- Person
- Michael S. Brown
- Lived
- b. 1941
- Field
- Molecular genetics, cholesterol
- From
- American
The story
Soon after arriving at the University of Texas Southwestern Medical School in Dallas in 1971, Michael Brown dissolved and partly purified HMG-CoA reductase, the enzyme that sets the pace of cholesterol production in the body. With his friend Joseph Goldstein he set out to learn why patients with familial hypercholesterolaemia had such high cholesterol. In 1973 the pair discovered the LDL receptor, which pulls cholesterol-carrying LDL particles out of the blood and into cells, and showed that cholesterol entering the cell tells it both to stop making cholesterol and to make fewer receptors.
That feedback loop pointed to a way to lower blood cholesterol. If liver cells are prevented from making their own cholesterol, they respond by making more LDL receptors and clearing more LDL from the blood. In Japan in the 1970s Akira Endo discovered the first statin, a compound that blocks HMG-CoA reductase, and Merck’s lovastatin was first marketed in 1987. By the time of their 1985 Nobel Prize, the Nobel committee could report that drugs including cholestyramine and mevinolin (lovastatin) increased LDL receptors and lowered cholesterol in patients with the milder form of the inherited disease.
Brown and Goldstein kept digging. In 1993 their trainees Xiaodong Wang and Michael Briggs purified SREBPs, proteins anchored in cell membranes that are cut free when cholesterol runs low and travel to the nucleus to switch on the genes for making cholesterol and fats. Goldstein later wrote that this feedback system explains the mechanism of statins step by step: blocking cholesterol synthesis in the liver activates the SREBP pathway, which increases LDL receptors and reduces LDL in the blood.
Statins have become among the most widely prescribed medicines in the world and are on the World Health Organization’s list of essential medicines. UT Southwestern describes the Brown and Goldstein discovery as one that led to the development of statins, improving the quality of life for millions of people and saving lives.
Why it matters
Brown’s discoveries explain how statins clear cholesterol from the blood, medicines that lower the risk of heart attack and stroke for many millions of people.
About Michael S. Brown
Brooklyn-born physician-scientist who, with Joseph Goldstein, discovered how cells pull cholesterol out of the blood, explaining inherited heart disease and how statins work. Nobel Prize 1985.
Sources
- Press release: The Nobel Prize in Physiology or Medicine 1985 NobelPrize.org
- Michael S. Brown, Biographical NobelPrize.org
- Joseph L. Goldstein, Biographical NobelPrize.org
- Statin Wikipedia
- Nobel Prize 1985: Michael S. Brown, M.D., and Joseph L. Goldstein, M.D. UT Southwestern
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.