As time goes by, the cloning technology that brought Dolly the sheep into the world has shown that it isn't a one-hit wonder. Researchers are producing clones from fetal cells with relative ease. Others have shown they can combine cloning and genetic engineering to produce cows and sheep that produce therapeutic proteins. There seems to be no doubt that our future is a future filled with clones.
In fact, nearly every month, there's news of how cloning technology is poised to change our lives. From agriculture to medicine, from psychology to law, our special report gives you an instant update -- as well as looking at the wider issues. What molecular magic makes cloning possible? What would it be like to be an exact copy of your parent? Is anyone working towards human cloning? Could cloning be the end of humanity, and the start of something quite different?
Caution, you are entering the clone zone....
Clones are not the perfect replicas we thought.
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. 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 Wilmut 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 But if only cow mitochondria remain, there may be unforeseen problems. "This confirms what has always been a worry," says Steven Stice of the University of Georgia in Athens.
The birth of the first cloned animal created using the egg of another species is imminent.
The first animal created by putting the DNA of one species into the egg of another is due to be born in the next week. Some scientists hope the technique could be used to bring extinct animals back from the dead.
Noah is the clone of a rare wild ox, the gaur. He was created by fusing skin cells from a gaur that died in 1993 with cow eggs stripped of their nuclei - the same technique used to create Dolly the sheep.
His foster mother, a cow called Bessie, is due to give birth "in the next week or so", says Robert Lanza of Advanced Cell Technology in Massachusetts, US.
Lanza's team had predicted a birth last November, but he told New Scientist: "The published gestational period for the gaur was reported at 270-280 days. But recent data from the US suggest that in fact it's over 300 days."
Multiple pregnancies
Creating Noah wasn't easy, says Lanza. Eight foster cow mothers became pregnant with the embryo clones. But five miscarried, and two the pregnancies were terminated early, so the scientists could monitor the development of the embryos.
"Those numbers actually look very good," says Lanza. "Usually it takes 10-20 pregnancies to get one live animal - and that's from a cow embryo in a cow, not from one species to another."
The team now plan to use normal goat eggs to clone the bucardo, a Spanish mountain goat that became extinct last January.
Cells from only one dead female are available for cloning. Critics of the project pointed out that the team will not be able to clone males, and so create breeding pairs.
But Lanza believes this problem can be overcome: "Modifying the chromosome to create a male goat will require some work - but it is definitely something that will be feasible in the next couple of years."
Extinction need not be the end of the line.
An extinct species could soon be brought back from the dead. Advanced Cell Technology of Worcester, Massachusetts, plans to clone the bucardo, a species of Spanish mountain goat that died out earlier this year.
The company has shown that it can be done by cloning a wild ox called a guar using the eggs of domestic cows. When "Noah" is born next month, he will be the first animal ever created by putting the DNA of one species into the eggs of another.
Conservationists warn that the breakthrough should not be an excuse to relax efforts, though. "As a last ditch effort for conservation, it might be useful," says Gordon Reid, director of Chester Zoo. "But it would be daft to imagine that cloning alone could save species," he adds.
The Spanish mountain goats will be cloned using tissue samples from the last surviving female, which was killed in January by a falling tree. But all the animals created this way will be female. Chromosomes from closely related species would be needed to create male goats.
The lack of diversity among clones of a single animal could be another problem. "If you produce lots of animals that are identical, you get inbreeding," says Bill Holt of the Zoological Society of London. "They can't adapt to stresses, which is what evolution is about and why you need biological diversity."
To create Noah the guar, Robert Lanza and his colleagues at Advanced Cell Technology (ACT) employed the same technique used three years ago to create Dolly the sheep. They took 692 skin cells called fibroblasts from a dead guar and fused them with cow eggs stripped of their nucleus. Of the 81 that developed into embryos, 44 were implanted into cows.
Eight foster mothers became pregnant, but five miscarried. Lanza and his colleagues removed three fetuses from two other mothers, and found that they were apparently healthy.
Noah is the only remaining fetus. "Right now, all indications via ultrasound are that there are no foreseeable problems," says Philip Damiani of ACT.
There might still be problems, though. "There have been reports of high mortality in cloned cows and sheep," he says. Clones have died hours or days after delivery or had abnormally high birth weights.
However, Noah won't be pure guar. All his mitochondria--cellular organelles that contain their own DNA--will have come from the cow egg used to create him.
Damiani accepts that cloning won't solve everything. "Our objective was to prove it could be applied to endangered species," he says. He envisages "frozen zoos" holding tissue from many members of endangered species, such as the giant panda. If numbers fell dangerously low, these tissue banks could be used to increase genetic diversity.
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