XENOTRANSPLANTATION: The Benefits and Risks of Special Organ Transplantation
In August 1999, the results of a study were announced which found no evidence of PoERV infection among 160 people who had previously received medical treatment with living pig tissue. A number of patients in the study did show evidence of circulating pig cells, but no evidence of PoERV infection, potentially demonstrating that pig tissue can survive long-term in the human body with no ill effects. Among the patients included in the study were a few individuals who had been pharmacologically immunosuppressed and therefore presumed to be at greater risk of infection. Another study, conducted by the Mayo Clinic, will test pork slaughtering and processing workers to determine whether PoERV is transferred to people who have a history of extensive exposure to swine tissues and fluids. At this time, there is no evidence that PoERV has been transmitted in vivo or that it poses a risk to humans; however, researchers are proceeding with caution to address these outstanding safety concerns. If PoERV’s are found to pose a risk, strategies are being developed that may provide a solution to the problem.
U.S. and International Regulation of Xenotransplantation
While governments of the United States, the United Kingdom, Spain and elsewhere share similar hopes and concerns regarding xenotransplantation, each is working independently to establish or revise guidelines regarding the regulation of xenotransplantation research. In the U.S., the Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research published its guidelines in 1999. The guidelines, shaped in part by public dialogue, include long-term monitoring of recipients and the establishment of a registry to archive patient records and donor samples. The various agencies of the U.S. Department of Health and Human Services, including the FDA, the Centers for Disease Control and Prevention and the National Institutes of Health, have encouraged open communication about xenotransplantation at public workshops for several years.
In the United States, several scientists who attended the public conference in January 1998, "Developing U.S. Public Health Policy on Xenotransplantation," urged the FDA to ban cross-species transplantation research until ethical issues and health risks are resolved. They specifically discussed the potential risk to public health from a viral transfer across species that could result in a new disease epidemic. In April 1999, the FDA released a guidance document stating that any clinical protocols proposing the use of nonhuman primates should include sufficient clinical evidence addressing the risks of such use. At the time of the guidance document, the FDA felt that this evidence did not exist. The FDA decided it was appropriate to allow well-defined and highly controlled clinical trials, which are proceeding at a cautious pace.
The U.S. Department of Health and Human Services is developing several important mechanisms to facilitate participation by the public, scientists and industry in the progress of xenotransplantation. The DHHS is establishing the Secretary’s Advisory Committee on Xenotransplantation (SACX) to review clinical protocols, conduct discussions and make recommendations about the appropriate conditions for use of nonhuman primate organs. In October 1999, the DHHS announced the creation of the SACX and requested nominations for the committee membership. The U.S. Public Health Service is also planning to develop a national patient registry and a biological specimen repository for tissues. The biotechnology industry continues to work closely with the government in the responsible development of regulations and guidelines on the appropriate safeguards for xenotransplantation.
Spain and the UK announced their guidelines in June and July 1998, respectively. Prior to the start of human clinical studies, according to Spain’s regulations, preclinical studies must demonstrate a minimum six-month survival and function period of cells, tissues and organs to be transplanted and the absence of infectious pathogen transmission. People who receive organs, as well as their families and friends, will have to sign informed consent documents indicating that they understand and accept the medical risks and inconveniences involved in these early transplant procedures, such as potential for infections, life-long medical surveillance and potential media attention associated with xenotransplantation. In January 1999, the parliamentary assembly of the Council of Europe called for a worldwide moratorium on xenotransplantation, until technology is evaluated and guidelines are established. A month later, members established a Working Group for the purpose of drafting xenotransplantation guidelines.
The UK’s guidance documents were developed by the UK Xenotransplantation Interim Regulatory Authority (UKXIRA), which is charged to regulate cross-species transplantation on a non-regulatory basis. The guidelines include the following safeguards: the UK Secretaries of State for Health will review each application for a human trial for an organ transplant and make a decision based on advice from UKXIRA; the welfare of animals bred for human transplants will be protected; and the existing Advisory Committee on Dangerous Pathogens will advise on the risks of infection from different types of xenotransplantation therapies proposed.
Ethical Issues Surrounding Xenotransplantation
