During the first critical months of research on HIV, the work of the LTCB scientists was far behind that of the scientists at the IP. The reason the LTCB scientists lagged behind was a misplaced focus on the "HTLV" (human T-cell leukemia virus) family as the probable source of the cause of AIDS. Not only did this incorrect focus misdirect the work of the LTCB scientists, for a time it misdirected the work of much of the scientific community, due to Dr. Gallo's preeminent position vis-a-vis human retrovirus research.
In early 1983, scientists at both the IP (Montagnier et al.) and the LTCB (Gallo et al.), searching for the cause of AIDS, attempted to isolate a retrovirus (a virus that reproduces itself using RNA as well as DNA) from AIDS and pre-AIDS patients. Dr. Gallo frequently asserted it was he who first proposed the idea to look for a retrovirus as the cause of AIDS. But Dr. Gallo's early theorizing about the AIDS virus mistakenly placed that virus in the "HTLV" (for "human T-leukemia virus," later changed to "human T-lymphotropic virus") family (see, e.g., Medical World News, August 14, 1982, p. 9).
By Dr. Gallo's own admission (see below), his misunderstanding of the fundamental nature of the AIDS virus associated with the mistaken belief that HIV was an "HTLV" resulted in significant confusion and delay in the work of the LTCB scientists. Even for years after HIV had been discovered and its true defining features identified, Dr. Gallo fought a losing battle to keep the AIDS virus in the "HTLV" family by retaining the name "HTLV-III," rather than HIV (see below).
Dr. Gallo himself acknowledged in his November 1986 sworn declaration before the USPTO, that in the Spring of 1983,
"...I thought that the best idea of the causative agent of AIDS was most likely to be a new variant of HTLV-I ... our thinking at the time was that the AIDS virus was likely to be a close relative of HTLV-I" (Declaration of Robert C. Gallo; November 8, 1986, p. 10).The IP scientists isolated and began to grow their virus in January/February 1983. Some of the early IP experiments characterizing this virus used reagents provided by Dr. Gallo, for which contribution Dr. Gallo was acknowledged in the first IP paper, published in May 1983 (Barre-Sinoussi
The IP scientists recognized early on that their virus, first called "LAV" for "lymphadenopathy-associated virus" (lymphadenopathy is a pre-AIDS condition) appeared to be distinctly different from the known human retroviruses, HTLV-I and II. The AIDS virus, unlike the other human retroviruses known in 1983, is strongly "cytopathic," i.e., it kills the cells in which it grows. The IP scientists recognized the cytopathicity of the virus and kept their virus cultures alive by adding fresh cells to the cultures or by "passaging" the virus to fresh cell cultures (see e.g., Barre-Sinoussi et al.,1983; Montagnier et al., 1984; Barre-Sinoussi et al., 1984).
By contrast, the LTCB scientists, because they were looking for a variant of HTLV-I (the human T-cell leukemia virus), which immortalizes the cells in which it grows, did not comprehend that the virus they occasionally detected in AIDS patients' samples actually was killing the cells. Consequently, the LTCB scientists, for a prolonged period of time, were unable to keep their AIDS patients' virus cultures alive. Consequently, by their own accounts, the LTCB scientists repeatedly discarded AIDS patient cultures, when the cultures died out or failed to grow. Again and again the LTCB scientists unsuccessfully attempted to grow an AIDS virus using methods suitable for an "HTLV" -- not an HIV-type virus.
Meanwhile, throughout all of 1983, the only contribution the LTCB scientists made to the scientific literature and dialogue concerning possible causes of AIDS was to reiterate that "HTLV" was "... a very attractive candidate" (Gallo remarks at 7/18/83 meeting of the NCI AIDS Task Force).
Dr. Gallo was not content to rely on his own papers to support his thinking about "HTLV" and AIDS; while serving as nominal "peer reviewer," he actually altered the contents of the seminal paper by the IP scientists (Barre-Sinoussi et al.; Science, 1983, 220, pp. 868 - 871), composing a misleading abstract, adding to and otherwise revising the text of the paper to strengthen the apparent relationships between the IP virus and "HTLV," defined by Dr. Gallo as "human T-cell leukemia viruses." Later, during the French/American dispute, Dr. Gallo, HHS officials, and DOJ attorneys compounded the damage to the IP scientists' work by blaming them for the very "errors" of understanding -- particularly the alleged close associations of the IP virus with the leukemia virus -- that Dr. Gallo introduced into their paper (see below).
Dr. Gallo argued to OSI that the changes/additions he made to the IP scientists' paper were fully substantiated by what the IP scientists originally wrote. But the Subcommittee staff's review of various drafts of the paper showed that the most significant passages Dr. Gallo offered to justify the changes/additions he made to the paper were themselves itself written by him! An example is Dr. Gallo's alteration of a sentence in the body of the paper that originally referred to "... this virus [the IP virus] as well as HTLV isolates" to read "... this virus, as well as all previous HTLV isolates ..."
Dr. Gallo's actions vis-a-vis the Barre-Sinoussi et al. paper were characterized by the NIH Office of Scientific Integrity (OSI) as, "gratuitous, self-serving, and improper" and by the Office of Research Integrity (ORI) as reflecting, "... Dr. Gallo's propensity to misrepresent and mislead in favor of his own research findings or hypotheses."
Curiously, despite his admitted failure to grow the AIDS virus, Dr. Gallo frequently claimed it was he who developed the methodology for detecting and propagating the AIDS virus and that he taught these methods to the IP scientists. Like Dr. Gallo's claim concerning the "idea of a retrovirus" as the cause of AIDS, the claims about the method for growing the virus played an important role in the U.S. effort to defend the patent of Gallo et al.
In a July 1985 letter to Dr. Claudine Escoffier-Lambiotte, Medical Editor of Le Monde, Dr. Gallo wrote that among his contributions to the IP scientists, he provided,
"...the major techniques to grow the T-cells (the same as used for HTLV-I)."In his 1991 book Virus Hunting, Dr. Gallo described an occasion on which allegedly instructed the IP scientists concerning the growth of their new retrovirus:
"In January 1983, Chermann called to tell me about their positive reverse transcriptase in this one sample and to ask for my advice about how to keep the culture going. I suggested that he add human T4 blood lymphocytes obtained from the umbilical-cord blood of newborns as target cells, an approach used earlier for HTLV-2. Applying this information he succeeded in saving their virus ... by obtaining and adding new umbilical-cord blood cells every few days" (p. 147).Dr. Gallo repeated to OSI the claims that he taught the IP scientists how to grow the AIDS virus and that Chermann and Montagnier themselves acknowledged this was a Gallo contribution. Here is what Dr. Gallo told OSI:
"Both Chermann and Montagnier have acknowledged openly Gallo for suggesting adding cells, either directly, that is Chermann by telephone acknowledges this, or indirectly, that by way of his published work in the case of Montagnier. This was the standard technique of cultivation for retroviruses that our lab had developed. The notion that the French group had enormous clarity of thought while we blundered about with HTLV-I is just a bit of nonsense" (8/3/90 OSI interview; transcript p.236).But Dr. Gallo's claims do not square with the facts. His claims also are contradicted by accounts of the IP scientists, including even Dr. Chermann, an occasional ally of Dr. Gallo. Speaking to OSI, Dr. Chermann was both more discriminating concerning what Dr. Gallo "suggested" to him and more complete in his account of the significance of Dr. Gallo's suggestions. Dr. Chermann said Dr. Gallo told him that, "...we can use also cord blood lymphocytes" to grow the AIDS virus, but according to Dr. Chermann, the basis for Gallo's suggestion of the use of cord blood was not because Dr. Gallo recognized the cell-killing property of the AIDS virus but,
"... because in HTLV-I it is better to use cord blood cell" (10/5/90) OSI interview; transcript p. 4).More importantly, according to Dr. Chermann, weeks before Dr. Gallo offered the suggestion of adding cord blood, the IP scientists, having already discerned the cytopathic nature of their virus, were already adding fresh cells to their LAV/BRU cultures.
Similarly, in a July 26, 1989 letter to Dr. Gallo, a letter Gallo has frequently invoked as evidence of Chermann's acknowledgement of Gallo's putative contribution, Dr. Chermann made clear how limited was the suggestion reportedly conveyed in the telephone conversation with Dr. Gallo.
Dr. Chermann said this:
"...we requested to you sera to do immunofluorescence and ... you suggest we also to use cord blood lymphocytes."Dr. Chermann wrote tellingly about these matters in a preface he prepared to the French edition of Dr. Gallo's Virus Hunting. In the preface, Dr. Chermann said that in the telephone call with Dr. Gallo early in the IP scientists' work,
"Gallo also told me that the lymphocytes in the blood of the human umbilical cord are very sensitive to human retroviruses ... Gallo and his team had postulated the existence of a cousin to HTLV-I, and the search for this 'cousin,' in addition to attempts to culture it directly, was one of the reasons the American team got behind."Dr. Chermann employed a vivid metaphor to describe the different approaches of the LTCB and IP scientists in their attempts to detect and propagate the AIDS virus, a metaphor that makes clear the limitations and limiting consequences of Gallo's HTLV-I-focused approach. Speaking of Gallo's approach, Dr. Chermann said this:
"He [Gallo] used a key for which no one could identify the lock. We, on the other hand, looked for the lock and made the key afterwards."On another occasion, Dr. Chermann used another vivid metaphor to describe the differences in the IP and LTCB approaches to growing the AIDS virus:
"We grew the plant until it bloomed and we could see what kind of flower it gave. The Americans kept examining seeds and shoots and trying to see if they would turn into the plant they wanted" (AP story in The Cleveland Plain Dealer, 5/1/84).Drs. Montagnier and Barre-Sinoussi denied outright that they were instructed by Dr. Gallo about how to grow the AIDS virus. Writing to Gallo in December 1989, Montganier said this:
"... I did myself the passage of LAV/BRU to human cord blood T lymphocytes as early as March 10, 1983 ... This was the second passage of BRU virus on normal T lymphocytes, the first being on T lymphocytes from an adult blood donor ...Most recently, Dr. Gallo himself significantly downplayed the significance to the IP scientists' work of his reportedly having "given the protocol" to Dr. Chermann. Speaking to Subcommittee staff in the Summer of 1994, Dr. Gallo said this:I used cord blood lymphocytes for many years for EBV transformation ... I really do not think that it was Chermann who gave the idea after he was told by you" (12/29/89 Montagnier-to-Gallo letter; p. 1).
"I never said I helped Barre-Sinoussi or Montagnier. I gave the protocol to Chermann. All they had to do was ask Chermann. Chermann doesn't get asked. I don't want to tell you that I believe that was necessary. I don't know that. Montagnier and Barre-Sinoussi would probably disagree with Chermann. I'm just saying I sent it. And Chermann says that. That's the truth. I'm not lying."
Not only did Dr. Gallo not teach the IP scientists how to grow the AIDS virus, because of his commitment to the leukemia virus as a potential cause of AIDS, Dr. Gallo and his associates, for a prolonged period of time, failed utterly in their own efforts to grow the virus. The reason Gallo et al. failed was because they did not discern the cell-killing nature of the virus.
By Dr. Gallo's own admission, it was the IP scientists who revealed the cytopathicity of the virus to him, and not the other way around. Here is an early account of the circumstances, based in part on an interview with Gallo, as published in June 1984 in the Baltimore Sun:
"...Dr. Chermann helped Dr. Gallo solve a problem that had him stymied in his AIDS research ... one day in his NCI laboratory, something Dr. Gallo had heard Dr. Chermann say in France 'hit me like a ton of bricks.' It was, in retrospect, a simple observation. Dr. Chermann had said the cells kept dying because the virus killed them" (6/17/84).The early secret of success in growing the AIDS virus was not the use of cord blood per se. Rather, the secret was in understanding that the virus was killing the cells and the corollary understanding that because of the cytopathicity of the virus, one way to succeed in its propagation would be to replenish virus culture with fresh cells, either by feeding the existing cultures or passaging the virus to fresh culture material.
It is on this key point that Dr. Gallo's claims that he taught the IP scientists how to grow the AIDS virus fail on logical as well as substantive grounds, i.e., if Dr. Gallo really knew early on that cell-replenishment was the key to propagating the AIDS virus, and if he disclosed this key methodology to the IP scientists in early 1983, why then, for months thereafter, did Gallo and his associates continue to fail in their efforts to grow the AIDS virus? In particular, why did Gallo et al. not use cell-replenishment themselves?
Dr. Gallo recognized the illogic of his claims. When asked by OSI if he fed his cultures with fresh cells, he replied,
"Not as fast as I would like to have done. No, we weren't. We were trying to grow with IL-2 [interleukin-2, also known as 'T-cell growth factor," or TCGF]. It is ironic that I am telling Chermann to add more cord blood cells ... We didn't do it with ours. We thought we could grow it with IL-2. I don't know when more primary cells were added back. I don't know who did that the first time" (9/23/90 interview; transcript pages 83-84).In fact, in an earlier OSI interview, Dr. Gallo dated the LTCB's initial use of cell-replenishment to "late summer, early fall of 1983," many months after the IP scientists began using the technique (7/25/90 OSI interview; transcript pp. 51-52). Shortly after this interview, Dr. Gallo gave OSI what is probably his most authentic account concerning the prolonged inability of the LTCB scientists to grow the AIDS virus -- and the reasons for that failure:
"... I could kick myself [for] not concentrating earlier and trying alternatives to grow the HTLV-I negative specimens" (7/27/90 OSI interview; transcript p.104).Dr. Gallo attempted to argue that "this is science," but he acknowledged the LTCB scientists' failure to grow the AIDS virus was directly related to their failure to understand its intrinsic nature. Speaking of the many specimens the LTCB scientists failed to grow, Dr. Gallo said this:
"... they were always in bad shape. They were in bad shape because they often came far and because the cells were being killed. But we didn't understand yet they were being killed. So, you say, why didn't we just keep -- Yes, now I wish we would have tried other experiments to do anything to keep those samples going. But, if you -- At the time, you are seeing crud and you are losing RT positivity very rapidly, you put it away and you say, 'I will try again. Give me another AIDS specimen.' That is what our whole pathway was" (op cit., p. 104).Indeed, for many months, that was what the "whole pathway was" for the LTCB scientists. Again and again, they attempted the same experiment -- short-term culture of suspected viruses from AIDS/pre-AIDS patients, using the old HTLV-I culture techniques -- failing every time. When they failed, they discarded the cultures, assigning the failure to the circumstance that the "cells were in bad shape," failing to realize why this was so -- i.e., because the cells were being killed by the virus.
Actually, long before his admissions to OSI, in a rare moment of candor, Dr. Gallo acknowledged his failure to recognize the cytopathic nature of the AIDS virus, and his consequent failure to grow it. Speaking of the cytopathic effects of the virus, Dr. Gallo said this to Science magazine:
"We just didn't believe that is what this kind of virus could do ... It is certainly true that in that period of time in summer and certainly by early fall (1983), Chermann had recognized the cytopathic effect of that virus and I had not ... As I look back now, I could bang my head against a wall that we were so stubborn in trying to grow those cells long term in IL-2 ... We went through loss of months with that problem" (230, 1985; p. 520).Thus, by Dr. Gallo's own admission, he either did not possess the secret of growing the AIDS virus or if he did possess it, he inexplicably failed, for many months, to use it. On multiple grounds, Dr. Gallo's frequent claims that he discovered how to grow HIV and "taught" the method to the IP scientists are without foundation.