Generative Optogenetics

> 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.

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...