Advance May End Stem Cell Debate

Thomson, a shy and laconic laboratory researcher whose 1998 discovery made him the focus of religious opprobrium and repeated congressional hearings, expressed relief that he may 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" the cells.

Thomson's and Yamanaka's reports were released online yesterday by the journals Science and Cell, respectively.

Human embryonic stem cells, from days-old embryos, can multiply without limit and also develop into all of the 200 or so types of cells that make up the body. But because extracting them typically destroys the embryo, experiments with them 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, too, raised concerns because large-scale harvesting of eggs from women can be 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 at high levels together, can turn countless other genes on and off in just the right pattern to make skin cells almost indistinguishable from embryonic stem cells. Yamanaka 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, the skin cells took on virtually all the characteristics of embryonic ones.

Because the rejuvenated cells did not come from embryos and behave slightly differently from embryonic stem cells, Yamanaka named them "induced pluripotent stem cells," or "ips" cells (pluripotent means "able to become virtually every kind of").

He immediately tried the same technique on human skin cells but failed repeatedly. What he did not realize, he said, was that the process takes weeks in human cells, compared with just days in mouse cells. After waiting several days for signs of colonies, he had been throwing out his cultures in frustration.

"We were not patient enough," he said.

Ultimately, he found he could get about 10 ips cell colonies from every 50,000 skin cells, an acceptable ratio given how easy it is to grow thousands of skin cells from a tiny sample. He coaxed the ips cells to become nerve cells, heart cells that beat in the dish, and other major cell types. And he showed that they were exact genetic matches to the skin cells they came from, suggesting that tissues or organs grown from them could be transplanted into the donor of the skin cells and not be rejected.