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Harden: Hadn't things popped up from time to time here and there; they kind of came and they went and–I think it would be hard to...
Wyatt: Right, but it wasn't like the other epidemics. One might think about, what's a good example–a dengue-like outbreak or something like that that might occur in a particular part of the world. AIDS wasn't so circumscribed; it wasn't so definable. And of course, there was no agent associated with it. It didn't have the characteristics of, for example, Legionnaire's disease with characteristics of an acute infectious disease that we were accustomed to or might think about as working in the area of infectious diseases. At any rate, it didn't take very long before it to begin to sink in that it was going to be important.
Rodrigues: But, it is difficult to reconstruct the way people were thinking back then because with all we know now we can look back and things seem to be very clear. But at the time, as a number of people said, when you were actually living with the problem, it was very confusing. Certainly there were no easy answers.
Wyatt: That's right. There really weren't easy answers. I was just looking back in my files knowing you were coming, and I found an article that appeared in–let's see, it was March 17, 1983, in the Washington Post. It was actually the conclusion of a series they did called “New Death–Disease of the Immune System Becoming a U.S. Epidemic.” That was March–that was about the same time that we did a workshop that we can talk about some more. There were about 1,300 cases at that time. Some of the people who were involved at that time are still very much involved today. It was just coming–the cases in hemophiliacs were being very clearly recognized. Some of the same people are being quoted; here's Tony Fauci being quoted in this particular news report. You are welcome to have this, if you will give me a copy back.
Harden: That's marvelous. Thank you.
Wyatt: There were certainly more behind that, but that was the one that I happened to keep.
Rodrigues: I was looking through an interview that Vicky had taken with Dr. Sell, let me pass it to you. He's talking about their decision–NIAID's decision–as to how they were going to proceed as far as looking at different possible causes. He mentions the work that you were doing.
Wyatt: He did ask me to come over and help. I was still in the Laboratory of Infectious Diseases, but between sometime early in 1983 and the following year, I was sort of a special assistant to the scientific director of NIAID on AIDS-related research. It was never actually that formal an arrangement, but the activity–while I did some laboratory research on AIDS, albeit very little– initially involved organizing a workshop to consider the various possible etiological agents of AIDS. It was interesting to go back over the workshop in preparation for talking to you, because I happened to save a file on it. It was quite clear just looking through the program that, although we thought the agent was probably a virus, we really weren't leaving any stones unturned at that point. You can almost tell the direction based on the way the program unfolded. We considered a variety of viruses to begin with, including cytomegalovirus, and I think Dr. Gerald Quinnan advocated cytomegalovirus as the etiologic agent.
Harden: So, there were actually advocates promoting things as opposed to...
Wyatt: Oh yes. I don't recall if there was an advocate for the Epstein-Barr virus. We certainly talked about it; we talked about herpes virus; adenovirus; the hepatitis viruses, in part because with hepatitis-B, the routes of spread seemed to be quite similar. We did have a talk on retroviruses, although I didn't see that in the first draft of the program. I found it in a subsequent draft where it was clearly introduced and Dr. Robert Gallo was there to present it. This was a typical NIH workshop, and we were leaving plenty of time for questions. We began to lag behind schedule and Dr. Gallo had to leave. Dr. Edward Gelmann was the scientist working in his lab at the time, and he actually made the formal presentation. I don't have detailed notes on his presentation but my recollection was that he was talking largely about HTLV-I [human T-cell leukemia virus 1] at the time and the similarities that they were drawing there with AIDS. There may be a recording of this still around. I think the session was actually recorded, which would be of interest. I know there was also a recording made of a summary that [Dr.] Albert Sabin did. You may have seen that. It's very rough and it's never been edited. I have a crude transcript of it. We had a fair amount of discussion on parvoviruses, which seemed to have some interesting features that made us think that there might be a clue there. We also talked about some methods for detecting viruses. We talked specifically about immune electron microscopy [IEM] that we'd been working on at LID [Laboratory of Infectious Diseases]. Dr. Kapikian gave a nice talk on IEM using the analogy of how one goes about trying to find a virus or the agent using the materials from the disease. Dr. Phil Russell talked about possible arboviruses that might be implicated. At one point, we thought we might even discuss various kinds of bacteria and parasites that could somehow be involved. That sort of fell away. I guess we realized we couldn't be so inclusive, and we limited most of our discussion specifically in these various virus groups. But we had a variety of experts–Dr. Clarence (Joe) Gibbs was there to talk about slow viruses, Dr. Maurice Greene, from St. Louis University, to talk about papilloma viruses. We really covered the waterfront and, in fact, in Dr. Sabin's summary, one of his conclusions was that to find the agent, “We must cast a wide net.” At that stage in the search for the AIDS agent, we weren't to the point where we could really focus as much as we might have liked. The other thing that I remember specifically was that Dr. Anthony Fauci had talked about T4 cells specifically, that had intrigued Dr. Sabin, and he was urging the search to focus on the T4 cells. This was early April 1983.
Harden: May I ask you a few more procedural things? You set up the workshop for people from across the country who were interested in AIDS–this came out of NIAID–out of the intramural director's office as opposed to anywhere else, and...
Wyatt: There were participants from the Cancer Institute. Ed Gelmann was a participant, and Dick [Dr. Richard] Adamson actually talked on the second day about grant support for studies to search for the AIDS agent.
Harden: Was there any input or initiative from the Public Health Service or the Department? We're just trying to kind of pin down various sources from which initiatives were coming.
Wyatt: They were certainly a part of the program, because I remember meeting with Dr. James Curran on occasion in Ken Sell's office. He gave one of the opening talks–an epidemiological overview of AIDS. As best I can recall, this particular workshop was something that Ken Sell wanted to do. So he was talking to Jim Curran and others at the time. Tony Fauci was at that time a lab chief within the NIAID intramural program, and he also had studies that he was interested in.
Rodrigues: Another thing I came across was a list of some of the different projects that NIAID was pursuing. Some of these became well known; for instance, the work that Tony Fauci and Cliff Lane did as far as attempting to reconstitute some of the patients by transplanting cells from an identical twin. But many of these other efforts were not pursued. Were these ever published? Or did negative results of this type never get into the literature?
Wyatt: Most negative results don't get into the literature. I think the list probably reflects the interests of Ken Sell. He really wanted the intramural program to think about various ways that we could approach the problem. They were ideas that we wanted to try to develop. One of the problems was simply adequate facilities in which to conduct the different projects. I mentioned earlier the rotavirus study, which was a major effort that was ongoing at the time, and now, seven years later, it's still going strong. We're much closer to a vaccine and, in fact, candidate vaccines exist and are being tested. It becomes a management decision on whether to divert attention from another major project that is also a public health problem. In terms of the rotavirus study, if you look at the impact of rotavirus on infantile mortality, it's extreme. It's a very major infectious diseases problem. Ken wanted to try to tap into the expertise that was there and have people think about what they could do, using their skills and using the techniques available in their laboratories to look for the agent. It wasn't long after that, the HTLV-III/LAV [lymphadenopathy-associated virus] story came about, so, quite naturally, a lot of these ideas were not pursued.
Harden: When did NIAID begin publishing the AIDS Memorandum?
Wyatt: I’m not sure, but I know it was Ruth Guyer's work.
Harden: We were sharing an office and she was in the middle of it when I arrived.
Wyatt: Ruth helped out with this same workshop and, in fact, we each drafted a summary of the workshop from our individual perspectives. She was involved right at the same time. It probably was some time in 1983, but I'd have to go back and look.
Harden: Was this another intramural idea to try to disseminate information more rapidly, and was it based on the hepatitis memorandum, too?
Wyatt: That's right. Ruth was working for Ken at that time. The idea was to disseminate information as quickly as possible, including those negative studies that you mentioned that don't find their way into the literature. It didn't make sense for multiple groups to go out and repeat the others' errors. I don't know how long it continued, but that was the beginning.
Rodrigues: There was one other study that I thought was interesting, at least by the title of it. You were looking at macrophage cultures for potential AIDS agents. Given the fact that the macrophage is now considered a reservoir of the virus, you may have been looking at the right thing.
Wyatt: I remember an interesting story about those cultures. Tom Folks was doing them up on the 11th floor in the ACRF [Ambulatory Care Research Facility]. He detected a fungus growing in the culture. Ken may have told you about this. There was a thought that maybe this particular fungus was producing a cyclosporin-like compound that might be playing a role in the etiology of AIDS. There was a letter published on it, not a full article, and nothing much happened after that. But, it was a product of doing the macrophage cultures.
Harden: When did you get into the project of testing all the different kinds of things that you did?
Wyatt: I don't think we really tested all kinds of things. One of the ways I got involved in the AIDS work was as a result of the idea that we should have multiple samples to test. I became project officer on a contract with the New York Blood Center, and we spent most of our time simply designing a system to try to get the right samples, because we didn't know what we were looking for. We knew we wanted to have white cells; we wanted to have populations of T4 cells to study at some point in the future, and we wanted to have them appropriately stored away. We also wanted to collect them from a spectrum of subjects who were being followed and were recruited by the New York Blood Center, so that when we had the right tests, we could go back and look at them. That meant getting the cells frozen away in liquid nitrogen and getting the various other specimens that we stored appropriately catalogued, making sure that we had the a good data collection system. I wasn't project officer for too long because I moved to the Office of Intramural Affairs in the Office of the NIH Director, and Dr. Lois Salzman took over for a period of time. I can't say exactly how valuable those samples were, because LAV and HTLV-III came up shortly thereafter. But that would have been a valuable repository of specimens from the point of view of studying the natural history of AIDS, because we had earlier specimens from people who subsequently came down with AIDS. Also, the New York Blood Center had specimens already collected on many of the subjects before AIDS was diagnosed, so it was a contract that was set up specifically with the idea of looking at the natural history. The effort expanded rapidly into universities and medical centers around the country.
Harden: What happened to those specimens? Are they still there?
Wyatt: As far as I know, they're still in the freezers. We had a routine set-up for sending them to Bethesda and for storing them away, but I don't know how many of them have been used or studied. There was an elaborate scheme set up to do the collections.
Rodrigues: After you came over to OD [Office of the Director, NIH], did you have any continuing involvement with AIDS?
Wyatt: I got pulled into it at a time when Dr. Robert [Bob] Gordon was the person designated to attend the PHS [Public Health Service] AIDS Executive Committee. Bob became ill and wasn't able to go, and Dr. George Galasso was also recruited as a substitute. There were times when he couldn't go, so I found myself during a period of time, in late 1984 or early 1985, going to the Humphrey Building to attend the PHS AIDS Executive Committee meetings and reporting on some of the activities that were going on. I was never extremely involved in that. Not too long after that Tony Fauci began to play a much more prominent administrative role.
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