Struggle Limited Success Struggle Design Fabrication Endy MIT
Struggle, Limited Success, Struggle… Design & Fabrication Endy, MIT BE, 20 May 2004 Devices? System? ? Application
Struggle, Success, Predictable Success Design Parts & Fabrication Systems Tools Registries Measurement Synthesis Endy, MIT BE, 20 May 2004 Applications Application
Enabling Biological Engineering • Standardization of Components – Predictable performance – Off-the-shelf – ME, 1800 s • Abstraction – Insulate relevant characteristics from overwhelming detail – Simple artifacts that can be used in combination – From Physics to EE, 1900 s • Decoupling Design & Fabrication – Rules insulating design process from details of fabrication – Enable parts, device, and system designers to work together – VLSI electronics, 1970 s Endy, MIT BE, 20 May 2004
Abstraction Hierarchy Systems Devices Parts Endy, MIT BE, 20 May 2004
Parts Zif 268, Paveltich & Pabo c. 1991 Endy, MIT BE, 20 May 2004
Devices CI Lac. I OLac RBS l c. I-857 CI Lac. I Endy, MIT BE, 20 May 2004 T
Devices Lac. I CI Lac. I CI inverter Endy, MIT BE, 20 May 2004
Systems Inverter. 1 Endy, MIT BE, 20 May 2004 Inverter. 2 Inverter. 3
Interfaces Systems Devices Inv. 1 Inv. 2 Inv. 3 Lac. I CI inverter CI Parts Zif 268, Paveltich & Pabo c. 1991 Endy, MIT BE, 20 May 2004
Parts/Device Interface A Lac. I X Devices Lac. I A CI B inverter B CI X Parts Zif 268, Paveltich & Pabo c. 1991 Endy, MIT BE, 20 May 2004
Device/System Interface Systems Devices Endy, MIT BE, 20 May 2004 Inv. 1 Inv. 2 Inv. 3 A A B inverter B C C D inverter D E E F inverter F
Device/System Interface X Systems Devices Endy, MIT BE, 20 May 2004 X A B E F X C D A A B inverter B C C D inverter D E E F inverter F
Device/System Interface A D Systems X A B E F X C D X Devices Endy, MIT BE, 20 May 2004 A A B inverter B C C D inverter D E E F inverter F
Device/System Interface c. I Lac. I Po. PSin OLac RBS l c. I-857 T Ol Po. PSout c. I Po. PSout Lac. I Endy, MIT BE, 20 May 2004 Po. PSin
Polymerase Per Second = Po. PS! Po. PSOUT Po. PSIN RBS T l c. I Ol c. I Po. PSOUT Po. PSIN INVERTER Po. PSOUT Po. PSIN Endy, MIT BE, 20 May 2004
Device/System Interface A Systems B C X Devices Endy, MIT BE, 20 May 2004 Po. PSIN A Po. PSOUT Po. PSIN B Po. PSOUT Po. PSIN C Po. PSOUT
Interfaces Systems Devices Po. PS Inv. 1 Inv. 2 Inv. 3 Po. PS Inv. 1 Po. PS Parts Zif 268, Paveltich & Pabo c. 1991 Endy, MIT BE, 20 May 2004
E. colibrator, Polkadorks @ IAP 2004 Endy, MIT BE, 20 May 2004
Device-Level System Diagram Endy, MIT BE, 20 May 2004
Parts- and Device-Level System Diagram Endy, MIT BE, 20 May 2004
DNA Layout Endy, MIT BE, 20 May 2004
System-Level Timing Diagram Endy, MIT BE, 20 May 2004
Population-Level Simulations Endy, MIT BE, 20 May 2004
Characterization and Debug Trigger Test Circuit Endy, MIT BE, 20 May 2004
MIT Registry of Standard Biological Parts http: //parts. mit. edu/ Endy, MIT BE, 20 May 2004
DNA Synthesis Bases of DNA Person Day Year Carlson, Pace & Proliferation of Biological Technologies , Biosec. & Bioterror. 1(3): 1 (2003) Endy, MIT BE, 20 May 2004
Hacking the Living World? Endy, MIT BE, 20 May 2004
Biological Risk: Background Technology Classes Relevant to Biological Risk (current relative capabilities) Manipulation Detection Analysis Response Endy, MIT BE, 20 May 2004 Risk
Biological Risk: Tactics as “Strategy” Anthrax vaccine SARS assay Ciprofloxacin VHF therapy (under construction) Plague vaccine (under construction) Endy, MIT BE, 20 May 2004 Smallpox vaccine Maginot Line France, 1940
Biological Risk: Future Strategy Technology Classes Relevant to Future Biological Risk (needed capabilities) Manipulation Detection Risk Analysis Response Endy, MIT BE, 20 May 2004
Biological Risk: Suite of Solutions Number of Individuals Basic Researcher Garage Bio-Hacker Disgruntled Researcher Bin Laden Genetics, Inc. honorable Endy, MIT BE, 20 May 2004 Individual’s Intent dishonorable
A Constructive Society Endy, MIT BE, 20 May 2004
D 2 L Sph. I D 1 L Bst. EII D 1 R D 3 L D 4 L Bsp. DI Hind. III D 5 L D 6 L Bss. HII Sex. AI D 2 R D 3 R D 4 R D 5 R D 7 L Mlu. I D 6 R TR/ SRL 63 35 A 0 88 370 316 øOL A 1 A 2 Box. A D 22 L Bst. EII D 9 R D 10 L Eag. I D 9. 5 R 355 1102 0. 6 A/B 0. 7 D 24 L D 25 L D 23 R Eco. RI D 24 R Xma. I D 10. 5 L Pac. I D 11 L Eco. RI D 10 R Nsi. I Pci. I 158 0. 4 R 0. 5 D 23 L Avr. II D 22 R 52 D 9. 5 L Sac. II D 8 R Nhe. I 183 R 0. 3 D 9 L Rsr. II D 7 R Sac. I 210 D 8 L Bsi. WI D 12 L Pfo. I D 10. 5 R D 11 R D 12 R Mfe. I 91 C 1 D 26 L D 25 R Bam. HI D 15 L Apa. I D 16 L Nco. I D 13 R D 14 R D 15 R 139 ø 1. 1 A R 1. 1 D 27 L D 26 R Eag. I 148 80 1099 65 ø 1. 1 B ø 1. 3 1. 2 R 1. 3 D 28 L D 27 R Sac. II D 18 L Avr. II D 29 L D 28 R Pci. I D 19 R D 20 R 35 279 D 21 R Sap. I 173 1. 3 TE D 20 L D 21 L Xba. I Age. I D 19 L Aat. II D 18 R Spe. I 275 1. 1 D 17 L Kas. I D 16 R D 17 R Apa. LI 2708 R 1 D 13 L D 14 L Eco. O 1091 Xma. I ø 1. 5 1. 4 Bcl. I 110 35 1. 5 D 30 L D 29 R Sal. I ø 1. 6 164 443 1. 6 1. 7 D 30 R Bgl. II 175 209 1. 8 D 31 L Bsi. WI D 31 R Xba. I 35 Ø 4 c D 50 L Bsi. WI ø 2. 5 2 723 438 464 2. 5 2. 8 478 3 75 ø 3. 8 3. 5 D 32 L D 33 L D 34 L D 35 L D 36 L D 37 L D 38 L D 39 L D 40 L D 41 L D 42 L D 43 L D 44 L Eag. ID 32 R Asc. ID 33 R Sgr. ID 34 R Hind. III D 35 R Pfo. I D 36 R Nhe. I Sph. I Nco. I Bam. HI Sac. IID 41 R Apa. I Xma. I Sac. I D 37 R D 38 R D 39 R D 40 R D 42 R D 43 R Aau. I Bgl. I Eci. I Sca. I Ava. I Spe. I 1762 4 A/4 B/4. 1/4. 2 35 Ø 4. 3 213 270 4. 3 4. 5 R 4. 7 D 51 L D 52 L D 50 R Pvu. I D 51 R Eco. RI Dra. I Bsp. HI 69 Ø 4. 7 D 53 L D 52 R Sac. II D 53 R Nsi. I 408 Rsr. II Ase. I 2115 4. 7 D 54 L Bam. HI Xba. I 5 357 464 478 464 5. 3 5. 5 5. 7 5. 9 D 55 L Fsp. I D 54 R Xma. I D 56 L D 55 R Apa. I Bss. HII 903 114 Aat. II 3. 8 D 45 L D 46 L D 47 L D 48 L D 49 L Eco. RI Pvu. I Rsr. II Pst. I D 44 R Xho. I D 45 R D 46 R D 47 R D 48 R Aat. I Xca. I Nsi. I 73 Ø 6. 5 D 57 R 75 R 3. 8 6. 3 R 6. 5 6 D 57 L D 56 R Hind. III Eci. I 306 255 267 6. 5 6. 7 D 57 L Hind. III 402 7 D 58 L D 57 R Pfo. I Ava. I Pac. I 300 D 58 R D 49 R Bst. EII 223 172 7. 7 7. 3 D 59 L Avr. II Eco. RI Pac. I Nde. I 1611 35 ø 9 8 D 60 L D 61 L D 59 R Bsi. WI D 60 R Pvu. I 14 Ava. I 2244 15 Endy, MIT BE, 20 May 2004 35 D 63 L D 62 RSac. II D 63 R Sca. I Bst. BI Apa. LI 3520 16 437 464 ø 10 9 D 62 L D 61 R Eag. I Nci. I 591 1038 10 A D 64 L Hind. III ø 17 591 Tø 1662 17 Kas. I Bgl. I 2382 D 67 L D 68 L D 66 R Apa. I D 67 R Eco. RI Blp. I 204 17. 5 270 18 2382 53 460 E 3 12 D 69 L D 68 R Bsi. WI Bsp. DI R 18. 5 3 12 11 D 65 L D 66 L D 64 R Bam. HI D 65 R Xma. I Fsp. I 35 73 D 70 L D 69 R Pst. I Dra. III Acv. I 62 R 13 417 ø 13 D 71 L D 70 R Sal. I 13 D 71 R Aci. I 1761 18. 5/18. 7 19/19. 2/19. 3 Kpn. I 35 øOR 150 19. 5 160 SRR/TR
Kuroda-Kawaguchi et al. , Nature Genetics 29: 279 (2001) Endy, MIT BE, 20 May 2004
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) Endy, MIT BE, 20 May 2004
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