The world's most famous case of early onset arthritis in a non-human may never have existed. Dolly the sheep, the first animal cloned from an adult cell, has long been thought to have had osteoarthritis at an early age. This has been used as evidence for the dangers of cloning. A re-examination of her skeleton has thrown this claim into question.
Dolly's cloning in 1996 was among the biggest scientific stories of the 1990s, opening up a great array of scientific and ethical debates. In 2003, however, the happy pictures of Dolly gamboling in fields or caring for her daughters were replaced with something darker. At the age of 6 – very young for a sheep – Dolly was euthanized to save her from a painful death from lung disease.
Fears that this indicated something fundamentally unhealthy about cloning mammals were compounded by the reports she suffered from early onset osteoporosis. One premature disease might be a misfortune, but two looked like a warning. However, other cloned sheep, including some from the same cell line as Dolly, have lived healthy and full sheepy lives, leading Professor Kevin Sinclair, of the University of Nottingham, UK, to question if Dolly really was that sick.
In Scientific Reports, Sinclair and colleagues describe X-raying the skeletons of Dolly and her daughter Bonnie. For good measure, Sinclair and co-authors also examined Megan and Morag, the first two mammals cloned from differentiated cells, unlike the undifferentiated mammary cell from which Dolly sprang. Bonnie and Megan both showed osteoarthritis in many of their joints, but this is typical of sheep at 11 and 13, the ages these two reached. Dolly, on the other hand, had no signs of arthritis in the majority of her joints. Those joints that were arthritic were judged by three independent veterinary orthopedic specialists to be mildly to moderately affected.
Sinclair's suspicions were aroused by his previous work finding little sign of early onset arthritis in 13 cloned sheep. “No formal, comprehensive assessment of osteoarthritis in Dolly was ever undertaken,” Sinclair said in a statement. “We therefore felt it necessary to set the record straight."
There seems little doubt Dolly was lame in her left hind leg, but this could have been caused by many things, not all of them genetic. The belief she suffered unusually early arthritis appears to come from a single mention in the abstract of a conference paper, something that became accepted without investigation. None of Dolly's original radiographic records were preserved, but luckily for Sinclair's team, her skeleton is still in the National Museum of Scotland. And cloning, at least for sheep, may be safer than we thought.