Chicago Tribune (CT) - SUNDAY August 16, 1987
John Crewdson, Chicago Tribune Writer

The Los Angeles Times called the study "the first evidence of heterosexual female-to-male transmission of the AIDS virus in the United States." The Washington Post characterized it as "strong new evidence that the virus thought to cause AIDS can be spread sexually between husbands and wives."

The public furor generated by such reports was nothing compared with that inside the research community.

The first shot was fired when a group of doctors from the New York City Department of Health, in a letter to JAMA, asserted that the Walter Reed study had been "based on questionable data and unsound epidemiologic reasoning," and that the evidence presented for female-to-male transmission of AIDS was "unconvincing."

Among other things, the New York group pointed out that admissions of either homosexuality or hard drug use were grounds for an involuntary discharge from the military.

The Walter Reed group remained unshaken by the attack.

"We are unaware," it wrote back, "of any evidence to support the often-repeated statement that soldiers are more likely than civilians to lie to their personal physicians," even about such things as homosexuality and drug use.

At that point the fray was joined by several members of the El Paso County Health Department in Colorado, which reported having examined some 20 active military personnel with AIDS.

When the soldiers first had been questioned by military doctors about how they might have acquired AIDS, the Colorado group said, only four acknowledged that they were homosexual and just one admitted using intravenous drugs.

But when the same questions were asked by the civilian health department doctors, 14 of the soldiers admitted being homosexual and 3 said they had used intravenous drugs.

Dr. Timothy Dondero, the epidemiologist who heads the AIDS surveillance program at the Centers for Disease Control, attributes much of the current confusion over how heterosexuals acquire AIDS to "self-described experts" like Maj. Robert Redfield, the Walter Reed physician who is the Army's chief AIDS researcher.

"Bob Redfield's a very sincere man, very good with patients," Dondero said in a recent interview, "but he's not an epidemiologist."

The CDC, on the other hand, has not been without troubles of its own. The first reports of AIDS were greeted there in the summer of 1981 with what one scientist termed "a great sense of urgency," and it was not unusual for researchers arriving in the early morning hours to encounter colleagues leaving for home. Before long, however, the enormous pressure took its toll.

"Everyone had their own experiments," the scientist said. "They needed to collaborate to avoid duplication, and they needed leadership to help them collaborate. But both the leadership and collaboration were lacking, not to mention laboratory facilities and money. Eventually the exhaustion and the paranoia set in."

An investigation last fall of alleged internal sabotage by disgruntled CDC researchers turned up at least "five separate incidents of suspected intentional tampering with laboratory equipment," including the contamination of cell cultures in the CDC's AIDS lab, according to a report.

The tampering, said the investigators, had taken place in "an environment of distrust and dislike," in a facility that lacked "team spirit" and was hobbled by "internal competition."

The CDC is by no means the only American research facility where such vivid competition exists. But the greatest rivalry of all is that between the CDC's sister federal agency, the National Institutes of Health (NIH), and the Louis Pasteur Institute in Paris.

Eighteen months ago, researchers at the Pasteur Institute filed a civil lawsuit against the U.S. government.

The charges they brought were complicated, involving technical questions of breech of contract and patent infringement in connection with the rightful ownership of the test currently being used in the U.S. to determine whether humans are infected with AIDS.

What the French were really alleging, however, was that a team of scientists led by Gallo at the National Cancer Institute, an arm of the National Institutes of Health, had appropriated samples of the AIDS virus first discovered by the French, and the Americans had claimed it as their own.

The first cases of AIDS were reported in the summer of 1981, but it would be some time until the nature of the disease was understood. Many scientists suspected from the outset that a virus was involved. Some believed it was a special kind of virus--a so-called retrovirus that, unlike ordinary viruses, reproduces itself inside the body of its host.

Only two human retroviruses had thus far been discovered. The first was human T-cell leukemia virus type one, or HTLV-I, first identified by Gallo in 1978. The second, a variant named HTLV-II, was discovered by Gallo in 1982.

Both caused a rare blood cancer by infecting the white blood cells, known as T-cells, that control the body's immune system and causing them to multiply uncontrollably.

According to the scenerio set down by the French lawsuit, it was a team of scientists at the Pasteur Institute, headed by the noted virologist Luc Montagnier, who early in 1983 discovered a third retrovirus in the body of a patient who later developed AIDS.

The French team assumed at first that the retrovirus must be another variant of HTLV, but major differences soon became apparent. The first was that while cells invaded by HTLV multiplied in typical leukemia fashion, cells infected with the AIDS virus died.

The other difference emerged in February, 1983, when the French were first able to photograph the AIDS virus with an electron microscope and found that it did not look anything like HTLV.

In May, 1983, the French published their photos in the American journal Science, along with a paper describing the discovery of the virus. The French paper went practically unnoticed, but two papers by Gallo in the same issue of Science received much more attention.

Despite the French discovery that the AIDS virus behaved in a profoundly different way than HTLV and was clearly not a leukemia-causing virus, the Gallo papers nonetheless suggested that the cause of AIDS must be HTLV.

In September, 1983, Gallo and Montagnier attended an international virology conference at Cold Spring Harbor, N.Y., where Montagnier gave a talk about the virus he had since named LAV, for lymphadenopathy associated virus. Lymphadenopathy, or swollen lymph glands, is a condition that often precedes AIDS.

Among other things, Montagnier reported that his team had found LAV antibodies in 22 of 35 patients suffering from lymphadenopathy--fairly conclusive evidence that LAV was the cause of AIDS, which is why some of those present recall being surprised at the force with which Montagnier's ideas were attacked by Gallo.

The attack is particularly surprising in retrospect, because Gallo and his colleagues at the National Cancer Institute had been trying to replicate the French experiments for months, but without success.

In the spring of 1983, according to documents contained in the French lawsuit, Gallo had written to Montagnier, with whom he had a longstanding professional relationship, asking for samples of LAV from which the NCI team hoped to be able to grow the virus on its own.

The material was supplied in July, 1983, but Gallo was apparently unable to grow the virus. He asked for more and, on Sept. 23, the obliging Pasteur Institute forwarded two more samples of LAV to NCI.

The basis for the institute's lawsuit is its claim that NCI later breached the stipulation which accompanied the samples: that the virus "not be used for any industrial purpose" without Pasteur's consent.

In May, 1984, Gallo and his colleagues at NCI published news of their own "discovery" of the AIDS virus in Science. It was nearly a year to the day after the magazine had published the French paper on AIDS, but the Gallo article makes no mention of LAV.

After many trials and errors with the French virus, the NCI team said, it had finally isolated the virus from the blood of 10 American AIDS patients. Despite its dissimilarity to either of his previously discovered HTLV viruses, Gallo named his AIDS virus HTLV-III.

There were, however, two problems. One, later uncovered by the Manhattan law firm representing the Pasteur Institute, was that the photographs of HTLV- III that ran with the Science article were really photographs of the French virus samples supplied to NCI by Pasteur--photographs taken at a time when Gallo said he had been unable to grow the French virus.

The other problem was that the genetic structure of LAV and HTLV-III were not quite identical, but nearly so--an improbable similarity even for two strains of the same virus, and particularly improbable for the highly mutable virus that causes AIDS.

A few weeks before publication, Gallo sent the CDC some of his AIDS- infected cells. As one CDC official described it later in a memo, "It was a tense moment, fraught with the possibility of non-delivery."

The tension arose when the CDC offered to microscopically compare Gallo's virus with the French LAV. According to the memo, "Dr. Gallo declined each time, stating that such work would be done in his lab."

Donald Francis, then a senior CDC researcher who is now with the California Department of Health Services, made the comparison anyway. It was mainly because of that test, Francis recalled in an interview, "that we at CDC told NIH, 'You can't announce you've discovered AIDS, because the French already did.'"

Gallo has tried to explain the similarity between LAV and HTLV-III by suggesting that the French male homosexual from whom LAV was cultured originally had actually contracted AIDS during a visit to New York City, where some of his AIDS patients had also contracted the disease.

In their lawsuit, however, the French assert that "Dr. Gallo and certain of his colleagues essentially took LAV, renamed it HTLV-III and then claimed and exploited it as their own."

It is another way of saying that Gallo's team never independently isolated the AIDS virus and that, whether by accident or otherwise, the NCI virus cultures had become contaminated with LAV.

Apart from the questions of competition, contamination and intent, there is the far larger matter of what was lost. In a lengthy article on the dispute last February, the respected British magazine New Scientist quoted Cambridge biologist Abraham Karpas as declaring that "a full year was wasted" because of the dispute.

"In that time many lives could have been saved, many infections could have been prevented," Karpas was quoted as saying. "Gallo's preoccupation with HTLV as the cause of AIDS led many people in the wrong direction at a critical stage in AIDS research."

If so, it was a year during which blood supplies in this country could have been tested for AIDS, a year during which individuals infected with AIDS remained unaware of their condition and continued to spread the disease, a year in which progress toward an AIDS vaccine was delayed.

Asked whether such an assessment was an overstatement, JAMA editor Lundberg replied, "It's unfortunate, but it may be true. I'm just embarrassed about the whole thing."

The real problem, Francis says, was that, like Gallo, many American researchers "couldn't accept that the French had found this important virus before we did. I was very heavily influenced by Bob. But by September of 1983, it became clear that we had all made a very big mistake.

"Everyone is sick about it. This controversy has polarized the scientific community. It has hurt the field. No one wants to talk about it."

The fact that the AIDS virus does not belong to Gallo's HTLV "family" of human retroviruses was recognized officially last summer, when the International Committee on the Taxonomy of Viruses changed its name to Human Immunodeficiency Virus, or HIV.

But Gallo continued to call the virus HTLV-III until last spring, when an out-of-court settlement of the French lawsuit was announced. The announcement followed an informal agreement by President Reagan and French Prime Minister Jacques Chirac that neither science nor diplomacy had anything to gain from a protracted public battle.

The French were accorded equal recognition as the discoverers of AIDS and an equal share of the profits from patent royalties paid by the makers of AIDS testing kits. As a condition of the settlement, everyone involved has agreed not to speak publicly about the dispute.

The settlement, which halted the production of thousands of pages of NIH documents, including some of Gallo's lab notes, also has left unresolved the major questions about what happened. But one source close to the case says, "It's an open secret at NCI that there never was an HTLV-III."

Francis agrees. "The viruses are too similar," he said in a recent interview at his laboratory in Berkeley, Calif. "Bob (Gallo) should have compared them, should have known that he had the French virus. He had all that information from Cold Spring Harbor, but he was ignoring it. Regardless of how it happened, LAV got into his culture."

For his part, Gallo has consistently rejected any suggestion of unethical behavior. In a brief telephone conversation last week, he dismissed the French allegations as "the same stupid innuendo, and I've had it with stupid innuendo. I don't care what you write. This is our last conversation. Don't call my lab again."

CAPTION: Graphic: AIDS spending By U.S. Public Health Service agencies In millions of dollars per fiscal year (1982 thru '86++). +Estimate ++ Appropriate

Chicago Tribune Graphic; Source: U.S. Public Health Service.

Photo: SIPA photo. Dr. Robert Gallo of the National Cancer Institute: His claim that an AIDS virus he isolated in Nigeria posed no known danger, and represented no "reason for panic," confused some researchers.

Photo: SIPA photo. French researcher Luc Montagnier, who clashed with American researchers, including Gallo, over an AIDS advance.

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