Karl Deisseroth

That's the story HHMI wants to rewrite. In 2008, HHMI issued a call for applications from early-stage, tenure-track researchers in biological and related fields (for example, bioinformatics) for six-year, nonrenewable, all-expenses-covered appointments as HHMI Early Career Scientists (ECS). Beyond salaries and staff, HHMI would underwrite the purchase of critical equipment and the leaseback of their lab space from their home institutions. In all, HHMI would earmark $200 million over six years to support the ECS investigators. More than 2,000 applications flooded in. This March, HHMI unveiled the first 50 ECS investigators—9 women and 41 men from 33 institutions. Maria Spies is 1 of the 50.

“These scientists are at the early stage of their careers, when they are full of energy and not afraid to try something new,” says Jack Dixon, HHMI vice president and chief scientific officer. “They have already demonstrated that they are not apt to play it safe—and we hope they will continue to do something really original.”

Given HHMI's long-time preference for choosing “people over projects,” it's not hard to see why certain ECS candidates jumped out of the pack. But even being among the best and the brightest was not enough. The selection committee was looking for something beyond sterling credentials, impressive publications, and glowing recommendations. Call it style, originality, grit, or fearlessness. Or call it a compelling story.

Karl Deisseroth tells a dazzling story about controlling neural activity, neuron by neuron, in freely moving mice with a pulse of light. Deisseroth, a physician-scientist at Stanford University, calls his technique “optogenetics.” He gave it a grand demonstration of principle in 2007 by waking up mice, not by shaking or startling them but by switching on light-sensitive proteins deep within their brains. Deisseroth's experiment was also an in vivo test of recent genetic findings linking human narcolepsy, a chronic sleeping disorder, to a defective set of cells in the lateral hypothalamus that produce proteins called hypocretins.

To rouse the sleeping mice, Deisseroth borrowed a light-sensitive switch from a microbe (in this case, a single-celled alga) and used a virus to deliver it into the cell membrane of neurons deep in the hypothalamus on the underside the mouse brain. Then he and colleagues fired laser bursts down an optical fiber, bathing the switch in blue light and opening the microbial ion channel. Sodium ions flooded into the neurons, exciting them and causing them to release hypocretins. Deisseroth's mice were a wake-up call to a new day in neuroscience when targeted neurons in living animals can be flipped on or off by light.

Photo: Linda A. Cicero / Stanford News Service

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