Growing up on a farm in eastern Pennsylvania, Sean Quirin was surrounded by the familiar -- the land, once flush with apples and peaches, had been in his family for nearly two centuries.
But as he slept outside in the grass on summer nights, what captivated him was the unknown: the vast tableau of stars above.
The future Stanford Medicine researcher knew he someday wanted to explore uncharted territory, perhaps even brush against the limits of human understanding. But he had no idea what to do with that feeling, or with his life.
And he had no inkling it would eventually lead him to probe some of the brain's deepest mysteries.
A curious journey
Quirin's path was winding and full of serendipity. As a kid, he earned decent grades but was more interested in finding adventure on his family's property -- hunting for berry brambles or building forts from fallen trees.
The family farm was no longer profitable because all the fruit trees had been ravaged by disease just before Quirin was born. His father found work as a school bus driver, and his mother began drafting architectural blueprints to help make ends meet after spending years as a homemaker.
As the oldest of three, it was up to Quirin to chart his own course. Not knowing where to start, he followed his father's advice to attend community college. There, he chased his curiosity through a succession of majors -- languages, math, computer science.
He picked up work restoring wooden boats with his best friend. (It's also how he happened to meet his future wife, while attending a party on one of the boats.)
One day, a customer asked Quirin if he would do some coding for his industrial construction business. That gig took him into research labs at universities and companies in the Philadelphia area, where he wrote computer programs to automate heating, ventilation and air conditioning systems. While he'd visited the city before, the labs were a foreign world he'd encountered only in movies. "I remember thinking, 'Wow, these places are so cool. Everything is shiny; these people know what they're doing,'" he said. "It was utterly fascinating."
Quirin kept following his curiosity. Next up: The pursuit of a bachelor's degree that could land him in one of those labs. Inspired by his love of outer space and films like Star Wars and Contact, he chose to study astronomy and astrophysics at the University of Colorado, Boulder.
"I wanted to build these awesome telescopes -- something super complex where it takes two decades and can measure something never seen before," he said. "Just being able to reach out and touch something unknown felt exciting."
Just being able to reach out and touch something unknown felt exciting.
Sean Quirin
After graduating, Quirin spent four years working for an optical equipment startup near Boulder. His colleagues all seemed to have PhDs, and he thought delving deeper into optics -- the study of light -- sounded interesting. Plus, he learned that if he was accepted into a program at his alma mater, the National Science Foundation would subsidize attendance. "There was no reason not to do a PhD, because I was having fun with it," he said.
Quirin returned to the University of Colorado to pursue a doctorate in electrical engineering. One day, during his last year in the program, he opened a magazine covering the latest developments in his field. He read a feature on optogenetics, then a new field of study in which researchers could control brain cells using light after genetically modifying neurons to be light-sensitive.
The story featured the work of a Stanford Medicine professor, a psychiatrist and bioengineer named Karl Deisseroth, MD, PhD, one of the field's pioneers. His innovations had the potential to illuminate how the brain functions and lead to therapies for everything from Parkinson's disease and blindness to anxiety and depression.
Quirin was fascinated. His research had already shifted from the design of telescopes to building optical tools that could extract an unprecedented level of detail from microscopic images using computer algorithms and track individual molecules across nanometer-long distances. He realized that the devices he had developed could be applied to study the brain.
"I felt like, 'Wow, this is what I've got to do -- it's too good,'" he said. "Looking at the brain is like looking at the night sky and trying to imagine what's going on. Instead of looking at stars, I can look at neurons."
Looking at the brain is like looking at the night sky and trying to imagine what's going on. Instead of looking at stars, I can look at neurons.
Sean Quirin
Quirin had never even taken a biology or chemistry course, but he resolved to master neuroscience. After earning his PhD, he took a postdoctoral position at Columbia University, developing tools for imaging neural circuits in animals. Then he became a research scientist at Mitre, a Virginia-based nonprofit conducting government-sponsored research on the brain.
In the spring of 2015, Quirin got a call from a friend who'd heard that a professor of psychiatry at Stanford Medicine was looking for someone who could build the type of custom optical devices he specialized in. The professor's name? Karl Deisseroth.
Illuminating the brain
Quirin soon joined Deisseroth's lab as a senior engineer. At the time, Deisseroth, the D.H. Chen Professor, was about to embark on an experiment no one had attempted before. Back in 2012, he and his team had shown that it was possible to use beams of light to trigger single cells in a petri dish. But he wanted to do something much more complex: control cells using light in a living, moving mammal. It required technology only a few people in the world could build, and Quirin was one of them.
"He brought a new level of technological brilliance and right away made a huge impact on the lab," Deisseroth said.
Quirin built a device that can project light in three dimensions through an animal's skull and into its brain, allowing researchers to control more than a thousand individual neurons simultaneously. Known as a spatial light modulator, the palm-sized device can be programmed to act like a lens, a mirror or a spectrometer, which diffracts light into different colors.
By changing how light is affected as it passes through the device, the tool allows researchers to simultaneously target specific neurons of interest. "Having a microscope that can dynamically change itself helps us figure out whether these neurons matter and what about them makes them important," Quirin said.
The resulting research, published in Science and Nature in 2019, showed that researchers could trigger visual hallucinations in mice or control other aspects of their behavior by shooting light into certain brain cells.
In the following years, Quirin applied his expertise to numerous projects in Deisseroth's lab. Last year he launched his own lab, which focuses on understanding which neurons are associated with certain outcomes -- and learning how his optical devices can be used to affect the activity of those neurons. All his research involves animals, but the intent is ultimately to shed light on the workings of the human brain.
"Our neurons coordinate their activity to contribute to the shape of our personalities, what we find pleasure in, what we are afraid of, how we interpret the world," said Quirin, who in 2022 was named assistant professor of psychiatry and behavioral sciences at Stanford Medicine. "My questions are related to seeking out how important any individual neuron is to all this. If we find that answer, what about any 100 neurons? We have a very precise picture of how an individual neuron works in isolation but much less is known about how ensembles of neurons coordinate to derive these experiences."
We have a very precise picture of how an individual neuron works in isolation but much less is known about how ensembles of neurons coordinate to derive these experiences.
Sean Quirin
That research is important to understanding psychiatric illnesses, many of which may stem from disruptions to webs of neurons sending signals together. Quirin's lab advances the optical tools necessary for this research, and he collaborates with investigators studying specific psychiatric diseases. Eventually, this work could inform more precise and effective therapies for conditions such as Alzheimer's disease, schizophrenia and depression.
Embracing challenges
Quirin is not put off by the inevitable failures that arise during the scientific process. "When we do experiments and they don't work, we have a unique opportunity in our lab to figure out how we can change the tools to do something new," he said. "We flourish when things are not working."
Deisseroth, who has taken his own multi-dimensional path, believes Quirin's career journey has helped him excel in the field. "The fact that he hasn't been on the traditional academic rollercoaster probably helped him think bigger and be more thoughtful," he said.
Karl Deisseroth's
Human Neural Circuitry program seeks to investigate deepest mysteries of brain function, dysfunction
It was only after they had been collaborating for nine years that Quirin told his mentor about that magazine article that changed the course of his life. "That speaks to his humility," Deisseroth said. "He probably never thought that his origin story was something he should go around sharing, not realizing how interesting it was."
Taking an unorthodox path was not without its challenges. Quirin said he sometimes suffered from imposter syndrome. "Every step of the way, you have in the back of your mind, 'I'm not good enough,'" he said. "If I were to give advice to somebody else who felt that way, I'd say, 'Don't give up.' You've got to convince yourself that this is what you want to do."
For Quirin, that has meant leaning into his sense of adventure and curiosity. "Every time I had to make a decision, I made what might've been the riskiest but most exciting decision without knowing what the consequences would be," he said. "Each time, I got lucky."
Beyond luck, Quirin owes his success to his determination to take on challenges that others find intimidating. Sometimes, that manifests as a resolve to fix anything that breaks at home or in his lab -- even when that means accidentally totaling his car by shorting out its electrical system. In his academic work, that impulse motivates him to keep going in moments when solutions seem elusive.
"I love being lost in problems that take years or decades or can never be solved," he said. "I don't find that daunting -- I find that enchanting."
Photo illustration: Emily Moskal
More Unconventional Paths
- How she flipped traditional genomics analysis on its head
- How archaeology inspired a path to family medicine
- Rock climber turned trauma surgeon
- Merging computation and biology
- From monasteries to medicine
- Bohemian wannabe turned Stanford nutritionist
Have a suggestion for a future subject of Unconventional Paths? Email sm_editors@stanford.edu.
