(UPDATED: See below.)Two research groups have just reported ways to “reprogram” ordinary cells in ways that cause them to revert into a primordial state resembling that of embryonic stem cells. Those embryonic cells have long been controversial because they’re derived from five-day-old embryos in a destructive process, but also hold the promise of unlocking the body’s ability to regenerate damaged or diseased organs because they’re capable of transforming themselves into any type of tissue.
The new techniques — more specifically, improvements on this early work, which essentially functions as a proof of principle in humans — could potentially break the political logjam over stem-cell research. For more than six years, anti-abortion politics have held back the field, thanks to a presidential order that blocks funding for any work that doesn’t involve a handful of stem-cell lines that existed in 2001. Although states like California, which has just begun spending $3 billion that voters authorized for stem-cell work three years ago, have picked up the slack, the federal restrictions have clearly held scientists back and forced some to relocate overseas. (For our previous coverage of stem-cell issues, see the end of this post or click here.)
If it’s possible to produce embryonic-like stem cells (technically, “pluripotent” cells) without destroying embryos, however, moral objections to the research should fall away. “My personal barometer of optimism has gone up a bit,” says James Thomson, the University of Wisconsin researcher who first isolated human embryonic stem cells almost a decade ago and who led one of the teams reporting results today. “This will remove the restrictions [on stem-cell work]… and the research will accelerate.” Thomson believes that the federal limitations may have cost the field three to four years of lost time.
In its current state, however, the new technique isn’t yet a panacea. The two teams — Thomson’s in Wisconsin, which published its findings in the journal Science, and a separate group at Kyoto University in Japan, which published in Cell — both achieved their feat by transplanting four genes known to be active in embryonic stem cells into ordinary “somatic” cells, the non-reproductive cells that compose almost almost all of the body’s organs. (Thomson’s team used fetal skin and a newborn’s foreskin, whereas the Japanese group used skin and connective-tissue cells from adults.) The Japanese team, led by Shinya Yamanaka, a stem-cell scientist who recently accepted an appointment at the UCSF-affiliated Gladstone Institute (see our coverage here), laid the groundwork for this approach when they successfully reprogrammed mouse skin cells into stem cells back in June (our coverage here).
That technique, however, involves the use of retroviruses that integrate new genes into the cells’ genomes — a risky process that can inadvertantly make the cells cancerous. The two teams also use different sets of genes, one of which — the c-MYC gene used by Yamanaka’s group — is also linked to cancer.
Scientists still have to figure out what these genes are doing and whether there are other simpler and less dangerous ways of achieving the same effect. It’s also still not clear whether the reprogrammed cells are identical to the embryonic cells, although Yamanaka’s group has reportedly already coaxed the reprogrammed cells to transform into heart and nerve cells.
Still, the reports represent a giant step forward for stem-cell research, although Thomson and other experts caution that it’s far too soon to abandon work on the original embryonic stem cells. After all, it was a decade of research into those cells that made the reprogramming technique possible in the first place. The reprogrammed cells may already be useful in searching for new drugs and in unraveling the genetic components of disease, since for the first time it should now be possible to produce pluripotent cells with a known genotype — at least without using the also-controversial cloning process known as somatic-cell nuclear transfer (SCNT), which is sometimes called “research cloning.”
The reprogramming experiments come just a week after Oregon scientists reported obtaining embryonic stem cells from cloned rhesus-macaque embryos. Primates had never been successfully cloned before. The primate results will serve as a useful backstop for the reprogramming work, since it should be possible to compare the resulting pluripotent cells to determine how different they are. If both methods produce equally potent cells, “the whole field is going to completely change,” Jose Cibelli, a primate stem-cell researcher at Michigan State University, told Science. “People working on ethics will have to find something new to worry about.”
The mainstream press is all over the story, of course. For more, see the NYT, the WaPo, and the LA Times for starters. The Science piece linked above has more technical detail. Also, the Center for Genetics and Society has a timely, albeit opinionated, release about the work.
UPDATED: Expanded considerably from original version.