drew endy endy@mit mit/endy/www/talks/ file here []

1Endy, MIT April 2005

Drew [email protected]

http://mit.edu/endy/www/talks/ file here [.ppt]

http://parts.mit.edu/ Registry of Standard Biological Parts

April 11, 2005MIT

Policy Opportunities Related to the Engineering of Biology


Previous Page

Sequence (BNL)

Dunn & Studier, J. Mol. Bio. 166:477 (1983)


Wild-Type T7 Genes 2.8-3

----------------2.8----------------->acgcaaagggaggcgacatggcaggttacggcgctaaaggaatccgaaa <--3-RBS---><----------------3--------------


Wild-Type T7 Genes 2.8-3

----------------2.8----------------->acgcaaagggaggcgacatggcaggttacggcgctaaaggaatccgaaa <--3-RBS---><----------------3--------------

T7.1 Parts 28 & 29

acgcaaGgggagAcgacaCggcaggttacggcgctaaggatccggccgcaaagggaggcgacatggcaggttacggcgctaaa----------------2.8-----------------><D28R|D29L><--3RBS------><---------------3----


A0TR/SRL

øOL A1 A2 R0.3BoxA 0.30.4 0.5R0.5 0.6A/B 0.7CR1 1

ø1.1A ø1.1BR1.1 1.11.2

ø1.3R1.3 1.3 TE 1.4 1.5 1.61.7ø1.5 ø1.6A2

NsiI PciI MfeI SpeI BclI

B


A0

63

TR/SRL

øOL

35

A1

88

A2

316

R0.3BoxA 0.3

370

0.4

183

0.5

158

R0.5

52

0.6A/B

355

0.7

1102 91

CR1 1

2708 139

ø1.1A ø1.1BR1.1 1.1

148

1.2

275 80

ø1.3R1.3 1.3

1099

TE

65

1.4

173

1.5

110

1.6

279

1.7

164

ø1.5

35

ø1.6

35

A2

210 443

NsiI PciI MfeI SpeI BclI


SacI

D1L BstEII

D1R

A0

D2L SphI

63

TR/SRL

D2R

øOL

D3L BspDI

35

D3R

A1

D4L HindIII

88

D4R

A2

D5L BssHII

316

R0.3BoxA

D6L SexAI

D5R

0.3

370

D7L MluI

D6R

0.4

183

D8L BsiWI

D7R

0.5

158

R0.5

52

D9L RsrII

D8R

0.6A/B

355

D9.5L SacII

D9R

0.7

1102

D10L EagI

D9.5R

91

CR1

D10.5L PacI

D10R

1

2708

D11L EcoRI

D10.5R

139

ø1.1A ø1.1BR1.1

D12L PfoI

D11R

1.1

148

D13L EcoO1091

D12R

1.2

275

D14L XmaI

D13R

80

ø1.3R1.3

D15L ApaI

D14R

1.3

1099

D16L NcoI

D15R

TE

65

D17L KasI

D16R

1.4

173

D19L AatII

D18R

1.5

110

D21L AgeI

D20R

1.6

279

D21R

1.7

164

D17R

ø1.5

D18L AvrII

35

D19R

ø1.6

D20L XbaI

35

A2

210 443

NheI NsiI PciI MfeI ApaLI SpeI SapI BclI


SacI

D1L BstEII

D1R

A0

D2L SphI

63

TR/SRL

D2R

øOL

D3L BspDI

35

D3R

A1

D4L HindIII

88

D4R

A2

D5L BssHII

316

R0.3BoxA

D6L SexAI

D5R

0.3

370

D7L MluI

D6R

0.4

183

D8L BsiWI

D7R

0.5

158

R0.5

52

D9L RsrII

D8R

0.6A/B

355

D9.5L SacII

D9R

0.7

1102

D10L EagI

D9.5R

91

CR1

D10.5L PacI

D10R

1

2708

D11L EcoRI

D10.5R

139

ø1.1A ø1.1BR1.1

D12L PfoI

D11R

1.1

148

D13L EcoO1091

D12R

1.2

275

D14L XmaI

D13R

80

ø1.3R1.3

D15L ApaI

D14R

1.3

1099

D16L NcoI

D15R

TE

65

D17L KasI

D16R

1.4

173

D19L AatII

D18R

1.5

110

D21L AgeI

D20R

1.6

279

D21R

1.7

164

D17R

ø1.5

D18L AvrII

35

D19R

ø1.6

D20L XbaI

35

A2

210 443

NheI NsiI PciI MfeI ApaLI SpeI SapI BclI

D23L AvrII

D24L EcoRI

D26L BamHI

D27L EagI

D28L SacII

D30L SalI

D22L BstEII D22R D23R D24R D26R D27R D28R D30R

ø2.5 32.8ø3.8

3.5 3.8R3.8

D25L XmaI D25R

2.5

D29L PciI D29R

1.8 2

BglII

175 209 35 723 438 464 478 75 306 75

D32L EagI

D33L AscI

D35L HindIII

D36L PfoI

D37L NheI

D43L XmaI

D31L BsiWI D31R D32R D33R D35R D36R

D40R

4.7 5.7

D34L SgrID34R

4.5

D41L SacII

D42R

4A/4B/4.1/4.2 4.3

1762 35 213 270 69 408 478 903 73

Ø4c Ø4.3 Ø4.7R4.7

D38L SphI

D37R

5

2115

D39L NcoI

D38R

5.3

357

D40L BamHI

D39R

5.5

464

D42L ApaID41R

5.9

464

6

D44L SacI

D43R

114

6.3Ø6.5

R6.5

D45L XhoID44R

D46L EcoRI

D45R

255

6.5

D47L PvuI

D46R

267

6.7

D48L RsrII

D47R

402

7

D49L PstI

D48R

300

7.3

D49R

7.7

223 172

BstEIIXbaI AauI BglI EciI ScaIAvaI SpeI AatI XcaI NsiI

FspI AvrIID50L BsiWI

D51L PvuI

D53L SacII

D54L BamHI

D55L XmaI

D57L HindIIID50R D51R D53R D54R D55R D57R

ø9 10A Tø 12

D52L EcoRI D52R

9

D56L ApaI D56R

8

PacI

1611 35 1038 35 464 73 591 2382 3

ø10 11

DraI RsrIIXbaI

BssHII AatII AvaIBspHI EciINsiI

NdeI

AseI

D57L HindIII

D59L EcoRI

D58L PfoID57R D58R

12 13

PacI

2382 62 4173

ø13R13

D60L BsiWI

D62L EagID59R D60R D62R

16

D61L PvuI D61R

15

ApaLI

591 2244 3520 437

14

NciIScaI

BstBIAvaI

D64L HindIII

D65L BamHI

D67L ApaI

D68L EcoRI

D69L BsiWI

D71L SalI

D63L SacII D63R D64R D65R D67R D68R D69R D71R

ø17 18.5/18.718E

19/19.2/19.3 19.5R18.5

D66L XmaI D66R

17.5

D70L PstI D70R

17

35 1662 204 270 53 460 1761 35 150

øOR SRR/TR

160

KasI BspDIFspIBglI

BlpI DraIII AcvI AciI KpnI


Section alpha Section beta

(1 8,311 bp) (8,311 12,179 bp)


Wild-Type T7 (T7+) Refactor[1-12,179]:T7+


Kuroda-Kawaguchi et al., Nature Genetics 29:279 (2001)


Nature & Change

- Pre-existing- Immutable- Changing- Evolution

Human & Engineer

- Pre-existing- Immutable- Changing- Evolution- Rational design- New- Decoupled

[e.g., disposable]

Nature & Form

- Pre-existing- Immutable


Carlson, Pace & Proliferation of Biological Technologies, Biosec. & Bioterror. 1(3):1 (2003)


Goto PartsGoto NCBI. Goto BH Goto Cinnagen


• 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


Biological Risk

(1) Past and ongoing work- Breeding- Animal release- Recombinant DNA technology

(2) Liberal democracy in context of living world


Risk

Biological Risk: Background

Technology Classes Relevant to Biological Risk

(current relative capabilities)

Manipulation

Analysis

Response

Detection


Risk




Analysis

Response

Detection

Manipulation


Biological Risk: Tactics as “Strategy”

Maginot LineFrance, 1940

Ciprofloxacin

Smallpox vaccine

Anthrax vaccine

SARS assay

VHF therapy(under construction)

Plague vaccine(under construction)


Risk




Analysis

Response

Detection

Manipulation


Biological Risk: Future Strategy

Risk

Technology Classes Relevant to Future Biological Risk

(needed capabilities)

Detection

Analysis

Response

Manipulation


Biological Risk: Suite of Solutions

Nu

mb

er

of

Ind

ivid

uals

Individual’s Intenthonorable dishonorable

Bin Laden Genetics, Inc.

DisgruntledResearcher

Garage Bio-

Hacker

BasicResearch

er


Biological Risk: Hack the Living World?


From: XXXXSubject: Endy LetterDate: January 6, 2005 9:45:17 AM ESTTo: [email protected]

Dr. Endy,

I am a sophomore at XXXXX High School in Connecticut and have recently taken an interest in Synthetic Biology.I am writing to ask for your help because i am having difficulty in obtaining information,and understanding some of the information i already have. Anything you can send my way would be greatly appreciated…

…I will soon begin working on a proposal to create a BioBrick, any information you can send me on their creation would be excellent.

-Sincerely, XXXX XXXX XXXX High School -Grade 10


A Constructive Society


UT SB Competition Team

c/o Jeff Tabor


Photons

PoPS

Light PoPSReceiver

PoPS ColorConverter

BBa_I15010BBa_R0082

BBa_B0034BBa_E0033BBa_B0015


c/o Jeff Tabor


Lens ripped off of overhead projector

Casserole dishPile of cells/agar

Thermostable chassis


c/o Jeff Tabor



c/o Jeff Tabor


2003 - MIT IAP (Blinkers)2004 - MIT IAP (Polkadots)2004 - BU, Caltech, MIT, Princeton, UT Austin (FSMs)2005 - Intercollegiate Genetically Engineered Machine (iGEM) Competition

CaltechDavidsonHarvardMITTorontoUCSF/SFSUUT Austin

2006 - Intercollegiate Genetically Engineering Machine (iGEM) Competition

iGEM 2005, 2006, …

OklahomaPrincetonCambridgeETH ZurichPenn StateUC Berkeley


• Technology Opportunities – General Infrastructure Supporting the Engineering of Biology

• Built from early days with foresight– Detection, Analysis, Response

• Students running a bio-detector on the corner of Ames & Main

• Education Opportunities

– Undergraduate Program in Biological Engineering– Code of Ethics & Standards of Practice for Biological Engineers

• Would likely need to be backstopped by a professional society(s)

• Policy Opportunities– Coherent (?!) organization of federal funding– Integration of research and policy– Broad societal acceptance of responsibility for manipulating genetic

information– International transparency?– Transition from “threat specific” to “capabilities-based” strategy– Distribution of technology? Open or closed?


Acknowledgements

I would like to acknowledge Adam Arkin, Frances Arnold, Ralph Baric, Roger Brent, Jehoshua Bruck, Carlos Bustamante, Barry Canton, Rob Carlson, Leon Chan, Austin Che, Jim Collins, Lynn Conway, Ron Davis, Mita Desai, John Doyle, Eric Eisenstadt, Michael Elowitz, Stephanie Forrest, Timothy Gardner, Seth Goldstein, Homme Hellinga, George Homsy, Joe Jacobsen, Tom Kalil, Jay Keasling, Heather Keller, Doug Kirkpatrick, Tom Knight, Sri Kosuri, Patrick Lincoln, John Mulligan, Richard Murray, Radhika Nagpal, Richard Newton, Carl Pabo, Randy Rettberg, Pamela Silver, Brad Smith, Christina Smolke, Gerry Sussman, Samantha Sutton, Claire Tomlin, Jeffrey Way, Chris Webb, Ron Weiss, Scot Wolfe, Aarne Vesilind, other members of the lab and the MIT Synthetic Biology Working Group, and the students and instructors of the 2003/4 MIT IAP Synthetic Biology Labs and the 2004 Synthetic Biology Competition for their direct contributions to the material presented here and to my current thinking about how to best engineer biology.

drew endy endy@mit mit/endy/www/talks/ file here []

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