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The Scicurious Brain

The Scicurious Brain

The Good, Bad, and Weird in Physiology and Neuroscience

The BRAIN Initiative: BAM or BUST?

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In his State of the Union this year, President Obama referred to increasing support for science and technology, and mentioned the “Brain Activity Map”. Of course neuroscientists were instantly atwitter. It was the first we’d all heard of any Brain Activity Map. What is it? What did it mean?

After a lot of speculation and some quickly formed opinions about whether or not it was a good idea…the White House has now unveiled what the project actually is: BRAIN, Brain Research through Advancing Innovative Neurotechnologies. And what is the project exactly? Will the BRAIN project end up as a BAM (Brain Activity Map)? Or a BUST (Badly Underfunded S**T)?

I’d like to explore what I know, and I’d like to hear what everyone else knows as well. Am I wrong? Am I too optimistic? Too pessimistic? Have at.

It does, at least, come with some very pretty pictures. Source

What is the BRAIN Project about? What are its goals?

Well, nobody knows, actually. I certainly don’t know. But it appears that no one else knows either.

“This working group, co-chaired by Dr. Cornelia “Cori” Bargmann (The Rockefeller University) and Dr. William Newsome (Stanford University), is being asked to articulate the scientific goals of the BRAIN initiative and develop a multi-year scientific plan for achieving these goals, including timetables, milestones, and cost estimates.”

So basically, BRAIN is a very fancy initiative, with a fancy name…and so far, no goals. And of course, we’re all excited and trying to figure out what it’s going to be and whether or not it will work. Maybe it would have been in the better interest of the White House to wait until there were…you know, goals.

But there is one goal that seems established here: new technologies.

New technologies you say?

The thinking is like this: right now we have the capability to do certain things in terms of understanding brain function. We can see changes in bloodflow in response to stimuli (that’s fMRI), we can see different receptor concentrations (that’s PET), we can use surface electrodes to look at the electrical activity of very large neuron populations in various areas of the brain (that’s EEG). And we can insert electrodes, sometimes many of them at a time, to each capture a single neuron and record that neuron’s firing rate, and watch it change as we do something to it (that’s electrophysiology). We can even do other things, take neurotransmitters or receptors out entirely, only in a single region of the brain (knockouts), we can insert light-activated channels that will cause only the cells possessing them to fire (or not) in response to light (that’s optogenetics). We can insert new receptors into specific neuron populations, receptors that can ONLY be activated by designer drugs that activate no other receptors (those are DREADD receptors). We can insert probes to take samples of the neurotransmitters and other chemicals present in the brain (microdialysis).

So we do have technologies to look at the brain and what’s going on in it. But it’s true, they are limited. Especially in humans, many of those techniques can only be carried out in animal models (though the animal models are still incredibly important and informative). So we do need new technologies, and project like BRAIN could give us the funding to develop some technologies that are currently in their infancy.

Yes, but what’s the end point?

When they first announced the BRAIN project, there was some mention of mapping out all the connections in the human brain. That’s around 100 TRILLION connections made by 85 billion neurons. It’s a Herculean task at best.

But it’s also, to be honest, impossible in the way that most people imagine it. The reality is you don’t just have a brain full of connections and some people have different connections and that’s why they have trouble with math or something. Instead, each person’s connections within their brain are individual. Sure, this is true for the human genome as well, nobody’s two genomes are exactly the same (except identical twins). But the brain connections are more than individual, they are always CHANGING. Everything changes your brain. Whether you’re stressed, what languages you speak, whether you ate breakfast. All of these things, even the smallest, can change small connections in your brain and alter your future responses and behavior. So a map of all the connections in a healthy human brain (probably an adult male of around 35) from which we can determine who deviates from the norm and what that means? It’s an idea that is doomed from the beginning.

So we’re not going to have a Brain Activity Map like many people first assumed (though we might see some really cool fruitflies and zebrafish). What will we have? Again, we don’t know.

If we don’t know, how do we get these new technologies?

A good question. What goals do you set, what questions do you ask, to BRING OUT the new technologies we need…when we may not even know what new technologies we need?

This isn’t the neuro version of the human genome project. By nature, it CAN’T be. The genome, for all its many twists and turns, is a relatively simple problem to solve in terms of sequencing (though, it’s important to note that we have no idea what each gene actually DOES). They knew how to sequence, but it was a very slow and laborious process. During the Human Genome Project, and partially as a result of it, sequencing became a fast and beautifully streamlined technique, so much so that many universities now have sequencing cores which will do your sequences for you in record time.

So the Human Genome Project did provide some really great techniques (as well as the important knowledge from sequencing disease-specific areas). But it was a concrete goal, one where new technologies could focus. Without a goal that is similarly concrete (in some way), I’m not sure how BRAIN will get the technologies that it wants.

Show me the money.

According to the White House Fact sheet, the BRAIN initiative will be getting $110 million to start up from the National Institutes of Health ($40 million), the National Science Foundation ($20 million), and the Defense Advanced Research Projects Agency ($50 million). Part of me feels terrible that here’s the NSF giving $20 million to BRAIN when they just cut all political science research and are already funding at major reductions, and the NIH is suffering similar issues. They’ve also gotten support from private groups, in particular the Allen Institute for Brain Science ($60 million), the Howard Hughes Medical Institute ($30 million), the Kavli Foundation ($4 million), and the Salk Institute ($28 million). All of that ($232 million) is scheduled for Fiscal Year 2014.

At first I thought (from the press releases) that it was only going to be $100 million or so for the whole project. That, in research dollars, is NOT a lot of money at all. Many grants to individual neuroscience researchers are about $1 million over 5 years, so you’d only get about 50 grants (the project is proposed for 10 years) out of it, max. I don’t think you’d be getting piles of new technologies there, even if they did pick the brightest and best (as I’m sure they will). The $232 million per year is a much better sum and makes me look more optimistically on the backing for the project.

On the other hand, it’s important to keep in mind that funding rates for grants to independent researchers are at some major lows. Many people are having a tough time keeping their labs afloat. All of this money? It may just be a stopgap to put the funding in neuroscience a little closer to where it’s been previously (to say nothing of the other disciplines forced to struggle on without their own acronymed initiatives).

What do we want? BRAIN! When do we want it?! Yesterday!

The timeline on the BRAIN initiative is currently 10 years. While that seems like a long time to many people, in terms of science…it’s really not that long. In fact, it’s not really long enough to get much of anything done. I could see some cool new techniques being developed in that time, but would those techniques be able to produce the huge results that could be the goal of the project? There’s not enough time for that. It can easily take 2 years to get a project ready for publication in a journal, 6 months after that, and then for other labs to take it up, you’re looking at another 2 years or so to get the preliminary data and the funding, and then the other labs can start THEIR 2 year experiments and try and publish…we’re already over 6 years in, and that’s for just the technique, not the massive upscaling and development that might be required for, say, research within the human brain. Some techniques do go faster, but drastically new, and primarily theoretical ones may be much slower. Again, we don’t know what the goals are, but I think the “dream team” better be very careful coming up with them, or in 10 years we’ll we looking at a pile of empty promises.

It doesn’t have to be that way. If the creators of the project are careful and moderate in their goals, they may be achievable and cool things might happen. But will that be enough for the public? Will it be enough for the BRAIN initiative? Will it justify the PR?

Is this really going to be the great job creator?

This part is where I get very skeptical. How will the funding be balanced? Is this going to be the rich old labs with the rich old guys getting richer, with more postdocs and grad students under them? If so, where will those postdocs and grad students be in 10 years if the initiative is gone? As the postdocs and grad students move on…where will get go? Will there be funding for them? Right now we have a real issue in biomedical science training, one which neuroscience is not immune from: we have too many trainees. There are too many trainees and not enough tenure track research jobs for them. Many will go on to do other things, things that their scientific training has often ill-prepared them for. And this will continue to happen with the BRAIN initiative, unless the funding is structured to provide for younger investigators. But I’m inclined to think this is going to end up a rich get richer situation.

So will we obtain a full “’brain activity map”? It looks unlikely, though who knows, goals can be big. But this IS a good bit of funding dedicated to neuroscience initiatives, and in this time of sequester, when getting funding is difficult indeed, it feels like a bit of a last minute save. That’s good for neuroscience (though I do feel bad for other fields, who have it just as bad). Will it succeed? Will it fail? I think we can’t tell until we know what the goals are. I think we need the new technologies, but I wonder if any achievable goals will be enough for the bigness of the BRAIN initiative. But until we have some real goals (not due until 2014, which makes me wonder WHAT all that $232 million set aside for fiscal year 2014 will be going to in the meantime), whether BRAIN is BAM or BUST, or both, remains to be determined.

The views expressed are those of the author and are not necessarily those of Scientific American.

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