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Adult pig clones in sudden death shock

(Saturday, Aug. 30, 2003 -- CropChoice news) -- Helen Pearson, Nature, 08/27/03: New fears have been raised about the health of cloned animals after three cloned adult pigs dropped dead from heart attacks.

The pigs were created using a variation on the technique that made Dolly the sheep. A Taiwan-based team rammed a whole adult cell into a fertilized egg that was emptied of its own genetic material1.

Of four piglets born, one died within days. The remaining three have now collapsed and expired of heart failure at less than six months of age, team leader Jerry Yang of the University of Connecticut in Storrs revealed this week. "It was totally shocking," says Yang. He has dubbed the fatalities 'adult clone sudden death syndrome'.

The pigs' demise is a stark reminder that cloned animals are far from normal. Many fall ill or die just after birth Dolly herself passed away at the relatively tender age of 6. Their problems probably arise because the adult DNA is not properly reprogrammed to drive embryo growth. Yang is now hunting for the genes responsible, perhaps those that govern the heart's function.

The deaths call into question the idea of transplanting hearts or livers from cloned pigs into humans. Researchers have already genetically engineered partly humanized pig cells and then cloned them to make whole pigs, whose organs might avoid rejection by human recipients. "It may raise concerns," says Yang.

But Randall Prather, who has cloned pigs at the University of Missouri-Columbia, says that these dangers can be sidestepped by breeding from the first-generation clones. Cell reprogramming is completed when cloned animals make sperm and eggs, so their offspring should be normal. "You've wiped out the problems," Prather says.

Whole in one

Yang remains confident that his new whole-cell injection technique might one day prove a boon to biologists. It avoids the potentially damaging step in standard cloning where DNA is sucked out of the donor cell before it is inserted into an egg. It might also use fewer eggs than the current alternative technique, in which egg and adult cell are fused with a flash of electricity.

Whole-cell injection may ultimately have a higher success rate. Nearly 40% of Yang's clones survived the first few days of growth - two or three times more than the typical rates achieved with other methods.

Researchers had thought that such an approach would fail because the cell's coat would prevent the egg's enzymes from working their way in to its DNA. But the method may in fact encounter no such stumbling block. "Technically, it may be worthwhile," concedes Konrad Hochedlinger, who clones animals at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts.

Clones' ill health means that most scientists rule out reproductive cloning of humans as inherently dangerous. But they say that therapeutic cloning to grow replacement human tissues or organs should be safe. Here they extract cells from early human embryos, which can be selected or treated to ensure that they are healthy.

References

# Lee, J-W. et al. Production of cloned pigs by whole-cell microinjection. Biology of Reproduction, published online, doi:10.1095/biolreprod.103.015917 (2003).

Source: http://www.nature.com/nsu/030825/030825-2.html