William H. Prusoff, a pharmacologist at the Yale School of Medicine who, with a colleague, developed an effective component in the first generation of drug cocktails used to treat AIDS, died on Sunday in New Haven. He was 90 and lived in Branford, Conn.
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William H. Prusoff worked at the Yale School of Medicine.
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George Ruhe for The New York Times
The death was confirmed by his son, Alvin.
Dr. Prusoff spent most of his long career studying molecular derivatives of thymidine, a building block of DNA. His work led him to develop two important antiviral drugs.
In the early 1950s, he synthesized idoxuridine, a successful treatment for infant keratitis. The condition, an inflammation of the cornea caused by the herpes simplex virus, was the leading infectious cause of blindness. Idoxuridine disrupted the virus’s ability to reproduce.
This was an important breakthrough. At the time, it was believed that antiviral agents powerful enough to be effective would be too toxic for human use and that those safe for use would be too weak to counteract a virus.
Idoxuridine overturned medical dogma and, after winning approval by the Food and Drug Administration, became the first clinically used antiviral drug. For this reason, Dr. Prusoff is sometimes called the father of antiviral chemotherapy.
In the mid-1980s, as the AIDS epidemic spread, Dr. Prusoff and a Yale colleague, Tai-shun Lin, began looking at thymidine derivatives that had been developed to treat cancer but discarded when they proved ineffective. One of these was stavudine, also known as d4T, a molecular cousin of the first AIDS drug, AZT. Both had been synthesized in the 1960s by Dr. Jerome P. Horwitz at the Michigan Cancer Foundation, now the Karmanos Cancer Institute, in Detroit.
Dr. Prusoff and Dr. Lin resynthesized the molecule and found in laboratory tests that it short-circuited the viral enzyme in H.I.V., causing it to produce short, incomplete pieces of DNA rather than complete strands.
Yale took out a patent in the doctors’ names and licensed it to Bristol-Myers Squibb for development. In 1992, it became the first drug to be tested under the F.D.A.’s parallel-track policy, which allowed patients with life-threatening illnesses to obtain drugs undergoing clinical trials.
After F.D.A. approval, stavudine was brought to market in pill form in 1994 and sold under the brand name Zerit. It joined three other drugs, known as nucleoside analogs, approved for treating H.I.V.: zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC). Eventually, these were joined by a new generation of drugs known as protease inhibitors.
Because of its potential side effects, notably numbness, burning sensations and loss of fat in the feet, legs or hands, the drug is now used primarily in poor countries, where it is cheap and widely available.
Stavudine earned tens of millions of dollars for Yale each year — more than the total amount for all its other licensed medicines combined. It also made millions for Dr. Prusoff, who became a vocal supporter of a campaign initiated by Doctors Without Borders to persuade Bristol-Meyers to lower the drug’s price in sub-Saharan Africa, where AIDS was rampant.
In March 2001, the company announced that it was reducing the price of the drug in Africa to 15 cents for a daily dose, from $2.23, and removing barriers to the sale of generic equivalents there.
“We weren’t doing this to make money,” Dr. Prusoff told the Yale School of Medicine Chronicle. “We were interested in developing a compound that would be a benefit to society.”
William Herman Prusoff, known as Bill, was born on June 25, 1920, in Brooklyn. His parents, Jewish immigrants from Russia, ran a small grocery.
He earned a degree in chemistry from the University of Miami in 1941. Rejected by the Army because of his poor vision, he spent World War II inspecting fuses at a munitions factory in Memphis and, as a health inspector, checking the water supply and the kitchens in Miami Beach hotels where pilots were billeted.
Urged by his parents, he applied to medical school, without success. He later enjoyed recalling that Yale deemed him so unqualified that it refunded his application fee in a gesture of pity.
Instead, he earned a doctorate in chemistry from Columbia in 1949 and then taught pharmacology in Cleveland at Western Reserve University (now Case Western Reserve) before joining the pharmacology department at Yale in 1953.
Dr. Prusoff used some of his patent money to create the William H. Prusoff Foundation, which supported numerous programs, including the Yale Initiative for the Interdisciplinary Study of Anti-Semitism. He also endowed lectureships in virology and pharmacology at Yale and several scientific prizes.
In addition to his son, Alvin, of Fairfield, Conn., he is survived by a daughter, Laura, of Ortahisar, Turkey, and three grandchildren.
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