Jerome Horwitz, a medical researcher at Wayne State University in Detroit, had spent more than a decade developing a drug he hoped would work against cancer. But the compound failed to help the lab mice he tested it on, so in 1970 he “dumped it on the junk pile,” wrote up his disappointing findings and moved on. He didn’t bother applying for a patent.
What Horwitz didn’t know was that the drug — AZT — was destined for success.
Almost 20 years after he had begun his work, scientists at the National Cancer Institute discovered AZT slowed the development of what had been thought to be an untreatable scourge, AIDS. In 1987, AZT became the first drug approved by the Food and Drug Administration for use against the disease caused by the human immunodeficiency virus, HIV.
The drug company that patented and marketed AZT helped establish a chair at Wayne State in Horwitz’s name, but the chemist never shared a penny of the billions of dollars made because of his work. As he told the Chronicle of Higher Education many years later, “if I was ever bitter, it’s long since passed” because of the millions of lives AZT has saved.
Once described as “one of academe’s most under-recognized inventors,” Horwitz died Sept. 6 in West Bloomfield Township, Mich. He was 93 and had heart problems, said his wife, Sharon Horwitz.
Horwitz “didn’t have a patent, he didn’t make money, but there is no question that what he did really dramatically accelerated the development of anti-retroviral drugs,” Dr. Paul Volberding, director of the AIDS Research Institute at UC San Francisco, said this week. “It’s impossible to be sure, but it would have taken a considerably longer time without his pioneering work.”
When AZT made headlines in the 1980s, Horwitz briefly held the spotlight: People magazine named him one of the 25 most intriguing people of 1986 and he appeared on television news shows.
AZT was a controversial therapy because of its harsh side effects and prohibitive price — about $8,000 a year. It has largely been replaced by less toxic drugs. But Horwitz developed two other drugs that have remained in the anti-AIDS/HIV arsenal, including dideoxycytidine, the second drug approved for AIDS patients, and stauvudine.
Horwitz also created a solution called X-Gal that is widely used to identify proteins.
“I didn’t patent it — story of my life,” he told the Chronicle upon his retirement from Wayne State in 2005.
Horwitz was in his 80s when he shared in a five-year, $900,000 grant from the National Cancer Institute to refine drugs capable of treating solid tumors. That work led to Horwitz’s first royalty check at 86.
Born in Detroit on Jan. 16, 1919, Horwitz was the son of a businessman who sold poultry. Disinclined to spend his life cleaning up chicken coops, he found his own path early in his teens, when he read “Microbe Hunters” by Paul de Kruif, a 1926 classic about groundbreaking scientists. “A light bulb went on,” Horwitz recalled in the Detroit News in 2001. “I knew what I wanted to do.”
He graduated with a degree in chemistry from the University of Detroit in 1942, earning a master’s there two years later. Barred from World War II service because of high school football injuries, he went on to the University of Michigan and obtained a doctorate in chemistry in 1948.
In 1951, he joined the Illinois Institute of Technology, where he was part of a team developing solid rocket fuels for the Navy. He did not enjoy working with explosive materials, however, and in 1955 returned to Detroit to work at what became the Michigan Cancer Foundation. It is now called the Barbara Ann Karmanos Cancer Institute at Wayne State University.
In addition to his wife, Horwitz is survived by two daughters and five grandchildren.
In 1964, with the war on cancer in full swing, many scientists were randomly pulling drugs off the shelf to test their potential as anti-cancer agents, but Horwitz found this approach intellectually unsatisfying. He wanted to analyze the cancer cells and design a drug that would disrupt their growth.
Knowing that the cells divide using raw materials called nucleosides, he created what he called “fraudulent nucleosides” that were so similar to the real thing the cell would be tricked into using them. The fakes, he theorized, would gum up the cell’s replication machinery and halt the development of the tumor.
Horwitz was ahead of his time in his approach, now called “rational drug design.” Instead of trial-and-error, rational drug designers create a drug for a specific biological target, such as a cancer cell.
“He was able to take his scientific understanding and say ... ‘I am going to devote my life to design a therapy that will strike at the heart of the disease,’ ” said Wei-Zen Wei, a longtime colleague and associate director at the Karmanos Cancer Institute. “At the time it was risky. He took a chance.”
When Horwitz tested AZT, or azidothymidine, on leukemic mice, nothing happened. He admitted defeat and didn’t think about it again until the mid-1980s, when scientists were randomly testing drugs in a frantic search for one that would combat AIDS.
At the National Cancer Institute, a group of researchers found the compound curbed the activity of HIV, a strange virus from a family known as retroviruses. Retroviruses were barely known at the time of Horwitz’s work on the drug.
Horwitz learned that AZT had come back to life when a colleague pointed out a report on the results published by the researchers in 1985.
“My colleagues and I said that we had a very interesting set of compounds,” he told the New York Times in 1986, “that were just waiting for the right disease.”