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Unfortunately, Hirsch was not Midas, and he couldn't afford to pay his postdocs more than the standard $18,000 yearly stipend. To support his family, Ho started moonlighting in Mass General's walk-in clinics. It turned out to be the right time to be in that place too. "The clinics are where you see the flus, the colds, the common illnesses," Ho says. In the mid-1980s, however, he started seeing gay men with what appeared to be an unusually severe flu. They always got over their illness without any of the hallmarks of AIDS. Still, he wondered, could there be a connection? Could these flu-like ailments be the signs of the men's very first exposure to HIV?
Sure enough, blood tests showed that the "flu" corresponded with the sudden appearance of HIV--and the total absence of any influenza viruses. Then, after a few weeks, the antibodies in the immune system would jump sharply while HIV disappeared from the circulation. It was the first evidence that HIV triggered an active infection. But not even Ho would recognize its significance until years later.
LEARNING FROM FAILURE
Despite rising casualties, Washington kept tight purse strings on funding for AIDS research for much of the 1980s. By 1987, though, even Ronald Reagan knew that AIDS was a serious threat. The plague had encircled the globe, stretching from Africa to Asia. The antibody test revealed the presence of HIV in the blood supplies of the U.S., France and Japan. The FDA approved use of the antiviral drug AZT in a record 14 weeks.
At that time, scientists across the U.S. were excited about a possible breakthrough treatment: soluble CD4. They knew that HIV does not infect T cells at random. It must first attach itself to a particular protein, called CD4, on the T cells' surface. Perhaps, researchers reasoned, if they flooded the bloodstream with free-floating CD4 molecules, the molecules would act as decoys and prevent HIV from infecting the T cells. Preliminary tests on viral samples grown under laboratory conditions showed that soluble CD4 worked beautifully.
Ho had taken a junior faculty position at UCLA and moved his family back to California. He contacted Dr. Robert Schooley of the University of Colorado Medical Center in Denver, and together they embarked on a clinical trial of soluble CD4 in two dozen patients, many of them in the later stages of AIDS. Unfortunately, Ho and Schooley wound up proving that soluble CD4 doesn't work. In the process, however, they discovered something very interesting--that there were tens of thousands of infectious viral particles in their patients' bodies, a lot more than anyone had expected.
It took Ho only a few weeks to figure out why soluble CD4 didn't work. The early tests on the treatment were done on weak strains of virus grown in the lab. Somehow wild viruses could tell which CD4 molecules were decoys. Ho and the rest of the AIDS scientists had just learned a valuable lesson. They would have to test all their potential treatments on viruses that infected real patients.
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