Polio vaccines and the origin of AIDS
which in turn is part of Brian Martin's website on suppression of dissent.
In his concluding speech at the Lincei conference of September 2001, later published under the title "Emerging Persistent Infections: Family Heirlooms and New Acquisitions" [Weiss, 2003], Professor Robin Weiss devoted a section to the origins of AIDS debate.
However, like his other interventions in this debate at the Royal Society conference on "Origins of HIV and the AIDS epidemic", and in the pages of Nature, this paper contained many observations that were flawed, misleading, or simply untrue.
Let me give specific examples.
(a) Misrepresenting the OPV theory. Weiss devotes much of his brief analysis of the OPV theory to the earlier version of that theory which was propounded by Tom Curtis in 1992, and which was based on the idea that African green monkeys might have been involved in making the vaccine used in Africa. As made clear in The River [Hooper, 2000], I never subscribed to this version of the theory, and realised from the start that the theory would only work if chimpanzees (and specifically the chimps of Lindi camp, mentioned in passing by Curtis) had somehow been involved with the manufacture of the vaccine. (Indeed, this has turned out to be the case.) Weisss focussing on Curtiss account is simply not relevant to the present debate, and appears to be a fairly blatant attempt to marginalise the theory, by highlighting an early and now discredited version.
(b) Making misleading claims about phylogenetic analysis. Professor Weiss claims that "the most telling answers" about the provenance and timing of the HIVs come from phylogenetic analysis. He argues that phylogenetic dating confounds the OPV theory, since it indicates that the Most Recent Common Ancestor (MRCA) of this group existed "around 1931, with 95% confidence limits of 15 years". Weiss is correct with regard to the provenance of the HIVs, since phylogenetic analysis provides important evidence about which SIVs are their closest non-human relatives. However, the use of phylogenetic analysis to date the epidemic is highly controversial, as Weiss is well aware. Significantly, he makes no reference to this.
This omission is doubly surprising, given that (a) his fellow-organiser from the Royal Society meeting, Simon Wain-Hobson, has revealed major shortcomings in this aspect of phylogenetic theory [see below], and (b) Professor Weiss heard the presentation made at Lincei by Mikkel Schierup, which focused on the shortcomings of phylogenetic dating.
In his conclusion, Weiss states that Schierups paper [Schierup and Forsberg, 2003] merely suggests that "the confidence limits might widen a little" on that date of 1931 plus or minus 10 to 15 years. However, this is a misrepresentation of what Schierup and Forsberg write in their important, indeed ground-breaking, paper.
They report that there is substantial evidence of recombination having occurred both between and within the subtypes of HIV-1, and they find evidence of extensive recombination even in datasets such as that used by Bette Korber in her famous 2000 paper, "Timing the Ancestor of the HIV-1 Pandemic Strains" [Korber et al., 2000], which the authors claimed to have "cleaned" of potential recombinant sequences. Schierup and Forsberg demonstrate that ignoring this recombination would lead to placing the MRCA too far back in time.
This conclusion has since been greatly reinforced by the work of Andreas Meyerhans and Simon Wain-Hobson, who report evidence of "massive" recombination in HIV-1 [Wain-Hobson et al., 2003]. These latter authors calculate that the rate of recombination in HIV-1 is some ten times greater than the rate of "point-substitution" (ie normal mutation). Ignoring recombination, they estimate, would lead to overestimating the age of the MRCA by as much as 45%. (This should not be taken as indicating an upper limit; it may well be that the phylogenetic dating approach would involve considerably greater errors than this.) However, even correcting for a 45% error would bring Korbers mooted MRCA up to about 1950 (range: approximately 1940 to 1957), and Paul Sharps putative 1940 MRCA up to about 1957 (range: approximately 1948 to 1963). In other words, the OPV trials of the 1950s would now fall within the time estimates.
However, Schierup and Forsberg go much further than that, for they call the whole basis of phylogenetic dating into question. They write that the very high rate of recombination between subtypes "is important, because it indicates that recombination may have been prevalent also before the diversification into subtypes, ie early on in the evolution of the present diversity." Later, in their conclusions, they write that: "If recombination has occurred in the viral population originating from the MRCA [ie early in the evolution of HIV-1], it is not valid to use a phylogenetic method to obtain the time estimate, and our results suggest that doing so would give a certain overconfidence in the previous estimate of 1931 +/- 10 years". [My bracketed insert and italics.] What Schierup and Forsberg are actually stating here is their belief that recombination probably did also occur early in the history of HIV-1 (recombination that would neither be detectable, nor removable by the "cleaning" methods advocated by such as Korber and Sharp). They are further stating that such early recombination would mean that phylogenetic dating theory is inherently flawed, and should not be used to date HIV-1.
Yet all Professor Weiss hears is that polite, throw-away line about previous studies demonstrating a "certain over-confidence". Weiss was meant to provide a balanced summing-up of the papers presented at the conference, but in fact he has minimised the import of Schierup and Forsbergs work. It is as if he has only read the last two paragraphs of their paper, and has lifted out the one phrase that fits with his preconceptions.
The simple truth is that phylogenetic dating is now revealed as an inappropriate technique for dating HIV-1, as is acknowledged by a growing number of scientists, both in print (Schierup and Forsberg, Wain-Hobson, Meyerhans, Jon Cohen of Science [Cohen, 2002]), and verbally (as at least half a dozen other statisticians and geneticists have done in conversation with me). Weisss claim that "the confidence limits might widen a little" is disingenuous, and appears to be an attempt to retain some credibility for phylogenetic dating. The only conclusion that can reasonably be drawn from the work of Schierup and others is that phylogenetic dating theory is innately flawed, and therefore unsafe, when applied to HIV-1, and should therefore not be used as a basis for estimating the age of AIDS viruses in humans.
One final point. Weiss states that what convinces him of the accuracy of Korbers start date of 1931 is that this scenario successfully predicts two "known dates of sampling": the 1959 Leopoldville sequence, and the 1986 date for the emergence of subtype E in Thailand. In reality, both claims are questionable. Korbers actual prediction for the date of Leopoldville sequence is 1957, with 95% confidence intervals [95% CI] of 1934-1962. Yet, as I have explained in pages 173-176 of Dephlogistication [Hooper, 2003], there is considerable doubt about the dating of the Leopoldville sample; a wide range of evidence (including testimony from the three main authors of the genetics papers about these samples - Motulsky, Vandepitte and Fraser) indicates that this sample was certainly obtained later than the declared date of "early 1959", and it may have been obtained as late as 1963 (which would fall outside Korbers confidence intervals).
Again, Korbers best prediction for the Thai subtype E founder sequence (using the full set of Group M sequences) is actually 1984 [95% CI: 1980-1986]. Yet, on the basis of the discussion in her own paper, 1987 would appear to be a more plausible date for the origin of the Thai subtype E epidemic than 1986 - and again, 1987 would fall outside her confidence intervals.
Korber encountered similar problems with her estimates of the putative date of the first American subtype B sequence (though Weiss omits to mention this). She has four different guesses at this one, but the best guess, based on the envelope gene, places the first US subtype B sequence in 1967 (95% CI: 1960-1971). As several observers, most notably Gerry Myers, have pointed out, this seems far too early when the first confirmed American HIV-1 isolate is from 1977, and the first proven case of American AIDS is from 1979.
In all three instances, therefore, it seems that the real dates of the sequences in question are more recent that Korbers estimates, falling either at the upper limit of her 95% confidence intervals, or outside them. Leaving aside the question of whether phylogenetic dating works, this suggests that her estimates for these dates (including her famous 1931 estimate) are set considerably too far back in time.
Coming back to Robin Weiss, it appears that he has not taken the trouble to recheck the actual dates and confidence intervals in Korbers paper, for the details which convince him that her 1931 estimate is correct, if examined closely, actually do the exact opposite. In reality, they consistently suggest that her 1931 estimate is too early.
(c) Claiming that adapting a theory is unscientific. Weiss writes that "like HIV itself, the OPV hypothesis has undergone mutation and adaptation as scientific advances disproved the early theory". He presents the process as a desperate attempt to "rescue" the theory in the face of overwhelming scientific evidence to the contrary. This is a deliberately misleading account of what actually happened (which is recounted in some detail in The River,which Weiss claims to have read from cover to cover). Furthermore, Weiss fails even to mention that with my latest paper, and in particular with the latest accounts of local vaccine preparation in Stanleyville, I have presented new and highly significant scientific evidence in support of the theory. In any case, as Weiss surely knows, adapting a hypothesis as more and more relevant data comes to light is the usual way in which theories evolve and scientific knowledge advances.
(d) Asserting primacy for his own ideas. Professor Weiss is not slow in his attempts to claim primacy in scientific matters, and he presents me as changing my view about where the vaccine was made after he first proposed the idea of local vaccine preparation in his review of The River in Nature magazine. As I have now related in various articles, Professor Weiss had been aware of this possibility since at least 1994, though the way he alluded to it then was deliberately, it would seem, obscure (as "the potential of contamination by chimpanzee tissues in the Congo"). Although I began to twig that something might have happened locally just before I submitted the final version of The River to the publishers in 1998 (see pages 720-724 for my musings on that subject), I still did not seriously imagine that this had happened. This was mainly because at that stage I was still swayed by the testimony of the five major witnesses who had been involved with preparing or feeding the vaccine (Koprowski, Plotkin, Gelfand, Osterrieth and Ninane), all of whom maintained that the vaccine used in the Congo had been made in the US or Belgium, and that local vaccine preparation was not possible. (However, Ninane did initially state, on three occasions, that the vaccine had been prepared in chimpanzee kidney cells, and only backtracked when I told him that the papers of the time had alluded only to monkey kidney cells. Furthermore, Koprowski made certain equivocal statements in his second interview in December 1993, statements which seemed designed to float the possibility that the Belgians might have done something to the vaccine in the Congo without telling him about it.)
Despite these hints, I had no choice when writing The River but to accept the version of events that the vaccinators eventually settled upon: that vaccine could not have been prepared locally. My position on this only really changed after revisiting Kisangani (Stanleyville) in April 2001, when I was able to interview four key African witnesses. These were Joseph Limbaya Mwenge and Baelo Alukelo (former workers at Lindi camp from 1956 to 1959, with Joseph, the "camp nurse", having been chief of the African staff there); Philippe Elebe (microbiology department at the Laboratoire Medicale de Stanleyville, LMS, 1956-60); and Jacques Kanyama (virology department of the LMS, 1958-1960). Together, they provided a comprehensive network of evidence about the routine sacrificing of the Lindi chimps, including many chimps from which blood and organs were harvested while they were anesthetised, but still alive; the preparation of chimpanzee tissue culture from the harvested organs; the supplying of this tissue culture to Paul Osterrieth and Gaston Ninane over a lengthy period; and the preparation by Dr Osterrieth of fresh batches of polio vaccine whenever new requests for OPV came in.
It is reported that no other tissue culture (TC) was available in the LMS until the middle of 1958 (when a small amount of baboon TC was apparently prepared). The only reasonable conclusion is that before and after the baboon TC episode, Osterrieth was growing the vaccine in chimpanzee tissue culture.
Tellingly, much is made of the baboon TC in the 1958 LMS annual report, whereas no mention at all is made of chimpanzee TC. This strongly suggests that the use of chimpanzee TC for human vaccines was known to be risky, even back in the 50s, and that even then this experimentation with substrates was being done secretly.
Since April 2001, this major new evidence about local vaccine preparation has been further confirmed by several new Belgian sources, some of whom were directly involved with the vaccinations themselves.
Every step of the process is now confirmed by at least two independent sources, but on some key details (for instance that OPV was being locally prepared in Stanleyville), I now have as many as seven independent confirmations.
So, it was not Dr Weisss theorising that put me on to local vaccine preparation, and I was not searching for facts to fit a theory when I returned to Kisangani in 2001. If anything, I stumbled across the evidence of what had actually been happening.
But significantly, whereas Weiss was happy to theorise along these lines in 1994 and 1999 (perhaps because in those days such theorising seemed to exonerate the original vaccine-makers, such as Koprowski), now that I have provided evidence that this is exactly what did happen, he is suddenly unexpectedly keen to deny it. First he rushes to proclaim that such evidence would mean "that the Wistar Institute can be omitted from the loop", and then, in the same breath, he rushes to dismiss the evidence itself. Why? Because Professor Osterrieth denies it, apparently.
I believe that this rather amusing doubling-back reveals Robin Weisss true agenda. First and foremost, this agenda seems to be to deny and discredit the OPV theory at all costs. Secondly, it seems to be to exonerate senior scientists like Koprowski, and institutes such as the Wistar, from responsibility for the debacle. It is, in short, a whitewash.
(e) Trying to exonerate certain scientific instititions. In fact, Dr Weisss claim that if this new evidence is correct, it would mean that "the Wistar Institute can be omitted from the loop" is patently wrong. Dr Osterrieth trained at the Wistar in tissue culture techniques (and worked on polio) for four weeks in late 1957, and he went there at the specific invitation of Hilary Koprowski. So it seems highly unlikely that Osterrieth would have cultured the polio vaccine in chimpanzee tissues without the express approval, and indeed direction, of Dr Koprowski, the man who was the mastermind behind Lindi camp and the chimpanzee experiments. I find it significant that both Weiss and Wain-Hobson have been premature in their desire to absolve Koprowski, Plotkin and the Wistar Institute of any involvement, and believe that this provides some important clues about their motivation.
(f) Analysing evidence in a biased fashion. Dr Weiss asserts that I have "postulated" that Osterreith expanded the vaccine in local tissues, but he makes no reference to the overwhelming supporting evidence (including testimonial evidence) that I have presented. By contrast, Weiss presents Osterrieths conflicting (and self-contradictory) account as a "statement", and Plotkins conflicting account as "testimony". This shows frank bias.
(g) Treating arguments and evidence selectively. Throughout his brief analysis, Dr Weiss deals selectively with the evidence, picking out only those things which support his increasingly unscientific argument. He states that he is sceptical about the OPV theory because of phylogenetic dating, and the unproved use of chimp kidneys. I deal with both these issues at length in my paper [Hooper, 2003], but he ignores these arguments altogether.
(h) Summing up in a prejudiced fashion. At the end, Dr Weiss invites me personally "to contemplate more deeply whether the OPV hypothesis really remains plausible". I have indeed considered more deeply, as illustrated by the arguments presented in my lengthy paper, and I clearly believe that the OPV theory is not merely plausible, but compelling. Professor Weiss, by contrast, merely repeats redundant and outmoded arguments from the past. Therefore, his invitation to me to "contemplate more deeply" is not only patronising, but is also dishonest. I would propose that it is he who needs to undertake some fresh thinking.
(i) Repeatedly implying that I have fabricated evidence. Weiss urges me not to "attribute base motives to those who disagree with [my] views". I do not attribute base motives to people without good reason. What is very significant is that, in contrast to his public statements about the OPV theory (which retain a modicum of decency, even if they are frequently inaccurate), Dr Weisss private statements, for instance to reporters, repeatedly contain allegations that are untrue - and which he knows to be untrue. Most notable among these are his repeated claims that I have cited a witness to the events of Lindi camp in the 1950s who was actually not born until the 1960s.
This false allegation seems to be based (if it based on anything) on the paperback postscript to The River, which recorded that on my penultimate day in Kisangani in 1999, I asked one of the Lindi caretakers, "Antoine", to attempt to trace his former boss at Lindi - the camp nurse, Joseph. Antoine returned to tell me that he had found some people from Josephs home town, Basoko, who had told him that Joseph died in 1964, after growing thin in his final days. I wrote about this in the new River postscript published in May 2000 [Hooper, 2000], expressing doubt that this could be AIDS, but pointing out that it might be. It was only on my return to Kisangani in 2001 that I discovered that Antoine had tracked down the wrong Joseph. In reality Joseph Limbaya Mwenge, the Lindi camp nurse (and boss of the African "caretakers" at the camp), was still alive, albeit in his mid-seventies. Joseph Mwenge gave two interviews on camera (one in April 2001, the other in November 2002), and I have since been informed that he died on May 3rd, 2003, at the age of 77.
Even though I explained in some detail at the Lincei conference in September 2001 that "Antoine" had been mistaken about the identity of the Joseph who had died in 1964, and that the real Joseph (the Lindi camp nurse) had since been tracked down and interviewed, and although I reported this again in my Lincei paper, published in April 2003, such committed opponents of the OPV theory as Robin Weiss and Paul Sharp (both of whom were present at Lincei) and Stanley Plotkin (who was not) have continued to state, or to imply, in letters and e-mails that I have been citing a non-existent witness. The fact that Professor Weiss keeps repeating this false implication is especially telling, for I personally handed him a copy of my speech during the Lindi conference. He was also the summarising speaker at that conference, the proceedings of which were published in April 2003, so he presumably must have seen the longer written version of my paper, which also clarifies the Joseph issue. Despite this, he has repeated this falsehood to journalists who contacted him in October 2001 and June 2003, long after he must have been aware that such a conclusion was, at the very least, both far-fetched and highly questionable. To my mind, this further underlines the fact that Professor Weisss in this debate is frequently insincere: he is more interested in trying to discredit me than in reporting events truthfully. It also, I believe, raises questions about his suitability as a conference summariser.
So when Robin Weiss urges me not to "attribute base motives" to him, I should make my position clear. The only reason that I attribute base motives to Dr Weiss is because there is substantial evidence to support such a conclusion.
Just as he did at the Royal Society meeting on "Origins of HIV and the AIDS Epidemic", Professor Weiss misused his position at Lincei as a "neutral arbiter" in order to deliver a biased and partisan closing speech. At the Royal Society, he was able (albeit on rather flimsy and selective grounds) to claim that scientific evidence presented at that conference argued against the OPV theory. In my Lincei speech (and in the much longer paper that followed) I have demonstrated that every significant piece of scientific and historical evidence that scientists like Weiss, Plotkin, Sharp, Hahn and De Cock have presented as an alleged "disproof" of the OPV theory is either questionable, flawed, or provably incorrect. Despite this, Professor Weiss persists in asserting that the OPV case is not plausible.
By misrepresenting the evidence in this fashion, Weiss no longer weakens the OPV/AIDS theory. He merely calls into question his own judgement and integrity.
I now believe that Dr Weiss has a prior agenda, which is to do whatever is necessary to try to discredit the OPV hypothesis. Perhaps he sees himself as a defender of Science against the ugly theories proposed by non-scientists. Perhaps he believes that if the real story of CHAT in the Congo comes to be widely known, it will irrevocably shake popular confidence in vaccination, that cornerstone of public health.
I believe that during the last four years, Weiss has shown himself to be a man who is more concerned with public relations than in genuinely searching for the truth - and, at least with regard to the origins debate, he has proved himself to be more a doctor of spin as a doctor of science.
I think it is now time to reveal the identity of "Antoine". I clearly indicated in a River footnote that names which first appeared in quote marks in the book were not the real names of those persons. Even if Dr Plotkin had not read this particular footnote, my placing Antoines name in quote marks the first time it appeared must have indicated to him, at the very least, that this might have been a pseudonym. However, in his Royal Society postscript, Plotkin affected not to realise this, and sought to prove that the Antoine who had apparently worked at Lindi in the 1950s had died in 1986 or 1987 - and therefore could not have been interviewed by me in 1999. This was another flagrant attempt to discredit me, and the evidence that I have carefully, and gradually, put together on this issue.
In the May 2000 paperback edition of The River, I used "Antoine" as a pseudonym for Baelo Alukelo, a man who had worked both at Lindi camp in the late fifties (when he was a teenager), and at the LMS thereafter. I used a pseudonym for Baelo expressly because I suspected that he might be tracked down by members of the Plotkin team and pressurised to "modify" his evidence, just as many others have been previously. And this is indeed exactly what happened. At some point during the year 2000, Baelo was approached by Dudu Akaibe, a senior professor of science at the University of Kisangani. And in November 2000, Baelo was introduced by Akaibe (who by then was collaborating with Stanley Plotkin) to Paul Gigase, a visiting Belgian professor whom I have known since interviewing him in 1993. I went to see Professor Gigase again in May 2003, and in a recorded interview he explained that he had spoken with an African man who had been working at Lindi, and who had told him that the doctors had indeed been taking kidneys from the Lindi chimps. However, in a subsequent e-mail, Gigase claimed that his African informant had been Baelo Alukelo, and that Alukelo had told him that they had only taken kidneys from dead chimpanzees, meaning (Gigase asserted) that the kidneys could not have been used for tissue culture. Gigase presented no evidence to support this claim, which I believe to be untrue. For in April 2001, after Gigases visit, Baelo Alukelo was interviewed again, this time on camera, and he once again explained that on many occasions the Lindi chimps had been anaesthetised, but still alive, when their organs were extracted. At the time of the dissection, he said, you could see that they were still breathing, and that their eye-balls were still flickering. Moreover, you could hear them "speaking" (making small noises). This conformed exactly with what Baelo had previously told me (albeit in rather less detail) in July 1999.
Professor Akaibe also interviewed Joseph Limbaya Mwenge, but under false pretences (which apparently included claiming that he was a colleague of mine), in an attempt to find out what the Lindi camp nurse had previously told me. But his involvement did not end there. He also took revenge on the young man who had served honourably and ably as our translator during our time in Kisangani by expelling him from his university course, and refusing even to meet with him to explain his decision. I believe that this is a disgraceful abuse of his role as a university professor.
Amusingly, however, Professor Akaibe has apparently not yet grasped which version of events it is politic to repeat to others. It seems that someone had sent him a copy of The River, which he duly read. But when the co-director of the MFP/Galafilm documentary, Peter Chappell, returned to Kisangani for more filming in November 2002, Akaibe explained to him that: "Hooper got it wrong in the book. The vaccine wasnt made in America or Belgium. It was made here in Stanleyville."
This, I believe, represents the ninth confirmation from someone who should be treated (at least on this issue) as an independent source, that in the late 1950s Koprowskis oral polio vaccines were being made locally (ie regrown in locally available tissue culture) in Stanleyville.
Four of these nine persons confirm that the tissues used were those of the chimpanzee.
All this ties in directly with the crucial testimony by the chief technician of the LMS, Pierre Doupagne, that for a lengthy period in the late 1950s he was making chimpanzee tissue cultures and supplying them to Paul Osterrieth and Gaston Ninane, "to do what [with], I do not know".
These independent accounts directly conflict with the versions of events favoured by interested parties such as doctors Plotkin, Koprowski and Osterrieth.
Slowly, but inexorably, the attempted cover-up about the local preparation of CHAT vaccine in Stanleyville is being revealed.
EH January 14th, 2004; updated February 13th, 2004; posted 26 February 2004
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