Buffler, Patricia A.
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Warren Winkelstein, Jr., was born in Syracuse, New York, on 1 July 1922. He received an MD from Syracuse University in 1947 and an MPH from Columbia University in 1950. He worked in Buffalo, New York, from 1950 to 1968, first at the Erie County Health Department and then at the State University of New York. In 1968, he joined the faculty at the School of Public Health of the University of California at Berkeley, where he is Professor of Epidemiology. He served as Dean of the School from 1972 to 1981. His scientific work has ranged from the 1954 polio vaccine field trials to pioneering studies in the 1960s on health effects of air pollution. He was among the first to suggest that smoking causes cervical cancer. In the early 1980s, his research turned again to infectious diseases and the HIV/AIDS epidemic. He maintains a keen interest in the history of science and has completed biographic studies of Abraham Lilienfeld, Edward Jenner, Janet Elizabeth Lane-Claypon, and John Snow. Dr. Winkelstein is a member of the Institute of Medicine, a Fellow in the American Association for the Advancement of Science, and recipient of the Abraham Lilienfeld Award of the APHA. In 1991, he received the Berkeley Citation, the highest honor conferred by the campus on its faculty.
PB: Few people start their careers with the intent of becoming an epidemiologist. Can you describe how your past brought you to epidemiology?
WW: I'm not sure. My father was a prominent attorney, very much community-oriented, active in the Jewish community, and one-time unsuccessful candidate for city council. My mother ran our house like a salon. We lived near the university and whenever someone would come to speak on some social issue, my mother would arrange a dinner party. So, there was a lot of intellectual ferment in our home. A close friend of the family was the Chairman and Professor of Medicine at Syracuse University College of Medicine during the 1920s, and he had a very broad social orientation. Then, I attended an experimental, progressive high school, the Putney School, which had been founded and directed by a woman associated with Jane Adams at Hull House in Chicago. So, I think my background led me in a direction of social concern.
When I went to medical school, I actually intended to go into public health, which was very unusual at that time. I started in public health administration, but then drifted into epidemiology because that is what interested me and that is what public health is all about, especially at the local level.
PB: Who would you identify as the single most influential person in your career?
WW: The single most influential person is very difficult to say, because there are really many. Certainly, my mother and father had a strong influence on me. Carmelita Hinton, the Director of my high school, introduced me to the ideas of Jane Adams—pacifism, activism, social justice.
When I trained for public health in the New York State Health Department, I was the only trainee and treated like the prodigal son. My fellowship was for 2 years. Edward S. Godfrey, Jr., one of the founders of the American Epidemiological Society, had been State Health Officer from 1927 to the early 1940s. Godfrey had instilled epidemiologic principles into the department and its programs. Although Dr. Godfrey retired before I became a trainee, I had some interaction with him because my first paper reported on an outbreak of nasal diphtheria in Port Byron, New York.1 Diphtheria had been Dr. Godfrey's specialty, and my mentors in the department sent the paper to him to review. He was not very happy with some of the things I said, particularly about his work. So, there was correspondence between Dr. Godfrey and myself and, of course, I revised my manuscript to address his suggestions. I remember that he had talked to my supervisor, Ann Balke, and she wrote me a note saying, “I spoke with Dr. Godfrey and he was chuckling over the phone when he said, ‘We sure gave Winkelstein a hell of a time, didn't we?’ ”
I was indoctrinated particularly by outstanding epidemiologists—Mort Levine, who trained with Wade Hampton Frost and Abraham Lilienfeld—assuredly one of the leading epidemiologists of the last half of the 20th century. After I completed my public health training in 1950, I accepted a position at Erie County Health Department in Buffalo. That department pioneered new programs in public health and emphasized research-based programming.
Then, the Korean War began. Because I had received my medical education in the Army during the Second World War, I was in the Reserves and was called to military duty. I spent 2 years on assignment to the U.S. Technical and Economic Mission to Cambodia, Laos and Vietnam. I was stationed in Hanoi from 1951 to 1953. All of these experiences conspired to push me forward into my public health career and into epidemiology.
PB: Many people have commented on how epidemiology has evolved and how it differs today. What do you think is the biggest difference?
WW: I am not sure that my experience is typical, because I worked in such favorable environments. When I was working in the New York State Health Department, the distinction between the organization and delivery of medical care and the organization and delivery of public health programs was more distinct. In the last 40 to 50 years, there has been more integration of medical care and public health.
There is also more emphasis on clinical epidemiologic investigation today. Nevertheless, many of the problems continue to be similar. As we speak, epidemiologists are deeply involved in studying new disease outbreaks such as the acute respiratory disease outbreak (SARS), as well as addressing issues of bioterrorism.
Also, the field of epidemiology has grown. When I began my career, the main forum for discussion of issues was the Epidemiology Section of the American Public Health Association (APHA). Today, the APHA Epidemiology Section continues to play a role but is no longer “the” place to be. The focal points of epidemiologic activity today are the Society for Epidemiologic Research, the American Epidemiological Society, and other specialty epidemiologic groups.
PB: What do you think are some of the biggest differences in the teaching of epidemiology?
WW: Epidemiologic teaching was very much influenced by Wade Hampton Frost's program at Johns Hopkins. Many of the epidemiologists under whom I had trained had done their work at Hopkins. The ideas and structure of the teaching was based on case studies, an approach that had been introduced by Frost.
Here at the University of California School of Public Health and at other schools, there is now more emphasis on epidemiologic methodology and biostatistics. We do have courses in surveillance and epidemiologic investigation, which provide some orientation to field operations. Furthermore, today epidemiology is recognized in medical training to a much greater extent.
PB: What have you found to be the most important ingredient of successful collaboration and what were some of your most successful collaborations?
WW: The key to successful collaboration is mutual respect. My entire career has been built around collaboration. My skills in epidemiology do not include much microbiology, for example, and my statistics are not exactly strong. If you look back over my research, whatever it might be, it has always been, right from the beginning, collaborative. You can make an awful lot of mistakes individually, but by collaboration you eliminate a lot of dumb errors.
There is also a certain amount of luck that accompanies this. When I began working in the Erie County Health Department, I had the good fortune of meeting a brilliant pediatric virologist, David Karzon, who went on to become Chair of Pediatrics and Virology at Vanderbilt University College of Medicine. He and I, with several other colleagues, conducted a series of investigations. We were the first to describe epidemics of human cytopathic human orphan virus.2 Also, I would go on rounds with him at the Children's Hospital. He would begin by discussing the clinical aspects of a case, and then I would discuss some of the public health implications.
Also, right from the beginning, I have always worked with statisticians. My last major research project was on HIV/AIDS in San Francisco. The study was based on a probability sample of single men. It was, to say the least, interdisciplinary. At any one time, there were between 12 and 14 senior scientists working on the project.
PB: Who do you regard as the 2 or 3 most important epidemiologists during your lifetime and why?
WW: I can start by naming the person I consider to be the most important. That was Abe Lilienfeld. Abe was constantly asking questions about disease phenomena and trying to address those questions through epidemiologic research. His work was elegant and rigorous. He pioneered multicenter epidemiologic investigations. Furthermore, he influenced public health policy by serving on innumerable advisory committees, as well as directing the staff of President Johnson's Commission on Heart Disease, Cancer and Stroke. Abe Lilienfeld once wrote, “Without epidemiology, there can be no public health, and without public health there is no need for epidemiology.”3
There are many epidemiologists whom I consider important. Certainly, my colleagues Len Syme, who pioneered social epidemiology, and Bill Reeves, the world's leading arbovirology epidemiologist, belong in my roster of “greats.” I would also include in that roster Alex Langmuir, who had an immense impact on American epidemiology by creating the Epidemic Intelligence Service, which for many years and continuing today introduces a constant flow of trained personnel to the field.
PB: Which do you think has been your most influential paper?
WW: Let me answer your question this way. There are 4 areas of research that I think represent my best work. The first was a case-control study of coronary artery disease and risk factors in women. I conducted this study under the tutelage of Abe Lilienfeld when I was a Fellow at the Roswell Park Memorial Institute, when I first went to Buffalo. We found that women who had spontaneous abortions and surgically induced menopause were at higher risk than controls. This finding was consistent with subsequent clinical and epidemiologic research relating hormonal factors and risk. This could have been the first epidemiologic study of coronary disease in women.4 Nevertheless, this study was largely ignored.
The studies that my colleagues and I carried out on the adverse health affects of air pollution in Buffalo were probably the most influential because they were the basis for setting up air quality standards for the United States.5
I guess my most controversial paper was the brief note advancing the hypothesis that cigarette smoking was a risk factor for cervical cancer.6 This association was dismissed by such an eminent cancer epidemiologists as Sir Richard Doll as the result of confounding.7 Now, after 25 years, the working group on tobacco smoke of the International Agency for Research on Cancer has recognized smoking as a contributing causal factors for cervical cancer.8
When the AIDS epidemic surfaced in San Francisco, I became involved as principal investigator in a large cohort study that went on for a dozen years. Our group published over 150 papers. This study of HIV/AIDS was, I believe, the first to be based on a probability sample of an affected population. It provided important information on modes of transmission, infectivity of the virus, risk factors for progression, and duration of the incubation period. The initial publication indicated the subsequent scope of the investigations.9 From a research point of view, I think those are the high points of my research career.
PB: How have you selected the research questions that you have addressed?
WW: It seems I have just fallen into them. However, perhaps there is something to what they say about “a prepared mind.” I had the benefit of being exposed to wonderful, brilliant, and innovative investigators during my training period.
I remember going to a talk given by a Chicago cardiologist who suggested that coronary disease in women did not appear until menopause. I was working at the Roswell Park with Abe Lilienfeld at the time, and Abe had just published his classic paper on breast cancer, showing the incidence of breast cancer by age increases exponentially up to the age of menopause. After that, the increasing rate is constant, but at a much lower rate than it is premenopausally.10 After hearing this talk by the cardiologist, I went back to my office and plotted the age distribution for the mortality from coronary heart disease in women. I found that it was essentially linear from approximately the age of 25 on, and menopause did not represent any break point in susceptibility. That led me to the hypothesis that you could identify the risk factors for coronary disease in women by looking at premenopausal factors, and that led to the design of our case-control study.
I studied air pollution because I had become the epidemiologist for the County Health Department, and Buffalo had a lot of heavy industry—a huge railroad center, the sixth largest steel mill in the world, shipping on the Great Lakes, and a chemical industry. There was a lot of pressure on the Health Department, both from the community and from the Public Health Service, to study air pollution. I resisted and said we should not do a study because the effects of air pollution would be confounded with social and occupational factors. Eventually the Health Officer, Bill Mosher said, “Warren, I am not asking you to do this study, I am telling you to do this study.” So I said, “Yes, sir.” We designed the study and managed to separate the social, occupational, and other factors to demonstrate adverse health effects of air pollution.5
I pursued the cervical cancer and tobacco smoke association because, in considering one of my doctoral students’ work on asbestos and lung cancer, it struck me that the major histopathologic type of the smoking-related cancers was squamous cell, and cervical cancer is predominantly squamous cell. The obvious consequence was the hypothesis that smoking would be a risk factor for cervical cancer.6
PB: Of your many contributions to epidemiology, which would you like to be most remembered for?
WW: Certainly, the case-control study of coronary disease in women, the work my colleagues and I did on air pollution effects, and our HIV studies—the cervical cancer and smoking study as well.
Recently, since the AIDS study terminated, I have been doing a series that I call “Vignettes of the History of Epidemiology.” These are short pieces dealing with various issues, designed really for public health students. One example is my study of Janet Elizabeth Lane-Claypon. Her work on breast cancer has been largely forgotten. My brief article on her life and work will be published in the Oxford Dictionary of National Biography to be published in March 2004. I have also published one on Edward Jenner, largely about his major scientific contribution to the understanding of mitral valve disease, rheumatic fever, and heart disease. This work was known but not fully recognized.
Right now I am writing a piece on Alice Hamilton, the occupational health epidemiologist. Her work is pretty much forgotten by young epidemiologists, and I think it is important to keep our new generation of epidemiologists aware of the important work and the obstacles that people have had to overcome. Alice Hamilton, who was the first woman to be appointed to the faculty of Harvard University, was terribly discriminated against in her academic career. Yet, she made immense contributions to epidemiology.
PB: Having watched the field evolve over your career, how would you describe the state of the profession, the state of epidemiology?
WW: I think it is pretty healthy. Taubes wrote an article a few years ago about “The Limits of Epidemiology.”11 I do not buy this idea of limits, and I do not think most epidemiologists do. Although it is very difficult to conduct epidemiologic studies that distinguish between “no risk” and “some risk,” new tools from the field of molecular biology are increasing the effectiveness of such studies. The increasing recognition of complex social, cultural, and economic issues as factors in disease occurrence present daunting challenges. Furthermore, factors such as the effects of civil unrest, climate change, energy generation, famine, and violence have hardly been addressed by epidemiologists.
PB: What are some of the biggest risks that epidemiology faces?
WW: The biggest risk would be marginalization, because epidemiology has become an expensive science. When I did the study of coronary disease in women, I think it cost us $600 to pay a medical student to collect the data during summer vacation. Today, it would probably cost $600,000 to do the same study. If other areas such as molecular biology become more dominant in terms of funding, then epidemiologists will be forced out of the field. I think that is a big danger.
PB: What advice might you pass along to a young epidemiologist who is starting their career?
WW: I usually say, “Be yourself, and try to realize whatever it is you want to do with your life.” Although it has gone out of style, we used to talk about a liberal education—studying broadly—society, history, economics, not just one thing. Public health and epidemiology are very socially oriented fields. They benefit if their practitioners have a similarly broad view of life and society. I have been very impressed by my colleagues who have benefited from a liberal education and have become very productive. Therefore, its practitioners need to have a broader view of the world. I would probably tell a young epidemiologist that life is much broader than just epidemiology, if you are interested in what is going on and are involved. Alice Hamilton is a good example of this approach. She lived at Hull House where the whole idea was to address multiple issues and to look at people and things as they are, and try to make some kind of contribution to the betterment of one's fellow human beings.
About the Interviewer
PATRICIA A. BUFFLER, Professor of Epidemiology and Dean Emerita at the University of California–Berkeley School of Public Health, was recently named to the Ken and Marjorie Kaiser Endowed Chair in Cancer Epidemiology. She was a student at UC Berkeley School of Public Health when Warren Winkelstein first joined the faculty in 1969 and has worked with him as a colleague since she returned to UC Berkeley in 1991. Her current research interests are evaluating the role of genetic factors and environmental exposures, including exposure to tobacco smoke, in the etiology of childhood leukemia.
The journal gratefully acknowledges the support and cooperation of the Department of Epidemiology at the UC Berkeley School of Public Health for making possible the video recording of this interview. Judy Eshelman carried out the initial transcription of the interview. Nanette Cowardin-Lee assisted in editing the final manuscript and assembling the accompanying materials.
1.Winkelstein W, Jr. Modified nasal diphtheria in immunized persons. NY State J Med. 1950;50:1117–1118.
2.Winkelstein W, Jr., Karzon DT, Barron AL, Hayner NS. Epidemiologic observations of an outbreak of aseptic meningitis due to ECHO virus type 6. Am J Public Health. 1957;47:741–749.
3.Lilienfeld AM. Epidemiology and the public health movement: a historical perspective. J Public Health Policy. 1982;3:140–149.
4.Winkelstein W, Jr., Stenchever MA, Lilienfeld AM. Occurrence of pregnancy, abortion and artificial menopause among women with coronary artery disease: a preliminary study. J Chron Dis. 1958;7:273–286.
5.Winkelstein W, Jr., Kantor S, Davis EW, Maneri CS, Mosher WE. The relationship of air pollution and economic status to total mortality and selected respiratory system mortality in men. 1. Suspended particulates. Arch Environ Health. 1967;14:162–171.
6.Winkelstein W, Jr. Smoking and cancer of the uterine cervix: hypothesis. Am J Epidemiol. 1977;106:257–259.
7.Wright NH, Vessey MP, Kenward B, McPherson K, Doll R. Neoplasia and dysplasia of the cervix uteri and contraception: a possible protective effect of the diaphragm. Br J Cancer. 1978;38:273–280.
8.Plummer M, Herrero R, Franceschi S, et al. IARC Multi-centre Cervical Cancer Study. Smoking and cervical cancer: pooled analysis of the IARC multi-centric case-control study. Cancer Causes Control. 2003;14:805–814.
9.Winkelstein W, Jr., Lyman DM, Padian NS, et al. Sexual practices and risk of infection by the human immunodeficiency virus: The San Francisco Men's Health Study. JAMA. 1987;257:321–326.
10.Lilienfeld AM, Johnson EA. The age distribution in female breast and genital cancers. Cancer. 1955;8:875–882.
11.Taubes G. Epidemiology faces its limits. Science. 1995;269:164–169.
Editors' Note: Voices is a project of the journal to provide personal, historical and scientific perspectives on the field of epidemiology, as seen through the eyes of the field's most senior and accomplished practitioners. Subjects are selected by the Editors. Readers are welcome to nominate candidates for Voices.
© 2004 Lippincott Williams & Wilkins, Inc.