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Cloning Youth
April 27, 2000
Close-up image of a cloned cattle
Unlike Dolly, these cows don’t show any sign of early aging. Also unlike Dolly, they have unimaginative names (like "Pass-10-A" and "Pass-8", above).

When Dolly the sheep was unveiled as the world’s first animal to be cloned from an adult cell, she created a controversy over the ethics of cloning and its implications for humans. But it turned out she also had a practical problem. She was old before her time. More precisely, the cells inside her thought they were the same age as her genetic mother.

Recently, however, scientists announced a major step in refining the process of cloning. They’ve solved the problem of premature aging. Now, six healthy cows grazing in a remote pasture in the upper Midwest are the next generation in cloning. Their markings reveal they are identical in every way, and they show no signs of aging prematurely. In fact, the scientists who made them claim that, at age one, the cows are biologically younger than a newborn calf.

A tail of two telomeres

Cells give away their age by the length of their telomeres, DNA "tails" at the ends of their chromosomes, which shorten like a burning fuse every time the cell divides. New cells have longer telomeres than older cells, while senescent cells—cells near the very end of their lifespan—have the shortest telomeres of all.

The telomeres are the pink ends.
image: Shay/Wright Lab

Dolly the sheep was born with telomeres as short as those of her 6-year-old mother’s donated cells, causing many scientists to believe all clones might suffer from premature aging. "Dolly was so important that she set the trend," says Jose Cibelli of Advanced Cell Technology in Worcester, Mass., and co-author of the research paper, which appeared in in the journal Science. "Everybody thought cloning was not resetting the clock."

The cow clones originated from senescent cells, yet their telomere clocks somehow got turned back by the cloning process, the researchers say. Most surprising of all, the researchers report, the now one-year-old clones have telomeres even longer than those of normal newborns. "It’s really intriguing," Cibelli says. "We cannot explain it at this time. It looks like we brought back the clock not only to zero, but to minus!"

"Cloning," Cibelli adds, "can take old cells and bring them back to a newborn age."

Longer lifespan?

Dolly the Sheep
Dolly the trendsetter

Jerry Shay, a telomere expert at the University of Texas Southwestern Medical Center in Dallas, is more skeptical about the significance of telomere length as a measure of aging. "This is an important advance in that it demonstrates that fully senescent cells can be rejuvenated and produce a complete organism," Shay says. But, he adds, "the fact that the telomeres were slightly longer is not very important and may be due to random variations in telomere measurements or to a mechanism that causes very short telomeres to slightly overelongate their telomeres.

"Telomere biology may only account for 10 percent of what makes us age," says Shay. "It would surprise me if the cow had an extended lifespan. It would also surprise me if Dolly the sheep, which has slightly shorter telomeres, has a shortened lifespan."

Shay and the Advanced Cell scientists do agree on a key point—that we’ll have to wait at least 20 years in the case of the cow clones to know whether there has been any effect on their lifespan. In the case of Dolly, it’s more like 12 years.

But, Cibelli points out, researchers at Rockefeller University in New York have cloned mice using the same technique used for the year-old cows. He says that group should size up the mice’s lifespans, not to mention their telomeres, a whole lot sooner.

Stem cell controversy

The researchers say the discovery means it will be possible to clone young, healthy human cells and organs even from the very elderly. Cell or tissue replacement could eventually benefit people suffering from liver disease, diabetes, heart disease, arthritis, Alzheimer’s and Parkinson’s disease. "The potential cloning has for therapy is tremendous," Cibelli says, "but we should be very clear on the fact we are years from having products to put into patients."

And the first such products will likely rely on the use of embryonic stem (ES) cells, controversial because currently the only way to produce them is from human embryos. Federally-funded scientists remain banned from conducting research on human embryos, while private companies like Advanced Cell are aggressively pursuing such therapies.

Shay predicts scientists will ultimately understand how to clone ES cells in the lab. Theoretically, a human cell nucleus could be put into a bovine egg cell to start the development process. "After a few divisions the cells could be isolated and these would be equivalent to human embryonic stem cells. Thus, we could essentially have ES cells that are human without taking them from human aborted fetuses." But, Shays cautions, such techniques are probably "in the distant future."

Cloning: A Brief History

Scientists started cloning animals from embryo cells in the1960s, but it wasn’t until 1997—with the birth of Dolly the sheep—that an animal was successfully cloned from an adult cell. Since the onset of Dollymania, researchers have successfully cloned other vertebrate species, and now pet cloning has even sparked interest in the nonscientific community and is considered to be a growing industry. The following is a list of recent cloning advances:

February, 1997: Dolly is created by Roslin scientists using adult mammary gland cells.

March, 1997: Two rhesus monkeys (Neti and Ditto) are cloned from embryo cells at the Oregon Regional Research Center.

July, 1997: Roslin scientists create another sheep, Polly, using fetal cells engineered for the production of human clotting factor to treat hemophiliacs.

August, 1997: ABS Global Inc. announce the birth of a cow, Gene, created with partially-specialized fetal cells.

July, 1998: Researchers at the University of Hawaii produce female mouse clones.

August, 1998: An American millionaire hires cloning expert Dr. Mark Westhusin, director of cloning at Texas A&M; University, to clone his pet dog Missy. An internet-based pet cloning company called Clonapet claims to have stored "frozen" DNA from more than 15 cats and dogs. This DNA will eventually undergo the cloning process.

December, 1998: Japanese researchers clone eight calves from the cells of one adult cow.

May, 1999: American scientists report the cloning of three goats containing human genes that produce a protein which prevents blood clotting.

June, 1999: A Hawaiian research team produces the first male mouse clones. Out of 274 transplanted embryos, only three reach full-term growth.

March, 2000: PPL Therapeutics of Edinburgh, Scotland, announce the cloning of five healthy piglets. This research paves the way for producing genetically modified pigs whose organs can be successfully transplanted into humans.

April, 2000: Researchers solve the problem of premature aging in clones.

by Sotiria Lafazanidis

Elsewhere on the web:

Extension of Life-Span by Introduction of Telomerase into Normal Human Cells

Advanced Cell Technology fuses cow & human cells to make embryonic stem (ES) cells

Joint Steering Committee for Public Policy – scientists lobbying for government funding of ES cell research.

Do No Harm – ES cell research opponents.

Anything but "Pass-A"

Suggest names for the cow clones and we’ll post them here.

by Joyce Gramza

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