Published online: 16
October 2005; | doi:10.1038/4371072b
'Ethical' routes to stem cells highlight
political divideSplit opens over methods to
create nonviable embryos.
Erika
Check
& Carina Dennis
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Researchers claim to have found
an ethical way to harvest embryonic stem cells.
©
Getty | | Religious and ethical concerns are
forcing researchers using human embryonic stem cells to seek
ways to sidestep these issues. In a first attempt, biologists
this week revealed details of two techniques for deriving the
cells that do not involve the destruction of a viable
embryo.
Both methods work in mice and, in
principle, could be applied to human embryos. But scientists,
ethicists and politicians are split over the merits of the two
techniques.
Embryonic stem (ES) cells can
develop into any tissue in the body, so have great potential
for a range of therapies. And if they are cloned from a cell
in the patient's body, the resulting cell line would
genetically match that individual. This can be done using a
technique dubbed 'therapeutic cloning', in which the nucleus
from the donor cell is inserted into an egg stripped of its
own genetic material. Earlier this year, researchers in South
Korea became the first to use this method to derive human ES
cells that genetically matched the patient (see Nature
435, 393; 2005).
But the ethical concerns inherent
in destroying an embryo to create the cell lines are too much
for some, especially religious groups, and many countries have
restricted the research that can be done. In Germany, for
example, the use of ES cell lines created since January 2002
is illegal and carries a penalty of up to three years in jail.
And in the United States, federal funds for ES cell work is
only available for a handful of cell lines derived before
August 2001.
But there is currently heated
debate on the issue in the US Senate, where lawmakers are
considering loosening the restrictions. Some senators unhappy
with those proposals have suggested that 'alternative' methods
of deriving the cells, which don't requir e the destruction of
viable embryos, could help to bridge the ethical divide (see
Nature 436, 309; 2005).
Until now, such
methods have been purely theoretical, but in work published
online by Nature this week, two teams report their
successful use in mice. Rudolf Jaenisch and Alexander Meissner
of the Massachusetts Institute of Technology describe a
variant of therapeutic cloning called altered nuclear transfer
(ANT), in which a gene in the patient's donated cell is
switched off before the nucleus is transferred into a
fertilized egg. The resulting egg grows into a normal ball of
cells called a blastocyst from which ES cells can be derived,
but the deactivated gene means that the ball lacks the ability
to implant in a uterus and so develop into a baby (A. Meissner
and R. Jaenisch Nature doi:10.1038/nature04257;
2005).
In the other paper, a team led by Robert Lanza of
Advanced Cell Technology in Worcester, Massachusetts, plucked
single cells called blastomeres from eight-cell embryos. They
derived new ES cell lines from the blastomere, while the
embryos went on to form apparently healthy mice (Y. Chung
et al. Nature doi:10.1038/nature04277; 2005).
This method is similar to a technique used in in
vitro fertilization (IVF) called preimplantation genetic
diagnosis (PGD), in which a blastomere is removed from the
eight-cell embryo for genetic tests before it is implanted.
The work by Lanza's team raises the possibility that fresh
stem-cell lines could be derived from human embryos being used
in IVF before they are transferred to the uterus.
Although the quality of the work is impressive, there
is much disagreement over the ethical benefits of each
strategy. Some scientists seem more convinced by the PGD
method.
In the balance
"In my
mind, this takes away the ethical dilemma of destroying
embryos," says Alan Trounson, a reproductive biologist at
Monash University in Melbourne, Australia.
There
is currently a moratorium on therapeutic cloning in Australia,
due for review at the end of this year, and Trounson has
applied to the country's major medical funding agency to do
similar work with human PGD embryos.
But there is the
practical disadvantage that the resulting cell lines can come
only from the embryos of couples undergoing IVF, so wouldn't
be genetically matched to patients. And ethicists are troubled
by the question of whether the extracted blastomere itself has
the potential for life. "If you grow it in certain conditions,
it could divide and differentiate to have the same properties
as embryos," explains Yuri Verlinsky, chief executive of the
Reproductive Genetics Institute in Chicago.
Although the number of successful births from PGD
embryos indicates that removing a single cell early on doesn't
compromise the baby, it is still possible that it might have
subtle long-term consequences. "You are getting a live birth,
but are you getting the same child you would otherwise get?"
asks William Hurlbut, a consulting professor at Stanford
University and a prominent advocate of ANT. "It is
uncomfortable to me to endorse such a strategy."
Because
of this, Hurlbut says that the PGD method is unlikely to get
past the Dickey Amendment, which is passed by the US Congress
every year and forbids federal funds being spent on
experiments that endanger or destroy an embryo. And President
George W. Bush's Council on Bioethics, on which Hurlbut sits,
dismissed the idea earlier this year in a white paper on
alternative means for deriving ES cells.
The ANT
method of altering the genetic make-up of an embryo troubles
some scientists, but seems more acceptable to conservative
ethicists and religious figures. "I think this is an
artificial concept and I'm not comfortable with it," says
Trounson. "You do an engineering step to essentially destroy
the embryo so that you can then use it." Because of this, some
argue that ANT might itself fall foul of the Dickey
Amendment.
George
Daley of Harvard Medical School in Boston is also unconvinced,
partly because the effects of the genetic modification don't
kick in until the eight-cell stage. "A normal embryo and the
embryo created by this method are indistinguishable until that
stage," he says.
But Hurlbut maintains that the
altered embryo has no moral status. "You have the embryonic
equivalent of brain death," he says. "This changes the dynamic
of the political debate," agrees analyst Eric Cohen of the
Ethics and Public Policy Center in Washington DC.
Hurlbut
is doing all he can to push ANT, and has compiled a public
letter supporting it signed by scientists, ethicists and
religious figures. And in August 2004, he persuaded William
Levada, one of the most prominent Catholics in the United
States, to write to President Bush encouraging him to consider
the method. The president's bioethics council also gave the
idea tentative support in its white paper.
Some
observers warn against overreacting to the work. "If science
gets us to the point where we don't need embryos any more
that's fine, but right now policy-makers are making a huge
mistake if they say 'we've got one paper and we'll make policy
based on that'," says Sean Tipton of the Coalition for the
Advancement of Medical Research in Washington DC.
And
either way, the ethical debate over what constitutes life ? or
the potential for life ? looks set to dog the field. "The
challenge is to define what an embryo is," says Hurlbut. "We
need to sort that out or we'll be having this argument all the
way along."
References
- Meissner A. Jaenisch R. . Nature
advanced online publication doi:
10.1038/nature04257 (2005).
- Chung Y. et al. Nature
advanced online publication doi:
10.1038/nature04277
(2005).
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