Monday, February 18, 2013

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.



Works Cited:

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 :-)

Works Cited:

Wednesday, February 13, 2013

SOTU REAX

Behold, insight:

Biden’s purple tie is color mix of Obama’s (blue) and Boehner’s (red) - is this why he is the bipartisan deal closer?

Boehner stood up like once in the beginning, then did nothing except for when Obama mentioned raising the minimum wage, at which point his face was all "As if!" 

Obama a bit disingenuous to claim that reduction in illegal border crossings linked to his enhanced security when biggest factor is crap economy.  Same thing goes for reduction in greenhouse gas emissions (crap economy + natural gas boom) although I suppose he wasn't trying to take any credit for that.

Aha! Biden has Terminator eye  - this is how he gets the deals done!

Obama said "frequency and intensity" when talking about extreme weather!  Yay accuracy.   Although at this point not much reason left to keep scaring us shitless when we've got nothing left to poop.  Especially since the denialists on the far right are way too constipated for any warnings to matter anymore.

Pelosi mouthed “let’s see how many of them stand up for that” I think when obama was talking about getting them to pass violence against women act.  hahahaha.  Then shortly after a shot of repub. women gettin' their scowl on.

Rubio endorsing 4 trillion budget deficit reduction mark?  Oops!
  
Rubio can’t control his mouth.  (!!double entendre!!)

Rubio trying too hard, hasn't learned how to give a rehearsed speech and still sound like he means it.

“Exploration” = "C'mon, just the tip!" when it comes to oil and natural gas drilling.

“Because God gave it to us” is a gauzy bullshit reason to use a natural resource.  If you're into the whole God thing, then what do you think about the rainforests He gave us?  The oceans?  God gave us the Colorado and salmon runs in northern California but hey we figured we had better ways to use that shit.  We’re just muddling around on Earth doing our best to balance our needs and the planet's.  Leave God out of it.

Monday, February 11, 2013

Eric Cantor Empiricism

Ok, maybe it's too easy to mock a political speech.  Nevertheless, let's dive into Eric Cantor's preview of what he will do after ousting Boehner  major policy address.

He did, in fact, back up his statements with many facts and figures:

In America, in Kitty Hawk, North Carolina, two bicycle shop mechanics gave mankind the gift of flight. The Wright brothers flew only 22 feet, 18 feet in the air, but they performed a miracle. As a result, only 66 years later, this great country of ours put a man on the moon and brought him back. We can do an enormous amount. That’s who we are.

The Wright brothers’ father, Milton, first inspired his sons with a toy helicopter. But he never wanted Orville and Wilbur to fly together, for fear he would lose them both. In 1910, seven years after the boys’ first flight, Milton gave them permission to fly together, the only time they ever did, and it lasted six minutes. Later that day, Orville took 82-year-old Milton on the only flight of his life. It lasted seven minutes, rising 350 feet, while his elderly father shouted: “Higher, Orville, higher.”

What a great commentary. In America, we do have higher expectations for our nation.

Yes, this is the most quantitatively-precise passage in the speech.   And perhaps appropriately, it's also a full-throated endorsement of an American future that resembles the Icarus myth.

____________

In America, the son of a shoe salesman can grow up to be president. In America, the daughter of a poor single mother can grow up to own her own television network. In America, the grandson of poor immigrants who fled religious persecution in Russia can become the majority leader of the U.S. House of Representatives.  

Ronald Reagan!
Oprah Winfrey!
and...
Eric Cantor!!!
_____________

That's why we worry so much. Where can you find an affordable home in a good neighborhood to raise your kids? Which health care plan can I afford that allows you to see your doctors? Will the children make it through high school and get into a college of their choice, and if so, can you afford it? What about a career? Will that be available to them? These are real life concerns.
"What's eating you?  You look worried."

"Can't figure out what guild I should join.  Can't even figure out what class my character should be.  Hell, I don't even know what the best NAME for my avatar is.  If only Congress would do something about it."

"..."

"What?  These are important fake-life concerns."
______________

Each year our colleges and universities graduate approximately 40,000 foreign nationals with Masters and PhDs, many of whom are then forced to leave the country because there are not enough visa slots in our immigration system to permit them to stay. So rather than being able to invent things here in America, grow businesses or start one on their own, they do all of those things somewhere else. 

Yeah yeah I'm all for this too - but recognize that not all these PhDs are going to be out there inventing stuff and creating jobs.  The only PhDs that are in demand right now are those with good computer science / coding skills.  What percent of those 40,000 have those?
_______________

What tax form are you supposed to fill out, is it more beneficial to file jointly as a married couple or separately? Is a truck or gas mileage deductible or are you forgetting something that the IRS gives you credit for?

In 1935, the Form 1040 was accompanied by a two-page instruction booklet. Today, taxpayers must wade through over 100 total pages of instructions. 

"You know what the problem with taxes is?"

"Well, how much we have to pay, of course!"

"No, the REAL problem is how damn long it takes to read these instructions."

"...aren't you a Republican?"
_______________

Loopholes and gimmicks benefitting those who've come to know how to work the system in Washington, are no more defensible than the path of wasteful and irresponsible spending we've been on for decades.

This will be a fun quote to remember the next time you hear a Republican say "Obama got his taxes.  Now it's our turn to get spending cuts."
_______________

Leading up to April 15th, families will be besieged by concerns over their taxes. But it’s health care and a concern for a healthy family that always worry parents most.

ERIC CANTOR:  Oh this is hopeless!
OBSEQUIOUS FLUNKY:    Sir?
CANTOR:   How am I supposed to transition from talking about taxes to talking about health care?  It's impossible!
FLUNKY:   Have you considered using the word "But"?
CANTOR:  Brilliant!!!
_______________

There is an appropriate and necessary role for the federal government to ensure funding for basic medical research. Doing all we can to facilitate medical breakthroughs for people like Katie should be a priority. We can and must do better. 

Wait what?  Maybe Republicans want to raise the NIH budget?!

Funds currently spent by the government on social science – including on politics of all things – would be better spent helping find cures to diseases.

....oh.

1) Sucks to be a social scientist!
2) They get like 250 million total a year.  NIH gets 30 billion for biomedical research.
______________

"Higher" – Milton Wright once shouted from the air. “Higher.” Making life work for more working people, and all who want to work, is the best way to a future of higher growth and more opportunity.

I'm tired of hearing about growth and opportunity like they're always going to get bigger and better.  The American trajectory isn't linear, nor is it exponential.  Hell, I'd settle for nice sigmoidal with a lovely happy plateau at this point.  Anything to get off whatever crazy sinusoidal path we're on now.

Thursday, February 7, 2013

Where'd we come from? Part 2

The mystery remains...

Last time I mused about the pool of potential biomedical PhDs vs those that actually try to get them.  It dawned on me later that "potential pool" = "biology majors" and I wondered how the numbers of biology majors had changed over time.  If the NIH doubling coincided with a rise in biology majors, then conditions would have been extra-ripe (overripe?) for the resulting explosion in biomedical PhDs.  Growth in bio majors could have come from people were getting more interested in biology.  Or maybe more women were being encouraged to explore science and therefore switched from non-STEM majors they might have wound up in earlier.

Nope!



Source is this concise NYTimes article from 2011*.

So the proportion of bio majors have stayed flat (around 5%, with some wiggle) since the '70s, while this was happening to the number of biomedical PhDs:




Source is this pdf, which seems to be one of the only solid chunks of data floating around out there on PhD outcomes.

The rise in biomedical PhD seekers must have cannibalized the numbers pursuing other career options.  Next question then is what the non-post-graduate-degree seekers with Biology majors do with their lives and how that's changed over time.  Back to the googling...


_________________________

*check out this passage from the NYTimes article:

Spending six or more years to earn a doctorate doesn’t pay off, either. There is such a glut of biology Ph.D.’s that only 14 percent find tenure-track academic jobs within six years.
Younger Ph.D.’s face the biggest problems. Many entered graduate school when federal financing for health research surged a decade ago. But most of the money to fight cancer and search for other breakthroughs went to established researchers. At the same time, in the face of financial realities, universities are clamping down on tenure-track spots in all fields. As a result, many new Ph.D.’s are stuck in one postdoctoral research job after another, helping run laboratories set up by senior scientists, waiting to see if they can win permanent academic appointment.
Starting pay is low, $37,000 to $40,000, and more than a third of biologists are still working in these and other non-tenure track jobs six years after receiving their Ph.D.’s. Others teach at community colleges or high schools, jobs that would not have required as much training, or work for industry or the government.

Nail on the head!

Tuesday, February 5, 2013

Where did we come from?

And by "we" I mean all of us trying to get our PhD in the biomedical sciences:


Back in the 70s and 80s, we were floating along nice and constant-like.  Then, poof, government investment and away we went.  (Then the government investment flatlined [or never really materialized] and the academic jobs dried up - but that's another story for another day.)

So where did we all come from?

Here's my totally made-up-data way of visualizing that question:


Two (reasonable?) assumptions:
  • The total size of the pie increases with time (increased population and all that)
  • The relative portion that is attempting graduate school is also increasing
Then to restate my question: What careers are all the folks in the green chunk of the pie pursuing?

Are they really doing the "alt-careers" that all of us now consider, knowing the odds of landing an academic job are so low?  In the '70s and '80s, was there really a higher proportion of science writers, consultants, industry technicians, and high-school science teachers?  Industry was smaller then, bio-based consulting surely was nonexistent and I can't imagine science teachers have declined.  Science writing has taken a hit, but that's been more recent.

Looking back, medicine would have been the biggest career alternative for most of us.  However, their numbers have held constant while ours have risen, which I suppose means that getting into med school has gotten easier over the past decade.  Or maybe there's such an oversupply of people wanting to be doctors that average admit rates haven't been affected?

Sheesh, what do all the failed MD applicants end up doing with their lives??

Addendum:

I guess the real way of answering this question is to look at career outcomes for bio majors over time.  Yet those data seem to not like being readily googleable.  So who knows.



Monday, February 4, 2013

Nitpicking the News: NYTimes

Even the mighty grey lady has its strange moments.  Take a moment to peruse their fancy graphic on girls vs boys in science testing.


Things that are written about:
  • In the US, boys outscore girls.
  • Blue dots are left-shifted more than yellow and pink dots.
Things that are not written about:
  • The overall triangular shape of the distribution.  In fact the whole y-axis is ignored despite something kind of interesting going on there - low scoring nations tend to have wider gender-related score disparities than high scoring nations.
  • Why the colors?  I mean, why are all of the Americas lumped together?  Why are Western and Northern Europe separated from Southern and Eastern Europe?  Why isn't the Middle East its own color?  And did someone forget to invite Africa to the party?  The article tries to make some vague East vs West points, but then it splits the West up?
  • If the purpose is to relate nationality to test score and gender disparity, then maybe the dots should be colored by something more interesting.  Maybe groupings based on how much is spent per capita on education?  Maybe (given the article's thrust) lump those with similar cultural norms together, as scored by another independent metric?
  • This is ubernitpicky, but it would be way more awesome if when you clicked a dot two vertical box-and-whiskers plots would pop up showing the actual distribution of scores for both boys and girls in that country, not just the average.  Might there be more variability, again, in the lower performing nations?  Would increased variability in within-gender score range (outlier effects) possibly correlate with increased between-gender disparity?
Bottom line: this is a one step forward, two steps sideways kind of thing.  It's cool that the NYTimes brings us these interactive graphics and ways to think and visualize data.  But it's not so cool when the presentation and analysis of the data are shallow and unrefined.

As my editor-in-chief puts it, "Why show the nuance of all the data if you're just going to sum it up with a simplistic takeaway message about the 'anti-science stigma' felt by girls in the US?"