INSTITUTIONAL RESPONSE TO THE HIV BLOOD TEST PATENT DISPUTE AND RELATED MATTERS

V. COMPARING THE VIRUSES

A. The HHS Press Conference

On April 23, 1984, HHS held a press conference for the international media. The press conference was scheduled on short notice, when news of the LTCB "discoveries" began to leak to the public. During the press conference, HHS Secretary Margaret Heckler announced that:

"... the probable cause of AIDS has been found -- a variant of a known human cancer virus, called HTLV-III ... a new process has been developed to mass produce this virus ... we now have a blood test for AIDS which we hope can be widely available within about six months. We have applied for the patent on this process today" (emphasis added; press conference transcript, p. 4)

Secretary Heckler, in her written text, spoke of the IP scientists' work, particularly their prior discovery of "a virus which they have linked to AIDS patients." Secretary Heckler said,

"... within the next few weeks we will know with certainty whether that virus is the same one identified through the NCI's work. We believe it will prove to be the same" (Heckler prepared remarks, p. 3).

For his part, Dr. Gallo made the aforementioned unsupportable claims that he and his colleagues,

"now have produced more than 50 isolates ... in mass production, and in detailed characterization" (op cit., p. 9) and "... we've been mass-producing it for six months" (op cit., p. 31).

Remarkably, Dr. Gallo also disparaged the IP scientists' virus on grounds that it "did not react with the reagents we had." This statement was significantly misleading, since (1) LAV did react with the LTCB's AIDS/HIV reagents while (2) it not reacting with HTLV-I and II reagents, which is exactly what one would expect with a truly novel retrovirus. Dr. Gallo went on to say that his "HTLV-III" isolates "clearly do belong to the HTLV family." Thus, he said, he was not certain that the IP virus and his own were the same, although he added this:

"It's probably because they really didn't have enough material. They didn't have enough material to send to us. That's what's been the delay. They don't have a mass producer. As of a few weeks ago, they didn't have it successful in a cell line ... I'm not sure they have enough quantity to do everything I'd like to do ... The problem before is there could not be a definitive answer from lack of amount of material that was sent to us" (op cit., pp. 31-32).

The tension within the HHS press conference concerning the work of the IP scientists vis-a-vis the claims of Gallo et al. was but one manifestation of a much broader tension, one that broke into public view in the days immediately leading up to the press conference. During this period, first the Associated Press and then, in a front-page story, TheNew York Times heralded the IP's discovery of LAV, plus the development of the LAV antibody blood test. Concerning the blood test, the AP wire story cited the IP test's performance in detecting,

"... evidence of the virus in 80 percent to 90 percent of American AIDS patients whose blood samples were sent to Paris by the CDC ..."

"... is different from the human leukemia virus that Dr. Robert Gallo ... and others have suggested is a possible cause of AIDS ..."

"... believed a virus discovered in France was the cause of the acquired immune deficiency syndrome ..."

"Dr. Mason and other scientists familiar with the research said that they presumed HTLV-III, LAV and a third virus known as IDAV [another IP HIV isolate] were different names given to the same virus. But tests have not yet been made to determine whether the viruses are the same or not. 'Logic would lead you to believe that we are dealing with one agent with perhaps some closely related variants,' Dr. Mason said ...

"Isolates of viruses similar to the LAV have been made in several laboratories and dozens of papers from these research groups are being written or have been submitted to medical journals...

"One of Dr. Gallo's papers concerning HTLV-I and AIDS appeared in the issue of Science in which the French researchers published their results of the LAV virus last May...

"... Dr. Mason said he was speaking out because of the urgency of the AIDS epidemic. 'We have to move forward on the assumption that this virus [LAV] is the cause in order to speed up trials of possible new therapies for the patients who are dying from AIDS,' Dr. Mason said."

The next day, Dr. Mason arrived at HHS, where, according to Dr. Brandt, he and Mason met alone. Dr. Brandt said that some time earlier, Dr. Mason had told him about the IP scientists' discovery of the probable AIDS virus and development of an HIV antibody blood test. Documentary evidence substantiates this account. Dr. Brandt mentioned in particular that on the day of the press conference, Dr. Mason told him about the "triple-sample" testing (i.e., the CDC comparative serology). Brandt said he came away from his meeting with Mason convinced that Mason believed the IP scientists deserved the credit for the discoveries attributed to them in the New York Times story.

Dr. Mason told Subcommittee staff he had a vivid recollection of being severely scolded by one of Secretary Heckler's senior "public affairs" officials. Dr. Mason said this official accused him of "demeaning the American contribution" to AIDS research and of having "embarrassed Secretary Heckler." Not surprisingly, it was a very subdued James Mason who appeared at the HHS press conference.

By the time of the HHS press conference, Dr. Brandt had determined it was imperative that a careful comparison of "HTLV-III" and LAV be carried out, not to determine if the viruses were genetically identical, for at the time, this issue had not been raised, but to determine if the viruses were the same type and were both the cause of AIDS. (Drs. Gallo and Montagnier agreed between themselves to compare the viruses, during Gallo's visit to the IP, two weeks before the HHS press conference.)

Dr. Brandt told Subcommittee staff the imperative for the virus comparisons was partly "political," i.e., the press and the world were demanding to know if the viruses were the same. But also, said Dr. Brandt, the comparison was a matter of public health concern, since development of a blood test, development of possible vaccines, and development of potential treatments all might vary, if in fact there were two distinct viruses etiologically associated with AIDS. Dr. Gallo, in contrast, asserted to Subcommittee staff that comparisons of the viruses "did not affect public health." But Dr. Brandt told Subcommittee staff he considered comparison of the viruses and development of the HIV antibody blood test as his highest priorities, during the days and weeks immediately following the HHS press conference.

Accordingly, by Dr. Brandt's account, the very day of the press conference, he relayed an order to Dr. Gallo, via NCI Director, Dr. Vincent DeVita, to move immediately to compare the viruses.

B. Comparisons in the Spring/Summer of 1984

Three kinds of comparisons of LAV and HTLV-III (with IIIb as the prototype) were carried out in the Spring and Summer of 1984. No results from these comparisons were ever published.

1. Serological Comparisons: A paper describing the results of the serological comparisons based on the CDC samples (see above) was written, but never published. Dr. Gallo evidently did not favor publication of this paper. A draft, prepared by CDC scientist Dr. Donald Francis, concluded this:

"Overall a high proportion of patients' serum reacted in all laboratories whether HTLV-III or LAV prototype strains were used as antigens."

"... I hardly think this [the serological comparison]is very important since we have said from the first that the viruses are likely to be the same, and since the data was obtained all of us have publicly reported it. A comparison of sera with both is nice but not of any real concern" (emphasis added; 12/27/84 Gallo-to-Francis letter).

"... neither you nor anyone else should be making serological comparative papers."

"I think it is silly ... for you to persist in the LAV (first) HTLV-III nomenclature ... LAV is clearly an inaccurate name and AIDS virus or AIDS related virus is the dumbest name I have yet heard... Clearly, human T lymphotropic virus III is as accurate, as innocuous, and as consistent with the past ... as any name possible."

"... last June, Jim Curran and Dr. Murphy assured me this would be the CDC name when our lines(s) and other reagents were distributed."

Dr. Gallo further said in his letter to Dr. Francis that, "If LAV procedes (sic) HTLV-III in this paper as a title then I will be last author. If not, I don't care who the last author is." Dr. Gallo added this ultimatum:

"One or the other Don, but not both for your friends abroad."

"If there is a problem for you then let's just forget the whole thing."

2. Immunological (Proteins) Comparisons: Besides the serological comparisons, immunological comparisons of the viral proteins and molecular comparisons of the nucleic acids also were carried out. Two manuscripts resulted. Scientists from both the IP and LTCB were coauthors on both papers; the "proteins" paper was authored principally by the IP scientists (Chermann et al.), although the LTCB scientists performed several of the reported experiments. The nucleic acids paper was written by LTCB scientist, Dr. Flossie Wong-Staal. Neither paper was ever published.

The comparisons of the viral core proteins of LAI/LAV and LAI/IIIb were accomplished by early-June 1984. These comparisons were initiated in mid-May, when Dr. M. Sarngadharan travelled to Paris, taking with him samples of "H9/HTLV-IIIB," both lysate and live virus. The decision to send a live cell line to the IP scientists seems to have represented a unilateral, last-minute change in plans at the LTCB. It was a decision that would have significant consequences. According to Dr. Montagnier:

"At the beginning, the agreement was that we would not exchange live virus, but only detergent-treated lysates. But at the last minute, he changed his mind [Gallo] and on May 15, 1984, his associate Dr. Sarngadharan brought live HTLV-IIIb growing in H9 cells to our lab" (6/12/91 Montagnier-to-Hadley letter, p. 2).

The virus lysate that Dr. Sarngadharan took to Paris was used for proteins comparisons carried out in mid-May. The IP view of these experiments was expressed in a May 21, 1984 telephone call from IP scientist Dr. Jean-Claude Chermann to the CDC's Dr. Donald Francis. According to Francis' notes, the information about the experiments conveyed by Chermann was this:

"Competition -- Sarang -- infected cells: competition by Francoise -- p25 [the viral core protein] same ... French side of comparison done."

"We have sent Sarngadharan to you to compare the proteins of LAV and HTLV-III using our hyperimmune sera to HTLV-III. As you know, there is substantial cross-reaction as anticipated" (7/3/84 Gallo-to-Montagnier letter; p. 1).

The comparisons of the viral core proteins demonstrated the essential functional identity of the IP and LTCB prototype viruses, while the results of the Western blot experiments indicated that the IP scientists' failure to demonstrate the presence of the key envelope protein, gp41, was due to methodological deficiencies, rather than any real difference in the IP and LTCB viruses. Consequently, Dr. Gallo and his associates, around mid-June of 1984, made several on-the-record statements to the effect that the IP and LTCB viruses were "closely related." Thus:

"'There is data now that they could belong to the same virus group of the same virus family,' said Gallo head of the team that made the American discovery" (June 14, 1984; Washington Post).

"Additional observations of a retrovirus likely belonging to the HTLV-III group were independently made by other investigators. A virus designated lymphadenopathy associated virus (LAV) was first reported in cultured lymphocytes from a patient with lymphadenopathy by Barre-Sinoussi et al. (1983). The same group also reported additional isolates called IDAV, from patients with AIDS (Vilmer et al., 1984). Preliminary comparisons between these viruses and HTLV-III demonstrated that they are closely related" (Sarngadharan et al., "Seroepidemiological Evidence for HTLV-III Infection as the Primary Etiologic Factor for Acquired Immunodeficieny Syndrome" (May 1984; Scientific Symposium of the American Red Cross; Published in Dodd, R.Y. and Barker, L.F. (Eds.), Infection, Immunity, and Blood Transfusion, Alan R. Liss, Inc., New York, 1985).

"... there is mounting belief that the retrovirus recently identified by National Cancer Institute (NCI) investigators (Bethesda, MD) and the lymphadenopathy virus (LAV) reported last year by a group at the Institut Pasteur, Paris ... are the same.

"... from the pattern of antibody reactions, I would be surprised if there is very much difference,' said M. G. Sarngadharan, Ph.D., ... a member of the NCI group" (JAMA, June 8, 1984, 251, No. 22; p. 2901).

"Two human retroviruses have been recently implicated as the causative agents of Acquired Immune Deficiency Syndrome (AIDS). The first virus described was designated Lymphadenopathy Associated Virus (LAV) ... Another human virus, named HTLV-III has been also recently identified as a prime candidate for AIDS ... Several lines of evidences (sic.) argue strongly that both viruses, LAV and HTLV-III, are similar and are indeed the primary cause of AIDS" (Emphasis supplied; "Comparative Immunological Properties of LAV and HTLV-III'; p. 1).

"They both show a preferential tropism for OKT4+ T lymphocytes ... and have cytopathic effects on this target T cells (sic.) ... A high prevalence of antibodies to each of the viruses have been found in the sera of patients with AIDS or pre-AIDS ... and both viruses have been frequently isolated from all individuals at risk for the disease" (Emphasis added; op cit., p. 1).

"... presented data of only 20% sera reacting with their isolate. With HTLV-III we had 90% or better" (8/29/85 Gallo-to-Fischinger memorandum, p. 1).

The Chermann et al. manuscript also contained the important information that LAV had been grown on the H9 cell line. This information would take on added significance during and after the blood test dispute, when Dr. Gallo would claim Dr. Popovic had not been able to grow LAV in H9, and thus, there was reason to believe LAV was a different virus than IIIb. The information in the Chermann et al. manuscript cast significant doubt on Dr. Gallo's assertion.

The "Results" section of the Chermann et al. paper began with this significant observation:

"Several reports on the characteristics and properties of either LAV ... or HTLV-III suggest that these viruses are probably the same or closely related viruses" (op cit., p. 4).

"... the pattern of antigenic immune recognition presented here demonstrates that LAV and HTLV-III are antigenically identical" (op cit., p. 6).

"... these results indicate that LAV and HTLV-III are either the same virus or variants belonging to a (sic.) same family of retroviruses" (op cit., p. 5).

"Several lines of evidences (sic.) argue strongly that both viruses, LAV and HTLV-III, are similar and are indeed the primary cause of AIDS,"

"... I was satisfied that HTLV-III had been proven to be the cause of AIDS, but I saw no evidence of this for LAV up through the allowances of the Gallo patent" (11/8/86 Gallo declaration; p. 14).

The failure to disclose to PTO the conclusions contained in Chermann et al., plus a number of other papers at around the same time, did not relate merely to the Gallo et al. parent blood test patent application. More detailed declarations than those in the parent application, denying prior art, were made by Gallo et al., in July and August 1984, in submitting two CIPs to the parent application. In submitting these applications, (one for isolation and detection of antibodies to the core protein of "HTLV-III," (the 610 CIP), one for "immunological test kits" for assaying retroviruses such as HTLV-III (the 715 CIP), Gallo et al. said, under penalty for making false statements, that

"... we verily believe ourselves to be the original, first and joint inventors"

"... we do not know and do not believe that the same was ever known or used in the United States before our invention thereof or patented or described in any printed publication in any country before our invention thereof ..."

3. Molecular (Genetic) Comparisons: The immunological comparisons of LAV and IIIB, significant as they were, did not touch on the issue that soon would become the focal point of the French/American dispute, namely, the genetic identity of the isolates, particularly, whether IIIb was derived from LAV. This issue was reflected in molecular comparisons of the nucleic acids of LAV and IIIb, comparisons conducted at the LTCB in the Spring and Summer of 1984.

The circumstances and results of these comparisons were never thoroughly examined prior to the Subcommittee's investigation. OSI was misled and disadvantaged by being given false and significantly incomplete information, and thus failed to recognize telling discrepancies that, when examined by Subcommittee staff, led to important new revelations.

Dr. Gallo told OSI that the first molecular comparisons of LAV and IIIb occurred in,

"... August to September 1984 after an HIV probe was available" (5/25/90 OSI interview; transcript p. 49).

In addition, Drs. Gallo and Popovic repeated many times the charge that the LAV/B sample they received was contaminated with an animal retrovirus. Concerning the LAV/B sample, Dr. Gallo said this:

"This is a B cell line ... which we know has contamination. It was for a monkey retrovirus. This was cultured for a short time and given to Beatrice Hahn for DNA analysis. The cells were found to be contaminated -- Popovic found they were contaminated with squirrel monkey retrovirus ... Therefore, he didn't keep these cells in culture. The contamination was due to the Paris group's use of BJAB, a B cell line now know (sic.) to be contaminated with this lentivirus ... They should never have used that line" (op cit., p. 50).

Dr. Gallo told OSI that the August/September 1984 LAV/IIIb DNA comparisons, in addition to LAV/B, also included a DNA sample designated as "AM." (A prior, undated LAV/IIIb comparison experiment -- in Dr. Beatrice Hahn's notebook -- included only IIIb and LAV/B.) Concerning the AM sample, Dr. Gallo described it as follows:

"The AM DNA possibly, it is almost certainly -- refers to Ti7.4/LAV cells because the origin of that cell line, Ti7.4, is Abby Maizel, which Dr. Popovic remembers giving to Dr. Hahn, but neither Popovic or Hahn is certain of the identity of this DNA ... The AM DNA did not show the same restriction enzyme pattern as IIIb. So this is the confusion now. We begin now to document the source of the confusion" (emphasis added; op cit., p. 50).

"The final analysis of LAV DNA was carried out on November 27, '84 with DNA received directly from Chermann. This DNA hybridized to the HTLV-III probe, that would be IIIb ... November 27, however, '84 is long after there is reagents on both sides of the ocean.

The CEM LAV and the HTLV-IIIb DNAs gave identical results with the restriction enzymes used. So that is our first comparison we are the same, but it comes from the November DNA, November 27th DNA. They had had for many, many months by then our IIIb producer cell line" (op cit., p. 51).

-- the claim that the first molecular comparisons of LAV and IIIb were carried out in August/September 1984 is inconsistent with other statements by Dr. Gallo indicating such comparisons occurred as early as June 1984 (see below for information concerning these other statements);

-- the claim that the "AM" sample (of uncertain identity but believed to be Ti7.4/LAV) "did not show the same restriction enzyme pattern as IIIb" is misleading. The statement is contradicted by Dr. Gallo's own testimony elsewhere to OSI that the AM sample,

"... could be a subset of the clones in HTLV-III (i.e., HXB2)" (Supplement to IIIb Exhibit 24B; Part 1, p. 3).

-- the assertion that the November 1984 CEM/LAV -- IIIb DNA comparison "is our first comparison we are the same" is not correct. By Dr. Gallo and Dr. Hahn's testimony, LAV/IIIb comparisons from months before, including but not limited to the "AM" sample (which dated from September 1983) and the B/LAV sample received at the LTCB the previous July, showed the IP and LTCB viruses were genetically identical;

-- the observation that the November 1984 results showing LAV and IIIb were genetically identical were based on LAV obtained from Paris after the IP scientists "had had for many, many months by then our IIIb producer cell line" is significantly misleading. The implication of this observation is that the IP scientists contaminated their cell lines with IIIb, when the live virus was sent to Paris in mid-May 1984. But at the time Dr. Gallo made this statement to OSI, in May of 1990, he had known for over a year that genetic tests had shown to a high statistical probability that his virus had to be descended from the IP virus, not the reverse (see below for further information on this point).

Furthermore, evidence from the LTCB itself shows that by at least as early as December 1984, the LTCB scientists possessed information that cast significant doubt on any possible "reverse contamination" of the IP virus by IIIb. The evidence, a page in Dr. Hahn's notebook "IV," is headed, "First Patient LAV-1"; the page appears to contain a history of the culturing of the IP isolate, during 1983 - 1984 (the unnumbered page appears between numbered pages 44 and 45 in Dr. Hahn's notebook). Particularly relevant to the present discussion, the page shows that the IP virus, "frozen" in "September 1983," was "thawed" and used to infect the CEM cell line in September 1984. This LAV/CEM cell line presumably is the cell line provided by Dr. Chermann to the LTCB scientists (notably, the page in Dr. Hahn's notebook contains the entry, "J.C. Cherman [sic.] 12/10/84]).

This "First Patient LAV-1" notebook page is important because the chronology contained on the page shows that the CEM/LAV cell line -- the cell line that, by Gallo's own admission was "identical" to IIIb -- was infected at the IP with LAV from a freeze made the previous September, not LAV that post-dated the transmission of IIIb to the IP scientists, i.e., LAV/B. This information, in conjunction with the LTCB scientists' information that their own cell line, Ti7.4/LAV -- also dating from the previous September -- was identical with IIIb, rendered impossible both the "reverse contamination" scenario and other scenarios posited by Gallo et al. to explain the genetic identity of the LTCB and IP prototype viruses (see below).

As the Subcommittee staff began to review this matter, evidence began to emerge that there were other LAV/IIIb comparisons performed at the LTCB, in the Spring/Summer of 1984, comparisons not disclosed to OSI. The first piece of evidence to this effect was the manuscript by Wong-Staal reporting the results of the molecular comparisons of LAV and IIIb (hereafter, the "Lancet manuscript"). Dr. Gallo did not provide this manuscript to OSI; in fact, he told OSI the paper was "never written" (4 /17/90 "HTLV-IIIb" List of Exhibits; p. 16).

A copy of the manuscript reached OSI anonymously; when Dr. Gallo was confronted with it, he confirmed its authenticity. Dr. Gallo then revised his account from the assertion that the manuscript was "never written" to the assertion that he had been unable to locate it. The manuscript was an important source of new information. In particular, the Subcommittee staff's review of the manuscript revealed that it reported a set of comparison experiments different from the August/September experiments described by Dr. Gallo to OSI, i.e., different enzymes were used and several DNA samples other than those in the August/September experiments were analyzed. Of particular note, the Lancet manuscript specifically stated that Ti7.4/LAV was analyzed, although the manuscript did not make clear this was the LAV received the previous September.

Most important of all, the results actually reported in the Lancet manuscript -- scanty as they were -- showed that Ti7.4/LAV and IIIb appeared to be genetically identical; yet the manuscript asserted, contrary to the reported results, that,

"... LAV and HTLV-III are independent isolations of the same virus" (emphasis supplied; Wong-Staal et al., p. 7).

"... showed that each virus isolate, including LAV, could be distinguished provided enough restriction enzyme cleavage sites were examined..."

A second piece of evidence indicating the performance of LAV/IIIb comparisons other than those reported to OSI by Dr. Gallo is a letter from Dr. Gallo to IP molecular biologist Dr. Simon Wain-Hobson. In July of 1991, following the publication in Science of the Wain-Hobson et al. paper, reporting the origins of the prototype LAV in patient LAI, Drs. Gallo and Wain-Hobson had an exchange of letters about the IP and LTCB analyses of archived samples of LAV. In one of these letters, Dr. Wain-Hobson chided Dr. Gallo for claiming there were no "M2t/B/LAV derivatives" remaining at the LTCB that could have been analyzed and compared with IIIb (M2t/B/LAV was the September 1983 LAI/LAV sample used by Dr. Popovic to infect the Ti7.4 and HUT-78 cell lines). Dr. Wain-Hobson asserted he had been told by some of Gallo's own LTCB associates that samples of M2t/B/LAV did exist.

Dr. Gallo's July 24, 1991 response to Dr. Wain-Hobson adverted to comparisons of September 1983 LAV with IIIb and indicated those comparisons showed the isolates were genetically identical. Here is what Dr. Gallo said:

"You say that we had M2t/B derivatives available to us. I imagine this is your greatest misunderstanding. This is not the case. The only Ti7.4/LAV remnant that we have been able to locate is a Southern blot performed by Beatrice Hahn with four to six enzymes using DNA from a culture grown in the Summer of 1984. This pattern looked like that of IIIb and LAV-1, but we had a number of other samples at the time, which looked like IIIb. These all occurred in one incubator, and fortunately did not harm our several other independent isolates like RF, MN, JS and SC, which were cultured and kept elsewhere in the lab. Our conclusion was that we had a serious contamination problem, and as a result, the validity of the blot with Ti7.4 was very much in question. We could not find any freezes of cultures of Ti7.4 despite a very extensive search through our freezers. It was apparently long ago thrown out by Mika (Emphasis in original; 7/24/91 Gallo-to-Wain-Hobson letter)."

However, it is important to note that the existence of (apparently) bona fide "IIIb"-contaminated samples did not provide a basis for Dr. Gallo's attempted dismissal of the results of the LAV/IIIb comparison. The other allegedly IIIb-contaminated samples were grown in the H9 cell line, and according to Gallo, H9 was the likely vehicle by which the supposed contamination occurred. But there was no H9 involved in the Ti7.4/LAV culture; thus the occurrence of apparent H9/IIIb contamination of other LTCB cultures did not explain why LAV and IIIb were genetically identical; neither did it show that "IIIb" had contaminated LAV, and not the reverse.

Besides the Lancet manuscript and the July 1991 Gallo-to-Wain-Hobson letter, other statements by Dr. Gallo alluded to the possibility of LAV/IIIb comparisons well before the August/September 1984 experiments described by Dr. Gallo as the first molecular comparisons in 1984.

In the initial interview of the OSI inquiry, Dr. Gallo said this:

"Shortly after our papers appeared in May '84, three of these isolates, RF, MN, and JS, as well as the IIIb, of course, were analyzed and shown to be distinct from HTLV-I and HTLV-II, from each other by restriction endonuclease analyses. RF, MN, and JS were also shown to be very different from LAV, but IIIb was similar to LAV" (4/8/90 OSI interview; annotated transcript p. 34).

"Originally when the restriction maps gave the same pattern [LAV and IIIb] we were not so surprised. The restriction maps of HTLV-I are usually the same, as are many animal retrovirus isolates. Then we got RF and a couple of other isolates that showed differences ..." (op cit., p. 43).

In his book Virus Hunting, Dr. Gallo said this:

"About this time (June-July 1984) Wong-Staal compared the genetic material of LAV with our isolates ... we learned that there was considerable variation in the viral genome when comparing one isolate to another ...

"Last, and most unsettling, we discovered that one of our own HTLV-3B isolates was much closer to LAV than was typical of our other isolates ... Practically all were genetically different from one another. Yet LAV and our IIIb isolate(s) were distinctly close to each other" (pp. 197-199).

When Dr. Gallo was questioned by Subcommittee staff about these matters, he acknowledged there were earlier LAV/IIIB comparisons than those he reported to OSI. However, Dr. Gallo was unable, during the staff interview, to account for the data from the earlier experiments, although he continued to pursue the matter in follow-up telephone contacts with Subcommittee staff. During these contacts, Dr. Gallo at first asserted that "there are no new data." Gallo asserted that "if it's in the paper [the Lancet manuscript], we have data for it," and he claimed that all the relevant data were in the hands of OSI. Later, Dr. Gallo retreated from those assertions (see below).

In one follow-up contact, Dr. Gallo pointed to an experiment dated July 19, 1984, the protocol for which is found in Dr. George Shaw's notebook #3. Dr. Gallo suggested this was one experiment that might be relevant to the Wong-Staal et al. paper. The experiment to which Gallo referred, headed "Characterization of AM infected line," is one of the experiments for which Drs. Shaw and Hahn's data are unaccountably missing; thus, the results of the experiment are unknown. However, the date of the experiment and some aspects of its design indicate it might be the Ti7.4/LAV-IIIb comparison experiment referenced in Dr. Gallo's 1991 letter to Simon Wain-Hobson, in which, according to Gallo, the Ti7.4/LAV restriction pattern was identical to IIIb. However, both the enzymes utilized and the DNAs analyzed are different from those reported in the Lancet manuscript. Thus, it is clear the July 10 Shaw experiment is not the one reported in this manuscript. The data for the manuscript, therefore, have never been produced.

Dr. Gallo stated in follow-up telephone contacts with Subcommittee staff that his personal attorney, Joseph Onek, had in his possession data or copies of data that might include the data Drs. Shaw and Hahn said they could not find. Dr. Gallo said the data were given to Onek "for safekeeping" at the time of a "break-in" at the LTCB:

"I think we stashed it all with him."

As for the Lancet manuscript and the July 1991 Gallo-to-Wain-Hobson letter, Dr. Gallo attempted to distance himself from both these documents. Concerning the manuscript, Dr. Gallo initially sought to assert that the Wong-Staal et al. paper was not significantly misleading with respect to the relationship between LAV and IIIb. Dr. Gallo argued that the paper,

"... doesn't work in our favor. It says the viruses are the same."

"The paper says the blots are the same."

"... each virus isolate, including LAV, could be distinguished provided enough restriction enzyme cleavage sites were examined ..."

Confronted with these statements from the paper, Dr. Gallo acknowledged "there are no data in the paper" to substantiate that LAV and IIIb are independent" (op cit.) and he added this:

"The worst interpretation that can be made is that the writer exaggerated the differences between LAV and IIIb. But it was not done by me" (7/27/93 telephone contact with Subcommittee staff).

"I did not do one thing. I got the paper handed to me in the form you saw it" (7/27/93 telephone call to Subcommittee staff).

These claims cannot be substantiated; the Subcommittee staff obtained an early draft of the paper that bears Dr. Gallo's handwritten notes throughout the entire text. Notably, Drs. Shaw and Hahn, listed as coauthors on the paper, denied ever having seen it before it was presented to them by Subcommittee staff, during interviews in September 1992. In addition, neither Dr. Shaw nor Dr. Hahn had any recollection of performing the experiments reported in the Lancet manuscript or in the July 1991 Gallo-to-Wain-Hobson letter.

As for the letter to Dr. Wain-Hobson, Dr. Gallo told Subcommittee staff that another LTCB scientist, Dr. Marvin Reitz, "helped" with the letter, obtaining information from another Gallo associate, Dr. Howard Streicher. Dr. Streicher, according to Dr. Gallo, gathered the information he gave to Dr. Reitz from data previously provided to OSI. But Dr. Gallo eventually acknowledged the data most likely were not provided to OSI.

C. Accusation

The Subcommittee staff also interviewed witnesses and reviewed a number of documents bearing on what Dr. Gallo said and did in the Summer of 1984 concerning the apparent genetic identity of LAV and "IIIb." The primary focus of the interviews and documents was a telephone call Dr. Gallo made to Dr. Luc Montagnier, variously dated from "early-June" to late-August 1984. In this telephone call, according to Dr. Montagnier and at least one independent witness, plus at least two documents contemporaneous with the events in question, originating with Dr. Gallo, Gallo told Montagnier he had compared LAV/B with IIIb and found they were identical. Dr. Gallo also accused Dr. Montagnier of having contaminated LAV with IIIb.

If these accounts of Dr. Gallo's actions in the Summer of 1984 are correct, they would be very significant. If Dr. Gallo actually believed, in the Summer of 1984, that LAV and IIIb were genetically identical, it would raise questions about his subsequent, adamant assertions (as well as those of the U.S. Government) that the isolates were definitely genetically independent. Furthermore, if Dr. Gallo actually accused Dr. Montagnier of having had a contamination in Paris, it raises obvious questions about what possible basis, if any, Dr. Gallo could have had for such a charge, since LAV clearly arrived at the LTCB long before "IIIB" was even "isolated," much less sent to Paris.

Dr. Gallo's accounts of the telephone call to Dr. Montagnier were not consistent with those of Dr. Montagnier, the independent witness, and/or the documentary record. Dr. Gallo's accounts emphasized his and Montagnier's alleged nonchalant attitude toward the possibility of a contamination. Dr. Gallo also minimized or omitted altogether his accusation of Dr. Montagnier and his associates. For example, Dr. Gallo said this to OSI:

"I called Montagnier to tell him our two are close, but our others -- the IIIb and LAV are close -- but we have others that are not close, and it was like a 'so what,' you know? Groupings of the virus will be one way and others will be other ways. So we didn't make too much about it then, the common restriction enzymes of four or six enzymes" (4/11/90 OSI interview; transcript p. 66).

"To me, down deeply, it didn't matter at all until now ... and I didn't care if it was -- you know, when I called Montagnier, I assumed he made a possible problem" [edited by Dr. Gallo to read, "I then assumed if it was a contamination he made it"]. "I was letting him know. But then he convinced me he was unlikely to be a problem and, more or less, that I thought 'who cares anyway.' And it's okay. He had a virus earlier and he detected things and he has other detections and so what? Why would I want to make a case out of it? You know?" (op cit., p. 80).

"Well, I mean, at the beginning, remember, my first reaction was 'could it be?' An early reaction in time of this data accumulating when I was first thinking about it was 'could it be, could it be cross-contamination,' and quite frankly my early assumption was that if it was, it was in Montagnier's laboratory, and I called him to tell him the result, and I said, 'You know, IIIb and LAV are rather close.' And he said, more or less, 'So what? They should be close. They're the same kind of virus.' And I said, 'Yes, but we have this RF guy,' and now we have another one coming out, MN, and I've forgotten what else ... And his point was different viruses group, and how can you say this on the basis of just two things. But then my thinking, I can tell you exactly what my thinking was. 'Well, who cares?'" (4/26/90 OSI interview; transcript pp. 48-49).

"I mean, I wasn't concluding this was a contamination; it was a thought, that it was a possibility and I wanted to discuss this with him ... when I was there in March they hadn't successfully cloned yet. I mean their coworker there said they hadn't cloned anything, and they were certainly successful shortly thereafter, so I wondered if they had a cross-contaminant with IIIb which was growing very, very well. And when we had the discussion, I figured, you know, so what? It was clear that they had a virus before we brought them IIIb and if IIIb became a contaminant in their lab I, quite frankly, wasn't particularly concerned" (op cit., p. 50).

"In June 1984, I called Montagnier and told him of this last finding [the identity of LAI/LAV and LAI/IIIb] and of how odd I thought it. He seemed rather indifferent, however, remarking that 'they should be very close -- they were all the same virus after all.' I said yes, but also told him that we'd obtained data showing variations between different isolates, data that would be published in late 1984. He commented that maybe there were different groupings. I realized that one possibility was that LAV/BRU and HTLV-IIIb were actually the same isolate, maybe an accidental contamination occurring in his or my lab. I thought his attitude then was appropriate, however, and who would care? After all, there was no doubt that early on he had his own isolate because I knew we had received a bona fide novel retrovirus in 1983 from him, and I knew we had isolates other than the IIIb strain" (Virus Hunting, op cit., p. 199).

"I wondered about that possibility originally [contamination in Paris], basically because of my concern about their science competence."

"It was really not important to me ... I never accused Montagnier of a contamination in his laboratory. I may have speculated about it in the bowels of my lab. But I never accused him ... it was not important to me" (7/22/93 interview with Subcommittee staff).

"I believe he called me on [the] telephone in June 84 saying that he had analysed LAV (not the early sample of September 83 'he could not grow,' but the virus produced in B cells (B/LAV) that I sent to him on his request ... and found it having the same restriction map as IIIb. He was surprised since he had analysed other isolates and found different restriction maps and wondered whether I could have contaminated our B/LAV by the IIIb we received on May 15, 1984.

I told him (the version in his book is incorrect) that if there were to be contamination, it could only be the other way round, IIIb contaminated by LAV, since we had LAV long before and had sent this virus to other laboratories ...

I deny to have said to Dr. Gallo, 'So what? Different AIDS viruses may group together.' This may be rather his reply.

On the contrary, I was shocked by Dr. Gallo's accusation and decided soon afterwards to break off our collaboration, including the publication of joined papers for the comparison of LAV and IIIb.

Further comments: It is clear now, since Dr. Gallo has admitted the contamination of IIIb by LAV/LAI, that the latter virus was grown in his laboratory, presumably in the continuous lines, for some time in 1983-84.

Therefore, Dr. Gallo has not said the truth in 1984, or he was not informed by his collaborators of what was going on in his lab" (Montagnier-to-Hadley; 6/18/91).

"... soon afterwards to break off our collaboration , including the publication of joined papers..."

Most important of all, Dr. Montagnier's account makes clear that he told Gallo there was positive proof that IIIb had to be descended from the IP virus, and not the other way around. That proof was the fact that the IP scientists "... had sent this virus [LAV] to other laboratories..." before IIIb was sent to Paris. In this regard, two scientists in the United States received LAI/LAV before the May 15, 1984 transport of "IIIb" to Paris -- Drs. Malcolm Martin and Murray Gardner. These circumstances would figure importantly in subsequent developments relating to the genetic identity of "IIIb" (see below).

Testimony of an independent witness provided additional important information concerning events at the LTCB relative to the LAV/IIIb comparisons in the Spring/Summer of 1984. The witness, Dr. Stanley Weiss, now of the New Jersey College of Medicine and Dentistry, wrote to OSI in 1990, describing events he observed at the LTCB in the Summer of 1984, while he was serving as a Medical Staff Fellow at the NCI. Excerpts from Dr. Weiss' letter to OSI follow:

"One afternoon, I came to 37/6A09 [Gallo's office] to meet with Dr. Gallo to discuss data related to a manuscript. Dr. Gallo was delayed. I have a distinct recollection regarding why. Dr. George Shaw was waiting as well; he was scheduled to meet with Dr. Gallo first. While we both were waiting, Dr. Shaw talked to me a bit concerning some data he was about to present to Dr. Gallo, for the first time. This was the result of the molecular analyses (restriction endonuclease maps) he and Dr. Hahn were doing on HTLV-IIIb and LAV-1. They appeared to be the same!

At the end of Dr. Shaw's meeting with Dr. Gallo, they both came into the hallway and involved a few of us who were around in a brief discussion. Dr. Gallo clearly did not want to create new troubles, but he felt he needed to let the French know that somehow the French group must have contaminated the LAV-1 stock in France with some of the HTLV-IIIb that Dr. Gallo's group had sent them. The French had sent IIIb back to Dr. Gallo in error! The conversation focused on to whom among the French Dr. Gallo should first communicate this news. No one suggested that the direction of contamination might have been the reverse. It was absolutely clear that the news from Dr. Shaw had been a total surprise to Dr. Gallo. I had had the opportunity to get to know Dr. Gallo well enough that I feel confident that this must have been absolutely new. It was one of those instances where, in the presence of close colleagues, he rattled off his evolving thoughts. This included some harsh words regarding the French -- Dr. Gallo was chagrined at the wasted effort, at all the work that his lab had just done to compare the virus, only to find that they'd been given back IIIb, when there was so much else to do!

I did not get to meet with Dr. Gallo privately that day. He retired to his office to solicit advice from other colleagues around the country. I believe he eventually called Dr. Montagnier later that evening to relate that it looked like the French had contaminated their LAV with material from LTCB ...

"In summary, it is inconceivable to me that Dr. Gallo knew, or indeed in any way suspected, that the LTCB HTLV-IIIb isolate was derived from LAV-1" (emphases supplied; op cit., pp. 1-2).

"Stanley Weiss, an epidemiologist now working in New Jersey, was at NCI at that time and happened to have been near my office when I made this call. My concern, he recalls, was more for the likelihood of a contamination in Montagnier's lab, and he confirms the relaxed attitude I have described. Later I had reason to think that if the two viruses were so closely related that they might have been mixed up (accidental contamination), the mix-up would like have occurred in my laboratory. In any case, because we had many other isolates and had made other key scientific advances, not to mention the enormous scientific-medical problems that still lay ahead of us, my co-workers and I did not think this likelihood terribly important" (emphasis supplied; op cit., p. 199).

Subcommittee staff interviewed both Dr. Weiss and Dr. Gallo about the reported incidents at the LTCB, in an effort to resolve the discrepancies in their accounts. Dr. Gallo seemed to contradict himself, when he denied his previous nonchalant characterizations of his affect:

"I don't say anything is casual."

"Weiss doesn't really know me that well."

"Bob was emotional. I had never heard Bob curse before.... He was angry and frustrated. Here was everything here to be taken care of and he wanted to get on with the science and here was something else in the way and going to take up his time..." (Subcommittee staff interview, July 9, 1993).

The first document is a memorandum "To the record," dated August 24, 1984, referenced "Telephone conversation with R. Gallo - 8/24/84." The unsigned memorandum is written in a manner characteristic of Peter Fischinger; both Gallo and Fischinger acknowledged that Fischinger was the author of the memorandum. The memorandum bears a number of hand-written notations, appearing to be in the hand of Dr. Vincent DeVita. Dr. DeVita confirmed to Subcommittee staff the notations were his.

The August 24, 1984 memorandum to the record was never provided by Dr. Gallo to OSI, neither was the memorandum ever provided by the National Cancer Institute or any component of HHS in response to any of the Subcommittee's numerous document requests. Neither the August 24 memorandum nor a related October 25, 1984 memorandum (see below) was ever provided to the IP attorneys, in response to their document requests under the Freedom of Information Act (FOIA).

Significant passages of the August 24 memorandum follow:

"Gallo's data:

Original LAV sent to Bob several months ago has now been cloned and is different from prototype HTLV-III, i.e., it resembles the other HTLV-III that have been cloned, all of which have some variations.

The LAV-containing B cell line sent by Montagnier has only a low per cent of cells infected with LAV, i.e., 1 in a 100.

When this virus for the B cell line is compared, it is identical to the HTLV-III prototype, nucleotide for nucleotide!

Gallo called Luc Montagnier and told him the above data ... It ... implies that what Montagnier is sending out to others as the LAV-infected cell line is HTLV-III and not LAV."

The memorandum's subject line reads, "Record of Telephone Conversation with Dr. Luc Montagnier on August 23, 1984." the text of the memorandum, in its entirety, reads as follows:

"Montagnier was informed that we routinely find genomic diversity in our isolates of HTLV-III. He stated that he has cloned his virus and finds no variation among isolates. Of the cell line we received from Montagnier, one of one-hundred cells is producing the virus. The cell that is producing the virus has not been fully characterized yet, however, the virus looks like the H9/HTLV-IIIb virus. We went back to the original LAV that they had sent to us and when analyzed it was found to be different from the virus growing in the culture they recently sent. All isolates we have found are microheterogenous (sic.). We presume, therefore, that the cell line we received from them probably contains our virus. They had our producer cell line for months before we received theirs."

Dr. Gallo himself, when he was questioned by Subcommittee staff about the matter, had no answer. In fact, when asked to explain the statements in the memoranda about "original LAV" being analyzed and found different from IIIb, Dr. Gallo acknowledged that,

"We have no data analysis of the original LAV until 1991."

D. Stonewalling the Assistant Secretary

Certainly the analyses were not revealed to the official who ordered them in the first place -- the Assistant Secretary of Health, Dr. Edward Brandt. Documentary evidence and testimony of several witnesses, including Dr. Brandt himself, shows that throughout the Spring, Summer, and Fall, Dr. Brandt prodded and questioned NCI administrators and scientists, seeking the results of the virus comparisons. But as Dr. Brandt told Subcommittee staff, "I never got them."

What Dr. Brandt did get, in response to his repeated queries, was a series of denunciations of the IP scientists for allegedly delaying the virus comparisons, along with repeated promissory notes for results of the virus comparisons at some future date. But Dr. Brandt continued to push. Thus, according to minutes from the July 30, 1984 meeting of the Public Health Services (PHS) AIDS Executive Committee; cited in a memorandum written by Peter Fischinger:

"Dr. Brandt also criticized Dr. Gallo for being so slow to produce a definitive statement on the identity (or otherwise) of LAV and HTLV-III. In April, he had promised this publicly within 30 days. Dr. Brandt says he wants a 2 or 3 page statement detailing the present status of these investigations (with scientific content, not only reasons for delay)" (8/9/84 Fischinger to Brandt memorandum; p. 1).

On August 13, not having received a satisfactory response, Dr. Brandt raised the issue again, at another meeting of the PHS AIDS committee. Notes of the meeting, contained in a memorandum to the record written by the Special Assistant to the then-NIH Director, James Wyngaarden, said this:

"Dr. Brandt again brought up his concern that the issue of identity versus difference between HTLV-III and LAV is not yet settled publicly. He believes that the continuation of this uncertainty undermines public and congressional confidence that either party knows what it is doing. He is aware of the French foot-dragging, and offered to try to contact his counterpart in the French Ministry of Health to try to break the logjam. Dr. Harmison proposed a meeting next week between NIH and CDC to see if these PHS agencies could settle the issue; they have all the necessary materials. However, no American investigator is happy to proceed to do, with the samples supplied by Institut Pasteur, what the source seems unwilling to do. Possible implications for the commercial concern working with LAV were discussed, but no one present has all the information on legal ramifications" (emphasis added; 8/24/84 "Notes from PHS AIDS Executive Task Force Meeting 8/13/84," pp. 1-2).

"We acknowledge receiving some extracellular virus from you, but this is, of course, not permanent and small in amount."

Dr. Fischinger told Subcommittee staff his August 9, 1984 response to Dr. Brandt was based on information provided to him by Dr. Gallo. However, not only is there no evidence that the IP scientists were not cooperating with the virus comparisons, the evidence that exists shows that weeks before Fischinger wrote his memorandum, in mid-July, 1984, Dr. Gallo wrote to thank Dr. Montagnier for sending his LAV/B virus, telling Montagnier this:

"Now we each have the proper lines and reagents and I look forward to an era of cooperation and good-will" (7/13/84 Gallo-to-Montagnier letter).

"Unfortunately in the previous letter I wrote to you recently I neglected to mention that my letter was prompted not by failure of you to cooperate with us but rather by some medical articles in the U.S. which had repeatedly stated that we had not made reagents available to you" (emphasis added).

The details of what happened after the August 13 PHS meeting are not entirely clear, but it appears that a strategy for a series of CDC-coordinated comparisons of the viruses was devised. Pursuant to this plan, on August 17, 1984, Dr. Donald Francis wrote to Drs. Montagnier, Chermann, and Gallo, seeking their cooperation. Dr. Francis' letter indicated the recipients already were aware of and had agreed to CDC's involvement:

"As you know, the proposal has been made that CDC coordinate the comparisons of prototype strains of LAV and HTLV-III. The data from these comparisons, subject to approval of designated scientists, would be published in a scientific journal with authorship agreed in advance" (8/17/84 Francis-to-Montagnier, Chermann, Gallo letter; p. 1).

Drs. Montagnier and Chermann responded jointly to Dr. Francis' letter on August 29, 1984, noting their understanding that the proposal for CDC's coordination of the comparison studies "was a specific request from the Secretary of Health in a meeting where NCI and CDC representatives agreed that this comparison should be urgently completed." Montagnier and Chermann also committed immediate shipments of LAV virus and a LAV DNA clone. They also agreed that there should be a paper on the serological study, "dealing with the data obtained by ELISA LAV and HTLV-III on the 300 sera given by CDC to Dr. Gallo and us."

Still, Drs. Montagnier and Chermann cited reservations about the comparisons that supposedly were already underway (the reader should keep in mind that the Gallo-to-Montagnier "reverse contamination" call had only recently occurred):

"As you are aware, Dr. Gallo had the possibility to do this comparison on its own, since he had our LAV virus at least from September 23, 1983. After the isolation of HTLV-III was announced, we accepted to make a direct comparison with him between HTLV-III and LAV-1."

"We want to ensure you of our willingness that this comparison will be made by all the concerned laboratories ... It is important for the sake of public health that this comparison be achieved as soon as possible."

Dr. Gallo, for his part, never responded to Dr. Francis' letter; none of his superiors, it appears, ever directed him to cooperate with the supposedly agreed-upon plan. Despite the CDC and IP scientists' willingness to proceed with a CDC-coordinated comparison of LAV and IIIb, the comparison never got off the ground, because NCI and Dr. Gallo would have no part of it. And Dr. Brandt continued to be frustrated in his requests for the facts. In fact, at the very next meeting of the PHS Task Force, on August 27, Brandt addressed the issue again. The official minutes of the meeting say this:

"Expressing his concern about the lack of cooperation of L'Institut Pasteur, Dr. Brandt re-stated his belief that a comparison between LAV and HTLV-III should be completed soon ... Reporting this effort to be on track, Dr. Harmison suggested that a meeting between Drs. Gallo and Montagnier may need to occur."

"I am ... advised that a paper has been prepared that shows that LAV and HTLV-III are essentially the same. It is my understanding that the paper will be presented in Rome in September. Since you and I will be testifying on AIDS on September 17, and since this will be an issue at that hearing, it is imperative that I be advised of the situation."

There is no record of Wyngaarden's response to Brandt's request. Wyngaarden, like all the other major NIH/NCI players, told Subcommittee staff he had no recollection of these matters. What is known is that on September 17, 1984, when Dr. Brandt (accompanied by, among others, Drs. Mason, Wyngaarden, and Harmison) testified before the Subcommittee on Health and the Environment of the House Committee on Energy and Commerce, Dr. Brandt, after praising the LTCB scientists for their "discovery" of "HTLV-III," said this:

"Scientists from the Pasteur Institute in Paris also isolated a retrovirus, termed lymphadenopathy-associated virus (LAV), from a homosexual man with the lymphadenopathy (sic.) syndrome and published their results in April 1983 (sic.). Recently, scientists at the NCI have determined that LAV is an HTLV-III virus. CDC and other groups have described additional virus isolates of the HTLV-III family" (emphasis added; statement of Edward N. Brandt, Jr., M.D.; p. 18).

The failure to provide a full and accurate accounting of the LAV/IIIb comparisons to Dr. Brandt was not Dr. Gallo's alone. According to Dr. Brandt, the original order to make the comparisons was delivered by him to Dr. DeVita, and there are indications Dr. DeVita made some effort to comply. Most notably, the October 25, 1984 Gallo-to-DeVita memorandum bears a handwritten note (confirmed by Dr. DeVita to be his) to Dr. Brandt, that says this:

"11/9. Ed. Interesting point. Doubtful that with the variations in the HTLV lines that the line from Montagnier could be coincidentally the same. Vince."

Dr. DeVita told Subcommittee staff he could not explain why Dr. Brandt would not have received his (DeVita's) note and Dr. Gallo's memorandum. Dr. DeVita said he was "sure" the memorandum had gone to Dr. Brandt's office, but DeVita added this:

"By this time, Harmison was there [i.e., was Science Advisor to the Assistant Secretary for Health] ... He could have stopped it ... By this time, Harmison almost assumed ownership of Gallo" (5/3/93 interview with Subcommittee staff).

E. Aftermath of the Comparisons

Although in the Summer of 1984, Dr. Gallo had told top NCI officials that LAV and IIIb were genetically identical, by late 1984/early 1985, Dr. Gallo was taking a very different line. Following Dr. Montagnier's rejection of Dr. Gallo's assertion that he (Montagnier) had contaminated LAV with IIIb, Dr. Gallo began to assert that the two isolates, although very much alike, actually were independent. Thus, as previously described, the Wong-Staal et al. manuscript reported -- without substantiation -- that,

"LAV and HTLV-III [IIIb] are independent isolations of the same virus."

"LAV is closely related to HTLV-III"

"HTLV-III, LAV, and ARV are variants of the same virus (emphasis supplied; 313, 1985, pp. 636-637).

"... because the individuals from whom these isolates were derived acquired the virus at a similar time and place."

Other papers by Gallo et al., published in the Fall of 1984, did little more than note the existence of LAV and give brief mention to the results of the immunological comparisons that had been performed, including the LAV/IIIb comparisons. The already-completed molecular comparisons were not revealed; in fact, molecular comparisons were described as work remaining to be done in the future. Thus, Hahn et al. wrote in Nature, in November 1984:

"The availability of the cloned HTLV-III genome should also now allow direct comparison of this virus with a similar group of retroviruses described by other investigators ... which has also been linked to the pathogenesis of AIDS and which appears to be immunologically and morphologically indistinguishable from HTLV-III (M. Sarngadharan et al., unpublished)" (312, 1984, pp. 166-169).

"The availability of molecular clones of HTLV-III will now permit the direct comparison of this virus to other retroviruses detected in patients with AIDS or ARC. These viruses, named variously as LAV, IDAV1, IDAV2, and ARV (27, 33), are morphologically indistinguishable from HTLV-III and, for those isolates tested, immunologically indistinguishable as well ... On the basis of these results and of our detecting viral sequences in LAV-infected cells using HTLV-III probes ... we believe that HTLV-III, LAV, IDAV1, IDAV2, and the most recently described AIDS-associated viral isolate, ARV, are all essentially the same virus. However, given the diversity in the genomic restriction pattern of HTLV-III reported herein, we would expect similar differences to be present in these other viral isolates" (226, 1984, pp. 1165-1171).

F. The Sabotaging of Bryant et al.

Dr. Gallo's reversal of his original conclusion that LAV and IIIb were genetically identical and his adoption of the "close but not the same" argument may account for his strongly negative reaction to a manuscript he received during the Fall of 1984. Coauthored by Dr. Murray Gardner, a specialist in simian AIDS at the University of California, and a young postdoctoral fellow, Dr. Martin Bryant, the paper reported a comprehensive series of studies, including molecular studies, comparing LAV, IIIb, and ARV ("AIDS-related virus," isolated by Dr. Jay Levy, University of California).

The Bryant et al. virus comparisons were precisely the kind of studies Dr. Gallo attempted to prevent in his materials transfer agreement (see below). Dr. Gardner, who obtained IIIb from an LTCB contractor, was not required to sign the "no comparisons" agreement, and he apparently had no idea what a transgression the Bryant et al. comparison studies would represent. Nor could Gardner have anticipated what a threat the results of the comparison studies would pose. Notably, neither the Bryant et al. manuscript nor any of the correspondence related to it were provided to OSI or to the Subcommittee by the LTCB or any other component of HHS.

The Bryant et al. draft reported, concerning the molecular comparisons, that "ARV can be readily distinguished from the LAV and HTLV-III," but "LAV and HTLV-III are identical" (emphasis added). The paper also reported that LAV was found to contain "two nearly identical viruses," i.e., "strain polymorphism." The same Hind III polymorph was found independently in LAV, by Dr. Malcolm Martin, and it was found in IIIb by Gallo et al. (Hahn et al., Nature, 1984; Shaw et al., Science, 1984). The presence of two identical virus variants in both LAV and IIIb, i.e., the Hind III polymorph, was compelling evidence that these two allegedly independent isolates were, in fact, one and the same.

Dr. Gallo acknowledged to OSI that Dr. Martin's data convinced him (Gallo) that IIIb was identical to LAV and that IIIb was derived from LAV and not the reverse:

"... I assumed that we made a cross-contamination ... and I kept thinking, well, what the hell is the difference, and then also we know that a person, as you know, who is not friendly to me [Martin], had said that he received the Pasteur virus about two weeks before we gave Montagnier IIIb ... Therefore, if he made the same analysis, I always assumed that it had to be -- that there was a contamination but who really cared?" (7/10/90 OSI interview; transcript p. 8).

"In time, because of one individual's data and because of realizing that we had crowded conditions, I, in my mind, accepted the notion, if it was contamination, if it could be proven to be contamination, it probably happened in our laboratory, one because of the crowded conditions and the move that Popovic made, and secondly because Dr. Martin at NIH had stated that he got LAV just before we brought IIIb to France" (4/26/90 OSI interview; transcript p. 50).

When Dr. Gallo saw the draft of the Bryant et al. paper that Dr. Gardner sent to him for comment, Gallo's reaction was strongly negative. According to Dr. Bryant, at first there was no reaction from the LTCB. Weeks went by following the transmittal of the manuscript, and when Dr. Gallo finally contacted Gardner, he (Gallo) alternately harangued and pleaded with him to delay or abort altogether publication of the Bryant et al. paper. Dr. Gallo reportedly did not question any of the results on scientific grounds. Rather, Dr. Gallo reportedly stated that he and Dr. Montagnier were "sorting out" the virus comparisons, that the LTCB scientists were more expert at such studies, and that he and his colleagues desired to inform the scientific community about the virus comparisons in their own terms, according to their own timetable.

Dr. Gallo also reportedly appealed to Dr. Gardener's patriotism, implying it was unAmerican to publish the Bryant data. Dr. Peter Fischinger also reportedly became involved, telling Gardner, "You would be well-advised not to get in the middle of this." Dr. Gardner was so upset by these communications that he called a colleague at the University of California, Dr. Jay Levy, to tell him about the pressure being exerted on him by NCI. Levy in turn called Dr. Malcolm Martin, who memorialized the conversation in a November 28, 1984 memorandum to the record stating this:

"At 4:30 today I received a telephone call from Dr. Jay Levy. He was quite upset because of pressure being put on Dr. Murray Gardner by the NCI staff not to publish data presented at the Montana workshop [the molecular data in Bryant et al.]. He likened the situation to a 'Watergate coverup' and stated that all data pointed to apparent theft of the French AIDS virus."

G. Fate of the Comparison Papers

None of the three virus comparison papers was ever published. The serology paper died due to Dr. Gallo's evident lack of enthusiasm and his failure to provide any input to the paper other than objecting to the virus designation and the order of authorship (see above). Concerning the proteins and nucleic acid papers, Dr. Gallo for years asserted that Dr. Montagnier stopped publication of both papers. Here are examples of Dr. Gallo's statements on this issue over the years:

"We worked together ... We made the comparison. We planned the publication. The papers are written. The drafts are ready. Montagnier decides we don't need to publish. I get blamed for not making comparisons" (8/3/90 OSI interview; transcript p. 105).

"Of course I wanted. No, I wanted him with it. If he didn't want it I would ... I was all for the publication of the papers at all times. Montagnier convinced me. I said it is not unreasonable since the sequence is going to be out, why would we really need it?" (op cit., p. 105).

"It was planned to make new publications with the Pasteur group in the Summer of 1984 ... This was worked on in June of 1984 in which some of our isolates would be compared to their LAV/BRU. You will recall from multiple times mentioned in these inquiries that I told you, we wrote two papers, one in which Chermann was coauthor, one in which Flossie was coauthor, Wong-Staal. But on Montagnier's suggestion to me, we did not publish those papers" (9/23/90 OSI interview; transcript pp. 14-15).

"'... we were set to publish an analysis of IIIb and LAV to show how close they were: Flossie Wong-Staal had a paper written on the molecular biology, Chermann had one on the protein comparisons. He wanted to publish, we wanted to publish, but Montagnier changed his mind and decided we shouldn't: he said he thought it was superfluous, no longer needed. Once the sequencing had been done for both LAV and IIIb, anybody could see the similarity. I agreed'" (Mark Caldwell, "Robert Gallo and the Virus," unpublished manuscript, p. 96).

"I actively pushed for a joint comparison of HTLV-IIIB and LAV. In April of 1984, before publication of the Science papers, I visited the Institute Pasteur, described some of our data and arranged for a collaboration to compare the two viruses. Approximately two weeks after publication of the Science papers, one of my associates (Sarngadharan), visited the Pasteur and began the initial comparison of the viruses. That summer and fall, further analysis took place, resulting in two joint manuscripts. (Ultimately, Dr. Montagnier chose not to publish the two manuscripts because the separate sequencing work was moving ahead so rapidly.)" (6/3/94 Gallo-to-Adamson).

On January 2, 1985, Dr. Montagnier wrote to Dr. Gallo,

"... to let you know our opinion (Francoise, Jean-Claude, Simon and I) about the projects of joined papers."

"1) Paper on proteins: This paper is close to the final form. We gave a copy to Sarngadharan at the NCI meeting, with the original figures. He basically agreed on this version and proposed some minor corrections. If you also agree, please send back to Jean-Claude the copy with original figures and the proposed corrections, so that he can send it to the Editor of Lancet.

2) Molecular biology paper: We do not wish to co-sign this paper because a) it is essentially the work of Flossie, and we have not really participated; b) sequence data on LAV, HTLV-III will be published very soon, so that the paper may be obsolete when it will appear."

It was Dr. Gallo, not Dr. Montagnier, who stopped the preparation and submission of both the comparison papers. Dr. Gallo responded to Dr. Montagnier's letter on January 25, 1985, saying this about the nucleic acids paper:

"Flossie has spent a lot of time to prepare that paper, and it is unfair to her at the final stage to say you do not want to publish. Although she did most of the work, had your group provided the data, she would have gladly incorporated them. Therefore, I feel that we should either publish both papers or neither. I hope you can understand my position."

Dr. Montagnier then voiced the concern underlying much of the tension between the IP and LTCB scientists, ever since the HHS announcement:

"Wasting time on both sides should have been avoided from the beginning, if in one of your Science papers of May 1984, you had published the comparison with the LAV1 sample you had received from us six months earlier."

H. Dr. Gallo's Explanations

When Dr. Gallo was questioned by Subcommittee concerning the Summer 1984 comparisons of the IP and LTCB viruses, he initially responded with such comments as, "I don't know why this is interesting" and "It wasn't important to me." Subsequently, Dr. Gallo acknowledged that in the Summer of 1984, he had believed the viruses were identical, but he offered a variety of explanations he said he entertained concerning these circumstances, explanations that according to Dr. Gallo, reflected "absolute proof there is confusion" at the LTCB concerning the genetic identity of the viruses .

Dr. Gallo's explanations are itemized below, to permit the reader to make an independent evaluation of their credibility; however it first is important to note that if, as he now admits, Dr. Gallo actually believed or suspected -- during the Summer/Fall of 1984 -- that the LTCB and IP viruses were genetically identical, no matter how this came about, it would be very significant. The greatest significance lies in the fact that no disclosure of the possible identity of the LTCB and IP viruses was ever made to the USPTO nor to the U.S. Court of Claims, nor -- for a prolonged period -- to the scientific community or the general public. Instead, even before the blood test patent dispute was formally initiated, Dr. Gallo asserted in the scientific literature that the IP and LTCB viruses were different isolates of the AIDS virus.

Subsequently, with the initiation of the blood test patent dispute, Dr. Gallo asserted vehemently that the viruses were not, could not be the same isolate. Based on these assertions, the attorneys representing the U.S. Government made unqualified, strident representations in numerous briefs and pleadings, of which the following are representative:

"The scientific evidence is clear that HTLV-III and LAV are not so similar that HTLV-III can be said to be the progeny of LAV" (Defendant's Rely to Plaintiff's Memorandum in Opposition to Defendant's Motion to Dismiss the Complaint; p. 6; U.S. Claims Court);

"Continuing research revealed that LAV and HTLV-III were two different isolates of the AIDS virus" (Brief for Appellee the United States; p. 4; U.S. Claims Court).

Among the explanations proffered by Dr. Gallo concerning how the IP and LTCB viruses might have come to be identical, Dr. Gallo said that based on Dr. Popovic's report to him -- "even earlier than the Summer of 1984" -- that the September 1983 IP virus sample behaved differently from the July 1983 sample, he (Gallo) and Popovic believed it was possible that the IP virus had been contaminated by Dr. Popovic with one of his own viruses, at the LTCB! But this extraordinary assertion is suspect on many grounds. In the first place, the mere fact of apparent biological differences in the July and September IP virus samples might have been due to a number of circumstances other than possible contamination by another virus; Dr. Gallo offered no explanation for why he and Dr. Popovic -- reportedly -- seized so readily on the contamination explanation.

Casting further doubt on the credibility of Dr. Gallo's account of his and Dr. Popovic's speculations, there is no known likely candidate among Dr. Popovic's contemporaneous samples for the supposed LTCB contaminant virus; Dr. Gallo did not himself identify a candidate. Finally, the claim of a possible LTCB-to-IP virus contamination is completely undercut by
Dr. Gallo's knowledge -- in the Summer/Fall of 1984 -- of Dr. Murray Gardner's data showing genetic identity of LAV and IIIb, data based on LAV obtained directly from IP (see above), and later, of comparable data from Dr. Malcolm Martin. In short, the explanation of a possible contamination of LAV by an LTCB sample is entirely bogus.

Dr. Gallo offered two other possible scenarios to explain the identity of the IP and LTCB viruses, both of them variations on a theme of deliberate sabotage. According to the first scenario, as related to Subcommittee staff by Dr. Gallo, Elizabeth Read-Connole (one of Dr. Popovic's research assistants) reported to him (Gallo) -- in February 1984 -- that some of the cultures in her hood had been "tampered with." According to Dr. Gallo, Read-Connole told him that on one occasion, she found the quantities of some of her cultures had changed: "the volumes changed overnight," according to Dr. Gallo.

But Read-Connole gave a very different description of this incident to OSI. According to Read-Connole's testimony to OSI, on the occasion in question, she returned from a weekend to find a strange coffee cup next to her incubator, and some of her cultures "turned around." Read-Connole made no mention of changes in the volume of any of her cultures, neither did she mention the possibility of "tampering." Read-Connole told OSI she gave the same account to Dr. Gallo. When the discrepancies in their accounts was described to him by Subcommittee staff, Dr. Gallo said he would have to check into the matter. Dr. Gallo never raised the matter again.

The second sabotage scenario described by Dr. Gallo was alleged to have occurred later than the "tampering" incident, i.e., in June 1984. Dr. Gallo insisted to Subcommittee staff that he would not identify the alleged perpetrator, a person who Gallo said "stood to economically gain," who according to Dr. Gallo, approached Frederick scientist Dr. Raymond Gilden, telling him it could be to their mutual benefit to "set up Gallo," i.e., to "show the identity of LAV and IIIb." According to Dr. Gallo, the individual in question -- a former NCI scientist -- had been "in and out" of the LTCB on several occasions; it was one of these occasions, presumably, that the deed was done, i.e., the supposed pilfering of "IIIb" and its transfer to the IP scientists in France.

Dr. Gallo hardly needed to have been so reticent about naming names in connection with the alleged "set up Gallo" incident. As early as August of 1985, Dr. Gallo wrote a memorandum to Dr. Fischinger, telling him about the alleged approach to Gilden, including the name of the suspect scientist. Later, in his widely disseminated April 1986 "Key Events ..." document, Dr. Gallo repeated the allegation, twice, naming the individual both times. And Dr. Gallo repeated variations of the story, on several occasions, to OSI. But there is no independent substantiation for Dr. Gallo's account. Even if it were substantiated that some sort of an approach had been made to Dr. Gilden, there is no evidence that it had anything to do with the fact that IIIb is actually the IP virus, LAI.

If, in fact, Dr. Gallo and his colleagues were "confused" about the origins/identities of the LTCB and IP prototype viruses, in the Summer/Fall of 1984, they managed to hide their confusion well, insisting in numerous published papers in late-84/early 85 and thereafter that the viruses, while functionally the same, were genetically independent (see above). Dr. Gallo's own accounts to Subcommittee staff varied from one occasion to the next, ranging from the sabotage scenarios to the supposed "contamination" of the IP virus by an LTCB sample, to the assertion that Dr. Montagnier had contaminated the IP virus with IIIb, at the IP laboratories in Paris.

In the final analysis, according to Dr. Gallo' s statements to Subcommittee staff, eventually he "learned certain things" that made it "too likely the contamination is in our lab" (the contamination of the LTCB virus by the virus from the IP). Dr. Gallo acknowledged to Subcommittee staff that he had "held out for more proof ... perhaps I held out longer than I should have." But, added Gallo, "... there is something subjective about being human" (7/22/93 interview with Subcommittee staff). Dr. Gallo's "bottom line" assessment of his actions vis-a-vis the genetic identity of the viruses was this:

"There is nothing I can be criticized for" (7/28/93 telephone call to Subcommittee staff).