irgc sb final 07jan web

8/2/2019 Irgc SB Final 07jan Web

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Policy Brie

international risk governance council

Guidelines for the Appropriate

Risk Governance ofSynthetic Biology


2/52international risk governance council Guidelines for the Appropriate Risk Governance of Synthetic 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:


3/52international risk governance councilGuidelines or the Appropriate Risk Governance o Synthetic Biology

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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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4/52international risk governance council Guidelines or the Appropriate Risk Governance o Synthetic Biology

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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



P 16

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



P 17

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



P 18

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



P 19

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



P 20

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



P 21

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



P 22

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



P 23

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



P 24

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



P 25

(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.



P 26

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



P 27

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



P 28

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



P 29

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


30/52


31/52international risk governance councilGuidelines for the Appropriate Risk Governance of Synthetic Biology

P 31

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



P 32

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



P 33

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

irgc sb final 07jan web

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