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Animal Parts: Learning the Tricks
Karen Hopkin
They’re the stuff of mythology: satyrs, free-spirited critters with the head of a man and the body of a goat, that prance through the woods, cracking wise and looking for trouble. Or the Minotaur, a nasty beast with a man’s body and a bull’s head. Or mermaids, sweet ladies with fish tails and a fondness for song.
Now, we know better. There’s no such thing as people who are part human, part animal. Right? In fact, more than a few people today are walking around with a bit of the beast in them. Over the past five years, some 200 people have received transplants of animal cells or tissues to replace or assist their own failing organs.
How did this strange arrangement come to pass? Doctors have been experimenting with xenotranplantation—the practice of transplanting parts from animals to humans—for a long time, with precious little success. But that may soon change. Physicians and researchers are looking to xenotransplantation as a possible solution to the chronic shortage of donor organs for people with failing kidneys, livers, or hearts, and they hope to battle chronic diseases such as diabetes and Parkinson’s with implants of animal cells.
But the road toward successful xenotransplantation has not been smooth, nor is it complete. So far, few whole-organ transplants from an animals have worked for very long, because the human immune system is quick to destroy foreign tissue. Despite these failures, researchers doggedly press on in the hope that learning more about how the immune system recognizes and attacks foreign cells and organs will reveal how physicians can put the brakes on transplant rejection. Click your way through the timeline to find out more.
Timeline
1682 - Doctors repair the damaged skull of an injured Russian nobleman using a bit of bone taken from the skull of a dog. The surgery is said to be successful, but the Russian church threatens the nobleman with excommunication. So he has the dog bone removed.
1905 - The pace of xenotransplantation picks up, and physicians begin to graft animal tissues into humans with some regularity. For example, a French surgeon transplants slices of a rabbit kidney into a 16-year-old boy suffering from kidney failure. "The immediate results were excellent," he declares. But the patient dies two weeks later. Over the next 20 years, doctors try to transplant organs from pigs, goats, lambs, and monkeys into various patients. All the grafts fail, but no one understands why.
1953 -
Sir Peter Medawar, Nobel Laureate and the "father of transplantation biology."
Peter Medawar of the University of London finds that animals exposed to foreign tissues while they’re young—still embryos—don’t reject them. MacFarlane Burnet of Melbourne University postulates that this is because the immune cells that patrol the bloodstream in search of foreign invaders somehow learn very early on to accept whatever tissues are there as part of the body, and only attack things that show up later. In 1960, Medawar and Burnet win a Nobel Prize for their discoveries.
1954 -
Surgeons perform the first human organ transplant
Surgeon Joseph Murray performs the world’s first successful human organ transplant when he transfers a kidney from one identical twin to the other. Soon after, researchers develop the first generation of drugs that suppress the immune system and prevent organ rejection. Doctors begin using these drugs routinely to inhibit organ rejection in human-to-human kidney, liver, and heart transplants.
1963 - After a lull of nearly 40 years, physicians again try their hand at xenotransplantation. Keith Reemtsma, then at Tulane University, transplants more than a dozen kidneys from chimps to humans. One woman survives for nine months, even returning for a time to her job as a school teacher. Thomas Starzl, then at the University of Colorado, performs an additional six transplants using baboon kidneys. His patients survive from 19 to 98 days. Although many patients now survive for weeks or months, not all the operations are such "success stories." In one strange case, the kidneys taken from a chimp work—much too well. They produce an astonishing 54 liters of urine in one day, compared with the modest two liters considered normal for humans. The patient suffers a stroke and dies of heart failure three days later. (The surgeons had transplanted both of the chimp’s kidneys, which, they later comment, "maybe we should not have done.")
1964 - James Hardy of the University of Mississippi Medical Center attempts the first cardiac xenotransplant, using a heart from a chimp. The primate heart—too small to support the patient’s circulation—functions for only two hours. Two other transplants, using pig hearts, fail due to hyperacute rejection. Outside the clinic, researchers studying animals are learning more about the causes of hyperacute rejection. They discover that human blood contains natural antibodies that can recognize cells from pigs, dogs, or other animals. When these antibodies encounter foreign tissue, they trigger a chain reaction that destroys the graft within hours.
1979 - Christian Barnaard, the surgeon famous for performing the first successful human heart transplant, tries to use baboon and chimpanzee hearts as temporary backup pumps in two patients whose hearts don’t function properly after cardiac surgery. The transplants do not help the patients survive.
1984 -
Baby Fae, baboon heart recipient
The world holds its collective breath as Baby Fae, an infant born prematurely with a malformed heart, receives a heart from a baboon. She lives for almost three weeks—longer than any other recipient of a heart xenotransplant—but then rejects the organ, due to a blood type incompatibility (Fae was type O; the baboon, type B). Although it didn’t save Baby Fae, cyclosporine—the granddaddy of immunosuppressive drugs—is gaining widespread use for human transplants. By the end of the 1980s, newer and even more powerful immunosuppressive drugs, including FK506, come into vogue.
1992 -
Thomas Starzl and colleagues give a man a baboon liver
Xenotransplantation grabs headlines again when Starzl and his colleagues, now at the University of Pittsburgh Medical Center, perform a pair of baboon-liver transplants. One patient survives more than two months; the other, 26 days. Both die from postoperative infections that prove deadly because their immune systems are shut down by antirejection drugs. Starzl puts his xenotransplantation program on hold until the problems are better understood. Around the same time, researchers at Duke University receive permission to use a pig liver as a "bridge" to keep a critically ill woman alive as she waits for a human liver transplant. She survives only 32 hours. Back in the lab, researchers at Massachusetts General Hospital discover that it’s a particular sugar on the surface of pig cells that provokes the attack of the natural antibodies. If scientists can use genetic engineering to create pigs that no longer put this sugar on their cell surfaces, the animals’ organs should be less irksome to the human immune system. Other researchers generate pigs that make proteins that can preemptively disable the very part of the immune system that would otherwise lay waste to the xenotransplant. Several biotechnology companies set out to make these "humanized" pigs and win approval for using the pig organs in humans.
1995 -
Baboon bone marrow recipient, Jeff Getty
Jeff Getty receives a baboon-bone marrow transplant, in hopes that the immune cells in the baboon’s marrow will replace the immune cells that Getty has lost to the AIDS virus. The baboon cells—which are naturally resistant to HIV—only function for a brief time, but Getty remains healthy (and is still alive today). Getty’s transplant may not have been a technical success, but many scientists continue to investigate how pretreating transplant recipients with marrow taken from donors might create a "chimeric" immune system that contains cells both animal and human. Such "preconditioning" might trick the body into accepting subsequent xenografts as not really foreign after all.
1997 - Clinical studies suggest that transplants of isolated foreign cells may fare better than whole organs. In 1997, researchers report on the first clinical trial using nerve cells from fetal pigs to treat a dozen patients with Parkinson’s disease. The patients show marked clinical improvement—one even takes up golf after being totally bedridden. In another recipient (who died of unrelated causes eight months after the transplant), the injected pig cells appear to survive and grow. Meanwhile, other researchers try wrapping animal cells in a capsule that prevents immune cells from getting at them. The capsule—made of material containing very tiny pores—still admits nutrients and allows the cells to deliver their molecular products to the patient. For example, researchers at a biotech company in California encapsulate pancreatic islet cells from pigs for use in treating people with diabetes. The cells secrete insulin (which diabetics can’t make themselves) and could help control patients’ blood sugar levels. And about 100 cancer patients receive encapsulated adrenal cells—from fetal calves—that secrete natural painkillers called enkephalins and other neurotransmitter molecules that help to ease their pain.
Tomorrow - The future of xenotransplantation is still uncertain—technical difficulties and the possibility of accidentally introducing animal pathogens into people may yet prove to be show-stoppers. But one thing seems clear. As society debates the ethics of transplanting animal tissues into humans, scientists will probe the secrets of the human immune system. And their discoveries will undoubtedly boost the success of transplantation, whether the organs come from a caring relative or an engineered pig. |
