Karl Deisseroth, Peter Hegemann and Gero Miesenböck Awarded Horwitz Prize for Foundational Work on Optogenetics

NEW YORK, NY (September 7, 2022)—Columbia will award the 2022 Louisa Gross Horwitz Prize to Karl Deisseroth, Peter Hegemann, and Gero Miesenböck, for research that laid the foundation for the field of optogenetics. The prize will be presented at a ceremony held in New York City on February 16, 2023.

Optogenetics has revolutionized the study of the nervous system, helped scientists understand how brain circuitry controls behaviors such as learning, sleep, vision, addiction, and movement, and increased the potential for treating diseases like epilepsy, spinal injury, multiple sclerosis, and Parkinson’s disease.

Before optogenetics, the tools scientists had at their disposal to probe the brain were more limited. Using electrical stimulation to excite neurons proved too imprecise, as it also triggered neighboring brain cells. Drugs that targeted neurons acted too slowly and indiscriminately. Optogenetics changed everything because the technique finally let scientists target a set of neurons and control their activity, quickly and accurately.

The name of the technique comes from a combination of the words “opto-”, as the method involves using proteins that are responsive to light, and “-genetics,” because getting the proteins into neurons requires genetic engineering. The proteins used in optogenetics are called opsins, which are found in cells that sense light, like eye cells. Scientists first discovered opsins in the 1800s, but it wasn’t until the 2000s that they were first used as tools in neuroscience experiments.

Early in 2002, Gero Miesenböck’s group used genetic engineering to smuggle a set of opsin  genes from fruit fly eyes into rat nerve cells in a dish. The researchers showed for the first time that shining a light on opsin-altered neurons could trigger the cells to fire electrical impulses. A few years later, Miesenböck’s lab implanted light sensitive ion channels deep into the brains of fruit flies and demonstrated that optogenetics could also work in living creatures. In this experiment, light precisely stimulated two of the fly’s neurons without triggering any neighboring neurons, and controlled the insect’s ability to fly away.

While it made sense that the opsin utilized in the first optogenetic experiments came from eye cells, this early system was slow, taking several seconds to switch on and off. Fortunately, light sensitive molecules can be found in many other places in nature, and it turns out that the key to unlocking the full potential optogenetics was hiding in pond scum.

After studying the behavior of algae for several decades, in 2002, Peter Hegemann’s group discovered and isolated channelrhodopsin, a form of opsin that prompts green algae to swim towards light to capture and store energy from the sun. Compared to rhodopsin, its eye cell counterpart which requires multiple components to function, algal channelrhodopsin is a simpler system, comprising a single protein channel. Hegemann’s team successfully inserted the channelrhodopsin gene into frog eggs and human kidney cells and showed that the channel could transmit a current across the cell membranes.

In 2005, Karl Deisseroth’s group took the next step by modifying a harmless virus so that it could deliver the channelrhodopsin gene from algae into animal neural cells grown in a culture dish. The result was an optogenetic system that was quicker, more sensitive, and simpler-to-use than earlier iterations. Deisseroth’s team then worked out how to deliver bursts of light into the brains of living mice using a long, flexible optical fiber. This breakthrough expanded the use of optogenetics into more complex model organisms.

Optogenetics has continued to evolve after the initial pioneering work of Miesenböck, Hegemann, and Deisseroth. For instance, Deisseroth and Hegemann then together led discovery of the key principles of light-sensitive channel structure and function; they showed it was possible to produce “designer” opsins that respond to different speeds or colors of light, that move different kinds of ions, expanding the range of brain functions that can be studied. Researchers have since implemented optogenetics to study behavior in a wide range of organisms including fruit flies, worms, fish, mice, and even monkeys. Starting out as something that only specialists could use, the method is now so accessible that it has swept through hundreds of labs around the world and transformed the field of neuroscience.

Beyond basic research, optogenetics is also starting to aid the discovery of new treatments. In mouse models, scientists have used optogenetics to activate brain cells to restore memories that appeared to be lost, and relieve signs of depression. Researchers are developing biological pacemakers made from stem cells that can switch the heartbeat on and off with light, potentially offering a relatively complication-free treatment for patients. And last year, scientists used optogenetics to help a blind patient see again. The versatility of optogenetics suggests that many more exciting advances lie ahead.

Deisseroth, Hegemann, and Miesenböck are the 109th, 110th, and 111th winners of the Horwitz Prize, which is awarded annually by Columbia University for groundbreaking work in medical science. Of the 108 previous Horwitz Prize winners, 51 have gone on to receive Nobel Prizes.

Awardee Biographies

Karl Deisseroth, MD, PhD, is a professor of bioengineering and a professor of psychiatry and behavioral sciences at Stanford University, USA. He is also an investigator at the Howard Hughes Medical Institute. Deisseroth received his undergraduate degree from Harvard University, and completed his PhD and MD from Stanford.

Peter Hegemann, PhD, is a Hertie Professor for Neuroscience at the Institute of Biology and Experimental Biophysics at the Humboldt-Universität zu Berlin, Germany. Hegemann completed his undergraduate studies in chemistry at the University of Münster and LMU Munich, and received his PhD from the Max-Planck-Institut für Biochemie, Martinsried.

Gero Miesenböck, MD, is the Waynflete Professor of Physiology and director of the Centre for Neural Circuits and Behaviour at the University of Oxford, UK. Miesenböck completed his undergraduate studies at the University of Innsbruck in Austria and Umeå University in Sweden, and received his MD from the University of Innsbruck Medical School.