Viruses Pose Problems for Xenotransplants
by Robert Taylor

Unlikely Organ Donor. In the wild, baboons don't eat peaches. But at the University of Washington Regional Primate Research Center, this baboon sometimes get a treat.

The use of animal organs, tissues, and cells for human transplantation is promising, says Amy Patterson, a scientist in the Office of Recombinant DNA Activities at the National Institutes of Health (NIH) in Bethesda, MD. If researchers can solve problems with immune system rejection of tissue from other species, animal organs may end the acute shortage of useable human organs and save human lives, she says. Unfortunately, animal organs may bring with them unwanted viruses and other infectious organisms, which could potentially harm not only the patient getting the animal organ, but other people as well. "We need to know more about these risks so we can carefully assess the transition from the research laboratory bench to human patients," says Patterson.

Researchers don't yet know how dangerous any viruses carried along with a transplanted animal organ or tissue might be. They do know, however, that animal viruses can sometimes cross the species barrier and cause human disease. Most researchers agree that the risk of such an animal-to-human viral jump is greatest from closely related primate species such as baboons, but viruses have also come into the human population from other species, including horses and birds.

The risk that animal viruses might infect transplant recipients greatly complicates future prospects for xenotransplants, as animal to human transplants are called. But that danger would be weighed against the potential benefit of the transplant.

Unfortunately, potential dangers from animal viruses don't stop with the transplant recipient, says Patterson. An animal virus could conceivably go on to infect others—someone in a nearby hospital bed, for example, or even people with whom the transplant recipient has contact long after he or she recovers. In fact, the nightmare scenario some researchers worry about is a xenotransplant that introduces a deadly but unrecognized virus into the human population that spreads widely before the danger is discovered. Risks to people not involved with the transplant—who, after all, don't directly benefit from the operation—must also be taken into account when considering how to proceed with xenotransplant research, says Patterson.

One way doctors can reduce risk is to screen animals for any known viruses and reject infected animals as donors. This is not always possible, however. For example, all pigs carry multiple copies of a retrovirus in each cell's DNA. In 1998, scientists at the Institute of Cancer Research in London showed that this virus, called PERV (for Porcine Endogenous Rertrovirus) can infect human cells in laboratory culture. It would be extremely difficult, if not impossible, to rid pigs of these retroviruses—and pigs genetically engineered to avoid provoking the human immune system are currently front-running candidates to be sources for xenografts.

Other unknowns face xenotransplantation researchers. Patterson notes that screening for viruses only takes you so far, because you can't screen for what you don't know, and animals sometimes silently harbor viruses that scientists have not yet discovered. Moreover, the kind of exposure that occurs with xenotransplantation is not like anything that occurs naturally, in that a xenograft is placed permanently inside the patient, whose immune system is often partially shut down to prevent rejection. Researchers aren't yet sure how animal viruses, known or unknown, might behave under these circumstances.

Xenotransplant researchers recently got some reassurance that PERV won't be a show-stopper for the use of pig organs. In August, 1999, a study published in the journal Science showed that of 160 people exposed to living pig cells in one form or another, none showed any evidence of a PERV infection.

Despite that encouraging result, all the uncertainty gives policy makers reason to worry, and they are studying the problem. The Department of Health and Human Services (HHS) has issued guidelines to govern screening of donor animals, and long-term follow up of xenotransplant recipients. Researchers are still looking for sign of infection in people who have already received animal tissues. And HHS has formed a national advisory committee to study policy questions for many aspects of xenotransplantation, including the danger from animal viruses.

"There are many unanswered questions that concern all of us, and policy makers must find the right balance between the risks, and benefits," says Patterson. "The risk of introducing new viruses into the human population through xenotransplantation is not something that we can just dismiss."