Baruh Benacerraf American immunologist. Winner of the Nobel Prize in Physiology or Medicine 1980 Date of Birth: 20.10.1920 Country: Venezuela

1. Biography of Baruch Benacerraf
2. Early Research and Career
3. Contributions to Immunology
4. Personal Life and Recognition

Biography of Baruch Benacerraf

Baruch Benacerraf, an American physician and immunologist, was born in Caracas, Venezuela, into a family of wealthy textile merchants. His father was a Spanish Jew, while his mother was an Algerian Frenchwoman. In 1925, his family moved to Paris, where they stayed until the start of World War II in 1939. After that, the family returned to Venezuela and a year later, they moved to New York. It was in New York that Benacerraf completed his education. After graduating from the Columbia University College Preparatory School in 1942, he enrolled in the medical college at the University of Virginia. Despite being drafted into the American army after finishing his medical degree, Benacerraf was allowed to continue his studies. In 1943, he became an American citizen. Two years later, he earned his medical diploma and the rank of senior lieutenant in the medical service of the United States armed forces. After serving two years in Nancy, France, Benacerraf was demobilized.

Early Research and Career

Due to his childhood struggles with bronchial asthma, Benacerraf became interested in the mechanisms of immune hypersensitivity, which is the abnormal reaction of the body to foreign agents. Many scientists he consulted with advised him to collaborate with Elvin Kabat, an immunochemist working at the Neurological Institute, College of Physicians and Surgeons of Columbia University. After receiving an invitation to collaborate from Kabat, Benacerraf began studying allergy mechanisms in 1948. The following year, he accepted an invitation to work at the Brasse Hospital in Paris, where he continued his immunochemical research. Although Benacerraf's work on studying the functions of leukocytes was fruitful, he was unable to establish his own laboratory in France necessary for further scientific growth. He believed that the position of a foreign scientist impeded progress in European scientific circles. Therefore, when Lewis Thomas invited him, Benacerraf returned to the United States in 1956 and became an assistant professor of pathology at the New York University School of Medicine. Here, he set up his own laboratory and resumed his research on hypersensitivity mechanisms, focusing on cellular hypersensitivity. In 1960, he became a professor of pathology. At New York University, Benacerraf directed his efforts towards studying cells involved in immune responses – the body's protective reactions to foreign substances or antigens. In the early 1960s, he worked with Gerald M. Edelman, who was studying the structure of antibodies produced by the immune system in response to antigen invasion. Edelman's research was complicated by the fact that animals usually produce a mixture of different antibodies for a single antigen. Benacerraf decided to test whether immunizing animals (initially conducting experiments on guinea pigs) with very simple synthetic antigens could induce the production of more homogeneous antibodies. "I found," he later wrote, "that some animals [reacted to the antigen] by producing antibodies, while others did not." This fact allowed Benacerraf to establish that the ability to respond to specific antibodies is genetically determined. He named these corresponding genes IR genes (from Immuneresponse). In 1965, Hugh McDevitt and his colleagues discovered similar genes in mice and found that they were located in the major histocompatibility complex (MHC), which had been first described by George D. Snell in the late 1940s. The MHC complex is a group of closely linked genes called transplantation genes, as the differences between the donor and recipient antigens, which are controlled by these genes, lead to organ rejection. The human MHC complex, known as the HLA complex, was mainly discovered through the work of Jean Dausset. In 1968, Benacerraf and some of his colleagues moved to the National Institute of Health, where he became the head of the Immunology Laboratory. Here, he and his colleagues confirmed McDevitt's findings using inbred lines of guinea pigs grown at the National Institute of Allergy and Infectious Diseases.

Contributions to Immunology

In 1970, Benacerraf simultaneously held positions as a professor of comparative physiology and chair of pathology at Harvard Medical School. Two years later, he and his colleagues from Harvard independently discovered the restriction dependent on the IR locus, a phenomenon related to the function of two types of lymphocytes - B and T cells. These cells play a crucial role in the immune system's ability to recognize specific substances of invading microorganisms and react to them. B cells produce antibodies that interact with foreign antigens, while T cells directly interact with foreign cells. Different types of T cells can destroy cancerous or virus-infected cells, as well as enhance or suppress the activity of specific B cells. The interactions between T and B cells are restricted by the MHC complex: T cells influence the production of antibodies by B cells only if both types carry the same IR genes. In 1976, other researchers discovered that T cells can destroy virus-infected cells only if both the infected cells and the T cells carry the same transplantation antigens (proteins encoded by genes of the MHC complex discovered by Snell and Dausset). It soon became clear that, although the proteins encoded by IR genes and transplantation genes differ in their chemical structure, their functions are closely related. Both can be considered products of the MHC complex. The products of transplantation genes, found on the surface of most cells in the body, are now called class I molecules, while the products of IR genes, which are part of the immune system, are called class II MHC molecules. "The evolutionary role of MHC restriction, as well as the significance of MHC antigens, becomes clear when considering T cell immune responses as mechanisms primarily responsible for recognizing 'self' and 'non-self' substances on the surface of cells. T cells must determine whether a particular cell has become malignantly transformed or infected with a virus and, therefore, needs to be destroyed," wrote Benacerraf. He hypothesized that products of class I MHC in infected cells are altered for various reasons, and T cells specialize in recognizing even the slightest changes, particularly when combining normal class I molecules of the organism with tumor or viral antigens. Benacerraf suggested that this phenomenon could explain why foreign organs are rapidly rejected during transplantation. T cells of the recipient react to the class I MHC antigens of the donor (which normally differ slightly from the recipient's antigens), destroying cells carrying them, just as they destroy cells whose class I antigens have been altered due to viral infection or tumor transformation.

The ability of T cells to regulate the activity of B cells, as well as the recognition of T cells by infected cells, depends on their recognition of the smallest changes in MHC products. It is believed that B cells inform T cells about the specific antigen they will react to by "presenting" this antigen together with a class II molecule. Based on the role of these IR gene products (HLA-D antigens in humans) in the interactions between T and B cells, one can speculate about the involvement of IR genes in immune responses. If a person lacks T cells that recognize a specific combination of HLA-D and antigen, that antigen will be "invisible" to them, and no immune reaction will occur. The increasing recognition of the crucial role of the MHC in immune responses led to Benacerraf, Snell, and Dausset being awarded the Nobel Prize in Physiology or Medicine in 1980 "for their discoveries concerning genetically determined structures on the cell surface that regulate immune reactions." In his congratulatory speech, researcher George Klein from the Karolinska Institute said that Benacerraf, Dausset, and Snell "were able to translate initially purely specialized fundamental research on inbred mice into a field that concerns a major biological system, which plays a primary role in the study of cell recognition mechanisms, immune responses, and transplant rejection."

Personal Life and Recognition

In 1943, Benacerraf married Annette Dreyfus, the niece of Jacques Monod, whom he had met at Columbia University. They have a daughter named Beryl, who works as a radiologist. Students and colleagues describe Benacerraf as a person with "keen, clear thinking." Lewis Thomas, with whom Benacerraf worked at New York University, called him a "remarkable scientist."

Benacerraf has received the Rebbie Shai Shaknai Award for research in immunology and cancer from the Hebrew University of Jerusalem (1974) and the Dacie Jones Memorial Award from the Helen Hay Whitney Foundation (1976). He has also been awarded an honorary degree from the University of Geneva. He is a member of the National Academy of Sciences, the American Association of Immunologists, the American Society of Experimental Pathology, the Society for Experimental Biology and Medicine, the British Society for Immunology, and the French Society of Biological Chemistry. He served as assistant editor of the American Journal of Pathology and the Journal of Experimental Medicine, as well as a member of the board of trustees of the Weizmann Institute, advisor to the World Health Organization, and president of the Sydney Farber Cancer Institute.