-Caveat Lector-

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.


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