Does this mean a beginning of a new era in cloning? Scientists find clones developed along with Dolly, healthy
When Dolly the sheep was born 20 years ago, The University of Edinburgh’s famous girl was the first mammal created by way of true cloning. Her embryo was created not using the sex or stem cells of another sheep, but from mature cells taken straight from the donor’s mammary tissue.
Then, at age 5 — middle age, for a sheep living the good life in a research facility — Dolly developed osteoarthritis. She died at the age of 6, riddled with joint and lung problems reminiscent of old age. When researchers examined the length of her telomeres — structures at the end of DNA that shorten with each replication, creating cells with shorter telomeres as the body ages — they found that her biological age surpassed her chronological age; her cells looked as if they’d been ticking for longer than she’d been alive.
Poor Dolly never stood a chance. Or did she?
Meet Daisy, Diana, Debbie and Denise. “They’re old ladies. They’re very healthy for their age,” said Kevin Sinclair, a developmental biologist who, with his colleagues at the University of
Nottingham in Britain, has answered a longstanding question about whether cloned animals like Dolly age prematurely.In a study published in Nature Communications, the scientists tested these four sheep, created from the same cell line as Dolly, and nine other cloned sheep, finding that, contrary to popular belief, cloned animals appear to age normally.
They were subjected to a battery of tests of age-related diseases, such as obesity, hypertension, and osteoarthritis. Under anesthetic, they were given X-rays and MRI scans, radio-telemetric assessments of heart rate and blood pressure, and a full musculoskeletal examination, as well as tests for glucose tolerance and insulin sensitivity. The results were then compared to a control group of naturally-bred six-year-old sheep.
“Healthy aging of SCNT clones has never been properly investigated, says Sinclair. “There have been no detailed studies of their health. One of the concerns in the early days was that cloned offspring were aging prematurely and Dolly was diagnosed with osteoarthritis at the age of around five, so clearly this was a relevant area to investigate. Following our detailed assessments of glucose tolerance, insulin sensitivity, blood pressure and musculoskeletal investigations we found that our clones, considering their age, were at the time of our research healthy.”
According to the team, none of the sheep showed indications of diabetes, high blood pressure, or clinical degenerative-joint disease. Only Debbie showed signs of moderate osteoarthritis, but did not require treatment. The upshot is that cloned animals can live long and healthy lives.
SCNT involves removing the DNA-containing nucleus from a cell other than an egg or sperm, a skin cell, for example and implanting it into an unfertilized egg from which the nucleus had been removed.
Sinclair says that because SCNT involves the use of the same techniques used in fertility treatments, more work is needed on the long-term effects of cloning.
“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,” says Sinclair. “Given that SCNT requires the use of assisted reproductive procedures it is important to establish if similar diseases or disorders exist in apparently healthy aged cloned offspring.”
Dolly made history as the first animal to be cloned from an adult cell using the SCNT technique. She was cloned by Sir Ian Wilmut, Keith Campbell and colleagues at the Roslin Institute, part of the University of Edinburgh in Scotland.
Dolly was born on July 5, 1996 and died from a progressive lung disease five months before her seventh birthday.
As for the sheep clones in Sinclair’s care, he says “they will continue to lead normal sheep lives.” Once they reach the ripe old age of about 10, they’ll be euthanized and the researchers will do a detailed postmortem analysis of their bodies.
