Researchers have found serious abnormalities in the clones of mice, a finding that strengthens the belief of many scientists that the technique used to create Dolly the sheep should not be tried on humans.

The findings are based on the use of embryonic stem cells in cloning. The report, appearing today in the journal Science, comes as the Bush administration considers whether to allow federal funds for non-cloning stem cell research.

Many of the mice clones in the experiment appeared to be normal, including their genes, but there was evidence the genes did not work properly during embryonic and fetal development.

In human clones such flaws eventually could affect personality, intelligence and other human attributes.

The researchers found evidence that the way normal-appearing genes in the animal clones made proteins was flawed and unstable. In effect, even though the biological blueprint was intact in the clones, the way the blueprint was read and interpreted was flawed. This could result in abnormal tissues and organs, they said.

A number of scientists doing cloning experiments with mice, pigs, sheep and cattle have reported that even apparently normal animals develop disorders later in life.

The investigators said that extreme obesity has developed in many cloned animals. That includes Dolly, the first mammal cloned from an adult cell. Dolly was created in 1996.

Development is a finely orchestrated ballet of cells forming tissues and organs at the right place and time," said Prentice. It takes only one going awry at the wrong time and place to have a seriously flawed individual.

In the study, the researchers made the mouse clones using embryonic stem cells, the primordial cells known to be able to form virtually any tissue in the body. The DNA from the cells was removed and inserted into a mouse egg that had been stripped of its own DNA. The resulting embryos were then implanted in mother mice and allowed to grow to birth.

The researchers monitored the expression, or action, of genes that play a role in embryo and fetal development. They found that the genes, even from nearly identical stem cells, worked differently. In fact, stem cells are unstable in gene expression even in the laboratory dish.

This instability raises the possibility that using stem cells to treat health disorders may not work as well as some scientists have suggested.

Some researchers have suggested that embryonic stem cells could be cloned from a patient and used to grow cells that in turn could be used to restore that patient's ailing heart or liver or other organs.

Genetic instability is not likely to block the curative use of embryonic stem cells. In developing cells for therapeutic use, researchers would harvest and inject into patients only those cells that are normal.

During cloning, no such selection is possible because an embryo must use the DNA provided and cannot select only that which is perfect.

Dr. David Humpherys from MIT is the senior author of the study (jaenisch@wi.mit.edu)

Science Volume 293, Number 5527, July 6, 2001, 95-97