More Bad News For Cloning

Cloned mice developed obesity when they reached adulthood, according to a new study that raises doubts about cloning animals for human transplantation and about cloning humans themselves.

Ian Wilmut, the pioneer researcher who cloned the sheep Dolly, says the report raises the question of whether any clones are entirely normal.

Duane C. Kraemer, a veterinary professor at Texas A&M University, said the finding is "another reason to continue the research."

"I would not indict the entire process of cloning," Kraemer said. "We just have to have a lot more information than we have now to evaluate the consequences of such abnormalities."

The new report, published in Friday's issue of the journal Nature Medicine, comes from a team of scientists led by Dr. Randall R. Sakai at the University of Cincinnati College of Medicine.

The cloned mice were not merely larger than normal mice. They showed several characteristics of obesity, including a significantly higher percentage of body fat and increased levels of insulin and leptin in their blood, Sakai reported.

Insulin is used by the body in the processing of sugar and other carbohydrates. Leptin is a hormone thought to be an appetite suppressant; excessive amounts can indicate resistance to its effects.

In cloning, scientists remove the nucleus from an egg and replace it with the nucleus from an adult cell, which contains the DNA of the donor. The egg is allowed to develop into an embryo.

The cloned mice were compared to two other groups of mice. One group reproduced naturally; a second - called IVEM - mated normally, but the embryo was then removed and developed in the same lab setting as the clones.

"The clones and the IVEM control animals develop increased body weight as adults, with the clones being even fatter than the IVEM controls," Sakai said. "This suggests that some factor associated with manipulation of the cells in culture may be producing the effects."

In Sakai's study, when the cloned mice were allowed to mate and reproduce normally, their offspring were not obese.

This indicates that either the donor cells used or the method of transfer itself may be related to the development of obesity, Sakai concluded.

In a commentary accompanying Sakai's paper, Wilmut said, "It is questionable whether there are any clones that are entirely normal."

The widespread patterns of death and abnormal development indicate that current methods of nuclear transfer for cloning are inefficient and error-prone, he said.

"In short, cloning by the present methods is a lottery," said Wilmut. "Several coins are thrown and must all come up as heads if normal life is to result."

In January, scientists in the United Kingdom reported that Dolly, the world's first cloned sheep, had developed arthritis at the relatively young age of 5 1/2 years. In 1999, scientists noticed that the cells in her body had started to show signs of wear more typical of an older animal.

Worldwide, there are now hundreds of animal clones, including cows, pigs, mice and goats, many of them appearing healthy.

But many attempts to clone animals have ended in failure, with deformed fetuses that died in the womb, had oversized organs or were born dead. Still others died days after being born, some twice as large as they should have been.

The successes and failures of cloning have generated heated debate in many countries, particularly as some scientists have suggested cloning humans.

"We must be very cautious about prematurely applying the technology in humans," Sakai said. "As far as we can tell, the cloning procedure has not been proven to be medically and genetically safe."

In January an advisory panel of the National Academy of Sciences recommended a ban on cloning aimed at making new human beings, concluding that it's unsafe for both mother and child. But the group said that cloning should be allowed to produce cells that promise to treat disease.

In so-called therapeutic cloning there is no attempt to produce another live human. Instead, cloned cells only develop into the blastocyst stage - 30 to 150 cells - to produce stem cells that may be used in medical treatment.

By Randolph E. Schmid