Transplantation's Next Frontier: The Promise of the Pig
Slasman, Peggy, The Saturday Evening Post
Using organs from animals to replace failing human organs is a burgeoning technology in the United States and England. It's known as xenotransplantation.
At this very moment, approximately 50,000 people are on the national waiting list for an organ transplant; only 20,000 of them will receive one. Nearly ten people die each day, waiting and hoping for that lifesaving organ. And those who actually make it onto the waiting list represent only a subset of those who potentially could benefit from organ transplantation.
"We know these patients, and we see them becoming weaker and sicker while they wait for an organ," says A. Benedict Cosimi, M.D., chief of the transplant unit at Boston's Massachusetts General Hospital. "We have the technology and skill to save lives, but we don't have the organs. Too often we stand by helpless and frustrated, watching patients die, seeing families torn apart. If we had enough organs, we could restore lives to patients, preserve families."
Inspired by these patients, Massachusetts General researchers and clinicians are advancing along the path toward what is widely seen as transplantation's next frontier: using organs from animals to replace the failing organs of humans, a technology known as "xenotransplantation." David H. Sachs, M.D., director of Massachusetts General's Transplantation Biology Research Center (TBRC), has spent more than a quarter century-virtually his entire scientific career-bringing xenotransplantation closer to reality. Along the way, he says, he has learned much about the body's immune response. A deliberate and confident man, Sachs explains that solving the organ shortage is a matter of finding an organ source that is plentiful and safe. The most promising source, he says, is the pig.
The anatomy and physiology of pigs are remarkably similar to those of humans. Their digestive, respiratory, pulmonary, and cardiovascular structures parallel those of humans. And the organs of the specific breed of miniature swine that Sachs has developed over the years are similar in size to human organs, fitting the tiniest newborn baby to adults 300 pounds or greater.
Other benefits of pigs include their early sexual maturation and frequent large litters, enabling rapid production of significant numbers of animals. The pigs are raised in a controlled, clean setting and harbor few or no diseases. Finally, because society has long regarded the pig as food-last year more than 90 million pigs were raised for food-the use of pig organs for transplantation, compared with organs from nonhuman primates, such as baboons, elicits fewer ethical concerns.
Yet transplanting an organ from pig to human is fraught with difficulties. When any nonhuman organ is transplanted into a person, the body recognizes it as foreign. The immune system swings into overdrive, mounting an attack so fierce, so swift that within minutes the transplanted organ is rendered useless. This intense response is known as "hyperacute rejection." Beyond hyperacute rejection, other immune system warriors, such as the white blood cells, or lymphocytes, stand at the ready to fight off the foreign tissue.
Sachs and his research team are exploring ways to overcome these various phases of rejection. One of the most promising means involves inducing "tolerance," coaxing the recipient's body to accept a donor organ with little or no immunosuppression, keeping immune defenses intact to stave off infection.
"We're achieving success with tolerance right now in the laboratory with same-species kidney transplants," Sachs says, describing animals that have thrived for more than three years with mismatched organs without longterm immunosuppresive drugs. "We're also making progress in achieving tolerance in cross-species transplants."
A research team led by Megan Sykes, M.D., has been studying tolerance achieved by first transplanting bone marrow from the donor into the recipient. …