Tuesday, April 9, 2013

Obama’s Incoherent BRAIN

We have a good understanding of the sense of smell at the biological periphery. We know how odor receptors work and how the sensory information they convey is organized in the nose and olfactory bulb. Beyond that, however, things get murky. We know the higher brain areas of olfaction only in broad brush strokes. We have barely an inkling how odor intensity and pleasantness are modulated by brain areas dealing with memory and emotion. Wouldn’t it be great to have it all mapped out, from the physical molecule of trimethylamine to the behavioral yuck response?

That is the allure of President Obama’s $100 million brain research initiative. But it isn’t easy to get a handle on what exactly the project consists of.

Susan Young’s piece yesterday on the MIT Technology Review website is subtitled “Obama calls for $100 million to develop new technologies to understand the brain.” She makes it sound like a technology development initiative.

But today’s WSJ op-ed by Paul Allen and Francis Collins calls it “a federally coordinated effort to unlock the secrets of the brain,” to “gain powerful insights into neurological diseases and mental-health disorders.” That sounds like basic research, not technology development. So which is it?

Allen and Collins note that neuroscientists have a host of research techniques at their disposal. They observe that we can study small, isolated neural circuits but we don’t yet understand how the brain works as a whole. To understand “this piece of highly excitable matter” we need a massively scaled up effort, broadened to include “a range of disciplines, from physics and biology to nanoscience, computer science and engineering.” Or, as Allen and Collins say, “All hands must be on deck.”

But here’s what Young sees: “The BRAIN initiative proposes to develop new technologies that can record the activity from thousands, if not millions or billions, of neurons simultaneously at timescales matching behavior and mental activities.” Among the new technologies she lists are nanochips, nano particles, nanoprobes with wireless data transfer, novel optical techniques, voltage-sensitive fluorescent molecules, synthetic biology, improved calcium-imaging methods and enzymes that build ion concentration-sensitive errors into DNA.

So would new techniques get us closer to the Big Picture in odor perception? Perhaps. But it’s not as if we’re hurting for technology. Among the techniques used to study smell are calcium imaging, single cell recording, patch clamp recording, cell ensemble recording, fluorescent imaging of gene expression, optical tracing of trans-synaptic connections, autoradiography, fMRI, EEG, recording of chemosensory evoked potentials, magnetoencephalography, transgenic expression of receptors (a.k.a. “synthetic biology”), genomics, and computer modeling of receptor activation. There is no one path to understanding the Secret of Odor Perception—it is being attacked with a diverse arsenal of technology by a lot of really smart people focused obsessively on smell.

The BRAIN project, in contrast, sounds like a plan invented by the Underpants Gnomes: (1) create technology, (2) ?, (3) unlock the secrets of the brain. Like the Underpants Gnomes, BRAIN fans are adamant about wanting one thing: more. More technology, more researchers, more money. More underpants.

To be fair, Allen and Collins say “progress will also hinge on the cooperation of the public and private sectors, a welcome aspect of the president’s “BRAIN” initiative. We’ll need creative, nimble management to ensure the best work out of both sides.” It’s a bit ironic to hear Francis Collins call for nimble management. He led the federal government’s enormous Human Genome Project which, you’ll remember, was nearly beaten to its goal by Celera Genomics, J. Craig Venter’s private company which started later but moved faster.

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