MESSAGE FROM THE EDITOR
Big Neuroscience “ Information is the oil of the 21st century, and analytics is the combustion engine.” -Peter Sondergaard Excitement around big data is all around us: in the media, in the news, and in science.1 The capacity to interrogate huge datasets of health information from millions of individuals, carry out complex global clinical trials, analyze millions of genetic variants in parallel from diverse populations, or measure the complete repertoire of gene activity from a single cell, have become standard tools of biomedical research. Another buzzword of modern biology is the concept of emergence, in which novel relationships are appreciated only when different types of biologic data (for example genomic and imaging information) are co-registered and analyzed together. When dealing with big data, success still requires the creative touch of a great investigator, but also requires state-ofthe-art data management and informatics support. In addition, the investments required to make data big are also large and are only justified when there are many uses and users. These specific characteristics of big data have accelerated a broader change in the way science is performed. Big data has led to big science as small groups have coalesced into large teams. In the United States, these are certainly tough financial times for scientists, with sequestration, declining real dollars from the NIH, and prospects of lower reimbursements to academic health care systems restricting their capacity to invest in discovery. For the neuroscience community these strains are particularly gut-wrenching, given the opportunities at hand to extend spectacular advances that are illuminating, with newfound clarity, problems as diverse as Alzheimer’s, autism, multiple sclerosis, depression, and pain. These advances, if pursued, are certain to reveal new and better treatments, repairs, and perhaps even preventions for these increasingly common and frequently devastating afflictions. A few failed clinical trials, in Alzheimer disease for example, can have a chilling effect on industry’s willingness to invest in neurologic therapies, thus stable government support is needed if the discoveries of the past few years are to bear fruit at the bedside. The concerns of seasoned investigators that research funding is at risk in this new economy, of course, is not lost on young people who today are
deciding if they should embark on careers in biomedical science. Against this background, we were delighted to learn of an ambitious new neuroscience program, first leaked by officials of the Obama administration in mid-February, then obliquely referred to in the President’s State of the Union address as a great new goal for the nation, and then formally introduced as the BRAIN Initiative at a White House gathering on April 2nd. Our enthusiasm was tempered only by uncertainty about what this was really all about. Even administrators whom one would expect would be in the know, for example Story Landis at the NINDS, seemed initially uncertain,2 echoing the comments of other leaders in systems neuroscience and neuroimaging (personal communications). The new brain mapping initiative appeared to represent a top-down decision, made by a small number of individuals to create a new program designed to capture the imagination and enthusiasm of the public. The President’s plan was based on a proposal for a “Brain Activity Map (BAM) project” initially conceptualized at a small workshop in the U.K. sponsored by the Kavli Foundation in September 2011;3,4 attendees included Paul Alivisatos of the Lawrence Berkeley National Lab at the University of California (UC) Berkeley, Ralph Greenspan from UC San Diego, and George Church from Harvard University, a pioneer in human genetics and a leader in the Human Genome Project. The outline, communicated as commentaries in Neuron5 and Science,6 enjoyed the strong support of Francis Collins, the NIH Director, and the White House’s Office of Science and Technology Policy (OSTP).3 In concept, BAM proposes to combine connectivity mapping with spike activity mapping of individual neurons and circuits to understand the functional relationships between individual nerve cells and broader neural networks on a real time basis. New tools (perhaps based on nanotechnology and on optical and calcium imaging methods currently in use) will be developed to image neurons, record and modulate their activity, and understand how circuits function. The work would begin in simple systems (for
C 2013 American Neurological Association V A5
ANNALS
of Neurology
example in C. elegans with only 302 neurons), then move to more complex systems such as Drosophila, and only later tackle higher order mammalian systems. Answers to problems such as autism, depression, schizophrenia, and Alzheimer’s disease are promised. Interestingly, the news of BAM followed closely on the heels of another, equally ambitious, neuroscience initiative announced with some fanfare by a Swiss-led European consortium, this one designed to build an artificial, simulated, nervous system. The importance of systems neuroscience, including its potential to elucidate mechanisms of disease, is unquestioned, and we thus view the President’s new initiative with considerable enthusiasm. Although the outline of the project is still vague, and any human applications seem aspirational rather than immediate, as for the Human Genome Project we can be reasonably confident that a “Manhattan Project” for neuroscience would give birth to new technological advances that are unimaginable today. This said, numerous serious questions remain, and skeptics are easily found.7–10 Exactly how will the project be implemented, who will implement it, and under whose direction will it operate? Does the funding for BAM, estimated at over $3 billion, represent new dollars or will it be taken out of current NIH (or National Science Foundation or Department of Defense) budgets? Unless BAM is funded with new resources, the initiative will certainly erode other priorities that could also produce useful translational discoveries – might be realized in the short term. Nobody wants to slow work to develop inhibitors of aggregated proteins involved in neurodegeneration; remyelinate denuded axons in multiple sclerosis lesions; and image phosphorylated tau in traumatic brain injury; among many other areas that are currently ripe for progress. And was this process for selecting the next multi-billion dollar grand challenge adequate, based on the input of only a small number of scientists, some with clear self-interest? Why this and not countless other priorities, some with realistic potential for health improvement in the next decade? During its lifetime, the Human Genome Project was derided by many as an inefficient top-down project for big science that would not produce the medical advances that were promised, or even the economic benefit predicted. In 2013, the naysayers are in clear retreat, with compelling evidence that genetic discoveries have improved public health, and have also produced enormous economic advantages to society at large. One
A6
analysis concluded that the Human Genome Project cost $3.8 billion and generated nearly $800 billion in economic impact and more than 300,000 jobs.11 Like BAM, the genome project in its early stages also suffered from a sketchy roadmap, with many of the critical technology needs not yet discovered, yet today it is paying huge dividends. We believe that the same will be true for a national initiative in systems neuroscience, and as we congratulate the President for his audacious vision we await the details with some trepidation. Stephen L. Hauser MD and S. Claiborne Johnston MD, PhD Editors
References 1.
Smolan R and Erwitt J. The Human Face of Big Data. Against All Odds Productions, Sausalito California. 2012.
2.
Markoff J. Obama Seeking to Boost Study of Human Brain. The New York Times; February 17, 2013 (http://www.nytimes. com/2013/02/18/science/project-seeks-to-build-map-of-human-brain. html?_r50).
3.
Markoff J. Connecting the Neural Dots. The New York Times; February 25, 2013 (http://www.nytimes.com/2013/02/26/science/ proposed-brain-mapping-project-faces-significant-hurdles.html?page wanted5all).
4.
Wadman M. Behind the Scenes of a Brain-Mapping Moon Shot. Nature; March 6, 2013 (http://www.nature.com/news/behind-thescenes-of-a-brain-mapping-moon-shot-1.12543).
5.
Alivisatos AP, Chun M, Church GM, et al. The Brain Activity Map Project and the Challenge of Functional Connectomics. Neuron; 2012;74:970–974.
6.
Alivisatos AP, Chun M, Church GM, et al. The brain activity map. Science 2013;339:1284–5.
7.
The Brain Activity Map: Hard Cell. The Economist; March 9, 2013 (http://www.economist.com/news/science-and-technology/21573089ambitious-project-map-brain-works-possibly-too-ambitious-hard).
8.
Mitra P. What’s Wrong with the Brain Activity Map Proposal. Scientific American; March 5, 2013 (http://www.scientificamerican. com/article.cfm?id5whats-wrong-with-the-brain-activity-map-proposal).
9.
Dittrich L. All the President’s Neuroscientists. Esquire; March 12, 2013 (http://www.esquire.com/the-side/feature/obama-braincontrol-map).
10.
Marcus G. Obama’s Brain. The New Yorker; February 18, 2013 (http://www.newyorker.com/online/blogs/newsdesk/2013/02/obamasbrain.html).
11.
Battelle Technology Partnership Practice. Economic Impact of the Human Genome Project. Battelle; May 2011.
DOI: 10.1002/ana.23903
Volume 73, No. 4
Big Neuroscience “ Information is the oil of the 21st century, and analytics is the combustion engine.” -Peter Sondergaard Excitement around big data is all around us: in the media, in the news, and in science.1 The capacity to interrogate huge datasets of health information from millions of individuals, carry out complex global clinical trials, analyze millions of genetic variants in parallel from diverse populations, or measure the complete repertoire of gene activity from a single cell, have become standard tools of biomedical research. Another buzzword of modern biology is the concept of emergence, in which novel relationships are appreciated only when different types of biologic data (for example genomic and imaging information) are co-registered and analyzed together. When dealing with big data, success still requires the creative touch of a great investigator, but also requires state-ofthe-art data management and informatics support. In addition, the investments required to make data big are also large and are only justified when there are many uses and users. These specific characteristics of big data have accelerated a broader change in the way science is performed. Big data has led to big science as small groups have coalesced into large teams. In the United States, these are certainly tough financial times for scientists, with sequestration, declining real dollars from the NIH, and prospects of lower reimbursements to academic health care systems restricting their capacity to invest in discovery. For the neuroscience community these strains are particularly gut-wrenching, given the opportunities at hand to extend spectacular advances that are illuminating, with newfound clarity, problems as diverse as Alzheimer’s, autism, multiple sclerosis, depression, and pain. These advances, if pursued, are certain to reveal new and better treatments, repairs, and perhaps even preventions for these increasingly common and frequently devastating afflictions. A few failed clinical trials, in Alzheimer disease for example, can have a chilling effect on industry’s willingness to invest in neurologic therapies, thus stable government support is needed if the discoveries of the past few years are to bear fruit at the bedside. The concerns of seasoned investigators that research funding is at risk in this new economy, of course, is not lost on young people who today are
deciding if they should embark on careers in biomedical science. Against this background, we were delighted to learn of an ambitious new neuroscience program, first leaked by officials of the Obama administration in mid-February, then obliquely referred to in the President’s State of the Union address as a great new goal for the nation, and then formally introduced as the BRAIN Initiative at a White House gathering on April 2nd. Our enthusiasm was tempered only by uncertainty about what this was really all about. Even administrators whom one would expect would be in the know, for example Story Landis at the NINDS, seemed initially uncertain,2 echoing the comments of other leaders in systems neuroscience and neuroimaging (personal communications). The new brain mapping initiative appeared to represent a top-down decision, made by a small number of individuals to create a new program designed to capture the imagination and enthusiasm of the public. The President’s plan was based on a proposal for a “Brain Activity Map (BAM) project” initially conceptualized at a small workshop in the U.K. sponsored by the Kavli Foundation in September 2011;3,4 attendees included Paul Alivisatos of the Lawrence Berkeley National Lab at the University of California (UC) Berkeley, Ralph Greenspan from UC San Diego, and George Church from Harvard University, a pioneer in human genetics and a leader in the Human Genome Project. The outline, communicated as commentaries in Neuron5 and Science,6 enjoyed the strong support of Francis Collins, the NIH Director, and the White House’s Office of Science and Technology Policy (OSTP).3 In concept, BAM proposes to combine connectivity mapping with spike activity mapping of individual neurons and circuits to understand the functional relationships between individual nerve cells and broader neural networks on a real time basis. New tools (perhaps based on nanotechnology and on optical and calcium imaging methods currently in use) will be developed to image neurons, record and modulate their activity, and understand how circuits function. The work would begin in simple systems (for
C 2013 American Neurological Association V A5
ANNALS
of Neurology
example in C. elegans with only 302 neurons), then move to more complex systems such as Drosophila, and only later tackle higher order mammalian systems. Answers to problems such as autism, depression, schizophrenia, and Alzheimer’s disease are promised. Interestingly, the news of BAM followed closely on the heels of another, equally ambitious, neuroscience initiative announced with some fanfare by a Swiss-led European consortium, this one designed to build an artificial, simulated, nervous system. The importance of systems neuroscience, including its potential to elucidate mechanisms of disease, is unquestioned, and we thus view the President’s new initiative with considerable enthusiasm. Although the outline of the project is still vague, and any human applications seem aspirational rather than immediate, as for the Human Genome Project we can be reasonably confident that a “Manhattan Project” for neuroscience would give birth to new technological advances that are unimaginable today. This said, numerous serious questions remain, and skeptics are easily found.7–10 Exactly how will the project be implemented, who will implement it, and under whose direction will it operate? Does the funding for BAM, estimated at over $3 billion, represent new dollars or will it be taken out of current NIH (or National Science Foundation or Department of Defense) budgets? Unless BAM is funded with new resources, the initiative will certainly erode other priorities that could also produce useful translational discoveries – might be realized in the short term. Nobody wants to slow work to develop inhibitors of aggregated proteins involved in neurodegeneration; remyelinate denuded axons in multiple sclerosis lesions; and image phosphorylated tau in traumatic brain injury; among many other areas that are currently ripe for progress. And was this process for selecting the next multi-billion dollar grand challenge adequate, based on the input of only a small number of scientists, some with clear self-interest? Why this and not countless other priorities, some with realistic potential for health improvement in the next decade? During its lifetime, the Human Genome Project was derided by many as an inefficient top-down project for big science that would not produce the medical advances that were promised, or even the economic benefit predicted. In 2013, the naysayers are in clear retreat, with compelling evidence that genetic discoveries have improved public health, and have also produced enormous economic advantages to society at large. One
A6
analysis concluded that the Human Genome Project cost $3.8 billion and generated nearly $800 billion in economic impact and more than 300,000 jobs.11 Like BAM, the genome project in its early stages also suffered from a sketchy roadmap, with many of the critical technology needs not yet discovered, yet today it is paying huge dividends. We believe that the same will be true for a national initiative in systems neuroscience, and as we congratulate the President for his audacious vision we await the details with some trepidation. Stephen L. Hauser MD and S. Claiborne Johnston MD, PhD Editors
References 1.
Smolan R and Erwitt J. The Human Face of Big Data. Against All Odds Productions, Sausalito California. 2012.
2.
Markoff J. Obama Seeking to Boost Study of Human Brain. The New York Times; February 17, 2013 (http://www.nytimes. com/2013/02/18/science/project-seeks-to-build-map-of-human-brain. html?_r50).
3.
Markoff J. Connecting the Neural Dots. The New York Times; February 25, 2013 (http://www.nytimes.com/2013/02/26/science/ proposed-brain-mapping-project-faces-significant-hurdles.html?page wanted5all).
4.
Wadman M. Behind the Scenes of a Brain-Mapping Moon Shot. Nature; March 6, 2013 (http://www.nature.com/news/behind-thescenes-of-a-brain-mapping-moon-shot-1.12543).
5.
Alivisatos AP, Chun M, Church GM, et al. The Brain Activity Map Project and the Challenge of Functional Connectomics. Neuron; 2012;74:970–974.
6.
Alivisatos AP, Chun M, Church GM, et al. The brain activity map. Science 2013;339:1284–5.
7.
The Brain Activity Map: Hard Cell. The Economist; March 9, 2013 (http://www.economist.com/news/science-and-technology/21573089ambitious-project-map-brain-works-possibly-too-ambitious-hard).
8.
Mitra P. What’s Wrong with the Brain Activity Map Proposal. Scientific American; March 5, 2013 (http://www.scientificamerican. com/article.cfm?id5whats-wrong-with-the-brain-activity-map-proposal).
9.
Dittrich L. All the President’s Neuroscientists. Esquire; March 12, 2013 (http://www.esquire.com/the-side/feature/obama-braincontrol-map).
10.
Marcus G. Obama’s Brain. The New Yorker; February 18, 2013 (http://www.newyorker.com/online/blogs/newsdesk/2013/02/obamasbrain.html).
11.
Battelle Technology Partnership Practice. Economic Impact of the Human Genome Project. Battelle; May 2011.
DOI: 10.1002/ana.23903
Volume 73, No. 4
