Cori Bargmann Talks BRAIN
Earlier this fall, the (most excellent editor Eliza Strickland at IEEE Spectrum) invited me to write an article about the BRAIN Initiative. Initially I had many reservations: I knew about the project mostly through news articles written when its original, nebulously-defined-but-mostly-about-neuron-recording incarnation was announced in April, and what I’d read had irritated me. The proposal seemed much too narrow (what about data storage? interpretation? and everything that’s not a neuron?) and the grand-challenge-of-our-time rhetoric swollen with hype.
I also had, and still have, reservations about the importance attached to neuroscientific explanations, particularly of complex human behaviors. What’s so condescendingly referred to as “folk psychology” might better be called “knowledge produced through other social processes than the institution of science,” and includes all those endeavors encompassed by literature, history, art, the social sciences and collectively distilled experience. To illustrate this, I like to use the example of love: What if we had a billion-dollar love project, intended to better understand and promote love? Neuroscience would have just one of many seats at the table, and it probably wouldn’t be at the table’s head.
That said, after poring through various NSF and NIH documents associated with BRAIN, and speaking to roughly a dozen neuroscientists, I feel much better about the project. I’m impressed by its scope, fascinated by the questions seeks to answer and those it might generate. It is, in a word, exciting. I also feel that the people involved are more thoughtful and modest than I’d expected. And of all the scientists, I was profoundly impressed by Cori Bargmann, the Rockefeller University neuroscientist who oversaw the NIH’s interim BRAIN report. Below is the interview we conducted by email.
Q: Something I wanted to ask first, in case the other questions turn the discussion dry, is: What scientific questions are the most exciting to you? What it is that fascinates you, that keeps you thinking late at night … and do you hope the BRAIN Initiative will answer these questions?
Bargmann: The human brain is a miracle. It gives rise to infinitely many thoughts, emotions, memories, actions. How can one biological organ, a collection of cells, do all that? No matter how long you’ve been a neuroscientist, it is still an amazing that this complexity emerges from such mundane biological components. That’s what motivates me. Yes, I think the answer will come from understanding brain circuits and dynamics, and electrical and chemical signaling, and theory. (I have a mental picture of how this works in the tiny worm, but it’s not proved yet; in larger brains, even the mental picture is elusive.)
Q: The Initiative has evolved a great deal since its conception (and, as an aside, it’s been tremendously heartening to see criticisms articulated and incorporated into the interim NIH report; that sort of thoughtful, constructive, perspective-harnessing process is really science at its best, and makes this bystander proud.)
Bargmann: Thank you! We were very fortunate because many people were willing to give us advice. On very short notice, flying around the country. It’s also been heartening that several other independent groups have arrived at overlapping ideas (NSF, the Allen Brain Institute, the Kavli think tank, others). It gives us more confidence that we’re on the right track.
Q: Do you expect it to continue to evolve over the next year, and in what ways — will we continue to see substantive additions, such as the attention newly paid to glia, or are the next stages more about deciding how to apportion emphasis among the research priorities?
Bargmann: This is an interim report. We hope this is the right direction, but we want feedback. We may realize that we’ve missed something important, and add an area. We will definitely try to sharpen and focus the ideas.
This will be both informal and formal. Formally, we will meet with “partners” and “stakeholders” (Washington-speak). For example, in theory we are just an advisory group to NIH, but there are many groups involved in the BRAIN Initiative. All of these groups should talk about what everyone will be doing, and who else should be involved. This will happen soon — the people who are already in the loop are NSF, DARPA, Allen, Kavli, HHMI. In the longer tern, I’m excited to say that several tech companies are expressing interest in being part of the BRAIN Initiative! Microsoft, Google, Intel would have a lot to provide. And then there is broader input from neuroscientists (eg SFN), clinical and translational scientists (eg AAN), and patient advocacy groups.
Q: Timeline-wise, assuming the shutdown ends tomorrow, what do you expect this year from the agencies and foundations? Do you think we’ll see priorities set and grants reviewed by year’s end?
Bargmann: Oh, this is so upsetting. We worked hard on the interim report, with much advice, all pro bono, from leaders across the field. The interim report went in, it was accepted with enthusiasm, and now it’s in the hands of the government. NIH was poised to formulate and issue requests for proposals. Scientists across the country were getting ready to submit grants and review them (which needs to get set up by NIH). And if that all went well, we could have been starting the science in months! And then the government shut down, and now the start of the BRAIN project in 2014 is definitely at risk. No external force could do as much damage to research in the US as this is doing — can you imagine how we’d react if a foreign government sabotaged our scientific enterprise for this kind of time?
Q: Among the priorities, are there some that strike you as being preconditionally necessary — e.g., we can’t start collecting large-scale data without the platform for sharing it? Is there any concern that early priorities may preclude others — e.g., if the push is to develop technologies for recording electrical activity in brain cells, it’ll divert attention from the potential importance of chemical activity?
Bargmann: Science is always creative chaos — you can’t wait for things to be perfect to get started! Parallel work has the best history of success. The nature of the data determines the best design for data platforms, for example. Some areas will have great new ideas and a spurt of growth, other may take a while to reach the next level. This is how bottom-up science works best — set out the problems, and then find the people who have the best solutions.
Q: In the report, you point out the difficulty of measuring internal cognitive processes and mental states in animals, and the importance of doing so in a careful way. This difficulty has certainly received much attention over the last few years, particularly in regards to the limitations of mouse models for complex psychological states. Are those concerns something that the Initiative can address directly — e.g., by making more-informative use of animal models possible, or even reducing our reliance upon them — or are the concerns simply something to keep in mind?
Bargmann: Not sure I have a great answer to this. We’re getting pretty good at interpreting certain complex processes in the mouse brain, such as representation of space in the hippocampus. We can even tell based on brain activity when a mouse is “thinking” about going right versus going left in a maze, which is pretty cool. However, at this point we can’t say with confidence that we can recognize a complex psychological state like depression, let alone schizophrenia in a mouse. What we can say is that we recognize patterns of brain activity and behavior that are similar to those we might observe in a depressed person, and that respond to some of the same medications. I just want to point out that these states can also be challenging to identify in humans! We need to be appropriately humble at every level.
Q: A concern I’ve heard raised by researchers who are supportive of the BRAIN Initiative is the gap between what we now understand and the project’s ambitions. The C. elegans example is the usual one — “We can record every neuron in a C. elegans brain, and still can’t explain _____.”
Bargmann: Well, we can’t do that in a worm yet, or at least no one has yet done so. We have fragments, one neuron at a time. We need a more global picture of their relationships. That’s exactly why we need a multi-pronged approach: structural maps, activity maps, the ability to record and manipulate in the context of behavior, and theory
Q: The C. elegans reservation isn’t offered as a reason not to pursue the Initiative, but a restraint on what to expect from it in the near future (and perhaps not without more money than is presently being discussed.) What are your thoughts on this? How does one walk the line between overpromising in order to secure funding, or being so restrained in expectation as to discourage it?
Bargmann: I think that in ten years of the Brain Initiative, we could have a fundamentally different picture of how information flows through the brain in space and time, and what that means. I do not think we should promise that cures will come tumbling out of this initiative in the short term. I think we should promise that we will shed light on many core properties of the normal, active brain. And that with that illumination, we can turn to translational researchers, physicians, engineers, biotech, and big pharma, and begin a new era of translation into the brain disorders that cast a shadow on all of our lives — because even if you aren’t affected, your grandmother or nephew or best friend may be suffering from Alzheimer’s, or autism, or post-traumatic stress disorder.
Q: Do you get a sense of whether the NIH, NSF and DARPA funds will be new, or coming from existing budgets? To what extent, if any, are they guaranteed beyond 2014?
Bargmann: Not really — but I think everyone knows that a grand challenge takes more than one year! Ten years seems more like it.
Q: It’s certainly very early, but it seems some themes are emerging: a general unity of purpose/sense of what’s necessary between the NIH and NSF, with the NIH leaning towards the “wet” side of things — working with organisms, collecting the data, making the connections to disease, behavior and cognition — and the NSF leaning towards the “dry”: developing the recording technologies, data-analysis techniques, data-sharing platforms, and so on. Does that seem like a fair assessment to you? Do you have a sense of what DARPA and the private foundations will emphasize?
Bargmann: I like this formulation but it’s not my place to tell anyone what to do, especially not outside the NIH! My sense is that DARPA has a major commitment to injured veterans, and therefore has a big push on brain-machine interfaces and brain-computer interfaces, for example. Private foundations have their own interests, some overlapping closely with the Brain Initiative’s goals. HHMI/Janelia is making genetic reagents for the fruit fly, and developing sophisticated new microscopes. Allen is mapping long-range physical connections throughout the brain with their new tracing methods.
Q: In the interview with Eliza you referred to the multi-agency, public-private collaborative nature of this as “an interesting experiment.” Is there a precedent for this type of collaboration? So far it seems the various players have listened to the conversations each has led, but remained autonomous in setting their own priorities; do you get a sense of how everyone will continue to interact, especially when it comes time to decide what gets funded?
Bargmann: There’s plenty for everyone to do. Right now there is also a lot of good will; the tone of the conversations between different partners has been positive and collaborative. We know that resources are limited — we will get much further if we share ideas, technologies, and data.
Q: I’ve had a question bouncing around my head for a while, and wasn’t sure whether to pose it because I don’t think it bears directly on what I’ll write for IEEE … but what the heck:
Why should brain science deserve such a prominent seat at the table when it comes to understanding “the interior terrain of thinking, feeling, perceiving, learning, deciding, and acting to achieve our goals”?
For understanding behavioral disorders like extreme depression, to prevent and treat dementia and Parkinson’s, to help victims of stroke or brain-damaging circumstance, I can *absolutely* understand the paramount importance of neuroscientific research. But for understanding our inner lives, it seems to me like the sort of physical scales at which neuroscience works, the questions that can be asked within its methodological frameworks, and ultimately the answers generates, are not necessarily more illuminating than what emerges from the humanities.
Put another way, to live with grief, or guide the education of my godchildren, I do appreciate the insights neuroscience (and cognitive science and psychology) provides me — but also those from literature, poetry, history, religion, philosophy and all those endeavors by which humans seek to understand ourselves. This isn’t a zero-sum, either-or choice, obviously — either science or humanities! — but when regarding the BRAIN Initiative, which right now seems like our society’s flagship expedition into the interior terrain, it feels disproportionately tilted toward one side.
Thanks for bearing with that ramble, and I hope it doesn’t sound combative — I think the BRAIN Initiative is an excellent and exciting thing, and would like to see it receive quite a bit more funding. And, like I said, the answer to the “Why brain science?” question isn’t immediately IEEE article-relevant; but if you’ve a chance to reply, I’d very much appreciate it for my own edification.
Bargmann: This is an excellent point. It is not either-or; science and human culture are both essential ventures. Recently I read the Bhagavat Gita, and there is nothing from brain science that helped me think about my relationship with the world as deeply as it did. On the other hand, writing the Gita did not require high-end microscopes, electrodes, and data analysis, and therefore it’s not the topic of a technological initiative. Science and technology make progress in different ways than the humanities and philosophy make progress, at least in our era.
You are right that much of our understanding of the mind is still more in the humanities than in the sciences. I also find it stupid when people take naive biological approaches to profound human questions. When people tell me my personal decisions are genetically determined by my ancestors on the African Savannah, I reach for my revolver. I suspect that the brain sciences will eventually lead to a deeper understanding of more profound issues. For example, the relationships between cognition and emotion don’t seem to me to be well-defined in either the sciences or the humanities yet. Biology may have something to say about that.
You are also right that in our time, the sciences are given priority over the humanities in our public discourse. But the humanities are also flowering compared to historical standards. Many more people are literate than at any time in the past. More voices and viewpoints are heard. Universal education is becoming a reality.
With respect to disorders of the brain, I think you and I agree that many, most, probably all have some biological cause and biological manifestation in the brain. That doesn’t mean it’s the only cause. I would say that the biological part may be the easiest to solve right now, and maybe that’s the reason to focus on it in our time. Memory is a rich, emotional, cognitive experience. But narrative memory is linked to the hippocampus in the most irreducible way. No hippocampus means none of that rich experience of personhood that comes from memory.
Q: Also, one other question, this one more article-relevant: Why weren’t more ethologists invited to the discussions? I’d think that with so much riding on animal models, and an acknowledged need for innovation in their use, it’d make sense to have some animal people there.
Bargmann: We had implicit ethology and what you might call techno-ethology. Implicit, through people like Eve Marder and David Anderson, who think about it extensively. Techno, Kristin Branson from HHMI spoke; she worked with Mike Dickinson, the ethologist who was featured in yesterday’s NY Times Science magazine. (High-throughput ethomics in large groups of Drosophila. Branson K, Robie AA, Bender J, Perona P, Dickinson MH. Nat Methods. 2009 Jun;6(6):451-7.). Plus Bill Newsome, my co-chair, considers himself a hard-core behaviorist. He’s the source of the “Nothing in the brain makes sense except in the light of behavior” line, a references to Dobzhansky of course, that appears in the report.
Even 80 neuroscientists is not very many when you consider that we were trying to go from math and physics to human brain imaging — we couldn’t invite very many of anything! We tried to find people who would take a broad view, and I have to say, the message of the importance of behavior came from many directions. That message is probably the biggest difference between the Brain Initiative in its current form and the original Kavli idea of the “Brain Activity Map” (BAM).