Where did Aids really come from?

LONDON (Telegraph.co.uk) – 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.

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.