Fact Check: Stem Cell Funding

The Bush campaign has put out a statement about his record on funding stem cell research. It reads, in part:

"The Facts Are:

President Bush delivered the first funding ever for embryonic stem cell research.  Prior to the President's announcement of new funding, federal funding of embryonic stem cell research was $0.

The President's announcement did not ban, limit or restrict stem cell research.

It is inaccurate to say the President "limited federal funding" of stem cell research, as such funding did not exist to limit.  This language misleads voters to believe that the President put restrictions on existing federal funding.

The President did announce the first ever federal funding of stem cell research with ethical requirements on which stem cell lines are funded."

Since various claims and counterclaims are being made about this, I decided to provide some background against which to assess them. I am not doing this in a partisan spirit; I work on this stuff, and I just thought it would be good to have a clear account of the history.

The History: Years before stem cells had been isolated, President Clinton issued an Executive Order banning federal funding for research in which human embryos were created for research purposes, and Congress followed this up with a ban on federal funding for such research, and for any research in which human embryos were discarded or destroyed. In 1998, human embryonic stem cells were isolated for the first time, raising the question whether federal funding for research on them was permissible. At this point, the NIH asked for an opinion from the General Counsel of the Department of Health and Human Services about whether the ban on funding embryo research covered research on human stem cells, and President Clinton asked his National Bioethics Advisory Commission to consider the ethical issues raised by stem cell research. In 1999, the Counsel to DHHS ruled that the ban did not cover research on human embryonic stem cells, since those cells were not embryos. (The ban would cover deriving those cells from embryos, however.)

Given this ruling, the NIH decided that it would fund research into human embryonic stem cells derived without the use of federal funds. However, when the NIH reaches a decision like this, it doesn't just call up stem cell researchers and offer them checks; it has to go through a lengthy process. It published draft guidelines for comment in Dec. 1999, and final guidelines in August 2000; only at this point was the grant application process initiated, making it possible for researchers to submit grant requests. No applications for funding had been approved by the time President Bush took office, however, and he cancelled the first scheduled meeting of the committee that would have evaluated grant applications for embryonic stem cell research so that he could formulate a new policy.

In August of 2001, President Bush announced his new policy, which allowed research only on lines in existence as of the date the policy was announced. At that time he claimed that "more than 60 genetically diverse stem cell lines already exist", which turned out not to be true. (As of today, 22 are available; earlier, the number was much lower.) Once the policy was in place, grants could (once again) be solicited, and some have been funded.

All of this relates only to the federal funding of human embryonic stem cell research. The research itself has never been banned or restricted (except for various restrictions that apply to all research, e.g. informed consent etc.)

Fact Check: President Bush is right to say that no research on human embryonic stem cells got any federal funding under any of his predecessors, and that he announced the first ever federal funding of stem cell research. However, this is not because Clinton banned such funding; it's because human embryonic stem cells were only isolated in 1998, and it took time to do the various things the bureaucracy has to do before it hands out money. 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. This is what was happening during 1999 and the first half of 2000; however, the proposal that was making its way through the bureaucracy was to fund embryonic stem cell research subject to fewer restrictions than Bush put in place.

President Bush is also right to say that he has not banned, limited, or restricted stem cell research. The question is strictly about providing researchers with federal funding.

He is also right to say that he did not put restrictions on existing funding. I find the claim that he did not 'limit federal funding' of stem cell research disingenuous, however. Clinton had in place a policy that allowed federal funding of embryonic stem cell research subject only to the sorts of restrictions that cover any research, along with one further restriction: that the stem cell lines not be derived using federal funds. Bush replaced this policy with a different one, which placed much greater restrictions on the research eligible for federal funding. To say that this does not count as limiting federal funding for stem cell research on the grounds that no grants had time to be approved under the first policy is, as I said, disingenuous.

One more thing: You might wonder whether President Bush's restrictions really matter. The answer is 'yes', for various reasons. First, stem cell lines are not identical, like hydrogen atoms; they have individual properties. Some are better at one thing, some at another; some are not very good at anything at all. It helps researchers a lot to be able to use lines that are good at whatever it is they want the lines to do, and the quality you'd get from using the best of 22 lines will normally be worse than the quality you'd get if you could choose from more lines.

Also, when we get to the point of developing actual therapies for disease, the President's restrictions will cause further problems. When the President announced his policy, stem cell lines were grown on layers of mouse cells, and could therefore be contaminated by various mouse diseases. Since then, researchers have developed ways of deriving stem cells that do not run this risk; but the President's policy does not allow research to be done using these newer, safer lines. Doing human trials with the stem cell lines allowed under the Bush policy might expose subjects to completely unnecessary risks. 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.

If you think that it is wrong to use embryos from IVF clinics, which are voluntarily donated and which would otherwise be discarded, to derive stem cell lines, then none of this should matter to you. (It doesn't, and was not intended to, settle the moral issue.) But if you're wondering why scientists make a big deal about Bush's restrictions, these are some of the reasons.

Comments

[democritus]

Nice facts, great post.

Thanks hilzoy.

[blogbudsman]

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.

[Bernard Yomtov]

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.

[Sebastian Holsclaw]

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'.

[hilzoy]

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.

[hilzoy]

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.

[Sebastian Holsclaw]

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.

[Bernard Yomtov]

Sebastian,

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

[hilzoy]

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.

[hilzoy]

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.

[Sebastian Holsclaw]

"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?

[hilzoy]

"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.

[carsick]

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.