SBPWG:Meetings/Nov 15 2011

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Meeting Notes: November 15 2011

November 15th 6:30-8:30pm @ UCSF Mission Bay (room TBA)

  • Chris Anderson, assistant professor of Bioengineering at UC Berkeley and SynBERC PI, joined the working group to pitch, discuss and get feedback on several prospective biosafety-related projects addressing challenges in biological design, education and management.

Attendees

  • Megan Palmer (Stanford)
  • Ryan Ritterson (UCSF)
  • Jay Vowles (Stanford)
  • Connie Eaves (UCSF)
  • Veronica Zepeda (UCSF)
  • Andy Chang (Stanford)
  • Josh Wolf (UCSF)
  • Nathan Hillson (JBEI)
  • Kevin Costa (SynBERC)
  • Chris Anderson (Berkeley)
  • Derek Greenfield (LS9)
  • Mike Fero (Teselagen)
  • Eduardo Abeliuk (Teselagen)
  • Ellick Chan (Stanford)

Slides

See slides here

Audio

Pictures

Notes

Notes transcribed by Ellick Chan

Please see the timestamps below to jump to a particular section.

16:00

  • Start
  • Working Group Origins at Synberc Spring retreat. Issues covered in practices. Translation, safety, security.
  • Recombinant DNA, film
  • Discovery Days science festival
  • Biotech bootcamp


18:30

  • Megan intro to Safety issues


19:00

  • Chris: topics covered
    • 1) Containment
    • 2) Training
    • 3) Assessing risk

Don't want people making smallpox - not directly issue of synthetic bio. No one is working in that area.

Politics of biosafety - economics. Models for risk. Responding to risks. No financial collapse. Actively mitigate risk.


23:00

  • Making an effective containment strategy - Auxotrophy
  • Self-kill device in cell: problems
  • containment of org
    • codon swapping
    • containment of DNA
    • Dapd auxotropes
    • unnatural amino acid dependence
    • self destruct device
    • synthetic auxotrophes
  • What's the edit distance to something dangerous?
  • What is dangerous?
  • Lack of a theory to assess danger


28:00

  • modifications cannot escape by complementation
  • cannot revert through natural mutation
  • sufficiently inexpensive to use in a bioreactor
  • no adverse impact on viability of the cell
  • be extensible to industrially relevant organisms


31:00

  • pick a gene that can't be knocked out or complemented
  • small molecule dependency
  • allele exchange of new copy with mutant copy
  • 300 essential genes in ecoli
  • tour based selection system


36:00

  • another paper based on a similar technique
  • politics
  • design to contain nature. if it breaks out, it may be our fault.
  • what's the bar for regulation?
  • assay to prove safety/effectiveness
  • not our role to set our own bar - someone else should set it


39:00

  • ques: academic research on rates? chris - industry will say so


41:00

  • training
  • NSF needs curriculum for SynBERC
  • Berkeley has classes, but most other institutions don't
  • Ethics class?
  • Online training module for biosafety
  • heart of the problem - no theory on safety
  • BUA - Biological Use Authorization -> NIH guidelines
  • explosion of genes - no one knows all the risks of them off the top of their head

49:00

  • risk assessment
  • 6 categories
    • virulence
    • environmental stability
    • communicability
    • quantity
    • vaccine
    • allergenicity
    • potential for nefarious use
  • sign off by committee if necessary
  • never seen them say no. may give you recommendations
  • rarely/never re-review in the case of new identified risk


54:00

  • quizzes are basically a checklist of thoughts that the student should consider
  • megan - does such a flowchart exist?
  • biosafety guys aren't that scared of synth bio compared to other risks
  • subjective questions
  • risk should be considered from factors other than the originating organism


64:00

  • assessment
  • risk based on features
  • if it can be programmed, there should be enough formalization to do so
  • formalism simplifies things
  • evaluation of risk depends on biologist's perspective
  • first attempt

70:00

  • minimize risk - example in radiation safety
  • payload delivery
  • risk group is max risk at any stage
  • transposon not caught
  • chassis can be dangerous
  • device can be more dangerous than sum of its components
  • substance could be dangerous in a different context


80:00

  • unintentional promoter can express gene in unknown ways
  • accidental recombination
  • act ontology
    • feature, family, device
  • autorepression device

88:00

  • verification and synthesis
  • families - by hand
  • features - partially automated
  • main issue: how to populate list
  • all knowledge in literature, but not enough manpower to pursue
  • inference of devices resulting from modifications


92:00

  • map dangerous functionality to devices
  • scenarios of things that are dangerous, but not obviously dangerous
  • engineered peanut allergy on salmonella
  • curate high level families for danger
  • what's the difference between a strain (cell+genome+plasmid mods) and a device(modification, composition of devices can create a strain)?
  • strains as combination of devices. complex network.
  • look at interactions between added features + original genome


100:00

  • Peanut peptide combining with transporter
  • Megan: is there a theory on what constitutes danger on a given agent. Weaponization of anthrax - what's the special knowledge needed to make it harmful
  • 2001 list doesn't consider starting path and possible paths to dangerous agents
  • megan: can we classify existing dangerous agents and process of creation?
  • megan: how do we hedge our bets in making sure we're doing good work in this area? From DARPA's perspective? Safe chassis development vs automated monitoring vs surveillance vs forensics
  • megan: partnerships/funding
  • nsf cares about training
  • containment
  • megan: orthogonal genome vs selective growth environment


112:00

  • orthogonal genomes very academic, but probably not industrializable - whole platform required to make this work
  • what are axes of risk?
  • danger from synergistic reaction adding to risk
  • expert system, review committee


120:00

  • megan: is there a politically-safe way to get a group to look at these issues? what would pr think?
  • most of these are obvious
  • is there an arms race for risk assessment schemes?
  • ACT theory is open knowledge
  • value will be in list of devices to query for risk
  • this can be used to find dangerous devices…


Wrap-up:

  • Naming devices and rubric is interesting
  • Doing exercise around context of training module
  • Siebel foundation event coming up


  • New ways to fund biosafety
  • OSTP request for info - december 6th
  • Leaders in practice, 1 week bootcamp in summer - in DC