Pioneers of the "Supergene"

A trio of top immunologists wins the Nobel

The rumor in Stockholm a year ago was that the Nobel Prize in Physiology or Medicine would go to a trio of scientists for basic research in how the body defends itself against external agents and maintains its internal wellbeing. The prediction proved wrong--but only by twelve months. Last week Sweden's Karolinska Institute announced that the 1980 award, worth $212,000, will be shared by three pioneering immunologists: Jean Dausset of France and two Americans, George Snell and Baruj Benacerraf.

The three, working independently, have been studying a group of genes that are intimately linked to the body's immune response. Snell, 76, of the Jackson Laboratory at Bar Harbor, Me., laid the groundwork with studies using mice. Attempting to transplant first tumor cells and then normal tissue, he discovered that the success of the operations depended on protein molecules on the surface of cells. These proteins, called antigens, have characteristic shapes and structures, but combinations differ from individual to individual. Snell found that the more antigens the subjects had in common, the more likely was the graft to take. Investigating further, he learned that the formation of antigens was controlled by a group of genes on a specific chromosome in a cell's nucleus. He called these genes the "major histocompatibility complex," since it was the prime factor in determining whether transplanted tissue would be rejected.

But did such a complex exist in humans? Dausset, 63, of the Saint-Louis Hospital of the University of Paris, found that it did. Comparing the white blood cells (leukocytes) of patients undergoing transfusions with those from blood donors, Dausset identified distinct antigens on cell surfaces. Then he located the controlling genes. Because they were first found in white blood cells, the surface proteins are called human leukocyte antigens (HLA), though they exist in all tissues. Over 40 antigens have been identified.

Snell's and Dausset's discoveries have led to better matching of donor organs with recipients. Further, since the HLA molecules give everyone except identical twins a unique biochemical profile, HLA "typing" has become a major tool in forensic medicine. It has helped identify rapists through semen stains, and in one paternity case it showed that a pair of fraternal twins were sired by different fathers. Researchers have found that certain HLA groupings are associated with particular diseases, including multiple sclerosis and rheumatoid arthritis. Through HLA typing, it may one day be possible to tell an individual what illnesses he is most likely to contract. Caracas-born Benacerraf, 59, who teaches at Harvard, has further defined the histocompatibility complex. He was intrigued by the variable nature of the immune response--the body's defense against such foreign invaders as viruses. In experiments with mice and guinea pigs, Benacerraf found that the genes that control the vigor of the immune response are part of the major histocompatibility complex.

It will take years of study to figure out how the histocompatibility complex works, but the Nobelists have already shown that it is a sort of command center for the cell. To researchers it is known affectionately as "supergene."

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