RESEARCHERS DISMISS AN AIDS VIRUS DISCOVERY

By John Crewdson

Chicago Tribune 18 Feb. 1988

A 2-year-old claim by scientists at Harvard University to have discovered a second virus capable of causing AIDS in humans has been dismissed as "not authentic" in a highly unusual paper to be published here Thursday by a rival team of Harvard researchers.

Writing in Nature, the prestigious British scientific journal, scientists affiliated with Harvard's medical school said neither the purported AIDS virus, nor another AIDS-type virus said to have been isolated from the African green monkey, ever really existed.

When they were broken down biologically into their component parts, the article said, it became evident that the two "new" viruses were really contaminants of simian immunodeficiency virus, or SIV, which had been isolated from the rhesus macaque more than a year before.

Because it is unusual for one group of scientists to openly contradict the work of others, and practically unknown for researchers to investigate and disprove the work of colleagues at the same institution, the full implications of the Harvard affair remain to be seen.

One thing that is already clear, however, is that the episode represents a belated victory for a team of French scientists at the Pasteur Institute in Paris.

Although the Pasteur team had isolated the second principal human AIDS virus, now called HIV-2, several months before the Harvard group came up with its now disproved findings, publication of the Pasteur team's paper reporting the discovery was apparently held up in the United States to allow the Harvard team to publish first.

The Harvard affair is also illustrative of what many researchers say is the undue haste with which much AIDS research is being conducted, partly out of an urgency to save lives but also because being first to publish significant new findings carries substantial rewards, financial and otherwise.

It was just a few months after he published his paper on the new human AIDS virus that Dr. Myron "Max" Essex, the Harvard virologist in whose laboratory the contaminations occurred, received the Lasker Award, second in prestige only to the Nobel Prize, for a body of work that included the two viruses in question.

While more than 40 Lasker Award winners have gone on to become Nobel laureates, Essex's candidacy for that most sought after of prizes is now in doubt.

Moreover, the now unavoidable recognition that an American paper containing erroneous results was published before an earlier French paper containing accurate results is bound to raise questions about the extent to which some American scientific and medical journals overlook, or ignore, research from abroad.

Accompanying the article in Nature is a critique written by Carel Mulder, a professor of microbiology at the University of Massachusetts.

In unusually stern language for a scholarly journal, Mulder writes, "This episode should serve as a strong warning for all virologists working with multiple isolates (of different viruses) to check any new isolates against viruses present in the laboratory."

Mulder also hints at larger problems on the horizon when he writes, "I am aware, or have been told, of at least five instances in other laboratories in the United States and Europe where non-infected cell cultures became infected with HIV-1," the principal virus believed to cause acquired immune deficiency syndrome (AIDS) in humans.

Although there is only one reported case of HIV-2 infection in the U.S., it is now the predominant AIDS virus in western Africa.

The Nature article contains an unusual reply by Essex and one of his coworkers, Phyllis Kanki, in which they "acknowledge the results of others and agree that certain isolates initially reported by us . . . should be considered SIV unless proven otherwise."

When the "new" AIDS virus was announced by Essex and Kanki, it appeared in an article in the April 13, 1986, issue of Science, the journal of the American Association for the Advancement of Science. The same publication carried the group's report of the green monkey virus a few months before. The new AIDS virus, the article said, had been found in blood samples taken from "apparently healthy people in Senegal, west Africa."

It seemed, at first, one of the most promising and important discoveries in the panoply of AIDS research. Because the second AIDS virus was nearly identical biologically to the purported green monkey virus, the authors suggested that the similarities "may expand our understanding" of the origin of the human AIDS virus.

The highly publicized article led to broad speculation about the possibility that the human AIDS virus had originated in African monkeys and then been passed somehow across the "species barrier" into humans.

Although the Essex-Kanki article was published in Science less than three months after it was received by the journal's editors, the article from the Pasteur Institute about the isolation of what has since proved to be the genuine HIV-2 did not appear until July of 1986, more than 13 months after it was submitted for publication.

Editors at Science failed Tuesday to return a telephone call from a reporter seeking information about why the French article was withheld from publication for so many months, and whether the journal would now publish a retraction or correction.

Because of the intra-institutional rivalries involved-sources said the Essex affair had bruised egos and strained friendships at Harvard-no one involved in disproving the Essex research would agree to be quoted by name. But several of those with knowledge provided the following account of events:

In 1985 scientists at the New England Primate Research Center, an adjunct of Harvard Medical School, isolated the virus they called SIV from a group of captive rhesus macaques, which are classified as Asian old world primates.

The researchers at the primate center sent a sample of SIV to the Essex laboratory at the Harvard School of Public Health, with the understanding that workers there were interested in studying the biological makeup of the virus.

The Essex laboratory, meanwhile, had discovered that nearly half of African green monkeys possessed chemical evidence of an infection with a virus not unlike SIV, and researchers there began trying to isolate a variant of SIV from that species.

Nine samples of green monkey blood were obtained from a primate center on Long Island, and within a matter of days the Essex team had isolated what it was calling a new simian immune-deficiency virus from eight of the nine.

A few months later, the Essex lab reported that it had isolated a new human AIDS virus that was remarkably similar to the green monkey virus from the west African human blood samples.

Replication is the touchstone of science, and the first doubts about the Essex findings occurred when scientists in other labs, including those at the primate research center, were unable in independent experiments to isolate either of the two new viruses.

Then, when samples of each of the new viruses were compared with other samples of the same virus, they proved to be far more alike than would be expected to have occurred in nature.

But the real concern began to develop when workers at the primate center compared the green monkey virus with the new AIDS virus directly-and found that they, too, were not only similar but virtually identical.

When both those viruses also proved to be identical to the sample of SIV that the primate center researchers had originally lent to the Essex lab, it became clear that a major contamination had occurred.

Researchers agree that the threat of laboratory contamination-the possibility that a virus from one dish or flask will somehow invade a culture in another dish or flask-is a constant worry.

But they also agree that proper laboratory procedures can lessen such concerns. They add that when a contamination is suspected, and especially before an important new virus is announced, routine checks should be performed in which the new virus is compared with existing viruses in the laboratory.

If Essex and his coworkers ever performed such a comparison, they never announced the results. Indeed, some of those familiar with a meeting at the Pasteur Institute last fall say he continued to deny the possibility of a cellular contamination.

"We had to do something," said one of the scientists involved in disproving the Essex research. "Already 21 or 22 other articles had been published that were drawing on his paper."

Ironically it was only after another two years of work that the primate center researchers were able to report that they had finally isolated a true variant of SIV from the blood of the African green monkey. *