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Gallo: There are two questions. What is happening and what is its impact? I believe that what is happening is nothing unique, except that we live in a time of media–cameras, instant action, and wide transmission of information–so many more people have a chance to get involved, but it is no different than it has been in all of human history in medicine or in related fields. The media, currently, and particularly with regard to AIDS, can make an instant expert out of anybody–somebody who has not paid their dues, somebody who just talks, somebody who does not work on a problem or does not have any expertise on the problem. So, as soon as you say something about AIDS, if you have any kind of a degree, or even if you have no degree, often you are treated as the equal of somebody who has been thinking about it, or of all the scientists involved collectively.
All you have to do is say something astonishing related to AIDS and you know that you can get attention.
In the first place, part of what is happening is the modern media. I do not mean to blame it. I just think that is the way it is. There are many more opportunities for many more people to be out in the public. That is obvious.
But, if you look back in history at almost every epidemic, every plague, every serious disease–and even now with cancer–there were always people saying all kinds of things. It just did not get as much play in the media. There are many people who think that cancer is a curse from the devil, or a curse from God, or that cancer is caused by eating almost anything you want to name. Any theory goes, doesn't it? If you wanted to play every time somebody had a theory about the cause of cancer and make a cult out of it, you would have dozens of them in cancer.
But if you look beyond the “Black Death," the Pasteurella pestis plague, you can find parallels where people were blaming.... In my book I have a chapter, as you know, on the cause of diseases with special emphasis on HIV and AIDS. But, in another chapter, “A Single Disease With A Single Cause," is the title, I believe–somebody was showing it to me yesterday–I have a long quote of Alessandro Manzoni's statement in his classic book The Betrothed, which is a 19th-century Italian book about a young man and his wanderings around Lake Como. It is something like The Canterbury Tales in a way. In any case, Manzoni has a wonderful statement about how first the notion of the disease, of the epidemic, of the plague, did not exist and then, after a while, of course, it did, but it was not as serious as one thought. Well, of course, it does exist, and it is as serious, and then comes, “You caused it," or “Somebody else caused it," or “It is not what you think," or “It is due to foreigners," or “It is due to this or that.” These things happen all the time, and, with AIDS, the media have given tremendous opportunities for this to grow.
Now, it is also seductive. It is a theory that is seductive. But if I came along and told you that I have a blood test and you were HIV-infected, the first reaction of some people was, “My God, this is like in World War II, when Jewish people got the stamp.” They were worried. People infected were worried that this was a stamp on them. But then they realized, certainly in a short period of time, that this was the way the epidemic could be monitored, the way the disease could be treated and followed, the way that we could save people's lives by testing blood. But if somebody else–instead of bringing you this bad news and the test–said you have a disease which may be fatal and a bad virus, maybe you know that you have infected somebody else, so you have a certain feeling of responsibility. But if somebody else comes along and says, “That is not the cause; there is no cause, everything is the cause, lifestyle is the cause," you feel much better. Young people especially are prone to this because a percentage of young people are rebellious and they are often rebelling against their father figures, or the establishment. I think if you put all this together it is not difficult to understand the criticism.
The impact? I think the impact is serious. I think, for a while, from my vantage point and from the vantage points of many people who are involved, the idea was so incredibly ridiculous that it strained one. You do not want to talk about it and you do not want to respond to it because it does not do any good to respond to it. As you pointed out, they [Drs. Blattner and Temin] responded in Science. I wrote a chapter. I tried to deal with every argument. It does not seem to have done any good. The arguments change in time and are modified. With some people I think it is due to confusion or a lack of adequate information. In fact, I have evidence of that, that I think is incontrovertible. I talked to a professor who followed this idea that HIV is not the cause of AIDS, who was from Berkeley. It was not Duesberg, but a more elderly scientist. His argument was that he knew plenty of people who were promiscuous and they did not have AIDS, therefore HIV could not be the cause of it. He said that this was a reaction against freedom of sex. I asked him if he understood the difference between exposure and infection, and, quite frankly, I do not think he did. It was quite remarkable, but this is true.
I think the idea that HIV is not the cause will last as long as we do not have a cure for AIDS–or, let me put it this way–as long as we do not have an extremely effective therapy it will last. All kinds of theories and passions will last, all kinds of misrepresentations, distortions, historical and otherwise, will last. When the right therapy comes all these things will settle down. But there is no experiment that would effectively counter such arguments. If tomorrow we developed a successful vaccine, would you say, “That settles it?" I doubt it. Somebody would argue, “It is nonspecific stimulation of the immune system.” You will never win the argument because, in fact, science is never–almost never–100 percent certain. Either you spend your life focusing on the .0001 possibility, or you get on with the problem and attempt to save life. But I think the impact of not believing HIV is the cause of AIDS is serious, particularly on young people, particularly in some of the big cities in the United States and in parts of Germany today.
Harden: Let me go back, just briefly, to the Science articles and ask, when you were working in this period of great discovery between 1982 and 1985, when information was developing rapidly, how did your thinking evolve about the nature of this virus? I know initially you thought that it might be HTLV-I, or if not, something close to it.
Gallo: No question about that. In 1982, when we first began thinking about the virus–we means myself in discussions with [Dr. Myron] Max Essex–we thought that the best idea was that it was a T-lymphotropic retrovirus. That was correct. That is what has turned out to be right. But we were basing this on our knowledge of HTLV-I and HTLV-II, in other words on the HTLV family. Our reason was, as I have indicated to you before, that feline leukemia virus with a minor modification of its envelope could cause immune deficiency. That had been demonstrated.
Exactly at the time that Essex was reminding me of that, in our laboratory–and also Dr. [Anthony S.] Fauci's laboratory at the time, I remember, was working with HTLV-I, partly in collaboration with us and partly independently–we saw that with HTLV-I and HTLV-II there could be immune impairment of T-cell function. When it was not immortalized in the T cells, it could modify T-cell function. You think about that a little more and you realize that it targets T cells. You start thinking about how HTLV-I is endemic in Africa and Haiti and there is reason to suspect a Haitian connection, and a Haitian to African connection in AIDS, and a heck of a lot of monkeys are infected with related viruses and you have just discovered HTLV-II. We have HTLV-I and HTLV-II, and we are in the midst of discovering modifications of HTLV-I, something we called HTLV-IB, HTLV-IC, so we thought the best idea for the cause of AIDS was a new virus, not HTLV-I, but an HTLV-I based virus. In fact, I wrote a memo to Dr. [Vincent] DeVita sticking my neck a million miles out and predicting there would be a variant in what we call the 3' region of the genetic information for the virus, namely where the envelope is, and where some of the regulatory genes for HTLV-I known as tat and rev are located, the X region. We were predicting that the region that makes the core proteins and the reverse transcriptase would be kept common, be more HTLV-I related, but the 3' end of the molecule would be different.
I will not go into all the thinking that led to that, but that was, in any case, how we started out. That was in 1982 and early 1983. It lasted until about the middle of 1983.
How did the thinking evolve? I should say that there was reason to be stimulated further in that direction by some data that was not, in the end, correct, and I will summarize that as we go along. But one important piece of data was that Montagnier, in early 1983, said he had a new retrovirus, but that his retrovirus, in a certain test reaction, had a one-way cross-reaction with HTLV-I, or at least with HTLV-I infected cells, If I remember the experiment correctly, the serum from their patient reacted with that. That turned out to be an inaccuracy, but it gave further credence to the notion that there might be an HTLV-I relatedness.
You have to know the context of the field. The idea of a retrovirus was not accepted, as far as I know, by anybody. I remember [Dr.] Paul Black wrote a letter to the editor of the New England Journal of Medicine pooh poohing the idea that a retrovirus could cause anything other than a cancer, not being aware–he was a DNA virologist–of some of the things retroviruses could do. The climate was not ripe for a virus as the cause.
But our thinking intensified. Montagnier did not have linkage to AIDS, but, nonetheless, here was a new retrovirus and it was early 1983.
Now, by then, we had already seen evidence of a new retrovirus too, but could not put the pieces together.
Essex used HTLV-I infected cells in people with AIDS who were something like 35 percent positive on the assay system he used. Montagnier, using what turned out to be the right virus, was only 18-20 percent positive. We did not know both results were wrong. We suspected that they might be, but we did not know that. In any case, this gave us further reason to believe that, if this new retrovirus was involved in AIDS, it was HTLV-I related. Finally, and ironically, in Montagnier's paper, where there was not much characterization of the virus, there were three things that further spelled an HTLV relatedness in my mind:
One, he called the virus Type C. HTLVs are Type C. We now know that HIV is not; it is a lentiretrovirus, not a Type C.
Two, the size of the central core proteins that he described was 25,000 Daltons. Now, I knew that among retroviruses HTLV-I and II had small core proteins, 24,000 Daltons and something, but all the other retroviruses we knew about were bigger–28,000, 30,000 and 32,000, something like that–so that fit.
Finally, Montagnier's assay for reverse transcriptase that he referred to was his optimum. He referred to the assay they used and, in discussions, that was his optimum, and that reference was to our 1980 paper on HTLV-I. It seemed to me to be self-evident that the new virus would be very close to HTLV-I.
Now I come back to what we were starting to see. We got tremendously misled–let us say we lost half a year–again by something quite ironic. The truth is better than some of the nonsense. There is a book that just came out called The Dancing Matrix, and the author's name is Robin Marantz Henig. Anyway, she starts the book with Mr. Chardon. Mr. Chardon, a young Frenchman, goes to Haiti, gets in an accident, has blood transfused, and gets AIDS.
If I remember correctly–I have to go back to my own book–but I think it was in the summer of 1982 or in late 1982 that I was having discussions with [Dr.] Jacques Leibowitch. Jacques Leibowitch was a clinical immunologist in Paris in the Hôpital Raymond-Poincaré and Jacques Leibowitch was interested in things that I had just written in August 1982, and elsewhere, proposing that a retrovirus was the cause of AIDS. He became excited and interested in this and encouraged me to work more on AIDS than I was doing. He was another provocateur. Instead of working with one or two fingers on the phone, Jacques came over with one of these containers of liquid nitrogen filled with samples from AIDS patients. The most interesting one was this one from Mr. Chardon. “CC” we called him, but since his name is in the book [The Dancing Matrix], I guess it is all right to say his name. This became some of the material that we focused on hard because Jacques was such a pusher and so dynamic and said that we had to get more involved in it, and so on.
Parenthetically, the story of how the French got involved in looking for a retrovirus is that Jacques returned to France–I just met the man, [Dr.] Paul Prunier, who is the Head, I think, of Pasteur Diagnostics–and he told Prunier about our work. Prunier told the people at the Pasteur Institute to follow our ideas. That is how they got started. It is not a secret. Dr. Montagnier has already published that in several of his research papers and elsewhere. So, that started the two laboratories, their laboratory and our laboratory, going on this, and there was also Max Essex. I think the three laboratories were the only ones working on this at that period of time. In fact, I am quite sure we were alone.
Coming back to the story of Chardon and the irony in what happened to us, Chardon's cells grew. Previously, in looking for HIV, or looking for the AIDS virus, or looking for a retrovirus, what did we see? Prior to Chardon we had a few short-term cultures. Sometimes there would be an HTLV-I reactivity, but most of the time there would not be. We would have a little bit of reverse transcriptase and we could not interpret the data. Were these really isolates? It depends on how you define isolates. As short term cultures? I do not want to say how we would define this. But we had these as early as late 1982. When we were in the patent discussions, the lawyers looked back in time and asked, “When, in retrospect, did you first detect this?" In retrospect, it was in the late part of 1982. We do not want to claim priority for that. That has been misrepresented by my unauthorized biographer many times. We do not claim that. That response was in answering lawyers' questions. In retrospect, that is what our books showed. We had no clear interpretation of those data. I will be the first to say that. The first publication is what counts with regard to “firstness.”
In any case, we had these detections and we did not exactly have good production of anything. But Chardon's cells immortalized and they grew forever. What were we getting? We were getting exciting results, exactly fitting the theory, namely the virus coming out... Chardon's cells were growing forever in the laboratory and they were producing a reasonably good quantity of virus. The exciting thing was that the virus was able to kill target T cells. It was producing a cytopathic effect. That was extremely exciting. So we figured we had the virus, but we had not linked it to AIDS yet. In keeping with the theory, when we tested those cells for whether they had any gag proteins related to HTLV-I, the answer was yes, they were expressing p19 and p24, core proteins of HTLV-I, and they fit the theory perfectly. In fact, it was at that point that I became more certain of the hypothesis.
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