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Floating Brains and Invasive Minds

Note: this article first appeared as a guest blog post in Scientific American with only the top accompanying image.

ghost shell MRecently, two studies surfaced almost simultaneously that led to exclamations of “Vulcan mind meld!”, “Zombie armies!” and “Brains in jars!” One is the announcement by Rajesh Rao and Andrea Stocco of Washington U. that they “achieved the first human-to-human brain interface”. The other is the Nature paper by Madeline Lancaster et al about stem-cell-derived “organoids” that mimic early developmental aspects of the human cortex. My condensed evaluation: the latter is far more interesting and promising than the former, which doesn’t quite do what people (want to) think it’s doing.

The purported result of brain interfacing hit many hot buttons that have been staples of science fiction and Stephen King novels: primarily telepathy, with its fictional potential for non-consensual control. Essentially, the sender’s EEG (electroencephalogram) output was linked to the receiver’s TMS (transcranial magnetic stimulation) input. What the experiment actually did is not send a thought but induce a muscle twitch; nothing novel, given the known properties of the two technologies. The conditions were severely constrained to produce the desired result and I suspect the outcome was independent of the stimulus details: the EEG simply recorded that a signal had been produced and the TMS apparatus was positioned so that a signal would elicit a movement of the right hand. Since both sender and receiver were poised over a keyboard operating a video game, the twitch was sufficient to press the space bar, programmed by the game to fire a cannon.

Here’s a partial list of problems with the wide-bore conclusion of “Mind meld!”: 1) The space bar is by far the largest keyboard item, as well as the one closest to the user’s fingers. I bet that if the desired move had been programmed by, say, one of the tiny F keys, the results would be negative. 2) It’s unclear that input specifics mattered. The obvious control is to see if any EEG signal (or a computer simulation of an EEG signal without a human at its end) gives the same result with an identical TMS setup. If yes, we’re back to square zero. If no, further experiments would be interesting and useful, though still extremely limited for applications. 3) The response was a reflex action, not a thought-induced one. This makes the setup an inefficient and Pentagon-expensive on/off switch, not a method to elicit fine-tuned actions.

The overall result, complicated input/output paraphernalia notwithstanding, is par with having frog legs twitch when they receive an electric current, or with people’s legs jerking when hit at the knee with a doctor’s hammer. To his credit, Rao pointed out that this is not a technique for thought transfer. Such technology may well end up enabling people who are paralyzed by either accident or disease to exert some control over basic commands, if the setup can be made less cumbersome. Most certainly it’s not a preamble to “passengers landing planes when the pilot is incapacitated”, as touted by Stocco. Passengers in such jeopardy would do better to stick with the traditional frantically shouted instructions shown in all those Airport movies. And the zombie army plans will have to be put on hold.

So what about disembodied masterminds that could control these zombie armies? Lancaster et al developed experimental conditions under which either embryonic (ESC) or induced pluripotent (iPS) stem cells differentiate into small balls that exhibit several of the properties of embryonic cortex. These include migration of the proto-neuronal cells to form laminar structures (which in real brains go on to become such compartments as the hippocampus) and bursts of electrical activity that are sensitive to cognate neurotoxins. The organoid attributes resemble those of a bona fide brain but aren’t the same. Additionally, they are limited in size and further development/self-organization by the intrinsic absence of the micro- and macro-contexts of native brains during their formation.

The fundamental premise of this research is not novel: it extends the trial-and-error attempts of cell biology to induce desired cellular properties and structures in culture. It is an interesting stroke of random luck that ESCs and iPSs are (relatively!) easy to turn into proto-neurons. Given the experimental parameters, such structures will almost certainly never recapitulate a full-size, fully functional brain even if they’re given 3-D scaffolds and circulating nutrients that mimic blood supplies. However, brain organoids derived from iPS cells of humans suffering from brain disorders are tremendous assets for figuring out what goes awry in specific contexts. Lancaster et al already did a neat (and directly relevant) proof of principle: they demonstrated phenotype-congruent differences in organoids cultivated from the skin of a microcephaly case caused by a mutation in CDK5RAP2. Among its functions, this protein regulates the mitotic spindle and hence the crucial balance between cell proliferation and differentiation – vital not only for cancer, but also for correct brain development.

This new tool in our kit promises to bypass two major bottlenecks in basic and applied biomedical research: work with “equivalence” models in non-humans is strewn with species-specific artifacts and limitations, whereas research on humans is fraught with moral dilemmas. In other words, it will allow us to identify human-specific details that make the difference in truly understanding and eventually short-circuiting diseases that are unique and critical to us – brain malformation and deterioration most prominently among them. Furthermore, it will do so without destroying embryos, making its funding less of a political football than usual.

So the outcome of this type of research will not be masterminds in silicon jars, but better maintained brains in carbon bodies. This is modest, prosaic – but real and concrete, unlike the overhyped “mind melds” which will have a hard time catching up with (let alone overtaking) our fine-tuned, sophisticated tool for such endeavors: language.

Meld

Sources and further explanations:

Direct Brain-to-Brain Communication in Humans: A Pilot Study

Lancaster MA, Renner M, Martin C-A, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA (2013). Cerebral organoids model human brain development and microcephaly. Nature doi:10.1038/nature12517.

Cloning Brains with Science. PZ Myers, Pharyngula, Aug. 29, 2013

Images: Top, Ghost in the Shell showcases both “brains in jars” and “mind melds”; bottom, Spock mind-rapes Valeris in The Undiscovered Country.

6 Responses to “Floating Brains and Invasive Minds”

  1. Susan says:

    Interesting reading, Athena, thank you. Somehow the “modest” conclusion at the end is more interesting and elegant than the sci-fi tropes beforehand. Personally I would like my thoughts to remain contained in my head :)

  2. Athena says:

    Agreed. I hate to think what would happen to human interactions if we could actually hear thoughts (though that would partly depend on how much/what layer we had access to; but regardless of details, I strongly suspect it would be close to unmoderated internet discussions).

  3. Alex Tolley says:

    I think you are spot on. The “mind meld” experiment was not particularly interesting and the PR for it was the usual sensationalist stuff. It was really just another small brick in the development of neural interface technology.

    The authors of the embryonic brains study were, by contrast, quite modest about their achievement and where they thought it was headed. I personally think that it will have a lot more value than just medical applications as it will allow us to tease apart functionality in simpler models than a developed brain. Technology may well allow much further development of the brain to occur, although it may need to be done in non-humans for ethical reasons. We are still struggling with 300 cell C. elegans brains, but clearly living embryonic vertebrate brains in a variety of species will be of potentially enormous use in understanding function.

  4. Athena says:

    One difference may be that the organoid study was peer-reviewed and had to tone down accordingly (not that this stops everyone, as the “arsenic” bacteria fiasco illustrates). Indeed, I suspect that additional aides will allow further organoid development, though it will be fascinating to see what context is absolutely required to truly capture and recapitulate normal brain organization.

  5. Christopher Phoenix says:

    Interesting post, Athena- the real subtleties of scientific research are often lost in the hype, thanks for your excellent efforts at untangling these stories! C:

    It strikes me that biological systems seem to be very much defined by their specific micro-and-macro contexts. This seems to apply to ecosystems as well. For instance, over the years I have thought much about multigenerational interstellar arks, and I though of the Earth’s self sustaining ecology and a generation arks CELSS as being basically similar, separated only by scale.

    But, per this article, the different scale and contexts are VERY important. You just can’t stick a bunch of organisms into a bottle and expect them to exactly mimic the Earth, or even create an ecology we can be a part of. The context of Earth is so much larger and more varied than any space habitat could be (expect maybe for SF megastructures) that it just won’t work the same. A mix of mechanical and biological methods are suggested, i.e. recycling some waste with bacterial vats while incinerating the rest, using air scrubbers to clean the air while allowing plants to provide some of the oxygen and so forth, to adapt to this new context.

    This makes me wonder if the opposite extreme might have surprises as well… the very largest SF megastructures- like habitat rings encircling entire stars, balloon worlds, or the fabled Dyson spheres- might have a habitable area equal to thousands of Earths or more. Assuming we could manage materials science and engineering equal to fashioning such constructions, might we find that an ecosystem will not behave the same when we try to fill our new home with Earth-type life?

  6. Athena says:

    There’s no doubt that any assembled ecosystem will end up subtly — or radically — different from its Earth 1.0 version. If it has enough resources, it will eventually stabilize. A pertinent question is if its human component will survive the adjustment.

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