Pigs May End Organ Shortage.

New research may allow pig-human transplants.

The plight of patients with failing organs is grim. There are roughly 63,000 such patients in the United States, but only about 20,000 organs each year are available for transplant. Patients must wait a year or more, and many die before

In the far future, replacement organs may be grown from a person's own cells, but in the near future, organ transplants from animal donors to humans, a process knows as xenotransplantation, will be the best bet, say David K.C. Cooper and Robert P. Lanza, authors of Xeno: The Promise of Transplanting Animal Organs into Humans. Cooper is an immunologist at the Transplantation Biology Research Center in Massachusetts, and Lanza researches tissue engineering and transplants at Advanced Cell Technology, Inc.

Although experimenters have transplanted organs from apes (such as the baboon) to humans, pigs are more-promising organ donors, say the authors. Most apes are too small for their organs to function well in a human body, and apes may harbor viral infections, such as HIV, which is believed to have spread from monkeys to humans. In addition, most apes are endangered, so rearing and killing large numbers of them would be socially unacceptable.

On the other hand, pigs breed fast, they are the right size, and their anatomy and physiology are "surprisingly similar" to humans, the authors say. In addition, the risk of viral contamination from pigs is less than from apes, in part because there has already been considerable contact between pigs and humans.

However, there are still many obstacles to overcome before pig organs can be successfully used in humans. Rejection of an organ by the recipient's immune system is the chief problem with any transplant, even from human to human, and this difficulty is especially tough for pig-human transplants. Pigs have a particular molecule on the internal lining of their blood vessels that is also found on the surfaces of certain bacteria, viruses, and parasites. The human immune system recognizes this molecule, a form of galactose (Gal), and will destroy pig tissue as if it were an infectious organism.

One way around this problem is to genetically engineer pigs that don't produce Gal. This could be done using the so-called gene knockout technique to remove the gene that directs pig cells to produce Gal. Although Gal-knockout mice have been produced in the lab, scientists have not been able to produce a Gal-knockout pig. Another possibility is to give pigs extra genes that would compete with the Gal gene and direct pig cells to replace Gal with a more benign molecule--something the human immune system wouldn't attack.

But by far the most radical approach to the rejection problem involves tricking the human immune system into accepting pig tissue as its own. First, the immune system would be "wiped out" by a combination of radiation and drugs. Pig cells would then be injected into the patient's bone marrow. As the immune system recovered, it would have to "re-learn" which tissues were its own and which were foreign. Any tissue in the body at that time would be considered to be "self," so the immune system would accept. the pig cells and all subsequent pig tissue introduced to the body.

Experiments along these lines with baboons have been promising, but much more work needs to be done before such technology could permit trouble-free pig--human transplants. However, the authors envision a time when all humans may be made pig-tolerant through a variation on this technique: Pig cells would be injected into fetuses before the immune system is fully formed, thereby conferring lifelong tolerance to pig tissue. Everybody would then be able to accept a donor organ from a pig, if needed.

"With the quite amazing advances taking place--seemingly almost on a weekly basis--the remaining hurdles of xenotransplantation will undoubtedly be overcome," the authors conclude. "Xenotransplantation will be established as an important therapy for thousands of patients, in many of whom it will prove life-saving."

Source: Xeno: The Promise of Transplanting Animal Organs into Humans by David K.C. Cooper and Robert P. Lanza. Oxford University Press, Inc., 198 Madison Avenue, New York, New York 10016. 2000. 274 pages. $30. (Save 25% by ordering online at www.wfs.org/specials.htm.)