- Person
- Jerome Horwitz
- Lived
- 1919–2012
- Field
- Medicinal chemistry
- From
- American
The story
In 1964, the same year he made AZT, the Detroit chemist Jerome Horwitz and his collaborators published the first production and demonstration of another compound: 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside, mercifully known as X-gal. The X may come from indoxyl, the part of the molecule that carries its colour.
X-gal is a chemical cousin of lactose, the sugar in milk. It is colourless, but when it is broken down by beta-galactosidase, an enzyme many bacteria use to digest lactose, it releases galactose and a second fragment. That fragment pairs up with another and oxidises into an intensely blue, insoluble dye related to indigo. Scientists can therefore see at a glance whether the enzyme is active in a cell.
That simple colour change became one of the most widely used tricks in molecular biology. In blue-white screening, researchers use a circular piece of DNA called a plasmid that carries a fragment of the enzyme's gene. In specially engineered strains of the bacterium E. coli, that fragment combines with a partial enzyme made by the host cell to create a working enzyme, and colonies grown on X-gal turn blue. The spot where scientists insert a new gene sits inside that fragment, so a successful insertion breaks it and the colony stays white. Successful clones can be picked out by eye from a dish of colonies.
Common cloning vectors built for this test include pUC19 and pBluescript, and the plates usually also contain IPTG, a chemical that switches on production of the enzyme. X-gal is also used in two-hybrid experiments that reveal which proteins interact with each other, as well as in histochemistry and bacteriology, and chemists have created variants that give other colours.
The method has been used in countless gene-cloning experiments in laboratories around the world, saving researchers the slow work of checking each colony by other means.
Why it matters
X-gal made gene cloning faster and cheaper, helping power the biotechnology revolution, from basic research to medicines made by engineered cells.
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.
- Horwitz's ddC became one of the first HIV drugsDideoxycytidine (ddC), first made in Jerome Horwitz's lab in the 1960s, was approved by the FDA in 1992 as one of the earliest HIV/AIDS treatments.
- 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.
Sources
- X-gal Wikipedia
- Jerome Horwitz Wikipedia
- Billions from drug bypassed creator InvestSmart (obituary reprint)
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