Sometime this fall, English researchers will take the heart of a genetically engineered pig and implant it in a human whose own heart is dying.
It will not be the first time surgeons have attempted to use an animal organ in a human. But it may well be the first time such a transplant succeeds because researchers have given the pig heart human genes that make it less likely to be rejected.
The ability of biotechnologists to create "transgenic" animals with human immunological characteristics, combined with the development of powerful anti-rejection drugs, has brought surgeons to the brink of a new era, in which animal organs may routinely be implanted in humans.
That gives hope to many patients and doctors who are buoyed by sharply increasing success rates for human organ transplants, but frustrated by the shortage of donors. Because the demand for organs has grown while the supply of donors has remained constant, many patients whose lives could be saved die on transplant waiting lists.
Proponents argue that so-called xenotransplants of kidneys, livers, hearts and even brain cells could save the lives of tens of thousands of patients each year.
Tempering that promise, researchers still face a number of stumbling blocks, both scientific and ethical. And many scientists fear that transgenic organs will be a source of infectious diseases rivaling AIDS in their potential for devastation.
"Xenotransplantation is critical to the future of transplantation" if all the scientific hurdles can be overcome, said Dr. Hugh Auchincloss Jr., an animal transplant researcher at Massachusetts General Hospital in Boston.
The field seems poised for a major expansion from the laboratory to the clinic.
Britain's main bioethics advisory group recently approved the use of pig organs in humans. The U.S. Food and Drug Administration and the Centers for Disease Control and Prevention are on the verge of issuing broad guidelines permitting xenotransplants.
Some researchers already have been trying such operations. Baboon livers have been used in several unsuccessful operations. Surgeons at Duke University Medical Center are expected to begin using pig livers--which are more widely available--later this year.
Fetal pig cells have been transplanted in the brains of at least five people with Parkinson's disease in an effort to replace dead brain cells. Results have not yet been reported.
If the experiments with pig hearts and livers are successful, transplants of pig kidneys and lungs may follow quickly.
"We're flush with excitement, but it's a long road ahead," said Dr. Fritz H. Bach, a transplant surgeon at Harvard Medical School.
The driving force behind using animal organs is the rapid improvement in human organ transplants. New anti-rejection drugs, new preservation methods and refinements in surgical techniques have greatly improved the survival rate of transplanted organs over the last five years while cutting the procedure's cost nearly in half, according to Dr. Ronald W. Busuttil, head of the liver transplant program at UCLA. The cost of a transplant ranges from $50,000 for a kidney to as much as $200,000 for a liver.
These changes have triggered a sharp increase in transplants in the United States--from 12,786 in 1988 to 19,017 in 1994, according to the United Network for Organ Sharing.
But this 49% increase has been accompanied by only a 37% increase in donors, to 8,114. (Several organs can be taken from one donor.)
Meanwhile, the number of patients on waiting lists more than doubled during that period, to 56,066 in 1994. In that year, 3,072 patients died waiting for organs. Perhaps as many as 100,000 more died before even getting on a list.
"These are patients who would most likely be alive today if only there had been enough organs to go around," said O. Patrick Daily, assistant executive director of operations for the organ sharing network.
But humanitarian concerns are only part of the story. Financial analysts suggest that successes with xenotransplants could lead to at least 100,000 such operations every year at an average cost of $10,000 per organ. This potential billion-dollar market for breeding the animals and supplying organs is enticing several biotechnology companies into the arduous and scientifically challenging field.
Some people express concern that patients' desperation and the financial allure may be seducing surgeons into premature experiments with animal organs.
"I desperately want to do it [perform xenotransplants]," said Auchincloss, who has been researching the subject for more than a decade. "But I don't think we are ready to do it in people, because it isn't going to work." Researchers, he argues, have not credibly demonstrated that the organs will survive in humans.