Baruj Benacerraf dies at 90; Nobelist made key discoveries about immune system

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Dr. Baruj Benacerraf, who shared the 1980 Nobel Prize in physiology or medicine for his pioneering work explaining why some people are able to fight off infections and tumors while others are not, died Tuesday at his Boston home. He was 90.

The cause was pneumonia, according to the Dana-Farber Cancer Institute in Boston, where he spent most of his career.

"Dr. Benacerraf's seminal discoveries about genetic control of the immune system made possible much of what we now know about basic disease processes such as infection, autoimmune disorders and cancer," Dr. Edward J. Benz Jr., president of Dana-Farber, said in a statement. "His work has shaped everything from organ transplantation to AIDS treatment to, most recently, the development of therapeutic cancer vaccines."

When Benacerraf and his co-laureates, George D. Snell of the Jackson Laboratory in Bar Harbor, Maine, and Dr. Jean Dausset of the University of Paris, began studying the immune system after World War II, it was a mysterious entity whose functions were largely unknown. Over several decades, they explained the genetic basis for how the immune system functions.

Snell originated the work in mice, demonstrating that the rodent's ability to recognize its own tissues and distinguish them from those of other mice was the result of specialized protein/sugar complexes on the surface of cells called antigens. He christened these structures histocompatibility antigens, from the Greek "histo," or tissue.

He also showed that these antigens were generated by a specific set of genes in what is now called the major histocompatibility complex. Researchers now know there are at least 80 separate genes in the complex in mice.

Dausset demonstrated that the same type of histocompatibility complex exists in humans. He originally studied the antigens in white blood cells, and named them human leukocyte antigens (HLA). HLA typing made it possible to perform transplants that were much less likely to be rejected than transplants of tissues chosen at random. He also showed that certain HLA antigens are associated with an increased propensity for certain diseases.

Benacerraf, working with guinea pigs, stumbled on his contribution almost by accident. He was injecting the animals with a specific foreign substance similar to an antigen, intending to provoke an immune response in them. However, only about 60% of the guinea pigs responded.

Through an intensive series of breeding experiments, he determined that the guinea pigs' ability to mount an immune response to the foreign material was controlled by specific genes in the major histocompatibility complex. These genes were subsequently found in humans and other mammals as well.

Researchers speculate that the genes allow at least some members of a species to survive an attack by a mutated virus or bacterium. Unfortunately, the genes also allow the development of certain types of autoimmune diseases, in which the immune system attacks parts of a person's body.

Baruj Benacerraf (pronounced bar-OOK ben-ah-seh-RAHF) was born Oct. 29, 1920, in Caracas, Venezuela. His father was a Moroccan Sephardic Jew and his mother was Algerian. The family moved to Paris when Baruj was 5 so his father could purchase textiles to sell in Venezuela. As a child, Baruj suffered from asthma, which he later said contributed to his interest in immunology and immune diseases.

The family fled the Nazis in 1939, first returning to Venezuela and then moving to New York in 1940 so Benacerraf could receive an American education. He graduated from Columbia University with a degree in biology in 1942 but because he was both Jewish and a foreigner was rejected from nearly 25 medical schools.

Ultimately, the father of a close friend secured him an interview at the Medical College of Virginia in Richmond, and he enrolled in 1942. He was drafted a year later by the U.S. Army along with other medical students and, after receiving his medical degree in 1945, trained at Queens General Hospital in New York City.

He became a U.S. citizen in 1943 and joined the Army Medical Corps in 1946, serving for nearly two years in Paris and Nancy, France.

After two years on the faculty at Columbia University, he moved to Paris in 1949 to take over the family business but still conducted research. Because he was not French his chances for academic advancement were limited, and he returned to the U.S. He joined the New York University School of Medicine and began his work on the immune system.

During this period, he also managed a New York bank, Colonial Trust Co., which was owned by his family and associates. Eventually, he withdrew from the business world for research, because he considered the challenges "much greater in my chosen profession."

In 1970, he was offered the chair of pathology at Harvard Medical School, which had once rejected his school application. A decade later, he became president of Dana-Farber, which is affiliated with Harvard. He presided over tremendous growth there as he recruited top clinicians and researchers and oversaw the construction of two major research facilities.

He stepped down from the presidency in 1992 but continued his research until well into his 80s.

Benacerraf's wife of 68 years, the former Annette Dreyfus, died June 3. He is survived by a daughter, Dr. Beryl Benacerraf of Boston; two grandchildren; and his brother, Paul, of Princeton, N.J.

thomas.maugh@latimes.com

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