By Amy Barth
Stopped at a red light on his drive home from work, Karl Deisseroth contemplates one of his patients, a woman with depression so entrenched that she had been unresponsive to drugs and electroshock therapy for years. The red turns to green and Deisseroth accelerates, navigating roads and intersections with one part of his mind while another part considers a very different set of pathways that also can be regulated by a system of lights. In his lab at Stanford University’s Clark Center, Deisseroth is developing a remarkable way to switch brain cells off and on by exposing them to targeted green, yellow, or blue flashes. With that ability, he is learning how to regulate the flow of information in the brain.
Deisseroth’s technique, known broadly as optogenetics, could bring new hope to his most desperate patients. In a series of provocative experiments, he has already cured the symptoms of psychiatric disease in mice. Optogenetics also shows promise for defeating drug addiction. When Deisseroth exposed a set of test mice to cocaine and then flipped a switch, pulsing bright yellow light into their brains, the expected rush of euphoria—the prelude to addiction—was instantly blocked. Almost miraculously, they were immune to the cocaine high; the mice left the drug den as uninterested as if they had never been exposed.
Today, those breakthroughs have been demonstrated in only a small number of test animals. But as Deisseroth pulls into his driveway he is optimistic about what tomorrow’s work could bring: Human applications, and the relief they could deliver, may not be far off.
For all its complexity, the brain in some ways is a surprisingly simple device. Neurons switch off and on, causing signals to stop or go. Using optogenetics, Deisseroth can do that switching himself. He inserts light-sensitive proteins into brain cells. Those proteins let him turn a set of cells on or off just by shining the right kind of laser beam at the cells. That in turn makes it possible to highlight the exact neural pathways involved in the various forms of psychiatric disease. A disruption of one particular pathway, for instance, might cause anxiety. To test the possibility, Deisseroth engineers an animal with light-sensitive proteins in the brain cells lying along the suspected pathway. Then he illuminates those cells with a laser. If the animal begins cowering in a corner, he knows he is in the right place. And as Deisseroth and his colleagues illuminate more neural pathways, other researchers will be able to design increasingly targeted drugs and minimally invasive brain implants to treat psychiatric disease.
Optogenetics originally emerged from Bio-X, a multidisciplinary project spearheaded in part by Stephen Chu, then a Stanford physicist and now the U.S. Secretary of Energy. Bio-X takes some of Stanford’s best engineers, computer scientists, physicists, chemists, and clinicians and throws them together in the Clark Center, where an open, glass-clad structure makes communication unavoidable. Deisseroth, whose beat-up jeans and T-shirt practically define the universal academic wardrobe, proved a natural at working across disciplines. Over the past decade, his omnivorous quest has filtered far beyond Bio-X into a thousand institutions around the world.
Although his Bio-X work involves esoteric genetics and animal experiments, Deisseroth has never forgotten the human needs that motivated him in the first place. He still divides his time between his basement lab and the psychiatry patients who desperately need his research to pay off.