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- It is a long way from the Wistar Institute in Philadelphia
to the Royal Society in London. But the participants in a meeting at the
society earlier this week, innocently entitled Origins of AIDS and the
HIV epidemic , might have been forgiven for thinking that they could hear
sighs of relief from the other side of the Atlantic ocean. For the real
purpose of the meeting was to debate the accusation that some of the Wistar
s researchers may have been inadvertently responsible for the global AIDS
epidemic and by the end of the meeting that notion had more or less been
laid to rest.
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- In the late 1950s a group at the Wistar, led by a virologist
called Hilary Koprowski, created an oral polio vaccine called CHAT. The
hypothesis was that some batches of CHAT were accidentally contaminated
with the virus that became HIV-1, the strain responsible for most cases
of AIDS. These batches, so the theory went, were given to several thousand
people in what was then the Belgian Congo and its associated UN Trust Territories
(now, respectively, the Democratic Republic of the Congo, and the states
of Rwanda and Burundi). With such a start in life, an enterprising virus
could hardly fail to become epidemic. And so, according to the theory,
it did.
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- Although he did not invent it, this theory s most vocal
proponent is a writer named Edward Hooper. He outlined his reasons for
believing it in a book called The River , which was published almost exactly
a year ago. He noted that the earliest known sample of HIV-1 was collected
in 1959 from a Congolese man (administration of the vaccine began in 1957).
He suggested that early cases of the disease, or of infection with the
virus, were closely correlated with places where vaccine trials had been
carried out. He wondered if Dr Koprowski s connections with a chimpanzee-research
station at a place in the Congo called Lindi had led him to mix a few chimpanzee
kidneys with the monkey kidneys that were used to grow the polio virus
needed to make CHAT. (HIV-1 appears to be a chimpanzee virus that has leapt
the species barrier to man.) And he suggested that the institute make
available for study the small number of samples of CHAT that remained in
its freezers to see if there was any trace of either HIV-1 or chimpanzee
DNA in any of them.
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- It duly did so, and the results of the analyses were
announced at the meeting. All seven remaining samples were investigated
by three separate and independent laboratories. All were pronounced as
clean as a whistle. And in a conference that bubbled with barely suppressed
vitriol, most of the other speakers undermined Mr Hooper s ideas so badly
that by the end his edifice was barely standing.
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- CHAT up Some of the most convincing evidence came from
analyses of the virus s evolutionary history. These are done by looking
at differences between the genetic material of the seven or eight main
subtypes of HIV-1 and asking how long those differences took to arise.
Although this is a theoretical process, the reliability of a given method
can be checked by asking it to hindcast the age of viral samples taken
from people in the past, and the reliability of the whole idea can be checked
by seeing if the results from the different methods agree.
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- The CHAT theory obviously relies on AIDS happening after
the introduction of the vaccine. But two of the speakers, Bette Korber
from the Los Alamos National Laboratory in New Mexico and Anne-Mieke Vandamme,
of the University of Leuven in Belgium, employing three different methods
of calculation between them, showed that the most recent common ancestor
of the existing subtypes probably existed in the 1920s or 1930s. That complicates
the CHAT theory enormously, for it would mean that the vaccine must have
introduced all the subtypes separately each, presumably, from the kidneys
of a different chimpanzee that was infected with the relevant virus.
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- The correlation between vaccination sites and early records
of HIV-1 was also called into question. On the face of it, that correlation
seems close. According to Mr Hooper, 64% of the early instances of AIDS
were at or near places where CHAT was tried out. But a closer analysis
by Stanley Plotkin, one of Dr Koprowski s original collaborators, who now
advises Aventis, a Franco-German drug firm, suggested that this correlation
is in fact spurious.
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- First, both the vaccination campaigns and the sites of
origin of the samples and medical records that show early HIV-1 infections
are concentrated in places which it is easy to get to. That, alone, might
be enough to explain the coincidence. But in addition, many of the samples
and records come from big cities. To vaccinate a few hundred people in
a village and find a disease there a decade later is one thing. To do the
same in a city is another. The chance that those who were vaccinated are
those who succumbed is far lower. And on top of that there are both vaccination
sites with no early HIV-1 record, and records that are hundreds of kilometres
from a vaccination site.
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- Another damning observation was made by a speaker called
John Beale. He examined the way CHAT was made, and estimated how many HIV
particles would get through each stage of the process, if any were present
in the first place. His conclusion was that one particle might survive
for every 10,000 billion that started. Even the body of a person with full-blown
AIDS contains only a few hundred million HIV particles. A mere kidney would
have far fewer.
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- The crux of Mr Hooper s argument, however, was that Dr
Koprowski did, indeed, use chimpanzee kidneys to make some of his vaccine.
Dr Koprowski, who was one of the speakers, denied it. So did Dr Plotkin
and Paul Osterrieth, another collaborator on the CHAT work. Dr Koprowski
explained that his connection with the laboratory in Lindi was because
he was testing CHAT on chimps prior to unleashing it on people. He was
not collecting kidneys.
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- Mr Hooper fought back, with reports of interviews with
people who had worked in Lindi and at another laboratory connected with
Dr Koprowski in Bujumbura in Burundi. They recalled kidneys being removed
from chimpanzees in these places, and then shipped out. But there is no
evidence that such kidneys were used to make CHAT.
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- The CHAT theory of AIDS, in other words, has sunk. Or
if it has not (the clinching evidence would have to be a human HIV-1 sample
from before 1957), it is holed below the waterline and is going down fast.
But disproving it does not bring researchers any closer to working out
what really happened, and Mr Hooper, though he has turned out to be wrong
on the specifics, has raised a general point that needs answering because
for AIDS to emerge at the time it did was a very peculiar thing.
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- No good deed goes unpunished One peculiarity is that
people have shared Africa with chimpanzees for as long as mankind has existed.
So why should it take until the early decades of the 20th century for the
virus to cross from one to the other? Another is that, although HIV-1 (or,
more strictly, HIV-1 group M) is the main cause of AIDS, it is not the
only one. A smaller epidemic caused by HIV-2, a virus that comes originally
from a monkey called the sooty mangabey, is raging in West Africa. And
two other versions of HIV-1, known as groups N and O, are so different
from group M that they must have separate origins in the chimpanzee population.
That one AIDS-causing virus should have leapt into the human population
at the moment it did is odd enough. That four should do so at more or less
the same time stretches coincidence to breaking point. It seems far more
likely that some human agency was involved in the transfer. But what was
it?
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- One theory is that population growth is to blame. This
was outlined by Albert Osterhaus, of Erasmus University in Rotterdam. More
people means more and bigger cities. And urban folk have more opportunities
for promiscuity than rural ones or at least more potential partners to
choose from. In the past, HIV might have passed naturally from a chimp
to a man in the forest on many occasions (the so-called cut hunter theory,
which hypothesises a bloody encounter of one sort or another between the
two species) but been unable to sustain itself for lack of subsequent hosts.
Population growth could have put paid to that constraint and allowed the
virus to spread.
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- Another consequence of population growth is a demand
for new farm land. In Africa, this means cutting down forests, which would
increase the amount of contact between man and chimp. Rather than cut hunters,
you would end up with cut farmers.
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- Both of these ideas emphasise changes in human exposure
to animal viruses. But there is another possibility: that the animal viruses
themselves were somehow changed by human intervention.
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- Preston Marx, of Tulane University in Louisiana, made
a suggestion about what might have happened. He observed how the price
of syringes dropped after their invention, reaching a point between the
first and second world wars when they were cheap enough to be deployed
widely, but expensive enough to require re-use. He also noted that when
monkey viruses similar to HIV are moved experimentally from one species
to another, and then moved from animal to animal in the second species,
their virulence increases significantly.
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- Careless re-use of syringes, he suggests, could have
had the same effect in people transferring a benign chimp virus from a
cut hunter or farmer to another host, where it became nastier, and then
to another where it become nastier still. Once nasty enough, this virus
would start spreading by more conventional means. Such a process could
work in parallel for different viruses in different places, explaining
the existence of four different types of AIDS virus
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- This idea is, of course, as speculative as Mr Hooper
s, and it could end up being shot down in flames as easily. But then again,
it might be right. If it were, it would be one of the saddest examples
of the law of unintended consequences in history.
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