Interview with Dr. Anthony S. Fauci
This is an interview with Dr. Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID), in his office at the National Institutes of Health (NIH), Bethesda, Maryland, on 29 June 1993. The interviewers are Dr. Victoria A. Harden, Director of NIH Historical Office and the DeWitt Stetten Jr., Museum of Medical Research, and Mr. Dennis Rodrigues, Program Analyst, NIH Historical Office.
Harden: Dr. Fauci, we want to begin in late 1980 or early 1981 and discuss the early cases of what became known as AIDS. When did you first hear about these cases, what was your initial reaction, and how did you approach the initial problem?
Fauci: I first heard about the cases that ultimately turned out to be AIDS from the Centers for Disease Control (CDC) Morbidity and Mortality Weekly Report. The cases were those reported in June 1981. I remember very clearly. I picked up the MMWRand read of these unusual cases among gay men of a strange immunosuppression associated with opportunistic diseases. I remember looking at the report, thinking first that possibly some sort of a drug that the men had taken was toxic to their immune systems, but in the back of my mind was the question that maybe they were infected with an unusual strain of CMV [cytomegalovirus]. We were very well aware that CMV was an important cause of infection in gay men. I thought maybe there was some mutation of CMV that gave a very virulent course in these individuals and was suppressing their immune systems. But I put the idea to the back of my mind.
Then, when the second report came out later that summer, I started to get a little worried thinking that this might be the emergence of a new disease. Very soon thereafter, still in 1981, towards the early fall, it became clear that IV [intravenous] drug users were getting AIDS. I can remember that I started to get goose pimples. I said, “My goodness. This could be an infection that is transmitted by blood and by sex, and I do not have the foggiest idea of what it is.”
We do not usually think of new and emerging microbes as causes of diseases unless we are aware of a new and emerging microbe. We had had a relatively minor experience with Legionnaires' disease. It turned out to be something that was clearly not a public health hazard, though people get it as an opportunistic infection, and some people as a primary non-opportunistic infection. I can remember thinking about AIDS as a potential new disease and saying, “This is something that is really very serious.” I called in people in my group, particularly [Dr.] Cliff [Clifford] Lane, who was still a Postdoctoral Fellow in the laboratory, and I went downstairs to talk to [Dr.] Joe [Joseph] Parrillo, who was the head of the ICU, the Medical Intensive Care Unit. I said that we should get some people with this syndrome in to NIH and study them. Our expertise was immunology, and we were interested in immunopathogenesis. We did not have the expertise to isolate viruses, because we were not virologists. Subsequently, we have all become retrovirologists by necessity, but at that time we were looking at it from a purely immunological standpoint.
Cliff Lane was working on a project about the regulation of the immune system, which was the fundamental area that my laboratory had been involved in since 1968. I asked him, “Cliff, would you be interested in studying a few of these patients?” He said, “It sounds very interesting to me. I want to continue what else I am doing, but maybe I can study some of these patients on the side.” I remember saying, “If we bring these patients in, they are going to get very sick, so maybe we should go and talk to Joe Parrillo and find out if Joe would be able to handle the ICU type patients?”
Joe Parrillo was very enthusiastic. Joe was also a former trainee of mine. He was a fellow in my laboratory, and then he went to New York Hospital, Cornell. Later, he came back to NIH. That is how the connection between us and [Dr.] Henry Masur came about. Henry Masur was a medical student at Cornell when I was Chief Resident in Medicine at the New York Cornell Medical Center. We knew that Henry was very interested in AIDS because he had been part of the group in New York that first reported it. It was almost a simultaneous reporting from New York and Los Angeles. I thought that it would be good to get Henry Masur to NIH and get him involved in the research. Sure enough, Henry came to NIH and joined Joe Parrillo.
From there, there was a gradual, and then an accelerated, transition of my laboratory. It had been 100 percent fundamental immunology, predominantly looking at diseases of hyper-reactivity of the immune system, namely the vasculitides, and the hypersensitivity diseases. I made the decision that we would have to switch over to research on this disease [AIDS] because, as every month went by, I became more convinced that we were dealing with something that was going to be a disaster for society. In fact, I wrote an editorial in the Annals of Internal Medicine in 1982 making a prediction that this was not something that was going to stay confined to a small group. I discussed it with people like [Dr.] John Gallin, one of my close friends and colleagues, and told him that people might think that I was a little strange switching my laboratory over to the study of a new and strange disease–this is the end of 1981, the beginning of 1982–but it was clear to me that this disease would turn out to be a major public health problem.
When you deal with infections that are sexually transmitted and bloodborne, if you think about it, there is no reason to believe they will stay confined to a small group of people, because sex is a universal thing and people donate blood. We did not even have any idea what it was that we was dealing with. Some people, I remember, were a little–I would say–concerned about me. They said “He has been so successful in what he is doing with fundamental immunology and the hypersensitivity diseases. Why does he want to switch over to an area where we do not have any idea what the disease is and in which he is not an expert?” But the fact was, nobody was an expert yet.
In those months, from the summer of 1981 through 1982, we put together our small AIDS group. Cliff Lane, although still a trainee, was interested in making that a major part of what he did; I had the commitment and cooperation of Joe Parrillo; and Henry Masur arrived. We decided that we could do the research. You had to have a group in place. You could not admit patients in a vacuum because these people were too sick. Then we started to switch virtually the whole laboratory over to AIDS research. When the virus became recognized as HIV [human immunodeficiency virus], then what we could do with the research exploded in a mushroom fashion.
Harden: I want to ask you one question before we discuss the early patients. Clearly what you did in your research changed when AIDS came along. Where did you think your career might go before that and how has it been different since?
Fauci: I was on a certain research track, and had been for several years. This was 1981. I had been at the NIH since 1968. I had already, I believe, made some impact on the field of human immunobiology, and I was very happy with that because immunology is a very exciting field. My goal was to continue to dissect out the immunoregulatory mechanisms of the immune system. In fact, that is what I am still doing, only I am doing it within the context of HIV and AIDS. I had a vision that I would continue indefinitely to dissect out the immunoregulatory mechanisms of the immune system, and to apply this knowledge to diseases like the vasculitides, the arthritides, and those other diseases of hyper-reactivity of the immune system. I had a very clear vision of what I would be doing for the next however many years.
When AIDS came, it turned my work around, but not as much as it would appear on the surface. The focus was still the regulation of the immune system, and I would be studying AIDS from the context of what the immunoregulatory defects are. That is the reason why we now study immunopathogenesis from a number of different standpoints. Although AIDS is a terrible epidemic, it is an extraordinary model for gaining insights into the immune system, the likes of which cannot be obtained from any experimental in vitro or animal model.
Harden: Dr. [Richard] Krause recalled the arrival of what I believe to be the first official NIAID AIDS patient (and the second AIDS patient at the NIH Clinical Center). He said that he was at NIH during a snowstorm when a telephone call came from a physician who was referring someone. He said he thought you would be interested in the case. You were here and took the patient. Can you tell us more about this patient and about the first group of patients? These people were very sick. What was your initial strategy?
Fauci: The strategy was to do pure clinical observation and the fundamental laboratory tests that we had at our disposal. I can remember that call very clearly, because it was in the middle of a snowstorm. A patient, who was in a hospital locally in the Virginia area, had a strange syndrome. Interestingly, it was someone who was a twin. One of the first AIDS patients at NIH was someone who had a twin. This was the beginning of the twin studies that Dr. Lane and I have been involved in now for well over ten years. We started them in 1982. The other twin was uninfected. I remember saying that we should bring this patient in and see him. That got the ball rolling. We were going to take a look at the patient and study whatever it was that we could study.
Of interest–and this is why science is so beautiful–is that we had been looking for years at the B-cell limb of the immune response, the regulation of human B cells, hyperactivity of B cells, particularly in diseases of hypersensitivity. We were one of the leading laboratories in the world looking at the abnormalities of human B-cell immunoregulation. We found out, in a paradoxical way, that in the immunosuppressed state of these patients, their B cells were inappropriately hyperactive and turned on. The patients were hyperglobulinemic, they were spontaneously making immunoglobulin.
One of the first papers that we ever wrote was about this. We made the observation back in 1982. We reported in The New England Journal of Medicine in 1983 the polyclonal activation of B cells in patients with this strange immunosuppressed state, even before the virus was recognized. As it turned out, we know now that aberrant immune activation is one of the most puzzling, but nonetheless relevant, pathogenic events that occurs in an HIV-infected individual. It is paradoxical that as such individuals are becoming immunosuppressed, their immune systems are inappropriately turned on. It may be the persistent immune activation which contributes to the immunopathogenic event. We made that observation without having any idea of what we were dealing with. I think that speaks for sound scientific and clinical observation. You make the observation and you do not know what it means. Then, ten years later, you find out that one of the major pathogenic events of AIDS is hyperactivity of the immune system.
I can remember very clearly making this observation. We were following these patients and doing the whole panel of immune parameters on them. We were doing the study to develop a profile of all the patients' immunological reactivity. I remember going into the laboratory from my office to where Cliff [Lane] was doing the tests. I said, “Look at these patients. They all have hyperactivity of B cells. Isn't that interesting?” This hyperactivity of B cells stood out like a sore thumb. Our paper on it turned out to be the first paper that reported inappropriate hyperactivation in patients with AIDS.
Harden: Would you discuss the twin study a little more? This is one of the very interesting areas of research that you have continued through time.
Fauci: What happened is that we admitted a patient, and then several patients thereafter, who were identical twins. One of each pair of twins was HIV-infected, or sick with AIDS–we did not know what the infection was at the time–and the other was well. We immediately said that if somebody was immunosuppressed, we should try to see if we could “re-boost” the immune response of the sick person by transfusing what we call syngeneic lymphocytes from the identical twin donor who was uninfected, as well as doing a bone marrow transplantation. It was a simple, clear cut approach.
The difficulty at the time was that the only patients that we had who had AIDS were patients dramatically and drastically ill. We had no way of screening patients, bringing them in early, and studying them the way we do now. In order to become recognized as having the syndrome, a person had to have been sick. Once a person got AIDS–since very little could be done for them–the clinical course of the disease was usually fulminant. I can remember the intensity of those first couple of years when everybody that we admitted to the Clinical Center at NIH was very, very sick. There were no people coming in who were asymptomatic, HIV-positive. It was like living in an intensive care unit all day long. It was very stressful.
Harden: If I recall correctly, when you initially attempted to reconstitute the immune system of a patient, you got a brief response.
Fauci: We got a transient response, and then it went away. We were able to get a little blip in CD4-positive cells; then it disappeared, and the patients continued to deteriorate. We did lymphocyte transfusions, and we did bone marrow transplantations. It was clear that something was destroying the cells that we were reinfusing. That was certainly indirect evidence that we were dealing with an infectious agent. Everybody essentially knew by this time that we were dealing with a transmissible disease. We did not know what the agent was though. Since there was a seemingly selective defect in CD4-positive T cells, there was much speculation that we were dealing with a retrovirus that was T-lymphotropic. This is the reason why people started looking for HTLV-1, or an HTLV-1-like microbe. The original studies that [Dr.] Bob [Robert] Gallo and others did used techniques to look for retroviruses, because the agent was behaving like a retrovirus in that it was selectively destroying CD4-positive T cells.