Blitzing the AIDS Virus

updated 03/08/1993 AT 01:00 AM EST

originally published 03/08/1993 AT 01:00 AM EST

SETTLING DOWN TO DINNER, YUNG-KANG Chow had an idea so powerful he nearly choked on a mouthful of rice. "That moment is crystal clear," says Chow, recalling the evening of Aug. 11, 1991. "I was so excited, all I could say was 'ahhh.' " His wife just smiled when he rose from the table and began jumping up and down; she was used to bursts of enthusiasm when the 31-year-old Harvard medical student had a brainstorm.

But this was no ordinary brainstorm. Chow's idea led researchers at Boston's Massachusetts General Hospital to the announcement two weeks ago of a radical new approach to AIDS research. In test-lube experiments, Chow's novel strategy succeeded in preventing HIV, the virus that causes AIDS, from growing and spreading to other cells.

Traditionally researchers fight an unwanted microbe—such as a virus—by combination therapy, hitting it with several drugs aimed at different targets in the organism. Chow's idea, now called convergent combination therapy, was to attack only one part of the virus—in this case, the enzyme that replicates HIV's genetic code—with a simultaneous barrage of drugs. Explains Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md.: "As a virus, you get a deadly choice. Either you don't mutate and one of these drugs is going to kill you, or you mutate enough to avoid all the drug, and the mutation is so profound you're out of existence."

It took seven months for Chow and a team of six scientists at Mass. General's Infectious Diseases Unit to con-duet preliminary experiments and concoct lethal brews of AZT, ddl (both already marketed as anti-HIV drugs) and one of two experimental drugs, pyridinone or nevirapine. Chow was consumed by the problem. "I was thinking about it day and night," he says. "When I ate, when I went to the bathroom, when I did everything." Sometimes he worked without sleep for several nights in a row, sustaining himself with vending-machine burgers.

Once the combination of drugs had been determined, the team bombarded test-tube cultures of HIV. After 35 days, no HIV infection was found. A colleague recalls that the normally reticent Chow punched the air and cried, "Yes!" when he saw the results. "That was a special moment," says Chow.

Still, AIDS researchers remain cautious. "The human body is a much more complex system than working in a test tube," says Dr. Martin S. Hirsch, director of AIDS research at Mass. General. "First, all drugs have toxicity, so we don't know if this will be too much for patients to tolerate. Second, each infected person carries an enormous amount of virus, which may be able to mutate and evade this therapy. Third, there may be parts of the body that can hold reservoirs of the virus we can't reach." Tests of the therapy on 200 volunteers who are HIV positive will begin this spring at 10 medical centers across the country. Ironically, Chow, who is in the sixth year of a seven-year combined M.D.-Ph.D program, is not yet a physician and won't be able to participate officially.

Chow has wanted to be a doctor since boyhood. When he was 8, his father, a cardiologist with a strong streak of idealism, moved the family from a comfortable life in Taiwan to Libya, where doctors were in short supply. "I would go with him to his clinic and watch him put the stethoscope to people's chests," Chow remembers. "He didn't speak much Arabic; they didn't speak any English. But somehow a feeling of caring came across."

There was little other diversion. "When you grow up living in the Sahara, there isn't a heck of a lot to do," says Chow. He was taught bridge at 8, while his brother, Yung-Chiong, learned the game at age 3. "We needed a fourth," explains Chow. At 14, Chow was sent to a prep school in up-stale New York. He earned a B.A. in biology at Rutgers and became an endocrinology researcher at Columbia. "I enjoyed medical research very much," he says, "but I wanted to take care of people."

The program at Harvard leaves Chow little time to spend with his wife, Sabrina, 26, a pharmacist, and their 3-month-old daughter, Tiffany, in the suburban Chestnut Hill house they share with Sabrina's mother and sister. "Sometimes, when I'm in the lab all alone at 3 a.m., I wonder, 'What kind, of a life is this?' " says Chow. Then he considers the hope and expectations his discovery has created. "I feel an awesome responsibility," he says.

MARILYN ACHIRON
HEIDI J. LAFLECHE in Boston

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