Baruj Benacerraf





Venezuelan-born medical researcher Baruj Benacerraf (born 1920) shared the 1980 Nobel Prize in Physiology or Medicine for his investigations into the workings of the human immune system.

Today immunology is one of the hottest topics in medical science, affecting such vital fields as cancer treatment, organ transplantation protocols, and research into autoimmune disease. When Benacerraf entered the field, however, the immune system was much less well understood than it is today. Snell, one of Benacerraf's collaborators on the research that led to their joint Nobel Prize, reputedly said, according to William Borders of the New York Times , that the number of people who understood his work at the time could be "counted on his fingers." But Benacerraf's research laid the groundwork for a host of future scientific developments. As a researcher, an educator, and an administrator, Benacerraf has been a highly influential figure in modern medical science.

Had Multicultural Background

Baruj Benacerraf (pronounced Bar-OOK Ben-ah-se-RAHFF) was born into an immigrant Jewish family in Caracas, Venezuela, on October 29, 1920. His father had come to the Americas from Spanish-controlled Morocco in search of improved economic prospects; he started a shoe and textile business in Venezuela and prospered, eventually establishing other enterprises, including an import operation and a bank. Benacerraf's mother came from France, and Benacerraf was educated mostly in the French language. The family moved to Paris when he was five, but in 1939, with the outbreak of World War II, they returned to Venezuela and to the family businesses that had continued to flourish. In 1940 Benacerraf was sent to the United States, where his family felt he could get the best university education.

The hope was that Benacerraf would take over his father's place in those businesses, but Benacerraf showed no inclination to do so. Teachers had inculcated in him strong interests in both science and the arts; he became a competent flutist. Benacerraf, however, strove for a compromise. "The only thing that was considered appropriate, that would lead to a career in the mind of people who are self-made like my father, was the profession of doctor, lawyer, and engineer. Being a doctor was what appealed to me most," he explained to Otile McManus of the Boston Globe . In 1940 Benacerraf enrolled at Columbia University's School of General Studies, a branch of the school aimed at nontraditional and foreign students. He blazed through the program in three years, finishing the pre-medical requirements and earning a bachelor of science degree in 1942.

Benacerraf then began applying to medical schools, but found his way blocked. "At that time, it was very hard for Jews to get into medical school," he told McManus. "This country was strongly anti-Semitic in the 1940s. There were quotas. In addition, there was a tendency not to take in foreigners." Benacerraf applied to some 25 schools, includ-

ing several where he later held top positions, but was turned down by all of them despite his strong accomplishments as an undergraduate. Finally, a friend who worked as an assistant to the president of the Medical College of Virginia smoothed the way for his admission there, and he entered the school in 1943. He was also drafted into the U.S. Army that year but was allowed to finish his schooling with the understanding that he would use his skills in service to the military after receiving his degree.

Also in 1943 Benacerraf married his wife, the former Annette Dreyfus. She too had been raised in France, and the two met in Columbia's French club. She was a descendant of both Alfred Dreyfus, the French Jewish military officer whose wrongful arrest precipitated the "Dreyfus affair" scandal of the 1890s, and of Nobel Prize-winning French biologist Jacques Monod. Annette Benacerraf would often assist her husband in his laboratory work but always refused credit for her contributions. Benacerraf received his medical degree after three years of study, did an internship at Queens General Hospital in New York, and was commissioned as a first lieutenant in the Army Medical Corps in 1946.

Served in France

Pleased to be sent to France, Benacerraf served in Paris and in the city of Nancy before being discharged in 1947. Then, "motivated by intellectual curiosity," he wrote in the autobiographical statement he supplied upon winning the Nobel Prize, he "decided upon a career in medical research at a time when such a choice was not fashionable." Partly because he had suffered from bronchial asthma as a child, he had become curious about allergies and the immune system. He consulted scientists in New York to whom his teachers in Richmond had recommended him, and they steered him toward the laboratory of a pioneering immunologist, Elvin Kabat. Benacerraf began working in Kabat's laboratory in 1948.

"Training with Elvin Kabat was one of the significant experiences in my development as a scientist," Benacerraf wrote in his autobiographical statement. In two years of work with Kabat, Benacerraf obtained a solid grounding in scientific rigor and in the importance of quantifiable results, and he began to gain a deeper understanding of hypersensitivity mechanisms and immune system malfunctions that lead to such phenomena as allergies. Benacerraf's daughter, Beryl, was born in 1949. She grew up to become a radiologist who made major clinical advances in the interpretation of ultrasound fetal images.

Beginning around that time, Benacerraf's career was disrupted, but not derailed, by family problems. His father, by then living in Paris, suffered an incapacitating stroke, and Benacerraf moved there to be closer to him. For six years Benacerraf juggled family business commitments with his own research. He was lucky, at first, to find a job at Paris's Broussais Hospital in the lab of immunology researcher Bernard Halpern, the discoverer of antihistamines. There, working with Italian researcher Guido Biozzi, Benacerraf performed experiments that deepened his understanding of the way phagocytes—cells that eat material extrinsic to the healthy body, such as contaminants—do their work.

Halpern, however, finally informed Benacerraf in no uncertain terms that as a foreigner his chances of establishing a permanent career in France were slim. The truth of Halpern's information was driven home when Benacerraf tried but failed to find a job with another lab in Paris. He returned to the United States in 1956 and was happy to be recruited for the position of assistant professor of pathology at New York University (NYU). The agent responsible for bringing Benacerraf to NYU was Lewis Thomas, the popular physician and essayist who later wrote the book The Lives of a Cell . Benacerraf was elevated to associate professor in 1958 and to full professor in 1960.

Investigated Genetic Susceptibility to Disease

The late 1950s and early 1960s were professionally satisfying for Benacerraf as he entered his most productive years as a researcher. "The scientific atmosphere at New York University during that period was particularly favorable to the development of Immunology. Numerous immunologists worked enthusiastically and interacted profitably," he wrote in his Nobel Prize autobiography. Benacerraf worked on various topics as part of several separate teams of researchers. Most far-reaching, however, was the work for which he eventually received the Nobel Prize.

That work was carried out by Benacerraf together with geneticist Snell of the Jackson Laboratory in Bar Harbor, Maine, and Dausset of the University of Paris, France, over a long period in the 1950s and 1960s, and involved major advances in the understanding of the operation of the immune system. Benacerraf's contribution involved complex work but sprang from a common-sense observation, one related to a phenomenon everyone has experienced: some people tend to be more susceptible to certain diseases than others, even under identical conditions. Benacerraf, working with guinea pigs, noticed that some of the animals produced antibodies to specific antigens (an antigen is any substance that stimulates an immune response, and may be internal or external), while others did not.

As he worked, Benacerraf realized that the sensitivity of the cell surface molecules that initiate an immune response was not random. In fact, it was likely to be controlled by an individual's genetic makeup. Benacerraf demonstrated the existence of a previously unknown gene within the Major Histocompatibility Complex or MHC, the group of genes that controls whether cells within the body coexist or attack each other. This new gene controlled the behavior of cells as they encountered irritants or invaders. In the words (as quoted by the Jewish Virtual Library) of the Royal Swedish Academy of Sciences, the administrators of the Nobel Prize, Benacerraf won the 1980 prize for the "discovery of the Major Histocompatibility Complex genes which encode cell surface molecules important for the immune system's distinction between self and non-self." Nobel Prizes tend to be awarded after several years during which work done by the recipient is shown to be valid and useful; Benacerraf's 1980 prize was given for work done in the 1960s. The new gene Benacerraf discovered is now known as an immune-response gene or Ir gene for short.

Benacerraf's research led him to more prestigious positions within his field. In 1968 he accepted the post of chief of the immunology laboratory at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, developing experiments that would further elucidate the operation of the Ir gene. But he missed the academic environment and the opportunity to interact with students. As a result, he moved to Harvard Medical School in 1970, serving as professor and chairperson of a new department of comparative pathology. He remained in that post until his retirement in 1991, settling in Boston after a lifetime of moving around the country and the world. Beryl Benacerraf also established her radiology practice there, and the family remained closely knit, vacationing together in a large summer home in Falmouth, Massachusetts. Benacerraf was closely involved in the training of young scientists, and made that a favorite theme when he addressed professional conferences. In the 1970s he wrote several major immunology texts, including Textbook of Immunology (1979).

Still another professional accomplishment lay on Benacerraf's horizon: in 1980 he was named president and chief executive officer of the Dana-Farber Cancer Institute at Harvard. In that post, Benacerraf had the chance to oversee a body of research that depended in many cases upon his own work as one of its pillars. But the work also drew on the other major theme of his life: the experience as a business executive gained from his intermittent management of his family's enterprises. He stabilized the institution's finances and proved an effective fundraiser. The center added two new buildings under Benacerraf's leadership, including a 14-story research tower. Dana-Farber Board of Trustees Vice Chair Vincent O'Reilly told the Harvard University Gazette that he had expected to encounter in Benacerraf "an individual of great intellect and scientific acumen. My expectations were met, but what surprised me was how open he was to new ideas from a business perspective and how adept a businessman he was." These ultimate contributions formed a fitting close to a remarkable professional career that Benacerraf summed up in a 1998 autobiography, From Caracas to Stockholm .

Books

Benacerraf, Baruj, From Caracas to Stockholm , Prometheus, 1998.

Notable Scientists: From 1900 to the Present , Gale, 2001.

World of Anatomy and Physiology , 2 vols., Gale, 2002.

Periodicals

Boston Globe , September 21, 1987.

New York Times , January 22, 1963; October 11, 1980; October 12, 1980.

Online

"Baruj Benacerraf: Autobiography," Nobel Prize Official Site, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1980/benacerraf- utobio.html (December 18, 2006).

"Baruj Benacerraf," Jewish Virtual Library, http://www.jewishvirtuallibrary.org/jsource/biography/benacerraf.html (December 18, 2006).

"Benacerraf Donates Library to Dana-Farber Cancer Institute," Harvard University Gazette , http://www.hno.harvard.edu/gazette/1998/04.23/BenacerrafDonat.html (December 18, 2006).



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