[Edward Hooper’s response to the latest brief communication in Nature by Michael Worobey, Beatrice Hahn and colleagues, entitled “Contaminated polio vaccine theory refuted”. Nature; 2004; 428; 820.]
Background
The first thing to notice about this one-page paper by Worobey et al. is the media blitz that has preceded it. It has been heavily promoted on Nature‘s web-site for five days before publication, and features an embargo date, in the hope of ensuring coordinated media coverage.
The second important detail is the title. This reveals that only secondarily is this paper an attempt to clarify the ancestry of HIV-1. First and foremost, it is an attempt (yet another attempt) to disprove the OPV/AIDS theory.
In this, it is no more successful than its predecessors. This, however, is hardly surprising, for like all such recent articles in the mainstream literature, it is predicated on the premise that the OPV theory is wrong.
The title of Worobey’s communication brings to mind the titles of earlier papers and commentaries. Back in October 1992, after an expert committee convened by the Wistar Institute (the place where CHAT vaccine was developed) had discounted the OPV theory, Science reported that: “Panel nixes Congo vaccine as AIDS source”.
More recently, in April 2001, a series of papers was published simultaneously in Nature and Science which variously declared: “Disputed AIDS theory dies its final death”, “it’s really most sincerely dead”, and “some beautiful facts have destroyed an ugly theory”.
If the OPV theory was already as dead as these august journals claimed, then why is yet another attempt required to refute it?
This can best be answered by pointing out, once again, that both Nature and Science have shown consistent and unwarranted bias against the OPV theory. Since neither journal has ever agreed to publish a single paper or communication which expounds or supports the theory, it is hardly surprising that the repeated “refutations”, “disprovings” and accounts of its demise are full of holes.
To date, every such alleged refutation has been flawed. Not one has been based on good science.
But the second reason for this article’s appearance in Nature relates to the timing. There has been a great deal of advance publicity (for instance in listings magazines and trailers) for the forthcoming broadcast in France of the 90-minute MFP/Galafilm documentary, “The Origins of AIDS”. [The documentary has already shown in five countries, to considerable acclaim, and will be shown on the France2 channel at 10-45 pm on Friday, 23 April.] What this film reveals is that, in contrast to the repeated denials of the vaccine-makers, an oral polio vaccine (OPV) called CHAT, which was administered to about a million Africans in the late 1950s, was indeed (as has long been hypothesised) prepared in the cells of the common chimpanzee, Pan troglodytes.
This animal is host to SIVcpz, the variant of simian immunodeficiency virus (SIV) that is now widely accepted to be the closest ancestor of the AIDS pandemic virus, HIV-1. The startling new information in this film is that (as revealed by a range of Congolese and Belgian witnesses) the final version of the vaccine administered in Africa was prepared not in the US or Europe (as previously believed), but in Africa itself, at the medical laboratory in Stanleyville, Belgian Congo (now Kisangani, Democratic Republic of Congo, DRC).
Using some remarkable archival footage, the film shows the chimpanzee colony that was set up at Lindi Camp, 10 miles from Stanleyville, where some 600 chimps were sacrificed in the course of four years. Many of these chimps had their organs removed while they were anaesthetised, but not yet dead, which is how organs are removed for making tissue culture, and for propagating polio vaccines.
As has been documented in my book, The River, the first appearances of HIV-1 and AIDS in the world (between 1959 and 1980) occurred in the very same towns and villages in the DRC, Burundi and Rwanda where this vaccine had previously been administered.
A forthcoming statistical study finds the correlations between the African trials of CHAT vaccine and the first recorded instances of HIV-1 infection to be “highly significant”, meaning that there is a less than 1 in 1,000 chance that they are the result of coincidence.
“Brief communications” such as the present paper can be inserted into a journal like Nature at very short notice, provided they have already been vetted. All this helps to explain the timing of the present paper, and the considerable advance publicity afforded it. The paper is co-written by eleven authors. The lead author is Michael Worobey (formerly a member of Eddie Holmes’s group at the University of Oxford Department of Zoology). The list of authors also features Andrew Rambaut, from the same department, and two arch-opponents of the OPV theory, Beatrice Hahn and Paul Sharp. [See “Authors” section, below.]
The content of the Nature article
So what is this “brief communication”, of less than one page, all about?
It focuses on a claim that has been made by these scientists several times previously: that the SIV of the eastern subspecies of the common chimpanzee (Pan troglodytes schweinfurthii), which is found mainly in the DRC, is less closely related to HIV-1 Group M (the AIDS pandemic virus) than is the SIV of the central subspecies of chimp (Pan troglodytes troglodytes), which is found mainly in west central Africa, in Cameroon, Gabon, and Congo Brazzaville.
(This is despite a paper that was published three years ago, which argued that the genetic differences between the two alleged subspecies are minimal, and proposed that they should perhaps be redefined as a single subspecies.) [Gagneux et al.; Philosophical Transactions of the Royal Society (London), Series B; 2001; 356; 889-900.] The Worobey et al. communication reveals that two of the ten chimp urine samples that were collected from Wanie-Rukula (near Kisangani) during Bill Hamilton’s final expedition in January 2000 showed typical SIV protein bands on Western blot analysis.
Surprisingly, this is the first reporting of this important discovery. Simon Wain-Hobson, who agreed to collaborate with Hamilton by testing samples from his two trips to the Congo (with this author, in July 1999, and with Worobey and Jeff Joy, in January 2000) has never formally reported any results. Furthermore, he has not made a meaningful response to any of the five e-mails which I have sent him over the intervening years, requesting feedback on his research, or that he release the samples to someone else who would be willing to do the testing.
Later on (in late 2000, I believe), Michael Worobey unilaterally decided to share the remaining Hamilton chimp samples with that arch-opponent of the OPV theory, Beatrice Hahn. Her team did carry out proper analysis, and before long (at some point in 2001, I believe), they obtained repeatedly positive results on two of the urine samples. However, for reasons that are not clear, these significant findings have never been reported until now. “This result confirmed that natural SIVcpz [chimpanzee SIV] infection was present in chimpanzees in the Kisangani region”, write Worobey et al. in the new paper. So far, so good. The paper then relates that further fieldwork was conducted in February 2003 at three different chimpanzee sites near Kisangani, and that of 97 faecal samples collected, one sample was found to contain the RNA of SIVcpz. (It seems that although urine is a better indicator of SIV-positivity, faeces are required in order to extract the virus itself, a process that is only successful in a certain proportion of cases.)
This latter virus was sequenced, and was found to be a fairly typical Pan troglodytes schweinfurthii SIV, similar to the five previously identified schweinfurthii sequences (four from the same site in north-western Tanzania, and one from an undetermined location in the DRC). The authors comment: “These results indicate that chimpanzees in the vicinity of Kisangani are endemically infected with SIVcpz that is highly divergent from HIV-1, thereby ruling out these apes as the source of HIV-1 and refuting the OPV theory.”
Refuting the refutation
Worobey et al.’s conclusion is not supported by the data, and there are three major reasons why.
1) The assertion that schweinfurthii SIV is “highly divergent from HIV-1” is misleading and wrong. The reality is that schweinfurthii SIV is roughly 70% similar to HIV-1(M), and troglodytes SIV is about 80% similar to HIV-1(M). However, of the thirty or so known SIVs from African primates, these are the only two SIVs that closely resemble the pandemic AIDS virus. Both these chimp SIVs have the same range of genes, including a crucial identifier, the vpu gene. However, it is important to note that neither virus is identical to HIV-1 Group M viruses.
By contrast, the SIV of the sooty mangabey and the second human AIDS virus, HIV-2, are virtually identical, proving fairly conclusively that HIV-2 is actually sooty mangabey SIV that has transferred (by whichever route) to humans.
So, although some sort of chimpanzee SIV is almost certainly the direct ancestor of HIV-1(M), it would seem that the immediate precursor of the human virus has not yet been identified. As the Gagneux et al. article cited above comments: “it seems reasonable to speculate that a chimpanzee population or populations may exist which both harbour the putative HIV-1 ancestor, and which have remained reproductively isolated from other chimpanzee populations over the [relevant] timescale”.
In addition, see point (3), below.
2) Worobey’s group has assessed chimps from three sites close to Kisangani. But the chimps sacrificed during the polio vaccine research at Lindi camp were collected from a huge area of the Belgian Congo rain forest, extending across some 300,000 square miles. Chimps were collected from as far east as Mambasa (over 300 miles east of Kisangani), as far north as Zapai (about 500 miles north, near the border with the Central African Republic), and as far west as Mbandaka territory, over 600 miles to the west.
In short, although Worobey et al.’s new research is helpful, the chimp groups the team has sampled are far from being representative of the chimpanzees that were used for the polio vaccine research at Lindi camp. Two of the aforementioned places are especially interesting. In 1961, a paper which featured some of the Lindi researchers reported on the blood components of 175 of the Lindi chimps, and concluded that the samples from the Mambasa chimps were so unusual that these chimps should be treated as a special group, which might, they surmised, be linked to other chimpanzee subspecies to the west. [Annales de l’Institut Pasteur; 1961; 101; 82-95.] According to this analysis, therefore, there could be genetic links between the Pan troglodytes schweinfurthii chimps from Mambasa, and the Pan troglodytes troglodytes chimps from Cameroon and Gabon, about a thousand miles to the west. The evidence that Lindi camp held at least one chimp from Mbandaka is also interesting, for the territory of Mbandaka lies on the opposite bank of the River Congo to the range of both Pan troglodytes schweinfurthii and Pan troglodytes troglodytes. If the Mbandaka chimp was from the latter subspecies, it could readily have infected schweinfurthii chimps at the camp with the variant of SIV which Worobey and Hahn insist is the only true ancestor to HIV-1.
This is because chimps at Lindi were routinely co-caged and group-caged (sometimes ten at a time), and because the Mbandaka chimp is known to have survived at the camp for the unusually long time of two years. There would thus have been ample opportunity for cross-infection between different animals.
A journalist who worked in Stanleyville throughout the 1950s, and who was a frequent visitor to the chimp camp, has recently told me that chimpanzees from the western end of the Belgian Congo/DRC (ie troglodytes chimps) were frequently brought up-river on the steamers, and that some of them may well have been sold to the Lindi scientists.
3) However, the most important reason why Worobey et al.’s research does not refute the OPV/AIDS theory is that HIV-1 Group M may well have come into being not through gradual mutation (during adaptation of a chimp virus to a new species, Homo sapiens), but through a different method entirely.
It is increasingly clear that HIV-1(M) may have evolved as a result of recombination between two or more different chimpanzee SIVs, as might happen in a tissue culture (for instance a polio vaccine culture) that had been prepared from different SIV-infected chimpanzees.
There is evidence that chimpanzee serum was used as a nutrient medium for at least some of the chimpanzee cultures prepared in Stanleyville, which greatly increases the likelihood that there was pooling of materials, which would have facilitated viral recombination. (SIV recombination could also, of course, have occurred in vivo, among chimps that were caged together.)
The work of Mikkel Schierup demonstrates that recombination events may well have occurred at the very beginning of HIV-1, events that would be undetectable by present-day phylogenetic analysis. [“Recombination of phylogentic analysis of HIV-1”, Atti dei Convegni Lincei; 2003; 187; 231-248.]
Recent papers by authors such as Schierup, Wain-Hobson and Andreas Meyerhans, have highlighted the fact that SIVs and HIVs are extraordinarily prone to recombination (which might be defined as the exchange of slabs of genetic material originating from two different viruses, when they meet in an individual cell). [Preceding Schierup reference, plus: Journal of General Virology; 2003; 84; 885-895. Swiss Medical Weekly; 2003; 133; 451-454.]
Like HIV-1, both schweinfurthii SIV and troglodytes SIV carry the crucial vpu gene, which suggests that if two or more samples of either virus recombined in the past (either in vivo, or in vitro – in tissue culture), they could have produced an ancestral HIV-1(M) virus. In June 2003, I sent an e-mail to Beatrice Hahn in which I acknowledged our past differences, and then tentatively proposed the foregoing idea (about SIVs recombining in an OPV tissue culture).
Her response was as follows: “Ed, you are in no position to make any scientifically sound predictions concerning the phylogenetic or biological consequences of ‘in vitro recombination in an OPV substrate’. I am not going to discuss this, because it is going nowhere. You are obviously entitled to an opinion and to express this opinion in any way you want, but don’t kid yourself (or others) into believing that you have the necessary scientific background to make a judgement call on this matter.” However, I have since then floated this idea with a number of geneticists and virologists, who agree that there is no scientific reason why recombination between two schweinfurthii SIVs could not have been the source of HIV-1 Group M, the AIDS pandemic virus.
In other words, it seems that HIV-1(M) could have come into being during the procedures at Lindi camp and/or Stanleyville, irrespective of whether any Pan troglodytes troglodytes chimpanzee was ever present there.
All three arguments (but the last in particular) refute the claims by the Worobey group that their new sequence represents “clear-cut evidence” against the OPV theory, evidence which “should finally lay the OPV/AIDS theory to rest”.
The authors of the Nature article
The lead author of this paper is Michael Worobey, the young Canadian scientist who, with Jeff Joy, accompanied Bill Hamilton on his second expedition to the Congo in January 2000, to collect samples of faeces and urine from wild chimpanzees in the vicinity of Kisangani. An indirect and tragic result of this expedition was Hamilton’s collapse into a coma in late January, and his untimely death on March 7, 2000. Worobey has long declared himself to be “unconvinced but open-minded” about the OPV/AIDS theory, but many of those who have had dealings with him realised some time ago that he was actually a fairly frank supporter of Beatrice Hahn, and of geneticists such as Paul Sharp and Eddie Holmes, whose major work of the last decade depends on the OPV/AIDS theory being disproved.
At least one person who knew Worobey before his 2000 trip to the DRC believes that he was already firmly opposed to the OPV theory even before he set off on that expedition.
Worobey was recently (at a relatively young age) appointed head of his own evolutionary biology laboratory in Tucson, Arizona. In addition, it seems that he may be being “groomed for stardom” by members of the anti-OPV lobby. In the last eighteen months, his name and work have been conspicuously promoted by Nature, the magazine which, over a period of nearly two decades, has declined to publish any paper expounding the OPV theory, while consistently (and falsely) declaring that the theory has been disproved. Professor Robin Weiss, one of the UK’s leading retrovirologists, is apparently highly influential in the way that the subject of AIDS is reported in Nature, and he has spearheaded the campaign to “destroy an ugly theory”. Unfortunately, Weiss’s own articles and commentaries on the subject feature systematic inaccuracies, and it is now clear that he is a deeply biased commentator, despite his frequent claims to the contrary.
Because of this bias, it was unfortunate that Professor Weiss was the man who gave the summing-up speech at the end of the September 2000 Royal Society conference on the “Origins of HIV and the AIDS epidemic”. [Philosophical Transactions of the Royal Society (London), Series B; 2001; 356; 781-977.] This meeting had originally been proposed by Bill Hamilton, as had another similar meeting on “Origin of HIV and Emerging Persistent Viruses”, which was staged at the Accademia Nazionale dei Lincei, in Rome, in September 2001. [Atti dei Convegni Lincei; 2003; 187; 1-314.] In general, this meeting was much more balanced than its predecessor in London. However, the supposedly neutral final speaker and summariser was, once again, Robin Weiss. For the first time ever, I was moved to walk out on a meeting, shouting “This speech is a disgrace!”
Apart from Weiss, the major speaker at Lincei on behalf of the pro-bushmeat anti-OPV lobby was Paul Sharp, from the University of Nottingham. Professor Sharp gave pretty much his usual speech, in which, on the basis of phylogenetic analysis and phylogenetic dating, he claimed that HIV-1 could be traced back to the 1930s or 1940s. However, his arguments were neatly demolished by Mikkel Schierup from the University of Aarhus in Denmark, who demonstrated that phylogenetic dating in simply an inappropriate tool to use for viruses such as SIV and HIV, which evolve mainly through recombination.
For some reason, Professor Sharp’s speech never appeared in the final published proceedings of the Lincei conference. Neither did his comments made in the discussion session, in which he claimed that Michael Worobey had changed his mind about the impact of recombination on phylogenetic dating, after spending time working with another member of the anti-OPV lobby, geneticist Bette Korber. This was the first public indication that Worobey was now a member of the Hahn/Sharp/Korber camp, and shortly after this it became known that he had been appointed head of his own lab in Tucson.
Those who are familiar with Beatrice Hahn and her approach to science will not be surprised by the tone of her reply to my June 2003 e-mail. In many ways she is not dissimilar to her former boss, Robert Gallo. She is a hard and determined worker, certainly. But all too often her science seems to be based as much on assertion as on careful observation and sound reasoning. Furthermore, many of her colleagues seem intimidated by her, just as many were by Gallo.
Her recent work (and that of associates such as Sharp and Worobey) is almost exclusively based on a dogged insistence with respect to the following points: (a) that the bushmeat theory of origin is right (and the OPV theory wrong); (b) that HIV-1 is derived only from the SIV of the Pan troglodytes troglodytes subspecies of chimpanzee, and (c) that phylogenetic dating proves that HIV-1 existed back in the 1930s and 1940s, before the OPV trials in Africa. The first two claims are not supported by any facts, merely by assertion and repetition. The third claim is increasingly widely recognised as being false, for phylogenetic dating only measures the rate of point substitution of SIVs and HIVs, whereas most of the evolution of those lentiviruses occurs through recombination. Recombination cannot be measured by phylogenetic methods, all of which are based on the premise that there is a constant “molecular clock” which governs evolution. To attempt to date HIV-1 through phylogeny is like trying to measure wind speed with a theodolyte.
[A fuller discussion of the scientific arguments relating to the origins of AIDS features in my February 2004 article “The latest scientific evidence strongly supports the OPV theory”.]
Conclusion
Some people wonder why eminent scientists like Robin Weiss, Paul Sharp and Beatrice Hahn (and apparently up-and-coming scientists, like Michael Worobey) should be so virulently opposed to the OPV theory.
One simple reason is that they believe that it is championed by someone whom they like to characterise as a “journalist” (ie myself) rather than by a “proper scientist”. This makes it even more difficult for them to accept that such a theory might have merit. On a more crucial level, however, it should be noted that the very basis of their recent scientific endeavours, together with their public image, their credibility (and, of course, their research funding) are all inextricably linked to their version of events being declared right, and the OPV/AIDS theory being publicly refuted.
The debate about the origins of AIDS has never been solely a scientific debate, for there is now a multitude of examples in which the anti-OPV scientists have been caught out cheating, whether by making inaccurate statements, by ignoring or misrepresenting counter-arguments, by lying (or trying to persuade others to lie on their behalf), or, as here, by misrepresenting the significance of their data. More than ever it has become a political debate, a battle for hearts and minds, and a battle for control of the media.
What this latest communication in Nature reveals, once again, is a medical establishment (again spearheaded by the same scientists, and the same scientific journals) that is prepared to go to almost any ends to try to dispose of this uncomfortable theory.
The arguments put forward to refute the theory almost all depend on assertion and insistence, not on sound scientific method. Truth and accuracy have been jettisoned, because the scientists in question are determined at all costs to achieve a preordained outcome.
Jon Cohen, the principal AIDS reporter for Science magazine, is one of those who is deeply opposed to the OPV theory. In 2001 – in homage to the Munchkins – he reported in Science that “the theory is not only merely dead, it’s really most sincerely dead”. Although this comment was clearly tongue-in-cheek, the real agenda was revealed by the title of his commentary: “Disputed AIDS Theory Dies its Final Death”.
Now, with this latest misleading paper in Nature, Worobey would apparently have us believe that it’s been laid to rest all over again.
Haven’t these scientists and science reporters noticed that something is wrong here – that this body they keep consigning to the earth keeps resurrecting itself? Doesn’t this suggest to them that maybe, just maybe, “the reports of [its] death were an exaggeration” – to paraphrase the equally inappropriately interred Mark Twain?
Just as disgraceful as these premature death notices are the repeated implications by the pro-bushmeat lobby that discussion of the OPV theory is threatening the global campaign to eradicate poliomyelitis. I have addressed this subject several times, and have demonstrated that modern fears about the safety of polio vaccines are part of a long history of concern in the developing world that vaccines may be contaminated with such items as “family planning drugs”, “cancer”, or “AIDS”. Past claims by Hilary Koprowski, the developer of CHAT vaccine, that polio vaccine protests in Kenya were linked to The River and the OPV theory have been demonstrated to be false, and based on fabricated references. Equally, the recent anti-vaccine protests in northern Nigeria are related to the ongoing religio-political conflicts in that region, rather than to the OPV theory. [For further discussion, see my article “As far as is known, modern polio vaccines are safe”.]
For five years now, ever since The River was published, those who oppose the OPV theory (whether for reasons of self-interest, or because they fear law-suits, or because they fear that the hegemony of vaccination as a public health measure could be threatened) have sat out in the fields, crying wolf to all who would listen.
It is a dangerous game to play, for the real wolf is closer than they think – and is getting restless. In the months to come, “The Origins of AIDS” documentary, plus further scientific and historical evidence which is yet to be published, will reveal to a wide population not only that the OPV theory could have happened, but that it is almost certainly the way in which the AIDS pandemic got started.