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5-Animals: Dolly the sheep may age prematurely

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TITLE:  Dolly the sheep may age prematurely
SOURCE: American Press, by William McCall
DATE:   May 26, 1999

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Dolly the sheep may age prematurely

Dolly the cloned sheep may be susceptible to premature aging and
disease because her genes were copied from a 6-year old sheep,
Scottish scientists say. There is no direct evidence that Dolly
will die prematurely. She is a healthy 3-year-old Finn Dorset
sheep and has delivered lambs in the past two years. But the
older DNA in her cells shows telltale signs of wear that are more
typical of an older animal. Geneticists said the finding,
published in Thursday's issue of the journal Nature, provides
further evidence that cloning has its limits and that researchers
cannot endlessly manufacture copies of animals without the
original genetic blueprint wearing out.

"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." In 1996,
Dolly became the first large animal to be cloned from genetic
material extracted from an adult cell. Scientists inserted a cell
from a ewe's udder into an egg from the same animal after
removing the egg's DNA. The bioengineered embryo was implanted in
the ewe's womb and Dolly developed as a clone. Her birth at the
Roslin Institute in Scotland was announced in 1997 and caused an
international sensation.

Now, researchers at PPL Therapeutics, a firm associated with the
Roslin Institute, have determined that the "caps" on Dolly's DNA
that regulate a cell's lifespan 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. The shortened
telomeres had been predicted as one outcome of cloning, said Alan
Colman, research director for PPL. As a result, Dolly could age
faster and be more at risk for cancer, which occurs when cells
fail to self-destruct and begin uncontrolled growth. Sheep have a
life expectancy of 13 years. "You'd also expect reduced
fertility," said David Corey, another UT Southwestern Medical
Center researcher.

Genetic tests are continuing on Dolly's offspring, including
Bonnie, born in 1998, and a set of triplets born this year. Tests
on Bonnie showed no significant telomere shortening, but she was
conceived naturally, and half her DNA came from her father.
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." Corey said sequential
cloning would be like making a copy on a photocopying machine,
and then putting the fresh copy into the machine and repeating
the process. Eventually, the copies are unreadable-- just as the
genetic code would be unreadable. 


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