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FEATURE STORY 61
anemia, among other things. Rats with damaged spinal cords
regained some mobility after injections of neural precursor
cells made from embryonic stem cells. Stem cells transplanted
into rats heart tissue can help heal damaged heart muscles.
But before similar therapies can be tested in people, sci-
entists will need to resolve the problem of immune rejec-
tion. Transplanted stem cells, which are now derived from
discarded embryos, are genetically di erent from their recip-
ients; like donor kidneys, they thus car ry the risk of provok-
ing an immune response. That means that even the most
advanced treatments are still years away from clinical use.
Therapeutic cloning is one way to make stem cells suitable
for transplant, since it yields cells that share their recipi-
Theoretically, cloned stem cells could help Friedmann s
patients; scientists could x the genetic defect in the cells
before implanting them. The prospect of such revolution-
ary treatment is what has most captivated both the public
and the media. But Friedmann and Snyder are focusing on
an application that could have much broader implications---
and is closer at hand. Instead of using the cells as a form
of therapy themselves, the researchers plan to use them to
study Lesch-Nyhan disease and test new treatments. Experts
say this type of application could dramatically improve our
understanding of how any disease with a genetic component
unfolds at the cellular level. "You could make a stem cell
line that has ALS or Parkinson s, using DNA from a patient
that really has the symptoms," says Snyder.
Scientists could prod the cells to develop into the type
of cells damaged by a disease, such as dopamine neurons
in Parkinson s, and study the intricate progression of the
disease from its earliest stirrings to its nal cellular death
knell. Because the cells would be genetically identical to
the patient s DNA, they would undergo many of the same
molecular changes that underlie the patient s disease.
Ian Wilmut, the British scientist who helped clone Dolly
the sheep, hopes to turn stem cells in a dish into motor neu-
rons, the type of nerve cells ravaged in Lou Gehrig s dis-
ease (also known as amyotrophic lateral sclerosis, or ALS).
Creating a stem cell line with the disease would allow sci-
entists to study how these neurons sicken and die and to
search for ways to slow or stop the downward spiral of the
disease. "I think that disease models, such as the ones we
plan to create, will do more in the short term, and maybe
the long term, to treat disease than cloning stem cells for
tissue transplants," Wilmut says.
One of the major advantages of cloned stem cells is that
they would enable scientists to create accurate models of a
disease without rst determining the underlying genetics.
"With a lot of sporadic diseases, we know there is a genetic
component, but it s not clear what it is or how it contributes
to the development of the disease," says Larry Goldstein, a
neuroscientist at UCSD who studies Alzheimer s disease.
"We have a lot of hypotheses, and I think this methodology
will put us in a position to test those hypotheses. And if one
is cor rect, we ll have a direction to go for therapy."
A stem cell model of Alzheimer s would also allow scien-
tists to study what the disease does before symptoms appear
and perhaps create early-diagnostic tests. By the time an
Alzheimer s patient goes to the doctor with cognitive prob-
lems, the brain is signi cantly---and possibly irreversibly---
damaged. "Studying the brains of people who have already
died is like studying a plane crash after the plane hit the
ground---you re looking at the wreckage," says Goldstein.
"We want to look at the black box of Alzheimer s disease.
What happens in those cells before the crash?"
To search for early signs of the disorder, scientists could
generate stem cells using DNA from an Alzheimer s patient,
then prod the cells to di erentiate into neurons, monitoring
them for the production of speci c proteins or other molecu-
lar changes not seen in neurons derived from healthy embry-
onic stem cells. The same approach might work with cancer,
which is characterized by a series of har mful genetic changes.
"We want to know what s the earliest you can detect di er-
ences in disease cells," says Renee A. Reijo Pera, codirector
of UCSF s human-embryonic-stem-cell biology program.
Cloned stem cells may also provide a much more e ec-
tive way to test drugs. "Very often the animal models that
exist for a particular disease really don t authentically rep-
licate what s going on in a human," says Snyder. Using
models based on stem cells, scientists could test drugs at
di erent stages of disease, searching for compounds that
could prevent a person at risk for, say, Alzheimer s, from
ever developing the disease in the rst place, or for com-
pounds that stop or reverse the progression of damage in
people who already have the disease.
Snyder eventually hopes to create stem cell models of
many di erent neurodegenerative diseases. His rst step,
"The real work suffered because this guy was playing some game,"
Robert Lanza says. "I know I will be criticized for saying this, but I
truly believe we had a protocol that would have been reproducible
and straightforward, and we could have started on therapies by now."
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