AZT was not a cure, and it had downsides, including sky-high costs and dangerous side effects. But it was the first treatment that significantly decreased HIV-related mortality rates — at a time when many scientists considered HIV an untreatable disease. It later became part of a drug combination that curbed deaths even further.
Even as those “cocktails” were supplanted by other more effective regimens, scientists say, AZT has continued to serve as a model for treatment of the disease.
“AZT stood up and said, ‘Stop your pessimism,’ ” said Samuel Broder, a National Cancer Institute scientist who headed a group of scientists that helped discover the therapeutic nature of AZT in the 1980s. “ ‘Stop your sense of futility. Go back to the lab. Go back to development. Go back to clinical trials. Things will work.’ ”
Dr. Horwitz died Sept. 6 at 93 at a hospital in West Bloomfield Township, Mich. His death, from pneumonia and a heart attack, was confirmed by his wife, Sharon Horwitz. He had worked for nearly five decades at Wayne State University in Detroit and the affiliated institution now known as the Barbara Ann Karmanos Cancer Institute.
His most noted achievement — the creation of AZT — began with a moment of frustration in 1964, when he was director of chemistry at the oncology institute. At that time, floundering in their efforts to find a cure for cancer, medical researchers were testing any drugs with even the most remote potential to see what worked.
“I got tired of randomly selecting drugs for cancer, just pulling chemicals off the shelves and trying them out to see if they would work,” he told The Washington Post in 1986. “It was necessary, but there was no satisfaction, no challenge in it.”
So Dr. Horwitz decided to begin creating his own chemical compounds and testing them on cancer cells. One of them was azidothymidine (later widely known as AZT, and also sometimes called zidovudine).
The compounds would work, or so he hoped, by interfering with the division and growth of cancer cells. To divide, cells use base elements called nucleosides to produce new DNA chains. Dr. Horwitz referred to his compounds as “fraudulent nucleosides.” Like chemical Trojan horses, the compounds would enter the cancer’s DNA and sabotage its growth.
At least that was the idea. Scientists tested AZT in mice with leukemia and watched it fail utterly. He compared the feeling to “a blow to the solar plexus.”
He wrote a paper on the topic, decided not to pursue a patent and put the compounds on a shelf. For two decades, they were occasionally tested for new uses — as is often the practice in the scientific community — but mostly collected dust.