Cloning did not cause Dolly the Sheep to suffer from arthritis, a new study found.
In 2013 there were reports Dolly, the first animal cloned from adult cells, was suffering from osteoarthritis at the age of five-and-half.
This led to considerable scientific concern and media debate over the possibility of early-onset, age-related diseases in cloned animals.
But radiographs of Dolly’s skeleton show no signs of abnormal osteoarthritis, experts from the universities of Nottingham and Glasgow found.
The same team showed last year that the eight-year-old Nottingham ‘Dollies’ had aged normally.
Dolly was cloned at the Roslin Institute in Midlothian in 1996 and its remains are on display at the National Museum of Scotland.
The four Nottingham ‘Dollies’ - Debbie, Denise, Dianna and Daisy - were derived from the cell line that gave rise to Dolly.
A new study involved the radiographic assessment of the skeletons of Dolly herself, Bonnie her naturally conceived daughter, and Megan and Morag, the first two animals to be cloned from differentiated cells.
Their findings published in the journal Scientific Reports showed the skeletons bear radiographic osteoarthritis similar to that observed in naturally conceived sheep and Nottingham’s healthy aged clones.
Kevin Sinclair, Professor of Developmental Biology in Nottingham’s School of Biosciences, said: “Our findings of last year appeared to be at odds with original concerns surrounding the nature and extent of osteoarthritis in Dolly - who was perceived to have aged prematurely.
“Yet no formal, comprehensive assessment of osteoarthritis in Dolly was ever undertaken.
“We therefore felt it necessary to set the record straight.”
The four Nottingham ‘Dollies’ originated from studies undertaken by Professor Keith Campbell between 2005 and 2007 which sought to improve the efficiency of somatic-cell nuclear transfer (SCNT).
The Dollies were his legacy to the University of Nottingham.
Professor Sinclair, together with Professor of Small Animal Orthopaedic Surgery, Sandra Corr, and Professor of Physiology, David Gardner, carried out the study.
They concluded the Nottingham Dollies had aged normally with no clinical signs of osteoarthritis.
They had radiographic evidence of only mild or, in one case, moderate osteoarthritis.
These results, published in the journal Nature Communications last July, were in apparent stark contrast to Dolly the Sheep’s diagnosis of early onset osteoarthritis.
However, the only formal record of osteoarthritis in the original Dolly was a brief mention in a conference abstract which reported that Dolly had osteoarthritis of the left knee.
In the absence of the original records the Nottingham team decided to take to the road and find out for themselves whether the concerns were justified.
So they tested Dolly’s bones and those of her contemporary clones, which are stored in the collections of National Museums Scotland in Edinburgh.
Professor Corr, who has since moved to Glasgow University, said: “We found that the prevalence and distribution of radiographic-osteoarthritis was similar to that observed in naturally conceived sheep, and our healthy aged cloned sheep.
“As a result we conclude that the original concerns that cloning had caused early-onset osteoarthritis in Dolly were unfounded.”
Commercially, sheep are rarely kept beyond the age of six to seven years.
Their natural life expectancy rarely extends beyond nine to 10 years.
The Nottingham Dollies, who would now be over 10 years of age, have been humanely euthanased but their legacy continues.
Professor Sinclair and his team are currently undertaking detailed molecular studies to gain a greater insight into the ageing process.