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Studies cite new process for stem cells

Teams avoid ethical issues tied to embryos

Scientists in Massachusetts and Japan say they have created embryonic stem cells using procedures that might overcome many of the ethical objections to the controversial research, since the process does not destroy embryos.

In a separate study, meanwhile, a Harvard team said it had found a way to accelerate research to clone human embryonic stem cells, although embryos would still be destroyed.

Most dramatically, three independent research teams reported yesterday that they used a highly experimental approach to produce stem cells without destroying embryos, which critics equate to taking a life. Instead, they manipulated genes to coax ordinary skin cells of lab mice to regress to a state where they essentially behave like embryonic stem cells.

In effect, the researchers "turn back the clock from adult to embryonic stem cells," said Konrad Hochedlinger, a Massachusetts General Hospital researcher and leader of one of the teams. No eggs were used, no embryos destroyed -- a stunning advance, although perhaps difficult to replicate in humans.

Religious and political conservatives, whose moral objections to embryonic stem cell research have blocked most federal funding of the work, generally applauded the research. But the scientists warned that it could take years to figure out how to use the technique to create human stem cells. Meanwhile, they said, it is imper ative to follow other avenues of human stem cell research, including those that destroy embryos.

The US House is scheduled to vote today on a bill that would loosen federal funding restrictions on embryonic stem cell research. Some scientists have expressed worry that the mouse-skin research will provide ammunition to opponents of the legislation, by letting them argue there are alternatives to obtaining stem cells from embryos.

Embryonic stem cells are progenitor cells that can transform into any of the 220 basic tissue types in the body, from bone cells to brain cells. Scientists predict research on human embryos will yield insights, and potentially cures, into spinal injuries, diabetes and an array of other diseases.

The animal research methods, reported yesterday in print and online editions of two scientific journals, Nature and Cell Stem Cell, should eventually work in humans as well, scientists say.

"These new studies, done with mice cells, point the way to experiments that can be tried with human cells," said Douglas Melton, a Harvard stem cell scientist. "This represents some of the most exciting work in stem cell biology and genetic reprogramming."

In a fourth paper published in Nature yesterday, Harvard Stem Cell Institute researcher Kevin Eggan pointed to a new, readily available source of embryonic stem cells, fertilized eggs from fertility clinics, that would allow researchers to bypass a bottleneck in efforts to clone human stem cells genetically matched to a patient with a particular disease. Harvard has been unable to find women willing to donate unfertilized eggs for the research.

It had been long standing scientific belief that fertilized eggs cannot be used to clone embryonic stem cell lines, but Eggan showed that somatic cell nuclear transfer -- cloning, the same process that was used to make Dolly the sheep -- would work by removing chromosomes from a single-cell fertilized egg and replacing it with DNA from a mature cell. The modified cell began dividing, and Eggan said he harvested stem cells from the resultant embryo.

Although less razzle-dazzle than the techniques used by the other teams, Eggan's work holds the best prospect of creating human embryonic stem cell lines in the near future, authorities say.

"It's hugely important," said Dr. George Q. Daley, a stem cell scientist at Children's Hospital Boston. "It should make it much easier to establish human stem cell lines for medical research."

The study by Eggan suggested that researchers could use genetically defective fertilized eggs, discarded by the tens of thousands at fertility clinics across the United States. These eggs are stuck at the single-cell stage and are treated as waste because they stand no chance of attaching to the womb and forming a healthy embryo.

The Harvard Stem Cell Institute has already obtained such eggs and has begun using them in research aimed at "therapeutic cloning" of human embryos, according to Eggan.

"This represents a wonderful way of obtaining something good, medical research that could lead to therapies for human disease, out of something that would just be thrown away," Eggan said.

By taking advantage of an existing supply of fertilized eggs, scientists would not expose more women to health risks from the hormonal therapy required to stimulate egg production, a concern that has been raised by some women's groups.

The studies by the MIT-affiliated Whitehead Institute for Biomedical Research, Harvard-affiliated Mass. General Hospital, and Japan's Kyoto University represent the most successful attempts to date to find new ways to make embryonic stem cells that might overcome the ethical opposition to the destruction of human embryos.

"All in all, this is encouraging, exciting progress that shows real willingness among scientists to weigh ethical concerns even as they pursue science objectives," said Dr. William B. Hurlbut, a neuroscientist and ethicist at Stanford University who serves on the President's Council on Bioethics.

Hurlbut, an opponent of research methods that destroy human embryos, champions efforts to find alternative methods of creating stem cells. "The science is critical, of course. But so are many ethical concerns."

Scientists have made earlier advances on making stem cells without destroying embryos, but their results have typically either not been verified by other researchers or been too preliminary for grand claims.

But now, in nearly identical experiments, scientists from the three major institutions have replicated and strengthened earlier research by Dr. Shinya Yamanaka of Kyoto University, who last year discovered that the activation of four genes in mouse skin cells could forge a cell that behaved like an embryonic stem cell.

The research was regarded as incomplete, however, since Yamanaka was unable to generate live mice from the cell lines. In the latest experiments, the genetically derived cells were able to produce other forms of tissue and gave rise to generations of new mice.

"These reprogrammed cells are, by all criteria that we can apply, indistinguishable from embryonic stem cells," said MIT's Rudolf Jaenisch, leader of the Whitehead team. "But it will be a while before we know if this can ever be done in humans."

One big problem: The kind of viruses used to activate the genes are known to also trigger cancer.

Research on human embryonic stem cells has been slowed in the United States since President Bush, citing concerns about destruction of embryos, sharply limited federal funding of the science in 2001. But critics of the work applauded the latest research.

"Every research brings ethical questions, but in this research they seem more ordinary: what might be the eventual risks if this is someday used therapeutically" in humans, said Tadeusz Pacholczyk, a Roman Catholic priest who trained as a neuroscientist and who serves as director of education for the National Catholic Bioethics Center in Philadelphia. "It doesn't raise the huge issue of destroying human embryos. Instead it seems to clear up the ethical landscape."

He was much cooler toward Eggan's research using fertilized eggs, noting that it's a variation on cloning methods that entail destruction of the embryo to obtain stem cells.

"It's still heading for human cloning. It's still a powerful researcher putting a helpless embryo in a petri dish to be strip-mined for biological starter material," he said in an interview.

Eggan offered no apologies for his embryonic stem cell research.

"The moral status of embryos is one of the great issues in stem cell research. It deserves debate," he said, while stressing that he thinks it would be a tragic mistake for science to abandon traditional cloning methods to satisfy opponents' demands. "I believe in what we're doing and believe human embryonic stem cell research serves a greater medical good."

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