Case Study: A Xenotransplantation Protocol

Abstract

Imagine a moment in the (possibly not too distant) future, when xenotransplantation is considered clinically feasible. Animal studies--say, transplantation of pig kidneys into baboons--have been successful, with survival of six to twelve months at a clinically acceptable level of immunosuppression. Genetic engineering has succeeded in creating a lineage of pigs whose endothelial cells do not contain the glycoproteins that would trigger hyperacute rejection. Systematic human trials are now proposed--protocols for both kidney and heart transplants are being developed. Faced with the real prospect of ameliorating the chronic shortage of organs and moving gravely ill patients off transplant waiting lists, how ought we to evaluate proposals for human clinical transplantation research using animal organs? commentary by Mark J. Hanson Xenotransplantation raises a host of complex issues, challenging divisions between individual and public health, human and animal identity and welfare, and scientific progress and public concern about risk. Clearly, any technology that has the potential to ameliorate the very real suffering experienced by those waiting for organs should be explored, but given the uncertain circumstances the temptation actually to employ it should not be too quickly indulged. The central question is whether xenotransplantation could transmit to humans a disease found in the animal--a zoonosis. While most transmissible diseases can be screened out of source animals, two problems remain. First, scientists can only screen for known pathogens, and there may be transmissible diseases that are yet undiscovered. Second, the consequences of infection by retroviruses from the source animals requires rigorous study. The effect of porcine retroviruses in human organ recipients over time is unpredictable and might not result in disease for many years, if ever. The risk may be extremely small, but the potential consequences of spawning a new pandemic are catastrophic. Compounding the issue is the possibility that zoonoses could spread beyond the individual xenograft recipient to their intimates, to health care professionals, or even ultimately into the general population. Thus xenotransplantation represents a potential threat to the public health even if it provides a benefit to individual patients. Before clinical trials begin, therefore, scientific investigation of disease transmission risks must be as thorough as possible, with information made widely available. The potential public health consequences of xenotransplantation complicate the moral obligation not to impose risk without the informed consent of those affected. The nature and degree of risk for disease transmission entail a moral obligation that consent be sought not only from the patient but also from his or her intimates and even--through some mechanism--from the general public itself. The ability for diseases to spread across borders makes xenotransplantation a truly global issue. Complicating the issue of disease risk is uncertainty surrounding the assessment of that risk. Because the public health threats have not been demonstrated, the risks may appear hypothetical and thus not compelling in the face of medical benefit. But such reasoning is too easy; for the benefits of xenotransplantation, until they are demonstrated, are also hypothetical. Obligations to minimize risk entail that appropriate risk management strategies be implemented. On the local level, this includes case review by appropriately staffed institutional committees. Nationally, regulatory agencies should utilize such controls as protocol review bodies, patient registries, and tissue archives for humans and animals. As important as issues related to zoonoses are, however, a focus exclusively on disease risk reduces the breadth of considerations to essentially technical, scientific questions--answerable only by experts. …