Bob Gallo: [00:00:00] Good late morning. I want to take one second to thank and say what a fantastic job the co-organizers did, Bruce [Walker] is standing right next to me, and John [Coffin], who was a ball of fire and sometimes a lot of discussions. I never had so many discussions over a meeting, but it was really turning out to be very worthwhile, so thank you, guys. It was great to work together.
I wanted to turn the clock back to a moment when I came to the National Cancer Institute in the middle of the 1960s. Yes, it's a long time [00:00:30] ago. I had a general feeling at the time that there was a healthy respect for serious epidemic diseases still. There was a belief that viruses were involved in cancer and maybe even retroviruses. If you look at a book written by David Oshinsky, a historian at New York University, on polio, polio vaccine, you see that by then when polio began in the early '50s, there was a feeling that there was no longer a need to be so vigilant for serious epidemic diseases, we had more or less [00:01:00] conquered them, and polio took people by surprise. (1)
It was about 30 years since influenza, and it occurred to me that much as the same about AIDS, from polio to the time of HIV is about 30 years, and we tend to forget what happened maybe further than 20, 25 years ago. In any case, what I want to do is turn back to the '70s because, after the '60s, things changed, I don't want to say by—certainly, not by everybody, certainly maybe not by the majority—but there was an atmosphere that said [00:01:30] serious epidemic diseases were over in the industrial world, therefore, we can forget about it and the problems for tropical disease institutes and things like that.
Retroviruses don't infect humans, and there were a lot of reasons for believing that, and some of them very good reasons. No viruses really cause cancer or play any role in cancer in man. In fact, there was another Cold Spring Harbor meeting, Robin [Weiss] referred to one, RNA tumor viruses, last night. (2) There was [00:02:00] another one, the Origins of Human Cancer, organized by [John] Cairns (1922–2018). (3) It was a huge meeting. There were three virologists that I remember being there: one was [Max] Essex, myself, and I think Harald zur Hausen (b. 1936, German virologist). The conclusion of the meetings said there was no cancer playing any role—Excuse me, no virus playing any role—in any human cancer.
As everybody here is aware, the biases were rather overcome by the early '80s. The virus is now known to be involved in about 20% of human cancers; [00:02:30] retroviruses found in humans have shown to cause some leukemias; the same virus causes a fatal, really awful neurological disease; modest immune abnormalities, as Max said last night; other blood dyscrasias. These are HTLV-I and, as Robin noted last night, HTLV-II—you know, it's amazingly similar in its genome and sequence homology to HTLV-I, yet it's very poorly pathogenic, not true of HTLV-I, as I'll come back to in a moment. And then we're here for the last one, another retrovirus [00:03:00] causing that great pandemic.
This is an opinion piece really, so it's from where I sat. As I was talking with someone, I mentioned that once a French industrialist said to me that all of life is your view, how much of the rainbow you see depends on the angle you're sitting, so consider that I'm looking at my own angle.
Anyway, these are the things that impacted me. The arguments against human retroviruses were there is very high [00:03:30] replication in the known animal models. They should have been easy to find if they existed in man. Bovine leukemia virus had not yet been discovered when this was going on, which replicates very minimally and causes naturally-occurring leukemia in cows.
There was little evidence in primates as disease-causing agents until the late '70s. Then [Thomas G.] Kawakami found a gibbon ape leukemia virus causing myeloid leukemia, and a few years later, we found one that caused T cell leukemia in the same species. Human sera was reported by a California group to lyse animal retroviruses, [00:04:00] therefore, humans were protected. Unfortunately, they tested only small animals, the gamma retroviruses. Human research then was less appreciated. Cancer as "catching" seemed to be a very primitive concept, but let's appreciate it, it was actually a bit looked down upon, kind of the opposite of today.
The field of revtrovirology was dominated by endogenous as opposed to infectious retroviruses. See Essex's talk last night and Weiss' talk, the Huebner-Todaro so-called “virogene” oncogene theory. Bill Jarrett said to me at [00:04:30] that time, "Endogenous viruses cause one thing: publications. Stick with the search for the infectious ones." Perhaps most important of all, and it was referred to last night by Robin, the decades of repeated failed attempts and many claims.
In particular, Sol Spiegelman's group had developed an assay called “simultaneous detection” and which led to reports of a different cancer virus in a different human cancer almost roughly every two months in PNAS. This was an [00:05:00] endogenous, ribonuclease-sensitive, DNA polymerase activity, associated with an RNA, banding at 1.16 density just like a retrovirus. Again, Robin referred to this last night, I'll be very brief. A clinical associate, who just went right into clinical medicine, Sam [N.] Bobrow, reported with me and Marv Reitz at the time that normal human lymphocytes contain the same activity: a ribonuclease-sensitive endogenous DNA polymerase, distinct from a viral reverse transcriptase [00:05:30] or an RNA directed DNA polymerase. (4)
Marv Reitz, in the slide below in [Biochemical and Biophysical Research Communications], brought it home. (5) That's what Robin referenced last night, in which we showed that this was DNA polymerase gamma associated with mitochondria, the RNA was a primer. It was directed by DNA. It's mitochondrial DNA synthesis. That's what the Simultaneous Detection assay was picking up, so then things changed.
I believe the key advances leading to the discoveries of human retroviruses, from my, perspective were these: the finding of mammalian retroviruses [00:06:00] that caused leukemia and immune disorders, first by Ludwik Gross (1904–1999) in mice, second by William Jarrett, and then Max Essex and Bill Hardy in cats.
As I mentioned to some last night, Ludwik Gross, in the discussion period, was really very much looked down upon. The late Leon Jacobson (1911–1992) told me that people moved out of an aisle when he sat down next to it. He worked originally out of the back seats of his car and his trunk before he got a small laboratory at the Bronx VA Hospital. He was a Polish refugee, but it was a great contribution, [00:06:30] crude but a great, original contribution.
We heard a lot about Howard [Temin] (1934–1994) and the provirus theory, the discovery of reverse transcriptase already, but these, clearly, had major impacts to what we wanted to do. Providing an outline of retrovirus genetics and replications—you couldn't have done better than listen to John's talk and some of what Harold and Robin said last night as well. Making reverse transcriptase assays sensitive to be a surrogate for finding a retrovirus and to make [00:07:00] sure we could distinguish them from human cellular DNA polymerase, alpha, beta, and gamma.
David Baltimore's lab and our group, we certainly spent a great part of the 1970s doing exactly this, purifying those enzymes and purifying reverse transcriptase from various animal retroviruses, making comparisons, getting antibodies to them, looking at the polymer templates that are available and commonly used today in all kinds of assays like the poly(A) oligo(T), for instance, or the oligo(dC), [00:07:30] what is it, poly(C) oligo(dG). (6)
The other thing that drove us towards T cells, one was our capacity to grow human T cells. This was the discovery of the T cell growth factor or interleukin-2 (IL-2) by our group in 1976. (7, 8) I want to remind you that came up once earlier, that lymphocytes were really only starting to be distinguished sometime in the late 1960s and the day we—not the day—we were writing the paper for publication for Science [00:08:00] on this observation when there was a clinical immunologist from Yale who gave a talk saying everybody knows that T cells can't grow, that if you stimulate them, they divide once and then they die. They were terminally differentiated. Needless to say, we thought, we got worried, but in any case, you can grow with IL-2, at least some T cells. That was very important for us to explore because to isolate the virus, we needed to grow primary cells, and we were using blood cells, so [00:08:30] interleukin-2 was indispensable for the vast majority of isolates of human retroviruses, if not all.
Then in that same period of time or a little later, we isolated a T-leukemia virus strain, pardon me, of gibbon ape leukemia virus, so we started to focus on T cell malignancies.
There are some unique features of pathogenic human retroviruses like HTLV-I and HTLV-II. For the first time, we see a complex genome [00:09:00] not known before in retrovirology, the same for HIV; complex RNA splicing, also not known before, the same for HIV; novel regulatory genes like [00:09:10] rex and tax, which really predicted rev and tat of HIV; a novel mechanism for oncogenesis unknown in animal retroviruses, not insertional mutation, not a viral oncogene with a cellular homolog, but nonetheless, as Harold said last night, consider it an oncogene, the Tax [transactivator protein].
Now it's more complicated. There's another [00:09:30] HTLV gene, HBZ (hemoglobin subunit zeta), which also has amazing properties, and I'll refer to that in just a second. There's also now the—antisense gene HBZ, which also, now we have one for HIV, AST. What they do is the subject of maybe a whole-day symposium. That's perhaps the most interesting part of the field today.
Also unknown in animal retroviruses, HTLV can immortalize its target cells, that is, for a virus that doesn't carry a conventional oncogene. [00:10:00] It's transmitted as a provirus, that is, it's transmitted as a cell rather than as a virus, thus transmission is highly inefficient, and for the survival of the virus, there must be a mechanism for propagating those T cells. It means from a virus point of view, it wants T cells to grow. I believe that T cell leukemia is an accidental consequence of that viral strategy. When you think of tropism of a virus and its strategy to replicate, you sometimes can almost predict the nature of the disease it might produce.
The provirus, either of [00:10:30] two genes, tax or the antisense gene HBZ, can reproduce T cell leukemia with similar cell morphology—that starry cell that Robin [Weiss] showed last night—in a mouse transgenic model. I also think it's rather unusual to have such strong evidence of being a direct cause of human cancer. From the epidemiology type linkage, the type of virus, which was predicted for leukemia, the laboratory data, that, is the clonal integration of the provirus, which varies from patient to patient [00:11:00] of where it's integrated. It doesn't have to be near a certain oncogene, it can be here in this chromosome or there or there or there, but within the population of tumor cells, all proviruses are in the same spot, verifying clonal integration, and that the virus came in before the cell was transformed, rather than after as a passenger, also, and as I've already said, reproduction of the disease in transgenic mice with the provirus or even a single HTLV-I gene and its ability to immortalize its target cells. [00:11:30]
This is a picture, among the first pictures taken of a human retrovirus, that's HTLV-I, budding from the surface of leukemic T cell. In the middle, is the first patient from which a human pathogenic retrovirus was ever isolated. That man was dead within a short time of this picture. It's usually but not always a very aggressive disease, the skin lesions are infiltrates of leukemic cells. On the right of the slide is the first Caucasian that we isolated the virus from, and he had both the fatal neurological disease, which is what he'd died from, [00:12:00] as well as the leukemia. That is unusual, but he had both.
Now, just a brief word on the epidemiological information. The number infected [by HTLV-I] globally is really unknown. I always ask Veffa [Genoveffa Franchini], "What's the latest information on that?" and I get this, number 10 to 20 million. That's obvious that we don't know because a large part of the world has never been studied. It is an underfunded problem, an underfunded disease, and an underfunded virus, for many reasons. That's one, that we don't even know where [00:12:30] in the world else it might be important.
It is of public health importance, not in America, not in Europe, but certainly, in Japan. When Robin mentioned the various countries, he left out a couple, Indonesia, Iran, which I learned about only this last year. In Iran, [Ali] Bazarbachi, who is a clinician in Lebanon, did a brief study, and he said about 7% of the population of Iran is HTLV-I positive. Certainly, the Caribbean Islands, as was mentioned yesterday, certainly, parts of Africa, [00:13:00] but South America, very potently in Peru, for example, and Brazil, a very important causal disease.
I visited Bahia during the height of the epidemic of HIV, when people were dying, and their wards were more in Bahia, a resort, filled with HTLV disease as opposed to the HIV disease. There's only about 100,000 infected people in the United States. It's "fixed" tightly in a population, almost like a genetic marker. It varies greatly among neighbors, some Caribbean Islands are 3% to 5%, and some are almost nothing, [00:13:30]dependent on where in Africa they came from, or tribe and so on.
The summary is that this is the first pathogenic human retrovirus, the only leukemia virus we know of man, and it's not known to need one or more exogenous co-factors. It can provide immortalized growth for cells, both CD4 and CD8, useful in the lab, therefore, and we've used it for things successfully in the lab. It gives us insights into the mechanism of leukemia, different from animal [00:14:00] retroviruses, and it could be more carcinogenic than any known human tumor virus.
It might be challenged by HBV [hepatitis B virus], I don't really know the calculation for HBV. It's an important public health problem in the areas that I've already mentioned. Lastly, and relevant for this meeting, it provided an impetus, ideas, and some key tools to search for other human retroviruses, which helped lead to the discoveries of HTLV-I-II and HIV, as well as some other ones now being found in Africa with no known [00:14:30] disease causation yet.
This is the first submission of the paper on HTLV-I and my friend, Bob Wagner's (editor of the Journal of Virology) statement in the middle, "I completely agree with Reviewer 1"—I hope that wasn't John Coffin, [laughs]—"that there is [chuckles] a little point in perpetuating this controversy about the ‘presumed viral nature of this material.’” It was started like a "Dear, John" letter, a, "Dear, Bob" letter, like [00:15:00] "Take your apples and go home." It was a little bit depressing, and thank God for PNAS, and help at that time from Henry Kaplan, the late Henry Kaplan, and David Baltimore. (9)
Let me switch to AIDS. We've heard about ideas for AIDS. Actually, I went through all of them—not here because I leave some out, but some of them had an impact on us, impact negatively, usually. It was non-infectious ideas, you heard some of that yesterday, "poppers," amyl nitrate, particularly [00:15:30] from FDA by that time. But I noted from Jim Curran's slide, that he used to be at CDC, Harry Haverkos.
Then, there was from NIH, actually from NCI, autoimmunity to autologous leukocytes, which had a lot of interest from the immunology community in supporting it. That idea was maybe you have rough sex, you get leukocytes in your blood, you attack the leukocytes, you start attacking your own cells. One objection would be that maybe rough sex existed for about 3 million years. Another was, what we are hearing from Jim [Curran] already about the hemophiliacs [00:16:00] and other blood transfused people, another was infants that were getting infected from their mother, it was becoming clearer.
This idea could not explain much. Infectious ideas were multiple, some of them quite good, but there were some not so good. Dr. [Shyh-Ching] Lo, at the Armed Forces Institute of Pathology, proposed mycoplasma as the cause of AIDS, and Luc Montagnier, that it was an essential co-factor for AIDS, neither have been borne out. There was a new fungus [00:16:30] from NIAID, some of the administrative leadership—I want to emphasize we have eras at NIH, there is the pre and post-Tony Fauci, you know, AC/BC (nb.: might mean “BC/AD”)—this is before Tony. But the fungus notion was, for a moment and time, quite significant. I got a call from the NCI director, it was February 1984. I was in San Francisco, and our papers were just being submitted, and he said, "You assured me this was going to be due to a retrovirus" and then he told me there was going to be an announcement [00:17:00] that evening that it was a new fungus, "A new fungus?" and that the fungus was making a new molecule, new then, ciclosporin—a new molecule that knocks off specifically CD4 T cells? I recall [Albert] Einstein said, "Mother nature is not cruel, but she's never completely simple." It was a little too much.
Then, of course, I knew, from the epidemiology people, about hemophiliacs, and I knew hemophiliac material was then filtered, we didn't have a pure molecule, the filtration would remove the fungus. [00:17:30] I took a deep breath with the heart palpitating and said, "I think they're going to be wrong." There was a little announcement on television, but not much and then this went away, it was withdrawn. Max talked about the proposals on a new T lymphotropic retrovirus.
At the bottom is our friends Kary Mullis (1944–2019, inventor of PCR and prominent HIV/AIDS denialist) and Peter Duesberg (b. 1936, molecular biologist and prominent HIV/AIDS denialist)—I hope you know I say that the intent to be malicious—“There is no cause, and really no AIDS.” Remember? First it was, "There's no AIDS." [00:18:00] Then it was, "It's lifestyle." What did that mean, lifestyle? Lifestyle, doing, what does it lead to, what happened? Then, "HIV, okay, it exists, but it's a passenger." Then we have created, by a man named [Jakob] Segal (1911–1995), a geneticist in East Berlin, that this was created by, who else, the US government [Operation INFEKTION]. Jim Curran was probably involved in that, in time, Tony, of course, perpetuating it all over the world, of course, and me.
That was actually not so insignificant [00:18:30] because, for three weeks, I got some assassination letters that I'd be dead in three weeks, and I used to have to go home with dogs and this police sent from, I don't know what offices of the government, because the person cut out from the newspaper that I would be killed in three weeks. This was not a happy time, completely.
Why do we postulate? Max [Essex] dealt with this, but from my perspective, and we hadn't gone over each other's stories, it was the feline leukemia virus story that [00:19:00] I was learning about, but we just found these other human retroviruses. That's not a great reason, but they came out of Africa as far as we could tell, that's beginning to be a reason. HTLV-I, as Max mentioned, also causes immune disorders, mild but still significant in the absence of leukemia.
Importantly, they're transmitted by blood, by sex, by mother to infant, related to the risk groups that were being described by Jim Curran at CDC for AIDS. They target CD4 T cells that we learned from the clinicians, [00:19:30] even as early as the original [Michael] Gottlieb and [Frederick P.] Siegal and those people's papers, [Alvin E.] Friedman-Kien, and so on, and Bijan Safai. (10, 11, 12, 13) These are the very cells that clinicians are describing as a decline in AIDS. A new variant of HTLVs was a reasonable idea, maybe a very logical idea, from our perspective.
Our first AIDS experiments seeking for a new retrovirus began in May of 1982, a postdoctoral [fellow], Ed [P.] Gelmann, started using HTLV [00:20:00] probes with loose conditions of hybridization, he really was not finding anything, but then there came a few cases that caused confusion. This is both positive and negative. The first continuous growth of HIV was a total accident, but it taught us something, it also set us back about six months. We had a double-infected patient, he was—why does it go back to the French?—a French young man [00:20:30] visiting Haiti, he got a blood transfusion after an accident, but he got sick.
Meanwhile, Françoise [Barré-Sinoussi’s] paper came out in May of '83 while we were struggling to understand what was not understandable: that is, we had immortalized cells from him. (14) What does he have? It's a double infection. Look, it's the same cell! Remarkably, we used to think of [viral] interference. I wasn't good enough to distinguish these were two different viruses. Look at it today, [00:21:00] you'd say, "Obviously, one's HTLV-I, one's HIV, if they're human and not a contaminant," but we didn't. We said, "Oh, this is just going along to our predictions."
This was cross-reactive with our antibodies, HTLV-I and HTLV-II, so it fit. But it wasn't exactly the same, and it was cytopathic. But in retrospect, this was the first permanent cell line culture of HIV, and it's February of 1983, but we had to put it aside because we couldn't make anything out of it until moons later when we were able to separate [00:21:30] the two viruses by growing them in different cell cultures situations, but that caused help and confusion.
Finding the virus was one thing, showing causation was another. This presented rather unique challenges in my mind, unlike past viral epidemics, or the recent SARS, MERS, or Zika, or Ebola outbreaks. The clinical latency was long. Jim [Watson] said he did ask people what they did a long time ago, but most public health people and most doctors don't ask what you did three, four, or five years ago. [00:22:00] That was one, by the time you had AIDS, there were multiple other microbial infections, so we were challenged all the time. How do you know that one is causing the disease? There are a lot of other infectious agents there.
I want to acknowledge that we had a lot of clinical help, clinical help meaning the supply of samples but more than that. Most of the people on that slide, several of whom are here, like Barton Haynes and Bob Redfield, and Sam Broder (also on the slide are James Oleske, Jim Hoxie, Jerome E. Groopman, and Mirk Hiram) also made intellectual input into this work when we discussed things with them. Everything we did would not have been [00:22:30] done without the help of the people on that slide. Maybe all of them wouldn't have been needed, but certainly, some of them were absolutely essential.
This is a kind of a summary of the isolates that we had in that first paper in May of '84 but take a look down and you'll see that we didn't do so well with adult patients with an opportunistic infection: adult AIDS with Kaposi, only 30%, 47%, but clinically normal heterosexual donors, we did 115 and [in] none [00:23:00] could we find a virus. (15) Look who has the most: pre-AIDS or clinically normal mothers of juvenile AIDS patients. Why? They have T cells left, but the other people have no T cells in their blood, we were dealing with crap, dealing with just a small number of T cells, most of which were dying and we'd get: positive result, positive result, then four negatives in a row, then a positive, so we're tearing our hair out, "How come we can't make any linkage?" This was going on throughout the bulk of 1983 until [00:23:30] a little bit later, as you'll see.
Frequent detection or isolation of the virus, as well as some additional isolates from the Paris group, which Françoise will be discussing, were, in my mind, nonetheless, insufficient likely to conclude that HIV was the cause of AIDS because verification is necessary. Verification by virus isolation was going to be difficult. Tissue specimens were limited and not even allowed in some institutions. I remember that about MIT, the fear factor. [00:24:00] T cell culture technology with interleukin-2 was available to immunologists, but very few virologists at that time. AIDS had to be clinically recognized. By that time, as I've already said, the patients generally had very few T cells to culture, making virus isolation tricky, and giving us many negatives. The consequence: few groups were involved, and for us, more was needed to make a linkage.
[In] the fall of '83 came a key advance. Thinking back about that French patient, that HTLV-1 [00:24:30]immortalized cells could grow HIV, a cytopathic virus and that there were two infections, we turned back to T continuous cell lines. This was principally the work of [Mikulas] Mika Popovic and my technician, Betsy (Elizabeth) Read-Connole, now a project officer in NCI. Not long after, Robin Weiss succeeded in doing the same independently. We did this with a total of seven if you count that first guy, the French patient, and if you count the cross-contaminant from a patient called Lai, which eventually overtook LAV and that [00:25:00] contaminated our lab and many other labs, at that time, it grows like a weed.
If you take those two away, then there's five on the next slide, and which is shown here: R. F., S. N., B. K., L. S., W. T. (initials of patients from whom isolated HIV strains are taken) and while we were writing these papers, MN (HIV-1 MN, a strain of HIV), which is used in vaccine research, it was used by VaxGen (a defunct HIV vaccine developer), it's used today in a lot of laboratory experiments, was also put into permanent culture. (16) For us, the blood test was able to verify etiology. [00:25:30] Why? Because the blood test was safe, simple, sensitive, accurate, inexpensive, and rapid. Verification came almost instantly. It enabled surveys of many thousands of serum samples all over the world. We were now rather sure of the cause. We also had learned about this case of the technician that I told you about, being infected with a clone of HIV.
Participant 1: It was an Italian restaurant.
Participant 2: No, it was French.
Bob: Actually, ironically, it was French. Yeah. Again, against my better judgment, by the way, I said I'm going to get cursed in here. We exchanged the envelopes and Jim had sent, you know what would happen. Then he sent the sera, I think with donor-recipient AIDS-matched for blood transfusion or whatever, and [00:26:30] it was all coded, and we had our results, and we looked at the results, we smiled, we shook hands, and we left the restaurant.
I've always denied eureka moments in this thing, I said there was always a hic, always something bad happening, always stress, but that was my modest eureka moment. I knew if CDC was satisfied, we'd be okay. Then the second thing was when we succeeded with the cell line cultures because we know for sure, we're going to know. We don't know the answer yet, but we know we're going to know the answer. We knew [00:27:00] in October, November in 1983 that we will know, one way or another, whether this causes AIDS or not.
That's the antibody paper that's published in Science with the other papers. (15, 16, 17) And this came out three weeks later in Lancet. (18) The key thing is a double-blind study, and 100% of AIDS sera scored positive. Somebody asked about antibody and virus. This is a retrovirus. If you've got the antibodies, you're infected. That was not understood by public health officials. A really great public health guy, King Holmes, was [00:27:30] in the newspapers, saying, "We don't know what the blood test means. It could mean protection, or it could mean just exposure." You shouldn't argue in the media with those mistakes, so I'd argue back, "You may not know, but we know it means you're infected because this is a retrovirus. It's going to integrate within a day, this guy has integrated, and that means you got the virus."
Anyway, the blood test was the ELISA (Enzyme-Linked Immunosorbent Assay) plus the Western blot. That was the first time the Western blot came into clinical medicine, I believe. Now, what did the blood test do right away? It saved the blood supply and in preventing infections from [00:28:00] the [blood] recipient going to other people. This is key, I think probably the most important point, it allowed the epidemic to be followed. You didn't have to wait for somebody to get AIDS.
And the culture system allowed the first screening of anti-HIV drugs that helped open the door to the historic development of anti-HIV drugs, and I refer you to the talks of Sam Broder, John Martin, and Ray Schinazi. When therapy became available, we could determine who to treat as well as blocking mother-to-child transmission. For us, it was really important as a verification [00:28:30] tool ,that HIV was linked as the cause of AIDS. In summary of the science of finding HIV and linking to AIDS as the cause: the first scientific contribution I think is the clinicians and the people who described CD4 cells as declining, that gave us the hint that things might be in CD4 T cells.
Then there was the epidemiology data, principally from CDC and the town crier, Jim Curran, going around and activating people to work on it. It's by chance and that's something maybe [00:29:00] we learned from this epidemic, we don't want things to be by chance, and that's what pushed me to form the Global Virus Network, but I think things are a lot better administered and organized now, but it was just—I happened to hear Jim’s talk, [that] everything was happenstance. He did make the comment, something along the lines of "Where are the virologists?" This was a time of all kinds of crazy theories, however, very clear that Jim was thinking of a new, infectious virus, those three things, I mean there's no doubt. [00:29:30]
The idea of a retrovirus in 1982, so '81 to '82.
The technology to grow human blood T cells, 1976, once again, I remind you that T cells, as such, we thought we were growing B cells, and it wasn't interesting until Ethan Shevach assayed those cells and said they have no B cell markers, then we knew we had something novel, but this was really strange because T cells weren't supposed to grow. That was key. It's useful in immunology, of course, it's sometimes useful in therapy, but critical for virus isolation on primary blood cells. [00:30:00]
And the sensitive assays for a retrovirus already mentioned (i.e. reverse transcriptase assays), the first detection of the new retrovirus, the first finding of it, the first isolation of it by Françoise and colleagues in '83, and the linkage of HIV to AIDS by many isolates of the virus, and blood tests, large-scale screening, etc. And of course, much later, the use of anti-HIV drugs, which is more than the frosting on the cake.
Some additional key studies in the earliest years from our group came to the discoveries of HIV variability and microvariants in the same isolate, that was by Flossie [Wong-Staal] , [00:30:30] Beatrice Hahn, and George Shaw when we were all together.
The first results that led to the beginning of success on anti-HIV drug therapy—now here I maybe go too far. Although the work was begun in a little lab in our lab, this is really the primary work of Sam Broder. I look at this and say I co-authored it, but everything thereafter falls to Sam and Burroughs-Wellcome in developing AZT.
In my mind, it's not 1995, '96 and the protease [cocktail]: [00:31:00] that's important on a practical level, but it had no new concept. Targeting different steps in a virus replication cycle was new, but targeting things from a different angle was old, in terms of tuberculosis, syphilis, cancer. The idea of combination therapy was not new, the breakthrough was getting the pharmaceutical industry into the problem. The breakthrough is believing you could actually have specific antiviral therapy and proving it objectively, where CD4's going up, patients are doing better. Sure, it was toxic, [00:31:30] so it's not perfect, but it really was the straw that broke the camel's back. That's the historic paper, it's AZT, no matter what you think of AZT. (19)
I won't get into the neutralizing antibodies because it's going to be a subject of someone else's talk, but we were involved, at the very first year, in that kind of stuff.
Later and this will, I think, be the last of these things, Jay [A.] Levy had been describing an endogenous factor that was inhibiting HIV replication. I think that, never mind, he might be still looking for that [00:32:00] endogenous factor, but we published the identification, what we believed are these factors, but they're not just from CD8 cells, they're from CD4 cells as well. (20) These are the beta chemokines, the natural ligands for the CCR5, which is, as you know, a co-receptor. We, in no way, found the co-receptor this is chiefly, by far, chiefly the work of Ed Berger and his colleagues, but I think this paper helped push towards CCR5. He had already identified, I believe, CXCR4. [00:32:30] That's now up to '95, now I'm going to close this, am I doing okay with time?
Bob: No, it would be a miracle if I was, I'd be the first at the meeting.
Bob: This is going to be my last, second last. You know what we need for the future, you don't need me here harping on that. We worked on PEPFAR (President's Emergency Plan For AIDS Relief) for years in Africa, sure. Functional cure, [00:33:00] we're really not doing a lot on that. It's really past stuff that I'll show you in a few slides, and I was going to present what we're doing on a vaccine, but I omitted those slides now.
What I want to say is, this work that we did relevant to cure today was done without thought for anything to do with therapy or cure. These were just observations, this becomes a science when particularly Bob Siliciano and his colleagues quantify, discover the real nature of the reservoir, the importance of the reservoir. [00:33:30] And others like [John Mellors] here, have put, into scientific aspects, the framework. But this was the first evidence of latency with Mary [E.] Harper, it was by in situ hybridization (ISH), and a follow-up paper showed that activation of latently infected cells left the virus expression. (21) This was a collaboration with my French colleague, Daniel Zagury. (22) Coming to the last of this, we also found that children and adults' brains were [00:34:00] infected. (23) So I'm not saying this is a reservoir, I'm saying we don't know for sure. And that macrophage was a targeted infection, which was mentioned last night also by Robin. (24)
In my last slide, these are our current interests, and I'll end with this. Could we have done better? One thing haunts me. We are always proud of how fast the US got the blood test and brought it out. Yet sitting with the hemophiliac's whole family, it [00:34:30] was in Paris. His whole family were infected and he says, "Oh, you couldn't have done anything about it, it was in July of '84." I'm sitting here thinking, "We had the blood test in February of '84 in our lab."
If we were thinking and you got, what, four more technicians, just to do a routine screening of hemophilia to combine plasma in those days, couldn't we really have tested all the hemophiliac concentrated factor VIII, if not in the world, certainly in America and probably in a good part of the world with a little extra [00:35:00] technicians even in February, March '84? When did it become out and available to everybody? January or February of 1985, so if there was a Mark Harrington then around us, he would have said, "Why aren't you doing something for hemophiliacs?" We just never even thought about it, nor did anybody up the ladder think about it in those days. I'll leave you with that. Thanks.
Bruce Walker (Moderator): [00:35:30] Thanks, Bob. We'll have some questions.
Bob: It wouldn't be a talk if we didn't have a question.
Wasif Khan: Actually, the HTLV-1 and HIV double-infection is curious, and I was thinking about the implications of that. Is there--
Bob: It's not uncommon, in our first studies, it was close to about, I think it's about 5%, 6% of all the people we were studying. [00:36:00] I admit, there was a lot of drug addicts included there. In the United States, where HTLV-1 is not so common, there's about 5% in our first studies that are double-infected.
Wasif: That's important information. I was thinking about in areas of the world where HTLV-1 is very common, is the incidence of HIV, because the T cells are now living much longer or activated state--
Bob: There's literally no funding for such studies that I know of, and I don't know any data that's [00:36:30]relevant to it. The place I would want to go, go to Miami, you get the Caribbean, Caribbean is the source, and they get a lot of Caribbean patients that get a lot of HTLV-1 disease, that's where the study could be best on. [William J.] Harrington[, Jr.] (1954–2009) who died, unfortunately, premature, like his father who was head of that clinic, would be the right person to do that, but it's an open issue. I thank you for the question, but I can't answer it really.
Genoveffa Franchini: Rob, there are three papers on that HTLV and HIV coinfection and the one says that the HTLV [00:37:00] pre-infection increased the incidence, the other one says the opposite, and the other one says that there is no difference. [crosstalk]
Bob: That's why I didn't mention it, Veffa, that's why I couldn't answer that question because there's no data on it. We can say anything we want, right? I mean, you would think you'd be much worse off, because HTLV-1 is immune-deficient-causing. You'd say it's got to be worse off. But on the other hand, it's driving the proliferation of T cells, so maybe you can't see it as easily. I don't know what to say, [00:37:30] we never studied it, obviously. As I said, I don't know how easy it would be to get a grant for that.
Participant 2: Maybe this might be easier to detect clonal HIV because of the T cell [unintelligible 00:37:43]
Bob: I'm not hot on cloning it, I believe it for the importance of the reservoir of what John and others are doing, but I don't believe it for a moment for malignancies, too many look at. We have other ideas with the malignancies that we're pursuing. [00:38:00] I don't think it's going to be genes of HIV. There's one guy back up there.
Moderator: Robin, somebody over here? Hi, Paul.
Robin Weiss: I don't think you should be filled with retrospective remorse about not using an antibody test to test the clotting factors [factor VIII] back in February of 1984, because those clotting factors were pooled from a vast number of donors. I think the antibody would have been [00:38:30] diluted out. You wouldn't have got a very positive signal even though there was still an infectious virus hidden in the pool samples. I could go back and test it because I suspect it would be very, very [crosstalk]
Bob: I get your point, it's interesting, and I never thought of it, thanks. You got a very good point.
Participant 6: I have one back here, Rob.
Bob: Yes, sir.
Michael Worobey: I'm going to talk later tonight about the [00:39:00] molecular epidemiology of the virus in Haiti, and I'm curious about that coinfected patient that was transfused in Haiti. Have you sequence that virus and is it a consistent implication?
Bob: I don't remember because I hated that story, as we look at it in retrospect, oh, yes it gave us the idea, but in those days I was in a competitive spirit, it really caused us mass confusion because I was [00:39:30] too quick to want to believe the specific—Look, the T-lymphotropic retrovirus idea bore fruit, but we were really thinking it had to be the HTLV family. Good lord, we had spent so long to show one category of retroviruses, now we're going to have another whole category.
That thing was cross-reacting with monoclonal antibodies to HTLV-1, yet it was different, it was cytopathic, it had other differences. It really held us back. So I probably would have wanted to throw it down in the sink, and we never published that. [00:40:00] It's on the cover of the American Journal of Pathology from a Johns Hopkins pathologist because he wanted this story, and he heard about it, so we gave it to him, but we never formally published that, but I very much doubt if we sequenced it. Do you remember, Flossie [Wong-Staal], or anybody?
Flossie Wong-Staal: I don't think so.
Michael: And you didn't throw it down the sink? Someone could still sequence that?
Bob: Maybe it's still there, I hope probably in the freezer, I would guess so. No, we wouldn't throw it down the sink, no, freezer. We drink that water.
Mila Pollock: Bob, [00:40:30] this is not a scientific question. The past feels pretty bad in the future, in my opinion. What helps a scientist to survive, regardless, inside difficult situations, not only in the lab but in life?
Bob: What is the question?
Participant 3: The question is for the future researchers.
Bob: I get your question. You want to know why I lived?
Participant 3: Yes, I want to know how to survive.
Bob: [00:41:00] The answer, I guess, is your temperament, your nature that you can't really change, you're still driving a competitive spirit to understand more, a competitive spirit sometimes with colleagues, friends. I think I bank on friends and family. I don't know what else to say. I couldn't have had—Those days were a lot of problems but beyond that—and support from the leadership of your institute, I never [00:41:30]lack for that. I could say that, if I had acknowledgments, part of the acknowledgments are to the leadership of NIH, and to institutes at NIH that made the environment able to survive.
Bruce: Take one last question.
Participant 4: Hi, great talk. Just in the context of the reservoir, we are looking for diminishing amounts of virus in very rare cells. In the old days, there was buckets of [00:42:00] virus, and it took a while to determine the difference between HTLV and HIV. Do you think it's important, as we consider the reservoir, to exclude HTLV in our detection methods, whether they're co-constitutive or…?
Bob: No. Well, maybe in Africa and the Caribbean and places where it's endemic. I’d certainly not in the United States, where it's a much more unusual infection. I forget what, but it's like, 0.1% or 0.05%, so I don't think so. I think that [00:42:30] would be a loss of money, not well spent.
Participant 4: But if we were looking at sub-Saharan Africa or more [crosstalk]
Bob: It's a tough question for me. It depends where in Africa, some tribes have a lot of virus, and some tribes don't have it. You'd have to know the endemic background, and if you knew the endemic background, I think you'd make an interesting study. The people studying reservoirs right now, we all feel, have enough problems of their own.
Bob: Where is Bob [Siliciano]?
Participant 4: [crosstalk] [00:43:00] contamination with HTLV could be one of them that we don't know about, potentially?
Bob: Also when you shock and kill, you may be activating more HTLV. I don't know why this came up, it may not come up in the meeting again, but I just got a paper on my desk that says after shock and kill, the reservoir grows, which John Mellors said to me last night earlier today, which itself is not shocking if you’ll pardon the pun.
Bruce: [00:43:30] Thanks very much, Rob.
Bob: Thank you.
[00:43:34] [END OF AUDIO]
- Oshinsky, David M. Polio: An American Story. Oxford: Oxford University Press, 2005.
- Weiss, Robin, Natalie Teich, Harold E. Varmus, and John M. Coffin, eds. RNA Tumor Viruses. Vol. 1. Cold Spring Harbor Monograph Series. Cold Spring Harbor Laboratory Press, 1982.
- Hiatt, Howard H., James D. Watson, and Jay A. Winsten, eds. Origins of Human Cancer. Cold Spring Harbor Conferences on Cell Proliferation, v. 4. Cold Spring Harbor Laboratory Press, 1977.
- Bobrow, Samuel N., R. Graham Smith, Marvin S. Reitz, and Robert C. Gallo. “Stimulated Normal Human Lymphocytes Contain a Ribonuclease-Sensitive DNA Polymerase Distinct from Viral RNA-Directed DNA Polymerase.” Proceedings of the National Academy of Sciences 69, no. 11 (November 1, 1972): 3228–32. doi:10.1073/pnas.69.11.3228.
- Reitz, Marvin S., R. Graham Smith, E. A. Roseberry, and Robert C. Gallo. “DNA-Directed and RNA-Primed DNA Synthesis in Microsomal and Mitochondrial Fractions of Normal Human Lymphocytes.” Biochemical and Biophysical Research Communications 57, no. 3 (April 8, 1974): 934–48. doi:10.1016/0006-291X(74)90635-4.
- Baltimore, David, and Donna Smoler. “Primer Requirement and Template Specificity of the DNA Polymerase of RNA Tumor Viruses.” Proceedings of the National Academy of Sciences 68, no. 7 (July 1, 1971): 1507–11. doi:10.1073/pnas.68.7.1507.
- Morgan, Doris A., Francis W. Ruscetti, and R. Gallo. “Selective in Vitro Growth of T Lymphocytes from Normal Human Bone Marrows.” Science 193, no. 4257 (September 10, 1976): 1007–8. doi:10.1126/science.181845.
- Ruscetti, Francis W., Doris A. Morgan, and Robert C. Gallo. “Functional and Morphologic Characterization of Human T Cells Continuously Grown in Vitro.” The Journal of Immunology 119, no. 1 (July 1, 1977): 131–38.
- Poiesz, Bernard J., Francis W. Ruscetti, Adi F. Gazdar, Paul A. Bunn, John D. Minna, and Robert C. Gallo. “Detection and Isolation of Type C Retrovirus Particles from Fresh and Cultured Lymphocytes of a Patient with Cutaneous T-Cell Lymphoma.” Proceedings of the National Academy of Sciences 77, no. 12 (December 1980): 7415–19. doi:10.1073/pnas.77.12.7415.
- Gottlieb, Michael S., Howard M. Schanker, Peng Thim Fan, Andrew Saxon, Joel D. Weisman, and I. Pozalski. “Pneumocystis Pneumonia—Los Angeles.” MMWR Morbidity and Mortality Weekly Report 30, no. 21 (June 5, 1981): 250–52.
- Gottlieb, Michael S., Robert Schroff, Howard M. Schanker, Joel D. Weisman, Peng Thim Fan, Robert A. Wolf, and Andrew Saxon. “Pneumocystis Carinii Pneumonia and Mucosal Candidiasis in Previously Healthy Homosexual Men.” New England Journal of Medicine 305, no. 24 (December 10, 1981): 1425–31. doi:10.1056/NEJM198112103052401.
- Siegal, Frederick P., Carlos Lopez, Glenn S. Hammer, Arthur E. Brown, Stephen J. Kornfeld, Jonathan Gold, Joseph Hassett, et al. “Severe Acquired Immunodeficiency in Male Homosexuals, Manifested by Chronic Perianal Ulcerative Herpes Simplex Lesions.” New England Journal of Medicine 305, no. 24 (December 10, 1981): 1439–44. doi:10.1056/NEJM198112103052403.
- Jaffe, Harold W., Keewhan Choi, Pauline A. Thomas, Harry W. Haverkos, David M. Auerbach, Mary E. Guinan, Martha F. Rogers, et al. “National Case-Control Study of Kaposi’s Sarcoma and Pneumocystis Carinii Pneumonia in Homosexual Men: Part 1, Epidemiologic Results.” Annals of Internal Medicine 99, no. 2 (August 1983): 145–51. doi:10.7326/0003-4819-99-2-145.
- Barré-Sinoussi, Françoise, Jean-Claude Chermann, Françoise Rey, Marie-Thérèse Nugeyre, Sophie Chamaret, Jacqueline Gruest, Charles Dauguet, et al. “Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS).” Science 220, no. 4599 (May 20, 1983): 868–71. doi:10.1126/science.6189183.
- Gallo, Robert C., Syed Zaki Salahuddin, Mikulas Popovic, Gene M. Shearer, M. Kaplan, Barton F. Haynes, Thomas J. Palker, et al. “Frequent Detection and Isolation of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and at Risk for AIDS.” Science 224, no. 4648 (May 4, 1984): 500–503. doi:10.1126/science.6200936.
- Popovic, Mikulas, Mangalasseril G. Sarngadharan, Elizabeth Read, and Robert C. Gallo. “Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS.”Science 224, no. 4648 (May 4, 1984): 497–500. doi:10.1126/science.6200935.
- Sarngadharan, Mangalasseril G., Mikulas Popovic, L. Bruch, J. Schupbach, and Robert C. Gallo. “Antibodies Reactive with Human T-Lymphotropic Retroviruses (HTLV-III) in the Serum of Patients with AIDS.” Science 224, no. 4648 (May 4, 1984): 506–8. doi:10.1126/science.6324345.
- Safai, Bijan, Jerome E. Groopman, Mikulas Popovic, Jörg Schüpbach, M. G. Sarngadharan, Kathy Arnett, Ann Sliski, and RobertC. Gallo. “Seroepidemiological Studies of Human T-Lymphotropic Retrovirus Type Iii in Acquired Immunodeficiency Syndrome.” The Lancet, Originally published as Volume 1, Issue 8392, 323, no. 8392 (June 30, 1984): 1438–40. doi:10.1016/S0140-6736(84)91933-0.
- Mitsuya, Hiroaki, Kent J. Weinhold, Phillip A. Furman, Marty H. St. Clair, Sandra Nusinoff Lehrman, Robert C. Gallo, Dani Paul Bolognesi, David W. Barry, and Samuel Broder. “3’-Azido-3’-Deoxythymidine (BW A509U): An Antiviral Agent That Inhibits the Infectivity and Cytopathic Effect of Human T-Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus in Vitro.” Proceedings of the National Academy of Sciences 82, no. 20 (October 1, 1985): 7096–7100. doi:10.1073/pnas.82.20.7096.
- Cocchi, Fiorenza, Anthony L. DeVico, Alfredo Garzino-Demo, Suresh K. Arya, Robert C. Gallo, and Paolo Lusso. “Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells.” Science 270, no. 5243 (December 15, 1995): 1811–15. doi:10.1126/science.270.5243.1811.
- Harper, Mary E., Lisa M. Marselle, Robert C. Gallo, and Flossie Wong-Staal. “Detection of Lymphocytes Expressing Human T-Lymphotropic Virus Type III in Lymph Nodes and Peripheral Blood from Infected Individuals by in Situ Hybridization.” Proceedings of the National Academy of Sciences 83, no. 3 (February 1, 1986): 772–76. doi:10.1073/pnas.83.3.772.
- Zagury, Daniel, Joëlle Bernard Bernard, R. Leonard, Rémi Cheynier, Michael Feldman, Prem S. Sarin, and Robert C. Gallo. “Long-Term Cultures of HTLV-III-Infected T Cells: A Model of Cytopathology of T-Cell Depletion in AIDS.” Science 231, no. 4740 (February 21, 1986): 850–53. doi:10.1126/science.2418502.
- Shaw, George M., Mary E. Harper, Beatrice H. Hahn, Leon G. Epstein, D. Carleton Gajdusek, Richard W. Price, Bradford A. Navia, et al. “HTLV-III Infection in Brains of Children and Adults with AIDS Encephalopathy.” Science 227, no. 4683 (1985): 177–82. doi:10.1126/science.2981429.
- Gartner, Suzanne, Paul Markovits, David M. Markovitz, Mark H. Kaplan, Robert C. Gallo, and Mikulas Popovic. “The Role of Mononuclear Phagocytes in HTLV-III/LAV Infection.” Science 233, no. 4760 (July 11, 1986): 215–19. doi:10.1126/science.3014648.
- 1.1 James D. Watson — Welcome
- 1.4 Robin Weiss — Retrovirus History and Early Searches for Human Retroviruses
- 1.5 John Coffin — The Origin of Molecular Retrovirology
- 1.6 Harold Varmus — Animal Retroviruses and Cancer Research
- 1.7 Max Essex — From Feline Leukemia Virus to AIDS in Africa
- 2.0 Michael Gottlieb — Introduction to Session 2
- 2.1 Paul Volberding — The First Patients
- 2.2 James Curran — Deciphering the Epidemiology of AIDS
- 2.3 Mark Harrington — The Importance of Activism to the US Response
- 2.5 Françoise Barré-Sinoussi — Discovery of HIV
- 3.2 Samuel Broder: The First Clinical Trials of Antiretroviral Drugs
- 3.4 Raymond Schinazi — Discovery and Development of Novel NRTIs
- 3.6 John Martin — Making it Simpler: A Single Pill to Treat HIV
- 4.3 Beatrice Hahn — Apes to Humans: The Origin of HIV
- 4.4 Michael Worobey — Spread of HIV in the New World
- 5.1 Flossie Wong-Staal — Discovery of Human Retroviral Transactivators
- 5.4 Edward Berger — Discovery of HIV Co-receptors
- 6.3 Bruce Walker — Role of T Cells in Controlling HIV Infection
- 6.4 Barton Haynes — Development of HIV Vaccine: Steps and Missteps
- 6.6 Robert Redfield — The PEPFAR Program to Treat HIV in Africa
- 8.1 John Mellors — MACS and Beyond: Epidemiology, Viremia and Pathogenesis
- 8.4 Robert Siliciano — The Challenge of the HIV Reservoir
- 8.6 David Baltimore — Bringing it to an End (And Where Are We Going?)
- Africa, sub-Saharan Africa
- antibody test, antigen test, serological test, serology
- antibody, immunoglobulin
- AZT (azidothymidine)
- Bethesda, Maryland
- blood — banks, donors, plasma, screening, transfusions, clotting factors (factor VIII)
- bovine leukemia virus (BLV)
- Burroughs-Wellcome & Company (GlaxoSmithKline)
- Cairns, John (1922–2018)
- Caribbean and West Indies
- CCR5 (chemokine receptor type 5)
- CDC (Centers for Disease Control and Prevention, US)
- cell culture, tissue culture, immortalized cell line
- contact tracing
- control — experimental control, control group, blinded experiment
- counterfactual history
- cure vs. remission of HIV/AIDS
- DNA polymerase
- Duesberg, Peter H. (b. 1936)
- early theories of AIDS etiology
- enzyme-linked immunosorbent assay (ELISA)
- epistemic object becomes the technical object
- FDA (US Food and Drug Administration)
- feline leukemia virus (FeLV)
- Friedman-Kien, Alvin E.
- Gelmann, Edward P.
- gibbon ape leukemia virus (GaLV)
- Gross, Ludwik (1904–1999)
- Hardy, William D., Jr.
- Harper, Mary E.
- Harrington, William J., Jr.
- Haverkos, Harry W.
- highly active antiretroviral therapy (HAART), combination antiretroviral therapy (cART)
- HIV-1 MN strain
- Holmes, King K.
- HTLV (human T-lymphotropic virus)
- Huebner, Robert J. (1914–1998)
- in situ hybridization (ISH)
- influenza pandemic of 1918–1920 (Spanish flu)
- Jacobson, Leon O. (1911–1992)
- Jarrett, William (1928–2011)
- Kawakami, Thomas G.
- lab safety, biosafety levels, safety protocol
- lab vs. clinic
- Lancet (journal)
- Levy, Jay A. (b. 1938)
- Lo, Shyh-Ching
- MERS (Middle East respiratory syndrome)
- microscope — electron and optical
- Montagnier, Luc (b. 1932)
- mother-to-child transmission of HIV
- Mullis, Kary (1944–2019)
- National Cancer Institute (NCI)
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Institutes of Health (NIH)
- natural selection, evolutionary selection, evolutionary fitness
- NYU (New York University)
- oncogene (onc)
- Operation INFEKTION (Jakob Segal, Operation DENVER)
- pediatrics, pediatric AIDS
- peer review
- PEPFAR (President's Emergency Plan For AIDS Relief)
- pharmaceutical industry
- PNAS (Proceedings of the National Academy of Sciences)
- Popovic, Mikulas
- poppers (amyl nitrate)
- public health
- Read-Connole, Elizabeth
- Reitz, Marvin S.
- reverse transcriptase
- reverse transcriptase assay
- Safai, Bijan
- San Francisco, California
- SARS (Severe acute respiratory syndrome)
- Science (journal)
- scientific competition and collaboration
- sensitivity and specificity; false positive, false negative; biological specificity
- Session 2: The Pandemic Begins, Early Discoveries
- Session 7: Prospects for an HIV Vaccine
- Siegal, Frederick
- Spiegelman, Sol (1914–1983)
- styles of scientific thought
- Temin, Howard M. (1934–1994)
- Todaro, George J. (b. 1937)
- tropical disease, tropical medicine
- tuberculosis (TB)
- United States
- VaxGen (1995–2016)
- viral reservoir, viral latency, disease reservoir
- Wagner, Robert R. (1923–2001)
- Western blot
- Yale University, Yale School of Medicine
- Zagury, Daniel
- zur Hausen, Harald (b. 1936)
Found 47 search result(s) for Gallo.
... human Tcell lymphoma virus III, was the name used by the group led by Bob Gallo at the National Cancer Institute ARV, or AIDS associated retrovirus, was the name used by the group ...
Mar 07, 2021
... human retroviruses during the 1970s gave up and said, "They're not really there." Bob Gallo persisted, and was rewarded in 1980 with a genuine human retrovirus infection. (9) If you're interested ...
Apr 27, 2021
... one who I have to say paid a lot of attention to it rapidly was Bob Gallo. #scientific competition and collaboration Then, soon after that, within a couple of years or so, we ...
Apr 27, 2021
... research, Dingell led separate fraud investigations against David Baltimore and Bob Gallo in the 1980s and early 1990s
Mar 06, 2021
... gave me as a topic to work on an antiviral drug, HPA23 (antimonium tungstate). Bob Gallo, do you remember that, HPA23? Bob: Yes, you know, you had ...
Apr 27, 2021
... Elizabeth "Betsy" ReadConnole, a technician in the Gallo lab in the 1980s
Jan 03, 2021
... American virologist, cofounded the Institute of Human Virology (IHV) with Robert Gallo and Robert R. Redfield in 1996 at University of Maryland
Jan 08, 2021
... blood cells. Interleukin 2 stiumlates the growth of T cells, and was discovered by Bob Gallo and others in 1976–77
Jan 01, 2021
... 00:03:30 laughter I probably wasn't at the first meeting that Bob Gallo gave because in the fall of 1986 I went off on a sabbatical in England, so ...
Apr 27, 2021
... Pasteur, led by Luc Montagnier and Françoise BarréSinoussi, and the team at the NCI, led by Bob Gallo
Jan 03, 2021
... see discovery and naming of HIV/HTLVIII/LAV/ARV The HTLVI was discovered by Bob Gallo in 1980, the HTLVs as a whole are the only known oncogenic human retroviruses. (See Bernard ...
Jan 26, 2021
... 2.3 Mark Harrington — The Importance of Activism to the US Response https://libwiki.cshl.edu/confluence/pages/viewpage.action?pageId=12943620 2.4 Robert Gallo — Discoveries of Human Retrovirus, Their Linkage to Disease as Causative Agents & Preparation for the Future https://libwiki.cshl.edu/confluence/pages/viewpage.action?pageId=12943622 ...
Mar 06, 2021
... years was, because of my friend Bill Blattner, he introduced me to Bob Gallo. I got to also go to that monthly lab meeting, which gave me ...
Apr 27, 2021
... because that is exactly—" You know, if you're doing a film, and you interview Bob Gallo, you'll have one and a half minutes, but in reality, I have an hour. They said ...
Apr 27, 2021
... Many of these physicians—including Sam Broder, Jim Curran, Tony Fauci, Bob Gallo, Doug Richman, and Harold Varmus—were derided as "Yellow Berets," but as historian Raymond ...
Jan 08, 2021
... clinical syndrome 00:03:00, and that was through the work of Françoise BarréSinoussi and Bob Gallo and JeanClaude Chermann (b. 1939) and Jay Levy (b. 1938). This is a slide from ...
Apr 27, 2021
... Laboratory Isolation Facility. It was designed to work on cancer viruses. With Dani, we joined the Gallo AIDS working group, which means you go to the Gallo monthly lab meetings. My job was to find a hemophiliac cohort, which 00 ...
Apr 27, 2021
... diagram above and the nomenclature for HTLV and HIV genes were codified in Robert C. Gallo et al., “HIV/HTLV Gene Nomenclature,” Nature 333, no. 6173 (June ...
Mar 01, 2021
... 00:00:30 faces and also, especially my previous coworkers, Bob Gallo, Beatrice Hahn, Veffa Franchini, and hopefully George Shaw later on. When I ...
Apr 27, 2021
... 00:03:30 I think just a few months before the Bob Gallo and coworkers four publications in Science magazine (on May 4, 1984, see 4 ...
Apr 27, 2021
... when I came into public health—probably like Tony Fauci and Bob Gallo—as a commissioned officer 00:01:00 during the Vietnam War. When we ...
Apr 27, 2021
... meeting. It has been really an enormous honor and pleasure to be able to interact with Bob Gallo and with Bruce Walker to put it together over the last year or so. I'm going ...
Apr 27, 2021
... admission. You've heard the unbelievably brilliant work from Dr. Robert C. Gallo and Professor Françoise BarréSinoussi 00:03:30 on the discovery of the pathogenic retrovirus, which ...
Apr 27, 2021
... 00:06:30 memoirs. Here, we see the memoirs written by Bob Gallo and Luc Montagnier (b. 1932) about the research on identifying the AIDS virus. (6 ...
Apr 27, 2021
... foggy hypothesis: more pathogen, more 00:01:30 disease. Bob Gallo, I didn't put the slide up here, but you and Flossie WongStaal published ...
Apr 27, 2021
... time though was that the only person at the NIH who had larger lab than Gallo was Flossie WongStaal. laughs 00:01:00 It's shown pretty well ...
Apr 27, 2021
... French have discovered the cause of AIDS. Then there's a press conference at which Bob Gallo, who's here and helped organize this meeting is with Margaret Heckler (1931–2018), the secretary ...
Apr 27, 2021
... Biology at the NIH, where I was a postdoc starting in 1982. I met Bob Gallo in Munich, in the Nymphenburg Gardens, he hired me, and I don't really know ...
Apr 27, 2021
... than the number of cells expressing viral RNA. (1) In early studies, Bob Gallo and Flossie WongStaal showed that the same thing was true in HIV infection. (2) And a number ...
Apr 27, 2021
... 01:00 begins in 1985 when Joe Sodroski, and Flossie WongStaal, the Robert Gallo lab, and the William Haseltine lab, first identified an activity in HIVinfected cells that greatly ...
Apr 27, 2021
... new mysterious illness. I'm also very grateful that in the spring of 1984, Bob Gallo allowed me to train in his lab for a week. This may not be known to someone like ...
Apr 27, 2021
... emergence of new diseases. Then something else really pivotal happened, and that is, this guy, Bob Gallo, came to Mass General in May of 1984, to talk about his discovery. To me ...
Apr 27, 2021
... HIV patients on highly active antiretroviral therapy (HAART), the great work that Bob Gallo 00:08:30 described earlier, David had contributed as had Marty ...
Apr 27, 2021
... Thank you. Historically, I started to work on the HIV vaccine together with Bob Gallo, early on in the mid'80s. We started really to look at different possibility of different ...
Apr 27, 2021
... lymphomas in AIDS patients, I really don't know the answer to that question, Bob Gallo, or others?. John Mellors: There is one tumor currently that's been reported with a BACH2 ...
Apr 27, 2021
... very important people that did so much with this epidemic. Thanks especially to Bob Gallo for inviting me. Heard about this I think about when I was giving ...
Apr 27, 2021
... Ray Schinazi: Thank you Bob Gallo. Thank you for inviting me and the rest of the gang. It's a pleasure to be here. I ...
Apr 27, 2021
... refactors released by CD8 T cells that are able to suppress HIV infection. From the Gallo lab, Paolo Lusso, they identified three proteins RANTES, MIP1 alpha and MIP1 ...
Apr 27, 2021
... Pollock, Executive Director of Libraries and Archives, Cold Spring Harbor Laboratory Bob Gallo John Coffin Bruce Walker Warner: 00:00:00 —Is maybe to have ...
Apr 27, 2021
... want to thank the organizers for inviting me. I want to particularly thank Bob Gallo who actually when he called me up and invited me, asked ...
Apr 27, 2021
... 00:00:00 Okay, well, I also have to thank Bob Gallo for the invitation and the team that put together the conference. Bob suggests this title, said you ...
Apr 27, 2021
... morning. First of all, thank you very much to John Coffin, Bob Gallo, and Bruce Walker for convening this meeting and inviting me. It's quite a humbling experience ...
Apr 27, 2021
... have with TB in the country, but as you know there, it's a huge problem. And once Bob Gallo? was telling me that he thought we needed a PEPFAR (President's Emergency Plan ...
Apr 27, 2021
... Human Services, HHS) secretary Margaret Heckler (1931–2018) announced that Bob Gallo discovered the virus he called HTLVIII or human Tcell leukemia virus 3 ...
Apr 27, 2021
... worked in the Congo were teachers that were working under a UN program. Bob Gallo: In the end, I think it's a kind of a barroom talk because, who gives ...
Apr 27, 2021
... many have said, it's a great honor to be invited to be here, and thanks to Bob Gallo, John Coffin, Mila Pollock, and Bruce Walker for the invitation. I didn't have ...
Apr 27, 2021
... hands on the virus, to actually bring it to the laboratory to work because there's a story of Bob Gallo. Bob was very gracious. I remember Ed and I actually called you ...
Apr 27, 2021
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