Stem Cell Issue Resolved? 'Fraid Not

Time has a great article about the recent breakthrough in stem cell research (that certain types of skin cells can regain pluripotency)--specifically on whether this so-called resolution to the stem cell debate might help the GOP.

Stem cell research has been the albatross around the neck of Republicans for a while now. Its getting harder and harder to feign outrage over the moral ambiguity over a clump of cells, when thousands of Americans (who, unlike blastocysts, vote) die of varied diseases that may benefit from stem cell therapy. Bush's repeated vetoes of federal funding for embryonic stem cell (ESC) research flies in the face of popular support, and is a act of hypocrisy by an administration who complains America is losing its innovative edge.

As someone interested in research to test potential ESC therapies (specifically for deafness and Alzheimer's), I look on with sadness as the US falls farther and farther behind more progressive nations who welcome the opportunity to fund innovative therapies that we refuse to.

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The trouble with the more progressive nations who are doing the innovative research is they don't have nearly as much as money as you Americans. So everyone loses.

Not a bad article, though it doesn't give a good rundown of exactly why ESC research shouldn't be stopped. It just notes that those who found this last breakthrough still say it should continue. PZ Myers gave a pretty good run down on the issues involved with this.

1) The method currently in use causes cancer. You can restart the cell but you do it with a jackhammer by forcing in new copies of four genes, rather than activating the ones in the cells already. Those genes can land anywhere causing a number of problems.
2) Once the cell is reset, we don't know how to make them turn into anything. We need to study differentiation and know every step the cell needs to take to get to the kind of cells we want.
3) The discovery was not American, it was Japanese. They actually get to do research on stem cells.

We need to know how the cells work and develop, and how to activate the reset genes without the cancer. And how to make them turn into all the stuff we want them to turn into. For that information, we need embryonic research.

The problem I have with all this is that most, if not all, of the relevant research regarding how stem cells work and how their commitments could be engineered could be done with Rhesus monkeys, or some other primate.

In the long run, IMO, it will be standard medical procedure to acquire toti-potent stem cells from every developing embryo and archive them so if/when the growing child, or grown adult, needs medical procedures requiring stem cells their own can be used.

The actual medical procedures could certainly be pioneered with Rhesus monkeys, until a low-risk (read effectively 0-risk) procedure had been developed. Once developed, this procedure could be used to provide stem cells for research without endangering the life of the embryo. And once the research had been done, the cells could be used for treatment of their owner, rather than risking implanting somebody else's cells.

In the end, this looks like a tempest in a teapot to me, with scientists insisting on something they don't really need that badly, and religious fanatics using the "right to life" issues to hide some other agenda. I can only wonder what it is.

Strictly speaking, even if you **did** do research on monkeys, there is no certainty that the specific gene sets in question are 100% correlative, that their are not unknowns in the human gene system that would require a *different*, but similar, set of activations, and a whole host of other issues AK. We are not looking for a single genetic marker that says X disease is present and that Y treatment can to some extent prevent, stabilize or control the disease. We are talking about base level controls on a complex process, which we don't clearly understand yet. And, by all estimates, using the latest data, **most** of the maybe 2-3% of genes *in* monkeys vs. humans are ones that **regulate** gene expression, of which we are, basically, looking for the master switch. So, if 90% of the genes that *do* differ between us and an ape are **directly** associated with the very mechanism we are trying to manipulate here, it would seem to me that it could be problematic to go looking for answers in a species that only shares maybe 80% of those developmental genes, and far less of the other sets of genes, which code proteins, instead of telling the cell when and how much to make.

Or, to put it another way, it wouldn't do a lot of good to, for example, find some cure for Alzheimer's that uses stem cells, base your attempt to use them on something from a Rhesus monkey, and end up fudging the activation, such that you get tissue growth which fails to properly differentiate into the proper cell, or worse, in which you accidentally activate some old pathway, which may still exist, which has been superseded by a new one, and end up with something that doesn't work like the human version of the cell you where trying to trigger. There may be sufficient redundancies in the genetic system to prevent that, but without being sure, you can't be really certain it won't happen.

Point being, it doesn't matter **what** species you use initially, you eventually have to test human tissue, to make sure it ****does**** have the exact same effect in a human as it did in the species you tested the original ideas on. And, truth be told, that is **usually** the way its done anyway, with all gene based research, so thinking you can somehow skip that step, or even worse, that we are not past that step in some cases, and *have to* use human cells, is as silly as the argument that some moron from Bush's group made about how this discovery somehow *justified* their stance on what sort of research to allow.

I agree Kagehi. Animal work is important to prove that a therapy is viable, but means little when it comes to developing a *human* therapy involving the introduction of new cells/tissue. I work on Notch signaling, which is an important cell signaling system which directs cell fate and differentiation decisions in stem cells (and other cells). This is just one example where the differences in the effects on downstream gene cascades between species is very large, and is especially important in neurological diseases where the constellation of gene expression has changed drastically during evolution. Observing cell integration, proliferation, and repair in even a *good* animal model of, say Huntingtons or Alzheimers, may look very different in monkeys vs humans. Also, much research has already been done. Stem cells introduced to models of Huntington's disease have differentiated into dopamine-producing neurons and relived symptoms. Similar results have been shown in Parkinson's disease monkey and rat models. Rats with crushed spinal cords have regained some ability to walk again following stem cell therapy. Heart valves have been mended in models of heart disease. Much of that was 4-5 years ago, eons in 'science time,' but we can't take the therapy any further than that.

Proof of concept is one thing. Styming research due to strawman moral arguments, while other countries grab the ball and run, is another.

i am always in favor of stem cell research and i hate republicans.

My, isn't that helpful.

Anyway, I'm glad to see you hitting this, Shelley. I commented elsewhere, recently, that if I never saw another pundit expostulated on research into pluripotent and totipotent stem cells when they wouldn't know a stem cell from a watch stem, it'd be three weeks too soon. It's nice to see someone who actually *does* have clue touch on it.

By Charlie (Colorado) (not verified) on 02 Dec 2007 #permalink