Stem-cell breakthrough might erase controversy

Teams of scientists reported Tuesday they've succeeded in reprogramming human skin cells so they behave like highly prized but controversial embryonic stem cells. If the work overcomes "serious" hurdles, the breakthrough could benefit science without the controversy that has dogged stem-cell research.

While these cells don't have every attribute of the infinitely reprogrammable stem cells from embryos, they also don't present the moral quandary of those cells. Until now, such versatile stem cells could be obtained only by destroying a 4- to 5-day-old discarded embryo, which has bogged down the research in a nasty scientific and political quagmire.

The work appeared online in two prestigious journals, Cell and Science. The Cell paper comes from a group led by Shinya Yamanaka of Kyoto University in Japan. The Science paper comes from a group led by Junying Yu and James Thomson at the University of Wisconsin-Madison. Five months ago, the Yamanaka group reported similar success with mouse cells, setting the stage for the effort to get the technique to work in human cells.

Because human embryonic stem cells can develop into more than 200 tissue types in the body, many scientists envision them one day being used in laboratories to grow muscles, nerves and even whole organs, which could be used to treat ailments such as diabetes and spinal-cord injuries.

But both groups of scientists Tuesday said they don't know how close to true embryonic stem cells these new lines are.

While the work represents a tremendous scientific milestone and "a new era for stem cells," it doesn't mean that it's "ready for prime time," said Robert Lanza, chief science officer of Advanced Cell Technology, a company working to derive stem cells from cloned human embryos.

"Bottom line: There are very serious hurdles left to overcome," he said. "While this is exciting basic research, it could still take years to get this to work in humans in a way that could be used clinically."

News of the feat sparked huge interest, particularly among those who oppose research using stem cells derived from human embryos.

"The science has overtaken the politics," Karl Zinsmeister, the chief domestic-policy adviser to President Bush, said Tuesday. "If you set reasonable parameters and offer a lot of encouragement and public funding, science will solve this dilemma, and you don't have to have a culture war about this."

White House press secretary Dana Perino issued a statement saying Bush was pleased: "By avoiding techniques that destroy life, while vigorously supporting alternative approaches, President Bush is encouraging scientific advancement within ethical boundaries."

In 2001, Bush ordered that federal funds could be spent only on human embryonic stem-cell research using cell lines already in existence.

Yet study leader Thomson, who co-discovered human embryonic stem cells in 1998, said political barriers have hindered all such work and stressed that the new research would not have been possible without insights gained from embryonic cells.

"My feeling is that the political controversy set the field back about four to five years," Thomson said. He credited Bush with providing some funds for the field starting in 2001 but said the president's funding limits "represented very bad public policy as far as I'm concerned."

Several experts said that in retrospect, the most fundamental step forward came in Yamanaka's study last year that used mouse cells. By studying which genes are most active in mice's embryonic stem cells, his team picked out four genes that seemed crucial to making stem cells so versatile that they can form most kinds of tissue. Inserting the genes in ordinary mouse cells gave them the properties of embryonic stem cells.

In the new research, scientists activated dormant genes to coax the cells back to a point in embryonic development before they had committed to becoming skin.

The roots of such work can be traced to the birth in 1996 of Dolly the sheep, the first animal cloned from an adult cell.

Dolly showed that researchers could reset an adult cell's clock by placing its nucleus in an egg cell. Thomson said the challenge was to find a faster and more practical approach that could reset that clock by manipulating just a few genes.

In the study results released Tuesday, both teams used viruses to introduce the suite of genes into the cells. One hurdle now will be to find ways of adding the genes without viruses, or removing the viruses once they've done their work.

In addition, one of the genes the Japanese team used is an oncogene, meaning it has been linked to certain types of cancer. Thomson's group avoided using that gene, and other researchers say they are already pursuing safer methods.

In 2002, a Paris study with an experimental gene-based treatment that used a retrovirus added to stem cells was halted after four infants developed cancer and one died.

However, it may be possible to insert the genes without retroviruses, perhaps by using an agent that doesn't linger in the cells long enough to cause cancer, said Renee Reijo Pera, director of Stanford's Center for Human Embryonic Stem Cell Research and Education.

She cheered the studies.

"This really accelerates our field," she said.

Both Thomson and Yamanaka said they are trying 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.

Thomson, a shy researcher whose discovery of embryonic stem cells made him the focus of religious contempt and repeated congressional hearings, expressed relief that he now might be able to work without being at the center of what had become America's other abortion debate.

"What a great bookend," Thomson said. "Ten years of turmoil and now this nice ending. I can relax now."

Compiled from USA Today, Chicago Tribune, San Jose Mercury News, The Washington Post and Los Angeles Times.