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Policy Brie
international risk governance council
Guidelines for the Appropriate
Risk Governance ofSynthetic Biology
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ATC AirTrafcControl
BWC BiologicalWeaponsConvention
CCS CarbonCaptureandStorage
COP ConferenceoftheParties
CBD ConventiononBiologicalDiversity
DNA Deoxyribonucleicacid
ENMOD EnvironmentalModicationConvention
EPA USEnvironmentalProtectionAgency
EU EuropeanUnion
FAO UNFoodandAgricultureOrganization
FDA USFoodandDrugAdministration
GATT GeneralAgreementonTariffsandTrade
GM Geneticallymodied
GMO Geneticallymodiedorganism
GURTs Geneticuse-restrictiontechnologies
IASB InternationalAssociationforSyntheticBiology
ICGEB InternationalCentreforGeneticEngineeringandBiotechnology
ICT Informationandcommunicationtechnologies
IP Intellectualproperty
IRGC InternationalRiskGovernanceCouncil
LMO Livingmodiedorganism
NIH USNationalInstitutesofHealth
NGO Non-GovernmentalOrganisation
OECD OrganisationforEconomicCo-operationandDevelopment
RNA Ribonucleicacid
SRM SolarRadiationManagement
TRIPS Trade-RelatedAspectsofIntellectualPropertyRights
UN UnitedNations
US UnitedStatesofAmerica
USDA USDepartmentofAgricultureWTO WorldTradeOrganization
InternationalRiskGovernanceCouncil,2010.
ReproductionoforiginalIRGCmaterialisauthorisedprovidedthatIRGCisacknowledged
asthesource.
ISBN978-2-9700672-6-9
Abbreviations used in the text:
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Contents
PreaceExecutive summary
Introduction
1. What is synthetic biology?Box: Genetics and molecular biology
2. Current developments in synthetic biology
2.1 Current and past activities
2.2 Some potential uture applications
3. Risks o synthetic biology
4. Existing policy and regulatory rameworks, and their decits
4.1 Regulatory and governance contexts
4.2 Risk Governance Defcits
5. Risk governance in synthetic biology
5.1 The concept o appropriate risk governance
5.2 Regulation and governance o frst-generation synthetic biology5.3 Policy and regulatory strategies in biosaety and biosecurity related to research,
innovation and technology development
5.4 Intellectual property (IP) issues and maintaining incentives or innovation
5.5 Risk regulation and barriers to innovation
5.6 Local, regional and international perspectives on regulatory oversight and risks
5.7 Technological risk management options
5.8 Policy and regulatory strategies related to public and stakeholder dialogue
6. Guidelines Avoiding uture risk governance decits or synthetic biology
6.1 Guidelines relevant to research and technology development
6.2 Guidelines relevant to public and stakeholder engagement
6.3 Systemic guidelines
Conclusion
Reerences and bibliography
Acknowledgements
About IRGC
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TheInternationalRiskGovernanceCouncil(IRGC)aimstoimprovethegovernanceofemerging,systemicrisksthroughhelpingdecision-makers,particularlygovernments,
toanticipateandunderstandsuchrisksandtheoptionsformanagingthembefore
they become urgent policy priorities. IRGCs risk governance recommendations
are communicated to policymakers to inform their work in designing policies and
regulations,drawingtheirattentiontoaspectsoftheissuethatmightbeinappropriately
neglectedorignored.
IRGCscoreprocessinworkingonsyntheticbiologycomprisedthefollowing:
Analysing the scientic and technological developments and their associated
opportunitiesandrisks,aswellastheinstitutionsandriskgovernancestructures
andprocessesthatarecurrentlyinplaceforassessingandmanagingthese;Identifyingpotentialissuesofconcernattheearliestpossibletime;
Identifyingandunderstandingriskgovernancedecitswhichappeartohinderthe
efcacyoftheexistingriskgovernancestructuresandprocesses;
Developingguidelinesthataddressthesedecits.
ThispolicybriefonsyntheticbiologyispartofIRGCsworkontheriskgovernanceof
innovativetechnologies.PreviousIRGCprojectsonsuchtechnologiesincludeworkon
nanotechnology,carboncaptureandstorage(CCS)andsolarradiationmanagement
(SRM).IRGChasidentiedsyntheticbiologyasanewtechnologyforwhichtheremay
besignicantdecitsinriskgovernancestructuresandprocesses,inpartbecauseof
uncertaintiesaboutthedirectionsthatthetechnologymighttake.
OfparticularconcerntoIRGCisthatimportantsocialandeconomicbenetsofferedby
innovativetechnologiesarenotcompromisedbyinadequateriskgovernance,which
could result in unduly restrictive regulation. Synthetic biology has the potential to
providepotentialsolutionstosomeofthechallengesthattheworldfacesintheelds
ofenvironmentalprotection(e.g.,detectingandremovingcontaminants),health(e.g.,
diagnostics,vaccinesanddrugs)andenergyandindustry(e.g.,biofuels).Atthesame
time,IRGCaims toensure that risksare not underestimatedbythosedeveloping
the eld, and it recognises that some potentially severe risks might demand the
recommendationofnewprecautionarymeasures.
InOctober2009,IRGCorganisedamulti-stakeholderworkshopinGenevaentitled
RiskGovernanceofSynthetic Biology, atwhich manyoftheissues raised inthis
policybriefwerediscussed.Itwasattendedby24participantsfromtheUnitedStates
(US),Canada,ChinaandmanyEuropeancountries,includingexpertsfromacademia,
governments, non-governmental organisations (NGOs) and the private sector. An
IRGC concept note [IRGC,2009b] was published asa brieng document for this
workshop(availableonIRGCswebsite,www.irgc.org.)
Thispolicybriefdoesnotintendtoproposeawideandexhaustivereviewoftheeldof
syntheticbiology,buttoreectandelaborateonthediscussionsattheworkshopand
subsequentriskgovernancedevelopmentsintheeld.Moreover,IRGCrecognises
thatgovernments,industryandothersectorsarealreadyseekingwaystoresolvethe
uncertaintiesassociatedwiththeriskgovernanceofsyntheticbiology.Theaimofthis
policybriefistoprovideguidancetodecision-makerstoachievethisgoal.
Preace
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Executive summary
Synthetic biology is a new scienticdiscipline emerging from the convergence ofbiotechnology,geneticsandadvancesinthesystems-scalefundamentalunderstanding
oflivingorganisms,alongwithaspectsofphysics,chemistryandcomputerscience.Itis
predicatedonanengineeringapproachtobiology:anunderstandingofthemechanisms
bywhichlivingcellsfunction,coupledtotheavailabilityoftoolsforinterveninginand
alteringthesefunctionsatthegeneticlevelorevenforrebuildingsomebiological
entitiesandprocessesfromscratchusingchemicalmethods.Thisismakingitpossible
todesignlifeinmuchthesamewayaswemightdesignanautomobileoranelectronic
circuit.Insteadofrelyingonhaphazardtinkeringorsmall-scalegeneticmodicationto
directlivingsystemstowardsnewobjectives,itmaybecomepossibletoradicallyalter
whatcellsandorganismscanachieveinarational,systematicway.
Thisdisciplineoffersgreatpromiseinareassuchashealthandmedicine,chemical
manufacturingandenergygenerationandconversion.Butthereareattendantrisks,not
justintermsofthesafetyofengineeredorsyntheticorganismsbutalsoinabroader
senseofhowsuchapowerfultechnologicalcapacitymighttransformtheenvironment
and society, affect economic development, and alter existing power relationships
betweenbasicscience,industry,consumers,governments,andnations.
This document develops the concept of appropriate risk governance: one that is
enablingofinnovation,minimisesrisktopeopleandtheenvironment,andbalancestheinterestsandvaluesofallrelevantstakeholders.Itprovidessuggestionsforhow
anappropriate trade-offbetween thesefactorsmightbe attained,andargues that
regulationmustnotsimplyprohibitorrestrictanydevelopmentforwhichpotentialrisks
canbeadducedbutshouldseektherightbalancebetweenpotentialsocialbenets
anddangerseventhoughthesemaybothbeuncertainandspeculativeatthisearly
stageintheeldsevolution.
Someofthenear-termresearchinandapplicationsofsyntheticbiologywillbealready
governedbyexistingregulatoryframeworks.However,thesearenotalwaysmutually
compatible or consistent, and there are some areas of potential conict between
different aims and priorities. Moreover, such frameworks have shortcomings and
loopholeswhenappliedtosomeofthepotentialoutcomesofsyntheticbiologyforexample,safety risks for geneticallymodiedorganisms mightnot bebest judged
fromthebehaviouroftheparentorganism,oncemodicationispursuedatthedeep
systemic level that synthetic biology should enable.The objective here is to seek
waysofaddressingsuch riskgovernancedecits thatallowa voice toall relevant
stakeholdergroups.
Withthisinmind,thepolicybriefoffersaseriesofguidelinesforpolicymakersinvolved
in regulatingorotherwiseguiding oraffectingthe course of syntheticbiology.The
guidelinesaddressfactorsrangingfrombiosecurityrisksinthefundamentalresearch
and development stages, to the questionofhow tobalance transparencyagainst
theneedforcommercialcondentiality.Amongthekeyconsiderationsare thatnew
regulationsshould not repeat the mistakesof existingones,that theyshould take
carenottoforeclosefutureadvancesthatcouldbeofsignicantsocialbenet,and
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thatthereshouldbeaninternationalefforttostandardiseproceduresandregulationswhilerecognisingthatparticularregionsandnationsmayhavespecicrequirements
orvulnerabilities.
Furthermore,aneffectiveapproachtoriskgovernanceofsyntheticbiologymustbe
capableofevolvingasscienticandtechnicalknowledgeexpandsandaslessonsare
learnedaboutthemostappropriateformsofregulationandgovernance:forexample,
ifandhowthetechnologycanregulateitself,andhowintellectual-propertyframeworks
mightbeststimulateinnovationinasustainableway.Thisrequiresexibilityintheface
ofuncertaintyabouttheeventualapplications,products,processes,benetsandrisks,
whilerecognisingthedangersofirreversibleharms.
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Introduction
SyntheticbiologyisoneofarangeofdevelopmentsinscienceandtechnologythatIRGChasidentiedasraisingchallengesforriskgovernance.Buildingondevelopmentsin
thelifesciencesoverthepastseveraldecades,inessenceitinvolvestherepositioning
ofbiologyasanengineeringdiscipline,sothatlivingorganismsbecomeamenable
torationaldesignandsynthesis.Advancesinbiotechnologyandgeneticengineering
inthepastseveraldecadeshavepresagedtheemergence ofthisneweld, but it
nowpromisestotaketheirapproachtoanewlevelinourabilitytoplan,controland
manipulatelivingsystems.
Syntheticbiology represents just one illustrationof how rapidadvancesin the life
sciencesareopeningupahostofpotentiallydramaticnewapplicationsinmedicine
andhealthcare,agriculture,industrialchemistryandenergyproduction,amongother
elds. Thesedevelopments also introduce possible new risks thatarenecessarily
speculativeandhardtoassess.Yetthereisoftenpressurefordecision-makingabout
riskgovernanceandregulationtobeginmanyyearsbeforeactualproductsappearon
themarket.Errorsofjudgementattheseearlystagescanhaveamajorimpactonthe
trajectoryofanewtechnology,aswellasontheeffectivenessandefciencyofrisk
governanceitself[Tait,2007].
Such decisions, taken in a context of high uncertainty, also affect the investment
environmentforinnovativetechnology.Complexregulatorysystemsgiverisetolong
leadtimesfornewproductsandthustotheneedforlong-terminvestmenttosupport
development. But investors are reluctant to commit funding without knowing what
futureregulatorysystemswilllooklikeandthuswhatthelikelycostsofcompliance
willbe.
Thesepressures onpolicy-makers to take early decisionsabout risk governance,
basedonincompleteormerelyspeculativeinformationaboutthescaleoftheactual
risks,makeitdifculttoapplyconventionalriskgovernanceapproaches.Thereisa
needforexibility,includingacapacitytomodifyearlydecisionsinthelightofemerging
evidenceaboutrisksandopportunities.Suchanadaptiveapproachmust,however,
alsoacknowledgetheneedtoidentifyandavoidpotentialirreversibleharms,which
cannotbeamelioratedbylateradjustmentsinpolicy.
Theconceptofriskgovernancethatweadoptheretakesabroadviewofrisk.Itincludes
bothwhathasbeentermedriskmanagementorriskanalysis,aswellasconsidering
howrisk-relateddecision-makingunfoldswhenarangeofactorsisinvolved,requiring
coordinationandpossiblyreconciliationbetweenaprofusionofroles,perspectives,
goalsandactivities[IRGC,2005].Ourgoalistodevelopguidelinesforappropriate
risk governance of innovative technology that integrate in-depth, independent
understanding of threekey areasand their interactions: (i) strategies for scientic
researchandinnovationstrategiesinthepublicandprivatesectors;(ii)regulationand
governanceofnewtechnology;and(iii)theinterestsandperspectivesofthepublic
andotherstakeholders[Wield,2008].Ithaslongbeenunderstoodthatdecisionson
riskregulationaredeterminedbyinteractionsamongthesethreeconstituencies;here
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weaimtoassesstheiroutcomesintermsofsocietalbenetsdeliveredorforegone.Thetargetaudienceforthispolicybriefincludespolicymakers,politicians,companies
andresearcherswith interestsinbiotechnology,energy,health,agriculture,climate,
environment,tradeandsecurity.
Policy-makers and regulators can increasingly be seen as shaping, rather than
responding to, innovative science and technology. They may inuence the future
developmentofthescience,guideproductdevelopmentincertaindirections,andeither
generateordiminishconictbetweenstakeholdergroups.Theguidelinesproposed
herefocusonwhatpolicy-makersandregulatorscanachieveinthiscontext.Whilewe
cannotpredicthowtheeldwillevolve,someregulatoryrethinkingmaybeneededif
syntheticbiologyistogrowintoamature,safeandacceptedsetoftechnologies,with
innovativeandsociallyvaluableproductsbroughttomarket[Rodemeyer,2009].
Section1 ofthispolicybrief outlines the scopeand meaning ofsyntheticbiology,
and Section 2 describes current developments and potential applications. Section
3 considers the associated risks, and Section 4 outlines the existing regulatory
frameworks for handling theseand identies potential risk governance decits. In
Section5weconsidertheissueofappropriateriskgovernanceofsyntheticbiology
and suggest approaches orguidelines for risk assessment and management that
couldenablethepotentialbenetsofsyntheticbiologytobedeliveredwhileavoiding
or minimising associated risks and ensuring proper accountability. Section 6 then
proposesasetofguidelinestosupportpolicydecision-making.Twopreviousconcept
notes[IRGC,2008;2009b],andalsoanIRGCworkshopinvolvingdiverseexpertsin
syntheticbiology,haveprovidedbackgroundmaterial.
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1. What is synthetic biology?
Syntheticbiologyappliestheprinciplesofengineeringtolivingorganisms,regardingthemassystemsthatareamenabletodesignandfabricationforpredictableandclosely
speciedfunctions.Bytailoringthepartsofanorganismthegeneticinstructions,the
moleculesandmolecularassemblies,and theinteractionsbetweendifferentgenes,
moleculesandcellsitaimstocreateorganismsthatfunctionandbehaveinways
quitedifferentfromthenaturalspeciesonwhichtheyarebased.
Throughout the twentieth century, cell biologists have steadily characterised the
molecularcomponentsoflifeinincreasingdetail.Itisapparentthatlifearisesfrom
theinteractionsoftheseparts:genesencodedinDNA,proteinsencodedingenes,as
wellascellularcompartments,ionsandothersubstancesinthecelluid(cytoplasm),
smallRNAmoleculesalsoencodedinthegenome,andothercomponents.Howthose
interactionsareorchestratedremainsoneofthebigquestionsofmolecularbiology,in
particularhowinformationandorganisationaretransmittedthroughoutahierarchyof
sizescalesfromindividualmoleculestothewholeorganism.
At the same time, biologists have sought to intervene in and to modify these
interactions,changinganorganismsfunctionandphysiologytoinuencehuman
health,forexample,ortoalterthepropertiesofagriculturalcrops,ortoconferuseful
technologicalbehavioursonmicro-organisms.Theseeffortshaveresultedinaviewof
lifesmechanismsthatowesastrongdebttoengineering.Theuseoftermssuchas
bioengineeringandgeneticengineeringtestiestothewaytheengineeringparadigm,
whichinvokesprinciplesofdesignandcontrol,hasalreadyimposeditselfonthelife
sciences.Nonetheless,onthewholeourinterventionsinbiologyhavetendedtobe
directedtowardseithercrudesabotageoftheprocessesoflifepreventingmicro-
organismsorcancercellsfromproliferating,say orminor,adhocmodicationsof
existingbehavioursinwhichmuchofthemechanicsremainsablackbox.
Syntheticbiologynowaimstousetheengineeringparadigmformuchmoredramatic
andsystematicinterventioninbiology:toapplyingbasicdesignprinciplesinorderto
producepredictableandrobustbiologicalsystemswithnovelfunctionsandproperties
that do not exist in nature. It has been described as the engineers approach to
biology[Breithaupt,2006]andsomesyntheticbiologistsclaimthattheiraspirationistomakebiologyintoanengineeringdiscipline[Endy,2005;ArkinandFletcher,2006],
somethingthatrequiresareductionistunderstandingofbiologicalcomplexity[Pleiss,
2006].Thisengineeringapproachtobiology,combinedwithsyntheticbiologysheavy
reliance on information technologies, makes the eld intrinsically interdisciplinary.
Althoughsomeresearchersapproachsyntheticbiologyasadiscoveryscienceatool
forinvestigatinghownatureworksitisultimatelylikelytobecomeamanufacturing
technology,offeringnewsyntheticroutestosuchthingsasmedicines,newmaterials
andfuels,environmentalorphysiologicalsensors,andmicro-organismsthatcleanup
pollutants.
Severalofthefundamentalscienticissuesandcurrentappliedobjectivesofsynthetic
biologyoverlapwiththoseinother,morematureelds,especially biotechnology and
Synthetic biologyaims to apply basicdesign principlesin order to produce
predictable and
robust biologicalsystems with novelunctions andproperties that donot exist in nature
It is ultimatelylikely to becomea manuacturingtechnology, oeringnew synthetic routesto such things as
medicines, newmaterials and uels
Atypicalanimalcellwithits
specialisedcompartments
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systems biology.Traditionally,biotechnology involves themanipulationofbiologicalmolecules, cells orwhole organisms to address technological challenges. But the
degreeofmodicationinvolvedhastendedtobesmallandoftenbasedonastrongly
empiricalapproachthatdoesnotredesignanorganismorcomponentatadeeplevel.
Forexample,therearenowwelldevelopedwaystointroducegenesfromonespecies
intothegenomesofanotherandtostimulatetheexpressionofthoseforeigngenesto
produceanexcessoftheproteinproduct.Butwhenanaturallysynthesisedcompound
involvesthecoordinatedactionofmanygenes,thesetechniquesstruggletoachieve
therequiredcoordinationintimeandspace,inpartbecausetheinteractionsofgenes
arepoorlyunderstood.Thislimitsthescopeofwhatbiotechnologycando.
Itishopedthatmuchoftheunderstandingneededformoredramaticinterventionsand
redesignofbiologicalsystemswillcomefromthedisciplineofsystemsbiology[Ideker,
2004;Kitano,2002].Thisinvolvesthemappingofpathwaysandnetworksofinteraction
betweengenes,proteinsandotherbiomolecularcomponents,soas toascertainthe
logiccircuitryofnaturalorganismsatthelevelofcellsandsub-cellularcompartments,
tissuesandthewholeorganism.Whilecellandmolecularbiologyandgeneticshave
beenlargelyconcernedsofarwithstudyingindividualcomponentsandsmallgroupsof
theminisolation,systemsbiologyaimstodiscoverhowtheyallttogetherinarobust,
functionalsystem.Assuch,itshouldprovidetheanalyticalframeworkinwhichsynthetic
biologywilloperate.Simulationtoolsandmodelsdevelopedinsystemsbiologywillbe
usedinsyntheticbiologytodesignandengineernovelcircuitsorcomponents[Barrett
etal.,2006].Inthisrespect,syntheticbiologywillinvolveusingsystemsbiologynotfor
pureunderstandingofnaturalsystemsbutforpracticaldesignofsemi-synthetic,and
ultimatelyperhapswhollysynthetic,ones.
Itisimportanttoemphasisethat,asiscommonforanemergingtechnology,there
isno consensus aboutwhere the boundariesofsynthetic biology lie orwhat form
itmightmostproductivelytake.Itmay(andatpresent,generallydoes)involvethe
useandmodicationofexistingorganisms;butthede novodesignandsynthesisof
organismsisalsoagoalofsomeresearchers.Itiswidelybelievedthatthedesign
elementshouldinvolvetheuseofstandardisedpartsandfollowaformaliseddesign
process [ArkinandFletcher,2006]that takesit beyond thecapabilitiesofpreviousformsofgeneticengineering.Greatersophisticationandcomplexitymighttherebybe
achieved,offeringtheabilitytomovefrominsertingonegeneatatimeintoanexisting
biologicalsystemtotheconstructionandinsertionofwholespecialisedmetabolicunits
[Stone,2006].Syntheticbiologyisnotrestrictedtousinggeneticorotherbiological
materialfromexistingorganisms[POST,2008],andinvolvestinkeringwiththewhole
systeminsteadofindividualcomponents[Breithaupt,2006:22].
Despitethediversityanduiddenitionsofsyntheticbiology,fourinter-relatedresearch
areascanbeidentiedthatcurrentlycontributeitsmajorthemes:
Electronicdevicesaredesignedtoperforminawell-denedwaywheninserted1.intoanycircuit.Itiswidelythoughtthatthegenecircuitcomponentsofsynthetic
Synthetic biologyinvolves tinkering
with the wholesystem instead
o individualcomponents
There is noconsensus
about where theboundaries o
synthetic biologylie or what orm
it might mostproductively take
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biology,whichmightforexampleturnothergenesonandofforotherwisemodulatetheiractivity,willhavetobesimilarlystandardisedandreliable,sothattheycan
besimplypluggedintocircuitsandperformpredictably.Theengineeringprinciples
ofstandardisation,decouplingandabstraction[Endy,2005]maybeadoptedto
develop biological components that are interchangeable, functionally discrete
andcapableofbeingeasilyandreliablycombinedinamodularfashiontoenable
predictableperformanceinawidevarietyoforganisms.
Genome-drivencellengineeringfocusseson thedesignandsynthesisofwhole2.
genomes something that has been made possibleby advances inchemical
technology that will rapidly synthesise long stretches ofDNA with a specied
sequence(thelinearorder of thebasicchemicalunits,whichencodesgeneticinformation). DNA synthesis is now a commercial technology and offers DNA
sequences approaching the length of entire bacterial genomes.To use these
constructsforsyntheticbiologyinvolveseithereditingthegenomicsequences
ofexistinggenomestomakeamorestreamlinedandefcientgeneticchassis,
whichcouldprovideaplatformformakingorganismswithnewgenomes[Gibson
etal.,2010],or(moreambitiously)thewhollydenovodesignandsynthesisof
genomes.
Thechemicalcreationofprotocellswithlifelikefunctionssuchasreplicationand3.
metabolism,forexamplebyinsertingnaturalormodiedbiomolecularcomponents
intoarticial,hollow,cell-likesacscalledvesicles[Szostaketal.,2001].
Morerevolutionaryresearchapproachesincludeattemptstocreateanalternative4.
genetic alphabetwith new nucleotidesbeyond the four found innatural DNA.
This could lead to pseudo-biomolecules or even synthetic proto-organisms
thatare invisible tonaturalbiologicalsystems,as wellas suggestingways of
commandeeringnaturalcellularmachinerytomakesubstanceswithachemical
basisdifferentfromthosefoundinnature.
Someoftheseareasareexplainedinmoredetailinthenextsection.
Box: Genetics and molecular biology
InthetraditionalpictureofgeneticsdevelopedsincethediscoveryofDNAs
chemical structure in 1953, the double-helical molecule of DNA encodes
in its sequence of chemical building blocks (called nucleotide bases) the
informationneededtoconstructaproteinmoleculefromaminoacids.Mostof
theseproteinsareenzymesthatenablebiochemicalprocessesinthecellto
takeplace.Eachproteinisencodedbyaseparategene,andthenucleotide
sequenceofageneonDNAistranslated(expressed)bycellularmolecular
machineryintoasequenceofaminoacidsthatdeterminesthecorresponding
proteinsshapeandfunction(Figure1).ThusDNAwasseenasarepositoryof
encodedproteinstructures.
DNAdoublehelix
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While this basic picture still holds, it
is now complicated in many ways.
Most importantly, the interaction of
genesandproteinsistwo-way:some
proteinswillattach themselves(bind)
to DNA to regulate the way other
genesareexpressed(turningagene
onoroff,say),sothatineffectgenes
caninuenceothergenes.Thiscross-
talk between genes means that theyare linked into a complex network of
interactions,leadingsomeresearchers
todescribegeneticsusingmetaphors
such as a society of genes, rather
thanthetraditionalpictureofabook
ofinformation(Figure2).Tracing
these interactionnetworks ineffect,deducingthe wiring diagram of the
cellsgeneticcircuitry(Figure3)isakeyaimofsystemsbiology,andthis
informationisessentialifwearetodesignnewgenenetworkswithspecic
functions,whichcanbeinsertedintogenomesusingthecuttingandsplicing
toolsofbiotechnology.
Figure 1:Thetraditionalpictureof
genetics:howgeneticinformation
ofDNAisconverted,viaRNA,into
proteinstructureswithawell-dened
shapeandfunction.
Figure 2:Partofthenetworkofgenesrelatedtothefunctionofaproteincalled
DISC1,whichplaysavarietyofrolesinthefunctioningofcells.Mostgenesand
theircorrespondingproteinsareembeddedinnetworksofinteractionlikethis
one.[Copyright:2009Hennah,Porteous;originalsource:http://www.plosone.
org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004906]
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Figure 3:ThegenenetworkthatregulatesthebehaviourofTcells,involvedin
theimmuneresponse.Thefeedbacksandinteractionsareanalogoustothosein
computerlogiccircuits[FromGeorgescuetal.,2008;Copyright(2008)National
AcademyofSciences,USA]
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Parallelshavebeendrawnbetweentodayssyntheticbiologyandtheearlydaysofthecomputerindustry.Ontheonehand,thisimpliesthatthetechnologicalrevolution
broughtbysyntheticbiologywillbeasimportantastherevolutionininformationand
communication technologies (ICT)brought aboutby electrical engineering [NEST,
2005;NEST, 2007;RoyalSociety, 2008]. On the otherhand, it suggests that the
preciseformandcontentofthatrevolutionisashardtopredictatthismomentasit
wasforICTinthe1970s.
Becauseofthefundamentalchangethatitproposestointroduceinthemethodology
for modifying living organisms, synthetic biology may beable to fullmany of the
promises that traditional biotechnology is still struggling to full,in such important
areasasbiomedicine,thesynthesisofpharmaceuticals,thesustainableproduction
of chemicals and energy, and safeguarding against bioterrorism. While traditional
biotechnologyhashadsomenotableachievementsinseveraloftheseareas,they
havegenerallybeenslowand expensiveto develop. Incontrast,syntheticbiology,
withits rational,knowledge-basedapproachto biologicaldesign,mightattainsuch
goalsmorequicklyandcheaply.Itwillalsoenabledevelopmentsthatarenotobviously
feasiblewithconventionalbiotechnologicaltools,suchasthecoordinationofcomplex
sequences of enzymatic processes in the cell-based synthesis of useful organic
compounds.Thus,whilerst-generationsyntheticbiologyis likely tosimplyenable
straightforwardextensionsofwhattodaysbiotechnologycanachieve,ultimatelyits
goalsanditscapabilitieswillnotbemereextrapolationsofthissortbutmaydifferin
qualitativeways, probablybringingaboutapplications thatwe cannot yetenvisage
[IRGC,2008].Examplesofsomeofthecurrentachievementsandprojectedaimsare
detailedbelow[seealsoNEST,2005].
2.1 Current and past activities
2.1.1 Synthetic gene circuits
Mostofthekeyearlyworkinsyntheticbiologyinvolveddevisingsimplesyntheticgene
circuitsandusingthetechniquesofbiotechnologytoinsertthemintobacterialgenomes
and look for the correspondingchanges inthe behaviour ofthe cells[Elowitzand
Leibler,2000;Gardneretal.,2000;Weiss,2004].Manyofthesecircuitswereinspired
bythoseusedinelectronicengineeringforthelogicoperationsofcomputation:for
example,switchestoturnothergenesonoroff,oroscillatorsthatinduceregularbursts
oftheproductionofcertainproteins.Inoneinstance,oscillationsinthesynthesisofa
uorescentproteinproducedbybacterialcellscausethemtoashwithasteadypulse
whenilluminatedwithultravioletlight[ElowitzandLeibler,2000].
Aswellasdemonstratingaproofofprinciplethefeasibilityofdesigninggenecircuits
thatcancontrolcellbiochemistryinpre-determinedwaystheseeffortsmighthave
genuine technological and biological applications. They mightenable genes tobe
activatedandreactivatedatwill,orinresponsetooutsidesignals.Theycanbeused
totesttheoriesofhowinformationprocessingworksinnaturalcells forexample,
Parallels have beendrawn between
todays synthetic
biology and the earlydays o the computer
industry
Synthetic biology
may be able toull many othe promises
that traditionalbiotechnology is still
struggling to ull
Greenuorescentproteinexpressedinthecellsofaleaf
[FromSantaCruzetal.,1996);
Copyright(1996)NationalAcademy
ofSciences,USA
2. Current developments in synthetic biology
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howthedetectionofparticularchemicalsignalsatthecellsurfacetriggersachangeincellbehaviour.Logic-processingoperationsincellsmightalsobeusedtodevelopnew
kindsofbiologicalsensorsthatsignalthepresenceofpollutantsorbiomoleculesinthe
environmentorthebody,andtoenablebacteriatocommunicatewithoneanotherin
newways[Butleretal.,2004].Theengineeringoflogicgatesinmammaliancellsmight
signicantlyextendtherealmofsyntheticbiologytomedicalapplications.
To develop these capabilities in a systematic way analogous to the evolution of
microelectronic circuitry, it seems fruitful to learn the lessons of the electronics
industry:tocreatestandardisedcomponents(suchasswitchesandoscillators) that
canbereliablypluggedintoanycircuit,forexample,andtoestablishalibraryofwell-
characterisedgenedevices.Somestandardisedbiologicalparts,devicesandsystems
(sometimescalledBioBricks)arebeingmadefreelyavailableonlineinanopenaccess
library called the Registryof StandardBiological Parts. BioBrickscan beused for
creatinggeneticcircuits,forexamplebyusinglogicgatesandoscillators,revealing
directanalogieswithelectronicengineering[Lowrie,2010].
Oneexampleofthewaysuchresearchmightbeappliedisanattempttodevelopa
plantwhoseleafshapeorowercolourchangeswhenalandmineisburiedbelow
it,bygeneticallyalteringtheplantrootstodetectexplosivestracesinthesoilandto
communicatethatinformationtotheleavesorowers[Antunesetal.,2006].
2.1.2 Creation o synthetic organisms
Theannouncementofasyntheticorganismin2010byCraigVenterandhisco-workers
[Gibsonetal.,2010]highlighted,amongother things,howambiguous thisterm is.
Venterandcolleaguesdidnotbyanymeansbuildabacterialcellfromscratch;rather,
theyreplacedthegenomeofanexistingcell(aparticularlysimpleformofbacteriaof
thegenusMycoplasma,whichhasanunusuallysmallgenome)withonedesigned
andmadebychemicalmethods.Thisnewgenomewasbasedonthenaturalone,
butwithsomeadditionsanddeletions.ThustheMycoplasmacellswereessentially
reprogrammedwithanewsetofgeneticinstructions,whichhadthemselvesbeen
designedandmadeinthelaboratory.
Thiswasanaturalandanticipateddevelopmentinexplorationsoftheconceptofa
minimalgenome,whichVenters groupand othershadbeenpursuing forseveral
years[Glassetal.,2006;Glassetal.,2007;Lartigueetal.,2007;Gibsonetal.,2008].
The idea is that a genome strippeddown to the bare minimum ofgenesneeded
toensure the organisms survivalcould act asa chassis onwhich new genomes
couldbedesignedandbuilttoconfernewfunctionsbiosynthesisofanewfuelfrom
naturalsources,sayontheorganism.Theverynotionofaminimalgenomeisitself
ambiguouswhatgenesacellneedsmaydependonwhatenvironmentalchallenges
itwillfacebuttheunderlyingconceptthatbacterialgenomescanbesimpliedand
tailorednowseemstobevindicated.However,itremainstobeseenwhetherwecanunderstandthegenecircuitryofeventhesesimplebacterialgenomeswellenoughto
enablewide-rangingandsystematicdesignofnewones.
The underlyingconcept thatbacterial genomescan be simpliedand tailored nowseems to bevindicated
New kinds obiological sensorsthat signal thepresence o
pollutants orbiomolecules in theenvironment or thebody
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2.1.3 Biological computationThewayinwhichgeneticinformationisencodedandreadoutincellsisakindofdigital
computation.Thishasledtosuggestionsthatsuchlogicmightbeusedbothtocontrol
andmodifybiologicalprocessesin cells, formedicinesay [Benensonet al.,2004],
and to use biological systems for purely technological information processing, for
exampleinsensortechnologies.Onegroupisexploringcomplexlogicsystemsbased
onribozymes(catalyticformsofRNA)thatwillenableexternalmolecularsignalsto
activatedrugs[StojanovicandStefanovic,2003].OthershaveshownthatarticialDNA
moleculescanbedesignedtoperformlogicoperations,computationsandcontrollable
behaviouringeneral[LaBeanetal.,1999;Seeman,2003;Rothemund,2006].Synthetic
biologymightpermitsuchsystems,whichhavebeenmadeandinvestigatedinvitro,tobeincorporatedinlivingcells.
2.1.4 Building articial cells or compartments rom scratch
Incontrasttothetop-downre-engineeringofnaturalorganismsexempliedbythework
ofCraigVentersgroup,someresearchersarepursuingthegoalofmakingcell-like
entitiesfromscratch,puttingthemtogetherfromeithernaturalorsyntheticmolecular
components [Szostak et al, 2001; see http://www.protocell.org]. This bottom-up
constructionofarticialprotocellscouldofferatestinggroundforideasabouthowlife
beganonEarth,forexamplebyelucidatingtheminimalrequirementsoflife-likesystems
thatcangrow,divideandevolve.Suchcellsmayalsohavepracticalapplications,forexampleactingasfactoriesfor thesynthesisofbiologicalmoleculesmuchas
geneticallyengineeredmicro-organismscan,exceptthatsucharticialsystemswould
bemuchsimplerandthereforeeasiertodesign,control,adaptandsustain.Asystem
inwhichmicroscopiccompartments(vesicles)thatassemblethemselvesfromthelipid
moleculesthatconstitutecellmembranesencapsulatepared-downgeneticmachinery
(DNAandRNA)hasbeenshowntogenerateproteinswhenprovidedwiththeraw
ingredients[NoireauxandLibchaber,2004].
Onekeyaimistodevelopsyntheticprotocellsthatcanreplicateandpassongenetic
information,probablyusingmodiedformsofthegeneticmachineryofnaturalcells.
Very simple forms of self-replication have already been reported, for example in
vesicleslikethosementionedabovebutmadefromself-assemblingmoleculeswhose
formationiscatalysedbythevesiclesthemselves[Luisi,2006;Luisietal.,2006].
2.1.5 Materials and nanotechnology
Oneprominenttheme innanotechnology involves themimicryofnaturalmolecular
systems that have evolved effective solutions to engineering problems of a sort
encountered in technology, suchas storing information, harvesting lightor making
materialswithatomic-scale precision.But it sometimes turns out thatsuch natural
systems can themselves becommandeered for that purpose,oftenwith chemical
modicationsthatmightbeimplementedatthelevelofthegenesthatencodethem.In
thisrespect,syntheticbiologypotentiallyhasmuchtooffermolecularnanotechnology
[Ball,2005].
Some researchersare pursuing the
goal o making cell-like entities rom
scratch
This bottom-upconstruction could
oer a testingground or ideas
about how liebegan on Earth
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Forexample,protein-likemoleculeshavebeengeneratedusingdirectedevolutionofbiosyntheticpathwaysthatwillrecogniseandbindtoarangeofinorganicmaterials(for
example,semiconductors)andthatcanactastemplatesandadhesivesforassembling
functionalinorganicparticlesandthinlms,providingapotentialinterfacebetweenthe
biologicalandinorganicworlds[Whaleyetal.,2000;Sarikayaetal.,2003].Molecular
rotarymotorproteinshavebeenusedtorotatemicroscopicmetalblades[Soongetal.,
2000],andtheproteinsresponsiblefortransportingsmallpacketsandobjectsaround
incellshavebeenharnessedforthecontrolledtransportofarticialsmallparticles,
offeringmolecularshuttlesthatmightbeusedtocreatecomplexmaterials,repairtiny
defectsonsurfacesorinlivingcells,andtostoreandretrieveinformation[Hesset
al.,2001].Chemicallymodiedviruseshavebeenusedastemplatesforcrystallising
metallic and magnetic nanowires [Mao et al., 2003]. All these uses of biological
molecularpartsmightgaininpowerandversatilityfromtheuseofsyntheticbiologyto
assisttheirsynthesisincellsandtheirorganisation.
2.1.6 Developing genomes rom using non-natural nucleotides, proteins
rom non-natural amino acids
Althoughproteinsand nucleicacidsare astonishinglydiversein theirstructuresand
functions,theyincorporateonlyaverylimitedrangeofbasicbuildingblocks:20(amino
acids) forproteins,four (nucleotides) forDNA. It ispossible thattheir repertoireof
functionsmightbewidenedbyincludingmorediversebuildingblocksforexample,makingproteinsmorewater-repellentortemperature-resistant,ormakingDNAmore
electricallyconducting.ExpandingthegeneticcodeofDNAcouldalsoallownewtypes
ofinformationtobeencoded.Severalgroupshavemanagedtoincorporatenon-natural
aminoacidsintoproteins[Wangetal.,2001;Chinetal.,2003,MontclareandTirrell,
2006]andnon-naturalnucleotidesintoDNAandRNA[Kool,2002].Onegrouphas
modiedbothbacterialandyeastcellstogeneticallyencodenon-naturalaminoacids
sothattheymaybeinsertedintoproteinsatspeciedlocations[Wangetal.,2001;
Chinetal.,2003].Insomecases,thecellsareabletomakethenewaminoacidsfrom
simplerawingredientsintheenvironment.
Partofthemotivationforsuchworkisfundamental:toexplorethelimitsofbiological
informationtransferorthestructurespaceofproteinmolecules.Butthesestudies
haveimportantpotentialapplicationstoo:forexample,drugsthatinteractwithnatural
proteinsandnucleicacidsinnewways,orprotein-basedmaterialswithnewstructures
and properties. For example, one aim of some articial genetic coding schemes
thatusenon-naturalnucleotides[Kool,2002]istousechemicallymodiedDNAto
detectthesmallgeneticmutationsthatcausecanceranddrugresistance.Articial
genes incorporated intomicrobescanencode non-natural proteinswith interesting
materialproperties(forexample,onesthatformliquidcrystalsandmaterialsfortissue
engineering),includingsomewithnon-naturalaminoacids[Tirrelletal.,1991].
2.1.7 In-cell synthesis o chemicals and materialsThereisawell-establishedeldcalledmetabolicengineering,whichaimstogenetically
Anaminoacid
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engineerthemetabolicprocessesofsimpleorganismssothattheyproduceusefulchemicalsonanindustrialscalesomevitaminsandnechemicals,forexample,
aremadethisway.However,thishasoftenreliedontinkeringratherthanrational,
design-basedstrategies,frequentlyleadingtoonlyminorchangestothecellssynthetic
capabilities.
Syntheticbiologycouldgivethisapproachthemorerationalavouroftrueengineering.
Theabilitytoharness,combine,modifyandadaptthegeneticallyencodedroutesby
whichcellsmakecomplexorganicmoleculeswillopenupnewandefcientroutes
to natural and non-natural compounds with medicinal and industrial value. These
modulesmightbeengineeredintobacteriatogreatlyexpandthepowerofthekinds
offermentationprocessescurrentlyusedwithgeneticallymodiedbacteriatomakepharmaceuticals.Somesuccesswiththisapproachhasalreadybeendemonstrated
withtheengineeringofE.colibacteriatoproducetheantimalarialartemisinin,anatural
productfoundinverysmallquantitiesinaspeciesofplant[Martinetal.,2003;Withers
andKeasling,2007].Becauseofthemulti-stagenatureofthesynthesisofartemisinin
inplants,thisre-engineeringofbacteriaisbeyondthereachofconventionalgenetic
modication,requiringacomplicatedredesignofthebacterialgenome.
2.2 Some potential uture applicationsThe developments described above open upsome new, often rather speculative,
possibilitiesforsyntheticbiology.Someareasfollows.
2.2.1 Biomedicine
A smart drug would be one that contains an autonomous diagnostic capability; it
coulddirectlysensemoleculardiseaseindicators,whichmayinitiatedrugactivation
orrelease.Ideally,asmartdrugwouldbedeliveredtoapatientlikearegulardrug,
but wouldonly become active incellsaffectedbya disease.The techniques and
philosophyofsyntheticbiologyhavealreadybeenusedtodevelopprototypesofsuch
drugsbasedonakindofcomputationperformedbysyntheticstrandsofDNA.
Synthetic biology could help in the design of biocompatible devices, e.g., smallassembliesofmoleculesthatwillsensechangesinparticularbiochemicalsignalssuch
ashormonesandwillproceedtosecreteachemicalorbiologicalcompoundinresponse
[Benensonetal.,2004].Thiskindofdevicecouldbeusedtosensedamagetobody
tissuessuchasbloodvesselsorbone,andtorepairthem.Syntheticbiologycould
providewaystogeneratethesedevicesthemselves in situwithincellsinresponseto
physiologicalsignalsofdamageordistress.
Modiedvirusesarecurrentlybeingexploredastransportagentsforgenetherapy,
whichcanpenetrate cellsanddeliverhealthy genesto the target tissue ina way
thatpromotestheirintegrationwiththecellsgenome.Syntheticbiologymightoffer
greatexibilityforthedesignandmodicationofsuchvirusvectors.Theymight,for
example,betailoredtorecognisespeciccellsandtargetthemfordrugdeliveryor
destruction.
Synthetic biology
could open up newand ecient routesto natural and non-natural compounds
with medicinal andindustrial value
A smart drugwould be delivered
to a patient like aregular drug,
but would onlybecome active in
cells aected by a
disease
Artemisiaannua
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Onevisionofpersonalisedmedicineistodevelopdrugsthatareadaptedintheirmodeofaction, formulation, dosage, and release rates tothe individual requirements of
thepatient.Butthisisfeasibleonlyifsuchmedicineswithsubtledifferencescanbe
manufacturedreliablyatasmallscale.Syntheticbiologymightbeusedtodevisecells
thatwillmanufacturesuchdrugsaccordingtoprecisegeneticspecications.
Itispossiblethatwewillbeabletomodifyhumancellstogivethemnewfunctions
notpresentinourbody.Onemightimagine,forexample,cellsinvolvedintheimmune
responsebeingprogrammedbydesign to recogniseandattack specic virusesor
bacteria. Not only would this address the growing problem of antibiotic-resistant
pathogenic bacteria but it could also reduce the chance of resistance spreading
rapidly.
2.2.2 Applications o non-natural biopolymers
Thereiscurrentlygreatinterestindevelopingdrugsfromnucleicacids,suchassmall
RNAmoleculesthatinterferewiththeexpressionofgenes.Modiednucleicacidswitha
non-naturalchemicalcompositionmightbegivenadvantageouscharacteristicsfroma
pharmaceuticalperspective,forexamplepassingmoreeasilyacrosscellmembranes.
Organismswithanexpandedgeneticcodethatallowsmorethanthe20naturalamino
acidstobeincorporatedintoproteinsshouldlikewiseenablethemanufactureofprotein
drugswithnovelorenhancedproperties,forexamplebylengtheningtheirshelf-life
ormakingthemlessormorepronetointerfereinunintentionalwayswithbiochemical
processes.Enzymeswithnon-naturalaminoacidsmightalsoshowgreaterorless
catalyticactivitywhenusedfortheproductionofpharmaceuticals.
Pseudo-biomolecules with non-natural chemical structures could be designed to
beinvisibletothenaturalchemistryofthecell,forexampleenablingthedesignof
biomolecularsensorsthatoperateindependentlyfromnaturalproteinnetworksand
pathways.Amongthepotentialusesofsuchinvivomolecularsensorsmightbethe
veryearly detectionofcancer signals.Encodinggenetic information innon-natural
nucleicacidsmightalsoreducetherisksofgeneticmodicationofnaturalorganisms,
becausetheuseoftheaddedgenescouldthenbemadedependentonanexternal
supplyoftheingredientsneededtomakethenon-naturalnucleicacids:withoutthem,
theaddedgenescouldnotbereplicated.Thiswouldofferasimplewaytoswitchthe
geneticmodicationonandoff,forexamplebywithholdingthenecessaryingredients
fromatransgenicplant.
Nucleic acids have been recognised asversatile components for the synthesisof
nanoscale structures and devices [Seeman, 2003; see above]. Expanded genetic
alphabetsshouldallowthecell-basedsynthesisandreplicationofDNAnanodevices
withawiderrangeofproperties:greaterrobustness,say,ortheabilitytointeractwith
inorganiccomponents.
Synthetic biology
might be used todevise cells thatwill manuacturedrugs according
to precise geneticspecications
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2.2.3 Sustainable chemicals manuacturing and energy productionTheinevitabledwindlingoffossil-fuelreservesduringthiscenturywillforceindustrial
chemistrytondanewsourceofrawmaterialsformakingproductssuchasdrugs,
fuelsandplastics.Oneofthecurrentgoalsinsyntheticbiologyistodevelopengineered
micro-organismsthatcangenerateusefulcarbon-based(organic)chemicals,of the
sortcurrentlyobtainedfrompetroleum,fromnewfeedstockssuchasbiomass.This
isa particularly valuableobjective in thearena of fuelproduction, wheremicrobial
productioncouldbebasedonrenewablesources.Oneofthekeyaimsoftheminimal
genomeapproachto syntheticorganisms[Glassetal.,2006] is todesign themto
turnbiomass,perhapsespeciallythe recalcitrantparts ofplants thatare noteasily
degradedbyexistingmicro-organisms,intobiofuelssuchasethanol.
2.2.4 Environmental remediationBioremediationtheuseofnaturallyoccurringorganismssuchasbacteriaandfungi
tobreakdownorganicpollutantssuchasoilandsewage,ortoconcentratetoxicheavy
metalsfromsoils hasemergedin recentdecadesas oneofthebesttechniques
for decontaminatingnatural and man-made environments. Synthetic biology might
enablesuchorganismstoberationallydesigned,bothtoimprovetheirefciencyand
tobroadentherangeofpollutantsthattheycandegradeorremove.
2.2.5 Systems-scale molecular nanotechnologyAsshownabove,thereareseveralways inwhichengineeredproteins, virusesand
organismsmightassistinthedevelopmentofnewmaterials,suchasthoseusedin
biomedicine,microelectronics,mechanicalengineeringandenergyconversion.
So far, much of the work in this area has demonstrated specic functions using
individualbiologicalcomponents:forexample,desalinationorltrationusingproteins
thatperformananalogousfunctionincellmembranes,ortransportofnanoparticles
usingmotorproteins.Butinlivingcells,suchsystemsaretightlycoupledtoothers
inanintegrated,autonomousmolecularassemblythatbuildsandrepairsitselfand
generatesitsenergyfromambientsources.Itwouldbedesirabletoachievethissort
ofintegrationinsyntheticsystems[Ball,2005].Forexample,couplingphotosyntheticdevicestomotorproteinscouldenablelight-drivenmolecularmotion.Itisconceivable
thatthebestwaytodothiswillbetoincorporateallofthecomponentsintothegenetic
programsofengineeredorganisms.Inotherwords,syntheticbiologymighthelpus
tomimicnotjustsomeofthemolecularengineeringprinciplesoflivingcellsbuttheir
systems-scaleoperation.
One o the key aimso the minimal
genome approachto synthetic
organisms is todesign them to
turn biomass intobiouels such as
ethanol
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Syntheticbiologyisanemergingdisciplinewithhugepotentialandscope.However,thereisnodirectcorrespondencebetweenthenatureandextentofthebenetsandthe
associatedsafetyandsecurityrisks.Eachnewdevelopmentwillneedtobeassessed
on its merits, balancing risks and benets and, where necessary or appropriate,
considering innovativeapproachestoenablinginnovationwhileavoidinghazardsto
peopleortheenvironment.
IRGChasidentiedtwoframesofsyntheticbiologydevelopment:
rst-generation evolutionarysyntheticbiologythatbuildsonexistingapplications
of genetic engineering, deploying more rapid development methodologies
accessibletoawiderrangeofactorsatreducedcosts;and
second-generation revolutionary developments where feasible forms of
innovationandapplicationareasarelesscertain.
Eachoftheseregimeswillhaveadistinctsetofrisks,withtheformerobviouslyless
speculativeandmorewell-denedthanthelatter[Mukundaetal.,2009].Adistinction
alsoneedstobemadebetweenthechallengesofregulatingthe conductofsynthetic
biologyresearchitselfandtheneedtoregulatetheproducts and practical outcomes
of that research. For basic research and knowledge generation, risk governance
shouldfocusmainlyontheresearchprocessesthatarelikelytogiverisetohazards.
Forproductsandotherapplicationsarisingfromthisknowledge,on theotherhand,
governanceshouldfocuslessontheprocessesinvolvedandmoreontheproductsandoutcomesthemselves.
Inconsideringproductsandpotentialapplications,thispolicybrieffocusesonrst-
generation developments, for whichwedohave some informationon likely future
outcomes.However,commentsontheconductofbasicresearchonsyntheticbiology
wouldapplytobothrst-andsecond-generationdevelopments.
Reportsassessingpotentialrisksassociatedwithsyntheticbiologyhavebeenprepared
byanexceptionallydiversesetoforganisations.Theseincludeofcialgovernmental
bodies[NSABB,2006;POST,2008],nationalacademies[RoyalAcademyofEngineering
2009;RoyalSociety2008,2009;DFG,2009],foundation-and/orgovernment-funded
consortia[BalmerandMartin,2008;Caruso,2008;Gaisser,etal.,2008;Garnkel,et
al.,2007;NEST,2007;Rodemeyer,2009]andNGOs[FriendsoftheEarth,2010;ETC,
2010].Thesereportshavefocussedonthefollowingareas:
Insufcientbasic knowledge about the potential risks posedby designedand1.
syntheticorganisms.Forexample,arecentEuropeanUnion(EU)reporthasraised
questionsaboutourabilitytoassessthesafetyoforganismsthatcombinegenetic
elementsfrommultiplesources,thatcontaingenesandproteinsthathavenever
existedtogetherinabiologicalorganism,orthatincorporatebiologicalfunctions
thatdonotexistinnature[EuropeanCommission,2009].
Uncontrolled release of novel genetically modied organisms with potential2.
environmentalorhumanhealthimplications,eitherarisingfromaccidentalrelease
Each newdevelopment willneed to be assessedon its merits
Regulatingthe conductosynthetic biologyresearchRegulatingthe products
andpractical
outcomeso thatresearch
3. Risks o synthetic biology
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intotheenvironmentorfromapplicationsentailingdeliberaterelease(forexample,bioremediation and some varieties of living therapeutics) [e.g. Friends of the
Earth,2010].Areexistingbiosafetymeasuresadequate?Whoisresponsiblefor
ascertainingandquantifyingrisks,andforimplementinganyclean-upmeasures
thatmightneedtobeundertaken?
Bio-terrorism,biologicalwarfareandtheconstructionofnovelorganismsdesigned3.
tobehostiletohumaninterests.Geneticmanipulationoforganismscanbeused,
orcanresultbychance,inpotentiallydangerousmodicationsforhumanhealthor
theenvironment.Bioterroristsmight,forexample,createnewpathogenicstrains
ororganisms resistant toexisting defences. It has even been suggested that
pathogens mightbe engineered toattackonlyaparticulargeneticsubset ofa
population[Garnkeletal.,2007].Itisbynomeansclearthatsuchabusescouldbe
entirelyeliminated,anymorethantheycanbeforotherdual-usetechnologies.
Asidefrom theriskofabusescoordinatedbygovernmentsororganisedgroups,4.
there are concerns about the emergence of a bio-hacker culture in which
lone individuals develop dangerous organisms much as they currently create
computerviruses.Thebasictechnologiesforsystematicgeneticmodicationof
organismsare widely availableandarebecomingcheaper, although it iseasy
tounderestimatethedegreeoftechnicalprociency,experienceandresources
neededtomakeeffectiveuseofthem.Manyresearchersintheeldanticipatethat
therealharmsthatmightbeinictedbysuchhackeractivitiesareprobablysmall,
buttheynonethelesswarrantcarefulconsideration,anditishardtoseehowthey
mightbepreventedthequestionismoreaboutlawenforcementthanscientic
protocol.Onesuggestionistoaimtoremovetheglamourwhich,byanalogywith
computerviruses,mightbecomeattachedtobio-hacking.
Patentingandthecreationofmonopolies,inhibitingbasicresearchandrestricting5.
productdevelopmenttolargecompanies.
Trade and global justice, for example exploitation of indigenous resources by6.
enabling chemical synthesis of valuable products in industrial countries (e.g.
artemisininproductionformalariatreatment),ordistortingland-useagendasfor
geneticallyengineeredbiomass[FriendsoftheEarth,2010;ETC,2010].
Claims that synthetic biology is involved in creating articial life, and related7.
philosophicalandreligiousconcerns.TheaccusationofplayingGod[Peters,2002]
hasalreadybeenlevelledatsyntheticbiologyinthewakeoftherstorganismwith
asyntheticgenome[Gibsonetal.,2010;VandenBelt,2009].Aswithreproductive
technologiesandstem-cellresearch,thelackofasharedconceptualframework
makesithardtodebatethisissueamongthevariousinterestedparties:thescience
mayhaveoutstrippedourethicalpointsofreference.
Many of these ethical and safety issues have already been acknowledged and
discussed extensively by the synthetic-biology community [Schmidt, 2009b]. The
increasinglyactivedebatearoundtherisksofsyntheticbiologyfocussesinEuropeon
theexperienceofsimilardebatesaboutgeneticallymodied(GM)crops[Tait,2009b],
Genetic
manipulation oorganisms canbe used, or can
result by chance,in potentially
dangerousmodications or
human health or the
environment
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whichhaveresultedinadefactomoratoriumonmanypotentialapplications.IntheUS,publicattitudestoGMcropshavebeenmuchmorepermissive.Ananalogyisoften
madeinthesynthetic-biologycommunitywiththeAsilomarConferenceonRecombinant
DNAin1975,atwhichguidelineswereagreedonhowthistechnologymightbeused,
andavoluntarymoratoriumwasestablishedoncertainkindsofexperiments,suchas
thecloningofDNAfrompathogenicorganisms.
It is easy (and perhaps appropriate) for an enumeration of the potential risks of
syntheticbiologytosoundalarming.Butthesemustbeweighedagainstthebenets,
notleastinthesensethatthereisanethicalcomponenttothedecisiontoforegoa
newtechnologytoo:therecanbesociallysignicantpenaltiestotheseeminglysafe
option of doing nothing. Forone thing, thepowerful capabilities syntheticbiology
mightprovidefordevelopingandmanufacturingdrugs,includingonessorelyneeded
indevelopingcountries,shouldnotlightlybesetaside,justaswedonotprohibitall
drugsthathaveside-effects.Itisconceivablethatinthelong-term,syntheticbiology
mightofferoneofthemostpowerfulapproachesforamelioratingnaturalbiologicaland
ecologicalhazardssuchasthespreadofinfectiousdiseases[Mukundaetal.,2009].
Moreover,sincethebasictechniquesnecessaryforconductingsomeformofsynthetic
biologyalreadyexistandarepubliclyaccessible,curtailingscienticresearchinthis
areaprovidesnoguaranteeagainstpotentialabuses.Itislikelythatmisuseforthe
purposesof,say,bioterrorismandbiowarfaremightbemosteffectivelypreventedor
remediatedbythetechniquesofsyntheticbiologyitself.(Itcouldalsooffernewways
tocounteralreadyexistingmanifestationsofthesethreatstoo.)Inshort,thegenieis
alreadyoutofthebottle:thetechnologymightbecomeitsownbestsafeguardagainst
someofitsrisks.
It is easy or anenumeration o thepotential risks osynthetic biologyto sound alarming.But these must beweighed against the
benets
The technologymight become itsown best saeguardagainst some o itsrisks
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4.1 Regulatory and governance contextsThe Organisation for Economic Co-operation and Development (OECD) views
synthetic biology as a potentially revolutionary technology that could transform
biology and biotechnology from a largely scientic toanengineeringdiscipline. In
thenear-term(to2015),theOECDseestheuseofmetabolic-pathwayengineering
toproducechemicalsthatpreviouslycouldnotbeproducedbiologicallyasthemost
likelycommercialapplicationofsyntheticbiology.In thelonger-term,applicationsof
syntheticbiologyinprimaryindustrialmanufacturingandinhealthcaremaybecome
widespread.Commercialisationof theselatteruses wasconsideredunlikelybefore
2015,becausesuchapplicationswillbesubjecttothesameregulatoryproceduresas
otherbiotechnologyproducts,whichgenerallyrequirealeadtimeofbetween5and7
years[OECD,2009a].
Thereiscurrentlyacomplexarrayofnationalandinternationalregulatoryinstruments
thatmayberelevantfor,oractasprecedentsfor,theregulationofsyntheticbiology,
particularlyrst-generationproducts[e.g.ByersandCasagrande,2010].Thereisa
historyofdecisionsbeingtakeninveryearlystagesofproductdevelopmentthatturn
outtohaveunforeseenandoftencounter-productiveoutcomeswhicharethendifcult
tochange.Thisisparticularlyevidentwhereregulationhasbeendesignedtoreassure
thepublicratherthantoaddressgenuineexpectedrisks,aswasthecaseforGMcrops
inEurope.Also,wherearegulatoryregimehasevolvedoveralongperiodoftimeinresponsetoseveralgenerationsofscienticdevelopment,itcanbecomeinexibleand
difculttomodifyinwaysappropriatetothelatestadvancesandopportunities[Byers
andCasagrande,2010].Thiscanunnecessarilylimitopportunitiesforinnovationand
representagovernancedecitinitself[IRGC,2009a].Theappropriateriskgovernance
ofinnovative technologies thusneedsto beinformedby anunderstandingof how
governanceandengagementapproachesinteractwithinnovationprocesses.
TheEuropeanviewon risk regulation insyntheticbiologyis thatit willbecovered
byexistingregulations for genetic modicationand releaseofGM productsto the
environment [Royal Academy of Engineering, 2009]. However, these regulations
are themselves controversial (see Section 5.2) and are already inhibiting the
commercialisationofpotentiallybenecialGMproducts,suchas pest- ordrought-
resistantcrops[WagnerandMcHughen,2010].
Internationallawhasanimportantbearingontradeinbiotechnologicalproducts,the
mostfamiliarexamplebeingtherestrictionsontradeingeneticallymodiedorganisms
(GMOs)orproductsderivedfromthem.Someregulationsmayberelevanttoproposed
applicationsofsyntheticbiology,suchastheglobalmoratoriumonoceanfertilisation
(foramelioratingclimatechangebypromotingoceaniccarbondioxideuptake)under
theConventiononBiologicalDiversityandtheprovisionsof theBiologicalWeapons
Convention (BWC). The next review conference of the BWC will beheld in2011,providingtheopportunityfortheinternationalcommunitytomakebindingdecisions
on the oversight of synthetic biology. The Environmental Modication Convention
There is currentlya complex arrayo national and
internationalregulatory
instruments thatmay be relevant or,
or act as precedentsor, the regulation o
synthetic biology
The appropriaterisk governance
o innovative
technologies needsto be inormed byan understanding
o how governanceand engagement
approaches interactwith innovation
processes
4. Existing policy and regulatoryrameworks, and their decits
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(ENMOD), an international treaty prohibiting the military or other hostile use ofenvironmental modication techniques such as alterations to weather patterns or
oceancirculation,mayalsoapplytosomepossibleusesofsyntheticbiology.
TheAgreementonTrade-RelatedAspectsofIntellectualPropertyRights(TRIPS)isthe
mostcomprehensivemultilateralagreementonintellectualproperty,settingstandards
to be met in domestic patent law. Most applications and techniques of synthetic
biologywouldbepatentableunderArticle27.3(b)oftheagreement,whichdealswith
intellectualproperty(IP)protectionofgeneticresources.
LimitsontheexploitationofIPrightsstemfromothereldsoflaw,suchashuman
rightslawandinternationalenvironmentallaw.Trade-offsmayberequiredwheresuch
issuesaspublicaccesstoinnovativemedicinesareatstake.Inthisregard,compulsory
licensingremainsanoptionundertheTRIPSagreementforpatentsinanyeld.In
the2001DohaDeclarationonTRIPSandPublicHealth,WorldTradeOrganization
(WTO)membergovernmentsstressedthatitisimportanttoimplementandinterpret
theTRIPSAgreementinawaythatsupportspublichealth.
TherearepotentialconictsbetweentheTRIPSpatentingregimeandtheConvention
onBiologicalDiversity,aswellastheInternationalUndertakingonWorldFoodSecurity
negotiatedat theUnited Nations FoodandAgriculture Organisation (FAO).These
conictsaregenerallyseenas political rather than legal, and may lead todispute
undertheWTOdispute-settlementsystem.
TheCartagenaProtocolonBiosafetytotheConventiononBiologicalDiversityregulates
internationaltradeingeneticallyengineeredproducts.TheProtocolestablishescore
proceduresandasetofstandardsrelatingtotheimportandexportoflivingmodied
organisms(LMOs).AlthoughtheCartagenaProtocolrecognisesinitspreamblethat
tradeandenvironmentagreementsshouldbemutuallysupportive,itisgroundedina
morerobustapplicationoftheprecautionaryapproachthantheWTOrules.Currently,
157nationalpartiesparticipateintheProtocol,includingChina,Brazil,Indiaandmost
Europeannations,but not the US(wheresignicant researchanddevelopmentin
syntheticbiologyistakingplace)orotherpotentiallyimportantinternationalplayerssuchasAustralia,Russia,ArgentinaandCanada.
ThereareclearareasofoverlapbetweentheProtocolandtheWTOrules.Inaddition
toTRIPS,theAgreementonTechnicalBarrierstoTradeandtheAgreementonthe
Applicationof SanitaryandPhytosanitaryStandardsare relevant.ArticleXX of the
GeneralAgreementonTariffsandTrade(GATT)providesforexceptionsfromGATT
rulesinordertoprotecthealthortheenvironment.Theseagreementsformedthebasis
ofthedisputeraisedbytheUS,CanadaandArgentinaundertheWTOsystemover
theEuropeanCommissionsregulationofGMOs.Thedifferentfundamentalobjectives
of the international trade and environmental regimes may lead to conicts in the
regulatorymeasurestakentoachievetheseobjectives.Strengtheningthecoherence
ofthesetwosystemsrequiresmeasurestobetakenatnationalandsupranational
levelstoensuretheyareimplementedinamutuallysupportivemanner.
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Developments in synthetic biology could lead to gaps in the risk assessmentframeworksetoutintheCartagenaProtocol,sinceestablishedpracticesmaynotbe
capableofdealingwithcomplexhybridsofgeneticmaterial(includingsomethatare
whollysyntheticindesignandorigin)andthepropertiesandeffectstheydisplay.The
sameproblemis faced bynon-participatingstates.In theUS,the riskassessment
framework in the National Institutes for Health Guidelines for Research involving
RecombinantDNAMolecules[NIHGuidelines,2009;ByersandCasagrande,2010]is
consideredbyregulatorstobesufcientatpresentforhandlingrisksthatmightarise
insyntheticbiologyattheresearchstage.Theframeworkusestheriskgroupofthe
parentorganismasastartingpointfordeterminingthenecessarycontainmentlevel;
butsynthetictechniquesmayenable thedevelopmentof morecomplexorganisms
forwhichtherisksoftheparentorganismarenotanappropriateprecedent[Byers
andCasagrande,2010].Notenoughisknownatpresentforrobustriskassessments
relatedtocontainmentofpartiallyorwhollysyntheticorganisms.Thereisalsosome
concern that intellectual property rights claims couldbeused to restrictaccess to
risk-relatedinformationandtherebycompromisethecredibilityofriskassessments
infuture.
4.2 Risk Governance Decits
Severalaspectsofriskgovernancerelevanttoinnovativetechnologiesareconsidered
hereinrelationtosyntheticbiology:Theuncertaintyaboutfutureresearchandindustrialdevelopments,andthusabout
theactualopportunitiesandrisks.
Theinhibitingeffectoninnovationofuncertaintyaboutfutureregulatorysystems,
particularly for products with long lead times for delivery from conception to
market.
The need for a better understanding of how different regulatory approaches
interactwithinnovationprocessestodeterminethefateofinnovations,including
therelativecompetitiveadvantagegainedbycompaniesandcountriesoperating
indifferentregulatoryregimes.
Thepotentialtoadaptexistingregulatorysystemsandtoapplythesetoinnovative
technology, and inparticular the importance ofadopting the most appropriate
regulatoryprecedent.
The potential for lack of harmonisation between different national regulatory
systemstoleadtotrade-relatedandotherconicts.
Problemsofstakeholderandpublicengagementaboutinnovationswhere,forall
partiesinvolvedindiscussionanddecision-making,thereisignoranceoratbest
uncertaintyabouttheeventualnatureofnewproductsandprocesses.
Thevolatilenatureofpublicopinionaboutinnovativetechnology,sothatdecisions
basedonthebalanceofstakeholderattitudestodaymayfaceaverydifferentset
offuturepublicopinions.
The need to take decisions on a balanced basis, particularly where there is
irreconcilableor ideologically basedconictoverinnovativetechnology and its
application.
Not enough isknown at present
or robust riskassessments related
to containment opartially or wholly
synthetic organisms
There is concern
that intellectualproperty rights
claims could be usedto restrict access
to risk-relatedinormation and
thereby compromisethe credibility o
risk assessments inuture
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These considerations suggest that any effective approach to risk governance ofsyntheticbiologymustbecapableofevolvingasscienticandtechnicalknowledge
expands,requiringexibilityinthefaceofuncertaintyabouttheeventualnatureof
products,processes,benetsandrisks.Wehavefocussedhereontheconceptof
risk governance decits1 deciencies or failures in risk governance processes
orstructures and have aimedto identifyweak spots inhow risksare assessed
andmanagedin thekey areasof policyandregulation, innovationand technology
development,andpublicandstakeholderengagement[IRGC,2009a].
ParticipantsattheIRGCworkshoponsyntheticbiologysoughttondanappropriate
balance between current scientic knowledge and uncertainty about future
developments,andtheneedtorealisticallyassessthepotentialoftheeld.Abalance
isalsoneededforpolicyandregulatoryoptions,includingthepotentialtotransform
existing policies and regulatory frameworks that may be difcult to adapt to the
challenges raised by innovative technologies. The participants were concerned to
ensurethattheopportunitiesofferedbysyntheticbiologyasthetechnologydevelops
bekeptopen,butalsorecognisedthatthereispotentialheretoopenupnewmodels
ofpublicandstakeholderengagement.
One general themeto emerge from the workshopwas the concern that synthetic
biologywasalreadybecomingtoobroadasetofdevelopmentstobedealtwithunder
one heading.As is already the case with nanotechnology, this diversication will
makeitincreasinglynecessarytogoverntheareausingadiverseandexiblesetof
regulatoryprecedentstailoredtoarangeofspecichazardsandtheneedsofdifferent
industrysectors.
Theworkshopdiscussionsalsoexploredpotentialinteractionsamongriskregulatory
processes,innovationsystems,andstakeholderandpublicperspectivesinrelationto
syntheticbiologydevelopments.Theyidentiedthe followingdecits[IRGC,2009a,
pp.64-65]asbeingmostrelevanttopotentialdevelopmentsinsyntheticbiology(in
orderofperceivedimportance).TheguidelinesproposedinSection6aredesignedto
helppolicy-makersandregulatorstoavoidorreducethesedecits.
Potential defcits in risk assessment:
Lackofknowledge,includingtheprobabilitiesof variousdiscoveries,inventions
and events and the associated economic, human health, environmental and
societalconsequences.
Lackofknowledgeaboutvalues,beliefsandinterestsandthereforeabouthow
risksareperceivedbystakeholders.
Failuretoidentifyandinvolverelevantstakeholdersinriskassessmentinorderto
improveinformationinputandconferlegitimacyontheprocess.
Theprovisionofbiased,selectiveorincompleteinformation.
Lackofappreciationofthemultipledimensionsofariskandhowinter-connected
risksystemscanentailcomplexandsometimesunforeseeableinteractions.
Failuretoovercomecognitivebarrierstoimaginingeventsoutsideofaccepted
paradigms.
(1)TheconceptandalistofthemostcommonlyobserveddecitsinriskgovernancehavebeendescribedinanIRGCreport
availableathttp://www.irgc.org/IMG/pdf/IRGC_rgd_web_nal.pdf.
Any eectiveapproach to risk
governance osynthetic biologymust be capable oevolving as scientic
and technicalknowledge expands
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Potential defcits in risk management:
Insufcientexibilityinthefaceofunexpectedrisksituations.
Failure to balance transparency (which can foster stakeholder trust) and
condentiality(whichcanprotectsecurityandmaintainincentivesforinnovation).
Failure of the many organisations responsible for risk management to act
cohesively.
Failuretomusterthewillandresourcesto implementriskmanagementpolicies
anddecisions.
Failure to design risk management strategies that adequately balance
alternatives.
Failure of managers to respond and take action when risk assessors have
determinedfromearlysignalsthatariskisemerging.
Diversication will
make it increasinglynecessary to govern
the area using adiverse and fexible
set o regulatoryprecedents
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5.1 The concept o appropriate risk governanceIRGCdenesappropriateriskgovernanceasthatwhich,intheeldofinnovative
technologies,enables innovation,minimisesrisktopeopleandtheenvironment,and
balancestheinterestsandvaluesofallrelevantstakeholders[Tait,2007],whileavoiding
simplisticcomparisonsacrosssectorsandtechnologies.TheIRGCriskgovernance
framework[IRGC,2005]hasbeenappliedverysuccessfullytoarangeofriskissues,
includingforexampleNanotechnologyApplicationsin FoodandCosmetics [IRGC,
2009c].However,syntheticbiologypresentschallengesfortheusualapproachesto
riskgovernance.Initscurrent,earlydevelopmentalstage,bothbenetsandrisksof
syntheticbiologyarelargelyconjecturalandmostpreviousreportsonthisissuehave
thereforefocussedonaspectsthatarecoveredonlyin theinitial(pre-assessment)
phaseoftheIRGCframeworkspecically,
howrisksareframedbystakeholders;
whetherthereareanyapplicablelegalorotherexistingrulesorprocessesthat
covertechnologydevelopments;
thescienticcharacteristicsofthetechnologyanditspotentialapplications;
thehopesandconcernsofmajorstakeholdergroups.
Regulationof basicresearchon syntheticbiologyshould beconsideredseparately
fromproductregulation.Giventhelikelyrangeofapplicationsofsyntheticbiologyin
differentindustrysectors,however,itwouldbeunwisetoattempttodeviseanoverall
frameworkforriskgovernanceofsyntheticbiology.Instead,riskgovernancehasto
beapproachedonaproduct-by-productbasis,payingparticularattentiontocurrent
regulatoryapproaches,theextenttowhichtheyaretransferabletothenewproducts,
and the implications of such choices for the options for future development. For
example,productsthathaveapplicationstohumanoranimalmedicine,agricultural
crop development and the production of biofuels will come under the scrutiny of
differentexistingregulatorysystems.
However,someareasofsyntheticbiologywillnotbecoveredbythisapproach.For
example,tradinginbio-bricks(genesequencesthatcanbeusedbybothresearchers
andcommercial companiesto developnewgene circuitry)canbedealtwithusing
regulatoryinitiativessimilartothosebeingdevelopedtoregulatetheresearchstage.
Ontheotherhand,whensyntheticbiologyisusedtodevelopnewprocessesforthe
manufactureofcomplexbiologicalmolecules,theresultingmoleculesthemselvescan
beregulatedbyexistingsystemsfordrugsorotherchemicals,butnewregulationmay
alsobeneededforthenovelorganismsusedintheproductionprocess.
5.2 Regulation and governance o rst-generationsynthetic biology
Forsomelikelynear-termapplicationsofsyntheticbiologyforexample,inbiofuels
and industrial applications, pharmaceuticals and health diagnostics, and genetic
Risk governance hasto be approached
on a product-by-product basis,tailored to a rangeo specic hazardsand the needs odierent industrysectors
5. Risk governance in synthetic biology
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research laboratories or other commercial companies. This approach is supportedby some scientists, who point out that the likely control of DNA synthesis and other
key technologies by a small number of very efcient companies [Bhattacharjee, 2007]
could make such monitoring relatively easy and reduce biosafety concerns.
As the gene-synthesis market has become more competitive, two groups of companies
have proposed different standards for screening orders for gene sequences to enable
identication of any that could present a potential biological hazard [Hayden, 2009].
The International Association for Synthetic Biology (IASB) code of conduct [IASB, 2009]
includes a review step by an expert in the eld, while DNA 2.0/Geneart has suggested
an automated process. The Federation of American Scientists has considered this
problem of multiple standards, and is working towards a consensus, at least among
American scientists and companies [FAS, 2010], on how screening might be done.
Guidelines for screening of DNA synthesis have been formulated by the US Department
of Health and Human Services [DHHS, 2010], but these are voluntary, apply only to
double-stranded DNA, and have been criticised by some researchers as representing
no improvement to the security risk [Ledford, 2010].
Furthermore, if these technologies become ever more accessible [Carlson, 2010],
so that gene sequences can be procured by means other than through companies
with sophisticated screening procedures, this will create stiffer challenges for risk
management. Some feel that the threat may be much greater from state-sponsored
terrorism (for which DNA synthesis would be hard to control or monitor) than from
amateur activities. However, it is important not to underestimate the difculty of moving
from research in a laboratory, let alone a bio-hackers garage, to a functioning product
that can be disseminated widely. Incorporating engineering techniques into research
on biology does not mean that the resulting products can be developed as if they were
just another piece of hardware or software.
The dissemination of the technology, knowledge and capabilities involved in synthetic
biology beyond the professional biotechnology community will have two (potentially
overlapping) strands:
Professional groups such as engineers and computer scientists, educated in1.
disciplines that do not routinely entail formal training in biosafety, may acquire
these capabilities. In consequence, there needs to be a dialogue among all relevant
researchers on what responsible conduct might entail in this eld, and education
about the risks of, and guidance on best practice for, biosafety principles and
practices applicable to synthetic biology. A review of biosafety standards should
also be conducted to identify differences between standards and actual laboratory
practices.
Dissemination may extend beyond academic and professional circles as biological2.
engineering becomes more accessible [Mukunda et al., 2009]. This may include
less responsible individuals and organisations. Moreover, the most appropriate
The synthetic biology
community has
generally supported
approaches to
oversight that rely on
voluntary measures
developed and
implemented by the
community itself
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balancebetweenpromotinginnovationandcontainingriskwillnotbethesameinallpartsoftheworld.Legitimateresearcherscanhelpgovernmentsandregulators
tondwaystopreventotheractorsfromusingthetechnologyforillicitpurposes.
Anappropriatebalancealsoneedstobefoundbetweentop-downcommandand
controlandbottom-upeducationandawarenessinitiatives,includingthefostering
ofa culture ofresponsibilityand the de-glamorisation ofthe kind ofantisocial
activitiesalreadyevidentinthecreationofcomputerviruses.
A summary of US Federal Regulations that relate to synthetic biology [Byers and
Casagrande,2010]haspointed toseveral inadequacies, includingNIHGuidelines,
EPA,USDAandFDARegulations,DepartmentofCommerceRegulationsandSelect
AgentRules,as currentlyapplied todevelopments in syntheticbiology that involve
micro-organisms.Thecurrentapproachtothedenitionandclassicationoforganisms
accordingtoperceivedhazardlevelswillnotcovertherangeofpossiblemodications
arisingfromsyntheticbiology,whetherlegitimateormalicious.Theruleswillneedto
beadaptedtonewcircumstances.
Policy-makers need to take a lead in developing and implementing standardised
procedures and preferred practices for screening sequences and for mitigating
biosecurityrisksasawhole.TherecentlypublishedUSNationalStrategyforCountering
BiologicalThreats[USNationalSecurityCouncil,2009]isanimportantstepinthis
direction.Inthecontextofbiologicalthreatsofallkinds,includinganyarisingfrom
synthetic biology, the strategy advocates an international, systemically organised
approachthatseekstopromoteacultureofresponsibilityinthelifesciences,backed
up by legal mechanisms, coupled with surveillance and improving intelligence on
deliberatethreats.
Oneofthekeyissues,whichlacksanycurrentconsensus,istowhatextentavoidance
ofbiosafetyriskscanbeensuredbyvoluntarymeasures(forscreeningofcommercial
DNAsynthesis,say)asopposedtotop-downregulation.Forexample,Mukundaet
al.recommendtheadoptionofasafetyholdnormofthesortcurrentlyusedbyAir
TrafcControl(ATC)systems,wherebyanyproposedchangetoATCsystemscanbe
blockedbyanymemberofthecommunitywhobelievesthattheyarelikelytocausesafetyconcerns[Mukundaetal.,2009].
Amajorplankofthestrategyproposedhereistherecognitionthatusingthelifesciences
tocombatbothnaturalandmaliciousthreatsmaybethebestwaytominimiseharm,
giventhatthereisnofoolproofwaytoforestallmalicioususeofthetechnology.This
couldincludetheuseofmethodsinsyntheticbiologytodevelopimproveddisease
diagnosticsandvaccines.Inthiscontext,itisimportanttorecognisethattherisksto
humanityfromnaturallyoccurringzoonoses(infectiousdiseasesthatcanbetransmitted
fromanimalstohumans)andotheremergingpathogensarelikelytobegreaterthan
thosearisingfrommalicioususeofsyntheticbiology.
The mostappropriate balancebetween promoting
innovation andcontaining risk willnot be the same in
all parts o the world
One o the keyissues, which
lacks any currentconsensus, isto what extent
avoidance obiosaety risks
can be ensured by
voluntary measuresas opposed to top-
down regulation
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5.4 Intellectual property (IP) issues and maintainingincentives or innovation
In any innovative technology, thegrantingof limited exclusive rights in intellectual
propertycansupportinnovationbutcarriesthedangerofcreatingadisproportionate
concentrationofmarketpower.Inareasoftechnologicalconvergence,IPrightsmay
befragmentedacrossmanyowners,andaresometimesgivenanexcessivelybroad
interpretation, whichcan pose obstacles tothe developmentofthe basicscience.
Moreover,wherescienceisdevelopingrapidly,theneedsoftheresearchcommunity
forIPprotectionarenotnecessarilyalignedwiththoseofproductdevelopers.
Manyscientistsworkinginsyntheticbiologyhaveexpressedaprincipledcommitment
toanopensourceethos,modelledontheopen-softwaremovementinICT[Heller
andEisenberg,1998].Suchstronglyheldviewscanmakeitmoredifculttobalance
thesocietaltrade-offsthatneedtobemadebetweenopenaccesstoinformationand
commercialrealities,particularlyinthecontextofthelengthyandonerousregulatory
processes that apply in many areas of life sciences (which tend to impose high
developmentcosts).Theclaimoftenmadeforopen-sourcebiotechnologythatitcan
realisethebenetsofcommercialtechnologytransferwhilecreatingarobustscience
andtechnologycommonsthatcansustaininnovationhasyettobetestedincases
likesyntheticbiology.
Aswellasawhollyopen-accessapproach,variousotheroptionshavebeenproposed
forhandlingintellectualpropertyinsyntheticbiologythatgobeyondthetraditionaloption
ofpatenting,typicalofbiotechnologyandthepharmaceuticalindustrytoday[Raiand
Boyle,2007].Therecould,forexample,beprovisionforcopyrightingofinnovations,
forcontractsto govern their use,or forhighlyspecicsui generisstrategies.Each
hasadvantagesanddisadvantages,andnoneisobviouslypreferableto theothers.
OyeandWellhausenarguethatcurrentapproachescanbedistinguishedbothbythe
degreeofpublicversusprivateownershipofIPandbytheextenttowhichproperty
rightsareeitherclearlyorambiguouslydened[OyeandWellhausen,2009].They
pointoutthatthereisnoconsensusontheseissuesamongresearchersintheeldofsyntheticbiology,partlybecausethereisnoagreementontheextenttowhichprivate
ownershipisneededasanincentivetoinnovation.Intheshort-term,privatisationofIP
maybeimposedbytheinstitutionaldemandsoftheresearchers,butasapplications
of synthetic biology inareas such as energy and climate gain pace, international
pressuresmayencourageashifttoamorecommons-basedapproach.
Fornear-termapplications that resemble thosein current genetic engineering and
whichrequirelargeinvestmentstobringaproducttomarket,patentingseemslikely
topredominate.Andaspatentapplicationsintheeldofsyntheticbiologyarelikelyto
containclaimsforbiologicalmoleculesormicro-organisms,andformethodsofproducing
andapplyingthem,theywillbemostlyindistinguishablefromsimilarapplicationsin
otherareasofbiotechnology.Patentauthoritiesholdprimaryresponsibilityforensuring
The needs o theresearch communityor IP protectionar
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