Baruj Benacerraf Biography (1920-)

pathologist, immunochemist

Baruj Benacerraf is a Venezuelan-born immunologist whose major contribution to modern immunology was the discovery of the immune-response gene (Ir) , which triggers the body's war on disease. For his work linking Ir genes to the major histocompatibility complex or supergene, which controls the nature and vigor of the body's immune response, Benacerraf was awarded the 1980 Nobel Prize in physiology or medicine, which he shared with two other immunologists.

Benacerraf was born on October 29, 1920, in Caracas, Venezuela, to HenrietteLasry and Abraham Benacerraf. His father was a Sephardic Jew who had emigrated from North Africa to Venezuela, working his way to wealth and prominence asa financier and textile importer. When Benacerraf was five, the family movedto France where Benacerraf attended the Lycée Janson and received a classic French education in pre-World War II Paris. In 1938, fearing the outbreak of war in Europe, the family returned to Venezuela; Benacerraf was sent to the United States to follow in his father's footsteps, enrolling as a student in the Textile Engineering School of the Philadelphia Museum of Art. To his family's regret, he left after only two weeks and entered Columbia University to pursue a career in science and medicine.

He graduated in 1942 but was rejected by twenty-five medical schools, including Columbia, Harvard, and Yale, due to his Jewish background and Venezuelan nationality. Eventually, he was accepted by the Medical College of Virginia inRichmond and became a naturalized citizen. In 1943 he married Annette Dreyfus, niece of Nobel laureate Jacques Lucien Monod and descendent of Captain Alfred Dreyfus of Devil's Island fame. They had one child, a daughter, Beryl, who would later become a medical radiologist.

Benacerraf interned at Queens General Hospital in New York and then spent twoyears in the U.S. Army Medical Corps. He was nearly thirty before he began his training in experimental immunology as an unpaid research fellow at the Neurological Institute of Columbia University. The director of the institute, Elvin Kabat , was a pioneer in immunology.

Immunochemistry in the 1950s was an esoteric backwater of biology awaiting the development of powerful electron microscopes, DNA modeling, and a commitment of massive government funding. Only the most general principles of immunitywere understood: that proteins called antibodies were manufactured by the body to fight off substances called antigens produced by invading bacteria, viruses, and environmental pollutants. How antibodies were made, by which cells,and how the body distinguished self from nonself were still mysteries.

At Columbia, under Kabat's stern tutelage, Benacerraf learned the importanceof precise measurement in immunological research and the value of critical thinking based on firm, empirical evidence. His first experiments dealt with the nature of hypersensitivity, the body's allergic reaction to the overproduction of antibodies. As a child Benacerraf had suffered from bronchial asthma,and his later research would focus on the relationship between allergic diseases and immunological response. In 1949 he moved to Paris to work at the Broussais Hospital with Bernard Halpern, the discoverer of antihistamines. In Paris, Benacerraf studied the action of phagocytes , the cellular scavengers responsible for cleaning the body of diseased cells and foreign contaminants. With Guido Biozzi , an Italian immunologist, Benacerraf developed the equationsthat describe the amount of particulate matter phagocytes can remove from the liver and spleen.

Due to a heart attack that had crippled his father, Benacerraf was forced todevote considerable time each year to overseeing his family's financial interests in Venezuela. Trips to South America sometimes lasted as long as six months and dealt with such unscientific matters as accounting, high finance, andpersonnel management. Not until 1956, when he received his first paid appointment as assistant professor of pathology at the New York University School of Medicine, was Benacerraf able to devote his full attention to research andshake the suspicion that he was only a dilettante in science. Later he wouldcome to see that his years of business experience gave him a distinct advantage as an administrator of university departments and government agencies.

In retrospect, Benacerraf came to view the late 1950s and early 1960s as thegolden age of his career. His family's finances had been successfully transferred to the United States; he spent only one day a week managing the ColonialTrust Company from its headquarters at Rockefeller Center. At New York University he received a well-equipped laboratory, ample funding, and the supportof enthusiastic and innovative colleagues.

With Gerald M. Edelman of Rockefeller University, Benacerraf undertooka series of experiments on antibody structure that eventually led Edelman tothe 1972 Nobel Prize and Benacerraf to the discovery of a completely unknowngene. Seeking to produce identical immunization in a group of guinea pigs, Benacerraf discovered by accident that when guinea pigs were injected with thesame foreign substance, some made antibodies and others did not. By breedingthe "responders" with the "nonresponders," Benacerraf isolated a gene that appeared to control immune response. He called the gene Ir (for immune response) and traced it to a hitherto unmapped region of the MHC, or major histocompatibility complex , an intricate and ancient supergene located within a specific chromosome.

Scientists were busily mapping the MHC in a variety of mammals and soon 30 Irgenes were identified for the mouse, guinea pig, rat, and rhesus monkey. Itwas only a matter of time before researchers began mapping the supergene in humans. By then a great deal more was known about the immune response at the cellular level. T-cells (from the thymus) apparently triggered the response and performed a variety of functions. "Killer" T-cells moved to neutralize anddestroy the invader; "helper" T-cells joined with B-cells (from bone marrow)to help manufacture antibodies; and finally "suppressor" T-cells slowed and stopped the attack after the enemy had been destroyed. Benacerraf's work had broad medical implications and shed light on why some individuals were more susceptible than others to diseases such as multiple sclerosis and rheumatoid arthritis. His research in the chemistry of suppressor T-cells opened the possibility of controlling the immune response and treating so-called autoimmunediseases, where the body mistakenly mounts an attack against its own tissues.

In 1968 Benacerraf left New York University to become chief of the laboratoryof immunology at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. Two years later he was appointed chairman of the Department of Pathology at Harvard Medical School and Fabyan Professor of Comparative Pathology. In July 1980 he became president and chief executive officer ofthe Dana Farber Cancer Institute in Boston.

In October of 1980 it was announced that he would share the 1980 Nobel Prizein physiology or medicine with immunologists Jean Dausset and George Snell for their joint elucidation of how the immune response was controlled by the MHC supergene. What had begun as an arcane branch of biology hadled in barely twenty-five years to a series of genetic discoveries of vital importance to medicine, cancer research, virology, and developmental biology.

Benacerraf is the author of more than five hundred scientific papers, a fellow of the American Academy of Arts and Sciences, and a member of the NationalAcademy of Sciences. He has also been an associate editor of several periodicals, including American Journal of Pathology, Laboratory Investigation, and Journal of Immunology and Immunogenetics.

A gregarious, cultured man, he has enjoyed a life of rich professional contacts. At home on three continents, he is intimately acquainted with the disparate worlds of immunochemistry, international banking, and classical music. Professionally, he cultivates a skeptical, even pessimistic frame of mind. Wellversed in the anecdotal history of science, he believes that accident and error play a far greater role in scientific discovery than historians like to admit.

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