By Lisa Seachrist
BETHESDA, Md. — In an era that sees thousands of patients dying for lack of human donor organs, molecular and genetic techniques offer the hope that xenotransplants could mean the end of patients languishing on "the waiting list."
But that promise is tempered by the sinister possibility that xenotransplants could transfer life-threatening viruses across species barriers, leading to an epidemic.
The FDA, National Institutes of Health and the Centers for Disease Control cosponsored a two-day conference titled "Developing U.S. Public Health Service Policy in Xenotransplantation." At the conference, Fritz Bach, a transplant surgeon and researcher at the Sandoz Center for Immunobiology, in Boston, urged the FDA to place a moratorium on clinical trials of xenotransplantation until adequate protections can be designed to ensure research is conducted ethically.
"We see this as a proximal danger," said Bach, the lead author of a February Nature Medicine paper outlining the case for a moratorium. "The potential risk to the public requires that a public mechanism be in place to ensure the public can offer its consent to the risk. The problem cannot be dismissed by talking about education alone; the public has its own concerns."
In his paper, which served as a lightening rod for much of the discussion at the meeting, Bach and his colleagues refer to xenotransplantation as the inverse of immunization. "Immunization is intended to protect the population at the risk of having the occasional individual experience adverse reactions to the immunization," he argues. "Xenotransplantation, on the other hand, offers potential benefit to the individual while putting the population at risk."
For that reason, Bach and his colleagues urge that a public deliberative process take place for decisions about whether xenotransplantation is in the best interest of society. In addition, the authors propose that a national body be established to regulate and manage xenotransplantation, should their proposed moratorium ever be lifted.
"I agree with everything in the Bach paper except the conclusion," said Daniel Salomon, a molecular and experimental medicine researcher at the Scripps Research Institute, who served on a panel at the meeting. "I don't think there is a need for a moratorium for a public discussion. They seem to ignore the very public and successful work that has already been done in this area."
The FDA handed down a moratorium of sorts in October 1997, when it placed a clinical hold on all pig xenotransplantation after porcine endogenous retroviruses (PERVs) were shown to infect human cells in vitro. The clinical hold was issued in order for researchers to develop assays to monitor PERV infection. An FDA advisory panel convened Dec. 17 told the agency that public health concerns could be examined with animal studies and the evaluation of patients already treated while some clinical trials proceeded.
The agency has responded by lifting the hold on an ad hoc basis. Diacrin Inc., of Charlestown, Mass., is transplanting porcine neuronal cells to treat Parkinson's disease, Huntington's disease and epilepsy.
Irrespective of the agency's decision to allow some xenotransplantation protocols to proceed, the participants at the meeting seemed to agree that xenotransplantation requires a different mechanism to oversee it. Harold Vanderpool, a professor of history and philosophy of medicine at the University of Texas Medical Branch, in Galveston, outlined four ethical issues that need to guide the conduct of xenotransplantation trials.
"[Xenotransplants] call for considered judgments regarding permissible harm-benefit thresholds for the initiation of clinical trials and raise questions regarding the need to secure informed consent from medical personnel, the patient's close contacts and other groups," Vanderpool said. "In addition, they add serious difficulties to the securing of informed consent from research subjects and raise problems with respect to how clinical trials should be governed and approved."
Vanderpool advocated that a national body set mandatory guidelines determining the makeup of the institutional review boards that will review xenotransplantation protocols, and argued that such a board must contain transplant recipients as the recipients' best spokespersons.
Leroy Walters, panel member and director of the Kennedy Institute of Ethics at Georgetown University, in Washington, went a step further and recommended that a national review body similar to the recombinant advisory committee review xenotransplant protocols and serve as a public forum to air concerns and oversee research. Walters also proposed a public listing of all clinical trials, a registry to track volunteers and potentially their immediate family members and an annual accounting of the number of animals used.
Official guidelines will be released in the Federal Register. *