Transplantation of kidneys, hearts, livers, pancreata and other organs has enjoyed extraordinary and increasing success in the last decades. This accomplishment has generated a problem of its own: donor organ shortages have placed clear limits on the number of patients that can be treated. Even optimistic estimates forecast a continued scarcity of certain donor organs. For this reason, the transplantation community has turned once again to the possibihty of using xenogeneic organs for transplantation to humans. Xenotransplantation is laden not only with formidable biological problems, but also wlth ethical concerns that need to be addressed. It is the emerging feeling that non-human primates should not, for both medical and ethical reasons, be used as donors Attention has turned to the use of pigs as donors, given the acceptable size, availability and potential for genetic manipulation of these animals. The purpose of this article is to review tho particular problems that transplantation of vascularized or~ ans from pig to human would pose and to discuss our present investigations in these areas. A conceptual framework of immunological issues attendant to xenotransplantation that form the basis for our experiments is presented.

It has been known since early in this century that when an organ from an animal of one species is anastamosed to an animal of a phylogenetically distant species, the organ will rapidly~ nd inexorably fail due to hyperacute rejection~ 4. S~, Roy Calnc-studied recipients of such grafts that have circulating antibodies that can agglutinate red blood cells (R~ Cs) of the donor species, and referred to such species combinations as discordant". The antibodies, which exist in all members of a speoes without overt evidence of sensitization, were called natural antibodies f'. Closely related species _~ uch as humans and chimpanzees have little or no detectable antibody; such combinations are defined as concordant". Although vascularized grafts between concordant species are not subject to hyperacute rejection% such grafts are unlikely to provide an answer to the sho~ age of donor organs for the reasons mentioned above.