Thursday July  5  7:03 PM ET
Study: Stem Cell Cloning Flawed
By PAUL RECER, AP Science Writer

WASHINGTON (AP) - Researchers have found serious abnormalities
in cloned mice, a finding that strengthens the belief 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 (news - web sites).

David Humpherys, 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 Humpherys. ``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.

Humpherys 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.

Humpherys 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 Humpherys, 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 (news - web sites)
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.

On the Net:
Science: http://www.eurekalert.org
Cloning: http://genomics.phrma.org/cloning.html

http://dailynews.yahoo.com/h/ap/20010705/sc/stem_cells_cloning_2.html

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