Xenotransplantation: a view to the past and an unrealized promise to the future

Since the early 20th Century when Emerich Ullman transplanted a pig kidney into the arm of a woman (1902), Princeteau implanted portions of a rabbit kidney into the kidney of a child who was dying of renal insufficiency (1905), Jaboulay transplanted two kidneys from a pig and a goat as donor sources (1906), and Unger implanted a monkey kidney into a human (1910), xenotranplantation has made some strides, mostly related to advanced surgical techniques, improved knowledge of immunological principles, and to steps associated with the development of the most effective immunosuppressive therapy. Innovative surgical techniques were introduced by Alexis Carrel in the first decade of the 1900s, so that vascular anastomoses could be realized without a considerable amount of thrombotic/embolic problems, long before heparin times. Inasmuch as these advances were soundly characterized, it became evident that the results were far from expected and that the time was not ripe for xenotranplantation. It took 50 years (1963) before Keith Reemtsma transplanted 13 kidneys from chimpanzees into patients with kidney failure. Remarkably, one patient survived for 9 months before dying from electrolyte imbalance. In the ensuing years, Starzl (1964), Hardy (1964), Cooley (1968), Ross (1968), Barnard (1977), Bailey (1984) and a few others entered this new field with less than satisfactory accomplishments. The unsolvable barrier of hyperacute rejection required persistence and ingenuity. The recognition of xenoantibodies and their requirement for full depletion, through ex vivo porcine perfusion, plasmapheresis, immunoabsorption and complement inhibition, facilitated important advances in this field. The introduction of accommodation and molecular chimerism has further improved the knowledge of this newly conceived field. Advanced molecular engineering techniques have recently permitted the creation of the clonal Gal-deficient pig by eliminating the alpha-1, 3 galactosyltransferase gene. These discoveries together with better immunosuppression raise hope for the yet unrealized promise of xenotranplantation.