Living Foundries Approved for Public Release, Distribution Unlimited 1 Living Foundries Polymers Catalysts DNA instruction set Heterogeneous, functional materials Cellulose Natural gas Molecules Sugar Fuels Pharma CO2 Coal Chemicals “cell-like” factory Multi-cellular constructs Disruptive capabilities in materials, therapeutics, sensors and manufacturing paradigms Approved for Public Release, Distribution Unlimited Self-repairing systems Sentinel Organisms 2 Engineering Biology: Prohibitive Cost, Time, Complexity minimal bacterium 10 Effort (total $ * yrs to develop) [$*yr] 11 1.00E+11 10 10 1.00E+10 yeast DARPA annual budget DuPont 1,3 propanediol 2002 109 1.00E+09 Amyris Artemisinin 2009 108 1.00E+08 107 1.00E+07 SOA 106 1.00E+06 10 1.00E+055 Living Foundries 10 1.00E+044 103 1.00E+03 metabolic engineering complex genetic circuits 11 10 10 genome rewrite 100 1,000 10,000 100 1,000 10,000 Complexity (# genes inserted/modified) 100,000 100,000 Problem: Engineering biology is prohibitively time and money intensive, blocking disruptive capabilities across materials, sensors, medicine and manufacturing. 3 Approved for Public Release, Distribution Unlimited “There was a gap between the sorts of systems we could visualize and what we could actually get into hardware in a timely way.” Lynn Conway on VLSI Approved for Public Release, Distribution Unlimited 4 Comparison: integrated circuit design and fab Central metabolism Intel 4004 Year - 1971 Pyruvate + G3P OH dxr ispD ispE Synthase ispF ispG ispH idi ispA ADS FPP O Amorphadiene CPR p450 P H O- Artemisinic Acid H OPP O- OPP H3 C Hydroxylase Unit O O OHC dxs DXP Pathway CO2H OPP HO H H O Artemisinic acid production in yeast dual-feedback oscillator Approved for Public Release, Distribution Unlimited 5 Comparison: integrated circuit design and fab Conway and Mead Design Principles Technical • Simplification and Standardization • Raise abstraction level of design • Design Rules Intel 4004 Year - 1971 • Design Tools Structural • Decoupling of Design and Fab • Access to rapid prototyping services (common infrastructure) • Enable open collaboration Approved for Public Release, Distribution Unlimited 6 Building a new technology base to enable transformative applications Living Foundries: ATCG New tools to enable rapid engineering of biology Living Foundries: 1000 Molecules Foundries Enable scale and rapid prototyping of genetic designs never before accessible Demo New Capability 1000 Molecules 1000 new chemical building blocks for new materials 100x faster DBT cycle for engineering biology Enable Impossible Projects ... IMPACT: Open up new avenues for innovation Enable access/new entrants Engage and Seed industrial/academic partnerships Approved for Public Release, Distribution Unlimited Fundamental shift in chemical/materials industry 7 BTO Biology as Technology Approved for Public Release, Distribution Unlimited 8 Traditional DoD View of Biology Biology = Medicine for the Warfighter Approved for Public Release, Distribution Unlimited 9 Traditional DoD View of Biology Technology National Security Biology = Medicine for the Warfighter Approved for Public Release, Distribution Unlimited 10 www.darpa.mil Approved for Public Release, Distribution Unlimited 11