Two American scientists won the 1985 Nobel Prize in medicine yesterday for research that revolutionized scientific understanding of the role of cholesterol in heart disease and pointed the way toward practical means of prevention and treatment.
The $225,000 award will be shared jointly by molecular geneticists Michael S. Brown, 44, and Joseph L. Goldstein, 45, who first met in 1966 during medical training in Boston and have worked closely together for more than a decade at the University of Texas Health Science Center at Dallas.
The Nobel Assembly at Stockholm's Karolinska Institute said the Texas team had "revolutionized our knowledge" about how the body processes cholesterol, including the genetic and dietary contributions to the abnormal buildup of cholesterol in the blood.
The institute said that the researchers' discoveries had "far-reaching implications" for the prevention and treatment of coronary artery disease and heart attacks, "a major cause of death in most industrialized countries." Diseases of the heart and blood vessels are the number one killer in the United States, accounting for nearly 1 million American deaths each year. More than 42 million Americans suffer from heart disease.
Most coronary disease is the result of hardening of the arteries, or atherosclerosis, in which excessive fats and cholesterol in the blood slowly clog the inner walls of these vessels. When a blood clot blocks a narrowed artery, a heart attack can result. Researchers have long known that high blood cholesterol is a major risk factor for heart disease, but the complex pathways were difficult to unravel.
Cholesterol, which is crucial in low levels to cell functioning, is produced in the body, predominantly in the liver, as well as consumed in foods. It is carried in the blood predominantly in particles known as low-density lipoproteins (LDL).
The Nobel citation noted that a "milestone" occurred in 1973 when Brown and Goldstein discovered special receptors that regulate the intake of LDL to the body's cells from the blood. These receptors operate as a sort of border patrol on the surface of cells that control the entrance of the LDL and thus the amount of cholesterol entering the cells.
Some individuals are genetically predisposed toward high blood cholesterol, an illness known as severe hereditary familial hypercholesteremia. Brown and Goldstein found that an underlying cause for this genetic disease is a complete, or partial, lack of working LDL receptors. The most severe form occurs in about one-in-a-million people, but a milder form is much more common, afflicting about one in 200 to 500 people.
But they also suggested that in normal individuals the high dietary consumption of cholesterol, particularly through red meats and dairy products, may interrupt the natural cholesterol cycle and reduce the number of LDL-receptors on the cell surface. Fewer receptors in turn lead to increased cholesterol in the blood and the buildup of deposits on the artery walls, they said.
While the dietary role of cholesterol has been debated for years, a prominent National Institutes of Health panel concluded late last year that the risk of heart attacks could be significantly reduced by lowering blood cholesterol levels, preferably through dietary changes as well as the use of cholesterol-reducing drugs in high-risk cases.
Brown and Goldstein, in a recent article in Scientific American cited by the Nobel panel, endorsed a diet "moderately low in animal fats" as prudent for most people. But, they speculated, testing of new drugs that increase the number of LDL receptors may one day make it possible "for many people to have their steak and live to enjoy it too."
Brown and Goldstein learned of the award while attending a symposium at Massachusetts Institute of Technology at which they were featured speakers. They held a news conference there and then rushed to the airport to return to Texas for a celebration at their laboratory and another news conference.
Although the researchers expressed surprise at the honor, their colleagues said it was only a matter of time. The duo had already won a string of major scientific prizes for their work in recent years.
"It's no surprise to the community of biologists and biomedical researchers," said MIT Professor Monty Krieger, who formerly worked in their laboratory. In addition to the heart disease applications, Krieger said that the Brown-Goldstein collaboration on the cholesterol receptors had been a model for understanding other basic molecular pathways.
Dr. David Bilheimer, who works with them at the University of Texas medical center, said that the basic research had also had dramatic payoffs for an 8-year-old Texas girl named Stormie Jones who was dying of the severe, cholesterol-raising genetic disease. She underwent an unprecedented heart-liver transplant last year that triggered an 80 percent reduction in blood cholesterol levels, apparently by providing new LDL receptors.
Bilheimer said that the award is "a wonderful honor for them and for the institution . . . . This is the first Nobel Prize for work done in Texas. This was home-grown work. That's what's so thrilling about it."