2026 Nobel Prize in Physiology or Medicine: Deisseroth, Hegemann, Nagel
nobelprize.org
nobelprize.org
I participated in early work in optogenetics in larger brains, and Karl was my postdoc adviser. He is a deeply thoughtful and generous scientist. His book Projections unpacks some of his thinking as to how these tools may unravel and treat a panel of psychiatric conditions. The company MapLight he started is working to make these treatments a reality via ongoing clinical trials https://maplightrx.com/pipeline/
https://www.centerwatch.com/clinical-trials/listings/NCT0511...
https://www.entandaudiologynews.com/features/ent-features/po...
There’s a big contrast there to how some scientists operate - hoarding ideas, being cautious in collaboration, demanding credit. I’m so pleased for him!
The lectures themselves were, unfortunately, quite boring. This was the introductory course for freshmen, covering a lot of material that students ought to have learnt in school already. Much of the time, the professor appeared to be as bored by it as many of the students were, but I guess it had to be done and someone had to do it...
Of course my long game is to add cuttlefish-style "pulsing, glowing" tattoos to humans.
Imagine implanting a light guide and then setting a translucent port to allow a pathogens safe way to couple into nerves deep inside the brain, imagine transient gene therapies that introduce channelrhodopsins and holographic projections that create volumetric excitation patterns.
Seriously, thinking machines are super impressive, but that stuff really alien in its possible applications.
My prediction is that true neural interfaces will be based on light not wires.
(To be clear, since it's probably necessary, I'm asking a curiosity-driven question about the mechanism here, not throwing shade on the work. Given it's won the researchers a Nobel prize it's obviously highly significant.)
Ahead of time, you either use viral tools or other genetic modifications to make specific cell types express the photorecrptor.
*there is an effect of light/heat that all cells are subject to, and good experiments try to control for this as best they can
Also, just like with CRISPR, there were others thinking along the same lines at the same time, but who didn't get the high profile publications: https://www.scientificamerican.com/article/he-may-have-inven...
Crick’ original challenge: https://www.scientificamerican.com/article/controlling-the-b...
He said later: One of the next require- ments(asdiscussedabove)istobeabletoturnthe¢ring of one or more types of neuron on and o¡ inthe alert animal in a rapid manner. The ideal signal would be light, probably at an infrared wavelength to allow the light to penetrate far enough. This seems rather far- fetched but it is conceivable that molecular biologists could engineer a particular cell type to be sensitive to light in this way.
https://pmc.ncbi.nlm.nih.gov/articles/PMC1692710/
It’s rather neat that we can go from wish to mechanism at least sometimes, in this fashion. Lots of hard work and ingenuity in between, and worth celebrating.
Looking at the basic science results I could not decide if they were bringing in really novel understanding or basically repeating a lot of the old electrical stimulation results.
I do remember a staggering amount of money was pumped into the field and it was super trendy in the 2010s.
now replace dopamine with any cell type you can think of in the brain, and you can even be more clever and do genetic tricks like "only this type of cell in this part of the brain that only receive input from this other part of the brain, but not others"
it really truly unlocked the entire era of neuroscience we are in, with the focus on circuits.
I predict the next likely era after circuits is networks, and the cool thing about opto is the scalability and the way we can precisely control and shape light to ultimately control networks.
From my understanding, this discovery is on the level of what transistors were for electronics - unlocking a completely new way to understand and design the electronic circuits, which later on enabled the rise of computing.
Since compared to biology our computing is still highly primitive, it seems like next step in compute power will be biological and quantum computing.
You have to imagine, before opto, EVERYTHING in neuroscience was either genetic or observational, nothing really good with manipulating circuit function directly except for the only real intervention we had - ablation of an entire region without any specificity, especially with regards to passing axons.
Now, I literally expect any neuro paper that even touches behavior or circuits to have some sort of validation with opto, or it's harder for me to believe.
Maybe there's a bit of an over reliance on it in my above comment, but if you have a better causal tool to suggest, be my guest.
Many people involved in optogenetics, it must have been hard to select 3.
Optogenetics allows you to control neurons with light.
Here's an overview from Karl himself: https://pmc.ncbi.nlm.nih.gov/articles/PMC6814250/
And here's a step by step example protocol: https://pmc.ncbi.nlm.nih.gov/articles/PMC3490315/