Pig donor 'breakthrough' claimed

The four cloned pigs in Virginia which could herald a scientific breakthrough

LONDON, England -- The prospect of pigs providing humans with an endless supply of transplant organs looks closer with a first claimed by the company who cloned Dolly the sheep.

PPL Therapeutics, the Scottish firm that in 1997 helped make Dolly, the first mammal cloned from adult cells, announced that four healthy piglets had been born without the two genes that make human beings reject pig tissue.

What the company calls "double knockout" pigs were born at the company's U.S. subsidiary in Blacksburg, Virginia.

PPL Therapeutics says the breakthrough could end a worldwide shortage in transplant organs.

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Pigs are considered a possible good source for organs, as they are readily available, easily bred and are roughly the same size as people. Heart valves from pigs, which just contain cartilage, are already very widely used in people.

The company said in a statement: "Four healthy piglets were born at PPL Therapeutics Inc, USA on 25 July, 2002 and continue to do well. A fifth piglet died shortly after birth of unknown causes.

"The gene that has been double 'knocked-out' in these pigs is responsible for making an enzyme that adds a sugar to the surface of pig cells which is recognised by the human immune system as foreign.

"This pig sugar triggers an immune response in the human patient, leading to hyperacute rejection of the transplanted organ or cell within minutes.

"The ability to delete or 'knock-out' both copies of the gene, therefore, provides a vital step in producing pigs with organs and cells which can be used in humans. Because both copies of the gene have been inactivated, tissues from these pigs have been shown to be completely devoid of the pig sugar that cause the hyperacute rejection to take place."

"This advance brings us closer to the promise of a potential solution to the world-wide shortage of organs and cells for transplantation." said PPL's chief operating officer, David Ayares.

In the United States, Britain and other countries, organ failure is the major cause of death and disability and -- except for the kidney -- the only treatment is transplantation.

Because of the shortage of human organs, a fraction of people who need transplants get them, and many die while waiting.

In the U.S. more than 80,000 people are waiting for an organ transplant. Last year, about 24,000 transplants were performed and 6,000 people died waiting for their operations.

"Developing another source of organs would have a profound impact on society, so from a practical perspective this is a very important advance," Dr. Jeffrey L. Platt, head of transplantation biology at the Mayo Clinic in Rochester, Minnesota, told The Associated Press.

"And even if it doesn't solve the problem, it will answer very important questions in the field."

In January, PPL Therapeutics and competitor Immerge BioTherapeutics both said they had created pigs that lacked one of the two copies of the critical gene, called the GGTA1 gene. That step proved that the science was possible.

"People believe that the difference between the human heart, which doesn't have the sugar, and the pig's heart, which does, is an evolutionary process," said Geoff Cook, chief executive officer of PPL Therapeutics

Cook predicted that studies testing pig organs in humans could start within two years -- two years sooner than predicted earlier this year before the "double knockout" experiment.

The next step is to transplant pig organs into other animals, such as baboons, to see whether the organs can survive in the primates for at least three months.

Robin Weiss, a virologist at University College in London, told AP he was sceptical that the double knockout brings cross-breed transplants, or xenotransplantation, closer for humans.

In 1997 he and his colleagues documented two infectious strains of a porcine retrovirus that could infect human cells in the lab.

"It will take a decade or more to knock them out and there is no diminution of the potential risk of infection. On the contrary ... genetic changes such as knockout that help to overcome hyperacute rejection actually might increase the risk of infectivity of pig viruses for humans," Weiss said.

Platt said eliminating the sugar from the pig organs might make infection more likely, but also might make it less likely.

"It could go either way and that's because sugars can be used to help the immune system clear viruses, but sugars can also be used by viruses to enter cells, so it's possible that these pigs can be made less likely to be infected by viruses."

In any case, it is not clear whether the virus Weiss referred to is important for humans, Platt said.

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