Brown, Michael

Michael S. Brown

UT Southwestern Medical Center

Goldstein, Joseph

Joseph L. Goldstein

UT Southwestern Medical Center

For the discovery of the basic mechanisms controlling cholesterol metabolism, opening the way to a new pharmacologic approach to the treatment of coronary heart disease, the leading cause of death in the Western world

In 1973, there was no clear understanding of how low density lipoprotein (LDL) and cholesterol were removed from the circulating blood and metabolized in cells. Drs. Brown and Goldstein discovered the cell surface receptor which binds circulating LDL and removes cholesterol from the bloodstream. They went on to delineate at the molecular level the way cholesterol is taken up by cells in a process they named receptor-mediated endocytosis. In addition, these elegant and incisive observations had broad explanatory power in illuminating how large molecules such as insulin and epidermal growth factor are taken into cells.

Their discovery of the LDL receptor and pathway represents a monumental contribution, not only to the important field of lipoprotein and atherosclerosis research, but also to fundamental understanding in the larger domains of medical genetics and cell biology.

Their pioneering work on the disease familial hypercholesterolemia (FH), characterized by abnormal accumulations of cholesterol in the bloodstream, provided the key to their basic discoveries. One in 500 people is estimated to have this condition. They found that patients with FH were unable to bind and internalize circulating cholesterol because of missing or deficient LDL receptors. They identified and eventually isolated and purified the gene in FH that caused the absence or deficiency of these receptors.

To Drs. Brown and Goldstein, the consummate physician-scientists who link the intellectual insights of science with the human concerns of medicine, for their extraordinary work in elucidating cholesterol metabolism, and for opening new approaches to the treatment of atherosclerosis, this 1985 Albert Lasker Basic Medical Research Award is given.