Scientists find flaws in stem cell cloning

By PAUL RECER, Associated Press

WASHINGTON (July 6, 2001 12:44 a.m. EDT) - Researchers have found serious abnormalities in cloned mice, a discovery that strengthens the opinion of many scientists that the technique used to clone Dolly the sheep should not be used on humans.

The findings are based on the use of embryonic stem cells in cloning and come as the Bush administration considers whether to allow federal funds for non-cloning stem cell research. The research appears Friday in the journal Science.

"This study confirms the suspicions of many of us that cloning of humans would be really dangerous," said Rudolf Jaenisch, senior author of the study and a researcher at the Whitehead Institute for Biomedical Research and at the Massachusetts Institute of Technology.

David Humphery, first author of the study, said that many of the mice cloned in the experiment appeared to be normal, including having normal genes, but there was evidence that during embryonic and fetal development the genes did not work properly.

"It is quite likely that just the animals that are most nearly normal make it to birth (in cloning), but our study shows that doesn't mean they are completely normal," said Humphery. "There may be changes in gene expression that could affect them later in life."

In cloned humans, Jaenisch said the gene expression flaws could affect personality, intelligence and other human attributes.

Humphery said there was no evidence that the genes in the cloned animals were altered but that the way in which the genes made proteins was flawed and unstable. In effect, the researchers found that even though the biological blueprint was intact in the cloned animals, the way that the blueprint was read and interpreted was flawed. This could result in abnormal tissues and organs, they said.

Humphrey and Jaenisch said that 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. Jaenisch said that extreme obesity has developed in many cloned animals, including Dolly, the first mammal cloned from an adult cell.

Dr. David A. Prentice, an Indiana State University professor of life sciences, said the MIT-Whitehead study shows the hazards of the current cloning technology.

"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 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, said Humphery, 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, said Dr. Joann A. Boughman, vice president of the American Society of Human Genetics.

"When we grow (embryonic stem) cells for a curative situation, we will need to precisely control the process," she said. "This paper shows that we've got a very long way to go to fully understand this whole process."

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

Jaenisch said that it is unlikely that genetic instability would block the curative use of embryonic stem cells. He said in developing cells for therapeutic use, researchers would harvest and inject into patients only those cells that are normal.

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

Regulations that would permit federal funding of embryonic stem cell research has been delayed by President Bush who ordered a review of the whole issue. Some in Congress oppose embryonic stem cell research because obtaining the cells involves the death of a human embryo. Many scientists, however, believe that embryonic stem cell research could relieve suffering for millions of patients with a variety of disorders.