The line between man and beast has held an eternal fascination for philosophers, theologians and scientists. Greek myths had satyrs, sphinxes and chimeras that mixed human and animal forms. In science fiction, men turned into wolves and scientists became flies. Now in medicine -- most recently with the much-publicized "Baby Fae" with her transplanted baboon heart -- the boundaries that divide the species are being chipped away.
As the demand rises for human replacement parts and the supply of human organs for transplantation fails to keep pace, scientists are looking at some animal relatives as potential organ sources.
Cross-species transplantation, called xenografting, is possible because of the recent development of potent drugs that suppress the natural rejection of foreign tissue. But as the medical success of xenografting becomes more likely, the ethical debate over the appropriateness of using near-humans as organ sources intensifies.
Early xenografts were, in general, failures. In the early '60s, surgeons implanted a few primate kidneys and livers into patients who died within months. In 1964, for example, a Mississippi man lived for a few days with a chimpanzee heart. Baby Fae was given a heart from a baboon in November 1984, when she was 12 days old, and rejected it and died 20 days later.
Today, research into cross-species transplantation, or xenografting, is at a crossroads, largely because of the shortage of experimental chimpanzees, the animal whose organs seem most suitable for human transplants. Chimps are not only an endangered species, but they are the only animal model available for AIDS research to test potential drugs and vaccines. They are also viewed as highly intelligent animals. For all these reasons, ethical objectons have been raised to the sacrificing of healthy chimps for the sake of using their organs in humans.
Would the objections be different if transplant surgeons could use more distant relatives, such as pigs, as donors? (Pig valves, after all -- treated by a tanning process -- are already used routinely to replace failing human heart valves.) Should scientists be more aggressive in finding ways around the immunological barriers to such cross-species transplantation? Is the day ahead when animals are raised in colonies specifically for their use as organ sources?
"I think implantation of chimpanzee hearts into humans is inevitable; the only question is when," said Dr. Eric Rose, director of the heart transplant program at Columbia University.
According to Rose, who has been transplanting hearts from one primate species to another, such xenografts have rejection rates no higher than transplants between primates of the same species.
In fact, in some aspects of the immune response, the body might fight off an organ from a different species less vigorously than one from its own species, said Dr. David H. Sachs, chief of the immunology branch of the National Cancer Institute.
The immune response has two parts: cellular immunity, which involves lymphocytes -- cells that attack specific invaders, and humoral immunity, which involves antibodies circulating in the bloodstream.
For eons, species had no need for a cellular immune response that rejected tissue from other species; tissue from foreign species just never made its way into the system. Because of this, according to Sachs, a cross-species transplant might meet very little resistance at the cellular level.
But the second part of organ rejection, the antibody response, forms a very important barrier to cross-species transplants. All animals have a natural antibody, which circulates outside the cell, that fights off tissue from all other species. Sachs said this immune response probably evolved to fight off microorganisms such as bacteria, to which an animal is constantly exposed. These natural antibodies lead to a phenomenon called hyperacute rejection against any tissue from a different species. Hyperacute rejection occurs in most xenografts, and the further away in the animal kingdom the two species are, the more intense the hyperacute rejection is likely to be.
Sachs and his colleagues are trying to block this rejection process by identifying the substances with which natural antibodies react and then using those substances as a trap to lure the natural antibodies out of the patient's bloodstream. This process, called immunoadsorption, is currently used to filter out toxic chemicals, such as digitoxin, from the blood.
Once the natural antibodies are captured, the expectation is that "they may not come back," said Sachs, who is "hopeful" that this approach can find clinical application within five or 10 years.
Sachs' goal is eventually to use miniature swine as organ donors. Miniature swine grow to about 200 pounds, instead of the half-ton of full-size swine, and have organs "remarkably similar" to those of humans, he said.
Other investigators, however, are pinning their hopes on closer relatives, primarily chimpanzees. And it's with chimps that most ethical objections arise.
"What I find troubling is the prospect of farming chimps simply for the purpose of harvesting their hearts," said Arthur Caplan, director of the Center for Biomedical Ethics at the University of Minnesota. "Chimps, and all primates for that matter, have enough mental capacity that they should be accorded some sort of moral standing."
"The ethics of taking another animal's life to sustain a human being gets to be very problematic when the animal is that close" to man, said Dr. Barbara Orlans, research fellow at the Scientists Center for Animal Welfare. "With chimpanzees, you're talking about an animal with 98 to 99 percent of the same genetic material as humans. In my own personal opinion, I have serious questions about using chimpanzees in this way. It's not an avenue of research I would want to pursue."
Animal rights activists and National Institutes of Health officials were among the experts assembled at Columbia University last October to review Rose's proposal to implant chimp hearts as a temporary "bridge" -- a way to buy time until a matched human donor is found -- in patients who would otherwise die waiting.
According to Dr. Robert Whitney, chief veterinary officer of the Public Health Service, who attended the meeting, "There are so few chimps when compared to the number of people who need these hearts as bridge transplants, that I don't think it's a viable option." In the end, Rose's proposal was turned down by Columbia's animal use committee.
Whitney said that of the nearly 1,400 chimps in research facilities in the United States, about 700 are owned or supported by the federal government, and half of those are in breeding colonies to keep the supply from dying out. He said that because chimps are so valuable in AIDS research, the government is especially reticent to give up even a few of them for xenograft research.
"To use a chimpanzee in research into AIDS, a disease that will kill millions of people, is one thing," said Whitney. "To use it for a one-on-one transplant, when you're saving the life of one 50- or 60-year-old man, is quite another."
What's more, if the chimp hearts are being used only as bridges, xenografting might actually create more problems than it solves.
"You're not going to save more lives if the supply of human organs is still scarce," said Caplan of the University of Minnesota. "You're just going to change which lives you save." And, he added, the use of these bridges introduces an additional ethical complexity to the allocation of human hearts.
"Who will go first?" Caplan asked. "The one with the chimpanzee heart or the one whose own heart is failing?"