Date: Fri, 21 Jul 2023 21:16:55 -0700
From: Bret Victor
Subject: Re: CCC talk
This is just a straight transcript of my handwritten notes from yesterday's meeting.  I had started organizing them and adding additional thoughts, but it was getting out of hand, so I'll send a more organized set of ideas in a later email.


Rich 1956
Random AU won't make a polymer. (ref?)  PolyA + polyU will make a polymer.
Simulate enzyme making random AU vs polyA, polyU.
Macroscale vision (what Rich saw) vs microscale vision (what was actually going on)

Seeman 1982
(Influence? Who read this paper?)
Demonstrate replicational junction and replication
Recombination junction, the crossover.
  Biological inspirtaion for crossover.
  Comic strip of frames -- snapshot of frame 2 -- "this could be a primitive"
  Structural direct-manipulation vs dynamics simulation (zip DNA with our hands, vs thermal motion)
Immobile junction
  Show why recombination junction slides and immobile does not
  Introduce abstract representation that shows routing but not sequence.
Sticky ends & lattices
  Show tile formation
  Proteins docked in crystal
Timeline of Ned's software tools?  Ned's physical models?

Seeman 1991  (DNA cube)
Go through Seeman history on timeline
Attempts, vast expanses of time
Checking off checklist on 1982 paper 

Seeman 2009
3 oligos. Structure in the PDB.
They made 9 different crystal designs.  Turn knob to explore across them.
Doesn't seem to scale -- no clear path to Ned's original vision
  Cryo-EM doesn't need crystals
  but still needs positional control (e.g. goniometer)
macro-scale object, and he knows where every atom is
Compare to microchips, other technologies
  e.g. DRAM/Flash or other regular structure, $10B fab vs $20 of oligos and a test tube
  Generic geometrical description (programming language or graphical language)
    which compiles into both a bio nanostructure and a semiconductor structure
    so you can compare what it takes to fabricate the same shape in each technology
  Ashwin's talk on bottom-up vs top-down

Rothemund 2006 
"DNA" written in origami vs "IBM" in boron atoms
Show helix and crossover geometries.
Emphasize the arbitrariness of the design.  A large design space demands a CAD tool.
Asymmetric fully-addressable shape, not a crystal.
Ned's crystal is to DRAM as origami is to CPU.
Rod model -- how do you raster with DNA?
Rigidity of ssDNA vs dsDNA -- demonstrate and explore parameters.
Discovery of DNA's preferred twist
Growing intimacy with DNA
  DNA as building material, understand it like understanding steel
  Design tools require knowledge of the material
    which then allow you to build better test objects, and get better knowledge, etc
Explore the happy face in depth with Realtalk.
What would happen if you deleted half the staples?
Paul missed:  global twist, local strains
Can we show thermal fluctuations? Does oxDNA simulate them?

We could lead the talk with cell playgrounds as scientific motivation
  then ask "How could you ever make anything like that?"

- Introduction to Realtalk
- Cell playgrounds
- History of DNA nanotechnology
- Lab of the future

Show protocols from the papers in our Realtalk plates and racks.
Put a paper down on your lab bench and immediately start replicating the experiment.

Generate "our paper" as augmented paper
The presentation itself captured in a paper.
Show the presentation within the presentation.

Use vertical surfaces, not just for timeline, but for multiple views of bricks editor, oligo orders, etc.
  surrounded by context