Dolly: Young on  the Outside, Old  on the Inside?

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 a May 1999 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 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.

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.