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Rodrigues: I may have missed the answer to this question in your book, but I would like to understand why HTLV-I seems to be isolated in various geographic regions around the world?
Gallo: That is a very good question.
Rodrigues: From my reading, it seems as if the method of transmission of HTLV-I is very similar to that of HIV, and HTLV-I has obviously been around for a long time.
Gallo: HTLV-I is limited geographically much more, at least in causing large numbers of cases in endemic areas, to select parts of the world than HIV has already become. The reason is that HTLV-I, though it is transmitted by precisely the same routes as HIV, is transmitted less efficiently because it does not transmit as an extra cellular virion. Remember that I told you we isolated HTLV-II from fluid. That was very difficult. The retroviruses are very poorly infectious as free virions, we believe, because the envelope is very fragile. The envelope falls off very easily. To get HTLV-I to infect, the whole cell and cell-cell contact are needed. So we think that HTLV-I is mostly transmitted as the DNA provirus rather than as a virus. Consequently, it does not mutate as much because that is a more stable form and with fewer rounds of infection, there are fewer chances to mutate. HTLV-I tends to stay within families and be transmitted with particular difficulty. The usual route of transmission is mother to child by milk. Transmission can occur in sex, but it is more difficult. It can occur in blood transfusion.
In studying HTLV-I in endemic areas of the world, it is almost like studying a gene. You can follow migrations of people in ancient times. [Dr.] Carleton Gajdusek has used it in this way as a tool, in his laboratory, in studying Melanesian people and aboriginal Australians in areas where HTLV-I is endemic. It can be used to follow some of the demography–or whatever the right word is–when you study populations, their movements, their genetics, and so on.
Harden: It is time to shift towards AIDS. I will ask you first the one question that has fascinated me, and actually was raised by Mirko Grmek in his History of AIDS, about whether AIDS is an ancient disease or a modern disease. Why did this disease, in your opinion, appear almost immediately after the first human retrovirus had been identified? It almost seems mystical. Grmek suggested that a shift in the balance of diseases in the world occurred: we eradicated smallpox and along came AIDS. But do you have any opinions about the fact that just after the first human retrovirus was identified, we had a retroviral epidemic?
Gallo: AIDS being identified right after the discovery of the first and the second human retroviruses is one heck of an extraordinary phenomenon. All I can say is that it appears to be a coincidence. It has actually misled me. As well as leading me right, it also led me wrong. I put that in my book. For me, AIDS could not conceivably be a different category of a retrovirus. We predicted it was a retrovirus; we were right. We dictated, of course, that it would be in the HTLV family. It was not. So, actually, I think our level of confidence, that we were getting good at predicting, or hypothesizing, probably cost us six months in working on this problem. When I look back on it, we should have had this problem solved in 1982, before the first experiments were even done in France. We started reasonably early, by May of 1982, and should have been done by the fall of 1982, by the end of 1982 at the latest, but we just could not conceive... This is another example of knowing too much, but also not enough. From our experience with HTLV-I and HTLV-II, we thought that we could predict how best to isolate this virus, and we were following our procedures a little too blindly.
But I cannot explain the appearance of AIDS, other than by coincidence. It is possible to say that HIV was identified because of the experience with HTLV-I and II. We were able to think about a retrovirus because we had HTLV-I and II, and we had all this technology, so that made the identification fast. If it were not for that, it might have taken fifteen years. Then you would not say it was close; the events were fifteen years apart. But even that is close. I have to say I think it is a coincidence. I do believe I know the origins of the virus and the origins of the epidemic. I believe I have given the same story since 1984. I do not believe that I have changed my mind in a decade and I do not think any data have appeared that are against what we first said in 1984. But that does not help me in answering the question you raised.
If you want to go through the origin and evolution of HIV and why it became visible in our time, I think I could explain that, but I cannot explain it as following on the heels of HTLV-I and II.
Harden: I have one related question. We have asked many people, and we would like to have your opinion as well, that if AIDS had struck in 1955, instead of when it did, how would we have responded to it?
Gallo: This is not an opinion. No one can give you a different answer unless they do not have any information–and you would not be talking to anybody like that. Everyone has to give the same answer. Obviously we would have been in a dark box. We would not have known the retrovirus existed for I do not know how long. In 1955 we did not know T cells from B cells. We only knew lymphocytes. So, first of all, we would never have known about a decline in CD4 cells. We would not have known to look at CD4 cells. Secondly, we could not have grown T cells to culture. Thirdly, we had no framework to think about the genome of a retrovirus, so all the advances in understanding of it could not have come.
Could the retrovirus have been isolated? Possibly, but with enormous difficulty, or through some freak accident, because we could not grow T cells. We would not have been able to churn enough in the primary cells to put them in the cell line, as we did, and were only able to do, by late 1983. Very few people had done this at all even then, so I do not see how the virus would have been identified in 1955. Certainly no one would have believed in this kind of virus. They did not even know what this kind of virus was. This was before Ludwik Gross. 1955? All that was known was a chicken sarcoma virus and you did not even have mouse mammary tumor virus by then. You did not have anything. This was just a chicken virus that produced a sarcoma, and these Visna kind of viruses were probably not even known then. Maybe they were. I do not know. Certainly nobody on earth knew them but a couple of veterinarians. There is nobody who could answer your question by saying that we would have moved quickly.
Harden: Not even in recognizing epidemiologically that we had a...
Gallo: Sure. If you did the epidemiology before HIV was known to be the cause, you said, “Geez, it's in gay men.” Eventually you got some people acquiring it through blood transfusions, so you would have known that it was in gay men and people who had had blood transfusions. I doubt if you would have seen it in heterosexuals. You would never have figured it out. The mother-infant transmission would eventually have become known, that something was being transmitted–the theories that it was noninfectious would have gone away, little-by-little.
When I proposed a retrovirus as the cause of AIDS in 1982, the leading theory for the cause of AIDS, which continued until mid-1983, was that semen was the cause. [Dr.] Gene Shearer of NCI, for example, thought that. I walked into the Cold Spring Harbor Laboratory Meeting–I think I put this in the book–opened the door, and [Drs.] John Fahey, [Robert] Bob Goode, and several other prominent immunologists were in the front row discussing this theory with great enthusiasm. I remember I did the wrong thing, I chuckled. I was in the back and they all turned around and I said, “Women," They just looked at me and they buzzed to each other and they said, “We are talking about a special form of sex.” I looked at them and I said, “Women. If semen was the cause of AIDS, I think women would have got AIDS some time ago.” That was the central point. It is good sometimes to think simply and not be too complicated. They had these very complex immunological theories of antibodies to leukocytes and semen that got into the blood through the rectum and then this produced this and it cross-reacted with T cells. It was really an interesting theory. But, I would say, the theories about the cause reverted to infection by the middle of 1983. Most people were accepting the notion of an infectious cause by then. That had not come out before HIV was discovered.
But, look, in March of 1984, NIAID had announced that a fungus was the cause of AIDS. So, there was a great reluctance to think of a retrovirus as the cause of AIDS. My friend [Dr.] Paul Black wrote a letter to the New England Journal of Medicine about why it was ridiculous to think that a retrovirus could be the cause of AIDS. After all, we know retroviruses cause cancer. Right?
Rodrigues: I found your comment interesting that looking back on the situation now you feel as though things could have moved faster than they did.
Gallo: No question.
Rodrigues: But yet, from our perspective, it seems as if the NIH's mission and its commitment to long-term research goals were opposed to its capability to deal with rapidly evolving public health problems, as the CDC was able to do. There was not much collaboration with CDC, or historically that was just not going on. NIH did not immediately tackle those sorts of problems.
Gallo: We did not move on them? Look, it has been said that work on AIDS from 1983 to 1985 was the fastest progress in the history of medicine from the inception of a new disease. I agree with that. I think it was enormously rapid progress. Whatever you want to give credit to, molecular biology, immunology, perseverance, NIH funding, hard work, and good ideas all had something to do with it. Whatever that sounds like, that is the truth. It was not some simple thing, and NIH did the bulk of the work. That is, I think, important to understand. Now, if one wants to be self-critical, CDC did the bulk of the epidemiology, but the bulk of the laboratory work in eliminating the virus causes of disease and in finding the right one was done at NIH. The problem was we really did not have a mission, or do not have a mission. I only worked on finding the cause by accident, by chance, by whim, by feeling that we ought to work on it, that we could, and that maybe it was a good idea.
But, in saying that things could have gone faster, I did not mean NIH could have gone faster, I meant me personally. That does not mean that we were not a little thick in the 1982 period by not being open enough to what was in our... But I really think that, with a little more attention to a couple of details, I could have had the cause of AIDS in hand sooner by a solid year. I was just too much influenced by what I understood from HTLV-I and II. I was waiting for things to be happening in exactly the precise way that they would if it was a member of that family. If you want, I could elaborate on that, but it is a little technical. It is not very difficult technical material, but it may be boring.
Regarding collaboration with CDC, at that time, remember, we had not done research on a public health problem before, at least my laboratory had not. I did not even know what CDC was. I had barely heard of them. I only know that when I wanted donor-recipient matched blood, because clinicians were calling me to say they liked the idea of the retrovirus and wanted us to get an aliquot of the blood, the blood went to CDC and it was not easy to get. Maybe I should not be saying that, but maybe I should, since at least one person from CDC has never been bashful. That was the origin of many problems. We did not get donor-matched blood–it was going elsewhere–that would have helped greatly in determining the etiology data. There was not that kind of cooperation.
Harden: I would like to come back to that in a moment. First, I would like to go through events chronologically. In September 1981, the NCI sponsored a conference on opportunistic infections and Kaposi's sarcoma. This was the first official meeting relating to AIDS. Can you recall that conference and what your thoughts were at that particular time?
Gallo: I get the conferences mixed up.
Harden: This was in 1981, right after the first publication from CDC. The very first one.
Gallo: There were two conferences I went to that affected me. The one that affected me most was when [Dr. James] Jim Curran was provocative, but I do not know which one that was.
Harden: That was later.
Gallo: That was later? I do not think the disease was exciting to me, to be honest, the first time that I heard about it. Yes, it was interesting, but it was small... Early on, things like that were used against everybody in the government, against NIH. It was said that we did not care because it was gay people who had the disease, but this was certainly not true among scientists. As a matter of fact, I cannot comment beyond my experience in my laboratory, but at NIH itself I never saw anything like that.
The fact was that it was an obscure disease of a small number of people at the time. I was working on leukemia, working–a little bit–at the time on lymphoma, and on a plastic anemia. We already had these viruses in hand. If somebody tells you that a disease called Kaposi's sarcoma, that you had heard about but did not know much about, a rare disease in old Jewish, Italian, and Greek men, has now been found in some gay men in San Francisco and in New York, you say, “Okay, it's interesting.” But how many interesting things do we hear about every week in NCI or at NIH? If I started looking in a newspaper and responding to every report about disease incidence, I would be working on a different disease every two weeks. So we did not pay too much attention, although [Dr. Edward] Ed Gelmann, who is now the Associate Director of the Vince Lombardi Center, was my postdoctoral fellow then, and we talked a little about it. Ed decided–or we decided together–that he would probe Kaposi DNA for HTLV-I related sequences part-time. This was at the beginning of 1982.
I think the first experiments in this laboratory were in February of 1982. By May of 1982 [Dr. Mikulas] Popovic started doing some culturing, part time, and by the summer of 1982 so did [Dr.] Prem Sarin.... So I already had two people culturing samples part-time by the spring/summer of 1982. That is a fairly early involvement for the National Cancer Institute, with nobody asking us to do this, and no obligation to continue.
Now, you can argue that maybe NIH should have had some mission of working with CDC at a higher level saying, “Hey, here's a new disease. Let's put some good virologists on to this and some on to that. Let's hear their ideas and support them to do something.” But that was never done. Collaboration was all by chance.
Jim Curran of CDC was a positive provocateur. He was saying, “Where the heck are the virologists in this?” He really tried to stimulate some response at NIH, and I listened to him and I got stimulated.
Harden: Dr. Curran was telling us that he thinks your decision to begin work on AIDS was made at the meeting of the National Cancer Advisory Board where you were supposed to be honored for your 1982 Lasker award. He more or less upstaged you because he was giving an epidemiological report on AIDS. But you chatted with him beforehand and became intrigued because the disease involved T cells, on which you were already working. Can you recall that conversation?
Gallo: My memory is funny. I recall more that it was a sunny day, and I recall more the walk back to the laboratory. I recall more that he provoked me, in a way. I was not angry, but it was a little disturbing to be challenged as to “How come there are no virologists involved? Where are the virologists?” and so on. Curran was certainly thinking of a viral disease as early as anybody in the world, I would say.
I think he was telling me that this was an interesting disease, that it was now more than just a few cases, that it was growing, and that it was important. Things like that I remember. But I probably learned, even though it was published by clinicians, about the CD4 drop from him. And here we were, a laboratory that was doing a lot of work in T-cell biology, and also in virology, and I came back from this meeting and I remember that there was no loss of time in having a discussion with people in the laboratory. I said Curran has got a point. He is an epidemiology fellow from this place that I was now beginning to hear more about, I guess, based somewhere in the South that follows the epidemic. Maybe we should be looking at some of these cases and maybe we should talk to some clinicians. That is how it went.
But he is right. He was the prime mover. If I looked at this historically I think he has been somewhat forgotten, but I would say that he was the prime mover in the entire government. From my perspective, Jim Curran was the prime mover to get people thinking about the disease and doing something.
Rodrigues: We have been going through many records, and one of the groups that seemed to be formed very early on was a Cancer Institute AIDS Task Force, or Advisory Committee.
Gallo: That is right.
Rodrigues: I gather that you chaired this group?
Rodrigues: The part of the story of that group that we could not uncover is actually how it got together, how it was formed. What was the genesis of that group?
Gallo: I think it was just me telling [Dr. Vincent] Vince DeVita that we needed to do something. I needed to get together a band of people. I did not know exactly how to do it. Could I get a little help? Could I get their travel paid for or something like that? I had not had any administrative experience before on something like that. I just said I wanted to do this.
I gathered people together. First, it was my laboratory and then a few people from around the campus, such as Tony Fauci and Sam Broder came. [Dr. Robert] Bob Redfield came over from Walter Reed [Army Medical Center], so it did not cost anything. But then we wanted to bring in a few people, such as [Dr. Myron] Max Essex and later [Dr. William] Bill Haseltine, and [Dr.] Dani Bolognesi, and some clinicians like [Dr.] Jerry Groopman. As I already said, Redfield came, and [Dr.] Marc Kaplan, people whose thinking I had confidence in, and we hashed over some ideas. Others were Peter Fischinger, and a few people at Frederick. Little by little it grew into a larger group. [Dr.] Wade Parks was another. We just met and debated and thought about what were priorities in trying to figure out what was going on.
That is how the Task Force happened. I think that I just called DeVita up. We had that kind of relationship. That is what is important about access to a Director for the scientific staff. It was not always the same. I had a good relationship with DeVita. I just called him on the phone and said, “I think we should do this," and he agreed.
Rodrigues: How long did that group stay together?
Gallo: The person to get all that history from, she recorded just about everything, is Ann Slisky. Ann Slisky left here to go with her husband to Merck, and then she worked at Rutgers [University] for a while. I think, because of having babies, she is now staying at home. But, if I think again, maybe I have heard that she is back working somewhere. But we have her telephone numbers. She is wonderful. She remembers things. She took notes at every one of those meetings. I do not know where all her notes are right now, but Nancy Miller, who is now one of Fauci's administrative persons and who used to work here, would know where those records are. Ann Slisky's notes would be important, I think. She recorded all the people that were there, and when the meetings were held, and basically what was said and done.
Harden: Was there any formal connection between that group and [Dr. Robert] Bob Gordon's working group out of Building 1?
Harden: We have identified a number of different AIDS Working Groups.
Gallo: Yes. It was the first and only administrative thing I ever had responsibility for in my life, other than this laboratory.
Gallo: I did not even know Bob Gordon had one. No. I started the vaccine group too. I thought I would continue with this kind of activity and, immediately, when we knew the cause of AIDS, I went to talk to [Dr.] Hilary Koprowski. We had a meeting in his office with Dani Bolognesi and Peter Fischinger and we tried to do the same thing, have a discussion group for a vaccine. We continued our discussions for a while, but the politics were strongly against it. That group did not last.
Harden: We will stop for now, and continue later. Thank you, Dr. Gallo.
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