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FEATURE STORY 65
Brambrink, a postdoctoral researcher in Rudolf Jaenisch s
lab at the Whitehead Institute for Biomedical Research in
Cambridge, MA, is searching for the genetic switches that
control reprogramming---a poorly understood transforma-
tion that takes place during cloning, reverting an adult cell
to its embryonic state.
All cells in an organism share the same genes, but the
pattern of a cell s gene activity deter mines whether it will
become a stem cell or a di erentiated cell. During repro-
gramming, some still-unknown factors in the egg tur n o
the genes that make a cell, say, a neuron and turn on the
genes that are expressed in embryos. To uncover the genes
controlling this conversion, Brambrink has engineered adult
cells to express the genes that are selectively activated in
eggs. If a particular gene expressed by one of these cells is
crucial to the reprogramming process, it will activate genes
that are known to be involved in the process s later stages;
those genes have been tagged with markers that make the
cell glow green. In the best-case scenario, the activator gene
might trigger reprogramming itself, creating a clump of
stem cells where once sat di erentiated broblasts.
Reprogramming cells in a dish would be a huge break-
through for the eld of therapeutic cloning. Once scientists
understand the process, they can create new technologies
to turn adult cells directly into stem cells. Such technolo-
gies would eliminate the ethical controversy surrounding
embryonic stem cells, because they would not require the
creation and destr uction of human embryos. They would
also eliminate the need for human eggs, which could make
therapeutic cloning much more e cient and therefore more
broadly useful. Such an advance could truly usher in a new
era of regenerative medicine, where a tailored stem cell
transplant is available to anyone who needs one.
Scientists have already shed some light on the repro-
gramming process. In a paper published in September,
Rick Young, a biologist at Whitehead, and colleagues iden-
ti ed a set of genes that are kept inactive in undi erentiated
stem cells. Researchers theorize that when these genes are
turned on, they produce transcription factors that spur the
cells along di erent developmental paths.
Scientists caution that a clear picture of reprogramming---
one that would enable the production of stem cells without
eggs---is likely decades away. However, the little known so far
is already helping scientists develop new, less controversial
techniques for creating stem cells. For example, scientists are
searching for ways to create genetically altered embryos that
no longer have the potential to develop into human beings,
thus eliminating some of the ethical controversy surround-
ing nuclear-transfer research. Markus Grompe, director of
the Oregon Stem Cell Center at Oregon Health and Science
University in Portland, hopes to create such a technology by
forcing donor cells to express genes normally found only
in embryonic stem cells (see "10 Emerging Technologies:
Nuclear Reprogramming," March/April 2006).
In fact, nuclear transfer may turn out to be a transitional
technology. But even if it is, and for all its controversy, it might
still be vitally important as the key to developing newer tech-
nologies that are able to nally free embryonic stem cells
from ethical quandaries. "Nuclear transfer is the only way
we can currently do reprogramming. This is our model and
our yardstick to learn what s important," says Whitehead s
Jaenisch. Adds Snyder, "If we don t know how to do nuclear
transfer, or we re not allowed to do it, then this potentially
debate-solving technique becomes impossible to pursue."
Lanza is also working on new reprogramming technolo-
gies to get around the shortage of eggs. But like Snyder, he
worries that too much focus on uncertain alter natives could
derail progress on therapeutic cloning, which scientists know
works. "Let s develop all these technologies and see what
works best," he suggests. He adds that months and years of
grappling with the ethical and legal issues surrounding stem
cell research, rather than the science, have worn him down.
But the thought of stem cell--based therapies pushes him to
keep going. "I ve often gone home and thrown up my hands.
But then I say, We can t give up that easily."
Emily Singer is the biotechnology editor of Technology Review.
U.K. FRONTRUNNERS In 2005, Miodrag Stojkovic and Alison
Murdoch (left) at the University of Newcastle upon Tyne announced
they had created an early-stage cloned human embryo (above).
CRAIG CONNOR/NORTH NEWS & PICTURES/REUTERS/CORBIS (RESEARCHERS); RBM ONLINE/REUTERS/CORBIS (EMBRYO)
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