BOSTON — In January 2002, the Campaign for Responsible Transplantation, a US-based non-profit group, brought a lawsuit saying that the US Food and Drug Administration (FDA) is flouting the Freedom of Information Act by not releasing documents that could show whether xenograft trials have caused any adverse reactions. This month, quite unrelatedly, the FDA released guidelines that have been some three years in the making, recommending that xenotransplant recipients and their intimate contacts should not donate blood or blood plasma.
North of the border, the Canadians have just completed a public consultation into xenotransplantation (the transplant of animal cells, tissues and organs to humans). In Italy, the Vatican recently endorsed the practice. And ReNeuron, a UK-based company last week announced that, as its work with human cells has hit a snag, it intends to try treating Huntington's disease with mouse brain cells.
So, from the Vatican to the columns of the financial press and the courtrooms of the US, xenotransplantation has become one of the hottest ethical, legal and social issues of the moment. And it's an issue that is becoming more urgent as advances mean that transplant of animal tissue has the potential to become a routine treatment. Against this background, delegates at the annual meeting of the American Association for the Advancement of Science (AAAS) in Boston this week heard speakers raise some of the ethical and safety issues and describe government responses.
Perhaps the most acute worry of proponents and opponents alike is that an endogenous animal retrovirus might move into the human population — just as HIV did. As endogenous retroviruses lurk in an animal's genome, they are not easily screened for and could remain dormant for decades, according to David Cooper, president of the International Xenotransplantation Association and a surgeon at the Massachusetts General Hospital.
Speaking at the AAAS, Cooper warned of the danger of xenotourism — shopping around the world for a research venue in a country that does not have stringent regulations in place. He suggested drawing up an international agreement for a xenotransplantation regulatory framework that could, perhaps, be overseen or coordinated by the World Health Organization.
The call is timely. Although surgeons have occasionally transplanted organs from non-human primates to people, the patients have died following immunological rejection of the organ. Now immunologists are pushing the science forward but using pigs — seemingly seen by the public as more acceptable sources of donor organs than primates. Within five years it is possible that researchers will have genetically engineered a pig that does not carry the main marker that provokes an immune response by humans, and that it will be available for routine transplantation said Cooper.
If so, informed consent will be important but perhaps not just from the recipient. Society as a whole would need to accept the risk that pig endogenous retrovirus could transfer to the human population. Clearly, governments and scientists need to consult the public.
One country deep into public consultation about xenotransplantation is Canada, which last year established a number of 'citizen juries', and put them in contact with expert panels comprising a transplant surgeon, an immunologist, a bioethicist and an organ recipient. After workshops and discussions, the juries produced a joint report recommending that alternatives to xenotransplantation should continue to be sought. These could be preventative medicine, increasing numbers of organ donors or research into embryonic stem cells and therapeutic cloning as alternative sources of organs, tissues and cells.
In the meantime, the juries recommend that preclinical research on xenotransplantation should go ahead, public education should begin and stringent regulations be adopted to control eventual xenotransplantation. Edna Einsiedel, from the University of Calgary, told the AAAS that the Canadian government will decide later this year which of these recommendations to adopt.
Xenotransplantation, however, is about much more than organ donation. For example, research is under way to find xenotransplant treatments for Parkinson's disease and Huntington's disease. In February 2002 ReNeuron announced plans to start clinical trials implanting tissue from the brains of mouse fetuses into patients with Huntington's. Endogenous viruses are less of a problem with mice, said the company's chief scientist, John Sinden, because humans are genetically further removed from mice than they are from pigs.
The company is turning to xenografts because chromosomes in the human cell line they hoped to use become increasingly misaligned as the number of cell divisions increases. "We know how to solve this problem," said Sinden, "but in the meantime we have had promising results with transplants from mice to primates."
The mice are immortomice, so called because they are genetically engineered so that every cell contains a gene that permits cell division
Animal studies show that a damaged area of the brain can attract injected brain cells to the site of damage. ReNeuron's clinical trials will explore whether the same holds true in people. "We want to set up the trials in the US rather than the UK because the FDA has experience regulating xenograft trials, and as yet there are no such trials under way in the UK," explained Sinden.
Increasingly, then, xenotransplantation is becoming more feasible, for everything from major organ donation to neural regeneration. With these advances come challenges to ethicists, lawyers, policy makers and the public. To ignore this engagement with democracy is to court opposition, argued Fritz Bach from the Harvard Medical School, and he cited genetically modified crops as a warning of what can happen when scientists and governments allow their enthusiasm to run away with them instead of consulting the public.