Home' Technology Review : May June 2006 Contents 62 FEATURE STORY
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in collaboration with Friedmann, will be to use the frozen
skin cells housed at UCSD to create stem cells with Lesch-
Nyhan disease. Snyder originally hoped Hwang would teach
him the cloning process. But now the scientists plan to
embark on the therapeutic-cloning project on their own
and are working on getting regulatory approval and state
or private funding.
To generate normal stem cell lines, scientists start with a
fertilized embryo, usually discarded from an in vitro fertili-
zation clinic. They collect a specialized ball of cells, called
the inner cell mass, from the embryo when it is just ve
to six days old. Cultured in a dish, the cells develop into
a line of embryonic stem cells that can, depending on the
conditions, either regenerate itself or di erentiate into spe-
cialized cell types, such as heart cells, liver cells, or brain
cells. Scientists must continually make new stem cell lines,
because existing lines may accumulate mutations, making
them un t for therapies and many types of research.
Cloned stem cells, however, are even more di cult to
make than regular embryonic stem cells. Scientists take the
DNA from a di erentiated cell, such as a skin cell, and insert
it into an egg that has been stripped of its own DNA. The
egg then starts dividing, much as a regular embryo would. If
it sur vives long enough, its inner cell mass can be har vested
and used to grow stem cells. Scientists have generated stem
cells from cloned mouse embryos but have not replicated that
feat in humans. Unlike naturally fertilized embryos, cloned
embryos are hard to keep alive long enough---almost a week---
that their inner cell masses can be gathered.
Hwang had claimed to do this with remarkable e -
ciency, using a small number of eggs. Human eggs are a pre-
cious resource that is very di cult to obtain, so the fr ugal
use of eggs is critical to making nuclear transfer practical.
But subsequent investigations revealed that Hwang and col-
leagues lied not only about their results but also about the
number of eggs they used in their experiments. According
to a report from South Korea s National Bioethics Com-
mittee, Hwang used 2,221 eggs in his failed experiments,
rather than the 427 eggs reported in his two Science papers.
Scientists now have no idea how many eggs are required to
successfully clone a line of human stem cells.
When the nucleus of an adult cell is put into an egg, some
unknown factors in the egg turn back the clock on it, revert-
ing it to its embryonic state. "It s like pushing the refor-
mat key on a computer. You reformat it to become some
other kind of cell," says Snyder. "We don t understand the
molecular pathways that do this....As far as we know, the
only thing that can do this is the egg."
According to Kevin Eggan, a molecular and cellular bi-
ologist at Har vard who is seeking approval from his uni-
versity to start nuclear-transfer research, "It s not clear how
many eggs we need or how many women will step for ward
to donate eggs." Eggan, who also sits on the ethics review
board of the California Institute for Regenerative Medicine
(and was a member of the 2005 TR35), says he s spent much
of the last year learning about the ethical and medical issues
associated with egg donation. Many scientists say access
to eggs will determine the success of therapeutic cloning.
"We have a therapy that could have revolutionized medi-
cine like antibiotics, but we have a bottleneck that shoots
it down," says Lanza.
The egg donation procedure is uncomfortable and poten-
tially painful and carries some medical risk. Women must
undergo hormone treatments to stimulate ovulation, coun-
seling sessions to understand the risks involved, and a medi-
cal procedure in which a needle is inserted into the vagina
to remove eggs from the ovary. A small percentage of donors
develop ovarian-hyperstimulation syndrome, which in rare
cases can cause kidney failure.
Even ardent supporters disagree over the most ethical ways
to handle egg donation. Some scientists don t want to use
human eggs at all. "We feel it s inappropriate to put women
through a risky and potentially dangerous procedure when we
don t know what the e ciency is," says Stephen Minger, a sci-
entist at King s College London who is planning to apply for
permission from the British government to clone human stem
cells using animal eggs. Those who do want to use human
eggs disagree about whether women should be paid for their
donations. Opponents worry that payment could encourage
some women to undergo the procedure without understand-
ing the risks. But others think compensation is the most ethi-
cal approach. "When ACT did this, we paid egg donors," says
Green. "I continue to think that s the best way to do it. It s fair
and open and the least likely to lead to evasion."
According to Lanza, all the women who recently con-
tacted ACT about donating eggs dropped out of the process
when they learned how much time was involved. Lanza says
he still plans to proceed, as soon as he can get a new source
of eggs. "If I were just starting, I probably wouldn t do it," he
says. "Sometimes I spend more time on the phone with law-
yers than I do on the science....But we ve invested so much
time and energy and so much of ourselves that we want to
see this to completion. I still feel there is a very important
role for [nuclear transfer] in di erent diseases."
Lanza suspects that, because of the shortage of eggs and
the unknown e ciency of the cloning process, the thera-
peutic use of cloned stem cells will end up looking more
like a kidney transplant than like the ingestion of a widely
prescribed dr ug. "We do recognize it s not the broad cure
we had hoped, but I m convinced it will save some indi-
viduals," he says. "Perhaps a mother would donate a round
of eggs to create stem cells for her sick child."
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