"The tools he's developed are so broadly applicable," said Craig Forest, assistant professor at Georgia Institute of Technology. "Is it a stretch to say it's like the microscope for the brain?" He adds, "Optogenetics is the, kind of, microscope for neuroscience right now."
An accelerated career
The seeds of Boyden's career were planted in childhood. Growing up north of Dallas, he wanted to understand something about humanity and why we are here. He liked math better than science at first: "Math was the way of getting to the inner truth of things," he said. But then he wanted to know how our minds are able to understand math.
His thoughts gave way to an idea he now calls the "loop of understanding": Math is how we understand things at a deep level, our minds do math, the brain gives rise to our minds, biology governs our brains, chemistry implements biology, the principles of physics rule over chemistry, and physics run on math. It's a loop from math to math, with all the knowledge in between.
"I don't think I came up with that eloquent way to describe it until I actually came to MIT, but yeah, I was very interested in these kinds of things as a young teenager," he said.
His interest in science wasn't entirely a surprise; his mother has a master's in biochemistry, and conducted research on nicotine, but stayed home to take care of Boyden and his sister. His father was a management consultant (both parents are now retired).
"I was really a workaholic from age 10 onwards, I guess," he said.
Boyden remembers a statewide science fair in Texas when he was 12, where science-minded kids went to present their research.
It's hard to get him to talk about it now, but when I pressed him on the topic, he admitted, matter-of-factly, that he won the fair.
"Oh, you did! Do you remember what it was?" I asked of his project.
Boyden looked slightly uncomfortable, as if it were an embarrassing secret. "Uh, it was an area of geometry that has to do with the number of points on a plane and how they're connected and so on. It's not very easy to explain, nor frankly anything valuable."
However trivial his school-aged projects seem in retrospect, Boyden got to skip two grades. He enrolled at MIT when he was 16. On campus, he chose to live in a dormitory with a partying reputation. "I was very quiet, and so I went there to try and learn how to interact more with people," he said.
Today, he seems to have no trouble in that regard. Said Forest, who works on technologies with him to study individual neurons, "Not only is he just an incredible innovator, but he is just a really nice guy."
When Boyden arrived at Georgia Tech in February to give a lecture in the "Young Innovators" series, his puffy North Face jacket, slightly tousled curly locks and frizzy beard contrasted with Forest's pressed suit, lilac collared shirt and short salt-and-pepper hair -- almost like an Apple vs. PC commercial. The two communicate almost every day.
It's obvious how much respect Boyden has for his collaborators. Speaking to a standing-room-only lecture hall lined with dozens of students and faculty members, he spent the last minutes of his presentation reading off the names of students, post-doctoral fellows, collaborating groups and funding sources from a projected slide that listed even more of them. Then, he looked to the crowd and, almost in a whisper, said, "Thanks."
The idea that you could silence or activate neurons with light is a powerful one in combination with the tools that Boyden and Forest are working on together.
The two met at a social event at the MIT Museum while Forest was working on his Ph.D. at MIT. At that time, Forest was developing an instrument for genetic analysis involving thousands of glass tubes. Boyden told him about his own work in neuroscience, and about a problem that involved glass tubes for measuring neurons.
Forest didn't know anything about neuroscience, but he and colleagues "had a lot of expertise in how to build great devices," Boyden said.
The two researchers realized they could combine forces by creating a bundle of glass tubes, similar to what was being used for DNA analysis, for recording the electrical activity of individual neurons.
Neuroscientists often use mice, which have brains that structurally resemble those of humans, to test new technologies. Mice were the subjects of their first tests.
"We had no idea what we were doing at first," Forest said. "We went from a bundle back to one tube. We got that to work after three years of trial and error."
Those years paid off. Boyden and Forest, working with Forest's graduate student Suhasa Kodandaramaiah, developed a robotic system to record activity of a single neuron in the living brain using a tiny glass tube. The general technique, which has been around for about 30 years, is called "patch clamping," but this is the first time it has been fully automated through the assistance of a robot. The researchers have demonstrated the effectiveness of this technique in living mice, both awake and asleep.
Recording the neurons
Scientists know that the tube -- the "micropipette" -- has hit a neuron by measuring the electrical resistance between the tube and the brain. Resistance increases dramatically when the small needle bumps up against a neuron, as the tube forms a tight seal with the nerve cell.