A History of Clinical Transplan ta tion

H transplantation came to be a clinical discipline can be pieced together by perusing two volumes at reminiscences collected by PaulL Terasaki in 19911992 from many of the persons who were directly involved. One volume was devoted to the discovery of the major histocompatibility complex (MHC), with particular reference to the human leukocyte antigens (HLA) that are widely used today for tissue matching. l The other was focused on milestones in the development of clinical transplantation.2 All the contributions described in both volumes can be traced back in one way or other to the demonstration more than a half century ago by Peter Brian Medawar that the rejection of allografts is an immunological phenomenon.3,4 Ten years later (1953), Billingham, Brent, and Medawars showed that tolerance to skin allografts could be induced by inoculating fetal or prenatal mice with immunocompetent spleen cells from adult donors. Because of their immunological immatunty, the recipients were incapable of rejecting the spleen cells whose progeny survived indefinitely. Specific nonresponsiveness to donor strain tissues was retained as the recipient animals grew to adult life, while normal reactivity evolved to third-party grafts and other kinds of antigens. This was not the first demonstration that tolerance could be deliberately produced. Analogous to the neonatal transplant model, Traub6 showed in 1936 that the lymphocytic choriomeningitis virus ILCMV) persisted after transplacental illiection of the embryo from the mother, or alternatively by In]ection into newborn mice. However, when the mice were ~ntected as adults, the virus was eliminated immunologically. lmllar observations had been made in experimental tumor ~odels. Murphy 7 reported in 1912 the outgrowth of Rous ~ leken sarcoma cells on the chorioallantoic membranes of lick or pigeon egg embryos, which could be reversed by inOCUlatIOn of auult chicken lymphoid cells 8 whereas sarcoma lib 1 . . ' P antatlOn mto adults was not possible. the The observations of Murphy and Traub did not influence ttl early development of transplantatIOn. Instead, the Impe~ and rationale for the experiments of Billingham, Brent, an Medawar,5,9 and similar studies in chickens by Hasek !O Ong . , mated With Owen, II who demonstrated that freemartin Immunologial Screening . . . . . . . . . . . . . . . . . . . . .. 1390 Allograft Acceptance Versus Acquired Tolerance .... 1391 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . 1394 References ................. . . . . . . . 1395