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

III. CLAIMS AND REALITY CONCERNING THE LTCB'S HIV RESEARCH

A. Claims about the LTCB's "Early Isolates"

Although during 1982 and much of 1983, the LTCB scientists' efforts to isolate and grow the AIDS virus failed again and again, during and after the blood test dispute, Dr. Gallo, HHS officials, and DOJ attorneys ascribed extraordinary significance to those early efforts. In particular, Gallo et al. repeatedly asserted that the first HIV isolates were obtained at the LTCB in late 1982-early 1983.

The reason for these claims was simple. The Gallo et al. blood test patent application was submitted months after the application of the IP scientists. By the fundamental criterion of priority of invention, the IP scientists should have been awarded the blood test patent. But once the Gallo et al. patent issued (due both to PTO's extraordinary incompetence and Gallo's failures of candor and disclosure), and an "interference" between Montagnier et al. and Gallo et al. had been declared, PTO rules provided a potential "out" for Gallo et al. by which they could attempt to demonstrate that they were first to invent.

Under U.S. patent law, a domestic inventor may be able to demonstrate priority by "swearing behind" the submission date of another's patent application, by demonstrating "conception" of an invention prior to the conception date of a competing inventor, together with diligence in practicing the invention to the point of its reduction to practice. An individual who thus conceives and diligently practices an invention may be afforded priority for that invention even if his/her reduction to practice occurs after the reduction to practice of the competing inventor. "Swearing behind" was the central tactic of the U.S. Government, during the blood test patent dispute, in its attempt to defend the patent of Gallo et al. The assertion of "early isolate" claims was an integral element of that strategy.

1. Claims in the Scientific Literature: The LTCB's "early isolates" claims actually began before the formal legal proceedings of the French/American dispute. In early-to-mid 1985, Gallo et al. wrote that,

"The first HTLV-III isolates were obtained in this laboratory in November 1982, and HTLV-III was subsequently isolated from approximately 100 patients with AIDS or ARC or from healthy individuals at risk for AIDS" (Gallo et al., in AIDS: Etiology, Diagnosis, Treatment and Prevention," 1985, p. 34).

"Since the fall of 1982, independent isolates of HTLV-III have been obtained in this laboratory ... from 101 AIDS and ARC patients and healthy donors at risk for AIDS" (Salahuddin et al., PNAS, 82, pp. 5530-34).

"The minimum criteria used to identify new HTLV-III isolates were (i) release of particulate, Mg2+-requiring, viral reverse transcriptase into cell culture supernatant fluids...; (ii) transmission of virus to cultures of normal human peripheral blood mononuclear cells or to permissive T-cell lines with resulting characteristic cytopathic effects and release of virus ...; and (iii) detection of HTLV-III proteins by indirect immunofluorescence assays using virus-specific monoclonal antibody ... or hyperimmune sera ..." (emphasis added; op cit., p. 5531).

"All 101 virus isolates were classified as members of the type-III subgroup of HTLV based on their immunological reactivity with specific monoclonal antibody or hyperimmune antisera and by their cytopathic effect on normal peripheral blood mononuclear cells in vitro" (emphasis added; op cit., 5533).

In fact, no sample could have been tested with HIV-specific reagents in 1982 -- or at any time prior to February 1984 -- for the simple reason that no such reagents existed before that time. Theoretically, virus isolates obtained in 1982-1983 could have been frozen and tested later, after proper reagents became available. This is what Dr. Gallo claimed to have done. Thus, in January 1987, writing in Scientific American, Dr. Gallo articulated the claim that once he had developed HIV-specific reagents, particularly the hyperimmune rabbit antiserum, he used the reagents to analyze and type archived samples, samples that he dated as early as 1982:

"By December (1983) substantial quantities [of virus] were being grown, and soon afterward reagent production was underway. With reagents in hand, we could go back and identify the many stored viral isolates. Initial testing showed that 48 isolates from AIDS patients or members of risk groups were of the same type" (p. 50).

Among the "critical published facts" cited in this "official" chronology was the following:

"May 1984. Gallo's group (1984) reports ... (2) 48 virus isolations ... The use of anti-p24 hyperimmune sera proves that the 48 isolates belong to the same kind of virus" (op cit., p. 436).

"The first reagents for specifically typing this virus were rapidly made. Employing those reagents, it was shown that 48 isolates obtained beginning in early 1983 from AIDS patients and people in risk groups were all the same type of virus, which was called HTLV-III on the American side" (259, October 1988, p. 44).

"... we had more than 50 detections and more than 10 true isolates of HIV-I (emphasis added; 4/26/90 OSI interview; transcript p. 58).

"... there was about 10 by the time of our publications" (op cit., p. 62).

More recently, in May 1994, when Dr. Gallo was asked by NCI Director, Dr. Samuel Broder, to substantiate the claims in the PNAS paper, particularly the claim of 1982 isolates, Dr. Gallo again responded with lists of samples, only one of which dated from 1982. This sample was clearly noted in the data summary provided by Dr. Gallo himself as "ND" (for not done, not determined, or not determinable) against HIV-specific reagents. Other documents in the package submitted to Dr. Broder by Dr. Gallo included several handwritten tallies of samples including six samples started in culture in 1982. None of these samples is indicated to have ever been tested with HIV-specific reagents.

Dr. Gallo has suggested the possibility that stored 1982 samples were later sent for testing with HIV-specific reagents; however, he has produced no evidence documenting that this actually occurred. In fact, concerning the late-1982 LTCB samples he later would claim as HIV (see below), Dr. Gallo said this to OSI:

"... these cultures did not survive long enough to test with HIV-specific reagents" (9/23/90 OSI interview; transcript p. 81).

2. Claims in Legal Proceedings: The absence of evidence to substantiate claims for 1982/early 1983 isolates did not stop the United States Government from asserting such claims before the USPTO, during the blood test patent interference proceeding. One document submitted by the U.S. Government particularly laid out the framework for false claims about early AIDS research efforts at the LTCB. This document -- titled "Preliminary Statement of the Party Gallo et al." -- was submitted to USPTO at the outset of the PTO interference.

As required by PTO's rules, the Gallo et al. preliminary statement specified the conception and reduction to practice dates Gallo et al. claimed for their invention. PTO rules specify that if a party to an interference fails to submit a preliminary statement, that party is precluded from attempting to "swear behind" the other party's filing date, during the interference. Furthermore, according to PTO rules, as "Junior Party" in the interference, Gallo et al. would not have access to the preliminary statement of Montagnier et al., unless they (Gallo et al.) filed a preliminary statement of their own. Thus, on multiple grounds, a preliminary statement was essential to the U.S. Government's defense of the Gallo et al. patent.

But the U.S. Government ran a significant risk in filing a preliminary statement on behalf of Gallo et al., because the contents of a preliminary statement are required to be absolutely truthful; violation of this precept carries significant penalties. The USPTO's "Patent Rules" state that:

"A party shall be strictly held to any date alleged in the preliminary statement" (37 CFR, Appendix R, section 1.629)."

"... will be resolved against the party filing the statement by restricting the party to the earlier of its filing date or effective filing date or to the latest date of a period alleged in the preliminary statement as may be appropriate" (op cit.).

The central claims laid out in the U.S. Government's preliminary statement to the USPTO concerning the LTCB's early AIDS research were as follows:

"The invention was first conceived prior to May 1, 1982."

"The invention was first disclosed to another person prior to May 1, 1982."

"The first written description of the invention was made on December 15, 1982."

"The invention was actually reduced to practice on October 6, 1983."

"Active exercise of reasonable diligence toward reducing the invention to practice began on December 15, 1982."

Examination of the Read-Connole notebook pages appended to the preliminary statement reveals how weak was the evidence submitted by the U.S. Government in support of Gallo et al. The data were not HIV blood test data, rather, they represented the LTCB's putative initial "isolation" of the AIDS virus. This was at least ironic, because ever since the charge of misappropriation was made, Dr. Gallo and HHS officials alike have argued that the discovery of the AIDS virus was distinct from and not critical to the blood test invention.

Even viewed from the limited perspective of virus isolation, the data produced with the preliminary statement to support the Gallo et al. invention were extremely weak. The notebook pages contained only two kinds of data, "RT" or reverse transcriptase data, and anti-p19 (HTLV-I) data, marginal data at that. The RT results recorded for the two circled samples were only "+/-," which in other circumstances, when it suited his purposes (e.g., interpreting results with LAV) Dr. Gallo termed "marginally positive" (Gallo "LAV" submission to OSI; 5/15/90).

The data were otherwise exceedingly limited. They were obtained on a single occasion; there was no evidence that the cultures continued to grow, nor was there any evidence that the one-time, December 15 results were replicated. The most anyone could have deduced from the December 15 data was that there were two samples that seemed to be weak producers of reverse transcriptase and thus, apparently contained a retrovirus, a retrovirus that appeared not to be HTLV-I. But there was no testing with HIV-specific reagents performed on the samples. Thus, what the new retrovirus was -- and whether it had anything to do with AIDS -- that information could in no way be deduced from the scanty December 15, 1982 data.

Dr. Gallo knew this well. In September 1985, Dr. Gallo wrote a memorandum to Peter Fischinger, responding to a number of questions Fischinger and others had raised about, among other things, the LTCB's putative early HIV isolates. Dr. Gallo's remarks to Fischinger on this occasion made clear the vital significance of HIV-specific reagents. Speaking of his late-1982 "isolates," Dr. Gallo said this:

"... there were no reagents to HTLV-III/LAV at that time because the virus could not be mass-produced by anyone then" (September 23, 1985 Gallo-to-Fischinger; p. 1).

"What good would it do me or the field to slip in a few sentences that another retrovirus is occasionally detected (at that time it was only occasional) and that it is not HTLV-I or II; but we have no evidence that each time this new virus is detected it is one and the same virus, i.e., this could have been an HTLV-III in patient one, no virus detected in patient two, ... and when detected again in, say, patient seven it could have been an HTLV-IV, i.e., not the same as HTLV-III ... Proper specific viral reagents were, in my mind, required to establish the identity of what was believed to be a new virus" (emphasis in original; p. 1).

3. Dr. Gallo's Statements to OSI and Subcommittee Staff: When questioned by OSI investigators about statements he and government attorneys made concerning his putative discoveries, particularly the claims of early isolates, Dr. Gallo professed naivete about the patent process and, by implication, his obligation to tell the truth, both in the patent applications and in the subsequent legal proceedings in defense of his patents. Dr. Gallo also portrayed himself as entirely dependent on the instructions he received from United States attorneys.

Here is what Dr. Gallo said to OSI about his 1982-isolate claims:

"... I was asked by the United States Government to draw a lineage to the first time we detected this virus to show lineage of our work. You see what has happened as a scientist I am being put into a legal position, which I am not used to ...

"When the government sat down with me they asked me, look, we just want to have lineage from your earliest detection of something that you were reasonably confident was not pure HTLV-1 or 2 ... We went back to our records. I didn't have it in my brain. I didn't make any claim" (5/16/90 OSI interview; transcript pp. 99-100).

"... we have some samples that were HTLV-I, HTLV-II negative by antisera and that are RT positive. Those were not data that allowed me to publish. They were not data that convinced me of the cause of AIDS. They were not even enough to say with absolute certainty this is a great new virus that I can handle and play with. Therefore, we didn't publish. But when I am asked to go back and draw lineage to our first experiments that have positive indications, that is what I did for the government" (emphasis added; op cit., pp. 100-101).

"...that is obvious that that is lineage, isn't it? You had it detected in December '82, February '83 clearly, it is not HTLV-I, right ... You have got RT positive, yes. That is the lineage. You know, that is what you write. That is the advice from the consulting lawyers.

"But that wasn't for me to get scientific credit. Just suddenly I am in a legal thing, I am back to a morality ethics thing issue. They are asking me to draw lineage from the day we first detected a non-HTLV-I and II virus and to show that the mind was a little bit open.

"... for a legal case, I was asked to draw the lineage, I presented our notebooks and I sat down with the consulting firm ... and with the Health Department lawyers, who had scientific backgrounds" (op cit., page 109).

"... you are asking me to defend something that I don't -- I don't claim we had the cause of AIDS discovered in February 1983 or December 1982" (emphasis added; op cit., page 110).

"You had it detected in December '82, February '83, clearly. It is not HTLV-I, right, no, it is not HTLV-I. You have got RT positive, yes. That is the lineage" (5/16/90 OSI interview; transcript p. 109)/

"Is that HIV in December '82? You bet it is. Is it there in February '83? You bet. You tell me what it is if it is not" (5/25/90 OSI interview; transcript p. 28).

Dr. Gallo attempted to assign responsibility for his statements in U.S. Government legal pleadings to the lawyers who defended the claims of Gallo et al. In a statement that seemed to sum up his account of his dealings with the patent attorneys, concerning his alleged "early isolates," Dr. Gallo told OSI that,

"... I repeatedly emphasized to U.S. Government lawyers and consultants that I never made any claim for priority in any discovery of the AIDS virus based on those samples ... The only relevant dates are dates of peer reviewed publications."

As for the claims in the legal papers submitted in defense of Gallo et al., the attorneys pointed to Gallo et al. as the original and sole sources of information used in that defense. One outside attorney asserted that the content of motions he prepared for the U.S. government "were based on what we were told" by Gallo and his colleagues. According to this attorney, "we didn't know enough to lie."

Another outside patent attorney said that for the most part, he had to rely on interviews with Dr. Gallo or his associates as a source of information. The attorney said he asked the LTCB scientists, "Do you have data to support these claims?" and, "Sometimes the data were provided; often they were not." But, said this attorney, "I never had any reason to doubt what I was told." When confronted with significant pieces of data that contradict the claims of Gallo et al., this attorney responded, "You're telling me things I know nothing about."

Concerning the USPTO preliminary statement, the outside private attorney who prepared the statement said he asked Dr. Gallo to provide him with the earliest documents he had that supported the isolation of HTLV-III, not "documents showing RT+, p19- samples," as reported by Dr. Gallo. In response to the attorney's request, Dr. Gallo reportedly provided the December 15 data pages. Dr. Gallo did not explain to the attorney the contents of the December 15 data pages, particularly how, if at all, they supported his claim to have isolated HIV, much less his claim to have invented the HIV antibody blood test. The attorney said he had no understanding of the data independent of what Gallo told him about them.

A U.S. Government attorney provided similar testimony. This attorney said he conducted a number of interviews with Dr. Gallo and his staff. The attorney said he asked Gallo "if he had documents to support his statements and Gallo said 'yes' or he believed so." No one, it appears, asked Dr. Gallo if there were data or other pieces of evidence that would contradict his claims.

Another U.S. Government attorney offered this description of the process by which "facts" were obtained and "verified":

"Here's this guy, almost a Nobel prize winner, you walk in his office and see all these awards all over his walls -- if he tells us he did something, are we going to question it?"

During one OSI interview, Dr. Gallo was asked about statements attributed to him by the Chicago Tribune, citing a telephone conversation with Gallo in which his "early isolates" data were discussed. According to the Tribune, in the telephone conversation, Dr. Gallo reportedly said:

"The December '82 data is really marginal ... The data were equivocal. At the time they were not even real data" (Chicago Tribune, 11/19/89).

"We stuffed them in the freezer. When we measured RT we couldn't do anything with it. The cells died. I can't make any claim for that. Some people would" (op cit.).

"Probably the bulk of what he has there is right in our conversation" (5/25/90 OSI interview; transcript p. 28).

"It is not much different than what I said here ... I never made a claim in the literature for the December '82 samples. I am saying that we knew we had virus particles that weren't HTLV-I .. I never fully characterized them. We never succeeded in growing them in long term. Have I ever claimed differently?

"He is getting me to get into legal issues, rather than the scientific issues, of what is published. We didn't publish these claims in any publication. I am a scientist. I go by what I publish" (emphasis added; op. cit., pp. 26-27).

"For all of '82? ... Can I have the reference? I would like to see that in writing if I said that ... I don't believe I would have any reason to say that in PNAS. I mean, it doesn't sound like me" (5/16/90 OSI interview; transcript pp. 103-104).

Also in a follow-up conversation with Subcommittee staff, when he was asked if he really tested any 1982 samples with HIV-specific reagents, Dr. Gallo said it was "absolutely right" no 1982 samples had been tested. Yet in May of 1994, when he was required by Dr. Samuel Broder to substantiate the PNAS claims, Dr. Gallo responded with this:

"No one should have any reason to believe we would not have the isolates claimed in view of our past record..."

B. How the LTCB Scientists Benefited from their Knowledge and Use of LAV

1. Knowledge of the IP Work with LAV: Following publication of the May 1983 papers, the IP and LTCB scientists continued on their different tracks vis-a-vis the AIDS virus. By mid-summer 1983, the IP scientists had developed an ELISA (enzyme-linked immunosorbent assay) to test human blood samples for antibodies to their newly-discovered virus. The IP scientists also made important discoveries about the characteristics of the virus, including the size of its proteins, its morphology, and, particularly important, its selective tropism for human T-cells. Additional isolates of the virus and results of its further characterization were reported by Dr. Montagnier at the July 1983 meeting of the NCI AIDS Task Force, headed by Dr. Gallo. Particularly important were election micrographs (EMs) of the IP virus, showing its distinctive lentivirus morphology, different from that of the leukemia virus, HTLV-I.

Initial results of the IP ELISA and more aspects of the characterization of the virus the IP scientists now called "LAV" (for lymphadenopathy-associated virus) were presented by Dr. Montagnier at a September 1983 meeting at Cold Spring Harbor, New York. Simultaneously, in Great Britain, the IP scientists filed a patent application for their virus antibody blood test.

Documentary evidence, witness testimony, and Dr. Gallo's own statements to OSI show that he was present at both the July 1983 and September 1983 meetings. Dr. Gallo heard Dr. Montagnier's presentations at both meetings. Moreover, documentary evidence shows that even before the Cold Spring Harbor meeting in mid-September, 1983, some LTCB scientists, including Dr. Gallo himself, knew about and made use of the IP virus antibody blood test. On September 2, 1983, LTCB scientist Dr. Marjorie Robert-Guroff transmitted to Dr. Montagnier a set of human blood samples, to be assayed "for specific reactivity against your AIDS virus-producing cells by immune fluorescence or against the AIDS virus antigens by your ELISA approach" (emphasis added). Robert-Guroff's letter was copied to Dr. Gallo.

About six weeks later, at a meeting in Europe of the Association for Cancer Research, Gallo and Montagnier exchanged written observations and requests concerning the IP's early serology, including serology of the LTCB samples. A note in Dr. Gallo's hand shows that he asked Montagnier to,

"Please send enough [virus] particles ... for about 200 assays ... Also, please let me know data with sera recently from us. Also, when available, some of your sera."

It was at the Cold Spring Harbor meeting in September 1983 that Dr. Gallo mounted an aggressive attack on Montagnier, questioning the quality and significance of his data, particularly the data that demonstrated how different the IP virus was from HTLV-I. Dr. Gallo now admits that his aggressive questioning of Montagnier, " ... widened the growing chasm between the two labs ..." (R. Gallo, Virus Hunting, 1991, p. 170 ).

Dr. Gallo also was present at a November 1983 meeting in Japan at which Dr. Barre-Sinoussi gave a detailed, wide-ranging review of the IP data, including detection of viral antibodies in significant proportions of pre-AIDS and AIDS patients (74% and 38%, respectively). The detection rate in pre-AIDS patients was particularly impressive because for blood screening purposes, what is most important is the ability to detect virus in individuals who have not already been diagnosed with the disease.

The November 1983 data on characterization of the IP virus were also impressive; they showed how far the IP scientists had come in their understanding of the nature of the virus. Dr. Barre-Sinoussi reported on T-cell tropism of the virus, particularly its selective affinity for OKT4+ cells, on the RT (reverse transcriptase) of the virus, and on the identification of viral proteins.

Besides attending meetings at which the IP scientists presented their data, Dr. Gallo also received prepublication copies of a number of the IP scientists' papers, including both the Barre-Sinoussi et al. May 1983 paper and a chapter by Montagnier, published in a volume of the Cold Spring Harbor meeting proceedings (Dr. Gallo was editor of this book).

None of these circumstances was reported to the USPTO, despite their obvious significance to the patent claims of Gallo et. al. Neither was there any disclosure by Gallo et al. of an important paper by the IP scientists, published weeks before Gallo et al. submitted their patent applications. In this paper (Vilmer et al., The Lancet, 1984, pp. 753 - 757), the authors described the methods of the IP ELISA. Vilmer et al. also reported that antibodies to the core protein of their new retrovirus,

"... are widely distributed in the population at risk of AIDS ..." (p. 757).

"...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..."

"... anticipated by or, in the alternative, ... as obvious over Barre-Sinoussi et al. ... or over the disclosures of Montagnier (Cold Spring Harbor Meeting 9/1983...)" (2/11/86 PTO Office Action, Gallo et al., SN #635,610).

"... deemed to be drawn to subject matter which is the same as or substantially the same as that taught by Barre-Sinoussi et al. or Montagnier et al." (2/11/86 PTO Office Action, Gallo et al., SN# 635,610);

"... unpatentable over Barre-Sinoussi or Montagnier et al. ..." (4/4/86 PTO Office Action, Gallo et al., SN# 643,715).

"... the methods taught by Barre-Sinoussi for the assay of LAV appear inherently to anticipate or render obvious the claimed methods drawn to assay of HTLV-III" (op cit.).

2. Use of LAV at the LTCB: It is clear from the rulings of the USPTO that the work of Gallo et al. benefited from the prior work of the IP scientists. But these benefits were far from the whole story; benefits at least as substantial accrued to the LTCB scientists through their actual use of the virus samples provided to them in 1983 by the IP scientists.

One of the major foci of the 1985-87 French/American dispute was the assertion of IP representatives that the LTCB putative "prototype" virus, "HTLV-IIIb," was actually the IP virus, which the LTCB scientists received from the IP long before IIIb reportedly was isolated. For years, Dr. Gallo and his associates, particularly Dr. Popovic, not only denied that they had willfully misappropriated LAV, they also argued strenuously that (1) the viruses were not really identical (see below) and (2) even if they were identical, there could not have been even an innocent "contamination" of the LTCB cultures with LAV, because, the LTCB scientists claimed, they could not grow the IP virus.

Over the years Dr. Gallo modified these claims as the truth gradually was revealed. During the OSI, OIG, and Subcommittee investigations, vital new information concerning the LTCB's use of the IP virus emerged. This information, derived from LTCB laboratory notes, submissions to OSI by the LTCB scientists (principally Gallo, Popovic, and Elizabeth Read-Connole [Popovic's laboratory assistant]), and interviews by OSI and Subcommittee staff produced the following facts.

(a) Dr. Popovic's Notes: First, a word about Dr. Popovic's laboratory notes is in order. Dr. Popovic singlehandedly carried out the most important early HIV experiments at the LTCB, yet his laboratory notes are extraordinarily sparse and fragmentary. Numerous experiments claimed to have been performed are not recorded at all; notably absent are records of the inception of several putative cultures, including the "mystery virus," MOV. Moreover, such notes as exist are suspect on several grounds, particularly the dates on which the experiments allegedly were performed.

Dr. Gallo told OSI, concerning Dr. Popovic's notes, the following:

"As a senior scientist doing cell culture, he did not keep a daily laboratory notebook. He relied on technician notes as far as I can tell, his brain, his observations and cryptic notes periodically" (12/2/90 OSI interview; transcript p. 45).

"... we were finding stuff in drawers, pieces of paper ... I mean, we pulled out stuff that Mika didn't even know he had and there it was, you know, old stuff, old archaic papers with scribbles on them ..." (op cit., p. 140).

"Part of them existed, part of them I think was put together a little bit later I would say ... Obviously, those protocols are fragmentary and could be used very effectively against me and against the lab ...

"... usually I relied on the notes that Betsy had, partly what Ersell had, and also we send the samples out to Sarin, Sarang, that was a part of our protocols ...

"So I did not put down on the paper notes for weeks. So this is one thing I have to tell ..." (6/26/90 OSI interview; transcript p. 57 - 59).

"... how we recorded certain things we just wrote it on the flask. Others (tissue culture people) I know that they do it. If you don't have time, so you put the particular flask (with the note) away and it is recorded (from the flask) significantly later, into the protocol. So this would be an explanation of my protocols, how it was done. I dated significantly later, some told me that I changed the date, and so. Of course, many experiments were not recorded parallel at all" (op cit., p. 59).

"And when the litigation started, the patent problem came up, suddenly I was asked for notes. So I was a little bit surprised ...

"the system over in the LTCB (tissue culture lab) was that I scribbled on some paper of experiment pointing out some important details and I used to put such notes on the hood (for Betsy, for myself, for Ersell) and then eventually I put it in my protocol or I rewrote it and put it in my protocol, which I didn't consider as a protocol. It became a protocol only when the litigation started and they told me I have to give all notes (any paper regarding my work) otherwise I would go to jail if I would not provide all my notes (obstruction of the [sic.] justice). So I told take whatever I have. I don't want to go to jail" (emphasis supplied; op cit., pp. 57 - 59).

1. Two shipments (April and July 1983) of DNA from patient "BRU" (the individual who was the source of the original LAV isolate);

2. At least three shipments of BRU serum (July, August, and December 1983). BRU serum was the principal reagent Gallo et al. used, prior to the development of the HIV-specific hyperimmune rabbit antiserum, to test cultures for the presence of the suspected AIDS virus; yet no results from any of the LTCB's experiments with BRU serum were ever reported, neither was any acknowledgement of the serum's use ever made. In fact, during the blood test patent interference proceeding at PTO, attorneys for the Department of Justice submitted a key motion in which they asserted that,

"The receipt of sera by Gallo from Montagnier taken from the patient [BRU] ... is ... of no significance ... there is no evidence to indicate that the sera contained any antibodies to the AIDS virus" (Opposition of Gallo et al. to the Motion for Judgement of Montagnier et al., USPTO interference; p. 13).

The September 1983 shipment of LAV contained two samples with somewhat different identifiers -- "JBB/LAV" and "M2t-/B/LAV." At the time, both samples were believed to contain the same virus, from patient BRU. In reality, as demonstrated in 1991 by Wain-Hobson et al. (Science; 252, pp. 961-965) and confirmed by the Roche analyses, in 1993 (Nature, 363, pp. 466-469), the M2t-/B/LAV LAV/BRU sample had been accidentally contaminated at the Institut Pasteur and overgrown with virus from another patient "LAI." Consequently, in September 1983, Gallo et al. received a sample of BRU (JBB/LAV) and a sample of LAI (M2t-/B/LAV). These samples were both IP HIV isolates. LAI is the source of the LTCB's "HTLV-IIIB."

The September virus samples sent from the IP to the LTCB were accompanied by a transfer agreement that stipulated the virus would:

"...not be used for any industrial purpose without the prior written consent of the director of the Pasteur Institute."

"...not to disseminate the virus in any form (to companies or other scientists) without the prior written authorization of the Director of the Pasteur Institute."

"... by the recipient himself, exclusively, and only for the following research purposes ...: (a) biological; (b) immunological and (c) nucleic acid studies."

The knowledge and experience Dr. Gallo and his colleagues gained from their work with the IP virus, even before it was renamed and claimed as an LTCB isolate, were very substantial. The Richards Committee said on this subject that,

"The Gallo lab 'went to school' with the French virus..." (emphasis in original; 2/19/92 Richards to Healy; p. 2).

"... he has excellent data there. He was most advanced. There is no question about that. He picked out the correct virus ..." (op cit., p. 48).

"... was just to repeat the experiment which was described by Montagnier et al. .... They (French) defined it at that point, from the point of a novel retrovirus, relatively well. They (French) had good data in this regard" (op cit., p. 109).

(1) The July 1983 virus sample was used for a number of important experiments at the LTCB. Among these experiments was the electron microscopy (EM) of the July sample that provided the first LTCB identification of the AIDS virus as a "lentivirus." The EM results for the July virus sample were conveyed to Dr. Popovic in an October 3, 1983 letter from the EM specialist, Dr. Matthew Gonda. Gonda's letter, which included the notable observation that the morphology of lentiviruses "is quite distinct from type C or HTLV particles," was copied to Dr. Gallo. Thus, there is good reason to believe that early on, Dr. Gallo know Dr. Popovic was working with the IP virus and knew that virus was clearly distinct from the "HTLV" family.

(2) Another important experiment in which a number of samples, including July LAV, were tested by immunofluorescence assay (IFA) against BRU serum and other reagents, showed that LAV was the only sample tested that was positive against both AIDS/pre-AIDS patients' sera while also negative for HTLV-I. During the French/American dispute, DOJ attorneys told PTO that this experiment represented the LTCB scientists' "reduction to practice" of their HIV antibody blood test "invention." The DOJ attorneys did not reveal to PTO that this claimed reduction-to-practice was achieved with the IP virus tested against serum from an IP patient. To have done so would have demolished Dr. Gallo's argument, made under oath in November 1986, that he did not believe the IP and LTCB viruses were even substantially the same.

More broadly, Dr. Gallo denigrated the significance of the July sample of the IP virus to the work of the LTCB, even to the point of denying that the sample contained any useable virus. Here is what Dr. Gallo told OSI:

"I always took the position that the July sample didn't survive. Because that was our results in our lab at the time. We never went back to reprove the thing ... in my mind, the July specimen was not a useable specimen. There was no significant virus there. That is what I told Montagnier" (7/18/90 OSI interview; transcript p. 65).

"That was apparently the first indication in our lab that we can grow this virus, that this virus infects the cells ... The French came out with this one first, as I saw, this virus is here and has this type of characteristics. So we tried to confirm their observations ... we came to conclusion that, of course, this type of virus we have in our samples as well. We are on the same track" (6/26/90 OSI interview; transcript p. 108 - 110).

"... it was the best defined isolate from an AIDS-like patient and was available isolate. But most importantly, there was substantial evidence that the virus is not immortalizing T cells" (12/1/90 OSI interview; transcript p.50).

Confirmation of the successful growth of LAI was obtained in two sets of experiments-- IFA and EM -- whose results were recorded on December 14, 1983. In the IFA experiment, two LAI cell lines -- "HUT-78/LAV" and "Ti7.4 LAV" -- (these were the surviving lines of five originally infected) reacted positively when tested against BRU serum, but did not react with HTLV-I anti-p19. In the EM experiment, the same two LAV cell lines were reported as follows:

"Productive lentivirus infection with all forms of virus maturation." (Gonda-to-Popovic letter; December 14, 1983).

The status of these cell lines as observed by EM directly contradicts Dr. Popovic's assertion that in mid-November, because the LAI cell lines were doing poorly, he was forced to reinfect the cell lines with the IP virus. There is no substantiation for this claim. In fact, according to Read-Connole's notes, the entire amount of the M2t-/B sample was consumed in the original inoculation. The only thing that may have happened is that Dr. Popovic added HUT-78 cells to the two LAI cell line cultures (or he passaged both cultures to HUT-78). Betsy Read-Connole told Subcommittee staff she believed the latter event occurred; however, there are no notes to substantiate this occurrence.

Even if the LAI cell lines were passaged to HUT-78, the virus remained alive. In other words, the LAI cell lines were continuous. Contrary to the assertions of Drs. Gallo and Popovic, the cell lines did not have to be "restarted."

Still other successful experiments were performed with the permanent cell lines infected with LAI/LAV. On November 9, 1983, Dr. Prem Sarin reported the results of RT assays n the five original LAV cell lines, using samples taken on October 27, 1983, one week after the initial infection attempts were made. Dr. Gallo, in his testimony to OSI, described these results as three "marginally positive" and two "negative," but according to Dr. Sarin's notes, one LAV cell line was "?-" three were "+/-," and one was clearly "+." (It is noteworthy that when it came to the LTCB's own cultures, Dr. Gallo cited "+/-" results from Dr. Sarin as "positive." The most important examples of this are the late-1982 LTCB samples, whose "+/-" RT results Dr. Gallo [and later the U.S. Government] would cite as proof that Gallo et al. had "isolated" the AIDS virus before 1983.)

The most significant result of the LAV cell line experiments was the demonstration that the new cytopathic retrovirus believed to be associated with AIDS could be grown and produced in substantial quantities in certain specific permanent cell lines. Dr. Popovic and the LTCB scientists, rightly, deserve credit for this accomplishment, an accomplishment that opened the way to numerous other major advances in HIV research. At the same time, it must be recorded that the LTCB success was attained with the IP virus, a virus selected for the initial attempt at infecting cell lines precisely because of the careful early work of the IP scientists, work confirmed in important measure by Dr. Popovic.

Here is how Dr. Popovic assessed the significance of the cell line experiments with the IP virus:

"In my evaluation the first LAV sample from HUT-78 tested by Sarang
[Dr. Sarngadharan] was positive and it was positive enough ... So the conclusion from this experiment was that it can work with HUT-78. We have to continue to use these (permanent) cell lines which are immortal. These cell lines are susceptible to infection with these cytopathic viruses. We can productively infect them ... We picked up these two cell lines, HUT-78 and Ti7.4 as targets (6/26/90 OSI interview; transcript pp. 141 - 142).

"... the first indication came from LAV that LAV can infect the permanent cell line" (op cit., p. 159).

(4) According to Dr. Gallo's testimony to OSI, the LAI/LAV cell line cultures were frozen on January 13, 1984. Dr. Gallo implied that the entire stock of the cell lines was frozen:

"In early January of 1984, Dr. Gallo recalls that he asked Dr. Popovic to concentrate on work with isolates from LTCB ... and not give so much time to LAV. Accordingly, on January 13, 1984, Dr. Popovic froze Htu (HUT-78)/LAV and Ti7.4/LAV..." (5/15/90 "LAV" submission to OSI, page 7).

It also bears mention that the LAI/LAV freeze page was not provided to the IP attorneys under FOIA, during the blood test patent dispute. Furthermore, according to testimony of top NCI officials such as Drs. Vincent DeVita and Peter Fischinger, they were never told that LAV cell lines were frozen at the LTCB, nor were they told the cell lines even existed. Indeed, Fischinger and DeVita said, they were repeatedly told that LAV was not/could not be grown.

One of the most significant uses of the LAV cell lines, subsequent to their reported freezing, occurred in February 1984, when what appear to be the LAV cell lines were used for the initial testing of the first HIV-specific reagent -- the hyperimmune rabbit antiserum. Dr. Gallo provided a written submission on the rabbit antiserum to OSI. According to the Gallo submission, the first use of the rabbit serum to characterize a virus culture occurred on February 24, 1984, when the serum was used to test two samples identified as "H/L and "H/TI/L." According to the Gallo submission, these cultures were "coded samples from a now unknown source."

The laboratory notebook page on which this experiment is recorded (page 25 of Read-Connole Book III) shows that the two "L" cultures were positive against the rabbit antiserum, as well as positive against both BRU and ET patient sera, but negative against serum from an HTLV-I+ patient and normal rabbit and human sera. These data show that the "L" samples were infected with the AIDS virus. Relatively few samples were tested at this time against the rabbit antiserum; since the "L" samples were the first samples so tested, it is reasonable to assume that Gallo et. al were particularly interested in confirming the identity of the virus in these samples -- or else they were confident of the identity of the virus in the samples and thus, believed the samples would provide a useful test of the rabbit antiserum.

There are a number of compelling reasons to believe the "L" samples are the LAI/LAV cell lines. The "L" identification is an obvious clue; Gallo et. al. were unable to provide any other identification for the samples. In addition, a review of the laboratory notes by Subcommittee staff failed to reveal any other sample cultured at the LTCB around this time for which "L" was used as an identifier.

The existence of two "L" cultures, in two different cell lines in February 1984, is consistent with the two LAV cell lines established the previous fall. The identifiers for the cell lines match the identities of the LAV cell lines, according to LTCB conventions: "H/L" represents HUT-78/LAV; "H/TI/L represents Ti7.4/LAV, except for the additional "H," which indicates a co-culture of Ti7.4/LAV with HUT-78. In fact, Elizabeth Read-Connole told Subcommittee staff she recalled the Ti7.4/LAV cell line was co-cultivated with HUT-78. Read-Connole also told Subcommittee staff she could not provide any additional information about the "L" samples, which she said were given to her by Dr. Popovic, for testing against the hyperimmune rabbit antiserum.

The positive results of the LAI/LAV cell lines against the HIV-specific rabbit antiserum in February 1984 were vitally significant. The results confirmed that LAV was the AIDS virus and thus were proof against any subsequent claims that LAV and HTLV-III were substantially different viruses, or that LAV might not be the cause of AIDS. Yet such claims were made by Dr. Gallo in the Popovic et al. May 1984 Science paper, when he itemized several findings that he said "suggest HTLV-III and LAV may be different." And in his November 1986 sworn declaration, Dr. Gallo said:

"At the time the Gallo patent was filed, my colleagues and I did not consider LAV and HTLV-III to be the same or even substantially the same. Quite clearly, the data available to us indicated that the two viruses functioned differently and reacted differently" (Page 13).

"At no time prior to the filing of the Gallo application, was it appreciated by anyone that LAV and HTLV-III were the same or even similar viruses" (Opposition of Gallo et al. to the Motion of Montagnier et al. for Judgement; page 22).

(c) The "Host Range" Experiment: One other experiment said to have been performed with the IP virus needs to be mentioned. The so-called "host range" experiment, said to have been performed in January/February 1984, purportedly included use of LAV to attempt infection of clones of the HUT-78 (HT) cell line. The experiment is important because during the French/American dispute, Dr. Gallo and the U.S. Government attorneys attempted to use it as evidence that LAV and "IIIb" were different viruses because LAV, unlike IIIb, allegedly did not grow in "H9." The evidence said to support this claim was sparse indeed, a single EM report from Dr. Matthew Gonda, dated February 22, 1984.

The claims about the significance of the "host range experiment" include Dr. Peter Fischinger's August 1985 report of his "investigation" into the claims of Gallo et al. In this report, based on information obtained from Gallo et al., Dr. Fischinger wrote this:

"... Dr. Popovic later attempted to infect the parental uninfected H9 cells with the LAV isolate ... the total amount of reverse transcriptase obtained (~20,000 cpm) was inadequate to initiate an infection of continuous cells" (8/27/85 Fischinger-to-Harmison memorandum; Background Information; p. 8).

In his November 1986 sworn declaration, in which he sought to argue that at the time he submitted his blood test patent application, neither he nor any of his colleagues believed LAV and "HTLV-III" were even substantially the same virus, Dr. Gallo invoked the February 1984 experiment in support of his assertion:

"... the data available to us indicated that the two viruses functioned differently and reacted differently. One such difference was shown by the fact that we could grow the HTLV-III using the H9 cell line, and we could not do this with LAV" (11/8/86 declaration; p. 13).

"... tried the H9 cell line with LAV but was not able to produce virus with that cell line,"

The U.S. Government attorneys told PTO, in their Opposition to the Motion for Judgment of Montagnier et al., that,

"He [Popovic] was not able to infect this cell line [H9] with LAV" (Appendix, p. 14).

(a) The entire rationale for the experiment, particularly its performance at the time it allegedly was done, makes no sense. Why would Dr. Popovic, in the middle of the "rush to save the blood supply" with "IIIb," suddenly decide to perform a laborious experiment comparing MOV, LAV, and (allegedly) IIIb (identified in the experiment as "HTLV-A"), an experiment that reportedly involved taking LAV from the previous September from the freezer, thawing it, and using it for attempted cell line infections (of five different cell lines), within two-to-three weeks of Gallo's order to Popovic to freeze LAV and "concentrate on our own isolates"?

Up to the time of Dr. Gallo's reported order, Dr. Popovic had been growing LAV quite successfully, in permanent cell lines. Why then would Dr. Popovic, weeks later, suddenly feel the need to attempt the LAV experiments all over again?

Dr. Popovic told OSI he did the experiment to,

"... discriminate different isolates ...[using] several markers for evaluation" (6/26/90 OSI interview; transcript p. 142).

(b) Dr. Popovic's reliance on a single index of viral infection, a notoriously insensitive index -- electron microscopy -- for so important an experiment is another significant enigma. It is informative to recall that whenever it suited his purposes, e.g., arguing the viability of an LTCB isolate, Dr. Gallo argued strongly that a negative EM does not provide definitive evidence of the absence of virus:

"... not finding virus by EM is neither qualitatively or quantitatively definitive. It is probably more of an art than a science. Correctly interpreting the complex data is more important than an EM report" (8/3/90 OSI interview; transcript p. 243).

"... not felt by me ever to be a key criterion except possibly for a first-time publication of a new virus or virus detection ..." (12/2/90 OSI interview; transcript p. 37).

"... a negative EM report does not mean the cultures are negative" (10/23/90 draft "Rebuttal"; p. 67).

(c) There also is the matter of the laboratory notebook page not provided to OSI, a page associated with the "host range" experiment, bearing an "X" next to six of the 15 samples that were tested. The "Xs" appear next to the two samples that were reported EM+, plus four of the five LAV samples, all of which were reported EM-. This suggests the possibility that there were data from experiments other than the EMs reported in the February 22 Gonda-to-Popovic letter, either alternative EM results, or perhaps more likely, RT or IFA results, results that showed the LAV cell lines were infected and were producing virus.

The page bearing the "Xs" is a handwritten copy of another notebook page, a page bearing the same date, but without the "Xs," a page that was given to OSI. Both pages are in the hand of Elizabeth Read-Connole, who was questioned by Subcommittee staff about the hand-copied version of the February 13 notebook page. Read-Connole confirmed the page was written by her, but said she could not recall why she recopied the entire page. Read-Connole also said she could not explain the "X" entries on the page not provided to OSI. She said she was not aware of other data that existed for the cultures, but she made it clear she did not grow them, but merely received samples from Dr. Popovic, for transmittal for electron microscopy.

The bottom line is that the data from the February experiment are, at the very least, not conclusive evidence of anything, first because the data consist of nothing more than EMs. Even if the results of the experiment had indicated that LAV and IIIb grew differently in H9, that would not prove the viruses were functionally and genetically independent. Dr. Gallo himself told OSI that the putative differential "target specificity" of two viruses such as LAV and IIIb,

"... doesn't mean two viruses are not derived from the same person or sample, because it is conceivable that minor variants might not behave precisely the same way" (4/8/90 OSI interview; transcript p. 28).

"It was done in a rush, comparative experiment with IIIb, MOV and LAV. We tried to find out differences between these isolates" (6/26/90 OSI interview; transcript p. 147.

"I was afraid that, okay, god knows what could happened with that sample in February 1984. Those negative data is difficult interpreting ... That comparative study that I did in February was done in rush and not carefully monitored for all the parameters" (op cit., p. 149)

Dr. Gallo particularly denied the permanent grown of LAV, e.g., in the May 4, 1984 Popovic et al. Science paper, in which Gallo wrote that LAV "... has not yet been transmitted to a permanently growing cell line for true isolation..." This is the statement for which ORI found Dr. Gallo guilty of scientific misconduct, of which the consultants nominated by the National Academy of Sciences to oversee the OSI investigation said this:

"The statement that LAV had not been transmitted in a permanent cell line is simply false, and was known to be false at the time the paper was written. This is one of the most glaring faults in the paper and is part of the pattern of misrepresentation in the discussion of the problem of continuous culture. There is no way in which Dr. Gallo can be excused from sharing the blame for this misstatement" (2/19/92 Richards- to-Healy: p. 5).

At the same time, Dr. Gallo has frequently asserted that in the comparison papers written jointly with the IP scientists (see below), he did inform them, albeit after-the-fact, about the LTCB scientists' growth of September 1983 LAV in the "Ti7.4" cell line. This assertion is not true. The collaborative papers never reveal that the LAV cell line for which data were reported was derived from 1983 LAV, and Drs. Montagnier and Barre-Sinoussi told Subcommittee staff they understood the Ti7.4/LAV cell line reported in the papers was infected with the LAV sent to LTCB in the Summer of 1984, both because of Dr. Gallo's repeated denials that he had grown the earlier LAV and because of his urgent demands, in the Summer of 1984, for additional samples to enable him to complete the comparison studies. This understanding is consistent with what Dr. Gallo himself told Dr. Chermann in June of 1984. Speaking of the virus sent to the LTCB in 1983, Dr. Gallo said this:

"Obviously we now know that the material you sent to us was inadequate for comparative studies" (6/15/84 Gallo-to-Chermann letter; p. 1).

"...when I got the data with the permanent cell lines, including his LAV (Montagnier), in the end of November '83, I again called him up at his home, and I told we got it, learned how to handle the virus...

What I didn't tell him was that the virus grows very well in permanent T-cell lines" (6/26/90 OSI interview; p. 111).

"I didn't consider that it was my duty to inform him in detail, that we have a breakthrough with this virus. So at that point we didn't" (op cit., p. 112).

As for Dr. Gallo, by at least early Spring of 1984, he knew that Dr. Popovic had grown LAI/LAV in permanent cell lines.. In fact, in an early draft of Dr. Popovic's May 1984 Science paper, Dr. Gallo personally added a statement that LAI/LAV had been grown in a permanent cell line at the LTCB (see below). But Dr. Gallo deleted this sentence from the paper prior to its submission, and he added to the conclusion of the paper the unqualified assertion that LAV,

"... has not yet been transmitted to a permanently growing cell line... " (Popovic et al., p. 500).

"...have never been characterized nor transmitted permanently to recipient target cells. Therefore, no one has been able to work with their particles, and because of the lack of permanent production and characterization, it is hard to say they are really 'isolated' in the sense that virologists use this term" (Emphasis added; 3/5/84 Gallo-to-Ian Munro letter; p. 1).

"... he had a virus growing to a very high titer on a continuous cell line and he believed it was the cause of AIDS. When I asked him whether this virus was similar to LAV, he refused to answer" (6/18/91 Montagnier-to-Hadley letter; p. 1).

Dr. Gallo's 1984 denials that he grew the IP virus often were associated with his apparent efforts to preempt a charge of contamination/misappropriation of that virus, a charge that -- at the time -- no one but Gallo had raised. In his June 15, 1984 letter to IP scientist Dr. Jean-Claude Chermann, Dr. Gallo said this about the IP virus received at the LTCB in 1983:

"What we received from you was minute amounts of extracellular virus on two occasions. The first time there were no detectable virus particles. The second time there were, and we confirmed your transmission of these to fresh T-cells and the ensuing cytopathic effect. We did not 'mass produce' these for characterization of them. We assumed that was your job. We also did not want to cross-contaminate our lines..." (p. 1).

Similarly, on June 28, 1984, Dr. Gallo telephoned the CDC's Dr. Donald Francis. According to Francis' telephone notes, in the course of a long conversation, Dr. Gallo said this about his use of the IP virus:

"I don't have their virus growing ... In this field once you receive a virus -- open to criticism. Don't mass produce two viruses in same lab. If I had of waited and mass produced them I would have been told I got cross-contamination."

"The sample of the virus you sent us the first time had, upon arrival, no detectable virus..." (p.1) and this: "... we did not grow LAV. We confirmed your transmission and cytopathic effect. To keep it going in production would have required considerable work which we would have been doing for you, not us. I work for NCI, not you. Second, clearly we would be accused by many of cross-contamination, i.e., we would run the risk of not being able to convince the 'tough' that we had independent isolates" (p. 3).

"Gallo indignantly disputes this allegation on several counts, including the fact that the viruses are not identical and that the amount of virus Montagnier sent would not have been sufficient to infect a cell line" (230, p.642).

"...contained 11,000 counts per minute of reverse transcriptase activity, a level that Gallo says is considerably less than is required to infect a cell line ... Gallo and Popovic say they infected fresh lymphocytes with the virus Montagnier sent, but when the reverse transcriptase activity declined they put the material in the freezer" (op cit., p. 643).

"...some experts have speculated that Gallo may have mistakenly contaminated his experiments with the French virus.

'That's the height of outrage,' responds Gallo, who adds that 'it was physically impossible' to grow the particles of virus sent by Montagnier" (1/13/86).

"...Dr. Gallo said that his lab had been able to infect human cells with the virus sample received from France only 'transiently.'"

"... achieved transient growth ... but for one week only and in small quantity" (320, 1986, p. 96).

Dr. Gallo also made strong representations to HHS/DOJ officials/attorneys, throughout the blood test patent dispute, that he did not grow the IP virus and that he gained little or nothing from his use of that virus. These claims were accepted uncritically and were incorporated into official papers and legal pleadings of the U.S. Government. At the very outset of the patent dispute, Dr. Gallo wrote to the official charged with investigating the LTCB scientists' claims -- Dr. Peter Fischinger -- that July LAV "... did not contain detectable virus" (8/19/85 Gallo-to-Fishinger memorandum; p. 2). Concerning September LAV, Dr. Gallo, in the same memorandum, said only that his colleague, Dr. Popovic, "... was able to detect RT in these supernatants ..." (p. 2).

In April 1986, Dr. Gallo prepared a document titled "History of Key Events and Side Issue of the HTLV/LAV Discovery." This document, which was widely circulated within the upper echelons of NCI, NIH, and the Public Health Service, as well as DOJ, appears to have been a forerunner of Dr. Gallo's November 1986 sworn declaration. In the April 1986 document, concerning the LTCB's use of September LAV, Dr. Gallo said this:

"...there were only two things we could do: a) EM & b) RT. We did both and confirmed it was a retrovirus and immediately told them so. To try to do EM's and to try to grow it, Popovic transmitted it to human cord blood T-cells, to a T-cell line -- HUT-78 and another T-cell line. All transmissions were transient" (p. 3).

Concerning the July LAV sample, in his 1986 sworn declaration, Dr. Gallo said this:

"...we could find no detectable virus in the sample ... subsequently some minute viral activity was noted in the sample but this was so small that nothing could be done with the sample ... the sample I received did not show meaningful viral activity" (op cit., p. 11).

"I always took the position that the July sample didn't survive ... So in my mind, the July specimen was not a usable specimen. There was no real significant virus there ... That is what I told Montagnier. But when the report came back six weeks later as EM positive, we knew we had something there and so we saved it" (7/18/90 OSI interview; transcript p. 65).

In other interviews, Dr. Gallo specifically referred to his earlier denials that he grew the IP virus:

"...there has been confusion in the response of what we did to LAV. In my response during the passionate period ...'oh we never grew LAV' and of course we did grow LAV" (5/16/90 OSI interview; transcript p. 87).

"There is a point where I say I didn't grow LAV. And, of course, LAV was grown ... Quite frankly, it wasn't so germane to me at the time and I was just anguished as to what was coming out of the newspaper. At that moment bombs were going off" (5/25/90 OSI interview; transcript p. 13).

"... the statement is somewhat misleading ... If it misled anyone, I am sorry. I am also sorry for my certainty of being right."

The "Richards Committee" was not willing to excuse Dr. Gallo on the basis of his passion/anguish, nor on the basis of "bombs going off." Referring to the May 1984 Popovic et al. Science paper, to which Dr. Gallo added the unqualified assertion that LAV,

"...has not been transmitted to a permanently growing cell line for true isolation..."

"The Gallo lab failed to mention the fact that they had propagated the French virus and stated (in the Popovic et al. manuscript) that the French virus had never been transmitted to a permanent cell line. Given the quality of the information derived from propagation of the French virus, we believe that this constitutes intellectual recklessness of a high degree -- in essence, intellectual appropriation of the French viral isolate" (emphasis in original; 2/19/92 Richards-to-Healy; p. 3).

C. LAI/LAV By Another Name

Laboratory records and Gallo/Popovic's retrospective accounts show that the LTCB's seminal experiments, particularly experiments associated with the development of the LTCB HIV antibody blood test and the genetic sequencing of the LTCB's putative "prototype" HIV isolate, were performed with an isolate called "MOV" (for "MO/Variant") and later, with an isolate called "HTLV-IIIb."

MOV and IIIb are LAI/LAV. Experiments performed for OSI by Roche Molecular Systems, using the earliest samples that could be located (samples frozen since 1984), demonstrated conclusively that this is so (Chang et al., Nature, 363, pp. 466 - 469). Drs. Gallo and Popovic asserted to OSI that MOV and IIIb were independent of LAV/LAI. Following revelation of the Roche results, they modified their accounts to claim that MOV and IIIb, originally independent samples, had been accidentally contaminated by LAI/LAV.

In a letter to Nature, written shortly after publication of a paper by the IP scientists that demonstrated the LAI/LAV origins of IIIb (Wain-Hobson, et al., Science, 1991) Dr. Gallo said this:

"It ... appears that cultures of virus from people with AIDS became contaminated with HIV-LAI at NIH ... (1991, 351, p. 358).

The evidence is compelling that "MOV" and "IIIb" were merely different names given to the single readily-usable isolate Popovic/Gallo had in late 1983/early 1984 -- LAI/LAV. Following is an account of the pertinent evidence:

1. LAI as "MOV": Dr. Gallo patented and claimed as his HIV prototype an isolate he identified as "HTLV-IIIb," an isolate he said originated in a pool of virus samples (see below). But IIIb is not the first HIV isolate Gallo et al. produced in large quantities. IIIb is not the isolate Gallo et al. used to develop their HIV antibody blood test or their first HIV-specific reagents. Neither did Gallo et al. perform any of their initial, significant experiments with "IIIb." Rather, these accomplishments all were achieved with another, "mystery" isolate, the existence of which was not acknowledged until the OSI investigation, an isolate identified in LTCB records as "MOV." Yet no scientific paper reported any of these experiments as performed with "MOV." Rather, the experiments were described as performed with "HTLV-III," Gallo/Popovic's generic name for the AIDS virus, or -- in several instances -- experiments recorded as being performed with MOV were reported to have been done with "IIIb."

(a) The Transformation of LAI to "MOV": Here is what the LTCB laboratory records and Gallo/Popovic's OSI testimony reveal about LAI/MOV:

o The designation "MOV" appeared without explanation in Dr. Popovic's notes for November 22, 1983, alongside two infected permanent cell lines in which LAI/LAV was growing. No HIV isolate other than LAI/LAV ever grew simultaneously in these two cell lines at the LTCB; neither is there any record of any attempt to infect these cell lines with an isolate other than LAI/LAV.

o The actual notebook entries that lead to the emergence of the LAI/MOV cell lines are as follows:

10/21/83: Elizabeth Read-Connole inoculated five cell lines with LAV, including HOS, Ti7.4, and HUT-78

(Read-Connole Book 1, p. 222);

(Read-Connole performed the inoculations because at the time, Dr. Popovic was travelling in Europe.)

10/24/83: Read-Connole's notes show five LAV cell lines "in culture," including LAV/HOS, LAV/Ti7.4, and LAV/HUT-78.

(op cit., p. 223);

11/08/83: Dr. Popovic's notes show these entries:

"HOS - dead cells
HUT-78 cell increase slow
Ti7.4

Giemsa: Giant cells multinucleated
More in HUT-78RT - Sarang"

(Popovic notebook; p. 29)

11/10/83:

"HOS- does not grow - discarded
Ti7.4 - O.K. viability 70%
HUT-78 - O.K. " 65%

(op cit., p. 32)

11/11/83:

"HUT-78/V cell number 6 x 105/ml
Ti7.4/V cell number 4.3 x 105/ml"

op cit., p. 32)

11/15/83:

"HUT-78/inf. +++
Ti7.4/inf. +++"

(op cit., p.33)

11/22/83:

"HUT-78/V; Ti7.4/V = MOV."

(op cit., p. 34).

"Following my arrival back in the U.S. ... sometime between November 1st and 4th, we co-cultured patient cells with HUT-78 and Ti7.4. (I think it is most likely that it was patient HM's cells, but as I said, I am not absolutely sure.) On November 8, 1983, I noticed the presence of giant multinucleated cells in both of these cocultures. Aliquots of culture fluids from these cultures were sent to Dr. Sarnagadharan and he detected reverse transcriptase activity in both, the levels of activity being higher in the HUT-78 culture. We then 'scaled up' the HUT-78 culture for further biochemical and serological analysis" (3/4/91 Popovic submission to OSI; "Final Version of Preliminary Responses" pp. 36 - 37."

It is clear that Dr. Popovic, in his March 1991 statement to OSI, was referring to his November 8 notebook entries as entries for "MOV." But the November 8 notebook entries are entries for the LAI/LAV cell lines; proof of this assertion is seen in the fact that the November 8 entries include not only the two cell lines Popovic referenced in his "MOV" statement -- Ti7.4 and HUT-78, but also HOS, the LAI/LAV-infected HOS cell line that was dying (note that Dr. Popovic's November 8 entry says for "HOS," "dead cells"). Only LAI/LAV was used to infect all three of these cell lines, and Betsy Read-Connole's OSI testimony confirms that the notebook entries Popovic invoked as the origins of MOV actually are entries for LAI/LAV. Here is what Read-Connole said about her initial LAI/LAV experiments:

"The initial experiment that I set up in October, I kept until he returned [Dr. Popovic]. I guess only three of the cell lines were struggling along by the time he got back ... I believe soon after that the HOS culture died. I believe, he repeated the isolation from mine because mine were pretty well dead or dying when he returned. So, I had done the initial experiment and I kept them while he was gone and then I gave them all back to him ...So, from the second isolation that he did in the HUT-78, he once again saw the giant cell formation like I had been and that was sort of when we decided maybe we should try using HUT-78 for some other isolates" (6/6/90 OSI interview; transcript p. 46).

It remains only to be noted that Read-Connole's mention of Dr. Popovic's observation of "giant cells" in the HUT-78/LAV culture, an observation that reportedly led to the decision to "try using HUT-78 for some other isolates" is directly reminiscent of Dr. Popovic's statement, concerning "MOV," that he observed RT in the November 8 cultures, "the levels of activity being higher in the HUT-78 culture," upon which, "We then 'scaled up' the HUT-78 culture for further biochemical and serological analysis" (3/4/91 Popovic submission to OSI; p. 37).

In short, it is clear that the November 8, 1983 entries in Dr. Popovic's laboratory notes reflect the point at which the two identities of the single isolate used for the first attempt to infect permanent cell lines -- the identities "LAV" and "MOV" -- overlap.

(b) Gallo/Popovic's Explanations:

o Gallo/Popovic told OSI that "MOV" originated with patient HM. But the Roche analysis found no HIV in a sample taken from patient HM, and the LTCB's own records show that HM samples and cultures were repeatedly negative in a variety of tests for the presence of virus;

o Gallo/Popovic told OSI that the two virus-infected cell lines were retrospectively-designated "MO/Variant" because they were found to be immunologically cross-reactive with HTLV-II, which the LTCB had designated "MO/Virus." This putative cross-reactivity, according to Gallo/Popovic, caused them to "phase-out" the LAI/MOV cell lines and replace them with H9/IIIb. Dr. Popovic also told OSI that his inability to determine the origins of MOV was one of the reasons he,

"phased it out as soon as I could ... avoiding its inclusion in any of the publications (op cit,. page 159).

"I don't care which virus. I am not going to ask him [Popovic] what is the patient history of every virus. You know, it wasn't something to focus or to care about and MOV doesn't get -- doesn't really play any further role" (5/16/90 interview, page 64).

"... even with IIIb one can get such cross-reactivity and I think even RF or so on" (12/1/90 OSI interview; transcript p. 90).

"Later on we found the same thing with the IIIb and other viruses too, so the original reason for calling it was suspicion of contamination, but it was not true ..." (1/29/91 OSI interview; transcript p. 55).

"... concluded that the two virus preparations were antigenically similar" (12/1/90 OSI interview; transcript p. 8).

(a) LAI/MOV was sent in large quantities from the LTCB to its contractor Bionetics, where it was used to make the HIV-specific rabbit antiserum and to make and refine the LTCB HIV antibody blood test.

(b) LAI/MOV was sent to LTCB contractor Electro-Nucleonics Inc. and to Biotech Laboratories, for large-scale production, by February 1984.

(c) LAI/MOV was repeatedly sent from the LTCB contract laboratories to LTCB scientist Dr. Suresh Arya, throughout at least the first quarter of 1984, for use in the LTCB's seminal HIV molecular biology experiments. One particularly important aspect of the experiments with LAI/MOV was the production of the first cDNA probe for HIV.

An additional intriguing aspect of the LTCB's LAI/MOV molecular biology experiments is that, in several instances, they were reported to have been performed with "IIIb." Several clones (identified by the letter "C") were produced by Dr. Arya; according to Arya's notes, as confirmed by him, these clones originated with "MOV." But when three of these clones were partially sequenced, they were published in a 1985 paper which describes the "C" clones as derived from a,

"... permanent T cell line... infected with pooled blood samples from a number of different patients with AIDS or ARC,"

When confronted with the obvious question -- why clones derived from MOV were described as having originated with IIIb -- the first author of the paper, Dr. Lee Ratner, told OSI Dr. Arya told him the clones were from IIIb. Dr. Arya (a coauthor of the paper) was unable to explain the discrepancy, and Dr. Gallo said he did not remember ".. being told who, what, when, or from where samples came" for the clones (May 6, 1991 letter to OSI).

Another even more significant instance of LAI/MOV experiments reported as performed with "IIIb" is a paper by Arya et al., published in Science in August, 1984 (225, pp. 927-929). Dr. Gallo is a coauthor of this paper, whose senior author is Dr. Flossie Wong-Staal, at the time, the LTCB's senior molecular biologist. Dr. Wong-Staal, according to Drs. Arya and Wong-Staal, actually wrote the paper.

There are several significant points to be made about Arya et al. Submitted on May 1, 1984, one week following submission of the Gallo et al. blood test and cell line patent applications, it was the first published scientific paper ever to specifically cite use of the putative "pool" isolate, "IIIb," described as,

"... obtained from pooled supernatants of short-term lymphocyte cultures of AIDS patients" (p. 928).

"... support our proposal that this virus ["HTLV-III"] should be classified within the HTLV family" (op cit., p. 929).

Dr. Arya further wrote, concerning the results in Arya et al., that,

"Where we may have slightly erred was the interpretation or rather the over-interpretation of the hybridization results."

"This was an honest mistake reflecting our insufficient appreciation of the complexity underlying the hybridization reactions and the theoretical basis of the kinetics of hybrid formation and hybrid stability" (12/22/88 Arya-to-Crewdson letter).

Even more important than the spurious homology data is the fact, discovered during the Subcommittee investigation, that the experiments reported by Arya et al. as performed with the "pool" virus, "IIIb," actually were performed with LAI/MOV. This is a very significant finding, for it is a concrete instance of what had long been suspected, namely, that "IIIb" was not a genuine, independent isolate, but merely a different name for the isolate the LTCB previously called "MOV," itself merely a new name for what was originally called "LAV."

Neither Dr. Gallo nor Dr. Arya denied the validity of the Subcommittee staff's findings with respect to the misreporting of LAI/MOV experiments. Instead Gallo and Arya attempted to explain and minimize the significance of the findings. But in so doing, Gallo and Arya opened up new, even more significant concerns about other possible misrepresentations -- whether witting or not -- in the scientific literature.

Specifically, in response to questions posed to him in May 1994, by NCI Director Dr. Samuel Broder, relating to the MOV/IIIb identity, Dr. Gallo said this:

"Since it [MOV] came from an early Mika isolate in a cell line ... I think he [Dr. Arya] and others in the molecular biology group assumed that it was equivalent to the pool virus, i.e., IIIb, only later realizing their different history."

"... no recollection of the specifics, but the more I think about it the more I feel that when Dr. Wong-Staal wrote our manuscript for the Science 1984 paper, we used the term HTLV-IIIb as a common or generic term for the various preparations that were thought to have originated in Dr. Popovic's laboratory ..." (5/27/94 Arya-to-Gallo memorandum).

The "innocent assumption" explanation for the substitution of "MOV" with "IIIb" is belied by an act of apparent deliberate deception, namely, the deletion -- from a chart provided to OSI -- of information showing that Dr. Arya used "MOV" to make the cDNA reported in (at least) the Arya et al. and Ratner et al. papers as derived from "IIIb" (see below for more information concerning these matters).

The "assumption" explanation also opens up an entirely new area of concern, namely, how far did this erroneous "assumption" extend? How many LTCB scientists made the same "assumption"? How many papers were published reporting putative "IIIb" experiments which in fact were performed with "MOV"? And since LAI, MOV, and IIIb are now proven to be the same isolate, what if any evidence is there to show that any experiments actually were performed with a genuine LTCB prototype, i.e., Dr. Popovic's putative "pool"?

Concerning the issue of scientific papers, Dr. Gallo himself, in his June 3, 1994 response to Dr. Broder, said this:

"The papers as I saw them simply called the clones IIIb-derived or pool virus derived. Obviously, I assumed they were from IIIb. Some were. Others were MOV derived."

It also bears mention that according to Dr. Gallo's statement, at some point, Dr. Arya and his colleagues "later realized the different histories" of "IIIb" and "MOV". The obvious questions are when was this realization achieved, and why -- when it was achieved -- was no effort made to correct the literature concerning the misreporting of the putative "IIIb" experiments?

As this report is being written, these questions are before the Director, NCI. It remains to be seen how he will deal with them.

(d) MOV was provided by Dr. Arya to Drs. George Shaw and Beatrice Hahn, for molecular studies that extended at least into the Summer of 1984. Among these studies were comparisons performed in April 1984 that, according to Dr. Gallo and his attorney, Joseph Onek, indicated "MOV" was genetically identical to IIIb. Dr. Gallo's attorney actually wrote to Subcommittee staff that these experiments showed MOV had been "contaminated by IIIb," but this is a significant misrepresentation of what the experiments showed, and what the LTCB scientists believed they showed. Testimony of Dr. Gallo to OSI, cited by attorney Onek as evidence to substantiate a IIIb/MOV contamination, actually emphasized apparent differences as well as similarities between MOV and IIIb. Leaving aside for the moment the evidence showing MOV and IIIb never were independent isolates, there is a significant inconsistency between Gallo/Onek's claim that the LTCB scientists knew of a "IIIb/MOV" contamination -- in the Spring/Summer of 1984 -- and the fact that over one year later, they published a paper citing comparisons of MOV and IIIb as if they were genetically independent isolates (Wong-Staal et al., Science, 229, 1985). Finally, even if Gallo et al., in April 1984, did believe MOV and IIIb were cross-contaminants, contrary to Onek's assertion, there was no reason to believe MOV had been contaminated by IIIb, and every reason to believe it was the reverse, since MOV existed well before the putative IIIb was isolated.

(e) LAI/MOV was sent from Biotech Laboratories to the Frederick Cancer Research Center, in May 1984, apparently for commercial-level production;

(f) LAI/MOV (identified only as "HTLV-III") was used in a number of published serological and protein analysis studies conducted by Dr. M. Sarngadharan and his colleagues (see below). Several of these studies were included in the Gallo et al. HIV blood test patent application; the description of these studies did not identify the virus isolate as MOV, but merely as "HTLV-III," although the patents declared that the "cell line corresponding to the present invention is H9/HTLV-IIIb."

Testimony of Drs. Gallo and Popovic shows that, in the case of Dr. Gallo, he knew or had reason to know that MOV could be the IP virus, and in the case of Dr. Popovic, if his testimony is to be believed, he simply did not care. Speaking of Dr. Popovic's experiments that allegedly led to the "isolation" of MOV, Dr. Gallo said this:

"See he [Popovic] has got the two positive samples. One is labelled 'LAV' and one has a number on it. And the one with the number on it he thinks is 'HM,' but we cannot prove it... We didn't know what was going on. Whether cross contamination with LAV, whether the culture would last..." (5/10/90 OSI interview; transcript pp. 63).

"Was LAV the same as this new thing? If so did -- you know, would they cross react with HTLV-2? Was the new thing one thing or a mix? Anyway, I have got these two things growing. And he simply called the virus HUT-78 because it was in HUT-78 virus. He didn't know what name to give it." Dr. Gallo added, "My belief is Mika is not certain as to what the origin is" (op cit., pages 70-71).

"At that time it didn't matter too much ... as concerning the AIDS virus, what did matter was its growth in high titer that one could work with it. It didn't matter in terms of its precise origin" (6/26/90 OSI interview; transcript p. 160).

2. LAI as "HTLV-IIIb": For purposes of their patent applications and for many publications, Gallo/Popovic claimed the existence of another HIV isolate, designated "IIIb," an isolate said to be derived from a "pool" of ten patient samples. The "evidence" for the existence of the pool consists of Dr. Popovic's word, plus a few cryptic pages of laboratory notes. But as described in the report of the HHS Office of Inspector General, there is reason to doubt that the IIIb "pool" experiment, as described by Gallo/Popovic, really was done, or if it was done, that it ever produced anything other than LAI/LAV. Among the facts that call into question the putative "pool" experiment are the following:

(a) The entire rationale for the experiment -- i.e. that by pooling several virus-positive samples, one would boost the titre of the resulting culture -- is belied by what Dr. Popovic actually did. Specifically, Dr. Popovic (contrary to the claims in his May 1984 Science paper and claims in other fora by Dr. Gallo) did not use only RT+ samples for his "pool," neither did he test the putative pool samples for virus (specifically, for RT) before he pooled them. Dr. Gallo himself said, in a memorandum to the NCI's Peter Fischinger during the French/American dispute, that the samples for the pool came from "several patients who showed high RT activity in primary culture" (8/19/85 Gallo to Fischinger memorandum; p.3).

In fact, as revealed by examination of the LTCB laboratory notes, most of the putative pool samples were not tested for RT, or if tested, they were found to be RT-. Consequently, Dr. Popovic had no idea if most of the samples he used contained any HIV, and in fact, fully four of them did not. Yet Dr. Popovic reportedly added the virus-negative samples to the pool at precisely the point at which he feared that "... I would lose the culture ..." (early January 1984). Such an action defies rational explanation.

(b) The samples -- contrary to the Popovic et al. Science paper and the Gallo et al. cell line patent application -- did not all come from AIDS/pre-AIDS patients. Two of the patients whose samples reportedly were used for "the pool" were diagnosed with hemophilia and one with "chronic lymphatic leukemia."

(c) Many of the samples allegedly used for the pool were noted in the LTCB records to be contaminated with mold, one was terminated the same day it allegedly was used for the pool, and for one sample, there is no indication a viable culture was even in the laboratory at the time it allegedly was used.

(d) There is no evidence there ever was a "IIIb" isolate independent of LAI/LAV. There are no laboratory data showing the independent existence of a pool isolate and, notably, there is no sample of "the pool" in the LTCB freezers, although samples of all ten putative constituent samples were found. Every "IIIb" sample sequenced by Roche Laboratories was found to be LAI, except for the earliest putative IIIb sample, one dating from February 1984. This sample was found to contain no HIV at all. While it is possible that -- as asserted by Gallo et al. -- this last sample was a mislabelled, uninfected control, it remains the case that the latter-day claim of Gallo et al. that IIIb was "contaminated" by LAI cannot be substantiated because there is no evidence there ever was a IIIb to be contaminated by anything.

The affidavits of Dr. Francoise Barre-Sinoussi concerning Dr. Popovic's reported admission that he deliberately used LAV in the experiment that resulted in the putative "IIIb" may explain the anomalies concerning the nonexistent "pool." According to these affidavits, in 1992, Dr. Popovic told Dr. Barre-Sinoussi he combined LAI/LAV with other virus samples to obtain a high-titre cell line, not knowing that LAI/LAV would grow out of the pool.

A Chicago Tribune story about the Barre-Sinoussi affidavits reported that Dr. Popovic now denies admitting to Dr. Barre-Sinoussi his deliberate use of LAI/LAV. Yet Dr. Popovic came very close to making the same admission to OSI. Describing his "pool" experiment, Dr. Popovic said this:

"If I have a cell line which is virus positive and I take another virus-positive cell line and mix together and put together LAV, is it bona fide experiment? What is difference if I take from one of these flasks, I have two different and mix together, and then I put in one cell line, or I have cell line which is positive and I take the virus and put it there. What is the difference between these two" (6/26/90 OSI interview; transcript pp. 69 - 70).

3. The HUT-78/HT/H9 "Breakthrough": Dr. Gallo's discovery of how to grow the AIDS virus in quantity occurred when Dr. Popovic used another scientist's cell line (HUT-78; developed by Dr. Adi Gazdar and his colleagues) to grow another scientist's virus isolate (LAI/LAV; isolated by Montagnier et al.). In the process, as was true for the virus, Gallo/Popovic gave the cell line a new name: "HT/H9" -- HT was the parent line, H9 a clone of that line -- giving no credit to the true originators, and thereby, tacitly as well as explicitly claiming the "discoveries" as the LTCB's own. The true origins of the cell line were finally, convincingly, documented in the scientific literature (Mann et al., AIDS Research and Human Retroviruses; 5, 1989, pp. 253 - 255), following an investigation ordered by the Director, NIH.

The results of the investigation showed that:

"... the original cell line HUT-78, H9 utilized for HIV isolation, and the ATCC versions of these lines are genetically identical and were derived from the same individual" (op cit., 5, Page 254).

Dr. Popovic used a CD4+ T-cell line taken from the LTCB freezers, identified as "HUT-78," in his initial attempts at permanent growth of the AIDS virus, in the Fall of 1983. HUT-78 had previously been provided to the LTCB by the scientist who discovered it and published its derivation, Dr. Adi Gazdar. The cell line originated with a patient diagnosed with Sezary Syndrome, a type of lymphoid leukemia. Shortly after his initial successful experiments growing LAI/LAV in HUT-78, Dr. Popovic cloned the parental cell line on two separate occasions (November 1983 and January 1984), reportedly for two reasons: one, to ensure that the cell line did not harbor any contaminating virus, particularly HTLV-I, and two, to obtain single-cell clones that would maximize the growth of the AIDS virus. These experiments produced over 50 clones, of which Popovic selected the eight "best growers" for use in his "HTLV-III" experiments. "H9," reported to be the best growing of the clones, was obtained in January 1984.

Meanwhile, Dr. Popovic renamed the parental cell line, changing the name from "HUT-78" to "HT." The principal reason offered for the change is that Popovic was uncertain that the cell line in which he succeeded growing the AIDS virus was the authentic HUT-78. Subsequently, beginning in the Popovic et al. May 1984 Science paper, and in numerous papers and public speeches, as well as numerous legal briefs, Gallo et al. and the U.S. Government represented "HT" and its H9 clone, as new, "breakthrough" discoveries of the LTCB. Another major theme of the claims by Gallo et al. and the U.S. Government was that the putative "discovery" of the cell line enabled the "isolation" of the LTCB's prototype HIV isolate, which was followed immediately thereafter by the development of HIV-specific reagents and the HIV antibody blood test, all this beginning in the Fall of 1983. These claims, in significant respects, are contradicted by the facts.

(a) Claims that HT/H9 Was "New": Statements claiming credit for the "discovery" of HT/H9 appeared first in 1984, in the Popovic et al. Science paper. The published version of the paper contained this description of the cell line in which Popovic grew the AIDS virus:

"One neoplastic aneuploid T-cell line, derived from an adult with lymphoid leukemia, was found to be susceptible to infection with the new cytopathic virus isolates. This cell line, termed HT, has produced HTLV-variants in sufficient quantities to permit the development of specific immunological reagents and nucleic acid probes..." (p. 498).

The evolution of the cell line description through successive drafts of the Popovic et al. paper is informative. Early drafts of the paper correctly reported the cell line, not identified, as originating "from a patient with mature T-cell malignancy (Sezary Syndrome)..." In draft 3, the reference to the patient's diagnosis as "Sezary Syndrome" was dropped; inserted in its place was an obscure reference to a "mature T-cell malignancy." In draft 4 of the paper, Dr. Gallo made an important change that significantly misrepresented the cell line, making it appear to be a de novo discovery, i.e. the addition of the word "new" to the sentence,

"We report here the establishment and characterization of a new immortalized T-cell population which is susceptible to and permissive for HTLV cytopathic variants."

Lest there be any doubt as to whether Dr. Gallo was claiming the cell line as a discovery of the LTCB, his words at the Beecham symposium, delivered shortly after submission of the Popovic et al. paper, bear mention. On this occasion, Dr. Gallo said this:

"The breakthrough occurred for us when we learned how to transmit this [the AIDS virus] to a particular cell line developed in our lab. That happens to be H4 [another "HT" clone], a new line" (emphasis added; 4/5/84 Beecham "Symposium on Infective Agents and Their Effects").

At the same time as Gallo/Popovic obscured the HUT-78 origins of H9, Dr. Gallo withheld H9 from a number of scientists who sought to obtain it (see below). HUT-78 was freely available to scientists through the American Type Culture Collection (ATCC), where it was deposited in 1981. But, scientists seeking H9 were not able to avail themselves of this ready access because they did not know H9 was HUT-78.

The combination of these circumstances led the Richards committee to make these observations:

"... the so-called HTLV-III virus was thus established and introduced to the world with no reference to or discussion of two crucial facts ... the cell line utilized [HUT-78] was one that had been obtained from the Minna laboratory [Dr. Minna was Dr. Gazdar's laboratory chief] ... Although others could have obtained HUT-78 from the ATCC ... the essential identity of HUT-78 with H9 had been effectively obscured" (2/19/92 Richards-to-Healy; p. 3).

"The fact is I never really thought it was important. And quite frankly, I still don't and I don't understand the people who do."

"I don't consider it so brilliant. In my mind, there is no credit for a cell line. If it happens by accident you have a cell line, so freaking what?" (Science, 248, 1990; p. 1507).

"By the fall of 1983, Popovic had developed such a line [a permanent cell line] using H9 cells" and ".. once the permanent cell line for HTLV-III was developed, HTLV-III was produced in substantial amounts and used to prepare reagents for testing against AIDS sera ..." (Emphasis added; Page 14).

"... in the fall of 1983, Dr. Popovic discovered that a few cell lines but in particular a cloned cell line, designated H9, was resistant to the retrovirus and could be effectively used to produce the virus in relatively large amounts of a consistent composition. Dr. Popovic accomplished this by November, 1983 ..." (Page 7).

"... some references to the 'H9' cell line -- one of the most successful lines for growing the AIDS virus -- are actually describing an earlier cell line known as 'H4'" (11/14/91).

"... this was a mistake that does not significantly change the conclusion of the declaration or the basis of the agreement."

Dr. Gallo's claim that H9 existed and was infected with the AIDS virus in November 1983 was a material misstatement related to some of the central themes of his declaration, including the claim that Gallo et al. made the breakthrough discovery that led directly to their HIV antibody blood test in the Fall of 1983. But Dr. Gallo's prototype isolate, IIIb, the virus Gallo et al. said "corresponded to" their blood test invention, did not even exist in November 1983, neither was it used to infect the H9 cell line until at least late January 1984.

The false claims in the U.S. Government pleadings were anticipated by equally false statements in documents generated by Dr. Gallo and his colleagues at the outset of the patent dispute, in the Summer of 1985. Dr. Peter Fischinger, in his August 1985 report to Lowell Harmison, described "HT" as a "relative" of HUT-78, a relative "developed by Dr. Gallo." Dr. Gallo signed an affirmation that the Fischinger report had been reviewed for accuracy by him and were substantiated by LTCB data (see below).

Dr. Gallo himself wrote to Dr. Fischinger that Dr. Popovic "... developed the H9 clone in early November 1983" (9/23/95 memorandum, page 5), even though Dr. Gallo knew from a September 6, 1985 memorandum from Mikulas Popovic that the final cloning of "HT" and the subsequent infections of the clones did not take place until January 1984. In the September 6 memorandum, Dr. Popovic also said that H9 represented,

"... a single cell clone obtained by limiting dilutions from a continuously growing T-cell which we originally thought to be HUT-78" (emphasis supplied).

"Since primary non-cultured HUT-78 cells are not available, we cannot make a definitive conclusion whether the designated HT cells are identical with the original HUT-78 or not."

"I don't consider so exciting the work aimed at tracking down precisely the origin of HUT-78 cell lines each time" (6/26/90 interview; transcript page 183).

"... I did not consider it my responsibility to work out the confusion surrounding HUT-78..." (p. 9).

(c) H9's Hidden Defect: One other matter relating to the H9 cell line needs to be mentioned; the defect had a significant, deleterious impact on the HIV blood tests licensed under the Gallo et al. blood test patent. Both this patent and the two Gallo et al. cell line patents described H9 as,

"... a representative and preferred (cloned) cell line in accordance with the invention."

During 1985, the LTCB scientists published at least two papers referring to the H9 false positives problem. Dr. Popovic told OSI, concerning the second of these papers:

"We considered important to stress using the confirmatory (Western blot) assays, because of HLA class II [the defect that caused the H9 false positives]. It was important" (6/26/90 OSI interview; transcript p. 184).

"H9 is a mature T cell. It has characteristics very similar to ATL cells ... It has Class II antigens ...

"At the beginning we favored this cell line [H9] because of pressure to have a source of virus as soon as possible for the blood bank assays. Later I was not favoring it and I was not favoring it for a simple reason. When the viral budding occurs it takes also HLA-II with it, so the viral prep has also Class II antigens, cellular antigens. So that means if individuals let's say, got blood transfusion in the past, it can have a false cross-reactivity with the virus in ELISA. This reactivity does not have anything to do with the AIDS virus (HIV). The companies worked hard to establish negative controls ...

"At the beginning the H9 was pulled out because of the speed. However, they (Mr. Roberts, patent attorney) told us that we can come later with other T4 cell lines ... The virus which would be produced from such cell lines, for instance, as Molt 3 which doesn't have Class II antigens, gives far less unspecific cross-reactivitiy in ELISA" (6/26/90 OSI interview; transcript pp. 176 - 178).

"H9 is a representative and preferred cell line in accordance with the invention."

Last section; next section.