Xenotransplants Spur Fears Of The Next Big Plague

By Adam Pasick

Xenotransplantation, the implanting of animal organs or tissue into humans, has gone from being an idea to reality. Some 12 clinical trials are under way in the United States for diseases like diabetes and Parkinson's.

Pigs, which are genetically similar to humans and are easy to breed, are the favored animal for xenotransplantation procedures.

But concerned scientists are warning that humans who come into contact with living pig tissue could be the sparking point for the next great human plague. Diseases that suddenly jump from one species to another have been responsible for some of the most deadly and virulent epidemics of the 20th century: HIV, influenza, "mad-cow" disease and Ebola.

Current biotechnology trials include implanting fetal pig tissue into the brains of Parkinson's patients, whose neurons have been destroyed by the disease, and using a pig liver to "clean" the blood of humans waiting for a transplant.

"We know that when you transfer a live organ or cell from animal to human, you're bypassing all the body's defense mechanisms," said Alix Fano, director of Campaign for Responsible Transplantation, a coalition of scientists seeking a ban on xenotransplantation research. "You're basically injecting somebody with viruses."

Sleeping Viruses

Pigs - like virtually all complex organisms, including humans - have sleeping pathogens hardwired into their genetic code. These so-called endogenous viruses are passed down from parent to child, are not infectious and seem to be largely asymptomatic.

"Endogenous viruses are actually part of the DNA," said Louisa Chapman, a medical epidemiologist for the Centers for Disease Control and Prevention. "They're like fossil remnants of past diseases. ... You could try to breed them out, but you probably would not succeed."

But nobody knows whether these viruses can be passed on from pig to human - and what effect they might have. "You can't predict what the outcome will be," Chapman said. Of particular concern is Porcine [pig] Endogenous Retrovirus, or PERV, which virtually every pig in the world has encoded into its genes. Retroviruses - HIV is the most notorious - are feared because they can hijack a host's own cells, churning out billions of copies of the virus itself.

Even worse, from the perspective of disease control officials, they can lie quietly in wait for years while they infiltrate and replicate inside their host. There are tests for HIV, hepatitis and other diseases, but a newly emerged virus could spread unchecked through the population and even the nation's blood supply before it was detected.

Pigs Save Lives

Despite the potential danger, xenotransplantation has its boosters, who predict a future where currently scarce organs and tissues are abundant. And the direct beneficiaries of the work are eager to hype its benefits.

James Finn of Newport, R.I., was debilitated by Parkinson's when he was given the chance to enroll in one of the first xenotransplantation trials in 1996. "They offered me the chance for an experiment and I jumped at it - I had nothing to lose," he said.

After surgeons implanted fetal pig tissue in his brain - boring holes in his skull while he was still conscious - he experienced a near-miraculous turnaround.

"Before the surgery I could barely walk," said Finn, now 52 years old. "I was in a wheelchair, my voice was very weak and I couldn't practice my hobby of repairing sports cars because my hands were impaired," he said. Six months later, he was back working on cars again.

He is aware of the risks of contracting a new virus - but the dangers are outweighed by the second chance he's received from an anonymous pig.

"I knew there was a possibility that I could die from the procedure, but I was at the point where it didn't make any difference," he said. "I volunteered to go back for another procedure - the results have been so good."

Biotech Firms Push On

The Food and Drug Administration, responsible for overseeing xenotransplantation clinical trials, halted research in 1998 after British researchers showed that PERV could infect human cells in the laboratory. But the FDA reversed its freeze on research after a 1999 study in the journal Science showed that 160 exposed to the virus were not infected.

"We've allowed [trials] to resume on a case-by-case basis," said FDA spokesperson Lenore Gelb. "We've also published guidelines for the industry." Citing confidentiality rules, she declined to specify exactly what clinical trials were under way. "The FDA generally doesn't really answer those types of questions," she said.

Fano dismissed the results of the Science study, funded by biotech giant Novartis AG, which has major investments in xenotransplantation research. She said that four patients tested positive for PERV antibodies, possibly signaling that their bodies were fighting off an infection by the pig retrovirus.

"Besides," she said, "just because this virus is not appearing now doesn't mean it won't appear tomorrow." Her group is looking into filing suit against the FDA, which she says is cowed by biotech industry pressure, to halt xenotransplantation research.

"I don't think anything short of legal action is going to stop xenotransplants," she said. "People are not interested in slowing down; biotech companies want to keep their investors happy. ... It's nice that [patients like Jim Finn] are feeling well, but we're hoping they don't come down with a horrible illness down the road. These viruses can remain latent for a long time."

As for Finn, he says he doesn't feel any different because of the pig cells that are now part of his brain. "But I will tell you one thing," he said. "I've heard about every darn pig joke there is."

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