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Mice stem cells made without harm to embryos

Scientists provided the first definitive evidence Sunday that embryonic stem cells can be grown in laboratory dishes without harming healthy embryos, an advance that some believe could make the research more politically and ethically acceptable.
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Two teams of scientists provided the first definitive evidence yesterday that embryonic stem cells can be grown in laboratory dishes without harming healthy embryos, an advance that some scientists and philosophers believe could make the medically promising field more politically and ethically acceptable.

The work, done with mouse cells, generated several colonies of mouse embryonic stem cells without destroying any embryos that otherwise could have developed into mice.

If the new approaches were to work with human cells, as many scientists suspect, they could help defuse a moral maelstrom that has raged since human embryonic stem cells were discovered seven years ago. But the new techniques raise ethical issues of their own, leaving their ultimate value uncertain for now.

Stem cells from days-old human embryos can morph into virtually every kind of tissue, including nerves to replace those destroyed by spinal injuries and cardiac muscle to fill in for cells lost in a heart attack. Scientists see stem cells as the key to a new era of regenerative medicine.

Until now, however, the only way to get these cells was to destroy young embryos — which, though smaller than the period at the end of this sentence, are deemed by some people as "the youngest members of the human family" and deserving of certain human rights.

An alternative acceptable to all?
The new work suggests an alternative may be possible.

"This establishes the scientific feasibility of the idea that you can obtain fully functional embryonic stem cells from an entity that is not a natural, normal embryo," said William B. Hurlbut, a Stanford University professor and member of President Bush's Council on Bioethics.

But few scientists, ethicists or others, it turns out, are convinced that the new methods transcend the problems inherent in traditional stem cell approaches. Many say the new work only reveals how intractable the problem remains and how unlikely it is that science will resolve what is essentially a matter of spiritual belief.

That is because one of the new methods still subjects a human embryo to a small added risk, and, even more controversially, the other approach involves deliberately creating an embryo with a disabled version of a gene that is crucial to normal development.

Doomed from the start
Although some people condone experiments on such gene-altered embryos because they have no potential to grow into babies, others see the work as the purposeful creation of fatally hobbled beings to use as research subjects.

"The concern is that an embryo is being generated that is doomed to die very soon," said Markus Grompe, a geneticist who runs the stem cell program at Oregon Health & Science University in Portland.

Alexander Meissner and Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Mass., created those altered embryos by first disabling a gene called Cdx2 in a skin cell taken from a mouse. That gene is not normally active in skin, but during early embryo development it governs the creation of the placenta, which allows a developing fetus to feed and survive in the womb.

As described in yesterday's online issue of the journal Nature, the team fused that cell with a mouse egg whose own genetic material had been removed — a now-commonplace cloning procedure that leads to the growth of an embryo in a lab dish. In this case, though, with every new cell in the growing embryo lacking Cdx2, the embryo had no hope of growing a placenta.

Treading tricky ethical ground
That raises the tricky philosophical question of what moral standing, if any, such balls of cells have in their first days, and whether their creation is a mere experiment in cell biology or an act of cruelty.

"Nobody should be speaking too quickly here on either side," said Robert P. George, a Princeton professor of jurisprudence and a member of Bush's bioethics council. "The way to find out is to do the careful studies to figure out exactly what you've got here. It's not a spiritual question. We're not looking for a soul. The question is, 'Does it have the [biological basis] for self-construction and self-organization, or is it a fundamentally disordered growth?' "

Hurlbut emphasized that the experiments simply proved the approach's potential. He acknowledged that less controversy might arise if scientists knocked out genes that are crucial even earlier in development so the embryo is disabled essentially from the moment of its creation.

"This is just the beginning of the conversation," Hurlbut said. "It's time for everyone to humbly enter a constructive dialogue and listen deeply here."

Potential for life debated
Robert Lanza of Advanced Cell Technology in Worcester, Mass., describes a different approach in the same issue of Nature. His approach involved the removal of a single cell from an even younger, eight-cell mouse embryo. Previous research had shown that such seven-celled embryos can develop as normally as eight-celled ones.

But in the new work, Lanza showed that under the right culture conditions, the single removed cell can be prompted to grow into a colony of embryonic stem cells.

Several researchers said that Lanza's technique is the less useful of the two, because Jaenisch's cloning step allows researchers to design stem cells specifically matched to a patient's needs.

Others expressed concern that the single cell that Lanza starts with might itself have the potential to become a new embryo. Scientists do not know whether that is true, but if so, the approach would not pass muster with those who insist that embryos must not be created for research purposes.

Congress has been mulling several bills related to stem cell research, including one that would loosen restrictions on the federal funding of human embryonic stem cell research and others that would provide new funding for alternative approaches such as Jaenisch's and Lanza's.

Like many scientists, Lanza said he favored more research dollars for traditional and alternative approaches to making the cells.

"It would be tragic," he said, "not to pursue all the opportunities and methods available to us to get this technology to the bedside as soon as possible."