Transplants? Pigs might fly
Saving human lives with animal organs seems less likely after a report last week revealed new genetic concerns. Could we still put pig hearts in our chests?
Monday 20 January 1997
But for thousands of people waiting for organ transplants, it may be an important fact, and could mean that the science of xenotransplants - animal-to-human transplants - will not work.
Pigs' goutlessness points up some significant differences between humans and pigs; and it highlights some of the significant gaps in our scientific knowledge in this area.
First, the background. Last week, a report into the ethical and scientific issues of xenotransplants, by a committee chaired by Professor Ian Kennedy of King's College London, approved the procedure on ethical grounds.
But they were less sure about the scientific ground. They were especially concerned about new evidence suggesting that genes coding for Aids-like viruses known as retroviruses, which have become incorporated by evolution into pigs' DNA, could pass to humans undergoing xenotransplants.
Accordingly, they recommended a delay on allowing xenotransplants until the scientific evidence is clear. The Government, still smarting from the effects of BSE and worries over Creutzfeldt-Jakob Disease (CJD), seemed happy to accept such advice.
Even the basic science of xenotransplants is complex. Each of our cells contains a "flag" on its surface which identifies it as, first, ours, and secondly, human. If you were to transplant a pig organ into a human, the blood vessels of the implanted organ would be broken down within hours by an immune reaction generated by the human system. It was tried in India last year. Both organ and patient died.
There is no denying the demand for more organs. At least 6,000 people are waiting for transplants in the UK.
Imutran, a Cambridge-based company which includes transplant specialists from Papworth Hospital, has thus developed pigs which contain human genes. This means that each of the pigs' cells carries a human "flag". In theory, at least, this should mean that you could implant one of those organs into a human being and, using the same immuno-suppressive drugs as in a human-to-human transplant, extend the patient's life. Monkeysgiven pig hearts in trials by Imutran have survived for up to 63 days, says Christopher Samler, the company's chief executive.
But that doesn't compare well with people, where a human heart or kidney transplant can give years of added life. And there are still areas in which the whole science of xenotransplants is very vague.
Retroviruses received the most publicity. These incorporate their genetic material into the host's; it is copied each time that cell reproduces. Eventually, the virus is activated, when it may kill the host - or do nothing. Examples have been found in mice, chickens - and, crucially, in pigs. Humans may have them too, lurking in DNA.
A pig retrovirus, though, might have a devastating effect on a human, and on the human population. Nothing would be predictable about its infectiousness or effects. It may not harm pigs - they've had millions of years to adapt to them. Humans have not.
Last year, Professor David Onions, of Glasgow Veterinary School, discovered such a retrovirus in pig DNA. It could multiply in human cells in laboratory culture. But, he says, "that doesn't necessarily mean that it is expressed in the whole animal." He explains: "The bulk of evidence is that these [retrovirus] genes are totally switched off in normal situations. We have the molecular sequence of the retrovirus, so we can see if it is expressed after the transplant."
He expects that the results will be available before autumn. He hopes they are negative: "If they are, it's for others to review them, but I would think you could go ahead with the transplantation trials in humans, providing they were fully informed of the risks."
But Professor Robin Weiss, of the Institute of Cancer Research, thinks that would be premature, overlooking the reality of results which are known - that new infectious diseases can pass from animals to humans, and that they can be more serious in the new form than in the old.
"What if a microbe grows in the recipient's tissue and is passed to everyone they contact? People say that's far-fetched, but it has happened. Where did HIV come from? It was unknown in the human population 30 years ago. It seems to have transferred across from monkeys. We don't know how; it was a very rare genetic event, probably, but it adapted very quickly to us.
"In Australia, there have been two deaths of people who have caught a measles-like disease from horses which have been suffering from a disease resembling distemper. Some forms of influenza come from pigs, such as the great flu epidemic of 1919." The trouble with Professor Onions' new experiment, he says, is that the check for the retrovirus's expression cannot be comprehensive. It may only need to happen once to be catastrophic.
This takes the debate into that of balancing "acceptable risk" against "possible harm" - an area where it is almost impossible to get agreement between those such as Imutran, eager to realise commercial potential of xenotransplants, and critics who want to know everything about the science behind the topic.
The whole enterprise might be overturned by some odd physiological facts about pigs. Professor Mark Walport, of the Royal Postgraduate Medical School in London, explains why pigs don't get gout. "They have an enzyme which breaks down uric acid into soluble products. Humans have lost this enzyme at some point in our evolution. That means pigs' kidneys aren't used to filtering blood containing uric acid. But we excrete 50 per cent of it through our kidneys. How would a pig's kidney cope?"
Similar unknowns may lurk in the heart, and liver transplants between species will never be a reality because of the complexity of the processes that livers perform.
There is a mountain to climb before xenotransplants to humans become reality. "I hope something will go ahead in the long run," says Professor Weiss. "I just think that we shouldn't run before we can walk." Or, indeed, trot.
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