The New York Times - Friday, January 23, 2004
Andrew Pollack

One of the nation's most prominent AIDS researchers is partly retracting a scientific paper in which he claimed to find an elusive substance that protects some people from the disease.

In addition to being an embarrassment to the researcher, Dr. David Ho, the admission means that one of the great mysteries of AIDS -- why some people with H.I.V., the virus that causes AIDS, do not become ill -- remains unsolved.

In his retraction, Dr. Ho says the substances he identified were not produced by the cells he thought produced them but were introduced into the experiment by contamination. The substances are nevertheless active in test-tube experiments against H.I.V., he says.

The retraction appears today in the journal Science, which published the original paper in 2002. The findings caused a stir at the time, but many scientists were skeptical, and yesterday some said they were not surprised by the retraction.

"It's gratifying to see they recognize this and came forth to correct it," said Dr. Jay A. Levy of the University of California at San Francisco, editor in chief of the journal AIDS. "It's very tough to get someone to retract a paper."

Dr. Levy and some others said they did not think the reputation of Dr. Ho, the director of the Aaron Diamond AIDS Research Center in New York, would be harmed.

"We've all done things we tried to repeat and they didn't work," said Dr. Douglas Richman, an AIDS expert at the San Diego Veterans Affairs Medical Center. "That's the nature of the frontiers of science."

Still, some pointed out that the retraction is attracting attention because the initial paper got so much publicity. "What made it a little special and a little provocative was the way the first paper was handled, or nobody would have noticed the correction," said Dr. Robert Gallo, director of the Institute of Human Virology at the University of Maryland.

Researchers have long been intrigued that a small percentage of people infected with H.I.V. live 10, 15 or even more years, with no treatment, without progressing to AIDS.

Dr. Levy first observed in the 1980's that certain immune cells of these people, known as long-term nonprogressors, produce something that seems to keep the virus at bay. Since then a race has been on to identify this substance, called CD8 antiviral factor, or C.A.F., after the type of immune cell that produces it.

"It's exciting to think there are natural antivirals that we don't know yet that could be exploited," said Dr. Mary E. Klotman, chief of the infectious diseases division at Mount Sinai School of Medicine.

In their paper in 2002, Dr. Ho and his colleagues said alpha-defensins, small proteins the body produces to kill bacteria, were "a major component of the long-sought-after C.A.F."

But in what Science today calls a "retraction of an interpretation," Dr. Ho and his colleagues say the alpha-defensins are not produced by CD8 cells.

In an interview, Dr. Ho said the finding that the defensins have activity against H.I.V. could still be important, even if they are not produced by CD8 cells. "We are saying the anti-H.I.V. activity of the defensins is not in question," he said.

But others said that the antiviral activity of alpha-defensins had already been known and that their usefulness for helping treat AIDS was uncertain.

Even when the original paper was published, some scientists said a potential flaw in Dr. Ho's experiment was that he grew the CD8 cells in culture along with some other white blood cells. Some of those other cells might have produced the defensins, they said. And that is indeed what happened.

Dr. Ho and Dr. Linqi Zhang, the first author on the paper, said in an interview that the cultures were supposed to contain only B and T cells. But they contained a tiny amount of other white blood cells, called neutrophils, which produce defensins.

Dr. Ho and Dr. Zhang said they used a technique that had been commonly used in the field to prepare cultures, assuming that neutrophils would be kept out. "What we have taken for granted in the field over the years is not necessarily correct," Dr. Zhang said.

The retraction comes after the publication of two papers -- one by a group led by Dr. Levy and the other by Dr. Klotman and colleagues -- reporting that no defensins could be found in cultures of CD8 cells. But Dr. Ho and Dr. Zhang said they found the error on their own.

Dr. Levy said Dr. Ho's paper had delayed the search for the factor by causing some scientists to drop their search for C.A.F. and others to spend time studying alpha-defensins. "We're closer than a year ago, but we had to spend a lot of time ruling out the alpha-defensins," he said.

Still, some say that molecules called beta chemokines have already been identified as partly responsible for the antiviral effect, and it is not clear whether there is more to be found or how important the finding will be.

"I've always had a sense of skepticism about whether it exists and, if it does, whether it's important," Dr. Richman of San Diego said. "How many years do you have to spend looking for it before you conclude it doesn't exist?"

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