Comparison in practice: The case of cigarettes

This material is excerpted from a teaching module on the Visionlearning website, to view this material in context, please visit Research Methods: Comparison.

In 1919, Dr. George Dock, chairman of the Department of Medicine at Barnes Hospital in St. Louis asked all of the third- and fourth-year medical students at the teaching hospital to observe an autopsy of a man with a disease so rare, he claimed, that most of the students would likely never see another case of it in their careers. With the medical students gathered around, the physicians conducting the autopsy observed that the patient's lungs were speckled with large dark masses of cells that had caused extensive damage to the lung tissue and had forced the airways to close and collapse. Dr. Alton Ochsner, one of the students who observed the autopsy, would write years later that "I did not see another case until 1936, seventeen years later, when in a period of six months, I saw nine patients with cancer of the lung. All the afflicted patients were men who smoked heavily and had smoked since World War I" (Meyer, 1992).

The American physician Dr. Isaac Adler was, in fact, the first scientist to propose a link between cigarette smoking and lung cancer in 1912, based on his observation that lung cancer patients often reported that they were smokers. Adler's observations, however, were anecdotal, and provided no scientific evidence toward demonstrating a relationship. The German epidemiologist Franz Müller is credited with the first case-control study of smoking and lung cancer in the 1930s. Müller sent a survey to the relatives of individuals who had died of cancer, and asked them about the smoking habits of the deceased. Based on the responses he received, Müller reported a higher incidence of lung cancer among heavy smokers compared to light smokers; however, the study had a number of problems. First, it relied on the memory of relatives of deceased individuals rather than first-hand observations, and second, no statistical association was made. Soon after this, the tobacco industry began to sponsor research with the biased goal of repudiating negative health claims against cigarettes (see our Scientific Institutions and Societies module for more information on sponsored research).

Beginning in the 1950s, several well-controlled comparative studies were initiated. In 1950, Ernest Wynder and Evarts Graham published a retrospective study comparing the smoking habits of 605 hospital patients with lung cancer to 780 hospital patients with other diseases (Wynder & Graham, 1950). Their study showed that 1.3% of lung cancer patients were nonsmokers while 14.6% of patients with other diseases were nonsmokers. In addition, 51.2% of lung cancer patients were "excessive" smokers while only 19.1% of other patients were excessive smokers. Both of these comparisons proved to be statistically significant differences. The statisticians who analyzed the data concluded, "when the nonsmokers and the total of the high smoking classes of patients with lung cancer are compared with patients who have other diseases, we can reject the null hypothesis that smoking has no effect on the induction of cancer of the lungs." Wynder and Graham also suggested that there might be a lag of ten years or more between the period of smoking in an individual and the onset of clinical symptoms of cancer; this would present a major challenge to researchers as any study that investigated the relationship between smoking and lung cancer in a prospective fashion would have to last many years.

Richard Doll and Austin Hill published a similar comparative study in 1950 in which they showed that there was a statistically higher incidence of smoking among lung cancer patients compared to patients with other diseases (Doll & Hill, 1950). In their discussion, Doll and Hill raise an interesting point regarding comparative research methods by saying, "This is not necessarily to state that smoking causes carcinoma of the lung. The association would occur if carcinoma of the lung caused people to smoke or if both attributes were end-effects of a common cause." They go on to assert that because the habit of smoking was seen to develop before the onset of lung cancer, the argument that lung cancer leads to smoking can be rejected. They therefore conclude, "that smoking is a factor, and an important factor, in the production of carcinoma of the lung."

Despite this substantial evidence, both the tobacco industry and unbiased scientists raised objections, claiming that the retrospective research on smoking was "limited, inconclusive, and controversial." The industry stated that the studies published did not demonstrate cause and effect, but rather a spurious association between two variables. Dr. Wilhelm Hueper of the National Cancer Institute, a scientist with a long history of research into occupational causes of cancers, argued that the emphasis on cigarettes as the only cause of lung cancer would compromise research support for other causes of lung cancer. Ronald Fisher, a renowned statistician, also was opposed to the conclusions of Doll and others, purportedly because they promoted a "puritanical" view of smoking. The tobacco industry mounted an extensive campaign of misinformation, sponsoring and then citing research that showed that smoking did not cause "cardiac pain" as a distraction from the studies that were being published regarding cigarettes and lung cancer. The industry also highlighted studies that showed that individuals who quit smoking suffered from mild depression, and they pointed to the fact that even some doctors themselves smoked cigarettes as evidence that cigarettes were not harmful (Figure 5).

While the scientific research began to impact health officials and some legislators, the industry's ad campaign was effective. The U.S. Federal Trade Commission banned tobacco companies from making health claims about their products in 1955; however, more significant regulation was averted. An editorial that appeared in the New York Times in 1963 summed up the national sentiment when it stated that the tobacco industry made a "valid point," and the public should refrain from making a decision regarding cigarettes until further reports were issued by the U.S. Surgeon General.

In 1951, Doll and Hill enrolled 40,000 British physicians in a prospective comparative study to examine the association between smoking and the development of lung cancer. In contrast to the retrospective studies that followed patients with lung cancer back in time, the prospective study was designed to follow the group forward in time. In 1952, Drs. E. Cuyler Hammond and Daniel Horn enrolled 187,783 white males in the United States in a similar prospective study. And in 1959, the American Cancer Society (ACS) began the first of two large-scale prospective studies of the association between smoking and the development of lung cancer. The first ACS study, named Cancer Prevention Study I, enrolled more than 1 million individuals and tracked their health, smoking and other lifestyle habits, development of diseases, cause of death, and life expectancy for almost 13 years (Garfinkel, 1985). All of the studies demonstrated that smokers are at a higher risk of developing and dying from lung cancer than non-smokers. The ACS study further showed that smokers have elevated rates of other pulmonary diseases, coronary artery disease, stroke, and cardiovascular problems. The two ACS Cancer Prevention Studies would eventually show that 52% of deaths among smokers enrolled in the studies were attributed to cigarettes.

In the second half of the 20th century, evidence from other scientific research methods would contribute multiple lines of evidence to the conclusion that cigarette smoke is a major cause of lung cancer. Descriptive studies of the pathology of lungs of deceased smokers would demonstrate that smoking causes significant physiological damage to the lungs. Experiments that exposed mice, rats, and other laboratory animals to cigarette smoke showed that it caused cancer in these animals (see our Experimentation module for more information). And physiological models would help demonstrate the mechanism by which cigarette smoke causes cancer.

As evidence linking cigarette smoke, lung cancer and other diseases accumulated, the public, the legal community and regulators slowly responded. In 1957, the U.S. Surgeon General first acknowledged an association between smoking and lung cancer when a report was issued stating, "It is clear that there is an increasing and consistent body of evidence that excessive cigarette smoking is one of the causative factors in lung cancer." In 1965, over objections by the tobacco industry and the American Medical Association which had just accepted a $10 million grant from the tobacco companies, the U.S. Congress passed the Federal Cigarette Labeling and Advertising Act which required that cigarette packs carry the warning: "Caution: Cigarette Smoking May Be Hazardous to Your Health." In 1967, the U.S. Surgeon General issued a second report stating that cigarette smoking is the principal cause of lung cancer in the United States. While the tobacco companies found legal means to protect themselves for decades following this, in 1996, Brown and Williamson Tobacco Company was ordered to pay $750,000 in a tobacco liability lawsuit; it became the first liability award paid to an individual by a tobacco company.