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Thursday, July 30, 1998 Published at 12:32 GMT 13:32 UK


The risks of animal to human transplants

Genetically modified pigs ready for use in transplants

Dr Corin Saville: We can answer safety concerns
A liver patient could get a temporary pig's liver if a UK company gets the go-ahead to perform a pioneering transplant operation.

The biotechnology company Imutran UK is seeking permission for a transplant as the government announces guidelines on the issue of animal to human transplantation.

[ image: Scientists are at the centre of an ethical debate over transplants]
Scientists are at the centre of an ethical debate over transplants
Scientists have long experimented with the idea of using animal organs and tissues to treat seriously ill humans.

Perhaps the most famous case occurred in 1984 when a two-week-old child with a fatal heart defect was given the organ of a young baboon. Baby Fae survived for three weeks before her immune system destroyed the donor organ.

Bursting cells

Hyperacute rejection is the great obstacle to using animal tissues in human medicine. The organs of animals and humans are very different, even though, as in the case of pigs, they may look very similar.

Professor Robin Weiss: Another Aids-type disease would be a disaster
The surfaces of porcine endothelial cells, which line the blood vessels of pig organs, have molecules that their human equivalents do not.

Human antibodies coursing through the blood recognise these molecules as foreign and bind to the pig cells. The binding sets off complex interactions that eventually burst the cells.

Viewed on a laboratory bench, a pig organ such as a pig's heart will turn black within 15 minutes of coming into contact with human blood.

Genetic engineering

Imutran claims to have overcome this problem by genetically modifying the pigs so that their organs appear human to our immune system.

[ image: Imutran want a patient to be given a temporary pig's liver]
Imutran want a patient to be given a temporary pig's liver
It is now preparing an application to the government committee which regulates this area of science to be allowed to link up a human patient to a pig's liver.

The liver would remain outside the body, hopefully functioning normally, giving more time for a human organ to become available.

Dr Corin Saville, Imutran's Chief Operating Officer, says the operation may be the patient's only hope, given the shortage of donor organs.

"A dialysis machine doesn't work for the liver, dialysis machines can do the function of a kidney, but the liver is much more complicated," she says.

But even if the procedure was successful Imutran have no plans to implant the pig organ directly into the human body.

"The liver is a very complicated organ and probably a pig organ could not support all the functions that a human liver can. What one would look at next would be to look at something a little bit simpler in function such as a kidney or a heart," says Dr Saville.

Pig viruses

The Advisory Group on the Ethics of Xenotransplantation told the government in 1997 there should be no ethical obstacles to such operations. But it warned of the dangers of diseases being passed from donor animals to human patients.

These fears were highlighted by a Nature paper last year which reported that viruses isolated from pig kidney cells had managed to infect human tissue in the laboratory.

Of most concern are "porcine endogenous proviruses" or PERVs. These would be extremely difficult to breed out of donor pigs because their genetic material is mixed in with that of the pig and is therefore passed to future generations in eggs and sperm.

[ image: Professor Robin Weiss: transplants could endanger the wider population]
Professor Robin Weiss: transplants could endanger the wider population
In addition, these retroviruses originate from a family of viruses that can cause cancer.

Professor Robin Weiss, of the Institute of Cancer Research, who authored the Nature report, says any human who becomes infected could also be a danger to the wider population.

"I think if you look at the risk benefits for the individual, you'd go ahead with the transplant - I would have it. But if I thought it [the infection] might pass on to my contacts and then on to the community at large and become a new Aids epidemic, that would be a disaster."

Safety concern

About 160 patients are now in a study to test these concerns. They are individuals who have already received pig tissue for a number of conditions.

[ image: Dr Corin Saville: Problems can be overcome]
Dr Corin Saville: Problems can be overcome
Parkinson's patients have been treated with the brain cells of foetal pigs. Diabetics have also been given insulin-making cells taken from the pancreas of pigs.

How these sorts of patients react will determine the future for Imutran in the UK. The company believes it can answer the concerns of its critics.

"We have taken a great deal of care to actually breed animals under special conditions so that many of the viruses and bacteria that could be of concern are not present in the herd of animals," says Dr Saville.

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