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Rodrigues: Are you saying that work helped to define the understanding of the component of the immune system that made those responses possible? If someone told you at that point that HIV was knocking out that particular cell, would you have known that that was the reason that there was this complete lack of immune response, or was the role of that particular cell not known yet?
Lane: I would say that the level to which that cell population was affected was not understood at that time. We knew the numbers were down, but we didn't know that there was not only a decrease in numbers, but really a selective and very precise functional abnormality in the cells of these patients. Now, there is a ton of literature proposing hundreds of hypotheses describing thousands of immunologic quirks of these patients. You take the T helper-inducer cell and you eliminate it, and it's sort of like taking a symphony orchestra and shooting the conductor and not telling them the score to play, and then saying, “O.K., play.” So some people are playing Beethoven and some people are playing Schoenberg; the thing is all discombobulated, and that's what happens in AIDS patients. The helper-inducer cell can't recognize specific antigen, as a result of which it can't call different elements of the immune system into play the way it should.
Harden: Is there some reason it can't recognize it, other than because it's been destroyed?
Lane: That's still unclear. It appeared that the memory subset of CD4 T cells is selectively destroyed by HIV. That's the way it appears right now. So it not only hits the T helper cell; it hits just that part of the helper cell you need to respond to recall antigens at the T-cell level. Everyone is probably exposed to Candida and Pneumocystis early in life and has memory cells to them. You have to believe that they are not well-described, because with these suppressed T cells, why do you get such profound problems with those [infectious] agents–not just in AIDS patients but in other patient groups as well.
Rodrigues: I think it's interesting the way you describe the different types of collaborations that are going on here–you mention folks in Critical Care Medicine; you mention folks in the National Cancer Institute. Some of the people that look at NIH from the outside don't appreciate the diversity; they tend to compartmentalize people in groups. Could you say a little bit about...
Lane: Sure. The early days of AIDS were great in that regard. The early days were really very nice because everyone was excited and everyone wanted to figure out what was going on. Everyone had their own different little area of expertise. [Dr.] Henry Masur had taken care of AIDS patients in New York and he was here. Over at the FDA, a guy named [Dr.] Alain Rook, working with Jerry [Dr. Gerald] Quinnan, had expertise in cytomegalovirus and the immune response to cytomegalovirus. They were interested in studying the AIDS patients as well. You had people like myself who were immunology-oriented. There were people from the Cancer Institute–Ed [Dr. Edward] Gelmann, who had been in Bob Gallo's lab working on HTLV-1, had left Bob and was over here [in the Clinical Center], with an interest in the retrovirally induced diseases. He was working on AIDS before we knew it was a retrovirus. And there were people like [Dr.] Dan Longo, who were a little bit more peripheral at that point in time. Dan was interested in lymphomas and chemotherapeutic regimens, trying to make some contributions. So, there were a lot of people with different backgrounds coming in who were thrown together–not just from NIH, but from the FDA as well. [Dr.] Abe Macher, who was down in Anatomic Pathology at that time, had a strong interest in what was going on. Abe is one of the people who was bringing cadavers in to try to understand the disease. He would bring cadavers, from all round the country, to try to see what kinds of problems the patients had died of. He was doing his fellowship in pathology at that time. He had already done a fellowship in infectious diseases. There was a lot of interaction like that. That was a good time, I think.
Rodrigues: Sounds as if there was an informal network of people that gradually came together.
Lane: Exactly, exactly.
Harden: Was there any connection with people at the CDC [Centers for Disease Control and Prevention] on AIDS–or were they basically doing epidemiology, and therefore, not seeing clinical patients?
Lane: Well, while they weren't seeing patients, they certainly were doing their own research. But until we had a virus, it was a lot of shots in the dark. I would see them at meetings. The meetings were so different; the meetings were small. The meetings were small and they were fairly intimate, where there were good exchanges of information. There you would interact with the CDC people. I can't remember talking with anyone from CDC up here myself. But then we weren't doing things that really were pertinent to them. When we had the virus, the guys from the CDC were up here all the time, talking to Bob [Dr. Robert] Gallo about samples of some coded sera and what he could tell from those sera. I remember seeing them in the cafeteria and talking to them about what was going on. They were very excited.
So, it was, as you say, sort of an informal network of people who began to interact. Those of us who were taking care of patients started to have weekly meetings where we got together, and we started to use some electronic databases to keep track of what was going on. Then it started to expand. The guys in the NCI [National Cancer Institute] were initially looking at lymphoblastoid interferon to treat KS, Kaposi's sarcoma, and I was doing the immunologic monitoring on those patients. It worked out well, because it was the sort of thing where one person couldn't have set it up because it requires too many things, but we had people who knew enough about the different pieces. We needed oncology, we needed infectious diseases, we needed immunology–and we had all of that here. We just fit the pieces in, and I think made a lot of progress pretty quickly.
Harden: I think one of the things that we are very interested in is trying to get a picture of just how this process worked, because I think many people and journalists don't have a sense of how it works. They have a sense that perhaps the way the government deals with things and should deal with things is by appointing a committee that will then direct things. This is not what we are hearing.
Lane: Oh, not at all.
Harden: It begins at the grassroots. Everybody finding people when they needed them.
Lane: We did that because we wanted to do it. No one said to me: “Listen, you have to work on AIDS now.” No one said that. The people were here because they wanted to [work on HIV/AIDS]. That's your best incentive to get people doing something that they like and they enjoy. As I say, it was just the right mix needed to get a productive effort going. There was a lot of collegiality; Henry [Dr. Henry Masur] and I still work very closely together. We built the NIAID intramural clinical program. It's my program and his program that stemmed from all of that. NCI had to develop their own intramural clinical program as that process evolved. But some of those things still exist from the past.
Harden: Did you have any trouble getting support from Ken [Dr. Kenneth] Sell and [Dr.] John Gallin over this period?
Lane: It was great. I can remember, when you say the word “bone marrow transplantation,” you think of a lot of money. Here, it was no money at all, because no one was charging anything. We got the beds and everything else. It was sort of a fixed cost for us, the way we work. When it came to the interleukin-2, I can remember calling this person or calling that person. Finally after getting this astronomical figure, I remember talking to Tony [Dr. Anthony Fauci]. I said, “Well, let's go talk to Ken Sell.” Ken was here at NIH. He was good; he made a great contribution that I don't know will ever get recognized, because it wasn't a publication or anything like that. But he saw the importance of AIDS. He put the resources into it. We went down to his office and explained to him why we wanted to use this [interleukin-2]. He said, “ Two-hundred-and-fifty-thousand dollars–well, sounds like it should be done. We'll do it.” I don't know if you went over to Dick [Dr. Richard] Krause and Chuck [Charles] Leasure, who was the executive officer at that time. I don't know where the money came from; it wasn't from a Congressional appropriation. Somewhere there was the money and we were able to get it. It wasn't a problem. Do you know Ken? Have you talked to him?
Lane: So he got the lab going over there; he brought the people over to culture LAV [lymphadenopathy-associated virus]; he put the resources in to get the thing. He really played a major role in getting the Institute galvanized. It was my perception that he was instrumental in getting this MACS [Multicenter AIDS Cohort Studies] work going. He said that we needed to look at these people. This was before HIV. This is not my approach to science–“Hey, I don't know what it is, but let's get 6,000 gay men and collect every secretion from their body and freeze it, and some day it will be useful.” But that's important to do. You need someone at that high a level to get it done. He was very instrumental and very supportive. I give him a lot of credit. It's a tough position. Everybody wants something from the scientific director. He clearly made this priority, and I was impressed by that.
Rodrigues: Do you remember any particular meetings at that time that were important in helping you make intellectual progress on these problems? We've heard people mention a number of meetings. There was one meeting in New York, I believe in 1982, that people have talked about as a very important meeting.
Lane: I think I know what meeting it was. The New York Academy of Sciences? I think these are the proceedings from that meeting. I didn't find that meeting to be particularly enlightening, to be honest. I found that meeting to be anecdotal. But it was the first time, I think, that a large group was brought together to discuss the problem. I was at that meeting, but I just didn't get that much out of it. I generally knew what was being said, because it wasn't a very scientific meeting. What I'm saying is that there was a lot of description. This is what Kaposi's sarcoma looks like. This is what Pneumocystis carinii pneumonia is. But then what? I guess that was all that could have been said. I wouldn't say that was a key point in my academic development.
Now, a meeting that was important, and people will probably mention, is the Cold Spring Harbor meeting shortly thereafter. That was a group that [Dr.] Bijan Safai put together. I don't have the proceedings from that. I don't know whether there were proceedings from that. That was the first time people talked about a retrovirus. Some people from [Dr. Luc] Montagnier's group presented some data, saying that this might be something. [Dr. Robert] Gallo was there presenting the stuff they had at that time on HTLV-I and serologic cross-reactivity. We presented the polyclonal B-cell activation for the first time there. There were a lot of things, as you start to think more. We were talking about acid-labile interferon being elevated–a lot of things that weren't generally known were coming out in discussion. It was a fairly informal setting. We met, had presentations, discussion, ate meals with these same people. We were there for about two-and-one-half days. I remember driving in from New York. It was snowing very heavily. I was in the cab with Marty [Dr. Martin] Hirsch who is a virologist from Massachusetts. I just can't think who the other person was. There were three of us in the cab. It was snowing so hard that the cab driver had to pull over, so he took us all out to a bar. We were sitting there discussing AIDS, well, trying to, because we didn't know anything about AIDS then. We had seen a few patients at most. But I remember those times so vividly.
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