Human organ donor rates are declining and genetically altered pigs reared to provide organs for transplants to people offer real hope. But there are serious concerns about the dangers of passing on viruses. Do the medical benefits outweigh the risks? Robert Weiss (left), a microbiologist, and John Wallwork, a transplant surgeon, offer two perspectives on the debate.
Since its humble beginnings over 30 years ago, organ transplantation has saved or transformed the lives of almost 250,000 people worldwide. When the first heart transplants were performed in the late 1960s, few of us imagined that transplantation would become the treatment of choice for many people with organ failure. However, with the aid of medical advances and increased technical know-how, it has achieved tremendous success.
I have been involved in several major advances including the world's first heart-lung transplant in the United States and the world's first heart-lung liver transplant here in the United Kingdom ten years ago. In most cases, transplantation really does give a new lease of life to recipients who had little quality of life beforehand. This is borne out by events such as the National Transplant Games, where the level of fitness among competitors puts many of those with original organs to shame.
To those on the transplant waiting list (6,000 in the UK, 40,000 in the US), organ transplantation offers immense hope, not only to save life, but also to transform it. Human donor rates have been static or falling for several years, owing to a number of factors. One has been the welcome reduction in road deaths due to seat belt legislation. However, this means that less that half of those who need an organ transplant will receive one. Most of these patients have diseases that could not have been predicted or prevented.
As it is not possible to rely on a future increase in suitable human donor organs, new options, including xenotransplantation, are being explored to solve the shortage. Xenotransplantation as a routine alternative to human transplantation is still many years away. However, although further research is still needed, there will soon come a time when this technology is ready to be tested in humans. Many questions have been asked about the technology and the ethics, with safety a particular concern. One thing we do know is that prions, known to cause BSE, are not carried in pigs.
The safety of xenotransplantation is of paramount importance. An enormous amount of work has been, and is still being, done by Imutran, the company now leading the development of transgenic pig organs for transplantation into humans. More than two years ago, Imutran brought together a forum of independent experts to provide the company with advice and guidance on safety issues, in particular the possible risk of disease transmission from pigs to humans.
These experts have advised on the extensive research and development programme at Imutran and have helped to develop protocols for the breeding of pigs that are not contaminated with any known disease-causing organisms.
The porcine retrovirus is a virus that is impossible to exclude from the donor organ. The chromosomes of all species, including those of pigs and humans, carry retroviruses that exist naturally throughout their lives and are passed on from one generation to another, causing no harm. There is no evidence to suggest that porcine retroviruses have ever caused any problems in human beings.
Porcine retroviruses have been known about for some years. Imutran is conducting independent research in collaboration with David Onions of the veterinary school at the University of Glasgow which has shown that retroviruses in experimental situations, such as cells cultured in the laboratory, can be induced across the species barrier. This experimental work gives no indication of whether this could happen as a result of a transplant or whether, if it did happen, it would cause any disease. However, it is anticipated that research due to be published later this year may be able to provide an answer to this problem.
Imutran's safety programme continues to research these questions and the company is setting up intensive monitoring procedures for both transgenic donor animals and potential recipients to provide continual assessment of the safety of xenotransplantation.
There will come a point when the research will be able to tell us no more and it will be necessary to move towards clinical trials. At this time it will have to be agreed when and which organ is transplanted first. But this is not a decision that Imutran will take alone, and it is one that is influenced by many factors, including safety. It is important to realise that all medical procedures involve some risk. The important issue is to balance the risks against the benefits.
John Wallwork is consultant transplant surgeon, Papworth Hospital, and founder and consultant to Imutran.