- Person
- Jerome Horwitz
- Lived
- 1919–2012
- Field
- Medicinal chemistry
- From
- American
The story
Jerome Horwitz did not stop at AZT. In the 1960s his laboratory at the Detroit Institute of Cancer Research and Wayne State University made a series of related molecules, all designed to imitate the building blocks of DNA. One of them, which Wayne State dates to 1967, was 2',3'-dideoxycytidine, known as ddC and later as zalcitabine.
The molecule is a close copy of deoxycytidine, one of the natural units of DNA, with a single change: a hydroxyl group at the 3' position is replaced by plain hydrogen. Inside a cell it is converted to an active form that a copying enzyme can pick up and add to a growing DNA strand. Because the missing hydroxyl group is exactly where the next unit would attach, the chain stops dead.
Like AZT, it had been intended to fight cancer. When HIV was identified in the 1980s, scientists at the US National Cancer Institute, Samuel Broder, Hiroaki Mitsuya and Robert Yarchoan, developed it as an anti-HIV agent, because it could trick the virus's copying enzyme, reverse transcriptase, into building a chain it could not finish. Since the NCI cannot market drugs itself, the National Institutes of Health licensed ddC to Hoffmann-La Roche, which sold it under the name Hivid.
The Food and Drug Administration approved zalcitabine on 19 June 1992, making it the third antiretroviral drug approved in the United States, after AZT and didanosine. For several years these three closely related drugs were the only approved medicines against HIV. In 1996 the FDA approved zalcitabine for use in combination with AZT, and pairing such drugs, and soon adding a protease inhibitor, became the basis of the far more effective multi-drug therapies that followed.
Zalcitabine had drawbacks: it had to be taken three times a day and could cause painful nerve damage, and its sale was discontinued at the end of 2006 once better options existed. But the chain-ending strategy it shared with AZT lives on in the nucleoside drugs that remain a backbone of HIV treatment today.
Why it matters
ddC gave people with HIV another option in the desperate early years of the epidemic and helped pave the way for the combination therapy that turned HIV into a manageable condition.
About Jerome Horwitz
Detroit chemist who made AZT in 1964 as a cancer drug that failed, two decades later it became the first approved treatment for HIV/AIDS, though he never earned a cent from it.
More about Jerome Horwitz
- Jerome Horwitz made AZT, the first HIV treatmentIn 1964 Detroit chemist Jerome Horwitz synthesised AZT as a possible cancer drug; in 1987 it became the first approved treatment for HIV, and he also first made two more HIV drugs.
- Jerome Horwitz fought cancer in the lab until 86Jerome Horwitz kept working on cancer drugs into his eighties, sharing a $900,000 NCI grant for solid-tumour drugs and retiring from Wayne State in 2005 at 86.
- Jerome Horwitz designed 'fraudulent' DNA building blocksIn the early 1960s Jerome Horwitz rejected random drug screening and designed 'fraudulent nucleosides' to trick cells into stopping DNA copying.
- Horwitz's stavudine treated HIV in poorer countriesStavudine (d4T), first created by Jerome Horwitz in the 1960s, was approved for HIV in 1994 and became widely used in developing countries for its low cost.
- Jerome Horwitz made X-gal, a staple of genetics labsIn 1964 Jerome Horwitz and colleagues first made X-gal, the compound that turns bacteria blue and lets biologists spot engineered DNA at a glance.
Sources
- Zalcitabine Wikipedia
- AIDS drug AZT inventor and famed cancer scientist Jerome Horwitz dies at 93 Wayne State University
- Jerome Horwitz Wikipedia
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