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New York Times
Saying Strategy to Find Cure for AIDS Has Gone Awry, Researchers Seek Redirection
GINA KOLATA
May 12, 1994

A new consensus has emerged among many leading scientists that the nation's $1.3 billion AIDS research program is on the wrong track.

The notion that the AIDS effort needs to be redirected has been discussed for some time, but little has changed. Emphasis on quick testing of drugs and vaccines has continued, in spite of a widespread feeling of frustration and a sense that the research is far more complicated than many scientists had thought.

Now, in a paper being published today in the scientific journal Nature, Dr. Bernard Fields, the chairman of the department of microbiology and molecular genetics at Harvard Medical School, has articulated a blueprint for change that crystallizes the issues and calls for looking more broadly at research that could bring a new understanding of the disease process. His paper was widely circulated among other leading researchers before publication, and many, including Dr. Harold Varmus, the director of the National Institutes of Health, say they endorse his comments. Federal AIDS administrators say they expect to make some changes along the line Dr. Fields is suggesting.

Dr. William Paul, the recently appointed head of the Office of AIDS Research, which directs the nation's AIDS research programs, has said he regards the new thinking as his "marching orders."

In the first 10 years after the virus was discovered, Dr. Fields writes, government research emphasized basic and clinical investigation on the virus and the disease, and in many aspects the research was "highly successful." Now Dr. Fields writes, we need to put increasing emphasis on understanding the basic biology of AIDS and of H.I.V., the virus that causes the disease. For instance, how the virus gets into the cell is still unknown. Wider Definition Sought

Reflecting the views of many scientists, Dr. Fields writes that the very definition of AIDS research needs to be broadened, to include research on diseases that might at first glance seem to bear little relationship to AIDS. The AIDS effort initially seemed straightforward, Dr. Fields said, because scientists had recently successfully combatted another deadly viral disease -- polio -- using an approach that could be summed up as "isolate the virus, develop a vaccine and prevent the disease." AIDS researchers were led astray by that success, Dr. Fields writes. The AIDS virus is far more complex than the polio virus and biologists need to understand its basic mechanisms before developing a vaccine or testing drugs.

"I think we got a little bit too cocky too early," said Dr. Arnold Levine, a molecular biologist at Princeton University who was among those given an early look at Dr. Fields's paper. H.I.V. has features never before seen in a virus or disease, Dr. Levine said. The biology of those features remains unclear. Among those features are the virus's propensity to mutate at a breathtaking rate, its ability to thrive with a multitude of mutations and its tendency to remain dormant for up to a decade before causing disease. "Inherent in the biology must be the weak spots, something we could attack," Dr. Levine said.

But Dr. Ashley T. Haase, who is chairman of the Department of Microbiology at the University of Minnesota Medical School and who is chairman of a group that advises the Federal Government on AIDS vaccines, said he was not persuaded of the need for change. A great deal of basic research is already under way, he said, and it is not clear that a large change is needed.

"It's premature to conclude that we are making the wrong bets," Dr. Haase said. "If you wanted to argue that you want to fine-tune the machinery now, to take some money in drug trials or vaccine studies and put it in basic research, that's an argument you could readily sustain," he said. "But every time you want to take a little money and move it, you have 15 scientific communities yelling at you."

Dr. Fields and others also say that it is time for a careful look at vaccine and drug-development programs. These are costly, draining money from other research, and, as Dr. Fields writes, "have little or no scientific rationale." For instance, a proposal by the National Institutes of Allergy and Infectious Diseases, which will be decided on next month, calls for tests of two vaccines to be given to people at high risk of H.I.V. infection. The full scale tests would cost $20 million to $30 million. But the two vaccines do not generate antibodies against the strains of H.I.V. that are found in people. Nevertheless, last month, an advisory committee recommended that the vaccine trials go on anyway, although, if possible, in a scaled down form.

Dr. Haase reluctantly defended the decision, saying researchers do not know what it would take to protect someone against H.I.V., so "the thing might work anyway." Nonetheless, Dr. Haase said, "it's the worst decision I've ever been involved with."

Dr. David Baltimore, Nobel laureate and molecular biologist at Rockefeller University, said, "That's anti-science. Science usually progresses by an accumulation of evidence leading to a particular conclusion. In this case, all the information leads to the conclusion that it won't work."

Dr. David Ho, director of Aaron Diamond AIDS Center in New York, said that although change is essential, it could be very difficult now, when so much is invested in the current system. "It's very hard to reverse momentum once it's built up," he said. "There have been quite a bit of targeted programs to develop drugs, to test drugs, to test vaccines. We have created a rather huge infrastructure," he said. "The question is, since we have relatively few vaccine or drug products feeding into this system, is it the right thing to have set up this infrastructure?"

The AIDS paradigm was articulated on April 24, 1984, by Margaret M. Heckler, who was then Secretary of the Department of Health and Human Services. Announcing the discovery of the AIDS virus, she predicted an AIDS vaccine within two years. Even though the prediction proved wrong, research has remained guided by the idea that finding the virus was the hard part, and vaccines could be made by simply injecting people with crucial viral proteins and drugs could be found to stop the virus from causing disease.

It is exactly this model for AIDS research that Dr. Fields and others are questioning.

Dr. Varmus, who was one of those who read the report before its publication, said, "Everyone agrees with Bernie's basic precept."

Dr. Paul, director of the Office of AIDS Research, said he asked leading scientists what directions to follow. And, he said, they basically told him what Dr. Fields said. "We take that as our marching orders," he said.

He said the AIDS budget for fiscal year 1995 has already been submitted, so it is essentially too late to alter it. But he said, "I think the 1996 budget will reflect a different emphasis."

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