Nature has an editorial and the actual papers on-line.
Here's the editorial:
The trials of xenotransplantation
While some researchers report progress towards the goal of producing pig organs for human transplantation, others have revealed new causes for worry about the potential consequences.
The stark dilemma over the wisdom of proceeding with clinical trials of animal organ transplants in humans is crystallized in two papers that, in the interests of public debate, are being released this week by Nature in electronic form before their publication in the journal. One, by scientists at the Scottish company PPL Therapeutics, shows for the first time the successful cloning of pigs from adult somatic cells; a similar paper based on fetal cells is expected to be published in this week's issue of Science. The breakthrough opens the way to creating genetically modified animals with great precision. Knock out the -1,3-galactosyl transferase gene, for example, and the pigs would lack the galactose sugar on their cell surfaces that is the principal cause of acute rejection of pig organs in humans.
But in another paper to appear in the same issue, Daniel Salomon from the Scripps Research Institute, and colleagues elsewhere, show that porcine endogenous retroviruses (PERV) can infect human cells in culture. Moreover, they go on to demonstrate that transplanting pig pancreatic islets into immunosuppressed mice leads to widespread infection with PERV.
Guidelines issued by the US Food and Drug Administration (FDA) in 1996 would have allowed weakly regulated xenotransplant trials. The agency has now toughened the guidelines considerably, pulling trials under federal (rather than local) control, for example, and placing a de facto ban on transplants from non-human primates (see Nature 405, 606–607; 2000).
Contagious viruses are a major worry in xenotransplantation, as they carry the risk of creating man-made pandemics. But unlike HIV and other retroviruses, PERV seem unlikely to jump from the recipient to others. And the work by Salomon et al. provides an animal model for basic research on viral transmission in xenotransplantation. This is likely to be followed by experiments with transplants into immunosuppressed monkeys.
Salomon points out that the techniques for studying PERV infection developed in the mouse model would also allow better monitoring for such infection in clinical trials. The FDA, the world's foremost regulatory health authority, is responsible for ensuring that trials are carried out safely. It is disconcerting that even this agency was, just four years ago, willing to endorse xenotransplantation trials of pig and other animal parts with little supervision. Pushing ahead with even limited trials could pave the way for widespread trials, perhaps in countries lacking authorities as competent as the FDA.
Xenotransplantation falls into the category of hazards where, although the risk is probably low — and the benefit to individuals undoubtedly substantial — the public consequences could be catastrophic. Indeed, Salomon's research also shows how little is known about PERV, while more dangerous viruses may also be present in pigs but remain undetected. The pathogenicity of animal viruses can also change unpredictably when they jump the species barrier. But there is virtually no research aimed at detecting and understanding such risks.
The FDA now requires trial sponsors to carry out a battery of tests, and all patients are monitored for infection. But more independent research on potential viral risks is needed. In risk assessment, absence of evidence is too often read as evidence of absence. What might we learn in four years that we do not know now? That is the case for a moratorium on clinical trials.
Here are the actual papers:
Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice
nature.com
(They showed reproduction of the PERV virus in SCID mice as well as in isolated human cells.)
Cloned pigs produced by nuclear transfer from adult somatic cells
nature.com
Peter |
