Tobacco Documents Online

CJRRENT DIGEST of Scientific Papers Relating to Tobacco Use (Compi!- d and Described for Informational Purposes Only for the Tobacco Industry Research Co, nmittee. The Summaries Are Not Intended to be Complete Scientific Abstracts.) Vol. VIII, [1o. 1 January 1963 Contents 1. Smoking and the Lungs 2. Cancer Research 3. Smoking Surveys 4. Heart and Circulation 5. Other Systemic Conditions 6. American Medical Association Clinical Session 7. National Conference on Air Pollution 8. California Air Pollution Conference (Part 2) 9. Medical Opinions - o 0 o - Attached to this issue of Current Digest is an author's index to Vol. VII - 1962. - o 0 o - 1. SMOKING AND THE LUNGS BOUCOT, KatLtarine R., M.D., Professor of Preventive Medicine and Clinical Professo- of Medicine, Women's Medical College of Pennsylvania, Philadelyihia "In consult=.tion." (Medical Tribune, December 10, 1962, page 13) S',,udies at the Philadelphia Pulmonary Research Project based on 6137 older ~,ten reveal only one proved lung cancer inn a non-smoker and only one in a man who smoked less than 20 years, the author says in replying to a question. "The incidence of lung cancer increases with increasing t.egree and duration of smoking to the shocking figure of one cancer amon,-; every 16 men who smoked cigarettes heavily for more than i+0 years, " : ,he says. '2'lomen have not smoked as long as have men. Forty years ago, teen-aged girls sneaked an occasional cigarette but it was still not considered 'lady-like' to smoke in public.... If smoking is the major factor involved in causing lung cancer, we should see a marked increase in squamous and undifferentiated cancer among women within the next ten years." CONFIDENTIAL: N1INNESOTA TOBACCO LITIGATION TIMN 0230914

2. FITZPATRICK, Martin, M.D., W i1l Rogers-O'Donnell Memorial Research Laboratories, Saranac Lake, New York "Chronic bronchitis." (Current Medical Digest, Volume 19, pages 71-73, November 1962) The msjor irritant to most of today's patients with chronic bronchitis is inhaled tobacco smoke, the author says. Little success is achieved in m_an_agement of the disease without total abstention. MAISIN, J. & TShLEPIS, G., Cancer Institute, University of Louvain, Belgium "Cancer of the _],ung and its treatment." (In Italian; Radiazioni di Alta Energia, Voli:me 1, No. 3, pages 125-138, 1962) Of 29~_, patients with lung cancer in this series, 257 or 85.9% were known to b: cigarette smokers, and information on the others is lacking. There were 291 men and only 8 women in the group; none of the women smoked ci,;arettes. The authors say that women go out less, are less exposed to air pollution, but are just as exposed as the men to .respiratory inf=!ctions. McKEE, Herbert, Swansea, Wales "Smoking and lurrig cancer." (Letter; Lancet, December 15, 1962, page 1277) Disc»z;sing Passey's suggestion that excessive mucus secretion helps to origin.te lung cancer (Current Digest, August 1962, page 8), and Sir R. A. Fisher's (1959) recording of the paradox that heavy smokers run a greater r-.sk of lung cancer if they do not inhale, the author says: "As the heavy s!ioker inhales over the years, basal hyperplasia continues. Cell growth requires anaerobic glycolysis and one would therefore expect that factors re=straining glycolysis would be produced in smaller amounts, until, by accidont, one or more of them were deleted -- i.e., until the potential cance;- cell was formed.... The smoker who inhales draws into his lungs not oril.y tobacco but-oxygen, and the relative overgrowth of potential cance~7 cells is delayed. People who smoke few cigarettes need to inhale much __onger to initiate the cancer; and, in them, accumulated mucus, by inter'ering with the oxygen supply of the potential cancer, acts as prime promot=sr." SIMPSON, J., M.D., DPH, Senior Lecturer in Public Health and Social Medicine, UnLversity of St. Andrews, Scotland "Chronic bronchLtis in England." (Journal of Chronic Diseases, Volume 15, pages 991-1000, October 1962) The correlation of bronchitis in England with air pollution suggests that a,iy occupational risk will have strong environmental connotations bu;, the influence of outdoor work in a densely populated area will be afE'ected in one way or another by individual habits and the way of life, th=~ author says. CONFIDENTIAL: TIMN 0230915 Ml "ESOTA TOBACCO LITIGATION

3 Discussing various papers relating smoking to bronchitis and lung cancer, he says: "Todd (T.M.S.C. Research Paper #1, 1959) showed that the countryman, on average, smokes two cigarettes fewer each day than does the l_ownsman. This is not a gross difference (9 against 11), but it does mean a difference of 730 cigarettes a year or 14,600 cigarettes fewer in %0 years and this cannot be ignored in partial explanation of the higher prevalence of aggravated bronchitis in the towns." 2. CANCER RESEARCH APPLEYARD, J. H., B.Sc., and JAFFE, A. A., B.Sc., Ph.D., Physical LaboratDries, University of Manchester, England "ElectricaL charges on the smoke from cigarettes and tobacco." (Physics in Medi,2ine and Biology, Volume 7, pages 195-199, October 1962) 'he authors report on their development of a simple method of measuring ;he net electrostatic charge on aerosols, and, among these, smoke from various types of cigarettes and tobacco. They found that the magnitude ;Lnd sign of the observed charge is a characteristic of the brand of c-•.garettes or tobacco, and that there are striking differences between dii'ferent brands. 'Iritish cigarettes A to E ranged from +22 to +31+ in mean charge per 35 cc. of smoke; a British/Turkish cigarette was +l0 and a Finnish ci,;arette +9. American cigarettes ranged from +13 to -13, and French cigarettes were -22 and -24. Cigarettes rolled from British pipe tobacco ranged from +12 to -8. The effect of a filter tip was neligible, the authors say. "A comparison of our results with the limited statistical data (Royal College of Physicians 1962) on the relation between smoking habits and the incidence of lung cancer suggests that a highly positive charged smoke may be more likely to be carcinogenic than one with a smaller charge," they say. "The correlation is stronger, for example, in Britain bhan in the U.S.A., and for cigarette smokers compared with pipe smokera. It is not possible at this stage, however, to decide whether the sign of the charge, or only its magnitude, appears to be significant. "`'he variation in sign and magnitude of the charge on the smoke of differen; brands may be due to the use of additives, which are absent from British cigarettes. It should be readily possible to control the charge in this way. We have readily obtained a blend of tobacco giving almost zero mean charge, for example, by mixing two brands which initially gave sample-, of opposite sign." CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION TIMN 0230916

4. DeBAKEY, Michael E., M.D., Baylor University College of Medicine, Houston, Texa:>, and BEEBE, Gilbert W., Ph.D., National Academy of Sciences-National Research Council, Washington, D.C. "Medical follow-ip studies on veterans." (Journal of the American Medical Association, )ecember 15, 1962, pages 1103-1109) "MortaLity from 1919 to 1956 for men treated for mustard-gas injury and for pzeumonia during the height of the 1918 pandemic was compared (Current Digest, February 1961, page 1) with that of men with wounds of the extremities to learn whether mustard-gas poisoning or 1918 influenza hid increased the likelihood of lung cancer," the authors say. "For influ=anza, no effect was found, but for mustard gas, the data are consist;_nt with an effect strong enough to double normal incidence." A study now bein.3 organized in twins is concerned with a wide variety of problems in humaa genetics, they say. HUEPER, W. C., M.D., National Cancer Institute, Bethesda, Md. "Environmental aad occupational cancer hazards." (Clinical Pharmacology and Therapeutics, Volume 3, pages 776-813, November-December 1962) Govern_nental, professional and private perties engaged in scientific and practical work in cancer have shown "astounding indifference and studied aloofness" in tha face of the "potentially dangerous development associated with the increasing artifactual carcinogenic contamination of the human environment and of goods produced and used in daily living," the author says. "It was only in recent years that a rather rude awakening from this lethargic state resulted from the acute concern of the general public regarding actual and potential cancer hazards.... (Among these are) the impressive aad progressive rise in the incidence of cancer of the lung during the past 50 years and its probable causal association with the growing pollution of the general and occupational atmosphere with more or less chemically well-definied carcinogenic industrial effluents and with the rapid growth in the degree of personal air pollution through the cigarette smoking habit." The author lists scores of known or suspected carcinogenic agents and includes in one table compounds suspected of causing arteriosclerotic difficulties, including nicotine. ROCKEY, E. E., M.D., SPEER, F. D., M.D., TH0MPS0N, S. A., M.D., AHIV, K. J., M.D. and HIROSE, T., M.D., Surgical and Pathology Departments, New York Medical College-Metropolitan Medical Center, New York City "Experimental study on effect of cigarette smoke condensate on bronchial mucosa." (Journal of the American Medical Association, December 15, 1962, pages 1094-1098) One-fourth of 1 cc. of cigarette smoke condensate provided by Dr. Fred Bock.was applied to the mesial wall of the left primary bronchus of 130 dogs 3 to 5 times weekly. In 25 dogs the same area was submitted to rubbing manipulations. The bronchial mucosa of 27 non-treated dogs was also examined. C CONFIDENTIAL: TIMN 0230917 MINNESOTA TOBACCO LITIGATION

5. Pap%llomas were produced in two of the dogs treated with smoke condensate, "' orecancerous changes" in 25, "carcinoma-in-situ" in 3, and invasive care'.noma in 1, according to the authors, and none of these changes occur~,ed in the other dogs studied. Inflamma.tory changes developed in ,he dogs of all three groups, but these changes "were not as persistent, a~,id the distribution was markedly smaller in the control dogs than in ~he cigarette smoke condensate group," they say. SHIMKIN, Michae1 B., M.D., Associate Director for Field Studies, National Cancer Institute, Bethesda, Md. "Symposium on chemical carcinogenesis. Introduction." (Clinical Pharmacology & Therapeutics, Volume 3, pages 774-775, November-December 1962) Discussing the symposium in chemical carcinogenesis reported in this jourral, the author says, "In this group of articles, little has been said abr-ut the most actively developing and the most promising approach to The study of neoplastic disease, that of the role of viruses. This biologic, environment of man is shared by other species, and it is no longer teiLable to consider that such entities as the Rous virus of chickens, thz: Bittner virus of mice, and the polyoma virus are one-species laboratory cti.riosities. Indeed, the neoplastic potentials in hamsters of the Simian V-_rus 40 and of the human Adenovirus 12 seem to be close to the very lock of the human neoplastic secret." 3. SMOKING SURVEYS ARNE'IT, John H., M.D., Drexel Institute of Technology, Philadelphia, Pa. "Smoking habLts of students at Drexel Institute of Technology." (Journal of American College Health, Volume 61, page 78, October 1962) In reply to questionnaires given to 1719 entering students in 1960 and 1961, the answers indicated that 508 or 29.6% smoked, the incidence of smoking being 30% in men and 24% in women. In June 1961 questionnaires mailed to all students who were about to graduate brought answers from 312 seniors; 115 or 36.9% smoked, including 37.5% of the males and 29.6% of the females. Eighteen broke the smoking habit while at Drexel, two due to advice from the health service, while 49 acquired the smoking habit at school. "We have thus been worsted by 10 per cent in the first round or our camp?,ign against lung cancer, and it behooves us to change our tactics nexi, season," the author says. "This we plan to do." CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION TIMN 0230918

6. BARRET, Kevin A., LRCP, S.I., L.M., DPH, Assistant City Medical Officer, Calgary, Alberta, Canada "High school st?idents' smoking habits." (Canadian Journal of Public Health, Vo1i?me 53, pages 500-506, December 1962) "Because of the increased death rate from lung cancer and the statistical asscciation between tobacco consumption and the occurrence of lung cancer nnd arteriosclerotic heart disease, the Calgary Health Department staft decided to make a survey of the city's high school students' smokir,g habits andd later to undertake an educational campaign in the schools wit17, a view to preventing young people from starting the smoking habit," the author says. A que-tionnaire type survey was given to 7682 students. It was seen that the students started to smoke at an early age, he says. Most students b__came established smokers between 12 and 16 years, the peak for boys bCing at 14 years and for girls at 15 years. There is a high percentage of smokers in Calgary's schools and many of these pupils buy their cigarettes illegally, he says. The highest percentage of sviokers come from upper social class parents. The smokers rate badly in o-oganized sport and very badly academically. They tend to follow the example of their parents in the adoption of the smoking habit. They took their first cigarette out of curiosity and continued to smoke because they de.oived pleasure from it. The vast majority of them smoked filter-tip cigar7ettes and would be prepared to stop smoking if the hazards were proved to 1;hem, he says. Only 20.1% stated that they would not give up the habit. CANADIAN TUBERCTTLOSIS ASSOCIATION BULLETIN, Toronto, Canada "Adults' bad ex;wple is followed." (Editorial; Volume 41, page 3, December 196:?) Answe7s to 8000 questionnaires filled in by school children in grades III to XIII in Kenora, Red Lake, Fort Frances and Dryden Schools indicated that 50 per cent of the children had their first cigarette before they wei-;: eight years old, the editorial says. The years 10 to 15 are the ones in which those children who smoke become regular smokers and it takes about two years to pass from the light to heavy smoking range, Dr. E. R. Langford. reported to the annual meeting of the Ontario Thoracic Society. "Chil•iren are surrounded by cigarette smoking adults and bombarded with :!igarette advertisements," he said. Smoking habits of parents undoubtedly affected children, analysis of the data showed. Academic achievem.ent is in inverse ratio to the amount of smoking. He advocated an effort to persuade tobacco companies to be more responsible in their advertising. Dr. R. B. Southerland, discussing lung cancer as an occupational disease stated that carcinoma-provoking substances were used in some industries but that cigarette smoking is the most commbn causal factor in lung cancer. CONFIDLwTIAL: TIMN 0230919 ,dI~SOTA TOBACCO LITIGATION

HORNER, J. Stuart, M.B., Ch.B., DPH, DIH, Deputy Medical Officer of Health, County Borough of Dewsbury, England "Cigarette smoking and health education." (Medical Officer, November : pages 305-308) This is the complete history of a "comprehensive campaign of health teaching and to evaluate its effects upon the pattern of smoking in a school with 210 boys and 228 girls aged 11 to 19. At the end of five weeks there were no significant changes in the pattern of smoking, although there was some evidence that the boys had been influenced rath than the girls. The author suggests that in order to assure greater accuracy in responses, an initial survey should be followed two months later by the "real" survey, by which means the confidence of pupils is more likely to be obtained. TAYLOR, R. M., M.D., FRCP(C), Canada "The impact of education." (Acta Unio Internationalis Contra Cancrum, Volume 18, No. 5: pages 702-708, 1962) Replies to a questionnaire addressed to a sample of 2000 women in cities and rural areas throughout Canada, compared to a 1954 survey among women in the Manchester area of England, showed that only 5% of the Canadian women cited "cut down smoking" as a possible action to reduce cancer, compared to 3% of the British women in 1954. "So much publicity has been. given to the possible evils of smoking that it might have been expected that more mention would. have been made of the possiblE value of its reduction or elimination," the author says. 4. HEART AND CIRCULATION 63ILENS, Sigmund L., M.D. and PLAIR, Cassius M., M.D., Laboratory Service, Veterans Administration Hospital, New York City "Cigarette smoking and. arteriosclerosis." (Science, November 30, 1962, pages 975-977) The authors reviewed findings in 989 consecutive necropsies Ln men performed between 1958 and 1961. Daily smoking of more than 1 1/2 oa.cks of cigarettes for many years was the criterion used to determine heavy smoker of cigarettes; moderate smokers were those who smoked :~. to 1 1/2 packs a day, and light smokers those who smoked less than a yack a day. Cigar and pipe smokers and tobacco chewers were small in 1-um.ber, they say. In a tabulation of the percentage of incidence of conditions associated with increased severity of arteriosclerosis, "it may be seen that there is no striking difference in the incidence of hypertension, diabetes, obesity, gallstones, or cortical hyperplasia of adrenals in n:)n-smokers and in the various categories of smokers," the authors say. "Lt is clear that cigarette smoking does not tend to promote development oE disorders that may contribute to the development of arteriosclerosis.. CONFIDENTIAL: 0230920 MINNE`'~OTA TOBACCO LITIGATION ~1MN

8. "A si,able minority of heavy smokers of cigarettes seem to develop scleroti.c changes inn their aortas at a faster rate than non-smokers and tend to hav.- slightly higher blood cholesterol levels. The incidence of myocardial iTfarction is only very slightly higher in heavy smokers of cigarettes t1r.an in non-smokers, and there is no consistent rise in the incidence oT' such lesions with degree of cigarette smoking. The incidence of otlrLer types of lesions related to arteriosclerosis is not affected by smo':ing habits. "The i'indings do not preclude the possibility that heart attacks due to myocard-i_.l infarction ma.y be more severe clinically, and more often fatal during th=:ir acute phase, in heavy smokers of cigarettes than in non-smokers." H:lsewhere the authors say, "The relation between cigarette smoking and heart attacks could be an indirect or even a fortuitous one. Heavy smokers m-oy have other habits or characteristics that make them vulnerable to m?rocardial infarets." 5. OTHER SYSTEMIC CONDITIONS POTTER, John F. M.D., Associate Editor, GP (Published at Kansas City, Mo.) "Cancer of the -_arynx." (Family Physician, Volume 3, pages 46-48, November 196<?) Two et;iologic agents of significance have been established in laryngeal carLcer, the author says. "This disease is seen most commonly among people who are heavy smokers and among those who have had a heavy con:;umption of alcohol." Cancer of the larynx is seen more commonly -t.<< men than in women in a ratio of about 1:10, and is seen in the l'ifth decade of life in both sexes, he says. SCHNEIDER, Mart_n, M.D., Professor of Radiology, University of Texas Medical Centor, Galveston "Epidermoid caroinomas of the oral cavity: A review." (American Journal of the Medic-Ll Sciences, Volume 244, pages 628-645, November 1962) Among the traumatic agents most frequently indicted in oral cancer etiology are chewing tobacco and sundry Asian mixtures, reversed cigar smoking aud pipe smoking, the latter suggesting "the likelihood of a chemical e;iology from the concentrated hydrocarbons carried by the tobacco smo?se," the author says. CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION TIMN 0230921

9. W-i-LSON, Edwin B., Ph.D., LL.D., Consultant, Office of Naval Researc:h, Boston, Mass. "NDte on the epidemiology of peptic ulcer." (Proceedings of the National Academy of Sciences, Volume 18, pages 1924-1927, November 1962) The author examined the tabulations on peptic ulcers provided by Hammond & Horn (J.A.M.A., March 15, 1958:1295), in part as follows: (T~Lble 1) Caise of death Number of deaths _ Smokin Observed Expected Ratio Gastric ulcer None 0 -- 1.00 Cigarette 46 0 Inf. Other 5 0 Inf. Duc iena.l ulcer None 8 -- 1.00 Cigarette 54 25 2.16 Other 11 12 0.92 "It is noted that those who never smoked never died of gastric ulc-:r," the author says. "This gave a zero under 'Expected' to go into the den' >minator of the expected deaths and accounts for the entry 1Inf.t (for infinity) in the ratio column. It is difficult to believe that with a mI_Lch larger sample one would continue to find that non-smokers never diet. of gastric ulcer, though the rate might be very small. The 46 cig?-rette smokers who died of gastric ulcer constitute enough to be really siTr.ificant statistically; but the 5 'other' smokers are too few to be si~+ificant and so the infinite ratio is not. "Turning to duodenal ulcer, we find 8 deaths among non-smokers, which is significa.ntly greater than 0 as found for gastric in the same popl?Lation. The figure of 54 for cigarette smokers is undoubtedly si&m-.Lfica.ntly greater than the 25 expected; indeed, of all the 14 different diseases or disease groups tabulated by Hammond & Horn in their Table 1, the laortality ratio of 2.16 for cigarette smokers for duodenal ulcer is the greatest except only that of non-malignant pulmonary diseases (for which it is 2.85).... Based on death statistics, the different sex ratio, the <Lifferent age distribution, a.nd the different reaction to smoking make the c:pidemiology of gastric and duodenal ulcer different," the author concludes. CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION TIM-S 0230922

10. 6. AMERICAN MEDICAL ASSOCIATION CLINICAL SESSION Following are excerpts from papers presented at the Clinical Session of the American Medical Association held at Los Angeles, California, November 25-27, 1962. BRESLOW, Lester, M.D., Chief, Division of Preventive Medicine Services, California State Department of Public Health, Berkeley "Environmental carcinogenesis." "Far ?'rom being a rare phenomenon, initiation of cancer by environmental a,-;ents may be the most common pattern of origin of cancer," the author said: "Probably the greatest stimulus to this idea has been the demonstratic)n by epidemiological research and other investigations that cigarette :imoking is responsible for the phenomenal increase in lung cancer. Already the leading site of fatal cancer in U.S. men, the lung is becomin~; a frequent site for female cancer as well -- due to cigarette smokirtg." HAAGEN-SMIT, A. J., M.D., California Institute of Technology, Pasadena "What is Los Angeles smog?" "Ther=~ is general agreement that at present the emissions from motor vehicles .:onstitute the largest smog source," the author said. KOTIN, Paul, M.)., Carcinogenesis Studies Branch, National Cancer Institute, Bethesda, Md. "Polluted urban air and related environmental factors in the pa.thogenesis of pulmonary cancer." "The real, and at least until recently, progressive increase of lung cancer appears almost certainly to be associated with the contamina- tion of our respiratory environment with carcinogenic agents and other environmental substances which serve to facilitate the action of these agents," the author said. "The specific epidemiological pattern of lung cancer incidence probably reflects the total of the combined effects of these exogenous environmental agents as modified by endogenous host factors. "The major emphasis of this presentation will be devoted to exogenous factcrs including polluted urban atmosphere, cigarette smoke, and viral infections. It must be emphasized that evidence for an exclusive environmental rource or factor acting in the pathogenesis of lung cancer is lacking. Tr.erefore, a discussion of air pollution and lung cancer, independent of its relation to other environmental factors, is unrealistic.... "Sinc,e the chemistry of polluted urban air and cigarette smoke are remarkably similar, it should be emphasized that much of what is being presente,_'. as pertinent to the former will also be applicable to the latter." CONFIDENTIAL: 1`.ZINNESOTA TOBACCO LITIGATION TIMN 0230923

11. MURPHY, Sh_sldon D., Ph.D., and PRINDLE, Richard A., M.D., Division of Air Pol.Lution, U.S. Public Health Service, Washington, D.C. "Effects oe automotive exhaust on pulmonary function." "During the past year, studies of the effect of exhaust mixtures on pulmonary function of guinea pigs have been continued as part of a pilot investigation," the authors said. "Guinea pigs are placed in body plethysmographs and exposed through face masks attached to a manifold ventilated with air or exhaust mixtures.... Measurements of pulmonary function w;~re made under two types of exposure conditions (While breathing clean air Ebr two hours, and tests every 15 minutes during four hours of exposure to exhaust-contaminated air).... "...the first phase of the response consisted of increased pulmonary E'low resistance and increased tidal volume and decreased respiratoi=_T rates. Flow resistance remained high during the exposure period, bub rapidly returned to air, pre-exposure, baseline values when animals were returned to clean air. Respiratory rates and tidal volumes, however, sliowed a biphasic response which had not been previously observed (Ln earlier tests). Thus, during the last two hours of exposure, respiratory rates rose, following an initial depression, to levels considerabLy higher than air control baselines. Tidal volumes decreased during the period of accelerated rates.... ''This laboratory work is, as yet, far from providing the clinical data that :)hysicians need in order to evaluate their patients' responses to 'smog.' As it progresses, however, and is supplemented by new information from epidemiological and environmental studies, it seems reasonable to hope that the n=:eded answers will be forthcoming." PHELPS, Lt. Col. Harvey W., MC, USA, SPOTNITZ, Maj. Murray, MC, USA, REUSCH, Capt. Clifford S., MC, USAR, GELDERMAN, Capt. Gwynn, MC, USAR and MtYri,EY, Hurley L., M.D., Professor of Medicine, University of Southerii California, Los Angeles "Tokyo-Yokohama asthma." °'Over 3000 patients have now been evaluated in the pulmonary function l~Lboratory at the U.S. Army Hospital, Zama. (Japan), during the past two yoars," the authors said. "Of this 3000, 620 patients have been diagnosed Ls having Tokyo-Yokohama asthma. All of these individuals have a ne-;Ltive history of asthmaa prior to coming to Japan. All but 18 patients wore moderate-to-heavy cigarette smokers. "Moderate-to-heavy cigarette smoking appears to be definitely involved ia the contracting of this disease. Perhaps the irritating effects of cigarette smoke makes the bronchial mucosa more suspectible to the irr.tating and sensitizing effect of polluted atmosphere.... If an individnal had this disease for many months or has had this disease on more than one tour in this area, he runs the risk of developing permanent lung -damag: !. " CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION TIMN 0230924

12. REID, Prof. D. i_i., Director, Department of Epidemiology, London School of Hygiene and Tropical Medicine, England "Chronic bronchi.tis and air pollution." "Mort=.lity from chronic bronchitis is highest in the congested and heavily polluted industrial cities," the author said. "The British excess in chron1c lung diseases mortality cannot... be attributed to such variations in inherent susceptibility associated with'sex, or aging or familial pretLisposition. Factors external to the individual are a more likely som•ce of the adverse British experience. Cigarette smoking, for example, ha:; been shown... to be related to the risk of subsequent death from chronic bronchitis." 7. NATIONAL CONFERENCE ON AIR POLLUTION Foll(yring are excerpts from papers presented at the National Conference on A.r Pollution held at Washington, D.C., December 10-12, 1962. DOHAN, F. Curti=a, M.D., Hospital of the University of Pennsylvania, Philadelphia '"The complexity of the relationship between air pollution and respiratory health." "Chrouic bronchitis, one of the most important health problems in England, has been statistically related to regional air pollution by coal smoke, and to personal air pollution by cigarette smoke," the author said. "Infection also plays a part.... (It) seems abundantly clear that the relationshi) of respiratory health to air pollutants is a complex one; that individual host response may vary; that pollutants and their combinations va^y in kind, concentration and effect; that weather variables are important; and, finally, that the effects of air pollution on bacteria and viruses and their host's resistance must be considered." GOLDSMITH, John R., M.D., Head, Air Pollution Medical Studies, California Department oP Public Health, Berkeley "Air pollution, morbidity, and mortality." "The rates for chronic bronchitis and lung cancer are in general lower in the UnLted States than in Great Britain, when comparable age and sex groups a.re compared," the author said. "However, both these groups of conditions are more common in urban that in rural areas and air pollution has been thought of as the possible factor to account for these increases. On the other hand, clear-cut relationships of cigarette smoking to both of these conditions have been established in this country as well as in Great Britain. "Because different patterns of decisions are needed for reducing the exposures, we may tend to separate the effects of cigarette smoking on chronic lung disease from those of community air pollution on the same conditions, but it is not reasonable to expect that the cells of the lung will make such a distinction." CONFIDENTIAL: TIMN 023091.5 MINNESOTA TOBACCO LITIGATION

13. KOTIN, Paul, M.D., and FALK, Hans L., Ph.D., National Institutes of Health, Bethesda, Md. "Air pollution and lung cancer." "The major emphasis of this presentation will be directed toward exogenous factors including polluted urban atmosphere, cigarette smoke, and viral iniections," the authors said. "It must be emphasized that evidence for an exclusive environmental source or factor acting in the pathogenesis of lung cancer is lacking. Therefore, a discussion of air pollution and lung cancer, independent of its relation to other environmental factors, is "nrealistic. "Hcwever, sufficient epidemiological, clinical-pathological, and experimental data exist to incriminate polluted urban atmosphere as an environmental source pathogenetically related to the development of lung cancer. Since the chemistry of polluted urban air and cigarette smoke are remarkably similar, it is possible that much of what will be presented as being pertinent to the former will also be applicable to the latter." Discussing anti-carcinogenesis, they said, "Experimentally, it has been possible to demonstrate that even the most potent carcinogens can have their effect reduced or totally obliterated in the presence of proper propoitions of inhibitors. This has immediate, practical significance in that in all environmental sources of carcinogenic PAH industrial effluents, automobile a:r-;d diesel exhaust, as well as cigarette smoke, a broad spectrum of non-carcir.ogenic and weakly carcinogenic hydrocarbons are formed. Experimenta7_1y these latter compounds unequivocally exert an inhibiting effect, and ?inder actual environmental conditions they, in all probability, exert a modi=ying or inhibiting effect on the total carcinogenic potency of the milieu, in which they exist." MITCHELL, Rou;er S., M.D., Webb Institute for Medical Research, Denver, Colo. "Concluding iemarks -- Panel C." "I, _ is my opinion that polluted air (from both community and individual scurces) is one of the causes of at least two major respiratory diseases: brc-nchogenic carcinoma and the chronic bronchitis-emphysema syndrome," tY.e author said. "One distinctly possible and happy dividend of the abate,;.ent of community air pollution would be a probable decrease in the hazard.s of cigarette smoking." NELSON, Nortun, M.D., Director, Institute of Industrial Medicine, New York University Medical Center, New York City "Effects of motor vehicle pollutants." In lung cancer, as in some other respiratory diseases, "the factor of smt-iking is of definite importance and, therefore, adequate allowance foi, the smoking history of individuals with lung cancer must be made in any statistical study aimed at determining the role of air pollution," !;he author said. CONFIDENTIAL: TIMN 0230926 MINNESOTA TOBACCO LITIGATION

CONFIflENTIAL: 14. MINNESOTA TOI3ACCO LIT.IC;-ATI()I1T "A _n_-mmber of statistical studies have made correction for this factor; these quite generally show higher lung cancer rates in cities than in rural areas when comparisons are made on the basis of equal smoking intensity or when the comparison is restricted to non-smokers.... "It is very clear that the part played by place of residence is small in comparison to the importance of smoking. However, as noted, there is a cleai~ trend showing somewhat higher cancer rates in urban dwellers after allowance for smoking.... Although an interpretation is difficult, it wculd be a prudent assumption, still not proven,•that community air pcllution makes a significant, albeit, secondary contribution to lung cancer cccurrence." SPICER, William S. Jr., M.D., Head, Division for Pulmonary Diseases, University oi Maryland School of Medicine, Baltimore "The complexity of the relationship between air pollution and respiratory health." "Respiratory health, in itself, is not a simple concept and has different meani=.gs for different investigators," the author said. "The recording of tho symptoms of chronic bronchitis, e.g., cough, sputum, wheeze, breathlr-ssness, etc., in a control population in relation to either daily or long-term levels of air pollutants differs from the recognition thatindividuals who have no clinical symptoms change in relation to environmental factors when tested by complex pulmonary function tests.... Uttei, confusion and misinterpretation will result unless we are constantly clear as to which particular aspect of respiratory health is being evaluated in any particular investigation." "Health considerations." "Both the products of industrial and automotive combustion and of cigarette smoke can temporarily paralyze the cilia and depress the self-cleansing mechanism of the respiratory tree, allowing the accumulation or irritants, irLcluding carcinogens." WYNDER, Ernest T,., M.D., and HOFFMANN, Dietrich, Ph.D., Sloan-Kettering Division of Cornell University Medical College, New York City "Air pollution =.nd lung cancer." "We r~-:gard it as established that the urban population has a somewhat higher rate of lung cancer than does the rural population as shown by the stl_Ldy of Hammond & Horn (1958)," the authors said. "Other evidence point-I=Lg to an 'urban factor' as recently presented by Haenszel and his assoeial;es (Current Digest, June 1962, page 4) indicates that individuals borfi in rural areas but who later lived in metropolitan areas had a higher rai;e of lung cancer than those who lived in metropolitan areas all their lives.... (This survey) also indicates that for non-smokers the difference _n rates in urban and rural areas is 'trivial.' "A major problem of the epidemiologist in evaluating the factor of air pollutioji is that the correlation between cigarette smoking and lung cancer is of such an order of magnitude as to overshadow other factors." TIMN 0230927

15. 8. CALIFORNIA AIft POLLUTION CONFERENCE (Part 2) :?ollowing are excerpts from seven papers presented at the Fifth AnnL=L1 Air Pollution Medical Research Conference, California State Department of Public Health, at Los Angeles, December 4, 1961, published in the Ame°ican Review of Respiratory Diseases, Official Journal of the American T'~ioracic Society, Volume 86, December 1962. REID, Dona_d, M.D., D.Sc., MRCP, Professor of Epidemiology and Director, Departma-:nt of Medical Statistics and Epidemiology, London School of Hygiene and Tropical Medicine, England "Diagnosti~: standardization in geographic comparisons of morbidity." (Pages 650-854) "For epidemiological surveys designed to follow up the clues provided b~~ the crude geographic comparisons of vital statistics, a greater diagnostic precision is required," the author says, describing British efforts to arrive at standard clinical diagnoses. Meanwhile, different practices i,n Britain, the U.S.A. and other countries result in an "excess" of chronic bronchitis in Britain. 'The question is whether the reported excess in the British population in general, or the urban British in particular, is an artefact due to difzerences between certifying physicians in habits of diagnosis and classification of diseases, or whether there is a real disparity in the disease level in the various populations concerned," he says. Tn Tables 1 and 2 he shows the varying diagnostic allocations of "standard" cases by some 30 hospital registrars in Boston, Mass., London, England and Bergen, Norway, on the basis of clinical records of a random sample of London hospital patients (Adapted excerpts): Cause of death per cent: Boston London Bergen Chronic broachitis 1 4 4 Chron. bron2h. and emphysema. 12 18 11 Emphys. (without ment. of bronch.) 5 1 6 Bronchiectasis 3 1 6 Other respj- ratory 4 1 2 Strokes 19 20 21 Cardiovasc»Lar 36 36 35 Renal 12 11 11 CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION TIMN 0230928

16. HAUSKNECH'P, Rit?,, Head, California Health Survey, Bureau of Chronic Diseases, CaT.ifornia State Department of Public Health, Berkeley "Experiences of a respiratory disease panel selected from a representative sample of thr: adult population." (Pages 858-866) Smok;_rLg histories and the effects of air pollution episodes together with hi.stories of bronchitis were collected in 1956 for a sample of 6939 persons aged 18 and over; an "original panel" of 1070 of those aged 30 and ove:r- who reported bronchitis, asthma or chronic cough; and a "residual panel" of 524- who were interviewed in four follow-ups from 1957 to 1959. !:n the general sample, 50% currently smoked cigarettes and 50% did not; in the "original panel" there were 62% smokers and 38% currently not smoking, and in the "residual panel" the figures were 65% and 35% respectively. Air pol.lution effects reported were (in part) as follows: Per cent: General Sample "Original" Panel "Residual" Panel Eye irritation 75 68 71 Nasal irritatio-a 35 50 62 Annoyance 15 14- 10 There were 41 circulatory, 5 respiratory and 9 other deaths in the panel group: of these 55 deaths, 9 had reported bronchitis or asthma without cough dzring the interviews, 15 bronchitis or asthma with cough, and 31 cough only. GOLDSMITH, John R., M.D., Head, Air Pollution Medical Studies Unit, BECHTER, H. a., PERKINS, Norman and BORHANI, Nemat 0., M.D., Head, Heart Disease Control Program, Bureau of Chronic Diseases, California State Department of Public Health, Berkeley T'Pulmonary function and respiratory findings among longshoremen." (Pages 86T-871+) Cigarette smoking alone and the presence of cardiac symptoms were found to hs.ve a slight effect (about 5 per cent in each case) on the pulmonary function tests on 3311 members of the Longshoremen's Union in the San Francisco Bay area, the authors say. CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION Th'4N 0230929

17. They computed coefficients for three types of respiratory measurements b-tised on 100 for those persons without respiratory conditions who had never :;moked. Adapted excerpts from their Table 9 follow: Including men with resp. cond. Excluding men with resp. cond. Smoking pattera Puff- Forced Total Puff- Forced Total meter exp.vol. vit.cap, meter exp.vol. vit.ca . Never smoked 1.00 1.00 1.00 1.00 1.00 1.00 Ex-smokers o.96 0.97 0.99 0.96 0.97 1.00 Light smokers 0.95 0•93 0.94 0.97 0.93 0.96 Moderate smoke~~s 0.92 0.93 0.96 0.95 0.94 0.97 Heavy smokers 0.92 0.94 0.98 0.98 0.95 1.03 Pipe/cigar smohers 0.96 0.95 0.95 0.98 0.97 0.96 (Ed. note: Thi-; tabulation shows better scores among heavy smokers than among light and mode~-ate smokers. The authors do not comment on this.) "If ~Lo effect were exerted by smoking and/or respiratory conditions, all of the peroentage values in table 13 would be distributed around 5 per cent because of the definition of an 'abnormal' test," they say. "A notable exception to t1his expectation is the 22.8 per cent of abnormal values among the cigarette =smokers who had respiratory conditions without shortness of breath. Cigar=:tte smoking in the absence of respiratory conditions had little effect on the oroportion of abnormal values." Table 13 (Adap,;ed) Per cent of subjects with "abnormal" pulmonary finction tests ------Never smoked------ ---Cigarette smokers--- Respiratory st-etus No.of erp son.s No.ab- normal % ab- normal No.of persons No.ab- % ab- normal normal No respiratory conditions 156 8 5.1 390 27 6.9 Resp.cond.without short. of breath 45 3 6.7 136 31 22.8 Resp.cond.with short. of breath 7 4 57.1 26 9 34.6 HECHTER, H. H., Bureau of Chronic Diseases, California State Department of Public Heal;th "Notes on a me;;hod for ascertaining the influence of smoking." (Pages 875-877) This is a biostatistical discussion of data compiled in the preceding pape.,•. Among other things, it indicates a high ratio of 2.32 for resp-f ~~a.tory conditions in smokers aged 35-44 compa.red to those who never smok.:d, and a low ratio of 1.22 for such conditions in smokers aged 65 and ov=~r compared to the non-smokers. CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION TIMN 0230930

18. SCHOETTLIN, Cha^les E., M.D., Medical Director, Rocketdyne Corporation, Canoga Park, Calif. "The health eff,:ct of air pollution on elderly males." (Pages 878-897) Resid~~nts of the Veterans Administration domiciliary and chronic disease hospital of Los Angeles, with a high prevalence of chronic respiratory disz~ase, were examined in June 1958. Five occupational exposure categocies -- cooking fats, gasoline and oils, coal dust, road dust, and wel_di.-1g fumes -- had significantly higher prevalences of selected criteria of chronic respiratory illness among exposed persons than among the remainder oE' the population, the author says. "Thoszs men who had smoked 10 years or more had significantly higher prevalen;e of the criteria of chronic respiratory illness than persons who had smoked Less than 10 years," he says. "Increasing prevalence of illness paralleLed increasing duration of smoking." MARTIN, C. J., -4.D., Director, Institute of Respiratory Physiology, Firland Sanatorium, Seattle, Wash., and HALLEZT, Wilbur Y., M.D., Pulmonary PhYsiology Laboratory, City of Hope Medical Center, Duarte, Calif. "The diffuse obstructive pulmonary syndrome: A factor in tuberculosis treatment failures." (Pages 898-901) The history of smoking was of no significance in this study, regardless of tze amount smoked or duration of the habit, the authors say. Evidence Df the diffuse obstructive pulmonary syndrome was found in 91% of 45 tuoerculous patients considered treatment failures. "This incidence was uarelated to age, sex, or smoking habits," they say. REVOTSKIE, Nich:)las, M.D., KA.NNELL, William, M.D., GOLDSMITH, John R., M.D., and DAWBER, 'P. Royle, M.D., U.S. Public Health Service, Framingham (Mass.) Heart Diseas-s Epidemiology Program (Except Goldsmith: California Department oE' Public Health) "Pulmonary function in. a community sample." (Pages 907-909) The authors tabulated the ratios of "observed" to "predicted" pulmonary function test values by smoking patterns and respiratory findings, in the manner raported for California longshoremen by Goldsmith et al. (supra), for mea and women in the Framingham study. Wide differences between the sex-as and between the classes of smokers and non-smokers are shown in the table. Not all of the subjects had all the respiratory tests, and the aumbers of subjects therefore are not suitable for estimating rates, a footnote says. CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION TIMN 0230931

19. 9. MEDICAL OPINIONS BAIRD, K. A., M.D., Lancaster, New Brunswick, Canada "Chronic iespiratory disease in the aged." (Journal of the American Geriatiics Society, Volume 10, pages 1062-1071, December 1962) One type of irritation in the respiratory tract is mechanical, the author says: "Examples would include house dust, road dust, and smoke -- whether from wood fires or burning tobacco leaves:" He also cites Garston (Current Digest, December 1961, page 12) on the association between cigarette smoking and air pollution and chronic respiratory diseases. BRITISH NiwDICAL JOURNAL, London, England "Effect of tobacco smoke on lungs." (Editorial; December 1, 1962, page 1457) The Journal reviews several 1961 and 1962 reports by Auerbach, Stout, H?mmond and Garfinkel, concluding: "Broadly, then, the frequency of atypicaL cells shows a direct correlation to the dose of tobacco smoke, being virtually nil in non-smokers. Commenting on the 1962 paper by Bock et al, on filter and regular cigarette smoke condensate tests on mice, it s-Lys: "This is further evidence that if moderation were the mark of smoking habits in Britain the death roll from lung cancer would not be so grim." GP, Published by the American Academy of General Practice, Chicago, Ill. "Welfare al~d the weed." (Editorial; Volume 26, page 79, December 1962) Discussing a recent statement by Secretary Celebrezze of the Department of Health, Education and Welfare, the journal says, "we tend to agiee with an expert who recently said, 'I don't know why cigarettes are harmful -- but I'm pretty sure they are.' The weight of evidence seems to confirm his conclusion. There is certainly enough evidence, in our opinion, to justify prompt HEW action. But the department, we suppose, is as human as a department can be. Think what would happen if Mr. Celebrezze slapped a ban on the sale of all tobacco products.... We humbly suggest that Mr. Celebrezze's boss would lose 40 million votes. The facts remain: Tobacco is apparently detrimental to human health -- and no one's doing much about it." JONES, HardLn Blair, Ph.D., Donner La boratory, Division of Medical Physics, University of California, Berkeley "Premature old age, major effect of smoking." (Science News Letter, Volume 82, page 288, November 3, 1962) T'ae author told a symposium on aging in San Francisco sponsored by the Kais=:r Foundation Hospitals that smoking brings on a shift toward old age ear,'_ier in life, and that the smoker of a package of cigarettes daily can e::pect his life to be shortened by seven years. The life-shortening process is n direct proportion to the amount smoked, he said; the extra-aging _stops whene-er the person stops smoking. TIMN 0230932

20. C®~1FTDENTIAL: MINNE50TA TaBACCO LITIGATIOrJ LAWTON, M. Powell, Ph.D., Norristown State Hospital, Pennsylvania "A group therapeutic approach to giving up smoking." (Applied Therapeutics, Volume 4, pages 1025-1028, November 1962) This is a study of a tobacco addiction cure which is based on the same principles as the cure for alcoholics as set up by the Alcoholics Anonymous. Several individuals from the American Cancer Society, the author, and others met to plan a group therapeutic approach to help confirmed adult smokers quit -- a program which would rely wholly upon psychological an_3 social treatment, the author says. "Considerable validity for the approach is attested to by the fact that some inveterate smokers did stop," he says. MEDICAL TRIBUNE, New York City "Smoking and the government." (Editorial; December 17, 1962, page 15) Taking Secretary A. J. Celebrezze to task for his "prohibition did not work" attitude on the smoking and health issue, the journal says, "It is unlikely that those who recognize the noxious effects of cigarette smoking advocate -- or will in the future advocate -- prohibition by ls.w of the manufacture, sale or smoking of cigarettes. What is strongly recommended is an educational program to tell the public of the hazards and to influence our youth not to acquire the habit. Isn't it the role of the government to do more than inform the citizen? If the day comes when scientifically irrefutable evidence links cigarette smoking with cancer of the lung, will it not be the duty of the government to educate the citizen to the hazards of an action that may be fatal for him." NIESS, Oliver K., Major General, MC, Surgeon General, United States Air Force "A united front against common killers." (Proceedings, 69th Annual Meeting, Association of Military Surgeons, Washington, D.C., November 12, 1962) "The relationship between cigarette smoking and lung cancer, pulmonary diseases, and cardiovascular diseases has been established by many studies over the past few years," the author says. "Our health education progrP m acquaints our personnel with the dangers of smoking in relation to these diseases." PUBLIC HEALTH S~:ftVICE, Washington, D.C. "Cancer cause and prevention." (Public Health Service Publication No. 959, pages 3-14, 1962) In a x=eview of information on various aspects of cancer cause and prevention, the publication says: "The question whether smoking causes cancer cannot be answered in a simple manner. But the Public Health Service, on the basis of research, has concluded that the weight of evidence at present shows that smoking -- particularly cigarette smoking -- is a principal reason for the rising death rate from lung cancer in the p?st 30 years. TIMN 0230933

21. "Unless the use of tcbacco can be made safe, the best way to reduce oae's risk of developing lung cancer is not to smoke," it says. "Studies have shown that persons who have never smoked have the best chance of avoiding lung cancer; and it is believed that, even after years of smoking, a person who stops improves his chances of avoiding the disease . ' Discussing air pollution, it says that laboratory studies strongly suggest a link between air pollution and human cancer. Research in the United States and Great Britain showed that the main cancer-c?,using substance in the tar was 3,4-benzpyrene. This chemical is also iound in the smoky atmosphere of industrial cities and in the exhaust cf internal combustion engines, it says. The publication also discusses radiation, food additives, exposure to sunlight, and occupational hazards. ROSENBERG, A., M.D., Copenhagen, Denmark "An atteui_pt to break the smoking habit." (Applied Therapeutics, Volume 4, pages 1029-1033 & 1064, November 1962) The author gives the various steps involved in a ten-day treatment for tobacco addiction, and outlines suggestions for future treatment:. The material is the result of the author's practice and the work cf the tobacco withdrawal clinic. "Nicotine has only a slight influence on the smoking habit. The main importance of the habit is the sense of being occupiez'a with tobacco," the author says. "In this way psychomotor tensions are quickly decreased, the nervous hand becoN-3s occupied and pauses in conversations are covered.... 'Tobacco a-9.dietion' should be used rather than 'nicotine addiction.'" SCOLTEN, A,9.rian H., M.D., Portland, Maine "Letter to the editor." (Journal of the Maine Medical Association, Volume i3, pages 275-276, November 1962) ,i'he author recalls that he wrote a paper "trying to link cigarette :moking to lung cancer" in the January 14, 1938, issue of "The Churei.World," and says it has disturbed him ever since to know that smoke;.s are not yet aware, that if they continue to smoke, they are likely to die of lung cancer. "That my years of preaching against smoking has had so little effect is one of the disappointing experiences in my many years of trying to be a dedicated doctor," he says. CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION TIM.N 0230934

22. SELTZER, Carl c;., Ph.D., Harvard University, Cambridge, Mass. "Why people smoke." (Applied Therapeutics, Volume 4, pages 1023-1024, November 19,32) This is an abstract of an article previously published in the Atlantic Month_y (July 1962) which studied the differences between smokers and noFi-smokers. "Rather than a superficial habit overlaid indiscriminate'Ly upon various persons, smoking appears to be a response to a wide varioty of personality and behavioral characteristics which have their ori.:;in, in part, in the biological or genetic makeup of the individual," tnae author says. TAYLOR, S. W., Auckland, New Zealand "Advertising o:" tobacco." (Letter; New Zealand Medical Journal, Volume 61, page 423, August 1962) Commnnting on the Royal College of Physicians report, the author says, ",'he legislative machinery will not move unless those responsible have their att-:ntion drawn directly to the need, and such, it would seem, must be our ta:;k. We should ask for no less than the complete prohibition of the adverti:;ing of tobacco products until such time (if ever) as further discovery or r=:search might call for review of the present findings." - o 0 o - Also received but not excerpted were the following references to tobacco and related re:>earch: APPLIED THIIiAP„UTICS, Ottawa, Canada, Vol. 4, November 1962. (Anti-smoking editorial a?id other adverse comment, scattered throughout issue) BORBELY, F., ri_'he toxicology of tobacco consumption." (In German) Zeitschrift fur Preventivmed. 7/2:118-134, 1962. (Inhalation of smoke) BUCKS COUNTY IA;MICAL MONTHLY, "Lung cancer rise reflects aging, better diagnosis." 53/12:8, Dec. 1962. (Quotes.Dr. M. B. Rosenblatt, 1962: Current Dig-~st, August 1962, page 11) CHEST & HEART f3SOCIATION, London, England, "Annual report -- 1961-1962," (Claims its anti-smoking policy has been "well received.") CLEMENT, Y., "I~e tabagisme," Lutte contre le Cancer, 40:23-28, 1962. (Chronic in~:oxication of heavy smokers) CROSS, C. E. e°'; al., "Coronary vasomotor tonus in moderate hypothermia," Am. J. Physiology 203/5:825-828, Nov. 1962. (T.I.R.C. grant) DARGENT, M. et al., "Anatomo-clinical documents on an association between cancer of the hypopharynx and cancer of the urinary tract," (In French) Bull. du CarLcer 49/2:169-184, April-June 1962. (Tobacco and alcohol possible fa,;tors in four cases) CONFIDENTIAL: TIMN 0230935 IVfINNESOTA TOBACCO LITIGATION

23. EASTCOTT, H. & G., "Rarity of lower-limb ischemia in non-smokers," (Letter) L;Lncet, Nov. 24, 1962:1117. (1 non-smoker among 114 such patients) GP, Review of "Tobacco and Health," ed. by G. James and T. Rosenthal, publ. by Charles C. Thomas, Springfield, Ill., 1962. GUDBJARNASON, S. et al., "Oxidation induction in heart muscle," Circulation 26/5:937-9)+5, Nov. 1962. (T.I.R.C. grant) HAREFUAH (Isrv.el), (Editorial) 63/5:184-186, Sept. 2, 1962. (Quotes Hammond and Horn) JOST, F., "Thorapeutic dehabituation of nicotine and tobacco smoking," (In German; Fortschritte der Medizin 80/16:625-628, Aug. 1962. (Lobeline recommended) JOURNAL OF TN,; FLORIDA MEDICAL ASSOCIATION, "Overstretched lungs," (Editorial; 49:1+11-412, Nov. 1962. (Suspicion of pulmonary emphysema in chronic "cigarette cough" or asthma) LANDAU, E. & EOBERTS, A., "Current air pollution field research in chronic respirator,r disease in the United States," Public Health 77/1:11-20, Nov. 1962. (Smoking histories among data collected in series of studies) LARSEN, R. I.; "Motor vehicle emissions and their effects," Pub. Health Reports 77/11:963-969, Nov. 1962. LEWIS, R. et z .1., "Air pollution and New Orleans asthma.," Pub. Health Reports 77/11:947-954, Nov. 1962. MEDICAL PROCEr;DINGS, "Cigarette smoking and lung cancer," (Review) 8/23:462, Pfov. 17, 1962. (Quotes from L. Shabad and W. Hueper at the 8th Intern.=.t. Cancer Conf. in Moscow) NAGUCHI, M. & TAKAKI, E., "Studies on nitrogen metabolism in tobacco plants. A. Part III:," Agr. Biol. Chem. 26/10:689-695,-oct. 1962. OCHSNER, A., "Treatment of malignant disease by cauterization," Surgery 52/5:837-8=;8, Nov. 1962. (No tobacco) OSWALD, N., "11-Ironchitis," Clinical Notes on Respiratory Diseases, 1:3-6, Winter 196~!. (Cigarette smoking and air pollution predisposing causes) PALUMBO, L. T:, & SHARPE, W., "Gastric ulcer: Is it benign or malignant?" Arch. of S?xgery, 85:705-710, Nov. 1962. (Peptic ulcer a malignant lesion; tolt_acco and alcohol must be eliminated) PRESCOTT, F., "The smoking problem in Britain," Applied Therapeutics, 4:10l8-l02~! & 1055, Nov. 1962. (Discusses RCP report and need for national c_mpaign against smoking) PRINDLE, R. A= & YAFFE, C. D., "Motor vehicles, air pollution, and public health," Pib. Health Reports 77/11:955-962, Nov. 1962. CONFIDENTIAL: TIMN 0230936 MINN ESOTA TOBACCO LITIGATION

24. ROBERTS, D. L. ~c ROWLAND, R. L., "Macrocyclic diterpenes. Alpha- and. beta-4,8,13-,luvatriene-l,3-diols from tobacco," J. Organic Chem. 27/11:3989-3995, Nov. 1962. RODGMAN, A. & CUOK, L. C., "The composition of cigarette smoke. XI. Heterocyclic nitrogen compounds from Turkish tobacco smoke," Tobacco Scielice 6:174-177, Nov. 30, 1962. ROSENBERG, A., "Tobacco withdrawal clinics," (Letter) Ugeskrift for Laeger 124/35:1297- .298, 1962. SMITH, C., "Giv.ng up smoking," (Letter) Lancet, Nov. 24, 1962:1113. SNYMAAN, H. W., "The 8th International Cancer Congress, Moscow, 22-28 July 1,)62," (Review) Med. Proceedings 8/23:462-468, Nov. 17, 1962. TOBACCO MANUFAc;,:?URERS' STANDING COMMITTEE, "Announces that its research laboratories at Harrogate (England) are now in operation," Medical Officer, Nov, 16, 1962:315 UNGHVARY, L. et al., "Effects of the concentration of total cateeholamines in whole blood and changes resulting from the effects of smoking," (In German: :;nglish summary) Cardiologia, 4l/5:316-323, 1962. (Concentration increased 1.0 gamma per cent in 5 minutes after one cigarette, arLd fell within 30 minutes) WEDGMANN, A. et al., "Catecholamine content of various organs in experimental hypertension." Am. J. Physiology 203/4:607-608, Oct. 1962. (T.I.R.C. grant) WILLIAMS, S., "i, cytological survey of hospital patients for lung cancer," .New Zealand Ilied. J. 61:401-404, Aug. 1962. (One unsuspected case of lung cancer ~_Liscovered among 2235 smokers and 306 non-smokers; his smoking history is not reported) CONFIDENTIAL: MI VNESOTA TOBACCO LITIGATION TIMN 0230937