ARE ANIMAL ORGANS SAFE FOR PEOPLE?

By Christine Gorman

JEFF GETTY SHOULD BE DEAD BY NOW. He has had HIV for about 15 years. His immune system is barely functioning. And on top of that, in a desperate attempt four weeks ago to reverse the course of his disease, doctors at San Francisco General Hospital infused him with an experimental bone-marrow transplant from a baboon. Immunologists warned that his body would eventually reject the nonhuman tissue and that the operation would almost certainly end his life rather than prolong it. However, Getty is not only alive, but last week he was healthy enough to go home from the hospital. No matter how much time he has left, friends and family call him a medical miracle.

But there is also a small chance that the technology that allows people like Getty to receive tissues from animals could someday unleash a medical disaster. The danger is that patients could receive a previously unknown microbe along with their transplants. When viruses or bacteria have made the jump from animals to humans in the past, they have often proved exceedingly virulent: HIV, which causes AIDS; Ebola virus; and hantavirus are all chilling precedents. In a worst-case scenario, such transplants could introduce humanity to a plague that would make all of those look tame. "This is a serious mistake," says Jonathan Allan, a virologist at the Southwest Foundation for Biomedical Research in San Antonio, Texas. "It only takes one transmission from one baboon to a human to start an epidemic. There's no way you can make it safe."

No one ever had to worry about such potential hazards before, because scientists hadn't been able to figure out how to make an animal-to-human transplant work. It's hard enough to trick an individual's immune system into accepting tissues from another person. But when organs from an entirely different species are stitched into the human body, immune defenses go into overdrive, leading to swift and irreparable destruction of the foreign tissue. Two years ago, when doctors at the University of Pittsburgh transplanted baboon livers into two seriously ill patients, both men died soon after the operation.

The advent of genetic engineering, among other things, has allowed researchers to begin breaching that natural barrier. Last spring scientists at Duke University Medical Center reported that they had successfully altered the genetic makeup of a strain of pigs. As a result, the researchers managed to fool the immune systems of three baboons into accepting pig hearts, for a short while at least. Using a similar technique, the British biotechnology company Imutran has produced a herd of 300 genetically altered swine. The company expects to transplant either a pig's heart or a liver into a human subject later this year.

In Getty's case, Dr. Suzanne Ildstad from the University of Pittsburgh proposed--and the doctors at San Francisco General agreed to follow--a different approach. Ildstad has developed a special filtering process that allows her to separate out the most mature baboon bone-marrow cells. The cells that are left behind are too undeveloped to provoke an immune reaction, and it's these that were dripped into Getty's veins. Ildstad believes the immature baboon cells can, in turn, work with Getty's body to create a hybrid immune system. If she's right--a big if--that would give Getty a tremendous advantage. Baboons appear to be impervious to HIV, so in theory the fortified immune system might be able to fight off the AIDS virus.

Unfortunately, baboons are known to carry a variety of nasty pathogens, ranging from fungal infections to viruses that trigger leukemia. In July the U.S. Food and Drug Administration asked the researchers to find another baboon donor because their first choice was already infected with several viruses. The scientists finally settled on a baboon whose only major infection was herpes papio virus, which is unlikely to pose a threat because it only affects cells that are presumably filtered out by Ildstad's method.

Even the most rigorous screening methods cannot guarantee human safety, however. At least two potentially worrisome baboon viruses, for example, don't show up on any existing commercial tests. Although neither one bothers baboons, they are both retroviruses, the same kind of organism that gives rise to AIDS. If the microbes really are dangerous to humans, it's conceivable that they could spread to many victims before revealing their deadly nature. That scenario appears to have already happened once: many scientists believe it did with HIV, which apparently originated in monkeys and then somehow jumped the barrier to people.

And those are the viruses scientists know about. There is no way of knowing how many other baboon viruses medical science hasn't discovered yet; there is clearly no way to screen for any of them. That's why many scientists prefer to experiment with pigs. People are nowhere near as closely related biologically to ungulates--pigs, cows and deer, for example--as they are to primates. Any virus that can infect baboons probably already has many of the biological characteristics needed to infect people. But a virus that has adapted itself to thrive in pigs may have a much harder time taking hold in the biologically unfamiliar territory of the human body.

"Humans and pigs have lived close together for millenniums," says Dr. David White, co-founder of Imutran. "And don't forget, we've been pumping pig insulin into [diabetic] people for generations." Any virus that can jump the barrier, such as the one that causes swine flu, probably already has. In addition, pigs are easier to raise than baboons and can be isolated in germ-free environments. That doesn't mean that pigs present no risk to people, just less than baboons do.

Considering all the potential problems with baboon transplants, it's a wonder the FDA allowed Getty to undergo the operation at all. Certainly compassion for a dying man played a role. But according to scientists who are familiar with how such decisions are made, there was probably another, more subtle reason. "The chance of that bone-marrow transplant taking [hold] and working in a human is zero," says Ronald Desrosiers, professor of microbiology at Harvard Medical School. Current techniques, he believes, are simply not yet refined enough for it to work. But they could be soon.

For that reason, the Getty experiment may count more for its cautionary value than for its medical importance. Better to put the scientific community and the public on notice that the question of cross-species infections needs serious attention and debate. Otherwise, no one will be prepared when the real breakthrough comes and a transplanted animal organ takes up permanent residence in a human being.

--Reported by Michael Brunton/London, William Dowell/New York and Greg Fulton/Atlanta

With reporting by MICHAEL BRUNTON/LONDON, WILLIAM DOWELL/NEW YORK AND GREG FULTON/ATLANTA