Transplant: From Myth to Reality (review)

Abstract

Reviewed by: Transplant: From Myth to Reality Leonard G. Wilson Nicholas L. Tilney . Transplant: From Myth to Reality. New Haven: Yale University Press, 2003. xii + 320 pp. Ill. $30.00 (0-300-09963-0). In his history of organ transplantation, Nicholas Tilney begins with its prehistory: early blood transfusions and transplantations of teeth and endocrine glands—all invariably failures. He then presents an admirably clear account of early attempts at Boston to transplant kidneys, culminating in 1955 in the successful transplantation of a kidney from one identical twin to another. He tells how in 1960 the English surgeon Roy Calne, while a surgical fellow at the Peter Bent Brigham Hospital in Boston, discovered the remarkable immunosuppressive power of azathioprine, a drug that made kidney transplantation a practical possibility. Tilney's history of transplantation after 1960 is less satisfactory. He wanders, and in doing so he occasionally introduces historical oddities. In discussing the eighteenth-century practice of smallpox inoculation, for example, he refers to the Reverend Cotton Mather as a judge at the Salem witch trials, which Mather was not. He says that Mather learned of smallpox inoculation "via a conversation [End Page 747] with Lady Montagu in London" (p. 86); fascinating though it is to imagine a conversation between Mather and Lady Mary Wortley Montagu, it did not occur: Mather never visited England. Tilney mistakenly identifies the ancient historian Herodotus as a medical historian. None of this matters much to a history of transplantation, except that it leaves an impression of vagueness. Dr. Tilney describes the formidable difficulties that surgeons faced in dealing with episodes of acute rejection of the transplanted kidney. They could not increase the dose of azathioprine because it suppressed bone marrow, with evil effects. Corticosteroids, particularly prednisone, would prevent or overcome many rejection episodes, but in large doses steroids were also harmful. At the University of Colorado in 1966, Thomas Starzl began to use an antilymphocyte serum, produced in horses, to prevent rejection. Dr. Starzl was obliged to inject the serum intramuscularly into patients; the injections were painful and had uncomfortable side effects, but they also improved the survival rates of both patients and implanted kidneys. At the University of Minnesota in 1969, John Najarian and Richard Simmons prepared a highly purified antilymphocyte globulin that could be given to patients intravenously, with few side effects, and by 1970 at the Massachusetts General Hospital, Paul Russell had prepared a purified antithymocyte globulin that also could be given intravenously. Dr. Russell persuaded the Upjohn Company to manufacture antithymocyte globulin (ATGAM), and they obtained FDA approval for its use. At the University of Minnesota, John Najarian obtained FDA approval to use antilymphocyte globulin (ALG) as an experimental drug, and distributed it to other transplant centers willing to participate in its investigation. The advantage of antilymphocyte and antithymocyte was that they attacked the cells involved in rejection without injuring the bone marrow or the thymus. The author discounts the value of ATGAM and ALG, saying that they did not improve ultimate graft survival and could result in anaphylactic shock and death (p. 132). Nevertheless, for more than twenty years Minnesota's ALG and Upjohn's ATGAM were used, together with azathioprine (and after 1978, cyclosporine) and prednisone, to treat successfully thousands of transplant patients. The use of multiple drugs permitted reductions in the dose of individual drugs. Anaphylaxis was avoided by testing the patient beforehand for sensitivity to the protein. ALG was particularly valued for its ability to overcome acute rejection. The successful use of antilymphocyte globulin led also to the development of monoclonal antibodies that perform similarly in overcoming rejection. Cyclosporine was such an effective immunosuppressant that its introduction in 1978 stimulated all forms of organ transplantation, but it had serious side effects: In kidney transplants it suppressed urine secretion, and proved most effective when given in low maintenance doses after the kidney had begun to function. Its long-term use harmed the physical appearance of patients. In 1986 the similarly powerful immunosuppressant FK506 (tacrolimus) was introduced, which also has side effects, but ones different from those of cyclosporine. Dr. Tilney describes the disillusionment following the first heart transplant in 1967 that led by 1971 to a general moratorium...