Stem Cell Breakthrough Defuses Debate

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NEW YORK — Scientists have created the equivalent of embryonic stem cells from ordinary skin cells, a breakthrough that could someday produce new treatments for disease without the explosive moral questions of embyro cloning.

Research teams in the United States and Japan showed that a simple lab technique can rival the complex and highly controversial idea of extracting stem cells from cloned embryos.

It was a landmark achievement on all fronts, defusing one of the most divisive debates in modern medicine and religion. It was lauded by scientists, ethicists and religious groups.

"This work represents a tremendous scientific milestone — the biological equivalent of the Wright Brothers' first airplane," said Dr. Robert Lanza, whose company, Advanced Cell Technology, has been trying to extract stem cells from cloned human embryos.

"It redefines the ethical terrain," said Laurie Zoloth, a bioethicist at Northwestern University.

"It's a win-win for everyone involved," said the Rev. Thomas Berg of the Westchester Institute, a Roman Catholic think tank. "We have a way to move forward which ... brings the kind of painful national debate over this controversial research to very much a peaceful and promising resolution."

At the White House, President Bush, who vetoed two bills to allow federal funding for stem-cell research, was described as "very pleased."

"The president believes medical problems can be solved without compromising either the high aims of science or the sanctity of human life," said a statement from his press secretary.

The new technique reprograms cells, giving them the chameleon-like qualities of embryonic stem cells, which can morph into all kinds of tissue, such as heart, nerve and brain. As with embryonic cells, the hope is to speed medical research. For example, one day an ailing patient might benefit from genetically matched healthy tissue that would replace damaged cells.

The research was published online Tuesday by two journals, Cell and Science. The Cell paper is from a team led by Dr. Shinya Yamanaka of Kyoto University; the team published by Science was led by Junying Yu, working in the lab of stem-cell pioneer James Thomson of the University of Wisconsin-Madison.

Both groups reported that the reprogrammed cells behaved like stem cells in a series of lab tests. Their papers ended a scientific race that broke into wide view just this summer, when the achievement was reported in mice.

The scientists themselves were startled by their success.

"I was surprised when we achieved our results with the mouse," Yamanaka said. "But proving what we could do with human cells really bowled me over."

Thomson said he was surprised it didn't take longer to discover how to reprogram ordinary cells. The technique, he said, is so simple that "thousands of labs in the United States can do this, basically tomorrow."

In contrast, the cloning approach is so complex and expensive that many scientists say it couldn't be used routinely to supply stem cells for therapy.

While the discovery seems likely to shift the direction of research, Thomson and others said it's too soon to give up on studying embryonic stem cells.

He said he believes the ethical turmoil surrounding the embryonic cells set the field back four or five years. The new results are "probably the beginning of the end for that controversy," he said.

But he said his team wasn't trying to find a way around the ethical debate by pursuing the new technique. "We just thought this was a more practical approach," he said.

An official of one group fiercely opposed to destroying embryos saw things differently, saying scientists should thank "pro-life voices" for pushing them to find alternatives.

"The results are groundbreaking studies like these," said Carrie Gordon Earll, bioethics analyst for Focus on the Family, a conservative Christian group.

The controversy over embryonic stem cells has been a touchstone of national politics. It inspired impassioned pleas by Nancy Reagan, the actor Michael J. Fox, who suffers from Parkinson's disease, and countless ordinary citizens arguing in favor of the potential medical benefits.

Equally heartfelt were objections that destroying embryos to extract the stem cells meant destroying human life.

No federal money was available for embryonic stem cell research until 2001, when President Bush allowed very limited funding. Some states like California and Connecticut responded to his restrictions by setting up their own programs to pay for it.

The new work shows that like cloning, "direct reprogramming" can also use ordinary body cells to create versatile cells that are genetically matched.

"It's a bit like learning how to turn lead into gold," said Lanza, while cautioning that the work is far from providing medical payoffs.

"It's a huge deal," agreed Rudolf Jaenisch, a prominent stem cell scientist at the Whitehead Institute in Cambridge, Mass. "You have the proof of principle that you can do it."

There is a catch. At this point, the technique disrupts the DNA of the skin cells, and that creates the potential for developing cancer. So it would be unacceptable for transplanting into a patient.

But the DNA disruption is just a byproduct of the technique, and experts said they believe it can be avoided.

For the new work, the two scientific teams chose different cell types from a tissue supplier. Yamanaka reprogrammed skin cells from the face of an unidentified 36-year-old woman, and Thomson's team worked with foreskin cells from a newborn. Thomson's team, which was working its way from embryonic to fetal to adult cells, is still analyzing its results with adult cells.

Both labs did basically the same thing. Each used viruses to ferry four genes into the skin cells. These particular genes were known to turn other genes on and off, but just how they produced cells that mimic embryonic stem cells is a mystery.

Both Thomson, 48, and Yamanaka, 45, had already produced notable achievements. Thomson made headlines in 1998 when he announced that his team had isolated human embryonic stem cells.

And Yamanaka gained scientific notice in 2006 by reporting that direct reprogramming in mice had produced cells resembling embryonic stem cells, although with significant differences. In June, his group and two others announced they'd created mouse cells that were virtually indistinguishable from stem cells.

Zoloth, the ethicist at Northwestern, noted that direct reprogramming avoids not only embryo destruction, but also the need for unfertilized human eggs to create embryos. Eggs are hard to obtain for research, and collecting them subjects women to drug treatment and surgery. Using eggs also raises the ethical question of whether women should be paid for them.

The embryo and egg issues were "show-stopping ethical problems," she said.

Another advantage of direct reprogramming is that it would qualify for federal research funding, unlike projects that seek to extract stem cells from human embryos, noted Doug Melton, co-director of the Harvard Stem Cell Institute.

Still, scientific questions remain about the cells produced by direct reprogramming, called "iPS" cells. One is how the cells compare to embryonic stem cells in their behavior and potential. Eventually, iPS cells might prove better for some scientific uses and cloned stem cells preferable for other uses. For example, scientists want to study the roots of genetic disease and screen potential drug treatments in their laboratories.

Scottish researcher Ian Wilmut, famous for his role in cloning Dolly the sheep a decade ago, has said he is giving up the cloning approach to produce stem cells and plans to pursue direct reprogramming instead.

Other scientists said it's too early for the field to give up studying stem cells from embryos.

Dr. George Daley of the Harvard institute, who said his own lab has also achieved direct reprogramming of human cells, said it's not clear how long it will take to get around the cancer risk problem.

His lab is pursuing both the reprogramming and cloning strategies.

"We'll see, ultimately, which one works and which one is more practical," he said,

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On the Net:

Journal Cell: http://www.cell.com

Journal Science: http://www.sciencemag.org

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