That could easily have been the shared title of a pair of articles in today’s New York Times discussing the science and political implications of two very significant stem cell papers published online yesterday. The biggest offender was Sheryl Stolberg:
It has been more than six years since President Bush, in the first major televised address of his presidency, drew a stark moral line against the destruction of human embryos in medical research.
Since then, he has steadfastly maintained that scientists would come up with an alternative method of developing embryonic stem cells, one that did not involve killing embryos.
Critics were skeptical. But now that scientists in Japan and Wisconsin have apparently achieved what Mr. Bush envisioned, the White House is saying, “I told you so.”
Conservative Republican presidential hopefuls like former Gov. Mitt Romney of Massachusetts are breathing a sigh of relief. And opponents of embryonic stem cell research are congratulating themselves.
I think I just threw up a little bit.
Oh no… there’s more!
On Tuesday, senior aides to Mr. Bush said he drove the experiments by holding his moral ground.
“This is very much in accord with the president’s vision from the get-go,” said Karl Zinsmeister, a domestic policy adviser to Mr. Bush who kept the president apprised of the work. “I don’t think there’s any doubt that the president’s drawing of lines on cloning and embryo use was a positive factor in making this come to fruition.”
OK, OK, that last part wasn’t Stolberg’s fault: it was just the Bush Administration being completely fucking insane! Yes, that’s right: by doing everything in his power to prevent embryonic stem cell research from happening, George Bush is now inexplicably its savior. The Administration is able to claim this with a straight face despite the fact that (1) this isn’t the end of the embryonic stem cell debate (see below) and (2) one of the two studies reported yesterday (and the original work that directly led to these breakthroughs) comes from Japan! Maybe what the Administration means is that by inhibiting embryonic stem cell research in the US to such a large degree, it all but ensured that this major breakthrough would come from overseas.
Getting back to the media coverage, I should note that although Stolberg has a tendency to write these disappointingly credulous articles, I have to admit that I reproduced only the worst parts here. Surprisingly, though, Gina Kolata’s article in the Times wasn’t much better. This is a shame, because the two papers published today are quite significant and very interesting.
I won’t go too much into detail about the science, since there already some good explanations in the blogosphere (Pharyngula, Denialism Blog, The Daily Transcript, Hope for Pandora) and in Cell. One paper (Takahashi et al.) was published in Cell and came out of Shinya Yamanaka’s group in Japan. The other (Yu et al.) was published in Science and came out of James Thomson’s group in Wisconsin. Thomson’s group was the first to isolate human embryonic stem cells in 1998, and Takahashi’s and Yamanaka’s work last year on mice first validated the approach published yesterday. Both groups yesterday reported infecting fibroblasts from grown humans with retroviruses containing four key genes. The expression of these four genes transforms these fibroblasts into “induced pluripotent stem (iPS) cells”, which are very similar to totipotent embryonic stem cells. Like embryonic stem cells, these iPS cells can differentiate into any type of tissue and (in mice, at least) can give rise to an entire organism. Interestingly, both research teams accomplished this feat with a different set of four genes. Both used Sox2 and Oct 3/4, genes that encode transcription factors (proteins that control the expression of other genes). In addition, Takahashi et al. included two other transcription factors: Klf4 and c-Myc (c-Myc is a notorious oncogene that when mutated or overexpressed can promote cancer development). This was the combination of four genes used in their original mouse studies, and I think that many scientists were surprised that this strategy worked in humans considering some significant differences between human and mouse stem cell biology. Instead of Klf4 and c-Myc, though, Yu et al. used Nanog (a transcription factor) and Lin28 (an RNA-binding protein involved in regulating the translation of RNA into protein). While Lin28 seemed to improve the efficiency of their system, it was not necessary for the creation of iPS cells.
The latest developments are very significant, and they will have a major impact on embryonic stem cell research. And, they have already made an impact on the debate over embryonic stem cell research, although most of this has been trumped up by the media. This certainly isn’t the first time that some newfangled finding has been heralded as the be-all and end-all to the stem cell debate. Here are a few reasons why those who claim the debate is over now are way out of line:
- Although these iPS cells are very similar to embryonic stem cells, they are not identical. Takahashi et al. found that “DNA microarray analyses showed that the global gene-expression patterns are similar, but not identical, between human iPS cells and hES cells.” Yu et al. reported that when injected into mice, different iPS lineages varied in how they tended to differentiate.
- The retroviral technology used in the current studies is not appropriate for clinical applications. Scientists cannot control where the retrovirus integrates into the host cell’s DNA, so it can potentially disrupt important genes, leading to complications down the line (cancer being the most likely). Also, Yamanaka reported earlier this year that 20% of the offspring of iPS-generated mice developed tumors at a young age, although this was attributed to c-Myc (one of the four genes used in creating iPS cells) being reactivated. The protocol of Takahashi et al., at least, avoids this particular downfall by not using c-Myc.
- This is the big one: iPS cells appear to be totipotent. That means they are fully capable of forming embryos themselves (this has been demonstrated in mice). If these cells are no different from human embryonic stem cells in that respect, I’m not really sure what ethical issues are being addressed here.
In short, these findings in no way validate Bush’s current ban on federal funding for human embryonic stem cell research (in fact, they happened in spite of the ban, since this work would not have been possible without prior and ongoing research on human embryonic stem cells). But, these findings are very cool and very significant. Although the press coverage has focused on clinical applications, these latest advances will be most valuable for basic research, allowing scientists to generate stem cells from patients with a variety of diseases to better understand the basic pathology. And, this will give scientists another effective tool for studying human development. This will surely lead to clinical breakthroughs down the line, and although the technology in its current form is not appropriate for therapeutic uses, after some tweaking it might be. But, not yet.
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., Yamanaka, S. (2007). Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell, 131(5), 861-872. DOI: 10.1016/j.cell.2007.11.019 (free access)
Yu, J., Vodyanik, M.A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J.L., Tian, S., Nie, J., Jonsdottir, G.A., Ruotti, V., Stewart, R., Slukvin, I.I., Thomson, J.A. (2007). Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. Science, 318(5858), 1917-1920. DOI: 10.1126/science.1151526