Xenotransplantation: Using Animal Organs for Humans

The idea of using animal organs to rebuild humans was once the stuff of Gothic horror stories. Even the medical term for the practice–xenotransplantation–has a sci-fi ring. But now, two pharmaceutical companies and their scientific partners are poised to make fiction into fact by transplanting genetically engineered pig organs into humans for the first time.

As creepy as it sounds, surgeons could potentially save thousands of lives if they could “harvest” organs from animals instead of the occasional accident victim. Once a delicate operation, transplants are now nearly routine. But, while patients are living longer, the supply of organs cannot meet the demand. About 5,000 people on the U.S. transplant waiting list died in 1998 for lack of a donor.

Animal rights activists, of course, say xenotransplantation is cruel, but biomedical researchers tend to brush off their concerns. In this case, however, critics raise another issue that potential pig transplanters can’t ignore. Xenotransplantation, they say, has the potential to cause a devastating epidemic by introducing animal viruses into the human population.

To make their point, the critics refer to the devastating Ebola virus and HIV, both of which probably began in apes and made the jump to humans. And those viruses had no help. In order for a transplant to take, doctors must chemically subdue the immune system. Without their natural defenses, humans could be more vulnerable to infection by once harmless, organ-borne animal viruses. So while animal-to-human transplants could save thousands, they could kill thousands or more as well, says Laura Purdy, a bioethicist from the University of Toronto, writing in Free Inquiry (Fall 1999). “In this respect, xenotransplantation looks different from previous experimental treatments, where patients have both stood to gain and undertaken most of the risk,” she notes.

Virus fears pretty much eliminated apes as organ donor candidates, even though the human body would be less likely to reject organs from our primate cousins. Instead, researchers began working with pigs in the hope that they could use genetic engineering to overcome rejection problems. But two years ago, scientists concluded that pigs carry something called porcine endogenous retrovirus, or PERV, which is so deeply embedded in their DNA that there is no way to breed it out.

Now, researchers for one of the companies working on the genetically altered pigs have produced a study suggesting that these viruses may not be an obstacle. Scientists from Imutran Ltd. of Cambridge, England, rounded up 160 patients from around the world who had been treated with cells and tissue from pigs. The group included burn victims who had received pig skin grafts and liver failure patients whose blood had been filtered through pig livers rather than a dialysis machine.

The study, published in the journal Science (Aug. 20, 1999), found that none of the patients had been infected with PERV, even though 23 of them still had pig cells circulating in their blood. The company’s press release concluded that the study “demonstrated that pig tissue can survive in the human body for long periods with no ill effects.” Writing in the same issue of Science, Robin A. Weiss, of the Windeyer Institute of Medical Sciences at University College in London, says the study offers “some reassurance on safety” but adds that questions remain, including those about other possible pig viruses.

“The possibility remains that, say, one among 1,000 xenograft recipients may become infected by PERV,” Weiss notes. “The concern then will be the potential for onward transmission from the rare, infected transplant recipient to his or her contacts. Lest we dismiss this notion as ridiculous, we should bear in mind that HIV-1 began as zoonosis (animal-to-human disease), probably from chimpanzees, and that the worldwide pandemic of HIV-1 subgroups may be attributable to a single cross-species event.”

In the meantime, Novartis Pharma AG, the Swiss pharmaceutical giant and Imutran’s parent company, has been testing its pig organs in baboons. So has its main competitor, Nextran, a Princeton, New Jersey-based subsidiary of medical product maker Baxter International. After the PERV study appeared in Science, Novartis officials said they need to “refine” their anti-rejection drug combination before they can proceed to human studies. They’ll also need approval, here in the United States, from the Food and Drug Administration.

But the pressure is on. Novartis makes cyclosporine, the drug nearly every transplant patient takes to fight rejection. If they succeed with xenotransplantation, demand for the drug will skyrocket. Weiss and Purdy agree that the potential benefits of successful xenotransplantation are huge for individuals suffering from organ failure. For the public, however, the risks are as high as they are speculative.

“Although it now seems unlikely that each of the long series of steps required for the worst-case scenarios would occur, we do not know this, nor can we forecast the consequences if just a few of those steps occurred,” Purdy writes. “Because xenotransplantation could extend life if rejection problems are overcome, it is hoped that these fears will prove groundless. However, because of the possibility of risk to third parties, the scientific community must show why it is reasonable to proceed.”

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