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Friday, January 19, 2007

Stem Cell Nonsense
Yuval Levin, a member of the Presidents Council on Bioethics writes an anti-stem cell op-ed for the NYT.

The kicker? He calls it, "A Middle Ground for Stem Cells". What a jackass.

How do we know he's a jackass and is full of shit? Well, this paragraph sums it up nicely:

But that does not mean the stem cell debate is about when human life begins. It is a simple and uncontroversial biological fact that a human life begins when an embryo is created. That embryo is human, and it is alive; its human life will last until its death, whether that comes days after conception or many decades later surrounded by children and grandchildren.

Ummm, no. It is a simple and uncontroversial fact that the Pope believes that life begins at conception, it is not a scientific fact. The scientific fact is that the sperm is alive, the egg is alive, and the fusion of the two is also alive. Levin's attempt to pass off the theology of ensoulment as science, and further that this is the "middle ground" is a total joke. Life began once, over a billion years ago, and it has been going strong ever since. There is no "dead" stage in human reproduction.

The jackass then goes on to assert that Thomas Jefferson was talking about embryos when he wrote that whole inalienable human rights thing.

America’s birth charter, the Declaration of Independence, asserts a positive answer to the question, and in lieu of an argument offers another assertion: that our equality is self-evident. But it is not. Indeed, the evidence of nature sometimes makes it very hard to believe that all human beings are equal. It takes a profound moral case to defend the proposition that the youngest and the oldest, the weakest and the strongest, all of us, simply by virtue of our common humanity, are in some basic and inalienable way equals.

Yes, that's right, these people believe that you, I, everybody, we're all equals with blastocysts. Little balls of a hundred cells that nature doesn't even see fit to allow to survive 50% of the time. These little blastocyst-Americans deserve every right in the constitution. By the way, that means no more abortions, IUDs, or IVF ladies, and probably no pill either, because pre-empting the release of the components to make blastocyst-Americans is also wrong. We certainly can't start discriminating against the right of any blastocyst-American to have a chance to come into existence. Sorry, it's up to you to make sure that blastocyst-Americans' rights aren't violated by being forced to carry every single one of them to term. And as far as IVF? Well, all those freezers holding those embryos are like Guantanamo bay for the most innocent Americans among us. We must set them free! I propose an immediate draft of all women of childbearing age, in the interest of the liberal belief in the inalienable rights of equals, to carry all 400,000 embryos being stored in freezers to term. We must not allow the false imprisonment of all of these precious blastocyst-Americans for one more day.

Can you imagine what the world would be like if we actually took such bad arguments as Levin makes seriously? Basically, women would be hostage to their freaking ovaries, and deep down I suspect that's what's behind all of this. This idea that women are punished for sex by getting pregnant, and the real concern is the control over the uterus. By promoting these idiotic "life begins" fallacies, they're trying to make reproductive control out to be murder, the natural consequence? Ending abortion, ending contraception, ending scientific pursuit of embryonic stem cells, and curtailing all the success in women's rights over the last 40 years.

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Friday, January 12, 2007

Democrats already fizzling?
Some news out of the Democratic congress remains encouraging, such as the minimum wage hike, and the embarrassing veto promised by bush to prevent medicare negotiating drug prices (anti-capitalist Republicans?) My favorite part is their justification for not allowing bidding.

"Government interference impedes competition, limits access to lifesaving drugs, reduces convenience for beneficiaries and ultimately increases costs to taxpayers, beneficiaries and all American citizens alike," the administration said in a written statement.

Government interference impedes competition? You mean, when they like, ask, for competition? That's one of those sentences you read and you feel like you've gone through the looking glass.

However, there are two troubling issues. Stem cells which have sailed through the house but await a presidential veto, and critics like Krauthammer are already touting this amniotic cell breakthrough as a sign from God that Bush has always been right, and that ES cell research is fundamentally evil. You think I'm kidding? Krauthammer seems to think that ES cell research is so insidious, and so soul damning that people who study it become evil as a result.

South Korea enthusiastically embraced unrestricted stem cell research. The subsequent greatly heralded breakthroughs -- accompanied by lamentations that America was falling behind -- were eventually exposed as a swamp of deception, fraud and coercion.

Get that? Hwang Woo Suk wasn't a dishonest scientist who made up results for personal gain, he was a victim of evil ES cell research! The poor poor man. Anyway, we could go on forever in all the ways Krauthammer is an asshole, but that's besides the point.

The point is, Giving Up is really only an ideal philosophy when an election is nearby that allows Republican idiocy and incompetence to be used for gain. Now we have real power, control of the House and Senate, and it would be nice to get things done. While it still will be embarrassing for the Republicans to admit that they fought research funding that 70% of Americans support, or a minimum wage increase that 70% of Americans support, or competition for prescription drug prices which 80% of Americans support, we'd have to wait two years to really get any real benefit from these terrible, terrible political decisions by these assholes.

Between that and the confusion directed towards the response to the president's surge and I think the Democrats are already starting to lose their way. What about having 70-80% of Americans agree with your policies has made this difficult to understand? 80% of people disagree with Bush on Iraq, you've got the support of the people Dems, why aren't you kicking ass and taking names?

Revoke the Authorization, kill funding for Iraq, pass ES cell legislation and if Republicans won't join you in supporting legislation that 80% of Americans want? Kick them out of committees, make them defunct, make them what you were for 12 years.

None of this fair play crap, I want to see some action.

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Monday, January 08, 2007

Adult Stem Cell Tripe
The WaPo, BBC, SfGate, CNN and many others are reporting on a ostensibly new type of stem cells derived from amniotic fluid (Nature Biotech link). While these come from amniotic fluid, they are not embryonic stem cells, since it's not clear that they are totipotent (can make all tissues), but the articles are suggesting that they might be.

Now, reading these articles and the Nature Biotech paper, I immediately had a bunch of red flags pop up in my head. Here's some of the problems that come immediately to mind.

  1. Nothing about these cells suggests they are any more or less novel than cord blood stem cells and many other "adult" stem cells types which can be transdifferentiated in vitro
  2. Atala's research does not suggest these cells have equivalent plasticity as embryonic stem cells (although they are quite plastic).
  3. Conflicts of interest exist that cause concern about the timing of this release - the potential for ES cell debate in Congress this week, Atala being on the board of the company that uses these cells etc.
  4. The method of purification of these cells (here's probably the most detailed article on them) is selection for c-kit, a common marker identifying adult stem cells - makes me think that these aren't any more exceptional than hematopoietic stem cells which can do many of the same tricks in culture but are of questionable in vivo untility for transdifferentiation.
  5. No functional in vivo data exists on the totipotency of these cells - namely the isolation of equivalent cells from rodents and formation of chimeras to show pluripotency. This is really too bad since the authors do say they isolated cells from mice and rats, a chimeric injection experiment really would have been definitive and as a reviewer I would have asked for it before publication.
  6. They only showed absence of fusion in vitro not in vivo in recent studies.
  7. No evidence exists these cells are totipotent so claims they can replace embryonic stem cells are just as inappropriate with these cells as every other adult stem cell line that has had promise and ultimately failed to perform.

If you want to see what testing for pluripotency looks like with adult stem cells check out this old post on the spermatagonial stem cells, which seemed to have real promise. Critically, the formation of mice using the stem cells which would be proof of real totipotency - contribution in vivo to all three germ layers. The experiment would be useful even if the cells aren't totipotent because they can compare the relative potency to ES cells, and determine which tissues, if any, these cells will not contribute to. Until then, with the literature not showing the necessary experiments to justify these claims of equivalence to embryonic stem cells, I find it irresponsible for the researchers or the press to suggest some incredible breakthrough - especially in this political climate. This is really too bad, because Dr. Atala is an excellent scientist with a really impressive body of research in tissue engineering, and I hope this isn't a purposeful effort to reinject yet another unproven adult stem cell line into the debate over stem cells. I wonder if that was even his intention; it is quite possible his research being highlighted at a particularly sensitive time to help drive a political wedge. This publication is certainly interesting, but I worry it's being over-hyped in preparation for our coming debates on this science.

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Tuesday, December 19, 2006

Good news ladies
Previously we wrote about an advance on generating embryonic stem (ES) cell-like cells from men by isolating spermatagonial stem cells from testes. These cells were powerful, and appeared to do most of what ES cells would do, at least in mice.

Now bona fide ES cells can be derived using oocytes to create parthenogenic embryonic stem cells (or pES cells). Here's the abstract from the Science article:

Genetically matched pluripotent embryonic stem cells generated via nuclear transfer (ntES cells) or parthenogenesis (pES cells) are a potential source of histocompatible cells and tissues for transplantation. Following parthenogenetic activation of murine oocytes and interruption of meiosis I or II, we have isolated and genotyped pES cells and characterized those that carry the full complement of major histocompatibility complex (MHC) antigens of the oocyte donor. Differentiated tissues from these pES cells engraft in immunocompetent MHC-matched mouse recipients, demonstrating that selected pES cells can serve as a source of histocompatible tissues for transplantation.

So, basically what the researchers did is freeze the cells destined to become mature oocytes (or eggs) in meiosis, which is the division of a diploid (in humans it's 2 x 23 chromosomes) cell that ultimately results in halving of the genetic material to create a haploid cell (once copy of each of the 23 chromosomes). The problem is that it's more complicated because of exchange of genetic material between chromatids could generate homozygosities where heterozygosities existed before, but the researchers accounted for this by subsequently screening the cell lines they generated for the correct Major Histocompatibility Complex (MHC) genotype. Apparently natural killer cells can also detect the absence of a MHC complex in what is known as "hybrid resistance" so a homozygosity generated in this process could potentially be detrimental for the recipient.

I realize that's complicated, but here I'll state it more simply. The researchers have figured out a way to make embryonic stem cells that are immunologically compatible to the woman who donates the oocyte, and additionally are nearly genetically identical. Because of recombination in meiosis, a heterozygous locus may become homozygous, but at least no new genes will be introduced that the body would then attack as foreign.

This is cool for many reasons. If this can be generalized to humans, which is likely, this means that women can have embryonic stem cells made that are highly-genetically matched to them, and immunologically compatible for the generation of replacement tissues. Initially I think treatments for diabetes - pancreatic islet cells - will follow, as well as hematopoietic stem cells for bone marrow transplant, and possibly liver and other tissues. Also, many lines can be generated and banked based on MHC profile.

The second reason it's cool is because it bypasses the idiotic religious belief some people have that life begins by some sperm-magic at conception. Not only does life not begin since it is continuous, but the whole sperm-magic thing is so tiresome. If they object to this procedure it can't be because a conception has been terminated, they'll have to come up with a new dogma to attack this.

Sadly, women won't be able to use this to bypass men altogether and just reproduce themselves (although I think they could if they figured out how to fuse two eggs and induce them to enter embryogenesis), since it would be the ultimate form of inbreeding. Pretty much any dangerous recessive gene you have would have the potential for becoming homozygous, and generating genetic disorders in the offspring. But for tissue generation? This is really cool.

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