- A discussion critiqued a recent proposal email from “Jeff,” noting that its spreadsheet and budget were vague and failed to address the real bottlenecks in genome engineering.  
- Participants argued that the four critical technical hurdles are (1) identifying which mutations to make, (2) cheaper DNA synthesis, (3) more reliable DNA assembly, and (4) delivering large DNA fragments into cells without shearing.  
- They emphasized that dramatically better DNA synthesis/assembly technology would itself unlock progress on delivery, because “biologists will claw their eyes out” to get access to a magic synthesis machine.  
- The group questioned whether Twist Bioscience’s ultra-low-cost DNA is still based on conventional phosphoramidite chemistry or has moved to newer, massively parallel micro-reaction formats.  
- Thermo Fisher and a French company (likely Molecular Assemblies) were cited as presenting enzymatic DNA-synthesis approaches at a recent conference, contrasting with traditional chemical methods.  
- Recombinase-mediated assembly was proposed as a promising route to improve large-fragment assembly fidelity, with a call to include pilot projects using this method in future planning.  
- Participants urged proposal authors to recruit polymer chemists and protein-engineering experts to evaluate whether chemical DNA synthesis is now obsolete and to explore enzyme-based alternatives.  
- A brief side debate recalled a corporate talk arguing that TALENs remain superior to CRISPR in several respects, though details were not elaborated.  
- A link to a Thomas Jefferson anecdote about arriving at meetings with better-prepared plans than the organizers was shared as motivation for submitting more rigorous proposals.  
- An OpenTimestamps bot (https://twitter.com/otsproofbot) was mentioned as a tool for cryptographic timestamping of documents or data.