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Monday, October 4, 2010

Mice with fully functioning human brains

I wouldn’t usually discuss politics in a blog like this, but a recent story caught my eye, as it provides an example of the depressing and sometimes bizarre level of scientific illiteracy among elected officials or some people who hope to be elected. The example is from the United States, which is an easy target in this regard, but we have had a similar episode in Ireland recently so I don’t think we (or indeed any other non-Americans) can feel particularly smug about it. This one is especially funny, though.

Christine O’Donnell has recently won the Republican nomination in Delaware for the upcoming election to the Senate. I just love her – for comic entertainment this woman is very good value. She makes Sarah Palin look like the most reasonable, well-informed, level-headed person around. Among many clangers that she has dropped in the past, the one that really got my attention was the following assertion, made during a debate on stem cells on The O’Reilly Factor show on Fox News a few years ago:

"American scientific companies are cross-breeding humans and animals and coming up with mice with fully functioning human brains. So they're already into this experiment."

That’s right, cross-breeding humans and animals. I’m not sure how she imagines that to have taken place and would rather not know. And yes, she did say: mice with fully functioning human brains. Now, the average mouse weighs around 20 grams. The average human brain (clearly there are exceptions) weighs around 1.4 kilograms. I’m not sure Ms. O’Donnell really thought that through, even from a purely mechanical standpoint. However, she apparently had the opportunity to qualify or alter her assertion but did not, so one can assume she meant something like what she actually said.

(She also thinks evolution is a myth, because if we evolved from monkeys, then how come the monkeys are not still evolving into humans? That some people buy that kind of “argument” exemplifies the poor grasp that many people have of geological time. And of the fact that we did not evolve from monkeys – monkeys and humans evolved from a common ancestor. It reminds me of an even funnier comment I read from another creationist: if we evolved from monkeys, then how come we don’t speak monkey? There’s just no answer to that.)

What the imaginative Ms. O’Donnell may have been trying to refer to was a story that got some press coverage at the time of scientists who had transplanted a small number of human cells into a mouse brain to see if they would migrate and integrate normally. Apparently, about 100 such cells survived, in a brain that contains over 20 million cells. So, transplantation, not cross-breeding, and not fully functioning human brains, but to be fair to her she did, in an incredibly inept and confused manner, raise an interesting issue.

That is the question of whether it is ever a good idea (or morally or ethically right) to create an organism whose cells derive from two different species – a so-called chimera (named after the mythically mixed-up creature). This is especially touchy when some of the cells are of human origin. Why, you might legitimately ask, would anyone want to do such a thing?

Well, there are lots of reasons, none of which involves playing God just for fun, or actually wanting to create a hybrid organism. Most of the studies that have carried out such experiments are designed to test the potential of stem cells for regeneration of damaged parts of the brain. Stem cells can be obtained from many different sources, including early human embryos, umbilical cord blood and bone marrow. New technologies now allow fully differentiated adult cells from various tissues to be retro-differentiated into stem cells (so-called induced pluripotent stem cells). All of these cell types hold great promise for regenerative medicine, especially ones that are of the same genotype as the prospective patient.

But how to test them? Just injecting them into patient’s brains doesn’t seem like the best approach, though actually it has been done in some cases of seriously ill patients in the late stages of Parkinson’s and Huntington’s disease. Initial results seemed to suggest some clinical improvement but larger, more carefully controlled trials have been largely disappointing. These studies involved injection of primary human fetal cells into the brains of adult patients and were not particularly sophisticated in terms of how these cells were treated prior to injection.

With better defined populations of stem cells it is now possible, for example, to differentiate them into particular types of neurons (or their direct progenitors) prior to transplantation. To determine the efficacy of such treatments, animal models have of these disorders have been used. Human cells will integrate fairly happily into a rodent or even a chick brain. (No chick jokes, please). The brain is immune privileged and grafts of foreign cells are generally well tolerated by the host. Using this approach it is possible to determine how such transplanted cells survive, migrate and integrate into the brain (under the assumption that such processes would be much the same in a human brain). More importantly, it is possible to determine whether transplantation of such cells results in any improvement in the animal’s condition.

Such studies are generating promising results in models of stroke, spinal cord injury and neurodegenerative diseases such as Alzheimer’s, Huntington’s and Parkinson’s diseases (see a few recent examples below). It is still early days, however, and a lot more pre-clinical research like this will have to be carried out to characterise how these cells behave after transplantation, before they will be approved for clinical use. So, nothing sinister, no witchcraft (sorry, Christine, I know you like that), no hybrid mouse-humans scuttling into the dark corner of the lab when the lights are turned on. Just scientists and clinicans trying hard to find cures for serious diseases. Nothing sensationalist at all really. Sorry.



Snyder BR, Chiu AM, Prockop DJ, & Chan AW (2010). Human multipotent stromal cells (MSCs) increase neurogenesis and decrease atrophy of the striatum in a transgenic mouse model for Huntington's disease. PloS one, 5 (2) PMID: 20179764

Salazar DL, Uchida N, Hamers FP, Cummings BJ, & Anderson AJ (2010). Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model. PloS one, 5 (8) PMID: 20806064

Lee HJ, Lim IJ, Lee MC, & Kim SU (2010). Human neural stem cells genetically modified to overexpress brain-derived neurotrophic factor promote functional recovery and neuroprotection in a mouse stroke model. Journal of neuroscience research PMID: 20818776

9 comments:

  1. I suppose it would be a cheap shot to say that O'Donnell is a tragic example of a human with a fully functioning mouse brain.

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  2. Yes, it's easy to make fun of Ms. O'Donnell. So let's begin... I was thinking how nice it would be if there were more humans with fully functioning human brains! (And for the guy who doesn't speak monkey, I expect he don't speak human too good either).

    More seriously, it is a stark example of how the education system in many countries manages to churn out secondary school and college graduates with a shocking level of scientific illiteracy. People for whom the scientific enterprise is a complete mystery and who are unequipped to evaluate contradictory claims. Science is unfortunately seen as an optional extra, rather than as a core component of a well-rounded education. And it seems to be getting worse for some reason. In the U.S. there even seems to be a strong anti-scientific feeling among certain groups. I think as scientists we need to look at ourselves for some of the reasons why that has happened.

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  3. I'm suppose you had to write about something. Christine O'Donnell provided you a dual opportunity to appear superior with your knowledge of science while also revealing your political leanings.

    Science today is more interested in making a buck, rather than educate. Science today will "adjust" data to garner more grants for "research". Science today is smug.

    What you believe today to be true will be foolish tomorrow.

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  4. Thank you Larry for your comments. I admit that was a little smug. I am not trying to appear superior with my knowledge of science (though the fact that I have some is why I write this blog). If anything, I am bemoaning the fact that anyone would think it superior to have such knowledge, which suggests they see science as something removed from their own lives. That is a shame, as we are all born scientists - all curious about how the world works, all exploring and experimenting to try to figure it out.

    Christine O'Donnell provided an opportunity to explore the issue of scientific literacy, which I think is an important one. It also provided the opportunity to discuss the real science behind her claims, which is very interesting and exciting.

    And she's funny.

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  5. "What you believe today to be true will be foolish tomorrow."

    Quite possibly, but what O'Donnell believes today is foolish today.

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  7. In 1996, I started researching the history of brain implants, and my paper was eventually credited as the basis for the wikipedia article on the subject. Years later, the public sector began studying neural computer chips.

    Back in 1965, Jose Delgado already developed remote-controlled animals, so it's really left up to the imagination how far scientists have secretly come so for.

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