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TNIS DOCUMENT SUBJECT TO . Pad 3 CONFIDENTIAUTY AGREEMENT. CiGARE'I1'E LABELING AND •ADYERTZSiNG-1969 COMMITTEE ON INTERSTATE AND FOREIGN COMMERCE HOIISE OF REPRESENTATIVES NINETY-FIRST CONGRESS 7TB,ST BZSSIOA ox H.R. 643 . sILL TO A1Q7rD ?EX siDL1tAI. CIOaEIIiT! L1ESLIIro AND .DVSrrtulio a,ar wrrs ssaPaor TG zas i.aszLU+O OF P.CC- AOTi OP CIOLtIfT•IZi, AMD !OE O?B3Y POE.POBES (.&A ss.IW sw.) H,R, 1237 A sILL TO DIRLQ? TEL PIDtLL COYYQN?ClT7ON'8 COUmIS• EIOA TO lBITABLI88 1TGpLATION'B PEOBIBITING CERT.LI1 sEOADCAB?INO OF 1.D\'t=IEI\0 OF CIGA.SDTIES (And Etmlhr BuI.) H.R. SQ55 A EILL TO /TiTNOTRiM TBZ TZDLL.L CIOLRL2TL 118ELI7:0 AND ADVERTISING •OI (.aa gl&Irr sw.) H.R. 6543 A BILL TO IiTPE\-D PUBLIC BLIdH PROTECTION WITH RE• EPECT GO CIGLE.OSTt lYOtIKG AND FOE OSSER PCEPOSES (Aad ttst4r DI)1.) APRIL 1S,1a,17,18, 21, 2Z, 29, 24, 25, 28, 2D, 90,1\D MAT I Serial No. 91-12 Prlate0 for tDs ae of the Commlttec on Intantate and ForeSrn Commerce D.E. OORt>rf[LNT PEIN7INO OTTIC! s= waasrnOrGr I u.. C T ~c H N 0 14 1722. Gj

10 DOCUMENT SUBJECT TO I~ QUNFlDENTtAIITY AGREEMENT. The CHAiRx:v. Our next witness is Dr. Sheldon C. So:!.:..,!=. pathologist,'NeR York,fi.Y. STaTEKERT OF DL SHELaOA C. 80]dVEES, PATHOLOGIST. NEW YOEB, N.Y. The CAAIRYAX. Welcome to the committee. Dr. Sommers.l'ou t..ar proceed as vou see fit- Dr. So"rns. Thank fou. Mr. Chairman. I atr, appearing a- t:,e reg uest of representatives of the tobacco industry. Mv name is Sheldon C. Sommers. I am a p}irsician specializ:r.:. :n patliolo~ and director of laboratories, Lenno: Hill Hospital. 'N ~~ York, clinical professor of prlthlo~, Columbia L'niver::rr Co:- Iegeof Phfsicians and Curgeons.?~eR 7 ork, enct clinical prnf~-=.•- ni patholo~s, I niversitp of Southern California School of ~ledicine. Lo= An~eles. I also teacb at Cornell Medical School, Tufts-New Er,_:~~.:~ Dfedicnl Center. and \evr York Medical College. I am a Veteran=' .A,d- ministration hospital coneultant in pathologr. I ani the P/l'tn:' ~.: Patholop• Annual, a eearlr scholarly publicathon composed nf F-= } Rritten br and for pntholoj:ists: I seth-e on the editorial boar(ls ~- t• journals,~hare about 220 medical publications. and am the coauth~r o` a gcnecolo, teztbook. My curriculum ritae and publicatio^= are attached. • For 2% rears I hace been on the Scientific Adrisorr Board. for Tobacco Resenrch, and am currently sen•in: on its subcomnii;-ee to reernlnate re.ettrch programs Rnd rlanninR in the field nf tnk-n and health. Reecntly, I have been appoinred research director of ::,e Council of Tobacco Researcb, as part of a newly initiated pro:ra^: to broaden the scope and sharpen the objectires of the siiPnr%r:-~ : e- search. The funds budgeted for these purposes hare been cor.=i-ae auRmented. At this point. \ir. Chairman. mac I present for the record br Dr. Clarence Cook Little, who is the scientific director. and Dr. Itnhert C. Hockett. the associate scientific director. of the Cov::..:? for Tobacco Research 1 The CaArRxAx. Without objection, they .rill be included in the rec- ord following your testimonv. ~~- D:. Soatsttxs. Cnnsideraticm htas been given ertensirelr in th- rent hearings to the question of smoking and health. )-Ione=- Ric? differences of opinion as to the importance of reported sociations between cigarette smoking and earinus diseasP= are }:e;d by presently actire workers in the pertinent fieldc nf medical -i~:,-. It would be unfair to denr the existence of eridence borh anposthe belief that cigarettes mac be or are associatrd = a- tisly vrith various human diseases. Eindividual Rorking in this field ir natur111c influenced ; particular scientific disci pline, ezperience, and the resvlts of his'oR-n experimental projects. I am a physician particularl~ interestrd i: human diseases, their causes, the stages of their derelopmer% and the consequent opportunities and strategies for their control ar.d pre- rention. Diagnosis of disease, patient care, and disease prerentiorn are the medically crucial issues. CTR HN 014*7227

IHtg ppCl1MENT SUBlECT TO 1081 WIiFlDEHTtALiIY AGREEMENT. Lnn" cancer ha= aroused the greatest public and governmental in- tere_t. The most common types affect males five or six titnes more often than females. No theorc of causation known has adequatelr ezrlained this striking sex diBerence. `1'utnen, whether they smoke or not, are less"susceptible. It is doubt- ful that notable benefit could be anticipated in preventing lung cancer anio::= women by any present public health program. Among men. vrho are relattvelc more likel.• to develop lung cancer. onlv a small number of even heacy cigareite smokers are fouwid to ha~F canoer. This association does not constitute causation. Of the totnl population most heacil.• exposed only a small minority su'.ryroup is affected, and .ncy is tinltaoRn. Lung canoer does not occLr :.: tl,e great majority of eitlter moderate or heavy smokers. Statistical cou:- pnri~ons het~ceen smokers and nonsmokers are difficult to make R•it.hout ~ntroducing two serious types of scientific bias: (1) people self-select RhPther to smoke or not. and the populations studied thus are not randoin: (2) no mathematics exists for statistical comparisons of nanra»dom or selected populations. - Medicnllc trained pathologists would not employ death certificate dlapl~o;es. unconft•med bc a study of tissues grossly and microicopi- calic at surgerT or autops;c, in sucb investigations. T)ie overall autopsy rate in the United States is below 10 percent, and without supporttng data there are too many death certificate errors in distinguishing betT, een primary lung cancer and secondary spread to the lung of orhp- cancers, among a number of difficulties in the scientific use of <1o^tlt PertlFlCat". L.ti,{ cancer is of various tcpes, and several have no implied rela- ticaahtp to any envirotunental-agent. It is a gross ovenimpltfication to 1umr together at leact nine different tumor types and ascribe them all to nnc agent. including cigarettes. Afier at least 30 ,reatrs of experimental ~•ork, and many snoke inl~alation experiments in animals. lung cancers of the most common. sqn:iuious cell human type have not been prodtked. It is usuallp difficult to prove a negat i~•e, but if cigarette smoke was a cause of lung cancer. it is tndeed surprising tltat no animal experiments have succeeded in its procluction. Skin painting studies are scarcely relecant to the lung. `!nt•r stud}- is urgentlr tueded of what other factors, such as ~•iruse,. urban air pollutants and degenerati.•e changes contribute to lung cancerderelopment in animals and rnan. \Iedical fashions change: for ezample.30 years ago authoritie: con- sidered tuberculosis the most common cause of lung cancer. It is also well to mention that understanding the formation of lung cnncers is one of the most complex and di.fficult problems in cancer research. not pre:e:a:r well understood and not yielding simple answers. A second even more serious medical problem is cardiovascular dis- eace. !:inre it causes about half the tot.al deaths in the United States and ocerall affrcts lnnFe.•iry more than lung camcer. Again, it attacks mi,lule-aged male.c more often than females, for unknown reasons. In respect to smoking as a possible cause or contributing factor. newer multifnctorial statistical studies also point to a farnily history of heart disease. diet. blood choleeterol. body weight and 6lood pi*csure as independent predictive factors. Rhich in various combinations are assoctated with increased rates of heart disease. Each factor alone, L, TR t ! N t..f 1">C'7d.. 6

1NlS DOCUMENT SU8IECT TO 1082 OWDENIUWTY AGREEMENT. including smoking is not a cause. A number of studies show no rela: i~:: of smoking to.heart disease and ought not be ignored. Aging ar:•i eoronary arteriosclerosis, of course, overshadow other processe; ti.a: contribute to the most common t~-pe of heart disease. Another difficulty with coronarf heart disease concerne hot- a : rately the diagnosis is made. When the most adcanced clinical tr_.= are employed, evidence for coronary disease is found in almost i:a:: of all men over 40 years. By this age racticalir all the coro::;,:- arteries show some pathologic lesions. ?ince both coronary and cigarette smoking are so common in the L"•.S. male porul: t: .•::. it is quite difficult to find adequate numbers of people for compar._-:. .cho have neither, or only one of these eonditions. A well-known sta-- tical fallacy is likely to exist when groups of such unequal size a~e compared. Emphysema has now been added to the list of diseases blamed c:: cigarette smolnng. The newest medical publications and gorernnien: a; reports emphasize how difficult are the diagnosis, the classificatior.. and thegr ading of severity of pulmonary emphysema, even amo:-.: tzperts. The cause admittedlr is tuilrnoern. One cotnmon form de- velops in every person with age, and lumping several types as if cLe comprised an entity is tutRarranted. Thus. death certifricate diagnose- _ or a routine pathologic diagnosis of emphcse.ma at present are =ci- enti6callv practically useless, except in a few specialized research centers. In the current era of relattre ignorance concerning how tc define and recogniae emphysema and other chronic lung disease:. no sweeping generalizations as to causation can be justified. In reneRing above a few selected discrepancies. d:fficultiee. oomings, and unsolved problerps in the field of smoking and hea!t:.. there is no .cish to denigrate the concentrated efforts made by workers to find ansRers. It is simply that the field is too neR. ;..~ techniques still being developed, and the conclusive proofs no; .~at in. It is less than 40 years since lung surgery began, for essn:, 'e. A few items in the testimony of others may justify commen:. Tae Surgeon General compared inability to deaionstrate the formatio:: of lung eancers i.nerpe rimental animals exposed to smoke Ricl; lac:: of experimental production of leprosy. However, leprosy has been produced in animals. Some confusion arose through use of the word "addiction" in co::- nection with tobacco use. Bfge nerallv accepted WHO criteria, sn;os- ing tobacco is not considered an addiction. Dr. Williams of the lmerican Cancer Societv stated that a ph~•s:- cian looking at a slide of lung cancer without utformation could tell in some detail about t,hepa rient'a social life, cigarette smoking for some 20 Tears, and so fort~h. On the basis of znv dailv experience as a pathologist. when one looks at a slide of lung cancer neitlier a pathologtst nor other physicians can tell whether it is from a n:a:: or .roman, and thus eannot accurately describe the social life. Fu-- ther, it is not possible grosslc or microscopicalls, or in any o::•,er .vas known to me, to d~atunguiah between the lung of a smoker or a nonsmoker. Blackening of lungs is from carbon particles, and smoe- tobacco does not introduce carbon particles into the lung. Ti,e Icational value of the various specimens shown the committee in this situation escapes me. C~~ M N 0 ~.~~e~'`22 9;

THIS DOCUMENT SUBJECT TO 1083 ppNFlDENIIAUTY: AGREEMENT. As to coronary heart disease, a spokennan quoted the dean of \fount Sinai Ifedical School to the effect that the relation of cigarette smok- ing is as firmlc established as the tbenpeutic use of anticoagulants for treating myocardial infarction. A recent publication from 2 ale \lydi- cal School anah•zes the use of anticoagulants and concludes that the studies are not .rell enough designed to draw any useful conclusioi;=. These are cited as overstatements or misst.tements of medical 1-noRl- ed~e made by some .~itnesses. The 3,4-benzpyrene is not proTed to be responsible for human lung cancer, and consequentlc its amount or the removal of it can scarcel.be considered at present crucial scientific matters. Cigarette sniokin is not a unique health hazard, as claimed L-y Chairman Hvde of fCC. As Dr. F.ot,in pointed out, no mystical prop- erties are attributable to cigarettes. Scientifically, cigarette smok;ng has not been proced to be a health hazard at all. 1fany figures were cited concerning 30,000 or 50,000, or 260,000 per- sons per cenr having or dying from ]ung cancer or the other diseases being considered. Since it ts not known what the causes of lung cancer, coronary beart disease,or bronchopulmonar~ disease are, the multipli- cation of numbers does 'not contribute to tmderstandinF them any better. One recent article on the millions of persons reported to ha,~e one of a long list of diseases concludes that there must be scarcely- any healthy people left- KoR to review briefly the specific areas of deficient knowledge and the research needed for better understanding of the major diseases claimed to be associated with cigarette smoking. As conoerru lung cancer, multifactorial statistical techniques are now in use epidemiologically, and they Snav be expected to provide quantit.ative estimates of the relatiTe statistical importance of urban residence, occupation. lung infection, and inherited tendencies amor.g other possible factors, including cigarettes. We strive for a better ajgreement on the classification of so-called ptr,cancerous lung condi- tions and cancers. and this is slowly being achieved, partlc by inter- national cooperation through WHO. Techniques to study ~-iruses, in- cluding chronic cirus infections, are now becoming more widely applicable. The predominance of males with lung cancer and tlie ecidence thnt men who hace lung cancer are endocrinologically ab- normRl aln deserves more study. In animal e:periments, a suit.able lung bioassac model for inhalation studies is earnestly sought and technical adcances mar be achieved within the next oear. New techniques of histologic, bistochemical and biochemical studc need wider application, and pathologists will need help to apply theae special methods more widely both to human and animal maurial. E:posures to both the gas phase and particulate phase of cigarette smoke must be designed so that the chemical resc- tions at particular sites in the lung may be understood. Doses and re• lated responses must be evaluated. Although hitherto not found, an animal model trystem for producing lung cancers like the common hu- man types st ill needs to be eought. In reference to cardiocascular diseases, additional multifactorial statistical analyses and pathologic studies are needed. We will endeavor to determine iccuratelc whether arteriosclerosis of the eoronarc ar- teries and aorta differs in its development or quality or in quintitc CTR HN 014~~'`~~

iHIS DOCUMENT SUBJECT TO 1084 QDNFIDENTIALITY AGREEMENT. between smokers and honsmokers. The.et3ects of smoking on blood clotting and clot dissolution are high priority sub)-ects for study. Coronary blood flow can now be analvzed overall and the nutritional flow measured as well. This makes feasible studies concerning both the possible acute and chronic effects of smoking, in persons with and without evidence of coronary disease. Myocardial metabolism, abnormal muscle proteins and carbon monoxide et3ects all need further study. Vasomotor activity and cardiac catecholamines like adrenalin are of currently greater interest. Cardiac reactions differ with age, and these diSerences need to be better understood. Chronic pulmonary diseases, such as bronchitis and emphysema, are rather poorly unaerstood. Further development of both the clini- cal and laborators techniques for their recognition is a pressing prob- lem, and a.ride educational program concerning the present ad~•anced methods available should be undertaken. Onlr then can standardiza- tion of diagnoses and scientific anal~ses be possible. The relations of chronic lung diseases to repeated or persistent bacterial and viral in- fections, aging, particulate and nonparticulate inhaled irritantF, changes in the bronchial secretion~ and to immune reactions of lung are all Raitin exploration in detail. Pulmonary function studfes over long periods ~roro adolescence on are badly needed. Vasomotor and catecholamine reactions of lung are of incre,asing importance. Bron- chiolar disease is an emerging entity of great interest and complexity. Animal models are urgeat.Ic needed tn these fields. This rerieR leaves unttientioned many area= where knowledge is equallc lncking. and other diseases clnimed to be smol-iing that are either rarer or with an even mor* tenuous relati-ir:- ship. The needs for research are Mat. perhaps esceeding the prezer.r number of qualified investigators and tpeir arailable time. Cooperative efforts by the Gocernment, private foundations and public charital.'e organizations are hoped for and necessarc in these tmport,ant health fields. We all want better health for the public. Chronic disea.:es like thn=e discussed above decelop over long periods and they do not havP ti:c• simple cause-and-effect relations Pasteur and others found in certain bacterial diseases. Simple solutions of these complex medical probleni= mny be hoped for but they are scarcely to be expected. Tension i= a ~ dnilc fact of life in the I'nited States, and reducing it is one nf ir' imrortnnt daily professional actiriti~. Smol-in:. 7ike alcohol n, %i cheRing gum or tobacco, is widely used to relax tencion. Ph}•sician; hare more work Rhenpeo ple hace no release for tension. Considerable time, effort and moneyare being expended now and more isbeing budgeted for bture inrestigntions in the field of ~tnokiij_ and health, by the AAL4-ERF and the Council for Tobacco Re.=ear.-b amorg other organizations. This reflects a growing 8eld of heart nr,,l lua research. If the answers .rere for practtcal purposes alreadv :it han~, augmented programs in this field would scaroel} be justified or attract researchers. Not much research on typhoid, poliomvelitis. a11d tuberculosis is going on now, as compat^ed io years ago. The currer.t upsurge of investagattre projects and grant requests in the field nf smol.-ing and health is one good indicator that at least among reaearch workers the answers we need ooncerninlt the caux3. developmental stages, diagnosis, and control of these diseases are not acailable. To CT~ HN 0 14731

1095 PtS DOCUMENT SUBJECT TO CONFIDENTIAUTY AGREEMENT, claim there is now sufficient scienti6c evidence to establisL that cig ;- rette sntoking causes diseace is in my opinion unjtutifiec]. (The attachinents to Dr. Sommera' statement fo11oR :) Ctasactrt.vst Vlrit otr Sttasro. C. SoscMna, M.D. Born : July 7. 2916, Indlanapolis. Indlana. Harried : November 6,1943, Edith Brius, no cbildren. S.B., Harvard Collete,10.37, cum laode. M.D.. liarcard 1>itdtcal Scbool.19l1, cum lande. intern : Chicago CnLeraitJ C1inIn.1911-19i'S. •aristaot Resident and Resident in PatbolotZT, New Ugland Deaconesa 8o•pitat. Boston.1UStl-i6. Anaistant Resident tn PatLolou, Ree Hospital for Womea, Brookilor, Ifs•. 1U/8. •ristant Resident In PatbologT. Boston Lylui<-Io Hospital, Boston, 1fNB-18. Resident in PatLology, lienry Ford Hospital, Detrolt, 1W9-S0. tamerican Board Certfiscate in Pathology (Clinical PatLolon--Patbologic Auat- oml).1930. vcaoclate Pathologist, New En`tand Deaconess Hoapital, Bocton.19;,G-;3. 4si.-ta.nt Pathologist, Harrard Cancer Commission, Bo.ton, 1650-53. Patbologlst, lfaucacbusetts )femorial Hoapitals, Boston. 1t1.3-81. PatLologist. Scripps Memorial Hotpital, IA Jolla, CalJfornia, 1681-C3. Associate Director of Laboratories, Francie Delabeld Hospital, XeR Iorl• 1:i#3- 67 ; Direrto-1987-8b. Director of Laboratories. Lenox Hill Hospltat, New Tork 1965-. Assistant in Patbolog7. Harvard Medical Scbool, 3946-49. Instructor if. Pj• tholoQ, 1934-5=, Aasoclate in Patbology,19.52-33. Ltt•turer in PatLologc. 1!,L+- G3. • Associate Profeasor of Pathology, Boston University School of lfedicine. Boston, 1t+33-fil. Ctiuic'l Professor of Yatboloay. L'nl.arsits of Southern California Sc•bool o' !f edicine, Los Antelea. 39G_-. Associale Profesor of Patbo)o9T. Colambia Unl.eraltT, College of Pbfsicians k Surgeons. \.T.. 19tf3r85, Professor of PatLoloF,r, 19db-8b. Clfnical Profess-,r of Patbolor?,1986-. Gptain.lfedical Corps, t'olted States Army. 14t2-4a. Sllrrr Star, Bronze Star. Croix de Guerre and Presldential Dnit Citatioc. Bergen County lfedical Societ.r, X.J. Americ•an Assoclation of Pathologists and Bacterlolosists. Cullet;e of American Patbologists. Amcrican Society of Clutic9l Pathology. TGe liistocbemical Societc. ' Ainerictiu Society of Ezperimental Pathology. \,•M ):;nstand lancrr Stxiet3. XrK Enilaad Society of Patbolorists : President, 39:,9-84. Intrrnational AcademF of Pathology. Society Exp. Biol. and Hrd. N.Y. A--sdrmc Mrd. \.)'.Academc Scl. Editnr. Pathology Annual. 3986-. Editnrial Roard-: Escerpta Uedica. J. Clin. Endocrinol. QMetal.. Sclrutillk• Adcisorc Board : Muocil for Tobacco Itesearcb. cosiutrrres Culirr of American PatboloRlsts. Commtttee on Clas, A Xomenclaturr of Ilt-~a•-. •uirrican Nocietj of Esprrimrntal Patbolo~, Liaison Delegate to .tw.r.,:,u Society of Clinical Patbulury in Cancrr. Fircretarc.Elect. New 1'urk PatboloFinl Soci.t.v, isr.ci-t ('ew•er Task Force. X.I.II.. Ad Hoc Pathology n'orl•inr Group. ('bairtu:rn. PvausarD asrnciss 1. Jacot,s. J. L. and Sommers. S. C.: The apecititp of forrnolised protrin=, J. Immunol.. 38 : 581-511,1937. '1. ]teoklu. V.. Ksdisb. aI. A. and Sommers. S. C.: Leukocctosis-prontotin} factor fo fotlammitorc e:udattr of man. Arch. Patb., E3: 3bS-192. 1fq_^. CTR' i Ii i 0 147322

T'NtS DOCUMENT SUBJECT TO 1086 GOdFIDEtiIIALITY AGREEMENT. 3 LrCumpte, P. 1f., Sommen. S. C. and Ltbrop, T. D.: Tumor of arotid body type arising tn the middle ear. Arcb. Patb1, 44 : 7E-81,19/7. 4. Warren S. and 8ommers, S. C.: Clcatrizina enterltL (regional lleltia) as a patbolotic entity. Lm. J. Patb., 24 :475-W1.14Nb. 6. R'arren. S. and Sommers. S. C.: Giantrell inclusions in cicatrizing enterltis. Proc. Soc. Exper. Bioi. k Med., 8: 461-463. 19aS. A. Warren S. and Sommers. S. C.: Patbogenesis of ulceratl.e colitis. Am. J. Patb.. 25 : 657-659. 1949. 7. Hertlg. A. T. and fiommer, S. C.: Genesis of endometrial arcinnon:a. I. Btady of prior biopsies. Cancer, 2: 94b-958,19t9. 8. Sommers, S. C.. Bertig. A. T. and Benaloff, B.: Geaeas of endotietrial car• ctnoma. 11. Cases lU to 35 years old. Cancer, 2: 9;.7-9C3, 1919. 9. Hertig, A. T., Sommers. S. C. and Bengloff, 8.: Genesis of endometrial car• cinoma. III. Carcinoma In situ. Cancer, 2: 964-971,19a9. :0. Sommers, S. C., LaR1e?. T. B. and Bertig. A. T.: A study of the placenc.3 in prernancy treated by stllbcstrol. Am. J. Obst. & Gynec., 55: 1010. l4HS. 31. Warren, S. and Sommers, S. C.: Proteoljsis in intestinal disease. Gastro enterolo4e, 14 : 522-32E, 1950. 11 WFatt, J. P. and Sommera, S. C.: Cbronlc marrow failure, mcelosclerosis and eztramedullarl bematopofesia Blood. 5: 329-3a7.1950. ]3. Meissner, W. A. and Sommers. S. C.: Postyarttua endometrlal bryerplasia tn diabetics treated with stilbestrol and prolgesterone. J. Clin. Endocrino?., 30: e0,3-409, 1950. 14. Sommers, S. C. and Jobnaon, J. N.: Conte.nital tricuspid atresla. Am. Heart J., 41: 1b4-143, 1951. 15. Sommers. S. C., Wilson. l. C. and Hartman. F. W.: LTmpbold leslons in poliomyelitis. J. EzDer. Yed..93 : 603-512.1951. 16. Warren. 8.. Holt. ]C W. and Sommers. S. C.: Some early nuclear effects of fonisin4 radiatJon. Proc. Soc. Exper. Biol. & 11ad.. 77: 2F.&-.'91. 1951. 17. Holt, M. W., Sommers, S. C. and Warren, S.: Preparation of tissue se<tlons for quantitative hlatocbemtcal studies. Anat. Rrc.. 112 : 1 -M-196. 195:. 18. 8ommers. S. C. and Telob. H.: O.arian stromal b,rperplasia tn breast cancer. Arch. Patb.. 53 : 160-166. 19dr. 19. R'arren. S., Bolt, M. W. and Sommers, S. C.: Some cytotogic and bistocbem• lcal studies of radiation reaction. Sm. J. Clia. Patb., 22 : 411-117, 1952. 20. 1fcltanus. R. G. and Sommcrs, S. C.: Breast cancer prornosis and ocarian cortical atromal bsperplasia. New Ent. J. Wed.. 246: 890-89C. 195:. 21.Sommers. S. C. and Yoang, T. L.: Ozspbil parathyrold ademomas. Am. J. P a t b.. 26: 67 3-6 8 9. 1952. 22. Edwards. J. L. and Sommers. S. C.: Radiation reacUoos in parablotic rats. J. Lab. and Clln. Med., 40: 342-115l.195_ 23. Cbnte, R. \. and Sommers. S. C.: Hemolytic disease aad polccptbemta in parabiosta intoxication. Blood. 7: 1005-1018, 195=. 24. Bollander. A. and Sommers. S. C.: Lepromatous leprosy. I:esc En` J. ]fed_, 247: 634, 193=. 3.",. Cbristrnsen. W. R.. Sommers. S. C. and Spaulding. C. E.: Et•rct of so•t roent3en rays on the rabbit skin. Am. J. Roent`enal.. 63: 801-1-Z0S. 26. Sonrmers. 8. C.. Cbut. R. N*. and R'arren. S.: Heterorransplanration of bu• man cancer. I. Irradiated rats. Cancer Res., 1:: 90A-911, 193: i'CA. Cbute, R. 2K., Sommers. S. C. and R'arren. S.: Beterntrnn-plantatiorn of bu• man cancer. 11. Hnmaer cbeek pourb. Cancer Rrs.. 12: 91°-91i*. lA-'_. 28B. Somtn^rs, S. C.. Sulliran. B. A. and Warren. S.: Hetero:ranspl^n:atioc o: buLuan cancer. III. Cborioa)lantoic membranes of embrFonnted eg;s. Cancer Res.. 12: 015-917, 1952. 2?. BroRn. W. J., R'lnston, R. and Sommers. S. C.: Membranous stlpbylococ al enter)ti-i after antibiotic tbrrapc. Report of tw•o area Am. J. Li;e-t 20: 73-75. 19;,3. 2c. Sommers. S. C. and ldcllauu!t. R. G.: Moltiple arsenical cancers of skln and fnturtml or;.ans. Caucer.6: 397IA .'i. i'A. Sommers. S. C., Anderron. l. M. and Warren. S.: BnRement membranes in cbrnnic lnrestinal dixa.es. Lab. Inrrxt.. 2:~-~6. 30. R'akeA.•IA. R. D. and Sommers. S. C.: Fatal mPmbranout starbylocnccal enterltis In surgical patients Ann. Surg.. l3r: 2a9-.^.i:. 1P .M. 31. alc?1anu-. R. G. and Sommers. S. C.: Si:niticancP of gnstric polFl,s accotz,• ran r ' inr cancer Am. J. Ciin. Patb., "-n: 746-i57.19:,3. 32 Sot>lmrrs. S. C.: Ovarian Rete Cysts Am. J. Patb.,'„4: 833-8`~9.1n:3. CTR HIN 0 14733

1'HIS D4CUMENT SUBJECT TO 1087 CDlIFIDENTIALITY AGREEMENT. 33. Sommers, S. C.: E0docrine cban8es after LemLdrenalectomy and total bcdy irradiation in parabiotic rats. J. Lab. & Clin. l+ted., 24: 36G-40i, 19W.. 3a. Bolt. 1\f. Vt'„ Sommers. S. C. and Warren, 6.: lotranuclear chantes resulting from ezposnre to tonisini radiatlon as detected in frosen-dried prepara- tions. Lab. Ineeft.. 2: 40b-418.1933. 33. Sommers. S. C., OeTer, B. B. and Cbute. R. 1\.: •otoradloirrapblc arsenic localization in adult and embryonic eplthellum and connective t:ssue. Proc. Soc. E per. BLo1. ! Med., 8{ : 234-259,1963. 3E. Sommers. & C., Telob. 8. L. and Goldman, G.: O.arian lnDuena opon #or• .iral tn breast eanca. A.rcL. Snrj., 67: 916-919.1963. 3i. Sommers. S. C. and Lombard. 0.1i.: Cancer aaaoclated with orarian st:omal bsperplasla. Arch. PatII.. 56:4Q2-ld5,19S3. 3S. Warren. S. and Sommers. 8. C.: Pataulor,c of regional Ueitls and nlceratl.e colids. J. A.m. bed. Assoc.,154 :189-193,1954. 39. •damson. N. E., Jr. and Sommer+. S. C.: Endometrial ossification. Am. J. Obat. and Gsaec.. 67:18i-190,1951. 40. Chute, R. r., Senton, B. B. and Sommers. S. C.: A laboratorj epidemic of buman•type tuberculosis tn Damstera. Am. J. Cttn. Path., 24: 223-'r8, 19M. 41. Lfarcial•RoJas, R. d. and Sommers. 8. C.: DttTerentlat.ed mocoepidermoid tumors of saliTar5 glands. Arch. Otolaryln`.. 59: 13u-140. ]i+:,i. 4:. Hollander. A., Sommers. 8. C. and Ortm.rade. L. E.: Histocbemical and ultraviolet mlcroacopic atudles of eIlronic dermatoses and the corium membrane. J. In.est. Dermat, 22: 33.'~-U8,1954. 43. Strande, A., Sommers. S. C. and Petrak, )lt.: Repozul enterocolltls ln cocker spaniel dogs. Arch. Patb., 57 : 857-362,1954. 44, Sommers. S. C. and Ivfeiaaaer. W. A.: Basement membrane cbanties in chronic tb, ~r ldltt and otDcr tLTrold dLeaaea Am J Clin PatII 24 • 434-A40 . s 45. Wood. J. S., Jr., Hol7ote, E. D., Clason, W. P. C., Sommers. S. C. and R'ar• s ren, S.: An experimental stade of the relatlonabip between tumor size and aumber of lung metaauaes Gnttr, 7: 48i-M3,19G4. 46. Goddard, J. W. and Sommers. B. C. Method for thyroid cell mapping. Lab. Invest.. 3:19i-210,19uL 47- Colcock. B. P. and Sommers, 8. C.: Protinoais in Paget's disease of the brust. Sure. Clin. N. Am., 3i* : i73-783,1954. 48. Burt. A. S.. Landing. B. H. and Sommers. S. C.: Ampbopbll tumors of the bypopbcsis tnduced tn mlce bc I° Cancet Res.. 14: 49i-W.. 19,1. 49. Sommers. S. C. and ]leisaner. W. A.: Dausual carcinomas of the pancreas. Arcb. Path., 58: ]01-171,1964. 60. Sommers, S. C., Ederards. J. L and Cbute, B. 1\.: Increase in hyper- sensitivity lesions and parablosls intoxication after adrenalectomy. J. Lab. and Ciin. Med., 4•1: 531-643.1954. 51. Sommers. S. C.. Crozier. Ii and Warren. S.: IIltra.lolet microscopy of glomerular diseases. Am. J. Patb., 30: 919-939,19.54. 51 Turner. D. D. and Sommers, S. C.: Medical lntellijence. New. Eng. J. a1ed., 231 : 74i-i 45. 2954. 53. Patterson. W. B.. Cbote, R. 1\: and Sommera. S. C.: Tranplantatlon of bumIn tumors into corttsoue-treated baausters. Cbancer Res., ]4: 16,;. 54. Goddard. J. W. and Sommers. S. C.: Thyroid atimulation in diabetes m.l• litus. Diabetes. 3: 1954. b5. Sommers. S. C.. Murphe, S. A. and Warren. S.: Pancreatic duct bTperplasle aud cancer. Gastroenterology. 27: d;#1-6-10. 39:a1. 54. Rohman, W. and Sommers. S. C.: A double primary carcinoma of tbe nrinnrc bladder. J. i:rol.. 72: 13ii-11T7,19:,1. 57. Somuter-. S.C.: Some applications of ultraTiolet microacoly t(. B31Q. 5: ln'-]0l;. 1954. ~S. Lrmnn, H. Af. and Sommers. S. C.: Clinlcopatbologic cor.ftrencr. AC . J. , Cl/n. Path.. 24 :1403-3a0i. ]9;,4. 59. Summers. S. C.. Crozier. R. and Warren. S.: A study of rbe u1rrav:oict micrr.scopc of rrnal rarvlar dlsease•. Circulatiou. ]1 : 3~-13. 60. Wl.nJ. J. S.. Jr.. Hnl~oke. E. D.. Sommrnt, S. C. and 1%'arrer:. f`.: of pitultar7 rroRtb Lormone on troatb and metatat:i~ farmation of n transPlantable mouse sarcousa. Bull. Johns Hopkins Hosp.. tk;: ^::-l6G. 7fiS,. 61. Somwers. S. C. aud R'arren, S.: Vleerative eolitla lesions in lrradiated rats. ar:,. J. DiZest. Dls., 22: 111, ] M. CTR HN 014734

62. Sommen. S. C.: Endocrlae abnormalities la women +rlth breast cancer. Lat. Ine est., 4 :166-174.19:r,. 63. HaleT, B. L, Dews+ G. H. ..nd Sommen. S. C.: A histocbemlcal comrariso_ ol Di't>:aar+, thyroid b7perplasia and ad"omatotu goiter. erch. Pa::... ~: . 69:.-640. 1935. 64. Zeefer, C. S. *nd Sommers. S. C.: ClinicopatboloSic Conlerence. t= J Clin. PatD., 25: 1063-3067,1955. 63. Bommen, 8. C., Gates, O. amd Goodof. I. 1.: Late recurrence of gracu,v•l eell tumors. Obat. & GJaec., a: 89S-39S.19.',:,. 66. Sommers. S. C.: Deeelopment of ra.earcb at 1[aasachuaetts Hemor:a: Ho•- pltats. B1SQ. 6 :113-11S.19GS. 67. Handler. A. H.. Daris, S. and Sommera. S. C.: Heterotramplantaticn rspt:: ments w•itb human cancers. Cancer Res.. 16: 32-3t.. 15SG. 6S. Parker. T. G. and Sommerr. S. C.: Adrenal cortical bsperplasia areoa.;•ac~- las cancer. Arch. Burg.. 7~ : 49;r•499.19SS. 69. Sommers, S. C.: Testicular spermatogenic cell bFpertropby arcou l~:.~::.; prosutic bcyertropbe and cancer. Am. J. Path.. 32: lb;,-1:>r•• 70. Sommerr. S. C. and Baler. K. H.: Bimilaritc of clomerular absorptions ln diabetes melUttts and after conlson therapy. rrv.. c.- E per. Blol. & lled., 91: 262-265,1956. i1 Sommers. 9. C. aod Chute, R. N.: Ckrcinotenesis aad altered host reacr.oc, !n Darablotic rats. Atch. Path.. 61 : 265-304. 1956. , 7.. Sommers. B. C.: lntroductlon to patLolop of neoDlautic diseases. J. Stu9~ut A.'dl.a.. 21-25, Aprll• 1W. 73. 8bakbasblr, T. and Sommers. S. C.: Chronic menstrual endometrlum. G'•s: & GFnec., 8:112-135. ]bSti. 74. Sommers• S. C.: Basement membranes. =roup snb4ttaoces and lympbo<c:i~ at;6r•qates to aEing ortans. J. Gerontol.. 11: 2v1-28U. 2956. 7, . Bria, )st. and Bommers. S. C.: A'•bUjbted" ascites tumor. Trausplan:. 8 :100..•10C.1936. 76. Sotnmers. S. C. and lt'adman. P. J.: Patbo,<enesis of polccfstic orar:e: A=. J.Ot•st. & Gyuec.. 62: 16(-164+. 1N:.6. 77. BotrBbton. G. A. and Sommers. S. C.: Renal chante< in sbt.(l: tres:- lerorterenol tLevopbed). Am. J. C1in. Yath.. =; : 21r34. 1a~:. 76. Barr. R. and Sommer•.. S. C.: taur.ual cau.es of deatb after surRery, Aw. Heart J. 53: 23Z-2339 19' T . 79. •Ddartel• A. and Sommers. S. C.: EnAocriue correlatioi,• in tuaa:mert o- - Obrosis and cbronic crstic maetitiE. Ann. SurF. 3•i3: 80. Sotnmers. S. C.: Endocrlne cban8es w-!tb prostatic circiauma. 1, 347-35S. 195:. 81. Iamhie. A. T.. Burrow•s. B. A.• aod Sotntners 8. C.: Cltticoyatbotot` 17.•t- fereuce. Rrfnctorc anemia. apmmasltrbul:aeniia. and mediastmaf ••t Am. J. Clin. Patb., 27 : 444-i52.19L7. 8,21. McXu1tT, J. R. and Sommers, S. C.: Seraroacanrhoma as a surtic•a1 pr.:••- losic entity. 8urj.. GYaec. & Obft.. 104: 66"a-665. 1957. 83. Jaoei. R. G. snd Somrnerr. R. C: Glumerular siterbtiou< in l:ldnr•p- treated with desosycorticosteronr. Arch. Path.. 64: 64. Salts. H.. Sommers. S. C.. aod Smlrb.rict. R. H.: CliaicopstbolorFic cnr-.;. - tiowt of renal blopiies from essential hypenensive padents. CtrcuiL;:i :. 16: 20i-212. 1957. l:,. Merriam. J. C.. Jr. snd Sommers. S. C.: Mammary peridtutai bpa:::. itu dialxtic w omen. Lab. lncr•t. 6: 41:-t-^0. lN: .:. 56. Meisaner, W. A., Sommen, S.C. and Sherman. G.: Endon,rtrial endometrial carclnoma. and endometriosis prnduce+d erprriu,rnta:.: ; estrojen. Caacer.10: b00-W9. It+:,7. E7. Sommers. S. C. and atriAanrr. R'. A.: Ao•t rrlarioashipa ln esiw-riu-.: ,. eadoaietrl.al carcinoma. Cancer. 30: 510-515. lli:,7. 8fi,. Somniers. S. C. and Nelssner. W. A.: Endocrine abnonualitles acco:a.• .+- intz hutuan endometrinl cancYr. Cauc•er. 30: 516-5'11. lQ.*.T. 6w. Eontter, L.. Sommers. S. C.. Relmati. A. S. anil Enmer,m:. C. P.: in the .urFi;•al management of themic rumor: Ann Snrg.. 14fl:•fY+-1 - 1957. 90. Bsrr. R. a'. and Romnfers. S C.: Endocrine abnormalities acro:w s::-. : bepatic clrrbosis and bepetoma. J. Clin. Eadnc•rtnol.. 17: 1017-1V.1•. 1:. . 91. U1lriet. W. C.. Lentini. E. A. and Sommer>. S.C. Exc•itabllttc at,,1 tractllitc of postmortem buman beart muscle. L.b. lnreft., 6: 191-1t. CTR HN 0 1 4"r -5zj

THIS DOCUMENT SUBJECT TO 1089 IDpNFIDENTIAUTY AGREEMENT. 9e-1 Sommera, S. C.: Host factors in fatal Duman lan8 cancei. Arch. PatL , 63 :104-111,1966• p3 Iderriam J. C Sommers S. C and Bmltbwiek R_ Ii : C11n1copatDolo ~;cal . J ~ eorrelations of reaal blopalea in bTpertenalon w1tL p7elonepbriti.. Circu- Ltlon. 17:243-246, 1966. W Hoefer, E. D., SRinton. r. W., Ltkinson, B_ P. and Sommer,, S. C.: Pantl dfacnWon on cbronic ttlcaratlva colJtis. Am. J. Gastroenttrol, 1b: E73,19:,k. 95. Isar, H. d and Sommers. Bt. C.: Betroperitonea] ectopic seminal vesicle eommunlcattns R-Jth a eontralataral solitary kidney. keport of a ca_t. J. Crol., l6 : 94-9b6,1O56. 96. Sommers. S. C., Relman. A. S. and Smlthaick. R. B.: Histolosic ,tudies of kidney biopsy specimens from panenta tritb bypertenuon. Am. J. patb.. 5/ : ES.r-71L, 1D58. 97. Sommeri, S. C.: Constitutional aspects of sastric carcinoma. Arcb. PatL. 66 : 487-493,195b• 96• IIUricl:, W. C., LentJnl. E. A. and Sommers. S. C.: OFLen consumption of poatmortem human beart muscle. Proc. Soc. Exper. Biol. & ]ted., bb: .'it~- 24T,19tib. 99. Sbamma, L H., Goddard. J. W. and Sommers. S. C.: A study of the adrenai atatos in bTpertenaon. J. Cbron. Dls.. 6: 557-M, 1956. 100. Sllra, T. F. and Sommers, S. C.: Renal biopsy chanje. with pbeocbromocs• toma, Am. J. 1Ued. Scl-, 238:700-704. 1958. 101. SeIDer. B, Lenson. K. and Sommers. S. C.: Carcinoma arising ln minor aaUvarS gland ducu of the lower Up. lm. J. Sura., >i7, : 79-82. lfr'.,br 10:. Strong, S. 11. and Sommers, S. C.: Bronchiojenlc carcinoma 1rcb. Oto- laryng. E8 : 764-769,193e. - 103. WilkSns, R. W. and Sommers. S. C.: CUnJcopatholosic Conference. Enlar`e• ment of the heart. cardiac failure a.nd loote, drJ .calj akin. Am. J. Clit:. Pa tb.. 31: 68-72.193b. 10a. Sommers. S. C.: Pituitary cell relations to body states. Lab. Invest., 8: SS~- E2L 193b. 203 CoQnttn, J. D. and Somwers. S. C.: Famllial p,uudozanthoma elasti:uu and ealcnlar heart disease. Ctr;ulatlon, 19:242-250, 195b. 106. Sommer., S. C.: Pathology of the Kiduey and adrenal gland in reiatio::• ship to bJpertension. ln: •'liypertenslon" W. B. Saunders Co.. 23. 11,_~,~ i kl S C l i 10~ d GD d S O i h an ommera ter cm ....,.. taa s : r a of t c cancer and c•lmic•a: Ln r ' ' correlations of tbemic• tumors. J. Tboracie Surg.. 37: . 3-2H0, 193:. 108. Androutsolaulus, N. A. and Sommers, S. C.: Postmenoyausal endometrios:> Obstrt. & G jnrc..14 : 240-24A.1959. 309. DUricl•, W. C.. Lentini. E. A. and Sommers. S. C.: Summation and tetsnu- in postmortem human heart muscle. J. Appl. PJtcsiol.. la : 587-56i. ]'-5:- 710. Hollander, A. and Sommers. S. C.: Current case of lepromatous lepro~-. acid-fast bacilli in epidermis. Conn. Ned. 23: 65tr~, 2939. 111. Thayer, C. I.- and Sommers, S. C.: Host factors in carcinoma of the uterinr ~ cervlz. Am. J. Obatet ! OFnec., 76:386-392. 1959. "Cl b l i " Bl tb J 1d B d 6 S C U l i ds ae ommers rr o omeru osc eros s oo ror : c 8 ....,.. A neral lesion asaoclated with belatic cirrboeis. Iib. Invest., 5:96.-97;. 11K,b. 113. Fuller. C. H. and Sommers, S. C.: The thyroid ttatus in relatlon to ar• terioaclerotic disease. B. 31Q. 10:1-2. 1919 114. Sancbes. G. C. and Sommers. S. C.: Peptic ulcer diatLesis with a a,ia-•1 adenocarcinoma of tDe pancreaa: Oase report. Gasuoenteroloe.r, 35: 41;.- 470. 19b0. 315. Sommers. S. C.: Renal a.nd adrenal pat.boloBS in hypertension. Conn. Med . 24 : 240-2•44, 1960. 116. Selis. J. R'. al.. Parsons, L, Friedell. G. H. and Sommers. S. C.: A patb~lotic atod. Jn 85 aatopsiea after radical surgery for cancer of the cersiz. Sur;, Gynec. and ODat.,110: 4x3-M.1980. 117. Hollander. A. and Sommers. S. C.: A blstochemical stndc of mucofpnlr• ucrbarJdea of leprosy of the skin. Acta. Dermat. Venerrol. Pro~. 11:1: r lnternat. Congr: Dermat. 8: 407-411, 195,'-1960. ~ 136. Bnckingbam. S. and Sommers, S. C.: Pulmonary byaUne membranes. J. Di:. CLlld., 99: 219-- "M,1980. 119. Patwn. B. B. and Sommera S C.: The biwpatdologc of iafarctlon and other ulcerative diseases of the esophagus. Am. J. Clin. Path., 33: S]G-5_a, ]:•tiv ?9-28G--6p-pt. 3 -71

® ® THIS DOCUMENT SUBJECT TO 1090 CONFlDENTIALlTY AGREEMENT. 120. Hollander, A. and kommers, 8. C.: Histocbemlal comparison of Boe^l•'s Sarcoid with other cutaneons sranul6mas: Arcb. Dermat. 81: 044-ts4G, 1980. 121. FrledelL G. H., SDerman, J. D. and Sommers, 8. C.: Spleen and IJrer in the anemla of tbe tumor-Learing hamster. Arch. Path., iU: liK,O. 122. Graasi. J. E. and Sommers, 8. C.: A case of carcinoma of tbr breast in a young woman with bamartomatous d7potbala.mic malformatioa. Am. J. 8 u rg..100 : 606-41 _, 1080. 123. Celoria, G. C., Friedell, C. -H. and Sommers. 8. C.: Raynaud's di•ease and primary pulmonary hypertens:on. Circnlation. 22: 10:,;r10J9, 1900. 124. Tnrgeon, C. and Sommers, S. C.: Jtutagiomernlar cell counta and bun.ao bTpertenslon. Am. J. Patb., 38: 227-241,1981. 125. Sommers. S. C. and Tvrg.on. C.: ]dorpbologic studies oo relarionshif+ of peelonepbrida to DTpertensJon ln: "Blolo, of ppelonepbr.ti~" Littie Brown and Company. Boston, 1960. 126. McAuley, R. L. and Sommers. S. C.: Mast cells in nonspecleSc ulceratire colJtis. Am. J. Digest. Dis., 6: 233-26, ]9C1. 127. Somtners. S. C. and Verendia. J.•B.: An appraisal of laboratory determina• tions of estrogens. Am. J. Clin. Pathl., 33 : 319-3_7. ]9C7. 128. Tln. P-H and Sommers. S. C.: Some patbologic eorrelatlons of orarian atromal byperplasia. J. Clin. Endocrinol. k ldettb., 21: 47:-47:. li'+(:1 129. Patalano. V. J. and Sommers. S. C.: Blopsy diagnosis of periarterius nudusa. Arch. Path.. 72 :1-7. 2961. 130. Tedescbi. L. G. aad Sommers. 8. C.: OxTtalan 6bers in sclerosing beman; o- mas. Arch. Dermatol., 84 : 1°-8-130, 1981. 131. Sommers. S. C.: Some patbolo8ic conditions associated with renal and ad- renal hypertension. J. A. M. A., 178: 715-717,1961. 132. lYledell. G. H.. Sherman, J. D. and Sommers. S. C.: Growth cnrres of bu- man cancer transplants during experimental chemotherapy. 14: 1117- 1721. 1981. 133. Sherman. R. P., Gratsi. 7. t. and Sommers, S. C.: Hamartomatons mal.for- mation of the postlateral hypothalamus. Lab. Inrest., 1] : 8tia7. 19G_. 134. tt'illiams. M. J. and Sommers, S. C.: Endocrine and certain otber changes in men with carcinoma of the lang. Cancer,1S: 10EA-1]7. 198''. 135. Ganem. K. tYiedell. G. H. and Sommers. S. C.: A stody of orarian tbecoms- tosls. California Medicine. 96 : 234-°±..~ 1962. 336. Tedeacbi, L. G. and Sommers. S. C.: Oijtalan dbers-dermal Dhromas and giant-cell tendon sheath tumors. Arch. Derm., 85: br-S:w, 1FE^. 137. SoerFel, K. H. and Sommers. S. C.: TDe alreolar epitbelial lesion of 1Cto- jntbic pulmonary bemosiderosis. Am. Rev. of Besp. Dis., 85: 510~3-, 1962. 138. Soerget. t'.. H. and Sommers. S. C.: Idiopathic pulmonary bemosiderosis and related srndromes. Am. J. afed., 33:499-511. lt;'G:. 13n. Sommerr. S. C.. alcLaut;hlin, R. J. and ]tcAnlec, R. L.: Patboio, of d?a- stolic DFtxrtensinn as agenerallsed .ascnlar dl-ease. Am. J. Cardio:., ]fac, ]963, 6a3-6:4. 140. Reeles, C. and Sr.mmert. S. C.: Endometrial bemosiderlo as eride:,,e of metrorrhaRia. O}iq and CT\..19 : 7AL-7412. l9^:. 141. RrcnNd%. C. T. and Smirbtrict. R. H, and Sommer~, q C : Ex,i,io- of adrenal adeanmu and •ympatbectomg In the therapy of bFpertr--ion. J. Surgery, 103: Q9(-701, 1982. 242. Nori.. B. 31. and St+xmert. S. C.: Statat M th(, myocardi:tl arteriule• In au:ina pectoris. Amer. Heart J.. 64: 32&-3°.3. ]AC2. 143. Recni-lA+. C. T. and Sonimers. S. C.: Scmv;itl,ertoruy for Elotneruio-n~yb-::i• with hypertension. Arch. Sur:.. C', : SP(ti-393. 144. Snmmr-f. >;. C.. Rhbinr. G. B.. Bal.iu. D. S. at:J Fnascl. C. T.: CL-<•r.'c pyelnnephritio. renal tubular atrophy and bypertenao:,. Arch. Ita. JI-1 . 110: 60;,-510, 1962 ]a5. n'hEkr,wnrl. J. ~1.. T.o.ra.. D and Somtner.. q C.: come bn.t fs•:~r< :c rhi• d^r.lnlvm"nt nf renal cell carcinoma. R'est J. of Sur,^.. nb<. Q( c,ec.. 70 : 254-'~S. 1902. 14G. B-iuchtlm. R. i1. anA Qnmm.r!. S. C.: A new eoncept of renal bSpcrtrn•:-u 3. C rololte, RA : 113-136. 1983. lal. Reere,. C.. LoR'eniztein. L. and Sommera. R. C.: A sugce!ted mPchar•.is::, nf er!rthrnpnJrtie control of Ju:taglomerulnr cells. AID. J. NJrd. q.i.. _'a'.: 134-187, 1883. CTR t~~~ 01419 ~'~

THIS DOCUMENT SUBJECT TO 1091 CONFIDENTIAUTY. AGREEMENT. 145. Harlc. B. and Sommen, .8. C.: Endometrial carettaae In diagnosis and therapy. Ost. & GSaec, 21: Q36-d38. 1963. . 149. Sommers. S. C., Weber. C. E. and Reeres. E.: A bematjlDtination resction of mothers and tntant+ of dlfferent LBO and Rb groups. Am. J. Clia. Pa tb., 39 : 482-4Si. 1963. 150. Russfleld, A. B. and Sommers. S. C.: The affect of malnotrition on tropic hormone storage 1n the bumau bypopbTsis. •rch. Path•. 75: 504. ]9G:. 1L]. Beaser. 8. B.. Salt. M. and Sommers. S. C.: lntloence of tn,alin therapy and pyelonepbrltis upon diabetic ilomeruloaclerosis in bamsters. lfeub. 12: T0•1•-709, 1968. 1'.:. Sommers. S. C.: Some endocrine and Immunolot;fc axpects of proRn,,si- in breast arclnoma. •cta t'nion lnt. Coatre Cancer 26: WJ-60. 1bC2 153. Reeref. G.. Figuerdo. A. and Somnrers. S. C.: A ea•e of breast carcinotr.a with hcpothalamic malformation. West. J. Surg. Obs. k Gyn. 71: lE+- 186, 1983. lS,f. Hatt, W. S. R, and Sommers. S C.: A c1lDicopatholoFic analcsis of biopsc •recimeas ln persistent slomerulooepbritls. Am. J. Patb. 43: 45'.H1;,, 1963. 153. Bowden. D. H.. Danis. P. G. and Solnmers. S. C.: Ata=ia•Telangiectasla. J. Xearopatb & E:p. N eur. 2_ : 549-553.1963. 236, Beaser. S. B.. Balc. W. F.. Donald>ou. G. R•„ McIwDrLlln, R. J. and com• mers. S. C.: Allozan diabetes in the golden hamster. ]fesocricetos Auratus II. Glomerulo•clerosis and fu relation to diabetic regulation. Diabrtea, 13: 4D~'.t, 1964. ' ]57. Williams. al., Barnes, W. D. and Sommers, 8. C.: H.poaatremis. antJ• diuretlc hormone secretioa and oat cell arcinoma of the lang. Dis. of Ch e s t. 44 : 95-99, 1963. 155. Monroe. L S.. Boughtoa. G. A.. and Sommers. S. C.: The aaaociation of Rastric epltbellal bTperplasia and cancer. Gatttrocnterology 46: 267-2-.=, 1964. 1;,9. Teel• P. and Sommers, S. C.: Vascular lnrasion as a protDostk factor in breast carcinoma. SDrt. Gynec. and Obstet. 118: 1006-]005. ]9fa. 160. Reeces. G.. Lo.censtein. L and Sommers. S. C.: The renal macuia densa and lasta8lomerular body and cirrhosis. Arch. Iat. lded. 1L^: 10~-715. ]9c-3. 161. R•/lliam. Jl. J. and Sommers. S. C.: Empb.sema, peptic nlcer and lun; carcinoma with pituitary Crooke's ceUs. Am. J. Dded. Scl. 247: 4_^2-tL,. 2964. e 16= Sommers. S. C. and Dixon. F. J.: Seminar on untoward reactione to trest- ment. Am. Society of Clinical Pathologists. Chicago. ]AG1. G-. pp. 163. Breslau. A. M., Gonkk. B. C.. Sommers. S. C. and Gere. L. B.: Patbo- tenesis of chronic pyelonephritis. Am. J. Path., 44: 679-705. 1964 364. WrJrbt. C. F.. afedeailta. G. A. and Sommers. S. C.: Perinatal deo:2 ! A clinicopatbological analy%ls of 99 cases. Calif. Dled. 1(j0: 336-;1). •196-1. 165. Sommers. S. C.: Abnormalities accompanYint carcinomas of the lar;e in- V~ testine. Dis. Colon and Rectum 7: 262-269. 1964 . I6C. $ennedJ. J. A., Ailliamx. 11. J. and Sommers. S. C.: CusbinF's sTOdrome and cancer of the lnnt;: Pitultarc Crooke Cell LTperplasia In pulmonary oat cell carcinoma. ADD. SDrg. 160:tNL-94. 11404. 167. Sommers, S. C.: Patbolorc of essential bFpertension, CYclo. 3fed. 4:0--15. 19F.L 16S. Buclinpbam. S.1fcNarJ, tC. F.. Jr.. and Sommers. S. C.: Pulmonary alreolar cell Inclusions: Their derelopment In rat. Sciencse, 345:]1J>:'-t3. 1PF-1 163. RuaiAeld. AFnes. B.. F/sbrr. Edwin. R. and Summers. S. C.: Disrociatinn of bnmof+bytleal content and urinary excretion of ronadntrnria in cinbusis Proc. Soc. Eip. & lfed..116:*a. 1M'_-]02a .-]02a. Aur-S«lrt. 1fM1. 1-,0. Somniers. S. C.: Pulmonary emphcsemot. bealed mFncardin: laforcts nnd otbvr diwse correlations with male breast structurc. AV J. 11rd. S.i.. 2aS :Selu. 1964. 341-3-N. 171. Sununers. S. C.. Gonick. H. C.. Salmanson• G. lf. and Gu:e. L. B.: Pn:bo- RenesJs of chronic pyelonepbritis. A)1. J. Path.. 45:*5 1214-T3q. \o. ]!Ka. 1'2. Friedell. G.. Bettl, A. and Suwmers. S. C.: Ttte proFnostic Talae of b:nod .sesel ineaslon and 1ymPocrtic iaCltrates ln breast carcinoma. Cauccr, 18 : *=. ] C.a-G0. Frb.196:~. 173. Kennedy. J. H.. W1111anm!t. !1. J. and Sommers. S. C.: Pituitary Cnoole Cell byiMrptasla in pulmonary carcinoma, Acto Calo Contra Cancrum, 20 :1;.,.` , ] t+G-L C~TR HN 01 ~'~r'`~~

1HIS DOCUMENT SUBJECT TO 1092 ODMFIDENTIALJTY AGREEMENT. 774. Gonlck. B. C.. Rabtal. 1!. D, Oleaaon• i. 0.. and Sommera, S. C.: The reno'. le.lon In foot. Ann. lot. Hed„ R2:6Cr-674,1983. 173. Sommers. S. C.: B7pettenslon and Sldne7 Disease. Prog. In Cardior;tscular Diaease. 8:230-S1. No.„ 1965. 17& Lalman.on. 0. li., Sotamers, 4. C. and Gose. L. B.: PJelonepbrittc 1'lI Ez• petimental aacendin8 lnfectlon w-itb pr'oRaaioa of lesions in the abse--ce of bacttria. Lrcb. Path., 80 :S09-S1E.196S. 177. Bee.er, 0. and Sommers. S. C.: Senaltirlb of tbe renal mscola denaa to arinary aodlom. Proc. Soc. E:p• Blot. Med.. 12U:3s4-x'6. 1b6;,. 17& Sommers. S. C.: Endocttrse pathology of prostatic bypertropby and csrc:- noma. Bull. N.Y. Aced. Med, 42:p248. Marcb. 1968. (ebstracti. 179. Berco.lti• Z T. and Somtaera, S. C.: Altered tn0ammatory reaction ic nc-- apeciDc nlceratl.e coUtis. Arcb. Iot. Med.. 117:54l. •pril. 1966 180. Friedell. G. H., Sommers. S. C., Cbote, R.N. and R•arren• S.: Orarinn genesis in irradiated parablotic rats. Cancer Res. 2K:4:7-434. 8t;. 151. lleissner, W. A. and Sommen, S. C.: Endometrlal cbana(•s after prolonged pro8esterone and testotterooe administratlon to r.bbits• Cancer Re-i 474Jt78. Marcb.1966. 182. More, B. 1f, Merdlnter• W. F. and Sommers. S. C.: Cbolec•rsltis and s:eco::: arterloaclerosia• Am. J. Ctin. Path. 46 :465-46?.198C. 188. Sommers. S. C.. Friadell, 0. HL and Bobtnson• C. R. : Cbemotberapy of 13u=sc Cancer 4lranaplanta pitb Yetbotrexat. (LmetLopterin) and Hor~e Seruzi. Cancer,19:a74--67& 1986. ' 184. BrLlndler, A. lrt and Soto.mers, 8 C: Diabetic Sclerosis of the Jtut.tiomeru• lar&pparattu. Lab.Iosaat.,15:877-884. MaJ,198G. 185. Sommers. S. C.: Renal Factors In HFpertmslon. HenrJ Ford Hosp. ?Ld. BtilL.14 :47-54, ldarcb• 1968. 186. BocYln=bam, S., Hetnemann• B. 0.. Sommera• S. C. and ]fcXary. W. F.: Pbospbolipld Byatbeais In tbe Large Pulmonary AlTeolar Ce11 : Its R-:a- t1on to Lung Sarfactants. Am. J. Path.. 48:1tY_Y-1W1• June. 1P80 187. So1oRa!• H. B. and Sommers. S. C.: Endocrioopatby Lssociated R::b ?a-.- creatic Carcinomas-Ree/eR of Host Factors Including Oonadotropic Activity. lnnaL of Sursery, 18•/:3UU-30-t• lP6t; 188. Lsraeb. J. H., 8eale.• J. E. and Sommers. S. C.: Patterns of edrer,al Ze' --- tion and trinary Excretion of Aldosterone and Plasnta Renir, ectic;:y i- Normal and Hlyertensl.e Subjects! Supplement 7 to Circulation Re:ea:.L. \'ols. XCII1 and rIS• 1-15b-1-174. June.l9f,C. 189. Cannon• P. J.. 8tason, W. B., Lemartini. F. E.. Sommers, S C. and Lsr2:*_. J. H.: Flypernricem3a 1•n Primary and Renal HSpertension. NeR Ei: J. l.fed.• 275: 437-i64. Septe.mber.1b88. 190. Sommers. S. C. and FYiedell, G. B.: StodJef of Carcinogenesis In Parab:••r:' Bata. Lnnala of New York •cademy of Sciences, 125:92S-932, JanusrT. 1966. 191. Slrter, S. J.• Sommers. 8. C., Haagensen. C. D. and Coolec, E.: Rr-erij~tj::o:% of Blood Vedsel In.asion as a ProRnostSe Factor iu Carcinou n oi tt- Breost. Cancer. lb :1313-L'1C. SrpteuLer. 19Gt;. 392. Hyman• G. A. and Sommerx. S. C.: The I),ecelnPmeut of Hod;l:in'- I.•-. •• and LTmpboma I)urin` Anticronvolsant TberayF. Bluod. 2S:a1c-IC'. :- 193. Sommers. S. C.: Mast Celle and Yanetb Celitc iu L'Icerative Colitis. Gn-:- -: t e r n l ogT. 31 : N41-F4 i.1 W. 194. Sommers. S. C.: Patbologc of Cen•lcal Corclnoma. In ••Xen• t uuwrt•r- : GyUecoloai(•al ODColoi;}•'' Iirhurmnuu K:rmyu-iuu,. 195. Sornmers. S. C.: The S1Rni6vanre of Endometrinl }lcperplasiss Ic °~- Concept• In Gynecological Uu(•olusc•' Habueujann .rml•naiuu,. ~-_ - 19fG. 19G. Sommers. 8. C. and Bercorlts. Z. T.: InAammatory Responseq In L'1(rrat:•• Culitis. N.r. State J. lf e(!., 88:3044-3U•i`•:.1t". 197. Ssoboda. A. C., Jr.. Snauer• C. St.. Gamble. C. N.. Sommers. R. C. sull >r •e L S. Problems In the Ear1y Iliasnosis of Peptic Esopba`iti,. Endoscope, Feb. 190' . 198. Caracaca, J., Dlmond• E. G., Sommers. S. C. and aenk. R:!'rr~r~ InAuced •tberosclrrosis by Perozidase. St•ience, 1961. 199. Rippey. J. H. and Somm-:ra. S. C.: Acpert.ropbiad plasma cells in enterlti*. Atn, J. Dig. Dis-• 12 :465. 1987. CTR- HN 0 14739

200. Leon. N. and Sommers,, S. C.: Cells of mascnltnlzinir tJpe'!n ovary of a patient w•itL feminine pbenot)pe. •cta Genetlca tt Stat. l+fed., 1-, :345, lf)8i. ' 201. Gor.ick, H. C., Paul. W., SommerR. S. C. and Gttse. L B.: lbnctional studiet Correlation between acid ezcreunt In e:perimenui pselonepbritis II . . t ablllt7 and ens.me b.Jstocbemistrj. Acid ezcretlon and enzcn,t bisiv- " ebtmi" in experimental pselootpbrJtis. Kepbron, 4:i5. 1967. 2U-. Goldenberg, V. E., Bucklngbam, S. and Summers, S. C.: Pulmonary alceo- lar lealons 1n.asotomiscd rats. Lab. in.est: 1E. 983. 2967. 203. Sommers. S. C., Reeves. G. and Reeves. E.: ImmonoloRic and cb•mnrhera• peutic e:dects on buman melanoma brterotransplants. Proc. Suc. Ezp. Biol. and Wed.. 123:740. 19Gi. 204. Buckingbam. 8.. Sommers, S. C. and SberRJn. R. P.: Iesions of the dorsal ragal nuclctta Jn the respiratory distress sTndrome. Am. J. Ctin. PatL. 4 B :289. 19ti7. 20.;. Sommers. S. C.: Srstematlsed nomenclature of pathology. Pat:boloeia et ]d icrobloloria. 80 :fC'8. 1987. 206. S:ranaa. 11. D., Sommera, S. C.: Medullary cystic disease and familial Jure- nile nephronopbtbiais. 'Ne+e En`, J. Med. 277:883. lAG7. 207. Elabi. E. H.. Long. M. E., Fricl-. H. C.. 11 and Sommera. S. C.: Lonr-term rurriral In dlaseminsted orarian carcinomr. Am. l. Obst. and G7oec.. 914: 5-".196i. 206. Dennins. C. lL. Sommers. S. C. and QniateF, H. J.: InfertilitJ ln male patients with ccstic tlbrosia. Peiliatrics. 41:7-17. 198F. 209. Barrington. J. T.. Sommers. S. C. and Sasslrer. J. P.: Atberomatous emboll with proCresslce renal failure. Renal arterioFraph7 as the probnbie mcit- Jng factor. Annals of Int. Med., 68: 152-180. 19f.6. 210. Cannon, P. J., Leeming. J. 111., Sommers, S. C.. Wtnter,. R. W. and Laragb. J. H.: Jaztaglomerular cell bFperplasia and secondary b.peraidocleroc- lam (Bamer'a Syndrome) : A reevaluation of the pat.bopbysiolo`c. 11edi- cI ne. 47 :107-131. 1985. 211. IwraRb. J. H.. Led/nRbam, J. G. G. and Sommers. S. C.: Secondary aldos:er- ouism and reduc.d l.lasmo renin In bypertensive disease. Traas. essoc Am. Physicians. IaX\ ab`]S1. 1965. 212. Marke.rltz. ]l.. Sommerr. S. C.. N-eenema. R. J. and Butler. !f. D.: Testi<u- lnr biopi-c artlfacts resulting from Improper tissue processing. J. 1-'roi . 100 : 44--f9. 198<<. 213. So¢mers. S. C.: In tJ.'•LB. B1nodRortb. ltiitorl "TeittK•ol• of Endocrine Patbologc^ TAyroid Glowd. Williams and Will-ins Co.. pp 133-180. 14i5 214. Sommers, S. C.: !n "Teztbook of Endocrine Patbnlogy". J.31.B. Blnnd- .cortL, editor. Eedoeriae acr;rir;ri of T'onendocrinc Tuaae Twnwr#. n'il- llams and a'ilkinF Co.. Baltimore. DId. 1985. 215. lltcbek. A.. •1briFbt. K. L and Sommer.. S. C.: The renal pathology of toxemia of preYnant:r. Ob. and Gyn.. 31 laC~. 216. BocktnRbam. S.. Sommers. R C. and WN*arc, W. F.: Exprriroental reeD:re- tnry distress rl'ndrome: I Central aotnnomlc and bumoral patboreuF::c factors in pulmonary /nJurc of rats lnduced with byperbaric oscceu and the proto-rtJee effects of barblturates and Tr:,cclol t£' Biol. \eonaL. 12 :281-251. 1986. 217. PaleJ. W. B_ Pbanenf. G. J. and Sommen. S. C.: Colneld.ntal prin:3rc prcoma and carcinnme of the cerrix. Ob. and Grn. 33:41-47. 19C9. 21B. Goldenberg. V. E.. BuckingDam, S. and Sommera, S. C.: Pilocarpine rt:n:u- latlon of granular pneumoc?Ye secretion. Lab. Inceat. 20:147-156. 19C?. _ 219. Elster. 8. J.. Bommerr. S. C.. AaaFen•en, D. C.. Friedell. G. H, and Coo1Fy. E.: Nuclear grade and sintu bistiocTtosis In cancer of the breast. Cancer. 23 :570-575. 1989. 220. Sommers. S. C.: Hi*tnlogic eDanjes In lneipient carcinoma of the brea~:t. Cancer, 23 := 1989. The CtlAiztlsAl:. Thank you, Dr. Sommers, for giring na the benefit of rour rieRs. Mr. V>,x DrxR.iN. Thank rnu. Mr. Chairman. Dr. ~Zommers, R'hat is the C'ouncil for Tobacco Research? Dr. Soldxtns. The Council for Tobaoeo Research. sir. is now a pprox i- mate)r 15 -rears old. At that time, the various tobacco cotnpanteQ-, the Ctm t`. t ! i `! t..A .t `"'~ •t` t `°t N,JF

THIS DOCUMENT SUBJECT TO 1094 OWpENTiAUn AGREEMENT.. major ones in the United Statesr got together and pt•oi•ided fund: to used for medical and biologtca`l research in the field relating to smoking and health. There was de%•eloped a scientific advisory board. The board is listed in one of the att.achments that, I hare inserted into the reci)rd. These are indii-idual scientists and physicians who act as a rerieo: board for any project request for monec to help research in these fields. There is a report of the 15 cears aeticitS by Dr. C. C. Little Ri::•:: has been published and is acailable. Mr. Vev Drrxr.rN-. Mat is the AILk-ERF ? Dr. Sosrarxxs. The American Medical Association has an educat and research foundation which was funded by the tobncco indu=tr%-. ~fr memorr is not ezact,but I beliex-e at fir~ they were gii-er, =_- millron and t)ten some cears later ,? million more in oider to uij.:rr- take ini•estigations in the fielr}of smoking and ltealrlj. This moner is administered and dispensed by the AM A tlirou::. n scientific board to inrestigators interested in the projectc in thi- ne?d. ),fr. t'A-. Dtzu.ix. There was criticism at the time. 3s I rer-". nf the AKX, for accepting money from this particular source for particular study. HoR lon.g ago Ras this? Dr. SousrtRS. I be.liece rt goes back 7 or 8 cears now. Mr. VA,, Dr.r.xr.i-.. Thank You, Mr. Chairman. The CaAntMex. Mr. Watson t Mr. WATSON. Mr. Chairman. I apologz e for being ]n'e in arrn•:.:. but I was unaA•oidabls detained. May l defer any question:n: un•i? I hace occasion to glance over the Ritness' statement ? The CRAgt.~rA--. Dr. Carter? Mr. Cax•mt. Tltank rou. Mr. Chairman. Doctor, it sePmiz that rou are quite a bu=r mnn. I1irP; ror of ln?. ,~- tories. Lenox Hill Hospital: clinicil prnfes~or of patLolnven-. C'nlt,n:' tnii•ersit~ College of Ph~sirians and Srueeons. \e~• 1 o:•k mPi-:~' profes.~or of pathology, and Lni%•ersitc of Southern California of Medicine, Los Angeles: You teach at the Cornell \Iedical ~'.. •~: Medical CenterandNeR• Yorhl+fedical Collefie. Also, the Veterans' Administration hospital consultant in rath, ~._c and editor of the Pathology Annual. cl:~ I think from these connections cort must be worthy and well Sed. I further think cou hare gicen a cerr good pre=entation. I read in the paper last Saturday that $ecretarr Finch of the I)~- partment of Health. Education, and I1'elfare had announced th.1• ii,• dustrr and Qorernment were enltaging in cooperatire efforts to es- plore the gaps in knowledge on the questaon oi smoking and he:tlr!;. Did vou read thatt Dr. $oarxctes. Yes. air; I saw that news release. R'hat has haPl•e,:e;l is at the time of the American Medical Association Convention in San Francisco in June last)ear, a committee was formed comprisir._ representatii•es of the Nattonal Institutes of Health. Dr. Endi-tt beu-g thechairman of that meeting, and also representatiTes froni tl:- Amertcan Medical Association-ERF and the Council for Tob,r:•o Research Scientific Adivaorv Board. The wish was to outline for all three groups the lack of 1-noRle ;_e or the places where knowledge was deficient in reRard to smoking and hµlth, and then to set ap priorities for research in this field. CTR HIN 0 14741

THIS DOCUMENT SUBJECT TU 1095 CONFiDENTIALITY AGREEMENT, The subcommittee was appointed, of which I am a member. It has met on several occasions since then. K'e are hopeful that in a month or so .ce will have a ring1e docu- ment that will reflect the combined feelings of the National Institutes of Health, the National Cancer Institute, the AMA Research Foun- dation and the Council of Tobacco Research Scientific Advisory Board as to the deficiencies in knowledge in this field and the order of priorities that one or more of theae groups will give. I very much hope we will get such a documenL I think it will be belpful to all of us in the next 5 years or so. Mr. Cs~. Realiution has dawned upon many of these people that there are many gaps in the causation of lung cancer, is that true t Dr. SouxEas. Yes, sir. If r. C.xm. Are you acquainted with, and have you had any asso- ciation with, any members of the Surgeon General's Adcisor~ Com- mittee which issued its report in 19641 Dr. Soxnna. Yes, sir. Professor Fieser, organic chemistry, taught me chemistry in college. I have known him for over 30 years. Dr. Emanuel Farber and I are friends and belong to a club together, a scientific club. ' I worked for Dr. Jabob Furth as his executive officer at Delafield Hospital for fire years, so I saw him every day. ,. Dr. Furth is awonderffiil man. He and Dr. Farber areexperimental patbologists. Their interest is in animal e:perimental models of dif- ferent diseases. I was very impressed with the committee and with the scientific re- port of the committee in 1964. As a matter of fact, I helped Dr. Furth to rewrite part of it because being originally Hungarian he bad some feeling hisnglish wasn't as good as it mi$ht be, but, in fact, it is verr So I was impressed. Then I read the report and I realized what had happened. They had simply done a selective recieR of the literature. They had not invest.igat,ed all aspects. The report simply didn't corer the entire field, in my opinion. It was a disappointmenf. Mr. C.>tTuL It was a disappointment i Dr. SoxxrRS. It was a disappotntment; yea. Mr. C..:rrx. It was not accurate as you see it, and did not corer all aspectst Dr. Souxtias. It is not, sir, that it was inaccurate. It Ras selective and it, so to speak, .rasn't guite equally Reighted on both sides. Mr. C.xt~a. It contained manvgaps, then 1 Dr. Soxiruta. Yes, sir; manv aefictencies. Mr. CNrrcx. I notioed vou mentioned primary ca. of the lung and also the secondary ca. of t}ie lung. According to tbe mortslitc tables which I hare, 21.000 people hed primary ca. of the lung last year, and aecondarf ca. of the lung Ras about the same. Secondary ca. of the lung may be due and often is due to problems from other parts of the bodS, is that not trueT Dr. Souxr.xs. Yes, sir. In one study, 25 percent of the cases thought to be primary lung cancer at autopsy turned out to be secondary carcinoma. CTR HN 0 14t~~

1096 THIS DOCUMENT SUBJECT TO (ONFIDENTIAUTY AGREEMENT. Mr. Catrrr.n. So many of the.ce reported cases.actuallc are meta- static and come frorrL lesions in other places in the bodc. prostrate. perhaps, or bone, or stomach 1 • Dr. Soxxzxs. That is correct; yes, sir. Mr. CaaTm. Inhalation of smoke. a¢ain, in experimental animals has never produced lung ca., is that true! Dr. Soxxs8s. That is my understandinF. Mr. Cexrrn. By the .rav, do you know if horses hace emph~sema ? Dr. Soxxrns. Yes, air.*Horses are a very good ezperimental model for one form of emphysema. ~1r. C.~rtzs. Do horses amoke 1 Dr. Soxmmta. No, air. Mr. Cexrm Thank you, sir. The Gw.a<Y.x. Ms. Pickle t Mr. Picat.a. Thank you, Mr. Chairman. Dr. Sonuners, I have been impressed with your testimony. You hare quite a background. You are research director for the Council of To- bacco Research, but I still must say that you have made some rerT strong statements that are in contradictton to the majority of the people who have testified here before this committee. Do ~ou have any recotnmendations for this committee with tr=~~ect to th~ problem facing us so far as the course of our le_islative ar.- proach is ooncerned t Dr. coxxraes. I would answer you as a physic:an. I beliere that the pre=Pnt labeling on the cigarette package to the effect that cigarette smnking mar be hazardous to rnur healtt. n5 the ritna•inn now Ftand=. iF sufficient. lt is about as much as I feel we know in the field of smo's• in and health. I don't believe that individuals or the Government should eo beyond srhat is proved in campaigns of any kind in the health field. I somewhat regret, as a cittzen..that that labeling became a laR becattse it seemed to me somewhat discriminatory. From mc own experience in reading. I would have thouglit that private airplane., would need to be called possibly hazardous to yot:- health. I read of young businessmen and their families almost every --- week killed in small plane crashes. biotorcccles \Ir. Ptcst.z. Doctor, with all due respect. I want to challenge your stntement. Of course they can be dangerous. But that is not to the poin; of ottr henrin'-. really, in my opinion. Dr. SouxcRC. Pardon me, sir. Mr. Pjcsi.E. Your testimony is that you think the present labelir: ir ntfficient. This is in strong opposition to the cerr heavy preponder- anee of evidence submittPd to this oommittee. CometSmpe. I wonder if we on the committee are cnnfuced. R"hn-r, do we belierPl Which Ray do.re go4 I.ronder if we should not hace an investigation of the investigators to try to find some facts of our own. Meanwhile. we are faced with the proposition that we are either going to renew the law that we hare on the books noa, and take no action, let the FCC probably ban all advertisement, or we are going to increase the Rarning. It seems to me that we have such a hearv amount of evidence that the Rarning should be increased that that is the proper approach. CT R I'LIN 0 14"r' 4 31

PIS DOCUMENT SUBJECT TO 1097 MHFIDENTIALITY AGREEMENT. I am a little surprised that you, representutg the Tobacco Council, would not recommend a stronF•er statement if, in fact, it can be shown that that is a truthful statement. • You question the statement, that if we strengthen it, it would not be u truthful statement. Dr. Sosncr.ua. Sir, I am an individual. I am not really a spokesman for anyone but m self. I am a praCucing pathologist. I am an inces- tigator in medical~science. I do not believe it would be justifiable to go further. I. m.•:elf. could not. with intellectual honest , make a statement that cigare:te smoking is dangerous to your health, and that it may cause cancer and other diseases. I think that is misleading, air, and I do not believe it has been demonstrated. Mr. Picr•tz. Thank vou. \ir. Chairman. The CxAmx.N. hir. Satter6eld t. Mr. Sarri:Kyinz. Thank you, Mr. Chairman. Doctor, I notice on page 4 of your statement oou made reference to figures that have been cited ooncerning ?60,000 people hacing'died of lung cancer and other diseases. Are vou familiar with the 800,000 excess deaths figure that the Surgeon General has used on otasion ! Dr. SoxxERS. Yes. sir; I hare heard that. Mr. SArrExrtat.n. Do You know, or can you tell us, have you any idea how thev arrived at that figure! Dr. SoxicERC. Sir. that is outside mc Seld of competence. I believe it is derived originally from death certi$cate-c. This kind of tnformation doesn't lend itself to cer• accurate rep~rt- i.nF of such dise,ases. as other witnesses hare mentioned. That Rould be my understanding, sir. Mr. SkrrEPxmw. I ask the question because I am quite intere;ted in trTing to get an answer. Over 2 weeks ago I a:ked the Sur:~o:: Gen eral to supply that information to us. It hasn't come in yet. I astume lie is either harirtg toruble reconstructing it or he doe_ rnt want it subjected to the scrutiny of the Ritnesses we are hearing tiia Reel: As a pathologist, Doctor, you have occasion to ezamine lun:= on autnps.•, do you' Dr. 5u]LYER.,. Yes, sir; surgical and autop:7 specimens almos: every dn v. 1fr. SArrLxrtEi.n. Can you tell the difference between the lttt:_ of a - smoker and a nonsmokerf • Dr. SoxatERS. No. sir. \either p•osslc or microscopicall}•, or an% other wav that I know can I tell the difference. Mr. SarrExrtt.t.n. Do vou know of anc new factual evidence that has been developed since 18G4 relating to the hazard of smoking and heal th ! Dr. SoKYERs. I do not know of any truly new or convincinE evidence bevond tchat was available SSears ago. 1 have read articles which state that there is nothing new in car- cinogenises of tobacco. and that verr few people hare applied tne:n- eelves recently in the field of the statistical proof or disproof. CTR HIN 014-ir"44

THIS DOCUMENT SUBJECT TO 1098 COdFIDEHTIAUTY AGREEMENT. So I think the information is about the aame as where we stood 3 yearsago . Mr. SerrExr~t n. Thank you, Doctor. The Cxanrtatax. Mr. Ec3chardt? Dir. EcsaaxnT. Tbank you, bir. Chairman. Doctor, I notice on page 4 of•your statement you state that a number of studies showed no relation of smoking to heart disease, and that these ought not be ignored. Can you give me any of those studies t Dr. $oxat.z:xs. Yes, sir. Aside from the general understanding that angina pectoris has no relation to cigarette smoking, there have been reports on twins in Scandana.-ia (Lundman. Acta Jied, Scandi, 1966, Supp. 455). He used twins in which one member smoked and the other didn't, and he could find no difference attributable to smoking and believed that constitutional factors.rere more important. Mr. EcsxAxaT. With respect to coronary heart disease? Dr. So>zxcas. Yes, sir. A study by Johnson. et al., American Journal of Public Health, 1968, found in survivors of the Hiroshima atom bomb explosion that the proportion of men .rho smoked was smaller in people with cnro- narr heart disease than the nonsmokers. There were more nonsmokers in Hiroshima that had coronarv heart di=ease. - ?kir. EcsxAnnr. These were persons subjected to the bomb ezplosion ? Dr. SoustsA. Yes. sir. Ther are being studied in a variety of ways. An article bc Bruhn, et al., Social Science and Medicine, 196S. ~Ie studied the poliulation of \azareth. Pa. In the men he could determir.e no effect of smoking on the presence of coronary disease. Then there is an article by Brown, et al., Journal American Geri- atrics Society. 1007. t-olume-15. TlieF studied individuals at the \-et- eran=' Administrntion Hospital in Portland, Oreg.. and they included both smokers and nonsmokers. These people were chosen because thec had nhsence of coronarv disease. There were quite a number of smokers. with manc rear of smoking, and they showed no evidence of coronarv disease. These are some of the Ftudies in which there has been no correlation. Mr. Ecsx.+r.nr. And there are a number of studies that do show a correlation; is that not correct? Dr. Svv>ttrs. 1'es, sir. ?tlr. Ect;xAnnr. Do cou have them convenient? Dr. Soaturr:s. Yes. 7he important ones are Hammond, two studie`, for the American Cancer Society; Doll and Hill, and their publica- tions. Mr. EcsxannT. That was the British Medical Journal? Dr. Soxxctia. Yes, sir. Then there is a Canadian study on pension recipients. That is Best as the senior author. That is iu the -C*nadian Medical Association Journal in 1965, volume 96. • Then there is a study by Aubry, and others, in the Canadian Journal of Public Health, 1966. Then there are studies of college students which have been referred to preriousl~• in the hearings. Thorne et a]., Am. J. Epideniiol., 196S, volume 87.

I!S DOCUMENT SUBJECT TO 1099 (DNFIDENTIALlTY AGREEMENT. Mr. Ecztiwanr. Then there is a study by Jenkins, et al., that was in• troduced here. And that, incidentallc, rather impresses me in that that study broke do.~n rarious factors that u ou referred to as being contributorS factors to heart diseise. ' It used cholesterol, beta alpha, cvatolic BP, diastolic BP, phrsical activit}•, amount of exerci.se, incomelerel, all of the above trigl~rceride_. and then made a separate study xith respect to some beharioral patterns. In all of these cases, the study came to the remarkably similar con- clusion, particularly in the age groups of 39 and 49, that heavv sniok- ers had about three times the incidence of coronary heart disease as nonsmokers. Do rou know of any studies that similarly used clinical obcer~•a- tion~-l gather this was from 1.000 persons actuallc examined-do you know of anr study that similarly attempted to break doRn or to correct for tlie sarious contributoi•c factors. and established the stati=tics on the basis of that correction?' Dr. Soxxnta. I know of some in progress. I don't know if you cited the Britain study which has beensroing on for years. One of their reports is Truett et al., Journal of Cluonic Disease. 196' , rolume•3~~. Tiier found seven risk factors, for example. \lr.*Ecxxaxa•r. From all of your considerations of these studies. do you not believe that there i!t at least a statistical relationship between hearr smoking and coronary heart disease 4 Dr. SoanrExs. Yes. I befiere there is a statistical relationship in several populations. There are other populations in which there does not seem to be a statistical r•elationshir. some of which I cited. So the explanation would be that. ,o. 1, cigarettes are the cau=sl factor in the relationship. No. 2. both the heart disease and the smoking reflect a third factor. ar.d. No. 3, that the statistical correlation is actuallr a chance findin:. Of those three, from my own work I beltere that the second is most likelc. T}iat is, that smoking and coronary disease are two reflections of a certain type of individual. A person has been described in various war_. T~pe A is one description. A person who lives in overdrive is another de~cription. Here we hare..•ou see. a susceptible sytbpopulntion. \!r. EcasAnns. But do ron not recall thnt in the ,Tenkins studv. both those who seem susceptible to smoking and to coronarr heart ili-eace because of their inclinations. both thote R•ho "m cuscePtible and those .cho did not seem tobe succeptible. seemed to hare had an eqnal increase with respect to the incidence of heart disease if thec were smoker=. I think in both cases smoking heavily resulted in about three times the incidence of heart disease in both tR•oups. Dr. Somxns. You ree..rhat is b~ther~ome to me alxmt the stn- tistical relationships. ie that, in a sense, if thec converge they infer a caurative relationship. But statistics can tiecer demonstrate the causative relationship. I work on kidnec,dieen" and we hare a statistical study.'~fr sta- ti=tical concultant !eenditme this paper from Scientific Research. Febru- ar. .1, 1969, by Prof. 'William Feller, Higgins Professor of .1fathe-

THIS DOCUMENT SUBJECT TO 1100 ppNFlDENTIAUTY AGREEMENT. matics at Prinoeton, in which he igrees life acientists are overawed by statistics. I fear.re have all been influenced by Rtatistical relationship= where if we had obserrational data we would discard them as not really c+o~nt. I fear that. DSr. EcsRaxm•. Let me ask you this question : Do you think it would be an ticcurate statement to sac that in men under $0, hear<• cigarene smokers have a higher incidence of heart disease than nonsmokers ? Dr. Somies. I.vould have to ask which men, because in a group of farmers reported by Morris (Canad. Med. Assoc. J., 196'. volume 96) it appeared that their farming protected them from any e9ect: that might have been due to cigarettes. In the American Indian population it was not proved. So I would have to 1rnoR which population. Mr. Ecssuxm. We aught say Japanese-!1.mericans Roultl l,r le== likely because of the study of Hiroshima. Di. So~curnF. No, sir. 'Thnt doean't aprlp to Japanese in I-iaraii and on the mainland of the United States. The Japanese coronary disease study by Simttra (Acta ked. Sca:;(l.. 19677, Suppl. 460) simply showed that smokers bad loRer bl•lod pressnre. Mr. EcsHanm•. But be<xuse we find specific areas where -t enn- trarc result is diseocered. does this mean that we cannot make a s:;tte- ment with respect to the general male population under S- ij our a&-tocintion stattsticall.• is as sharp as it appears to be in the xe~ortr Dr. SoxntrRs. No, sir; I would not want to make one beca,,=r I'- :: it would give an impression of certainty where stati=tic= ca:. give that impression. ~ I seriousli• mean this. sir. The CxAn:.rA.. Mr. Precer. Mr. P>uryEr.. Thank vou: hfr. Chnirman. Dr. Somnier=, you have challenged several ctatement= m^dr 1..N -!:w:- 'witne-se= here iri a direct R•av. On^ of mv colleazues tust menrinned that the heacv prePnnderance of the evidence we hnrl heard that smoking eauses disease. A few days aro, another colleague commentP•1 thnt a?ire-• Pr.•: • .vitness. with the esception of perhnrc one rniholo-:,tr. te=tifiPJ a physician could examine a lung and tell whether the per-oti v.: z : smoker or not. It seems to me that idea has been totally destrored here. It me that many of the thing= which the fienernl public feels are tri.• an;l which I think members of this committee thought were true. tn.i.y nvn in fact, be true. R'bat.ve are involved in is.reiRhing the evidence. to accrit•e a r::'n, to it. Your qualifications seem to be absolutelc impeccable. So 5nniv? of these mattem on which you challenge other Ritnesscc are imr.-+-tant. First, orr the black lung oantroversm•. ~on state flatl~• that ~on r.~r.^o' tell from a ltinr Rhother n per=nn is•rmn-:cr or norr-riokel.:1+: -V: challenge Dr. R'illiams of the American Cancer Society on tl:.it. He went so far as to sa.• you could determine ape t•son's social life fro::: ezamininp •a 1ung. I'ou say you can't tell .~•hether it is a m3:: o:' a woman, which is a drawbick in determining their social life. CTR MIN W 474r

THIS DOCUMENT SUBJECT TO 1101 CONFlDENTIALITY. AGREEMENT. You say flat.ly that you oan't distinguish between the lung of a tanoker and a nousmoker? • Dr. Sommr.ns. That is correct. I cannot tell the di$ererice. Mr. Pssrrx Is that the general feeling of most pathologistsY Dr. So. Sir, it is my belief that the knowledge of what the black pigment represeata, namel%• Urbon particles or coal dust, is 1-noRn to every well trained aeeond•year medical student, and that it is not possible to equate blackening of the lung to exposure to tobacco products lt is simply from the exposure to urban tir in general or, in the case of coal mineL, in their work tbeT inhale the coal dust particles. Mr. Px.zrm So that you 8rtl1~ challenge Dr. tit'illiams of the Ameri- can Cancer Societi• on that statement? Dr. Soxxr.a-s. fhat, in my opinion, is misinformation, sir-from looking at a slide of lung canoer, that a physician, he didn't sav a pathologist, can tell something accuratels about the social life of the patient. Une cannot tell anyt.hing beyond the fact that it is a cancer, and I believe you can tell it is a humuu-being. That is about as far as 1 oould go. Mr. PxErEa. Tou mentioned that the Surgeon General testified here that he gave as an example of the inability to du plicate human diseases in experimental animals the case of leprosy, which he said could not be introduced in ezperimental animals. You say that it has been produced t Dr. Jouuexs. 1 es, sir. Dr. Binford, who actually works for the Government demonstrated it some 5 years ago and he received a prize from tbe American Society of Clinical Pathologists for thi-. I am surprised that the Surgeon General had not know-n of this. INir. Prui-uc. Generall-.• speaking, is it t,tve that cou can duplicate must human diseaseb in e:perimental animals or tiot ? Dr. Soxxzas. Well, sir, it varies. Certain ba.cterial and viral diseases can be duplicated. Certain degenerative dise,ueK can be duplicated. OthPr de~enerative diseases are more difGcult to duplicate, for example, arteriosclerosis is more difficult to produce. There are some diseases which are,1 t.hink, not found in animal: but only in human beingz. Mr. Pntrtn. What 1was getting at wns how iuiponnnt is it to you as a cientist that we had been unable to dttplicate lung cancer, for exar..ple. in animals? Dr. Soxxr.rs. To me it is very important that we keep trying. Next month there are three new ttmoking machines going to be examined nnd compared. We must try to do our utmost to get an experimental modEl that corresponds to the common type of human lunr cancer. There are several reasons for that. Oiie is that we p-ill hace snnie aclva ntage then toward bioassay. I'ntil you have an adequate ezperi• tnental model it is awfullv hatd to take out various components of mixture and drptonstrate a change in the effect. A1~o. it is hard to analyze the chemistry that goes on in the tissue whrre there is some daniagc. Those are tRO reasons. There are a nuiu ber of other reasons. ]f we had a lung cHiwcr model comparable to the human in animals. we rould alter their hormone balance. We could alter their nutrition. C ~'R ~N C~1$•~''4S 6

THIS DOCUMENT SUBJECT TO 1102 CONFIDENTIALITY AGREEMENL. We could learn ibout the Qenetic component. There are many ti~ii:z= that would help us. ' Mr. Pxrrnt. Just one final question, Doctor, on some of the areat where you are cballenLnng our previous Ritnesses. Chairman Hvde of the FCC testified concerning the propo-Fd b.iii on eigareUe a6ertising by the FCC that it was justified becau=c cigp- retGe smoking was a"unique" bealth hazard. TLe charge that such a ban Ras discriminatory he dismis_ed vk it', tlie statement, "13ut this is only likely to occur here because smokin~ i; a unique health hazard." Dr. Somisrna. Well, there bare been studies in which smolin~ cigir, or pipes have shown statistical associations with sarious di=e:,=e=. ::•~ which ustn~ of snuff has been claimed to show a statistical relatiwn:i~a. So even lust in tobacco it isnot a unique situation. If I understood Dr. $otin's testimonv correctly, that is o:L•at he said, that there is nothing ms-stical about the cigarette, but ii, h:_ opinion it is just anot.her health problem. Mr. PaErEa. Thank you, Doctor. The Ctt.rxx... ],Sr.'BrotzmanY ' Dir. Bxonue.,c. I hace no questions. The Cxen:u.r. Mr. VS'atson t Mr. W.rsoN. Thank you, Mr. Chairman. Dr. Sommers, I am sorry I was not here to bear cour testimor:c. but I did hastily read through your prepared statement. I, to, a.s others, am in a state of confusion with all of the conP.ict:::: not only compctent but outstanding medical testimony. It just defies my understanding as a la~-man as to how we could hare someone as Dr. Williams come in and saf even the genera' Prac- titioner--at least that is the assumption I got from him-co::':J tE.: the difference between a smoker atld a non-smoker bc look:n~ a: 1::; lungs. Here cou are, an eminent pathologist, and you say there is abso?;ae;7 no RSC of doing that. Dr. SoxitEns. I cannot do so, sir. It is doubtful to me how one could arrive at that conclusion. A.tt erperiment could be set up te, tes: whether any pathologist in the country could do this. That is tfie only way I know of getting scientific proof of - or not it is possible. A witness cesterdae (Dr. Zeidman) stated be thought thar r4''~z r.,:: of 1,0tt0 patTiologists could not tell, and the two who could hrtd =ro..- divine $tutdance or something else in their facor. In some of these earlc lung cancer changes reported by one Ror:;~:. a panel of 12 other pathologists who were LnoRledgeable in the ne;c could not confirm his findinfts. So that was an ezperiment and it came out 12 to 1 aperainst t:.e ability to pick up early changes that are supposed to be smoke-re',a;i-d in thc bronchi. '.%ir. Wersox. That is a distressing fact. that we bare the Amer: people who are primarily being fed the other side of the picture. To:: know that. Your vieRpoint probably wouldn't get beyond the Ra11= of tl:a hearing room, or not very iar beFond that.

IHIS •DOCUME.NT SUBJECT TO 1103 CMDENTIAUTY AGREEMENT. You conclude that the blackening of lungs, or black lungs, as they call it, is the result of the inhalation of carbon particles, and you sat• tbat smoking tobacco does not introduce such carbon particles. I believe it was the doctor who gave us the risva7 demonstration hem,.rho happened to practice in a coal region of Illinois, so perhaps that might have something to do with it. I believe there is one tbing that all drictors and eversbodc else is agreed on medically, that Tou hare never produced lung cancer through the inhalation of smoke in the lungs. We all agree, the Surgeon General utd everybody else. Dr. SoxmT.Rs. Yes. Mr. «'.rsox. Of course, the public has a different idea because of all of the reports that hare gone out. But you have never produced it. Dr. Sozrxrxs. That is correct. Mr. WATSON. You hare spent how many millions of dollars, do you estimate, in trying to produce lung cancer through the inhalatiori of smole P Dr. Soitxr.rts. I personally could not answer that question. I would guess it is somewhere in e:cxss of $b million or $10 million. Mr. «.rsox. R'hen the Americau Tobacco Council ave this 510 million to the AhL~i for research in this particular fielgd, were there an strings atuched to it, so far as you 1rnoR g Lr. SoYaaats. Not to my knowledge. They were free to use the money as they saw St. Mr. WATSON. As I stated yesterday, I observed that apparently sotne had concluded on a.~ern s~a~ statistical basis that we have found the panacea, we have found the cure-all now. We hare this dragon and we are going to stop it. There is going to be a decrease in the research in this field. I know one of the laboratorT scientists yesterday was apprebensiee about that.. I know the Arnerican Tobacco Instiiute has committed $10 million to the AMA. They hare pledged another SS million. Do you happen to know boR much the Cancer Society is spending in tbis-field, in this particular field of research 3 ~ Dr. Soxattxs. No, sir, I do not know. Mr. WATSON. I think it might be interesting to find out. Certsinl.. I am not faulting them. I hnre served as a county chairman for ti1e Cancer Society at~d I am vitallc concerned in this. But I am afraid now that perbaps they are backing up and trying to look for an answer. You point out again, as I believe Dr. Rigdon of the Zniversitr of Texas Medical School did, that there has been quite a discrepancy in the medical profession so far as the diagnosis of the causes of death and such as that. You confirm that statement. Dr. Snxstnes. Yes, sir. Mr. WATSON. Do Tou recall that he pointed out cesterdac that in 1955, I believe in the State of Tetr Torl, ther found out, Rhen per- forming autopsies, that the causes of death listed on the death certifi- cates were wrong in more than 50 percent of the cases so far as the diagnosis of pneumonia t Dr. "ZoxxErts. Yes, sir. Mr. WATSON. I~ has been indicated earlier bere that in the state of the art of the medical profession rerhaps, now that we hare a greater C `~~ ~°~N 0 14 "r''5o

incidence of lung caneer it is bwause perhaps.•ou hare been diagno=ing it and listin~ it as something else in earlier years but all of a sudden we have decided aow to accurately diagnosis it as lung cancer. Thanh you very much. ' The CeAim c.x. Dr. Ctrter. Mr. CARrrx. Mr. Chairman, someone htzs said something. I believe. about the .oitnesses who have testified that the cause of fung cancer has not been proven, about the validity of these people. I would like to rerie.r just a few of these men who have teFtified and their qualifications. For instance, we hare had this morning the statement of Dr. Thomas H. Brem, professor ttnd chairm~n of tl,e department of medicine, University of Southern California School of Medicine and Director of Internal Ifedicine Los Angeles Countr-t SC Medical Center. And Dr. Sommers. who has so manv, manT teachin_,, conueotion-: director of laboratories, Lenox Hill I-#ospital, Columbia Cnirersitc. clinical professor of pathology. University of SouthPr•n California : Cornell IIniversitv Medreal School: Tuftsliedical Center. and so on. Then .reget to~Dr. Dwayne Carr, professor thoracic sur_er.•. 1-ni- •ersitv of Tenneseee. Dr. Langston. professor of surgery. tnicer=irr of Illinois; president of the American Thoracic Association. Dr. RiF- don. of the L'niversitc of Tezas, who appeared here yesterday: Dr. Rosemmnn. assistant cbief, department of medicine nn;d as:ociate di- rector of the Harobrun Institute for Cardiorascular Diseases. These are a fe.r•.'not all. But manr. manv eminent men throuchottt t11e Dnited States have testitied contrarr to what has been stare•1. Thanl cou, Mr. Chairman. ~ The CaArnxAx. Are there any further questions9 If not. Doctor, we want to thank you for coming to g•it-e us the benefit of oour rieRa. Dr. So4xcxs. Thank von, sir. The CaMM.x. At tbis time, if I may, I would like to place into the record, the ststemeat of Dr.. Clarence Cook Little. and a state- ment by Dr. Robert C. Hockett, immediately following the testimony of Dr. 8otnmers. Mithout objection, the statements of these two doctors will he plaoed into the record. (The statement of Dr. Little follo.rs :) Sr.rrxVWt or CtAas..cs Coot Lrrrts. 8cincnnc Daccroa, Tar Coc:;cn sw Toaaooo Buruca I am Clareaee Cook Little M Ellnrortb. Nalae. For Itt tifteen years of aztsteace I have been Scieatiac Director of The Council for Tobacco Researcb-t`.B.A.. aod for t.rentJ.aeven years Director and tblrr.f:• years Director Emerleva of the Jackson Laboratorr for Research In Genetics and Cancer. For sixteen years (1?2A-194S) I.cas ltanapng Di.rector of t6e Americaa Society for the Coatrol of Cancer. aoa the American Cancer SociPtv In 1931 1wa• President of the J.merican Asraoc(ation for Cancer Research aud was so elected for.a aecond tdme In 1840. 1[. acti.e Intere+t in cancer re_•earcD as a biologist corera a aqan of atm-two years from 19oT to the prrsent.' . TbrorsaDont that period I Lave al.ea.a been keenlT a.rare of the cotnrlezltr of cancer canutlon and La•e always advocated open-mindedoes.. p.cieo.e aud •DetaSled eorritdee rltae. taelodlas 1ay.rtascr tn eateerdty adatetstrntJon. 1s appeeded

® ~ IHIS DOCUMENT SUBJECT TO 1105 COdFlDENTIALITY AGREEMENT. humility in attempting to solre the problem of cancer causatlorr by research to flll the ezistlug CaPI. in our knowled`r. I stiU strongly ad.ocate thuse principlcs. T'our Sears ago I bad the privilege of sirlnt to, the members of Congress a statement of my interpretation of cancer as a dlsease. At that time I pointed out the extreme delicacy of Its origin in ao arw of actiHty either .rltDio a molr• '` cule or between molecwles. Tbe danger of allowing tDe groas and cruel clinical manifestations of the disease in its advanced stages to obscure 1ts estremrlF I delipte and mtnate origin was also emphasized. TDis situation remains uu• changed. In fact, research in the last four years has deflnitele tndicsted that the origin of cancer Is a process of extremely minute cellular biologc and biu• chemistry. Such an origin is bound to be complicated for the organization and re)ationahlp of cellular molecules can be modibed by manp agents to produce ' a single result such as the origin of cancer. Some of those ajents already reco;• t nized are genetic chantiea, gamma Irradiation and certain viruses. ~ I empbasize this dtoatlon again because it Is an unassailable arrument in ' fscor of the continued research which is essential to our understandina of the '{ oririn of canccr. The Council's philosophy in studying the possible effects of smoking on human health has been that the question cannot be adeptutelj desned nor its ansccer sicen except by intensive study of the diseases tLemselres which )aace been statisticallc Implicated. Although empDasis in Its program of support of iode•• pendent research bas natnrallJ evolved sa the direction of certain fields of research in which the greater amount of promise for the future appears to exist, the basic fact sti11 Dolds-tLat It is essential to carry on fundamental ` research in order to understand the complex mecbs.nisms by which each pf the three groups of chronic disease (cancer, cardiorascnlar disease and chronic respiratorJ disease) are initiated and encouraged. From the consideration of ~ both the nature of cancer and of the dtuation as a whole, the one answer to ,. the questions srhlch face us all is much more research to sire us much more {I!1!1! needed knowledge. How true this Is is sLos•n bc the expenditures by both gorernmental and prirate agencies running into hundreds of mlllions of dollars per year which are being made to try to determine the various causes of cancer, chronic heart diseare and chronic respiratorj disease and. if possible, to delay or circumcent their appearance. These expenditures are increasing rather tLan decreasinF and tbis indicates clearly that the problems presented by these diseases are unsolTed and that their canres are still an open question. in tlie meantinie a.ridesPreed..ce11-or(;anizrd and agFressice cuminiFo aFainst ciFarPtte swnkinE iit being waged bc botU goiAernmental and prirat~ aRenrir• ba%ed on the theory that tcd,acro smnkr Is either the major cau~e or an imlrrr:rnr = du.vl fnctnr in tbewe three groups of disear:es. Tbe reapousit,ilitc for siuFiiu; our a sintle agent as a causatice factor is a srare one. Ocersimplification. orerstatement. ooerconfidenre in and prematurr judenueut- of acientific research programs can delay or obstruct progress tov%ard the di:• eorery and recelation of the whole truth which still eludr= uc. _ The RaP, in our kno.cledt;e are still so great that those who do,^matically as~ert othersciFa---.rbether tbec state that there 1s or is not such a causal relat.iousbif-- - are premsturr in judgment. If anything. the pure biological eridence is pointing aaae from. not toward. the catt.ca) hTpothesis. With thif in mind. I should lll•e to rec)ett• brieflc three flelds in.rbfrh datn are being Rathered and analczed revealing Fapr in our knoRledRe oomwrnit,r th. Possible effects of smoking on human healtL. These tbree flelds are tl i ttatiati,*. =t (2t clinical obsercations, and (3) laboratory ezperiments. trrartancat It 1- gener:nllc agreed that while atatletical as.ncistinn ba-ed on study of n single pnir of factor>; ae. for example. antokinR and lung canmr. +no.v br tho rr~utr of a rnu~atice rflationsbiP, sneh studies can necer proce this poinc Tbe %n« ma jorite of statistical studies on smoking have been of this type. When ttratictical studire of many factors are made It is found that there ar-• mane such fartor+r that are statistically associatrcf with lunc rancc•r. It i- on1r I.c thita tyl* nf stodF of manc factors that the proper perspectire of tbr rolP• of ditSerpnt factors and of their real meaning in the associatiee proceea can 1r• determined. C T R HIIN 0 14* e''EJ-2

TNIS DOCUMENT SUBJECT TO 1106 WNFIDENTIALITY AGREEMENT. E:istluF statisticvl dau sbould be rretaminrd in cirR- of tLr r.rPd of Nu• h maltifactoriri aualcwis, anJ future can•fully coutrullyd eNidrwiulo,i ui sruJi~• should l,r yiannrd to inc•lude that analjtical metLoJ. , cuxtca Some patbologi+ts claim that tnbolatlnn of tobaa o smolr tnac Lc• fnllm•. •! 1: certain changes in the tissue of tbe lung surfacr. Tbe`r chnug• - l acr l,c•.r. u.•• : preted I,c some as belnf: significant precnrsors to luntr canc•rr. TL• r•• i•. •: definitr disagrecment among patbolotasts as to the sif;niM1cat.•* of .u,L cLnf.:• - it 1+ laintrd out that tLry oorur Iu cLi'.dreu acd aon•syul:rr- a- wrii ^. smnlrrs and are therefore not apeclGc fnr smc.lr exia•urr. and thar tL.; :r ttsuallc entirele recerstble and thus do not lead to c ancer ~IurL mnrr carefttllc controlled and eatenFice resrarcb 1; nrPC, tn dFtc!=.; the nctual effects of tobacco smol.-e and other aero-ol, on lung ti-•ut•. Ti.r 1•rr• : data leace much to be desired. t•f.twawrolT tflvrslvLrTs A.nimal esperimentation procides the most croncenient and n:o;t r^P:d tuP:l:••i of stod.flnr the effects of tobacco on carioo+ tlanes and orr.,irs For cr3rs. tL• commonest and most.rldespread method of tectinj such effect~ bas bern tbe u« •' an artlflNallF•prepared condensate of smoke inaccnrately called ••tar:' c:b:<L 1::,; Neen palnted on the skin of mice and other rodents in carines concer.trar:nz~ When this is done the painting ia followed in some cases by abnormai rr,•cctb of the skin and. in some of these cases. later t,:r stin cancer. In tbis retrPct tbe cnr.• densate of tobacro smoke Ioins more than 50n other substance•. aonny of .cl:'.c.l r• known to be entirely harmleu to man, In producing a more• or le•c stand3rdizr-'. effect on moo4Le skin. There Is nothing nna•ual or ix•c•nliarlc ch:racteristic ab-::• the reaction of these animals to smoke condeneate. Hnnecrr. an in.jortant f:, - which has been oeerlooted or ignored is tbat the relatice cancer-, rr.dnc•iuf eCe- of condensates of ciprette smoke, of pipe tobacr••o smoke and of ciFnr swoec u•- not follow the same order of acticitc or coincide with tbr rFCnrrrd drFre;-= of statistical association between caecer anA tLete tbrae t7re• of sc ckr man. Tbi~ di+crepaney is basie. lt showr that if we acc•ep: thr for a working bcfmtbesis we must al+o admit that skirn pair.tit.; wicl nf tobacco smnke !t; not a sitiniflcont or ealid method o' re•rin; thi- re1: ticF ,•a-.n :• forminF potentials of such smoke required by the ccork'.^e hcpot;,rci= 1:. r.:1.: .rordt. the employment of a different agent icondensate inctrad of 0:. :. different target organ (skin instead of lung) and on a dif!era::- :.!:::..r.: irr.(••- instead of man) is not a nrm basis on which to deceln;+ a t+road ar,d cra1f•reLer.c:.7e reAearcb pro;ram to determine the ptuntitatice efiects of cmoke on mau. Ecen more striking is the neptice enidence prncided ncer cenr- b< <rorr• e.' ezperiments in different laboratories incolcing the direct expi+-orr of tbc lu-.;. of experimental animals to tobacco smoke itself. It has been sbnt-n tLa: animals can snd do on occasion decelnp lung cancer of the runtnn t' rf*- ezfwsure to tobacco smoke. It is reasonahle therefore to exlpct ibni i! tr•' .1 smoke causes such cancers, or ftreatlF increases or BCCclor:ltts tbeir incidc:!• c. ri>:alEcantl< greater number of such human type of lung can„•r would nccnr ~ lowing exposure of animals to tobacco smoke. This bas not beeu tb. co!tc ;:. . mass of necati.e eridence remains as a factor Rbic•h certainly rni•e- tbr qur-: : as to w•bether there is any causative action of tobacco smoke in cancer frrn ^t:o, orsrnc rttntz:ccc It 1s clearly established that genetic insuences determine tbe inciden; c• r: •. and type of taatural cancer occorring in laboratory anim:tl>. TLi. ba• L,•.: especially clearly shown in mice srhere many inbred s;rain5 exist. in r:,.:. of which there occurs in generation after generation a ebaracteri%tir repeata!:• and predictable incidenee of cancer of differcnt tcpes. includinr lunr cat. ~r The truth of the principle of genetic influeoce has been estahlished bec: u• methods of inbreedinR practical In mice baee demonstrated its caliditc. Of c•nur- 0o such close inbreeding occurs or.rill occur in man. let the bunian populat in:. ,- made up of a mr•riad of different genetic types representlofr different de,^..•.•- of susceptibility or of rtslsunce to organ and tissue changes which prerede a:..: accompany tbe appearance of such diseases as cancer. ehronic heart disen%~ n:.('. chronic r1spirator}• disease. The study of human twins has indicated the influFnct CTR • 1• • 0147E53

M k folln" rd L;' Urr lrr•n iuter• b- tt. boRer(•r. e sbcb eban;r•o s• %eil a- in tbst tbe; nr,Y tspd methnrl Itir frars. tbr trn tbr nfr of 't<b;tA bA a atratioW fm.rtb of aqrct the con- e!.btrb ^-.• - aYadardit«! - t aMat 14nsnt fn,: r eQect! ®eke do - tlrmes of tsyosare in s-c Mri, (ooder.-.I t.. h taaft'• It otber tr•okr • Ot o ' 4 003 r eal:re l t r t THIS DOCUMENT SUBJECT TO 1107 CONIFIDENTIAUTY AGREEMENT. of genetic aimilarlte In the 1Dcidrn(•e uf chronic bearr dis;•u•t. L u4 ^r •:'• future rexarcb will iuclude much murr ftudy of butuau tw•in, ancL c• rb, d..:a from aucL stodieo accumulate. it trill bec-oml- inc•rcaxinFlq clrar th:,t tin• :.:•. :- nature of the human inditidual is the mo.1 important fac•tur iu urrrry::,iu~ pbysical and pbysiolorical reactions during bii life ezpcriencc•.• Of Crrat but ata eet unaua!ctrtl s1GnlArawr 1n all tlrrt•r of th,• irnr!i :u,l grool(s lu tuan is the diffrrer.ce !n sustel-tlbi:itc br•tw-rwu tLe %t•:.-<. The detertaluation of sex is a(:enetic pbt:nnmennn defr.t,dit._ tq...:. ;Lr• composition of tbe male se= eell .rbicL is lacolced In tbr f(•nii:cat:(u o; t,cL bttman orun,. ln incldrnce of lnng dncer• chronic heart disease and cbroni- rr;rirntort dir•ease au eXttss of tualrs is evidently a unicersul b1( iuy;l• al l,Lol,otur:,ut, o ct:r- rint iudeprudently of eucironmentyl factors lucludiua sm..l:ir,j: T,,r ..:--t-t. ta .%-by:• TLe answer may be protuundlS imyurtaut to our uud•_r,; t,~:r,~ o: causation. DI7TtzL'tCLe ttLTwt=< 1tAT10:ca International data on cancer incidence rereals sridearread and per:i-tenc differencex between nations in the relatire frequency of death fronm lun; ca.uc~r and from cnncer of otber sites. Such differeaces cannot be erplained by differeu:r, in r;tuoking habits. On the other band. we know that popnlatfons of dtfferent nations bace diSerezt Renetic complexer• and tbet tbis fact is consistent w•itb tbe similur 1,Lenotnenon of occurrence of different-rates and distributlon of cancc•r Incidence in animal populations w•brre different Irenetic complezei are knoRa to be the explanation COf CLIIelOC In the pre•cnt controversial r»tuatlon as reRarda smokinp and benltb. Ri=e and unemotioual camPaiFrts to point out the posaiLilitc of rariou> beala: ri%Y• i• ono thing n ith abicL few c•an quarrrl. Re;trictiom and ]trobibitions by decree or legislation to enforce or to limit tZes of buman bebarior in relatlon to amoklng are quite another macccr. Tre7- cat easily create a falt<e senst of acbiecement• replace reason by emotion and err^ -ur• aFe frar rather tben knowledge a, a motic•e f•,r action. They are a dat;e:r . at:d misleading xuLttitute for the acquisition of Mienti6c truth by pstient and reseorcij• and they can never replace it. Ct:atuct•Lt:u \'tret or Da. Ciwnrxct Coox LrrT:-t Dr. Cir.rence Couk Llttle, ScientlA(• Dirrctor of The CounrIl for Tnl•;tccc. R,• searclr-C.S.A.. C33 Third Avenue. Xetr Tork. New York. 10027. and Dire^r,r Emeritus. Roscoe B. 7ac1•=on lfemoria Laboratory, Bar Harl,or,,laine..ras larn in Brool-ine. 1ta s<racbuAettl. on October 8. 16bS. A graduate of Harvard i nlcerslrc. where be earned d-B.. S.V.. and D Sc. degrees. Dr. Little holds honorary deRrees from the t'nirenitc of \eR Hamp~l:ire Albion College. the Cnirersltr of \e.r Mexico. Colby College. the t'nirersir:r of lfainc. the tnirerslty of Chicago. Boston Znlcersity, Dickinsou Collere at.' Marietta College. He was Presldent of the L:nicersity of Maine (iB=: °Sr and of tbe L'nireraltz of lficbiran (192Ir29). He Is former President of tLe Amer.cat estociatlon for Cancer Research. Internntionaliy known in the tSeld of cancer lnrestlfation. Dr. Little rcas a ReaearcL Fellow in Genetics at Harcard• 1913-17: a Reaearcb dtsociate in Co=• paratlee Patbology. Harvard Medical School. 191?-16: a Researcb Associ9te at Harnrd Medical School. 1919-21, and Ladetant Director of the Station fnr E:perimental Evolution. CarneRie In.tltution of Washington. Hi• correr lncladrr tarrrlce as an Officwr in the Army In World R':rr I:Mor.r:r- fne 11ir•eetor of the American `Lociety for Control of Cancer. l1a_^a-•/;, r nOn- th•- Amerinn Can(er f`ociety) ; member of the EaRenlc. Oommltter of the l'nitrd State* since 19=: Directnr of the •Dterlcan Birth Control Le•ague sincc Prewident. 193t1-3R: member of the E:ecutlre Committee of tbe flrsr R'orl,i Populat)on Conference, Genera• 19_'",': Prealdent of the Race Betterment C>nn• Rre>«. 392A*•-29: Secretat? General and fhalrman of the Council of the Sixth International Consress of Genetics. Itbaa• 1932: member of tbe Xatinnsl Adri• C1' f~? H~•~ t~ 14r>i ~4

® ?HIS DOCUMENT SUBJECT TO 1105 CpNFIDENTIAUTY AGREEMENT. eory Counril, 1937-w0; and Prcaident (1931-33) of the >fount Dr.•ert BiulcTk:,l Lalaratnrc. A Fellmw of tLe \ational Academp of Sclencrs. tDe American Acad,•my of.krt- and Kdencer;. the Xew York Acaderny sf \ledic•ine, the Holln%'oud Ac•od.:uy c-' Medivinc, the American Association for the Adrancement of lxeinc•r, at:J tt,. Natiunal Instltute of Sucial Scieucc•. be bulda wrniberahit, fu tbe Ai,t-rWdl. t3ocietl of \aturalists, the American t5ocietY of Zaologl.ts, tbe Sucirtp of Lxt• n- mental Biology and )dediclne, the Eugenic Researcb A.asociatiut,. the Aw, ric.,t. PnLlie IjealtD dssuc•faUon, the Populatiuu Aawuclatiun of Amrrira, the :1l.-rican Eugrulcs SocietT, the Lmerican As*oMatiun of Auetotni,te. the Atnericuu of alammaloglsts, and the American Social Hygiene Association. Dr. Little ir the author of numerous Iwul•r and srticles on renetic., c•urvvr n- searcb and educational and .ocdal problemr. (The tttatemeat of Dr. Hockett follovcs:) BT.rtYncT ol• RosuERr C. Aoczcrr, Pa. D. Aaaoct.rrc Sctt:.Ttnc Dntcsoe. THt: Oooarcw ros Tosaoco Rtat.asca My name ts 8ot,ert Casad Hockett. I am Ansociate Scientific Dirertor of Tl ~ Council for Tobacco Researrb=i.S.A. and bare held tbl- position altl the Council and Ita predecessr. the Tobacco lndustrc Reseamb C'on,wittee. Fiw:f sbartlT after formation of the latter in ]9St. For the p.rt fort=-nre years I bare specialized in the tSelds of organic chen.- tatry and blocbemistrs, sdences tbat are "tly concerned with all life procesae, both normal and abnot•maL I tticeieed the Bachelor's. ]laster's and Doctor of Philosophy Degrees in these subjects from The Ohio State LnlrersiCc re>:pectire'.~ In ]92S. ]93R and 19.9. After a year and a half at a Rttrt scienti•r at the 1\ational Inttitutes of Health. U.S. Public Health Serrice. under aN*ationnl Research Cotmcli Felio.rablp, I became a member of the staff there to engage irL blochemical researcb related to medical problems. Bemeen 1934 and ]95U. I was successiselp Assistant ProfPS*or and A-cinre Profe*mr of Chemistry at the lfa.sacbusetts Institute of Terhnolory. conrinctin_ t^warch. training graduate students for higher degrees and acang as a cc•n- aaltant to pbarmaceutlcal. chemJcai and food industries. From 1944 to ]953 Iwaa Sclentiflc Director of the Sugar Re-earcb Foundari^n. tnperTlslDg spoDSored research In nutrition, food tecbnologT and in re1nt,-d medical >)elds. snch as dlabewt and dental caries. I bare antbored more t1:n:L sts-ty res<earcb papers published In Chemical journals and bace al-• Rrirto-r. numbers of papers for medical societies and bealtL associations on problems of fundamental research related to health. In ]AG.'P I bad the prlvliete of presenting to the Commlt!ee on Commerce nf rl,,• U.S. Senate a revie,< of tobacco and health ret<earch tponsored re tbic Counci: since tts lnception. in a contest of acfeotlbc fiadlnRs in this deld fron othe- sources. TEiR review was pablisbed In the record (p 1I07 tt) where it can be cor.- ,nlted. Heace my present statement proposes mainly to ap-0ate that re.iew bF describint some ne.r Sndlnp. to ezpaad certain sectionik. and pa rticula rl!r to out the lmplicationa of tbeae Sndintx. as I.ee them peraoaally. with re-perr rr• tobncco useln relation to human bealth. In ]Ws, 1 dreribed in considerable detail the nature. ortanlsation and wnd?-• opcrondi of the Council. and this description was included in the reeord '`ic nr•t: statement was supplemented by a complete background document outlinir.¢ rh, Conncil's blstorr. organization. acHentific prntram and publications Thi< a,., appears tn the record and need not be repeated bere. It will satbce no.c to summarize those statemeata as follo.re : 1 The research program of the Council bap aiwapt: been conduct.d tbrnus!. Rrnnts to rerornls,ed and ett.aAUabed incestlRators in medical scbocd=. bn< pitaU. onlrersltieA and research institute.a. 2. Pttll rrspoaaibU/tf for tJ,e program fs vested in a Scienti6c Adri=n-y Board conafating of independent scientists of bitbest caliber erhr. r.•~i:: their tnstitnional atbllatlons and bae•e ao connection with the tobacco it • dutrtrm. This Board operates with eomplete freedom of action In every res:•ec r A list of its present members 1s appended. 8. Iaeestigators who receive graau-in-ald have alrra.a been assored fu'.1 ftredom in conduct of research and in the presentatlon of resvlts at scienrinc meetings and In scientific pnbllcatfons. CTR HN 0147155

INlS DOCBMENT SUBJECT TO 1109 (bNF1DENTIAUTY AGREEMENT. 4. Since 19..i. the Scleatltlc Adrlaory Board has rceeited nrore tb3n -,1-, applications for research support. Researcb Mnts and fellonsLii.• barr totalled 11438u.0U0. Researcb grants bare been aRarded tn 231 scieati,t: in 213 wedical schools. bospitala and laboratories tDrouRbout tbis c•ountrc ar d abrnad. To date. Rrsntees have puhlished more than 7-17 papers in scientiG, yonrnals with acknowledgement of Council acrpport. 5. 8erreal public symPo~la on pertinent tqpics bare been auPtv+rte:l hr th~ Council In whole or in part, as well as a largr number of amallrr inforwul research planning conferences. TM ttLa[iscrt )aoca.tx Pr.posei awd Polieies The stated purpose of the Council at the time of Itt formnlatinn n:,- ••t.- aid and aa+a%t rexarcb Into tobacco u¢c• and (baman] bralth. and parti•ulsrtc int,. tbr alleged relationcbip between the use of tobacco and lung cancer.'• Thr Sciet, ti8c Adriwrs Board has considered irom the beginnin; that thi- purpo-r could bert be acbiered by concentrating stndy upon the d'vcoar+ tbat bore been rrlw•rtrd to be a•Niciated statist1ca11F .rith tobacco use. It is still their policy to sponsor inrestisatlon of the factors, ta>luenoes and agents. both Internal and ectrrn:,l. that mac br lnroiced in the can•ation tthat ta etiolorr t or derelopment of th- dl.ea,e+. Only within tnch a conteit can the possible effects of tobacco u-r rrcr be rrnluated realistically. Uforeorer etioitHrlcal studi" of tbie kind are th••-P n:r:-: likelc to produce practicable methods of prerenting soch maladies or delarint; their on~et. The dbealie• eo selected for principal study include dlaeatex of the bPnrt arol artetiea. cancer. especially cancer of the lnna. chronic respiratnrc alimrnt- an,1 pet.tk• ulrer. ar erell aR sereral others of relatirely l"•er imPortanrc r.- rau-e- r.f dl<nldlitr or death. 6ome.rbat later. the Board undertook fpon•or~hil, rd ir,rr-ti• tationx into tbe pxccbnpLarmacolngical• effectr of nicotine and emr.kir,_. in tl:r. bol.• of learning more about the cbaraneristics of persont wbn adopt and niain- tein the prnctiee of smoking. the needs they feel: to satldc by tLr prsc•ti, , an:l the extent to which rmotlng actoallj meets such needs. TLr eoeali/ufionoi dirroaca The major dken-e+ that bore been mentinnerl aMre all belonc tr• tl:& of rin.tilriirernl dknrdar=. Bc tbia we moan tbat th-y are brouFht n1,nc:. rt-•r I•c infrraiou• mir•nK-rcaniYma (like dirbtberia or tcphoiQ frvrrr r.r -nm• 1• t•:.t siuar rxternnl indurnce (like sunhunt or ars<enic rwi-nninRt Lnr 1,:r n rn-• prarlual cbanc,•. breat-rlnw-n or drrsncrment of the ordiunry b• r1:!c tu:: l:a:-r, or pna>.~-. rueh a< thn-e of di¢e,.tinn nud uretnbolhn,. tran-ir rr .•li. e:l.~tt-ion and contraction. Dow• of blood to l.br rariou- orFan•. diti-iru. ••f cr;l- anrt tht• like. Tbr• ron•titntlonal di<eaceit occur mnat often In older i+eopl<. nt Rr-uid I- e>- 1w`trrl. hrcau-r rbanF~ or deterioratinn of the bodily mn, hiner- and rr- ---. - i~ ucuollc Rradual and it likely to produce serGou~ dicahiliry otar l::trr in la• Ther arr wcn morr often in the population todn:r. lnrrr•lc becau-.- -r• mat•c Lat-e ex•rn wareJ frum early death from lufer•tinuk di;ea~r• and h: ,,licrd tr• a morr adranced eRr. Tbiq rrlatlre lncrea+e in preralenc;• of r.trriinrn-- n:ar di-• ea-es. cancer and rbronic disorders of the lujtc has led to the imhre><int, it, clu.o an oL.rJulc incrr::-~ ir: r-rv:: sbowiu ter~ tbot tbr•e di-.ex bore 1- a p qu r " ceur.. The trrta ^rlddrmic•" hax Leen applied tn thi~ inrrn•a+e anrt. or, t1L. of thi, a+>:umlrtinn. effort bni< heeu put Into the i,rarch fur -netv fwrrr< in th• enrirontneut" thnt micht e=plain suc•h an el-idemic incrra•e. On the .tl,er Lst,•'. tlu cnnrept of an rpidcruir increa-e ba• been questinurd in ea.h of thc•:• c:1•- Lc ri•rotal-ir lnreftit:atnr<. TDiq fact does not, of coor<e. dimini-h the imtrort»nrr• of the cct •:irnti~n~: direa.+•>; ars the primar•r challrnRe to tnedi~al reanrr-b in our :r•urratint:. t•u; it docit bare an intluence on the selectlun of and emhba-i> ol*m rarinu; al 1•r a• b.-< to these prohlem< thron_b retearrh. n'bile nrrr factors in tbr enrirnr.n:enr tr,u•* certainlc be atudied. manc lnenences that bring- about cbanrr< ir: tLr machinery and procernes bare alw'aes been with u- and tLe-r mu-t 1:•,: 1- neglected. •That 1• the .R-vt4 on tbe brain aod aerrons satem soch ar etimulatlon. trsoQal:v:::ar. mr•dtncattun of reEe:es. etc. CT~ H~``~ 0~•~~f ~~

THIS DOCUMENT SUBIECT T9 1110 WhFIDENTIAUTY AGREEMEN3 , Of coursc. atl tbese constirotionaI dise a<es occurred and moc: "~re t'•ta•ltr••• r, loDg before tLe use of ciprettea becnn,e precaleut. TDry s:ill o•::ur amohera. Eyidctnio/ogito: atrdPce of esnokiwp owdcwutirutionol di.caie, It e'ac jukt sucL coD•rtJtntlonal disease tbat rpidetaiolo:ical crnd,u • a f- Jears at o reyoneJ to be more frequrnt amuuF cieartt:r sn,••kr r• rl,:r:: Don•rmol•ers. Tbe lirt of dirma.es so a>:,oc•iah•d oxtrnJ• to a Acort 9-r Lf,n Tbese epidetuiol/aical studie, bare L*en anr' .tili ore the sut•i•.: of rrir• :• by ctatisticinnM e•itL ret1w-c•t to tbtlr reliab:!it>, nn t tar.i• al cn utrd•. at.•1 r... tfonsl resenrcbes eluteJ at rect]feln; sumr nf thrir rleti, itu, ,r- rom•• of tLr rurious contradic•f:••u• uLJ L•cr 1••-•-r r•• •.. ... .• lt ig a fact of bistnr}'. nrrerrb~lr-*• tbnt tbev r!•iJcn'• tu~r.:: r.•; •r:• •• the lmyrtu+ for the abuuda:a n•-e::n•h reistiu- in ou •%c,tr or aunrLrr I•• ": aud bealtn" thal bas sah-equeLt!p brea s'1MC•orrd nr•t oaic Lc deiicrtwvuts hut I;r a t:n:ul,•r of culuntnrc h••ultlr N:. : t-t. .. taciuJi::r TLt Cnunril for TuLuccn Herrar.L auJ tLt• A:t:rr:, c,t: :,i,d :• tlot,'4 EJu:ati•,:. uud Ite.err.•h }'uuuJaric•u. Ti,i• r.a• :, !r•c•, r;- -.• elttrc• u rrc..~uizr~-intl~tu. 16r r:,nof t;ridr•_.ira• r; r•-••; idrut:f:i art..- iL wbicL wort u.:u ar .u4 t•xtt::L,.A ~:uJtr• r,% v:L, rI• t•.... be n r3rJ• Supp:rutrn:•rrc atudirs art Dt•cvs.arc le'AU~c °: i-csi.er.alic rt• a Ptatiat:ctll u<•aciat:Gi c91t nrcrr. th•r r. rta.•li-i, n rau-:,i rr',r ••., . .. ..bnr• nLetb!•r tite stst:r,ic. :!c a.•uc•i:r,td fa• •• a n,a,. . r... ~ cau,al factor or no c:wusal fa.•tur at all. For exa:t:!:;e. a:: :rc-•• abot\• n-LltLer cl:.urettr awbY:=t ba(Qp'•L< lburrlt I.• 0•'r 10rnr;,q: I. t-- . . or c:uttrr .f lit'iuc bubita tb.jt 1•rrdi-lK,,.• In titr d:•• ,.r• o: t• :. out It•1•if t•riLL :bCoireJ CauVt.\'. Ndr lJll It fbuW Nhe•rher 1;•. nu•: Ili;•!y tn d.t•rkqr tht di•rr,-e ot: a•t•;•rr.! u' cbnrar•Irra:i,•j al-u have a.p<•cial uer•d or dt••L ~ r.• cutd:• . TLr,•e qurctinn~ Lare to iw umn'rrrd -rlr::rat• ;r fr•r o.wl, t:. •. r nqo: rrd tr,.rt ur mnre ofteu 1n su,ritce:. tbau in uun•ruo!:rr•. DtSL1st:S Or 7711- nC,tl:: w?:. Ar:LCt[- Mar•- of tl:e-e Jicer•q-s Larr their u:r:n::trv c-:_iu It nf t:u rea•r•] na:E• trrrer4-!rr-tk- ahirL ev.•a:unl;c or tu•lrk•u ler., a:ru c::: u: t`r bla.d >'u! Plc tn rnrinn• nr .: Lr;•r.ui: AnJ L:.••rr art~•l• rmcr.rardial ai, •a•_. :.1ri •l, c-r rurrr:,ll! tb- rr.ptr• r:rn=. nf it•. :' It P:'!7it'rr~alt)' rw•nztlirJ 1!tt: .. f r t• n:.c 1•, !• t11,• r:tr• • 7lrtrrlUct•ir•r.r.!• dr •.r•• . • r !n ::•tr,. ..•_ i . of nt•t:rr• rt-rnt•. Onr •~:t rr•.u1:~' li;t t~.et::~" c,t, 1 f ~ >;l:otvt: rrr barr .!'!: • a 1r• .:lct• or t~ rntic:ir•:,! n=• •• . di. .~,; •t r h«:.:•t and rrnrit•• tL:uk :r j. c•i: t••; .. r ortl••- rn I!!rqrat• a pr•r•clplr: 1. Hrrr•ditc or rr•ar'ic ••r . . r •' tor~' •. ~• Elerntrtl t•hole,tarnl or rbn'e•t,•r;r! c"r r• it, ihP I i-::. " r- 1:- .i ' prntrl:t< i:• tbn hln..d. 4. Hi:h !•'rr.t! pro,:r•rr. ' Hi-1. a.•r•r:,. : facr!t,r. el. 1'Ite.ir•n1 ootielty. ' l;trr•• nr l-n- i ~ tn h: r'.• . •;. . lonalitc f::rt:-r:, Ir. Pat:eno• uf bnrnvr ,- i •. •,• r,- t: •••! j•. '1•• ' 11. (t'+r•ir~. I°. Ci.^:Im:to sutnl:in: tb:r: t•n: rt:,r rr I• !- •tt•„ i•. 1.' ooffw. ten nnd comcto- dn;v• 19. '-rs !rr-i•Ir n:•r.• .n••-; . , ratir• of cL• r•1 •rn! In pbn-Irl.nHld:t< ih th - Id,ti•,1 ,Fr:IC• lt:. r. :c'S '• ' ntetn!rntl<rt:. 1T. ('rr•nln rlrrlrrxnr•lirr~~t.lti - nfrvl.rrlr•...rhtL: t•••r:: b!rnrrl.•!r.lli_Ltt'.+•:l:rcnlnnt( ncer-nnrrl•/tr:t or A h!_h prn!wr-tinn n' •ctnr'tn•',,.1n•', f:-r-. It 1• lrrrfrctly t•lcnr tbat thwe t><Pn: c far tr•r< nrP n•rt a!1 r,11;r !n aliry nart in:niic trndrnt.i:•+ are r.nrtir- nr,d thr•rr•f• n• rrl:,ricrlT dtft: "'r t•• ~ Pb>xical :i ticity 1• rsom.tbinr moct nf n< ran rrnard. CL••1••• rrnl :• :hr• I. •.+ •- got'ernod Iutrt)c t•3' br•redit,r and Partlc b} on:t:r.dluble fa,-tru• d:r r a:. i exrx•l-u•• Deareet nf accocLiNon In thc stati•tira: rt•tn!innc ht•ta-wv th,,,o tn • r•• •a and c•ardlol'a-oular d!sr:r-r+ car~' o•i4rlf and fn many ra~•• :Irr• un. ::, r. F.•: r~, •Faeror• nt4.r than rrt.rlna~lereetr rnm. c1111 anite mceterlous. s.em to M Iorolc.' b::: detalleA dl•cassion aould orerraead tblr er:eteau•tc. C TR HN 014715'"I"

rE ® THIS DOCUMENT SUBJECT TO 1111 ()ONFIDENTIAUTY AGREEMENT. ample. thor.;b hiFh blood rboleaterol iit associat(•d with Jncrravd.dangor o! l:cart attack•, it 1-~ not realle knoa-n .rbether the relation is casual. Hetire lf cbolet:erol Is loRered h) •omr' artiEcfal means• a• bF use of a droF. we st111 Eo no: kn,m wbet.Der thi=n*lll rcduce the dau;rr. TLIa kind of yrnblem r.•qulrrl s:udira beyonJ dlscot•ery of an a>-oclatlon t.etweeD cbole!terol and heart attacL,. R'beD lnformation on a rreat nnmber of sucb factors is collected upon a lar.e bumau polwlatlon, the stati<ti^lan i• presented witb a di(fic•nlt ta.k of Tbe firat ta>k ir a pnrrly matDr'motical one. A tecbnlQue callod mul::cariatt analc- sis mns: be applird In orde•r to rice relsti.e e•ei;hts to the fa••tur-. s(•p::r t••?- :: .d /n vroup=, a> wvthcn:oticol ••predlctnrt" of the.re-:tit. Soch ~tsti<tira! Reifl ;iti_. tbough it c::nnot establi.,b conutioD. can elimiuate rome fartnr- a>, untmiwr: t.t and sfat;iRht atbers for fnrther study Rc sppropriatc me1!:,-1•- in•:uJin; eal, :.• mrntal and cliuie•al ones. TLc• acallable st2ti•ti•a! methnd. bace 1•(•en SL;on zi!:i laborious and olso inadequetc to bnndle s++ many caricDlr* limultrncou-t% . The l'nuncii La- lreen s•-isting In the derelupwent of t.rtv oumpute: wctrnJ- f,,r nuDti-(•r> of vatLt:,le- simuit::nrot:1tc at.d rn:•i•ilc i• tbctr wvthod- avai!attle to scieuti-t, Rrnerollc, { strnu; 1r,trr.••: L: -ul, tk•rau•e ther, are va5t collreti••n-nf duta alreat]c ezittir; tcbich Lalt• D-~ r fully suniyzed on a(cour.t of tchnicai proLlew•. Applfeatinu of tbr ntic atetbods was re(entl!' made. In n prr)tminar.- Rar. to data from a current multifactorial study of factor., rrlnted tu tcas fouud tL:tt cigarette sruoLiug was. tnntbematJcaily /peakit:F. a ruD.na:iz~: ' of a gruul, (d ntLer faet(irs T%'hich. without inc•lnsion •d su:~d:iac. r•v:r 1•et:(•r predictors of len/rtb of lifc. Tbls matbematical analcsi- doP- n.•t s!tnw factors actualiy baee a dlrw-t nsual bearing on )encth of lifP but tbeT 6,• •l:'•R thDt o:ber< ~*L!cb tend to '•c:ustcr" Ritb swuL-i::; are as likely to b:• caa=: l1' rYlatr(1 as fDln);it:g fer •c. The data nsed in thi. pre:iaanary t!•!;: n•r+rc li:..i:• r? in ebarnct(•r and eitet:t. but It i= clear tLa metbods of tLi- tit:d nred to l•e appaed to nth(•r and larger bodieit of infotv atlon as a ste,^. tn Gete:!:,:uia; wbi'.!: fsctor- mnc re-n'.Iy Le c3u=a1 and the ezter.t t:• c:Li• h tSec C;tuc!I7' I In the tanu• lo~,^eeltc stud-, a.reulurity r,;lce: Ra.< di,v-Te'r~d tbac cr'::iJ esplalD lb- whr•le itati;th~tl arsoclatl(•n b^tRc:•n c•lro:ette smokit:; ^t:d lttiFth of Iifv. Th('n• L::A !»'•.•:t a(•baD;r orer the year- ir• lbe (:'.-tribution of ciear-rt( smol-in: in th+• ~tnrral ropu;atioa, so that sucb emwYin. 1- beavi'r :.:c:; of prefCLtl\' ypuu.rr tenerati:mr tban nwon; the o:dar our-. Hrtrr• if t-L tbou-aud u:ra ••cvrY co:lerteJ iu a ranu~n: aan:yle of tLr enrn'rt 1•Li;e•? ~- m:+le lsulroiatint, und c:er.• line:i uP and ezrcuted R•itC u,nrLiu.' Fu:.4. i: be found. s:3ti-tic• u1-. tL:,t t:ie bearier <L,ukrra ba(:. b; •auu•IarFr •!i(• 1 at aRes lha:", titr lieLt (.r uou•au:oLrr-. CleAric tyeir sL.o:il,; rou1J t,o: L•:,c- lrt: the cau-r of d(•atL. dfL(rosclert,eit Tbe Fr,:aua!!r tbickeuin: o: tbo• bL•od re•~:'l ~•alls bas hret: n.catinnrJ a::r uoderlyit:~ fac•h'r in many di-:nrder; of tbt• bpart an:l nn~riv,. Council rtudy of arterie-. ezemit:eJ and measured after @eatL. rfl'''n-' n.••r. tblcLeuing :artrrio>rlerosl-l in tl:e vessel• f:om per?r•nt wha h:ttd r. cigarette su.okiu; 'MranwLile. tt<c• otbrr simi!ar studie• in%u!riu: nt.!.: ,i•. t•ic•tim!, sbovv(•d thc• obt(•nc( ('f any relation hetRren art(•:in-, lrr-i< at:(: inR. Sitice tLPr(' wn: Iitt!o- or nn i•nfor•::ation io any of tbv-e stnJi- on ntbcr fact(•r~ tb-)t m!cht harr M•eu htcnh•e'J. sucb t- ~•rr.nualirc, eLL'itr bandle stre.- and frustratiou. eLnle,terol lecel- et;., aLi•-L likelc r i-1: t'tnokint:. tto firu, cnnrlu•inr.% '•nuld 1K drawn. I~till anrthFr t:udc di8 r•,tN,r: n relatian hrta•rc'n arterial c(,nalrinn cnd per-ouality (•f : kir.il thnt e a~ intlu<:.••: the ner'd or drAre to swoke. Henc•e tbr question nbetbar stnnl•in: affrct• arn ri• sclerosis ba« not be.'n settlyd conclusioelc but this vvrirbt of erideuce su;er>t- that It do(•s not• Studies tcith animal models. so far. baee been incrnelnsice. An effort i= Wur made to devrlop t*tter animal models. and netc' studies ou lath ar,imal- at.c1 bumans baTe been started to determine Rbetber Dlcotine or smokin: will wtua;:~ ~ni)uenee the incorporation of fatty materials frnm the b;nod-treau: into thP p?pues that line the arterial w•alls and may ecentually reurict ldood .VirotiNr pAonnorob.pJr A lorce numhe: o3 studies on the pbarmacoloEirnl effe°t• of nicntine and 'nr smoking bnce LerD sponsored. These baTe rnnArmed the transient nature of ruct effects. R'hile a great deal of Information bas been added to the stocYp11.. no::e CTR ~~ 014V ,~~6.

THIS DOCUMENT SUBJECT TO 1112 CpNf1DENTIAUTY AGREEMENT. of tbe.e studier+ has establisbcd nc contribution by nkotlne or smc.kinr to tl," causation. aaararatlon or precipitation of any cardidcasculsr diaea•r rl,a: ,- amona the present !m{tortant canaes of mortality. Blood rox ' \icotine 1Sas been shown to bare effects simllar to tho-e of li_I t cNr•r• i•r •:. the work of the heart. It tend% to tncreat+e noec of blood in th.. .kc•lat:,l u,u,,l• - and In tbe arteries of the heart It}e1f unless tbese are too bardrn~d by s, l.«no•'.- to expand. F1oR tn the skin m<< be reduced by nicotina in cold encironmen•- bnt expanded when external temperatures are bitb. R'bile nicotinr tand• ,, tncrea.e blood Sow• fn the coronar7 arteries. it 1s lea* clear w-bether tl,p extr:,-tv•:: of nutritive sabstanees from the blood is Increased corresPondlngly. Nieottae •netaboliim Extensive atudles bare traced the breakdoRn of nl^otJn. in the 1,.•dc ar,.! shoRn that !t ts rapidly converted tnto otDer sobstances of much In«er pLnrn.a• •• logical activitF. OeKCra l A large number of studies hare contribnted to botic knoRlydr~ c•f brnr• function, physioloce. metabolism. biochemistry and rr%ponse to druF-. aitLou• direct and Immediate relevance to tobacco or nicotine. The fact that pipe and cigar smokers do not experience heart aud art.rc disease any more often than non•smokers ralses the question wbetlwr uicc-;,;,•• plays any role in the development of these allments. since pipe aud cigar smolar, bace been sbow•n to absorb this alkaloid in substantial amounts. G"Ctt aTt'DIIs The claim that cigarette amoklnd is a major cauutlve factor in buwnu lur.z cancer is based cL1eDc oo eptdemloloti^al studies. It ls assertedly Luttre«ed t, certaln reports of patDologlcal changes observed in the lungs of Luman smokrr- and studies with certain animal models, particularly skin paintit:F. EpidnnfolopY The treneral statements that hare been made about Rtatistical multifnctorial causation of constitutional disea"x and the w-e of n.utr.caric,-- analcsls are just as applicable to cancer as to cardiocasculnr di~e•a.r, It. casr of cancer we stiil hace feRer leade with respectt to contrihutorc faernr= for the heart and arterc diseases. Hence in epiderniolo;ical •tudi--. it t- ti ditbcult to select the appropriste questbns to aRk. .4 tood esnmllF i: 1•r~nrt.. by the new developments in study of ciruseA as a cauze of cnnefr. \'Prr f-•• quenion>; with any bearing on this subject were asked in any of :l,r ~rll•lt o•t. epidcmiolot;ical cancer studies. The Council hat sponsored several epidemiological strdie!z in the cnccer fiPld One sbotcrd subttantial diCerences between the lung ca:tcer exl*ritnt-e of aF:. and R'omen and further strentabened the silppicion thnt there ic a real <-x differcnce. due potslbl.• to hormonal ef'ects. Otber Council studies bac, sLnx, :, the frequency with which soch secondarc cancerR arise in the lung h:r n•etn;ra-:- or spread from otber sites. and the eaae with which such %c•conrlarc cnu, rr- c.-.:. he mistaken for primary lung cancer. Rtati!ticf of lun.^ cancer itwirlc•m-wit! I.. profoundly afterted by eorrertion% to remove sucL metn,tati,- lnnr c•arwwr- t: the totnl of tbose now widely attributed to environmentnl exn,;urr-. Pathological $frdiei Proponents of the brpotbesls that cigarette smoking tt a primo f: crnr in cancYr bare placed be.R reliance on the repnrt.- that certnin cl,nt c.- ••abnorntalitie4" fn the lung are found more freqttently in on aur~;•-~ One important qoestion is whether such cbansrt: are propPrly n•¢ard.rl :,- caocerou.•''. Council sponw+red studies roRCe•1 that thac ah• t•nn.aoo iti, to external influencrs compars)de to the development of callnu•e< .•n th• f-f of tbo-e wbn walk borefoot. In aninul models they have nnt rn,rrr- . 1 ~.• dnrer. but disappear when tbe external in0uencr l- remnva,l. Thry u;: c 1,d produred by exposure to suhstnncea and influenres thnt arc• nnr cen••ral!; t, • Carnlyd as carcinogenic and they occar in children and non•.-a,.,ker<. CTR HN 0 147559

THIS DOCUMENT SUBJECT TO 1113 CONFlDENTIALITY AGREEMENT. JNimal twodtlf When the statistical reports indicting cigarettes in aacer w•ere Lrst publisbrd. many 1ncNtiFators. undertook to make aoimaly inbale clsarette smoke in thr expectation that tbey would detelop lung cancers and that tbe responcible sub- stances fn snioke could then he lsolated and eliminated. But. oeer the cear tbe+r man,r exl-Prlments ba.e all failed to produce human type lung cancern. T'be esrer/mental method that did produce an observable result was the painting of smoke oowders+ateu (tieneralle but erroneously called "t.r~") on tDP sklns of mice. The multlpilc.tioo of aucb skin painting experiments ha.e bPeo cbiedf reslwo+Jble for the wide-spread and apMrrntly confldent idea that the reputed dangers of human ciprette smoking with respect to lung cancer bnir a/rrady been traced to the amount of "car" in the attwke. I feel that this is not by any means correct and that a pause to consider some Terc simple and bnsk fartr will abow the tenoou.ness of the caae. Wc skepticiaa of the relevance of the skin painting studiea to the human lun; cancer problem Is based upon llre eerc fttndamental coosidrrationt : 1. Ttit relotirtly enormovt doaopti v+rd in the owintol skin txpcrinirnlt. Cal• culatlons have been made Indicating that a man would bace to rmokr frv.n, 3(t.0(Ki to 150.000 clEarettes a day and Inhale ererc puQ to get such a r1o-Ag• of *'tar" on an equivalent area of bis IunR: 2. Thr prcot difl'rrcnctp brtvete miot and the prinla/n., inNVdina n au. lu su•cePtibility to cancer•indacing chemical.. 'Afedioinal salces uvd Ritbout o1•• sprt•able harm by Lnmans will re.adilc produre akin cancers in mice. NP-nl;P-• rrfist Inde9nitPly the same akin treatments that will produce akin cancers in mkt in n tcw• ~cPek•. 8. Di1/'crcncrs Lcttttcn skin at+d Ivng. Council supported eiperimPnre hccr .bow-n tbev tissues to be far more resistant than the skin. Smoke conden~w~• intrc+duced directly lnto the lunR ba.e not produced cancers. On tbP orl:rr bano1 some strong carcinogenic chemicals will do so if "pl.nned doRn" so tbnt they remain in contact and are not pufcklc carried away by the cleansin; mechani=uj- of the lunt: isurb a* mucouf flo.r and the acarenr.r arbite cellel. 4. 6mokt QondtlMatta or "fart" •rt isof rpviraiMt to uholr. frCrL. fnOrwnl .ntol:r. Condennates of smoke collected by pass(nIr smoke through cold traP, at very lorc temperatures are not equivalent either in phcslcal or chemical rrnl.- Prties to whole smoke. Both chemical and physical changes occur. svme repidlr. following the formation of smoke in the bttrninR wne of a cigarette. The!Le continue to take place in the condensate after collection. Still furtDer, lt bss been shown that condep sates from pipe. cigar and ciFn- rette type tobaccos all exert a similar. tboo(rb teeble. activity on thc- skin- of mice. Yet the statistical incidence of lonR cancer Is very loa eren among pipe and cigar amoktn w•bo report that tbef inhale. It seems clear thet the ef'ert= of chronic. lona-term tnbalation of wbole. fresb, normal cigarette amoke can never be reali•tfcaliy appraised by means of smoke condensate studies. 5. The fiftb point concerning the relevance of mou" skin Paintiar exreriment; to the human lung cancer problem lles in the (nrpt(ootioni of viral apcnrt in lvrh espCrimrnM Thls tomplPx sobject obviously cannot be di!cros-Led in any detail here. It aboulJ rutllce to call attention to the fact that many ranimal canrtrf are nlwn<+ rwrtainly of Tiral oriRin. Some tTpes of riru.es may exiRt for a lont tlme DiA&-n In the ct•ils of the animel and repressed from expretsinF tbem.elres. Theu thrc mac be releared lnto actiHty by any one or more of a w•ide variety of int.rnnl or exterual IntlnPnra+. UPthndt for d.tectiu¢ snf•b riru-r- bncP drrrlorPrl rsl.• Idlc in the lnut frtv years and it h now pos+ll:1P tn mPar:ure t1:P dPt<rnv tu, nhirh they bare become ttnleasDed. long before any outward manife.tation of canrer ar:.re k•noR It has appeared. n1RrrPU.r- in the arparrnt su•celrtihilltc of rarinu• animal strain• and !:Pr• rle~ tn Pncir(bnmentnl intluenc•.c ar. bPinc Rhown to he duo. in many cnar~. rn the relntire concentration of onlearb.d virus in thete animnl.. Thnx n nP%% rfi- mension !s beint: added to animal hionit?ac methnd• In the flPid of canrrr cpno.ic. The state of the host animal is emerrin¢ ap a prrdonrinant f,tctor in detrrntininr hmc /t respoade to treatment with chemical and other agents. It bns 1nnr 1wrr known that Rent diCerencea in suorPptibilitc .xict amone Tariout atrnin; nr.A Rpecir of anlmals. but now a nea k1nA nf control upon this "host su.cwprinii0 -' has betome pos-tiblr. Strains of snimnl• with known 1Prrll of the 1rtPwin1 cancer-producinc clruset in the unlPa•hrd state. rromi.e to becomr th, tr<r animals of thP future. L'ndoubtedly the interpretation of many earlier esl>rri- CTR HN 014>~60

M 0 \ a, ® T}IIS DOCUMENT SUBJECT TO • 1114 CpNFIDENTIAUTY AGREEMENT. menta on the tadactioo of ancer bp cbemlcal agents will he profoundly a1• tered. TbJs reinterpretatJon and reKalnation .rtU ba.e to be extended also to all the animal work 13at haa been dooe inrolt•ina eitber the pintina of tobacm amoke condeasates or tDe inbaLtlon of smoke. Tbe txw vtrns atndles baye strongly raised the question whether Fimilar rtrna mecbaaismmJ.riU be found operatie•e In Lnmatu. TLe bDman lncestiRatfc,r•- are slowed by the Impqsalblllty of arrying out certain kind- of e=perimen+• witb human beings. He.noe tndlrect metDods must be worked out by more ln botiona•procesees but there ts good season to hope that they will be decelof~•] ancceadullS. caso'Cu rotMoNaar atar.au Such diseaw. including particolarle tbose calleC cbrnnir brnncLi:a. r-•:'• monary empbcsetua and bronebiel asthma. are more prrcalrn: toda- larc-'.- because of the lartte number of older persons who bate .rnrcir••d the a,n'- fatal Infections of earlier tlapes by the aid of the new dru:-. n•bethr•r tL.r- ts an absolute or aaerorreMed increaae 1s mncb les: clear. TLec rrr condltions and It is til•.lc tbnt the terms '•emphcfema'• and '•c-bronir hrr•r.cL•iri- .rill be replaced by a whole series of netc names that apply more s!.Wfical!c 1- particular eonditions as they come to be recoCnisrd. Thus epiJezntnio:irat studiF- Rill mean little until standardized techniques of rrcozniti•NI:. d(-n:,l-i,,r. nt.e. elassitlcatinn as well as uniform nomenclature can be widely al•hlird :n cari,u; countries and localities- ' Tbe Council It sponsoring lonR term clinlcal atudies desltnrrl tr, nt•cPr~e nt^r.r patient+ orer lone t+erlodR of time. eollert a rnin annunt of dr-ril•tite d:! about them and follow the proRres>: of their conditinns. with po=t mnr;~ exh=,• ination to manF cases. Tbe ase of mttl:icarinte analysi- is esr•cr-d t,• Ia:: Roup the various conditions into detlnite clinical en::tier: and to Itea• clec.•!r•; clinical diaFnostlc criteria that will correlrzte with morpbolo:i••nl Dndir::•. to etiolon. it btis beem indicated tbat there nrc herrditarc a+~-t• in !- u,. ••. th.•e diseo•es. tbct enzcme defects sometimes plny a llar;. and tLat recurrEt: Infections mny bace a role. An1ma1 models are in use for describin, the possit'.o causa? r•r effects of chronic inbnlation of sncb irritar.t tra•e, nc nxidr• cf .u':.•r dioiidc. o:onr. concentra;ed ozc.+ea and o;bcr-. TLe rffect- rd ,uclU rsl••"n: on the immunit; sestam% of tLe animals at:d on tLr lnnr m: crrq:.~_,- ~r. I,:: : obr;c•rcrd. Pilot atndies of chronic ciRarette smoke inbalatlnn by ar`.^:~i= '• ~Irr 1•r..:d cnrried out and are to be extended as tmproced equipment brru:ue• nc il,il•:F Ic1COTLSt: LXO TSC C[.~TlAt• NtMors aTSrZ)/ Smokers bnr•e often repnrted that rrnokin¢ '•)`,?I•• pick the•:• u:• a::d :• t'.r:. aning in the morntnF", and alsn tbat "it belp!t tl:e:n relr.s wL.•1: :: thc•e s'tatemrnts appcs•r eontrodictorc. tberr It nm.• n srltntiti. 1-°- f•r 1' 1n tbp flndin,^f of rr.rcbo-pbarmncnirrical !tnCle%. Rrndi-e o' 1•n:+.t. !-r' in enimnljt and man, bave sbotcv that nfcotine baoi sn r•fi. Inr= r!.• brain Rben it fs In a state of repose. R'hrn tl:v animel or l:t,l: i• :r. n- of aFiutlon. nicotine has an effect on the brain .cacex re~nll,?a.~ th-: r•f ~:.. of the tranqniliser*. One Council sponsored ineer<tlratnr has repnrtM thnt p•r-n; 1ik. ~ amoke sbow• a predominance of the brain R•ace ttlk• thnt tu•-r',r nn • and postulates that this tTpe of person smnke+ for tbe tranqnilizin:• r^'. * 1, not yet knntcn whether this tcpe of precniih rc encrpha:n:r^ h• ;• •trPr:, hereditary or whether It RiRnalp predi"sitinn to rccr•hn:nl,i:+tii• aR ulrer or cettaln heart conditlnna. but tLeze are Important prnt•L•nt• f••r fur!!•.•.r re"arc•b, some of which Is underway. Several studler baee also esplored tho ef±ert• of nirntinr nn the process in rats and other animals• A de}fnite posltice rffect h^~ Iw.-n artrnaa or rt3rtc oLCt[s A statistical association between cisarette smoklne and mnrralttT f:on, tlat disease has been reported.• The Council aponsored a series of srudle, to dete:- •Rtntlrtlnl .fudl•. of vleer lweierrtet r.ther than mortalltr t<enid her• hrn e%nr• m•nr- fnetnl,•ine. mn.t p.rsonA -bn d+eelnp tbe dlsen.e art kM•t ondr. m•d:chl c•ootrv; acJ er.ntn.l!s die from Mm. otber taur.. CTR HN 0147GI

® TNIS DOCUMENT SUBJECT TO 1115 CONFIDENTIALITY AGREEMENT. mine whethet smoking would affect any of the ph7atotosleal reactions that are belle.ed by many cliniciana to play a part in aker prodoction, partlcularlr the o.eraecretJon of acid by the stomach. No algnlDftnt differencea were found in any of ten mearnred responses bet.reen normal peraotu and ulcer p.tients, nor did amoking Iuat before or during meaa4rementa prodoce taf consistent pattern of adcal.ficant chan"a. On the other band, nloer L known to aMet cbfefly pcraono of a particular temperament, that is tDo.e roaceptible jo anzletJ, tenafon and fruatratioo. It 1, reasonable to suppose that avcb peraons would be e.nerlallc likely to seek relief from tension be smoking. Hence the welgbt of eridence aroRCestt that the rtatis::- eal association between elcer and smoking ia non•cauaal and probably attrlbutablr to an lncreated tendency of txmperament.lV nlcer-yrone persons to smoke ciarettes. tIIY]t~1T The Council for Tobacco Research-C.S.A., Las. in the last fifteen Tears. apor.- sored much research into the causes of the diseases with wbicii swokinc bsf been atatlstically associated. But there atill fa much to be learned befor•• tLe romples quesrlnns inrolced can be answered and the causal lactor: ascertait:ed. Coutloulng Council work will be deroted to that end. TEE Cot'.%caL soa Toaacco Rt:ar-scs-C.S.e. aCIL7C7rrIC ADC1ti01t7 IW12n }:enuetb Werrill Lcocli. M.D., rc.D.. LLD.. Chairman. Cbaucellnr and Prof.->•nr Emeritus of Patboloirr, Atedictil College of South Carolina. Cbarle=tca, Sou:b prullna •Hnvcard B. Anderront. Bc.D.. Sclentlf/c Editor. The Journal of tbe National C.ncer lnstitate: Bethefda. Maryland Richard J. 111nR. M.D.. Professor and Chairman. Department of afedicine. R'acne State t'nicersitr College of Medicine, Detrolt. Michigan It1cY.ern Catt,'.1. Pb.lt.. 21i.lt.. Professor Erutrita- of Pbarn,acolo,y. Corrr' t'ui- cerr'.tF 'Medionl Colle¢r.Iirvv Tork. ICew Tork Robert J. Huebuer. M.D.. Chief. Viral Grcinoaeneais Branch. National Cancer Institute. Betber<da. Maryland Leon O. Jarobonn. IM.D., Dean of the Dirislon of Eiological ~ciEn~e~. Rt;e:.steic, Prr-fc«t,r of Binlnrical SciencPs. L'nirertltj of Cbicaro. lla: ~i~ C1.Fenn G. Lncv~li. Ph.D.. ~t.Tt.. HertinF, Prote%snr of >irC • ir.• : nd Pat*-:-c-. t'uitersitc of Southern Califon:a School of 'tiedicin-. _. •. Clarrt,ce Cfoic Little. t?c.D., LLD., Litt.D., SclenttAc L-« - Tobanrn Rr.earcb-1'.S.A.. Director Emeritus. Ros_.- :. ..a; L*tw+rnrorr. Bar Aarbor. Mait:r R-illinm F. Rirnho8 Jr.. Nf.D.. Prnf.xaor Emeritus of Serrcr,r. JoL•r.- Hnp:::r.Q Cnicer<ity Sebnol of Medicine. Baltimore. Maryland Sheldon C. Sommera. M.D.. Profes"r of PatbolocT• Columhia L'nirers, 2.7 (':.l;e:- o! Pbcslciang & Snrgeont, Director of Lahoratorieu. Lenox Hill Tork. N«w Turk The Ctt.tlr.~:.~x. Our nest witne=- i< Dr. 7;cnalc? Oknst. a~)::e. laa- colo:rist from Lot Angeles, Cnlif. Welcome to the committee. Doctor. STATEMERT OF DR. EO^ALD OEM FHARMACOLOG.::. LOS dN(iELES, CALIF. TLe Cn.%ir:a.:. You may proceed. Dr. Or.t'x. Thank }•ou• I unl Ronald (1'•c;1n. '.\_'.T1.. dirertnr nr ical hl: trnlncn]ot~ at Cerltnr.=•Sinni \ietlic:,l ('onter ilt In~ r. _ C:alif.I anl a s,raduate of the i'nirersit}• of ('alifonlia. v:),cre I rl t. 1 dett•trc of \I.n.. nntl V.~. in llllartllnt•nln--v and toxicrdn_;-. -~ftel hnTin- completed a fe,lo~~~sltilt in clinical '1~?tannnn•ho~ ~ at .lohn= •R.tlred. C TR HN 0 1 47C.O.C.-