Science & Technology: MEDICINE
BOB GALLO'S NEW WEAPON AGAINST AIDS
A discovery of HIV-fighting natural chemicals-and a new institute-return him to the research forefront
Just a few years ago, Dr. Robert C. Gallo's life was "worse than a series of Kafka nightmares," he recalls. The National Institutes of Health and the feared Energy & Commerce Committee bloodhounds of Representative John D. Dingell (D-Mich.) were investigating the prominent National Cancer Institute scientist for possible misconduct. The charge: that the fiercely competitive, hot-tempered Gallo had grabbed too much credit for the discovery of the AIDS virus--perhaps even stealing HIV itself from French rivals.
His well-funded lab--famous for discovering the first human tumor virus, proving that HIV causes AIDS, and developing a blood test for the disease--was virtually paralyzed. "Depending on the time of day, I felt either like the Angel Gabriel or Lucifer," he says.
COLORFUL CAREER. Now, the 58-year-old virologist is definitely back on the side of the angels. The NIH probe never found any wrongdoing and the congressional investigation ended after last year's Republican victory. "We never did get to the truth," sighs former Dingell sleuth Bruce F. Chafin. Meanwhile, Gallo's colorful career is soaring again. On Dec. 19, a Maryland legislative committee approved $9 million in state money to set Gallo up as head of a new Institute of Human Virology at the University of Maryland. The same month, his lab scored another major coup in the struggle to understand AIDS--identifying long-elusive natural chemicals that cells use to suppress the virus.
"This is great for the field--and for Bob," says AIDS researcher Dr. Anthony S. Fauci, director of the National Institute of Allergy & Infectious Diseases. "In spite of the fact that the guy's been knocked around for the last five years, he's now got his own institute, and bingo, he has made a major discovery."
Gallo's rebound comes amid other encouraging news in the fight against AIDS. The past year has brought both major new knowledge about the virus and important new drugs. And the recently identified natural substances "open up a whole new avenue for thinking about how to control HIV," says Gallo. These developments, as well as progress with vaccines and other drugs in the lab, lead him to proclaim that "AIDS will be a clinically curable disease in the next 10 years."
Most researchers would be reluctant to stake a claim on so difficult a foe as AIDS. But the statement is vintage Gallo. "Sticking my neck out stimulates me to do more work," he says. Others wish the virologist would think more before he opens his mouth. "My mother told me this would be my death knell if I didn't cut it out," he admits.
He never will, of course. But Gallo's 10-year prediction could be more than just hyperbole. Last January, for example, David Ho of the Aaron Diamond AIDS Research Center in New York and George Shaw of the University of Alabama proved that HIV doesn't mysteriously lie dormant in the body only to emerge years later, as once thought. Rather, the virus goes on the attack from the very start, making up to a staggering 10 billion copies a day.
Yet confronted with this pernicious assault, the immune system does manage to keep the upper hand for years--sometimes even a decade or more (illustration, page 88). Scientists now believe that dramatic gains could be made by providing the body's natural defense with a little help early on. "This is the most hopeful thing to come out in years," says Dennis M. Burton of Scripps Research Institute. "The virus is not a sinister thing waiting to hop out. Instead, it wins just by grinding you down."
Simply reducing viral levels in the body might stave off the progression to AIDS for years. The first drug approved for the disease, AZT, doesn't do the trick because the rapidly mutating virus quickly develops resistance. But since November, the Food & Drug Administration has added to doctors' arsenals by approving Glaxo Wellcome PLC's 3TC and Hoffmann-La Roche's saquinavir. Along with others in the development pipeline at drugmakers such as Merck & Co., these treatments are not only more potent than AZT, but in various combinations, "they work infinitely better than AZT alone," says Max Essex, chairman of Harvard University's AIDS Institute.
No one expects combinations of drugs, however promising, to be the sole answer. The virus will develop resistance, and there are major questions about long-term toxicity and cost. That's why many scientists are excited by the identification by Gallo--and by Reinhard Kurth of Germany's Paul-Ehrlich-Institut--of naturally suppressive chemicals.
As far back as the 1980s, Jay Levy, a virologist at the University of California at San Francisco, showed that certain immune-system cells--called killer T-cells, or CD8 cells--release chemicals that suppress HIV in test tubes. But many scientists discounted the finding because no one could identify the chemicals.
Until Gallo. Originally, the NCI scientist stayed out of the search. But by 1994, some of his AIDS-vaccine experiments were giving contradictory results. There was no way of explaining why some vaccinated animals were protected against the virus and others weren't. "We got tired of saying, `Could the reason be the bloody CD8 factor?"' Gallo recalls. So when the answer didn't come from Levy or others, "I had to do it," he says.
TWO FINDINGS. Gallo's team, led by Paolo Lusso and Fiorenza Cocchi, had one big advantage. Over the years, his lab had generated a key research tool: a number of killer T-cell lines that could be grown indefinitely. Some of the cell lines produced copious amounts of natural substances for regulating the immune system. From there, it was conceptually simple, if technically challenging, to identify a cell line that suppressed the virus. Then researchers purified and identified the chemicals the cells made.
It turned out that there were three chemicals involved, and all three need to be present to suppress the virus. The substances were known "chemokines," a class of chemicals the body uses to call in immune cells. According to work by Germany's Kurth, another suppressive substance, interleukin-16, may also be involved.
These substances are unlikely to work as drugs. "We don't know how to control them, or what the side effects will be," explains Stanford University AIDS researcher Thomas C. Merigan. And Levy, for one, believes something else--still undiscovered--is the key CD8 factor. But when scientists learn exactly how the chemicals manage to block HIV in the test tube, it may be possible to develop drugs that mimic their action or boost their natural production. Gallo hints that he's close to figuring out how the chemokines work.
Having Gallo hot in pursuit of the mechanism is bad news for his competitors. Not only is Gallo likely to win, but many rivals resent the way he trashes their work in the process. "Gallo isn't the kind of person who can merely be a major player in a field, he has to monopolize it," according to one critic.
Gallo himself admits to past excesses of "vainglory" and temper. "My skin is probably way too thin for someone in the position I'm in and who exerts ego," he says. Yet his weaknesses may also be his greatest strengths. "He looks at a competitor almost like an enemy," explains one friend. "That gets him in trouble. On the other hand, that's the driving force that makes him great."
GAMBLE. Now, Gallo is bringing his determination to his new institute in Baltimore. The goal, he says, is nothing short of curing AIDS. As he sees it, the institute will be able to rush research advances into a clinical unit headed by Dr. Robert R. Redfield, former chief of retroviral research at the Army's Walter Reed Army Institute of Research in Washington. A company called Omega Biotherapies Inc. has been set up by Gallo and private investors to commercialize promising therapies.
The whole enterprise is a gamble for Maryland, which outbid Virginia, Pennsylvania, and South Carolina in wooing Gallo. "It was clear that this was a man whose scientific reputation was extraordinary," says James T. Brady, Maryland's secretary of business & economic development. But with Gallo's lab making progress not just with chemokines but also hormones and vaccines for tackling AIDS and its complications, it looks like the right move. "In the area of investments that people make in scientists, I think this is as good a bet as you can get," says the NIAID's Fauci. Gallo may never live down his controversial past, but at least his Kafkaesque nightmares are over.By John Carey in WashingtonReturn to top