For years surgeons have dreamed of relieving the perpetual shortage of human donors by harvesting hearts, livers, kidneys, pancreases and lungs from other animals. Primates seemed like the best bet, but so far the gonzo surgery has failed abysmally–Baby Fae died 20 days after California surgeons gave her a baboon heart in 1984, and both patients given baboon livers at the University of Pittsburgh (in 1992 and last January) died within 10 weeks. But hope hasn’t. Recently, says Dr. Jeffrey Platt of Duke University, “enthusiasm for animal-to-human transplants has increased dramatically. There’s a feeling that we can identify the obstacles and deal with them.” Last month more than 300 scientists met in England for the second international conference on “xenotransplantation” (transplants between different species) and heard upbeat reports from almost every transplant center in Europe and America. Researchers at Harvard Medical School have just launched the journal Xeno (short for xenotransplantation) to reflect what the editors call “the explosion of new information and ideas.”
The most explosive of all promises to be the idea of “organ farms,” where animals would be raised for their transplantable innards. The noble pig is the odds-on favorite for the first such farms. Pigs’ organs are about the same size as humans, they have a similar physiology (their hearts in particular closely resemble people’s) and they do not carry diseases dangerous to people. They also have the right image: slaughtering pigs for organ transplants provokes less fury than killing, say, chimps. Best of all, researchers are pretty adept at manipulating pig genes–the key to transplants. That’s the big difference from today’s transplants: when the donor organ comes from a cadaver, doctors flood the patient with drugs to suppress the immune system, which otherwise attacks the organ. But if the organ comes from an animal, scientists can leave the patient alone and tinker with the donor. By slipping human genes into farm creatures, researchers might be able to grow animal organs that human bodies will accept. “Genetic manipulation of animals is the future of the field,” says Dr. Hugh Anchincloss Jr. of Harvard Medical School.
Already, genetic engineering has fooled at least a few immune systems. Antibodies, killer cells and a shower of attack-dog proteins collectively called “complement” don’t take kindly to an organ from another person. When the transplant comes from a whole different species, the proteins tear it to shreds in minutes to hours. But at the meeting in England, researchers from Duke and DNX Corp. of Princeton, N.J., announced that they had taken the first step toward genetically altered pigs whose organs would survive this onslaught. The scientists microinjected human genes into fertilized pig eggs. (The genes make proteins that neutralize the attack of complement.) The eggs were returned to a surrogate mother. just under 10 percent of the piglets harbored the human gene. In most the genes performed as advertised: they mounted a defense against the human proteins that otherwise rip apart a transplanted organ. “This is the first demonstration that [putting human genes into an animal] could be used to inhibit the hyperacute rejection response,” says John Logan of DNX.
Down on the organ farm, the most valuable crop would probably be hearts, since only 15 percent of patients waiting for new hearts receive one in time. Also, the heart is little more than a squishy pump; it does not chum out biochemicals that could make, say, a pig liver incompatible with human biochemistry. Auchincloss believes that pigs’ pancreatic islet cells, which secrete insulin, would also work in a human body; surgeons in Sweden have recently transplanted pancreatic cells from pigs into diabetics. Pig kidneys might also work in humans.
All that is still years away. DNX plans to breed the genetically altered pigs and transplant their organs into monkeys or apes as early as next year; human trials could come in 1996. But Auchincloss warns that test-tube success does not always translate into operating-room triumph: “You might get a great effect in vitro but most people in the field are suspicious that it won’t happen in a real transplant.” For one thing, even if researchers neutralize the killer complement attack, the patient could still send antibodies, like those that reject organs from other humans, into the fray. No one knows whether these antibodies react more strongly against animal organs than they do against another human’s organ, or less.
But if it all works out, just think of the image boost around the sty. Pigs: they’re not just for bacon anymore.
