Scientists have reprogrammed skin cells into various types of cells, including heart, muscle and brain tissue. *

Image: Cell Press * In an unprecedented feat of biological alchemy, researchers have turned human skin cells into stem cells that hold the same medical promise as controversial embryonic stem cells.

Two teams of researchers – one led by Kyoto University's Shinya Yamanaka, the other by the University of Wisconsin's Junying Yu – used a virus to add four new genes to skin cells. Thus transformed, the reprogrammed cells became capable of changing into nearly any cell type in the human body. Embryonic stem cells also have this ability, and may someday be used to cure degenerative diseases, grow new organs and even replace limbs.

"It's a new era for stem cells," said Robert Lanza, chief science officer of Advanced Cell Technologies, a cloning company in California. "It's the holy grail. It's like turning lead into gold."

Scientists have hailed embryonic stem cells as one of the most promising research fields in medicine, saying they could lead to myriad therapies. But currently, many stem cells are derived from embryos, which is a lightning rod issue that crosses political and religious lines. The new technique could sidestep ethical issues involving the destruction of embryos and collection of human eggs.

If the new method proves successful, "we can disconnect the whole stem cell debate from the culture war, from battles over embryo politics and abortion rights," said Marcy Darnovsky, associate director of the Center for Genetics and Society.

In a field accustomed to breathless proclamations of breakthroughs, the research – published Tuesday in two papers appearing in the journals Cell and Science – has provoked wonder among many scientists. They say the advance is more significant to medical research than last week's announcement that scientists had cloned the first monkey embryo.

Even Ian Wilmut of Dolly-the-sheep cloning fame said he's abandoning cloning with the prospect of this new research.

The technique essentially reverts mature cells to an embryo-like state. Normally, skin and other mature adult cells are locked into their biological fate. Scientists say the cells have "differentiated." But in the new research, scientists added genes to mature cells that turned back their cellular clocks, or dedifferentiated them, restoring them to an immature, unprogrammed state.

"Nobody knows exactly what happens, but when we introduce the genes, it basically changes gene expression inside the cell, and that changes the fate of the skin cells," Yu said. "Some eventually turn into stem cells."

Yamanaka and Yu say they must now learn to guide their cells' development. So far, the reprogrammed cells have been successfully turned into heart, muscle and brain tissue.

Embryonic stem cell research is a lightning rod issue that crosses political and religious lines. Many anti-abortion activists oppose embryonic stem cell research, because it requires the destruction of four-day-old embryos.

Women's health advocates protest because therapeutic cloning – one method of deriving embryonic stem cells – requires a supply of human eggs, and getting them relies on potentially risky hormone treatments.

President Bush's first veto of his presidency was for a bill that would have expanded federal funding for embryonic stem cell research. In 2001, he announced a strict plan for limiting government-funded research only to cells (from pre-existing lines) approved by the National Institutes of Health.

It does have some unlikely supporters, including conservatives like Sens. Orrin Hatch (R-Utah) and Arlen Specter (R-Pennsylvania) support embryonic stem cell research, saying an embryo so young and existing only in a petri dish is not yet a human life.

Lanza of Advanced Cell Technologies tempered his enthusiasm for the new technique with a warning that it's too soon to know whether cell reprogramming will provide medical benefits.

"This is early-stage research. We should not abandon other areas of stem cell research. It's by no means certain they'll differentiate in the same way as a normal embryonic stem cell," he said.

Because adding new genes may cause unsafe mutations, the researchers must also figure out how to make the new genes delete themselves during cellular division. But they believe the hardest part is behind them.

"It could take years, but compared to identifying the deprogamming genes, we consider this much less of a problem," said Yu.

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