History of Immunology at Harvard
Edward Tyzzer
Courtesy of the Harvard Medical Library
Clarence Cook (CC) Little, a Harvard undergraduate in the early part of the 20th century was known on campus as “The Mouse Man”. He conducted brilliant studies on mouse genetics in the laboratory of William Ernst Castle, one of the doyens of vertebrate genetics and a pre-eminent biologist at Harvard. Little and Castle collaborated closely with Abby Lathrop, a one-time school teacher in Grantham Massachusetts. Lathrop had built a reputation as a breeder of “fancy” mice – inbred mice usually with genetically fixed odd behaviors. Little, Lathrop and Castle generated the DBA (dilute, brown and non-agouti) inbred mouse strain and initiated the systematic generation of inbred strains that proved vital to many subsequent discoveries in immunology. After graduating in 1910, Little remained with Castle as a graduate student and conducted studies on tumor transplant rejection with Edward Tyzzer, also at Harvard. These studies led to the enunciation, some decades later, of the laws of transplantation by George Snell. Snell performed his studies at the Jackson Laboratories at Bar Harbor, an institution single-handedly founded by CC Little in 1929. Little was a colorful, charismatic and controversial individual, often well ahead of his time, who accomplished much after he left Harvard. However it is at Harvard College in Cambridge and at the Harvard Bussey Institute at Jamaica Plain that Little, Castle and Tyzzer laid the foundations for the systematic study of immunology in inbred mice.
Albert Coons and colleague in the lab.
Courtesy of the Harvard Medical Library
Harvard’s contributions to the study of the immune system have been, and continue to be, in both basic and clinical immunology. Albert Coons, an HMS and Massachusetts General trained physician and immunologist, was the first person to conceive of and carryout the idea of coupling antibodies with fluorescent molecules or enzymes that generate colored reaction products, for the purpose of identifying antigens on microbes and in tissues. For his work on inventing these techniques of immunofluorescence and immunohistochemistry performed at HMS in the 1940’s, Coons was awarded the Albert Lasker Award in 1959, and was elected to the National Academy of Sciences in 1962. Charles Janeway Sr., the Physician in Chief at Childrens’ Hospital Boston from 1946 to 1974, pioneered the identification and treatment of primary immunodeficiency disorders and also made enormous contributions to the description and study of pediatric rheumatic diseases. He helped meld the knowledge of basic science with clinical immunology, and his influence went far beyond his many discoveries related to disease. Janeway was one of the greatest physicians in America in his time, and one of the most influential pediatricians of the 20th century on a global basis. He inspired many of his colleagues and trainees to work on vaccines against infectious agents.
(L-R) Thomas Weller, Frederick Robbins, John Enders
Courtesy of the Harvard Medical Library
Although Jonas Salk and Albert Sabin became household names in their time for developing polio vaccines, there would have been no vaccine without the enormous contributions made by John Enders and his colleagues Frederick Robbins and Thomas Weller, at Childrens’ Hospital in Boston. They pioneered the ability to grow the poliovirus in the laboratory, which was crucial for subsequent polio vaccine development. Enders, Robbins and Weller received the Nobel Prize for Physiology and Medicine in 1954.
Joseph Murray (L) accepting the Nobel Prize
Courtesy of the Harvard Medical Library
A Harvard surgeon, Joseph Murray, experimented on organ transplantation in large animals and recognized that genetic similarity between donor and host helped prevent rejection – in keeping with the laws of transplantation. In 1954, at the Peter Bent Brigham Hospital, Murray performed the world’s first successful human transplantation, providing Richard Herrick, who had end-stage kidney disease, with a healthy kidney from his identical twin, Ronald. Murray explored the use of immunosuppression in transplantation and in 1959, he also performed the first successful human organ transplantation that did not involve twins. In 1962 Murray performed the first human transplant using a cadaver donor and in 1990 he shared the Nobel Prize for Physiology and Medicine with E. Donnall Thomas.
Baruj Benacerraf
Courtesy of the Harvard Medical Library
Many decades after Little’s early contributions on inbred mice, Baruj Benacerraf, who was at Harvard for forty years, used inbred mice to help establish the genetic basis for the strength of immune responses, linking immune responsiveness to major histocompatibility complex (MHC) loci originally discovered in the context of organ rejection. MHC proteins were also first purified in the laboratory of Jack Strominger at Harvard, and the structures of these purified proteins were first determined, also at Harvard, by Pamela Bjorkmann and Don Wiley. Benacerraf contributed enormously to the growth of immunology and immunologists at Harvard Medical School from the early 1970s till the end of the 20th century, and Harvard’s large and dynamic immunology community today in part reflects his legacy. Benacerraf shared the Nobel Prize for Physiology and Medicine in 1980 with John Dausset and George Snell.
Outstanding, cutting edge immunology research has continued at a remarkable pace into the 21st century. Several current faculty members at Harvard who are actively involved in research in immunology are members of the National Academy of Sciences. These include Frederick Alt, K. Frank Austen, Christophe Benoist, Barry Bloom, Michael Brenner, Harvey Cantor, Diane Mathis, Stuart Schlossman, Jack Strominger, and Timothy Springer.
In 1974, the Committee on Immunology was formed under the direction of Albert Coons, and authorized by Harvard University to grant a Ph.D. in Immunology. This represented the first step in integrating and coordinating immunology education at HMS and all the teaching hospitals and other affiliated institutions. Another major step in advancing graduate immunology education occurred in 2007 with the creation of the Jeffrey Modell Center for Immunology at Harvard Medical School—a new home for the Program in Immunology, providing space for its many educational activities.