Dolly the Sheep, the world’s first animal cloned from a fully-grown adult, spent quite some time in the spotlight during her life and is still making headlines today, 14 years after she passed.
Dolly was born on July 5, 1996, as a result of a technique called somatic-cell nuclear transfer (SCNT), which turns adult cells into new embryos. She was humanely euthanized on February 14, 2003, after contracting a virus that causes lung tumors in sheep.
When she was 5-years-old, Dolly developed osteoarthritis in her left knee. Her diagnosis sparked a vivid debate in the media, due to growing concerns Dolly had aged prematurely as an effect of cloning and that SCNT could be responsible for the early onset of osteoarthritis.
But the claims that Dolly’s arthritis was attributed to genetic cloning have now been disproved by a study published today (November 23) in the journal Scientific Reports.
The research, conducted by experts at the University of Nottingham and the University of Glasgow, examined Dolly’s remains, as well as the skeletons of Bonnie, her naturally conceived daughter, and of two other cloned sheep — Megan and Morag, the first two animals to be cloned from differentiated cells.
The scientists compared these bones with X-rays of naturally conceived sheep and found no signs of abnormal osteoarthritis in the cloned animals.
The team had previously conducted another study investigating the healthy aging of cloned sheep. That paper, published last year in the journal Nature Communications, focused on the Nottingham “Dollies” — Debbie, Denise, Dianna, and Daisy — four sheep derived from the cell line that gave rise to Dolly.
Aside from the Nottingham “Dollies,” which were essentially Dolly’s clones, the research also examined nine other cloned sheep. X-ray and MRI analyses showed all the 13 sheep (8- to 9-years-old) had aged normally.
Although the scientists did find evidence of osteoarthritis in two of the animals, it was consistent with what one would normally see in similarly-aged non-cloned sheep. Moreover, in one instance the disease was only mild, while the other osteoarthritis case was described as moderate.
“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,” Kevin Sinclair, professor of developmental biology at the University of Nottingham, UK, said in a press release issued by the university.
According to Sinclair, the Nottingham “Dollies,” as well as the other sheep involved in the study, were in perfect health, save for the two cases of mild and moderate osteoarthritis.
“None of these animals presented clinical symptoms of this disease and they were otherwise perfectly healthy,” Sinclair writes in an article published today in the Conversation.
“This led us to question the nature and extent of osteoarthritis in Dolly and whether or not cloning by SCNT contributed to this disease in Dolly,” he adds.
Since no one had ever thoroughly investigated Dolly’s osteoarthritis, the researchers took it upon themselves to “set the record straight,” Sinclair explains.
In the absence of X-ray records of Dolly’s osteoarthritis, the team had no other choice but to travel to Edinburgh, where Dolly’s remains are preserved at the National Museum of Scotland — along with the bones of Megan and Morag.
Here, the researchers performed detailed X-ray analyses of the four skeletons (Bonnie’s included) and uncovered that Dolly didn’t develop premature arthritis after all.
Their findings showed the nature and extent of Dolly’s osteoarthritis resembled the two cases described in the Nottingham “Dollies” research, which were, in turn, no different from those of naturally conceived sheep of the same age.
“This is important because it means it should be possible to reprogram adult cells to be used for cloning without carrying over the legacy of ageing from the original organism.”
“In short, clones may be like brand new organisms rather than copies of old ones,” Sinclair writes in his article.
The X-rays also revealed Megan had suffered a more advanced form of osteoarthritis, which was to be expected in a 13-year-old sheep — the equivalent in human terms to someone in their 90s, Sinclair points out.
However, the study found no trace of osteoarthritis in the 4-year-old Morag, Megan’s clone, who died after contracting the same virus as Dolly.
“As a result, we conclude that the original concerns that cloning had caused early-onset osteoarthritis in Dolly were unfounded,” Sandra Corr, professor of small animal orthopedic surgery at Glasgow University, clarifies in a press release.
Just like Sinclair, Corr was also involved in both studies.
[Featured Image by Paul Clements/AP Images]