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Every species carries its own dormant viruses within its DNA--for pigs, there
are PERV's, porcine endogenous retroviruses. In 1997, virologist Robin
Weiss produced the first hard evidence that PERV's could infect human
cells: Of the 50 copies of the PERV virus pigs carry in each cell, Weiss
found, as many as three were at least theoretically capable of crossing the
species barrier. The FDA issued a temporary moratorium on all
xenotransplantation.
Since Weiss first published his results, much research has gone into the PERV
problem. Good news seemed to come in 1999, when a study by Imutran and the
CDC reported no signs of active infection in 160 patients who had received
pig tissues. Obstacles on the road to human clinical trials seemed to be
clearing. But, in late 2000 and early 2001, new reasons for caution emerged:
During a transplantation of pig cells into mice, scientist Daniel
Salomon recorded the first actual cross-species transmission of the PERV
virus. At the same time, both the International Society of Heart and Lung
Transplantation (IHLST) and the United Kingdom Xenotransplantation
Interim Regulatory Authority (UKXIRA), issued reports stating that human
clinical trials of whole organ xenotransplants were still "premature" and
facing serious scientific hurdles. Even if scientists minimize the threat of
PERV's, there is still the problem of hyperacute rejection of pig organs by
recipients: To date, the longest survival rate of a pig heart in a non-human
primate is 39 days.
Despite some of the setbacks, many researchers remain cautiously optimistic.
As Salomon explains to FRONTLINE: " I think that we've made tremendous
progress. I believe that there is nothing standing in our way that can't be
solved by further scientific research. But we're not there yet." Here's a
closer look at some of the recent reports:
In a 1999 report in the journal Science, Imutran, in collaboration with the
CDC, announced the results of a study of 160 people who had received various
pig tissues and/or cells. No active PERV infection was found in any of the
patients, although 23 people were found to have active pig cells in their
blood. However, since that study was published, more sensitive tests to
diagnose the PERV virus have been developed, and this raised new questions for
some. (According to UKXIRA's third annual report, "The findings from
studies using these assays inevitably bring into question the reassurance
offered by the Imutran/Novartis-CDC study.") Read commentary on the study in
Scientific American and the Bulletin of the World Health Organization.
Furthering fears about the PERV virus, Daniel Salomon of the Scripps Research
Institute reported the results of a study which found the first cross-species
transmission of PERV during a transplant. He recorded transmission of the PERV
virus while transplanting pig pancreatic cells into heavily immunosuppressed
diabetic mice. The PERV cells lasted for as long as two months before going
dormant. According to the report, "These results show that a concern for PERV
infection risk associated with pig islet xenotransplantation in
immunosuppressed human patient may be justified." In his interview with
FRONTLINE, Salomon notes that although the results showed PERV infection, none
of the mice became sick. The UKXIRA report concurs, noting that
evidence that the virus exists in the system does not necessarily mean it will
cause adverse effects in the recipient.
The International Society for Heart and Lung Transplantation, a nonprofit
organization whose members include doctors, scientists, ethicists and nurses,
contends that human clinical trials are still far in the future: "Current
experimental results indicate that a clinical trial of heart
xenotransplantation is premature. Experimental lung xenotransplantation is at
an extremely primitive stage of development and no consideration for a trial
can be given at the present time." The report advises that clinical
xenotransplantation trials should not be undertaken until authorities have
determined a minimal virus risk and 60% of pig organs survive in non-human
primates for a minimum of three months. However, the report concludes on a
reasonably optimistic note: "Xenotransplantation has the potential to solve the
problem of donor organ supply, and therefore research in this field should be
actively encouraged and supported."
In early 2001, UKXIRA, the regulatory body set up in 1997 to monitor
xenotransplantation in the UK, concluded that whole organ clinical trials in
humans "are clearly still some way off." However, UKXIRA has not written off
the potential prospect of xenotransplantation. According to their report,
"Although alternative therapies are in development, xenotransplantation may
still offer the prospect of a viable treatment within a worthwhile time frame."
In fact, UKXIRA faults overzealous researchers for inflated expectations about
the promise of xeno organ transplants: "Public statements by researchers, that
the initial hurdle of hyperacute rejection (HAR) had been largely overcome, led
certain quarters of the media to anticipate a move to clinical trials in the
near future."
While clinical trials for cellular xenotransplantation have been ongoing for
more than a decade, the most recent results have not given cause for much
optimism. In March 2001, Genzyme Corporation and Diacrin Inc. announced that
in a clinical trial involving patients suffering from Parkinson's disease, the
condition of those who received transplants of fetal pig cells did not improve
any more than a control group who had the surgery, but were not implanted with
cells. The study reported no detection of PERVs in the patients who had
received pig cells. The companies have said that they intend to reassess the
data before deciding whether to pursue further clinical trials.
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