Endy, MIT BE, 20 May Application Struggle, Limited Success, Struggle… System?? Devices? Design & Fabrication

Endy, MIT BE, 20 May Application Struggle, Success, Predictable Success Systems Parts & Fabrication Design Applications Tools Registries Synthesis Measurement

Endy, MIT BE, 20 May Standardization of Components –Predictable performance –Off-the-shelf –ME, 1800s Abstraction –Insulate relevant characteristics from overwhelming detail –Simple artifacts that can be used in combination –From Physics to EE, 1900s Decoupling Design & Fabrication –Rules insulating design process from details of fabrication –Enable parts, device, and system designers to work together –VLSI electronics, 1970s Enabling Biological Engineering

Endy, MIT BE, 20 May Abstraction Hierarchy Devices Parts Systems

Endy, MIT BE, 20 May Parts Zif268, Paveltich & Pabo c. 1991

Endy, MIT BE, 20 May Devices cI-857 O Lac RBS T CI LacI CI

Endy, MIT BE, 20 May Devices LacI  CI inverter CI LacI

Endy, MIT BE, 20 May Systems Inverter.2Inverter.3Inverter.1

Endy, MIT BE, 20 May Interfaces Devices Parts Systems Inv.2Inv.3Inv.1 Zif268, Paveltich & Pabo c LacI  CI inverter CI LacI

Endy, MIT BE, 20 May Parts/Device Interface Devices Parts Zif268, Paveltich & Pabo c LacI  CI inverter CI LacI XX A  B inverter B A

Endy, MIT BE, 20 May Device/System Interface Devices Systems Inv.2Inv.3Inv.1 A  B inverter B A C  D inverter D C E  F inverter F E

Endy, MIT BE, 20 May Device/System Interface Devices Systems E  FC  DA  B inverter B A C  D inverter D C E  F inverter F E X X X

Endy, MIT BE, 20 May Device/System Interface Devices Systems E  FC  DA  B inverter B A C  D inverter D C E  F inverter F E A  D X X X

Endy, MIT BE, 20 May Device/System Interface cI-857 O Lac RBS T cI LacI cI-857 RBS T cI O PoPS in PoPS out LacI cI PoPS out PoPS in

Endy, MIT BE, 20 May cI RBS T O PoPS OUT PoPS IN cI PoPS OUT INVERTER PoPS OUT PoPS IN Polymerase Per Second = PoPS!

Endy, MIT BE, 20 May Device/System Interface Devices Systems BCA A B C PoPS IN PoPS OUT X

Endy, MIT BE, 20 May Interfaces Devices Parts Systems PoPS Inv.2 PoPS Inv.3 PoPS Inv.1 Zif268, Paveltich & Pabo c PoPS Inv.1 PoPS

Endy, MIT BE, 20 May E.colibrator, IAP 2004

Endy, MIT BE, 20 May Device-Level System Diagram

Endy, MIT BE, 20 May Parts- and Device-Level System Diagram

Endy, MIT BE, 20 May DNA Layout

Endy, MIT BE, 20 May System-Level Timing Diagram

Endy, MIT BE, 20 May Population-Level Simulations

Endy, MIT BE, 20 May Trigger Test Circuit Characterization and Debug

Endy, MIT BE, 20 May MIT Registry of Standard Biological Parts

Endy, MIT BE, 20 May DNA Synthesis Year Bases of DNA Per Person Day Carlson, Pace & Proliferation of Biological Technologies, Biosec. & Bioterror. 1(3):1 (2003)

Endy, MIT BE, 20 May Hacking the Living World?

Endy, MIT BE, 20 May Risk Biological Risk: Background Technology Classes Relevant to Biological Risk (current relative capabilities) Manipulation Analysis Response Detection

Endy, MIT BE, 20 May Biological Risk: Tactics as “Strategy” Maginot Line France, 1940 Ciprofloxacin Smallpox vaccine Anthrax vaccine SARS assay VHF therapy (under construction) Plague vaccine (under construction)

Endy, MIT BE, 20 May Biological Risk: Future Strategy Risk Technology Classes Relevant to Future Biological Risk (needed capabilities) Detection Analysis Response Manipulation

Endy, MIT BE, 20 May Biological Risk: Suite of Solutions Number of Individuals Individual’s Intent honorable dishonorable Bin Laden Genetics, Inc. Disgruntled Researcher Garage Bio-Hacker Basic Researcher

Endy, MIT BE, 20 May A Constructive Society

Endy, MIT BE, 20 May D23L AvrII D24L EcoRI D26L BamHI D27L EagI D28L SacII D30L SalI D22L BstEII D22RD23RD24RD26RD27RD28RD30R ø ø R3.8 D25L XmaI D25R 2.5 D29L PciI D29R 1.82 BglII FspIAvrII D50L BsiWI D51L PvuI D53L SacII D54L BamHI D55L XmaI D57L HindIII D50RD51RD53RD54RD55RD57R ø9 10ATøTø12 D52L EcoRI D52R 9 D56L ApaI D56R 8 PacI ø10 11 DraIRsrII XbaI BssHIIAatIIAvaIBspHIEciINsiI NdeI AseI D57L HindIII D59L EcoRI D58L PfoI D57R D58R 1213 PacI ø13 R13 D60L BsiWI D62L EagI D59RD60RD62R 16 D61L PvuI D61R 15 ApaLI NciI ScaI BstBIAvaI D64L HindIII D65L BamHI D67L ApaI D68L EcoRI D69L BsiWI D71L SalI D63L SacII D63RD64RD65RD67RD68RD69RD71R ø / E 19/19.2/ R18.5 D66L XmaI D66R 17.5 D70L PstI D70R øOR SRR/TR 160 KasIBspDIFspI BglI BlpIDraIIIAcvIAciIKpnI

Endy, MIT BE, 20 May Kuroda-Kawaguchi et al., Nature Genetics 29:279 (2001)

Endy, MIT BE, 20 May Responsibility “Men have forgotten this truth,” said the fox. “But you must not forget it. You become responsible, forever, for what you have tamed.” Saint-Exupéry, Le Petit Prince (1943)