Scientists Hail Embryo-Free Stem Cell Coup ; Studies Using Human Skin Lauded As ‘a Huge Deal’

By MALCOLM RITTER, THE ASSOCIATED PRESS

Scientists have made ordinary human skin cells take on the chameleon-like powers of embryonic stem cells, a breakthrough that might someday deliver the medical payoffs of embryo cloning without the controversy.

Laboratory teams on two continents report success in a pair of landmark papers released Tuesday. It’s a neck-and-neck finish to a race that made headlines five months ago, when scientists announced that the feat had been accomplished in mice.

The “direct reprogramming” technique avoids the swarm of ethical, political and practical obstacles that have stymied attempts to produce human stem cells by cloning embryos.

Scientists familiar with the research said scientific questions remain but that the new work is a major coup.

“This work represents a tremendous scientific milestone the biological equivalent of the Wright Brothers’ first airplane,” said Dr. Robert Lanza, chief science officer of Advanced Cell Technology, which has been trying to extract stem cells from cloned human embryos.

“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.”

The White House lauded the papers, saying such research is what President Bush was advocating when he twice vetoed legislation to pave the way for taxpayer-funded embryo research.

There is a catch with the new technique. At this point, it requires disrupting the DNA of the skin cells, which creates the potential for developing cancer. So it would be unacceptable for the most touted use of embryonic cells: creating transplant tissue that in theory could be used to treat diseases like diabetes and Parkinson’s, and spinal cord injury.

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

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

Both reported creating cells that behaved like stem cells in a series of lab tests.

Thomson, 48, made headlines in 1998 when he announced that his team had isolated human embryonic stem cells.

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.

For the new work, the two men 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, who was working his way from embryonic to fetal to adult cells, said he’s still analyzing his 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.

“People didn’t know it would be this easy,” Thomson said. “Thousands of labs in the United States can do this, basically tomorrow.”

In New Jersey, Dr. Joseph R. Bertino, interim director of the Stem Cell Institute of New Jersey in New Brunswick, called the results “very exciting.”

Skin cells “can differentiate into different cell lines,” he said. “The process is not completely efficient yet, but it’s very exciting stuff.”

Any good laboratory, including those in New Jersey, could begin reprogramming skin cells within 6 months to a year, Bertino said.

“We’ll be talking about it in our lab, if we just had a few more bucks,” he said. Earlier this month, New Jersey voters defeated a $450 million bond issue for stem cell research as being too costly to taxpayers, and unethical to those who oppose research using human embryos.

Skin cells, however, do not pose the ethical and moral barriers presented by embryonic stem cells, he said.

“We’re not sacrificing embryos,” by using skin cells, Bertino said. “That’s the big ethical issue.”

Scientists prize embryonic stem cells because they can turn into virtually any kind of cell in the body. The cloning approach which has worked so far only in mice and monkeys should be able to produce stem cells that genetically match the person who donates body cells for cloning.

That means tissue made from the cells should be transplantable into that person without fear of rejection. Scientists emphasize that any such payoff would be well in the future, and that the more immediate medical benefits would come from basic research in the lab.

In fact, many scientists say the cloning technique has proven too expensive and cumbersome in its current form to produce stem cells routinely for transplants.

The new work shows that the direct reprogramming technique can also produce versatile cells that are genetically matched to a person. But it avoids several problems that have bedeviled the cloning approach.

For one thing, it doesn’t require a supply of unfertilized human eggs, which are hard to obtain for research and subjects the women donating them to a surgical procedure. Using eggs also raises the ethical questions of whether women should be paid for them.

In cloning, those eggs are used to make embryos from which stem cells are harvested. But that destroys the embryos, which has led to political opposition from President Bush, the Roman Catholic church and others.

Those were “show-stopping ethical problems,” said Laurie Zoloth, director of Northwestern University’s Center for Bioethics, Science and Society.

The new work, she said, “redefines the ethical terrain.”

Richard Doerflinger of the U.S. Conference of Catholic Bishops called the new work “a very significant breakthrough in finding morally unproblematic alternatives to cloning. … I think this is something that would be readily acceptable to Catholics.”

White House spokesman Tony Fratto said the new method does not cross what Bush considers an “ethical line.” And Republican Sen. Tom Coburn of Oklahoma, a staunch opponent of publicly funded embryonic stem cell research, said it should nullify the debate.

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.

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(SIDEBAR)

What ‘direct reprogramming’ means for future treatment Obstacles may be overcome

Embryonic stem cells can develop into all kinds of tissue. Scientists have long sought to find a way to create such cells that are genetically matched to patients, because of the potential for new ways to treat disease and injury.

They’ve pursued this through cloning, which uses embryos. But through a new method, “direct reprogramming,” scientists have found a way to produce cells that appear virtually identical to stem cells, without using embryos.

How big a breakthrough is this?

Huge. One researcher compared it to the Wright Brothers’ airplane. Ian Wilmut, who cloned Dolly the sheep, said he is dropping the cloning approach for stem cells to begin testing this new method.

What’s so great about this new approach?

It doesn’t require women’s unfertilized eggs to make embryos; human eggs are in short supply for research. And it doesn’t involve the destruction of embryos, which is required to harvest stem cells from within them. That destruction has led some groups to oppose the cloning approach for ethical and religious reasons.

Does this mean scientists will no longer need human eggs or embryos?

No. Scientists say research should continue on embryonic stem cells. But this new development will likely reduce the demand.

How does the new method work?

Four genes were inserted into each skin cell. Scientists knew these particular genes turn other genes on and off, but how the combination converted skin cells into mimics of stem cells remains a mystery.

Are these cells so-called “adult stem cells?”

No. That term refers to cells found in the body that already have the ability to morph into a variety of cell types. They don’t need the four-gene treatment.

Are there any drawbacks to this new approach?

At this early stage, the technique being used disrupts the DNA of the skin cells, which leads to a potential for cancer. For now, that makes it unacceptable as a way to create stem cells for disease treatment. But the DNA disruption is just a byproduct of the technique, and experts believe there is a way to avoid it.

What does it mean for average people? Can we expect to see new treatments anytime soon?

Not for years. Besides overcoming the cancer obstacle, scientists still have to answer basic questions about these cells. In medicine, these cells would probably be used first for lab studies like screening potential drugs.

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Staff Writer Bob Groves contributed to this article.

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