Peter Hegemann, a scientist trying to illuminate the brain

The brain has proved to be one of the more vexing organs to study. Because it has an almost unfathomable number of neurons (somewhere close to 100 billion), figuring out which cells, in particular, a researcher wants to investigate and how they might be connected to one another is like finding a needle in the proverbial haystack. This complexity has made research into neurological disorders, such as dementia and anxiety, an especially tricky endeavor.

As Hertie Professor for Biophysics and Neuroscience at the Humboldt University of Berlin, Peter Hegemann cracked the biochemistry of how light can be used to regulate the activity of neurons. This research, using what is now called optogenetics, has paved the way for others to create tools to track and map out neural networks and better understand the processes and behaviors they are responsible for. This work earned Hegemann the 2020 Shaw Prize in Life Science and Medicine, along with colleagues Gero Miesenböck and Georg Nagel. All three recently joined other Shaw Prize winners at the inaugural Hong Kong Laureate Forum, which brought the prizewinners together with young scientists to foster connections across different generations of researchers.

Benjamin Plackett spoke with Hegemann about his research, his academic identity, and the importance of basic research. This interview was edited for length and clarity.

Your job title hints at biology, physics, and neuroscience. What exactly is your field?

It’s complicated. My official title includes neuroscience because I’m funded by a foundation that supports neuroscience, but I’m not actually a neuroscientist. I trained as a chemist and then went on to do biochemistry. Then I worked in plant physiology. Now I’m a basic scientist using chemistry to study biology. These days, I call myself a quantitative photobiologist, which means I study the interaction of light with biology, but all my work is stimulated by my knowledge of chemistry.

Your area of expertise now has a name: optogenetics. What is it, and why did you choose to work in optogenetics?

It’s a way of controlling the activity of neurons and other types of cells with light. This is achieved by the expression of light-sensitive ion channels, pumps, or enzymes in the target cells.

I like optogenetics because light is one of the best mediums that you can use in science because it can be controlled in different ways. That makes photoreceptors attractive.

Tell us about your work and why you were awarded the Shaw Prize.

Along with colleagues, I discovered a photocurrent—that’s an electrical current which is induced by light—in the rhodopsin protein of green algae. The protein responds to light by opening channels to allow protons and cations to pass through cell membranes. We then encoded the genes for this protein into specific types of neurons, which allowed us to make them light responsive too. When these customized neurons are stimulated with light, the rhodopsin channels open, allowing ions to enter and activate the cells.

Why would we want to do this?

It means scientists can control neuronal activity with accuracy by using light. Neuroscientists have been asking for this for a long time because it would enable them to activate and study motor neuron cells more precisely, and this helps them study diseases such as Parkinson’s. It has also helped scientists to identify which cells are responsible for anxiety, which will hopefully lead to more treatments. Essentially, anyone who is interested in learning more about how the brain works could benefit from optogenetics.

Optogenetics can also improve animal model experiments, such as those used to study addiction and depression. You can now depolarize a cell with a short flash, and then you can observe the behavior of the animal over many minutes without any contact. This technique makes the findings more authentic.

Neuroscientists are now planning to use several different optical tools in parallel with each other and in different cells—and then combine them with monitoring systems to create more sophisticated experimental designs. The combination of optical tools for excitation with optical tools for recording is really exciting to me.

I must stress that I haven’t done any of this type of work; I’m not a neuroscientist, remember. I’m a basic scientist, but my work has enabled people to develop these tools. This is why basic science is important: it creates the knowledge for others to develop as they see fit.

So as a basic scientist, what’s next for your work?

The next step will be to insert artificial intelligence into the equation. So many genomes have been sequenced—just think of all the proteins we could investigate. Some could end up creating other new and exciting experimental tools for neuroscientists. We worked on infrared-sensitive rhodopsins, for example, but neuroscientists are now asking for far-red light because it penetrates tissue more deeply.

If you’re getting 20 new genes every week, then you can’t feasibly look into all of them [in the search for proteins that respond to far-red wavelengths]. You simply can’t study all of them. That’s why we need algorithms to predict which genes and which proteins might be worth our time. It wouldn’t need to be perfect, but if we could just get the computer to suggest candidates for what it thinks might be worth investigating, we could take it from there. This field of research has an exciting future.

Benjamin Plackett is a freelance writer based in London.