At age 3, Dolly the sheep's DNA shows signs of premature aging, raising ethical, medical concerns about cloning

Transplant News, June 14, 1999

Although Dolly the sheep is only 3, her genes show signs of premature aging--a not all together surprising discovery, considering she was cloned from a 6-year-old animal.

Dolly is a healthy yew and has delivered 4 lambs in the last couple of years. But the DNA in her cells exhibits the kind of wear typically found in an older animal. Geneticists said the finding, published in the May 24th issue of the journal Nature, provides further evidence that cloning, at least for now, has its practical limits. And it adds to the ethical and medical concerns about the consequences of human cloning.

"Only years from now, it would be a relevant question to ask if a cloned child would have a shorter lifespan even though it appears to be healthy and normal," said Marie DeBernadino, PhD, a biologist at the Allegheny University of the Health Sciences in Philadelphia, Pa.

In 1996, Dolly became the first large animal to be cloned from genetic material extracted from an adult somatic cell. Scientists removed the DNA from a ewe's egg and inserted DNA removed from another ewe's udder. The bioengineered embryo then was implanted in the first ewe's womb, and Dolly the clone developed. Her birth at Scotland's Roslin Institute created an international sensation when it was announced in 1997.

Researchers at PPL Therapeutics, a biotechnology company associated with Roslin, have determined that the telomeres that cap Dolly's chromosomes and prevent a cell's genetic code from fraying are shorter than would be expected for her age. Progressive shortening of telomeres at each cell division may make Dolly age faster, although it remains to be seen whether her lifespan will be shorter than the usual for sheep--about 13 years. Dolly's shortened telomeres also may increase her risk of cancer.

"I recall when the news first came out, somebody said that Dolly was a sheep in lamb's clothing," said Jerry Shay, PhD, a molecular biologist at the University of Texas Southwestern Medical Center in Dallas. "I think that's an appropriate quote now."

Other researchers said the finding does not have serious implications for agriculture. Ranchers, for example, might use cloned animals as genetic factories to reproduce desired traits in their herds. But because cloning is more expensive and less reliable than other breeding methods, they are likely to mate clones with uncloned animals.

"Maybe the cloned animals would have a slightly shorter lifespan," said George Seidel, PhD, a livestock geneticist at Colorado State University. "But their offspring would be normal."

For that matter, Dolly's breeders could have avoided the problem entirely by starting with DNA from a younger sheep or even a sheep embryo. Regardless, Alan Colman, PhD, PPL Therapeutic's research director, said the link between telomere wear and aging is not well-established, and that the only problem posed by telomere fraying could come if a clone were made from a clone, "but we see no reason why sequential cloning would be necessary."

Sequential cloning would be like making a photocopy and then using the copy to repeat the process. Eventually, the copies become indistinct and illegible.

Genetic testing continues on Dolly's offspring including Bonnie, born in 1998, and a set of triplets born this year. Bonnie was conceived naturally, and half her DNA came from her father. She shows no significant telomere shortening.