Reports that Matter

United States v. Philip Morris USA Inc.: Amended Final Opinion

Cigarette Smoking Causes Disease

Section 43 of 129

Cigarette Smoking Causes Disease

  1. Cigarette smoking and exposure to secondhand smoke (also known as environmental tobacco smoke or "ETS") kills nearly 440,000 Americans every year. The annual number of deaths due to cigarette smoking is substantially greater than the combined annual number of deaths due to illegal drug use, alcohol consumption, automobile accidents, fires, homicides, suicides, and AIDS. Approximately one out of every five deaths that occur in the United States is caused by cigarette smoking. TLT0960104-0112 at 0104 (US 87047) (Centers for Disease Control and Prevention, Smoking-Attributable Mortality and Years of Potential Life Lost -- United States, 1994, MMWR, 46(20) (1997)); VXA1000001-0604 (US 77217) (Thun M., Myers D., Day-Lally C., Namboodiri M., Calle E., Flanders W.D., Adams S., Heath Jr. C., Age and the Exposure-Response Relationships Between Cigarette Smoking and Premature Death in Cancer Prevention Study II, Chapter 5, Smoking and Tobacco Control Monograph 8: Changes in Cigarette-Related Disease Risks and Their Implications for Prevention and Control, National Institutes for Health – National Cancer Institute, p. 383-476 (1997)); TLT0930001-0949 (US 88621) (2004 Surgeon General Report).
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  1. Cigarette smoke contains carbon monoxide, nitrogen oxides, cyanide, benzopyrenes, radioactive polonium, arsenic, aldehydes, nitrosamines, numerous toxins, and other human carcinogens. Samet WD, 22:15-23:10. Carcinogens and toxins are absorbed into the bloodstream when cigarette smoke is inhaled. Samet WD, 23:11-24:3.

  2. Cigarette smoking causes lung cancer. VXA1601844-2232 at 1986 (US 64057) (1964 Surgeon General Report). Lung cancer kills 160,000 Americans each year, and 90% of all lung cancer cases are caused by cigarette smoking. The five-year survival rate for lung cancer is only 14%. Samet WD, 71:18-22, 80:1-3; Carmona WD, 1:18-21.

  3. The risk of developing lung cancer increases with an increase in smoking. Individuals smoking ten to twenty cigarettes per day have a ten-fold increased risk and individuals smoking forty or more cigarettes per day -- two packs and over -- have more than a twenty-fold increased risk of developing lung cancer. This rate of risk is referred to as "relative risk." Samet WD, 64:17-67:19; (no bates) (US 17141).

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  1. Cigarette smoking, including exposure to secondhand smoke, causes cardiovascular disease, including myocardial infarction (commonly known as "heart attack"), coronary heart disease ("CHD") and atherosclerosis. CHD refers to diseases which affect the blood vessels of the heart. CHD can cause a deprivation of oxygen to the heart, and thus, cause heart attacks. Atherosclerosis refers to the development of plaque on the arteries, which contributes to the blocking of blood flow to the heart. Samet WD, 107:18-118:21; (no bates) (US 17165); (no bates) (US 17158); (no bates) (US 17134); (no bates) (US 17159); (no bates) (US 17160); (no bates) (US 17204).

  2. Cigarette smoking causes chronic obstructive pulmonary disease ("COPD"). Samet WD, 81:4-90:21.

  3. COPD, previously referred to as "emphysema" or "chronic bronchitis," was found to be causally related to smoking in 1964. Id. at 81:10-83:14; VXA1601844-2232 at 1986 (US 64057) (1964 Surgeon General Report).

  4. Cigarette smoking causes bladder cancer. Samet WD, 90:22-91:4; 97:5-98:17; (no bates) (US 17103).

  5. Cigarette smoking causes cerebrovascular disease. Samet WD, 118:21-120:18, 121:15-122:14.

  6. Cigarette smoking causes esophageal cancer. Id. at 90:22-91:4, 94:5-95:13. Cigarette smoking causes kidney cancer. Id. at 90:22-91:4, 98:18-101:4.

  1. Cigarette smoking causes laryngeal cancer. Id. at 91:5-92:21. 521. Cigarette smoking causes oral cancer. Id. at 92:22-94:4.
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  1. Cigarette smoking causes pancreatic cancer. Id. at 90:22-91:4, 95:14-97:4. 523. Cigarette smoking causes peptic ulcer disease. Id. at 125:10-127:3. 524. Cigarette smoking causes aortic aneurysm. Id. at 122:15-125:9. 525. Cigarette smoking causes cataracts. Id. at 127:4-128:8. 526. Cigarette smoking causes low bone density in post-menopausal women. Id. at 128:9-

129:22.

  1. Cigarette smoking causes reduced fertility. Id. at 130:12-131:23. 528. Cigarette smoking causes adverse reproductive outcomes, including pre-mature

rupture of the membranes, placenta previa, placental abruption, pre-term delivery and shortened gestation, fetal growth restriction and low birth weight. Id. at 130:20-132:9.

  1. Cigarette smoking causes acute myeloid leukemia. Id. at 101:5-102:23. 530. Cigarette smoking causes stomach cancer. Id. at 103:1-104:9. 531. Cigarette smoking causes uterine and cervical cancer. Id. at 104:10-105:15. 532. Cigarette smoking causes liver cancer. Id. at 105:16-106:9. 533. Cigarette smoking causes diminished health status. Id. at 132:15-135:20. 2. Scientific Research on Lung Cancer up to December 1953 a. Scientists Investigating the Rise in the Incidence of Lung Cancer Linked Smoking and Disease before 1953 534. Dr. Allan M. Brandt was accepted as an expert in the history of science and medicine

without objection from Defendants. Brandt TT, 9/27/04, 642:19-643:3.

  1. Dr. Brandt is the Amalie Moses Kass Professor of the History of Medicine at Harvard Medical School and Professor of the History of Science at Harvard University, where he is the chair of the Department of the History of Science. Brandt WD, 1:3-6. Dr. Brandt has published extensively in the field of the history of science and medicine for a period of almost three decades. He received a Pulitzer Prize nomination for one of his works, and, during the past decade, has published more than 15 peer-reviewed essays and articles on the history of cigarette smoking. Id. at 3:17-15:3.
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  1. In the course of his historical investigation of tobacco, Dr. Brandt has reviewed and analyzed the archival materials from the 1964 Surgeon General's Advisory Committee at the National Archives, and numerous additional archival collections, including those of Harvard University (William Cochran); the Countway Library at Harvard Medical School (J. McKeen Cattell), the University of Maine (C.C. Little); Washington University, St. Louis (Evarts Graham); the Wisconsin Historical Society (Bruce Barton, John W. Hill, Robert Lasch, M.V. O'Shea); the Alan Mason Chesney Medical Archives at the Johns Hopkins Medical Institutions (Lewis Robbins); University of Washington, Seattle (Warren Magnuson); the Library of Congress (Edward Bernays, Harvey Wiley); Yale University (Chester Bliss, Lester Savage); Duke University (the John W. Hartman Center for Sales, Advertising and Marketing History); the Smithsonian (NC Ayer Collection, The Warshaw Collection of Business Americana); the National Library of Medicine (Stanhope Bayne-Jones); and the National Archives (The Surgeon General's Advisory Committee). He has also reviewed internal documents of Defendants, including correspondence, reports, and memoranda on tobacco industry activities and programs. Id. at 26:14-28:13.

  2. Much of the Government's evidence relating to the history of scientific research on lung cancer relies on Dr. Brandt's testimony. Defendants did not call any expert witnesses or present any testimony in this area.

254

  1. By the middle of the twentieth century, physicians and public health officials in the United States had widely noted an alarming increase in the number of cases of lung cancer. Virtually unknown as a cause of death in 1900, by 1935 there were an estimated 4,000 deaths annually attributed to lung cancer. A decade later, the estimate of deaths attributed to lung cancer had nearly tripled. VXA1601844-2232 at 1986 (US 64057) (1964 Surgeon General Report); Brandt WD, 31:16-32:1.

  2. The rise in lung cancer had followed the dramatic increase in cigarette consumption which began early in the twentieth century. Annual per capita consumption of cigarettes in 1900 stood at approximately forty-nine cigarettes; by 1930, annual per capita consumption was over 1,300; by 1950, it was over 3,000. Even though the increases in lung cancer cases and deaths substantially lagged behind the increase in cigarette use, the apparent association led to considerable speculation about what, if any, relationship existed between the two. VXA1601844-2232 at 1895-1898 (US 64057) (1964 Surgeon General Report); Brandt WD, 32:2-17; Samet TT, 9/29/04, 01031:13- 01033:25.

  3. The dangers of smoking, including its connection to lung cancer, began to attract the more concerted attention of scientists in the 1920s, when researchers began to focus on the specific health consequences of smoking. Brandt WD, 32:18-34:13.

  4. As early as 1928, researchers conducting a large field study associated heavy smoking with cancer. 2060544267-4274 (US 39010) (Lombard, Herbert L. and Carl R. Doering, Cancer Studies in Massachusetts: Habits, Characteristics and Environment of Individuals With and Without Cancer, New England Journal of Medicine, 196.10: 481-487 (1928)); Brandt WD, 33:14-34:13.

255

  1. In 1931, Frederick L. Hoffman, a well-known statistician for the Prudential Insurance Company, linked smoking with cancer, although the research left him with lingering methodological questions about representativeness, sample size, and the construction of control groups. VXA2510202-0219 (US 63597) (Hoffman, Frederick L., Cancer and Smoking Habits, Annals of Surgery, 93:50-67 (1931)); Brandt WD, 33:21-34:4.

  2. In 1938, a population biologist and biometrician from Johns Hopkins, Raymond Pearl, published one of the first significant statistical analyses of the health impact of smoking. Pearl's conclusion was that individuals who smoked could expect shorter lives. 503285883-5884 (US 20714) (Pearl, Raymond, Tobacco Smoking and Longevity, Science, 87:2253 (1938)); Brandt WD, 34:5-13.

  3. Early research efforts led to publication in Germany in 1939 of the first case control study that showed the connection between smoking and lung cancer. VXA2510202-0219 (US 63597) (Hoffman, Frederick L., Cancer and Smoking Habits, Annals of Surgery, 93:67 (1931)); VXA251-0239 (US 63595) (F. H. Muller, Abuse of Tobacco and Carcinoma of the Lungs, Journal of the American Medical Association (translation of the original from Zeitschrift fur Krebsforschung, Berlin) (1939)); Brandt WD, 34:5-36:7.

  4. In the 1930s, chest surgeons such as Alton Oschner and Richard Overholt published observations that the patients they saw with advanced lung malignancies were typically smokers. Oschner and another surgeon, DeBakey concluded that: "In our opinion the increase in smoking with the universal custom of inhaling is probably a responsible factor, as the inhaled smoke, constantly repeated over a long period of time, undoubtedly is a source of chronic irritation to the bronchial mucosa." 85868807-8823 at 8807 (US 63596) (Oschner, Alton, DeBakey, Michael,

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Primary Pulmonary Malignancy, Surgery, Gynecology and Obstetrics, 68:435-45 (1939)); Brandt

  1. By the end of the 1940s, more evidence linking smoking to disease began to appear. Beginning in 1948, under the auspices of the Medical Research Council, a unit of the recently created National Health Service in the United Kingdom, Bradford Hill and Sir Richard Doll conducted a study to investigate the rising incidence of lung cancer. Following World War I, Hill had become one of the most distinguished medical statisticians in Great Britain. Doll, a physician, also possessed sophisticated training in statistics and epidemiologic methods. They realized that questions concerning the causality of systemic chronic diseases would not readily succumb to experimental laboratory investigation (unlike the study of infectious disease where specific causality was important). TIMN0145510-5519 at 5510, 5518 (US 62855) (Doll, Richard, and A. Bradford Hill, Smoking and Carcinoma of the Lung: Preliminary Report, British Medical Journal (1950)); Brandt WD, 32:18-34:13; 40:19-44:2.

  2. From their data from lung cancer patients and a control group in late 1948 and early 1949, it became clear to Doll and Hill that cigarettes were the crucial factor in the rise of lung cancer. With data on almost 650 lung cancer patients, they concluded that "smoking is an important factor in the cause of carcinoma of the lung." The findings were impressive: among the 647 lung cancer patients in Doll and Hill's study, all 647 were smokers. They waited to publicize their results, however, until they had data on 1400 lung cancer patients, which further strengthened their conclusions. TIMN0145510-5519 (US 62855) (Doll & Hill, Smoking and Carcinoma), supra; Brandt WD, 42:1-44:2.

257
  1. In the early 1950s, Doll and Hill understood that some critics might dismiss findings linking smoking to disease as "merely" statistical -- which is precisely what Defendants did. As a result, Doll and Hill meticulously described the specific criteria that they required before an "association" could be identified as a genuine causal relationship. First, they worked to eliminate the possibility of bias in the selection of patients and controls, as well as in reporting and recording their histories. Second, they emphasized the significance of a clear temporal relationship between exposure and subsequent development of disease. Finally, they sought to rule out any other factors that might distinguish controls from patients with disease. This explicit search for possible "confounders" and their elimination marked a critical aspect of their arrival at a causal conclusion. They insisted on carefully addressing all possible criticisms and all alternative explanations for their findings. In this respect, Doll and Hill expressed a strong commitment to inductive science, hypothesis-testing, and scientific method:

Consideration has been given to the possibility that the results could have been produced by the selection of an unsuitable group of control patients, by patients with respiratory disease exaggerating their smoking habits, or by bias on the part of the interviewers. Reasons are given for excluding all these possibilities, and it is concluded that smoking is an important factor in the cause of carcinoma of the lung.

VXA2510117-0126 at 0125 (US 63604) (Doll & Hill, Smoking and Carcinoma of the Lung: Preliminary Report, supra); Brandt WD, 42:10-43:9.

  1. Noted historian Charles Webster observed of the first Doll and Hill paper, published in 1950:

This modest paper is now regarded as a classic. From these findings emerged the realization that smoking has been responsible for as many deaths per annum as were claimed by the great cholera

258

epidemics of the nineteenth century. Smoking was thus established as a major cause of preventable disease.

VXA2510301-0310 at 0301 (US 63589) (Webster, Charles, Tobacco Smoking Addiction: A

Challenge to the National Health Service, British Journal of Addiction, 79:7 (1984)); Brandt WD,

46:4-47:23.

  1. Doll and Hill's work withstood scientific scrutiny. Two years later, in a 1952 follow-up report, Doll and Hill offered additional evidence for sustaining their conclusion, again fully considering alternative explanations:

The present analysis of nearly 1,500 cases, or more than double the number dealt with in our preliminary report, supports the conclusion then reached and has revealed no alternative explanation -- for example, in the use of petrol lighters.

It has been suggested that subjects with a particular physical constitution may be prone to develop (a) the habit of smoking and (b) carcinoma of the lung, and that the association might therefore be indirect rather than causal (Parnell,1951). We know of no evidence of such a physical constitution characteristic of patients with lung carcinoma. If it does exist we should still have to find some environmental factor to account for the increased incidence of the disease in recent years.

VXA2510127-0142 at 0139 (US 63603) (emphasis in original) (Doll, Richard, and A. Bradford Hill,

A Study of the Aetiology of Carcinoma of the Lung, British Medical Journal (1952)); Brandt WD,

43:10-44:2. This alternative explanation for the relationship between smoking and lung cancer came to be labeled the "constitutional hypothesis" by Defendants. See also Section III(C)(1)(¶55), supra.

  1. Doll and Hill also sought to confirm the findings of their retrospective study through prospective investigation. They gathered data from 40,000 British physicians who were followed in order to see whether they would develop lung cancer. This study showed over time that heavy smokers had death rates 24 times higher than those of nonsmokers. Doll and Hill's research continued through June of 2004 when Doll and his colleagues published a fifty year observational study in the British Medical Journal. Brandt WD, 46:1-20; VXA2510001-0005 (US 63612) (Doll, Richard, and A. Bradford Hill, The Mortality of Doctors in Relation to Their Smoking Habits: A Preliminary Report, British Medical Journal (1954));VXA2510006-0021 (US 63611) (Doll, Richard, and A. Bradford Hill, Lung Cancer and Other Causes of Death in Relation to Smoking, British Medical Journal (1956)).
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  1. Other researchers studied the connection between smoking and lung cancer during the same time period. In 1949, Evarts Graham, a leading surgeon at Barnes Hospital in St. Louis, and Ernst Wynder, a medical student at Washington University, designed and implemented a study to address and directly resolve the persistent and increasingly important questions concerning the possible harms of cigarette smoking. Graham, a nationally known surgeon who had performed the first pneumonectomy, was a heavy smoker himself and skeptical of the cigarette-lung cancer hypothesis.

  2. Wynder and Graham collected extensive data on a group of 684 patients with lung cancer located in hospitals throughout the United States. These patients were extensively interviewed about their smoking levels and histories. Histological exams confirmed the diagnosis in all cases. This group was then compared to a "control group" of non-smokers, similar in age and other demographic characteristics. Wynder and Graham explained, "[T]he temptation is strong to incriminate excessive smoking, and in particular cigaret smoking, over a long period as at least one important factor in the striking increase of bronchiogenic carcinoma." They offered four reasons to support this conclusion. First, it was very unusual to find lung cancers among non-smokers. Second, among patients with lung cancer, cigarette use tended to be high. Third, the distribution of lung cancer among men and women matched the ratio of smoking patterns by gender. And finally, "the enormous increase in the sale of cigarettes in this country approximately parallels the increase in bronchiogenic carcinoma." These results were reported in the Journal of the American Medical Association ("JAMA"), a prestigious, peer reviewed journal, on May 27, 1950. VXA2510109-0116 at 0114 (US 63605) (Wynder, Ernst L., and Evarts A. Graham, Tobacco Smoking as a Possible Etiologic Factor in Bronchiogenic Carcinoma: A Study of Six Hundred and Eighty Four Proved Cases, JAMA, 143.4: 329 (1950)); Brandt WD, 32:18-34:13, 37:13-40:15.

260

  1. That 1950 issue of JAMA also included the report of an investigation reaching similar conclusions by scientist Morton Levin and others. In his commentary on research into the connection between cigarettes and lung cancer, Levin compared the current epidemiological research on cigarette smoking to research on the smoking/lung cancer connection done in the preceding twenty years, arguing that the past work was "inconclusive because of lack of adequate samples, lack of random selection, lack of proper controls or failure to age-standardize the data." In the case of the data gathered for his study, careful attention to "excluding bias" had been central. Levin concluded that "in a hospital population, cancer of the lung occurs more than twice as frequently among those who have smoked cigarets [sic] for twenty-five years than among other smokers or nonsmokers of comparable age." VXA2510106-0108 at 0106, 0107 (US 63606) (Levin, Morton L., Hyman Goldstein, and Paul R. Gerhardt, Cancer and Tobacco Smoking; A Preliminary Report, JAMA, 143:4 (1950)); Brandt WD, 39:23-40:18.

  2. By the 1950s, animal research was also pointing to the carcinogenicity of cigarettes. Wynder and Graham turned their attention to the question of the "biological plausibility" of their epidemiological findings. In conducting animal investigations, Wynder reasoned that if tumors could be produced in animals, it would be an important step in confirming the early epidemiologic findings. Noting that smoke condensates, also known as tars, contained benzopyrenes, arsenic and other known carcinogens, he painted the backs of mice to evaluate their effects. Fifty-eight percent of the mice developed cancerous tumors. Wynder concluded that "the suspected human carcinogen has thus been proven to be a carcinogen for a laboratory animal." These findings were reported in Cancer Research in December 1953. The study was often referred to as the Sloan-Kettering study because Wynder was affiliated with the Sloan-Kettering Institute of the Memorial Center for Cancer and Allied Diseases. CW00860130-0144 at 0137 (US 58868) (Wynder, Ernst L., Evarts A. Graham, and Adele B. Croninger, Experimental Production of Carcinoma with Cigarette Tar, Cancer Research, 13.12 (1953)); Brandt WD, 62:13-63:13; Harris WD, 62:4-63:10.

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  1. By late 1953, there had been at least five published epidemiologic investigations, as well as others, pursuing carcinogenic components in tobacco smoke and its impacts. These researchers' understanding of the link between smoking and lung cancer was markedly more certain than the case studies and preliminary statistical findings concluded earlier in the century. While some of the epidemiological methods were innovative, they were completely consistent with established scientific procedure and process. Epidemiology was not just based on statistics, but also was an interdisciplinary, applied field. The studies had substantially transformed the scientific knowledge base concerning the harms of cigarette use. Unlike earlier anecdotal and clinical assessments, these studies offered new and path-breaking approaches to investigating and resolving causal relationships. Brandt WD, 46:21-47:17.
262
  1. Medical historians would come to view these studies as among the most important contributions to public health and medicine in the twentieth century. They offered a sophisticated scientific methodology for resolving central questions of causality. Id. at 46:21-48:6.

b. By 1953, Defendants Recognized the Need for Concerted Action to Confront Accumulating Evidence of the Serious Consequences of Smoking

  1. The studies connecting smoking and lung cancer were receiving attention outside the scientific community by 1953. For example, published reports like a Readers' Digest article titled

"Cancer by the Carton" shared the scientific findings in national media, creating public concern.

03358234-8235 (US 46459); Brandt WD, 48:1-18.12

  1. The "Cancer by the Carton" article, published in 1952 explained:

A study of 684 cases, made by Ernest L. Wynder and Evarts A. Graham for the American Cancer Society and published in the AMA Journal, May 27, 1950, stated this conclusion: "Excessive and prolonged use of tobacco, especially cigarettes, seems to be an important factor in the induction of bronchiogenic carcinoma."

More recently Wynder, now associated with Memorial Cancer Center in New York, expanded the statement: "The more a person smokes the greater is the risk of developing cancer of the lung, whereas the risk was small in a nonsmoker or a light smoker."

  1. In late 1953, shortly after the Wynder and Graham study was published, tobacco stocks declined. Overall cigarette sales had also declined about 2% in 1952, which was the first time sales had declined since the Great Depression. Harris WD, 63:11-64:12; 01138541-8542 (US
263

  1. As already discussed, by 1953-1954, tobacco company executives were aware both of the significant scientific studies establishing smoking as a cause of lung cancer and the public attention the studies were receiving. Defendants' executives well understood that this new scientific evidence constituted a full-scale crisis for their respective companies. Brandt WD, 48:19-51:23.

  2. As evidence regarding the harms of smoking surfaced, Defendants engaged in advertising campaigns to induce the public to believe that cigarette smoking was actually beneficial to one's health. Some examples of Defendants' advertisements include: Kent Micronite filters, which were supposedly "developed by researchers in atomic energy plants," Kent cigarettes, which claimed "No other cigarette approaches such a degree of health protection and taste satisfaction," and a Chesterfield ad claiming to cite test results that "smoking Chesterfields would have no adverse effects on the throat, sinuses, or affected organs." ADV1100001-0003 at 0002-03 (US 88703); LW02427396-7397 at 7396 (US 74413); ADV1110007-0009 at 0008 (US 88728); ADV1100040- 0043 at 0042 (US 88715); Harris WD, 67:11-70:20.

  3. While continuing to insist that there was no indication that cigarettes were unsafe, Defendants moved aggressively to market products which they implied were safer. In 1953, Defendant Liggett hired Arthur D. Little, Inc. ("ADL") to test tobacco condensates on mice in an attempt to develop strategies for removing carcinogens, at the same time that it advertised that its filters were "Just What the Doctor Ordered." VXA2611190-1190 (US 63543) (Liggett Advertisement, "Fredric March Says -- This Is It L & M Filters Are Just What the Doctor Ordered").

264

  1. Defendants also developed the Tobacco Industry Research Committee ("TIRC") to sponsor research into "all phases of tobacco use and health" and to handle public relations for the tobacco industry in response to the growing body of scientific knowledge. See extended discussion of TIRC in Section III(C). The first Scientific Director of TIRC, appointed in 1954, was a well-respected geneticist and cancer researcher, Clarence Cook Little. A former president of the University of Maine and the University of Michigan, founder of the Roscoe B. Jackson Memorial Laboratory, and member of the National Academy of Sciences, Little quickly became a steadfast critic of the emerging scientific data linking cigarettes to cancer. Brandt WD, 86:4-88:5.

  2. A confidential report of a TIRC meeting held October 19, 1954, made explicit Little's and Defendants' agenda: "[Little] declared that both he and the members of the board were aware of the attacks which had been made on tobacco for over 200 years, and wished to build a foundation of research sufficiently strong to arrest continuing or future attacks." CTRMN007295-7297 at 7295 (US 22900); Brandt WD, 86:4-88:5.

  1. Little criticized those whose findings showed harms from tobacco use: The right of an individual to determine his own level or threshold of convincibility is unquestioned. There are and will always be individuals who are convinced without the need of experimental evidence that all tobacco in any form is evil, noxious and toxic. There are individuals with a similar attitude toward alcohol, coffee, and the use of drugs, sera or medicines. *** Such assumptions [that smoking caused cancer] stimulated some investigators to begin an enthusiastic hunt for the "component" or "components" in tobacco smoke that can be blamed for the unproved cause-and-effect relationship as well as for the reported production of
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skin cancer in some experiments with certain strains of laboratory mice.

501773418-3466 at 3428-3429 (US 20686) (emphasis in original); Brandt WD, 86:4-88:5.

  1. Little continually called for more research: "In the active and continuing discussions about tobacco use and health, there seems to be nearly complete agreement among scientists on only one point: The need for much more intensive research into the subject." 501773418-3466 at 3425 (US 20686); Brandt WD, 86:4-88:5.

  2. Under Little's leadership, the major thrust of TIRC was to emphasize that human cancers were complex processes -- difficult to study and difficult to understand. Little directed TIRC towards what he called "pioneer research." He claimed that studies which focused on cigarettes could "stifle or delay needed research to find the basic origins of lung cancer or cardiovascular diseases, which are most powerful, diversified and deadly enemies to our well-being." 85865874- 5946 at 5878 (US 21084); Brandt WD, 86:19-88:5.

  3. Little also argued that there were no known carcinogens in tobacco tars (despite Defendants' clear knowledge to the contrary, as addressed in Section V(A)(5)(b)). He repeatedly centered attention on the so-called "constitutional hypothesis," other environmental risks, and the need for more research:

Too little is known about many factors, including why people smoke or what kind of people become particularly heavy smokers. *** The problem of causation of any type of cancer is complex and difficult to analyze. All research on this so-called constitutional disease is, and must be, painstaking and time-consuming. There is not known today any simple or quick way to answer the question of whether any one factor has a role in causing human lung cancer.

266

Despite all the attention given to smoking as an accused factor in human lung cancer, no one has established that cigarette smoke, or any one of its known constituents, is cancer-causing to man [sic].

501773418-3466 at 3422-3423 (US 20686); Brandt WD, 85:10-86:3.