Michael S. Brown Biography (1941-)


Michael S. Brown, a genetics professor and director of the Center for GeneticDiseases at the University of Texas Southwestern Medical School, is one of America's foremost experts on cholesterol metabolism in the human body. In the1970s, Brown and Joseph Goldstein investigated familial hypercholesterolemia, a dangerous inherited disorder which causes elevated levels of cholesterolin the blood. Their research led them to the discovery of a protein in the membranes of a cell, called the LDL receptor , which plays a central role in the body's ability to lower cholesterol levels. For this discovery and their subsequent research on the LDL receptor, Brown and Goldstein shared the 1985 Nobel Prize in physiology or medicine.

Brown was born in New York City on April 13, 1941, to Harvey and Evelyn KatzBrown. He attended the University of Pennsylvania as an undergraduate, receiving his bachelor's degree in 1962. Following his graduation, Brown enrolled in the medical school at the University of Pennsylvania, where he was awardedthe Frederick Packard Prize in Internal Medicine for his research. He earnedhis M.D. in 1966 and served as an intern and a resident at Massachusetts General Hospital in Boston. It was during his residency that he met Joseph Goldstein, his future research partner, who was also on the staff at MassachusettsGeneral.

In 1968, Brown was made a clinical associate at the National Institutes of Health (NIH) in Bethesda, Maryland. He was assigned to the biochemistry lab, where he worked with Earl Stadtman , head of the laboratory for the National Heart, Lung, and Blood Institute. While at NIH, Brown focused his research on gastroenterology, particularly on the role of enzymes in digestive chemistry.In 1971, while studying a particular enzyme involved in the production of cholesterol, Brown was offered a position as an assistant professor at the University of Texas Southwestern Medical School in Dallas. He accepted, and Goldstein, who had also served at NIH in Bethesda, joined the Texas Southwestern faculty a year later. At this time the two began a collaboration which was to distinguish them as pioneers in genetics.

In Dallas during the 1970s, Brown and Goldstein examined skin samples from people who suffered from hypercholesterolemia, specifically those rare patientswhose condition was homozygous, meaning that they had not just one defectivegene but two. In these cases, patients often exhibited extremely high levelsof low-density lipoprotein, LDL , even during childhood. LDL carries cholesterol to the cells, and in excessive quantities can clog arteries and encourage heart disease. Brown and Goldstein discovered that the cells of these patients were missing a crucial protein, called a receptor , which binds to LDL and regulates its level in the body. Without the protein, the body can not break down LDL, and it accumulates in the blood. Brown and Goldstein's breakthrough was the discovery and isolation of this LDL receptor protein.

Brown and Goldstein not only identified the LDL receptor , they also locatedthe gene responsible for its production. By sequencing and cloning the gene,they were able to localize the gene mutations responsible for familial hypercholesterolemia, as well as other inherited conditions involving cholesterol metabolism. Their findings also led to possible drug therapies for people withcholesterol disorders. By administering a combination of drugs which would inhibit the liver's ability to synthesize cholesterol, Brown and Goldstein increased their patients' need for cholesterol from outside sources. The patients' bodies subsequently produced more LDL receptors, and their cholesterol levels fell sharply. They also found that a liver transplant can correct geneticdeficiencies in the production or expression of LDL receptors . In later research, Brown and Goldstein engineered a mouse which, because of its abnormally high numbers of LDL receptors, could eat a high-fat diet and yet show no significant rise in LDL.

In a remarkable series of experiments, Brown and Goldstein were ultimately able to define and analyze each step in the path of cholesterol through the body, from production to dissolution. They also demonstrated a mechanism by which a low-fat diet and regular exercise can decrease cholesterol levels. Brownand Goldstein's work had significant implications not only for genetic defects, but also for nutrition and fitness. In addition, the team's research methods contributed to a greater understanding of cell receptors in general, serving as a model for research on over twenty other receptors. In the words of the Nobel Prize committee, as quoted in the New York Times, Brown andGoldstein "revolutionized our knowledge about the regulation of cholesterol metabolism and the treatment of diseases caused by abnormally elevated cholesterol levels in the blood."

In addition to the Nobel Prize, Brown has received several honorary degrees and a number of awards for his research, including the Pfizer Award from the American Chemical Society in 1976, the Albert Lasker Medical Research Award in1985, and the National Medal of Science in 1988. He has been a member of theNational Academy of Sciences since 1980. He was appointed Paul J. Thomas Professor of Genetics and director of the Center for Genetic Diseases at the University of Texas Southwestern Medical School, positions he has held since 1977.

Brown balances his scientific and medial careers, and despite his success asa researcher, he still makes rounds at the hospital. He is also well known for his entertaining style of scientific presentations. While still in medicalschool at Penn, Brown married Alice Lapin on June 21, 1964, and they have twodaughters.

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