Nobel Prize in Physiology or Medicine 1980 for discovery “concerning genetically determined structures on the cell surface that regulate immunological reactions” or “discovery of the major histocompatibility complex genes which encode cell surface protein molecules important for the immune system’s distinction between self and non-self.”
Baruj Benacerraf was born on October 29, 1920, in Caracas, Venezuela. His parents, Abraham and Henriette Lasry Benacerraf, had immigrated to Venezuela from North Africa. Abraham was born to a poor Sephardic Jewish family in the 1880s in what then was Spanish Morocco. The Jewish ghetto where they lived lacked basic services such as water and sewage. When Abraham was 14, he moved to Caracas, Venezuela, to help a cousin in his textile import/export business. As Abraham became successful, he sent money to his family and several of his brothers joined him in Caracas. When Abraham wanted to marry, he sought a wife in the area where his family then lived, a Jewish community in French-speaking Algeria. There he met Henriette, who had been raised speaking French and no Spanish. After they were married in September 1919, they moved to Venezuela and lived in a large house with Abraham’s brothers and several servants.
About a year later, Baruj Benacerraf was born at home. Although his first language was Spanish, he also learned French. When he was five years old, the family moved to Paris to establish the purchasing side of the company, while Abraham’s brothers stayed in Caracas to manage that end of the family business. At age six, Benacerraf started school at the Lycee Janson where for 12 years he received a classical French education that focused on the humanities but was weak in the sciences.
Although his life seemed privileged, during his childhood and adolescence he had his share of tribulations. Throughout his childhood, Benacerraf had chronic asthma and undiagnosed dyslexia, so that he often was sick and required special tutoring. Eventually he overcame his language barriers and learning disabilities to become one of the best students in his school. In 1931, when Benacerraf was 11 years old, his brother Paul was born. As a teenager, before World War II, Benacerraf was able to enjoy the cultural life of Paris, even though he experienced discrimination both by being a foreigner (Venezuelan, born to a Spanish father) and Jewish, as antisemitism was evident in school, on the streets, and in the subway.
In 1938, Benacerraf passed the first of two exams required to obtain his Baccalaureate, similar to a high school diploma. In between exams, he took the opportunity to visit his uncle in Caracas, the first time he had been back to his birth country in 10 years. Upon his return, Venezuela felt both foreign and unfamiliar to him. His objective was to learn more about the family business. Under the guidance of his uncle Fortunato, Benacerraf got to know aspects of the business that were established in Venezuela. He returned to Paris by boat via New York City in the early spring of 1939 to prepare for his second Baccalaureate exam. War seemed imminent. Benacerraf returned to Venezuela as Paris was an increasingly dangerous place, yet he decided to continue his education in the United States. He enrolled in a textile engineering school in Philadelphia to start in the fall of 1939 and went to New York in July 1939 to learn English. Once he started in Philadelphia, however, he decided that he did not enjoy studying textiles, so he returned to New York and enrolled as a student in an extension program at Columbia University that taught English writing to foreigners. His parents and brother also moved to New York to establish the purchasing office for their family business, as Paris no longer was possible as a base of operations.
To finish his second Baccalaureate exam, Benacerraf enrolled at the Lycee Francais in New York. He became friends with two science teachers there, the chemist Paul Weil and the microbiologist Rene Dubos, who inspired in him an interest in the sciences. Having obtained his Baccalaureate diploma, Benacerraf enrolled in Columbia University’s School of General Studies in September 1940, in the pre-med track.
This was a perilous time for Europe and the United States. In June 1940, Germany invaded Holland and Belgium. As France fell to the Nazi regime, the Petain government was established in exile in the south of France. The United Kingdom was isolated. Pearl Harbor was bombed in December 1941.
For Benacerraf personally, this time in New York changed his life. While at Columbia, he joined French student organizations through which he met Annette Dreyfus, whose family had been prominent in the Jewish community in Paris. Family connections and friends helped the Dreyfus family escape Paris, first to London then to New York, where Annette was enrolled at Barnard College. As the Dreyfus family lived near the Benacerraf family, Baruj and Annette often would share a ride to the Columbia/Barnard campus. After receiving college credit for the Baccalaureate, Benacerraf was able to complete the pre-med degree in just two years. Upon completing his degree, he and Annette announced their engagement in June 1942.
Although Benacerraf had received good grades from Columbia and had a degree in chemistry with pre-med credits, he was not accepted into most of the medical schools he applied to, possibly because of being a foreign national with intentions of staying in the United States, possibly because he was Jewish. Through connections with friends, however, he was offered a spot in the Medical College of Virginia (MCV) in Richmond, to start in September 1942. He lived in a rented room in the home of Baptists who were impressed with his ability to speak French so well despite being Venezuelan.
Benacerraf noted differences between Venezuela and the South in general and Richmond in particular. In Venezuela, blacks were poor but had equal rights with other groups. Richmond in 1942 still had scars from the Civil War and was segregated, so that blacks were cared for in the teaching hospital of MCV but in facilities that were separated from those for white patients.
Because of the wartime need for medical officers, the usual four years of medical school were condensed into three years. During a short break between the first and second years in March 1943, Benacerraf went to New York City and married Annette in an orthodox Sephardic congregation, in keeping with his father’s tradition. Back in Richmond, Benacerraf was drafted and inducted into the Army unit connected with the medical schools and was trained to serve as a medical officer upon graduation. To be able to serve as commissioned officers in the US Army, all foreign medical students inducted into the Army also received US citizenship.
At the end of his final year, Benacerraf was accepted for an internship at Queens General Hospital, so he and Annette returned to New York City and moved into the Benacerraf family apartment in Manhattan. His 9-month internship started in July 1945. During this time, the war against Nazi Germany and Japan ended, and his wife Annette was diagnosed with and treated for pulmonary tuberculosis. When Benacerraf finished his internship and had to begin serving as a first lieutenant in the Army medical corps, the situation in Europe was much more secure. By the time he finished his basic training, Annette and her family had returned to Paris. Before Benacerraf could leave for Europe, however, his father (who then was in Venezuela) had a stroke, so he went to Venezuela and arranged to have his parents move to Paris, as well.
Benacerraf was sent first to Germany, then a medical hospital in Villejuif, south of Paris. France still was suffering from the effects of war; as industry and agriculture remained weak, there were shortages of food and energy. Annette’s father Ado Dreyfus was put in charge of the French governmental agency tasked with allocating surplus stocks that the American army donated to France in support of the recovery. When the medical hospital in Villejuif was closed, Benacerraf was reassigned to a medical unit in a French military hospital in Nancy, in the Alsace region of France. For 12 months, he was in charge of a 5-bed unit that provided community health services to American servicemen in the area. Once the year of service in Nancy was completed, Benacerraf was eligible for discharge from the Army and returned to the United States to finish his medical training.
For the next stage of his life in the United States, Benacerraf had dual careers. On the one hand, he started his medical career focusing on research rather than clinical work. On the other hand, he oversaw his father’s interest in the family business in Venezuela, as Abraham never fully recovered from his stroke. The experience of handling a business as well as making research discoveries was of major importance later in his life. In the mid-1940s, however, the family business aspect of his life helped support his medical career, as the two-year research fellowship he obtained at Columbia University was unpaid.
The fellowship was under immunochemist Dr. Elvin Kabat, at the College of Physicians and Surgeons. In part because of his childhood asthma, Benacerraf had decided to focus on immunology, which was a relatively new field in 1947 and little was then known about antibodies. Kabat suggested that he study hypersensitivity and hypersensitivity reactions. Using rabbits and guinea pigs, Benacerraf measured antigen and antibody concentrations. From Kabat, he learned the importance of accuracy and quantification as the basis for evaluating data objectively. Benacerraf found that the sense of discovery arising from such research was exciting.
In the spring of 1949, two major events happened for Benacerraf. In April, his daughter Beryl was born. Also, Benacerraf passed the New York Board of Medicine examination, which enabled him to practice medicine. He decided instead to devote his career to research. During his fellowship, Benacerraf had met Dr. Bernard Halpern, a French pharmacologist who helped develop the first clinically effective antihistamine. Halpern had an active research lab in Paris with work looking into hypersensitivity. Halpern offered Benacerraf a one-year appointment at his lab in the Broussais Hospital. Benacerraf accepted and moved to Paris with his wife and daughter to be closer to both sets of families.
Although Benacerraf found that Halpern’s lab lacked some of the more modern facilities and equipment that he was used to in New York, his one-year appointment turned into a six-year collaboration with Dr. Guido Biozzi. Using guinea pigs, rats, and mice for their experiments, the two studied the effect of antihistamines on the clearance of particulate material from the blood by phagocytes in the liver and spleen. Phagocytes are cells that circulate in blood and tissue, engulf foreign materials (such as microorganisms and debris from other cells), and ingest them, effectively clearing them from the blood and tissue. Benacerraf and Biozzi looked at natural phagocytic defense mechanisms involved in immune responses, in particular the concentration of carbon particles in blood and organs of the test animals to establish a pattern of clearance. Their study resulted in a general method to investigate the phagocytic capacity of the reticuloendothelial system (RES — a set of tissue and organs including the liver, spleen, and lungs) using mathematical equations to describe how the phagocytic system physiologically clears particulate matter from blood. Such work provided better understanding about how vaccination can activate some of those phagocytes to increase resistance against pathogens.
By 1959, the Centre National de la Recherche Scientifique (CNRS) was supporting French research personnel, but the only full-time position at Halpern’s lab was given to Biozzi. As Benacerraf was not a French citizen and had not earned his degree from a French medical school, his career in France would be limited. At an international meeting, he met Dr. Lewis Thomas, the chair of pathology at New York University (NYU), who offered Benacerraf a position as assistant professor of pathology. This allowed Benacerraf to return to New York.
While Benacerraf was in Paris, he continued to have two careers, dividing his time between the research in Halpern’s lab and the family business in Venezuela. Benacerraf separated his father Abraham’s interests from his uncle Fortunato’s interests in Caracas by converting Abraham’s part into a banking business, the Banco Union, that could be supervised from abroad. Banco Union was owned in part by Benacerraf’s family and by other associates in Venezuela. In 1953, Abraham fell into a coma and died, leaving Benacerraf to settle his father’s estate in Venezuela and manage his mother’s and brother’s shares in addition to his own. As part of this business management, in 1958 he used Banco Union to obtain the controlling interest in Colonial Trust Co., a small New York bank. Due to the political instability in Venezuela at the time, none of the Venezuelan associates were able to come to New York to manage Colonial Trust, so Benacerraf was appointed director and chair of the credit committee. His salary from Colonial Trust was substantially higher than his starting salary at NYU. After learning the basics of banking from the staff at Colonial Trust, Benacerraf managed the bank for several years before selling it for a profit. This management and business experience was very important later on in his medical research career.
As assistant professor and later professor of pathology at NYU, Benacerraf had his own lab and research support, and with several colleagues looked at a wide variety of topics, including hypersensitivity at the cellular level, immune complex diseases, anaphylactic hypersensitivity, tumor specific immunity, immunogenetics, and the structure of antibodies. At NYU he also worked with colleagues on phagocytic function in the RES, the effect of endotoxins on phagocytes, blood clearance of bacteria and viruses, inflammatory immune complexes, the role of mediators in inflammation, tumor immunology, and immunoglobulins. Annette trained as a technician to be able to help out in the lab.
Benacerraf also enjoyed training young scientists in the ways of research. He felt that modern medicine is scientific, so physicians and clinicians need to be trained to think like research scientists, not only as healthcare providers. Research supported by public funds in the United States requires grant requests to be meticulous, as only the most imaginative, skilled scientists will get funding. In his view, impartial peer review systems used to award grants also helps make American biomedical sciences so strong.
In part due to changes in the faculty at NYU, in 1968 Benacerraf was eager to concentrate more on research and less on academic responsibilities, so he accepted the position of Director of Immunology at the lab at the National Institutes of Health (NIH)/ National Institute of Allergy and Infectious Disease (NIAID) in Bethesda, MD. Continuing on work started at NYU, Benacerraf and his team used in-bred guinea pigs in immunogenetic research, which led to the identification of an immune response (Ir) gene located in a chromosome linked with the major histocompatibility complex (MHC). This gene was found to be associated with auto-immune diseases such as multiple sclerosis and rheumatoid arthritis, and with the body’s rejection of transplanted organs.
Moving from an academic setting to a governmental one did not end the difficulties Benacerraf encountered with personnel issues. Government regulations regarding hiring and firing practices allowed scientists whom Benacerraf regarded as incompetent to remain on staff. One of his complaints about this group of scientists was that they placed a greater value on prestigious titles than they did on the research work itself. To deal with this, he abolished many of those titles. As a result, many of those scientists resigned. Benacerraf reoriented the NIAID lab towards immunogenetics and cellular immunology, replacing the scientists who resigned with young scientists he considered to be highly competent. With this group he started a set of experiments that eventually revealed aspects of antigen processing and T lymphocytes.
And yet, after all, he missed academic life. In the spring of 1969, when he was 50 years old, Benacerraf was offered a position at Harvard Medical School (HMS), which had been in discussion before he became head of NIAID. HMS is affiliated with several Boston teaching hospitals and appoints the faculty who will teach at those hospitals, even though HMS does not control the clinical facilities themselves. As Chair of the Department of Pathology, Benacerraf continued his tendency to appoint young scientists who were starting their careers instead of those seasoned scientists who already had achieved some claim to fame. Among the staff he recruited for the pathology lab and the Department of Immunology was Dr. Emil Unanue, a Cuban physician chosen to head the Division of Immunology. Benacerraf also established a new program in immunology that was interdepartmental, run by faculty committee rather than a single department. The Department of Pathology shifted its focus from morphology to experimentation, especially in immunology, immunopathology, inflammation, cell biology, and vascular and renal pathophysiology.
Benacerraf continued his own research, focused on immunogenetic and cellular immunology. Along with colleagues, he worked to identify genes that encode immunological molecules linked with specificity and discrimination between self and foreign materials. They found that Ir genes are not related so much to the body’s ability to produce antibodies but to the ability of T lymphocytes to recognize foreign materials as antigens. In 1978, Benacerraf formulated the hypothesis that transplantation molecules expressed on the surface of cells are capable of specific interactions with processed peptide fragments of processed antigens. Processed antigens are those proteins that have been denatured, unfolded, and digested by enzymes of phagocytes to initiate the cellular immune response and are presented to the T lymphocytes of the immune system.
In part based on this work, in 1980 Benacerraf was awarded the Nobel Prize for the “discovery of the MHC genes which encode cell surface molecules important for the immune system’s distinction between self and nonself” or the “genetically determined structures on the cell surface that regulate immunological reactions.” The honor was amplified by being the first time a Venezuelan had received a Nobel Prize. It also was the first time a graduate of the Medical College of Virginia and the first time since 1954 that a member of HMS had won. When the Nobel Prize winners were announced, Benacerraf was contacted by multiple news outlets, friends, family, colleagues, and politicians. For the award ceremony, he traveled to Stockholm with his wife Annette, his daughter Beryl, and Beryl’s husband Peter, on the way stopping in Paris to visit his mother as she was unable to travel. As Benacerraf recounts in his 1998 memoir From Caracas to Stockholm: A Life in Medical Science, winning the Nobel Prize gave him a sense of independence from authority and feeling of having a mantel of protection. Ironically, he attributes his self-doubts to his winning the award and the other accolades in his life. Because he never was overly confident of his work, he always was very thorough in the lab and never took anything for granted or accepted a discovery as valid until it was verified multiple times. This gave him a reputation for having impossibly high standards and being too demanding, but it was such devotion to accuracy and reliable data that laid the foundation for his success.
His career reached its highest step earlier in 1980 when he was named president of the Sidney Farber Cancer Institute. A benefactor, Charles Dana, helped the institute build a new facility, so the organization was renamed Dana-Farber Cancer Institute (DFCI). Benacerraf’s work at Colonial Trust was very beneficial to him in this position as managing finances was an important aspect of his work. He began a five-year campaign for funds, which raised $60 million (starting with Benacerraf’s own Nobel Prize award money). This funding put the DFCI on a sound financial footing. While president of DFCI, a major project was the development of a new way to treat leukemia, in which a patient’s bone marrow is removed and treated with antibodies, then transplanted back into the patient after the patient has undergone radiation or chemotherapy.
Benacerraf remained as both chair of HMS Department of Pathology and head of the DFCI until 1991. After that time, he continued to work in his own lab well into his 80s. His wife Annette passed away in June 2011 and Benacerraf himself died of pneumonia later that year at the age of 90. His daughter Beryl continued in his footsteps, as a radiologist and professor at HMS, and director at Brigham and Women’s Hospital and of Massachusetts General Hospital, in Boston.
Sources:
Benacerraf, Baruj (1998). From Caracas to Stockholm: A Life in Medical Science. New York: Prometheus Books.
“Baruj Benacerraf Biographical” at http://www.nobelprize.org
“Baruj Benacerraf” at en.wikipedia.org
Newton, David E. (2007). Latinos in Science, Math, and Professions. New York: Facts on File, Inc.
“Barug Benacerraf (1920-2011)” at http://www.jewishvirtuallibrary.org
“Baruj Benacerraf: American Immunologist” at http://www.britannica.com
“Baruj Benacerraf Biography” at http://www.faqs.org
TRANSCIENCIA 