Dolly the cloned sheep stunned the world in 1996, but her early death raised doubts about cloning. Now the progress of her four genetic "siblings" have restored faith in the science. Photo/Toni Barros
The 9th birthday of four sheep who spend their days largely minding their own business in a quiet Nottinghamshire field might seem an unusual cause for celebration.
But because they are related to the most famous sheep in history, the anniversary is being hailed as a scientific milestone.
Dolly, the first mammal to be successfully cloned, stunned the world when she was born in 1996, but her subsequent ill health, premature ageing and death at the age of 6 and a half, raised doubts about the safety of the process that created her.
Yesterday, however, Dolly's genetic "siblings" - Debbie, Denise, Diana and Daisy - have been declared fit and well for their age, indicating that large cloned animals age normally.
The clean bill of health restores confidence in the process of reprogramming mammalian cells, according to biologists, and has positive implications for fields of human healthcare, such as the development of stem cell therapies.
The four sheep, dubbed the Nottingham Dollies, were cloned from the same line of cells as Dolly and are part of a flock of 13 being monitored by scientists at the University of Nottingham, which released a YouTube clip detailing their progress.
The animals underwent detailed musculoskeletal investigations, assessments of glucose tolerance, insulin sensitivity and blood pressure.
The also compared X-rays and MRI scans of the clones with images taken from healthy control animals.
Professor Kevin Sinclair, who led the research, said: "One of the concerns in the early days was that cloned offspring were ageing prematurely and Dolly was diagnosed with osteoarthritis at the age of around 5, so clearly this was a relevant area to investigate.
"We found that our clones, considering their age, were at the time of our research healthy.
"This shows that there are cells that can undergo complete reprogramming and be completely normal.
"So whether you're aiming for stem cells, or whether you're aiming for cloned offspring, there is a target you can aim for, and that target is normality."
The method used to create Dolly and her siblings, called somatic cell nuclear transfer (SCNT), involves transferring an adult cell nucleus containing an animal's signature DNA to an unfertilised donor egg whose own nucleus has been removed.
Electrical stimulus causes the egg to start dividing and form an embryo that is genetically identical to the donor of the adult cell.
In 1996, Dolly was the only lamb to survive to adulthood from 277 attempts by Professor Sir Ian Wilmut at the Roslin Institute in Edinburgh.
The Nottingham flock came about as a result of studies that were trying to improve the efficiency of SCNT.
Part of the cloning process involved reprogramming cells so that they became blank slates with limitless potential, which helped advance work in stem-cell science following Dolly's birth.
Professor Sinclair said several groups around the world were working to increase the success rate of SCNT, and there was reason to be optimistic.
"These improvements will stem from a bitter understanding of the underlying biology to the earliest stages of mammalian development," he said.
"In turn this could lead to the realistic prospect of using SCNT to generate stem cells for therapeutic purposes in humans as well as generating transgenic animals that are healthy, fertile and productive."
However, the biologist cautioned that the safety of these biotechnologies would have to be continuously tested as they go on to be used in the future.