Dolly clones have aged like other sheep, study says

Next genration seem to be healthy in their old age.

Dolly the Sheep started her life in a test tube in 1996 and died just six years later. When she was only a year old, there was evidence that she might have been physically older. At 5, she was diagnosed with osteoarthritis. And at 6, a CT scan revealed tumors growing in her lungs, likely the result of an incurable infectious disease.

Rather than let Dolly suffer, the vets put her to rest.

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 long-standing question about whether cloned animals like Dolly age prematurely.

In a study published this week 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 are not monsters,” Pasqualino Loi, a scientist who studies cloning at the University of Terama in Italy and was not involved in the research, wrote in an email.

Dolly’s birth, 20 years ago this month, blew the world away. Scientists had taken a single adult cell from a sheep’s udder, implanted it into an egg cell that had been stripped of its own DNA, and successfully created a living, breathing animal almost genetically identical to its donor.

But Dolly’s health challenges, along with other cases in which cloned animals developed symptoms of diabetes or obesity, made it harder to grapple with the ethical and safety controversies of the procedure. Not only did many countries, including Canada and Australia, ban reproductive cloning in animals, but the United Nations banned all kinds of cloning in humans in 2005. Last year the European Union made importing food from cloned animals or their offspring illegal.

The inefficiencies of cloning have fed into these prohibitions. Few embryos make it to the fetus stage, fewer fetuses develop past the age of 1 or 2, and even fewer become adults. Many blamed cloning when mature animals appeared to show signs of early aging.

Now, based on results of this new study, researchers have confirmed what most scientists believed years ago: Cloning does not lead to premature aging.

Sinclair and his colleagues started studying aging in these 13 sheep, which were originally intended for studies on efficiency and artificial reproduction, after Keith Campbell, who was in charge of Dolly’s relatives, died in 2012.

The cloned sheep were between the ages of 7 and 9, about 60 in human years.

To detect subtle signs of aging, the scientists conducted a battery of tests to check for symptoms of heart disease, Type 2 diabetes and osteoarthritis.

“All we wanted to establish was: Are they normal?” Sinclair said.

For the most part, they were. Glucose tolerance and insulin resistance tests revealed nothing abnormal, and their blood pressure was fine. The sheep were flexible and reactive in musculoskeletal tests, but some did show early signs of osteoarthritis. Debbie’s X-ray indicated her arthritis was slightly more advanced, but Sinclair said it was nothing out of the ordinary.

Similar evidence disproving premature aging in cloned animals was previously found in mice and cows, said Jose Cibelli, who studies reproductive cloning at Michigan State University. The study of the sheep confirms that once cloned animals survive the first few years of life, they won’t die any sooner than other animals.

“It really changes the perception of how people look at cloning,” said Charles Long, a scientist who studies artificial reproduction at Texas A&M University and was not involved in the study.

Many scientists hope that changes in perception will lead to advances in reproductive technology that will enable us to provide food for a growing global population, save endangered species and develop advanced therapies. Scientists involved in and separate from the study don’t think it will mean we might clone humans anytime soon, nor do they condone it, but they can’t say someone won’t try. But is cloning safe? “If they could speak, they would say, ‘Yes; it’s perfectly safe,’” said Sinclair. “They’re old ladies now, and for them, their whole process worked perfectly. But there are others who struggled to adapt after birth.”

Cloning won’t be truly safe until embryos survive at rates similar to those produced through natural conception or in vitro fertilization. Even then, welfare and ethical concerns will remain.

With recent advances, some scientists think safe and efficient cloning procedures will emerge in five to 10 years.

“Cloning is entering a new era,” said Loi.

Dolly’s relatives are expected to live for about another year. Scientists will then search for other abnormalities that may be lurking undetected. Meanwhile, Debbie is taking ibuprofen with her breakfast cereal.

JEFF J MITCHELL / GETTY IMAGES A staff member views Dolly the Sheep during the opening of a major new exhibit at the National Museum of Scotland on July 5 in Edinburgh. Dolly, the first cloned sheep, did not age well and eventually was put to rest.