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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
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