Dolly the sheep’s death not related to cloning: study

Dolly the sheep, the world's first clone of an adult animal, died in middle age. But a new study makes the case that the extraordinary circumstances of her birth did not play a role in her untimely death.

After examining more than a dozen cloned sheep old enough to be considered elderly - including four clones of the same ewe as Dolly - researchers concluded that they weren't growing old any faster than sheep born through more conventional means. The results were published on Tuesday in the journal Nature Communications.

''There was no evidence to suggest that these animals were ageing abnormally or prematurely,'' study leader Kevin Sinclair, a developmental biologist at the University of Nottingham, said in a video. ''They were aging in a perfect, healthy manner.''

Sinclair and his colleagues aren't interested in making carbon copies of sheep or other livestock. But they do want to know whether the technology used to create clones is safe, since they could be used to develop treatments for a variety of medical conditions.

Clones like Dolly are made by taking an egg, removing its nuclear DNA - the part that contains the vast majority of an animal's genes - and substituting the DNA from another animal. If all goes well, that egg will mature into an embryo that is a genetic twin of its DNA donor.

Scientists could use that embryo to create stem cells for regenerative medicine. Or, as in the case of the 13 sheep in this study, they could be transferred to a uterus and carried until birth.

Cloning technology has improved in the 20 years since Dolly's birth, but it's still pretty inefficient, Sinclair said. Cloned embryos often fail to implant in a uterus. Even if they do, they often fail to develop to term. If there is a live birth, the odds of death in the first few days or weeks are higher than for other animals.

But what happens to the cloned animals that survive all of this?

''It's never been properly investigated,'' Sinclair said. ''There've been no detailed studies in terms of their health.''

To change that, the research team focused on three crucial aspects of aging: cardiovascular function, type 2 diabetes and osteoarthritis.

Their primary subjects were 13 cloned sheep that were between 7 and 9 years old. (The ''natural life span'' of a sheep is usually less than 10 years, the study authors wrote.) Four of the clones were Debbie, Denise, Dianna and Daisy, each of which is a genetic twin of Dolly but born a few years after her death.

The sheep in the control group were also conceived with a little help from science. These animals were produced via embryo transfer - as with cloning and in vitro fertilization - but the embryos were not clones. The control sheep were somewhat younger, only 6 years old.

To assess heart function, the researchers measured the average blood pressure in the sheep's arteries during one cardiac cycle. The clones had readings between 102 and 111 millimeters of mercury, compared with 114 mm Hg for the controls. When given increasingly high doses of a hormone that narrowed their blood vessels, all of the sheep saw their blood pressure rise by a similar amount, according to the study.

The conventional sheep had a lower resting heart rate - 76 beats per minute, compared with 91 to 92 for the clones - but the clones were still within the normal range for sheep of their age, the researchers noted.

To test whether the animals were susceptible to diabetes, the researchers allowed them to gorge on hay for 28 weeks. Most of them - clones and controls - gained enough body fat to score a 4 on a scale where 1 means ''thin'' and 5 means ''obese.''

All of the sheep had fasting blood sugar levels within the normal range. The clones and the controls got similar scores for insulin sensitivity, but the clones fared worse in a glucose challenge. After the four Dolly-like clones were put on a diet, their insulin sensitivity improved. The researchers took this as a sign that body fat - not age - was responsible for their diabetic tendencies.

Finally, the researchers assessed the animals' degree of degenerative joint disease. This was a topic of particular concern because Dolly was treated for osteoarthritis starting around the age of 5.

Two of the 13 clones were judged to have an abnormal gait, though the differences were minor. All the cloned sheep had mild osteoarthritis in the hips, and most had it in their knees. But when the joints were examined by hand, ''no animal showed obvious signs of pain,'' the researchers wrote.

The sheep were put in MRI machines so the researchers could assess their hip joints in greater detail. Only one of the clones had any problems that were judged to be ''moderate to severe,'' according to the study

''Overall the results are suggesting that these animals are remarkably healthy,'' Sinclair said.