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�鶹��Ѱ�����Boulder��alumnus��and research faculty member Ken Douglas reflects on publishing his book about optogenetics just as the field earned this year’s Nobel Prize in Physiology or Medicine

Ken Douglas (PhDPhys’83) had a busy month and��wasn’t paying much attention to the Nobel Prize announcements. He had��written��a book that was nearing publication and had plenty else on his mind.��But in early October, he started getting��many emails from people he knew. The topic of his new book, optogenetics, had just become the focus of this year’s Nobel Prize in Physiology or Medicine.

“I was quite surprised,” says��Douglas of hearing the news.��

The 2026 Nobel Prize in Physiology or Medicine was awarded to three scientists for their work on optogenetics, a technique that uses very precise light and genetics to control the activity of neurons.��

Douglas spoke with the Department of Physics about his newest book, the science behind optogenetics and why the field has transformed neuroscience.��

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What inspired you to��write a book on optogenetics and neurotechnology, and why now?

Douglas: I’ve been��witness to many serious mental health issues. Optogenetics seeks to uncover the brain connections responsible for behavior in wellness and mental illness. I was especially interested in brain circuits that don’t work well, for example, in people suffering from clinical depression.��

I’ve known too many people who have been devastated by depression and similar disorders. The optogenetics literature allowed me to glimpse, albeit in animal models, the complex neural circuit dysfunction underlying the misery in people I knew. That allowed sympathy to replace my bewilderment.��

It also fired me up to read a lot more about optogenetics and other modern neurotechnologies.

For a long time, I was thinking about writing a book on bioprinting, which uses 3D-printing to create living biological tissue with vascular channels, or optogenetics. Then a friend of mine had a kidney transplant. Her transplant made me wonder what her experience might have been if bioprinting was already a mature technology. So, I first wrote a book on and when that was finished, I turned to optogenetics.��

Who is the book written for: neuroscientists, students or general readers?

The book is written for a general reader who may be curious about scientific subjects but doesn’t have a scientific background.

Can you share an example of how researchers use optogenetics to understand the brain?��

Researchers have used optogenetics to understand how memory is��allocated, encoded, stored, and retrieved in the brain.��

One remarkable set of experiments demonstrated memory formation in the absence of experience. A team led by Sheena Josselyn and Paul W. Frankland at the University of Toronto artificially implanted a memory for an otherwise never experienced event—namely, in the absence of any sensory experience.��

Mice were trained to form a real associative memory between a specific odor and a mild foot shock. The team was able to replace both the odor and the foot shock by optogenetic manipulation of the specific neurons that encoded the odor and the foot shock.��

The result was that “mice responded to an odor they had never encountered by avoiding a shock they had never received.” A better understanding of how memory works��could benefit a wide range of individuals, from those struggling with memory impairments to those enduring traumatic memories.

For people who may not be familiar with the field, why does optogenetics deserve to be considered a Nobel-level breakthrough?

For historical perspective, Spanish physician and scientist Santiago Ramón y Cajal won the 1906 Nobel Prize for Physiology or Medicine. Among his tremendous contributions, Cajal established that the nervous system is made up of discrete individual neurons and that the neuron is the structural and functional unit of the nervous system.��

But as Rafael Yuste of Columbia University has written, “As in other fields of science, there is a direct link between the techniques used and the concepts and paradigms that arose from these studies, as investigators cannot make discoveries beyond those that their techniques reveal.”

Apropos of this remark, Sheena Josselyn wrote, “Optogenetics ushered in an era of neuroscience in which neuronal circuits became the new basic unit of inquiry.”��

The overarching impact of this Nobel-level breakthrough is that it enables temporally precise, pathway-specific interventions in intact brains. Optogenetics has transformed neuroscience from only observational correlations��of neural activity with behavior to revealing causal relationships, the logic of brain function.

When researching and writing this book, what discovery or story surprised you the most?

That’s a tough question because I was so amazed by all the investigations I learned about.��

But I’ll point to work by Robert C. Malenka of Stanford and his colleagues (and mention en passant that Malenka was the post-doctoral mentor of Karl Deisseroth, one of the winners of the Nobel Prize for optogenetics).��

Malenka studied empathy circuits in mice. Empathy is an integral part of social communication and can be characterized as the adoption of another's sensory and affective state—specifically, states that are more appropriate to another's situation than one's own.��

His team induced three different affective states—pain, pain relief/analgesia, and fear—in demonstrator mice and delineated the distinct brain pathways required in the observer mice to share the diverse affective states of the demonstrator.

Among the memorable findings:

• Observer mice that had not been subjected to a painful stimulus showed heightened responses compared to the demonstrator mice. As neuroscientist Jeffrey Mogil of McGill University said, “Those [observer] mice act as though they’re in the same amount of pain and in more places. The behavior is astounding.”��
• Observer mice that��did not receive any soothing morphine analgesia behaved as though they also got the drug. As Malenka said, “You’ve actually relieved pain in this animal simply by letting it hang out with another animal whose pain was relieved.”

What do you want people to take away from your book?

One salient point is that the starting place for mammalian optogenetics was completely basic research, namely, the study of so-called algal opsin genes from microbes that are sometimes disparagingly alluded to as “pond scum.”��

A priori,��microbial opsins have absolutely��nothing whatsoever to do with how a vertebrate brain works or malfunctions.��

Even so, a couple of decades later, scientists by the thousands who are interested in how the mammalian brain performs, are putting these opsins, in the form of membrane proteins, smack dab into the very brains they’re trying to parse.��

This is a quintessential example of how basic scientific research can and often does impact discovery in a previously unrelated endeavor. And helps shape solutions to practical problems—say, how to target treatment for Parkinson’s disease.��

A second salient point might be encapsulated by Rob Malenka’s comment on the optogenetics book, “At a time when the importance of scientific research is being questioned, this book is particularly timely because it beautifully illustrates how scientific research leads to advances that will benefit human health and societies at large.”

This article was originally published by the �鶹��Ѱ�����Boulder Department of Physics. Read it here.

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