New material from Edward Hooper, to coincide with publication of the Royal Society's volume on "The Origins of HIV and the AIDS Epidemic" in summer 2001.

[Since some will ask... I think Hooper is probably correct about the formal prematurity of his theory's demise, in that it has not been disproven; I think he is probably wrong about OPV as a/the source of HIV; I think the theory is so plausible that for all practical purposes (learning from the past and all that) the scientific and medical communities should regard it as if it were correct while noting in small print that it's probably not. That's my personal call, as of September 2001 at least ;-)


The proceedings of last September's Royal Society meeting on the origins of AIDS are to be published on line on June 19, 2001, and a week later as a printed volume (Philosophical Transactions of the Royal Society, London, B; 2001; 376; 778-977).

As the author of "The River", the publication of which, in September 1999, sparked the current (often heated) origins of AIDS debate, I would like to place some new material in the public domain.

When I returned from two months of research in Africa at the end of April this year, I was horrified to find that the major scientific journals, "Nature" and "Science", which had just published a series of short communications on the origins debate, had accompanied these articles with commentaries that trumpeted the view that the oral polio vaccine (OPV) theory of origin was now disproved.

"Some beautiful facts have destroyed an ugly theory" was Robin Weiss's sound-bite in "Nature", while the "Science" article by Jon Cohen was headed "Disputed AIDS theory dies its final death".

As is demonstrated in the first of the accompanying pieces, these statements are, quite simply, incorrect.

The publication of the Royal Society volume provides a belated opportunity for a more balanced account of the debate to be heard.

The Royal Society "origins" meeting, held in September 2000, was the brainchild of the most prominent scientific supporter of the OPV theory, the evolutionary biologist Bill Hamilton. Following his tragic death in March 2000, the organisation of the meeting was handled by his two co-organisers, Robin Weiss and Simon Wain-Hobson, and its final format leant quite heavily towards the view of origin more favoured by the scientific establishment - the "cut hunter" or "natural transfer" theory.

None the less, the published proceedings of the Royal Society conference, which in many cases contain updated contributions from the speakers, represent the most comprehensive attempt, since the publication of "The River", to present all sides of the argument.

It is noteworthy that in his concluding remarks Robin Weiss is less outspoken than in his "Nature" commentary, even if he does conclude that "the OPV theory is less tenable now than one year earlier".

However, as explained in my own contribution, entitled "Experimental polio vaccines and AIDS", and in the articles which follow, there are flaws and discrepancies in all of the major arguments which have been proposed in opposition to the OPV theory. To date, no theory has been proven or disproven.

The Royal Society volume also includes three pieces written by doctors Plotkin and Koprowski, who developed CHAT vaccine back in the 50s.

These pieces contain many provable errors. I have only now had the chance to read them, and will be responding in due course.

However, I have included below my responses to the press releases made by the two doctors at the Royal Society conference, which contained a surprisingly large number of inaccurate assertions, and misinterpretations of what I had written in "The River". Sadly, many of these erroneous claims were reproduced in newspaper coverage of the conference.

In the four pieces which follow, apart from my position paper and response to Plotkin and Koprowski, I also include a backgrounder on the debate, and the text of the unpublished letter which I submitted to "Nature" after its publication of Robin Weiss's article.

Edward Hooper June 18th, 2001.

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Lize King, the Royal Society's press officer, is reachable at lize.king@royalsoc.ac.uk.

Further material on the origins of AIDS debate can be found at Brian Martin's web-site.



NEW MATERIAL ON THE "ORIGINS OF HIV/AIDS DEBATE", INCLUDING A RIPOSTE TO DOCTORS PLOTKIN AND KOPROWSKI.

By EDWARD HOOPER, June 14th, 2001.

(1) Position paper (June 2001), to coincide with the publication of the proceedings of the Royal Society conference on "The Origins of HIV and the AIDS Epidemic" [Phil. Trans. R. Soc. Lond. B; 2001; 356; 778-977].

(2) Inaccuracies and errors in press statements released by doctors Stanley Plotkin and Hilary Koprowski at the Royal Society meeting on "The Origins of HIV and the AIDS Epidemic", on September 11, 2000.

(3) Backgrounder on the origins of AIDS debate, following the Royal Society conference of September 2000 and its aftermath.

(4) Letter to "Nature", submitted May 9, 2001, but not published.

----------------

(1) Position paper (June 2001), to coincide with the publication of the proceedings of the Royal Society conference on "The Origins of HIV and the AIDS Epidemic" [Phil. Trans. R. Soc. Lond. B; 2001; 356; 778-977].

KEY POINTS:

Professor Robin Weiss, one of the organisers of the Royal Society conference on the origins of HIV and AIDS, recently declared the oral polio vaccine (OPV) theory of origin dead. "Some beautiful facts have destroyed an ugly theory", he wrote.

He is wrong. Not one relevant fact (beautiful or otherwise) has been produced to refute the OPV theory. The conference proceedings contain a wide range of alternative hypotheses and arguments, but each has its own flaws or limitations. The debate is still far from settled.

This is only underlined by Dr Plotkin's two papers, which contain numerous allegations that I have misquoted or misrepresented witnesses. However, in every such instance, I stand by what I have written. The persons concerned were quoted accurately, fairly and in context - and I have the tape recordings to prove it. It is for others to decide why some interviewees modified their statements when approached by Dr Plotkin and his team.

TEXT:

There has been a disturbing tendency on the part of many of the scientists involved in the ćorigins of HIV and AIDS" debate, including Professor Robin Weiss, one of the surviving organisers of the Royal Society meeting on this topic, to prematurely pronounce the oral polio vaccine (OPV) theory of origin disproved or deceased.

This tendency, which first became apparent during the meeting itself, became rather more apparent during the recent burst of publicity orchestrated by those twin pillars of the scientific establishment, "Nature" and "Science".

In late April, 2001, Professor Weiss announced in "Nature" that "some beautiful facts have destroyed an ugly theory". In "Science", meanwhile, journalist and AIDS specialist Jon Cohen paraphrased the Munchkin coroner in "The Wizard of Oz", concluding "the theory is not only merely dead, it's really most sincerely dead".

These claims, quite simply, are incorrect. Not one single relevant fact (beautiful or otherwise) has been produced to refute the OPV theory. And wishing someone (or, in this case, something) dead does not make it so.

Let us look a little more closely at the "facts" on which Weiss and Cohen base their arguments. A number of selected samples of American-made CHAT oral polio vaccine from the 50s and 60s have been released for testing, and found not to contain HIV, SIV or chimpanzee DNA. However, as I pointed out repeatedly at the Royal Society conference, many of the one million doses of CHAT which were fed in the Belgian territories of central Africa during the 1957-1960 period were made in Belgium, not the USA. Even more importantly, there is growing historical evidence that other batches of CHAT were produced locally in Africa itself.

It now becomes apparent that the CHAT pool numbers (such as 13 and 10A-11) are irrelevant, because different batches of each pool were made in different laboratories. (Unfortunately, Professor Weiss confuses the terms "pool" and "batch" in his "Nature" commentary.) It is the questions about where these batches of CHAT were made, and where they were fed, that are crucial. So far only samples of American-made vaccine have been tested ö and, despite claims to the contrary, there is no evidence to suggest that any of the recently tested samples were prepared for use in Africa.

The vaccine-makers claim that the CHAT pool 13 fed in the Congolese capital, Leopoldville, was made in the USA. However, these claims are undermined by the memory of Professor Henry Gelfand, who hand-delivered the vaccine from Brussels to Leopoldville, and who told me he was "99.9% certain" that it was made in Belgium. And they are further, crucially, undermined by the testimony of the late Dr Gaston Ninane, who was based at the medical laboratory in Stanleyville in the late 1950s, and who helped conduct many of the CHAT vaccinations in Africa. In the course of several interviews, Dr Ninane repeatedly told me that because of the difficulty of keeping live polio vaccine sufficiently cool during the long journey from the US to the Congo, only the very earliest CHAT vaccine batches fed in Africa came from the United States.

Much as I welcome the fact that any CHAT samples have been released (even after seven years of delay), the tests conducted to date do not prove, or even suggest, that the CHAT vaccine fed in Africa was HIV-free. The tests, quite simply, have been conducted on the wrong samples. The extravagant claims now being made for the testing suggest that the main purpose of the exercise was to convince the world that CHAT vaccine has been "exonerated". The testing, in short, was essentially a public relations exercise.

Secondly, contributors like doctors Sharp, Korber and Holmes propose that the Most Recent Common Ancestor of the AIDS pandemic (HIV-1 Group M) viruses seen today existed in or around 1931 (nearly 30 years before the polio vaccine trials), and that the various Group M subtypes existed first in humans, not chimps. This, they claim, "disproves" the OPV theory, or renders it "untenable". The data produced by these geneticists are useful, but I am surprised by the extrapolations they make from them. It is important to bear in mind that their work is theoretical, not empirical. In reality, the dating work is supported by just two partial sequences from before 1980, one of which (the small fragment of ZR59, allegedly originating from 1959) comes from a serum sample of uncertain provenance. Furthermore, phylogenetic analysis such as this does not make proper allowance for the possibility of recombination, one of the two ways in which lentiviruses like HIV evolve. A growing number of geneticists believe that if recombination occurred at or near the beginning of HIV-1 Group M (as might have happened, for instance, in a polio vaccine tissue culture), then it would both be impossible to detect by modern methods, and would invalidate attempts to date the Group M family tree. The phylogenetic work by Sharp, Korber and Holmes can be used to advance a hypothesis about the age of HIV-1 Group M, but it cannot prove a hypothesis like "cut hunter/natural transfer", or disprove a hypothesis like "OPV/AIDS".

The other alleged disproofs of the OPV theory, such as Professor Hahn's insistence that the ancestor of Group M comes only from chimpanzees from west central Africa (not those from the former Belgian Congo), or Professor Beale's assertion that a simian immunodeficiency virus from an infected chimpanzee could not survive through to a polio vaccine made from that animal's kidneys, are also unproven hypotheses. In the first case, the available data is inadequate to make such a claim; in the second, nobody has yet done the proper experiments.

Similarly, the contributions by doctors Plotkin and Koprowski (including the additional article which Plotkin has been allowed to include in the published proceedings, entitled "Postscript relating to new allegations made by Edward Hooper") are based largely on assertion, and contain many provable inaccuracies. [See accompanying article.] Indeed, Dr Plotkin in particular gives the unfortunate impression that he is trying to discredit the proponent of the OPV theory as much as the theory itself. Of special note are his several claims that persons quoted by me in "The River", or in my presentation to the Royal Society, either did not say what I claim they said, or were misrepresented. However, in every instance I stand by what I have written. The persons in question were quoted accurately, and in context - and I have the tape recordings to prove it. It is for others to decide why some interviewees modified their testimonies when approached by Dr Plotkin and his colleagues.

Against these various alleged disproofs must be set the evidence for the OPV theory. Central to this evidence is the finding that over 84% of the earliest examples of HIV-1 Group M in the whole of Africa (and therefore the world), and 70% of the earliest African instances of Group M-related AIDS, come from the same towns and villages where CHAT vaccine was fed in 1957-60. Despite the various claims that have been made, supporters of the "cut hunter/natural transfer" theory have not yet managed to propose a persuasive alternative explanation for the striking distribution of these first recorded examples of AIDS pandemic virus and disease.

In addition, there is a growing body of historical and scientific evidence to support the OPV theory of origin, most especially new evidence about the vast numbers of chimps which were sacrificed (and had their organs removed) by the scientists who were developing and testing CHAT, and about CHAT vaccine being made locally in the then Belgian colonial territories of central Africa.

To me, the most striking thing about this debate thus far is the number of scientists who claim to have disproved OPV, but whose evidence, when examined, is found to rely heavily on conjecture and "plain personal prejudice". This is regrettable, even if it perhaps partly derives from an understandable desire to protect the good name of vaccination.

An experimental OPV may have sparked the AIDS pandemic, or it may not have, but nobody is yet in a position to pronounce. What we have seen, however, is an unsettling eagerness by many scientists to persuade people - at all costs - that the debate is over. This suggests that any alleged "disproofs" which may emerge in future should be viewed with a healthy degree of scepticism ö unless the evidence presented is absolutely watertight.

Professor Weiss and Mr Cohen like to paraphrase famous lines, so let me also try my hand, using Shakespeare and Mark Twain as models. The gentlemen do protest too much, methinks. Reports of the theory's death have been greatly exaggerated.

POSTSCRIPT:

The above quotation about "plain personal prejudice" comes from Professor Robin Weiss's "Concluding Remarks" delivered to the Royal Society meeting last September. This welcome admission that his views might be prejudiced came at the end of a speech which had contained some vitriolic assertions about the OPV theory.

In marked contrast to his comments that day, and to his claims in "Nature" in April this year that the OPV theory had been "destroyed", is the far more balanced and conciliatory summing-up which he has now contributed to the published proceedings of the Royal Society meeting. I welcome Robin Weiss's reassessment of his position, in particular his acknowledgement that the OPV theory has not been refuted - and that this is still an ongoing debate, to which further salient contributions are likely to be made in the future.


(2) Inaccuracies and errors in press statements released by doctors Stanley Plotkin and Hilary Koprowski at the Royal Society meeting on "The Origins of HIV and the AIDS Epidemic", on September 11, 2000.

INTRODUCTION:

Like many other speakers at the Royal Society conference on "The Origins of HIV and the AIDS Epidemic" (myself included) doctors Plotkin and Koprowski later revised their oral presentations for the published proceedings, which are about to appear as "Philosophical Transactions of the Royal Society, London, B; 2001; Volume 356".

I shall be responding to their published articles (which contain many errors) in due course.

In the interim, I have decided to respond to the press statements released by the two doctors while at the conference.

MAIN TEXT:

On September 11, 2000, at the Royal Society conference on "The Origins of HIV and the AIDS Epidemic", Dr Stanley Plotkin released two documents for the press - a formal statement, and a backgrounder.

In these two documents, Dr Plotkin claimed that evidence from himself and others had disproved the oral polio vaccine (OPV) theory of origin, which proposes that the AIDS pandemic was sparked by the 1950s African trials of CHAT oral polio vaccine (developed by Dr Plotkin, Dr Hilary Koprowski and others at the Wistar Institute in Philadelphia).

However, it is my belief that both of Dr Plotkin's press releases were characterised by a high degree of inaccuracy and error, which has unfortunately been repeated in much of the subsequent reporting of the conference.

There were similar inaccuracies in Dr Hilary Koprowski's press release.

The following point-by-point analysis should help place these public statements in perspective.

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(A) "Press Conference Statement by Stanley Plotkin M.D."

DR PLOTKIN'S CLAIM: "We now know conclusively that the events postulated by Mr Hooper did not happen for three reasons".

RESPONSE: This key statement by Dr Plotkin is incorrect, because none of the "three reasons" he provides constitute anything approaching proof [see below].

PLOTKIN'S CLAIM: "Chimpanzee tissues were not used to make CHAT. Sixteen scientists with first hand knowledge say no, supported by documents of the time".

RESPONSE: This statement is doubly inaccurate. Firstly, the sixteen scientists in question signed forms stating that they "never saw/heard of chimpanzee cells" being used. They did not state that "chimpanzee tissues were not used to make CHAT", mainly because nobody (whether at the Wistar Institute, in Belgium or in Africa) could state such a thing with certainty. With regard to the Wistar, it is significant to note that the Institute did not have a monkey house. This means that for the last three years of the 1950s kidneys were arriving there already excised, and nobody has provided any physical or documentary evidence about their provenance. I am reliably informed (by a veterinary pathologist) that during the fifties it would have been impossible to distinguish between the kidneys of a macaque and those of a young chimpanzee. As for Africa, a former worker at the Bujumbura medical laboratory in the fifties has given detailed testimony about kidneys being removed from chimpanzees which were caged behind the lab, kidneys which were then sent both to Belgium, and to another lab in Butare, Rwanda. Although there is no evidence that they were used in Butare to produce CHAT vaccine, we know that other human vaccines were being prepared at the Butare lab at that very time, and that Dr Koprowski brought samples of CHAT and Fox (another of his OPVs) out to Bujumbura in February 1957. The second assertion, that this claim is "supported by documents of the time" is quite simply incorrect, for not one single document from the 1950s (the period in question) has been produced which describes the species of cells in which CHAT vaccine was made. Furthermore, even those articles which Dr Plotkin cites from the 1960s are ambiguous on this issue.

PLOTKIN'S CLAIM: "The logistical problems of getting chimp tissues from the Congo to the US or Europe means that many people would have been involved, and it is inconceivable that no one would remember it."

RESPONSE: Even if this statement is correct (which is questionable), its overall implication is misleading. People do remember that chimp kidneys were being dispatched overseas, but they are not Dr Plotkin's witnesses. We know that many shipments of biomedical materials were made from the Congo to both the U.S. and Europe during the key 1956-1959 period, as acknowledged by several of the doctors involved, including some of the witnesses cited by Dr Plotkin. The question is what was in those shipments. In fact, two of these witnesses (the head of the Stanleyville veterinary lab from 1956 to 1959, and the widow of Tom Norton, the Wistar lab chief) have testified that as far as they know, some of these boxes contained chimp organs, including kidneys. Furthermore, Ghislain Courtois, who was in overall control of Lindi chimpanzee camp during this period, told a conference on the use of monkey cell cultures in December 1967 "More than ten years ago we sent kidneys from the Congo to Europe and they were quite satisfactory" (for making tissue culture). There is no record of any kidneys other than chimp kidneys being available to Courtois in 1956 or 1957. Another important detail came from the late Dr Gaston Ninane, who worked at the Stanleyville medical lab and at Lindi camp, who told me that on ten or twenty occasions blood samples from CHAT vaccinees, packed around with ice, were dispatched on planes that travelled back to Europe and North America, stopping off en route at a US Air Force base in North Africa. If (as seems likely) the shipments of chimpanzee kidneys were dispatched by the same route (and we have documentary proof that at least six shipments of chimp kidneys were sent from Stanleyville to Philadelphia in 1958/59), the "chain of custody" could have involved as few as three people (one at each end, and the courier), none of whom would necessarily still be alive today.

PLOTKIN'S CLAIM: "Even if chimp kidney had been used, the work of three laboratories tells us that HIV started spreading in about 1930, long before the CHAT vaccination in the Congo."

RESPONSE: Again, this statement is inaccurate, for it seeks to turn theory into fact. These three laboratories have hypothesised that "the most recent common ancestor" of HIV-1 existed in about 1930 (in other words, before the polio vaccine trials). This is theoretical work, based on certain assumptions. However, it is now becoming apparent that each of the three labs failed to properly allow for recombination, which is recognised as a major factor in retroviral evolution. In October 2000, shortly after the Royal Society meeting, two important papers were published which highlighted the fact that failing to take recombination into account can throw phylogenetic dating into disarray, and invalidate apparently convincing results. One of the authors has since proposed that if recombination occurs early on, when a new virus has just evolved, such an event is unlikely to be detectable through present-day genetic analysis. He further proposed that all it would require to produce the HIV-1 subtypes and variants seen today would be two chimpanzee SIVs which recombined (either in a person or in a tissue culture) in the distant past ö the 1950s, for instance. This is exactly what the OPV theory proposes ö that cells from at least two infected chimps were used to produce a culture in which CHAT vaccine was grown. There is a growing sense in genetics circles that the three labs quoted by Dr Plotkin may have over-stated their claims. Another geneticist studying this problem recently told me: "everything which has been done on dating [the AIDS pandemic] up to now is a dog's dinner".

PLOTKIN'S CLAIM: "As Dr Beale will show, even if SIV contaminated cells had been used, they would not have survived the preparation of polio vaccine".

RESPONSE: Again, Dr Plotkin refers to theoretical work as if it were fact. Nobody has yet carried out a proper experiment to simulate the making of 1950s polio vaccine in cells contaminated with chimpanzee SIV (the immediate ancestor to HIV-1). It is worth noting that in October 2000 a major article in the American Journal of Nephrology announced that the epithelial cells of the kidney (the same cells used to make polio vaccines in the 1950s) represent an unexpected and hitherto unrecognised site of HIV-1 infection.

PLOTKIN'S CLAIM: "Even if the vaccine had been contaminated with SIV, the first cases of AIDS are not associated with CHAT vaccination. [T]he epidemiology of AIDS is consistent with sexual transmission but does not agree with the polio hypothesis."

RESPONSE: This is quite simply untrue. According to my latest data, 70% of the earliest recorded cases of AIDS in Africa (30 cases identified retrospectively through 1980) come from the same towns and villages where CHAT vaccine was fed between 1957 and 1960. And nearly 85% of the earliest recorded instances of HIV-1 infection in Africa (again through 1980) come from the same towns and villages where CHAT vaccine was fed between 1957 and 1960. The sexual transmission of HIV-1 (which is not in doubt) completely fails to explain why the first cases of HIV-1 infection and AIDS occurred almost exclusively in areas where CHAT vaccine had been administered.

PLOTKIN'S CLAIM: "Mr Hooper made significant mistakes in reporting where CHAT vaccination was done."

RESPONSE: This, to say the least, is grievous exaggeration. I have spent months assembling information about where CHAT vaccination occurred in Africa - information which doctors Plotkin and Koprowski were largely unable or unwilling to provide. In one single instance, Dr Plotkin may be correct, in that I have been unable to confirm whether the proposed CHAT trial at Lubudi, in the south of the Congo, actually took place. (However, such a trial is mentioned as forthcoming in a newspaper report of a 1959 press conference attended by Dr Plotkin, and a key contemporary witness from the area has stated that it "probably" did occur.) Because it has not been confirmed, I have now removed the Lubudi trial from my analysis. However, Lubudi has no effect on the percentage associations reported above between CHAT and AIDS (based on 27 other CHAT trials in Africa), or between CHAT and HIV-1. Dr Plotkin's references to "significant mistakes", and his claims that Lubudi is "key" to my argument (made elsewhere), are fundamentally inaccurate.

--------------------------

(B) "Backgrounder for press from Stanley Plotkin M.D."

[Here, I shall address only those claims which have not been dealt with above.]

PLOTKIN'S CLAIM: "The virology laboratory at Kisangani [Stanleyville] was primitive and incapable of producing vaccine in any cell culture, let alone chimpanzee."

RESPONSE: The fact that Dr Paul Osterrieth states that he produced baboon kidney tissue culture at Kisangani in 1958 after training at the CDC and the Wistar Institute in 1957 (a detail cited by Dr Plotkin) belies this claim, because any primate tissue culture is capable of producing "vaccine", if inoculated with a small sample of same (just as a small quantity of yogurt can be used to seed a new batch of yogurt in milk). Making polio vaccine was not an impossible, or even very difficult, process, even in Africa in the mid-fifties, as is indicated by the fact that from 1953 onwards, polioviruses were being grown in the kidneys of fifteen different African primates (including chimpanzees), and that live and killed polio vaccines were being produced in the cells of three of these species, at a small veterinary lab at Gabu, just 400 miles east of Stanleyville. In addition, human vaccines were also being produced during the fifties at two other labs in the Belgian colonies ö those at Butare (Rwanda) and Lubumbashi. There are no records of polio vaccines having been produced at either lab, but both had the potential of doing so, in that they possessed the necessary technical staff, equipment and materials.

PLOTKIN'S CLAIM: "Even if chimps had been used [to make polio vaccine], those housed in the Kisangani colony [Lindi] were almost all young, and unlikely to carry SIV since they weren't yet sexually active."

RESPONSE: This statement is based on a number of incorrect assumptions, as shown by the following observations. (a) Juvenile chimps can be infected with SIV. In fact, all of the first four chimpanzees found to be SIV-positive were juveniles, aged five or less, when they became infected. (b) Most African primate species become infected with SIV not through sexual activity, but through bites and scratches, which can occur at any age. [SOURCE FOR THIS? -Jim Moore] (c) Roughly 80 pygmy chimps (or bonobos) and 330 common chimps were present at Lindi between June 1956 and the start of February 1958 (during which period only polio research was conducted at the camp). Not only were individual bonobos and common chimps routinely caged together, but there was one large cage where up to ten young chimps could play at a time. The spread of SIV from chimp to chimp at Lindi camp may therefore have been quite extensive.

PLOTKIN'S CLAIM: "Actual experiments carried out in several laboratories showed that even if kidney cells had been contaminated with SIV, the virus would not have survived vaccine preparation."

RESPONSE: This is a significant exaggeration. No experiment has yet been conducted that faithfully simulates the making of polio vaccine, using 1950s methods, in cells contaminated with chimpanzee SIV. It cannot, therefore be "shown" that the SIV would not have survived through to the vaccine. Further research is needed. As for Dr Bealeās erudite and undoubtedly well-intentioned contribution to this debate, which concludes that the odds against SIV from kidneys surviving through to a final vaccine made therefrom would be several billion-to-one against, it has to be stressed that this is a theoretical calculation, based on how he believes any such vaccine would have been made.

PLOTKIN'S CLAIM: "Early cases of AIDS in the Congo were detected in cities, where sexual transmission was more likely, and where medical surveillance was better."

RESPONSE: This is a simplification. If we analyse the first 25 cases of AIDS in the Belgian colonies of Africa for which we can identify a place of domicile of the infectee, 16 came from cities, seven from small towns and two from rural areas.

PLOTKIN'S CLAIM: "Vaccination trials conducted in the United States and Europe with the same lots of vaccine did not result in AIDS."

RESPONSE: In interview, Doctor Plotkin admitted to me that the words "lot" and "pool" are not very precise terms with respect to vaccines; Koprowski's team was not alone in using both terms more or less interchangably. However, it is perhaps more relevant to speak in terms of "batches" of vaccine, each of which is produced at one place and at one time. There is documentary proof that a batch of CHAT pool (or lot) 13 was prepared at the Wistar for use in a small trial in Wyszkow, Poland. However, the large batch of CHAT pool 13 used in Leopoldville was, according to Henry Gelfand, the man who hand-carried it from Belgium to Africa, made at a lab just outside Brussels (probably the Rega Institute in Leuven). Similarly, different batches of CHAT pool 10A-11 (which was used in Africa on a large scale, and on a small scale in Europe and the U.S.) are known to have been made in different labs. It is therefore misleading to imply that because vaccine feedings conducted in Europe and the U.S. "did not result in AIDS", then the same must apply to the CHAT batches fed in Africa.

Additional note: In a letter published in "Nature" on October 26, 2000, doctors Plotkin and Koprowski stated: "as presented at the [Royal Society] meeting, only two batches of vaccine were used in the mass vaccinations conducted in the Congo before 1959, the date of the first confirmed HIV infection in a human". This is not only inaccurate, but it further clouds the issue, for the two doctors are now confusing three different terms: "batch", "pool" and "lot". In his presentation at the Royal Society conference, Dr Plotkin asserted that three different CHAT vaccine pools (8 or 9, 10A-11 and 13) were fed in the Congo in 1957 and 1958. (Each of these three pools could have consisted of any number of batches.) In addition, he revealed that vaccine was in short supply in 1958, and implied that, because of that shortage, Dr Koprowski (and/or others) sent vaccine (CHAT pool 10A-11) out to the Ruzizi Valley on at least three different occasions in February and March of that year. This implies that at least five batches of (presumably American-made) CHAT were fed in Africa in 1957 and 1958. But others, such as Dr Ninane and Dr Gelfand, are convinced that Belgian-made batches of CHAT were used in the Ruzizi valley and Leopoldville in 1958. This would mean that a minimum of seven different batches of CHAT were fed in the Congo (and Ruanda-Urundi) in 1957-8. It may have been many more than this if, as I believe, different experimental batches of CHAT were administered in different places during the early African field trials ö a proposition for which there is now some supporting evidence.

PLOTKIN'S CLAIM: "Several people quoted by Mr Hooper regarding transport of chimp kidneys deny they ever said what was attributed to them."

RESPONSE: In every instance of alleged inaccurate reporting cited by Dr Plotkin in his press statement or his speech (including, crucially, those involving doctors Bugyaki and Ninane), I have gone back to the original tapes and interview notes, and confirmed that what I have written in "The River" is correct. In other words, I have physical evidence to counter Dr Plotkin's claims. During two lengthy interviews in 1994 and 2000, Dr Louis Bugyaki, head of the Stanleyville veterinary laboratory during the fifties and a frequent visitor to Lindi chimpanzee camp, testified that chimp organs, including kidneys, had been sent to the USA at the request of Dr Koprowski, and that he had learnt this information from doctors Ninane and Osterrieth, both of whom worked both at Lindi and at the Stanleyville medical laboratory. On the second occasion he signed a written statement to this effect. However, at the conference we learnt from Dr Plotkinās speech that prior to the latter interview, Dr Bugyaki had already provided another written statement to members of the Plotkin team, which gave a different version of events, namely that he had no knowledge of chimp kidneys being sent to Belgium "or to other countries". These last four words were clearly in conflict with what he had twice told me. After the conference, therefore, one of my colleagues phoned Dr Bugyaki asking for clarification, and he reaffirmed that chimp kidneys had been sent from Lindi to the US in the fifties. This time, however, he added that he had heard about this not from doctors Ninane and Osterrieth, but from a sanitary agent, Jean Brakel, who had died in 1994. We are uncertain why Dr Bugyaki has recently modified his account of these events. As for the late doctor Ninane, one of his relatives told us that he was approached by three members of the Koprowski/Plotkin team during the final months of his life, when he was suffering from Parkinson's disease and Alzheimer's, and his denials that he ever made certain statements (which statements I have on tape) need to be viewed in that light. Another witness from the period who was approached repeatedly, and twice sent typed letters requiring only his signature, later told us that he could not sign statements which, as far as he knew, "were untrue". He described the approaches made to him as "a dishonourable proposition".

PLOTKIN'S CLAIM: "Although science can never prove a negative, I conclude from the above that the hypothesis of The River is highly improbable, and does not require further investigation."

RESPONSE: In the light of the above analysis of Dr Plotkin's press statements of September 11, 2000, I arrive at very different conclusions from him.

Dr Plotkin claims to be clarifying the issues raised in "The River", and showing that the OPV hypothesis has no basis in fact. In reality, many of his responses to "The River" are based on incorrect or misleading claims, or on misinterpretations of what I have written in the book. Far from clarifying the issues, he has confused them.

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(C) "Press Release by Hilary Koprowski, M.D."

DR KOPROWSKI'S CLAIM: "We have been left with the task of controlling damage done by 'The River', as a result of which people are questioning the vaccination of children; the Catholic church in Kenya has advised mothers not to take their children for polio vaccination as it was contaminated with HIV".

RESPONSE: When examined closely, this claim is revealed as highly questionable. The article in the Daily Nation of Kenya which Dr Koprowski cites in his speech is incorrectly referenced; no article about polio vaccines appeared on that date. However, a brief article was published one month earlier (in October 1999) which referred to "the Catholic church [in Nyeri district] calling for a boycott of the ongoing polio vaccination campaign", but which (in contrast to Koprowski's claim) gave no reason for the churchās action. A search back through the Nationās archives for the previous four years reveals that there have been seven other articles concerning rumours about polio vaccines, some of which referred to claims that they were laced with either contraceptives or HIV. However, all seven were dated before the first publication of "The River" in September 1999. The truth is that there is a long-standing history of rumours about vaccines, and in particular polio vaccines, in Kenya and elsewhere in Africa, and that these rumours are part and parcel of a religio-political debate that began long before my book was published, or indeed before the 1992 publication of Tom Curtisās article on the OPV theory. However, I also am doing my best to ensure that people are getting the right message. Wherever possible (for instance in interviews on BBC World Service or Africa-based radio stations), I have encouraged people to have their children vaccinated against polio, and stressed the fact that whereas I am questioning the safety of an experimental vaccine made in the 1950s, the polio vaccines of today are, as far as is known, entirely safe.

KOPROWSKI'S CLAIM: "The author approached his task from an intuitive model rather than the kind of deductive process that every scientist uses in developing a hypothesis after observing a phenomenon."

RESPONSE: Not for the first time, Dr Koprowski is claiming that I have searched for facts to fit a theory, rather than vice versa. However, this claim is untrue, as anyone who has read the full text of "The River" should know. The reason I find the OPV hypothesis persuasive is that it is based on some very powerful scientific and historical evidence which has grown, step by step, over the years, and contrary to Dr Koprowski's claims, I have attempted to test (or disprove) the hypothesis at every juncture. Whenever a new piece of information or data has emerged which seemed to support the OPV hypothesis, my first response has been to adopt the stance of devilās advocate ö and to see whether there was another possible interpretation. Also contrary to Koprowski's claims, I have been conscientious about including in the book as much relevant context as possible, including details which might run counter to the OPV theory. It is noticeable that much of the information which Dr Plotkin cites as evidence against the OPV theory is already documented in "The River", although he does not acknowledge this in his papers.

KOPROWSKI'S CLAIM: "Hooper conveniently overlooks the fact that Tom Norton and I were the first to take the vaccine"

RESPONSE: Dr Koprowski has frequently made claims along these lines, but the available records suggest that they may be incorrect. Although Dr Koprowski claimed to me in interview that he and Tom Norton had been the first to take his original oral polio vaccine, TN, the article about this trial in the American Journal of Hygiene states that the first vaccinee was in fact a six-year-old handicapped child, and that it was a year later that Tom Norton and Koprowski's then-boss, Herald Cox (not Koprowski himself) tested the vaccine on themselves. As for CHAT, the first human subjects to take this vaccine were, according to the literature, two infants born to female prisoners at Clinton State Farms, in New Jersey, U.S.A.

KOPROWSKI'S CLAIM: "The book is full of ad hominem attacks against me."

RESPONSE: In reality, the book contains a wide range of opinions and quotations, both positive and negative, from those who know Dr Koprowski from different walks of life.

KOPROWSKI'S CLAIM: "At the same time trials were conducted in the Congo, the vaccine was being given in New Jersey, Philadelphia, Switzerland and Poland. No one given that vaccine came down with HIV except for the Congolese. In other words, HIV was already present in Africa and had nothing to do with the polio trials."

RESPONSE: As detailed elsewhere, batches of CHAT intended for different trials were prepared in various laboratories, and in different substrates. The circumstantial evidence suggests that some experimental batches of CHAT may have been prepared in the kidneys of African primates, including chimpanzees. Whatever, there is no evidence that HIV-1 was present in Africa before February 1959 (when an HIV-1-infected blood sample was taken from Leopoldville, Congo). This is two years after CHAT vaccination began in that country.

KOPROWSKI'S CLAIM: "The publisher [of "The River"] received a letter asking for a chance to review the book for scientific accuracy. [T]he publisher was, perhaps, more interested in sensationalism than truth, and refused our request."

RESPONSE: Dr Koprowski's conjecture about the interests of the publisher are without foundation. In fact, both the American and British publishers took extraordinary care to guarantee the scientific (and general) accuracy of the book ö as did I myself ö and Dr Koprowski was courteously informed, before publication, that the publisher was confident about the accuracy of the text. The fact that, despite his protestations, Dr Koprowski has not managed to demonstrate a single significant inaccuracy in some 1,100 pages of text would seem to suggest that the publishers were thorough.

KOPROWSKI'S CLAIM: "The publication of this book and the totally erroneous arguments on which it is based has caused near hysteria, with Koprowski being called "the greatest murderer in history".

RESPONSE: To my knowledge, there has been no "near hysteria" caused by the book. And, apart from one misguided reader on Amazon.com, to whom I responded immediately, nobody apart from Dr Koprowski himself has used the totally inappropriate phrase "the greatest murderer in history".

Edward Hooper. December 5, 2000. Slightly updated and revised on June 14, 2001.

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3) Backgrounder on the origins of AIDS debate, following the Royal Society conference of September 2000 and its aftermath. (Originally prepared for World AIDS Day, December 1st, 2000, and slightly updated and revised on June 14th, 2001.)

It is now twenty years since the new condition of AIDS was first recognised and reported in a medical journal (by two Los Angeles doctors), and World AIDS Day 2000 sees a tragic situation. According to the World Health Organization, over 60 million people have been infected with HIV since the start of the pandemic, of whom nearly 25 million have died.

By the year 2003, the AIDS pandemic will represent the worst outbreak of infectious disease the world has ever seen.

I have now been investigating the emergence and origins of AIDS for the last eleven years, and I still firmly believe that the likeliest explanation for why AIDS emerged when and where it did is that there was a connection with the trials in central Africa, in the late 1950s, of an experimental oral polio vaccine (OPV) called CHAT. My book on the subject of origin, "The River", was published in September 1999, and has sparked a considerable - and often acrimonious - debate in the scientific community.

A central tenet of the OPV hypothesis is that some batches of CHAT were prepared in the kidney cells of chimpanzees, which are now known to carry the direct ancestor of the AIDS pandemic virus, HIV-1. (During the fifties, polio vaccines were routinely prepared in the kidney cells of primates, but the choice of primates was left up to the vaccine producer.) It is known that the scientists who developed and administered CHAT in central Africa - in what is now the Democratic Republic of Congo (DRC), Rwanda and Burundi - had a research camp in the Congo where approximately 250 chimpanzees were sacrificed between 1956 and 1958. For a number of reasons, not least the free availability of chimp kidneys to the CHAT researchers, I believe it likely that the kidneys of some of these chimps were used to make batches of CHAT vaccine. However, the vaccine's major developers, doctors Hilary Koprowski and Stanley Plotkin, deny this, saying they were using the chimps only to test the safety and efficacy of the vaccine.

However, according to my latest analysis, 70% of the earliest AIDS cases in Africa, through 1980, come from the same towns and villages in the DRC, Rwanda and Burundi where CHAT vaccine was fed, as do nearly 85% of Africa's earliest samples of HIV-1. These constitute the earliest examples in the world of pandemic HIV and AIDS.

In September 2000, in response to "The River", the Royal Society in London convened a two-day conference to examine "The Origins of HIV and the AIDS Pandemic". The meeting was attended by over 300 scientists and reporters. Although the main scientific supporter of the OPV theory, the renowned evolutionary biologist Bill Hamilton, had tragically died in March 2000, the two remaining conference organisers decided not to allow any additional main speakers on behalf of OPV. However, they did allocate additional main speaker berths both to the makers of CHAT vaccine, and to the proponents of the main opposing hypothesis of origin - the "cut hunter/natural transfer hypothesis".

The imbalance of speakers, and the frankly partisan closing speech by co-organiser Robin Weiss, gave many attendees the impression that the meeting had been convened with the intention of appearing to evaluate - and then dismissing - a hypothesis that the mainstream scientific community perceived as threatening.

Despite this, most scientific reports of the conference (even those which concluded that the OPV theory had been "weakened") pointed out that no evidence had been presented to prove, or disprove, either theory. Indeed, the conference report in "Science" ended by quoting social scientist Brian Martin, who predicted: "Whatever happens at this conference, this controversy will continue".

The main evidence offered against the OPV theory in London was that seven samples of CHAT vaccine from the U.S. had been tested in independent labs, and found not to contain any HIV, or its monkey relative (SIV), or the DNA of the common chimpanzee. However, as I pointed out at the conference, all seven samples of CHAT were from batches prepared for use in Europe and the U.S., rather than for use in Africa. It is the batches of vaccine fed in Africa that are under suspicion, and the tests done thus far therefore make no impact, either way, on the OPV hypothesis.

Shortly after the Royal Society meeting, there were three important new scientific developments which offered further support to the OPV theory.

First, American scientists revealed the remarkable information that the epithelium of the kidney is a hitherto unrecognised site of HIV-1 infection and replication. This is highly significant, because monkey kidney epithelium was the same medium used to prepare polio vaccines in the 1950s. [Journal of the American Society of Nephrology; 2000; 11; 2079-2087.]

Second, several hundred samples of HIV-1 from the Democratic Republic of Congo (the former Belgian Congo, where most of the CHAT trials were staged in the fifties) were analysed by Belgian, French and Congolese scientists. They concluded that there was a wider diversity of HIV-1 variants in the DRC than anywhere else, and suggested that the HIV-1 pandemic was indeed likely to have originated in that country. [Journal of Virology; 2000; 74; 10498-10507.]

Third, and perhaps most important, two Danish geneticists questioned the entire basis of the molecular dating of the HIV-1 epidemic by such as doctors Bette Korber and Paul Sharp. The latter scientists propose that the HIV-1 viruses seen today all stem back to a "most recent common ancestor" which existed in or around 1931, and many newspaper reports have focussed on their analysis, claiming (incorrectly) that it disproves the OPV hypothesis. In fact, the Danish geneticists propose that any molecular dating technique which fails to take into account recombination (a major method of retroviral evolution) is fundamentally flawed and unreliable. [Genetics; 2000; 156; 879-891. Nature Reviews Genetics; 2000; 1; 86. Molecular Biology and Evolution; 2000; 17; 1578-1579.]

Furthermore, one of the Danish researchers proposed that the HIV-1 variation seen today could have been produced by just two chimpanzee SIVs which recombined (for instance in a kidney cell culture back in the fifties - exactly what the OPV hypothesis proposes).

In the last 18 months, I and other researchers have obtained important eye-witness testimony that kidneys were being extracted from chimpanzees in two different research centres in central Africa in the late fifties - and that the scientists involved were the same men and women who were working with CHAT vaccine. The accuracy of these testimonials is disputed by doctors Koprowski and Plotkin. However, with these testimonials, and with the important new scientific developments detailed above, many scientists are acknowledging (albeit often privately) that the evidence in favour of OPV hypothesis is accumulating.

Edward Hooper. December 5th, 2000. Slightly revised on June 14, 2001.

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(4) Letter to "Nature", submitted May 9, 2001, but not published.

Dear Sir,

I have returned from two months' research in Africa to find four brief correspondences published in "Nature" [April 26, 2001] and "Science" which, it is claimed, finally pour cold water on the oral polio vaccine (OPV) theory of origin of AIDS. Robin Weiss's accompanying commentary concludes: "some beautiful facts have destroyed an ugly theory". The reality is rather different, for these communications provide no relevant "facts", new or otherwise, and no disproofs.

The paper by Eddie Holmes' team concludes that there was a single introduction of SIV from chimp to man, and that this occurred before the feeding of CHAT vaccine in central Africa in 1957-1960. Yet, like all phylogenetic reconstructions, this is entirely theoretical - a fact which he (and Weiss) glide over. In reality, given the gaps in the fossil record, and the very real possibility that recombination events may have occurred early in the history of HIV-1 Group M, there is no way of reliably determining whether there was a single or a multiple synchronised transfer, or dates for same. None the less, it is useful to have Holmes's confirmation that, as the OPV theory has long maintained, the Democratic Republic of Congo (former Belgian Congo) is "a likely location for the origin of HIV-1 Group M" - an awkward detail for those, like Beatrice Hahn, who hypothesise that the ancestral chimpanzee SIV comes only from the common chimps living in "west central Africa", in countries like Cameroon and Gabon.

The three papers which find no evidence of HIV, SIV or chimpanzee DNA in samples of CHAT pools 13 and 10A-11 from the fifties are also wrongly interpreted. As I wrote (perhaps not clearly enough) in "The River", and as I have repeatedly pointed out since, notably at the Royal Society "Origins" conference, what matters is not the testing of a specific pool number, but the testing of those CHAT batches which were prepared for use in Africa. (Weiss confuses this issue by wrongly describing CHAT 13 and 10A-11 as "batches", not "pools".) To date, such crucial tests have not been done. The tests conducted thus far show only that selected samples of CHAT vaccine fed in Europe and North America between 1958 and 1962 were SIV-free, and not made in chimp cells.

The inacurracies and exaggerations in the commentaries, news stories and press releases accompanying these four brief communications further confirm that on this most sensitive of issues there has been an interesting inversion, with the doyens of science seeking to "prove" their ideas through sound-bites, while ignoring or subtly misrepresenting much of the evidence documented in "The River". Professor Weiss invokes "beautiful facts" which do not exist. There are, however, new facts available about the OPV theory, and these will be published in due course.

Sincerely,

Edward Hooper, Bridgwater, Somerset.

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