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Cloned Mice Die Young

More evidence that copying comes with a price

MONDAY, Feb. 11, 2002 (HealthDayNews) -- Increasing evidence suggests cloning comes with a biological price, such as changes in an animal's immune system.

Now, researchers say cloning may also be linked to premature death.

A study of cloned mice by scientists at Tokyo's National Institute of Infectious Diseases found cloned mice had a significantly shorter life span than animals bred naturally.

The findings could raise questions about the use of cloned organs for transplantation, say the researchers.

Another expert who is familiar with the study that appears in today's online issue of Nature Genetics says this problem is the inevitable cost of manipulating an animal's genetic blueprint.

Senior investigator Atsuo Ogura, an investigator in the division of veterinary science, led a comparison of 12 mice cloned from immature cells found in the animals' testes versus seven normal mice. All of the mice were followed for 800 days, which would compare to a ripe old age in humans.

One of the seven normally conceived mice died within the 800-day period. However, among the cloned mice, animals started to die by day 311 of the experiment, and 10 of the 12 had died by the end of the 800-day period.

When the researchers performed autopsies on six of the cloned mice, they found evidence of severe pneumonia and liver failure. None of the normal mice had these problems.

The cloned mice also had significantly reduced antibody production, meaning their immune systems could have been weak.

"It is very probable that, at least for some populations of clones, some unpredictable defects will appear in the long run," says Ogura. "But these defects may vary, depending on species, sex, donor cell type, genotype and environmental condition."

However, he notes, some defects may not be harmful or affect life span.

Ogura says their findings could spell bad news for scientists cloning for the purpose of organ transplantation, usually involving pigs. He says some of the problems described in this paper may appear in other cloned animal species. Studies have shown cloned cows and goats may have defects in their immune systems. Even the first cloned animal, Dolly the sheep, is showing early signs of arthritis, and researchers who helped bring her into the world blame it on cloning.

Dr. Davor Solter, a professor at the Max-Planck Institute for Immunobiology in Germany, says it's not as clear from this study that cloned cells for therapeutic purposes, such as neurons to treat brain disorders, are unsafe.

"There's probably something not quite right with cloned animals," Solter says. "The logical conclusion is that cloning people is not to be attempted."

"Cloned [animals] die all the time, and my suspicion was that it was certainly due to cloning," he says.

Clones in which critical genes have been affected may not even survive implantation as an embryo, while others might die during pregnancy.

"Some small percentage, about 1 percent of the clones, will be born," says Solter. "But some of them are still damaged enough that they will die very soon after birth."

A small percentage will reach adulthood, he says. "But I doubt that actually any clone is completely normal," Solter says.

He also doubts that refined cloning techniques will get rid of this problem.

"You're taking a genome which was never designed to do what we are asking it to do," he says. "I don't think they will eliminate this problem."

Ogura and his colleagues are currently looking for abnormalities in tissue samples from cloned mice that died at several points between five months and one year old. They hope their findings will shed light on the overall health of cloned animals.

What To Do: For a primer on cloning, visit the Oak Ridge National Laboratory. Check out this article from about cloning cows with potentially longer life spans.

SOURCES: Interviews with Atsuo Ogura, Ph.D., investigator, Division of Veterinary Science, National Institute of Infectious Diseases, Tokyo; Davor Solter, M.D., Ph.D., professor, Max-Planck Institute for Immunobiology, Freiburg, Germany; Feb. 11, 2002, Nature Genetics
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