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Policy Opportunities Related to the
Engineering of Biology
Drew Endy
endy@mit.edu
http://mit.edu/endy/www/talks/  file here [.ppt]
http://parts.mit.edu/  Registry of Standard Biological Parts
April 11, 2005
MIT
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Previous Page
Sequence (BNL)
Dunn & Studier,
J. Mol. Bio. 166:477
(1983)
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Wild-Type T7 Genes 2.8-3
----------------2.8----------------->
acgcaaagggaggcgacatggcaggttacggcgctaaaggaatccgaaa
<--3-RBS---><----------------3--------------
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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----
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NsiI
TR/
SRL
A0
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øOL A1 A2 A2 BoxA
B
R0.30.30.4R0.5 0.5 0.6A/B
PciI
C
0.7 R1
MfeI
1
SpeI
ø1.1A
R1.1
ø1.1B
ø1.3
1.1 1.2 R1.3
BclI
ø1.6
ø1.5
1.3 TE 1.4
1.5
1.61.7
7
NsiI
210
TR/
SRL
63
A0
35
88
316
øOL A1 A2 A2 BoxA
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370
R0.3 0.3
183
52
158
0.4 R0.5 0.5
355
0.6A/B
PciI
1102
0.7
MfeI
91
C
R1
SpeI
2708
1
139
ø1.1A
R1.1
148
ø1.1B
1.1
275
80
ø1.3
1.2 R1.3
1099
65
1.3 TE
173
1.4
BclI
35
ø1.5
110
1.5
35
ø1.6
279
1.6
164 443
1.7
8
D1L
BstEII
D1R
D2L
SphI
D3L D4L
BspDI HindIII
D2R
D3R
35
88
D5L
D6L
BssHII SexAI
D4R
D5R
D7L
MluI
D6R
D7R
SacI
210
TR/
SRL
63
A0
316
øOL A1 A2 A2 BoxA
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370
R0.3 0.3
183
D8L
BsiWI
D9L
RsrII
D8R
NheI
52
158
0.4 R0.5 0.5
D9.5L
SacII
D9R
D10L
EagI
D9.5R
NsiI PciI
355
0.6A/B
1102
0.7
D10.5L
PacI
D11L
EcoRI
D10R
D12L
PfoI
D10.5R D11R
MfeI
91
C
R1
D12R
D15L
ApaI
D13R
D14R
D15R
80
1099
65
ApaLI
2708
1
D13L
D14L
EcoO1091 XmaI
139
ø1.1A
R1.1
148
ø1.1B
1.1
275
D16L
NcoI
D17L
KasI
D18L
AvrII
D16R D17R
SpeI
ø1.3
1.2 R1.3
1.3 TE
173
1.4
D20L D21L
XbaI AgeI
D19L
AatII
D18R
D19R
D20R
35
279
SapI
35
ø1.5
110
1.5
D21R
BclI
ø1.6
1.6
164 443
1.7
9
D2L
SphI
D1L
BstEII
D1R
D3L D4L
BspDI HindIII
D2R
D3R
35
88
D5L
D6L
BssHII SexAI
D4R
D5R
D7L
MluI
D6R
TR/
SRL
63
A0
370
316
øOL A1 A2 A2 BoxA
D9R
D10L
EagI
D9.5R
355
1102
0.6A/B
0.7
D24L
D25L
D23R EcoRI D24R XmaI
D10.5L
PacI
D11L
EcoRI
D10R
NsiI PciI
158
0.4 R0.5 0.5
D23L
D22R AvrII
D22L
BstEII
52
D9.5L
SacII
D8R
NheI
183
R0.3 0.3
D9L
RsrII
D7R
SacI
210
D8L
BsiWI
D12L
PfoI
D10.5R D11R
D12R
MfeI
91
C
1
D26L
D25R BamHI
D15L
ApaI
D16L
NcoI
D13R
D14R
D15R
139
ø1.1A
R1.1
D27L
D26R EagI
148
80
1099
65
ø1.1B
ø1.3
1.2 R1.3
D28L
D27R SacII
D18L
AvrII
D29L
D28R PciI
D19R
D20R
35
279
D21R
SapI
173
1.3 TE
D20L D21L
XbaI AgeI
D19L
AatII
D18R
SpeI
275
1.1
D17L
KasI
D16R D17R
ApaLI
2708
R1
D13L
D14L
EcoO1091 XmaI
ø1.5
1.4
BclI
110
35
1.5
D30L
D29R SalI
ø1.6
164 443
1.6
1.7
D30R
BglII
175
209
1.8
D31L
BsiWI
D31R
XbaI
D50L
BsiWI
438
2.5
2.8
ø2.5
2
35
Ø4c
723
464
478
3
75
ø3.8
3.5
D32L
D33L
D34L
D35L
D36L
D37L
D38L
D39L
D40L
D41L
D42L
D43L
D44L
EagID32R AscID33R SgrID34R HindIII D35R PfoI D36R NheI
SphI
NcoI
BamHI
SacIID41R ApaI
XmaI
SacI
D37R
D38R
D39R
D40R
D42R
D43R
AauI BglI
EciI
ScaI AvaI
SpeI
1762
4A/4B/4.1/4.2
35
Ø4.3
213
270
4.3
4.5
D51L
D52L
D50R PvuI D51R EcoRI
DraI BspHI
69
Ø4.7
R4.7
D53L
D52R SacII D53R
NsiI
408
RsrII
2115
4.7
D54L
BamHI
XbaI
5
357
464
478
464
5.3
5.5
5.7
5.9
D55L
FspI
D54R XmaI
AseI
D56L
D55R ApaI
BssHII
903
114
AatII
3.8
D45L
D46L
D47L
D48L
D49L
EcoRI
PvuI
RsrII
PstI
D44R XhoI
D45R
D46R
D47R
D48R
AatI
XcaI
NsiI
73
Ø6.5
D57R
75
R3.8
6.3 R6.5
6
D57L
D56R HindIII
EciI
306
255
267
6.5
6.7
D57L
HindIII
402
7
BstEII
223
172
7.7
7.3
D59L
AvrII
D58R EcoRI
D58L
D57R PfoI
AvaI PacI
300
D49R
PacI
NdeI
1611
35
ø9
8
D60L
D61L
D59R BsiWI D60R PvuI
14
AvaI
2244
15
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464
ø10
9
D62L
D61R EagI
NciI
591
1038
10A
D64L
D63L
D62RSacII D63R HindIII
ScaI
BstBI
ApaLI
3520
16
437
ø17
591
Tø
1662
17
KasI
BglI
2382
D67L
D68L
D66R ApaI D67R EcoRI
BlpI
204
17.5
270
18
2382
53
460
E
3
12
D69L
D68R BsiWI
BspDI
R18.5
3
12
11
D65L
D66L
D64R BamHI D65R XmaI
FspI
35
73
D70L
D69R PstI
DraIII AcvI
62
R13
417
ø13
D71L
D70R SalI
13
D71R
AciI
1761
18.5/18.7 19/19.2/19.3
KpnI
35
øOR
150
19.5
160
SRR/TR
10
Section alpha
(1  8,311 bp)
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Section beta
(8,311  12,179 bp)
11
Wild-Type T7 (T7+)
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Refactor[1-12,179]:T7+
12
Kuroda-Kawaguchi et al., Nature Genetics 29:279 (2001)
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Nature & Form
- Pre-existing
- Immutable
Nature & Change
- Pre-existing
- Immutable
- Changing
- Evolution
Human & Engineer
- Pre-existing
- Immutable
- Changing
- Evolution
- Rational design
- New
- Decoupled
[e.g., disposable]
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Carlson, Pace & Proliferation of Biological Technologies, Biosec. & Bioterror. 1(3):1 (2003)
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Goto Parts
Goto NCBI.
Goto BH
Goto Cinnagen
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Enabling Biological Engineering
•
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
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Biological Risk
(1) Past and ongoing work
- Breeding
- Animal release
- Recombinant DNA technology
(2) Liberal democracy in context of living world
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Biological Risk: Background
Technology Classes Relevant to Biological Risk
(current relative capabilities)
Manipulation
Detection
Analysis
Risk
Response
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Biological Risk: Background
Technology Classes Relevant to Biological Risk
(current relative capabilities)
Manipulation
Detection
Analysis
Risk
Response
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Biological Risk: Tactics as “Strategy”
Anthrax
vaccine
Maginot Line
France, 1940
SARS assay
Ciprofloxacin
VHF therapy
(under construction)
Plague vaccine
(under construction)
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Smallpox
vaccine
21
Biological Risk: Background
Technology Classes Relevant to Biological Risk
(current relative capabilities)
Manipulation
Detection
Analysis
Risk
Response
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Biological Risk: Future Strategy
Technology Classes Relevant to Future Biological Risk
(needed capabilities)
Manipulation
Detection
Risk
Analysis
Response
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Biological Risk: Suite of Solutions
Number of Individuals
Basic
Researcher
Garage
Bio-Hacker
Disgruntled
Researcher
Bin Laden
Genetics, Inc.
honorable
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Individual’s Intent
dishonorable
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Biological Risk: Hack the Living World?
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From: XXXX
Subject: Endy Letter
Date: January 6, 2005 9:45:17 AM EST
To: endy@mit.edu
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
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A Constructive Society
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A Constructive Society
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UT SB Competition Team
c/o Jeff Tabor
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UT SB Competition Team
Photons
BBa_I15010
Light
 PoPS
BBa_R0082
Receiver
PoPS
BBa_B0034
PoPS
 Color
BBa_E0033
Converter
BBa_B0015
c/o Jeff Tabor
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UT SB Competition Team
Lens ripped off of overhead projector
Casserole dish
Thermostable chassis
Pile of cells/agar
c/o Jeff Tabor
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UT SB Competition Team
c/o Jeff Tabor
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iGEM 2005, 2006, …
2003 - MIT IAP (Blinkers)
2004 - MIT IAP (Polkadots)
2004 - BU, Caltech, MIT, Princeton, UT Austin (FSMs)
2005 - Intercollegiate Genetically Engineered Machine (iGEM) Competition
Caltech
Davidson
Harvard
MIT
Toronto
UCSF/SFSU
UT Austin
Oklahoma
Princeton
Cambridge
ETH Zurich
Penn State
UC Berkeley
2006 - Intercollegiate Genetically Engineering Machine (iGEM) Competition
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• 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?
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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.
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