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Now, what was the reality and how did our thinking change? We continued looking at other patients. We got something from Chardon a few more times. But from the bulk of AIDS patients we did not. I brought [Dr. Phillip] Phil Markham, our contractor and close colleague from ABL [Advanced Bioscience Laboratories], into the problem and also another person in my laboratory, [Dr. Mikulas] Mika Popovic, in addition to the people already involved. Their goal was to try to see if we could establish linkage. They were not to worry about producing the virus for a long time; just to see if they could detect this new virus in patients with AIDS. By the summer or maybe the fall of 1983, they were starting to get a significant number of detections of this virus in short-term culture and, most of the time, no HTLV-I relatedness at all. Yet we had a few other immortalized cell lines coming along that also had this cytopathic retrovirus and that did have the HTLV-I relatedness. The light did not dawn yet, and I will tell you what was happening in a second.
By September of 1983, we were preparing for the Cold Spring Harbor meeting. What happened at that meeting? One, we learned that Montagnier's data had progressed some. He now had about five cases in which he had some, at least short-term, detection or isolation of this kind of virus. I did not present our isolates. We did not say anything yet. [Dr.] Marjorie Guroff presented our serology data, our antibody testing data, using HTLV-I and HTLV-II as probes. She said, “I cannot understand this. It is just 35 percent, and we are getting, with all kinds of assays and even with loosening the conditions, only eight to ten percent.” I looked at Popovic's records, at Markham's records, and at Salahuddin's records, and they were getting isolates of the virus less than 10 percent, somewhere around 5-10 percent, that were HTLV-I related. Yet a number of times they were finding something that we could not get a handle on, that did not grow well, but had no HTLV-I relatedness that we picked up.
It finally dawned on us that those instances where we had the HTLV-I relatedness were doubly infected. Chardon received blood transfusions in Haiti, an endemic area for HTLV-I. He was doubly infected.
Why did we not think of it earlier? It depends on how you look at it. Whether we knew too much, or too little. In a sense maybe we knew too little, but we knew, in a sense, too much. If you have an HTLV-I-related retrovirus as the cause of AIDS, or an HTLV-II retrovirus as the cause of AIDS, or something coming along that fits closely with that family, generally speaking there will be interference–if you are infected with one, you will not be infected with another–so I was not expecting two viruses. It was a whole new category of retrovirus. It was a lentiretrovirus infecting the very same cell. So we realized by September 1983 that we were seeing double infections in those that we had been trying to characterize the best. This probably cost us a solid six, or maybe eight, months in time of confusion, and that is what you can bang your head on the wall over. I try to think of what the lessons are in this, but I do not know. Certainly, coming back from the Cold Spring Harbor meeting, we knew exactly what to do. We needed to mass produce, in one way, by getting just the cytopathic retrovirus. Popovic already had that as a goal but, at the same time, was accepting anything that was HTLV-I related, from the double infections, and that would cause confusion. We could not use as a blood test to try to prove the...to get a lot of antibody data linked to AIDS because you would have the mixture of the viruses, so it would be a very difficult interpretation.
We were still not convinced of the etiology, by any means. We were convinced that this was the right path, the best path. You have to recall the time. This was the time when an adenovirus strain had been claimed by [Dr.] Marshall Horowitz, from Albert Einstein [Medical School], as a good candidate for the cause of AIDS. This was the time when according to an odd theory, EBV (Epstein-Barr virus) variants were thought to be the cause of AIDS by people from NYU [New York University], because there was so much B-cell proliferation. I do not think, in retrospect, that that idea was very good. It was also a time when some people were proposing chemicals. It was a time when people were proposing poppers. It was a time when [Dr.] Gene Shearer had proposed semen as the cause of AIDS, and I came to the meeting at Cold Spring Harbor and asked, “What about women who had been exposed for a few years before AIDS ever appeared?” But the immunologists were big on that theory. So the retrovirus theory was still not a forefront theory. But by that period, September 1983, we had enough short-term detections of the other thing to make this a very high priority–that is not the word, it was always a priority–but now it was becoming a probability instead of a good idea. But we still did not have the data in hand until the production came.
When the mass production came we knew. On 23 December 1983, there was a Christmas party here. That Christmas party was kind of a routine event at the time. But that day Sarang, our collaborator, [Dr.] M. G. Sarngadharan, came to see me and told me that there was an advance that was being withheld from me because they were afraid I would talk too much about it and get too excited. That step forward was, “That Mika [Popovic] knew how to culture the cytopathic retroviruses.” That was a plus. Indeed, it was a plus. Popovic had by then been able to put into cell lines several HIV viruses–not just the virus from France–which at the beginning was difficult to grow, but the virus that France sent us the last time was a contaminant which Mika was able to grow for the first time, but he lost one culture. The second culture he had–I did not check that data–but when I knew we had so many other isolates, I told him, “Focus on our isolates. Put that aside.” By February, let us say of 1984, we had enough data to conclude that this retrovirus was the cause of AIDS, for the most part. We had a lot of detections, short-term isolates. Popovic had 10 viruses in cell lines by then, HIVs. These were the first 10. Nobody else had any. Of those 10, in retrospect, by the time we submitted the papers there were 10, two were contaminated with French virus, but eight were not, and the 48 detections and isolates that I described were all documented in the most intensive evaluation probably anybody had ever been through. We felt this data established the cause of AIDS. But the production of virus in quantity was necessary to get enough pure virus, or relatively clean virus, free of cell debris, so there would not be cross reactions. Large-scale testing could be done rapidly. In my mind, this serologically defined this kind of virus as the etiologic agent, when it was combined with a large number of detections.
Then the other studies I told you about earlier were quickly carried out beginning in the spring of 1984.
Rodrigues: Our next question probably will not elicit a story as fascinating as that, but we were curious about the evolution of the nomenclature of HIV.
Gallo: That is a very good question.
Rodrigues: I am sure very few people outside of virology understand how viruses are named. We would be particularly interested to hear about the story of how this was negotiated.
Gallo: Sure. The question is about the nomenclature of human retroviruses; how it eventually got sorted out and how HIV became the name. I will tell you what I know and there are probably pieces of this that even I do not know. But let us go back to the first human retrovirus. What would you have called it? It was a Type C virus in association with a leukemia. If you looked to the animal systems you had many viruses named after people, such as Rous sarcoma virus, Raucher leukemia virus, Gross leukemia virus, Kirsten sarcoma virus, Moloney leukemia virus, Moloney sarcoma virus, Thelan cat leukemia virus, Harvey strain, Friend's strain, Rich strain. It was endless. So they were named after people. That began to change as the field moved above felines. In chickens, mice, and cats, viruses were often named after people, but with the name of the species, feline leukemia virus, the strain with a man's or a woman's name.
By the time we got into primates, cows, and other animals, it was just named bovine leukemia virus and the strain might be given a number or the name of a city or whatever you want. We tended simply to follow the pattern. Our virus was in humans. It was a leukemia virus, and it targeted T cells, and we were worried about just giving it a name, given that it was a leukemia virus. It was so specific for one form of leukemia that we figured we had better put “T cell” in, so it became “Human T-cell Leukemia Virus.” That was the name.
When we discovered another type of human retrovirus that was related to HTLV-I, we simply called it HTLV-II, and, right from the beginning, the plans were to name them sequentially. If there was another T-tropic human retrovirus, it would be HTLV-III. It was not dependent on whether or not it caused leukemia. That is also a point that has been distorted. It has been said that we changed the name to lymphotropic and that you could never call the AIDS virus HTLV-III because it was not causing leukemia. But please keep in mind that feline leukemia virus can cause aplastic anemia, it can cause immune deficiency, it can cause many things, depending on the strain, but it was still called feline leukemia virus. We were following a precedent. Some strains of the mouse leukemia virus can cause spastic paralysis and it is still called mouse leukemia virus. HTLV-I could cause a spastic, paralytic, neurological disease, but it was still called human T cell leukemia virus, and no one complained. This became politics in my view, scientific politics.
We changed the name to “lymphotropic," but it was not me who thought of that; that was a suggestion, if I remember correctly, by Dr. [Luc] Montagnier, who did not want to use the terminology of “leukemia virus” because it might cause confusion. So we called it “lymphotropic.” That was agreed upon.
In September of 1983, from the 21st to the 22nd, we were at the Cold Spring Harbor meeting on tumor virology. I think that meeting centered around human retroviruses. At that meeting, we had a subgroup meeting of people from England, Scotland, the United States, and Japan. We made a signed agreement, which sits in my drawer to this day, in which human retroviruses would be named in the order of they were discovered, simply by the number, and if it was T-cell tropic–not if it caused leukemia–it would be HTLV-III, HTLV-IV, HTLV-V. That was the pattern that was set. So I more than resent the notion–it is a false notion–that the discoverer of a virus can name it and therefore the other person has no chance to give it a name. We feel that we independently made isolates, including in 1983, and that there was an agreement and a precedent for the name of these viruses in the order of their discovery if they were T-tropic, as HTLV-I, HTLV-II, and HTLV-III.
However, certainly it was Dr. Montagnier and his colleagues' prerogative not to follow this, and they did not. They called the virus “lymphadenopathy virus.” I do not think lymphadenopathy virus was a very good name because it said the virus was associated with lymph gland enlargement, and that was not the key thing with this virus. Secondly, there was not much of a precedent for that in animal retrovirology; it was a very unusual name.
When this was going back and forth we agreed to give the virus a double name, with the hyphen, LAV-HTLV-III, or HTLV-III-LAV, which we knew would never last forever. Subsequently, a nomenclature committee was generated, and the current NIH Director [Dr. Harold Varmus] took a role in that. That was his entry into developing some interest in AIDS, so far as I know. I was asked to be a contributor to that committee, and so was Dr. Montagnier. In 1985 Montagnier wrote me a letter, in March of 1985–a very interesting month actually, but I will not go into that–in which he said that he wanted to keep the name “lymphadenopathy virus," because he felt that he had conclusive evidence that it caused mostly benign disease. He was wrong, of course, but he wanted to keep the name. We wanted to keep the name HTLV-III. So things were not working out. Suggestions were coming in.
In retrospect, I wonder if Howard Temin's idea would not have been the best. From the start he wanted me to make a break with the past and he said, forget HTLV-I, forget HTLV-II; let us just call them human retroviruses. No one can say anything. One, two, three, four. That way you cannot be accused of naming it HTLV-III because HTLV-I and HTLV-II were your babies from the past. That probably would have been the wise, quick thing to do to end this debate.
But I did not go in that direction, and Temin's idea did not win out. The name AIDS virus almost won out. I feared the name AIDS virus because what if, 5, or 10, or 20 percent of the people who got the AIDS virus as was then determined did not get AIDS? I preferred a more technical name like HTLV-III, or maybe human retrovirus III, but the name immunodeficiency virus won out in the voting. I cannot remember the exact date of that, but it was probably some time in late 1985 or in 1986. I hope that answers the question adequately.
Rodrigues: Our next question has to do with the level and intensity of the rhetoric that has appeared in the press. In the beginning you mentioned that this sort of coverage had been going on for over eight years. Has it taken a toll on your ability to function as a scientist?
Gallo: Yes. The press rhetoric, in some quarters, particularly since 19...there were press problems as early as 1984. The first time in my life I had press problems was at the beginning of AIDS research. It started in 1984, but then it got better. But from 1987 on, particularly with one reporter, it has been eight years relentlessly, sort of regular, often front-page, coverage. Yes, it took a heavy toll, emotionally, and time-wise, responding to the never-ending Freedom of Information requests, and also just responding to rumors.
On the other hand, I think we can be proud, and no one can take this away from us, of the fact that, in the decade of the 1980s, this laboratory was the most referred to laboratory in the world in science. Second, in the period from 1989 to 1992, which was in the midst of the worst of this business, we were still the most productive laboratory in publishing in the peer reviewed journals in which scientists publish.
But–I do not mean this to sound in any way as though I am just being diplomatic, or trying to be nice; it is the truth–if I did not have very good, young postdoctoral fellows this never would have happened. If NIH were not the right place to work, this never would have happened. I was saved in this period by the dedication, intelligence, and the abilities of wonderful postdoctoral fellows from all over the world.
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