Rules Outlined for Transplants From Animals

The Clinton administration, recognizing the potential in the experimental field of animal-to-human transplants, proposed strict safeguards Friday to protect against the transmission of serious animal viruses and other microbes into people.

“This is a tightrope,” said Dr. David A. Kessler, commissioner of the Food and Drug Administration, which developed the guidelines along with the Centers for Disease Control and Prevention and the National Institutes of Health.

“We are balancing a real need for treatment versus some very real risks,” he said. “There are a lot of concerns. There are a lot of unknowns.”

Researchers generally predicted that the proposed safeguards would encourage expanded use of animal transplants.

“I see these guidelines as a show of support from the government, from society, that the need is definite and no one really wants to stop science cold,” said Dr. Steven Deeks of UC San Francisco, who recently transplanted baboon bone marrow into an AIDS patient.

The recommendations cover all forms of “xenotransplantation,” as the practice is called, including the use of animal organs, cells and tissues. The rules would apply to internal transplantation, as well as the use of such material enclosed in a device outside the body as a “bridge” to transplantation from a human donor.

The guidelines are not final and will be subject to a 90-day public comment period.

From 1990 to 1995, an average of 4,835 people annually donated organs for use after their deaths. But many thousands more--about 48,000 individuals and growing--remain on organ waiting lists, making the use of animal organs, cells and tissues increasingly attractive.

Moreover, scientific advances in recent years have enabled researchers to develop animals whose organs are given certain human genes to make them less likely to be rejected after transplantation. This work, and the development of more powerful anti-rejection drugs, has reduced the likelihood of failure.

Such experiments, closely monitored by the FDA, are already underway. Baboon livers have been used in several unsuccessful operations, and pig livers are expected to be used in several forthcoming procedures.

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Fetal pig cells have been transplanted into the brains of several patients with Parkinson’s disease. And the most publicized recent case was the transplant of baboon bone marrow into Jeff Getty, a San Francisco AIDS patient, that aimed to bolster his flagging immune system.

Deeks said that Getty continues to do well, although the actual clinical impact of the baboon marrow is unclear. Moreover, there is no evidence that Getty has contracted any new virus as a result of the transplant, Deeks said.

But as these surgeries have proceeded, concerns have mounted over the possible transmission of infectious animal organisms to humans.

Often, microbes harmless to animals can change once they leave their natural host and move into a new species. The human immunodeficiency virus that causes AIDS, for example, is believed to have somehow jumped from African monkeys into humans, either through food consumption or during slaughter.

Animal-rights activists cited such concerns in reacting angrily to the proposed government regulations.

Dan Mathews, a spokesman for People for the Ethical Treatment of Animals, called the transplant experiments “costly, cruel and hopeless” and predicted that if allowed to continue, they would “pave the way for a plague worse than AIDS. It is really quite frightening.” The guidelines, similar to those released in Britain last March, urged that patients be fully informed of the potential risks of animal transplants to themselves, their families and close contacts, especially sexual partners. They also require that any planned procedure be thoroughly screened and approved by a series of local institutional review boards, as well as the FDA.

The agency recommended that any animals used be “procured from screened, closed herds or colonies that are well characterized and as free as possible of infectious agents.” Such animals “should have documented lineages and be bred and reared in captivity,” the FDA said.

There is a heavy emphasis on monitoring, follow-up and record keeping so that heretofore unknown hazards can be quickly identified. The agency proposed creating a national registry of patients who receive such transplants and will launch a pilot program to define the scope of such a registry.

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Acknowledging that it is impossible to screen animals for as-yet-unidentified viruses and other organisms, Kessler said the registry and other long-term surveillance measures were designed to help officials stay on top of unsuspected transmission.

The recommendations also require that the transplants take place at a clinical center associated with an accredited biology and microbiology laboratory. The team should include a surgeon, infectious disease specialist, veterinarian, transplant immunologist, infection control specialist and clinical microbiologist, the FDA said.

Jonathan Allan, an epidemiologist at the Southwest Foundation for Biomedical Research in San Antonio, said he was disappointed that the proposed regulations did not single out baboons for exclusion, as they are known to carry numerous infectious diseases that can easily be passed to humans. Pigs are believed less likely to do so.

“In my mind, it doesn’t make sense to be approving any studies involving the use of baboons because of the infectious disease risk,” Allan said.

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Animal Tissue Transplants

A broad variety of animal organs and tissues may be used to treat human ailments.

Already in use:

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Tissue type Used for Baboon bone marrow AIDS Baboon livers Liver failure Baboon hearts Congenital heart defects Fetal calf adrenal cells Pain relief in cancer Pig islet cells Diabetes Pig livers Liver failure (used extemally)

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Forthcoming uses *--*

Tissue type Used for Pig livers Liver failure (implanted) Pig hearts Heart failure Pig pancreases Diabetes

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Cimons reported from Washington and Maugh from Los Angeles.