New Role for Pigs: More Than Just "The Other White Meat"
There is a tempest brewing in the medical community over xenotransplantation the transplantation of live cells, tissue, or organs from animals to humans. This controversial procedure is being touted as a possible solution to the current organ donor shortage. Doctors have already made several attempts at xenotransplantation, using organs and tissue from baboons. However, the animal with the best potential for wide-scale xenotransplantation is the pig. Pigs are immunologically compatible to humans and their organs are similar in size to human organs.
The Department of Health and Human Services recently issued a revised draft of guidelines on xenotransplantation that, if approved, will open the door to greater experimentation with the procedure. (The draft guidelines were initially released in 1996. A substantial number of negative responses led to increased discussion and some revisions.)
"There are conflicting views on xenotransplantation," says Stanley H. Weiss, MD, associate professor, Department of Preventive Medicine and Community Health at UMDNJ-New Jersey Medical School. "In one corner are the transplant surgeons, who say, 'We're going to do this. Now just tell us how to do it as safely as possible.' In the other corner are the naysayers scientists who are concerned about the spread of new, potentially dangerous viruses from animals to people."
There is growing cause for concern. In the March, 1997 issue of Nature Medicine, a group of researchers reported on the infection of human cells by a pig endogenous retrovirus (PERV). In October, 1997, British virologist Jonathan P. Stoye, MD, discovered two additional PERVs that are also capable of infecting human cells. Based on these findings, researchers noted that it will be difficult, if not impossible, to breed virus-free pigs.
Endogenous retroviruses usually do not cause illness in the host species. The PERVs do not make pigs sick. Scientists cannot say for sure if these viruses would result in active infection in humans who received pig organs, whether such an infection would be harmful, how long it might take to induce illness, or whether the virus could be transmitted to others.
"It's not just PERVs we have to worry about," says Weiss. He explains that influenza variants in pigs play an important role in flu epidemics. In 1918 there was a particularly lethal worldwide influenza pandemic. Sequence analysis indicated that the culprit viral strain came from pigs. The hemagglutinin antigen of the 1918 flu strain led to enhanced clotting in some of the persons infected, triggering deadly, hemorrhagic complications in thousands of patients. The obvious clinical parallel is to the Ebola virus. A key difference is that influenza spreads much more readily, by coughing and sneezing. Thus, if such a flu strain were to reemerge the global risks are potentially far greater than the much-feared Ebola, since Ebola is much more likely to be contained.
"Obviously, this is a worst-case scenario, and a low-risk one, at that," says Weiss. "But it could happen."
In July, 1997, Weiss moderated a government-sponsored symposium, "Cross-Species Infectivity and Pathogenesis," where these and other issues were discussed at length. No consensus was reached, and the controversy continues. In the meantime, several companies in the US and abroad, viewing xenotransplantation as an excellent business opportunity, are gearing up to breed pigs on large-scale "organ farms."
"Those in favor of xenotransplantation say, 'Let's move forward, because lives are at stake. We'll deal with complications if and when they happen,'" says Weiss. But many questions still need to be answered concerning the risks of cross-species transplantation. Do pigs and other animal species carry other agents we don't even know about? Could these be spread to humans through xenotransplantation? And could they be spread from transplant recipients to others?
"We didn't even know about these pig PERVs until a few months ago. We need more basic research on xenotransplantation before we proceed full-throttle. The next steps need to be closely regulated and overseen," Weiss states.
Winter 1998 Table of Contents