Generative Optogenetics | Hacker News Reader

Generative Optogenetics

darpa.mil

55 pointsbirriel19 comments

This is soo cool. I've also came up with and been exploring this concept, as a side interest, on and off from 2017 - it is the thing that got me originally interested in SynBio. So happy that it finally got an "official" name and recognition. It is the next major thing to happen after AI.

someone already posted this idea at least 8 years ago:

> someone July 13, 2017 at 9:59 pm: if the bacteria can be made sensitive to different frequencies of light (like with rods and cones), and if the cell can be programmed to consider one wavelength a clock signal, another wavelength a data signal, perhaps it can become a cheap synthesizer for DNA fragments, optical UART to DNA bacterium

https://hackaday.com/2017/07/13/movie-encoded-in-dna-is-the-...

And then about (transcript) 1 year and 7 months later on Feb 13 2019 we have Thomas Shaddack saying 12:32 PM

>@thethoughtemporium i am nurturing a thought of light-controlled dna or rna printing. a variant on transcription, but with light pulses to energize the given nucleotide addition. it's a bit far in the left field, kind of an artificial anoparticle/"enzyme" that'd absorb at five wavelenghs, have one for each nucleotide (add to the growing chain on illumination), and one for reset (to prevent longer light intervals from making polynucleotides).

https://hackaday.io/event/163454-open-source-biology-and-bio...

Sometimes DARPA is real slow on identifying good ideas. (more than 8 years later today...) better late than never.

The most obvious route would be to first break up the task into subgoals which can be pursued in parallel:

1) achieve working ab initio and,or in silico simulation of reverse transcriptase

2) achieve working ab initio and,or in silico simulation of relevant proteins and molecules in phototransduction cascades (retinals, opsins, ...)

then:

3) analyze the phototransduction cascade in simulation and using current knowledge of known mechanisms, predict how to change wavelengths for phototransduction cascade, predict how to change end result (a conformational change, etc.)

4) analyze the reverse transcriptase and use current understanding of the mechanisms to change codon tables implemented by reverse transcriptase, analyze which conformational changes are responsible so it doesn't need the RNA input.

then:

5) test small modifications to observe shifts in wavelengths etc to verify the simulation from 2)

6) test modifications to reverse transcriptase: basically swap some elements in the usual correspondence (codon tables) between RNA and DNA bases, to verify the simulation of the reverse transcriptase

then assuming multiple teams were working either on the reverse transcriptase OR on the phototransduction:

7) form random pairs of teams and have each pair of teams try to combine their experience and workflows to achieve a single cell transducing light signals to DNA.

Interesting finds, did you pull those from memory or do you have a search method?

memory, my brain uses advanced forms of error correction.

Your ability to recall and locate specific comments like that is impressive!

> Sometimes DARPA is real slow on identifying good ideas. (more than 8 years later today...) better late than never.

Perhaps they noticed a development (breakthrough?) in an adjacent field that makes this now more interesting and/or practical/feasible.

Oh it's much older than 8 years... here is one such proposal from 2011: https://groups.google.com/g/enzymaticsynthesis/c/6GZT8zFNOfo...

I myself was bitten by a radioactive grad student in 2008 that was obsessed with this idea at the time, and have since learned that almost every major household name lab PI has thought about this in one form or another.

The archive.org mirror only goes back to 2017.

So let's say 2008 is the new infimum date, why do you think or suspect it is that DARPA is only interested in the idea 17 years later?

Especially since you consider it a household idea

Maybe you should check sources that have been around longer than 2017 or even 2008. Optogenetics has been established as a field since at least 2005 (you can also search pubmed for optogenetics 2005). The field had been established and well known among microbiologists for 12 years when you discovered it.

https://pubmed.ncbi.nlm.nih.gov/?term=optogenetics

happy to host an AMA style explainer and engagement.

Mike Koeris Director, DARPA BTO YC W22

Is there a reason why this specifically has to happen in living cells? I get that you can skip the hassle of DNA delivery, but it makes the entire thing about 1,000x more difficult - which seems to offset the posited benefits.

Not to mention that the requirements in the solicitation for speed, accuracy, and length of product are each at least an order of magnitude above what is possible in current in vitro oligo synthesis. And that's just for the intermediate, 19-month goal, much less the later ones.

Certainly, DNA synthesis has been a limiting factor in bio R&D and both the cost and turnaround time have remained fairly stagnant, especially for gene-length products and given the near-term explosion in demand from AI-designed proteins.

I can appreciate that DARPA is a fan of moonshots but would it be advisable to break this into sub-projects such as generally improving DNA+gene synthesis, developing new methods for cell transfection, error correction, in vivo assembly, etc? Focusing on in vivo and light-directed only (and together) might not be the best path forward, though it certainly sounds sci-fi.

Hi Michael,

Really cool of you to be willing to engage with people on this stuff, thanks. I would ask if there would be pathways or initiatives for smaller biotech research teams or med startups to collaborate with DARPA GO for their various goals? Seems like the possibilities are endless. In your mind, could GO one day be used to change traits in an organism that aren’t fixed at birth, but can be influenced by genes? Where do you see the impact or practical use cases for GO in 10-15 years?

Thanks again and looking forward to learning about whatever other crazy things you guys are working on!

This is cool but why is DARPA funding it?

"However, current methods for creating these molecules de novo face significant limitations in terms of scale, complexity, and environmental impact. "

Did I miss a Black Mirror episode?

This was a little over my head so I did some digging of course into the negative or potential harmful effects:

Covert biological manipulation: If cells in specific organisms (including people) are engineered to respond to particular light patterns, then light could be used as a trigger to turn on harmful genes or disrupt normal biology in targeted groups, raising concerns about new classes of biological or “neuro” weapons.

Military and control applications: In combination with existing neurotechnology and optogenetics work (e.g., brain interfaces and neural stimulation), there are concerns about using light‑controlled genetic tools for enhancement, interrogation, or behavior influence in military or intelligence settings.

Ethical and societal risks:

Autonomy, consent, and “mind control” worries: Optogenetics already raises concerns about manipulating brain activity, permanence of genetic changes, informed consent, and vulnerability of specific populations once their cells are engineered to respond to light. GO intensifies this by linking genetic programming directly to external optical signals, which magnifies fears of remote influence or coercive use.

Safety, equity, and regulation: There are unresolved questions about long‑term safety, off‑target effects, error rates in in‑cell DNA/RNA synthesis, and who gets access to beneficial applications versus who is exposed to risk, all in a regulatory landscape that is still catching up with advanced gene and neurotechnologies.

Sources: https://pmc.ncbi.nlm.nih.gov/articles/PMC10730653

https://unidir.org/wp-content/uploads/2025/11/UNIDIR_Neurote...

https://www.asimov.press/p/darpa-neurotech

https://www.bioinformatics.org/forums/forum.php?forum_id=154...

Do you have a source for this? Interested in reading more.

Unless it’s your personal summary, in which case curious what sources you used, or if it’s from an LLM in which case I’ll just ask it myself.

Sorry about that, added the sources

Best comment for this topic. Every point is true and should concern the whole world. And this lightcontrolled behaviour is not new and im pretty sure, already in use. Source? Could post a lot science papers on this topic in general now, that this tech exists, but thats not my point. Expirienced it,was not really a fun. And i know it sounds like a psychosis, but its not. Happend 2019, right before covid. Crap brought chaos to the world, people are not, or bareley aware of. Hate it to sound like a lunatic conspiracy theorist, but its on the topic it self. Who would believe you? Is there a rise in attacks, where the attacker heard voices? Or was somehow conected? Voices from Police, military, any alleged officials? Lazy way for induced voice, is pretending to be god... I bet the officials were more common recently. Sometimes people are aware of whats happening, when it happens.

Greetings from a ti with special interrests.

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