Dolly the Sheep siblings celebrate healthy old age
July 1996. The scientific world was stunned as news broke that the first animal had been successfully cloned from an adult cell. The product of an innovative new technique known as somatic-cell nuclear transfer (SCNT), the birth of history-making ewe Dolly the Sheep proved it was possible to clone a mammal from an adult cell, rather than an embryonic cell, and triggered a revolution in genetics and stem cell science. Although truly a revolutionary scientific step, the development of the technology has unsurprisingly raised questions about the potential effects on cloned animals, especially longevity and healthy ageing concerns.
Now, 20 years on from the epoch-making event a unique flock of cloned sheep living here at Nottingham – including four clones derived from the same cell line as Dolly – are the subject of new research into the ageing of cloned sheep. As the Nottingham Dollies – Debbie, Denise, Dianna and Daisy – celebrate reaching their 9th birthdays, we’re taking a closer look at these fascinating animals and what this new research means for the future of cloning technology.
Dolly’s siblings are born – Nottingham’s flock of clones
A pioneer in cell growth and differentiation, the late Professor Keith Campbell was instrumental in the development of the method of mammalian cloning that led to the birth of Dolly. After joining the University in 1999, Professor Campbell continued his research into reproductive biology, seeking to improve the efficiency of SCNT. Nottingham’s flock of cloned sheep originate from these studies and are the Professor’s legacy to the University.
Nottingham’s oldest clone was born in July 2006. The four Finn-Dorset clones – the Dollies – were born in July 2007, followed by eight Lleyn clones born between August 2007 and June 2008. Today Professor Kevin Sinclair, Nottingham developmental biology expert, tends to this unique flock and led the new research into these animals, the first detailed and comprehensive assessment into healthy ageing of cloned sheep.
“It is well established that prior to conception and in the early stages of pregnancy during natural or assisted reproduction subtle chemical changes can affect the human genome, leading to development and late-onset chronic diseases,” said Professor Sinclair. “SCNT requires the use of assisted reproductive procedures, yet healthy ageing of SCNT clones has never been properly investigated. There have been no detailed studies into their health. 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 five, so this was clearly a relevant area to investigate.”
A trip to the vets – sheep undergo health assessments
During 2015, Nottingham’s cloned sheep underwent a series of comprehensive assessments for diseases including obesity, hypertension and osteoarthritis – three major comorbidities which affect aged human populations.
The flock was tested for glucose tolerance and insulin sensitivity; underwent radio-telemetric assessments to check their heart rate and blood pressure; and had radiological examinations of all main joints followed by MRI scans of their knees, the joint most affected by osteoarthritis in Dolly. They also had a full musculoskeletal examination carried out by Dr Sandra Corr, Nottingham veterinary orthopaedic specialist and co-author of the research.
Once all assessments were complete, the health of the cloned sheep was compared with a group of naturally bred six-year-old sheep living under similar conditions at the University.
Happy healthy sheep – no adverse effects from cloning
Despite their advanced age (60 to 70 in human years) the cloned sheep – including the four Dollies – were showing no signs of diabetes, high blood pressure, or clinical degenerative-joint-disease. Although some of the animals were showing radiographic evidence of mild, and in Debbie’s case, moderate osteoarthritis none of the animals were lame and none required treatment for osteoarthritis. There is still a long way to go before SCNT is perfected. However, this research gives hope that cloned animals can live long and healthy lives.
“Following our detailed assessments we found that our clones, considering their age, were at the time of our research healthy,” explained Professor Sinclair. “There are several groups around the world working on SCNT efficiency, and there is reason to be optimistic that there will be significant improvements in future. These improvements will stem from a better understanding of the underlying biology, and 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, if these biotechnologies are going to be used in future, we need to continue to test their safety. Establishing if diseases or disorders exist in aged cloned offspring is an important step in this process.”
Read the full research piece online.