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Interview with Dr. Richard G. Wyatt
This is an interview with Dr. Richard G. Wyatt, Office of Intramural Research, Office of the Director, National Institutes of Health (NIH), who was formerly a Senior Investigator at the National Institute of Allergy and Infectious Diseases (NIAID). The interview is being conducted by Victoria Harden, Director of the NIH Historical Office, and Dennis Rodrigues, Program Analyst, on March 28, 1990.
Rodrigues: Maybe we could start with why individuals choose their line of work. Why did you decide on a career in medicine?
Wyatt: That goes back further than I thought you were going to go. A career in medicine in my case goes back to a high school interest in science fair projects. Initially, I made a photoelectric eye in the ninth grade; it won fourth place in the Lebanon [Missouri] High School science fair. After that I quickly switched to biology. During my sophomore year, in 1958, I did a project in tissue culture. I took some embryonated eggs, removed the embryos and transferred them over into some tube cultures and watched them grow to a certain extent. I'm not really sure how well they grew but that was my early tissue culture work. In 1959, I moved on to histopathology, comparative histopathology of liver tissue, where I took livers from various species beginning with crayfish liver, or at least a digestive organ. We even got a fixed specimen of a human liver from a local area pathologist.
Harden: Did you come out of a medical family that encouraged you to do this?
Wyatt: My uncle was a doctor, and he probably did influence me. It was interesting to compare the morphology on these different livers and also that same year, I remember that in our high school biology class–this was advanced biology, Biology 2–we sent away to the American Type Culture Collection for some Rous sarcoma virus. We injected the Rous sarcoma virus into a series of chickens and followed the tumors that developed. I don't think high school students would be doing that kind of experiment today, but that was in an era before things were highly regulated. It worked together very nicely with our histology studies; we sectioned them and looked at the histological features. I remember that several years later after I was here at the NIH, we went to a “Perspectives in Virology” meeting in New York–in about 1972. I met Mrs. Peyton Rous and was reminded of that project.
Rodrigues: Maybe you could move up in time, then, and tell us about your professional experiences immediately before you came to NIH, or perhaps why you came to NIH and the circumstances surrounding that.
Wyatt: When I came to NIH it was during the era when each of us, as a physician, had an obligation to the Federal government, that was the so-called “Doctors’ Draft,” and I had a choice to make. I was involved in pediatrics and I could go to the Army to continue my pediatric training or come to the NIH and do biomedical research as an NIH research associate in the U.S. Public Health Service Commissioned Corps. It was an easy choice to make because, as I mentioned, my interests in doing research went all the way back to high school and continued during college and medical school. In medical school at Washington University, we had the option of doing research in our senior year. I committed most of my senior year to conducting infectious diseases research with Dr. Ralph Feigen, who has moved on from Washington University to Baylor College of Medicine. He's now chairman of pediatrics there and still very involved in infectious diseases research. Making the decision to come to the NIH, and, specifically, to seek out an area in infectious diseases research, was a very easy one. Initially, I fully intended to go back to Washington University or to another university and continue in academic pediatrics.
Harden: I want to explore this a little more. I've been asking a number of people that I've been interviewing, was it just the interest in science or were you not interested in going into private practice? In other words, was it either academic medicine or research as opposed to private practice? I'm just taking a poll of various people to see what factors influenced that decision.
Wyatt: I tend to shy away from the routine that private practice becomes or would become or I thought might become. That was something that I came to without ever having experienced it. Since I enjoyed patient contact, however, I had every intention of going back at least into an academic setting that would have placed me squarely in contact with patients. Knowing that I like variety in what I do, biomedical research is a “natural” because it's constantly changing and there's never really a routine. There's always something new and exciting going on. That's probably the best quick answer.
Rodrigues: With your background and/or interest in infectious diseases, I assume that you then began your career at NIAID.
Rodrigues: Which lab did you work in–and whom did you work under initially?
Wyatt: I was with Dr. Robert Chanock and Dr. Albert Kapikian, who are both still in the Laboratory of Infectious Diseases. Dr. Chanock is the chief, and Dr. Kapikian is the head of the epidemiology section. That's where I landed in 1971. I was invited to be a research associate in that lab. When I came here, I didn't really know which of the three infectious diseases I'd be working on.
There were three options: respiratory syncytial virus; hepatitis, at that time largely hepatitis B work; and a new project that had just started a year or so before on infectious diarrheas. There were three of us as research associates who came that year. Dr. David Hodes, now at Columbia [University] is in pediatrics. His father was Dr. Horace Hodes, a well-known pediatrician and infectious diseases specialist many years ago. And Dr. Steve Feinstone, who continued in the Laboratory of Infectious Diseases until recently, when he transferred to the FDA [Food and Drug Administration] with Dr. Gerald Quinnan. He's still in hepatitis research, which is where he started in 1971. I began with the group that was just beginning to look at the etiologies of infectious diarrheas. At that point, we really didn't have any viruses in hand, so we had to start at the very beginning. We were working with a disease and looking for the etiological agents that were associated with that disease.
Rodrigues: Were there certain areas where this disease was more prevalent than other areas?
Wyatt: Well, yes. I guess, in a sense, as a pediatrician it attracted me because pediatric diarrheas are quite prevalent and serious in the very young children, and in the Third World countries in particular. That wasn't our initial focus of research, although it came to that eventually. The international aspect was of interest to me because I had spent two summers as a medical student with NIH support doing research in Guatemala City, at the Institute of Nutrition of Central America and Panama. There I met somebody who was interested in nutritional diarrheas and weanling diarrhea, as it was called. That was Dr. Leonardo Mata, who is still active in biomedical research in Costa Rica. He stimulated my interest not only in working in Third World countries, but also in the whole area of infectious diarrheas and malnutrition. It began to fit together. As it turned out, though, when I arrived in the Laboratory of Infectious Diseases at NIH, they were tackling the problem not of infantile diarrhea but of epidemic diarrhea and vomiting, which is a disease that affects all age groups. This disease moves through a family or an institution, causing diarrhea and vomiting: sometimes one, sometimes the other or sometimes both, in about 50 percent of the population. We became involved early on in reproducing that disease in volunteers by administering bacteria-free fecal filtrates. We would observe the disease that resulted, but even more importantly, we then had the diarrheal stools from those volunteers that we knew contained the infectious agent, presumably a virus, because we could passage the disease by making bacteria-free fecal filtrates from the diarrheal stools of ill volunteers and passing the disease again. It was ultimately by examining at those fecal filtrates with the immune electron microscopy that we were able to detect for the first time the Norwalk virus, a 27-nanometer virus-like particle that has been associated with the disease. Those studies were led by Dr. Kapikian.
Rodrigues: So, I take it there wasn't a good animal model for this disease.
Wyatt: No. In fact, there still isn't for Norwalk virus. We could infect chimpanzees, but without disease.
Rodrigues: Just like AIDS.
Wyatt: That's right. At any rate, animal models for that disease weren't there. Later on, we became involved in early studies in rotavirus diarrhea, which brought us into the pediatric age group specifically. It turns out that the rotaviruses are the most important cause of diarrhea in infants and young children under the age of two. It's a particularly important disease in Third World countries.
Harden: Rotaviruses are what you've been publishing on.
Harden: Were you still working on it when AIDS popped up?
Wyatt: Yes. In fact, at the time AIDS emerged there would have been features about our lab that would have made it an ideal laboratory to begin to delve into the etiology of AIDS. I've often thought about why we didn't do that, but it wasn't a direction in which the leaders of the laboratory moved us. A part of that had to do with the fact that we were making very good progress in rotaviruses, and at the time, we were developing potential vaccine strains. We had a lot of work going on in the lab dealing directly with preparations that might ultimately find their way into human subjects as candidate vaccines and, ultimately, as a vaccine that might be used worldwide to prevent rotavirus diarrhea.
Of course, when AIDS first came along, there wasn't any way of knowing what the agent was. We all suspected it was a virus, but we can talk about that some more. So to bring materials, possibly containing unknown etiological agents, into a laboratory where we were working on candidate virus vaccines didn't really make sense. Without setting up a totally separate area, it would have been extremely difficult to do that work in the laboratory, so my own “hands on” experience with AIDS research is rather limited. I recall once doing some studies with Dr. Robert Purcell, who worked on the second floor of Building 7; I worked on the first floor. We set aside one room in the Purcell lab to do some limited studies with materials from AIDS patients. We were particularly interested in to growing some cultures for fluorescence staining. We didn't actually grow the cultures; we just processed them. The product came, I believe, from Dr. Tom [Thomas] Folks, who worked with Dr. Kenneth Sell in Building 10. He was looking for any evidence of an infectious agent at the time. We were considering a couple of different possibilities, neither of which turned out to be the agent.
Rodrigues: Some of the people we've talked to–this may be somewhat of a digression–had mentioned that people working in the infectious disease area felt somewhat disenfranchised. There seemed to be so much emphasis on the chronic diseases, and the general level of support and concern expressed by the Congress and the public didn't seem to be as great concerning infectious diseases. But there were a number of people that maintained that this was a poor philosophy. How did you view the growth of support for the chronic diseases, and did you feel that it posed problems for those of you working in infectious diseases areas?
Wyatt: One brings one's own perspective to that question. I was, for the first 12 and a half years here at the NIH, working in Building 7 in a lab that had for many years been focusing on acute infectious disease processes, whether it was influenza or some of the other respiratory viruses, hepatitis, the infectious diarrheas, etc. In my world, we had an emphasis on the acute infectious diseases. I wasn't aware of that until, for example, I saw the emphasis on chronic diseases reflected in the program at the American Epidemiological Society. Both Drs. Chanock and Kapikian were members, and I was invited to become a member in 1982. We discussed that because this relatively small society had focused on acute infectious diseases or infectious diseases in general only a few years before; the society had begun to develop a strong chronic disease orientation. But in my own research, this emphasis on chronic diseases didn’t affect us because of our long-term commitment to acute infectious diseases.
Harden: I'd like to try to reconstruct the ignorance when AIDS first popped up. Can you recall when you first heard about the unusual cases, the kinds of conversations that went on, and the way the thinking went?
Wyatt: I remember specifically, the first time I heard about AIDS, I was in our office over in Building 7, and Dr. Harry [Harold] Greenberg, who later moved to Stanford, and who was in the lab for several years, came walking in with a newspaper article that had just appeared about what would later be known as AIDS. He said, “You know, this is really going to be something important.” I looked at the article, and I guess I wasn't as imaginative or creative or perceptive as he was. I said, “You really think so?” I didn't see that. It was very early on when the first cases were being reported in the newspapers, and so I didn't quite capture the importance of it as he had just from reading that initial news report. I don't recall at the very outset the extent of agreement as to the importance of this new disease complex.
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