March 5, 2024


 Ten years ago there was Dolly the Scottish cloned sheep and the race towards therapeutic cloning was on. Ten years later there are Japanese mice and the race could be over. Three different groups reported last week that normal skin cells in mice can be reprogrammed to an embryonic state. "Neither eggs nor embryos are necessary. I’ve never worked with either," says Shinya Yamanaka of Kyoto University, who first unveiled the technique a year ago to sceptical colleagues.

Now his results have been confirmed by two other teams, at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts and the Harvard Stem Cell Institute. The reprogrammed cells meet all the tests of pluripotent cells — they form colonies, propagate continuously and form cancerous growths called teratomas, as well as producing chimaeras. "Its unbelievable, just amazing," says Hans Sch?, a German stem cell expert. "For me, it’s like Dolly. It’s that type of an accomplishment."

What Yamanaka did was to take a mouse skin cell and introduce into it four proteins which trigger the expression of other genes to make it pluripotent. He calls the result induced pluripotent stem cells (iPS cells). "It’s easy. There’s no trick, no magic," he says.

Naturally, it’s easy only for experts at the moment. In practice, the four transcription factors reprogram cells inefficiently — only 0.1% of the cells in a skin biopsy. Then these cells have to be isolated. But Yamanaka has developed a technique for this as well. And there are some worrying issues to contend with: one of the proteins seems to contribute to cancers in 20% of the chimaeric mice.

But Harvard researcher Chad Cowan says that it will change the field: "The most amazing thing about these papers is you now take this whole idea of reprogramming out of the hands of cloning specialists and put it into the hands of anyone who can do molecular and cell biology." Now the race is on to apply the technique to human cells. "We are working very hard — day and night," says Yamanaka.

Executives from embryonic stem cell companies were not optimistic about the new technique. Because it involves tinkering with the genome, it could be dangerous, in the opinion of Thomas B. Okarma, of Geron. Getting approval from regulatory authorities would become far more complicated. And the head of the team at the Whitehead Institute, Rudolph Jaenisch, still insists that therapeutic cloning remains "absolutely necessary".

The ethical implications of this development were immediately seized upon by opponents of embryonic stem cell research. "Morally and practically, this new approach appears to be far superior," commented Richard Doerflinger, a spokesman for the US Catholic bishops conference.