The New York Times on Monday revealed that the Obama administration will in its next budget proposal seek to launch a major research initiative, known as the Brain Activity Map (BAM) project, that could ultimately greatly expand our understanding of the healthy and diseased human brain. ScienceInsider takes a look at some of the many questions swirling around an effort that has already been compared to the Human Genome Project and could demand billions in research funding to accomplish.
Q: What is a brain activity map?
A: Neuroscientists arguably can only crudely measure the activity of a brain now. They can turn to PET and MRI imaging that detect "activation" of broad regions through proxies such as oxygen use, or they can measure the electrical activity of individual or small groups of neurons. Some neuroscientists compare the problem to getting the right resolution in a digital photograph or TV screen—PET and MRI lacks fine detail, producing "fuzzy" images, while focusing on small groups of neurons is like looking at a few pixels up close, losing sight of the bigger picture. Researchers generally agree that critical brain functions such as thought and perception happen somewhere between these two extremes, involving anywhere from a few thousand to millions of neurons. Now, researchers can't monitor such large ensembles of neurons; to produce a brain activity map for humans will require developing new tools that can image and track an enormous number of cells in animal models, then finding a way to use those tools safely in humans. It's not clear yet what states of brain activity the proposed project would eventually map, but theoretically, such tools could help scientists understand what goes wrong in disorders, such as epilepsy and schizophrenia, that are suspected to originate from abnormal neural connections between different brain areas.
Q: Who's involved in the proposed effort?
A: The National Institutes of Health (NIH) will likely organize the initiative; the National Science Foundation, the Defense Advanced Research Projects Agency (DARPA), and the White House Office of Science and Technology Policy (OSTP) have also been involved in shaping the proposal. The Kavli Foundation has spearheaded the effort to develop and promote the project, along with the Allen Institute for Brain Science and the Howard Hughes Medical Institute (HHMI), which all support neuroscience research. Last month, Microsoft, Google, and Qualcomm participated in a workshop on how to analyze data from the project.
Q: How did the proposal arise?
A: In September 2011, George Church, the molecular geneticist who leads the Personal Genome Project, and Rafael Yuste, a neuroscientist at the Kavli Foundation and Columbia University, made waves at a meeting in England cosponsored by the Kavli, Allen, and Gatsby foundations when they proposed a massive, coordinated effort to develop technologies that can track the activity of functional connections in a living human brain, ultimately measuring "every spike from every neuron." Despite skepticism from some attendees, Yuste says, the proposal generated enough enthusiasm to produce a white paper, which Kavli Vice President of Science Programs Miyoung Chun took the lead in promoting, originally pitching the project in a series of December 2011 meetings to NIH, DARPA, and OSTP.
The project gained momentum at the January 2012 6th Kavli Futures Symposium in Santa Monica, followed by a paper in Neuron, which fleshed out the project's aims and details, focusing mainly on animal research. (Click here for a more extended version of the paper.) In the wake of OSTP's July 2012 request for proposals for "Grand Challenges" in science and technology similar to the Human Genome Project, Chun and other co-authors of the Neuron paper worked with officials at federal agencies—particularly OSTP Deputy Director for Policy Tom Kalil—to refine the proposal, tailoring it to focus more on human applications.
Q: Is this really about the human brain?
A: Early descriptions of the project [e.g., the Neuron paper] don't say much about human brain research, focusing primarily on animal models. In the last few months of conversations between Chun and colleagues and federal agencies, however, the group has increased its emphasis on human applications, inviting researchers like John Donoghue, who works on brain-controlled prosthetics, to join the conversation. Working with OSTP and NIH "really pushed" the group toward a more "socially responsible" version of the proposal with practical links to patient care, Yuste says. That new emphasis may explain some confusion over the project's real scope; The New York Times, for example, suggested that scientists intend to build a "comprehensive map" of the human brain's activity within a decade. In reality, the focus is much more on animal models, says Gerald Rubin, executive director of HHMI's Janelia Farm Research Campus in Ashburn, Virginia. "The NYT's article does a poor job in representing the breadth of the official plan," Rubin writes in an e-mail. "In particular, the vast majority of the money in the first 10 years will—for scientific and ethical reasons—need to be spent on experiments in "model organisms."
Q: How long will it actually take?
A: The planning documents for the project take a much more reserved approach than The New York Times article implies. After 5 years, scientists suggest that they will be able to monitor the equivalent of the whole brain activity of the roundworm Caenorhabditis elegans, which has 302 nerve cells and roughly 7000 connections. After 10 years, they expect to complete the whole brain map of the fruit fly model Drosophila, about 130,000 nerve cells. After 15 years, they predict that they will be able to observe the function of the zebrafish brain, or several areas from the mouse cerebral cortex.
Q: What exactly will the White House propose?
A: NIH and other federal agencies have not yet released a detailed proposal. However, in the Neuron paper and an updated document recently obtained by ScienceInsider, Chun and colleagues suggest initially focusing on technology development, which they break into four stages. First, they propose focusing on new imaging tools that use light to penetrate into brain tissue and detect and manipulate cell function; second, on next-generation electrical probes that could simultaneously monitor and manipulate large numbers of cells; third, on new nanotechnologies that could report activity from within individual neurons, and finally, on data-sharing and analysis systems inspired by the Human Genome Project.
Q: How much would the project cost?
A: The New York Times article said that scientists hope the project will receive $300 million a year over 10 years—comparable to the $3.8 billion spent on the Human Genome Project -- but there's no explanation offered for that estimate. (NIH officials said they cannot comment on funding until the president's fiscal year 2014 budget is released.) It's not yet clear how much of that money would come from repackaging existing neuroscience programs that fit BAM's aims. The Kavli Foundation expects its funding will make up $4 million to $5 million per year of the total; HHMI and the Allen Institute are doing related work that will be part of the larger project.
Q: Will it be controversial?
A: In a time of fiscal constraints in which science agencies are rejecting higher percentages of grant proposals, undoubtedly. The proposal is vastly more ambitious than the related Human Connectome Project, an initiative to map the static circuitry of the human brain, which itself has received criticism. It has already rekindle concerns about funding big science projects versus individual investigators, as evidenced by social media comments from various scientists. However, National Institute of Neurological Disorders and Stroke Director Story Landis suggests that initially the emphasis will be on developing new technologies, which usually happens in individual labs, not large centers.
Many of the innovations proposed in the project, such as new light-based technologies that can penetrate deep into brain tissue, are still "science fiction," according to Partha Mitra, a neuroscientist at Cold Spring Harbor Laboratory in New York. The neuroscience community was not widely consulted in the development of the project, he adds. He compares the process unfavorably to the recently funded European Human Brain Project to build a computer model of the brain's activity, which he says included more public discussion. (That effort has nonetheless also drawn criticism for being more hype than reality.)
The Human Genome Project received a barrage of similar objections when it was first considered, Yuste notes. Although creating a human brain activity map may prove a far more difficult and complicated task, he says that this Grand Challenge is needed to spur development of new tools and get scientists from many disciplines working together. As a field, neuroscience has "grown a little too big for its old clothes," he says. He hopes that this neuroscience project will mimic other large programs, like the National Nanotechnology Initiative and Human Genome Project, that have helped bring focus to their respective fields.
Q: Does it have a chance to happen?
A: Interest in neuroscience research has traditionally been bipartisan, but it's not clear if discussions on the proposed project have expanded beyond the White House to Congress. Most science agencies are also cutting back, not launching major new initiatives. And if sequestration takes place and NIH's budget is cut 5.1%, it seems unlikely that the agency will pour money into a large new program.
*Correction, 5:00 p.m. EST: The roundworm Caenorhabditis elegans has 302 nerve cells and roughly 7000 connections, not tens of thousands of nerve cells as originally reported.