Jerome Horwitz (1937–2012), Samuel Broder (b. 1945), Hiroaki Mitsuya (b. 1950)
In 1981, a mysterious disease was sweeping through the gay population of San Francisco and New York. The disease, which devastated the immune system, was caused by the human immunodeficiency virus (HIV) and designated acquired immune deficiency syndrome (AIDS). Once this retroviral target had been identified, the search began for a drug treatment and led to the discovery of AZT (azidothymidine).
In 1964, Jerome Horwitz at the Karmanos Cancer Institute in Michigan initially synthesized AZT as a potential anti-leukemia drug, but it was proven ineffective. It was shown to be active against a retrovirus in the 1970s; but at this time, AIDS was unknown, and there was little interest in retroviruses. All this changed in the early 1980s, when AIDS patients were dying in droves around the world.
The National Cancer Institute (NCI) assumed responsibility for leading the government’s efforts to find an AIDS treatment. To this end, the NCI’s Samuel Broder conceived of an unusual partnership with the pharmaceutical industry. Companies could send potential compounds to the NCI, where they would be screened for anti-HIV activity. Burroughs Wellcome (now GlaxoSmithKline) had expertise in working with antiviral drugs such as acyclovir. In 1984, virologist Martha St. Clair and chemist Janet Rideout were instrumental in identifying and sending AZT to NCI, where Broder and Hiroaki Mitsuya more exhaustively examined it. Their positive laboratory findings were confirmed in AIDS patients at Duke University in 1985—news optimistically received by more than 10,000 AIDS patients. Clinical trials were initiated in January of the following year, and in an incredibly short fifteen months, the Food and Drug Administration approved AZT, which was renamed zidovudine and marketed as Retrovir.
This remarkable triumph of drug development and the NCI–Burroughs Wellcome partnership were marred by subsequent disputes over discovery credits, patent rights, and what was perceived to be an exorbitantly high price for the medication. AZT is now an integral component of a successful multidrug combination (HAART) used to both successfully treat AIDS and to prevent mother-to-child transmission of HIV during pregnancy and delivery.
SEE ALSO Food and Drug Administration (1906), Acyclovir (1982), HAART (1996), Viread (2011).
The human immunodeficiency virus (HIV), which causes AIDS, is surrounded by red blood cells. Anti-AIDS drugs have been developed to interfere with specific steps in the life cycle of the virus.