Reality Check on an Embryonic Debate

When President George W. Bush vetoed Congress's latest stem-cell bill in June, he tried to soften the blow and minimize the political damage by arguing science, not politics. Sources of stem cells other than days-old human embryos, he said, offered just as much promise for understanding and treating disease. Bush, it turns out, was well briefed. Earlier this year scientists in Kyoto had announced a feat of biological legerdemain that promised to obviate the long and bitter stem-cell debate, which has pitted the moral status of days-old human embryos against the moral duty of biomedical researchers and society to seek cures for devastating diseases. The Kyoto University team had taken skin cells from adult mice and "reprogrammed" them, turning back the biological calendar so the adult cells could, like embryonic cells, turn into any kind of cell in the body. Bush knew from his advisers that labs were close to accomplishing that with human cells, too.

Now the Kyoto scientists and a team from the University of Wisconsin-Madison have in fact done it. The groups independently announced last week that they had taken a quartet of human genes, slipped them into adult skin cells, and thereby reprogrammed the cells to become stem cells. But although the feat is being hailed as eliminating the need to produce—let alone destroy—embryos as a source of stem cells, it doesn't. And the attention the discovery is receiving obscures an important change in stem-cell science. While the research was once hailed as leading directly to cures—by turning stem cells into neuronal cells that could be implanted in patients with Parkinson's disease, say—it now looks like something much more mundane: another laboratory tool to study different diseases, yielding insights that would launch the slow, years-long search for new therapies. "It's likely that studying human disease is on a faster track than using stem cells for transplant therapy," says Fred Gage of the Salk Institute. For that purpose, having the new method for creating stem cells is unlikely to lead to treatments and cures any sooner than having only the old one.

The magic of embryonic stem cells comes from the fact that, like a newborn baby, no life path has been closed to them. They can mature into a muscle cell or a liver cell or any other. Although adult cells contain the same genes as embryonic cells, most of their genes have been silenced. One way to make all the genes sing again is to inject them into an egg. Something in the goopy ovoid returns the genes to their embryonic state, allowing the egg to develop into a ball of stem cells. This approach has worked in mice and monkeys, but not humans. The Kyoto and Wisconsin scientists discovered another way to produce human stem cells: use a virus to ferry four human genes into an adult cell. The quartet reprograms the cell back to its embryonic state of unlimited potential.

If this recipe works reliably, notes the journal Science, which published the Wisconsin study, we "would not need human embryos or [eggs] to generate patient-specific stem cells—and therefore could bypass the ethical and political debates that have surrounded the field." But that's a big "if." For one thing, the virus used to carry the four genes has a bad habit of plunking itself into spots on a cell's chromosomes where it can trigger cancer. Also, one of the four genes is itself a cancer-causing gene. Malignant cells are unlikely to be very useful for either basic research or as transplants, says Konrad Hochedlinger of Massachusetts General Hospital.

But that's not why Kyoto's Shinya Yamanaka and colleagues call the claim that reprogrammed stem cells eliminate the need for embryonic stem cells "a serious mistake." For one thing, it will be years before scientists understand reprogrammed stem cells—how to get them to mature into different tissues, for instance. Also, embryonic stem cells will be needed as a benchmark, something to compare to the power of reprogrammed stem cells to treat disease (which embryonic stem cells have done in lab animals). "Applications of stem-cell science would be indefensibly delayed if [research on reprogrammed stem cells] is pursued at the expense of further human embryonic stem-cell research," Yamanaka and colleagues wrote last month.

To a public for whom stem cells equal cure, the real blow will be the realization that the simplistic picture—take a patient's genes, slip them into an egg, let the egg grow and divide into stem cells that are perfect genetic matches for the patient and transplant those cells to treat diabetes, Parkinson's, Alzheimer's—is more fiction than fact. "Creating cell lines for transplant is unlikely to come down the pike any time soon," Paul Nurse, president of Rockefeller University and a Nobelist in medicine, told the New York Stem Cell Foundation conference last month. "Opponents [of embryonic stem-cell research] recognized that this was an overselling of the technology." Instead of yielding cures directly, stem cells— reprogrammed and embryonic alike—will take their place alongside other lab systems for studying disease. They will reveal hitherto-unknown causes and pathways of illness, even pointing the way to new drugs. The typical time between such a discovery and a new drug is at least 15 years.

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