Researchers Turn Skin Cells Into Stem Cells
Researchers in
The unencumbered 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 today, 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 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 Q. 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 -- "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 mere 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
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 today 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 F. 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
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 today 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.
Because the rejuvenated cells did not come from embryos and behave slightly differently than embryonic stem cells, Yamanaka named them "induced pluripotent stem cells," or "ips" cells ("pluripotent" means "able to become virtually every kind of" cell).
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 to just days in mouse cells. After waiting several days for signs of colonies, he had been making the mistake of throwing his cultures out 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 efficiency given how easy it is to grow thousands of skin cells from a tiny sample. He coaxed the ips cells to become nerve cells, beating heart cells 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 person who donated the skin cells and not be rejected.
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."
His cells passed the same tests as Yamanaka's, though in his final recipe, two of the genes he used were different.
"Apparently there are various ways to get to Rome," said Rudolf Jaenisch, a stem cell researcher at the Whitehead Institute for Biomedical Research in Cambridge, Mass. "We don't have to do it like the egg. We can do it differently."
Stem cell experts were unanimous in their praise of the work.
"It verifies what we've been saying all along, that this is an area of biology with enormous promise," said Douglas A. Melton, co-director of the Harvard Stem Cell Institute.
Some of the hurdles to medical applications have already begun to be overcome. One of the genes that Yamanaka used, called c-myc, can initiate cancers, for example. But Thomson's recipe does not include c-myc, and in recent studies, Yamanaka has succeeded with a three-gene cocktail that excludes c-myc.
More generally, retroviruses are a problem because they disrupt a cell's DNA in random locations, which can trigger tumor growth.
Both Thomson and Yamanaka said they are experimenting with methods that don't involve retroviruses. Among the more promising approaches, they said, are adenoviruses and fatty bubbles called liposomes, which deliver genes to cells without harming DNA, or direct injections of the biochemicals that the added genes were producing inside the cell.
Scientists differed on how big a challenge it would be to transcend retroviruses, but several said they were not concerned. "I don't think it is a big hurdle," Jaenisch said.
Despite the excitement over the new work, experts predicted that the fight over embryonic stem cells will linger, since they remain the gold standard against which all alternatives will be compared.
"It's still not clear which will be the best for specific applications that might ultimately benefit people with these awful diseases," Battey said. "But I suspect both sides will use these papers to make their case. Opponents [of embryonic stem cell research] will say here's another reason why we don't have to do it anymore. Others will say that it's clear ips cells are not exactly the same, so we need to continue the research."
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