Issues in Xenotransplantation: An Expert Interview With Jeffrey Platt, MD

Laurie Barclay, MD

September 10, 2002

Sept. 11, 2002 — Editor's Note: Debates over practical and ethical issues in xenotransplantation continue, stirred up by a recent federal court ruling in favor of the Campaign for Responsible Transplantation (CRT), a coalition of public-interest groups arguing that xenotransplantation should be banned because it is dangerous, expensive, unnecessary, and inhumane. Under the Freedom of Information Act, the CRT had requested from the Food and Drug Administration (FDA) nearly 27,000 records documenting clinical trials in xenotransplantation. Earlier this month, the judge ordered the FDA to justify withholding these documents by November 10, 2002.

Jeffrey Platt, MD, a professor of surgery, immunology, and pediatrics at Mayo Clinic in Rochester, Minnesota, discussed these issues with Medscape's Laurie Barclay. In 1998, Dr. Platt established the Transplantation Biology effort in Rochester, and he was lead author of a report in the Aug. 27, 2002, issue of Circulation describing recommendations of the National Heart, Lung, and Blood Institute Heart and Lung Xenotransplantation Working Group. This group's mission was to identify obstacles to the clinical application of xenotransplantation and to recommend possible solutions to these problems, including immunologic and physiological barriers to xenotransplantation, limitations of current animal models, and the high costs of studies using nonhuman primates and genetic engineering of pigs.

Medscape: Why is xenotransplantation important, and what problems does it hope to address?

Dr. Platt: Transplantation is the preferred method to treat organ failure, but there are not enough human organs for people who need them. The ethical issues in human transplantation are far more pressing than those in xenotransplantation: how do you determine the best, most equitable way to distribute a limited, precious resource such as human organs? An obvious solution to this practical and ethical dilemma is to use animal organs instead, which has now been possible for over a decade.

Medscape: What are the difficulties inherent in xenotransplantation, and how can we overcome them?

Dr. Platt: The main problem is that the human immune system vigorously rejects tissue from other species. The possibility of controlling this immune reaction sufficiently to prevent rejection of the transplanted organ seemed remote until recently. But now we can genetically engineer animals to help control rejection, which is work I helped to pioneer. Our group was the first to report transplants from genetically engineered pigs. Unlike baboons and other primates, pigs are numerous enough to allow genetic engineering to be financially feasible. Except for the liver, most pig organs are sufficiently similar in structure and function to their human counterparts to allow successful xenotransplantation. The first question we have to ask is, "If you transplant a pig organ into a human, is it going to work?" and for the most part, the answer is yes. The next issue is cost. Genetic engineering and transplanting pig organs to primates, which has to be tested before organs can be transplanted to humans, is enormously costly.

Medscape: What are some of the ethical objections to xenotransplantation?

Dr. Platt: Some critics ask about animal rights, but a society that allows animals to be used as a source of food can hardly object to using them as organ donors. Xenotransplantation is necessary to save lives, whereas eating animals is optional and can be avoided by adopting a vegetarian diet. I'm not aware of specific religious objections to xenotransplantation, but if there are any, it boils down to a question of individual ethics and beliefs versus those of the society as a whole. If I feel on religious grounds that xenotransplantation is unjustified, then I have the right to turn down the opportunity to receive a pig transplant, but should I have the right to impose my view on anyone else and prevent them from receiving a needed organ? Public policy most likely will not allow individual views to restrict options for the society as a whole.

Medscape: What about critics who suggest that genetic modification might lead to some sort of "terror creature?"

Dr. Platt: It's science fiction! We wouldn't have the foggiest idea how to begin doing something like that. The pig has about 40,000 genes. In some cases, we add two genes, or we might take one away, or we alter one. This amount of genetic manipulation has a profound effect on the biology of xenotransplantation, but a negligible effect on the pig. Anyway, mutations in a gene or two spring up all the time in nature.

Medscape: Do you have any specific comments concerning the federal court ruling, or on the legal battle leading to it?

Dr. Platt: I'm not an attorney, so any legal opinions I might have are irrelevant. Nor can I speak to the motives of the CRT. But in general, requesting masses of documents, as the CRT did, tends to have a chilling effect on research. Most of us publish our findings anyway, so it's not as if the information's not out there.

Medscape: What are some of the public health concerns regarding xenotransplantation?

Dr. Platt: The major public health risk is the possibility that an infectious organism could be transferred from the donor to the recipient, and from the recipient to the society at large. This issue has been of great interest to researchers in the field for at least five years, and it has been studied rigorously. In clinical trials, there is very little evidence that an infectious organism could spread from donor to recipient, and there is zero evidence of spread from the recipient to society as a whole. Some types of genetic engineering could theoretically increase that risk, but ten times zero is still zero. The relevant question is if there is an infectious organism that can spread exclusively by xenotransplantation and not by any other means. If not, then banning xenotransplantation will not protect society. There are so many significant infectious risks to society, like spread of infectious agents through bioterrorism, research in animal laboratories, or even farming or pets. Relative to these exposures, the risks of xenotransplantation are negligible. Some of those who have raised the most questions about public safety in xenotransplantation have been employed by universities or centers in close contact with laboratory animals known to pass infectious agents to people. These centers have virtually no controls to guard against any potential public health threat, yet it's these people who advocate vigorous controls for xenotransplantation. It's an interesting phenomenon.

Medscape: What is the state-of-the-art regarding xenotransplantation? What degree of clinical benefit can we expect?

Dr. Platt: There continue to be steady advances in the field, so that it's possible to use animal organs to help people by treating organ failure. I'm not saying this is the only method — approaches like stem cells are promising but not as well developed yet, and we don't yet know their potential or all the hurdles we have to cross. When xenotransplantation is feasible and any remaining ethical objections have been forgotten or overcome, there may be better techniques. But we have a better understanding and more intense research foundation in xenotransplantation than we do with other methods. There are people walking around today who owe their lives to xenotransplantation — some because an animal organ kept them alive until they could find a suitably matched human transplant; others because they received porcine heart valves or plasma before human plasma could be fractionated. Right now animal organs are mostly buying time, but researchers in the field hope that permanent animal organ transplants will someday be feasible. The obstacles are more a matter of commerce and regulation than of science — we have the tools right now to make it happen. It's a very gratifying field to be in.

Medscape: Do you think that committees should be formed to deal with potential public health and ethical issues?

Dr. Platt: There have already been an incredible number of committees formed to deal with the ethical issues, and they can't all seem to reach the same conclusions. I have no objections to the committees, because, after all, they highlight the work that I do. But there are so many more pressing ethical issues with practical ramifications to debate, like will there be a war in Iraq, or should we regulate car emissions to prevent polluting our environment? If I were society, I'd move on.

In terms of the public health issues, the critics are looking at this upside down. It's much more likely that xenotransplantation could provide the answer to an epidemic or public health disaster rather than to cause one. If, for example, there were an outbreak of infectious myocarditis, we'd have nothing to offer the victims unless xenotransplantation of pig hearts were readily available. The government may need to step in to fund xenotransplantation research and to remove the red tape. The real question for public health committees ought to be how can we apply it broadly and hasten its clinical application to provide solutions to unforeseen disasters.

Reviewed by Gary D. Vogin, MD


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