Billions from drug bypassed creator

SCIENTIST

16-1-1919 6-9-2012

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 did not bother applying for a patent.

What Horwitz did not 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 US Food and Drug Administration for use against the disease caused by HIV, the human immunodeficiency virus.

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 cent of the billions of dollars

it made from his work. He said many years later that "If I was ever bitter, it's long since passed" because of the millions of lives AZT had saved.

Once described as "one of academe's most under-recognised inventors," Horwitz died in West Bloomfield, Michigan. He was 93 and had heart problems.

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," said Dr Paul Volberding, director of the AIDS Research Institute at the University of California, San Francisco. "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 $US8000 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 It has largely been replaced by less toxic drugs.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 stavudine.

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 said on his retirement from Wayne State in 2005.

Horwitz was in his 80s when he shared in a five-year, $US900,000 grant from the National Cancer Institute to refine drugs capable of treating solid tumours. That work led to Horwitz's first royalty cheque at 86.

Born in Detroit, Horwitz was the son of a businessman who sold poultry. He found his 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 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 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 analyse 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 theorised, would gum up the cell's replication machinery and halt the development of the tumour.

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

long-time 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 leukaemic mice, nothing happened. He admitted defeat and did not 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 learnt 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 that were just waiting for the right disease," he said in 1986.

In addition to his wife Sharon, Horwitz is survived by two daughters and five grandchildren.

"He never did it for the money," his wife said. "He went into science because he wanted to make a difference." After a pause she added: "He also went into science because he didn't want to go into the poultry business with his father."