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Baruj Benacerraf Dies

The Nobel Prize winner who discovered the gene that encodes the major histocompatibility complex passes away at age 90.

By | August 3, 2011

Baruj BenacerrafNATIONAL LIBRARY OF MEDICINE

Baruj Benacerraf, the geneticist and immunologist who earned the 1980 Nobel Prize for his discovery of the gene that governs the immune system’s reaction to foreign bodies, died on August 2, 2011 of pneumonia, at the age of 90.

Benacerraf started his Nobel Prize winning work with a chance observation. He had immunized a group of guinea pigs with a synthetic antigen, expecting to see all of the animals develop an immune response. But only about 40 percent of the rodents reacted, suggesting that individual genetic differences controlled the response. He then grouped the animals into responders and non-responders, and through a series of cross-mating experiments, confirmed that the response was controlled by a single dominant gene.

Interestingly, Benacerraf himself became allergic to guinea pigs as a result of the experiments, but it was “a small price to pay for the success of this project,” he wrote an autobiography published in the Annual Reviews of Immunology (ARJ) in 1991.

Hugh McDevitt and Allen Chinitz at Stanford University School of Medicine later discovered that Benacerraf’s “immune response” gene coded the major histocompatibility complex (MHC) molecule, which at the time was considered to be primarily involved in graft rejection. This connection illustrated that both graft rejection and pathogen rejection were mediated by the same molecule, and led the way for an understanding of autoimmune disease, organ transplantation, and differences in how individuals in a population respond to the same pathogen.

However, it isn't Benacerraf’s big discoveries that his former students remember most, but his passion for science. “There was that sparkle in his eye, a snap in his fingers” when you brought him an interesting result, said Ronald Germain, a section head at the Laboratory of Immunology at the National Institute of Allergy and Infectious Diseases (NIAID), and a student of Benacerraf at Harvard in the 1970s.

It was data, not prestige, that mattered, agreed Steven Burakoff, director of the Tisch Cancer Institute at Mount Sinai Medical Center, who worked with Benacerraf and Germain at Harvard. Benacerraf wasn’t concerned with where you were publishing, or giving a talk, Burakoff said. “He felt that if you focused on the research, and the quality of the data, and the insights it provided, everything would come from that.”

Benacerraf began his career as a doctor, but switched to immunology because of an intellectual curiosity that stemmed from his experience with asthma as a child. After completing his medical training and serving in World War II as a first lieutenant, Benacerraf returned to New York City and found a position working with young immunochemist Elvin Kabat at Columbia University. He credited Kabat with teaching him a deep respect for rigorous and quantitative science.

Eventually, Benacerraf started his own laboratory at New York University’s School of Medicine, where he completed his Nobel Prize-winning work. It was there he also began mentoring students, which he considered the most rewarding part of his career. “He regarded [his postdocs] as part of his larger family,” said William Paul, chief of the Laboratory of Immunology at the NIAID. “He loved to be challenged,” and would surround himself students who would do just that, said Paul.

But his students had to earn his esteem, Germain added. “You never crossed the threshold to his office [without] a knock and a ‘please come in’ permission. The goal was to get to the point where you could switch from ‘Professor Benacerraf’ to ‘Baruj,’ and where you could lightly tap and walk in,” said Germain, who says he eventually enjoyed a “reasonably close” relationship with Benacerraf.

After NYU, Benacerraf directed the Laboratory of Immunology at the NIAID for two years. He then was invited to be the chair of department of pathology at Harvard Medical School, and was appointed president of the Dana Farber Cancer Institute in 1980.

Over the course of his career, Benacerraf’s papers were cited more than 38,000 times, according to ISI. His most highly-cited paper, "The histocompatibility-linked immune response genes," (Adv Cancer Res, 21:121-73, 1975), was cited some 1,200 times.

He is survived by his daughter Beryl. His wife Annette Dreyfus died in June.

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