Two Labs Coax Skin Cells to Act Like Stem Cells Scientists Turn Skin Cells into Stem Cells in Breakthrough

By RICK WEISS

By Rick Weiss

The Washington Post

WASHINGTON

Researchers in Wisconsin and Japan have turned ordinary human skin cells into what are effectively embryonic stem cells without using embryos or women’s eggs – the two hitherto essential ingredients that have embroiled the medically promising field in a long political and ethical debate.

The ability to turn adult cells into embryonic ones capable of morphing into virtually every kind of cell or tissue, described in two scientific journal articles released Tuesday, has been the ultimate goal of researchers for years. In theory, it would allow people to grow personalized replacement parts for their bodies from a few of their own skin cells, while giving researchers a uniquely powerful means of understanding and treating diseases.

Until now, only human egg cells and embryos, both difficult to obtain and laden with legal and ethical issues, had the mysterious power to turn ordinary cells into stem cells. And until this summer, the challenge of mimicking that process in the lab seemed almost insurmountable, leading many to wonder if stem cell research would ever wrest free of its political baggage.

As news of the success by two different research teams spread by e-mail, scientists seemed almost giddy at the likelihood that their field, which for its entire life has been at the center of so much debate, may suddenly become like other areas of biomedical science: appreciated, eligible for federal funding and wide open for new waves of discovery.

“These are enormously important papers,” said George Daley, a stem cell researcher at Children’s Hospital Boston, who was not involved in the work. Like others, he spoke with stunned elation reminiscent of scientists’ reactions in 1997 to the cloning of Dolly the sheep from a skin cell, the first proof that adult mammal cells could have their genetic clocks turned back.

Their enthusiasm notwithstanding, scientists warned that medical treatments are not immediately at hand. The new method uses genetically engineered viruses to transform adult cells into embryo- like ones, and those viruses can trigger tumors. But the cells will be instantly useful for research purposes – “to move a patient’s disease into a petri dish,” as Daley put it. And some scientists predicted that, with the basic secret now in hand, it could be a matter of months before virus-free methods for making the versatile cells are found.

“This is a tremendous scientific milestone, the biological equivalent to the Wright brothers’ first airplane,” said Robert Lanza, chief scientific officer of Advanced Cell Technology in Worcester, Mass., a developer of stem cell therapies.

Especially gratifying to stem cell researchers was that some of their biggest critics seemed mollified.

Richard Doerflinger of the U.S. Conference of Catholic Bishops said he was at a Vatican-sponsored meeting recently where the technique was described.

“All the Catholic scientists and ethicists at the conference … had no moral problem with it at all,” he said. “This seems to be a way to get all the same uses that embryonic stem cells and cloning might be put to, without the moral problem.”

The White House released a statement praising the studies.

“President Bush is very pleased to see the important advances in ethical stem cell research reported in scientific journals today. By avoiding techniques that destroy life, while vigorously supporting alternative approaches, President Bush is encouraging scientific advancement within ethical boundaries,” the statement said. “The president believes medical problems can be solved without compromising either the high aims of science or the sanctity of human life.”

Another crucial vote of confidence came from James Battey, vice chairman of the National Institutes of Health’s stem cell task force, which oversees decisions about funding stem cell research.

“I see no reason on Earth why this would not be eligible for federal funding,” Battey said. “I think it’s a wonderful new development.”

Many teams had been racing to be first to create embryonic stem cells or their equivalents without embryos, building on a June report in which researchers found a way to do so in mice. Yet scientists around the world agreed that nobody deserved to win that race more than the two who did: James Thomson of the University of Wisconsin in Madison, who first isolated stem cells from 5-day-old human embryos in 1998, and Shinya Yamanaka of Kyoto University, who led the recent effort to obtain mouse stem cells without embryos.

Thomson, a shy and laconic laboratory researcher whose discovery of embryonic stem cells made him the focus of religious opprobrium and repeated congressional hearings, expressed relief that he might now be able to work without being at the center of what had become America’s other abortion debate.

“What a great bookend,” Thomson said in an interview. “Ten years of turmoil and now this nice ending. I can relax now.”

Yamanaka also expressed relief – and surprise upon learning that others were so close on his heels.

“Many people in other labs were kind enough to tell me they were working on it,” he said. “But I did not know they had actually generated them.”

Thomson’s and Yamanaka’s reports are being published Tuesday in online editions of the journals Science and Cell, respectively.

Human embryonic stem cells are the cells in the core of days-old human embryos. They can multiply without limit and also differentiate into the 200 or so types of cells that make up the body. But because extracting them typically destroys the embryo, experiments have been attacked by those who believe that even the earliest stages of human life have moral standing.

An alternative way of making the cells, in which scientists fuse a skin cell to an egg cell whose own DNA has been removed, proved that egg cells harbor chemicals that can turn adult cells into embryonic ones, apparently by turning key genes on or off. But this method raised concerns that large-scale harvesting of eggs from women was medically risky and exploitative.

The dream of doing in a lab dish what an egg cell does naturally began to come true in June, when Yamanaka’s team identified four genes in mouse skin cells that, when operating together, can turn countless other genes on and off in just the right pattern to transform skin cells so that they are almost indistinguishable from embryonic stem cells. He put copies of those four genes into retroviruses, Trojan horse-like viruses that insert their genetic payloads into the DNA of cells they infect. Once infected by the engineered viruses, the skin cells took on virtually all the characteristics of embryonic ones.

At the same time, Thomson, Junying Yu and colleagues were racing ahead. Working from an initial list of 14 genes that seemed to be crucial to embryo cells, they gradually narrowed the recipe to just four genes, too.

“It took us forever to get to the finish line,” Thomson said. A lot of that time was spent checking for the emergence of slow- growing, embryo cell-like colonies in dishes, so “there was no eureka moment. It was a drawn-out thing.”

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