Friday, March 29, 2013

BAM's (officially) coming!

 Giddy times!

What I'm watching for:

How much money, for real?

We've heard $10 billion, $3 billion, and there's also that whole sequesterbudgetmess thing that could have altered the bottom line at the last minute.

Who gets it and how much goes to what?

What percentage will be set aside to establish the BAM "brain observatories"?  What percentage will be available for the general neuroscience community to apply for?  How much explicitly set aside for tech development?  People are going to either be pleasantly surprised by this, really upset by this, or annoyed that they don't explain this enough.  Probably all three.

Who pays for it?

If this means a drop in NIH funding for everyone else, people ain't gonna be happy - expect the science Angstosphere to flip a lot of figurative tables in that event. Of course, no one wants that to happen, including none of the BAM scientists themselves.  It's only the White House that can screw up the funding.

How will Obama sell it?

Really interested to see if it's still all about Alzheimer's and humans or about what the scientists are actually proposing.  Will his statement become fodder for Twittersnark or will the skeptics be impressed? 

What will the Republicans say?

Correct me if I'm wrong, but I haven't seen any political coverage of BAM.  From my understanding, the Republicans still aren't big fans of the President, and they really don't like spending money.  On the other hand, they don't mind neuroscience as far as I know.  So... what will their statements say?  Bland?  Harsh?  Enthusiastic? Will they say anything at all?

Will the media care?

Lead story? One minute in the nightly news?  Overlooked completely?  The media needs a comparison or they won't know how to report it.  I'm fully expect comparisons to the Human Genome Project, but the cynic in me won't be satisfied until I hear some commentator explaining how BAM is nothing like putting a man on the moon. 

And if it's going to happen - when?

Hey, I want my slice of the pie already!

Saturday, March 9, 2013

Of moon backsides and ocean bottoms

Lazy Hook (n) - An overused rhetorical device used by writers who can't think of anything novel to engage their readers' attention.  That guy used a dictionary-style definition to start his post - what a lazy hook.

Today's Lazy Hook comes from the world of oceanography, where this aphorism has proved irresistible:

It’s an oft-repeated anecdote [note the misuse of "anecdote"] of ocean researchers that we know more about the moon than about the bottom of our own oceans.

On the one hand, there's the moon.  It's a thing, and a place.  Go outside and you can see it from your front porch.  "Wow," you might say to yourself, "that is a place that is hard to get to."  Now look out at the ocean, which you can also see from your front porch if, for example, you're me (deal with it, plebs).  "Wow," you say again, "that is also a place.  However I can get there by walking for five minutes."  Enter trite science writer: "Did you know that we know more about the surface of the moon than we do about the bottom of the ocean?"  And cue your mind exploding.

Then, as your mind starts putting its pieces back together, it might wonder, "Really?  Why are we comparing the moon to the ocean?"

First, some history.  Roger Revelle.  He's the famous geologist of Scripps Institution of Oceanography, which is a beach-side resort research-center in San Diego.  The place became very successful while he was there, and eventually decided it needed a university attached to it, so Revelle went and made UCSD happen (true story). 

Some time during the prime of  his career (the '50s-'70s) Roger Revelle originated the saying that would later be attributed to him in his obituary: "We know less about the ocean's bottom than the moon's back side."

Back then, this was apropos.  Lunar exploration was beginning scientifically and was already culturally profound.  Plus, we REALLY didn't know anything about what was going on at the bottom of the ocean.  Therefore it makes sense that Revelle, a geologist by training, would be interested in comparing the moon and ocean floor: here were two landscapes with interesting geographies and geologies, yet one - the far away one - was more explored.  Back then, it was novel and fitting - an effective hook.

But now...

Observe how the comparison is dredged up in contexts it doesn't belong in.  From UC Santa Cruz:

There’s a cliché in science:  We know more about our moon than the ocean’s depths.  And yet the sea remains Earth’s greatest frontier.  A reservoir of heat and life, the ocean controls and reacts to Earth's climate in myriad ways. Winds, currents, and nutrients dictate which species survive and where. Unknown stresses force so me [sic] microbes to release dangerous toxins. These cycles, from local to global, drive the research of ocean scientists at UC Santa Cruz.

How can you read that and not simply think, "Well, okay.  So I guess there's just more to know about the ocean?"  Because that's the uninteresting truth.  By that standard, there's more to know about a baboon's back-side than about the back side of the moon, but do primatologists claim to be studying  the final frontier?

For another example of the moon Frontierifying the ocean, let's return to the Discover magazine piece to see the Lazy Hook in its entirety:

It’s an oft-repeated anecdote of ocean researchers that we know more about the moon than about the bottom of our own oceans. Humans meet our match when it comes to probing cold deep bodies of water.
We are drawn to the deep by its ancient mysteries, chilling down below. But we also come up against our limitations there, battling against equipment failure, aching cold, and the frontiers of technology.
Research in the deep reveals the sometimes-shy face of science that turns away from a soundbite-infatuated media: halting, meticulous, even serendipitous. Like space exploration, exploring the deep can be delicate and dangerous—a stage for human victories and heart-rending mistakes. 

What a load of saccharine rah-rah.  Challenge!  Triumph!  Heartache!  The human conquest of the depths!

Is this really necessary to justify ocean research?  Read the rest of the piece here.  Notice how after that opening, the article hilariously forgets those stirring themes.  It's just a pretty straightforward look at four cool stories of ocean/lake science.  And none of those stories, by the way, deal with anything that can be remotely compared to the moon!  So why the need to motivate the reader with BS?

The right way to use the moon-ocean comparison is to restrict it within its original Revellian context.  As Gene Feldman puts it in an interview with NASA:

But even with all the technology that we have today -- satellites, buoys, underwater vehicles and ship tracks -- we have better maps of the surface of Mars and the moon than we do the bottom of the ocean. We know very, very little about most of the ocean. This is especially true for the middle and deeper parts far away from the coasts. 

See, science writers?  If you're talking geography (and maybe geology) it's fair to hook your audience by comparing the moon and ocean floor.  If you're talking biology, physical chemistry, or climate then go find yourself another angle.

Thursday, March 7, 2013

Clarifying BAM

A new white paper is out in Science Express today, written by many of those involved in the Brain Activity Map project (BAM).  It's paywalled, so I thought I'd share some initial key quotes from it and my reactions:

First, they seem highly aware of the criticisms - born of the comparison to the Human Genome Project - that BAM had vague goals.  Here they make directly explicit what was a bit fuzzy beforehand:

The BAM project is essentially a technology-building research program with three goals: (i) to build new classes of tools that can simulta-neously image or record the individual activity of most, or even all, neurons in a brain circuit, including those containing millions of neu-rons; (ii) to create tools to control the activity of every neuron individually in these circuits, because testing function requires intervention; and (iii) to understand circuit function. 

So, yes - this IS just tech dev.  Will be interesting to see if the "But this isn't a moon shot!!!!!!" critics will chill out after this.  Probably not.

Next, they have scaled back their ambitions.  No longer is it even mentioned that in 15 years research could be progressing towards primates (among those, humans).  Instead, they restrict themselves to the following timeline:

Within 5 years, it should be possible to monitor and/or to control tens of thousands of neurons, and by year 10 that number will increase at least 10-fold. By year 15, observing 1 million neurons with markedly reduced invasiveness should be possible. 

Note that human brains have 90 billion neurons.  They're talking about, at best, getting to a large chunk of mouse cortex in 15 years (still no easy feat), which should inure them to some of the criticism based on infeasibility/unreasonableness.

And among the model organisms they will use prior to mice:
Invertebrates such as the worm, fly, or leech are ideal for testing new technologies, where the results can be compared to extensive, growing bodies of data on the functions of identified neurons and smaller-scale circuits.

(I study leech neuro... it's pretty cool that the leech gets a shout-out here, as it's usually not on the shortlist of invert experimental organisms [that stops at worm and fly].  Bit of an oversight, though, that they omit the crab stomatogastric ganglion, as Eve Marder is also involved in this).

Next, there's a lot of blahblah about connections to human clinical work and diseases and such.  Lots of "may lead to" sentences and whatnot:

We believe that tools and knowledge created by the BAM project may lead to new approaches to rebalance disordered networks and treat [strokes, cerebral palsy, amyotrophic lat-eral sclerosis, or spinal cord injury].

Finally, there's another statement designed to soothe the critics:

We believe this initiative should be funded by a partnership between federal and private organizations. It is essential that those funds not be taken away from existing neuroscience initiatives, which we view as crucial. In addition, data from the BAM project should be made immediately public and accessible to all researchers.

So in sum, the new white paper doesn't add all that much - although it does clarify their goals and tighten up the proposal in response to criticism.  There're no new details about the "brain observatories" idea that's floated around in some press and interviews.  There's no new details about how the money will be structured.  And the biggest question still remains unexplored:

Will Congress even want to fund this?

Wednesday, March 6, 2013

BRAIN links


Please find the updated version of this post on the tab above:


Here be a repository for BAM BRAIN Initiative links!  If you have something I've missed (and I've probably missed tons) then please comment or hit me up @jipkin.  I'll endeavor to update this as the story progresses.

On the Internets:

Physical Principles for Scalable Neural Recording (arXiv) (July 2, 2013)
Physical principles for scalable neural recording (John Hewitt, medical express) (July 2, 2013)

Building a Brain (CBC Quirks) (June 22, 2013)
Hunting for the Brain's Hidden Treasures (SciAm, Dwayne Godwin, Jorge Chan) (July 1, 2013)
Reviewing the BRAIN Project (ASMB today, Jeremy Berg) (June, 2013)
Why mapping the brain matters (Nature Methods, editorial) (May 30, 2013)

Why You Should Care about Pentagon Funding of Obama’s BRAIN Initiative (SciAm, John Horgan) (May 22, 2013)
Update on the Great BRAINI Debates (Nucleus Ambiguous, Michael Carroll) (May 12, 2013)
My thoughts on the first BRAIN initiative meeting (Dam Bumbarger) (May 9, 2013)
Where are the BRAINI women? (Erin McKiernan) (May 9, 2013)
Neuroscientists put heads together at national brainstorming session (Medical Express, John Hewitt) (May 8, 2013) 
BRAIN feedback at NIH (NIH)
BRAIN Initiative (Scientopia, DrugMonkey) (May 7, 2013)
Workshop on the Physical and Mathematical Principles of Brain Structure and Function (NSF) (May 5-7, 2013)
#nsfBRAINmtg live blogging of DATA topic , THEORY , ELECTRICAL (Joshua Vogelstein, May 6, 2013)
livestream channel with VODs of nsfBRAINmtg (Livestream, May 5-7, 2013)
Neuroscientists brainstorm goals for US brain-mapping initiative (Nature, Helen Shen) (May 6, 2013)

From BAM to The BRAIN Initiative: A clearer view of a major neuroscience enterprise (The Incubator, Gabrielle Rabinowitz) (May 3, 2013)   

Interview with BRAIN Project Pioneer: Miyoung Chun (MIT tech review, Jason Pontin) (April 15, 2013) 
The BRAIN Initiative, first thoughts (Scientopia, DrugMonkey) (April 15, 2013) 
Why The Human BRAIN Initiative Is So Important To All Of Us! (HuffPo, Daniel Burrus) (April 17, 2013) [this is a funnily terrible article] 

An open letter to Larry Swanson: Why it is important for neuroscientists to debate the Brain Initiative in public (Justin Kiggins) (April 15, 2013) 
2 More Reasons Why Big Brain Projects Are Premature (SciAm, John Horgan) (April 10, 2013)

The ENCODE project: Missteps overshadowing a success (Current Biology, Sean Eddy) (April 8, 2013)
The BRAIN Initiative: BAM or BUST? (SciAm, Scicurious) (April 8, 2013)
The Moon is not Made of Cheese and Other Hypotheses (Nucleus Ambiguous, Michael Carroll) (April 8, 2013)

Skepticism about Obama's Brain Project (New Savanna, Bill Benzon) (April 7, 2013)
To crack human brain's code, a search for visionaries (Reuters, Deborah Zabarenko) (April 7, 2013)
What do you think of Obama's proposed "BRAIN Initiative"? (Quora discussion) (April 7, 2013)
Neuroscience needs its Einstein (Salon, Jonathon Keats) (April 6, 2013) 
Some still skeptical of BRAIN initiative as details remain fuzzy (Fierce Biotech Research, Emily Mullin) (April 5, 2013)
Obama's Brain Map Initiative Needs a Rethinking (Live Science, Donald Stein) (April 6, 2013)
Colbert gets fake EEG'd (Oscillatory Thoughts, Bradley Voytek) (April 4, 2013)  

Now or Then: Which Big Science Project are These Scientists Worked Up About (Wired, Greg Miller) (April 5, 2013)
A Leader of Obama's New BRAIN Initiative Explains Why We Need It (Wired, Greg Miller) (April 3, 2013) 
As White House Embraces BRAIN Initiative, Questions Linger (Science Insider, Emily Underwood) (April 3, 2013) 
Will Obama's new $100m brain mapping project be open access? (Open Knowledge) (April 4, 2013)
From Junk DNA to Junk Economics: Beware the Inexorable Sovietization of Big Science (Bio IT, Bill Frezza) (April 3, 2013) 
BRAIN (Scientopia, Neuropolarbear) (April 3, 2013) 
On The Frontiers of Brain Research (NYTimes, Editorial Board) (April 2, 2013) 
Obama's BRAIN Initiative (The Colbert Report, Stephen Colbert) (April 4, 2013) 

BRAIN Initiative Challenges Researchers to Unlock Mysteries of Human Mind (whitehouse) (April 2, 2013)
Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative (NIH) (April 2, 2013)
DARPA/NIH/OSTP Twitter Q&A (whitehouse) (April 2, 2013)
President Obama Speaks on the BRAIN Initiative and American Innovation (whitehouse) (April 2, 2013)

A New Push To Explore the Brain (The Loom, Carl Zimmer) (April 2, 2013)
Obama's BRAIN Initiative is a huge boost for new neurotechnology (extremetech, John Hewitt) (April 3, 2013)
President Obama's brain map project is hardly the next Human Genome (guardian, Erin McKiernan) (April 2, 2013)
Introducing the BRAIN Initiative (empiricalplanet, Jason Pipkin)
BRAIN Initiative (nee BAM) Made Officially Palatable (Nucleus Ambiguous, Michael Carroll) (April 2, 2013)
Obama: 'Braaaaaaains.' Partha Mitra: 'Whoa there, buddy.' (WaPo Wonkblog, Dylan Matthews) (April 3, 2013) this is misleadingly titled... Mitra is actually pretty much ok with the latest proposal from his answers.
Obama Invests in Brain-Mapping Project (KQED) (April 3, 2013) hate this title - they removed the "map" part for a reason when they went from BAM to BRAIN.
Barack Obama, Neuroscientist in Chief? (Brain Facts, Dwayne Goodwin) 

BAM, federal funding, and patents (Erin McKiernan) (March 30, 2013)
Somewhere Over the Brainbow: The Journey To Map the Human Brain (NPR) (March 31, 2013)
BAM's (officially) coming! (empiricalplanet, Jason Pipkin)

Is Brain Mapping Ready for Big Science? (GenEngNews, Patricia Dimond) (March 29, 2013) Rafael Yuste: More Bucks for the BAM (Nucleus Ambiguous, Michael Carroll) (March 14, 2013)
Obama's Brain Activity Map Needs a Compass (Real Clear Science, Brad Dickerson) (March 13, 2013)
The Three-Billion Dollar Brain (New Yorker, Gary Marcus) (March 12, 2013)
What's Not Wrong with the BAM Project and How to Fix It (Nucleus Ambiguous, Michael Carroll) (March 10, 2013)
Do the BAM Proponents Even Understand Open Access? (Nucleus Ambiguous, Michael Carroll) (March 9, 2013) 
Hard Cell (The Economist) (March 9, 2013)
Clarifying BAM (empiricalplanet) (March 7, 2013)

Behind the scenes of a brain mapping moon shot (Nature, Meredith Wadman) (March 6, 2013)
What's Wrong with the Brain Activity Map Project (Scientific American, Partha Mitra) (March 5, 2013)
Partha Mitra Makes no Sense (to me) (empiricalplanet, Jason Pipkin) (March 5, 2013) 
What is the Brain Activity Map? George Church Q&A (Kurzweil) (March 4, 2013) 
The Bloating of BAM and how to sell big brain science (empiricalplanet, Jason Pipkin) (March 3, 2013)

What's a connectome good for anyway? (empiricalplanet, Jason Pipkin) (March 1, 2013)
Proposed Brain Activity Map may also advance nanotechnology (Foresight, James Lewis) (March 1, 2013)
How the Brain Activity Map came together (Spoonful of Medicine, Nature Blog, Virginia Hughes) (March 1, 2013)
Neuroscience! Because Alzheimer's! (NeuroDojo, Zen Faulkes) (Feb 28, 2013)
BAM and the Molecular Ticker Tape (Nucleus, Ambiguous, Michael Carroll) - love this one! (Feb 27, 2013)
Bang or BAM? On respecting complex problems (Pascal's Pensees, Pascal Wallisch) (Feb 27, 2013)

A Manhattan Project to Map the Brain? (Brain Facts, Dwayne Godwin) (Feb 27, 2013)
A 3 Billion Dollar Mistake (The Incubator, Gabrielle Rabinowitz) (Feb 25, 2013)
Finding the Treasure: A practical view on where the Brain Activity Map will lead us (Neurdiness, Grace Lindsay) (Feb 24, 2013) 
BAM Matters (Nucleus Ambiguous, Michael Carroll) (Feb 24, 2013)
Brain activity map: boondoggle or bonanza? (Out of the Fog, Chris Palmer [former labmate of mine!]) (Feb 24, 2013)

Brain Project Draws Presidential Interest (Science Insider, Emily Underwood and Jocelyn Kaiser) - source of some good info! (Feb 20, 2013)
BAM! My thoughts on Big Bucks for Big Brain Science (Nucleus Ambiguous, Michael Carroll) (Feb 19, 2013)
BAM! Let's do neuroscience!(empiricalplanet, Jason Pipkin) (Feb 18, 2013)
BAM! Mind control! (empiricalplanet, Jason Pipkin) (Feb 18, 2013)
Brain Activity Map: Every Spike from Every Neuron (Bob Blum) - nice science overview! (Feb 18, 2013)

Major Media:

Obama Seeking to Boost Study of Human Brain (original newsbreak - NY Times)
Connecting the Neural Dots (NY Times follow-up)
Brain Activity Map Project (wikipedia)
Science Chronology:
Chicheley Meeting White Paper (no link, but there existed a white paper made by some of the people who met at the Kavli International Meeting in September 2011.  This would later go on to become BAM)
The Brain Activity Map Project and the Challenge of Functional Connectomics (June 2012, Neuron.  Initial look at what six of the scientists involved came up with).  
Data Deluge from the Brain Activity Map (Summary from January 2013 Caltech meeting)
The Brain Activity Map (Science, BAM major players)
Nanotools for Neuroscience and Brain Activity Mapping (ACS Nano, BAM players) 

Science Background:

Of Toasters and Molecular Ticker Tapes (PLOS compbio - first suggestion of using DNA to record neural activity at single-spike resolution, I believe)
Sequencing the Connectome (PLOS bio - Tony Zador group idea that might be explored with BAM)

Steering Committee:

Cori Bargmann
Bill Newsome
David Anderson
Emery Brown
Karl Deisseroth
John Donoghue
Peter MacLeish
Eve Marder
Richard Norman
Joshua Sanes
Mark Schnitzer
Terry Sejnowski
David Tank
Roger Tsien
Kamil Ugurbil

Ex Officio members:
Kathy Hudson (NIH) (went to my alma mater apparently)
Geoffrey Ling (DARPA)  
Note that this committee is dominated by scientists, not technologists.  I'm told that this was the intent - to only include tech people that were interested in applications (Ugurbil, Tsien, Deisseroth) not for the sake of tech.  The ostensible goal of this committee is to rally the larger neuro community and design the 2014 project goals, then the later goals. 

Major Players:

Rafael Yuste (includes some good links to his media appearances) 
George Church
Miyoung Chun
Ralph Greenspan
Paul Alivisatos
Michael Roukes
John Donoghue
Terry Sejnowski
Larry Swanson
Clay Reid
Christof Koch
Karl Deisseroth
Eve Marder 
Sebastian Seung
Paul McEuen
Paul Weiss


Tuesday, March 5, 2013

Partha Mitra Makes No Sense (to me)

The Brain Activity Mapping project (BAM) has a lot to be critical of.  There's the dubious/wise choice of selling it by promising Alzheimer's cures.  There's the funding angst - will the Administration choose to reduce NIH budget to accommodate this?  (Something, by the way, that no one, including BAM planners, wants to see).  There's the particular scientific techniques they want to explore, including the far-out "molecular ticker-tape" strategies.

But in terms of overall scientific goals, BAM should be unimpeachable.

The aspirations of BAM folks are to develop new technologies that will bring them closer to the goal of recording as many neurons simultaneously as possible.  This, as I've written before, is essentially what a large chunk of neuroscience is about.  We want to know how the brain works, so we record from brain cells!

Enter Partha Mitra, a Cold Spring Harbor PI who does, essentially, mouse connectomics (anatomical brain mapping) as well as computation/theory.  He's written a new article appearing in Scientific American that mind-bogglingly challenges the very notion that we should even TRY to record from as many neurons as possible:

The fundamental problem with the goal of measuring every spike of every neuron is one of conceptual incoherence: the proposal does not stand up to theoretical scrutiny.

So his argument is going to be that there's no point to recording every spike from every neuron - it's a fruitless task that can only end in "incoherence."

Let's go point by point through some of his contentions, and see how they hold up:

[...] the authors imply that this correlated or collective behavior cannot be deduced from other levels of observation (including the circuitry), hence the imperative need for the “measure every spike” project.

This is grossly misleading.  In fact, the authors "imply" exactly the opposite in the article he's referencing: 

Correlating this firing activity with both the connectivity of the circuit and its functional or behavioral output could enable the understanding of neuronal codes and their regulation of behavior and mental states. 

Note "connectivity of the circuit".  The whole point of BAM is to develop new tools and record from as many neurons as possible.  Then, of course, take all that information into the BAM lair and look at it in isolation from everything else!  Oh wait, that's stupid.  Of course the anatomy of the circuit is important.  That's why they want to start with organisms like C. elegans which has a defined connectome and progress to preparations like the mouse retina, which is already the subject of ongoing mapping efforts.


First, brains do not exist in isolation. Spikes are driven by two sources: the intrinsic dynamics of the neuronal network, and external stimuli. Even if one recorded all spikes from all neurons (and for the entire life span of the organism), to make any sense of the data one would have to simultaneously record all external stimuli, and all aspects of behavior. It gets worse: there will be individual variation among animals, and each animal will have a different environmental history. The “comprehensive” measurement exercise would extend ad infinitum. 

This is all true and all irrelevant.  He's arguing against the strawman, essentially saying "You can't measure everything all at once!  There's too much!"  But does that imply that there's no value in trying to measure as many cells as possible?  In developing the technologies that would make that possible?  Keep in mind, one can use these technologies for whatever behaviorally-limited purpose one wants, just as we already do.

Of course he does admit this:

One could moderate the number of neurons being recorded from, control the environmental variables, and so on — and then one has returned to the realm of what neuroscientists are doing in any case and we have a specialized technology development project, not a moon shot or a genome project.

And yes, this IS what we have.  It's not moon shot or human genome - it is what it is, and that's tech dev -> massive simultaneous single-unit recordings.  So perhaps a lot of what he's writing has to do with how grandiose BAM has been made out to be so far.  Yet he still has an objection to even the idea of doing massive recordings - why?

Still, to understand whether one should focus all energies on greatly increasing the number of neurons being recorded from, we need to answer the theoretical question of what we gain by recording every neuron. If we cannot successfully argue that comprehensive neuronal recordings solve all our problems, then partial observations certainly won’t.

True but false.  We cannot argue that massive recordings solve "all our problems".  But they can help solve some of them.  It's equivalent to the "Well the connectome can't do X, so there's no point in doing it at all" argument that is clearly illogical on its face (and he should be aware of that, given his research!).  Spikes may be all or nothing, but the value of an experimental approach isn't.

One is not really interested in the particulars of a given animal’s history of all spikes in the brain: one is interested in characterizing the potential dynamics of neurons, under all possible circumstances .

First of all, "one" can be interested in all sorts of things.  But to his general point - again true but false.  We can be interested in characterizing the potential dynamics under some circumstances and still have a valuable contribution to make.

Here is the rub: what sets the laws of the neural network? Well, it is precisely the circuit connections and the physiology of single neurons that the authors have dismissed. The paper would focus all resources into multi-neuron recordings, without any plan to complete the outstanding task of mapping out the anatomical circuitry, itself a huge project, which we have only begun to seriously address and which provides a much closer analog to the Genome project. The physiological properties of neurons depend on carefully studying individual cells or pairs of cells, also not something that is on the agenda. Once the circuit and cellular physiology is known, we can in principle derive the pattern of every spike from every neuron, under every environmental stimulus. Network structure and cellular physiology determine the dynamical laws governing the neurons, and therefore drive the spiking activity .

Yes, there is the rub.  Focus on the bolded sentence:

(1A) You cannot know cellular physiology without recording from cells.
(1B) There are many cells in the circuit, each with a unique physiology, even if some belong to classes or types of similar cells.
(1C) Therefore recording from as many cells as possible gives you the most cellular physiology.
(1D) Therefore... BAM, which seeks to develop new tech to record from many neurons simultaneously, is crap?

(2A) The circuit is knowable at any one given moment, say from a connectome.
(2B) Circuits change over time.
(2C) Therefore it is impossible to know the pattern of all spikes "under every environmental stimulus" except for the circuit in the state it was measured to be in.
(2D) Therefore that sentence should be objectionable to Partha Mitra himself on the basis of the same criteria he laid out earlier: "The “comprehensive” measurement exercise would extend ad infinitum."

Additionally, when speaking of issues with Markram's brain-from-the-bottom-up project:
The way to resolve this is not to measure every spike from every neuron, but to map circuit connectivity and measure cellular physiology.


I think what's motivating Partha Mitra's response is NOT what BAM is, but rather how it's being presented (and maybe a little bit of saltiness that his mouse connectome efforts aren't included in it...).  The record-every-neuron thing IS unfeasible, at least in humans and probably in mice too.  But to argue that it's also wrong to want to record from every neuron?

I guess I just don't get it.  He says, for instance, that recording from a single neuron, or pairs of neurons is okay.  But "every" neuron is not theoretically sound.  So, presumably, somewhere between 2 and "every", which we'll call 90 billion, there's a number at which it's no longer theoretically justified to look at individual neuronal spiking?  What?

In fact, he even writes:
Over the last two decades many labs have gathered spiking data simultaneously from dozens to hundreds of neurons. This has not yet led to any tremendous new insight: in fact, much of the dynamics can be captured by the study of correlations between pairs of neurons.
So, yeah, all you guys and girls doing calcium imaging and multi-unit recordings and multi-electrode array recordings... guess what?  You haven't produced any "tremendous new insight".  Only non-tremendous ones, I guess, but everyone knows those don't count.  There's only the behavioral level, and the single-cell level.  What's the point trying to bridge the gap?

Finally, I've ignored most of what he wrote comparing neuroscience and physics on the grounds that all analogies suck and that I'm not really qualified to argue whether we can expect truly emergent properties from these kinds of recordings or not.  Maybe that's his objection - he doesn't think there are emergent properties, so BAM is bad.  But that's fallacious because then he's just arguing against the motivations for what's being proposed, not what's actually being proposed.


There are issues with BAM, related to cost, possible opportunity cost, and, especially, how its communication tends to rely on the grandiose.  All of that is up for debate.  But the merits of the scientific goals?  There's no theoretical point to recording from a massive number of neurons?  Better to just wait and build a simulation from the bottom up?


Sunday, March 3, 2013

The Bloating of BAM and How to Sell Big Brain Science

The Bloating of BAM
a fictional retelling

OFFICE OF SCIENCE AND TECHNOLOGY POLICY (OSTP) : BAM planners!  We're very excited by the white paper you presented us following your Chicheley meeting.  Could you please shape this into a proposal for a Presidentially-endorsed project?

BAM:  Of course!  How about $10 million for developing new nanoprobes and improving imaging so that we can record from 100,000+ neurons at once?  These new technologies could accelerate systems neuroscience dramatically!

OSTP: (pause) Okay.  That sounds great.  But I don't think you understand - do you think we bother the President for $10 million?

BAM:  Sorry!  I meant $100 million!  We might be able to record over 1,000,000 neurons and maybe even get every neuron in Drosophila at once!

OSTP:  No.  We want a Presidential project.

BAM:  But we -

OSTP:  Higher.

BAM:  (gulp) Alright.  We need $3 billion.  We'll, uh, be able to do all the stuff before... and, uh, yeah we can totally do the entire human brain all at once.  Yep, all 90 billion neurons.

OSTP:  More.

BAM:  Oh, well once we've got that, curing Alzheimer's and Parkinson's should be a snap.

OSTP:  Great!  Done.


And that, Dear Reader, is how I imagine BAM ended up in the situation it's in.  The scientists behind BAM all seem like very reasonable people who would certainly tell you in private that it's ridiculous to expect to be able to record from every neuron in the human brain any time in the next 100 years.  Their language, in the initial Neuron article, is tentative on human research, and the minutes from the Caltech meeting this year suggest that "million-neuron march" (in mice) is what they see as a more realistic goal.  Yet there the President is, making oblique references to BAM curing Alzheimer's in the State of the Union, followed thereafter by the giddy announcement in the New York Times.

This is the critical communication problem for BAM: it's promising something it fundamentally can't deliver in any reasonable time frame.

So how do we resolve this dilemma?  Can we?  

Actually, wait a minute - should we even bother?  

As I thought about it more and talked to some people around campus here, I've come to think that maybe we shouldn't fix the communication problem.  I mean, here's the two basic ways to sell this thing, starting with what people are saying in interviews, but isn't showing up in the headlines:

(1) Retrench around "million neuron march" and technology development

It's both reasonable and excitingly ambitious to frame BAM this way: "Let us develop breakthrough technologies that will help us measure the brain on a scale we've never done before.  The tools we develop for generating and analyzing the data will revolutionize neuroscience and bring us closer to understanding how the building blocks of the brain are really put together." 

But this is also frustratingly abstract.  As a neuroscientist, hell yes!  As a member of the public, or Congress?  Yawn.  You don't get $3 billion for a "million neuron march".  And with that reality in mind,

(2) Why not oversell it?

Hey, why not claim that you're going to map the human brain and cure disease?  After all, that's what everyone in basic neuro ends up doing anyway in their grant proposals and publications. albeit on a smaller scale.  There was a period not too long ago when every paper about synapses had three sentences at the end about autism, even when nothing they did was anything other than remotely linked to the disorder.

The logic here is as follows: members of the public (and Congress) don't really pay attention to Big Science once it's been funded.  For instance, Michael Eisen has been dropping acid tweets about BAM since the news broke, mainly informed by his poor experience with something called ENCODE, another Big Science initiative.  But I didn't even know what ENCODE was until seeing his comments, and I'm a pretty-well informed member of the public (I think).

So it doesn't matter if BAM can't deliver on the human brain - after all we'd still be able to deliver on a bunch of other really cool things that actually might just revolutionize the field and benefit society in other ways.  One faculty member I spoke with compared it to stem cells - the public was initially sold on stem cells by arguing that we would be able to use them to cure all sorts of diseases in 5 years.  Naturally, California voters appropriated $3 billion to study themSo have we cured all sorts of diseases?  No, but good science got done and we're closer to those cured-disease endpoints than we would have been without the money (well, we think we are, anyway). 

I'm personally a bit uneasy about this approach (not a huge fan of lying and all), but I can't deny that there's a certain pragmatism to it.  There's no way anyone is going to give this much money to do basic neuroscience dressed as itself - so it's either you don't go for this much money or you bloat the project with grandiosity.  

Remember too that this is no superconducting super collider - even if Congress pulls the plug on this thing two years in, that's still $600 million dollars spent on basic neuroscience research.  Would that be such a bad thing?