After Dolly comes Polly, the sheep with human genes

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The Independent Online
After Dolly, the cloned sheep, say hello to Polly - the cloned sheep with human genes.

PPL Therapeutics, the Scottish biotechnology company, stunned the world in February by announcing that it had produced a lamb from a single cell of an adult sheep. Yesterday it followed that up by announcing that five lambs have been born carrying a human gene - providing proof of a technique which could eventually make human proteins, new drugs and even replacement organs.

Using the cloning technique that produced Dolly could, in future, guarantee flocks of genetically-identical animals which would be certain to produce exactly the same product, a system PPL has dubbed "pharming".

Previously, scientists could produce a single "transgenic" animal carrying another species' genes, or they could produce cloned animals. But they had not combined the techniques.

Polly and her four near-identical sisters were not produced by the same cloning method used to breed Dolly, which was the first mammal cloned from an adult cell. The new sheep were created by fusing a cell from a foetus to an egg cell. This is a slightly easier method of cloning, as embryonic cells are "totipotent" - they naturally have the potential to grow into complete animals, rather than being inclined to develop into skin, brain or muscle cells.

This time, the PPL team genetically modified the foetal cells before cloning them. As adding genes is a hit-and-miss affair, two of the five lambs have so-called marker genes - which are easy for scientists to find and verify in the animal - two have the human gene but not the marker, and only Polly has both.

"It was what we told everybody we were going to do, but it's nice to be able to say we have done it," said Ron James, managing director of PPL. "Three of them are carrying are carrying a human gene of therapeutic value. I'm not going to say what it is."

The company already has uncloned transgenic sheep producing alpha-1-antitrypsin, a blood protein used to treat the symptoms of cystic fibrosis.

They also have been genetically engineered to produce fibrinogen, factor VII and factor IX - all blood clotting products - and activated protein C, which prevents clotting.

The five lambs, all born within the past month to different mothers, did not come from the Scottish-based company's scrapie-free herd, so they will not be used to produce any commercial products, James said. Instead, they will be monitored and scientists will try to duplicate the technique in sheep guaranteed free of the brain-wasting disease.

But Dr James said the company did not intend to produce herds of clones. "We would only ever produce a few. We would then breed naturally to get the numbers needed for production, both because natural breeding is more effective and we have time to do that while trials are going on."

PPL's first cloned sheep, Megan and Morag, were announced to the world in 1996. They have now each had lambs, showing they are normal enough to reproduce.

The five new lambs will also breed eventually, Dr James said. If their human genes carry on into the lambs, the company has a winner. "It provides a solid platform from which PPL can now develop additional medical products using sheep and, hopefully, cows and pigs," he said.

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