Split opens over methods to create nonviable embryos.
Erika Check & Carina Dennis
10/17/05(news@...) - 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.