Coalition Exposes Flaws in Pig Transplant Study

Scientists Say Industry-Sponsored Study Proves Dangers of Cross-Species Transplants

August 23, 1999

A study implying that organs, tissues and cells from pigs would be safe to implant in humans is deeply flawed, and actually proves that cross-species transplants are dangerous says the Campaign for Responsible Transplantation (CRT), an international coalition of physicians, scientists and 75 public interest groups opposing xenotransplantation.

The study, co-sponsored by Novartis and the Centers for Disease Control, and published in the journal Science last Friday, tracked 160 patients in 9 countries exposed to living pig tissue over a 12-year period. One hundred and thirty one patients had their blood "filtered" and recirculated through pig spleens, kidneys, livers, or devices made with pig liver cells; 15 received pig skin grafts for burns, and 14 received injections of pig pancreas cells for diabetes.

Some patients in the study reported persistent rashes and strange fevers. Data from some patients were deemed "uninterpretable" due to a lack of sufficient DNA for analysis, and technological limitations. But most worrisome was the finding that 30 patients who underwent "splenic perfusions" tested positive for Porcine Endogenous Retrovirus (or PERV) DNA; 23 had pig cells circulating in their bodies 8.5 years after treatment; and four patients injected with pig cells produced antibodies against pig PERV, suggesting a potential active infection by pig viruses. Although the study's authors claim that there is no conclusive evidence of human infection by PERV, they admit that "PERV infection [cannot] be excluded."

"I think this study is far from reassuring; it demonstrates a proven risk of transferring pig viral DNA through xenotransplants," says Peter Collignon, a microbiologist in the Infectious Diseases Unit at Canberra Hospital in Australia.

Because PERV is present throughout the pig genome, Collignon suspects that the virus was likely transmitted to all of the patients in the study and may be lurking inside them undetected. Collignon says that, like the human herpes simplex virus, PERV may not necessarily show up in a blood test, but may instead be hiding in patients' brain or liver cells. To be sure it's not there, says Collignon, one would have to biopsy every cell type in each patient's body, or do an autopsy. Moreover, even the best screening systems can't detect unknown viruses. Like HIV, novel pig viruses could spread silently from human to human for years before they are identified.

"It would be dangerous to conclude that xenotransplantation is safe from this paper," states Dr. Mae-Wan Ho, a biologist at the Open University in Britain, and author of a book on genetic engineering. "The PCR [assay systems] used in the study do not give clear results, even by the authors' admissions," she says. Moreover, Ho claims, the assays are only screening for PERV; so they will not detect other types of viruses, or recombinant (pig-human hybrid) viruses. Oddly, Novartis and other companies are breeding pigs with human genes for xenotransplants, yet none of the patients in their study were exposed to tissue from such pigs. It is the very genetic modification/"humanization," of pigs, however, that could provide an opportunity for animal viruses to fool the human immune system, "hide" inside the human body, and become more virulent human killers. This study did not assess or address those risks.

Other scientists say that crucial pieces of information were omitted in the Novartis study, calling into question the authors' conclusions about the potential safety of xenotransplantation. Dr Emanuel Goldman, Professor of Microbiology and Molecular Genetics at New Jersey Medical School in Newark notes that a majority of the samples tested in the study were from patients whose blood had been flushed through pig tissue, and recirculated into their bodies, for very short exposure periods - on the order of minutes to hours. "Data from such experiments," says Goldman, "are hardly relevant to the kinds of conditions that would apply in whole organ xenotransplants." Data from the 14 subjects who received porcine pancreatic islet cells could be taken more seriously, he said. However, as with the burn victims, important information about these patients' exposure times and health and immunological status was missing.

In addition, the patients in this study were treated, and serum samples handled and stored, in 9 separate countries, making quality control on several levels almost impossible. Looking for PERV RNA is always suspect with serum stored for several years. Plasma samples are frozen at 70 degrees C and thawed at very high temperatures. Many viruses are very unstable; it is unknown whether such extreme temperature changes might alter PERV and affect test results. Negative responses could actually be false negatives; or false positives could be true results. We may never know.

Novartis and US health authorities are using this inconclusive and rather damning study to push for more clinical trials with pig organs, cells and tissues. This ironically comes at a time when the Food and Drug Administration (FDA) has placed an indefinite ban on blood donations from citizens who spent six months or more in Britain since 1990, due to the theoretical risk of transmitting "mad cow disease" through the blood supply. There is no antibody test for mad cow disease, and no convincing data to show that prion diseases can be transmitted via blood. With xenotransplantation, however, the public health risk is real, the evidence is there, and yet the FDA refuses to enact even a temporary moratorium on clinical trials. CRT believes this is incongruous and irresponsible.

"The notion that xenotransplantation is somehow "safe" now, because of the Novartis study, is ludicrous," says CRT's Fano. "Let us not forget that, in the early 1980s, Russians were assured of the safety of their nuclear reactors. Then in 1986 the people of Chernobyl were exposed to radioactivity 100 times greater than the Hiroshima bomb. It is estimated that over 15 million people have been victimized by the Chernobyl disaster in some way and that it will cost over $60 billion to make these people healthy again. More than 600,000 people were involved with the cleanup, many of whom are now dead or sick."

CRT believes that we could avert an infectious Chernobyl before it's too late by banning xenotransplants. Current lamentations about the alleged human organ and tissue shortages are misguided. Studies have shown that the U.S. organ procurement system is poorly managed, and that we routinely burn or bury a sufficient number of viable organs and tissues to meet clinical demands. Passing laws to increase human organ and tissue donation, and launching education programs to prevent organ disease, are safe, sensible and humane options that should be vigorously pursued by our public health authorities.