BAM! Mind control! (UPDATED)

About this time last year, I was at a recruitment event for our program when I got to talking to a professor who attended.  We got on to fancy new techniques, and somehow arrived at a moment in the conversation like this:

Him: "Well it's not just going to be about connectomes anymore.  People are in meetings now where they're talking about recording the activity of every single neuron and getting an 'activity-ome'. "

Me:   "What?  How is that even possible?  Are they going to make little nano-bots to attach to every neuron and somehow record from them?"

Him:  "Actually, yes that's exactly what So-and-So wants to do."

Now, this conversation was mainly about the Allen Brain Institute and where that was going, but it seems that these conversations he was referencing also eventually led to the Brain Activity Map Project now in the news (people from Allen, including So-and-So, are listed in the acknowledgments of the BAM project's NeuroView article in Neuron).

So, uh, what's this nanotechnology stuff then?  Here's their plan:

• Make a tiny synthetic cell (5 micron diameter)
• Fill said cell with synthetic DNA polymerases, a template sequence of DNA, and a bunch of free nucleotides (As, Cs, Ts, and Gs that are floating around freely, unconnected)
• The DNA polymerases will polymerize DNA (like they do).  This means they latch onto the template strand, open it up, and read the template all while constructing a copy made from the freely floating nucleotides.
• Every now and then, these DNA polymerases make mistakes.  For this purpose, the interesting part is that they make mistakes when there are high levels of calcium ions present.  It just so happens that when neurons spike, lots of calcium comes inside their membrane from where it was floating around outside.
• So, take this synthetic cell full of template DNA and synthetic DNA polymerases, and get it to fuse to the soma of a neuron (no problem...), perhaps via a gap junction (although that isn't mentioned).
• Now when the neuron fires, calcium enters it and freely diffuses into the attached synthetic cell, causing an error in DNA synthesis.  That error is recorded in the DNA.  They claim it's theoretically possible to record something like an entire week of spiking data in this manner.

Sound crazy?  Maybe.  What we do now is stick electrodes into neurons, which directly record their spikes by sensing the flow of ion-mediated currents.  That gets sent into an electronics box and eventually a computer that records the currents over time.  This approach is like making a biological electrode and recording system all in one tiny 5 micron package.

But wait - where does the mind control come in?  Well that comes from this passage in their paper (my emphasis):

Potential options for a human BAMProject include wireless electronics,safely and transiently introducing engineered cells to make tight (transient) junctions with neurons for recording and possibly programmable stimulation, or a combination of these approaches.

So the goal is to make these little biological recorders, and somehow introduce them "safely and transiently" into a person's brain.  Which, if I had to fill in the dots, basically means injecting a bunch of these into your spinal canal, and letting them diffuse into the brain through the ventricular system.  I can't see tiny cells getting across the blood-brain barrier otherwise.

Would this be safe?  Uh... maybe?  As a labmate of mine put it, "I'm not going to let some scientists transiently change the capacitance of my neurons."  This references the fact that by attaching a fake cell to your existing cell, you might be changing the properties that govern how your existing cell normally functions.  And that might not be a big deal, or it might be terrible.

What makes it transient?  Not sure; there's no mechanism proposed.

And once you're done with the week of recording, how do you collect all these biological recorders?  If they just come loose and you do a lumbar tap to suck them out later, how on Earth do you figure out where in the brain they did their recording?  The people behind this project are super-duper smart  so they must have some idea for solving this, but if so they're not putting it out in public yet.

Finally, what's this "possibly programmable stimulation" part?  Apparently there's some way to get these cells to not just record the neurons they're attached to, but also stimulate them.  In effect, to control what they do.  This isn't that novel an idea - we do it all the time in other animals.  In fact, we do this in humans all the time as well.  For instance, we take surgical patients and zap their exposed cortex to map out areas that control important functions so that they aren't damaged.  But to do so in a non-invasive setting with "normal" patients?

As they later admit:

There are also potential ethical ramifications of the BAM Project that will arise if this technology moves as swiftly as genomics has in the last years. These include issues of mind-control, discrimination, health disparities, unintended short- and long-term toxicities, and other consequences.

Uh...

Good on them for being up-front about the "potential ethical ramifications".  They could have left that point out, but they didn't.  I'm worried, though, that this might turn into a really nice Rush Limbaugh talking point:

"Obama wants to spend billions of your tax-payer dollars to make nano-machines that they can put in your brain and read your thoughts.  Not just that - they can do mind control.  Mind control.  I'm not making this up, folks.  It's in the paper these scientists wrote, verbatim.  Mind control."

After all, this is a minor thing.  It's not a proven technology.  It's just a dream on a piece of paper.  The rest of what they propose is great - and it's especially clever in setting up a nice funding side-pot for doing the basic neuroscience research that they wanted to do anyway.  But this part is already in the press.  In fact, it's the only part in the press:

One possibility is to build a complete model map of brain activity by creating fleets of molecule-size machines to noninvasively act as sensors to measure and store brain activity at the cellular level. The proposal envisions using synthetic DNA as a storage mechanism for brain activity. (NYTimes)

Which means this mind control thing is going to come up eventually.

So to the BAM people: better figure out how to communicate around this!  If this is your flagship technique that makes the whole thing worthwhile because you could do it in humans, you better have some good explanations for how the benefits of developing this technology outweigh the risks enough to justify the cost of the project.

Or maybe that won't matter because House Republicans don't want to spend on anything.

UPDATE:

Prescience confirmed, readers!  I am the Muad'Dib of neuroscience.  (too nerdy?)

Anyway, one small point:

Any objection to BAM that says "whoa, we can't do mind control!!11!" implies that not doing BAM means no mind control.  That's silly.  Technology plods ever onward - BAM only accelerates the pace.  The authors are right, as I said, to address the ethics now.  That said, they don't have an ethics problem right now.  Right now, it's a communication problem - they're selling this like a human project (or, at least, the NYTimes sold it that way) and this dream technique is all they've got for doing million-neuron recordings in humans.



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BAM! Let's do neuroscience!

Holy crap we're going to map the Entire Human Brain!!

Well... sort of.  I have to admit, as someone who does "connectomics", my first thought when I saw the headline in the NYTimes was "I'm going to have a job!"  So I won't be too critical...  but I thought my regular readers (that's you, Mom and Dad) might want a little background info about what's going on with this "Brain Activity Map Project" that Obama is apparently going to propose.  It's being compared to the Human Genome Project, and is being framed entirely from the human perspective:

The project, which the administration has been looking to unveil as early as March, will include federal agencies, private foundations and teams of neuroscientists and nanoscientists in a concerted effort to advance the knowledge of the brain’s billions of neurons and gain greater insights into perception, actions and, ultimately, consciousness.

Scientists with the highest hopes for the project also see it as a way to develop the technology essential to understanding diseases like Alzheimer’s and Parkinson’s, as well as to find new therapies for a variety of mental illnesses.

Moreover, the project holds the potential of paving the way for advances in artificial intelligence.

Jeez!  Heady!

So what's the deal?

Well the gist of it is that a bunch of really famous neuroscientists all got together and figured out how to fund what they want to do anyway.  I've read the outlines of their proposal as it stood last June (you can find it here) and I'll list briefly what they want to do:

• Do calcium imaging of neuronal circuits
• Do voltage imaging of neuronal circuits
• Make new multiunit electrodes to record neuronal circuits
• Play with some new ideas for recording from neurons by transiently attaching synthetic cells to neurons and using their DNA to record spike trains (another post on this part later...)

Basically, they want to do neuroscience.  Recording neuronal circuits, understanding their properties, linking them to structural connectomes, linking them to behaviors, understanding disease states... that IS neuroscience.  BAM = neuroscience funded outside the normal NIH pool.

It's clear that humans weren't an original focus either.  Rather, they state a modest progression: starting with C. Elegans and Drosophila, moving to the mouse retina and maybe, if they're lucky:

Finally, it would also be interesting to consider mapping the cortex of the Etruscan shrew, the smallest known mammal, with only a million neurons.

The Etruscan shrew!!!

Only in the most aspirational terms are humans mentioned:

For a long-term goal (15 years), we would expect that technological developments
will enable the reconstruction of the neuronal activity of the entire neocortex of an awake mouse, and proceed toward primates. We do not exclude the extension of the BAM Project to humans, and if this project is to be applicable to clinical research or practice, its special challenges are worth addressing early.

But!  Who knows how that's changed since June, when their article was published.  They obviously got someone important to listen (Collins?) and eventually Obama heard it too.

And from Obama's point of view, this makes great sense.  He's always looking for small ways he can do stimulus these days - this is one.  Everyone loves solving brain diseases.  And wouldn't that help slow the long-term growth in health-care costs?

Of course, there will be objections, including one that could give Republicans an opening.  The ethics of mind control.  More on that here :-)

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