David H. Sachs

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Megan Sykes Interview with David H. Sachs

Medawar Prize Lecture

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Russell-Winn Laboratory 1968

Dr. Sachs graduated summa cum laude in chemistry from Harvard College in 1963, following which he studied organic chemistry as a Fulbright Fellow in Paris, receiving a D.E.S. from the University of Paris in 1964. He then returned to Boston to enter Harvard Medical School, where he earned his M.D., magna cum laude, in 1968. During medical school, he became fascinated with the newly developing field of transplantation, particularly with the concept of transplantation tolerance, shown a decade earlier by Sir Peter Medawar and colleagues, to be inducible in mice by exposure to foreign cells very early in life. If similar tolerance could be induced in adults, patients might eventually be able to accept transplanted organs without long-term immunosuppression. In hopes of studying this problem further, he approached Dr. Paul S. Russell at the Massachusetts General Hospital (MGH) to request a position in his laboratory as a student research assistant. This was the beginning of a long career in the field of transplantation tolerance — and also of his long and continuing association with Dr. Russell, and with the MGH.

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with Paul Russell, Ben Cosimi & Emil Skamene (1970)

With the intent of becoming a transplant surgeon, as well as continuing his research career in this field, Dr. Sachs entered the surgical residency at MGH in 1968. He took a two-year leave of absence from that residency in 1970 to join the Public Health Service as a clinical research fellow at the NIH. A series of discoveries and promotions led to prolongation of that leave of absence for 21 years, during which time he became Chief of the Immunology Branch and developed a major program in transplantation research. In 1991, he returned to Boston as the Paul S. Russell Professor of Surgery and Immunology at Harvard Medical School and as the first Director of the Transplantation Biology Research Center at MGH, where he has continued to work until the present.

During his career, Dr. Sachs has trained more than 80 pre-doctoral and postdoctoral fellows, many of whom have gone on to outstanding careers as transplantation physicians and scientists. He has published over 700 scientific articles. He has served The Transplantation Society in the office of Vice President and as a Councilor for a total of 16 years during his career, and is a member of numerous other societies, including, the AST, the ASTS and the IXA. He was the Founding Editor and Editor-in-Chief of Xenotransplantation from 1994 to 1997 and has been one of the three North American Editors of Transplantation since 1997. He was elected to the Institute of Medicine of the National Academy of Sciences in 1996 and has received numerous other honors and awards, including the 2012 Starzl Prize, which he shared with his close colleague and friend, Dr. Ben Cosimi.

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TBRC yearly lab photo (2009)

Principal Scientific Accomplishments

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with Ben Cosimi and Tom Starzl at Starzl Prize award ceremony (2012)

Induction of transplantation tolerance through mixed chimerism: Dr. Sachs and his colleagues demonstrated in the late 1980's, that the survival of a small percentage of MHC-mismatched donor cells following bone marrow transplantation was sufficient to induce tolerance without the complications associated with complete marrow replacement. Since the original description of this phenomenon, called "mixed chimerism", in mice, pioneering studies have extended this work to large animals and most recently to clinical applications, including the first successful clinical protocol for the induction of transplantation tolerance across HLA barriers in patients receiving renal transplants.

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with wife, Kristina, at Rome Congress (2000)

Discovery of class II antigens: In 1973, Dr. Sachs was the first to report the serologic detection of cell surface antigens determined by genes in the mouse MHC that were expressed predominantly on B cells and which subsequently became known as class II antigens.

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with genetically engineered pigs at breeding facility

Development of miniature swine as a large animal transplantation model: More than 40 years ago, Dr. Sachs recognized the need for a large animal model for studies of transplantation and chose miniature swine because of their appropriate size (comparable to humans), physiologic and immunologic similarity to humans, and their breeding characteristics. The latter have made possible the establishment of MHC-homozygous and recombinant lines, making miniature swine the only large animal model in which one can reproducibly study the effects of selective genetic differences within the MHC. In their role as a preclinical animal model, these animals have provided numerous insights for understanding tolerance and histocompatibility.

Xenotransplantation: Dr. Sachs and his colleagues have utilized modern genetic engineering techniques to develop one inbred subline of miniature swine as an exceptionally appropriate donor for organ xenografts to primates. In addition, they are at the forefront of extending transplantation tolerance induction to this field.

Summary

In a career now spanning more than four decades, Dr. Sachs has worked consistently at the interface between basic science and clinical applications in the field of transplantation. His accomplishments can be measured not only in terms of basic science and clinical achievements, but also in terms of scores of scientists and clinicians who have been inspired by his enthusiasm and devotion.

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At 2012 celebration of 10th anniversary of the first successful tolerance transplant procedure, with several tolerant renal transplant patients
and members of the transplant team.

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