Daily Telegraph (UK), 21 September 2000
A ROYAL Society meeting to discuss one of the biggest medical mysteries of all - the origins of Aids - climaxed last week in the most remarkable media brouhaha in the scientific academy since it was founded in 1660.
Under the lights of television cameras, before a forest of microphones, and witnessed by a sweltering press pack, one scientist denied he was a mass murderer; a journalist rejected the claim that his theory might put lives at risk; and hacks groaned when one of their number revived the laughable idea that Aids was born when germ warfare research went horribly wrong.
Last year, the mystery was supposedly solved by Edward Hooper, a former BBC journalist. In his vast tome, The River, he built a mountain of evidence that suggested Aids could be traced to the time when Prof Hilary Koprowski, and Dr Stanley Plotkin, developed an oral polio vaccine called CHAT.
Rivals: Dr Stanley Plotkin (right) and Edward Hooper
Hooper said batches of the vaccine may have been grown in chimp kidney cells in the Congo, the Wistar Institute, Philadelphia, and Belgium. That way, he contended, the vaccine was contaminated with chimp SIV, the ape version of HIV-1 (the most common Aids virus). The vaccine was administered to about a million people in what was then the Belgian Congo, Rwanda and Burundi between 1957 and 1960: thus, Aids was born.
Hooper cited various evidence: an apparently strong geographical association between early cases of Aids and where the vaccine was used; the fact that Prof Koprowski never stipulated which primates he used to grow his vaccine and that chimp kidney was an obvious choice; and that relevant records and vaccine samples have disappeared from labs and government archives.
The case made by his 10-year quest, which left him £40,000 in debt, was circumstantial. But it was enough to enlist a powerful ally in Prof Bill Hamilton, who helped to organise the Royal Society meeting. Unfortunately, while seeking direct evidence in the jungle, Hamilton succumbed to malaria and died earlier this year.
Last week, Hooper produced new evidence. He cited Louis Bugyaki, a vet from Stanleyville in the former Belgian Congo, now Kisangani, who said he had been told that chimp kidneys were harvested to be sent to America, possibly to make vaccine. Hooper declared "two smoking guns have emerged in the last two months". The vaccine developers had erected "a smokescreen" and had refuted only "minor details".
Sceptics remarked that, though intriguing, Hooper relied too much on hearsay and too little on hard fact: extraordinary claims need extraordinary evidence. "There is no gun, there is no bullet, there is no shooter, there is no motive," said Dr Plotkin. "There is only smoke created by Mr Hooper."
Dr Plotkin has prepared a counter-attack. Hooper claimed the first Aids cases coincided with CHAT vaccination campaigns. But Dr Plotkin says that the first cases clustered in towns, which is hardly surprising for a sexually transmitted disease: "The opportunity for sexual transmission and prostitution is higher."
Unusual cases that were highlighted by Hooper as being linked to the vaccine are disputed by Dr Plotkin. In one, he claims the vaccine was used on children, when Aids was recorded in an adult. Another was attributed to a vaccination trial actually done 500 miles away and Dr Plotkin says Hooper "misinterpreted the location of the town".
Hooper even suggested that the Aids epidemic was seeded in America when infants of New Jersey prisoners were vaccinated with CHAT. But Dr Plotkin says he approached the doctor who diagnosed the first Aids cases and found they were not the same as the vaccinated infants.
Dr Plotkin also pointed out that one lot of the CHAT vaccine tested in the Congo (lot 13) was also used in the United States and Poland: yet no Aids cases resulted. Plotkin's attack shifted to Hooper's claim that chimpanzees were used. A colony was indeed kept by Prof Koprowski for vaccine tests near Stanleyville. The reaction of the apes to CHAT was safety tested before trials on people.
The provincial laboratory there was "primitive" and incapable of making vaccine, said Dr Plotkin. Nor do records suggest it was used to cultivate chimpanzee cells. The head of the virology lab and two other witnesses told Dr Plotkin that they had never thought of doing it. He found 40-year-old papers that refer to the use of "monkey kidney" - not ape (chimpanzee) kidneys - when macaque cells, which do not carry SIV, were freely available. "Why would you use chimpanzee cells?" said Dr Plotkin.
He tried to find out, approaching 16 members of the team that made CHAT. All denied that chimpanzees were used, only macaques. Some seemed to retract what they had told Hooper. At the meeting, Abel Prinzie and Paul Osterrieth of the Stanleyville Lab, were vehement that they had been misrepresented in The River.
During the press conference, Hooper claimed some witnesses had been approached with pre-written statements, which they refused to sign. One doctor who had signed had been dying from both Alzheimer's and Parkinson's disease: he was too ill to know what he was endorsing. Dr Plotkin responded that the witness was recovering from a respiratory infection, was lucid, and had been fit enough to return home before he died. He invited Hooper to inspect the transcripts used to draw up the statements.
Psychologists have known for years that eyewitness evidence is fallible. Conspiracy theorists would also argue that the vaccine developers would, of course, deny all charges. Scientists, on the other hand, are not content to rely on anecdote. They want hard evidence. Earlier tests on CHAT had found no HIV or SIV. But Dr Plotkin, among others, insisted on new tests in the wake of The River. Seven 40-year-old samples of the vaccine, including lot 13, and controls were prepared and blinded. Independent labs in France, Germany and the States did the tests. One looked for Aids-related virus, a second assessed the animal tissue used to make the vaccine. A third did both tests.
Prof Claudio Basilico of New York University unveiled the results. There were no traces of SIV, HIV-1 or evidence that the vaccine was made from chimpanzee cells. There was nothing to back the vaccine hypothesis, he said. But he doubted this would satisfy Hooper: "It is somewhat difficult to disprove a theory which is not based on any fact." Hooper countered that different batches were made in different labs and the tested batches did not include one used in the Congo.
The River came in for another attack from Dr Bette Korber of Los Alamos National Laboratory, New Mexico, and Prof Beatrice Hahn of the University of Alabama. "We don't rely on people telling us anything. We rely on the genetic sequence, which is like a fossil," said Prof Hahn.
To date, the only SIV closely related to HIV-1 has been isolated from chimpanzees from west central Africa, coinciding with the epicentre of the HIV-1 pandemic, while the Stanleyville chimps were captured in central equatorial Africa.
Studies of HIV at the molecular level "provide the clearest evidence about the origins of Aids", the meeting was told by Prof Paul Sharp of Nottingham University.
Hooper has tried to explain away the link between HIV and west central African chimps by saying that their SIV led to one group of HIV-1 (denoted N) but the more common, M group, of HIV was triggered by CHAT. This is "fallacious", claimed Prof Sharp, arguing that both M and N groups are equidistantly related to West Central African chimp virus: they were born in the same place. Hooper "does not understand how to interpret the evolutionary trees".
Differences in HIV and SIV, and knowledge of the virus mutation rate, can be used like a molecular clock to work out when the common ancestor emerged. This suggests that the "Eve virus" was probably born long before CHAT. Dr Korber explained that, given the diversity of Aids viruses today (there are 12 subtypes, plus minor variants), Eve emerged before 1940. Verification came from Dr Anne-Mieke Vandamme of the University of Leuven, Belgium, who used different methods and data. Hooper argued that different chimp SIVs may have crossed to humans in 1957-60, through different CHAT trials. In other words, he believes that many subtypes emerged to infect the Stanleyville chimps so the common viral ancestor - Eve - was in a chimp, not a human.
This version of the genesis of Aids would mean dozens of divergent viruses would have had to contaminate the polio vaccine, said Prof Sharp. This seems a profligate use of animals, given that a single kidney can be used to make 100,000 doses of vaccine. Also, if many strains had been used, and if there had been such a high rate of infection, there would have been a high rate of recombination - splicing - of virus types. But the evolutionary tree of group M shows distinct virus subtypes and little recombination during their early diversification. Prof Sharp also described new studies of how SIV turned into HIV which suggest that the protein coating of the ape virus adapted to humans "long before" Hooper claims that people were infected.
Yet another problem for Hooper was described by Dr John Beale: vaccine preparation would most likely kill SIV and HIV (the kidney is broken up using trypsin, an enzyme that would damage the viruses, as would the heat treatment and cycles of freezing and thawing).
The closing speech - described by one delegate as a "devastating critique" - was given by Prof Robin Weiss of University College London, co-chairman. Afterwards, Prof Weiss said that, if it had come to a vote, Hooper would have lost overwhelmingly. Hooper counters that the meeting was set up. "More than two dozen of those present have since contacted me to express disquiet at the way that certain sessions were loaded, at the last minute, with opponents, and to comment on Prof Weiss's partisan closing speech."
A "concerted effort" was made to annihilate his theory "and that effort failed", he said. The sceptics would convince him only if they found HIV samples that predate the use of CHAT (the oldest infection has been traced to the Congo in 1959).
Given that, even today, refrigeration is hardly commonplace in Africa, this apparently reasonable request for hard evidence is a tall order. Prof Weiss was "partisan" because, despite Hooper's protestations, many scientists now believe that his case is contrived and has been fatally weakened by the new evidence.
The great irony is that polio was considered an Aids-like crisis of the time, said Prof Koprowski, who tested CHAT on himself and his children. He complained that he had been dubbed the "father of Aids", and that Hooper's "fantasy" is even today harming efforts to combat polio in Kenya, where mothers have been warned by the church that polio vaccine is contaminated with HIV. Half a century after he fed the first vaccine to a child, one of the greatest efforts to eradicate a disease "may now be compromised".
So what did cause Aids? The prevailing theory is that a hunter or bushmeat seller became infected after being exposed to chimp blood when capturing or butchering the animal. This remains the easiest way to explain the molecular data: a single transfer of SIV to a human in around 1930. But it is not the only possibility. Prof Charles Gilks told the meeting that chimp blood was used to give patients chimp malaria, to induce a high fever to "cook" bacteria that cause syphilis. Aids may have been spread by the widespread reuse of unsterilised needles in the fight against syphilis during the Fifties, added Preston Marx of Tulane University, Louisiana. It was between the world wars that the price of syringes dropped to the point that they were used widely, but remained expensive enough to encourage reuse.
This could explain more than the spread of HIV-1: it may account for the emergence of HIV-2, the less common Aids strain, which is most closely related to a virus that infects another monkey, the sooty mangabey, in west Africa. But these ideas are speculative. The origins of Aids remain mysterious.