Tools for analyzing, repairing, and simulating brains

Ed Boyden, pioneer of breakthrough brain technologies such as optogenetics and expansion microscopy, gave this year’s keynote speech at the ZNZ Symposium. In our interview, he shares his vision for brain research, reflects on the challenges ahead, and discusses the ethical responsibilities that come with powerful new tools.

Hi Ed, welcome to Zurich! Your lab has developed a range of innovative tools for mapping and controlling neural circuits. Could you explain how these approaches are changing the way we analyze brain activity compared to more traditional methods?
The technologies we’ve invented are aimed at the “ground truth” – the fundamental building blocks of the brain.  Optogenetics lets us turn specific cells or cell types on and off. Expansion microscopy lets us map individual neural wires, or even individual molecules. Our multiplexed live imaging tools let us see many signals in a network. My hope is that we can understand the brain down to its fundamental building blocks. Then we can see how each mechanism contributes to a function or a disease.

You also focus on repairing the brain. How close are we to using these technologies to treat neurological or psychiatric disorders, and what hurdles remain before they can reach the clinic?
Our technologies are being used widely to discover principles of how to repair the brain – optogenetics and expansion microscopy have been used in thousands of studies to analyze the brain and other biological systems. Some of these principles are then being used to derive new treatment modalities for people. For example, our collaborator Li-Huei Tsai used optogenetics to discover that certain brainwaves can help clean up Alzheimer’s disease in mouse models, and now we are exploring how to use flickering lights and clicking sounds to achieve this cleanup in human patients. Some technologies, like optogenetics, are also in trials for human diseases such as blindness.

What are the biggest challenges for whole brain simulations and what accomplishments can we expect realistically in the next years?
Right now, it’s been hard to get people to believe in us. Just as it was hard for me to get a faculty job in 2005 after inventing optogenetics, and it was hard to get funding in 2015 for expansion microscopy, now in 2025 it’s a great challenge to move the concept of whole-brain simulation toward getting financial support. I hope we can simulate a small brain, like that of a fish or worm, in the next three years.

With increasingly powerful methods to record and even manipulate brain activity, ethical considerations become critical. How do you think about balancing innovation with responsibility in this field?
Ethics is at the core of all that we do. All animal and human experiments, of course, must be approved. But beyond that, we want to be proactive – what do we want to do with our tools? I proposed an international workshop to bring people together to discuss what ethical guidelines we want to put forth for our field. Just as molecular biology did in 1974, I hope our field can derive principles of self-governance.

Looking ahead, what areas of neuroscience research excite you the most, and where do you see the greatest potential for breakthroughs in the coming years?
I’d love to investigate consciousness more with our tools! It’s such a mystery – subjective experience. I’d love to pinpoint how it happens.

All the best for this research endeavor and thank you for the interview!

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Ed Boyden, Dept. of Brain and Cognitive Sciences, MIT