Mice with fully functioning human brains

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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

16 Comments

  1. Why is it incorrect to say humans evolved from monkeys? What evidence is there that the common ancestor from which humans and modern Old World monkeys evolved was anything other than a monkey?

  2. What evidence is there that the common ancestor from which humans and modern Old World monkeys evolved was anything other than a monkey?

    well, you do have an internet connection. why don’t you engage the post by actually posting links to the scholarship instead of just posing an interrogative question? anyway, this might be of interest….

    http://www.nature.com/news/2010/100714/full/news.2010.354.html

  3. As the article which Razib links to points out, the common ancestor of monkeys and apes (including humans) was neither a monkey nor an ape. Modern monkeys, apes and humans are all equally divergent, genetically speaking, from that common ancestor (just as you and your second cousin are equally divergent from your great-grandparents). The ancestor may have been morphologically more monkey-like than human-like, that is true (probably more lemur-like actually), but that does not make it a monkey.

  4. well, if we want to be cladistic nerds, ‘monkey’ is a term we should avoid in scientific discussion. it’s paraphyletic. monkey = primates which aren’t apes or prosimians. but the first commenter was probably talking in phenetic terms, in which case it would have been polite of him to actually sate his curiosity and look up the morphology of the last common ancestor. it’s what i would have done.

    a minor aspect of natural history not often discussed is that old world monkeys have only recently marginalized the apes. until recently apes were much more speciose than they are today, and filled many of the niches which monkeys did. but monkeys are better are being monkeys than apes obviously.

  5. I’m just waiting for the day when I can pay a doctor to inject tons of my own stem cells induced to become neurons into my own brain. Maybe I could even target it, more neurons in the occipital lobe, I need better memory, put some in my hippocampus…

    Is there any indication that this might one day be feasible?

    Unfortunately, if it is, I bet that the drug companies will find the most profitable location for stem-cell injections to be the penis…

    The next generation of spam: V1a9ra, cia1i5, 5t3M C311 1njecti0n5

  6. Almost all the EFFECTIVE anti-science agitation in recent decades has come from the environmental Left: i.e. fanatic opposition to all GM foods (and even to GM bacteria for fuel production), opposition to using animals in research, opposition to cloning of animals, opposition to DDT and other safe, vital pesticides, hysteria about vaccines, and opposition to embryonic stem cell research (the U.S. under Bush and now Obama maintained some modest limitations on federal funding, while the Greens in Germany pushed through a total ban on research that included criminal penalties for German scientists working on ESC anywhere in the world). In the US, AIDS “activists” for decades used agitation and political intimidation to prevent mass HIV testing and contact tracing. Tens of thousands died as a result– and few scientists had the courage to stand up to them.

    The measures successful implemented as a result of noisy leftist obscurantist campaigns have already resulted in millions of deaths from malaria and starvation in Africa.

    On the other hand American Christian doubts about evolution and other scientific issues have had no negative impact on human life or welfare anywhere.

    As for climate change, politicians on all sides are guilty of ignorance and group-think, but the original sin is Al Gore’s. His misleading and scientifically embarrassing documentary took a technical matter and turned it into a political war, where it has remained.

    And yet people who imagine they are standing for science ignore the ferocious anti-science efforts of the left, and instead obsess about irrelevancies. It’s impolite to challenge people’s motives, and I’m sure you think you are merely standing for science, but to me it looks like you are merely engaging in tribal identity politics. Until you face the real threats, you are letting science down.

  7. fanatic opposition to all GM foods

    i don’t think this is true. in the USA yeah, it is leftist-anti-science types who are freaked out and get a lot of press in the states, but opposition to GMO hasn’t gotten very far here. it’s in europe that the main source of opposition has been effective in getting it curtailed or banned, and there’s broad societal support for the bans, including from right-traditionalist groups. i think there’s a case to be made that the left has been more destructive to applied science than the right, but i think your maximalist position makes you less credible.

    (i poked around the survey data on this issue, and there’s a reflexive aversion to GMO across the political spectrum)

  8. Actually, I agree that anti-scientific thinking is not restricted to any particular political ideology. There are, as Barry Youngerman points out, many examples of issues that have been appropriated by various political groups, where willful ignorance drives policy. The thing is that is most regrettable is that when the general public is faced with arguments “from both sides” (which always sounds reasonable and fair), the majority do not have the wherewithal to evaluate the contradictory claims or viewpoints. This is because scientific education is seen as an “extra”, rather than as an integral part of a general education.

  9. Razib-

    I exaggerated for effect.

    My main point: the purpose of advancing scientific research and implementing its practical findings is not served by publicly ridiculing Christians and conservatives, who are NOT reflexive opponents of progress the way some European Greens have become.

    In any case, both groups have a right to advance their views, however religious or non-rational, and their values must somehow be accommodated in a democratic polity, as George Bush tried to do when he opened up NIH funding for SOME embryonic stem cell research (it had been prohibited by Congress and Clinton had ignored the issue). Even Green fanatics may serve a cautionary purpose, by forcing scientists and science-based corporations to test above and beyond what may have seemed sufficient.

    Most politicians on all sides happen to be ignorant of science, as are most non-scientists, and they all say stupid things. For that matter, scientists often sound naive, ignorant, or limited when they discuss politics. It would be easy to pluck out laughable quotes from any of them. Doing so with O’Donnell serves a partisan political purpose, not a scientific one. kjmtchl has a right to her partisan self-identification, but she shouldn’t confuse that with the cause of science.

    O’Donnell is running as a fiscal hawk and conservative skeptic of government, while her opponent is a standard left liberal. Intelligent voters will choose based on how they want their new senator to vote. The rest is twaddle, and doesn’t really belong in a science blog.

  10. Barry, I was not ridiculing Ms. O’Donnell because she is either a Christian or a conservative. I couldn’t care less to be honest – I only gave the details of her affiliation for information. The post is not about American politics. I was just lamenting the fact that someone who is running for office in a developed country in the 21st century is so willfully ignorant. As you say, that is not the preserve of politicians – lots of people are ignorant of science. She just happens to be the most high profile person to recently publicly advertise it.

    As I said, we have had a recent story in Ireland which shows we can’t be smug about it, where our Minister for Science was planning to launch an exceedingly non-scientific, creationist book. And our Greens are complete nutters – very anti-scientific on many issues, though they try to hide it.

    But my main point was that what Ms. O’Donnell was referring to was actually some very interesting and exciting science with a lot of potential to generate real medical advances. That’s why it’s in a science blog.

  11. The rest is twaddle, and doesn’t really belong in a science blog.

    hey, thanks for your editorial input! appreciated since we value your subscription!

    though seriously, it was just an intro as an excuse to discuss the post. common form on science blogs. it went a little longer than the usual, but i skipped over it pretty easily myself. if you can’t do so, that’s your business, doesn’t give you an opening to be unpleasant and demanding as to the nature of the content of the biases (the factual assertion as to “which side” is more anti- or pro-science is fine, as it doesn’t necessarily have to be presented in a hectoring fashion).

    this line of conversation is OVER.

  12. my last post didn’t go through…

    I was trying to change the topic back to what the possibilities are for direct injection of stem cells into the brain to actually work. Obviously more than 100 neurons would have to stick, but I don’t know much about this line of research… anyone know?

  13. Is there evidence about whether the problem with science education is mainly about educational priorities, or mainly about intelligence or specialization?

    That is, would (say) requiring a couple more science classes in high school make the citizens and politicians (who care mainly about what the voters and journalists think) less gullible about science? Or would it just move the complexity of the bullshit up slightly?

  14. “That is, would (say) requiring a couple more science classes in high school make the citizens and politicians (who care mainly about what the voters and journalists think) less gullible about science?”

    It wouldn’t probably wouldn’t make any difference.

    kjmtchl addresses salient points about the benefits and methods in a clear way. Ridiculing sincere concerns, however unfounded in reality, and dismissing the people who have those concerns does not win anyone over. Clear explanations in simple lay terms are far more effective. kjmtchl does a good job of that here in the second part of the discussion. Unfortunately many journalists do not. Perhaps because that doesn’t sell. I don’t know. The poor science reporting in the popular press likely has more to do with invoking hysteria among the scientifically illiterate (O’Donnell) than whatever they may (not) have studied years earlier in high school.

  15. This cartoon is very apropos:

    http://xkcd.com/154/

  16. My understanding is that “monkey” covers all non-ape members of Simiiformes, and that humans must, almost by definition, have an ancestor that matches that description. All of our ancestors which lived more recently than the Old World/New World monkey split but previous to the OWM/ape split would be monkeys according to the common usage of that word, right? We are descended from monkeys in precisely the same sense that we are descended from reptiles and fish.

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