Today's stem-cell news caught many people off guard—but not me.
American and Japanese researchers (one of them, Shinya Yamanaka of Kyoto University, is pictured here) demonstrated that a little genetic manipulation goes a long way. They both showed that introducing four genes will reprogram a skin cell into an embryonic-like stem cell. The transformed cell has the ability to become any cell type in the human body, just like an embryonic stem cell. (ESC)
Reprogramming is an idea I have been pushing since Bush won re-election, although its origins date back to the night after Bush's August 2001 stem cell restrictions. Frustrated that the restrictions would limit the ability of federally funded researchers to generate neural stem cells at will, I sat in my wheelchair going over the little I understood of biology at the time.
Then it hit me -- at the most basic level, a cell's abilities are determined by the genes it expresses. That's the only difference between skin, neural, and embryonic stem cells. Gene therapy had claimed what some were calling its first "true" success in 2000, so science had shown it was possible to modify the gene expression profile. A scientist confirmed for me that transforming adult cells into different cell types may in fact be possible, although the idea was considered controversial.
In 2001, my main emphasis in suggesting this approach was selfish -- I was only interested in creating neural cells for spinal cord injury research. My focus began to change in 2004 when it appeared that President Bush would remain in the White House for another four years.
I began preparing for a possible Bush re-election by thinking of ways to frame the reprogramming concept so that opponents of ESC research would embrace it.
When Bush won, I wrote an email to both the White House and ardent ESC opponent Senator Sam Brownback (R-KS) explaining that a human cloning ban being considered at the time would not ban all forms of human cloning. I described the theory behind the reprogramming process and how it could be used for cloning, but also how it could be used to create ESCs in an ethically uncontentious way.
No response came, but May of that year saw the publication of a white paper from The President's Council on Bioethics entitled Alternative Sources of Pluripotent Stem Cells. It discussed four methods that may, in theory, allow scientists to obtain embryonic stem cells without creating, harming, or destroy an embryo -- including what they dubbed somatic cell dedifferentiation.
I may have been biased, but reprogramming seemed to be the most practical choice.
The first proposal, deriving stem cells from organismically dead embryos, suffered from one insurmountable flaw: it relied on in-vitro fertilization (IVF), which is unacceptable to the Catholic hierarchy who opposed ESC research. Similarly, blastomere biopsy -- the second proposal -- relied on IVF and pre-implantation genetic diagnosis (PGD), both of which are verboten.
The third alternative, altered nuclear transfer (ANT), immediately faced criticism from ESC opponents who felt that ANT would intentionally create developmentally disabled embryos from which to extract its stem cells. Syndicated columnist Charles Krauthammer called the technique "repugnant and weird," among other objections from the pro-life community.
That left somatic cell dedifferentiation, or reprogramming, which had some major advantages over the others. It didn't rely on procuring eggs from women and it didn't rely on IVF leftovers. If proven, researchers could easily generate genetically diverse and disease-specific stem cell lines. Its only potential downfall is that an adult cell could be reprogrammed into the equivalent of a fertilized egg, but that concern could be addressed by criminalizing such acts.
The doubts of my pro-ESC friends about reprogramming led me to start a blog promoting the concept. The blog was targeted to address opponents of ESC research, hoping they would champion the idea since the pro-ESC camp would not.
Later that year I met with Senator Tom Coburn (R-OK), who had introduced legislation promoting the proposed alternatives, to lend my support. If he needed a disabled person to promote the bill, I told his staff that I was their man. (I was never taken up on that offer, sadly.)
The last two years have really changed the debate. Japanese researcher Shinya Yamanaka proved late last year that he could create mouse ESC-like cells with reprogramming, while this year saw his work verified and extended.
Today's announcement brings things full circle. Shinya Yamanaka proved that human skin cells could be reprogrammed into ESC-like cells that he calls induced pluripotent stem (iPS) cells. There's a little bit of work left before they can be used for human treatments, but they offer all the potential of ESCs in the lab. President Bush's executive order this past June will allow federal funds to be used on these iPS cells, giving researchers an incentive to focus on using them.
Many of my pro-ESC friends have asked me why I have pinned my stem cell hopes on an unproven concept -- an "if". Now they know.
