HISTORICAL PERSPECTIVE TOBACCO AND CANCER AACR MEMBERS AND JOURNALS LED PIONEERING RESEARCH

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1 1912 Isaac Adler (AACR member) writes the first monograph drawing attention to primary lung cancer, which in the early 20th century was considered a rare cancer, and suggests lung cancer is related to smoking based on its increasing occurrence in men rather than women, as women rarely smoked (1) A popular author, Samuel Hopkins Adams, writes an article on cancer for The Ladies Home Journal in which he notes the association between pipe smoking and lip cancer. The article was commissioned by AACR member Thomas S. Cullen, with the endorsement of the AACR Council, and was one of the first public discussions of cancer in a lay publication (2). Thomas S. Cullen, MD ( ) 1921 Joseph C. Bloodgood (AACR member) collects data to show that nearly all of his male patients with cancer of the tongue used tobacco (3). Bloodgood was a multitalented physician who worked in several specialties as well as serving on the AACR Council. Joseph C. Bloodgood, MD ( ) 1924 At the AACR Annual Meeting, Frederick L. Hoffman (AACR member) reports statistics showing a link between smoking and cancer (4); the abstract appears in AACR s Journal of Cancer Research. Seven years later, he writes a formal report linking heavy smoking to cancers of the mouth and lungs. Hoffman was a founder of the American Cancer Society. Frederick L. Hoffman, LLD ( )

2 1924 Sir Ernest L. Kennaway (AACR member) publishes a paper identifying substances in tar that cause cancer. He continues to publish studies on the incidence of cancer of the lungs and larynx throughout the 1930s and 1940s (6). Sir Ernest L. Kennaway, MD, DSc ( ) A series of articles on the harmful effects of tobacco by Angel H. Roffo (AACR member), from the Cancer Institute in Buenos Aires, appears primarily in German journals. Hitler later used these articles to launch his antitobacco campaign (7). Roffo is recognized at the end of the 20th century as one of the fathers of carcinogenesis. Angel H. Roffo, MD ( ) 1932 AACR s journal, the American Journal of Cancer, publishes two consecutive articles showing a likely association between smoking and cancer. These articles are cited decades later as evidence against tobacco companies (8, 9) Inhaling tobacco smoke did not become widespread until flue curing, a new process, made inhaling tolerable. Surgeons Alton Oschner and Michael E. DeBakey (AACR member) reported a strong link between inhaled smoke and lung cancer (10). Michael E. DeBakey, MD ( )

3 1941 Curtis M. Flory (AACR member) publishes an extensive review of tobacco tars and cancer in the first volume of Cancer Research (11). This article was part of his doctoral dissertation and was widely reprinted after its appearance in the journal At the AACR Annual Meeting, Harold L. Stewart (AACR member) and colleagues report one of the earliest studies using a smoking machine to test the effects of smoke on experimental and control mice (12). Such machines became a concern for animal rights advocates, primarily because of experiments in beagles, although smoking machines are still used in research. Harold L. Stewart, MD ( ) Morton L. Levin (AACR member) and colleagues conduct a case-control study, using patient data collected at Roswell Park Cancer Institute, to show the link between cancer and tobacco (13). Roswell Park later devoted considerable resources to studying the effects of smoking, even growing its own organic tobacco for study purposes. While he was still a medical student, Ernest L. Wynder (AACR member) convinced surgeon Evarts A. Graham to join him in conducting a case-control study, which shows a strong association between cigarette smoking and lung cancer (14). Graham, a 50-year smoker, quit based on the findings, but it was too late, and he died of lung cancer. Ernest L. Wynder, MD ( )

4 Sir Richard Doll ( AACR member) and A. Bradford Hill conduct a case-control study at about the same time as that of Wynder and Graham, although the Doll/Hill study is published later (15). British and Canadian public officials are quicker to make recommendations based on the findings than are U.S. officials. Sir Richard Doll, MD ( ) An early review by Robert Schrek (AACR Member) and coauthors (16) in Cancer Research covers the research to date linking smoking to cancer. Cancer Research publishes a casecontrol study (17) conducted in two U.S. cities that shows the correlation between cigarette smoking and respiratory tract cancer and cigar and pipe smoking and buccal cancer Pathologist Oscar Auerbach (AACR member) and coauthors are the first to report (18) an experimental method to study autopsy findings in smokers, findings that show precancerous pathology. Auerbach s studies of damaged cells are widely viewed as definitive evidence of smoking s effects and are more respected than statistical and observational studies. Oscar Auerbach, MD ( ) 1956 An advocate of smoking, AACR Member Clarence C. Little writes a guest editorial in Cancer Research asserting that a link between smoking and cancer has not been established (19). Evarts Graham rebuts (20, 21) and points out that Little chairs the Scientific Advisory Board of the Tobacco Industry Research Committee. AACR reconsiders its policy on guest editorials. Clarence C. Little, DSc ( )

5 1957 In an extensive response to criticism that insufficient animal experiments have been done to prove the association between tar and cancer, Graham, Chroninger, and Wynder report in Cancer Research the last part of their four-part series on evidence from animal experiments (22) Michael B. Shimkin (AACR member) is the NCI representative to the Study Group on Smoking and Health. Their report (23), issued 7 years before the 1964 Surgeon General s Report, states that evidence linking tobacco and cancer is unequivocal. Shimkin later remarks that if spinach were as bad for people as tobacco, it would already have been banned (Washington Star, 1961). Michael B. Shimkin, MD ( ) 1958 In a Cancer Research paper, Alfred A. Gellhorn (AACR member) demonstrates the effect of cigarette tar in causing cancer (24). These findings from an important researcher who was not previously involved in tobacco studies add considerably more weight to the evidence. Alfred A. Gellhorn, MD ( ) 1962 Surgeon General Luther Terry appoints a committee to assemble evidence on tobacco and cancer. Five of the 10 scientists appointed are AACR members (Stanhope Bayne-Jones, Louis Fieser, Jacob Furth, Walter Burdette, and Emanuel Farber). Their work takes over 2 years and is considered the most comprehensive review of evidence to date.

6 References Most of the articles in this list were cited in the 1964 Surgeon General s report. 1. Adler IA. Primary Malignant Growths of the Lung and Bronchi: A Pathological and Clinical Study, New York: Longmans, Green and Company, Adams SH. What can we do about cancer? The most vital and insistent question in the medical world. Ladies Home Journal, May 1913; 30(5): Bloodgood JC. Cancer of the tongue; a preventable disease. JAMA 1921;77: Hoffman FC. The causation of cancer, In: Proceedings of the American Association for Cancer Research, Seventeenth Annual Meeting, April 17, 1924, Boston, MA. J Cancer Res. 1924;8: Hoffman F.L. Cancer and smoking habits. Ann Surg 1931;93: Kennaway EL. The formation of a cancer-producing substance from isoprene (2-methyl-butadiene). J Path Bact 1924;27: Research summarized in: Roffo AH. The carcinogenic effects of tobacco (German). Monatsschrift für Krebsbekampfüng 1940;8(5). Reproduced in Bull WHO 2006;84(6): McNally WD. The tar in cigarette smoke and its possible effects. Am J Cancer 1932;16; Bogen E, Loomis RN. Tobacco tar: experimental investigation of its alleged carcinogenic action. Am J Cancer 1932;16: Oschner A, DeBakey M. Primary pulmonary malignancy. Treatment by total pneumonectomy. Surg Gynecol Obstet 1939;68: Flory, CM. The production of tumors by tobacco tars. Cancer Res 1941;1: Levin ML, Goldstein H, Gerhardt PR. Cancer and tobacco smoking: A preliminary report. JAMA ;143: Wynder EL, Graham EA. Tobacco smoking as a possible etiologic factor in bronchogenic carcinoma: a study of 684 proved cases. JAMA ;143: Doll R, Hill AB. Smoking and carcinoma of the lung. Preliminary report. Br Med J ;2: Schrek, R, Baker LA, Ballard GP, Dolgoff S. Tobacco smoking as an etiologic factor of disease. Cancer Res ;10: Mills CA, Porter MM. Tobacco smoking habits and cancer of the mouth and respiratory system. Cancer Res ;10: Auerbach O, Petrick TG, Stout AP, et al. The anatomical approach to the study of smoking and bronchogenic carcinoma: A preliminary report of forty-one cases. Cancer 1956;9: Little CC. Smoking and lung cancer [guest editorial]. Cancer Res 1956; 16: Graham EA. To the editor of Cancer Research [letter]. Cancer Res 1956;16: Little CC. To the editor of Cancer Research [letter]. Cancer Res 1956;16:817-8.) 22. Graham EA, Croninger AB, Wynder EL. Experimental production of carcinoma with cigarette tar. IV. Successful experiments with rabbits. Cancer Res 1957;17: Joint Report of the Study Group on Smoking and Health. Smoking and Health. Science 1957;125: Gellhorn A. The cocarcinogenic activity of cigarette tobacco tar. Cancer Res 1958;18: Lorenz E, Stewart HL, Daniel JH, Nelson CV. The effects of breathing tobacco smoke on strain A mice (abstract). In: Proceedings American Association for Cancer Research. Cancer Res 1943;3:122-4.

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