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Discovering Immune Response Genes

Discovering Immune Response Genes

The immune response (Ir) genes discovered by Baruj Benacerraf were only the first of several dozen closely linked genes determined to be within the major histocompatibility complex (MHC) of animals, including humans. Unlike other genes located within the MHC that were first described because of their role in transplant rejection, the Ir genes regulate the ability of immune cells to interact with each other, determining the body’s ability to respond to foreign proteins and also governing the level of that response. Products of the response genes, referred to as Ia antigens, are displayed on the surface of immune cells such as macrophages; the presence of receptors for these surface molecules on other classes of white blood cells such as the T lymphocytes determines whether such cells are activated, resulting in the immune response. While Benacerraf and others made their discoveries using inbred animals such as guinea pigs, nearly identical mechanisms regulate the immune response in humans.


See Also

Great Lives from History: Latinos

Baruj Benacerraf

by Richard Adler

Venezuelan-born Nobel Prize-winning immunologist

While studying the ability of inbred strains of animals to respond to certain foreign proteins or antigens, Benacerraf discovered a series of genes that regulated the interactions of immune cells. Benacerraf termed these the immune response (Ir) genes, and the discovery earned him a Nobel Prize.

Areas of achievement: Science and technology

Early Life

Baruj Benacerraf (bah-ROOK beh-NAH-seh-rahf) was born in Caracas, Venezuela, to parents of Spanish-Jewish (Sephardic) ancestry. His father, Abraham Benacerraf, was born in Tetuán in Spanish Morocco, while his mother, Henrietta Lasry, had been born and raised in French Algeria. His father was a prosperous textile merchant, and Benacerraf was raised in a (French) cultured, relatively wealthy household. When he was five years old, the family moved to Paris, where he spent most of his youth and received his early schooling. Benacerraf attended the Lycée Janson de Sailly, a prestigious high school, where he became fluent in French and was immersed in French culture.

Baruj Benacerraf.

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Recognizing the threat to France posed by the expansion of Nazi Germany, Abraham returned with his family in 1939 to Venezuela, where he continued his success in the textile import business. The following year, the family moved to New York, where Benacerraf continued his education at the college level. He first enrolled in a textile engineering school in Philadelphia but left after two weeks. Benacerraf then enrolled in the School of General Studies at Columbia University, from which, in 1942, he graduated with a bachelor of science degree. His father had expected Benacerraf to join the family textile business, but having also completed the general science requirements for admission to medical school, Benacerraf decided upon a career in medicine.

While his academic credentials were more than sufficient for admission to medical schools, Benacerraf’s religious and ethnic backgrounds resulted in rejection of his application by some two dozen schools, including Harvard, Yale, and Columbia. However, the father of a friend happened to be an assistant to the president of the Medical College of Virginia in Richmond, and he arranged an interview for Benacerraf. Benacerraf was accepted into the program in the summer of 1942. He became a naturalized American citizen the following year, and as a result of the wartime training program, he completed his medical training in three years and was drafted by the Army. In 1943, he also married Annette Dreyfus, a French refugee and relative of both Captain Alfred Dreyfus, who was convicted of treason in 1894 in the notorious “Dreyfus Affair” in France, and future Nobel laureate Jacques Monod. Benacerraf and Annette would have one child, a daughter, Beryl.

After a two-year internship at Queens General Hospital, Benacerraf received a commission as first lieutenant in the Army Medical Corps and was assigned to a position as head of a medical unit in Paris, where he served for two years.

Life’s Work

After his discharge from the Army in 1947, Benacerraf decided to continue his medical career. Because he had suffered from bronchial asthma in his youth, he decided to pursue research in the field of immunology with emphasis on hypersensitivity. In February, 1948, Benacerraf joined the laboratory of Elvin Kabat in the Neurological Institute at Columbia University, where he became adept at research in immunochemistry and experimental research methods in immunology. Benacerraf worked with Kabat for more than a year; however, because his father—who had returned to Paris—was incapacitated by a stroke, and Annette’s family lived there as well, Benacerraf decided to return to France in 1949. He spent six years there working with Bernard Halpern at the Broussais Hospital in Paris studying cellular immunology. Benacerraf came to realize, however, that as a naturalized American he stood little chance of becoming an independent researcher in France. He returned to the United States in 1956, accepting a position as assistant professor of pathology at New York University School of Medicine.

The research atmosphere at NYU was particularly productive during the years Benacerraf was on the faculty. The field of immunology was evolving from one that was primarily observational to one in which molecular mechanisms underlying the immune response were becoming clearer. Benacerraf had the opportunity to work with future Nobel laureate Gerald Edelman in his studies of antibody structure. Among the experimental results Benacerraf observed in his own study of antibodies was that when guinea pigs were immunized with small molecules (antigens), some animals responded well (“responders”), while others produced little or no antibody (“nonresponders”). Attempting to understand the genetic basis for the difference, Benacerraf mated responders and nonresponders and discovered the difference was related to genes that he termed the immune response (Ir) genes. He had now entered the field of immunogenetics, in which he would spend much of his later scientific career.

By 1968, Benacerraf had been promoted to professor of pathology; however, an opportunity for further professional advancement appeared when he was offered the position of director of the laboratory of immunology at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. The NIAID laboratory also provided him with a wide selection of strains of guinea pigs, allowing further analysis of the role played by Ir and other genes in regulating the immune response. For example, Benacerraf determined that these genes are found within the larger major histocompatibility complex, a region containing several hundred genes that regulate most aspects of immunity.

In 1970, Benacerraf was named chair of pathology at Harvard Medical School, where he had greater opportunity not only to direct his research but also to interact with students in the field. Among his discoveries was that in order for antibodies to be produced, antigens not only must be “presented” to lymphocytes by a class of cells known as “antigen-presenting cells,” but also that these cells all must share identical Ir molecules. In 1980, Benacerraf was awarded the Nobel Prize in Physiology or Medicine, primarily for his research on Ir genes. That year, he also was appointed to the presidency of the Sidney Farber Cancer Institute, which is affiliated with Harvard Medical School. Among Benacerraf’s other awards are the T. Duckett Jones Memorial Award of the Helen Hay Whitney Foundation (1976), the Waterford Biomedical Science Award (1980), and the Charles A. Dana Award (1996). Benacerraf also has received numerous honorary doctorates.

Significance

Prior to Benacerraf’s research, scientists knew that three classes of white blood cells were somehow involved in the immune response: macrophages, subsequently termed antigen-presenting cells, and B and T lymphocytes; however, they had little knowledge of the discrete functions of these cells. Benacerraf’s work led to an understanding of specific immune response genes that regulated immune processes. The Ir genes subsequently were mapped to the region of the major histocompatibility complex, a region in which gene products determine whether, and to what extent, white cells can interact with each other. The understanding that these gene products play a significant role in organ transplant rejection later was used to help improve the process of organ transplantation.

Further Reading

1 

Benacerraf, Baruj. From Caracas to Stockholm: A Life in Medical Science. Amherst, N.Y.: Prometheus Books, 1998. In this autobiography, Benacerraf describes his early privileged life and the challenges he faced in developing his scientific career.

2 

Coico, Richard, and Geoffrey Sunshine. Immunology: A Short Course. Hoboken, N.J.: John Wiley & Sons, 2009. A concise review of immunology, including the molecular basis for white blood cell interactions.

3 

Kurian, George Thomas. The Nobel Scientists: A Biographical Encyclopedia. Amherst, N.Y.: Prometheus Books, 2002. Contains a brief biography of Benacerraf and a summary of his historic work with Ir genes.

4 

Scientific American Presents Nobel Prize Winners on Medicine. New York: Kaplan, 2009. A collection of writings by Nobel laureates in physiology or medicine. While Benacerraf is not among the authors, the application of his work is noted in several articles by immunologists.

Citation Types

Type
Format
MLA 9th
Adler, Richard. "Baruj Benacerraf." Great Lives from History: Latinos, edited by Carmen Tafolla & Martha P. Cotera, Salem Press, 2012. Salem Online, online.salempress.com/articleDetails.do?articleName=GLL_10013240008001001.
APA 7th
Adler, R. (2012). Baruj Benacerraf. In C. Tafolla & M. P. Cotera (Eds.), Great Lives from History: Latinos. Salem Press. online.salempress.com.
CMOS 17th
Adler, Richard. "Baruj Benacerraf." Edited by Carmen Tafolla & Martha P. Cotera. Great Lives from History: Latinos. Hackensack: Salem Press, 2012. Accessed October 22, 2025. online.salempress.com.