Speculation, stringent reasoning, and science.

Dr Daar has provided a cogent review of recent developments in xenotransplantation that have attracted public concern. In 1993, the US Centers for Disease Control and Prevention (CDC) began to assess such concerns in response to requests for leadership in developing a national consensus on xenotransplantation. Those chairing academic human subject review committees, struggling to adopt responsible local positions on xenotransplantation clinical trials, were foremost among the petitioners. By 1995, at the initiative of the US Food and Drug Administration (FDA), the agencies of the US Public Health Service (USPHS) were working together to draw up national guidelines. An initial assessment of the issues, published in 1995 (1), can be summarized as follows. Infectious agents already endemic in human populations have been transmitted from donors to recipients through allotransplantation. Xenotransplantation carries a risk of transmitting infectious agents not recognized as classic zoonoses (and perhaps not capable of infecting humans under normal circumstances) from source animals to human recipients. The unusual circumstances of xenotransplantation, in which normally intact barriers are breached and the living xenograft serves as a persistent source of exposure to infectious agents, may permit transmission of xenogeneic infectious agents that do not pose a threat under normal circumstances. Once infected, the xenograft recipient may become a source patient, introducing new infections into the larger human community. Historic pandemics of zoonotic human disease, including the 1918 influenza pandemic attributed to swine influenza and the current HIV/AIDS pandemic, are precedents for these concerns. By September 1996 a draft USPHS guideline on infectious disease issues in xenotransplantation had been jointly drawn up by the FDA, the CDC, the National Institutes of Health (NIH) and the Health Resources Service Administrations, and published for public comment (2). As noted by Dr Daar, this draft provoked an extensive critical response. A revision of the guideline, based on this public response and the interim advances in science and public policy development, should be published in the near future. Foremost among the significant changes between the draft and the revised document is the requirement that all clinical xenotransplantation trials in the United States proceed under FDA regulation. Plans have also been made for forming a National Xenotransplantation Advisory Committee, which will have, among other responsibilities, that of providing a forum for the consideration of persistently contentious issues (such as concerns about the use of nonhuman primates as sources of xenografts). In the absence of hard data, attempts to assess risks and develop a rational policy are exercises in reasoned speculation. Prudence requires that one neither understate nor exaggerate risk when attempting to generate public discussion of these issues. As long as hypotheses remain untested, there will be a wide divergence of opinion among responsible scientists. These conditions provide an open field for sensationalism or unrealistically imaginative concerns by less responsible or less knowledgeable discussants. Responsible dialogue requires stringent reasoning with the available information. In this regard, Dr Daar has done an admirable job of walking a cautious line while attempting to facilitate public discussion of this topic. Dr Daar refers to the assumption that xenografts procured from nonhuman primates pose more risk of transmitting infections to humans than do those procured from pigs. This issue has generated much concern among both scientists and lay people and is an area in which science at present offers inexact guidance. While the simplest solution is to call for an absolute moratorium on the use of nonhuman primates, the wisdom of imposing one on the basis of fear rather than science is questionable. …