Will a Disruptive Technology Mothball Therapeutic Cloning?

By Michael Cook : BIO| 19 Jun 2007

The global grandees of therapeutic cloning recently gathered in sun-soaked Cairns, the gateway to Australia's Great Barrier Reef, for their annual conference. They have serious strategic issues to deal with along with their scientific papers and posters: persuading governments to open their wallets, ensuring that the Bush Administration's restrictions on their work are lifted, allaying the public's qualms about creating embryos solely for research.

But hovering over the buzz of morning coffee has been a dark cloud: as governments everywhere promote it, is therapeutic cloning going to be mothballed before it has produced a single cure?

Only a few days ago an article in the leading journal Nature brought amazing news. A Japanese team at Kyoto University has discovered how to reprogram skin cells so that they "dedifferentiate" into the equivalent of an embryonic stem cell. From this they can be morphed, theoretically, into any cell in the body, a property called pluripotency. It could be the Holy Grail of stem cell science: a technique that is both feasible and unambiguously ethical.

"Neither eggs nor embryos are necessary. I've never worked with either," says Shinya Yamanaka. The first instalment of his research appeared a year ago -- and was greeted with polite scepticism by his colleagues. At the time they were mesmerised by dreams of cloning embryos and dissecting them for their stem cells.

The previous head of the International Society for Stem Cell Research, Lawrence S. B. Goldstein, had even dismissed reprogramming as quixotic. "If there are scientists who morally oppose [embryonic] stem cell research and want to devote their energies to uncovering alternatives, that's fine," said Goldstein. "But in no way, shape, or form should we ask the scientific community and patient community to wait to see if these new alternatives will work." Now, however, ten years after Dolly, not one scientist anywhere using a cloned human embryo has created a stem cell line. Not one. And a Japanese Don Quixote has.

This is mainstream research, not an eccentric theory from a Romanian naturopathy journal. Yamanaka's work has been confirmed by two other teams affiliated with the Massachusetts Institute of Technology, Harvard University and the University of California, Los Angeles -- both of them headed by ardent supporters of embryonic stem cell research.

They say that 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 Schöler, 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. "It's easy. There's no trick, no magic," he says. Now the race is on to apply the technique to human cells. "We are working very hard -- day and night," says Yamanaka.

Even the Australian doyen of therapeutic cloning, Alan Trounson, of Monash University, is enthusiastic. "It would change the way we see things quite dramatically," he says. He plans to start experiments "tomorrow".

Will this disruptive technology open up ethical avenues in the promising field of stem cell research, avenues which do not involve turning women into battery hens for their eggs and destroying embryos?

At the moment, the stem cell grandees, like all establishment figures, have no plans to change their tune. One of the stars of the Cairns conference, MIT's Rudolph Jaenisch, told Nature that therapeutic cloning remains "absolutely necessary."

Executives from embryonic stem cell companies were not optimistic about the new technique either. Because it involves tinkering with the genome, it could be dangerous, warned Thomas B. Okarma, of Geron, the leading private company in the field. Getting approval from regulatory authorities would therefore become far more complicated. What else could he say? No doubt manufacturers of vacuum tubes muttered about serious flaws in semiconductors when they first appeared on the market.

With an ethical solution looking quite plausible, the pressure will be on scientists to explain why therapeutic cloning deserves to be legalised and funded. Two years ago, Dr Janet D. Rowley, an Australian working in the US who is an implacable foe of the Bush Administration's policy, dismissed ethical solutions like Yamanaka's. "We have extremely limited research dollars, and to use them to study these alternatives is wrong," she declared. "That money should be available for actual research." But now stem cells derived from embryos are starting to look like dead-end "alternatives."

Don't expect supporters of embryonic stem cell research to respond rationally, not in the short term, at least. The other day, Democratic Caucus Chairman Rahm Emanuel told the US House of Representatives as he voted to overturn the Bush policy: "It is ironic that every time we vote on this legislation, all of a sudden there is a major scientific discovery that basically says, 'You don't have to do [embryonic] stem cell research.' "

Connect the dots, Mr Emanuel. Maybe you don't have to.

Michael Cook is editor of the international bioethics newsletter BioEdge.

http://www.tcsdaily.com/article.aspx?id=061807D


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