Robert Alan Good, MD, PhD

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Robert Alan Good, MD, PhD, was a uniquely insightful immunologist and physician whose discoveries and life’s work distinguished the lineages of lymphocytes responsible for cell-mediated and humoral immunity. Dr. Good recognized and first demonstrated HLA compatibility as a key to the success of human allogeneic marrow transplantations and thereafter made seminal contributions to our understanding of the cellular interactions that contribute to the reconstitution of immunity and to the emergence of tolerance. His work directly led to the use of allogeneic hematopoietic cell transplants to correct lethal inherited diseases of the lymphoid and hematopoietic systems in humans and the potential of such transplants in models of autoimmune disease. Dr. Good died on June 13, 2003, at the age of 81. He had been active at his work until shortly before his death due to late complications of cancer.

Dr. Good was born and raised in Crosby, MN. In 1944, he graduated from the University of Minnesota. Despite a bout of polio, which weakened his legs, he went on to receive his MD and PhD degrees from the university in 1947. After residency training in pediatrics and a research fellowship at the Rockefeller Institute, he joined the faculty at the University of Minnesota School of Medicine. By 1962, he had attained the rank of professor in the Departments of Pediatrics and Microbiology; he was appointed a Regent’s Professor at the university in 1969. In 1973, Dr. Good assumed the position of president and director of the Sloan-Kettering Institute and director of research at Memorial Sloan-Kettering Cancer Center, where he fostered translational research and radically increased the proportion of research funded by peer-reviewed grants. In 1982, he moved to the University of Oklahoma as head of the cancer program at the Oklahoma Medical Research Foundation. In 1985, he moved to become chairman of the Department of Pediatrics at the University of South Florida and, until 2001, was physician-in-chief at the university’s All Children’s Hospital in St. Petersburg; thereafter, he continued his research as distinguished professor and director of the Children’s Research Institute.

Dr. Good’s research was initially focused on the role of plasma cells and antibodies in the immunopathology of autoimmune encephalitis. Thereafter, he gained acclaim for his studies delineating the pathogenesis of the Schwartzman reaction with Lewis Thomas, MD.

In 1962, Dr. Good first presented his work on the thymus and its role in the development of cell-mediated immune responses. His contributions and those of Jacques Miller, PhD, led to the recognition of separate thymus- and bursal-derived lymphoid lineages that, respectively, produce the T cells responsible for cell-mediated immunity and the B cells that generate antibodies. His detailed analyses of the lymph nodes, tonsils, and spleens of thymectomized mice and bursectomized chickens at different stages of embryogenesis characterized the development of each lineage within the lymphoreticular system. His studies with Max Cooper, MD, then defined the stepwise progression of the classes of immunoglobulins produced by B cells during embryogenesis. By comparing these findings in preclinical models with results of his detailed clinicopathologic analyses of children with impaired resistance to specific types of infections, he was able to establish a new conceptual framework for the identification and characterization of genetic disorders of immunity. Although he did not coin the phrase experiments of nature, he repeatedly demonstrated their potential to enlighten, to instruct, and to open doors to new possibilities. His capacity to recognize natural experiments presented by inherited disorders of immunity, to describe distinctive aberrations of lymphoid development and functions associated with each disorder, and to translate clinical and pathologic evidence of impaired resistance into new knowledge was unique and unequaled.

Dr. Good’s many contributions in the field of marrow transplantation evolved from this seminal work. In 1962, the year he first identified the distinctive functions of the thymus in immunity, he demonstrated the critical importance of the thymus-derived lymphocytes for skin allograft rejection. He also reported that spleen cells from neonatally thymectomized mice would not induce graft-versus-host disease (GVHD), thus providing a foundation for subsequent explorations of T cell-depleted grafts. In 1964, with Yunis, Hilgard, Sjodin, and Martinez, he also demonstrated that syngeneic spleen cells or isolated thymocytes would reconstitute the immune system and reverse wasting in mice thymectomized in the neonatal period. Early attempts to correct severe combined immunodeficiencies (SCID) in children with fetal thymus or small doses of adult marrow failed to engraft, failed to reconstitute immune function, or induced lethal GVHD. In 1968, Dr. Good and his colleagues were impressed by the prolonged survival of human skin allografts in hosts matched by mixed lymphocyte culture (MLC) and existing serologic typing for HLA reported by Bach and Amos and by Van Rood and Bernisse. They reasoned that these outcomes resembled those of H-2—compatible skin grafts in mice. Because their own experiments demonstrated that the use of H-2—compatible spleen cell transplants prevented fetal GVHD, they hypothesized that histocompatibility defined by MLC and serologic typing could be used to identify a compatible sibling donor for a child with SCID. This marrow transplant was the first to achieve sustained engraftment and successful long-term reconstitution of both lymphoid and hematopoietic function without lethal GVHD. The patient, now a healthy adult, remains a full chimera to the present day.

In subsequent years, Dr. Good provided critical support to Bo Dupont, John Hanson, and me in explorations of partially matched, MLC-compatible related transplants and the initial successful use of marrow from a histocompatible unrelated donor to correct SCID. His vision, encouragement, and steadfast support also sustained Yair Reisner and me in the development and applications of HLA haplotype-disparate parental T cell—depleted marrow grafts for the treatment of patients with SCID and leukemia. Similarly, his pioneering studies with Ikehara on the use of allogeneic marrow grafts for the prevention and/or treatment of autoimmune disorders, including nephritis and type 1 diabetes, in genetically susceptible strains of mice provided a strong scientific framework for the exploration of hematopoietic cell transplants in the treatment of selected autoimmune diseases in humans.

In addition to his seminal contributions in developmental immunobiology, marrow transplantation, and the biology of human immunodeficiency diseases, Dr. Good has also conducted pioneering research on the phylogenetic development of the immune system, the effects of nutrition on autoimmune diseases and aging, and the effector mechanisms that contribute to infection-associated immunopathology. Dr. Good’s energy and enthusiasm are legendary. This energy—coupled with his keen intellect and his singular capacities to assimilate new knowledge, detect potential biologic relationships, and formulate testable hypotheses—made him an exceptionally productive investigator. Dr. Good published more than 2000 articles, edited more than 50 texts, and received 13 honorary degrees and more than 100 awards, including the Albert Lasker Award for Clinical Research in 1970, election to the National Academy of Sciences, and founding membership in the Institute of Medicine. He fostered the development of several scientific societies and served as president of the American Society of Clinical Investigators (1968), the American Society for Experimental Pathology, and the American Association of Immunologists (1975–1976). He also served on President Nixon’s Cancer Panel.

For those who knew him, he is perhaps most vividly remembered as a spirited, uniquely engaging teacher who energized his students and colleagues alike to explore new ideas, to become fully absorbed in scientific inquiry, and to share in the exhilaration of discovery. One rarely felt more alert than at 5:00 am in the midst of a meeting with Dr. Good discussing a paper or grant or planning an experiment, or at scientific conferences answering probing questions about your experiments asked by this man in the front row, who took copious notes and had grasped, often with disconcerting clarity, both the contents and the potential of your work. Even those who vehemently disagreed with his hypotheses and interpretations enjoyed the joust, appreciated the intellectual integrity of the engagement, and knew that the argument would be decided on the merits of scientific evidence alone. He was also a gifted physician who consistently focused his work to address the mechanisms and consequences of diseases as presented by patients. His concern for their welfare galvanized his determination to develop transplantation and other effective treatments for all children affected with lethal debilitating disorders of immunity. His recognition of the singular demands and difficulties inherent in clinical research also encouraged and sustained many young investigators through rough times in centers throughout the world. He was a big-spirited man who enjoyed science and medicine and those engaged in it—a visionary endlessly intrigued by the order and complexity of nature; who laughed at the quirks of humankind, including his own; who trusted and vigorously espoused the potential of scientific research; and who, through his work, enriched us all.