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Stem Cell Advances May Make Moral Issue Moot

Working with early mouse embryos, the team has found that single blastomeres, when cultivated in dishes with embryonic stem cells, can become what appear to be embryonic stem cells themselves. Chemicals secreted by the embryonic cells apparently flip the right genetic switches in the blastomeres to make them act "stemmy."

About a quarter to one-third of blastomeres treated this way can be coaxed to become embryonic stem cells or closely related embryo cells, said Lanza, who declined to release specific data pending publication in a peer-reviewed journal.

If this technique were applied to humans, then a single cell taken from an eight-cell fertility clinic embryo could give rise to a self-replicating line of embryonic stem cells without compromising the donor embryo's odds of someday growing into a baby.

"The president has said it is wrong to destroy a life to save a life," Lanza said. "This might be a way to get some cell lines that the president . . . can get behind."

Other researchers are experimenting with variations on a second approach. Chad Cowan and co-workers at Harvard University, for example, use chemicals to get an adult human skin cell to fuse with a human embryonic stem cell. The two cells become one with shared cellular contents, including two full batches of genes.

Experiments indicate that something in the stem cell "reprograms" the skin cell's genes, putting the hybrid cell into an embryonic state. The team is now developing ways to remove the original stem cell's DNA after reprogramming is complete. What will be left is an embryo-like cell that can be made to grow into all kinds of tissues -- all of which will be genetically matched to the person who donated the original skin cell.

Alan Trounson of Monash University in Australia has been performing similar experiments involving the fusion of mouse skin and stem cells. He recently reported he has developed a relatively simple system for removing that extra DNA after the skin cell's genes have been reprogrammed, offering hope that Cowan's work in human cells will indeed work.

And Yuri Verlinsky of the Reproductive Genetics Institute in Chicago reported at a meeting last month that he has succeeded in making new human embryonic stem cells by first removing the DNA from a stem cell and then fusing the rest of that cell with a human skin cell.

He has made 20 lines of stem cells this way, he said in an interview, acknowledging that he has yet to complete the battery of tests that will prove they can do everything an embryonic stem cell can do. "It's a work in progress," he said.

Researchers said several key challenges remain. Lanza has found it difficult, for example, to keep his newly made stem cells in an embryonic state. Most want to mature quickly into one kind of adult cell or another. Other scientists say it will take time to show that the stem cells they have made are genetically stable and healthy.

The ultimate challenge, scientists said, will be to get beyond their reliance on harvested embryonic stem cells and turn people's mature cells into embryonic stem cells of their own. To do so, researchers will have to identify the specific, switch-flipping chemical factors inside stem cells.

"The end hope is to determine the exact molecular components of reprogramming and get it down to something chemically useful so you can get adult cells to turn into any cell type you want," Cowan said. "That's the science fiction goal that we'd all like to see come true."

That cocktail of chemicals, synthesized in a lab and available off the shelf, could be the closest thing to a true elixir of life that science is ever likely to make.


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