The discovery of arthritis in the left hind leg of Dolly the cloned sheep has dented public confidence in the viability of therapeutic animal cloning, the technology that aims to make up the shortfall in human organ donations by harvesting organs from genetically modified animals.
PPL Therapeutics, the commercial partner of the research team that cloned Dolly, saw its share price tumble 16% on the day after the announcement of Dolly's condition amid fears that the sheep is old before her time and that organs from cloned animals might have an unusually short life span.
It has been suspected since 1999 that Dolly, the world's first successfully cloned mammal, might age prematurely. In that year investigators found that her telomeres—DNA fragments that reside on the ends of chromosomes—are about 20% shorter than the average for a sheep of her age. Telomeres shorten with each cell division and are considered a marker of the ageing process.
While arthritis is not uncommon in sheep, the typical age at onset is about 10; Dolly is 5½ years old. Professor Ian Wilmut of the Roslin Institute in Edinburgh, the leader of the team that cloned Dolly, said that he was disappointed at the development but that Dolly was otherwise in good condition and had produced six healthy lambs. “There is no way of knowing if this is down to cloning or is coincidence,” he said.
The joints involved—the rear hip and knee—are abnormal locations for arthritis in sheep, who are more likely to develop inflammation in the forelegs. Several experts have noted that the pampered celebrity sheep has spent much of her life overweight. Dolly also has an unusual habit of standing on her hind legs to receive treats.
Dr David Lanza of Advanced Cell Technology in Massachusetts said it is unscientific to draw conclusions based on an individual case that could be a fluke. In this month's issue of the journal Nature Biotechnology (2002; 20:13-4) he was a joint author of a report of a survey of published studies reviewing the health of 335 cloned cattle, sheep, goats, pigs, and mice. “We found that 77% of them had no health problems, which is roughly in line with natural populations.”
Dr Lanza said that Dolly was cloned by a different method from that commonly used today: “They starved the cell to make it quiescent. We don't know what effects that might have.” Most animals cloned today come from cells that are still dividing.
Advanced Cell Technology has a herd of 24 cloned cows whose telomeres are longer than those of age matched controls, according to research published in the journal Science (2000; 288:665-9).