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Sad ending for three little pigs

THREE pigs killed by sudden heart attacks are the latest illustration of the unexpected health problems that can afflict cloned animals.

Clones have developed many different illnesses, but the problems are unpredictable and can affect many organs. In contrast, the latest report suggests that pigs cloned using a new technique may consistently develop heart problems, says Xiangzhong “Jerry” Yang of the University of Connecticut in Storrs, who led the team that produced the piglets.

The animals had seemed completely healthy until their deaths at the age of about six months. Indeed, Yang’s team had submitted a paper, which will be published this month, describing the animals as “normal, cloned piglets” (Biology of Reproduction, vol 69, p 995). “So it was dramatic and shocking when all three died suddenly from similar problems,” says Yang.

The sow from which the three were cloned is still alive and has shown no sign of cardiovascular trouble, suggesting the animals did not inherit weak hearts from her. The animals also had separate surrogate mothers, appearing to rule out some complication during gestation. That puts suspicion for the cause of death firmly on the cloning procedure, says Yang.

Cloning involves combining a donor cell with an egg that has been stripped of its genetic material. Proteins in the egg then seem to reprogram the genes in the donor cell, allowing it to begin developing as an embryo. But instead of combining the donor and egg by fusing the two cells, or by injecting the nucleus of the donor cell into the egg, as other researchers have done, Yang’s team injected the entire donor cell into the egg.

He says this proved to be an easy and efficient way to combine the cells. And when the technique produced four live piglets, the team declared it a success. One animal died from an infection three days after birth, but that is not unusual for cloned animals. But then the remaining three animals died.

“The good news is that unlike other cloning procedures, this one seems to create the same problem again and again,” says Yang. “That gives us a chance to figure out what the problem is and solve it.”

He says his team is already analysing tissue from the clones to see if genes involved in heart development or function had been affected by the procedure.

Jim Robl, a cloning expert at the Connecticut-based biotech company Hematech, suspects that the problem may lie in the skin cells that Yang’s team used as donors.

“In our experience, some cells work beautifully as donors and some are duds no matter what procedure you use,” he says. “My guess is these are just duds.”