Scientists unearth key to better cloning

TOKYO, Jan. 10 (UPI) -- Japanese researchers suggest genetic abnormalities that occur during cloning may not actually be due to the cloning process itself but to the conditions under which the process takes place.

Researchers at the National Institute of Infectious Diseases in Tokyo and at the Tokyo Institute of Technology found the cloning process may not be the reason behind genetic defects, but instead the conditions in which the cell cultures are placed might be creating an environment in which the genes behave strangely. These abnormalities can lead to birth defects, disease or chronic conditions that often cause the animal to die at birth or at a young age.

The team found that mice cloned from somatic cells -- cells that are not egg or sperm cells but come from elsewhere in the body and do not pass on genes to offspring -- did not show signs of genetic imprinting abnormalities as occurs when embryonic stem cells are used in the cloning process.

Genetic imprinting means certain copies of a gene are turned on or off, so in some cases an organism can inherit only one working copy of a gene.

"It's like your mother and father both gave you a Volkswagen, but only one has an engine that works," Randy Jirtle, a professor of radiation oncology and pathology, who also studies genetics at Duke University in Durham, N.C., told United Press International.

The somatic cell mouse clones were followed through their embryo, fetal and full-term animal stages. They compared these animals to normally bred mice. Both groups had offspring and the only significant difference between the cloned and normal mice was that cloned mice had placentas twice the usual size; however the reason why was unclear.

The offspring of the two groups of animals, however, showed no major differences, scientists report in the Jan. 11 issue of Science.

"Therefore, our cloned neonates (newborns) looked healthy and normal," researcher Dr. Fumitoshi Ishino told UPI. However, Ishino cautioned, "It is possible that placental abnormality affects embryos and neonates physiologically or it is also possible that some other genetic abnormality remains in them." Those other genetic abnormalities may be more subtle than an oversized placenta, he said.

The findings indicate that in some cases of cloning, embryonic stem cells may not be the best choice. Instead, somatic cells could be a more viable alternative. But how the environment these cells are placed in may be crucial in determining whether genetic problems ensue.

"The culturing conditions of these (cells) could be what's key here," Jirtle said. "That's the important point of this study. Putting any cell in a culture changes them... we don't know how to maintain them properly (and) from this study, it looks like using the somatic cells is better because there's less chance to screw the cells up irrevocably."

One of the major hurdles in cloning has been genetic abnormalities surfacing in the cloned animals. Understanding when these genetic abnormalities take place and learning how to overcome them are keys to cloning research and have implications for studying various therapies for diseases that affect humans.

Cloning often conjures up Frankenstein-like images of science in the United States, but James Pierce, an associate professor of genetics at the University of the Sciences in Philadelphia, said this study might demystify cloning.

"Adult cloning might be more do-able, I hate to use the word easy," Pierce said. "Whether the same rules or events we're observing in these experiments are true in humans aren't known...it's a complicated genetic dance."

What the optimal culture conditions would be to minimize genetic problems is "the million dollar question," Pierce added.

Not everyone agrees that these findings are so promising.

"I don't agree with these conclusions," said Rudolf Jaenisch, professor of biology at the Whitehead Institute for Biomedical Research in Boston. "The placenta is very important for embryo development," he explained, so just because an animal may look normal and healthy on the outside is not proof there might not be less visible genetic problems inside. Jaenisch said he would be cautious of "over-interpretations of very superficial data."

(Reported by Katrina Woznicki in Washington)