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October 06, 2004

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Nice facts, great post.

Thanks hilzoy.

Thank you hilzoy. My wife has Huntington's Disease and this community is very interested in how this issue plays out over the years. We take great pains to attempt to extract the appropriate politics from the disingenuous, as you say. The only comment I'll challenge is concerning the development of actual therapies. One never knows in this day and age, but that time seems to be very far into the future. As you present further..."Personally, I think it's a good thing that we check the legality of proposed policies, publish draft guidelines for comment, solicit and review grants, etc., rather than just giving out research funding at random." Hopefully, President Bush has brought this to the next level where we can deal with all concerns, assess the viability of this research and give it all the support it deserves. Thanks again.

Bush's policy is plainly based on religious beliefs. He could say that, concede that the policy severely restricts research possibilities, and demonstrate some integrity. But he won't. Instead he chooses to pretend that he is a great promoter of stem cell research. This is laughable of course, but it is in keeping with the general strategy: offer a grossly oversimplified sound bite that distorts the issue, but is not (usually) an outright lie. Trust that the issue is complex enough, his spinners loud enough, and the press lazy enough, that he can get away with it.

As a person who has seen my grandmother die in the grips of Alzheimers, with the grandfather on the other side slipping into the same, and thus someone who is likely to see it strike in my immediate family again, I'm not uninterested in brain-disease therapies.

I'm not thrilled by this: "Moreover, stem cell therapies work in some ways like transplants; in particular, they are like transplants in requiring a good genetic match between the cells and the person into whom they are introduced. This means that if we can use only 22 lines to create therapies, the number of people who will be able to use those therapies will be severely limited."

The unstated implication is that we are likely to need to harvest embryos for medical use if the therapies prove useful. I believe the suggestion was pooh-poohed in recent threads here and here .

Yet here we are again, only a few months later.

I also want to note that this is not hypothetical. There is research in fetal brain tissue transplantation being done right now. Please note carefully that is 'fetal' and not 'embryonic' and is 'brain tissue' not 'undifferentiated cells'.

Sebastian: I didn't intend that implication at all. It is true that if you want to have embryonic stem cells that are an exact genetic match for you, you'll have to use somatic cell nuclear transfer (aka creating an embryo to order, then harvesting its stem cells.) But there's an intermediate possibility: if it were permissible to federally fund research on embryos left over from fertility treatment, embryos that would otherwise be discarded, then the variety of genomes available would be dramatically increased.

For stem cells, as for transplants, an exact match is of course best, since it provokes no immunological response. But when an exact match is unavailable, i.e. most of the time, how closely the DNA of the cells/tissue to be transplanted matches your DNA matters enormously (which is, of course, why people talk about whether a match is 'good enough'.) There are different bits of DNA that provoke different parts of the immune system, and if you match some of them, those parts won't be provoked. (I am oversimplifying a bit, but the basic point is right.)

That means, as I said, that if you can work only with 22 lines, you are unlikely to get a decent match for the vast majority of people. If you can work with lines derived from excess IVF embryos, however, the potential number of lines, and thus the diversity in their genetic profiles, goes way up, and you can match more people without creating embryos to order.

Personally, I favor somatic cell nuclear transfer, but I don't think it's part of this argument.

Sorry, major mistake: in the 2nd para., I meant to say "if it were permissible to federally fund research on stem cell lines derived from embryos left over from fertility treatment..."

This wasn't a Freudian slip, just a typo.

How many stem cell lines are you talking about here? For transplants you often need to screen thousands. Are we talking about thousands of stem cell lines? Aren't you worried that people with IVF treatments don't represent a good cross-section of the general population?

What about the fact that the slippery slope has already traveled past the implications we are talking about? It isn't hypothetical if scientists are already doing it.

Sebastian,

I'm not sure I understand your point. Are you saying that embryonic stem cell research should simply be banned for moral reasons?

Sebastian: sorry, I didn't get your earlier point about fetal tissue research. As I understand it, that research is done using tissue from aborted, miscarried, or stillborn fetuses. This research has been perfectly legal for some time, as is research done on cadaveric tissue from infants, adults, etc.

The regs on fetal tissue research are here; the salient bits (to me) are that in the case of an aborted fetus, the woman must consent to its use for research purposes; she cannot be paid, or receive any other 'valuable consideration', for donating it, and the researcher can have "no part in any decisions as to the timing, method, or procedures used to terminate the pregnancy made solely for the purposes of the research."

The slippery slope, it seems to me, is not about using cadaveric tissue, fetal or otherwise, in medical research. That has been done forever, and I don't see why it shouldn't be. It's rather that in deriving stem cells, you actually destroy the embryo. (In the case of excess IVF embryos, they will be destroyed anyways; but the objection presumably is that it should not be done by researchers, for research purposes.) If anyone was doing this to fetuses in the course of research, that would be outrageous; and presumably that's what the regulations forbidding the researcher from having anything to do with the timing etc. are there to prevent.

Oh, and as to how many lines we're talking about: I don't know, but almost any increase in the number available will in turn make treatments available to more people. I am of course worried that IVF clinic patients aren't representative, but they are almost sure to be an improvement over the existing 22 lines, in terms of genetic diversity.

Anyways, the general point was: in my original post I was not trying to make a surreptitious argument for SCNT; just to point out why, exactly, scientists are worried about the existing restrictions as opposed to, say, the Clinton policy. There is a distinct set of scientific advantages to having SCNT available as opposed to not having it available. But none of this settles any of the moral issues, nor was it meant to. I only put in the last bit because, in talking to people about this stuff, I have encountered people who really do think, for instance, that stem cell lines are the same, and so if the scientists have 22, why would they want more? It's perfectly possible to say: yes, I see why they would want more, but it's wrong.

"As I understand it, that research is done using tissue from aborted, miscarried, or stillborn fetuses. This research has been perfectly legal for some time, as is research done on cadaveric tissue from infants, adults, etc."

And if the therapy for 'brain tissue transplantation' is effective, how will one get enough fetuses?

My point is that I am not spinning up random hypotheticals. I'm dealing with concrete problems implicated by actual, ongoing research.

Also, I now that I have thought about it some more, isn't one of the whole big deals about embryonic stem cells that they avoid nearly all of the transplantation/rejection issues by being undifferentiated and unexposed to various markers?

Isn't that they only argument in favor of using them instead of cord blood stem cells?

"Isn't one of the big deals...?"

Yes, in the popular media. (But that's why you have me!) (I'm sure you were wondering what the reason was...) In the research community, the big deals are two: therapies for diseases, and insight into cell differentiation and other basic research topics. The question whether any resulting therapies will be provided using cells with one's very own DNA (which requires SCNT, and would in any case not be feasible in any situation requiring speed, e.g. for strokes and heart attacks) or using the sorts of genetic matching plus immunosuppression used in transplants has always been a separate issue.

About embryonic stem cells vs. cord blood: the two are very, very different. The stem cells in cord blood are, oddly enough, 'adult' stem cells ('adult' in this context means: taken from a human being whose cells have differentiated.) Specifically, adult hematopoietic stem cells. Adult and embryonic stem cells have very different properties, and can be used in very different ways. Most notably, hematopoietic stem cells form blood cells and platelets, whereas embryonic stem cells can form any sort of human cell except for the placenta.

Also, I missed your earlier question about screening. -- One difference between normal transplants and stem cell transplants is that while e.g. a heart or a liver can be used only once, a stem cell line can in principle be used for indefinitely many patients. If the available lines were genetically characterized, and that information was made available, one would only have to scan down the list to see whether there was a good match, and a line that had been used once would still be available for other patients. Whether or not it would be necessary to search for a good match would depend on how many lines had already been created.

As a child of multiple generations of early-onset Alzheimer's victims*, I appreciate your knowledge on this.
I'm not so confident in embryonic cell research having any breakthroughs in that area for quite a long time but I have more than a few friends with MS who may see breakthroughs before they reach old age.
Thanks


* No symptoms yet so that is not an excuse for my frequently snarky posts but my sense of humor may have something to do with it.

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