fact that the cigarette consumption data in various countries do not correlate with lung cancer death rates in those countries. For example, the United States and Canada have the two highest per capita consumptions of cigarettes in the world, but rank tenth and sixteenth respectively, with regard to white male death rates from lung cancer. Conversely, while the United Kingdom, Finland and the Netherlands have lower per capita consumptions of cigarettes than the United States and Canada, they all have substantially higher•death rates from lung cancer. These data are in- consistent with the theory that the amount of cigarettes smoked is correlated with the incidence of lung cancer. The 1975 Report's disregard of scientific data conflicting with its position is again shown in its dis- cussion of the effects of cessation of smoking on lung cancer. It states that the ex-smokers' risk of lung cancer TIMN 450360

316 rnents of other industries. In the broadest sense, it is of legitimate concern to all Americans. For the proposed legislation ruises a fundamental question: IIow protective should the Government be of its citizens, and how much re- sponsibility should reside in the individnal ? The question assumes even larger magnitude as the definition of "en- viromnental healt]r factors" is broadenwd bcyond the toxic substanc.es to which mankind is exposed in the general environment, or in the specific work environment, and is extvnded to the kind and amounts of foods we eat, -the beverages we drink, and the personal style of life we follow. If the Government's proper role with reference to legal products is to inform the people, to give them the facts, to see that. advertising gives them the facts, and then to leave the exercise of free choice to the individual, then there may be no place for Government interven- t ion and nianipulation to rest rict suclr products. To give further meaning and support to this proposition, last June, T)r. Theodore Cooper, Assistant Secretary for Ilealth, said that. in his judgment, "we will achieve the greatest good not through absolute bans, but by giving our people the knowledge necessary to make ra- tional and informed personal decisions." I recognize that S. 200•2 does not call for absolrrte prohibition, but I submit that it calls for creeping prohibition through taxation. As in the Limbo dance, the "tar" and nicotine cont.entt could then be pro- gressively lowered to zero through fiscal controls. Throughout the United States today, low "tar" and nicotine cig- arettes are available to every smoker. Information concerning "tar" and nicotine content is available to every smoker from a variety of sources, including cigarette advertising and periodic reports by the I+'TC. This availability of a broad range of brands, together with informa- tion about their "tar" and nicotine content affords every smoker an opportunity to freely express his preference in the marketplace. As the free market mechanism works out, more than 80 percent of all cigarettes purchased in the United States are 19 mg. of "tar" or below. The sales weighted average "tar" level of U.S. cigarettes has dropped over 50 percent in the past 20 years to a present level of 18.5 mgs. In 1974, the most recent figures, cigarette advertising expendi- tures were weighted overwhelmmgly (over 95 percent) in favor of brands eonta;,,,ng 70 Senator Ki;NxFnY. Why do you think it is important to advertise this? I mean, you must put some kind of value on the low tar and low nicotine cigarettes, too. You just mentioned you spend 95 percent of the advertisement in that area. Your point to it proudly. As far as I am concerned, I think it is an extraordinary achievement. You must recognize that there is some relationship here. Mr. KoRNEQAY. For many years the low "tar" and nicotine brands have been available to the consumer. That has been traditional for many years. Now, your question is presently, why is so much emphasis being placed by the manufacturers on low "tar" and nicotine cigarettes? 317 My only answer to that-and it may not be perfect, but it is the best. one that I have-is that public demand has been created for lower "tar" and nicotine cigarettes. And I must say that the main reason that I can see for the present demand is the publicity and activity of the last few years, centered around this controversy. Senator KFNNEnY. We will have to recess. That is the vote. [Short recess.] Senator KE.NNr:nY.11'e will come to order. I apologize for the time. The leader told me that my bill on lead poisoning is coming up at 4 o'clock. So I ani going to have to floor manat;e that. So we have abont half an hour left for the rest of our witnesses. Mr. Kor,NECAY. I1Ir. Chairman, coulcl I make this suggestion-1)r. Sterling came all the way fronn ti'aucouver, ancl so I would respectfully suggest to you that I suspend reading the rest of my statement, supply it for the record, and then coure back, if tliat seems desirable, and that you move on to him. ['1'he prepared statenlent of AIr. Kornegay, with acconilranying ex- liibits, follows:] TIMN 450342

304 305 166. Kennedy, J.H., Williams, M.J. and So~ers, S.C.: Cushing's syndrome and cancer of the lung; Pituitary Crooke Cell hyperplasia in pulmonary oat cell carcinoma. Ann. Surg., 160: 90-94, 1964. 167. Sommers, S.C.: Pathology of essential hypertension. Cyclo. Med. 4: 9-15 1964. 168. Buckingham, S., McNary, W.F „ Jr., and Sommers, S.C.: Pulmonary alveolar cell inclusions: Their development in rat. Science, 145: 1192-1193, 1964. 169. Ruasfield, Agcue, B., Fisher, Edwin, R. and Sommers, S.C.: Dissociation of hypophyseal content and urinary excretion of gonadotropin in cirrhosis Proc. Soc. Exp. Biol. & Med., 1•16: #4, 1022-1024, Aug.-Sept. 1964. 170. Soamesera, S.C.: Pulmonary emphysema, healed myocardial infarcts and other disease correlations with male breast structure. Am. J. Med. Sci., 248: Sept. 1964, 341-344. 171. S oemere, S.C., Gonick, H.C „ Kalmanson, G.M. and Guze, L.B.: Pathogenesis of chronic pyelonephritis. Am. J. Path., 45:#5 729-739, Nov. 1964. 172. Friedell, G., Betts, A. and Sommers, S.C.: The prognostic value of blood veasel invasion and lymphocytic infiltrates in breast carcinoma. Cancer, 18: #2, 164-166, Feb. 1965. " 173. Kennedy, J,H., Williams, M.J. and Sommers, S.C.: Pituitary Crooke Cell hyperplasia in pulmonary carcinoma. Acto Unio Contra Cancrum, 20: 1523, 1964. 174. Gonick, H.C „ Rubini, M.D „ Gleason, 1.0. and Sommers, S.C.: The renal lesion in gout. Ann. Int. Med., 62: 667-674, 1965. 175. Sommers, S.C.: Hypertension and kidney disease. Prog. in Cardio- vascular disease. 8; 210-234, Nov. 1965. 176. Kalmanson, G.M., Sommers, S.C. and Guze, L.B.: Pyelonephritis VII. Experimental ascending infection with progression of lesions in the absence of bacteria. Arch. Path., 80:,509-516, 1965. 177. Reeves, G. and Sommers, S.C.: Sensitivity of the renal macula densa to urinary sodium. Proc. Soc. Exp. Biol. Med., 120: 324-326, 1965. 178. Sommers, S.C,: Endocrine pathology of prostatic hypertrophy and carcinoma. Bull. N.Y. Acad. Med. 42: p.248, March, 1966 (Abstract). 179. Bercovitz, Z.T, and Sommers, S.C.: Altered inflammatory reaction in nonspecific ulcerative colitis. Arch. Int. Med., 117: 504, April, 1966. 180. Friedell _ G_A- - Sn,.'.q.er~ . , . , . .. . . ., .. , ....,, . , ..,.., ~~,:,.... ,.n, 3.., .,.~:'.aan tumorigenesis in irradiated parabiotic rats. Cancer Ras. 26: 427-434, 1966. 181. Meissner, W.A. and Sommers, S.C.: Endometrial changes after prolonged progesterone and testosterone administration to rabbits. Cancer Res. 26: 474-478, March, 1966. 182. More, B.M., Merdinger, W,F. and Sommers, S.C.: Cholecystitis and stenotic arteriosclerosis. Am. J. Clin. Path. 45: 465-467, 1966. 183. Sommers, S.C., Friedell, G.H. and Robinson, C.R.: Chemotherapy of Human Cancer Transplants with Methotrexate (Amethopterin) and Horse Serum. Cancer, 19: 674-676, 1966. 184. Schindler, A.M. and Sommers, S.C.: Diabetic sclerosis of the juxtaglomerular apparatus. Lab. Invest., 15: 877-884, 1966, May. 185. Sommers, S.C.: Renal Factors in Hypertension. Henry Ford Hosp. Med . Bull., 14: 47-54, March, 1966. 186. Buckingham, S., Heinemann, H.O. and Sommers, S.C. and McNary, W.F.: Phospho- lipid synthesis in the large pulmonary alveolar cell: Its relation to lung surfactants. Am. J. Path. 48: 1027-1041, June, 1966. 187. Soloway, H.B. and So®ers,S.C,: Endocrinopathy associated with pancreatic carcinomas - review of host factors including hyperplasia and gonadotropic activity. Annals of Surgery, 164: 300-304, 1966. 188. Laragh, J.H., Sealey, J.E. and Sosmmers, S.C.: Patterns of adrenal secretion and urinary excretion of aldosterone and plasma renin activity in normal andhypertensive subjects. Supplement 1 to Circulation Research. Vola. XVIII and XIX,1-158 - 1-174, June, 1966. 189. Cannon, P.J., Stason, W.B., Demartini, F.E., Sommers, S.C. and Laragh, J.H.: Hyperuricemia in primary and renal hypertension. New Eng. J. Med., 275: 457-464, September, 1966. 190. Sommers, S.C. and Friedell, G.H.: Studies of carcinogenesis in parabiotic rats. Annals of New York Academy of Sciences, 125: 928-932, January, 1966. 191. Kister, S.J., S ommers, S.C., Haagenaen, C.D, and Cooley, E.: Re-evaluation of blood vessel invasion as a prognostic factor in carcinoma of the breast. Cancer, 19: 1213-1216, September, 1966. 192. Hyman, G,A. and S ommers, S.C.: The development of Hodgkin's disease and lymphoma during anticonvulsant therapy. Blood. 28: 416-427,1966. 193. Sommers, S.C.: Mast cells and paneth cells in ulcerative colitis. Gastroenterology, 51: 841-848, 1966. 194. S ommers, S.C.: Pathology of cervical carcinoma. In "New C oncepts in Gynecological Oncology" Hahnemann Symposium, 85-90, 1966. 195. Sommers, S.C.: The significance of endometrial hyperplasias. In "New Concepts in Gynecological Oncology" Hahnemann Symposium, 205-209, 1966. 196. Sommers, S.C., and Bercovitz, Z.T.: Inflammatory responses in ulcerative 197. 198. colitis. N.Y. State J. Med., 66: 3040-3042, 1966. Svoboda, A.C „ Jr., Knauer, C.M., Gamble, C.N., Sommers, S.C. and Monroe, L.S.: :'roi..ems :.n txe ear:.y c,f.agnosi:s of peptic esophsgitis. Gastrointest. Endoscopy Feb. 1967. Caravaca, J., Dimond, E.G., Sommers, S.C. and Wenk, R.: Prevention of induced atherosclerosis by peroxidase. Science, 155: 1284-1287, March, 1967. TIlVIN 450336

360 causes of emphysema are not known. It further stated "Since there are no clear cut leads as to the cause or causes of emphysema, no quick solution to the problem can be anticipated." In fact, as late as 1974, the Public Health Service in a booklet on chronic obstructive lung disease was still taking the position that "the basic cause of emphysema is not known." Nor does the Overview acknowledge that in April, 1969 the Surgeon General of the United States told Congress that no causal relationship had been established between cigarette smoking and emphysema. And, further, the Overview does not recognize that the mechanism or mechanisms whereby cigarette smoking supposedly causes bronchitis and emphysema "remain only partially understood," even though this is admitted by the Chapter on Non-neoplastic Broncho-pulmonary Disease. Indeed, scientists do not understand the pathogenesis of bronchitis or emphysema (any more than they do the pathogenesis of cancer or cardiovascular disease). Scientists do generally agree that chronic bronchitis and emphysema are multifac- torial. But which of the observed factors, if any, plays a role in their causation remains•unknown. „_ _ ~ « - -- - - -. . - - - - ..z.ruo..vec. .n e..uc:.c.a,,- ing the cause or causes of bronchitis and emphysema is that in many cases these diseases cannot be distinguished from 361 each other. This problem was discussed in the 1967 Report as follows: "Inability to distinguish between chronic bronchitis and emphysema has hampered medical research and exchange of information. The PHS- NTA task force Report states further: 'Although patients having only chronic bronchitis tend to have more cough and sputum than do those having only pulmonary emphysema, the array of symptoms, physical findings, and pul- monary physiologic abnormalities are similar in both diseases. Chronic bronchitis and emphysema coexist in many patients . . ."' As a result of this problem, the 1967 Report lumped these diseases together and discussed them under the heading of chronic pulmonary disease. But the 1975 Report does not even recognize this problem, let alone discuss it. The Overview indicates that cigarette smoking inhibits ciliary action "responsible for cleansing the respiratory tract." However, it ignores the studies show- ing that any ciliastasis which occurs as a result of cig- arette smoke is short lived. Dr. Kilburn recently observed that in smokers the total clearance per day is made up by increased activity during the non-smoking period at night. The Overview also ignores the human studies w:h'Lch indicate t,aa'; smo.,c'.ng coes nu', ac.ue.r:.,e:.y p:::-ec:^. :.uail, clearance. In contrast, the Non-Neoplastic Bronchopulmonary Disease Chapter discusses animal studies which suggest that TIMN 450364

306 199. 200. 201. 202. 203. 204. 205. Rippey, J.H. and Somera, S.C.: Hypertrophied plasma cells in regional enteritis. Am. J. Dig. Dia., 12: 465, 1967. Leon, N. and Sommers, S.C.: Cells of masculinizing type in ovary of a patient with feminine phenotype. Acta Genetica et Stat. Med., 17: 345, 1967. Gonick, B.C., Paul, W., Somabers, S.C, and Guze, L.B.: Punctional studies in experimental pyelonephritis. II. Correlation between acid excreting ability and enzyme hieto- chemistry. Acid excretion and enzyme histochemistry in experimental pyelonephritis. Nephron, 4: 75, 1967. Goldenberg, V.E., Buckingham, S. and Sommers, S.C.: Pulmonary alveolar lesions in vagotomized rats. Lab. Invest., 16: 963, 1967. Sommers, S.C., Reeves, G. and Reeves, E.: Imounnologic and chemotherapeutic effects on human .elanoma hetero- transplants. Proc. Soc. Exp. Biol. and Med., 123: 740, 1967. Buckingham, S., Sommera, S.C. and Sherwin, R.P.: Lesions of the dorsal vagal nucleus in the respiratory distress syndrome. Am. J. Clin. Path., 48: 269, 1967. Sommers, S.C.: Systematized nomenclature of pathology. Pathologia et Microbiologia, 30: 826, 1967. 206. Strauss, M.D., Sommers, S.C.: Medullary cystic disease and familial juvenile nephronophthisis. New Eng. J. Med. 277: 863, 1967. 207. Elahi, E.H., Long, M.E., Frick, B.C., II and Sommers, S.C.: Long-term survival in disseminated ovarian carcinoma. Am. J. Obst. and Gynec., 99: 522, 1967. 208. Denning, C.R., Sommers, S.C. and Quigley, H.J.: Infertility in male patients with cystic fibrosis. Pediatrics, 41: 7-17, 1968. 209. Harrington, J.T., Sosmers, S.C. and Kaasirer, J.P.: Atheromatous emboli with progressive renal failure. Renal arteriography as the probable inciting factor. Annals of Int. Med., 68: 152-160, 1968. 210. Cannon, P.J. Leeming, J.M., :ommerxi, -, rr„ °.,L' °^d Laragh, J.H.: Juxtaglomerular cell hyperplasia and secondary hyperaldoateroniam (Bartter's Syndrome): A reevaluation of the pathophyaiology. Medicine, 47: 107-131, 1968. 307 211. Laragh, J.H., Ledingham, J.G.G. and Sommers, S.C.: Secondary aldosteronism and reduced plasma renin in hypertensive disease. Trans. Assoc. Am. Physicians, I7CZ%: 168-181, 1968. 212. Markewitz, M., Soazoroere, S.C., Veenema, R.J. and Butler, M.D.: Testicular biopsy artifacts resulting from improper tissue processing. J. Urol., 100: 44-49, 1968. 213. Sommers, S.C.: In (J.M.B. Bloodworth, editor) "Textbook of Endocrine Pathology" Thyroid Gland, Williams and Wilkins Co., pp 133-180, 1968. 214. Sommers, S.C.: In "Textbook of Endocrine Pathology", J.M.B. Bloodworth, editor, Endocrine Activities of Nonendocrine Tissue Tumors. Williams and Wilkins Co., Baltimore 1968. 215. Altchek, A., Aibright, N.L. and Sosmers, S.C.: The renal pathology of toxemia of pregnancy. Ob. and Gyn., 31: 595-607, 1968. 216. Buckingham, S., Sommers, S.C. and McNary, W.F,: Experimental respiratory distress syndrome: I Central autonomic and humoral pathogenetic factors in pulmonary injury of rats induced rith ~yperbaric oxygen and the protective effects of barbiturates and Trasylol~(~) . Biol. Neonat., 12: 261-281, 1968. 217. Paley, W.B., Phaneuf, G.J. and Sommers, S.C.: l:oincidental primary sarcoma and carcinoma of the cervix. Ob. and Gyn. 33: 41-47, 1969. 218. Goldenberg, V.E., Buckingham, S. and Sommers, S,C.: Pilocarpine stimulation of granular pneumocyte secretion. Lab. Inveat. 29:.147-158, 1969. 219. Kister, S.J., Sommers, S.C., Hasgensen, D.C., Friedell, G.H. and Cooley, E.: Nuclear grade and sinus histiocytosis in cancer of the breast. Cancer, 23: 570- 575, 1969. 220. Sommers, S.C.: Histologic changes in incipient carcinoma of the breast. Cancer, 23: 822, 1969. 221. Markewitz, M., Veenema, R,J., Fingerhut, B., Nehme-Haily, D., and Sommers, S.C.: Cyproterone acetate (SH 714) Effect on Histology and Nucleic Acid Synthesis in the Testes of Patients with Prostatic Carcinoma. Invest. Urol., 6:638-649, 1969. 222. Schwartz, D.T „ Buda, J.A. and Sommers, S.C.: The Effect of Portacaval Transposition and Renal Artery Stenosis on the Rejection of Renal Allografts in Dogs. J. Surg.. Rea., 9: 455-460,1969. 223. Goldenberg, V.E., Goldenberg, N.S. and Somere, S.C.: Comparative t..1a 4nrr.d,uctal carcinoma and infiltrating ductal carcinoma of the breast. J. Amer. Cancer Soc., 24: 1152-1169, 1969. 224. (CPC) Sommers, S.C. and Lesser, G,I.: Recurrent Chyloue Ascites. N.Y. State J. Med., vol., 70: 282-290, Jan. 1970. TIIVIN 450337

216 Raprlntad fro® the A®eneae Jourmd of Pubtic HenltA Votn ta, Nu.®bn 9. se9t.rber 197a lr4nerd N U.B.A. A Critical Reassessment of the Evidence Bearing on Smoking as the Cause of Lung Cancer THEODOR D. STERLING, PhD The controversial claim that cigarette smoking is a significant cause of lung cancer is chall~ged in this critical reappraisal of some importaot population studies. 1 Introduction Many subsfances existing In slgnificant quantities in the industrial and community environment possess considerable carcinogenic potential. For example, recent National Cancer institute-sponsored experiments with 120 com- monty used chemicals found that 11 induced a significantly elevated incidence of tumon and 20 gave results that called for further evaluation-t Another recent survey found that "We can now reproduce essentially a wide spectrum of tumor responses In the different segments of the respiratory tract, from the nasal cavity down to the alveoli, and correhlte them with chemical activity of different cardno- gens" (p. 825 in Referena 2). A number of expertmental Dr. SteFling was, at the time of this study, with the Department of Applied Mathematics and Computer 8ci- enoe, Washington University, St. f.ou6, Missouri. He 4 now Director, Computer Science Program, Simon Fraser Univer- sity, Vancouver, British Columbia, Canada. This report was generated by a project at Washington University on the Review of Crucial Data Bearing on the Smoking and Health Isaue, with partial support from The Council for Tobacco Resaarch. In order to maintain a nonpartisan perspective, the author asked a number of experienced statisticians and scientists to criticize and review earlier drafts of this report. He takes this occasion to thank Profesaoes Alexander Brownlet, Robert Ferber, Ian Higgins, Frank Massey, Eleanor Macdonald, Tom ldancuso, and Milton Rosenblatt for their sharp and incisive reviews. This paper is the result of their review and of a subspuent discussion with Dn. C. Hammond. D. Hom. G. Hutchison. J. Iorn- .nd M- Kastenbaum at the symposium, "Smoking and Health Now," held as part of the 138th meeting of the American Association for the Advancement of Science in 1971. results on the oncogenic role of organic compounds that were puzzling for some time are better understood now. For instance, only relatively recently has it become clear that the carcinogenic properties of soot samples depend on the extent to which they carry benz[a]pyrene and other aromatic hydrocarbons.3 Also, it appears to be necessary for carcinogens to be brought into prolonged contact with lung tissues through particles of the right size, as those resulting from the incomplete combustion of organic fuels,4's or to injure the epitbelium through use of toxic vapora simWtaneously with the Introduction of carcinogens (as high concentrations of S01 or by the use of some halogenated ethers).a On the other hand, the belief that smoking is a major cause of lung cancer still lacks definitive experimental demonstration but depends almost exclusively on the result of statisticat surveys. The designs and execution of these surveys have been severely criticized (as well as hotly defended) In the past, and the discovery that the antecedents of lung cancer are found in many alternative and interactive causes may again create the need to reevaluate the results of these epidemiological studies.* • In part, a number of inst.ncn of reevaluation are on record already. The recent report by the Cotnmittet on Biological Effects of Atmospheric Pollutants has concluded that, after all, particular polycyclic pollutants may play a major role in the etiology of many cancers including lung Ith... h !hw rF /,,,..i.n .rnl M....a cigarettes.' Unfortututely, the National Academy of Sciences report falls far short of a critical e+nluation of lung cancer studies.' SMOKING AND LUNG CANCER 939 These needs are further strengthened by data released after the report of the Surgeon General's committee, SmohirtP and Health.e These data suggest that there is a serious possibgity that the apparent association between smoking and lung cancer obsetved in population studies, particularly that found in the two crucial studies conducted by the American Cancer Society (ACS), is possibly a spurious result of the selection procedure by which the study populations were assembled. This condusion Is further strengthened by the results of a prospective study started in 1965 comparing over a quarter million Japanese smokers and nonsmokers. This Japanese study avoided some of the "volunteering" aspects in the selection of subjects (and, with it, a major source of bias). One even more significant observation is that the lung cancer incidence in England and Wales, in Scotland, and in the United States appears to have leveled off and begun to decline for all but the older populations. For British males this decline appears to have started prior to 1955 for the age groups up to 44, prior to 1957 for the age groups 45 to 54, and prior to 1964 for the age groups 55 to 64 years of age. In the U.S. the same decline, somewhat less pronounced, also started approxi- mat®ly in 1955 but was restricted more to younger age groups. It is unlikely that this decrease can be related to a decline in smoking dating to 1965, especially If the latent period for tumorigenesis is 15 to 30 years (a reasonable estimate based on tumorigenic responses of man to known carcinogens). Neither can it be attributed to any decrease in cigarette tar and nlbotine levels since it is reported that the reduction of tar and nicotine levels began in the 1950s" and the popular use of the filters postdated 1955. The ACS Study Population Appears to Have Been ' Selectioely"Assembled Conclusions concerning the hazards of ciy{arette smok- ing were primarily based on seven prospective surveys (p. 81 in Reference 9). They all share the common chamcteris- tic that their study populations were assembled through sucxessions of "selection factors" which depended heavily upon the cooperation of, availability of, and ease of access to potential study subjects who also differed in crucial characteristics such as smoking habits, disease, occupational exposure to chemical carcinogens, and so on. The most important of these studies were those conducted by the volunteers of the American Cancer Society. While Dr. Hammond has not permitted public review of the ACS data, and despite the limitations imposed by the scant amount of data published about the actual characteristics of the population, a number of important and extremely remarkable conclusions can be drawn from his publica- Uons.* * Relevant information is scattered throughout Dr. Hammond's publications and often is given in terms of mortality ratios and rates per 100,000 population, which ' ii:; ,i-u,i .i.ur: un nloui how popufscSon curaccerst;a are actually distributed. There are abo many ambiguities in the published data for which answers are not easy to 940 AJPH SEPTEMBER,1976, Vo1.0E, No.9 217 20 ts s 10 5 0 35-39 4°44 45-49 50-5r 5551 b0-U 4549 1014 /5I1 t0r5 AG! FIGURE 1 Compar,son oe ACS and U.S. popu4t/ons: pernnt.pe dutnbunon by a0e. Tha a9s distrlbution of ACS ma.a m 19e0 comes erom Hammorsl" Comp,rable liauras tor a PoDut.hon of U.S. males between the yr ee 35 and 85 were computtd trom teb4es gnven in the 1980 U.S. osnrus report." Because the ACS population was restricted to house- holds containing at least one adult 45 years ot age or older, certain characteristics had to be expected that .re pecu8sr to the population residing In such households. Theat characteristics are present, but so are other features tktt betray that the ACS recruitment procedure was stron* influenced by factors associated with the composilion of the ACS volunteer group and with their likely atOtude toward smoking and disease. The workings of these spteW selection processes can be seen by comparing the ACi group to the U.S. population of the 1960 census (the yea the study population was selected). For instance, the ACS population contains appror4 mateiy 10 per cent fewer males and 10 per cent ston females than did the U.S. The age distribution of the ACS population does not have the pyramidal shape one woald expect for any cross-cut of a normally aging group (Fipua 1 and 2). Other comparisons show that the ACS popuit0sm is much better educated (Table 1), is much taller (Table 2), contains one-tenth the number of blacks found In the US. population, and has a predominance of Protestants aad native Americans (Tables 3 and 4). In addition, the md popudatidn is underrepresented, by far, as are vatlout nonindustrial regions of the country (Table 5). A certain amount of confusion has been created by Dr. Hammond In describing his sampling procedures. 1111 original description of sampling procedures gives !be impression that care was taken to obtain a repreuntstite sample. "The volunteer workers were so selected a lo obtain. An invitation waa extended to Dr. Hammond to meet with the advisory panel of our study to discur trsYs and means by which the ACS data could be nudeawiJabie for review and, at the same time, how his and A(S's interests and commitments could be safeguarded. Tdu advisory panel was made un of 10 lesdine seientuu and staU,st.lciiam from as many universities and laboratories. Dc Hammond declined to participate in this review or to msb hia data availabte." TITYIN 450292 11

$i' 362 cigarette smoke, or its components in isolation, might adversely affect lung clearance mechanisms. This contrast in human and animal observations again illustrates that animal studies, and particularly in vitro studies, fre- quentlY obtain findings inapplicable to humans in vivo. The 19.75 Report mentions the Netherlands study as demonstrating an increased prevalence of chronic obstruc- tive lung disease in areas of high air pollution. But the Report fails to note the authors' finding of no correlation between smoking and obstructive airway disease as measured by FEV1. Indeed, smokers in high pollution areas had less airway obstruction than the non-smokers. The 1975 Report discusses FEV1 differences in black smokers compared to white smokers but fails to rec- ognize that the observed differences might be of a genetic origin. The possibility of a genetic basis for these differences is supported by the author's finding that the racial variation existed even after adjustments were made for differences in amounts smoked. A genetic or consti- tutional hypothesis is also supported by the 1975 Report's lengthy discussion of alpha-1 antitrypsin deficiency, which it recognizes as a "genetic defect." The Overview notes that women who smoke during pregnancy have babies,with lower average birth weights than do non-smoking mothers. It also indicates that children 363 of smoking mothers have a higher risk of neo-natal mor- tality than children of non-smoking mothers. In doing so, however, it ignores the fact, acknowledged by previous reports, that some major studies do not find children of smoking mothers to experience higher neo-natal death rates than children of non-smoking mothers. The Overview also ignores the 1972 study by Yerushalmy of maternal smoking habits and low birth weights, from which he concluded that the higher incidences of low birth weight babies among smokers is "due to the smoker, not the smoking." In contrast to the Overview, Dr. Carol Buck, as recently as September, 1975, described Dr. Yerushalmy's work as "ingenious." And, commenting on Dr. Buck's thesis, Dr. A.Michael Davies made an observation that is partic- ularly pertinent not only to low birth weight questions but also to the overall question of smoking and health: "Two hundred years later, YerLishalmy (7) was pointing out that the first requirement for epidemiological studies seeking causal associations is that all groups or a random sample of the groups be included, not only those which support the hypothesis. He recalled that the lack of correlation between „_. _.. . . , . .,,~. . ~._ ..~... ~ L_.<...~.. .. _ .... . ~.... ~ .. :. ~ _ ...,. a c..,.r .... .. ...c... ~ .v... .??..:in certain African tribes and Eskimos, which did not support current hypotheses, was ignored. Yerushalmy's observations on maternal smoking habits and low birthweight, quoted by Carol Buck, have never been satisfactorily explained, although many attempts have been made to dismiss them." TIMN 450365

358 Report emphasizes a study by Kellerman and Shaw which postulates the theory that AHH is controlled by a single gene locus with two alleles. It also discusses the study by Kellerman and Shaw which reportedly found that a high percentage of lung cancer patients had high levels of AHH inducibility. But the 1975 Report's discussion of AHH is typically one-sided. For example, there is no reference to the recent study by Robinson, et al. suggesting that AHH activity is controlled by more than one gene locus. Also missing is reference to the fact that Dr. Shaw, at the llth International Cancer Conference in Florence, reported that he could not replicate his findings of high levels of AHH inducibility in lung cancer patients in a follow-up series of 25 such patients. The Report also fails to mention the published criticism of Kellerman and Shaw's study indicating that the AHH levels which they measured might have been an artifact of the mitogen used. Lastly, there is no mention of the fact that Ho and Furst reported production of squamous cell lung cancer in AHH non-inducible animals; this finding runs contrary to the . eu'.aeL.1.i.'..;a h ne.re)y --ung can- cer is produced. The Overview's discussion of non-malignant res- piratory disease (bronchitis and emphysema) is as one-sided 359 as its treatment of other diseases allegedly caused by smoking. The Report flatly asserts that statistical studies have established cigarette smoking to be the pri- mary cause of emphysema in the United States. This again ignores the 1964 Report's statement that causal relation- ships cannot be established by statistical studies. More importantly, the Overview also fails to explain how it is able to arrive at the conclusion that the relationship between smoking and emphysema is causal when the 1964 Report could r.ot arrive at this conclusion. The 1964 Report stated "A relationship exists between pulmonary emphysema and cigarette smoking but it has not been established that the relationship is causal." Subsequently, the 1967 Report also failed to reach a causal conclusion regarding cigarette smoking and emphysema. Instead, it posed the following question as "crucial" to reaching such a conclusion: "Does inhaled tobacco smoke have a direct toxic effect on the alveolar tissue in the lung parenchyma which is important in the pathogene- sis of pulmonary emphysema? At present, it can- not be answered." Neither the 1975 Report nor any other since 1967 has ever discussed, much less answered, this question. Nor does the Overview acknowledge the fact that, the Public Health Service in its 1968 publication entitled "A Special Report on Emphysema," stated that the cause or TIMN 450363

356 "related to the various carcinogenic and co-carcinogenic substances in the cigarette smoke," has never been estab- lished. To the contrary, these changes have been observed in persons who have never smoked, including young children who have suffered various lung diseases; and-such lesions in non-smokers are indistinguishable from those in smokers. Nor does the Report recognize that many actual cancers do not involve surrounding areas of either squam- ous metaplasia or carcinoma in.situ. (A recent study by Davis and Whitehead found no squamous metaplasia.in the epithelium of the main airways in rats with squamous cell lung cancer.) The Cancer Chapter states that tobacco smoke contains "carcinogenic substances" including tumor initi- ators, accelerators and promoters. But it fails to note the presence of tumor inhibitors in tobacco smoke, and also fails to recognize that some compounds, carcinogenic in test animals when applied in isolation, are anticarcino- genic when applied in combination with each other. Thus ignored are rQcent studies indicating that certain constit- uents of cigarette smoke are anticarcinogenic when applied with true carcinogens in test animals. Some of these studies, by Weber, et al. and Lotlikar, et al., suggest that.nicotine and carbon monoxide might inhibit the metab- olism of noncarcinogenic compounds to carcinogenic 357 metabolites.- The Cancer Chapter discusses a paper by Hoffman, _et al., which,reportedly found n-nitrosonornicotine in burned tobacco, but not in tobacco smoke. There is no un- indication, however, that this compound is absorbed into the body by persons who chew tobacco or use snuff. The importance of this omission is apparent from the 1975 Report's statement that this compound is not believed to act "topically." The Cancer Chapter's discussion of the animal study-by Schreiber, et al. illustrates the 1975 Report's predilection for any theory of disease causation unfavor- able to smoking. The Cancer Chapter suggests that lung cancer in smokers might be influenced by chronic bronchitis, which it also claims to be caused by smoking. Since the publication of the 1975 Report, however, a human study by Caplin, et al. of the relationship between lung cancer and respiratory disease has found a negative correlation be- tween obstructive bronchitis and lung cancer. The seemingly inconsistent findings of these studies illustrates the problem of extrapolating the results of animal experimenta- tion to humans. The 1975 Report's discussion of aryl hydrocarbon hydroxylase suggests that this enzyme might be a mechan- ism whereby cigarette smoking causes lung cancer: The TIMN 450362 Ailb,

372 consume an amount of tobacco so small that the risk of development of any adverse health effect would be nonexistent, on the basis of any available data in the literature today." 373 EXHIBIT D "TAR" AND NICOTINE LITERATURE REVIEW TIMN 450370 0 Y P4

364 The 1975 Report devotes a chapter to what pur- ports to be a review of the scientific literature regard- ing claimed health consequences of smoking upon the non- smoker. It is, however, a highly selective treatment of the scientific literature. For example, there is no mention of Professor Schievelbein's 1973 review of the scientific literature on this topic in which he concluded that "no proof of a threat to the health of non-smokers through .'passive smoking' can be found in studi4es Available to date." Nor is there any mention of the 1973 report by Fletcher, et al. - an expert group appointed by the anti-smoking organization known as Action On Smoking and Health - which concluded that there was no "evidence" that smoking is "dangerous to healthy non-smokers." When reference is made to the reports of in- dependent scientists or governmental bodies on this issue, the important conclusions indicating that cigarette smoking has not been shown to be a hazard to the non-smoker are omitted. Thus, there are references made to some of the findings of a Joint 1971 study by the Federal Aviation Administration,the United States Department of Health, Education and Welfare and the National Institute of Occu- pational Safety and Health on the health aspects of smoking on transport aircraft. But no mention is made of its conclusion: 365 " . it is concluded that inhalation of the by-products from tobacco smoke generated as a result of passenger smoking aboard commercial aircraft does not represent a significant health hazard to non-smoking passengers." This conclusion is supported by that of the U. S. Inter- state Commerce Commission's study of smoking on buses: "We agree with the examiner's conclusions that petitioner has failed adequately to demon- strate the deleterious effects of second-hand smoke upon the health of motor bus passengers." The 1975 Report mentions the recent workshop (organized by Dr. Rylander and others)'on this topic by scientists from all over the world, but fails to note that these scientists were unable to conclude that cigarette smoking is a hazard to non-smokers. Further, these scien- tists stated that: "For the majority of the population, the average exposure burden due to environmental tobacco smoke is probably much lower than that due to industrial air pollutants and in many cases also environmental air pollution or the lung burden due to dust clouds or other indoor air pollution." In view of these conclusions by governmental bodies and independent scientists, it is not surprising that some of the most avowed critics of tobacco have ac- knowledged that smoking has not been established as a cause of disease in non-smokers. Dr. Ernest L. Wynder of the American Health Foundat:.on recen'::.y ac.m:.~;,;ec. -:na " he does not believe that "passive smoking really hurts the health of somebody who sits next to you . . ." And even TIMN 450366

380 have substantially higher death rates from lung cancer. 141,142 These data too are inconsistent with the theory that the amount of cigarettes smoked is correlated with the incidence of lung cancer. One of the major arguments of those who hold the theory that smoking causes cancer in humans is that the rise in tobacco consumption in the United States was followed by a rise in the incidence of certain cancers, for 8xample lung cancer. For the reasons stated above, such statistical correlations merely point to areas for further scientific research; they do not establish that a cause and effect relationship exists. The rise in lung cancer is also statistically correlated with increased use of such diverse aspects of our way of life as nylon hose, refrigerators, super highways and asphalt roads. Nevertheless, in view of this argument, the trends for cancers of the larynx, oral cavity, esophagus, etc. quite interesting. In all these sites, there has been are little, if any, increase in cancers among white males and 143 females during the last 20-30 years. For example, even the Public Health Service recognizes that both the incidence of and mortality from oral cancer has remained steady over 41.an ~re«~.~~.. T-. a.. .!. .tt ...... ....i,.'Q-.... 1,;,.La,iuer among white males has decreased slightly during this period while 1 144 cigarette smoking has continued to increase. These 381 data are inconsistent with the theory that smoking causes these diseases or with the theory that the amount of smoking influences the risk of developing these diseases. Also of interest is the fact that, while the death rate from oral cancer has been declining among white males and remaining relatively stable among white females, it has been increasing among non-whites in both males and 145 females. Yet this trend too cannot be explained on the b'asis of available smoking data. As to a dose-response relationship between smok- ing and coronary heart disease, several studies show no 146-150 such relationship. For example, a study by Keys found that the very light smokers (1 to 10 a day) were much less susceptible to coronary heart disease than others in 151 the study, including the non-smokers. Moreover, those who quit smoking seemed to be the ones most susceptible to this disease. Similarly, a study by Doll and Hill found a slightly higher death rate from coronary disease among smokers of 1 to 14 cigarettes per day than among smokers of 15 to 24 cigarettes daily.152 An argument used against smoking is that epidemi- ological studies indicate that the risk of developing lung caneer decreases after smoke cessation. The imnliratinn here is that smoking plays a causal role in the etiology of this disease and that the cessation of smoking prevents its TE'IN 450374

370 such changes. However, this study was hardly conducted in a real-life situation since 150 cigarettes were smoked in a 170m3 unventilated test room during a 30-minute period. Professor Harke, in commenting upon these condi- tions, observed: "The smoking conditions described were selected to assure that the test subjects were exposed to smoke concentrations for at least 20 minutes, which could hardly have even been achieved in reality." The 1975 Report also refers to a study by Luquette, et al., in which children exposed to tobacco smoke experienced increases in heart rates and blood pres- sures. But the conditions of this study were no more realistic than the Report's description of it. During the test, groups of three children with average age of about 9.8 years were placed in a 12' x 7' unventilated chamber and shown movies on the harmful effects of smoking. In some cases the children were exposed to cigarette smoke and at other times they were not. The authors found that both test situations affected the children's heart rates and blood pressures. The bizarre conditions under which this test was conducted, however, are simply omitted by the 1975 Report. Likewise, the Report fails to note that the children experienced increases in heart rates and blood pressures even in the absence of cigarette smoke. The 1975 Report's speculation that children "are 371 thought to be more sensitive to the effects of air pollu- tion due to their greater minute ventilation per body weight than adults," is without foundation. This very issue was examined by the Rylander workshop which determined that more research is required before any conclusions could be reached. The 1975 Report discusses two studies by Colley and his co-workers in which they reported relationships between parental smoking habits and respiratory illness in their children. The Report notes that Colley also found a close association between the parents' respiratory symptoms and the children's respiratory sumptoms. But the Report fails to mention the author's important observation that the respiratory disease In both parents_and children might have a common genetic origin. Since publication of the 1975 Report, a study by Hammer, et al. of children 1 to 12 years old in the New York City metropolitan area found that "respiratory morbidity in children did riot vary with parental cigarette smoking." That (despite the unfounded specualtion in the 1975 Report) cigarette smoking has not been established as a health hazard to the non-smoker was recently emphasized by Dr. Huber. In editorial comment; on the study by Hinds and First, Dr. Huber stated: "Under the most severe concentrations of exposure in their study, the nonsmoker could TIMN 450369

;i 366 the then Surgeon General of the United States - Jesse Steinfeld - admitted after the 1972 Report was issued that he could not "say with certainty that exposure to tobacco smoke is causing serious illness in non-smokers." The 1975 Report's discussion of tobacco constit- uents in the atmosphere is highly misleading. For example, it suggests that carbon monoxide in the atmosphere as a result of cigarette smoking "in everyday situations" reaches 110 ppm - a level greatly in excess of the 50 ppm standard set by the American Conference of Government Industrial Hygienists as the maximum limit of carbon monoxide exposure during an eight-hour period. But the 110 ppm measurement referred to was ob- tained by Professor Harke under conditions which people "in everyday situations" would not tolerate. Three persons simultaneously smoked three cigarettes one after another inside a European car placed in a wind tunnel without any ventilation in the-car and with.no outside wind movement. As Professor Harke observed, these conditions do "not correspond to a normal traffic situation." And the subjec- tive reactions of the test subjects were revealing: 11. , a threshold is reached at roughly 20 ppmwhich normally prompts one to open a window or to turn on the ventilation." This view is supported by another study of Pro- fessor Harke in which he studied the carbon monoxide level 367 in automobiles- "in everyday situations," i.e., driving in traffic. When two of four passengers smoked two cigarettes in an unvent"ilated car, the carbon monoxide levels ranged only from 12.1 to 24.3 ppm. And those carbon monoxide levels decreased to the ambient air level within two to three minutes after the cessation of smoking. Elsewhere, the 1975 Report refers to Professor Harke's study in which the smoking of niRe cigars allegedly resulted in a carbon monoxide concentration of 60 ppm. However, this level of carbon monoxide was obtained in an unventilated experimental room 57m3. The Report fails to note that the aim of,the experiment was to determine the highest possible concentration of carbon monoxide that can exist in a smoke filled room under extreme conditions which - according to Professor Harke - "rarely, if ever, occur normally." When the room was ventilated, the maximum carbon monoxide level after smoking nine cigars was 20 ppm. only Throughout, the studies cited by the 1975 Report do not support its attempt to create the impression that smoking "in everyday situations" results in dangerous levels 1j:- car3on monoxide in the atmosphere. For example, the chapter reports the data of Bridge and mention their conclusion that Corn, but fails to "concentrations of CO (carbon monoxide) from ciCarette and cigar smol:ing do not present an inhalation hazard to non-smokers." TIMN 450367

374 Contrary to popular belief, cigarette "tar" is not something to which human smokers are exposed 1 So- called cigarette "tar'"' is a laboratory product which is obtained by passing cigarette smoke through a cold trap at extremely low temperatures 2 - circumstances simply not experienced by smokers.* Accordingly, any claim that "tar" is something inhaled or otherwise taken in by human smokers is inaccurate and misleading. The laboratory condensate is referred to as "tar" because of its dark viscous appearance. A similar type substance could be obtained in the laboratory by pas- sing the smoke from the burning of many other organic 3,4 materials through a cold trap.. A variety of test animals have been exposed to tO1TdC~C StrltlRe'`dt~YTdaYisata ("tar" ) either in combination with various solvents or in special media, such as warm bees- wax, implantation pellets, etc. These tests have had widely differing results. Indeed, some of these experiments have resulted in negative findings but, unfortunately, little attention has been paid them. For example, one such study * Unfortunately, the Federal Trade Commission uses the term tar to ces:.gna';e '~:ae ciry par;`.cu:.a,e ma,ev 'L aa cigarette smoke, which matter is collected by means of a Cambridge Filter. In contrast to cold trap "tar," little research has been directed to the FTC particulate matter and, therefore, not much is known about its effects, if any, upon biological activity. 375 found that condensate instilled into the trachea of test animals (ducks) did not result in any cancers of the res- piratory tract while such instillations of methyleholan- threne, a synthetic laboratory carcinogen not found in tobacco smoke, did result in such cancers 5'6 Ukewise, studies by Salley and Kreshover and by Reddy, et al. failed to establish the carcinogenicity of condensate in other animal species. 7-9 These studies also emphasize the diffi- culty in extrapolating the effects of animal experimentation from one animal species to another, let alone from animal to man. 10-15 Also ignored is the study by Davies and Whitehead indicating no statistically significant differences in animal effects between "tar" from one type of cigarette with a "tar"-nicotine content characterized by the authors as "normal" and the "tar" from filter tip cigarettes made from other types of tobacco with reduced "tar"-nicotine.l6 Another recent animal study, which reported no "broncho- genic tumors" in hamsters exposed for 1 year to tobacco smokes with differing yields of total particulate matter (TPM) and condensate, concluded "that the response of the bronchial epithelium to smoke exposure does not depend On the amniinr __ .. ,,. . . . , ..,., , ,. ,. ,,,., _,,,,... . .. . .. ~.,,. arettes." 17 The interpretation of laboratory experiments TIMN 450371

368 Furthermore, an analysis of Table 2 indicates that "in everyday situations'"' cigarette smoking will not result in dangerous levels of carbon monoxide in the atmosphere. Table 2 shows that in Professor Harke's study of carbon monoxide concentrations in office buildings (where smoking was permitted)-the carbon monoxide levels were less than 5 ppm - even in the building which was not air-conditioned. r Likewise, Table 2 indicates that in the study by Andersson and Dalhamn, where the subjects were allowed to smoke ad libitum, the average carbon monoxide leVel was only 4.5 ppm. These data are supported by the.recent findngs of Hinds and First of the Harvard School of Public Health. Their study, financed by the Massachusetts Lung Association, measured tobacco smoke in public places. In an editorial comment appearing in the issue of the New England Journal of Medicine which reported this study, Dr. Gary Huber of the Harvard Medical School stated: "The data of Hinds and First demonstrate that in public places nonsmokers could potentially consume 1/1000 to 1/100 of one filter cigarette per hour, a level of exposure that has had no known serious association with disease." • The'1975 Report indicates that as a result of nnsurn tn niRn»er~~ , .....~__ --~-,.,- - ,` - -. AY ~ .,,.... _ . . . ,... _ , ,,, ~ . ,. ..r.~... ,. ume.~.mes ex- perience carboxyhemoglobin levels'as high as 2.1% (Harke) and 2.6% (Russell, et al.). The Report then claims that 369 these levels of carboxyhemoglobin are "well within the range that has been shown to decrease the exercise toler- ance of patients with angina pectoris." Examination of the studies cited in support of this proposition indicates that the mean carboxyhemoglobin levels in those studies of sick people ranged from 2.7% to 5.1%. Conspicuously absent from the 1975 Report's discussion is mention of the many studies showing that a 10% carboxyhemoglobin level, which people reach when caught in city traffic, is rarely even noticed. Even a 15% level does not produce symptoms such as headache (which is one of the earliest) in most people. The 1975 Report relies on a 1957 study by Harmsen and Effenberger to suggest that, in the absence of ventilation, nicotine concentrations in the atmosphere reach 5,200 }ag. But this figure is out of line with the other nicotine data set forth in Table 2. The Report, how- ever, neither attempts to explain this discrepency nor mentions the recognition in the report of the Rylander workshopthat Harmsen and Effenberger's method of analysis "was not very accurate." The 1975 Report discussed the study by Harke in which smokers experienced a lowering of skin temperature and a raising in blood pressure; while non-smokers exposed to "extremely large smoke concentrations" did not experience TIMN 450368

384 -15 processing the tobacco and, to some extent, the way it is smoked by the individual smoker. In the past, much effort and research has been devoted to understanding tobacco use and health. Yet, in spite of all the research that has been done, no one has ever shown any ingredient as found in smoke to be harmful to smokers. This is particularly striking as regards lung cancer because so much attention has been focused on,this disease. Dr. Lijinsky, who is now with the Oak Ridge National Laboratory and is a critic of tobacco smoking, told Congress in 1971 that "In spite of 20 years work on tobacco smoke, we cannot identify or nobody has been able to identify a carcinogen to explain the incidence of lung cancer in'man."17o Dr. Lijinsky further stated while smoke is carcinogenic in test animals it is not sufficiently carcinogenic by itself to account for the high incidence of lung cancer in humans.171 Dr. Lijinsky also referred to benzo(a)pyrene and other polynuclear aromatic hydrocarbons which are fre- quently claimed by critics of smoking to be responsible ::or .ung cancer in humans. He stated that it is impossible "to correlate the infinitesimal amount of benzo(a)pyrene and other polynuclear compounds in tobacco smoke" with the high incidence of lung cancer in smokers.172 Because of the many hundreds of compounds present 385 in smoke and_their possible interactions with each other, it is highly artificial to focus upon the effects of any one compound in isolation from the others. It has long been known, for example, that certain smoke constituents act as anticarcinogens when tested in combination with 173-176 carcinogens in test animals. Whether these compounds have a similar cancer-inhibiting effect in human smokers, however, is still unknown. In any event, discussion of toxicity fails to recognize any distinction between toxicity and the causa- tion of diseases such as cancer, coronary heart disease and other chronic illnesses. It is difficult, if not impossible, to understand how toxicological effects can establish causation for such chronic diseases. Indeed, it has been observed that ". . . there seems to exist in certain respects, an antagonism between toxic and carcin- 177 ogenic properties of chemicals . . . Similarly, compounds which are carcinogenic in test animals, when applied in isolation, have been found to be anticarcinogenic when applied in combination with each other. And, constituents of cigarette smoke previously thought to be lacking altogether in carcinogenic activity have recently been found to be anticarcinogenic when applied with true carcinogens in test animals,183 Recent studles even suggest that nicotine and carbon monoxide TIIVIN 450376 ~~~

386 387 nicotine does not present a significant health hazard to smokers.189 After twelve years there is no data which would 1 might inhibit the metabolism of noncarcinogenic compounds to carcinogenic metabolites. 184,185 Accordingly, to name a few smoke constituents as toxic without considering their effects as found in tobacco smoke, i.e., in combin- ation with the other hundreds of smoke constituents, is scientifically untenable. With respect to the designation of specific compounds as allegedly harmful to human smokers, several points should be considered as to each: Tobacco Smoke Condensate ("Tar") As noted above, tobacco smoke condensate is some- thing derived in a laboratory and not something to which human smokers are exposed. 186-188 More importantly, studies show that there are qualitative, as well as quantitative, differences between laboratory condensate and fresh smoke to which humans are exposed. Also, as noted above, the results of animal experiments with tobacco smoke condensate are difficult to interpret in view of the fact that con- densate continually undergoes chemical change, even while test animals with condensate may have little, if any, bear- ing upon the human experience. Nicotine Even the Surgeon General's Report of 1964 concluded that based upon the then available scientific evidence warrant a change, in that conclusion. Nevertheless, the opponents of smoking frequently try to implicate nicotine as having some role in various :cardiovascular diseases though not in the causation of cancer. The Surgeon General's Report.agrees with the gen- •eral•scientific view that nicotine is not a carcinogen,190 The evidence cited to implicate nicotine in cardiovascular disease.derives-from.studies showing that nicotine affects the:release of catecholamines-from the adrenal glands. The •release of endogenous catecholamines,.however, may also -result.frnm such common activities as running, walking up stairs or undergoing emotional stress.191•The point is that, even if catecholamines are released by the adrenal glands as a result of nicotine exposure, this usual, and indeed vital, physiological reaction to many•stimuli has never been shown to cause disease in humans.192-194 This conclusion is supported by a recent animal study in which "clinically evident heart disease was not observed" in beagle dogs ex- posed to cigarette smoke and nicotine for up to 22 months.195 Although the pathogenesis of atheroscleresis ie Presently unknown,196-197a some have tried to assign nocotine a role in the causation of this disease. Such a theory, how- ever, has not been scientifically proven. iJor has any TIMN 450377

392 adverse health effects on smokers. 257 In view of the foregoing, it is not difficult, to see why previous attempts to regulate levels of "tar" and nicotine have been unsuccessful. The fact remains that no one has ever established any ingredient or group of ingredients as found in smoke to be harmful to humans. Therefore, there is simply no scientific basis for setting maximum levels of "tar" and nicotine or any other smoke constituent. It should also be recognized that efforts to reduce smoker exposure to various smoke components may well be unavailing. Studies suggest that there are sig- nificant differences between individuals in terms of carbon monoxide uptake after cigarette smoking, but there does not appear to be any difference when smoking differ- ent kinds of cigarettes.258 Moreover, as the Russell study demonstrates, individual smokers can easily compen- sate for decreased levels of smoke constituents by consciously, and perhaps unconsciously, varying their in- 259-262 smoking practices?59-262 According1 y, regulating levels of cigarette smoke components without regulating individual smoking practices may well be unproductive. „ae possibility must be faced that set- ting maximum levels of cigarette smoke components without a full understanding of the effects of all constituents as 393 found in tobacco smoke, i.e., in combination with each other, may result in hazards to smokers which do not presently exist. This may be illustrated by an experiment undertaken some time ago involving the toxic effects of filtered and nonfiltered smoke in test animals. The ex- perimenters believed that the filtered smoke would have less effect on the animals than the nonfiltered smoke. To their surprise, however, they found that the filtered smoke had a greater effect on the animals because the filtering allowed the animals to breathe the smoke more deeply into their lungs.263,264 Even Dr. Hammond recognized not long ago the possibility that for a number of reasons a so-called safe cigarette as to cancer might iricrease the risk to smokers from other diseases?65 And to illustrate this point from another field, one human study showed that persons on a low-fat diet had a decreased incidence of atherosclerosis but incurred a significantly increased incidence of cancer?66,267 Therefore, even well intended regulatory efforts - either by taxation or otherwise - in the absence of a scientific basis, could result in unforeseen health hazards. TIMN 450380 I

376 with smoke condensate is complicated, however, by the fact that there are constant chemical changes taking place in "tar."1S Hence, an older "tar" is chemically different from a fresher "tar" and, not surprisingly, observations of consequent differences in biological activity have been reported. 19 Similarly, the popular but unscientific notion that the exposure of smokers to various cigarette smoke constituents can be determined by analysis of cigarette consumption is untenable. The rate and amoun:. of absorption of various smoke constituents depends upon too many uncon- trolled factors which vary considerably among smokers, including, for example, the number, size and frequency of puffs; the length of time the smoke remains in contact with the mucous membranes; the acidity of the body fluids with which the smoke comes in contact; the depth and degree of inhalation; how accustomed the person is to smok- ing; the chemical and moisture contents of the tobacco smoke; the characteristics of the tobacco; the use of a filter; the acidity of the tobacco smoke; the agglomeration of smoke particles; the amount of moisture over which the 20-55 smoke travels; and even the time of day the person smokes.56 In turn, the tobacco arid tobacco smoke characteristics dPnnnd In larce measure upon the types of tobacco used, the way it is grown, the weather and other conditions during growth, the part of the plant from which the leaf is taken 57-78 d the wa the tobacco is cur d a d r d y e p ocesse . an n The sheer number of uncontrolled factors demon- strates that analysis of cigarette consumption cannot establish levels of cigarette constituents to which smokers are exposed. There are just too many variations in the smoking patterns of humans to draw conclusions about an individual's exposure from mere knowledge of the number of cigarettes smoked and certalnly no conclusions can be drawn about the exposure of smokers in genera1.79-85 For~exam- ple, Russell and his co-workers recently studied blood nicotine levels in people who had smoked cigarettes with varying amounts of nicotine. These researchers found that the blood nicotine levels of the smokers "bore no relation" either to the nicotine yield of the cigarettes used or to the number of cigarettes smoked. Thus, they concluded that smokers "regulate their nicotine intake in ways other than crude number of cigarettes smoked.° 86 As to the statistical arguments, there are re- ported statistical associations between smoking and some diseases. But, as many scientists have observed on numerous occasions, while statistical associations point to areass for further laboratory and clinical investigation, they cannot establish cause and effect. 87-99 70-087 0 - 76 - 25 'I'IlVIN 450372

378 Claimed statistical associations between smoking and various diseases, as well as overall mortality, are better explained by a genetic hypothesis (i.e., the smoker and not the smoking is responsible for the association) 100-10~Vhis is than by a cigarette-causation hypothesis. especially true where a small number of cigarettes (i.e., 1-10 per day) 'is said to account for large differences in disease rates between such light smokers and non-smokers 110 A genetic explanation for statistical association is sup- ported by such research as the studies of Dr. Yerushalmy relating to low birth weight babies and the twin studies 111-120 both in this country and in Sweden. The twin studies indicate that in monozygotic twins with discordant smoking 121,122 habits, smoking has no effect upon overall mortality. Scientists generally agree that chronic degen- erative diseases such as lung cancer, cardiovascular dis- ease and emphysema are statistically associated with many 123 factors other than smoking. Which, if any, of the observed factors play a role in the causation of these diseases, however, is as yet unclear. It may well be that some have nothing to do with causation but instead reflect one or 124-130 more underlying causes, such as a particular genetic type. This point is illustrated by Dr. Yerushalmy's observation, in connection with his study of the incidence of low birth weight babies among smokers and non-smokers, that the 379 higher incidence among smokers could well be "due to the smoker, not the smoking." 131 Critics of smoking frequently talk about dose- response relationships while ignoring any and all contrary data. For example, several studies have shown that the age of incidence of lung cancer does not depend upon either the age at which smoking commenced or the duration 132,133 of smoking or even whether or not one smokes. Like- wise, studies indicate that- the age of peak incidence of ,lung cancer is continually increasing even though, accord- 134-140 ing to some reports, people are smoking at younger ages. These data are simply not consistent with the thesis that the amount of cigarettes smoked determines one's risk for lung cancer. And,^even-though, as above noted, cigarette con- sumption data must be treated with caution when analyzing smoker exposure, the fact remains that.cigarette consumption data in various countries do not correlate with lung cancer death rates in those countries. For example, while the United States and 'Canada have the two highest per capita consumptions of cigarettes in the world, they rank 10th and 16th,•respectively, with regard to white male death rates -from lung cancer. Conversely, while,the United Kingdom, Finland and the Netherlands have lower per capita consumptions of cigarettes than the United States and Canada, they all TIMN 450373

388 mechanism whereby nicotine causes this disease ever been shown. Moreover, recent animal studies indicate that nicotine has no effect upon the development of atheroscler- otic lesions. 198-200 Lastly, it is frequently alleged that nicotine in cigarette smoke increases coronary arterial flow, thereby increasing a person's blood pressure. This response, how- ever, is of limited duration and, to the extent that it is activated by nicotine in cigarette smoke, it lasts only for a moment?01-203 It has never been established that this short term physiological effect produces disease in smokers. To the contrary, studies indicate that smokers generally tend to have lower blood pressures than do non-smokers.204-211 Frequently ignored are studies - both in humans and in animals - suggesting that nicotine might be bene- ficial to the smoker. ?12-214 The human studies su ggest that nicotine acts both as a stimulant and a depressant depend- ing upon the needs and mood of the individual215-217The animal studies show that nicotine facilitates learning and results in the improvement of various types of performances?18-22 While much more work remains to be done in this area, the possible beneficial effects of nicotine on humans must be considered in any objective analvsis nf cmn4i._ Carbon Monoxide In recent years, smoking critics have tried to 389 implicate carbon monoxide in cigarette smoke as a cause of cardiovascular disease. Despite considerable work, this still remains a theory rather than a scientifically established fact. Carbon monoxide is a normal body con- stituent created by metabolism; and the body can and does slowly destroy it. Without any exposure at all to external carbon monoxide in air, the blood contains from 0,2%to 1.0% of carboxyhemoglobin (the combination formed by this gas with the red blood pigment)?27. Many studies indicate that a 10% carboxyhemo- globin level, which people reach when caught in heavy city traffic, is rarely even noticed. Even a 15% level does not produce symptoms, such as headache (which is one of the earliest), in most people 2.28-232 One well known study reported that smokers, after smoking and inhaling from 10 to 15 cigarettes within a 33 lobin saturation period of two hours, showed a rise in he 2 to between 3.1% and 6.7% (average 4.3%). None experienced any symptoms attributable to carbon monoxide, which is not surprising since these levels are far below those ap- proved for long-time industrial exposure. Even if smoking does result in small increases L.n the :Level oY' earDoxy,nemog-.oD`~n _.n zmo,cevs, :L'c :li}s never been shown that these claimed small increases are harmful 234-237 to health. And, of course, smoking is only an intermittent TIMN 450378

232 ~umbees of cases and in the 5-year report these ratioe were 'aYer thm that for lun` cancer. There is an interesting contrast between Dr. Sterling's .,.usote lament that he must depend on unpublished (in ,entiGc journals) data from Hirayama's study and his glib -,orations of erroneous accounts In the lay press of the a+ied difficulties Hanunond and Aturbach encountered in yt>tiishint their studies of lung cancer In smoking beagles. oce I was assistant editor of the Archioes of Enuiron- -tn[al Health at the time, I can tesEify to the following !ctS: Dr. Auerbads did make his slides available for edrpendent review; the manuscdpts were not relected by NJoumal oJ the Americarr M.diealAtsociation, they were :ucmed to the authors for rwision; and the editor of the trchiues of Environmental Health subjected tbe manu- ,rriptt to out-ofotfice revi.wers who recommended publi- ation after certain rerlsions were made. The leveling off of lung cancer mortality rates Is an s><eetatloo? It la true that the rnte o/inaease bas begun :o diminish but mortaGty rates continue to rise except In re younger aY4 p'oups. But the younger age groups Netdbute propotitonately fewer cawa of lung cancer than :be older age groups. Undue emphesis 4{iven to the tunQes In the rates among the younger ap groups by 7lottin{ the rates on a loyarithmic scale. The relative .:npurtance of changes in the a8e-specific curves would be inter aen on an adthmetic scale. Furthermore, the few ,jnt cencer caset that occur In'the young may have a !i(fersnt etiqlog7r from those in older people, a possibility wuested by differences Lts the distribution of histological :pvs? Even If the {u a, ~r~~! et (riddence wen to level off, this vould not ' ~tql~ ~ atjument atainst the smoking-lunt tt could be readily explained by 1< a~tlon .fGek Only the most naive penon 4.deny` that chronic disewa Bke cancer have a aultitactodal etiolo`y. Since th4 occurrence of lung cancer m a Qartiaular indivldual depends not only on a major aRar but on other farxors `>ws weB, there Is a alling on its - 'meidena In a p.en populati.oa with a given aet of ronditlons. The proportlon ot susceptibies In the popula- iwn b'ilmlted by the'saeottdary factors. Therefore, after he level of smokiog has eeached a certain point in the 7epulation, further Increases In amobin(< may produce no mrresse ht the Incldeua of hm/ cancer: Dr. Sterling has proposed the procaa of selection as an erpdanation for miiny of the 1pldemlofdtlcal observations shicb favor the sawkin8-lutq canarhypothah.It Is easier lo show that the prauas of selection has operated In bis dlala of data to.oppose the hypothesis. For example, Ite naks "The eortstapt difference between men and women In !be iticldenct ot luri8 canaat bsr Pmiatad although the frequency of smoking among women has increased more rapidly than among men" and in 1975 he compares figures in 1965 with those in 1950. In 197z Burbanke showed that in recent years lung caneer ~'eatb rates have risen proportionately tnore rapidly in women than in men and his analysis suggested "that the difference between male and female rates is a simple function of the difference in their past cigarette tobacco use, a dose-response effect." Much of the rest of Dr. Sterling's paper is simple diversionary obfuscation, warranting no further comment. Truth is better served by recognizing that the evidence in favor of the smoking-lung cancer hypothesia Is overwhelm- ing. No matter where we look, the association is consistent, s4oft, and speciftc (considering the quantitative aspect of the araociat(on), smoking precedes the lung cancer, and coherence between the various Bnes ot evidence Is of a high order. The importana of this lias in the fact that the bypothesis provides us with a potent tool of disease prevention and control. The change in tJ7e risk of lung cancer among ex-amokus relative to the risk in continuing smokers Is a strong polnt in:- the evidence favoring the hypothesis. Whether the risk In exirnokera declines or stabilizes at the rate established at the time smoking is stopped,s the change is a salutary one which fits the observation~ of Auerbads et al.6 that the prevalence of atypical cells in the bronchial mueow of examokers decreaw with tbe passage of time after stopping imoking. As a clinician who treats patients with lung cancer, I find it very disheartening to deal with a disease so rapidly destructive and realize that In most casea the Blness would not have developed it the patient had not smoked. References 1. Boucot, lt. R., Cooper, D. A., Weiss, W., Carnahan, W. ' J., and : Seidman, H. 'The Philadelphia Pulmonary Neoplaama Research Project: Basic Risk Factors of Lung Cancer in Older Men. Am. J. Epidwniol. 95:4-16,1972. 2. Welsa, W. Predictions of Lung Cancer Mortality: The Dangers - of Extrapolation. Arch. Envfron. Health '' 28:114-117,1974. 3. Kyriakos, M., and Webbee, B. Cancer of the Lung in Young Men. J. Thona Cardiovasc. Surg. 67:634-648, 1974. 4. Burbank, F. U.S. Lung Cancer Death Rates Begin to . Rise Proportionately Mon Rapidly for Femalea Than for Mal.a: a Doee-Reeponw Effect7J. Chronic Dis. 26:473-479,1972. 6. Doll, R. 'ffie Age Distribution of Cancer:.lmplitattons for Models of Carciaopnesis. J. R. Stat. Soc. 134:133-186,1971. - 6. Auerbach, o., Stout, A. P.. Hammond, E. C., and Oarfinkd, L. Bronebial Epithelium in Former Smoken. ~ N. Esral. J. Med. 267:119-126,1962. cuntrnur: &Nn nANt.FR- A REBUTTAL 956 233 Commentary Smoking and Cancer.. . F.ditai s Nome: In rlre Septrmber 1975 issue of the Journal we pub- lishrd an arriclt by Theodor Sterling entitled "A Critiral Reas- senMent of EtmfeneS Bearing-un Smoking as tke Cause of Lang Cancer", fotlnaed by a rrbultul-by William Weiss. We publish hrre two letters concerning Dr. Sterling's paper, follawed by Dr. Strr- ling's.comments. An editorial on the sume subject appears on page 132 nf this isrur ofthe Journul. ' "Communication from Higgins' I should not like it to be thought by readers of the Ameri- can Journal of Public Health that my "sharp and incisive" review some five years ago of an earlier draft of the paper: "A Critical Reassessment of the Evidence Bearing on Smok- ing as the Cause of Lung Cancer" by Dr. Theodor D. Ster- ling• implies that I agree with his present publication. In fact my views are much closer to those expressed by Dr. W illiam - Weiss in his rebuttal. There are a few additional comments I should like to add to the points Weisg makes. 1. The leveling offoflung cancer mortality starting in 1954 - While this is true, as Dr. Sterling illustrates, at ages un- der65 in England and Wales it is not so inthe U.S. Figures 1, 2, and 3 show the age specific trends in mortality for men and white women in the U.S.r Among men, especially, non- white, the rates have continued to increase; among white women there was a dramatic increase in the rates during the 1950s. Far from casting doubt on the smoking-lung cancer hypothesis, the trends in women's mortality provide strong support for it. There is good evidence that women have in- creased-theirsmoking since 1955 (Table 1). U.S- national data are not available before that year. But there can be little . doubt that U.S. women were increasing their smoking in the 1940s, possibly. as in the U.K., particularly rapidly during World War Il? 2. Newer pruspectire sturlies Dr. Sterling's presentation of the'targe Japanese study conducted by Hirayama (1972)' was criticized by Dr. Weiss, who noted that the results again supported the smnking-lung cancer hypothesis. A tcn-year study of a representative sample of the Swedish population comprising 27,342 men and 27,732 women aged 18 to 69 has recently been published (Cedetlof. et af, 1975)! The relative risks among cigareUe smokers for lung cancer were comparable to those found in the other prospective studies (Table 2). , •See A1PH, September, 1975. pp. 939-953. AJPH February, 1976, Vo1.66, No.2 Deoth rater per u00,000 rrom n+ahenent neodacni at etw respuobry system, nd spec Anaa cs setondary (/60-aia) White moks uqed 25-74 In U.S 1940-1970 FIGURE t' In addition,.bigh risks were also found in pipe smokers, pos• sibly because of a greater tendency of Swedish pipe smokers to inhale. - ' 3, Other significant omissions Two serious omissions in addition to those noted by Dr. Weiss should be mentioned. First, the papers of Haenszel and his colleagues, 1962 and 1964s' e are ignored. This is all the more extraordinary since these studies, based on repre- sentative samples of the whole U.S. population, deal in de- tail wilh migration, mobility, and the urban fartor-all topics 'uf interest to Dr. Sterling. The'much larger gradients uf lung cancer_whh smoking thpn with these ot_hUfactqra wtrp Llear- ly demonstralcd. The atuhors commented on the univer- sality of the smoking class gradient in lung cancer mortality, there being no class that did not have a substantial excess risk among regular cigarette smokers. Second, the obscrvation made nearly ten years ago by 169 TIMN 450300

382 occurrence. Sometimes even the 1974 Doll study of British doctors is referred to as an example of evidence of a decreased risk of lung cancer after the cessation of smok- ing, but such reference is particularly inappropriate in light of Doll's views on this topic. As early as 1966, he stated that his study "suggested that the risk for acquiring the disease [lung cancer] remains almost the same as it was when smoking was discontinued and that the risk decreases in comparison with the risk of smokers only because the latters' risk continues to increase." 153 With the exception of a brief relapse in early 1974, Doll has maintained the view that cessation does not result in a decreased risk 154 and he confirmed this view as recently as October, 1974 at the XI International Cancer Conference in Florence, Italy. Moreover, recent analysis of Doll's data indi- cates that the cessation of smoking had little, if any, effect upon the incidence of coronary heart disease or 155,156 mortality in general. And Dr. Seltzer found that in three other prospective studies (i.e., Hammond, Kahn - Dorn and Framineham) cessation of smokinz by men over 65 did not result in a decreased risk for cardiovascular disease 1570ther studies indicate that the cessation of smoking results in 158-161 an increased risk for certain diseases. 383 In any event, cessation observations, as with other observations of statistical associations, establish a causal role for smoking. Those who 162-165 cannot choose to stop smoking are a self-selected group, i.e., they have not been forced by anyone to quit smoking and, therefore, their decision to quit is their own choice, not the result of a scientific study design. Accordingly, the decreased risk shown in some studies for ex-smokers may as easily be explained by a genetic or constitutional hypothesis as by a cigarette-causation hypothesis. 166,1617ndeed recent studies indicate that ex-smokers have a type of personality (i.e., Type B) more often found in non-smokers than in smokers. 168,169 As to the alleged "ha'rmful" constituents of cigarette smoke, critics claim that condensate ("tar"), nicotine, carbon monoxide, nitrogen oxides and hydrogen cyanide are the primary sources of toxicity. However, evidence concerning individual smoke components in isola- tion from each other cannot prove that such components as found in tobacco smoke are harmful to human smokers. Tobacco smoke is a highly complex mixture of Ii ~.. ,,._ , .....,~. ~ , .e. . c nnr.Pr~ ahnve, _ these ,.„.... G r...-.,, nn C,.... t.. cAa c. ingredients vary depending upon the'type of tobacco burned, the place where it is grown, the location on the stalk' from which the leaf is taken, the method of curing and TIMN 450375 I

390 activity, so that carboxyhemoglobin levels are reduced when not smoking. 238,239 Continuous breathing of air containing 50 parts per million of carbon monoxide will eventually increase the blood carboxyhemoglobin level to about 10~?~0 This air level has been set by the U. S. Occupational Safety and Health Administration as the ceiling concentration to which workers in industrial atmospheres may safely be ex- posed on an 8 hour time weighted average. Moreover, people - whether cigarette smokers exposed to small amounts of carbon monoxide or industrial workers exposed to large amounts - tend to develop increased tolerance levels to carboxyhemoglobin over time.241-243 With regard to chronic exposure to carbon monox- ide, it should be noted that several studies of men (tunnel and factory workers) exposed (10 to 18 years) in their work to high carbon monoxide levels have not shown any earlier or more substantial circulatory abnormalities at- tributable to atherosclerosis than the general population?4U0245 More recently, a human clinical study of a community in the United Kingdom found "no correlation between expired air carbon monoxide levels (in the population) and symptoms ~". . usr s:;gns oi ~ '.sc.aaem'.c heart disease:' 2~'' Hence, the general view has been that smoking was very unlikely to produce even any inconvenient effects, 391 let alone present any health ide. hazard, through carbon monox- nritro~en Oxides and Hydrogen Cyanide It is sometimes suggested that nitrogen oxides combine with secondary amines to form carcinogenic nitros- amines• While trace amounts of nitrosamines have been identified in tobacco smoke under laboratory conditions,247,248 there is still some question as to whether these compounds are present in fresh smoke inhaled by humans. 249-252 And, if present, the.quantities are so minute that substantial question still remains as to whether they could even possibly have any biological significance.253-255 Interestingly, Dr. Wynder - one of the foremost critics of smoking - has for many years been urging the use of tobaccos rich in cinogenicity of tobacco nitrates as a means of reducing car- smoke condensate 256 Since increas- ing the nitrate content of tobacco may result in increased levels of nitrogen oxides, a question arises as to how Dr. Wynder's suggestion can be reconciled with the position of those that claim that oxides of nitrogen are harmful to smokers. As to hydrogen cyanide, while it is known to be a toxic substance in large quantities, it has never been established that the relatively minute quantities of hydrogen cyanide, as found in tobacco smoke, have any TIMN 450379

253. Ingelfinger, F. J. Editorial. N E \1ed 293(25): 1319-1320; 1975. 254. Ncurath, G. Concerning the occurrence of N-nitroso compounds in tobacco smoke. I:xpcricntia 23(5): 400-404; 1967. 255. Neurath, G. The nitrogen compounds in tobacco smoke. Beitr Tabakforschung 5: 115-133; 1969. 256. Wynder, E.L., Hoffman, 1). Tobacco and Tobacco Smoke: Studies in Experimental Carcinogonesis. ew or : ca emic Press; . 257. Kensler, C.J. Components of pharmacologic interest in tobacco smoke. Ann N.Y. Acad Sci 90(Art. 1): 43-47; September 1960. 258. Cohen, S.I., et al., Carbon monoxide uptake in cigarette smoking. Arch Environ Ffealth 22(1): 55-60; 1971. 259. Armitage, A.K., et al., Pharmacological basis for the tobacco smoking habit. Naiure 217: 331-334; 1968. 260. Ashton,•1l., Watson, D.W. Puffing frequency and nicotine intake in cigarette smokers. Brit Med J 3(5724): 679-681; 1970. 261. Frith,.C.D. The effect of varying the nicotine content of cigarettes in human smoking behavior. Psychopharmacologia (Berl.) 19: 188-192; 1971. 262. Russell. A1.A.11., et al., Plasma nicotine levels after smoking cigarettes with high, medium, and low nicotinc yields. Brit Mcd J 2: 414-416; 1975. 263. Baettig, K., Driscoll, P. The differential effects of filtered and unfiltered cigarette smoke on two behavior.tests with rats. Fifth Int Congr Pharmacol 16; 1972. 264. Driscoll, P., et al., Effect of filtered cigarette smoke on rats. Nature 237(5343j:-37-38; 1972. 265. Statement made at the first public meeting of an ad hoc committee on Smoking and Health of the National Cancer Advisory Board, 9:00 A.M., Feb. 14, 1973, National Institutes of Health, Bldg. 31, Conf. Rm. 6. 266. Pearce, M.L., Dayton, S. Incidence of cancer in men on a diet high in unsaturated fat. Circulation 42(Suppl. 3): iii-52; 1970. 267. Pearce, a1.1.., Dayton, S. Incitlence of cancer in men on a diet high in polyunsaturated fat. Lancet 1(7697): 464-467; 1971. EXHIBIT E A REVIEW OF GOVERNMENT INTEREST IN "TAR" AND NICOTINE TIMN 450390

410 237. 224. Geller, I., et al., Effects of nicotine, nicotine monomethiodide, lobelinc, chToriTiazepoxi.7e, meprobamate and caffeine on a discrimination task in laboratory rats. Psychopharmacologia (Berl.) 20: 355-365; July 1971. 238. 225. Nelson, J.M., Goldstein, L. Improvemont of performance on an attention task with chronic nicotin e treatment in rats. Psychopharmacologia 20(4): 347-360; S eptember 1972. 239. 226. Nelson, J.M., Goldstein, L. Chronic nicotine treatment in rats: 1. Acquisition and performance of an attention task. Res Comm 240. Chem Path Pharmacol 5(3): 681-693; Ma y 1973. 227. Forbes, W.H. •'Carbon monoxide uptak e via the lungs. Ann N.Y. Acad 241. Sci 174(Art. 1): 72-75;. October 197 0. 228. Ilenderson , Y., et al., Physiological effects of automobile exhaust gas mid standards of ventilation for brief exposures. J_ Industr Hyg 3(3): 79-92; July 1921. 2112. 229.Ilenderson , Y., et al., Physiological effects of automobile exhaust gas and standards of ventilation for brief exposures. J Industr Hyg 3(4): 137-146; August 1921. 243. 230. Kensler, C.J. Components of pharmacologic interest in tobacco smoke. Ann N.Y. Acad Sci 90(Art. 1):43-47; September 1960. 231. Sayers, R.R., et al., Effect of repeated daily exposure of several hours to small amounts of:automobile exhaust gas. Public Health Bulletin No. 18G, United,States Public Health Service, as ington, , . 244. 245. 232. Stewart, R.D., et al., Experimental human exposure to carbon monoxide. Arch E-nviron Health 21(2): 154-164; August 1970. 246. : 233. llanson, H.B., et al., Effect of smoking on the carbon monoxide content of b1oU.-7MIA 100: 1481; 1933. 24'7. 234. Eckardt, R.E., et al., The biologic effect from long-term exposure of primates to carbon monoxide. Arch Environ Health 25(6): 248• 381-387; December 1972. 235. liofreutcr, D.11. ,, et al. , Carboxyhemoglobin in men exposed to carbon monoxide. Xr-cli Environ Ilcaith 4(1): 87-91; January 1962. 249. 236.hensler, C.J. Components of pharmacolol;ic interest in tobacco smoke. Ann N.Y. Acad Sci 90(Art 1): 43-47; Septembcr 1960. 250. 251, 252. 411 Stupfel, dl., Bouley, G. Physiological and biochemical effects on rats and mice exposed to small concentrations of carbon monoxide for long pcriods. Ann N.Y. Acad-Sci 174(1): 342-368; 1970. Hofreuter, D.11., et al., Carboxyhemoglobin in men exposed to carbon monoxide. Arcfi Environ llcalth 4(1): 87-91; January 1962. Kensler, C.J. Components of pharmacologic interest in tobacco smoke. Ann N.Y. Acad Sci 90(Art.1): 43-47; September 1960. DuBois, A.B. Establishment of "threshold" CO exposure levels. Ann N.Y. Acad Sci 174(Art.,i): 425-428; October 5, 1970. Henderson, Y., et al., Physiological effects of automobil6 exhaust gas and standards of ventilation for brief exposures. J Industr Hyg 3(3): 79-92; July 1921. Henderson, Y., et al.. Physiological effects of automobile exhaust gas and standards of ventilation for brief exposures. J Industr Ilyg 3(4): 137-146; August 1921. Sayers, R.R., et al., Effect of repeated daily exposure of several hours to small amounts of automobile exhaust gas. Public Health Bulletin No. 186, United States Public Ilealth Service, as ington, .; . Hickey, R. J., et al., Carboxyhemoglobin levels. JAMA 232(5): 486; 1975. Sievers, R. F., et al., Effect'of exposure to known concentrations of carbon monoxiae.7AMA 118(8): 585-588; February 1942. Rea, J. N., et al., Expired air carbon monoxide, smoking, and other variables: A community study. Brit J Prev Soc Med 27(2): 114-120; 1973. - Rhoades, J.W., Johnson, D.E. Method for the determination of N-nitrosamines in tobacco-smoke condensate. J Nat Cancer Inst 48(6): 1841-1843; June 1972. Rhoades, J.W., Johnson, D.E. N-dimethylnitrosamine in tobacco smoke condensate. Nature 236(5345): 307-308; 1972. Groenen, P. J. , ten Noevcr de Brauw, M. C. Determination of volatile N-nitrosamines in the vapour phase of the sYnoke from various tobacco products. B_eitr Tabakforsch 8(3): 113-123; 1975. Low, H. Nitroso compounds: Safety and public health. Arch Ecrviron Health 20(5): 256-260; 1974. Neurath, G. Concerning the occurrence of N-nitroso compounds in tobacco smoke. ExpCricntia :3(5): •10q-aU•1; 1967. Neurath, G. The nitrogen compounds in tobacco smoke. Beitr Tabakforschung 5: 115-133; 1909. TIMN 450389 I

424 F O O T N O T E S 1. Cigarette Advertising Guides, September 15, 1955 (see FTC Annual Report, 1960, p. 82). 2. Ibid. 3. Letter from William H. Brain, Attorney, Federal Trade Com- mission, to Bowman Gray, President, R. J. Reynolds Tobacco Co., dated December, 1959. 4. Smoking and Health, Report of the Advisory Committee to the Surgeon General of the Public Health Service, 1964, p. 75. 5. "I would endorse the Surgeon General's statement to you, which I believe in effect said he thought it would be better to leave the situation alone. It could result in some kind of misrepre- sentation or something misleading if one cigarette came out and said it had 1.5m tar, and so much nicotine in it, and another came out and said it had only 1. "Basically, this study has never arrived at what is a safe 'tar! and nicotine content, and they have not arrived at what in smoking is the agent as such that is causing cancer.. "They don't know whether to blame it [cancer] on nicotine, tar, or many other defined and undefined hydrocarbons and chemicals that take place, chemical reactions that take place when tobacco burns." Paul Rand Dixon, Chairman, Federal Trade Commission, Hearings Before the Committe_e on Commerce, United States Senate, 1965, Part I, pp. 419 & 455. 6. "While it seems at least plausible that cigarettes with lower tar and nicotine may present lesser health hazards, there is presently no proof that this is so." Surgeon General Luther L. Terry, 1965 Senate Hearings, supra, Part 1, p. 34. 7. 1965 Senate Hearings, supra, ftn. 5. 8. FTC News Release dated March 25, 1966. 9. Public Health Service technical report on "tar" and nicotine, Hearings Before the Consumer Subcommittee of the Committee on Commerce, U. S. Senate, August 23-25, 1967, pp. 7-8. 10. Reviewing Progress Made Toward the Development and Marketing of a Less Hazardous Cigarette, Hearings before the Consumer ~11tinr.T.ei 44.... ..F a- n--_ ~- , l - ... . .. ..,.,.. _ _ _, . ... .... ... ... ,_. ,.,_,:, ..I.~:..L..ie.cce ~ . aenate August 23-25,1967. ~ ~ ~ 425 11. 12. Federal Trade Commission, Report to Congress (Pursuant to the Federal Cigarette Labelling and-Advertising Act), dated June 30, 1967. Letter dated October 25, 1967, from Joseph W. Shea, Secretary, Federal Trade Commission to Howard H. Bell, then director of the NAB Code Authority. 13. Ibid. 14. 15. 16. Trade Regulation Reports Paragraph 18,959, Advisory Opinion - Digest No. 377, October 22, 1969. Committee on Interstate and Foreign Commerce Report on Public Health Cigarette Smoking Act of 1969, Report No. 91-289, June 5, 1969, p. 5. Hearings Before the Committee on Interstate and Foreign Com- merce, House of Representatives, April 15-May 1, 1969, p. 1118. 17. Ibid, p. 178. 18. Hearings Before the Subcommittee of the Committee on Appropria- tions, House of Representatives, March, 1969, Vol. 3, p. 57. 19. Letter dated October 23, 1970, to the Federal Trade Commission signed by representatives of Brown & Williamson Tobacco Corp., Larus & Brother Co., Inc., Liggett & Myers, Inc., Lorillard, a Division of Loews Theatres, Inc., Philip Morris, U.S.A., R. J. Reynolds Tobacco Co., Stephano Brothers, and United States Tobacco Company. 20. The Health Consequences of Smoking, A Report to the Surgeon General: 1972, U.S. Department of Health, Education and Welfare, 1972, p. xv. 21. 22. 23. 24. 25. 26. 27. Ibid., P. 212. Ibid., P• 216. Ibid., P• 215. Ibid., P. 216. Ibid. Ibid. Ibid., p. 220. TIMN 450396

416 dence "strongly suggests" that the lower the "tar" and nicotine con- tent of cigarettes, the less harmful the effects. (9) What was not answered, and has not been answered since, are the following criti- cal questions: Do "tar" and nicotine have health? any unfavorable effect on human If so, at what level of "tar" and nicotine does this effect occur? If so, how much lower in "tar" and nicotine content must one ciga'rette be than another to avoid this effect? These questions were not answered by hearings held in August 1967 as a result of claims made by the inventor and promoters of the "Strickman Filter" (not associated with the cigarette in- dustry). (10) Such hearings failed to produce support for the propo- ssition that "tar" and nicotine content was significant in terms of human health. Some statements made by witnesses invited by the government are contained in Exhibit A, attached hereto. In its first annual report (required_by.the.1965 Labeling Act) covering developments, trends and statistics in cigarette advertising, the FTC recommended to Congress in June 1967 that a '"statement setting forth the "tar" and nicotine content of each ciga- rette should be required to appear on the package and all such cigarette advertising." (11) In October 1967, the FTC released correspondence with NAB Code Authority Director Howard Bell confirming that the Commission 417 would not challenge representations of "tar" and nicotine content "where they are shown to be accurate and fully substantiated by tests conducted in accordance with the standardized testing methods and procedures used by the Federal Trade Commission." (12) .However, the FTC said "No matter how relatively low its tar and nicotine content, no cigarette may truthfully be advertised or represented to the public expressly or by implication, as 'safe' or 'safer'. ..." (13) In November 1967, the FTC published the results of the first of the semi-annual tests of "tar" and nicotine yields of 59 varieties of cigarettes which were initiated in August of 1967. Fifteen similar publications have been made since 1967. An advisory opinion was issued by the FTC in October 1969 rejecting advertising for a product claimed to be a "revolutionary invention that provides the answer to safer smoking" on the ground that none of the reports submitted in support of the invention shows that reduction in "tar, nicotine and benzopyrene content" results in a decrease of "diseases associated with cigarette smoking." (14) Congressional hearings in 1969 again failed to support the proposition that "tar" and nicotine content was significant in terms of health. Neither the 1965 Act nor the Public Health Cigarette Smoking Act of 1969 imposed any requirements with respect to "tar" and nicotine content. The 1969 report of the Committee on Interstate and Foreign Commerce of the House of Representatives (which followed what the Chairman described as the longest hearings he could recall) commented: TIMN 450392

414 A REVIEW OF GOVERNMENT INTEREST IN "TAR" AND NICOTINE CHRONOLOGY Government interest in the "tar" and nicotine levels of ' cigarettes dates back to the 1950's. Specifically in response to competitive marketing practices based on "tar" and nicotine content in cigarettes, the Federal Trade Commission in 1955 promulgated the Cigarette Advertising Guides forbidding health claims, either direct or indirect.(1) The Guides also prohibited representations based on "tar" and nicotine content when its significance ". . . has not been established by competent scientific proof. ..."(2) In 1959, the FTC informed cigarette manufacturers that it considered "all repre, sentations of low or reduced tar or nicotine, whether by filtration or otherwise, to be health claims."(3) The Surgeon General's Advisory Committee in 1964 reached no conclusion that "tar" and nicotine content of cigarette smoke had been proved to have health significance. The Committee expressly conceded, in fact; that nicotine in cigarettes "probably does not represent a significant health problem.".(4) During the 1965 Congressional hearings on cigarette label- ing bills, the Federal Trade Commission, the Public Health Service and the Departments of Commerce and Agriculture took the position that "tar" and nicotine had not been proved to have health signifi- cance. The 1965 report of the Senate Commerce Committee took par- 415 ticular cognizance of the views of the-Chairman of the Federal Trade Commission (5) and Surgeon General Terry. (6) The recognized facts were that there was (a) no proof that "tar" and nicotine had an unfavorable effect on health, (b) no proof that cigarettes with lower "tar" and nicotine content had less effect, (c) no proof of any "tar" and nicotine level above which there was an effect and be- low which there was no effect and (d) no evidence on which to base a determination of whether any difference in "tar" or nicotine con- tent between two cigarettes was or was not significant. During these hearings, the Chairman of the FTC specifically warned that calling attention to "tar" and nicotine figures'in advertising could result in "misleading" the public.(7) In March 1966, the Federal Trade Commission announced a. change in its position: cigarette manufacturers would be permitted to disclose "tar" and nicotine content in advertising. The only reason given was that the information "may be material and desired by the consuming public."(8) No new scientific evidence was described. Thereafter the FTC set up a cigarette testing laboratory. The Public Health Service held a one-day meeting of a small group in June 1966. No new evidence on "tar" and nicotine was announced following that meeting. The group did not demonstrate that "tar" or any specific ingredient was harmful, nor did,it venture to explain how the Surgeon General's Advisory rn~a,±Fee d. . __- in virtually exonerating nicotine.. Instead, the group merely stated in its "technical report" that the "preponderance" of existing evi-. TIl1ZN 450391

T T, , 394 It - 395 Okun, R. Statement presented i at Ilcarin s beforc the Consumer 14. . Subcommittee of the Committee on (.ommerce, Unitc States enate on f•c ruary ,, an 1, eria No. , pp. Z2TSZ39. 15. 2. Johnstone, R.A.W., Plimmer, J.R. The chemical constituents of tobacco and tobacco smoke. Chem Rev 59: 885-926; October 1959. 3, Bentley, H.R., Burgan, J.G. Cigarette smoke condensate: Preparation and routine laboratory estimation. Tob Man Stand Comm (4): 2-14, (15-19) ; 1961. 4. Chortyk, O.T., Schlotzhauer, W.S. Studies on the pyrogenesis of tobacco smoke constituents (a review). Beitr Tabakforsch 7(5): 165-178; 1973. S. Rigdon, R.H. Effect of tobacco condensate on respiratory tract of white Pekin ducks. Arch Path 69: 63-71; 1960. 6. Rigdon, R.H. Pulmonary neoplasms produced by methylcholanthrene in the white Pekin duck. Cancer Res 21:•571-574; 1961. 7. Kreshover, S.J. The effect of tobacco on epithelial tissues of mice. J Amer Dent Ass 45(6): 528-540; Novenlber 1952. 8. Saliey, J.J., Kreshover, S.J. The effect of topical application of carcinogens on the palatal mucosa of the hamster. Oral Surg 12(4): 501-508; 1959. 9. Reddy, D.G. et al. , Experimental production of cancer with cigarette tar. Tndian J Med Res 57(1): 125-127; 1969. 10. Hartwell, J.L. Surve of Co ounds Which Have Been Tested for Carcinogenic Activity. ..n e. ettes a, f.. ationa Cancer Tnstitute , ITJ3 .1-2. ll. Neyman, J. Assessing the chain: Energy crisls, pollution, and health. Unpublished Paper 31 pages; 1975. ~2. Reddy, D.C., et al., Experimental production of cancer with cigarette tar-li-Mian J Med Rcs 57(1): 125-127; 1969. 13. Shear, ?I.J., Leiter, J. Studies in caTcinogenesis. X1'I. Production of subcutaneous tumors in mice by miscellaneous polycyclic compounds. J Nat Cancer Inst 2: 241-258; 1941. Shear, M.J. Role of the chemotherapy research laboratory in clinical cancer research. J Nat Cancer'Inst 12(3): 569-581; December 1951. Shubik, P., Sice, J. Chemical carcinogenesis as a chronic toxicity test. Cancer Res 16: 728-742; 1956. 16. Davies, R.F., Whitehead, J.K. A study of the effects of altering the tar/nicotine ratio in experimental tobacco carcinogenesis. Brit J Cancer 24(1), 191-4, March 1970. 17. Reznik-Schuller, H., et al., Effects of cigarette smoke on the bronchial epithelium of Syrian hamsters: Ultrastructural studies. J Nat Cancer Inst 55(2): 353-369; 1975. . 18. Schonherr, H., et al., Aging of cigarette smoke condensate: Quantitative investigation of artifact formation via gas and particle phase reactions. Bietr Tabakforsch 7(1): 18-23; 1973. 19. Day, T.D. Carcinogenic action of cigarette smoke condensate on mouse skin: an attempt at a quantitative study. Brit J Cancer 21: 56-81; 1967. 1972. 20. Armitage, A.K., Milton, A.S. The release of adrenaline by nicotine from the adrenal medulla. in Tobacco Alkaloids and Related C~ o mP ou~nds~. U.S. von Euler (ed.). Oxfor : ergamon Press imite ; ~ _ 196 p 205-214. 21. Armitage, A.KK et al., Pharmacological basis for the tobacco .smoking habit. Aature 217: 331-334; 1968. 22. Armitage, A.K., Turner, D.M. Absorption of nicotine in cigarette and cigar smoke through the oral mucosa. Nature 226(5252): 1231- 1232; 1970. 23. Armitage, A.K., et al:, Absorption and metabolism of nicotine by man during cigarette smoking. Brit J Clin Pharmacol 2: April 1974. 24. Artho, A.J., Grob, K. Nicotine absorption from cigarette smoke. Z Praeventivmed 9: 14-25; 1964. 25. Ashton, 17., Watson, D.W. Puffing frequency and nicotine intake in cigarette smokers. Brit Mcd J 3(5724): 679-681; 1970. 26. Baumberger, J.P. The nicotine content of tobacco smoke J Pharmacol Exp Thcr 21(1): 35-46; February 1923. . 27. Beckett, A.II., Triggs, E.J. f:n_yme induction in man emnsoa t,W smoling. Nature 216: 587; 1967. 28. Bcncdict, R. C.. Lakritz. L. Simuttancn•ja dctermination of ph and redox potential: Application to cigarette smoke. Tutcicco,l77(1): 29-31; 1975. 29. British 'NIcdical Journal, Components of tobacco ssoke. Brit Med J 4(5b3S): 7Sb; 1963. 30. Bush, L.P., et al., influcnrc of puff frequency and puff volume on the alkalotd contcnt of s-iokc. .1 Agric Fd Chem 20(3): 676-678; TIMN 450381

418 "On the basis of these hearings, the Committee concludes that nothing new has been determined with respect to the relationship between ciga- rette smoking and human health since the hear- ings in 1964 and 1965. The arguments pro and con with respect to cigarettes are the same now as then, though supported by a larger statisti- cal base."(15) Statements to the House Committee in 1969 with respect to "tar" and nicotine emphasized that human beings do not smoke "tar"; that no relationship between laboratory reports on "tar" yield and human health has been established; that even if a disease producing substance were present in the "tar" it might be present in a very small fraction making the amount of total "tar" completely irrele- vant; and that nicotine in cigarettes, considered not to be an impor- tant health hazard by the 1964 Advisory Committee, has still not been scientifically established as hazardous.(16) Former Surgeon General Stewart said in 1969 that the "tar" and nicotine level "is a crude index and the'difference between one point, one milligram, probably doesn't make much difference."(17) During the 1970 House Appropriations Hearing, Surgeon General Stewart indicated, in fact, that the index was "very crude." [emphasis add- ed) (18) Despite such appraisals, the FTC in its 1969 annual report to Congress continued to recommend legislation which would require "tar" and nicotine listing on cigarette packages and in all adver- - ...,,. ... 7^ . _ . rnl a rpanirinQ "tar" and nico- tine listing in all cigarette advertising. In response to this action, U.S. cigarette manufacturers. agreed to voluntarily disclose 419 "tar" and nicotine content of cigarettes in all advertising. How- ever, this voluntary agreement concluded with a statement that the-submission or carrying out of this program does not con- ,titute an admission by any company that 'tar' and nicotine have any significance in relation to human health."(19) Subsequently, the FTC accepted the companies' voluntary plan by susiiending its rules making proceedings on "tar" and nicotine- didclosure in advertisements. The question of mandatory limits on "tar" and nicotine was, presented- to the American public in 1971 on "The Advocates," the popular series appearing on national public television. A viewing audience ballot following the nationwide broadcast indicated that 66% of the respondents disapproved of such government control. The 1972 Surgeon General's Report included a chapter (chapter 9) on allegedly harmful ingredients in cigarette smoke. This chapter was described as the "culmination of a one-day confer- ence held in June 1970."(20) It is curious that this meeting, which was deemed to merit the addition of a complete chapter to.the 1972 Report, was not even mentioned in the 1971 Report issued in January 1971, over six months after the June 1970 meeting. A full transcript of the meeting was eventually published in the record of Senate hearings held of the in February 1972. Examination transcript reveals how very little is known. Pertinent state- •ents of the conferees are set out in Exhibit B, attached hereto. The following excerpt from Chapter 9 illustrates the un- certainty which continues to exist as to the health significance of 1 I a TIMN 450393

420 various compounds, as found in cigarette smoke, including "tar", nicotine and carbon monoxide: "Of the hundreds of compounds identified in cig- arette smoke, some occur in the smoke in concen- trations which may be considered sufficient to present hazards to health. Other compounds ap- pear in borderline concentrations. Still others, although potentially harmful, are probably not present in sufficient concentrations to conti- bute to the hazard, and some maY be hazardous only when they interact with other substances in the smoke." [emphasis added)(21) s Chapter 9 of the 1972 Report also acknowledges several other important problems inherent in setting "tar" and nicotine limits: (1) Lowering "tar" and nicotine content may increase other effects claimed by some to be harmful.(22) (2) The possibility of "interaction" among various substances makes it "difficult to assess" reduction or elimination of any constituent.(23) (3) If smoking behavior is a response to "the need to reach a certain nicotine level ... lowering the amount of nicotine . . . might result in an in- creased inhalation of other hazardous substances." (4) There is a need for "better bio-assay systems to evaluate cigarettes" that may be modified.(25) (5) The individual smoker will continue to control "critical factors" regardless of variation in the product. These include the number- of cigarettes smoked, how far down the cigarette is smoked, and depth and frequency of inhalation.(26) Most of the articles cited as references in Chapter 9 merely identify certain compounds or gases in cigarette smoke or cigarette smoke condensate; they do not demonstrate that thPCP rnm- pounds or gases, as found in cigarette smoke, are harmful. It is 421 misleading to label them, as the 1972 Report did, "References on Harmful Constituents."(27) While three tables of substances are set out in Chapter 9, not one of the three (including the table which contains "tar", nicotine and carbon monoxide) is presented as listing known hazards. The strongest label attached (to Table 1) is "most likely." The only citation discussed in Chapter 9 is the "technical report" of "tar" and nicotine prepared by the Public Health Service in 1966 following the one-day meeting previously mentioned. In February 1972, hearings were held by the Consumer Sub- committee of the Senate Commerce Committee on Senate Bill No. 1454, which proposed empowering the Federal Trade Commission to set maximum "tar" and nicotine limits on cigarettes. Senator Frank Moss was the chairman of the Subcommittee and also introduced the bill being considered. Testimony presented to the Subcommittee revealed that there still was no basis to conclude that setting such limits would benefit the public health. Furthermore, while officials of the Department of Health, Education and Welfare and of the Federal Trade Commission endorsed the bill in principle, their testimony indicated that they were unwilling to be given the responsibility of implement- ing it.(28) Senator Marlow Cook, a member of the Subcommittee, commented on this inconsistency in his closing statement: "Their evasion of responsibility indicated to me that this proposal was seen, even by those who are disposed to crack down on tobacco when given half a chance, as being based on very tenuous scientific evidence. And as the record ~.L- nicotine content :...:::. ....:..... t.t,:.t _,,;. _.... ~...,,... nt of cigarettes had very little, TIMN 450394

426 28. 29. 30. 31. Hearings Before the Consumer Subcommittee of the Committee on Commerce, United States Senate, February 1, 3 & 10, 1972, pp. 27 & 51. ibid., p. 285. Minutes, Meeting of the Ad Hoc Committee on Smoking and Health (National Cancer Advisory Board), June 17, 1973, p. 1. The United States of America Before the Consumer Product Safety Commission, Petition of American Public Health Association and Senator Frank E. Moss for the Promulgation of a Rule Banning From Sale in interstate Commerce High Tar-Yield Cigarettes, February 1, 1974. 32. U. S. Consumer Product Safety Commission 33. 1974. News Release, May 17, Letter dated October 18, 1974 from President Gerald Ford to Senator Jesse Helms. 34. Ibid. 35 Federal Trade Commission, Report to Congress (Pursuant to the Public Health Cigarette Smoking Act), December 31, 1974, P• 7. 36. National Cancer Advisory Board, "Recommendation for Federal Government Regulation of Maximum Cigarette Yields of Noxious Smoke Components," Approved, November 19, 1974. 427 ExttIi31'1' A Ii1 YiEi'lli;t; I';;OC ;i ~~ :;?:';DE T3;iU 111E Di't'i LOi'MLfi1 Ai;D Ir1AuIKETI;';G 0F A LESS ]I,iZtinDOLS CIf yncTTE HEAT'~INGS Bsroar. xile CONS-LT1ILR SUBCO11I1IZTTLE OF TAC • CO1)ji~l't'~ E ~ 0' CORC +, UNITED STAT.CS SENATE \Ii;r:CrETFZ CONGRESS FIIt$T, SI•:jSiO-N P AUGUST 23, 24, AND 25, 1957 Seria2 No. 90-52 Printed for the usz of the Committee on Commerce * TIMN 450397 U.S. GOS-E:i.st;Csr I'f.lXTi\i: p;FICE .\l'_\$IlI\G1US : 19i:i

fl 422 if anything, to do with the cause of the con- . dition Senator Moss wants to cure."(29) Senate Bill No. 1454 was not reported out of committee. Senator Moss reintroduced a bill to limit "tar" and nico- tine in January 1973, and, despite FTC Consumer Protection Bureau• Director Robert Pitofsky's 1972 testimony [that any responsibility for regulation should be in the Department of Health, Education, and Welfare), continued to urge that the FTC be responsible for setting those limits. In 1973, Dr. Shubik of the Ad Hoc Committee on Smoking and Health appointed by the National Cancer Advisory Board, acknowledged the limits of scientific evidence in the area and instead of a manda- tory "tar" and nicotine content for cigarettes, he recommended a con- tinuation of voluntary industry reduction in "tar" and nicotine con- tent of cigarettes in response to consumer demand.(30) In February 1974, Senator Moss and the American Public Health Association petitioned the Consumer Product Safety Commission to prohibit sales of cigarettes yielding more than 21 mg. "tar", claiming that the limit "will remove the most dangerous varieties of cigarettes from the market."(31) After review by the Comptroller General of the U.S., it was announced in May 1974 that the CPSC "does not have the authority to act" on the Moss petition. (32) In August 1974, Senator Moss, the American Public Health Association and the _ . . . . ~ _ • • ' - ----- ----- -- -- - ~ ,~- . - _, _.. __....,.,,_.. .. .....,,,. , ....... _....,. _ .,.. .............~, .~.,.i: ~. .,,.., ,,.... _......, _ ..._ ..i ,. ' . D.C. Federal District Court to rule that the CPSC does have authority, to ban from interstate commerce cigarettes yielding more than 21 mg• 423 "tar". Presently various bills are pending which, if enacted into legislation, would confirm that CPSC is precluded from taking such action. In July 1974 Department of Health, Education and Welfare Secretary Weinberger requested Congress to grant authority to regu- late "tar" and nicotine content "and other ingredients shown to be injurious to health." (33) However, in a letter dated October 18, 1974, to Senator Jesse Helms, President Ford emphasized that the views expressed by Secretary Weinberger were solely his own and were not intended to represent the Administration's views on the advisability of legislative action to require regulation of cigarettes. (34) The 1974 FTC Report to Congress concedes the medical un- certainty which exists: ". ..( 'any suggestions) that concerns about the consequences of cigarette smoking are largely limited to those who smoke high 'thr' and nicotine cigarettes . . . are not supported by medical research. ..." (35) In late 1974, the ;dational Cancer Advisory Board recommended Federal legislative and/or regulatory action to empower a government agency to set maximum levels of "tar" and nicotine in cigarettes". ., that would become progressively - lower. . . ." (36) TIMN 450395

436 DR. DIETRICi: HOFFi•iAi:[. "DR. SCIaiELTZ: . . . The question is then do you want to reduce the NO in cigarette smoke? DR. HOFFi:ANti: I don't know; I'm not a health expert. I• don' t -- DR. KENSLER: L•7hat have you been voting on these health matters for?" p. 960 437 DP,. i,::':IEL HORN It seems to me that one of the questions that arises is-- one gets overwhelmed by th.~_ potential for the alteration in the significance of any one substance in the presence or absence of other substances, and the question is whether one knows enough to make anr judgments at all about the total, not knowing everythi:±g, or whether one can make some overall judgments. I am an amateur in this field." p. 866 "At the moment, we are the only consumers of this informa- tion and I v:ouldn't worry.a*-out outside consumers because the judgment as to what the group, as a whole, would agree on is quite separate from F::at gets transmitted as informa- tion." p. 882 "The question is: How much do we know about these substances and what are the probabilities? It is very different from saying that we know all there is to know about this. Tde are not expected to be in that position." - p. 889 "Now if scientists only had that degree of certainty about their level of knowledge, it would be easy to do these things. I think our t•:hole problem is that we are working in an area of uncertainty and the public health control side of it is trying to draw some.thing that at least has not so much the aF:earance of certainty but something that has a basis for action out of it." p. 898 "I hate to start with nicotine because I think it is fairlv obvious that this is so muc:, ., narL of s;~oking that it ~ ~aouldn't be smoking if there ,r.re not nicotine in it, or it wouldn't be the problam it is today." P_ 898 TIMN 450402

434 DR _ DhNIET, P. ASNES "'1'hc di.f:ficult y ficulty I find in loo7:ing up many of these components is that there isn't long term low level exposure data available. We are left with ma?:ing a judgment. These data are ungiven by themselves. S•7hen you get into interactions and the possibility that you have four or five or all of these at one dose in the same dose, then the data becomes almost non-existent. " p. 937 435 DR. ROBERT GRIFFITH "z couldn' t agree with this statement the way you have it here because I feel personally that just reduction of these things may not be the answer we are after. I have a strong feeling that nicotine is not as bad as a lot of other people feel it is. Actually, we might make more progress by trying to minimize things relative to nicotine than we would otherwise. r, personally, in terms of what I know, could not go along completely with this as you have it here. I think you can decrease all of these things and still may not end up with a safer product." p. 976 "DR. JARVIh: Would you say nicotine is an-innocuous substance? DR. GRIFFITH: I don't believe it will be as bad as 'we think." p. 977 "We could argue and express opinions. The i•;nportant thing is that we now have very low nicotine tobacco. Two-tenths percent nicotine. Very low. •-And we can a,-m What we are talking about now: I am expressing an opinion based on my years of experience which differs from your years of experience and we could all have our own opinions. The important thing is we now have material to use to test it and we can actually determine this. " subaect it to proper scientific tests, and we goinq to dn i.}„ p. 979 TIMN 450401

432 DR. UAiBLRTO SAFFIOTTI "A lot of our evaluations are really based on whatever little data we can find in the litera- ture, or produce, and in many, many cases we h ave found the data quite inadecu-,te to come up with any evaluation for individual compounds in the context of respiratory carcinogenesis." p. 885 "When- it comes to carcinogenicity, we have aone around this problem many times in different fields. There is so little data on respiratory carcinogene- sis that would be able to guide us in a discussion of carcinogenic agents by compound. I don't think we know enough." p. 886 - "All this is an approach that must be developed further. I find it very difficuit to evaluate hazards on the basis of very scanty data and come up with lists that are essentially pretending to say more than.ke actually know."- p. 888 433 DR. Cid::?LF.S KENSLER "As a general comimer.=, I would like to say that most of the regulatc=y actions that.are taken in advance are basec on scientific knowledge or based on animal exp~_rimentation. You find some- thing in this species or that species, so you say, well, it may very well do something like this in man. Therefore, let's eliminate this from our environirer._, if we can." • p. 875 "DR. LIPTON: Is it possible to give nicotine a clean slate with respect to effects on the respiratory epithe__um? DR. KENSLER: I do,'t know of any evidence that shows it to ha:•e a deleterious effect." pp. 899-900 "No, I don't have human evidence on any of this stuff. It's pretty skimpy." p. 939 . / "DR. JARVIK: The real problem here is whether nicotine is related to cardiovascular disease and whether coronary disease or atherosclerosis is related to nic^tine. That's the real central the disease with the greatest mortality in the U.S. DR. KENSLER: There are no data on that." p. 980 TIMN 450400

because of the relatively small number of heavy smokers. Also, heavy smokers may be especially subject to a variety of "selection° factors, uad, in addition, they tend to have characteristics that refiect a person, a state of life, and a mode of behavior which might indicate that the heavy smoker Is also an individud who behaves more recklessly with respect to hls health than do most of us. He tends to be a heary ddnker,vv't0 overeatet (usuadly inferred from heavler weights s hsokers or higher urum chodesterol lereh, or bodk). and underexarciser (see especially Tabie 16 tn Reference 9), aud is perhaps equally careless about other practices that may detract from his health. It is quite poedbie that the amount smoked Is, in a sense, a nwamre of hls'teeklessness." FinaOy, it is not always clear that the statement that a dpe.mponse curve exists is justified. Sometimes the zeal af ao inresOgator helps him see a dose-response relationship when none actua9y exists.ve•e 6,8 7 Halv About Evidence from Animal Studies7 tfuadlaer et al,se Leuchtenberger et al. e1 Shabad 90 aad Stewartvl reported a number of studies on mloking eonducted over a period of years In which cancer-prone aahrWs Inhaled cigarette smoke at rates approximating but usually exceeding that of human amokers. The results of all of these studles were negative. A two-part article by Hammond et al.vl in which they report the production of 1 lung cancer In beagles was, therefore, received as ap electrifying announcement by the scientific community. Unfortunately, the report of this experiment has been beset by many extraneous problems.* There haa been great dlscursion about this experiment. Much of the controversy revolves around whether or not slides and photographs submitted by the authors show any abnormalities.va.vc Another and a most surprising weakness is the failure of the authors to provide a control group. There are no controls Included which were subjected to comparable treatment but without exposure to cigarette smoke. Since dust and food particles were free to enter the lungs of the experimental animals along with the cigarette smoke, changes in lung tissue, Including cancers, would be expected. There seems to be no question that such particles were al9owed to enter since two dogs were reported to have died from asphyxiation caused by entering food particles during and right after smoking experiments and another four died from airborne Infections. It is well known that severe changes In the lung epithelium and true cancers result when foreign particles are embedded in lung s It started with a werl nnhlini"..t . preas ol' what had been found, which turned out to be quite different from what was finally reported!' Next, the investiaators refused to rnake their slides available for independent review." A manuscript submitted to the Jouma/ of the American Medical Auocintion wae turned down by a reported 12 reviewer.•' but was then immediately accepted for publication by the Archives of 8nuironmentat Health by the then-outgoing editor, without requiring the authors to furnish answers to the objectiona raised. 226 TABLE 12-Awnaa AaaAdlo.rad Mort.lity Ratu per LpOp00 MaMs f°r vears 1a68-19a7 f°r iHath '0f Ohte Reddwnta by Placa of Birth and Raa• Barn and d;ed'rn Ohio 94.66 85.36 Born in a souchern state 124.95 163.95 and died in Ohio Con+parabte U.S. ratn 98.78 136.35 • Saouu: ManNso aod Startina."• tissue.es,v~lo2 The failure to provide sham smoking experiments Is, therefore, almost unprecedented.t The authors pleaded two reasons for having neglected the necessary controls. First, they stated that nonsmoking humans do n:ot "smoke" unlighted cigarettes. Secondly, they pleaded a shortage of technicians.91 Neither exp4na- tion is of great relevance since humans do not Inhale smoke and air directly Into their lungs through a hole in the tntchea. Moreover, It would be preposterous to believe that In such an expensive and crucial experiment not enough money was provided to pay ns additional technician to ensure proper controls. Conclusion It would be very desirable If the antecedent for lung cancer turned out to be or only depended on sudt a simple event as smoking. The readiness with which the existing evidence has been accepted as demonstrating causality for cigarette smoking perhaps is the best measure for the desire to keep our world simple and orderly. But cancer is a complex disease. New important discoveries of how cancers are produced In animals continue to be reported. The role of many experimental conditions" of common pesticides,' or of nitrosamine compounds that have demonstrated high carcinogenic activity and may be produced in significant quantities by the Interaction of various common chemical components of our environmentio.,ios$ are but a few t The results of the experiment are in fact discounted by the recent NAB report on health effects of particulate polycyclic organic matter: "It may therefore be questioned what part of the effect in theae experiments can be attributed to smoking and what pert to other conditions imposed. Possible factors include the lesser degree of cleanliness of tubing in animals smoking cigarettes without filters and the _hyp_ersecretion in the smoking doab. The x' ncreaaec secret.ion in the smokers, with aspiration leading to infection; pulmonary damage; regen- erative changes; and bronchiolo-alveoler tumon" (pp. 178-179 in Reference 7; also see Reference 103). 4 The recent conference on occupational carcinogene- ses :o commemomte the 200th anniversary of Sir Percival Pott's monumental observation (March 24-27, 1975) summarizes the many recent discoveries on the relation between industrial and industrially caused ezposum and lung cancer. Unfortunately, much of the work disclosed there could not be inciutled in this paper.' °f a SMOKING AND LUNG CANCER 949 cases in polnt. But, the evidence for the claim that cigarette smoking causes lung cancer has never been without controversy. Severe criticism has been directed at key studies supporting this contention by some of the world's mostptominentstatisticians.3r•eo,so6-Ir3 Unfortunately, medical studies of lung cancer are published in medical joumals so that few, if any, of the many studies reporting a link between smoking and disease have ever been published in a principal statistical journal where the methods of sampling and data analysis would have received adequate review. Also, many of the widely circulated summades, testimonies, commission findings, and even direct reports of experiments have never been subjected to any scientiBc review whataoever. Consequently, a synthesis and reaaress- ment of this evidence at the present time would seem to be highly desirable. Since population statistics have contri- buted significantly to the belief of many that cigarette smoking is a cause of lung cancer, perhaps we should start by asking how population surveys and statistical studies can contribute to our understanding of the possibly complex causes of lung cancer or, in fact, any cancert This question Is basic since It Includes cigarette smoking as bne of the possible antecedents but does not ignore the rich evidence itrtplicating others. It It is true that existing population studies clearly indicate that cigarette smoking la the major cause of lung cancer, then additional large and expensive population surveys to uncover other causes may not be warranted. On the other haml, If this general conclusion Is not acceptable, then the groundwork may be Iaid for a much more Inclusive population study. Bertrand Russell once summarized the essence of acientific review as: ".. . it Is clearly imposdble that each of us should verify the facts of geogmphy; but it is Important that the opportunity for verification shouVd exist, and that Its occasional necessity should be recognized" (p. 620 in Reference 114). In a way, this report is an exercise In geography. It Is generally believed that existing evidence has established that smoking is a major cause of lung cancer. This project has undertaken to probe this belief-not to provoke or to please, but to dissect and to analyze. Because we adopt an analytical attitude, it may be difficult to avoid the impression that the focus of thia paper is on the critical side. The voluminous research on smoking and lung cancer contains many good as well as bad points. While a critical analysis tends to bring out Inadequacies, this should not be taken to Imply that none of the past studies are of value. Qalte to the contrary-many able Investigators have studied this difficult problem with great care and have gathered valuable data, and their analyses have significantly contri- but®d to the understanding of human disease. A critical ani yss o',:Zers an o s;ec:ive ,:ramewotit o.r irv i u.u: nl , n`_i; i used reaearch methods and analytic procedures but, unfortunately, without singling out Individual good or bad points or emphasizing how the work of many of theae scientists has enriched our knowledge. Bearing in mind these limitations, there Is yet one other pressing need to closely analyze the statistical studies and population surveys of the effects of smoking. Unfortu- nately, conventional procedures based largely on animal 950 AJPH SEPTEMBER,1976,VoI.86,No.9 227 studies are becoming ismcreaslagiy inadequate for determin- ing the toxicity of any eonsumed product or of a wide- spread pollutant.s 1 s'r 1 s Continuing surveys of human populations may be the major method for monitoring the health of large communities and protecting men from the untoward effects of the byproducts of his many activities. The smoking and health population studies form a model on how such surveys may be conducted. If this model h Invalid and possibly leads to rnlsleading conclualons, ae many respected statisticians and sclentists have claimed, then Incalculable damage may result in the long run If the shortcomings in thia model are not made pubitc. References 1. Innaa, J. R. M., QRland, B. M., Valerio, M. O.~ Petrucelli, L., Fiahbein, L., Hart, E. R., Pallotta, A. J., Bata., B. R., Falk, H. L., Gart, J. J., Rlein, M., Mitchell, I., and Patars, J. Bio.asay of Pesticides and Industrial Chemicals for Tnmorigenicity In Mice: A Preliminary Note. J. NaU. Cancer Inst. 42:1101- 1114, 1969. 2. Safftottl, U. Experimental Respiratory Tract Carcino- genesis. Prog. Exp. Tumor Res. 11:302-333, 1969. 3. Falk, H. L., Kotin, P., and Mahlar, A. Polycyclic Hydrocarbons as Carcinopm for Man. Arch. Environ. Health 8:721-730,1964. 4. Kotin, P., and Falk, H. L. Atmosphere Pollutants. Annu. Rev. Med. 16:233-264,1964. 5. SterBng, T. D., and Poliack, S. V. The Incidenca of Lung Cancer In the U.S. since 1956 In Ralation to the Etiology of the Disease. Am. J. Publlc Health 62: 162-168,1972. 8. Laskin, S., Kuschner, M., Drew, R. T., Capplello, V. P., and Nebon, N. Tumora of the Respiratory Tract Induced by Inhalation of Bia(chloromethyl) Ether. Arch. Environ. Health 23:136-136,1971. 7. National Academy of Sciencea. Biologic Effects of Atmospheric Pollutants: Particulate Polycyclic Or- ganic Matter. Report of the Committee on Biologic Effects of Atmospheric Pollutanb. National Aq(ddmy of Sciences, Washington, DC, 1972. ' 8. Bterling, T. D. Air Pollution and Smoking. Iritviron- ment 16:3-6, 25-26, 1973. 9. U.S. Public Health Service. Smoking and eslth. Report of Advisory Committee to the eon Genenl of the Public Health Service, U.S. part- ment of Health, Education, and Wdfara. U.B. Oovernmmt Printing Officr, Wadsington, DC, 1 64. 10. Wyndar, E. L. Etiolop of Lung Cancer: Reflectiom on Two Decades of Research. Carcinoma of the Lung: A Status Report of the National Cancer Institute4 Research. Cancer 30:1832-1339,1972. 11. Letter to the Editor. Science 173:676--677,1971. 12. Hammond, E. C. Smoking In Relation to the Death Rates of One Million Men and Woman. In Epidemi- olo/ical Approachea to the Study of Cancer and Other Chronic Diseases, edited by Haemul, W., pp- 19.-National Cancer fnstitute, Bethssda, MD, 11J66.• 13. U.S. Bureau of the Census. U.S. Census of Popula- tion: 1960. General Population Characteristio, United States Summary. Final ReportPC(1)-IB. U.S. Government Printing Office, Washington, DC, 1961. 14. Hammond, E. C. Some Preliminary Findings from a Prospective Study of 1,064,004 Men and Woman. Presented at the 90th Annual Meeting of tha American Public Health Association, Mi.ml Beach, October 15, 1982. TIMN 450297

440 DR. ER::=ST L. NYNDLI2 "DR. SCHt•!GLTZ: Is beta naphthylamine associated with bladder cancer? DR. HOFFMAN: There is an expert sitting here. DR. SCHI•iELT'L: Is bladder cancer associated with cigarettes? DR. WYNDER: If we have these substances as 'most likely' and 'possible'--'possible' is pretty good. We don't think we have evidence it is most likely to relate to bladder cancer but it is certainly _ossible. I would go along and give it the 'possible' rating. WE have agreed it is a carcinogen. It is possible it leads to bladder cancer in the concentration it is in cigarette sfoke. DR. SAFFIOTTI: Is anything not possible?" p. 911 . "We must make clear, Dan, that in none of the other substances about whic =we are not now speaking--with the possible exception of a high dose of carbon monoxide--do we have a-knot•in effect of concentration in man. We know about a number of these things as a to effect on animals. I take it your categories on the board has man at the end." 11-1 p. 931 "It seems to me the fact it has probably an effect ' is pretty good. I•fost likely, and, therefore, equated with our major disease entities; is diluting what we believe are to be the major things." p. 952 441 DR. MURRY JARVIK "of course, the problem is to determine the toxicity. How dangerous is it? I am sure there are a lot of problems there. Yet, this is something which I think the public and congressional committees and scientists would like to know." . 869 "That isn't the question. The question is whether nicotine is toxic, not addicting." p. 978 "That assumes the nicotine is innocuous. It's some- thing else iri the cigarette which is•the dangerous thing. I think assuming the nicotine is innocuous is unwarranted." p. 978, / TIMN 450404

396 31. Butler, J.T., ct al., A study of variables in analytical smoking 45. methodology. Toliacco Council Itesoarch Conference 1966. 10 pp. 32. Curran, J.G., Miller, E.G. Factors influencing the elution of high-boiling components of cigarette smoke from filters. Beitr 46. Tabakforsch 5(2): 64-70; 1969. 47. 33. Dalhamn, T., et al., Mouth absorption of various compounds in cigarette smoTe-.-Trch Environ Health 16(6): 831-835; June 1968. 48. 34. Greenberg, L.A., et al., The absor tion of nicotine in tobacco smoking. J Pharmaccl~xp Ther 104(2p): 162-167; February 1952. 35. flarke, H.P. The problem of "passive smoking". Munchen Med Wschr 112(51): 2328-2334; 1970. 49. 36. Isaac, P.F., Rand, M.J. Cigarette smoking and plasma levels of nicotine. Nature 236 (5345): 308-310; 1972. 37. Johnsop,-(4.R., et al., The distribution of products between mainstreamt..and sidestream smoke. Tob Sci 17: 141-144; 1973. 50. 38. Kershbaum, A., et al., Effect of cigarette, cigar, and pipe smoking on nicotine excretion: The influence of inhaling. Arch 51. Intern Med 120(3): 311-314; 1967. 39. Lakritz, L. , et al., Composition studies on tobacco. XXXVI. Changes in smoTce composition and filtration by artificial altera- tion of smoke pli: vapor phase constituents. Beitr Tabakforsch 52. 5(2): 71-73; 1969. _ 40. Lakritz, L., et al., Composition studies on tobacco. XXXIX. Changes in smoTce composition and filtration by artificial altera- 53. tion of smoke pH: formic and acetic acids and volatile phenols. Beitr Tabakforsch5(3): 104-108; 1969. 54. 41, Larson, P.S. Cardiovascular effects of nicotine and smoking: Part 1. The absorption and fate of nicotine:. Absorption of nicotine under various conditions of tobacco use. Ann NY Acad Sci 90(Art 1): 31-35; 1960. 55. 42. Larson, P.S., et al., Tobacco: Cx'erimental and clinical studies. - Baltimore: The Tt'ilTiams i•ins l.onpany; 1961. pp. . 56 43. Londvay, A.T., Laszlo, T.S. Cigarette peak coal tcmperature . . measurements.•Boitr Tabakforsch 7(5): 276-281; 1974. 57. 44. Morie, G.P. Fractiott of protonatod and unprotonated nicotine in tobacco smoke at various pll values. 'I'ob Sci 16.:__167; 1972. 397 Neurath, G. Tobacco products and smoke. General report. Beitr Tabakforsclt 4(1): 1-17; 1967. Ncwsome, J.R., et al., Vapor phase analysis of tobacco smoke. Tob Sci 9: 102-1T0; 1965. Norman, V. The effect of perforated tipping paper on the yield of various smoke components. Beitr Tabakforsch 7(5): 282-287; 1974. Russell, M. A. H. , et al. , Plasma nicotine levels after smoking cigarettes with high, medium, and low nicotine yields. Brit Me#_j 2: 414-416; 1975. Seehofer, F:, Wennberg, D. Effect of different puff profiles on yield and composition of tobacco smoke in machine-smoked cigarettes. Beitr Tabakforsch 6(1): 7-11; 1971. Sloan, C.H., Sublett, B.J. Moisture content of the particulate phase of smoke from filter and nonfilter cigarettes. Tobacco 160 (17): 28-32; 1965. Stedman, R.L., et al., Composition studies on tobacco. XXXIII. Changes in smokc coimposition and filtration by artificial altera- tion of smoke pH: pyridine and nicotine. Beiti• Tabakforsch 5(1): 13-17; 1969. Travell, J. Absorption of nicotine from various sites. Annals New York Academy of Sciences 90(1): 13-30; 1960. Wakeham, H. Recent trends in tobacco and tobacco smoke research. in The Chemistr of Tobacco and Tobacco Smoke. I. Schmeltz (ed.). New or : enum ress; . pp. . Waltz, P., Ilausermann, M. Investigations on smoking methodology. III. Method of approximation for the determination of the volume of smoke puffs on the basis of data from smoker observations. Mitt Gebie Lebensm Hyg 51(5): 325-328; 1960. Williams, T.B., Belk, C.W. An infared method for the determination of carbon monoxide levels in cigarette smoke. Beitr Tabakforsch 6(5): 210-215; 1972. Ague. C. Smoking patterns, nicotine Intake at different times of day and changes In two atrdiovascular variables while smoking cigarettes. Psychopharmacologla 30(2): 139-144; 1973. Artho, .1.J., Grob, K. Nicotine absorption from cigarette smoke. Z Prscvcntivmcd 9: 14-25; 1964. TIMN 450382 A61

404 146 iqcst, L.VV.R., ct al. , Summary oC a Canad ian study of smoking and hcalth. Canad ~l`diCss .J 96: 1104-1108; April 1S, 1967. 147. Dol1, It., Hill, A.B. Mortality in relation to smoking: 1'en years' observations of British doctors. Brit Mcd J 1: 1399-1410; 1964. 148. Doll, R., Hill, A.B. Mortality in relation to smoking: Ten years' observations of British doctors. Brit f•fod J 1: 1460-1467; 1964. 149. Doll R., Hill, A.B. Mortality of British doctors in relation to smoking: Observations on coronary thrombosis. in E idemiolo ig cal A roacites to the Studv of Cancer and Other Chronic aseases. 205'- 6 . pp. ationa l ancer nstitute lonograp o. 1; anuary 268. 150. Keys, A. , et al. , Mortality and coronary heart disease among men studied foi 23-years. Arch Intern Med 128(2): 201-214; 1971. 151. Keys, A., et al., Mortality and coronary heart disease among Aen studied-foi 23 years. Arch Intern Med 128(2): 201 214; 1971. 152. Doll, R., Hill, A.B. Mortality of British doctors in relation to smoking: Observations on coronary thrombosis. in E idcmio1orical A roaches to the Stud• of Cancer and Other Chronic iseases. , anuary . 19 ationa Cancer Institute onograp No. pp. 205-268. 153. Doll, R. Bronchial cancer and tobacco. Bronches 16(5): 313-324; 1966. 154. Doll, R. The age distribution of cancer: Implications for models of carcinogenesis. J Roy Stat Soc 134(2): 133-166; 1971. 155. Seltzer, C.C. Critical appraisal of the Royal College of Physicians' Report on Smoking and Health. Lancet 1(7744): 243-248; January 29, 1972. 156. Seltzer, C.C. Smoking and coronary heart disease. New Eng J Med 157. 158. 288(22): 1186; May 31, 1973. Seltzer, C. C. Smoking and coronary heart disease in the elderly. Am J i\1ed Scl 269(3): 309-315; 1975. L'pstein, P.li., ct al., l?pidcmiological studies of cardiovascular disease in a total community--Tecumseh, Michigan. Ann lntern Med 62(6): 1170-1187; 1965.. "'.-.. i.... ..,.. - t ys`cn 159. studied for*23-years Arch Intcrn Sicd 128(,`'): 201-21 4-, 1971. 160. Reid, D.D., ct al., Studies of discasc among migrants and native populations in Great Britain, Nori:ay, and the United Statcs. 111. Prevalence oC cardiorespiratory symptoms among migrants and nativc-born in thr United States. Nat Cancer Inst MonoGr 19: 321-3Jb; 19(~b. 405 161. Seltzer, C. C. Smoking and coronary heart discase in the alderly. Am J l.1ed Sci 2fi9(3): 309-315; 1975. 162. Burch, P. R. J. Death and coronary attacks after giving up cigarette smoking.~,Lancet 2(7896): 1564; 1974. 163. Friberg, L., et al., Mortality in twins in relation to smoking habits and alcohol problems. Arch Environ Health 27(S): 294-304; 1973. 164. Gordon, T., Kannel, tV. Multiple contributors ta coronary risk implications for screening and prevention. J Chron Dis 25(10-11): 561-565; November 1972. 16S.,Yerushalmy, J. Self-selection--A ma or j problem in observational . studies i P d n rocee in s of the 6th Bkl .ereey Symposium on lfathematic S tatistics an ro at i iv n P~ 166.Burch, P.R. J. Death and coronary attacks after giving up cigarette smoking. an t 2(7896): 1564; 1974. 167. Fisher, R.A. Dangers of cigarette-smoking.•Brit Med J 2(5039): 297-298; 1957. 168. Caplan, R. D. , et al., Relationships of cessation of smoking with Job streae, personality, and social support. A I P ch 60(2): 211-219; 1975. 169. Thomas, C. B. , et ai., Personality characteristics of medical atudents as reflectcd by the strong vocational interest test tvith special reference to smoking habits. Johns llopkins hled J 127(Oy: 323-335; 1970. S, .170. Lijinsky, iV. Statement presented at IlearinGs before a Subcommittee of the Committee on Covcrnmcnt 0 erations ouse o c resentatives, arc p. a . 171. Lijinsky, 4V. Statement presented at Ilearings before a Subcommittee of the Committee on Government 0 crativns uouse o emesentatives, larc t b-o0, 172.Lijinsky, tV. Statement presented at Ilearings before a Subcommittee of the Committee on Government 0 crattons ousc o eiresentatives, arc t b-a, i. pp. U- .W. TIMN 450386

398 58. Bates, W.W., et al.. Pro9uction factors affecting chemieal properties of the flue- 59. 60. cured leaf: Part VII. Influence of aging and procrssing. Tobacco 177(13): 48-50; 1975. Brunnemann, K.D., Hoffmann, D. On the pii of tobacco smoke. Presented at the CORESTA/TCRC Meeting, Williamsburg, Va. October 23, 1972. 19 pages. Brunnemann, K.D., Hoftlnann, D. The pH of tobacco smoke. Food Cosmet Toxic 12(1): 115-124; 1974. 61. Chang. C.S., Johnson, W. H. Moisture and weight distributions In brlghtleaf tobacco. Tobacco 177(2): 68-70; 1975. 62. Chaplin, J. F. Comparison of type 32 and flue-cured tobacco cultivars produced under fluetcured culture when.air- and flue-cured. Tobacco Science 177(20): 32-34; 1975. 63. Chortyk, O.T., Schlotzhauer, W.S. Studies on the pyrogenesis of tobacco smoke constituents (a review). Beitr Tabakforsch 7(5): 165-178; 1973. : 64. Curran, J.G., Dfiller, E.G. Factors influencing the elution of .high-boiling components of cigarette smoke from filters. Beitr Tabakforsch 5(2): 64-70; 1969. 65. Darkis, F.R., Hackney, E.J. Cigarette tobaccos: Chemical changes that occur during processing. Ind Eng Chem 44(2): 284-291; February 1952. 66. Elllott. J. M. The effects of stage of topping flue-cured tobacco on certain properties of the cured leaves and smoke characteristics of cigarettes. Tobacco Science 177(2): 28-30; 1975. 67. Kittrell, D. U., et al.. Effects of leaf numbers per acre and nitrogen rates on the agronomic, economic and chemical characteristics of bright tobacco. Tobacco Science 177(2): 63-66; 1975. 68. Legg, P. D., Collihs, ro.13. Part It. Influence of genetic factors. Tobacco 177(2): 10-12, Ifi; 0?a. 399 Ncurdth, G: Concerning the occurrence of N-nitroso cu.%Pu......n in tobacco smoke. Expcricntia 23(S): 400-404; 1967. 70. Norman, V. The effect of perforated tipping paper on the yield of various smoke components. Beitr Tabakforsch 7(5) : 282-287; 1974. 71. Rodgman, A., et al., The composition of cigarette smoke. YI. Comparison of-Uilferent tobacco types. Tob Sci. 5: 1-S; ]961. 72. Samfield, M. The anatomy of a cigarette. Part 1: Construction and combustion. ?owcco 177(12): 38, 40, 47; 1975. 73. Sensabaugh, A.J., Cundiff, R.H. A new technique for determining the pH of whole tobacco smoke Tob Sci 11: 25-30; 1967. 74. Spears, A. W. Summary. b cco 177(13): 51, 52. 56; 1975. 75. Terrill, T. R. Production factors affecting chemical properties of the fiuticured leat: Part V. Influence o:f harvesting variables. Tobacco 177(8): 72-74, 76; 1975. 76. Tso, T.C., Gori, G.B. Effect of tobacco characteristics on cigar- ette smoke composition. in The Chemistr of Tobacco and Tobacco Smoke. I. Schmeltz (ed.). New or : enum Press; 1972. pp. 31- -63. 77. Tso, T.C. Effect of farm production practices on nicotine and total particulate matter in cigarette.smoke. in Toward a Less Harm~ful Cig_~arette. National Cancer Institute Dfonograp o. 28. une,.IJ68. pp. 97-ill. 78. Tso, T.C., et al., Chemical studies on tobacco smoke: XXI. Correlatioa anTmultiple regression among selected cigarette- • smoke constituents and leaf characteristics of Bright tobacco. Beitr Tabakforsch 7(3): 190-194; November 1973. 79. Adams, P.I. Dteasurements on puffs taken by human smokers. Presented at the 20th Tobacco Chemists' Research Conference, Mi t -S l N ns on a em, . •, ovem er, pages. 80. Armitage, A.K., et al., Pharmacological basis for the tobacco smoking habit. Nasurc 217: 331-334; 1968. 81. Ashton, H., et al., Puffing frequency and nicotine intake in cigarette smTcers. Brit Aled J 3: 679-681; 1970. 82. Baker, R. R. Contributions to the draw resistance of a burning cigarette. Beftr Taittkforsch 8(3): 124-131; 1975. 83. Bentley, II.R., Burgan,'J.G. Cigarette smoke condensate. Prcparation and routine laboratory estimation. Tob l.Ian Stand Comm (4) 2 : -14, (1s-19); 1961. 84• Frith, C.D. Tne effect of varl•inl; the nicotine eo t n ent of cigarettos in humcut smoking bcha~•ior. 19: 188-192; 1971 Psychophacolofia ferl ) . . TIMN 450383 I

428 EXHIBIT A Statements of Witnesses Invited by the Government to Attend'the F:earings Before the Consumer Subcommittee of the Committee on Commerce, United States Senate, August 23-25, 1967. "A few words of caution are pertinent if filtration, absorption, and chemical modification of the smoke are planned as remedial steps. These include the possible inadvertant removal of carcinogen neutra- lizing substances from cigarette smoke, that is, anticarcinogens as well as possibly increased biological•availability. . . ." (Dr. Paul Kotin, Director, Division Environmerital Health Sciences, Public Health Services, p. 20) "But there is this innate hazard associated with assuming that if you reduce an agent known to be hazardous, that automatically you are doing this and,this alone. Corollary effects could neutralize your reduction, or even increase the hazard." (Kotin, p. 49) " . I know of no direct evidence based on human studies that one cigarette is less harmful than another in relation to death rates and to serious diseases such as lung cancer, coronary artery diseases, and emphysema." (Dr. E. Cuyler Hammond, Vice President, Epidemiology and Statistics, American Cancer Society, Inc., p. 167) - "I do not think at this time we have any conclusive evidence that the harmful effects as far as cancer in man is concerned is in the tar, or is in the nicotine, but it is a pretty good guess it is in one or both of them combined. . . . but a guess is . no evidence."• (Hammond, p. 169) "The big problem is to find out whether . . you have accomplished anything in rcducind the harmful e;:;:ects. My -quess iLs that reducing tar and nicotine does reduce tf:e harmful effects, but this is a long wa,y from yettind obj_ ctive evidence on it 7emphasis ac:ded)."(Hammond, p. 171) ' - - 429 "(ta ore research is required before it can be concluded with certainLy that chemicals (or some combination of c}u~micals) coni:ained in tar are mainly or entirely re- sponsible. . . . (Hamcond, p. 174) "F,ut nicotine is very, very rapidly eliminated from the body. And it is eliminated so fast that if you take it in the same amount in small dosages, spread over a period of many hours, it does very little except give some sensations that are probably pleas- urable." (Hammond, p. 168) "At this time, there is no evidence one way or the other as to whether nicotine is involved in the asso- ciation between cigarette smoking and the development of emphysema." (Hammond, p. 174) "(iQ)e simply do not know just what specific agents are involved." (Dr. George E. Moore, Director of Public Health Research, New York State Department of Health, p. 26) . . "It should be noted, however, that a specific threshold level at which no risk occurs cannot be deduced from the data." (Dr. Ernest i9ynder, Associate Member, Sloan- Kettering Institute for Cancer Research, New York, N.Y., p. 35) "It would remain for research, however, to determine what would be the tolerable level for different kinds of people." (Dr. William Stewart, Surgeon General, Public Health Service, p. 153) . "F:e are not sure we have everything that is in the tar; we need further pursuit of these avenues. We4eed a 'better understanding of the gaseous phase, what happens in that. We are not sure we have everything in there. tle need to do more research on what different components are added, when things are added to tobacco, different kinds of tobacco." (Stewart, p. 165) Y TIMN 450398

402 120. Yerushalmy, J. Infants with low birth weight born before their mothers started to smoke cigarettes. Am J Obstet Gynecol 112(2): 277-284; 1972. 121. Friberg, L., et al., Mortality in smoking discordant monozygotic and dizygotic twT_ns. Arch Environ Ilcalth 21(4): 508-513; 1970. 122. Fribcrg, L., et al., Mortality in twins in relation to smokir.g habits and alcohol problems. Arch Environ Health 27(5): 294-304; 1973. 123. Palmer, A. J. Diet and atherosclerosis. Med 3 Aust 1(17): 539-543; 1975. 124. Corday, E., Corday, S.R. Prevention of heart disease by control of risk factors: The time has come to face the•facts. Amer J Cardlol 35(2): 330-333; 1975. 125. De Faire. U., et al., Concordance with respect to mortality in ischaemic heart disease and cerebrovascular disease, a study on the Swedish Twin Registry. CVD Epidemiot Newsl 18(1): 21; 1975. 126. Ivlcilhany. M. L., et al., The heritability of blood pressure: An investigation of 200 pairs of twins using the cold pressor test. Johns Flopkins Med J 136(2): 57-64; 1975. 127. Murphy, E. A. Genetics In hypertension: A perspective. Circ Res 32(5): (Suppl. 1) 129-138; 1973. 128. Pesonen, E., et al., Thickenings in the coronary arteries In infancy as an Indlcation of genetic factors in coronary heart disease. Circulation 51(2): 218-225; 1975. 129. Shottz, R.1. , et al.. The relationship of reported parental history to the incidence of coronary heart disease in the aeestern Collaborative Group study. Am J Epid 102(4): 350-356; 1975. 130. Steinbach. M., et al., Familial clustering of degenerative cardiovascular diseases. Rev Roum Med Intern 13(1): 13-18; 1975. 403 131. Ycrushalimly, J. Infants with low birth weight born before their mothers started to smoke cigarettes. Am 277-234; 1972 J Ubstet Gynecol 112(2): . 132. fassey, R.D. Some problems of lung cancer. Lancet 2: 107-112; 1962. 133. Pike, M.C., Doll, R. Age at onset of lung cancer: Significance in relation to effect of smoking. Lancet 1: 66S-668; 1965. 134. Bcicher, J. R. The changing pattern of bronchial carcinoma. Brit f Dia Chest 69 247-258; 1975. 135. Burch, P.R.J. Smoking and cancer. Lancet 1(7809): 939-940; 1973. 136.Gilliam, A.G., et al., Trends of mortality attributed to carcinoma 628of; the 1961. lung: The declining •rate of increase. Cancer 14(3): 622- 137.Langston, H.T. Lung cancer--future projection. J Thorac Cardiov Surg 63(3): 412-415; 1972. 138.Lees, T. The'fall.of the cancer wave. Lancet 2: 443; 1965. 139.Lees, T.iV. Smoking and Luntt Cancer. Edinburgh: The Darien Press; 1959. pp. 1-~[. 140.Phillips, A.J. An analysis of the increase in lung cancer in Canada. Canad Ided Ass J 95: 1172-1174; 1966. 141.Lee, P. N. (ed. ). Tobacco Consumption in Various Countries. London: Tobacco Research Council; 1975 pp, 4.5, 142.Segi, M., et al., Cancer Mortalit for Selected Sites in 24 Countries Fo.•7 ~•~• (19 y apanes e ancer ociet 9 pP• , , 110, 1 1_ Y: ovem 143. U.S De t f er p, o Ilealth, Education, and Welfare, Public Health Service, The Ilealth Conse ucnces of Smokin : A Rep`tp the Surgeon ee1.1_: . p. , 144. Burbank. F. Patterns in Cancer Mortalitv in the United States: 1950-1967. Nationa (ancer nstitut e onograpt No. P~J0, 92 99 191 198 , , , . : ay 145. Ourbank, r•. Patterns in Cancer Mortal it.• inen_,ne- una.. r:mcer ns'titutc (otiograp~ o. ~~ • :es: 90,192, 99, 191, 198. ~ Y TIMN 450385

446 STATEMENT BY TXEODORE D. STERLING, Ph.D. February, 1976 447 I am Theodore D. Sterling, Professor of the Faculty of Interdisciplin- ary Studies and Director of the Computing Science Progras, at Simon Fraaer University. Formerly, I was a Professor in the Departiment of Applied N.the¢atics and Computer Science at Washington University, St. Louts, Nis- souri, Prior to that, I wes a Professor of Biostatistics at the College of Nadicine, University of Cincinnati. At vArious times, I have served as a consultant on Computer Data Nanagement and Statistical Problems to the National Science Foundation, Veterans' Administration, U.S. Public 8ealth Service, Department of Agri- culture, Environm®ntal Protection Agency, Federal Trade Commission, Environ- ment Canada, and various industries. I Iave served as expert witness on certain environwental contaminants at various times to a Royal C`olnaission In Canada and to cvmatttees of the U.S. Senate and State Legislatures. Ny curriculum vitae and list of publications are attached. I have also attached Appendices which discuss sore fully soee of the views presented in this statement. The field In which I teach and in which I conduct the majority of my research concerns the collection, processing, and interpretation of data. A large number of my research efforts have concentrated specifically on the analysis and interpr.etation of data concerning environmental health problems• such as the effects of lead, radiation, air pollution, and herbicide exposures. I was especially pleased to learn that this Committee plans to hold a series of hearings on Environ-rAi v",it~ 7, ,~.. ,,=re ~. am convinced that numerous, highly toxic environmental carcinogens are receiving inade- quate public attention. Nonetheless, I aA opposed to the Bill under consi- deration by this Coramittee. TIMN 450407

406 173. Akin. F. J. , Cbamberlain, 1W. J. Inhibition of tumor promotion by a nvutral fractton of cigarette smoke condensate. J Nat Canccr Inst 52(2): 613-615; 1974. 174. Finzi, C., ct al., Interference among polycyclic hydrocarbons in experimental s~n carcinogenesis. Europ J Cancer 3(6): 497-501; 1968. 175. Iloffman, 11.E„ Griffen, A.C. Action of cigarette tar and smoke on chemically induced carcinogenesis. Texas Rep Biol Aied 16(3): 333-345; 19S8. 176. Stedman, R.L. The. chemical composition of tobacco and tobacco smoke. Chem Rev 68(2): 153-207; 1968. 177. Hueper, W.C., Conway, W.D. Chemical Carcino enesis and Cancers. 19 Springfield, Ill.: Charles C. omas; • pp. 73-, 178. Falk, H.L., et al., Inhibition of carcinogenesis: Theeffect of polycyclic hy~crocarbons and related compounds. Arch Environ Health 9(2): 169-179; 1964. 179. Hill, W.T., et al.,, Inhibition of 9,30-dimethyl-l,2-benzanthracene skin carcinogenesis in mice by polycyclic hydrocarbons. Cancer Res 11• 892 89 - 7 9 i , 1 51. 180. Lacassagne,, A. , et al., Inhibition of the carcinogenic action produced by a weacly carcinogenic hydrocarbon on a highly active carcinogenic hydrocarbon. Brit J Exp Path 26: 5-12; 1945. 181.Riegel, B., et al.y dlelay of ine.thylcholanthrene skin carcino- genesis in mice-gy 1,2;5,6-dibenzofluorene. Cancer Res 11: 301-303; 1951. 182.Steiner, P.E., Falk, H.L. Summation and inhibition effects of weak and strong carcinogenic hydrocarbons: 1:2-benzanthracene, chrysone, 1:2:S:6-dibenzanthracene, and 20-methylcholanthrene. Cancer Res 11: 56-63; 1951. 183,Van Duuren,-B.L., et al., Carcinogenesis studies on mouse ikin and inhibition of.tu~nor-induction. J Nat Cancer Inst 46(5): 1039- 1044; 1971. 407 j84.Lotlikar, p.D., Za1~ts~TOxKnloft2~cetamidofluorenenby monoxide on the N- and ring Y Yiatio hamster microsomal preparations. Biochem J 144: 427-430; 1974. 185.Webcr, R.P., ot al., Nicotine inhibition of the metabolism of 3,4-benzopyrene,, a carcinogen in tobacco smoke. Science 184(4141): 1081-1083; June 1974. 186,Druckrey, H. Alkylating agents: Alkylating substances and their possible presence in tobacco, tobacco smoke, and polluted air (introduction). Alk Wirk Verb pp. 33-36; 1968. smoke, Chem Revh59ch885c926co0ctobern1959f 187.Lobaccon andRtobacco pr 188.Stedman, R.L. The chemical composition of tobacco and tobacco smoke. Chem Rev 68(2): 153-207; 1968. 189,U.S. Dept of Health, Education, and Welfare, Public Health Service, Smokin and Health: Re ort of the Advisor Comrpittee to the Sur eon enera.o tie u~.c Hea ti ervice, , p. . 190.U.S. Dept of Health, Education, and Welfare, Public Health Service, Smokin and Health: Re ort of the Advisor Committee to the Surgeon enera o tie u ic ea t~ ervice, , p. 144. 191.Ruch, T.C., Patton, H.D. (eds.). Physiology and Biophysics, W.B. Saunders Co., Philadelphia, 1~ .-p. IT44; - 192.Jenkins, C.D•, et al., Cigarette smoking: Its relationship to coronary heart iTisease and related risk factors in the Western Collaborative Group Study. Circulation 38: 1140-1155; December 1968. 193.Seltzer, C.C. The effect of cigarette smoking on coronary heart disease: Where do we stand now? Arch Environ Health ?0: 418-423; March 1970. 194.Tucci, J.R., Sode, J. Chronic cigarette smoking: Effect on adrenocortical and sympathoadrenomedullary activity in man. JA7•La 221(3): 282-285; 1972. 195•Ahmed, S. S, , et al., Cardiovascular effects of long-term cigarette smoking and nicotine administration. Am J Cardiol 37: 33-40; 1976. 19G.American Ileart Association, Twenty five years later...greater. hope and many solid achievements. Amet•ican Ileart Assoc Annual Report 1973. pp. 3-24. 197. Burch, G, E, Editorial: Viruses and artcrioscicro 1974, sis. Am Ilcart J 87(4): 407-412; • 197a.Cordav, E. , Corday, S.R. Prevention of heart disease by control of risk factors: The time has come to face the facts. Amer J Cardiol TIMN 450387 I I I 91

442 DR. FRED G. BOCK "DR. j•IYI.DER: Actually, I think the discussion is academic, to that extent, because we will next talk about 'tar'. We are in agreement that 'tar' is carcinogenic. Beta naphthylamine is part of the 'tar'. Whatever decision e:e make on 'tar', the whole thing applies to constituents. .- 'DR. BOCK: You might be.able to exclude this, such as you have done with pyrene. I think it is criti- cal to decide whether this is in tobacco smoke most likely to contribute to the health hazards of smoking. I, personally, have seen no evidence that it is most likely to contribute to the problem." ' pp. 908-909 TIMN 450405 r ~ 443 Senator KENNEDY. Fine. We will now hear from Dr. Sterling. STATEMENT OF THEODORE D. STERLING, PH. D., DIRECTOR, CO1Wi- PUTIN(I SCIENCE PROGRAM, SIMON FRASER UNIVERSITY, VAN- COUVER, CANADA Mr. STERLING. Mr. Chairman, my name is Theodore D. Sterling, I am a professor in the faculty of Interdisciplinary Studies, and director of the computing science vrogram at Simon Fraser University. I am here because I have published a great deal in the last year in the area of the statistics of smoking and health, and also because I have recently completed a study usrng data from the Department of Health, Education, and Welfare, the results of which will be of interest to your committee. I have another article coming out this month Senator KENNEDY. Do you have a statement? Mr. STERLING. Yes; I do. I have it right here. Senator KE-XNEDY. I am going to try to give you 7 minutes, and then the last panel 20 minutes, if we can work that out. I have an hour and a half that we can set aside tomorreWvwning. If we can work that out, that..vould be fine. Mr. STERLING. I will summarize very briefly. I would like to state seriously that Dr. Sommers is a very distin- guished man, and jokingly that the reason that lie could not remember some of my work ~is because I am a statistician, and like most physi- cians, Dr. Sommers does not consider statistics quite respectable. Let me go to an item I have come to in my review of statistics. Some material has been published in the American Journal of Public Health, but. I shall speak here of data which are of specific importance to this committee, and I shall restrict myself to the materials on pages 4, 5 and 6 of mv statement. One of the key problems in smoking and health studies, a problem which has been reviewed by statistician after statistician, has con- cerned the sufficiency of the information which has been used in these studies. Now, I am not just talking about my own criticism of these studies, but criticism by a group of statisticians whose names in the ranks . ,.,. . ,.i;~:; v v .xl:;,.i y cohl in the ranks of-Pres' in this countr Abe Linh..:_~ ~f thesmal'or areas in wh r `~`u It is in ~eneral ironic that one o ich criticism has been raised concerns a lack of information on occupational hazards, information which ha5 been left out of smoking and health studies con- stantly. It is ironic that while studies of environmental or occupar tional health effects are constrained to take population smoking habits into account, studies on smoking effects selclom bother to search for a report on occupational exposures. Rutt smoking habits are not at all independent of such factors, especially of the smokers' type and place of emplo,yment.. Two studies, largely ignored, had reported that smoking is more frequent among blue collar workers, especially blue collar workers who may be exposed to intensive amounts of toxic fumes and dusts. One other study even showed that smokers were more often exposed to a variety of chemicals, fumes, sprays, dusts, extreme heat and loud noises than were nonsmokers.

464 - 6 - restaurant bartenders). Heavy smoking is very frequent among workers who are exposed to gasoline fumes such as mechanics and repairmen in service stations (76%) or taxicab drivers (60%). 56% of printers smoke, 64% of wor- kers in yarn and fabric mills, and 70% of assemblers. Similar incidence rates of smoking are recorded for most blue collar occupations. On the other hand there are occupations in which smoking is infrequent. At the top of this list are individuals who work in welfare and in religious services, especially clergymen, of whom only 8% smoke. Only 27% of employees of educational institutions smoke (such as teachers and librarians) and university professors smoke with even smaller frequency, 29%. Among health workers we fi0d that 27% of physicians, surgeons and dentists smoke. Other occupations where smoking is infrequent are accountants (27%), lawyers (29t), aeronautical engineers (22%) and similar low rates prevail in occupa- tions requiring general management, professional, or highly technical skills. The frequency with which the different job classifications occur among occupations with the largest and smallest prevalence of cigarette smoking are summarized in Table 3. The same information is shown graphically in Figure 1. A striking and dramatic difference in distribution of blue collar workers on one hand and technicians/professionals/managers on the other is i®ediately apparent. 75% of the occupations in which there ts a high prevalence of smoking and only 25% of the occupation where smoking prevalence is low consists of blue collar workers. On the other hand, only 10% of occupai:j.ons wj.t,y hi:gh prevalence of smokers consists of individuals in technical, professional, and managerial work while 70% among occupations with 465 - 7 - the lowest prevalence of smoking consists of individuals in that last category.* The statistical significance of the shift is without a question. The statistical test indicates that the probability of such happenings by chance are less than 1 in a million. (X2 - 35.5, d.f. = 3 p < .0001) The Major Implications of The Coincidence Between Smoking and Occupation 1. Differences observed in the Incidence of Any Disease Between Smokers and Non-Smokers Could Just as Easily Be Due to the Differences in Proportion of Blue Collar Workers In These Two Groups Any comparison between smokers and non-smokers actually compares two groups of which one has a larger proportion of blue collar workers and the small proportion of professional, managers, and proprietors while the other group has a large proportion of technical workers, professionals and managers and a very small proportion of blue collar workers. 2. It is Really Not Surprising That Blue Collar Workers Would Show More of All Different Types of Diseases (Especially of Such Cancers as Liver Pancreas Bladder, and Lung) Than Professionals, Technicians, and Managers The finding that smokers have a high incidence of almost all diseases than do non-smokers has been a great puzzle. It has been pointed out by Berkson and by other leading statisticians that one indication of a biased population selection would be an all pervasive increased prevalence of smokers' mortality for all disease categories. And this indeed is exactly what was found by most studies. Smoking and Health reports that of 26 diseases, 25 had mortality ratios of 1 or larger and only one had a mortality ratio of smaller than 1. (Page 102, Smoking and Health). Proponents of smoking/disease links have refused to accept Berkson's arguments but have claimed instead either that •The same shift although to a lesser statistically significant extent is found among females not shown here. TIMN 450416

450 - 4 - The First Major Statistical problem Concerns The Information That Should Have Been But Was Not included In The Comparison Of Smokers to Non-Smokers All members of the modern society are exposed to a large variety of toxic chemicals and dusts. There has been an unfortunate universal tendency to ignore some of the major sources of exposure to hazardous materials in all statistical smoking and health studies. This is true especially for occupation of smokers. In some studies, such as those conducted by Dr. Hacmond of the American Cancer Society, information on occupation was not collected. Some studies, such as the new Swedish study by Cederlof et al, collected information on occupation but failed to analyze it. The same is true for the U.S. Veterans study which also collected information on occupa- tion but never reported on it. It is not known if the important Japanese study by Dr. Hirayaua collected information on occupation. He does not report on it. In general it is ironic that while studies of environmental or occupational health effects are constrained to take population smoking habits into account, studies on smoking effects seldom bother to search for a report on occupational exposures. But smoking habits are not at all independent of such factors, especial- ly of the smokers'type and place of employment. Two studies, largely ignored, had reported that smoking is more frequent among blue collar workers, especially blue collar workers who may be exposed to intensive amounts of toxic fumes and dusts.* One other studu even showed that smokers were often exposed to a variety of chemicals, fumes, sprays, dusts, extreme heat and loud noises than were non-smokers.** Unfortunately until recently information on smoking patterns by occupation was not even available. • Dunn, J.E. et a1, Amer. J. Pub. Health, 50:1475, 1960 and Higgins, M.Wt et a1, Amer. J. Epid., 86:45, 1967. ** Friedman, G.B. et al, Amer. J. Epid., 98:1975, 1973. 451 - 5 - Such information became available only In 1975 when the U.S. National Centre for Health Statistics released data on its Household Interview Sur- vey of 1970. In that ongoing survey, a large probability saeple of the U.S. population was queried about place of employment, type of work, and smoking habits during the 1970 survey. The recently completed computer and statia- tical analysis of these data by Dr. James Weinkai and myself showro that all aspects of smoking are heavily dependent upon type and place of employment. The pattern relating employment characteristics to smoking incidence clearly indicates that so-called smoking related diseases for the most part may be of occupational origin. The findings of this review are In the process of publication now (and are detailed in Appendix I). We shall briefly sumr marize the most relevant findings from this Household Interview Survey: 1. Any comparison between smokers and non-smokers actually compares two groups of which one (smokers) has a large proportion of blue collar orkers and a small proportion of professionals,managers, and proprietors while the other group (non-smokers) has a large proportion of technical workers, professionals and managers and a small proportion of blue collar workers. But many blue collar jobs expose workers to toxic fumes and dusts that have been demonstrated to cause different cancers, coronary heart disease and mortality and morbidity from many causes. Thus differences observed in the incidence of any disease between smokers and non-smokers could just as easily be due to the differences In proportion of blue collar workers in these tFO groups. 2. The findings that smokers have a higher incidence of almost all diseases than do non-smokers is really not surprising because blue collar workers, who make up a large proportion of smokers and a smaller proportion of non-smokers, are exposed to a large variety of hazardous chemicals and TIMN 450409

400 1~. naxunam, n. nca.au< <ianu~ •u L wa- o- ` "° "' •••"~° in Thc Chemistr of Tohacco aud 'fobaccoSmohc.yl. Schmcltz (cd.). New or :' enum ress; ' Pp• - ' g6. Russell, M. A.11. , et al., Plasma nicotine levels after smoking cigarettes with high, medium, and low nicotine yields. Orit Ivled ( 2: 414-a16; 1975. 87. Berkson, J. Smoking and cancer of the lung. Mayo Clin Proc 35: 367-385; 1960. i88. Berkson, J. Mortality and marital status: Reflections on the derivation of etiology from statistics. Amer J Public ilealth 52 (8): 1318-1329; 1962. 89. Berkson, J. Smoking and lung cancer. Med Proc 10: 327-336; 1964. 90. { Burch, P. R.J. Problems in the interpretation of cancer statistics with special reference to lung cancer. J Soc Occup Med 25(1): 2-10; 1975. 191. Fisher, R.A. - Dangers of cigarette-smoking. Br'it Med J 2(5039): 297-298; 1957. 92. Fisher, R.A. Cigarettes, cancer, and statistics. Centennial Rev Arts Sci 2: 151-166; 1958. 93.. Fisher, R•A. Lung cancer and cigarettes? Nature 182(4628): 108; 1958. 94. Fisher, R.A. Smoking: The Cancer_ Con_troversy: London: Oliver P, Boyd; 1959. pp. T-T . 95. Rigdon, R.H. Cigarette smoking and lung cancer: A conside;ation 96. of this relationship. Southern hied J 62(2): 232-235; 1969. Rigdon, R.H. Statement presented at liearin s before the Committee on Interstate and Forei. n Commerce House o e resentatives, pri - ay _,1 eria o. , pp. . 97. Schoolman, H.M. et al., Statistics in medical research: Principles versus practices. JZab Clin Mod 71(3): 357-367; 1968. , - 98. Seltzer, C.C. An evaluation of the effect of smoking on coronary heart disease. JAAL1 203(3): 193-200; 1968. 99. Yerushalmy, ,I. On inferring causality frOm observed associations. in Controverw in Internal Medicine, F.J. Ingelfinger, A.S. Relman, M. >.n an e s. . u a e p u a: M.B. Saunders Co.; 1966. pp. G59- 668. 100. llurch, P. R. J. Problems in the interpretation of cancer statistics with special . . ... . reference to lung cancer. Soc C cc. , ;. 2 101. Burch, P. R. J. Smoking and lung cancer. Lancct 2(7886): 950; 1974. 102. Fisher, R.A. Lung cancer and cigarettes? Natttre 182(4628): 108; 1958. 401 103. Fisher, R.A. Cancer and smoking. Nature 182(4635): 596; 1958. 104. Fisher, R.A. Smoking: The Cancer Controversy. London: Oliver 4 Boyd; 1959. 47 pagcs. 105. Ilickey, R.J., et al., Carboxyhaemoglobin: Envirodmental and constitutional (aclors. Lancet 1(7897): 40-41; 1975. 106. Hickcy, R. J., et al., Cigarette smoke as a carcinogen? Amer Rev Resp Dis 111(l): 105-106; 1975. 107. Karvonen, M., et al., Cigarette smoking, serum-cholesterol, blood- pressure, and Gody fatness: Observations in Finland. Lancet 1: 492-494; March 1959. 108. Seltzer, C. C. Smoking and cardiovascular disease. Amer Heart J 90(1}. 125-126; 1975. 109. Thomas, C.B., et al,, Personality characteristics of medical students as reflected 3y the strong vocational interest test with special reference to smoking habits. Johns Hopkins Med J 127(0): 323-335; 1970. 110. Katz, L. Statement presetited at HearinRs before the Committee on Interstate and Forei n Commerce House of e r~2 esent_ail.ves, April 15-May 1, b . eria ,o. , pp. • 111. Cederlof, R., et al., Hereditary factors and "angina pectoris". Arch Environ HealEii 14(3): 397-400; 1967. 112. Cederlof, R., et al., Ilereditary factors, "spontaneous cough" and smoker s cougli`r.-Xrch Environ Health 14(3): 401-406; March 1967: 113. Cederlo£, R., Friberg, L. Tobacco smoking and health: Results of epidemiologic•studies in twins. Lakartidningen 65(27): 2727-2734; July 3, 1968. 114. Cederlof, R., et al., Cardiovascular and respiratory symptoms in relation to toli-acco smoking: A study on American twins. Arch Environ Health 18(6): 934-940; 1969. 115. Cederlof, R. Statement presented at Hearin s before the Committee on Interstate and Foreign Commerce Iiouse oT tc resentatives, pri -May 1, 1909. bcria No. 91- , pp. 8 . 116, Friberg, L. et al., Mortality in smoking discordant monozygotic and dizygotic twins. Arch Environ Ilcalth 21(4): 508-513; 1970. 117.Priberg, L., et al., Mortality in twins in relation to smoking habits and alcohol problcuu. Arch linviron Ileaith 27(5): 294-304; 1973. 118.Yct•ushalmy, J. Mother's cigarette smoking and survival of infant. Amer J Ohstet C~•ncc SS(•1): 5115-518; February 15, 1964. 119,Ycrusitalmy, J. Letter to Editor. Amer J Obstet Gvnecol 91(6): &83-aSd 1965 ; . TIMN 450384

.q 458 APPENDIX 1 I 459 SMOKING PATTERNS BY TYPE AND PLACE OF EMPLOYMENT: HAS ATTENTIOIW TO SM47KING MASKED TRE EFFECTS OF MULTIPLE OCCUPATIONAL RISK FACTORS ON NEALTR? Smoking Patterns By Type and P1ace of Employment Theodore D. Sterling, Ph.D. February 1976 Data from a large population study conducted by the U.S. Department of Health Education and Welfare were analyzed by Drs. Theodor Sterling and James Weinkam at Simon Fraser University. The results of their study show that frequency and other aspects of smoking are heavily dependent upon type and place of employment (the occupation of a worker and the industry where he works). The pattern relating employment characteristics to smoking incidence clearly indicates that so-called smoking-related diseases for the most part may be of occupational origin. This Appendix briefly summarizes their findings from a series of reports now in the process of review for publi- cation. THE HISTORY OF THIS PROJECT Scientists always have been suspicious of results from studies based on answers obtained from self-selected individuals. Smol.ers and non-smokers are such self-selected groups. The decision to smoke or not to do so depends on many factors and some of the same factors that determine smoking habits also may determine other events including the incidence of disease. There are many examples where studies based on self-selected populations reached completely erroneous conclusions. The most famous example was furnished by the Literary Digest's attempt in 1936 to predict the American presidential election from a poll of some 10 million telephone subscribers. But during the Depression, telephone subscribers were "self-selected" from individuals with adequate income. These same individuals preferred a Republican administration while the majority of Americans, who were too poor to own telephones, rousingly defeated the Republican ticket in every state but one. (The Literary D1c~est subsequently went out of busineas_) Statisticians have pointed for many years to the self-selection problem in smoking and health studies. A long list of eminent statiticians;have TIMN 450413

457 -10- among smokers and non-smokers. In other instances claims about dose response effects are not supported by the data to which these claime refer. 5. Whether or not there is a benefit to giving up smoking is highly questionable. There is a definite self-selection factor involved in stop- ping to smoke. For instance, blue collar workers tend to make up a ssmll proportion while individuals from teaching, welfare, professional, or manage- rial occupations tend to make up a large proportion of former smokers. Thus groups of former smokers are constituted of similar occupations as are groups of non-smokers. They ought to have the same disease incidence. And this they do. 6. In most tnstances where information is available of cancer inci- dence by smoking and occupation, the effect of occupation dominates the development of lung cancer while the possible effect of smoking may be slight or in many instances completely absent. CQMCtUSIQN science arrives at the truth by successive approximations. There is now a growing understanding of how many diseases are caused by toxic dusts, fumes, and chemicals, most of them of industrial origins. The belief that smoking is the major cause of mortality and morbidity from these diseases initially may have rendered a valuable service by convincing the public that pollutants in man's environment may present a serious public health hazard. The same belief today distracts from the real hazards to which we are exposed in our modern industrial society. A large number of employed Americans and Canadians who are exposed to toxic materials in their surroundings also smoke. As it is primarily the blue collar worker who smokes, decreasing the availa- bility of cigarettes for such workers through taxation or outright prohibition constitutes a cruel hoax. Nothing will be done by Bi11 No. 2902 to lessen the burden on their health and well being except to support yet one more expensive bureaucratic comeission. With some charity I did not linger on the findings of the advisory coasv.ission to the Surgeon General of 1964 which found that neither environmental nor occupational exposure was a cause of lung cancer. Advisory cosrnissions have sometimes not been useful tools in directing and initiating needed health research and there is good reason to expect that the proposed commission will not further the elimination of preventable hazards. Finally, the new evidence is such that reasonable scientists and statis- ticians will agree that gross errors and omissions have occurred in the collection and evaluation of smoking and disease data. These errors will force a re-evaluation of unanimously accepted beliefs about the health effect of smoking within the next year. TIMN 450412 '!/I-f1H'/ 11 - 1. - -

452 - 6 - dusts and may be expected to die from a large range of different diseases many of them caused by occupational exposures. (For example, cancer of the pharynx, bladder, liver, lung are coaaoon occupational causes of death.) 3. Populations of former smokers and non-smokers are similarly co®- posed of a large proportion of teachers, welfare workers, managers and professionals and a small proportion of blue collar workers. The incidence of disease among former and non-smokers therefore ought to be similar. And indeed it is. This finding ts of exceeding importance because the apparent decline of risk from mortality of former smokers to a risk equivalent to that of non-smokers was considered to be the very strongest support for the belief that smoking causes an increased risk from mortality. Yet this decrease in risk of former smokers now turns out to have a simple explanation that may have little or nothing to do with smoking. 4. Blue collar workers start smoking at a younger age than professionals, health workers, teachers, or managers. Therefore the increased mortality among individuals who start smoking earlier in life is most likely related to their occupation and has little or nothing to do with smoking. 5. There are fewer blue collar workers among women than men and the decrease in age specific mortality rate of wmen smokers compared to men smokers is probably related to the differences in the proportion of blue collar workers among them. 6. The increased incidence of mortality from many diseases but especially from cancer of the lung among black males is probably due to the larger pro- ......a,..., nn).t.. w.-.rn.rs wrmna bl,eck:[_ 7. Blue collar smokers smoke more than other smokers. Thus the apparent dose response relationship between amount smoked and risk from mortality is no more than a difference in the distribution of blue collar workers among individuals who smoke less or smoke more. Another important 453 - 7 - observation relating to an apparent dose response between smoking and disease is the observation that black smokers smoke 40% fewer cigarettes than white smokers. At the same time there is an increased cancer rate among blacks, especially from lung cancer. 8. There is a larger proportion of blue collar workers among smokers of regular than of filtered cigarettes (47X vs 42% among white and 58% vs 54% among black males). Therefore the apparent decreased mortality among smokers of filtered when compared to smokers of unfiltered cigarettes is most likely related to the smaller proportion of blue collar workers among smokers of filtered cigarettes and may have little or nothing to do with the decrease in tar and nicotine content of cigarette smoke due to•filtering. As a final conclusion, then the weight of evidence would appear to affirm that smoking has been a cover for many other types of exposures to hazardous and toxic materials to which smokers and non-smokers are subjected in different amounts. The Second Major Statistical Problem Concerns Incnmplete And/Or Selected Study Populations Conclusions concerning the hazards of cigarette smoking in Smoking and Health and subsequent yearly reports on "The Health Consequences of Smoking" have been primarily based on seven prospective surveys. All these surveys share the common characteristics that their study populations were assembled by a succession of "selection factors" which depended heavily on the coopera- tion, availability, and ease of access to potential study subjects who also differed In crucial characteristics such as smoking habits, disease, occupa- tional exposure to chemical carcinogens, and so on. it is true that the result of all these studies were uniformly alike and that is impressive. whenever smokers and non-smokers were compared, smokers died with increased TIMN 450410

408 198. Chol, Y. Y. Effect of nicotine upoa dtolesterol-induced atherosclerosis in rabbits. New Mcd J 10(7): 49-61; 1967. 199. Fisher, E.R., et al., Influenco of nicotine on experimental atherosclerosis aZ its determinants. Arch Pathol 96: 298-304; November 1973. _ 200, Fisher, E.R. , et al. , Cigarette smoking and cholesterol atherosclerosis o'Frabbits. Arch Pathol 98: 418-421; December 1974. 201. Larson, P.S., et al., Tobacco: Ex erimental and Clinical Studies: A comprehensivc account o t e wor iteraturel a timore: te • Williams Ft Wilkins Co.; 1961. 202. Roth, G.M. Effects of smoking of tobacco on the cardiovascular system of normal persons and patients with hypertension. J Amer Geriat Soc 2(5): 271-273; May 1954. .203. Roth, G.bf., Shick, R.M. Effect of smoking on the cardiovascular system of man. Circulation 17: 443-459; March 1958. 204. Berglund, G., Wlihelmsen, L. Factors related to blood pressure in a general population sample of Swedish men. Acta Med Scand 198(4): 291-298; 1975. 205. Blackburn, H., et al., Common circulatory measurements in smokers and nonsmokers.Mrculation 22: 1112-1124; December 1960. 206. Clark, V.A., et al., Effects of various factors on systolic and diastolic blooZc ptessure in the Los Angeles Heart Study. J Chron Dis 20(8): 571-581; August 1967. 207. Edwards, F., et al., Arterial pressure in men over sixty. Clin Sci 18(2): 289-300; 1959. 208. Gyntelberg, F., Meyer, J. Relationship between blood pressure and physical fitness: Smoking and alcohol consumption in Copenhagen males aged 40-59. Acta Med Scand 195(5): 375-380; May 1974. 209. Higgins, bi.W., Kjelsberg, 1•I. Characteristics of smokers and nonsmokers in Tecumseh, Michigan. Amer J L•pidem 86(1): 60-77; 1967. 210.b;arvonen, M., ct al., Cigarettc smoking, serttm-cholestorol, blood- pressure, and Gody fatness: Observations in Finland. Lancet 1: 492-494; March 1958. 409 211. Sclt-ar, (:.(:. Gffect of smoking on blood pressure. Amer Ileart J 87(5): 558-564; Nay 197•1. 212.I+lyrstcn, A.L., et al., Changes in hchavioral and physiological nctivation induced-liy cigarcttc smokinl; in habitual smokers. i'sychopharctacologin (Rcrl.) 27: 305-312; 1972. 213. Smith, R.A., ct al. , Lcthality-modifying effects of nicotine on experimental rats. Itadiology 111: 733-734; June 1974. 214. Ncbcr, R. P. , ct al., Nicotine inhibition of thc mctabolism of 3,4-benzopyrene, a carcinogen in tobacco smoke. Science 184(4141): 1081-1082; June 1974. 215. Ashton, II„ ct al., Stimulant and depressant effects of cigarette smoking on brain activity in man. Srit J Pharmacol 48(4): 715-717; August 1973. 216. Ashton, II., et al., The effoct of caffeino, nitrazepam and cigarette smota ng on the contingent negative variation in man. IElectroenceph C]in Neurophysiol. 37: 59-71;'Ju1y 1974. 217. liysenck, II.J. Personal.ity and the maintenance of the smoking habit. in Smoking ISchavior: Motives and Incentives. h'.L. Dunn, Jr. (ed.) Washington: V.11. Winston an Sons; 1973. pp. 113-146. 218. ,1rmitage, A.1:., et al.. Pharmacological basis for the tobacco smoking habit. Naturc 217: 331-4; January 1968. 219. 1lalfour, D. I. K., Morrison, C. F. A possible role for the pituitary-adrenal system in the effects of nicotine on avoidance behaviour. l?harmacol Oiochem Ilchav 3(3): 349-354; 1975. 220. Rovet, U. Action of nicotine on conditioned behavior in naive and pretrained rats: Introd'ttction. in Tobacco Alkaloids and Related Com~ounds. U.S. von liuler (ed.) Oxford: 'crgamon Press imite ; 1S . pp. 125-136. 221. Oovet, U., et al.. Action of nicotine on spontarteous and •tcquired hcltavior in eata and mice. Annals iN.l'. r.cad Sci 142{Art. 1): 268- 276; March 15, 1067. 222.Itovct-Nitti., F. ,lction of nieotinc on cnnditioned behavior in naive and Itretraincl tats: 11, Comple.x Ibrms of acqttired hrhavior-• Iliscussion. ill 'I'uboc<o -11GaloiJs and Rrlatcd t'om.Lounds. tI.S, von liulot' (ed.) 0xforil I`crgaiiinu 1'rrs- I.iinitcJ-llibS. pp. 137-143. 2?3. Hrickson, t:.l:. Stu.lics on the mcrit:mism of avoidance facilitation by nicotine. t's ~hotirat'm;icolo:iv (itarl.) :2: 357-368; 1971. TIMN 450388 an.nH7 fl - 76 - 27

448 - 2 - Firstly, the Bill provides for setting up yet one more cumbersome bureaucratic commission rather than furnishing much needed funds for the investigation of preventable environmental factors or lending much needed support to agencies that are now concerned with prevention and alleviation of environmental and industrial hazards and that have been rendered nearly impotent by lack of an sdequate budget. Secondly the Bill tends to reinforce the current penchant for attacking cigarette smoking as the major public health problem facing us today. It thereby distracts attention away from the serious effects of exposure to industrial, environmental, and occupational carcinogens. I am particularly concerned about.this trend, because after extensive re-evaluation of the major statistical studies on which this current attitude is based, I have found errors, inconsistencies, and omissions of such proportions that they prevent a true assessment of how dusts, fumes, and toxic chemicals cause a large variety of preventable diseases and, at the sase time, they seriously question ssaking's role as a significant cause of lung cancer and certain other respiratory and cardiovascular diseases. I shall address sy rss~.rks to several key, erroneous assumptions on which the health argument of Senate Bill No. 2902 seesr to be based. These assumptions may be.sumeearized as two beliefsr 1. that smoking causes an increase in general mortality (especially from lung and coronary heart disease) whenever smokers and non- smokers are compared and under whatever conditions such compari- sons esy be carried outj 2. that smoking is the major cause of lung cancer. As many as 85% of lung cancers are caused by smoking. 449 - 3 - While these views are shared by some public health workers, they are considered with increasing skepticism by others. It is becoming increas- ingly clear that beliefs based on the 1964 report of the Surgeon General have to be modified in light of data accumulated since then. In order to provide a better overview of a complex issue, I shall briefly susmarize the relevant findings of many new studies in this introductory caoent section. Two appendices are included that present and discuss In detail these data and relevant studies. DOES SMOICING CAUSE AN OiVERALL ZNCRSASS FROM NORTALZTYT Scientists always have been suspicious of results from studies bssed on answers obtained from self-selected tndividuals. Smokers and non-ss,akers are such self-selected groups. The decision to smoke or not to do so depends on many factors and some of the same factors that determine smoking habits also sey determine other events Including the selection of sick or healthy smokers for a study, the association between smoking and other exposures to environment.l pollutants or toxic chemicals, or the compositions of groups of never, current, or former smokers with respect to other factors that affect the incidence of disease. Many eminent statisticians have for years counselled caution because of the self-selection problem in smoking and health studies.* However, their warnings were ignored despite the fact that conclusions about the health effects of swoking have been supported almost exclusively by statis- tical population studies. *The list of these statisticians reads very much like a Who's Who in Statis- tics. They include Sir Ronald Fisher of Cambridge, commonly called the father of andern statisticst Joseph.Berkson, formerly of the Mayo Clinic and the most eminent biostatistician in North Aaeericaj Jerzey Naysen of Berkeley, the single most dominant figure in statistics in United States, Dr. Allen Wallis, President of Rochester University and previous chairman Of the President Coamission on Federal Statistics, and many others including X.A. Brownlees of Chicago, A. Feinstein of Yale, D. Mainland, now retired, and J. Yerushalmy of Berkeley. ,r~-N 450408

438 "S:ell, do u:e have to discuss the evidence? Do c:e have to dis•cuss what it probably does and -how it is probably related to some of these diseases orr is there anybody 4;ho Would argue that this is a trivial part of the whole problem?" p. 899 "I don't think we ever know for sure. Negative evidence is so hard to be certain of. It tends to suggest you haven't done the right kind of study." p. 900 "I won't 1•et you spend a lot of time on this. If nobody in this group can cite someth'ing to say it belongs here, I don't thir-c it belongs here. It seems to me the accu- mulated knowledge here is sufficient to warrant that con- dition." • p. 903 "DR. KEhSLEP, . . I think the one good that would come out of putting it in Table 1 is that you would get some information back. DR. HORN: In a sense, by putting it into Table I we are saying we think rore research ought to be done on the role of this substance, what the techniques might be for removal of it." p. 914 e I-nn unpn- Wait a second. Do we mean by cancer that it is part of the carcinogenic process or c,o we mearr that it enters into the process r:hereby cancer is produced? Do we know that 'tar', by itsclf, , is carcin- oc,cnic. DR. IvYi:D :R: Yes . DR. i1oM:: In man? DR. DOCK: If you the tar out, you get fewer Good evidenco. DP.. tIOR~t: l•:c don' t kr.cw erha t el se is invo