Sunday, September 07, 2008

Britain squanders pioneer work on organ transplants

Scientists have been exploring the use of animal organs, mainly from pigs, as a way of ending organ shortages. The procedure is called xenografts or xenotransplantation. For an overview and discussion of the pros and cons see the Wikipedia article.

From Times Online:

By Robert Winston

A new patient is put on a waiting list for a transplant somewhere in the developed world every 15 minutes. Only a few of these people will get a transplant, the rest will die with increasing incapacity. Worse still, far more patients needing transplantation will not even get on a waiting list.

People waiting with crippling heart disease cannot walk more than a few paces, or sleep properly because of severe breathlessness. Patients with kidney and liver failure are slow-poisoned, alleviated to some extent with artificial blood-cleaning machines. Most of them have a hugely restricted life.

People needing a new heart or liver are waiting for someone else to die - usually a violent death in a traffic accident. So my team at Hammersmith hospital in west London has been trying to modify pigs so their organs might save the lives of humans.

Why consider animal organs at all? Well, human-made devices such as mechanical hearts never work as well as biologically produced organs. And although huge publicity has been given to the idea of growing organs - culturing hearts or livers possibly from stem cells - this technology is still very primitive and is very unlikely to come to fruition in the next 20 or 30 years, if ever.

Pigs’ organs are the right size for human transplantation, and they work similarly to human organs. Of course this raises a moral problem, but it is much more ethical to use a pig to save a human life than to use it for relatively unnecessary meat eating.

And pigs for transplantation are kept in scrupulously humane circumstances and killed under proper anaesthesia.

The key challenge is introducing the right genes into pigs. These genes do not change the pig - it feels and looks entirely normal - but the genes change proteins on the surface of their organs so they will not be recognised as “foreign” by the human immune system after transplantation. Patients will still need to take drugs to prevent rejection, but the graft should be tolerated.

One problem is that it is hard to get new genes into large animals. The technology works in mice, but is still inefficient and requires hundreds of mouse embryos to get the occasional successful “transgenic” - an animal carrying the genes needed. Obtaining embryos in large animals is excessively difficult and sometimes the surgery may not be as humane.

My colleague Carol Readhead, a scientist from California, and I hit on a drunken idea over a bottle of good burgundy a few years ago. Pigs’ embryos are difficult to harvest, but pigs produce copious semen. This is not something you may want to know over breakfast, but the average male pig produces a large cupful with each ejaculation - carrying perhaps 1 billion sperm.

Our drunken idea was to introduce the genes we needed into the sperm. Whenever the pig mated, the egg would fertilise naturally and any embryo would carry the genes. A simple injection of our gene product into the testicle of a piglet is all that is needed. As the male pig grows, it will continue to produce many modified sperm for years. And this single injection, under local or general anaesthetic, is painless.

One problem with animal organ transplants that has raised public concern is that animals such as pigs harbour viruses that could infect any human organ recipient. Some of these viruses might cause terrible diseases such as cancer. And another possibility is that viruses from pigs, once established in humans, might go on to infect many members of the population.

However, there are likely to be several strategies to minimise the risk. First, the evidence suggesting it may be possible to breed virus-free pigs. Similarly vaccines might be developed that could prevent any viruses taking hold in humans. And we also have evidence that pig viruses have not necessarily caused problems when pig tissues have been transplanted into other species. Pig valves are widely used in heart surgery without ill effects.

This technology is important for human medicine. As a bonus, it carries huge commercial opportunities if we develop and export it around the world. However, it has been difficult to pursue the research in the UK. Getting a Home Office licence to experiment with just six pigs took nearly two years with successive delays, even though the pigs do not suffer.

And having got pigs producing transgenic sperm, we were informed we could not mate them because of some Department for Environment, Food and Rural Affairs and European Union regulations. We are not even permitted to do postmortems on the pigs, so we cannot prove we have been successful. Years of work, and investment, have been mostly wasted. And we have had to say a sad goodbye to our committed scientific team.

In the present commercial climate it is difficult to get further UK funding, so the experiment will move to the States. Our US friends will benefit from our technology and yet another British innovation will be jeopardised; the income we might have generated for Britain will be lost. If we wish to ensure that we are in the forefront to alleviate suffering, we must avoid needless bureaucracy when developing important technological advances.

Lord Winston is a leading fertility consultant and broadcaster.

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