CLONING SPECIAL REPORDolly’s mixture Clones are not the perfect replicas we thought. By Philip Cohen Dolly the sheep does not have precisely the same genetic make-up as the adult sheep from which she was cloned. A study shows that the genes in her mitochondria-the powerhouses of cells-came from another sheep involved in the experiment. The result leaves scientists wondering: exactly how similar are Dolly and her genetic twin In a cloning technique called nuclear transfer, a donor cell is fused with an egg stripped of its nuclear DNA.

For Dolly, the donor was an udder cell from an adult ewe (see Diagram). The chromosomes of an animal that develops from this union come only from the donor, so the animal is its genetic twin or clone. But it was unclear whether such animals are true clones. The vast majority of a cell’s DNA is in the nucleus, but a few genes are found in mitochondria, which are separate structures. So did Dolly’s mitochondria come from the udder cell or the egg “I thought that in a cloned animal a mixture of the two mitochondria would persist”, says Eric Schon of Columbia University in New York. To test this, he joined Dolly’s creator, Ian Wilmot of the Roslin Institute in Scotland, and others to examine the mitochondria of Dolly and nine sheep cloned from fetal cells.

The team did not find donor mitochondria in the blood, muscle, milk or placenta of the animals, which means at least 99.5 per cent of their mitochondria came from the egg (Nature Genetics, vol 23, p 90). “For all practical purposes, the egg is the only source of mitochondria”, Schon concludes. So the 37 genes in Dolly’s mitochondria are not the same as those of her donor. And because mitochondria play a crucial role in cells throughout the body, this difference might lead to significant physical differences between the two animals. “How much of a difference that makes is a great question”, says Schon. In people, it might be the difference between a star athlete and a couch potato, he says.

“This experiment just points out that we have a lot to learn”. By comparing many animals cloned by this technique, researchers will now be able to find out how much impact mitochondrial genes have. The new result also gives hope that nuclear transfer technology could be used to prevent diseases caused by faulty mitochondrial genes. Nuclear DNA from an embryo at risk of mitochondrial disease could be fused with a new egg to give it healthy mitochondria. “The ethics here are still kind of murky, but this says it is technically possible”, says Schon.

But the findings are bad news for another application of nuclear transfer technology. Some researchers hoped to use the technique to create human tissue for transplants by fusing cells from people with cow eggs and harvesting stem cells from the resulting embryonic clone (New Scientist, 11 July 1998, p 4). But if only cow mitochondria remain, there may be unforeseen problems. “This confirms what has always been a worry”, says Steven Stick of the University of Georgia in Athens. From New Scientist, 4 September 1999.