For decades, scientists have fantasized about whether light, if properly harnessed, could be used to turn neurons on or off as a way to study behavior, understand decision-making and even treat disease.

In 1999, Nobel laureate Francis Crick described the idea as far-fetched, but conceivable.

Twenty years later, on Oct. 3, the Warren Alpert Foundation celebrated the four scientists who realized this far-fetched ideaEdward Boyden, Karl Deisseroth, Peter Hegemann and Gero Miesenbck, who together share the 2019 Warren Alpert Foundation Prize for their seminal contributions to the field of optogenetics.

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Today, the techniquewhich involves genetically modifying neurons to express light-sensitive proteins originally isolated from algaeallows neuroscientists to control the activity of neurons with unprecedented power and precision, simply by exposing them to light.

Taken together, these discoveries have fundamentally reshaped the landscape of modern neuroscience, said George Q. Daley, dean of Harvard Medical School, in his welcoming remarks at the 2019 Warren Alpert Foundation Prize Symposium.

They have set the stage for optogenetics-based therapies that could, one day, be used to restore vision loss, preserve movement following spinal cord injury or modulate circuits that fuel anxiety and depression, and many other applications, Daley said.

More than three decades ago, entrepreneur and philanthropist Warren Alpert established a foundation to recognize scientists whose research and achievements promised to revolutionize how we understand, diagnose and treat disease.

Since then, the Warren Alpert Prize, administered by the Warren Alpert Foundation and HMS, has awarded nearly $5 million to 69 scientists, 10 of whom have gone on to receive Nobel prizes.

Curiosity and wonder

The four pioneers of optogenetics now join this prestigious group. At the symposium held in their honor, they each presented short scientific lectures spanning different facets of a technique that has changed how we study the brain.

Peter Hegemann, the Hertie professor of neuroscience at Humboldt University of Berlin, presented on his current research and on the history of the development of optogenetics, which can be traced to more than a century ago, when scientists first observed that algae could sense light and move in response. Hegemann emphasized the importance of curiosity and wonder in scientific research and the beauty of unpredictability in science.

Edward Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT, associate professor of media arts and sciences at the MIT Media Lab and an investigator at the McGovern Institute for Brain Research at MIT, spoke about his efforts to develop next-generation optogenetic tools, such as expansion microscopy, to map, control and observe the brain to better understand its function.

Gero Miesenbck, the Waynflete Professor of Physiology and director of the Centre for Neural Circuits and Behaviour at the University of Oxford in the United Kingdom, presented his work using optogenetic and other approaches to unravel the mystery of the brains sleep-control systems and build a molecular interpretation of the cellular processes involved.

Karl Deisseroth, the D.H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University, spoke on his efforts to better understand the rhodopsin light-sensitive proteins at the heart of optogenetics. Insights into the inner workings of these proteins are allowing scientists to modify them and expand the power and scope of what optogenetics-based research can achieve.

Deisseroth, like Hegemann, also emphasized the value of basic science.

All the exciting advances weve made in understanding the brain and mammalian behavior and neural circuits across biology, is in many ways deeply rooted in botany and the basic science of studying plants, he said.

Also presenting at the symposium were junior researchers who spoke about how they are applying optogenetics to answer fundamental questions about the brain.

Kimberly Reinhold, a postdoctoral research fellow in the Sabatini lab in the Department of Neurobiology in the Blavatnik Institute at HMS, discussed her research into the neural circuits involved in reward-learning.

Charlotte Arlt, a postdoctoral research fellow in the Harvey lab in the Department of Neurobiology in the Blavatnik Institute at HMS, spoke about her work investigating the neural circuits involved in trial-and-error learning and spatial decision-making.

Optogenetics is credited, rightfully so, with bringing neuroscience into the realm of causal experimentation, said symposium moderator Bernardo Sabatini, the Alice and Rodman W. Moorhead III Professor of Neurobiology at HMS.

It has enabled basic discoveries of the brain that have led to new ways to study and treat neuropsychiatric disease, and in the future its possible that other conditions, such as blindness and paralysis, could be addressed with optogenetic manipulations of the brain, he said.

The four people honored today took this far-fetched idea and made it a reality, Sabatini said.

Photos by Gretchen Ertl

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