Nonhuman primates as organ donors

Baboons and pigs are potential source animals for human xenotransplantation. For practical reasons, baboons have been proposed by only a handful of US surgeons to demonstrate "proof of concept". The Loma Linda paediatric heart transplant performed by Leonard Bailey in 1986 received a lot of negative publicity because of ethical concerns about "experimenting" on a newborn baby. Nevertheless, further paediatric xenografts using baboon hearts are being planned (1). Two baboon liver transplants were performed in 1993 and they also failed for unknown reasons. This has precluded further liver transplant studies (2). AIDS activists helped to accelerate human xenograft trials in the case of an AIDS patient who received a baboon bone marrow in a high risk attempt at immune constitution (3). The monkey bone marrow failed to grow but the patient derived some benefit from the conditioning regimen used in preparing him for the procedure. This was not an ablative bone marrow procedure, so the patient's own marrow remained fully functional. Strong criticism of the experiment, based on a lack of significant scientific merit and the potential infectious disease risks, was voiced by many researchers, but in this case public health policy was determined by pressure from special interests. Some of these pioneering studies have done more harm than good to the xenotransplantation field because of negative publicity. On the other hand, they have made the transplant community more aware of the problems, and steered them towards using nonprimate species. There will always be a handful of individuals who want to be the first to succeed using primates, however, and this is where strict regulations can prevent new pandemics caused by cross-species infections. Widespread use of nonhuman primates is no longer foreseen, mainly because of serious risks caused by infectious diseases naturally carried by baboons (4). It is also unlikely that sufficient numbers of baboons could be made available even with tremendous commitments of time and money. Currently, the largest breeding colony of baboons is at the Southwest Foundation for Biomedical Research, where there are over 3200 baboons bred for use in research. Unfortunately, breeding practices there have not been developed with zoonotic infections in mind. For example, virtually all adult baboons in this colony carry simian foamy virus (SFV) a persistent retroviral infection that has recently been found in humans who work with primates (5, 6). A novel retroviral infection that can be transmitted to humans via wounds or needlesticks is not a good sign. Transplantation of tissues along with a cocktail of immunosuppressive agents would be an ideal way of transferring simian viruses to humans. Most baboons also harbour simian T-cell lymphotropic virus (STLV), another retroviral infection that causes leukaemia and T-cell lymphomas in baboons (7). The human form (HTLV) probably arose from cross-species transmission from nonhuman primates (8). Higher rates of infection for both retroviruses and herpesviruses are found in captive colonies than in the wild, indicating that intensive breeding may adversely affect the pool of nonhuman primates. Given the breadth of persistent infections, selecting baboons in this milieu would not be good public health practice. In addition, wild-caught baboons are occasionally introduced into the breeding programme, which could seed the established colony with new infections. Furthermore, many viral infections remain nonpathogenic in their existing hosts only to become pandemics when transmitted to new ones, as was the case with AIDS. We are currently unable to predict the outcome of such zoonotic infections in xenograft recipients, or to predict in vivo pathogenicity on the basis of in vitro studies. Most problematically, novel agents transmitted by xenotransplantation might circulate into the population for some time before evidence of new clinical syndromes comes to light through changes in disease prevalence. …