Dolly's arthritis raises fear of fast ageing in clones

The discovery that Dolly the cloned sheep has arthritis has raised fears that the cloning process may cause premature ageing, calling into question the ethics of producing animals that are destined to suffer unnecessarily.

Professor Ian Wilmut, who led the scientists at the Roslin Institute near Edinburgh who cloned Dolly in 1996, said for a sheep less than six years old to develop arthritis in the rear legs was unusual and that it could be the result of her being cloned from a six-year-old ewe.

"We know already there's an unusual incidence of death of cloned animals around the time of birth. What we need to go on studying is whether diseases like arthritis, which tend to be associated with older age, occur in a normal way or whether the incidence is changed," he said.

"The fact that Dolly has arthritis at this comparatively young age suggests that there may be problems. We do not know and it's very important that we look."

Dolly became lame in her left hind leg a few weeks ago. She was examined by veterinary surgeons from the University of Edinburgh who confirmed with X-rays that she had arthritis in the hip and knee of that leg. She is being treated with anti-inflammatory drugs.

Tim King, the university vet who examined her, said: "Arthritis in sheep is quite common, but it is comparatively unusual for it to be in these joints. The elbow is the most commonly affected joint."

Dolly became the first mammal to be cloned from the cell of an adult animal. Her birth raised the prospect of babies being cloned from the skin cells of adults or children.

The history of cloning research is littered with examples of the "inefficiency" of the process, which translates into failed embryos, oversized foetuses, stillbirths and congenital abnormalities. Dolly was the result of 277 cloning attempts.

She was created from a cell taken from a ewe's udder ­ named after Dolly Parton for that reason ­ and has produced six healthy lambs of her own, conceived normally.

Dolly has led a rather spoilt life for a Scottish sheep, living in the relative luxury of a barn. More contact with people than other animals has also made her tamer than other sheep.

One of the earliest questions to be raised after Dolly's birth was her age. Should six years be added to it given that all her cells are derived from a cell of a six-year-old sheep? If so, would she and her cells and tissues age prematurely?

Professor Wilmut stressed the near-impossibility of determine from one animal whether cloning could result in premature ageing.

"This emphasises the need to monitor the health of a considerable number of clones throughout their expected life span to discover if any conditions normally associated with age develop in unusually young animals," he said.

"The only way we can discover this is by collectively producing a very large number of clones and looking to see if the incidence of arthritis and other conditions is encased in clones as distinct from animals produced by normal methods."

In a study published in May 1999, Professor Wilmut and colleagues revealed that Dolly showed signs of ageing at the level of the chromosomes, the structures in the cell that carry the genes in the form of DNA.

As animals get older the structures on the tips of the chromosomes, called telomeres, tend to get shorter because of the continual division of the cells. In Dolly's case they were markedly shorter than they should have been.

If cloned animals are ever to be used for the supply of organs for human transplants then scientists will have to address the question of whether such tissue will age prematurely within a patient's body.

Professor Wilmut played down the risk yesterday, saying the shortage of organs made animal-to-human transplants a viable proposition provided other safety fears, such as the risk of infection with animal viruses, could be addressed. "It's clear that the present technique is very inefficient but the potential benefits have to be put into the balance ... The alternative for the patient might be that they die."

A brief history of cloning

Professor John Gurdon, a Cambridge scientist, was the first person to demonstrate the possibility of cloning by extracting the nucleus from the cell of an adult animal and putting it into an unfertilised egg with its own nuclear material removed. But his experiments in the Sixties were done with frogs and nobody managed in subsequent decades to repeat the work with "higher" animals such as mice or other mammals - that is until Dolly was born on 5 July, 1996.

In the Seventies and Eighties it had been assumed the cloning of mammals from adult cells was impossible. Most work concentrated on a different technique in which embryos were split into two, four or eight genetically identical individuals. Since Dolly was born, scientists have shown that it is possible to clone cows, goats, pigs, rabbits and even endangered wild animals such as the Indian ox. One of the most important breakthroughs came in 1998 when scientists in Hawaii finally succeeded in cloning mice. Because there had been so many failed attempts it was believed there was something intrinsic to the species that prevented the process.

Nevertheless, some species have proven to be remarkably resilient to attempts at cloning. So far scientists have failed to clone cats, dogs and monkeys using the Dolly technique. This raises the possibility that there might be an insurmountable barrier to the cloning of some species, including humans, even though an American company claimed last year to have achieved limited success in the cloning of an early human embryo which died after a few days.