Caracas, Paris and New York
Baruj Benacerraf was born in Caracas, Venezuela, on October 29, 1920, into a family he described as of Spanish-Jewish ancestry. His father, Abraham Benacerraf, a self-made textile merchant and importer, was a Sephardic Jew born in Spanish Morocco; his mother, Henrietta Lasry, was born and raised in French Algeria in the French culture. His brother, Paul Benacerraf, became a well-known philosopher.
When Baruj was five the family moved to Paris, where he was educated in French until 1939, an experience that shaped him for life. The Second World War sent the family back to Venezuela, where his father’s business continued to thrive, and in 1940 they decided he should complete his education in the United States. He moved to New York, enrolled at Columbia University’s School of General Studies, and graduated with a Bachelor of Science in 1942.
A door opened by kindness
His father hoped he would join the family business, but Benacerraf had decided on biology and medicine. He soon learned, as he put it, that getting into medical school “was a formidable undertaking for someone with my ethnic and foreign background in the United States of 1942.” Despite an excellent record at Columbia, he was refused by the many medical schools he applied to, a rejection that biographers attribute to his Jewish background.
He was rescued by an act of personal kindness. George W. Bakeman, the father of a close friend and an assistant to the president of the Medical College of Virginia in Richmond, heard of his difficulties and arranged an interview for one of the last two places in the first-year class. Benacerraf was accepted and began his medical studies in July 1942. During medical school he was drafted into the U.S. Army with his classmates and became an American citizen in 1943. That same year he married Annette Dreyfus, a fellow refugee from Paris whom he had met at Columbia; they remained together until her death in 2011.
From army doctor to immunologist
After an internship at Queens General Hospital in New York, Benacerraf served as a first lieutenant in the U.S. Army Medical Corps, spending nearly two years in France, in Paris and Nancy, at the head of a medical unit. Discharged in 1947, he chose medical research at a time when it was not a fashionable career. He had suffered from asthma as a child and was curious about allergy, so he sought out the demanding Columbia immunochemist Elvin Kabat, in whose laboratory he began research in 1948.
Family needs then took him back to France. His daughter, Beryl, was born in 1949, his father had suffered a severe stroke, and both families lived in Paris. For six years he worked at the Broussais Hospital with Bernard Halpern and the Italian scientist Guido Biozzi, studying how the body clears particles from the blood. But as a foreigner he found he could not establish an independent laboratory in France, and in 1956 he returned to the United States to join the pathology faculty at New York University School of Medicine. For a time he also managed a New York bank bought by his family’s Venezuelan associates, before deciding to give up business entirely for science.
Responders and non-responders
At NYU Benacerraf made the observation that led to his Nobel Prize. He immunised genetically varied guinea pigs with simple, carefully designed antigens, chemical groups attached to a synthetic chain of the amino acid lysine. The animals fell neatly into two groups: some mounted a strong immune response and others none at all. Benacerraf sensed that this was important. Breeding experiments showed that the ability to respond was controlled by dominant genes, which he called immune response, or Ir, genes.
With colleagues including William Paul and Ira Green, first at NYU and from 1968 at the Laboratory of Immunology of the National Institute of Allergy and Infectious Diseases, which he directed, Benacerraf showed that these genes lie within the major histocompatibility complex, or MHC, the cluster of genes that also determines whether transplanted tissue is accepted or rejected. His group and others went on to show how MHC molecules govern the way immune cells cooperate and recognise their targets, and why T cells recognise foreign material only in the context of the body’s own MHC molecules.
A guinea pig laboratory in Bethesda
In 1968, at the invitation of John Seal, Benacerraf moved with William Paul and Ira Green to direct the Laboratory of Immunology at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. The laboratory’s inbred strains of guinea pigs, each genetically uniform, were precious for his work: they made it possible to show cleanly which animals responded to which antigens and how the ability was inherited. Much of the insight into how immune response genes operate came from experiments there by Paul, Green, Alan Rosenthal, Ethan Shevach and Ronald Schwartz, using the systems Benacerraf had developed.
At Harvard from 1970 he and his colleagues, among them David Katz, Martin Dorf, Judith Kapp and Ronald Germain, extended the work to the regulation of immunity, showing that the same genes also control immune suppression, and studying how killer T lymphocytes recognise their targets. By then other laboratories had shown how much matching mattered in practice: the Nobel committee reported that 90 to 100 percent of kidney transplants between siblings with identical tissue types were successful, compared with about 50 percent when a kidney came from an unrelated deceased donor.
Why it matters to patients
In 1980 Benacerraf shared the Nobel Prize in Physiology or Medicine with Jean Dausset, who discovered the human version of the MHC, and George Snell, who had discovered it in mice, for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions. The Nobel committee explained that this knowledge helps explain why different people have different abilities to defend themselves against infections, why a cancer cell is eliminated in some people and grows into a tumour in others, and why certain people are predisposed to certain diseases.
Its most visible use is in transplantation. Matching donors and recipients for their MHC, known in humans as HLA, became, in the words of the Nobel presentation speech, indispensable for all forms of tissue and organ transplantation, from kidneys to bone marrow. Benacerraf’s immune response genes added the crucial idea that the same genes control the strength of each person’s immune response, a principle that underlies modern research on autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, and on why people differ in how well they fight infections.
Harvard, Dana-Farber and the training of scientists
In 1970 Benacerraf became Fabyan Professor of Comparative Pathology and chair of pathology at Harvard Medical School, where he helped start an interdepartmental graduate programme in immunology. He served as president of the American Association of Immunologists in 1973 and of the International Union of Immunological Societies in 1980. From 1980 to 1992 he was president of the Dana-Farber Cancer Institute in Boston, one of the leading cancer centres in the United States, combining research leadership with the care of cancer patients. He was also president of the American Society for Experimental Biology and Medicine in 1974, and in 1985 he was elected to the Institute of Medicine and received the Rous-Whipple Award of the American Association of Pathologists.
He considered training young scientists one of his most valuable and rewarding experiences and chose “The Training of Scientists” as the subject of his presidential address to the immunologists. Many of the young scientists who worked with him, including Lloyd Old, William Paul, Ira Green and Victor Nussenzweig, became leaders of the field. Among his other honours were the U.S. National Medal of Science in 1990 and election to the National Academy of Sciences in 1973.
A Sephardic Jewish heritage
Benacerraf’s background was unusual among American scientists of his generation. Rather than the Yiddish-speaking world of Eastern Europe, his roots lay in the Sephardic Jewish communities of North Africa: his father’s family in Spanish Morocco and his mother’s in Algeria, with a French cultural formation and a Venezuelan birthplace. He experienced exclusion twice, first in the closed doors of American medical schools in 1942 and later in the difficulty a foreigner faced in building a career in Paris.
He kept close ties to Jewish and Israeli institutions. He received a prize in immunology and cancer research from the Hebrew University of Jerusalem in 1974, and honorary degrees from Yeshiva University in 1982 and from the Weizmann Institute of Science in 1989.
Later years and legacy
Benacerraf published his autobiography in 1998. Annette Benacerraf died in 2011, and he died two months later, on August 2, 2011, of pneumonia, in Jamaica Plain, Massachusetts, at the age of 90. Their daughter, Beryl Benacerraf, also became a physician, teaching at Harvard and directing services at Brigham and Women’s and Massachusetts General hospitals.
His legacy is a central idea of modern immunology: that our genes, through the MHC, shape the strength and the targets of our immune responses. That idea links the success of an organ transplant, the risk of an autoimmune disease and the response to an infection or a vaccine. It began with a young doctor who was nearly shut out of medicine and who noticed that some guinea pigs answered a challenge while others stayed silent.
Sources & further reading
Baruj Benacerraf, Biographical, NobelPrize.org · Press release: The Nobel Prize in Physiology or Medicine 1980, NobelPrize.org · Award ceremony speech, The Nobel Prize in Physiology or Medicine 1980, NobelPrize.org · Baruj Benacerraf, Jewish Virtual Library · Baruj Benacerraf, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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