In memoriam: William H. Prusoff

William H. Prusoff, a member of the Yale School of Medicine faculty for 57 years and a pioneer in the development of antiviral agents, passed away on April 3.

William H. Prusoff, a member of the Yale School of Medicine faculty for 57 years and a pioneer in the development of antiviral agents, passed away on April 3.

A memorial service in his honor will be held at 2 p.m. on Sunday, April 17, at the Thomas More Center, 268 Park St. — directly across from Pierson College, where Prusoff was a fellow. A reception with friends and family will follow immediately afterward.

Prusoff was born in 1920 in New York City, the son of a grocer. Alarmed by the rise of pro-German sentiment and the prevalence of Nazi sympathizers in Queens in the late 1930s, the family moved to Miami, where Prusoff eventually majored in chemistry at the University of Miami. On several occasions during World War II, he tried to enlist in the armed forces and each time was rejected because of poor eyesight. He spent the war as a munitions inspector in Memphis and a water quality tester for troops stationed in Miami.

After the war and unsuccessful attempts to be admitted to medical school (including Yale), he obtained a Ph.D. in chemistry at Columbia University and then joined researcher Arnold Welch at Western Reserve University (now Case Western Reserve).

When Welch was recruited to Yale to head the pharmacology department in 1953, he brought Prusoff with him. Prusoff soon synthesized 5-iodo-deoxyuridine, one of the first nucleoside analogues. This compound was later shown to have antiviral activity, and it found widespread use as a preventive of herpes virus keratitis in infants. This was the first clinically used antiviral drug. Prior to the synthesis of this compound, it had been thought impossible to develop effective, nontoxic antiviral agents. For this seminal work, Prusoff has been called “the father of antiviral chemotherapy.”

In the 1980s, the AIDS epidemic was raging and was shown to be caused by a novel retrovirus, human immunodeficiency virus (HIV). Prusoff and his late Yale colleague Tai-shun Lin showed that a failed cancer compound, d4T, was active against HIV. After securing the patent for d4T, Yale licensed it to Bristol-Myers Squibb, which commercialized it as Zerit, which soon became a component of the first combination drug therapy for HIV. Millions of people worldwide have been treated with d4T, and the AIDS epidemic was slowed until more effective drug combinations were developed. This compound generated huge revenues in royalties for Yale, far surpassing the amount generated by all of its other licensed medicines combined.

Prusoff was the recipient of numerous awards, including the Peter Parker Medal, the highest award from the Yale School of Medicine, and the inaugural Lifetime Achievement Award from the Yale Comprehensive Cancer Center. He was featured twice in the recent bicentennial history of the Yale School of Medicine, for work done in two different decades.

In addition to his landmark scientific contributions, Prusoff was known for his generosity. Under his direction, the William H. Prusoff Foundation supported numerous programs, including the Yale Initiative for the Interdisciplinary Study of Anti-Semitism (YIISA). He also endowed several lectureships in virology and pharmacology at Yale, funded several scientific prizes, and supported the research of several individuals and laboratories at Yale. When Doctors Without Borders and Yale students called on the University and Bristol-Myers Squibb to make Zerit available at low cost in impoverished areas of the world, Prusoff actively joined in the campaign. “We weren’t doing this to make money,” he said. “We were interested in developing a compound that would be a benefit to society.”

Prusoff was married to the late Dr. Brigitte Prusoff and is survived by his two children, Alvin and Laura; his daughter-in-law Dr. Deborah DeRose Prusoff; and three grandchildren, Sarah, Zachary and Douglas.

Donations in Prusoff’s memory may be made to the William H. Prusoff Foundation, 880 Old Post Rd, Fairfield, CT 06824-8403.

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