President Obama’s April 2 announcement of the Brain Research through Advancing Innovative Technologies (BRAIN) initiative proposed a truly epic challenge: mapping the entire human brain, neuron by neuron.
Last Saturday afternoon, an extended panel discussion at the World Science Festival in NYC tackled the far less grand but still daunting goal of tracing the contours, borders, and principal features of the project itself. As BRAIN has been lauded as multidisciplinary “convergent science,” the WSF panel appropriately included a molecular biologist, a geneticist, a neurologist, a bioethicist, a cognitive roboticist, neuroscientists of various stripes, and a member of the Obama administration.
Moderator Gary Marcus, a cognitive psychologist at NYU, put The Brain Map on the map of neuroscience, asking panelists to identify by date events that made the project conceivable.
First was 1848, when a brain injury gave rise to the idea that specific parts of the brain subserve specific functions like self-control. Other landmarks included the 1891 paper that led to the “Neuron hypothesis” (a nervous system made up of individual, interacting neurons), and the Human Genome Project, an often-cited precedent for BRAIN.
The most important date, October 10, 2011, was when, according to Miyoung Chun of the Kavli Foundation, "a group of us sent an idea paper to the office of Science and Technology at the White House." The paper came out of a two-day gathering of neuroscientists, nanoscientists, physicists, chemists, and others.
Chun and the two other authors of the paper who were present at Saturday's discussion (George Church of Harvard and Rafael Yuste of Columbia) recalled its pivotal moment as a "blue sky session" at the workshop’s conclusion, where participants were asked what they would really like to do.
Yuste said his ideal would be "to measure every spike from every neuron in the complete neural circuit." When another participant dismissed the idea as "totally impossible," Church replied, "I don't think it violates the laws of physics, so it's not impossible." Objections to cost and the crushing burden of collecting and computing data were similarly met.
The white paper led to the White House initiative that panelist Philip Rubin of the Office of Science and Technology policy described as "an exciting opportunity to take on a grand challenge, an ambitious but achievable goal.”
Further discussions at Saturday’s salon characterized the challenge of mapping the brain’s 86 billion neurons and 100 trillion synapses. "We need to know not just where the connections are, but how strong they are, the distribution of receptors and vesicles that release neurotransmitters across the synaptic cleft,” said Kristin Harris of University of Texas.
On the other hand, she suggested that extensive sampling of the meshwork of dendrites, axons, glial cells, and synapses could yield “principles of how these things interact…[so] we don't have to know everything about every one of the trillion synapses."
Christof Koch of Seattle’s Allen Institute for Brain Science observed that despite differences between parts of the brain, “there’s something very homogeneous about it,” such as the columnar structure repeated throughout the cortex. “If we understand something about one of these columns, we take a gigantic leap forward toward understanding the neural process in general.”
There was controversy. Neurologist Douglas Fields called the project "not a brain mapping initiative, but a neuron-mapping initiative," suggesting that "the brain is perhaps the only organ we're attempting to understand by overlooking the major cells that comprise that organ—glial cells.”
Yuste objected to the implication they were “evil people keeping glia out of the picture," and proposed that the project is essentially about technology for the neuroscience of the future: "the tools we develop can be used for neurons and glia."
The interchange underlined questions about the true goal of the project.
NYU bioethicist Arthur Caplan called for clarity about aims and “finish lines,” citing the Genome Project experience, where "the investment of public money was justified by the possibility of curing every disease, disability, and disorder known to human kind. Scientists wanted it for basic research purposes to open the way to translational discovery…but there was a lot of disappointment for a long time because it didn’t deliver what it promised.” [In fact, Church observed, while the Genome Project cost some $3 billion, it has already yielded an estimated 140:1 return in clinical benefits.]
By the same token, while the immediate goals of BRAIN may be basic science, clinical applications are the ultimate inducement. "It’s not just about measuring neural activity, but interfering with it… to correct harmful, abnormal activity in patients," Yuste said.
The afternoon ended looking to the future. Marcus asked panelists to speculate on the state of neuroscience 50 years from now. "I hope we have a general theory of how the brain works, analogous to DNA," said Yuste. With this, "we can see ourselves from the inside, see what makes us human."
Research will generate advances in human-machine interfaces that will "galvanize industry," Chun forecasted. Neurotechnology is already a reality, Church observed, in the 100,000+ people receiving deep brain stimulation, artificial retinas, and cochlear implants. "It's impossible to predict the next 50 years, because the field is moving so quickly."
Caplan noted that neuroscience advances will raise knotty questions about law, personal responsibility, and the role of neurotechnology for enhancement as well as repair.
"Bioethicists," he predicted, "will be fully employed."
Carl Sherman is a science writer in New York City.