Down on the organ farm
New hope that animals could one day shorten the wait for a transplant
James Finn was desperate. Parkinson's disease was eroding his ability to move and speak, and none of the usual drugs helped. So when his doctor suggested an experimental procedure, he decided to go for it. On Sept. 24, 1996, he had holes drilled into his skull so that surgeons could implant millions of neurons to replace a chemical his brain was not producing. The transplant came from an unusual source: a pig.
Today, Finn's story traces the promise and disappointments of animal-to-human transplantation, a strategy that could one day ease the shortage of replacement organs like hearts and kidneys as well as tissues for treating illnesses like diabetes. Finn himself is convinced that the pig donation helped him: "It has allowed me to live a much more normal life." But Diacrin, the company that sponsored the study, decided to abandon animal-to-human transplants after lackluster results in other patients, joining other companies that fled the xenotransplantation field after a mid-1990s rush of enthusiasm. Now, however, there's a new, if cautious, optimism that animal transplants may yet realize their promise, and do so before the other great hope for replacement tissues, human stem cells. "We all hope for stem cells, but before that we will have xenotransplantation," says Bernhard Hering at the University of Minnesota.
Scientists believe they are making headway against the two big problems bedeviling the field: the intense rejection that normally occurs when animal tissues are put into the human body and the possibility that the transplants might introduce dangerous new animal viruses into the human population. At the American Transplant Congress in Washington last week, for example, researchers announced that insulin-secreting "islet" cells from pig pancreases survived and functioned for over two months when transplanted into diabetic monkeys. They also reported early results on organs from a new breed of cloned pigs, genetically altered in hopes of making their tissues more compatible with other species. While their organs still seem to face rejection, the studies hinted at new strategies for taming the problem. "A year or two ago there was a lot of concern that the field would be dead," says Daniel Salomon at the Scripps Research Institute in La Jolla, Calif. "The field isn't dead. It's coming back."
For decades, doctors have occasionally turned to animal organs for patients facing imminent death, like Baby Fae, the infant who famously lived with a baboon heart for 21 days in 1984. Monkeys are no longer seen as good donors, however, because their similarities to humans might make it easier for unrecognized viruses to jump the species barrier. So surgeons have turned to pigs, which have organs of the right size but lie a safer distance from people. Pig cells, however, look so foreign to the human immune system that they spark intense rejection.
In the mid-1990s, researchers genetically engineered pigs to give them humanlike cell-surface molecules. This helped overcome the first swift stage of rejection that normally would shut down transplanted pig organs within hours, allowing the organs to survive in monkeys for weeks and even months. By now, says Christopher McGregor of the Mayo Clinic in Rochester, Minn., a monkey given a pig heart in his program can often live three months or more. (To simplify the experiment, he leaves the monkeys' own hearts in place as well.)
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