Three teams of scientists said yesterday they had coaxed ordinary mouse skin cells to become what are effectively embryonic stem cells without creating or destroying embryos in the process -- an advance that, if it works with human cells, could revolutionize stem cell research and quench one of the hottest bioethical controversies of the decade.
Last year, Shinya Yamanaka of Kyoto University identified four genes in mouse cells that have the innate capacity to turn countless other genes on and off in the proper configuration to make a skin cell revert to an embryonic state.
Now Yamanaka and two American teams -- one led by Wernig and Jaenisch and the other by Konrad Hochedlinger of Massachusetts General Hospital and the Harvard Stem Cell Institute -- have gained good control over the process. They infected mouse skin cells with viruses genetically engineered to activate the four key genes.
The explanation is a bit garbled. In fact, the viruses contain the 4 genes and do not activate the copies in the mouse's chromosomes.
The discovery is of amazing interest as pure biology. I find the fact almost incredible. The ability to identify genes which control (or in this case reverse) differentiation of mammalian cells stuns me. I've been out of the biz for a while, but I didn't expect biologists to find this holy grail so quickly.
Weiss, however, is interested in human applications and political implications. He does mention one possible problem
The approach would have to be changed somewhat for use with human cells, Plath and others noted. The viruses used to turn on the four genes in mice are of a type that can cause cancer, so researchers are now studying alternatives -- using other engineered viruses, for example, or feeding the cells small molecules that can activate the key genes.
over at The New York Times, the risk that the approach causes cancer is not described as if it were hypothetical.
An immediate issue is whether the technique can be reinvented for human cells. One problem is that the mice have to be interbred, which cannot be done with people. Another is that the cells must be infected with the gene-carrying virus, which is not ideal for cells to be used in therapy. A third issue is that two of the genes in the recipe can cause cancer. Indeed 20 percent of Dr. Yamanaka’s mice died of the disease. Nonetheless, several biologists expressed confidence that all these difficulties would be sidestepped somehow.
That does seem to be an important drawback no ? 20% is not "could" it is "has". Also, since 2 vital genes can cause cancer a different viral vector would not eliminate the problem.
Now I would have a suggestion. Add a 5th gene , herpes Tk, to the viruses. This would mean that cells which carry the viruses can be killed with gangcyclovir (sp?). Thus any cancers caused by the treatment would be treatable. I have never understood why this is not routine in gene therapy (neither does my dad). Also the genes could be linked to promoters which are only activated when exposed to some reagent (I think metalothionine promoter activated by heavy metals but, like I said, I am out of the business. Then when the organ is grown, the genes, which are no longer needed, could be turned off.
Still, it is a really really big problem. The problem that 20% of subjects died of cancer should not be summarized with the word "could". posted by Robert
permalink and comments12:13 PM