Stem-cell advance opens up the field

Colonies of tiny cells flourishing in petri dishes in the US and Japan are reshaping the political and ethical landscape surrounding human stem-cell research.

In the process, these diminutive colonies also may level the playing field in stem-cell research – internationally and domestically.

These are some of the effects analysts say they see coming out of this week's announcements that two teams have genetically reprogrammed skin cells so that they take on the traits of embryonic stem cells.

Embryonic stem cells are the subject of intense medical interest because of their ability to develop into any of the major cell types in the human body. Over the long term, these stem cells could become the foundation for therapies for a range of diseases, scientists say. This week's announcement suggests it will be possible for scientists to study these cells without the ethical and political difficulties of harvesting them from unused human embryos.

For the emerging field of stem-cell research, "this is enormous," says Jesse Reynolds, a policy analyst at the liberal Center for Genetics and Society, based in Oakland, Calif. "I can't think of another development "that has been this big,"

"This is a paradigm shift," agrees Rev. Tad Pacholczyk, director of education at the National Catholic Bioethics Center in Philadelphia. "This will have a huge impact on the ethical debate."

That debate has centered on the sources for human embryonic stem cells – especially those that have the potential to be patient-specific. For research purposes, scientists have turned to fertility clinics where patients either have donated their nascent embryos to research or no longer need them to start a family. But the process of extracting the stem cells destroys these soon-to-be embryos, technically called blastocysts. The destruction is abhorrent to those who hold that human life begins at conception.

The ethical debate grows more heated when cloning – the most controversial idea for generating patient-specific stem cells – enters the picture. In 1997, a team in Scotland led by Ian Wilmut cloned Dolly the sheep from adult tissue by extracting the DNA from nucleus of adult cells and injecting it into the emptied nuclei of unfertilized sheep eggs. The eggs were fertilized, then implanted into ewes.

The approach is banned in humans. Last week, however, scientists from the Oregon National Primate Research Center in Beaverton, reported for the first time that they had used the technique to generate embryonic stem cells cloned from an adult primate – a macaque monkey. This strongly hinted that eventually the approach could work with humans.

But the technique, which in principle could draw on a patient's own cells to generate new tissue for treatments, is highly inefficient – requiring many eggs to yield one successful clone from which stem cells can be drawn and nurtured. It implies generating nascent embryos exclusively as stem-cell factories. And it raises the concern among many people that the approach will lead eventually to cloning humans as a means of reproduction.

By contrast, the US and Japanese teams discovered genetic triggers that could in effect turn back the clock on already-developed cells. Working independently, each team found four genes that, when introduced into the nucleus of skin cells, yielded cells indistinguishable from embryonic stem cells. The Japanese team, led by Kazutoshi Takahashi at the University of Kyoto, used the approach on mice last year. His lab, and one led by the University of Wisconsin's James Thompson, essentially tied for the race to test the approach using human cells.

For now, the two groups' work "changes everything and changes nothing; and caution is warranted," says Dr. Thompson. "This changes everything because these are not from embryos." But, he adds, it changes nothing because scientists still don't know how embryonic stem cells morph into the wide variety of cell types in the body. The caution comes because without that information, it's unclear if the new cells can live up to their promise. Thus, research on human embryonic stem cells is still vital, he emphasizes.

Still, some labs appear to be doing that. In Scotland, Dr. Wilmut announced earlier in the week that his lab is dropping the cloning approach and focusing on the genetic reprogramming approach as well.

If this is any indication, a shift in stem-cell research could follow. The new technique's relative ease, lower cost, higher output, and scrubbed-up ethics are likely to draw more labs into the field, Thompson suggests.

Moreover, such an expansion might further invigorate US research in the face of aggressive competition from countries like Britain and Japan.

The advance could trigger some interesting political shifts, some analysts suggest. For example, US restrictions on embryonic stem-cell research could become harder to change in light of these discoveries, according to Alta Charro, a University of Wisconsin law professor.

Already, the issue appears to be losing traction, Mr. Reynolds adds. Earlier this month, for instance, New Jersey voters rejected a plan to borrow $450 million for the state's stem-cell research program.

Indeed, the defeat, the discoveries, and the prospect that a new administration might loosen the federal purse strings for human embryonic stem research could add an element of uncertainty to existing or planned state stem-cell programs.

"Right now, all of the activities on the pro-stem-cell front in the states has been driven by the lack of federal funding for this research," says Patrick Kelly of the Biotechnology Industry Organization. "So if a new administration comes in and approves more federal funding, the need in the states is going to be diminished." But in states with existing programs "I don't think they'll ever be redundant."