The process of discovery.

Questions about xenotransplantation are often posed philosophically, in terms of right and wrong. This approach contrasts with the rest of evidence-based biomedicine, which rarely provides absolute answers to questions of merit. Should xenotransplants be performed? Do the potential benefits outweigh the theoretical risks? In general, such questions are examined in the light of current biological knowledge, and are subject to revision over time. As our database develops, hypotheses are reformulated. Certainty does not exist. Thus, when allotransplantation was introduced, knowledge of the infectious risks associated with immune suppression was rudimentary. Data about infection in allotransplantation has grown rapidly with basic science and clinical experience (1). This relatively recent information was central to the discussions on the risk to the individual (potentially great) and to society (thought to be small) when the transplantation of baboon marrow into a human with AIDS was reviewed for the Public Health Service in the United States. Those discussions were coloured by passions about science, AIDS and individual rights, but they resulted in a far safer experiment in terms of risks of infection. They were also of benefit for more general considerations of clinical xenotransplantation. The term "xenosis" was coined to reflect not only the experience in allotransplantation, but also the unique epidemiological aspects of interspecies transplantation -- the potential transfer into the general human population of novel or unknown pathogens derived from animal donors (2-6). In terms of basic science, the search for such novel organisms has already had a beneficial effect on studies of the microbiology of transplantation, for example the isolation and sequencing of the first full-length porcine endogenous retrovirus (7) and to virological studies which suggest the ability of such organisms to infect human cells in vitro (8-10). Such data have been used by the US Public Health Service, and by corporate interests, to develop testing strategies for pigs raised as potential xenograft donors. Such studies and discussions have also made it clearer to most investigators that infection is a critical consideration in the development of clinical xenotransplantation. Further studies are likely to find additional new, and possibly pathogenic, organisms in xenograft donor species, and the potential for human infection can be assessed for each. This discovery process adds to our understanding of the risks of xenotransplantation, and of the microbiology of immunocompromised hosts in general. It is a part of the evolution of the science of xenotransplantation. Microbiological guidelines for xenotransplantation should therefore be devised, to indicate what is currently known about infection for such procedures, and serve as a basis for future scientific investigations. Benefits of xenotransplantation The benefits of xenotransplantation must be seen in the light of the limitations of currently available technologies. Many patients die while awaiting cadaver donor organs. Cadaveric donors provide life-saving opportunities for a small number of fortunate recipients, but the organs have often been subjected to hypoperfusion, infectious contamination, or injury during surgical procurement. All of these are problems which may be eliminated by the use of planned xenotransplants. Allograft recipients may suffer from chronic infection or debilitation but these problems could be reduced if elective transplantation could be scheduled, as it is currently for living donor transplants. In addition to their potentially unlimited availability and correct size, xenogenic organs may be resistant to infection with viral pathogens of humans, including HIV (1 and 2), HTLV, hepatitis viruses, and herpes viruses -- including human cytomegalovirus (CMV), which has been shown in our laboratory to be unable to infect porcine cells in vitro (11). …