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Skin Cells Reprogrammed to Have Same Potential as Embryonic Stem Cells

By Malcolm Ritter, Associated Press, November 20, 2007

A new breakthrough in stem cell research could eliminate the moral questions of embryo cloning and produce new and ethical treatments. Scientists in Japan and the U.S. have created the equivalent of embryonic stem cells from ordinary skin cells.

The complex and highly controversial idea of extracting stem cells from cloned embryos can be rivaled according to Japanese and American researchers who used simple lab techniques to produce their results.

Religious groups, ethicists and scientists have applauded the groundbreaking discovery which has begun to defuse one of the most controversial debates in contemporary medicine and religion.

"This work represents a tremendous scientific milestone — the biological equivalent of the Wright Brothers' first airplane," said Dr. Robert Lanza, whose company, Advanced Cell Technology, has been trying to extract stem cells from cloned human embryos.

"It redefines the ethical terrain," said Laurie Zoloth, a bioethicist at Northwestern University.

"It's a win-win for everyone involved," said the Rev. Thomas Berg of the Westchester Institute, a Roman Catholic think tank. "We have a way to move forward which ... brings the kind of painful national debate over this controversial research to very much a peaceful and promising resolution."

President Bush was very pleased with the research. Earlier this year, he blocked federal funding for embryonic stem-cell research by vetoing two bills in favor of it.

"The president believes medical problems can be solved without compromising either the high aims of science or the sanctity of human life," said a statement from his press secretary.

Embryonic stem cells can develop into numerous types of body tissues. The new technique gives this same power to skin cells by reprogramming them. The new cells then have the potential to develop into brain, nerve, heart, and any other type of tissue. Using the discovery to boost the rate of speed for medical research is the hope say scientists. In the future, regenerative medicine may help a patient replace damaged organs with new, healthy, genetically matched tissue that has been developed cells such as the ones discovered by the Japanese/American research.

The journals Cell and Science both published papers on Tuesday regarding the breakthrough. Science published the work of Junying Yu, who was working in the lab of stem-cell pioneer James Thomson of the University of Wisconsin-Madison. Cell published a paper by the team led by Dr. Shinya Yamanaka of Kyoto University.

During a series of lab tests, both groups observed stem cell like behavior from the reprogrammed cells. When the achievement was reported in mice this past summer, a race began the both teams were able to finish with the publication of their respective papers.

The success of the research even surprised the scientists.

"I was surprised when we achieved our results with the mouse," Yamanaka said. "But proving what we could do with human cells really bowled me over."

The speed at which the ordinary cells were reprogrammed surprised Thompson the most.

The technique, he said, is so simple that "thousands of labs in the United States can do this, basically tomorrow."

On the other hand, supplying stem cells via cloning could not be done routinely say scientists. The approach is far to expensive and complicated.

Thompson said the ethical turmoil surrounding the embryonic cells set the field back four or five years. But that the new discovery seems likely to shift the direction of research.

The new results are "probably the beginning of the end for that controversy," he said.

Interestingly, the goal was not to find an ethical answer for embryonic stem cell research.

"We just thought this was a more practical approach," he said.

“Scientists should thank 'pro-life voices' for pushing them to find alternatives,” said an official from one group which is adamantly opposed to embryonic stem cell research.

"The results are groundbreaking studies like these," said Carrie Gordon Earll, bioethics analyst for Focus on the Family, a conservative Christian group.

National politics has been swayed and affected by the embryonic stem cell controversy. Countless ordinary citizens have argued in favor of the potential medical benefits, and more recognized individuals such as actor and Parkinson's Disease sufferer Michael J. Fox and Nancy Reagan have pleaded for embryonic stem cell research support.

Opposition towards embryonic research was equally strong, with the view that the research led to the destruction of human life.

President Bush allowed very limited funding for embryonic stem cell research in 2001. Prior to that time, no federal money was made available. But restrictions did not deter efforts in some states such as Connecticut and California where billions of dollars were allocated for the research.

Versatile cells that are genetically matched can also be created by using ordinary body cells with the “direct reprogramming” technique.

"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."

A tissue supplier provided different cell types to the two scientific teams. Thomson's team worked with foreskin cells from a newborn. Thomson's team, which was working its way from embryonic to fetal to adult cells, is still analyzing its results with adult cells. Yamanaka reprogrammed skin cells from the face of an unidentified 36-year-old woman.

Four genes were carried into the skin cells using viruses. Just how they produced cells that mimic embryonic stem cells is a mystery, but these particular genes were known to turn other genes on and off, and were therefore chosen for the experiments. In this regard, both labs did basically the same thing.

The two lead scientists are well versed in cellular research and are not unknown in the field.

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

And Yamnaka, who is 45, announced with two other groups in June, that they had created mouse cells that were virtually indistinguishable from stem cells. In 2006, he reported that direct reprogramming in mice had produced cells resembling embryonic stem cells, although with significant differences.

The need for unfertilized human eggs to create embryos as well as embryo destruction is avoided by direct reprogramming said Zoloth, who is the ethicist at Northwestern. Drug treatment and surgery must be used on women who are donating eggs, making them difficult to obtain. Also, the concept of paying a woman for her unfertilized egg raises even more ethical questions.

The embryo and egg issues were "show-stopping ethical problems," she said.

Doug Melton, co-director of the Harvard Stem Cell Institute said that unlike projects that seek to extract stem cells from human embryos, research involving direct reprogramming would qualify for federal research funding.

There are still questions surrounding the "iPS" cells that are produced by direct reprogramming. Scientists say that there is more research to be done before mankind can truly benefit from the discovery.

Regardless, the research has had a profound impact on the scientific community. Giving up the cloning approach to produce stem cells and switching to direct reprogramming instead, is Scottish researcher Ian Wilmut, famous for his role in cloning Dolly the sheep a decade ago.


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