The birth of clinical organ transplantation.

The task of describing the birth of organ transplantation was simplified by an historical consensus development conference convened on March 25–27, 1999 at the University of California, Los Angeles (UCLA). The purpose was to identify the principal milestones leading to the clinical use of the various transplantation procedures. The 11-member consensus panel included eight recipients of the Medawar Prize (the highest distinction of the Transplantation Society) and three Nobel Laureates (Figure 1). Figure 1 Participants at the UCLA historical concensus development conference on transplantation milestones. Front row (left to right): Robert A Good, Norman E Shumway,* E Donnall Thomas,† Joseph E Murray,† Jean B Dausset,*† Jon J Van Rood;* ... Carl Groth of Stockholm, president-elect of the Transplantation Society, was invited to chair the deliberations and to prepare an executive summary of the group’s conclusions. The summary, and personal reminiscences of the 11 individual participants, were published in the July 2000 issue of the World Journal of Surgery.1 The collection of articles was reprinted in monograph form for distribution to members of the Transplantation Society. Milestone status was granted only to contributions made at least a quarter of a century ago. By 1975, 32 years had passed since convincing evidence was produced, first by Gibson and Medawar2 in a skin-grafted burn victim in Glasgow and then by Medawar3 in controlled animal experiments, that rejection is a host versus graft (HVG) immune response. Within the next few years, it was demonstrated that the same principle applied to renal allografts in unmodified dogs (Figure 2B).4,5 Figure 2 Misleading historical context of transplantation immunology, defined by unidirectional cell-mediated immune reactions. (B) A host-versus-graft (HVG) response against a tissue or organ (here a kidney). (A) A mirror image version after bone marrow transplantation ... In addition, confirmatory observations were made in more than a dozen cases in which kidney allografts were transplanted to the anterior thigh6 or to the pelvis7–10 of unmodified human recipients. These cases included the first reported live organ donation;7 the mother’s kidney functioned for 3 weeks in her nonimmunosuppressed son before undergoing irreversible rejection. It is noteworthy that, as early as 1951, the French surgeons Kuss and coworkers,8 Dubost and associates,9 and Servelle and colleagues,10 had developed for human use the extraperitoneal pelvic kidney transplant procedure that soon would be used by Murray and colleagues11 for the historic identical twin and fraternal twin transplantations12 of 1954 and 1959, respectively. Procedures for transplantation of the other vital organs had been developed in surgical laboratories by the late 1960s. By the end of the decade, therapeutic regimens were available with which successful clinical transplantation of five kinds of organ allografts, as well as allogeneic bone marrow cells, were accomplished (Table 1). 12–17 Table 1 Historical Firsts: Prolonged Patient and Allograft Survival In my individual contribution to the UCLA conference,18 I pointed out that almost all of the clinical transplantation milestones could be traced to two seminal discoveries that were turning points from which divergent management strategies evolved; one leading to bone marrow transplantation and the other to organ transplantation. The first discovery, made in the experimental laboratory and eventually applied in the clinic, was that acquired tolerance to allografts could be induced. The second discovery, that organs could induce tolerance to themselves (ie, were inherently tolerogenic), was made by clinical surgeons and taken to the laboratory in search of an explanation. When no explanation for the organ tolerogenicity could be found, the engraftment of organs was incorrectly attributed by consensus to different mechanisms than those of acquired tolerance. The error did not prevent the development of organ transplantation to a high level of efficacy. But it deprived transplantation immunology of an intelligible context for nearly three decades.