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The ethical debate over stem-cell research could be over now that the UW-Madison scientist who grew the world's first human embryonic stem cells has created similar cells without using or destroying embryos.

James Thomson used a virus to deliver four select genes into human skin cells, which triggered the cells to revert to their embryonic state. It is hoped that the reprogrammed cells can then be coaxed into many of the body's cell types, helping scientists better learn the causes of diseases and possibly leading to cures.

Since the technique doesn't destroy - or even use - embryos, it could lift the controversy surrounding stem-cell research, which has created fierce political divisions, debates over federal funding and competition among states.

"You're no longer destroying a human life" to do the research, said Barbara Lyons, executive director of Wisconsin Right to Life. "Objections will be removed."

Added Richard Doerflinger, deputy director for pro-life activities at the U.S. Conference of Catholic Bishops: "This is an advance that everyone can praise."

Thomson reported the groundbreaking development Tuesday in the journal Science, the same day a Japanese researcher published the same feat in the journal Cell.

Thomson said the new cells likely will replace stem cells from embryos at some point but urged research on both kinds of cells to continue.

"A few years from now, this will be considered more important than the derivation of embryonic stem cells," said Thomson, who elevated Madison's status in the science world by growing those cells in 1998. "It really does change the landscape in a fundamental way."

The discovery holds a new promise: creating stem cells genetically matched to patients with diabetes, Parkinson's disease, spinal-cord injury and other conditions. That would minimize the risk of immune system rejection of therapies crafted from the cells.

The ability to customize the cells also could bring more diversity to the stem cells available to scientists, key to using such cells to screen new drugs.

The Wisconsin Alumni Research Foundation, the university's tech-transfer agency, has applied to patent the research, WARF spokesman Andy Cohn said.

Thomson and his research team - including scientist Junying Yu, who spent four years identifying and screening the genes - have grown eight lines, or colonies, of the reprogrammed cells.

When the team learned last week that their landmark paper would be published this week, they popped a bottle of champagne, Yu said. "It feels great to be able to contribute to something with such great potential," she said.

\ Replacing old cells

Tests have shown that the reprogrammed cells, of which some lines have been growing for several months, are indistinguishable from stem cells extracted from embryos, Thomson said.

But he said further testing could reveal differences.

Shinya Yamanaka, the Japanese researcher, said in a news release that while his reprogrammed cells also appear to be very similar to embryonic stem cells, it is "premature to conclude that (they) can replace embryonic stem cells."

Furthermore, Thomson said the technique must be refined because it produces cells with extra copies of the four genes.

Thomson's published experiment, meanwhile, used skin cells from fetuses and cells from foreskins leftover from circumcisions - not skin cells from adults, the ultimate goal of the research.

But his team is now growing reprogrammed cells created from adult breast and abdominal skin tissue. Thomson said he expects those cells also will hold up well. Fetal tissue won't be needed to pursue the research in the long term.

Yamanaka's experiment used facial skin cells from adults.

While Thomson said the research leading to his discovery was grueling, the technique of placing the genes into skin cells should be easily carried out by many labs, now that the four genes have been pinpointed.

Stem-cell researchers likely will start using reprogrammed cells instead of cells from embryos, Thomson said, but the switch might take a while.

"People have to kick these cells around the block for a few years," he said. Asked if reprogrammed cells will supplant stem cells from embryos, he said, "My guess is, over time, the answer will be yes."

\ Different approaches

Doug Melton, a stem-cell researcher at Harvard University, heralded the breakthrough.

Yamanaka, of Kyoto University in Japan, last year was the first to reveal the successful creation of reprogrammed cells in mice; he and two other research groups published improvements on that step this July. Many scientists thought it would take years to do the same with human cells.

"We appear to be closer than we ever thought we might be to a day when we could use this alternative method," Melton said in prepared remarks.

Though Thomson and Yamanaka both reprogrammed human skin cells using four genes, their methods differed slightly. They used different viruses to deliver the genes. Both used genes called Oct4 and Sox2, but Thomson used two others called Nanog and Lin28, while Yamanaka used c-Myc and Klf4.

It's possible other recipes also could produce cells equivalent to embryonic stem cells, Thomson said.

\ No moral concerns

Those who oppose stem-cell research involving the destruction of embryos embrace the new approach.

Doerflinger, of the U.S. Conference of Catholic Bishops, compared the new technique to a car that can run on water, without the environmental problems of gasoline. "I don't think there's any major moral concern about this at all," he said.

President Bush, in an executive order in June, called for more funding of research on alternative methods of creating stem cells, including reprogramming. His directive came as he vetoed, for the second time, a bill to expand federal funding for research on stem cells from embryos.

Bush, like many religious conservatives, believes the destruction of embryos for research is immoral - even days-old embryos left over in fertility clinics that otherwise might be discarded. In August 2001, he adopted a policy providing federal funding for research on embryonic stem cell lines created by that point.

About 20 such lines, including five produced by Thomson, qualify. Most are stored at the National Stem Cell Bank. It is located at WiCell, a subsidiary of WARF, in University Research Park on Madison's West Side.

The National Institutes of Health, which helped pay for Thomson's reprogramming work, announced in September a plan to boost funding for such alternatives. But money to study the 20 lines created from embryos will continue, said James Battey, vice chairman of the NIH's Stem Cell Task Force.

"It remains unclear which cell source will yield a therapeutic outcome with maximal efficacy," Battey said in an e-mail interview.

\ Level playing field?

Thomson's new work could alter the course of the 2008 presidential campaign and level the playing field for stem-cell research among states, said Alta Charo, a UW-Madison bioethicist.

Charo said candidates on both sides of the aisle who may have been vocal in supporting an expansion of federal funding for research on stem cells from embryos now likely won't speak up. "This is going to take the air out of the balloon," she said.

Meanwhile, states such as California, which has started a $3 billion state-funded stem-cell initiative in response to the federal funding limits, might dominate the national scene less because more funding likely will become available across the country for the new method.

"It does take away some of California's advantage," Charo said.

Thomson, who has tried to stay out of the political fray caused by his 1998 announcement, said he is nonetheless pleased his new work may ease the ethical friction.

"My life should get a lot easier than in the last 10 years," said Thomson, who called his new discovery a "bookend" on the decade.

He said he feels privileged to have achieved two major breakthroughs.

"We got lucky twice," he said. "Fate rarely smiles on you like that."\ \ THE RESEARCH TEAM

James Thomson, lead scientist

Here are the names of all of the UW-Madison researchers who worked on the groundbreaking development about stem cells being reported today in the journal Science: Junying Yu, Maxim Vodyanik, Kim Smuga-Otto, Jessica Antosiewicz-Bourget, Jennifer Frane, Shulan Tian, Jeff Nie, Gudrun Jonsdottir, Victor Ruotti, Ron Stewart and Igor Slukvin.


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