- Person
- Alfred G. Gilman
- Lived
- 1941–2015
- Field
- Pharmacology
- From
- American
The story
By the 1970s scientists knew that hormones such as adrenaline bind to receptors on the outside of a cell and that, inside, an enzyme then makes a “second messenger” called cyclic AMP. Martin Rodbell at the U.S. National Institutes of Health had shown that the message also needed GTP, an energy-rich molecule, and proposed that a separate transducer linked receptor and enzyme. Nobody knew what that transducer was.
Alfred Gilman, a pharmacologist at the University of Virginia and the son of the co-author of the leading pharmacology textbook, set out to find it. According to the Nobel committee, his group studied mutated leukaemia cells that had a normal receptor and a normal enzyme but failed to respond to hormones. They showed that the cells lacked the transducer, and after years of work, in 1980 they purified a protein from normal cells that, when transferred into the membrane of the defective cells, restored their response. Because it reacts with GTP, it was called a G protein.
G proteins work as molecular switches, turned on when a receptor is activated and off again when they convert GTP to GDP. Many different G proteins were soon found, relaying signals for hormones and nerve transmitters as well as for sight, smell and taste. The Nobel committee also explained that diseases such as cholera act by locking a G protein in the “on” position, and that faulty G proteins are found in some tumours and inherited hormone disorders.
Gilman shared the 1994 Nobel Prize in Physiology or Medicine with Rodbell. The receptors that work through G proteins became the largest family of drug targets: when the 2012 Nobel Prize in Chemistry was awarded for research on them, the committee noted that about half of all medications achieve their effect through these G-protein–coupled receptors. Gilman also spent two decades as an editor of Goodman & Gilman’s The Pharmacological Basis of Therapeutics, the textbook that teaches doctors how drugs work.
Why it matters
Understanding G proteins explains how about half of today’s medicines work and helps researchers design and improve drugs for many common diseases.
About Alfred G. Gilman
Pharmacologist who discovered G proteins, the molecular switches that relay hormone signals inside cells and explain how about half of all medicines work. Nobel Prize 1994.
Sources
- Press release: The Nobel Prize in Physiology or Medicine 1994 NobelPrize.org
- Press release: The Nobel Prize in Chemistry 2012 NobelPrize.org
- Alfred G. Gilman, Biographical NobelPrize.org
- Alfred G. Gilman Wikipedia
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.