THE DOCTOR’S WORLD

An Improbable Theory on AIDS Is Put to the Test

By LAWRENCE K. ALTMAN, M.D.

New York Times, Tuesday 21 March 2000, pp. D1-D2

Scientists in three laboratories in the United States and Europe are gearing up to test samples of an experimental polio vaccine stored for more than 40 years to determine whether it might have inadvertently been the spark that ignited the worldwide AIDS epidemic.

The scientists will be testing a highly controversial and seemingly far-fetched theory that holds that an oral polio vaccine, used in vaccine trials in what was then the Belgian Congo in the 1950’s, might have been made with chimpanzee tissue that might have been contaminated with an ancestor of the AIDS virus.

The Wistar Institute, a research center in Philadelphia, made the vaccine and has kept a few drops of material used in its preparation frozen since 1957. After the AIDS and polio vaccine theory was first raised in 1992, Wistar appointed an independent committee of scientists to look into the questions. The committee recommended testing the vaccine. But Wistar never carried out the tests, it said, because of a lack of scientific interest.

Now, responding to a book, “The River,” by Edward Hooper, an English journalist, published last fall by Little Brown, the institute has reactivated the panel and is having the tests performed. The findings are not expected before June.

This time, many laboratories relish the opportunity to test the material. Medical journals have taken the extraordinary step of asking for the rights to publish the findings even before the samples are shipped to participating laboratories.

“Labs are drooling over doing this, because it’s a sure publication in a high-profile journal,” said Dr. David Ho, who directs the Aaron Diamond AIDS Research Center in Manhattan and is a panel member.

Dr. Ho said that he had decided against having his team participate, partly because he is on the committee. He added, “Several of my colleagues were a little distressed over that decision.”

Chances are slim that the new tests will conclusively prove or disprove the theory, partly because no one can be sure that what is to be tested actually represents the vaccine that was squirted into the mouths of people in what is now known as Congo.

If there was contamination, it might have affected only a part of the vaccine, all of which was consumed in the trials. (The experimental vaccine was never marketed and is not the one that has been used to nearly eradicate polio.)

On Feb. 29, the Wistar Institute transferred the remaining polio vaccine to an independent laboratory that will prepare and divide the material for distribution to three laboratories and a fourth if there is enough material, Dr. Clayton A. Buck, the institute’s chief administrative officer, said in an interview.

By early next month, the material will be carried by hand to the participating laboratories. There, scientists will begin a number of tests aimed at detecting any AIDS-related virus and determining which kind of animal tissue was used to make the vaccine. The focus is on tissue from chimpanzees because they carry a simian virus that is believed to be the ancestor of H.I.V.-1, the virus responsible for the overwhelming majority of AIDS cases in the world.

All samples will be coded so that the scientists doing the tests will not know whether the samples represent the vaccine or something else being used as a quality control. The code, known only to the independent laboratory and the committee, will be broken after the scientists complete the testing.

The AIDS virus has infected 30 million people, making it one of the worst epidemics in history. The contaminated vaccine theory is based entirely on circumstantial evidence. But if it is correct, AIDS will also be the worst medically caused epidemic in history. With so little evidence but so much at stake, scientists are arguing passionately about the theory’s plausibility. While many scientists dismiss the theory out of hand, others believe it is possible, though unlikely. Learning how the AIDS epidemic arose could prevent similar epidemics in the future.

The most crucial test will be to determine the species of cell used to make the polio vaccine. Wistar scientists have said they never used chimpanzees to make the vaccine.

“The most compelling open-and- shut case of fact will be if the tissue is chimp,” said Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases. “If there is chimp DNA in the vaccine, then, oops!”

Yet finding chimp DNA in the samples would not prove the theory. Proof would require finding an AIDS-like virus in the polio vaccine samples. Although scientists have retrieved H.I.V. from blood that had been stored for decades, success depends largely on the quality of the material saved.

An AIDS-like virus could still lurk in the polio vaccine, even if the scientists do not detect it. Such a failure could occur if the material was degraded or the techniques, as advanced as they are, were inadequate to find it.

In 1992, Wistar appointed Dr. Claudio Basilico, chairman of the microbiology department at New York University, to lead the independent panel.

The committee said it was skeptical of the theory, in part because the evidence available then, now disproved, placed the origin of H.I.V. before the development of polio vaccines. Nevertheless, the committee urged testing of the remaining vaccine.

The tests were not done because only the federal Centers for Disease Control and Prevention in Atlanta was willing to do them, and more than one laboratory was needed for verifying findings, Dr. Buck said.

Critics said Wistar did not try hard enough to find additional laboratories.

“Wistar decided in error that the charges were not sufficiently serious, that the situation had more or less resolved itself” and “that the whole thing was unlikely and costly,” said Dr. Stanley A. Plotkin, a scientist who worked at the Wistar Institute. “They sort of let the ball drop.”

Now, Dr. Plotkin said, he is doing everything he can to promote the testing of the remaining Wistar vaccine. He has canvassed laboratories in several countries to determine which are competent to perform the tests and has submitted the list to the committee. Dr. Plotkin said that he was not involved in the selection and that some laboratories doing the tests were not on his list.

In selecting the laboratories, the panel has excluded those operated by the United States government, laboratories in Philadelphia, and any others that might be perceived as having a conflict of interest.

The committee is supervising the testing, the participating scientists are donating their time and Wistar is paying incidental costs estimated at $10,000. Dr. Buck and Dr. Basilico said their groups were sworn to secrecy on the identity of the labs until testing was completed.

Although the committee is not telling participating scientists who else is involved, the participants might stumble onto the information from discussions with colleagues.

The committee is retaining a few drops of vaccine “in case someone drops a sample” or some other accident occurs, Dr. Buck said.

There is no standard scientific blueprint, or protocol, for how the laboratories will conduct the tests.

“There are lots of wrong ways to do the tests, but not a single right way,” Dr. Basilico said.

A participant who asked not to be identified said the work in his laboratory would be done by two people working independently and one after the other on different days as an internal control for consistency of results.

Using different approaches might be beneficial because “if just by pure luck we all went for the same” target, and it was not the correct one, the team could miss detecting a virus, even if it was present, the participant said.

Each laboratory has submitted its plan for testing. “Five experts in the area are reviewing the protocols, and I don’t think they will miss any errors,” Dr. Buck said.

“If a red flag comes up,” he continued, “we will be concerned,” but “we can’t very well put them out for a public vote before we have the testing done.”

Others disagreed, saying that if methodological flaws were found after testing, it could be too late to get crucial information or interpret the findings.

Among the problems that could alter interpretation of the findings are what to use for quality controls and contamination.

Dr. Ho declined to discuss the specific controls beyond saying that it would be fair to send a participant an entire set of material that contained no stored vaccine because “it’s part of quality control.”

Any protocol will rely on a critical technique known as P.C.R., or polymerase chain reaction. It can detect DNA in only one virus and then grow endless amounts of it for further testing. But this technique has a notorious problem of contamination that produces false findings, and the team is expending enormous effort to avoid it.

After the code for the samples is broken, the scientists will analyze their findings as a group and submit a paper for publication. The paper will probably not be ready by the time the theory is discussed at a meeting at the Royal Society in London in mid-May, Dr. Buck and Dr. Basilico said.

“We are curious to find out the findings, but want it done carefully and without rushing,” Dr. Basilico said.

The scientists have been hampered by not knowing the full pedigree of the material stored at Wistar because records were lost over the years. “It would be very difficult to retrace the history of the samples unless someone spends six months in the archives,” and that is not the committee’s role, Dr. Basilico said. “We are not the F.B.I.”

The Centers for Disease Control and Prevention has agreed to send the committee more material from its stores of the Wistar polio vaccine. The material may be useful as scientific controls but not in proving or disproving the theory because one vial contains polio virus that the institution grew after it received the vaccine from Wistar many years ago, said Dr. Harold W. Jaffe, an official at the centers. Another vial contains Wistar polio vaccine, but its pedigree is not clear.

Because H.I.V. is less hardy than polio and other viruses, scientists differ on whether an AIDS-like virus could survive the process used to make the polio vaccine in 1957. Today, the Food and Drug Administration requires tests to make sure that unwanted live virus is not in vaccines. In the 1950’s, such controls were much less sophisticated and H.I.V. was not known. Experiments to determine if H.I.V. could have survived production methods used in 1950’s — which would strengthen the AIDS vaccine theory — have not been done.