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National oversight panel steers ahead with caution
With the recent formation of a multidisciplinary national oversight committee, xenotransplantation — animal to human transplants — continues to unfold as a cutting edge science with great potential for both risk and peril.
At opposite poles are the best- and worst-case scenarios. Some see a solution to the shortage in human transplant organs and cures for diseases such as Parkinson’s; others fear that grafting living animal tissue into humans could unleash a zoonotic retrovirus such as HIV.
Now both sides can sit around the same table as members of the newly founded Secretary’s Advisory Committee on Xenotransplantation (SACX). The 18-member panel, which convened its first meeting in February 2001, includes animal rights advocates, bioethicists, transplant scientists, and infectious disease experts. On
the panel, as well, is a xenotransplant patient, who had an injection of pig cells to treat his Parkinson’s disease.
With but one organizational meeting under its belt, the committee is described in recently published U.S. Public Health Service guidelines as "a mechanism for ensuring ongoing discussions of the scientific, medical, social, and ethical issues and the public health concerns raised by xenotransplantation, including ongoing and proposed protocols."
Passing the crossroads
"The SACX will make recommendations to the secretary [of Health and Human Services] on policy and procedures and, as needed, on changes to the guideline." Those same guidelines — recently updated from 1996 — outline rigorous measures for infection control, animal screening, and patient follow-up for clinical trials in xenotransplantation.1 (See Hospital Infection Control, December 1996, cover story.) With the guidelines and committee in place, the field is moving cautiously ahead.
"We’re a little bit past the crossroads, but we’re not far from it," says John Allen, PHD, a virologist and member of SACX.
"There is a small risk, but the risk is there. The issue is though, small risk [equals] potential big problem," Allen says.
On the other hand, another member of the xenotransplantation committee with decades of experience in infection control and health care epidemiology reminds that any new medical frontier entails an element of risk.
"The challenge for the committee is to weigh the science of real risk vs. all of the hypothetical risk that might be postulated," says William Scheckler, MD. "The bigger [concern] is not doing anything because you are hypothesizing something that could conceivably occur but for which there is no evidence. If we did that for every cancer chemotherapy drug or every new antibiotic, we would never try anything."
In his opening remarks to the committee, Scheckler reminded members that the patient safety movement has changed the tone of medical care, making any procedure that involves risk vulnerable to charges of blame and error.
On the other hand, the field of infection control’s history of infection surveillance and prevention measures should play a central role in xenotransplantation. "Key will be the ability
to define the infection of interest and to put in place a rational, cost-effective surveillance strategy to follow the infections," Schleckler told the committee.
Xenotransplant patients have to be followed for life, and banned from any blood or body donation, lest they carry a virus from the donor animal.
"[The committee is] quite nervous about is the whole issue of mad cow disease and prions, and the retroviruses that might sneak from an animal into a human," Scheckler says. "I think there are plenty of safety mechanisms in place in the current public health service guidelines. And with a committee like this, one everybody who would have any interest at all is well represented. The chances of doing something that doesn’t use good science or make ethical sense is virtually nonexistent."
Warnings heeded on baboons
Indeed, it is warnings by Allen and other infectious disease experts that have all but stopped any work with nonhuman primates like baboons. Pigs emerged as the favored donor animal, but then — somewhat surprisingly, given that this is an animal that has been domesticated and consumed by humans for centuries — a threat to human health also was identified in swine.
"There is still the unknown about this pig endogenous retrovirus that is found in every cell in every pig," Allen says. "And it replicates in human cells in tissue cultures. So we still, at this point, are not certain whether that virus would be transmitted to humans."
Another problem is that retroviruses have a long fuse, meaning disease may not show up for years and even then only in one patient out of a hundred.
"You know the virus is present, because if you introduce pig cells into humans the virus is going to be there," Allen says. "The question is whether or not the human actually gets infected’ or not. It may be the 100th person or the 1,000th person in which the virus replicates."
Are transplants worth the risk?
Given such unknowns, most current trials involve cellular therapies — as opposed to grafting whole organs, he notes.
"[They] probably have a smaller risk, but nevertheless a risk still is a risk. There are fewer cells inside the body, less contact, less time," Allen explains. "Most of them are fetal pig cells but, nevertheless, you still are waiting, and sort of holding your breath to see if somebody is going to pop out with an infection."
While there has been much discussion of using animal "bridge" organs for patients awaiting human organs, the problem is that xenotransplants don’t last, Allen adds.
"The real issue of using [whole organs] from pigs is to get them to actually function in humans. It may not last more than a few minutes or maybe a month," he points out. "That’s where most of the research is going from the companies; as far
as I know, there are no human trials planned with [pig] organ transplants, because they are not going to last long.
"With some of the cellular therapies, treatment of Parkinson’s, maybe Huntington’s, stroke victims —- the potential is there," Allen says. "As far as whole organ transplants, I am not as optimistic."
1. U.S. Public Health Service. PHS Guideline on Infectious Disease Issues in Xenotransplantation. Washington, DC; Jan. 19, 2001. Web site: http//www.fda.gov/cber/gdlns/xenophs0101.pdf.