Book Review

A History of Transplantation Immunology

N Engl J Med 1997; 337:136-137July 10, 1997

Article

A History of Transplantation Immunology
By Leslie Brent. 482 pp. San Diego, Calif., Academic Press, 1997. $35. ISBN: 0-12-131770-6

After seeing the burns suffered by a British airman in World War II, Peter Medawar resolved to find a means for inducing immunologic tolerance to allogeneic skin transplants. By 1953 he and his coworkers Rupert Billingham and Leslie Brent had published a landmark paper on the subject, which eventually led to Medawar's sharing the Nobel prize in medicine in 1960. Brent was a graduate student at the time neonatally induced tolerance in mice was first achieved, and it would be hard to imagine a more exciting initiation into the world of medical research. From that beginning there emerged a new school of cellular immunologists who, by using tissue transplantation and the genetics of histocompatibility, greatly advanced knowledge of fundamental immunologic mechanisms. In the clinic the promise of transplantation immunology has yet to be fulfilled; progress there has come largely from nonspecific immunosuppression and the HLA matching of donors and recipients rather than from the induction of antigen-specific tolerance.

This is all described by Brent, who in the course of his career has seen graft rejection defined in molecular terms and transplantation evolve from risky experiment to routine clinical practice. In 11 chapters he reflects on the field where he played, placing it in the context of what went on before he became a student of transplantation immunology and what has happened since his retirement. Not unlike a transplant recipient, this book is a chimera; in many ways a memoir, it is also a series of scholarly reviews. The reader senses this duality in Brent's use of the first person to comment on the work of others but the third person to describe his own papers and professional activities. Landmarks in immunology are surveyed in the first chapter, which sets the scene for subsequent chapters on the immunologic basis of allograft rejection, alloreactions resulting from blood transfusion, and the immunogenetics of histocompatibility. In Chapter 5, the story turns to neonatally induced tolerance and the research of Medawar's school. The next two chapters describe the unfinished quest to apply immunologic principles to ensure the acceptance of organ grafts and the serendipitous manner by which immunosuppressive drugs have emerged to fill the breach. Thereupon follow three chapters on distinct subspecialties within transplantation immunology: bone-marrow transplantation and graft-versus-host disease, xenotransplantation, and the tolerance of pregnant women to their histoincompatible fetuses.

Present throughout this history is the aura of Peter Medawar, whose quotations head all but the first chapter and who is 1 of 20 heroes whose biographical sketches are included at the ends of the chapters. Brent is best when describing the events in which he actively partook. In a loving and extensive reappraisal of that literature, he charts the flow of ideas and experiments, always emphasizing how the landmarks and breakthroughs were built upon strong foundations of incremental research. This all has to do with cellular immunology and animal models of transplantation. Since the early 1970s, the molecular questions raised by cellular immunology have been increasingly tractable and the answers have had a profound impact on all of immunology. In the preface to his book, Brent explains that his purpose is to provide starting graduate students and fellows with the necessary background for commencing research in transplantation immunology. Such a goal necessitates that he embrace the molecular advances of the past quarter century. Unfortunately, in this arena Brent lacks the perspective and insight that comes from participation, and his reliance on the published literature leads to an account in which achievements are recorded but the history is missing. What is ironic is that it was Peter Medawar himself who unabashedly pointed out that scientists, when writing papers, often abandon history for the most compelling story.

Any physician, surgeon, or scientist with an interest in transplantation can take pleasure in this book, and for teaching it is a valuable reference. For today's beginner in transplantation immunology, the cloning of the T-cell–receptor genes is ancient history and the questions and personalities that populate A History of Transplantation Immunology will seem even more remote from the job at hand. The students and fellows who could have benefited most from Brent's wisdom are now in their middle years, and for those still engaged in the field this quirky gem of a book provides a second opportunity to get the history straight.

Peter Parham, Ph.D.
Stanford University School of Medicine, Stanford, CA 94305