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Cloned Sheep May Age Prematurely

- By WILLIAM McCALL, AP

Dolly the cloned sheep is only 3, but her genes are already showing signs of wear and she may be susceptible to premature aging and disease - all because she was copied from a 6-year-old animal, Scottish researchers say.

There is no direct evidence that Dolly will die prematurely. She is healthy and has delivered lambs in the past two years. But the DNA in her cells shows signs of wear typically found in an older animal.

Geneticists said the finding, published in Thursday's 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 cloning humans.  ``Only years from now, it would be a relevant question to ask if a cloned child would have a shorter life span even though it appears to be healthy and normal,'' said Marie DeBernadino, a biologist at the Allegheny University of the Health Sciences in Philadelphia.

In 1996, Dolly became the first large animal to be cloned from genetic material extracted from an adult cell.  Scientists removed the DNA from a ewe's egg and inserted DNA from a cell taken from the ewe's udder. The bioengineered embryo was implanted in the ewe's womb, and Dolly developed as a clone.  Her birth at the Roslin Institute in Scotland created an international sensation when it was announced in 1997.   Now, researchers at PPL Therapeutics, a biotechnology company associated with Roslin, have determined that the ``caps'' on Dolly's DNA that regulate a cell's life span are shorter than average.

All chromosomes are capped with tips known as telomeres that prevent a cell's genetic code from fraying. When the telomere finally wears down after repeated cell division, it signals the cell to self-destruct as part of the aging process.  As a result, geneticists say Dolly could age faster and run a higher-than-usual risk of cancer, which occurs when cells fail to self-destruct and begin uncontrolled growth. Sheep normally live about 13 years.

``I recall when the news first came out, somebody said that Dolly was a sheep in lamb's clothing,'' said Jerry Shay, a molecular biologist at the University of Texas Southwestern Medical Center in Dallas. ``I think that's an appropriate quote now.'' However, Alan Colman, research director for PPL Therapeutics, said that the link between telomere wear and aging is not well-established.

Also, Dolly's breeders could have steered clear of the problem by starting with DNA from a younger sheep - or even a sheep embryo.  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 they are likely to mate clones with uncloned animals because cloning is more expensive and less reliable than other breeding methods.   ``Maybe the cloned animals would have a slightly shorter lifespan,'' said George Seidel, a livestock geneticist at Colorado State University. ``But their offspring would be normal.''  Colman said 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 copy on a photocopying machine, and then putting the new copy into the machine and repeating the process. Eventually, the copies become illegible.  Genetic tests are continuing on Dolly's offspring, including Bonnie, born in 1998, and a set of triplets born this year. Bonnie was conceived naturally and half of her DNA came from her father.  She shows no significant telomere shortening.

List of Cloned Animals

Scientists have cloned several livestock and laboratory animals in the two years since Dolly's arrival in a Scottish laboratory barnyard caused an international sensation. Some of the clones are designed to produce more reliable food products. Others are being bred for research purposes, including the production of pharmaceuticals.

- In April, geneticists at Tufts University in Massachusetts cloned three goats. The goats' genetic code has been altered to produce a protein in their milk to treat heart attacks and strokes.

- In Japan, researchers have cloned several generations of calves since 1997. Calves also have been cloned in the United States, New Zealand and South Korea.

- In July 1998, a research team at the University of Hawaii cloned 50 mice in three generations from a single mouse. It was the most successful cloning experiment to date.

- In the United States, Texas A&M researchers are trying to clone a dog. A Wisconsin biotechnology firm is trying to clone a pig.

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