Ed Boyden tilts his head downward, remaining still except for his eyes, which dart back and forth between blinks for a full 10 seconds. Then, as if coming up for air from the sea of knowledge, he takes a breath, lifts his head back up and begins to speak again.
During these contemplative moments, you have to wonder what's going on inside the head of this young scientist who, at age 33, has already helped invent influential technologies in the study of the human brain.
It made sense when he told me, on a cold February day in his office at the Massachusetts Institute of Technology, "I guess I was always a philosopher at heart as a kid."
The morning of our meeting, The New York Times had just reported the Obama administration is considering funding an initiative called the Brain Activity Map project.
This is a collaboration of researchers who are seeking tools to map the human brain in unprecedented detail. A better understanding of how thoughts lead to actions, and how neural circuits lead to disease, could influence treatments for such conditions as epilepsy, autism, dementia, schizophrenia and even paralysis. Boyden is already working on such tools.
Clearly excited, Boyden bounces from his computer, where he's getting "zillions" of e-mails about the Brain Activity Map news, to the small table where we're speaking. In December, he participated in a brainstorming session in Washington about the endeavor. After our meeting, he tells me, he'll lead a conference call with other researchers about next steps.
That was before the government's forced budget cuts, so it's unclear whether new federal money for brain research will come through anytime soon. But the Brain Activity Map proposal is mainly about innovative collaborations in neuroscience, which are taking place anyway. Boyden is a co-author of a new paper in the journal ACS Nano, describing the value of nanotechnology tools in mapping the brain.
His efforts are being rewarded, as evidenced by the hodgepodge of awards in his office (as well as a certificate for "Mr. Most Likely To Be Late Because He is Teaching Students How to Build a Microscope"). In mid-March, Boyden won the €1 million Grete Lundbeck European Brain Research Prize, shared with five other scientists, for his pioneering work in using light to manipulate the brain.
"If you had to make a list of all the people in the world who are innovating in neuroscience, I think he'd be at the top of it," said Garrett Stanley, associate professor of biomedical engineering at Georgia Institute of Technology.
Optogenetics: Lighting up the brain
When you electrically stimulate one part of the brain, a lot of nerve cells called neurons get hit at once. In order to understand what particular kinds of neurons do, there needs to be a way to target them separately. For this, Boyden and colleagues turned to nature.
"All over the tree of life, you can find organisms that use molecules to convert light into electricity for photosynthesis or photosensation," Boyden said.
One example is single-celled algae, which has a small eye spot -- a brown sphere -- that senses light, prompting hairlike structures called flagella to move and making the plant effectively swim.
What if you could take a small piece of DNA from the algae and transplant it into a neuron so the neuron now produces a light-sensitive protein (and installs it on the cell's surface)? Then, Boyden and colleagues reasoned, you would have a neuron that could be turned on or off with light.
As a graduate student at Stanford, Boyden would often get into late-night conversations with Dr. Karl Deisseroth, who was an M.D.-Ph.D. student at the time working in the same lab. Deisseroth and Boyden began exploring their common interest in how to control specific types of neurons in the brain. Together, they came up with the idea of inserting light-sensitive proteins in particular kinds of neurons.
It was August 4, 2004, around 1 a.m. when Boyden put a dish of cultured neurons under a microscope. The neurons were genetically altered with a light-sensitive protein called a channelrhodopsin. He shined a blue light at them. Amazingly, on the first try, the technique worked.
Boyden recalled that night of scientific discovery in an essay published online by Faculty of 1000. He wrote: "I e-mailed Karl, 'Tired, but excited.' He e-mailed back, 'This is great!!!!!'"
The data that Boyden collected that night demonstrated the ideas he and Deisseroth would later formalize in a 2005 Nature Neuroscience paper. Around that time, the term "optogenetics" was born to describe what they were doing. Deisseroth is also a co-recipient of the recent European brain research prize.
Today, at least 1,000 neuroscience groups worldwide are using optogenetics to study the brain. The technique has so far been used in monkeys and mice to control their behavior, which has its own importance because it can yield new insights about the brain in general, Boyden said. Developing treatments for humans is another goal, but for reasons of ethics and complexity, that takes a lot longer.
What you can do with light
Being able to turn individual cells on and off could be powerful in finding therapies for brain disorders. For example, researchers could explore whether particular kinds of neurons are involved in the symptoms of schizophrenia, and selectively turn those off while leaving neurons essential for thinking intact.
This also has implications for treating addiction. In one experiment, scientists altered a mouse's brain so dopamine neurons -- involved in the sensation of pleasure, as well as addiction -- could be turned on with light. They delivered brief light pulses through optical fibers, prompting the mouse to stick its nose in a small portal over and over.
"An activation in these neurons lasting one-fifth of a second is enough to make the animal do more of whatever it was just doing," Boyden said.
Neurons can also be selectively silenced with light when they express other kinds of proteins. This is an avenue of exploration for treatments for epilepsy, a condition in which an excess in activity of neurons produces seizures.
Optogenetics may also prove crucial to creating a treatment for blindness; the idea is that you could make cells light-sensitive, converting the eye into a camera and restoring vision, Boyden said.