Scientists to Debate Whether Polio Trial Triggered AIDS Epidemic

By Huntly Collins, The Philadelphia Inquirer, September 10, 2000

© 2000 Knight Ridder/Tribune News Service

Was a monumental effort to conquer polio, once the leading cause of physical disability, responsible for unleashing the world AIDS pandemic, which has stricken 53 million people, most of them in Africa?

That's the question that will be addressed Monday and Tuesday at an extraordinary meeting of the Royal Society of London, one of the world's most distinguished scientific bodies.

At issue is whether a massive trial of an oral polio vaccine developed by Hilary Koprowski, former director of Philadelphia's Wistar Institute, inadvertently triggered the AIDS epidemic.

The trial, conducted in the former Belgian Congo between 1957 and 1960, tested the oral vaccine on nearly 1 million Congolese people, most of them women and children.

In a 1999 book "The River: A Journey to the Source of HIV and AIDS," British journalist Edward Hooper suggests that Koprowski's vaccine may have been contaminated with the chimpanzee version of the AIDS virus which, through the trial, was passed into the human population for the first time.

Scientists, not journalists, usually prompt meetings of the Royal Society, chartered by Charles II in 1662 to promote the exchange of new scientific ideas. One of the group's first presidents was Sir Isaac Newton, the father of modern physics.

But in this case, Hooper, a former correspondent for the BBC in Uganda, has seized center stage because his heavily researched book _ 1,070 pages long and 10 years in the making _ ignited the controversy.

In promoting his hypothesis, Hooper captured the attention William D. Hamilton, a noted developmental biologist at Oxford University and member of the Royal Society.

Hamilton, 63, died last March after contracting malaria while on an expedition to Congo to collect chimpanzee stools as part of an effort to verify Hooper's theory.

The Royal Society symposium was originally organized by Hamilton, who was dismayed by what he considered the attempt by mainstream scientists to quash a thorough investigation of Hooper's findings.

In a forward to Hooper's book, he accused scientists of closing ranks about a medical accident "that is bidding to prove itself more expensive in lives than all the human attritions put in motion by Hitler, Stalin and Pol Pot."

Rubbish, say other scientists. The evidence now leans heavily against Hooper 's theory and, at a time when AIDS continues to ravage large parts of the developing world, scientists need to focus on an AIDS vaccine and better medicines to treat the disease, not an esoteric debate about its origins.

In his book, Hooper points to two key pieces of evidence to support his allegations:

__Koprowski set up a chimp colony in Congo that Hooper suggests was used as a source for chimp kidneys in which to grow polio virus.

__The sites of Koprowski's polio vaccine trials in Congo were also the places where some of the first cases of AIDS later emerged in Africa.

At the symposium, both Koprowski and Stanley Plotkin, his former deputy at Wistar and a world-class immunologist, are expected to present new evidence to counter Hooper's allegations.

They say that kidney cells from monkeys _ not chimps _ were used to grow the polio virus for the vaccine. And they contend that the geographic correlations cited by Hooper aren't as close as Hooper makes them appear.

It will be the first time, in nearly a decade of backdoor wrangling over the issue, that either Koprowski or Plotkin has addressed the topic head-on at an open scientific meeting.

"It is my duty to come to the meeting," said Koprowski, 82, now director of the Center for Neurovirology at Thomas Jefferson University. He said it was important to vindicate his work as the world approaches a medical milestone: the eradication of polio virus.

Though Koprowski lost the race to license an oral polio vaccine to Albert Sabin, his pioneering work on an oral vaccine, including the trials in Congo, is widely regarded as having advanced the effort to find a cheap, easily administered and effective vaccine to stop the spread of polio virus.

Plotkin, 68, a Doylestown resident who recently retired as medical director of Aventis Pasteur where he was working on an AIDS vaccine, has been preparing for the Royal Society meeting for months.

He said he has tried to locate people who used to work on the vaccine, re-interviewed some of the individuals interviewed by Hooper, and rummaged through old files to come up with documents supporting his contentions.

Both men have long and distinguished reputations on the line, but Plotkin, the former chief of infectious disease at Children's Hospital of Philadelphia and developer of the vaccine against German measles, said he was concerned not just about his legacy but also about the impact of Hooper's ideas on the future use of vaccines to combat infectious disease.

Vaccines are widely regarded as among the most important public-health advances that medicine has delivered. In recent years, however, they have come under heavy fire from a small but vocal group of critics, most of whose allegations about vaccine safety have turned out to be greatly exaggerated.

"It is being claimed that a vaccine [the oral polio vaccine] caused a catastrophe," said Plotkin. "The question is, did it happen?"

Other scientists who line up on both sides of the polio vaccine and AIDS controversy will also address the symposium.

"It's going to be a bit of a bonfire," said Robin Weiss, a noted AIDS researcher and virologist at University College of London, who helped organize the meeting after Hamilton's death.

Despite the polarization, almost everybody agrees on one point: that the HIV-1 M group of viruses which were responsible for sparking the global AIDS pandemic probably came from a chimpanizee _ likely several chimpanzees.

What's at issue, however, is how and when that virus jumped species and, once it had jumped into humans, how it spread from one person to another, fueling an epidemic that still rages out of control in Africa and parts of Asia.

Genetic sequencing studies, which attempt to date HIV by its mutation rate, indicate that the virus probably moved from chimps to humans several centuries ago and that the particular type of HIV that sparked the human epidemic probably emerged as a branch in the HIV family tree in about 1930, more than two decades before Koprowski's trial began.

Hooper, on the other hand, believes that the divergence of that branch had already occurred in chimps and that people weren't infected with that virus until Koprowski began his polio trials in Congo.

The earliest known case of HIV dates from 1959 in the Congo.

At the symposium, Simon Wain-Hobson, an AIDS researcher at the Pasteur Institute outside Paris, is expected to present the results of laboratory tests that could bear heavily on the issue.

Wain-Hobson has tested the fecal samples that Hamilton brought back from Congo. If those samples are found to carry chimp versions of HIV which have genetic sequences close to the HIV-1 M group viruses, then Hooper's theory would get an enormous boost.

So far, none of the viruses isolated from chimps in captivity in other parts of Africa have yielded any simian immuno-deficiency virus that is closely related to HIV.

In addition, the meeting will lay bare what could be another critical piece of evidence: laboratory tests of the last remaining vials of Koprowski's oral polio vaccine, which have been sitting in a freezer at Wistar on the campus of the University of Pennsylvania for some 40 years.

Those samples have now been sent to three independent laboratories for sophisticated tests to determine whether the polio virus that went into the vaccine was contaminated with SIVcpz, the chimp version of AIDS.

The testing may also determine whether the live polio virus used to make the vaccine was grown in the kidney cells of chimpanzees, as Hooper suggests, or in the kidney cells of African monkeys, as Koprowski and Plotkin contend.

While the meeting has its detractors, many scientists believe it will serve a useful end.

"It's an important meeting," said David M. Hillis, a microbiologist at the University of Texas, who has followed the controversy over Koprowski's polio vaccine trials. "It's important to determine where and how the AIDS virus got into the human population so we can prevent that from happening again in the future."

The issue is relevant not only to AIDS but also to a host of other diseases that have moved from wildlife to people.

Flu, for instance, is caused by bird virus that has used genetic tricks to establish itself in man. And most of the new emerging diseases, from Ebola to hantavirus to West Nile fever, originated in wildlife.

Scientists predict that such zoonotic diseases will occur more often as environmental changes, stepped-up global travel and suburban development put people in closer contact with nature.

"This is going to happen more and more," said David M. Morens, a medical epidemiologist at the National Institutes of Health.

What's more, the new field of gene-based therapy, which often uses viruses to deliver genetic material to cells, as well as advances in xenotransplantation, in which animal organs are used to replace those in people, up the odds that a potentially lethal microbe from another species could accidentally get introduced into the human population.

In that respect, the Royal Society symposium on the origin of AIDS could signal potential dangers in the future.

"There are lessons to be learned from the past," said Weiss.