Those who tuned in to President Obama’s State of the Union speech in February might have missed a brief mention of a project some say will catalyze an entire new industry devoted to understanding the brain. “Today, our scientists are mapping the human brain to unlock the answers to Alzheimer’s,” Obama said. “Now is the time to reach a level of research and development not seen since the height of the Space Race.”
This brain mapping effort is the Brain Research through Advancing Innovative Neurotechnologies (or BRAIN) Initiative, proposed jointly by the President and researchers. Obama has called it one of this century’s “Grand Challenges,” akin to mapping the human genome, or sending a man to the moon. His 2014 budget proposal includes $100 million in funding for the National Institutes of Health, National Science Foundation, and Defense Advanced Research Projects Agency to support the project. Additionally, the Allen Institute for Brain Science (created by Microsoft co-founder Paul Allen) plans to spend $60 million a year on the initiative, and the Kavli Foundation has said it will give $4 million a year for the next 10 years to BRAIN-related projects.
The initiative’s first phase aims to develop and scale up numerous technologies required to study the human brain. The entire project remains in early stages.
Though specific goals for the project are still being determined, the general goal, according to Terrence Sejnowski, head of computational neurobiology at the Salk Institute, is to develop tools for recording and influencing brain activity. Sejnowski, a member of the NIH working group setting detailed goals and timelines, says neuroscientists and engineers will work closely together to solve technical problems, including which parts of the brain make sense to study first.
Brain scientists spend a lot of time looking at neurons—brain cells that transmit chemical and electrical signals—and synapses, the pathways between individual neurons. Cold Spring Harbor Laboratory neuroscience professor Anthony Zador says scientists may need to examine activity down to the level of individual neurons firing in milliseconds, but that none of the available technologies is close to being able to record at that resolution. He plans to submit grant proposals to participate in the initiative. Another goal, he says, might be to figure out how neurons in a neural circuit are connected.
Currently, researchers can record activity from about 100 neurons at a time, Sejnowski says. But to truly understand the human brain, they have to be able to record the activity of one million. Sensors capable of recording a vast range of neuronal signals corresponding to different activities are needed. Nanotechnologists could help achieve this goal, he adds, because they work with a variety of different materials and miniaturization techniques.
Beyond creating the actual sensor, there are also other challenges, such as, “how do you get the information out of the brain?” Sejnowski says. “You can’t put a million wires in, so you’ve got to use light or radio waves.”
And once the data are collected, researchers must develop ways to analyze it. “Data accumulates very rapidly. How do you search it and even think about patterns of activity?” Sejnowski asks. “We have to develop new ways of analyzing the structure of the data.”
It’s already possible to sort through some kinds of brain activity data. Numerous pilot studies have begun mapping the brains of fruit flies, worms, mice, and non-human primates, Sejnowksi explains. Now, he says, it’s a matter of taking what’s been learned and scaling it up to study the human brain.
The mouse brain, for instance, has about 100 million neurons and each one makes about 1,000 synapses. In principle, neuroscientists would like to detect the 1,000 connections of each of those 100 million neurons. More than two decades ago, researchers used electron microscopy to track the 302 neurons and approximately 7,000 synapses in the worm. Now there are several projects underway to scale up that technology to handle the mouse’s 100 billion synapses.
Beyond opportunities for technological advances, Zador says, “you also want to know what those neurons are doing when the animal is thinking, perceiving, or behaving in various ways.” Technologies for doing that in vivo were developed more than six decades ago; all involve putting a thin piece of metal into the brain that records when a neuron produces a spike. More modern devices, called tetrodes, can record dozens of neurons at once.
Scientists assume that the basic principles of brain function are fairly consistent among most kinds of animals. “The idea is that we’ll be a lot closer to understanding how [human] brains work and what goes wrong in all sorts of diseases if we can understand the brain function of a rodent or a fish or a fly,” Zador adds.
Ultimately, Salk’s Sejnowki says, the purpose of developing all these new techniques and technologies is to use them to help treat people. “The first step is to understand how the neural circuits give rise to behavior, and how they go wrong,” he says. “The next step is to go in and influence the circuits to regenerate or rebalance what has gone wrong.”
Pharmaceuticals currently used to treat imbalances in the brain aren’t precise, aren’t targeted to specific subsets of neurons, and have side effects. If a way can be found to deliver a nanotech device to the human brain, new ways may be found to treat diseases like Alzheimer’s.
Obama noted in his State of the Union that every dollar invested in the Human Genome Project (HGP) ultimately returned $140 to the economy. (The HGP was declared complete ten years ago, an occasion commemorated on April 25, or “DNA Day.”) There could be a similar enormous payoff for the country and the research community if a tech boom accompanies the BRAIN initiative’s progress. “Sequencing the genome was an enormously impressive feat, like going to the moon, but the real payoff was the fact that sequencing the human genome now is a million times cheaper,” Sejnowksi says. “The real impact [of the BRAIN initiative] is going to be creating a new industry that will use these tools to better understand the mysteries of the brain and to help patients.”
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