BBC News | SCI/TECH | From pig clone to human transplant

Irina Polejaeva, a scientist and project manager with PPL Therapeutics, holds one of the clones

The world's first pig clones are full of life.

"They're wonderful, they're healthy, they're bouncing around," said Dave Ayares of PPL Therapeutics Plc, the biotech company which created the animals.

The world of science had been expecting the announcement for some months. It was also aware that the project was proving especially difficult.

Any cloning programme has large numbers of failures. The technology is in its infancy, and Professor Ian Wilmut, the man who led the Dolly cloning team, warned back in August that the pig project would take some time to come to fruition.

But the first pictures of Millie, Christa, Alexis, Carrel and Dotcom show that scientists have started to solve these problems.

Nuclear transfer

"These piglets were born by caesarean section," said Dave Ayares. "We wanted to have all of our bases covered and make sure that everyone of them was going to come out healthy."

The piglets were created using a variation of the technique that was used to make Dolly. Known as nuclear transfer, it involves the movement of genetic material from an adult cell into an empty egg cell. The egg is then activated and placed in a surrogate mother to bring the developing embryo to term.

But nuclear transfer in pigs marks another leap forward in the technology. A pig's reproductive biology is inherently more complex if for no other reason than that the animal needs a minimum number of viable foetuses to maintain a pregnancy.

If this condition is not met, all will be aborted including the healthy foetuses.

PPL have now applied for a patent on the methods they used to get around these problems.

Hyperacute rejection

The successful cloning experiment is a major step in achieving the company's goal of making modified animals whose organs and cells can be successfully transplanted into humans.

However, some major obstacles need to be overcome before this can happen. The first is hyperacute rejection. The surfaces of porcine endothelial cells, which line the blood vessels of pig organs, have certain sugar 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 and cause the organ to be rejected.

PPL's strategy is to "knock out" a gene that helps build the sugar molecules so preventing the catastrophic immune response. The cells that had been modified in this way would then be cloned to produce whole animals and provide organs in bulk.

Pig viruses

There are other modification issues, such as the different blood clotting mechanisms in an animal organ, that will also need to be resolved.

But one area that continues to worry opponents of xenotransplantion concerns pig viruses. These fears were originally highlighted by a Nature paper in 1997 which reported that viruses isolated from pig kidney cells had managed to infect human tissue in the laboratory. The fear is that animal to human transplants could unleash another Aids-like health crisis.

However, subsequent research in 160 patients worldwide who have already received pig tissue as part of various treatments suggests that viral transmission will not occur easily.

"I think there are still some challenges to be overcome," said Dave Ayares.

"In the lab, we feel we've conquered most of the immunological barriers to this technology. There are still some issues associated with porcine viruses that we are keeping track on, and that could affect some of the timelines, but we're hoping to be in clinical trials by the end of year four from now."


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