September 11, 2007

Pig Hearts for Humans

By Fiona MacRae

BRITISH scientists could be breeding designer pigs in just two years that would offer hope to transplant patients.

The research, led by fertility expert Professor Lord Robert Winston, eventually aims to breed genetically-modified animals with organs that would not be rejected when transplanted into desperately- ill men and women.

The animals would ultimately carry a ready supply of hearts, kidneys, livers and other organs for transplant into humans.

Lord Winston is known to millions as the presenter of TV series such as

The Human Body. Although the work, being carried out at Imperial College London, is still in the early stages, he is confident of producing the first designer pigs within two years.

This means organs grown in pigs could be used in human transplants within a decade.

The team has already created pigs with genetically-modified sperm, but it is not, at present, allowed to breed the animals.

Once this is permitted, the next stage is to genetically alter the sperm in such a way that it produces

Scientists' the body's immune system to believe that pig organs are human.

This is done by creating pigs carrying genes which alter key molecules on the surface of organs, hid- pigs with organs that won't be rejected by human immune systems.

More than 9,000 Britons are waiting for a transplant. This includes almost 100 who need a new heart, 279 waiting for lungs, more than 300 in need of a liver and almost 6,500 looking for kidneys. At least 400 are likely to die before a donor becomes available.

Co-researcher Dr Anthony Warrens said: 'There is a massive shortage of organs for transplantation.

'We are talking about a huge burden of human misery and anything that can circumvent that is potentially useful.' The research, presented at the British Association's Festival of Science in York, centres around tricking ing their origin from the human immune system. It is hoped the humanising of the organs will allow transplants to succeed.

Hearts, lungs, kidneys and other organs could also be used to test new medicines, cutting the risk of dangerous reactions when they are given to humans.

However, the biggest benefit is likely to be in transplants.

Addressing potential criticism about the use of animals in research, Lord Winston said: 'If we broadly as a society agree that it is fundamentally ethical to use large animals as a food source, then surely you could argue it is better to use them to save lives?' In early experiments on mice, the London researchers, working with experts at the California Institute of Technology, introduced dummy or test genes into mice. They then moved on to pigs and have altered the sperm of six pigs by inserting a test gene into their testicles.

But EU regulations mean that the researchers have so far been refused permission to breed from 9,000 Britons are waiting for a transplant

Scientists' century the pigs. This, combined with a 13-month delay for Home Office approval to inject the gene into the pigs, means further research may be carried out in the U.S.

So far, the alterations to the pigs' sperm have only been temporary.

But within two years, the scientists hope to have been successful in making long-lasting alterations - and in the birth of designer offspring.

Many more years of work will then focus on using genes thought to be able to trick the human immune system, and, finally, on testing the technique on people, with human transplants ten to 15 years away.

Professor Winston said: 'I am not saying we have got a cure for transplants around the corner..

The immunology is going to be very complicated but I think the ability to make a large transgenic animals [animals with foreign genetic material] is very close.' 'Had we enough investment we would be able to do that part of the work within a matter of two years.

'I think we could potentially envisage the humane breeding of these animals to maturity. Their organs could then be used as a source for human transplantation.' Transplant experts warned that while such developments were 'wonderful', they were still years from fruition. Others criticised the use of animals in research saying there is no guarantee the hearts will work properly in humans.

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THE dearth of organs available

THE dearth of organs available for transplantation has driven scientists to look for alternative sources.

Some focus on the ability of stem cells - the body's 'master cells' - to generate new tissue.

But others believe the answer lies in animal transplants.

To prevent the human body rejecting animal parts, Imperial College London researchers aim to humanise the organs by inserting genes that mask their origins. Pigs are used as their hearts are similar to human ones in shape, size and structure.

Scientists inject a cocktail of genes into the sperm-producing cells in testicles. This leads to genetically-altered sperm and ultimately to designer piglets.

In the piglets, these genes could alter molecules on the surface of organs that would otherwise lead to them being recognised as 'foreign' by the human body. Organs could later be harvested for transplant..