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A superstar exits the stage
By Nancy Touchette

Dolly the sheep is gone but not forgotten. The public will remember her as the first cloned mammal, and scientists will explore questions raised by her birth, such as how does a genome control the fate of a cell?

Dolly and her first born lamb Bonnie.

"Dolly was a kind of heroine, a superstar, really," says Minoru Ko, of the National Institute on Aging in Baltimore, who studies the genomes of cloned mice. "Her birth changed the whole field of reproductive biology and had a huge impact on basic biology."

On February 14th, the six-year-old sheep was put to sleep at the Roslin Institute in Edinburgh, Scotland, where she was created. Dolly had recently developed a cough that did not respond to treatment. Tests revealed that she had a fatal lung tumor caused by a virus, or sheep pulmonary adenomatosis, the Institute said.

The disease is common in older sheep and had nothing to do with the fact that she was a clone, according to Harry Griffin, the Institute's acting director.

"We hope Dolly will be remembered as the most dramatic evidence that cells in our body are much more versatile than we previously thought," says Griffin. "We thought cells were fixed in their ways, once they matured. Dolly demonstrated that this is not the case."

To clone Dolly, the nucleus of a sheep egg was replaced with the nucleus from an udder cell that came from a deceased sheep, a process called somatic cell transfer.

Cloning Dolly took nearly 300 attempts and the process remains an art. At best, only about two percent of somatic cell transfers result in live births. And genetic clones seem to develop health problems such as obesity, frequent bouts of pneumonia, and liver failure.

The problems associated with cloned animals arise from the "reprogramming" of the genome, according to Ko. To modify an adult nucleus into one that can develop anew, the whole genome must be reprogrammed. In a sense, the slate is wiped clean.

Studies of cloned mice by Ko's team and by Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, suggest that many genes are improperly regulated in cloned embryos and this may contribute to health problems.

Whether Dolly's death was caused by irregularities in her genome is not known. Griffin points out that Dolly did not live the life of a normal sheep. She was kept inside for security reasons, and lived much longer than is typical.

Shy Dolly.

Most sheep are killed and eaten in their first year of life, and those retained for breeding are rarely kept beyond the age of six, so little is known about health problems in older animals.

"Dolly's death probably means more to society than to the scientific community," says Ko. "It's not possible to know whether her health was compromised because she was a clone. We would need to study many more clones systematically before drawing those sorts of conclusions."

See related GNN articles
»Cloned Mice Have Genomic Flaws
»More evidence of genomic problems in cloned mice

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