Published online 18 February 2003 | Nature | doi:10.1038/news030217-6

News

Obituary: Dolly the sheep

Celebrity clone dies of drug overdose.

Dolly leaves a few surviving lambs.Dolly leaves a few surviving lambs.© AP.

For over six years, every bleat of the world's most famous sheep has been analysed for biological significance and hints of decrepitude.

No longer: Dolly was put down by a lethal anaesthetic injection last Friday. She was six and a half years old, and suffering from lung cancer caused by a virus.

Preliminary post-mortem results show that, apart from the cancer and her well-publicized arthritis, she was relatively normal, says Harry Griffin, assistant director of Dolly's home, the Roslin Institute in Edinburgh, UK. "There were no other signs of premature ageing."

Dolly was the first mammal to be cloned from an adult cell. Her chromosomes were taken from the udder cells of one sheep, and injected into an egg cell from another which had had its DNA removed. Dolly's nameless DNA-mother died three years before her birth.

The project showed that adult DNA, which has become fixed to do a particular job in its cell, can be reprogrammed to create an entirely new organism. This was the key breakthrough in her creation, says Griffin.

"In 20 years time, Dolly won't be remembered for the practical applications that she led to, but for opening our eyes to the idea that the cells in our bodies are much more flexible than we had thought," Griffin argues.

Not everyone accepted the uniqueness of Dolly's origins. In 1998, some researchers suggested that her DNA could have come from an adult stem cell or from a fetal cell - Dolly's mother was pregnant when the cell for the clone was taken. But DNA fingerprinting of frozen tissue cleared the argument up, and re-affirmed Dolly's status as a clone.

Dolly became an unlikely icon for the promise and threat of biotechnology. The electronics company Zanussi used her image in an advertisement for washing machines with the slogan 'Misapplicance of science'. She features in an opera by the American composer Steve Reich. And last year, Scottish anti-monarchists elected her as their preferred queen.

When her autopsy is complete, Dolly will be stuffed and exhibited in the National Museum of Scotland, Edinburgh. This is not the first Dolly relic: a jumper knitted from her wool is on show in London's Science Museum.

Ewe first

Dolly's lung complaint was the last in a series of medical problems. Last year, Ian Wilmut, the Roslin researcher who led the team that cloned her, said that had he been a hill farmer and Dolly a regular sheep, the size of the vet's bill would already have sealed her fate.

Early in life, Dolly had a weight problem. Then, in 1999, it emerged that caps at her chromosome ends called telomeres, which get shorter each time a cell divides, were 20% shorter than was normal for a sheep her age. This led to speculation that Dolly's biological age might equal that of her and her mother combined.

Early last year, Dolly was revealed to have arthritis, possibly related to her corpulence. Her celebrity may be partly to blame: "For the early part of her public career, she was fed a lot of excess food to get her to perform for the cameras," says Griffin.

“She was fed a lot of excess food to get her to perform for the cameras”

Harry Griffin
Roslin Institute

Dolly's breed, the Finn Dorset, can live to 11 or 12 years of age. Dolly's comparatively premature - if unnatural - death is typical of cloned animals. From conception onwards, clones suffer a higher mortality rate than non-clones. Studies in mice seem to show that this bad health persists throughout life.

Some seized upon Dolly's ailments as evidence that clones are invariably sickly and age prematurely. Although it can't be ruled out that her origins made her less robust than other sheep, it is not possible to make generalizations about clones' health from the fate of a single animal.

Since Dolly, other mammals - cows, rabbits, mice, cats, goats and pigs - have also been cloned. But the process of genetic reprogramming seems too complex and haphazard to control tightly, and its success rate has not improved much since Dolly's day - she was the sole surviving adult from 277 attempts.

Earlier this month, Matilda, Australia's first cloned sheep, born in 2000 and the first to be cloned outside the Roslin Institute, also died. Matilda's corpse was found in a decomposed state and was cremated. The cause of her death remains a mystery.

Dolly is thought to be survived by three or four of her six lambs. 

Roslin Institute