by Allan Brandt
Born in Boston in 1888, Little attended Harvard, where he earned a doctorate in science in 1914 while studying with noted geneticists W. E. Castle and later Edward Tyzzer. His earliest work focused on the genetics of mouse colors, but he soon turned his attention to susceptibility and resistance to cancers. His work was an important precursor to fundamental discoveries on the genetics of transplant immunology. Among his most important scientific discoveries was the murine mammary tumor virus. He also pioneered the use of strains of inbred mice for genetic research.57
Along with his research, Little assumed administrative roles that would increasingly become central in his career. After receiving his doctorate, Little joined the Harvard faculty, where he was appointed secretary to the Corporation, a notable administrative post. Then, following Army service in the World War I, he spent three years at the Cold Spring Harbor Laboratory, where he quickly rose to assistant director. As a result of Little’s obvious administrative skill, he was offered the presidency of the University of Maine in 1922 at the age of thirty-three. At that time, he was the youngest college president in the United States. Although Little’s identity as a scientist had been well established by his important laboratory findings, his scientific research would now come to be secondary as he emerged as a leading academic and scientific administrator. However, this work was not without controversy. At the University of Maine, Little quickly became embroiled in an intense conflict with Governor Percival Baxter over funding issues. He left after only three years to take the presidency of the University of Michigan. By now, he had come to be widely known for his vigor, energy, outspokenness, and arrogance.
At Ann Arbor, Little’s reputation for conflict and combativeness was soon enhanced. His public advocacy of eugenics, birth control, and sex education apparently outraged the regents and the faculty.58 And his support for prohibition of alcohol in fraternities alienated students. Little would denounce the impact of automobiles, coeducation, and liquor on campus as “splendid centres of hypocrisy” in American higher education. He also expressed his skepticism of the professoriate, noting “I know that of some of the most distinguished loafing in America is being done by American faculties in the universities.”59 Little tendered his resignation in January 1929, after having served for less than five years. At the time of his resignation, it had also become widely known that his first marriage of eighteen years was ending in divorce and that he had become romantically involved with a student. In the course of his presidency, he had alienated the regents, the faculty, and polite society.60
Little, however, had no shortage of ideas and energy, and he moved quickly to take on two other prominent positions. First, in 1929, he became managing director of the American Society for the Control of Cancer (ASCC), a part-time position. That same year, he founded the Roscoe B. Jackson Memorial Laboratory in Bar Harbor, Maine.61 The lab was named in memory of a principal donor, the president of Hudson Motors, who Little had come to know in Michigan and from vacationing in Bar Harbor for many years. Financial support also came from Edsel Ford, Richard Webber, and George B. Dorr, all of whom summered on Mt. Desert Island in Maine.62 Under Little’s spirited leadership, activities at the lab grew quickly. By 1933, Little, who had become widely known for developing strains of inbred mice for research, began to support the work of the lab by selling inbred mice to other research institutions in the United States and abroad. This program reflected to a considerable degree the central personal aspects of its founder. Little was both lab scientist and entrepreneur, administrator, and advocate.63
At the ASCC, Little helped to establish the Women’s Field Army, an educational and fund-raising campaign staffed by volunteers that urged early detection, treatment, and more scientific research. Together with newly appointed publicity director Clifton Read, Little successfully enhanced the visibility of the organization through the 1930s into the 1940s. Little’s simultaneous roles at ASCC and the Jackson Lab established him as a leading figure in the emerging program to establish a national cancer policy. U. S. Surgeon General Thomas Parran appointed him to the National Advisory Cancer Council at the time that Congress created the NCI in 1937. In these contexts, Little became a powerful advocate of more funding for basic science investigation.64
He also gained real prestige in the field with his combined work maintaining the Jackson Laboratory and directing the ASCC. In 1950, he received the American Cancer Society’s annual award for “distinguished service in cancer control.” Dr. Alton Ochsner, then-president of the ACS, presented it to him, calling him a scientist with “unprecedented vision.” In accepting the award, Little stressed his firm—and telling—belief that the “discovery of a ‘cause’ or a ‘cure’ for cancer will be made by an individual working alone and not by a team of scientists working on a project.”65
Given Little’s position as a “leading man of science,” his appointment to scientific director of the TIRC came to be widely praised initially. But his work on behalf of the TIRC would bear all the marks of his personal history as geneticist and eugenicist. As TIRC’s scientific director, Little 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.
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.66
While Little favored basic science investigations into the mechanism of disease, often utilizing animal models, he never confronted the critical issue of the relationship of translating such research from the laboratory to humans. Little, whose own work had rested so fundamentally on animal research, now often found himself dismissing animal studies as irrelevant to questions of human disease.
Other cancer researchers reacted to Little’s appointment as scientific director of the TIRC with surprise and distaste. “You may be surprised to know that Dr. C. C. Little was willing to become the chairman of that Committee,” noted Evarts Graham in a 1956 letter to Hill. “It seems astonishing to me that a man of his eminence in the field of cancer and genetics would condescend to take a position like that.”67 Graham went on to express his frustration with Little’s persistent skepticism in the face of mounting evidence. “Isn’t the evidence at hand sufficient to convince anybody with an open mind?” asked Graham. When the TIRC announced its first set of grants almost two years earlier in November 1954, Ochsner—already clearly disillusioned with Little after praising him so highly four years earlier—called the TIRC program, “a tapeworm research into the physical and chemical composition of tobacco.” According to Ochsner, the industry “sought to postpone a day of reckoning for the irresponsible advertising and sale of its products.”68
In Little the industry identified a leader with a distinguished scientific pedigree. But perhaps even more importantly, Little brought to his work on behalf of the industry considerable experience with, and attraction to, combat and controversy. Throughout Little’s career, he had become involved in a series of contests. In this respect, he seemed to relish a new public role in which he would be the lightning rod. Little, the inveterate contrarian, rediscovered the public limelight at this late point in his career.
Was Little disingenuous in his skepticism? Did he dissemble on behalf of his employer? The evidence on this question remains indeterminate. What we do know is that Little, by self-proclamation deeply committed to science and rationality, lost all capacity to evaluate his own biases as he assessed the question. Fiercely independent throughout his career, he failed to see how effective
ly he had come to do the industry’s bidding; he failed to comprehend the corrosive social and psychological mechanisms of conflicts of interest. Colleagues and friends came to question his judgment and rectitude: he had sold his science to industry. His starting salary in 1954, publicly announced, was $20,000 for the part-time position ($134,800 in 2006 dollars). No doubt Little’s opinions on tobacco science were subject to financial conflicts, but it seems equally apparent that Little prized the notion of his own intellectual independence in the face of attack. After all, this had been the story of his life. In Little’s view, he was defending science against emotion and hysteria; the integrity of objective experimentalism against the forces of moralism and ignorance.
Little’s role in prolonging the cigarette controversy, which was a central part of the TIRC’s public message, offers an important opportunity to explore the sociology of scientific skepticism. In examining the debates about the health risks of smoking in the 1950s, it is crucial to put the various protagonists into specific social and intellectual contexts. Did particular investigators and commentators bring existing assumptions to their assessment of the causal relationship between smoking and disease? What was the nature of their a priori assumptions about the harms of cigarette smoking? And how did they shape the character of ongoing debates about methodology and findings? As a geneticist who had devoted his lifetime to exploring genetic links to cancers utilizing laboratory experiments, Little had few inherent sympathies to the approaches taken in the early epidemiological investigations that were the linchpin to demonstrating that cigarette smoking caused lung cancer. Not only was he inclined not to trust these methods, he had a prevailing view of carcinogenesis that ran counter to the notion that cancers were caused by behavioral and environmental factors. As a result, Little steadfastly refused to acknowledge the growing evidence, repeatedly confirmed, that smoking was a cause of lung cancer. Little was not a physician, and perhaps this explains, in part, his ongoing demand to locate causality exclusively in the laboratory, as well as his apparent lack of concern regarding the medical questions involved.
Little also had a deep commitment to an increasingly anachronistic view of scientific discovery and innovation. His belief that the conundrum of cancer would eventually be solved by an individual scientist working alone harkened back to an image of Louis Pasteur or Robert Koch toiling long hours in their laboratories, unlocking the secrets of the microbes. But contemporary scientific investigation—as was so often true in the past—was both collaborative and iterative, rarely the work of a single scientist experimenting in isolation and rarely yielding definitive answers in a single stroke. Moreover, to solve multicausal questions, such as those associated with systemic and chronic diseases, would require the integration of methods and approaches across the biomedical sciences.
Little was convinced that the support of the industry for independent research marked an unprecedented boon to American science. In a 1956 guest editorial for the journal Cancer Research, Little explained:If those of us on the Board have the wisdom and vision to plan creatively, we may be able to justify this confidence placed in us. If we do justify it, the tobacco industry will have made its greatest contribution of service to mankind and may well establish a precedent or pattern which other industries will follow.
Should this occur, the stability and development of basic research in a democracy will be assured on a foundation of nonpolitical support, unselfish and idealistic in concept and execution.69
It was essentially this perspective that shaped Little’s approach to the question of cigarettes and disease. Given Little’s personal rigidities and conceit, no epidemiological findings could possibly unsettle such deeply held convictions. Little had no respect for clinical and field observations. He brought these unbending views to his work for the industry and structured its research program accordingly.
A related question would be the significance of his role working on behalf of the tobacco industry. Once Little became the scientific director of the TIRC, he demonstrated a complete unwillingness to be swayed from the positions he took in 1954. No new evidence ever convinced him of the relationship of smoking to disease. In his role with the TIRC, Little now had an important conflict of interest to open scientific and medical inquiry into the health impact of cigarettes. And he worked concertedly to direct the scientific program of the TIRC away from the most important immediate questions of the harms of smoking.
Little and his Hill & Knowlton colleagues constructed a basic science research program into aspects of carcinogenesis that had little or no potential to resolve the question that the TIRC had promised the American public would be at the center of attention: do cigarettes cause disease? Little became the industry’s primary spokesman for obscuring this question. The sharp disjuncture between the research agenda of the TIRC and the commitment to resolving the controversy about smoking and health is a major indicator of the essential PR goals of the TIRC. In the end, the TIRC was designed to direct attention away from the questions of immediate concern to the American public and American medicine: the health effects of smoking.
Little certainly brought a priori scientific and medical assumptions to his position, as well as conflicts of interest, but these were sustained by certain traits of personality. Throughout his career, Little had manifested a certain rigidity and combativeness that were now deployed to great effect on behalf of the tobacco industry. Certainly, skepticism is a valued attribute in scientific debate and controversy, but so too can it inhibit the production and legitimation of new and valuable knowledge. Just as it would be incorrect to simply view Little’s skepticism as a function of his remuneration from the industry, it would be inaccurate to view it simply as representing rationality and objectivity. Little’s skepticism reflected a deeply held worldview about genetics, society, and scientific investigation, perspectives that ultimately distorted the rationality and science of an individual who explicitly prized rationality and science.
Little would consistently maintain his public position on the scientific evidence and would repeatedly deny that there were any known carcinogens in tobacco tars (this despite clear industry knowledge to the contrary).
At the same time that he attacked the substantial scientific evidence indicating the harms of smoking, he had no compunction about offering unsubstantiated claims about the health benefits of cigarette use based on personal anecdote and social observation: “It is very well-known, for example, that tobacco has relaxed a great many people. It is a very good therapy for a great many nervous people.”70
By 1960, largely through the efforts of Hill & Knowlton and the TIRC, the tobacco industry had succeeded in creating a “cigarette controversy” within the American media. The very idea that cigarettes caused lung cancer had come to be vigorously contested by the companies, and the emerging scientific consensus of 1953 had by 1960 given way to widespread debate—even as new peer-reviewed findings repeatedly confirmed the causal link between smoking and disease. We cannot know what trajectory science and public health would have taken without the tobacco companies’ deliberate and studied interventions. But we can evaluate their impact.
Given that a number of scientists—even some epidemiologists—were skeptical of the smoking-cancer link, several historians have recently claimed that the “cigarette controversy” was real.71 By this, they apparently mean that there were substantive areas of scientific debate, independent of the actions of the companies to denigrate the emerging evidence. There is no question that there was a real controversy about tobacco. But it is important to evaluate the range of interests that were engaged in this controversy: What were its causes? What forces contributed to its resolution? And what interests contributed to its continuation?
To understand the nature of the controversy, it is critical to examine the trajectory of research, evidence, and skepticism as it developed through the 1950s. Many of the prominent cigarette researchers began their investigations with considerable skepticism—including importan
t figures like Evarts Graham, A. Bradford Hill, Richard Doll, and E. Cuyler Hammond. But by 1953, most of them had modified their positions in the face of new and convincing scientific research. For instance, Hammond doubted the link between smoking and lung cancer when only retrospective findings were available; but in July 1954, when the preliminary results of his prospective study had come in, he stated publicly, “In my opinion, it is now well established that cigarette smoking causes an increase in death rates from primary cancer of the lung.”72 To suggest, as the industry consistently did, that through the 1950s and 1960s eminent scientists equally and independently lined up on both sides of a “controversy” about the harms of smoking is to grossly misrepresent the historical record.73
Moreover, the nature of scientific skepticism to tobacco research evolved during the 1950s. Early in the decade, many physicians and scientists were unfamiliar with statistical and quantitative methods of research. These subjects were barely touched on in medical schools, and quantitative evaluations were not the routine feature of medical journal articles that they later became. This unfamiliarity led some to reject certain kinds of research as “merely” statistical. Many of these physicians and scientists had been trained in an era when the superiority of laboratory investigation over other forms of inquiry was an unquestioned assumption. The unique status and authority of the laboratory made some scientists and physicians skeptical of any knowledge produced by other means. Certainly, there were important epistemological questions about the character of scientific inference at stake. Still other skeptics brought a priori assumptions to their assessment of the evidence. Someone like Little, for example, who was deeply committed to the hypothesis that cancer was a genetic disease, would be skeptical of the suggestion that a particular behavior, such as smoking, might cause lung cancer. Such deeply held a priori assumptions often shape scientific controversies. Yet other scientists and physicians were swayed by personal psychological and sociological factors. They were concerned with defending their turf (the primacy of the laboratory) or were smokers themselves who did not want to accept the idea that their own behaviors put them at risk.