- Person
- Joseph L. Goldstein
- Lived
- b. 1940
- Field
- Medical genetics, cholesterol
- From
- American
The story
As a young doctor at the National Institutes of Health in the late 1960s, Joseph Goldstein cared for children with homozygous familial hypercholesterolaemia (FH), a rare inherited condition in which blood cholesterol is so high that heart attacks can strike before adulthood. Nobody knew what went wrong in their bodies. In Seattle from 1970 to 1972 he studied heart attack survivors and found that the milder, single-gene form of FH affected about one person in 500 and about one in 25 heart attack victims. Inherited cholesterol disease was a real public health problem.
Back in Dallas in 1972, Goldstein joined forces with his friend Michael Brown at the University of Texas Southwestern Medical School. They grew skin cells from healthy people and from FH patients. Normal cells, when bathed in LDL, the particles that carry most cholesterol in the blood, stopped making their own cholesterol. Cells from children with severe FH did not. In 1973 the two found the reason: normal cells carry receptors on their surface that capture LDL and draw it inside. Children with severe FH had no working receptors, and people with the milder form had about half the normal number. Without enough receptors, LDL stays in the blood and builds up in the walls of arteries.
Following the receptor’s journey, they also discovered receptor-mediated endocytosis, the process by which receptors cluster in coated pits that pinch off and carry their cargo into the cell before returning to the surface. It proved to be one of the basic ways cells take up substances of many kinds.
The Nobel committee, awarding Goldstein and Brown the 1985 Prize in Physiology or Medicine, said they had revolutionised knowledge of cholesterol metabolism and the treatment of diseases caused by high cholesterol. Their discovery showed that raising the number of LDL receptors could lower blood cholesterol, the principle by which statin drugs work. Families with FH could at last be diagnosed with confidence and treated according to what was actually wrong.
Why it matters
The LDL receptor discovery explains inherited high cholesterol and underlies how statins lower LDL, treatments that reduce the risk of heart attack and stroke for many millions of people.
About Joseph L. Goldstein
South Carolina-born geneticist who, with Michael Brown, discovered the LDL receptor and how the body controls cholesterol, the science behind statins. Nobel Prize 1985.
Sources
- Press release: The Nobel Prize in Physiology or Medicine 1985 NobelPrize.org
- Joseph L. Goldstein, Biographical NobelPrize.org
- 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.