Wednesday, November 21, 2007

Middle Ground For Stem Cells?

You've probably already seen the headlines: "Top Scientists Generate Stem Cells From Cloned Skin." My local Seattle paper has a story. So does the NYTimes. Not surprisingly, the Times article is really good. They tend to get it when it comes to stem cell science and politics. The articles there represent the science well and give a good breakdown of the political context of the announcement. But for a better breakdown, read Matt Nisbet's post on his Framing Science blog. He points out that middle ground in the stem cell debate is murky, if it even exists. I think the potential for middle ground would be greater if we could get away from the polarizing environment that make a presidential "I told you so" possible. I'll get to that in a minute. First the science:

Tonight I passed on reading about chronic pain to get the dirt on the research in the Cell and Science articles. And what do I get? Well at first it was a bunch of freakin' press releases and 'digested for the lay public' news articles. I started to think that this was just a ruse to provide a reason for me to give thanks tomorrow when the currency of science - the paper - was released. But then I found the Sciencexpress paper (you need a subscription, of course).

What do I think? These stories look pretty good. Okay, really good. The teratomas look a lot better than the sorry examples provided by the Yamanaka group in July of '07. (The Yamanaka paper in Cell also looks much better this time around.) The pathologist in me wants more than the H&E tissue sections the Thomson group provided. I want to see definitive lineage markers by histology. But none the less, I am pretty impressed. They set out to create a stem cell line that could produce all three germ layers. It looks like they did. The next question is whether these pluripotent cells are as pluripotent and as controllable as the embryonic stem cells. The only way we will know is by doing the experiments. My former dissertation adviser, Chuck Murry, has already put an order in for these cells and should have some in Seattle by January 2008. Can they be coaxed into beating human embryonic stem cell derived heart cells?

(By the way, if you are looking for a more detailed take on the science, please refer to Pharyngula, The Scientific Activist or Dear Science.)

Moving on to the political situation, there is plenty of hot air out there to get indigestion about. Fortunately, there are some level heads to provide the TUMS needed for me to get a good night's sleep.

From the New York Times article.
Karl Zinsmeister, a domestic policy adviser to Mr. Bush who kept the president apprised of the work said, “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.”

Mr. Bush’s critics say he should not be so quick to take credit. They note that the reprogramming method has some kinks to be worked out and say the research would never have proceeded without the initial embryo experiments. The critics say that far from encouraging research, Mr. Bush has stood in its way.
I got queasy reading the first paragraph (the aforementioned presidential "I told you so"). If you will allow me to continue with disease/treatment metaphors, its follower provided the anti-emetic I needed to keep my keyboard vomit-free.

Let's not overlook the quote from the only Republican senator I ever voted for:
“I really don’t think anybody ought to take credit in light of the six-year delay we’ve had,” said Senator Arlen Specter of Pennsylvania, the lead Republican sponsor of the bill that Mr. Bush vetoed in July 2006. “My own view is that science ought to be unfettered and that every possible alternative ought to be explored.”
Yeah! I think I would vote for him again!


What's not being brought to the table here is the notion that most of science is not about designing cures! It's about asking questions and answering them. Goal-oriented science and translational research is what pays the bills because it captures our imagination. But when it comes down to the bottom line in biomedical research, we need to understand mechanisms and systems before we go and use some new-fangled therapy in the clinic. Why is this important? I need only cite the unfortunate example of Jesse Gelsinger. Viral gene therapy was not ready for prime time, and a sick kid paid the price. Where do we begin to understand stem cell differentiation?

The thing is, embryonic stem cell researchers have always contended that the goal is to generate stem cell lines that don't need to come from blastocysts. After all, it's a good chance that ES cell-derived tissue replacements would need immune suppression to prevent rejection. If stem cells could be derived from other cells, that would obviate the side effect-prone rejection medicines. Embryonic stem cell research teaches us about cell reprogramming so that maybe there will be a clinical application in the future. Indeed, the same interventions that were used in these (what I think will amount to) monumental papers to generate these ES cell-like cells were studied in embryonic stem cells.

Science is and relies on progress. To say that the shortsighted policy made by George Bush and his puppet show of a Presidential Bioethics Committee is anything but a hindrance to science is not just disingenuous, it's an outright lie.


And I wonder why we can't all just get along. Let me tell you (and myself): It's because crazies like me are tired of the political misuse and misrepresentation of science.


golob said...

My solution for the political implications was to ignore them for now. In their current form, iPS cells would be outright scary in the clinic. But, for research applications I think they might be a revolutionary other choice to ESC--not necessarily a replacement.

I already have some ideas for what I would do with the virus cocktail...

And word on the Yamanaka paper being WAAAY better than Thompson's. The teratomas were better for Yamanaka this time, but check out the "gut epithelium." It's stratified! Gut, bronchiole--what's the difference? And the "neuron" section looks suspiciously like actual brain...

My post, pushing the boundaries of fair use as usual.

Nick Anthis said...

I agree that this is pretty compelling science (although what do I know? I'm just a protein guy), but I'm not really sure what sort of ethical issues are being addressed here if these cells are virtually totipotent.