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

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

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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.

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