Future Trends in Synthetic Biology—A Report - Frontiers

Synthetic Biology offers innovative approaches for engineering new biological systems or re-designing existing ones for useful purposes (see ... ThisarticleispartoftheResearchTopic 4thAppliedSyntheticBiologyinEurope Viewall 14 Articles Articles JeanMarieFrançois InstitutBiotechnologiquedeToulouse(INSA),France ChrisJ.Myers DepartmentofElectrical,ComputerandEnergyEngineering,CollegeofEngineeringandAppliedScience,UniversityofColoradoBoulder,UnitedStates VijaiSingh IndrashilUniversity,India Theeditorandreviewers'affiliationsarethelatestprovidedontheirLoopresearchprofilesandmaynotreflecttheirsituationatthetimeofreview. Abstract Introduction AdvancesinSyntheticBiology:TheStateofPlay TacklingtheChallenges TacklingRisk ConclusionsandRecommendations Author'sNote AuthorContributions ConflictofInterestStatement Acknowledgments References SuggestaResearchTopic> DownloadArticle DownloadPDF ReadCube EPUB XML(NLM) Supplementary Material Exportcitation EndNote ReferenceManager SimpleTEXTfile BibTex totalviews ViewArticleImpact SuggestaResearchTopic> SHAREON OpenSupplementalData PERSPECTIVEarticle Front.Bioeng.Biotechnol.,07August2019 |https://doi.org/10.3389/fbioe.2019.00175 FutureTrendsinSyntheticBiology—AReport MeriemElKaroui1*,MonicaHoyos-Flight2andLizFletcher1 1SynthSys-CentreforSyntheticandSystemsBiology,SchoolofBiologicalSciences,UniversityofEdinburgh,Edinburgh,UnitedKingdom 2InnogenInstitute,SchoolofSocialandPoliticalSciences,UniversityofEdinburgh,Edinburgh,UnitedKingdom LeadingresearchersworkingonsyntheticbiologyanditsapplicationsgatheredattheUniversityofEdinburghinMay2018todiscussthelatestchallengesandopportunitiesinthefield.Inadditiontothepotentialsocio-economicbenefitsofsyntheticbiology,theyalsoexaminedtheethicsandsecurityrisksarisingfromthedevelopmentofthesetechnologies.Speakersfromindustry,academiaandnot-for-profitorganizationspresentedtheirvisionforthefutureofthefieldandprovidedguidancetofundingandregulatorybodiestoensurethatsyntheticbiologyresearchiscarriedoutresponsiblyandcanrealizeitsfullpotential.Thisreportaimstocapturethecollectiveviewsandrecommendationsthatemergedfromthediscussionsthattookplace.ThemeetingwasheldundertheChathamHouseRule(i.e.,aprivateinvite-onlymeetingwherecommentscanbefreelyusedbutnotattributed)topromoteopendiscussion;thefindingsandquotesincludedinthereportarethereforenotattributedtoindividuals.Thegoalofthemeetingwastoidentifyresearchprioritiesandbottlenecks.Italsoprovidedtheopportunitytodiscusshowbesttomanageriskandearnpublicacceptanceofthisemerginganddisruptivetechnology. Introduction SyntheticBiologyoffersinnovativeapproachesforengineeringnewbiologicalsystemsorre-designingexistingonesforusefulpurposes(seeFigure1).Ithasbeendescribedasadisruptivetechnologyattheheartoftheso-calledBioeconomy,capableofdeliveringnewsolutionstoglobalhealthcare,agriculture,manufacturing,andenvironmentalchallenges(Cameronetal.,2014;BuesoandTangney,2017;French,2019).However,despitesuccessesintheproductionofsomehighvaluechemicalsanddrugs,thereisaperceptionthatsyntheticbiologyisstillnotyetdeliveringonitspromise. FIGURE1 Figure1.Syntheticbiologyisdevelopingintoabiodesignplatformwhereitwillbepossibletoapplythe“design-build-test-iterate(ordeploy)”topredictablycreatecellsororganismsabletoproduceawidevarietyofnovelmolecules,materialsorevencellsformultipleapplications. Moreover,therearesomeconcernsfromgovernmentsthatsyntheticbiologyexpandsthepoolofagentsofconcern,whichincreasestheneedtodevelopdetection,identificationandmonitoringsystems,andproactivelybuildcountermeasuresagainstchemicalandbiologicalthreats(WangandZhang,2019).Theparticipationofrepresentativesfromvariousgovernmentorganizationsatthismeetingistestamenttotheircommitmenttomaintaininganactivedialoguewiththesyntheticbiologycommunity.Inthisway,theyaimtokeepabreastofthechangingnatureofthreatsandprovidethebestadvicetogovernmentaboutinvestmentinscienceandtechnologyandtheintroductionoramendmentofregulatoryprocesses. ThecostofDNAsequencingandsynthesishavedecreaseddramatically(Carlson,2014;KosuriandChurch,2014)andwehaveaccesstomoregeneticinformationandmorepowerfulgeneticengineeringcapabilitiesthaneverbefore.Criticalinvestmentsininfrastructurearebearingfruitand,asisdescribedbelow,syntheticbiologyisincreasinglybecoming,atleastpartof,thesolutiontomanyofourpresentandfutureneedsinmedicine,foodandenergyproduction,remediation,manufacturing,andnationalsecurity.Sowhatisthepotentialofsyntheticbiologyandwhatchallengesdoesitstillfacetorealizethis? AdvancesinSyntheticBiology:TheStateofPlay SmallMolecules:ProductiononDemandaReality Despitethelackofpredictabilityinbiology,andcurrenttechnicalconstraintsthatlimitdatacollectionandanalyses,wecannowproducesmallmoleculesondemandusingsyntheticbiologyapproaches. ProbablythemostimpressiveexamplescomefromtheFoundryattheBroadInstituteofMITandHarvard.WhentheDefenseAdvancedResearchProjectsAgency(DARPA)puttheMIT-BroadInstituteFoundry'sdesigncapabilitiestothetest,itsresearcherswereabletodeliver6outof10moleculesofinteresttotheUSDepartmentofDefensein90days.This“pressuretest”confirmsthepotentialofsyntheticbiologytoaddressshortagesofkeycompoundsquickly(Casinietal.,2018). Indeed,manylabscannowdesignandconstructrelativelycomplexgenenetworkscapableofgeneratingawidevarietyof“designer”moleculesinarangeofhostcells;however,thisisoftenaslowiterativeprocessoftrialanderror. Asyet,veryfewsmallmoleculesinmedicinearemanufacturedusingasyntheticbiologyprocess;itremainsverydifficulttoengineermicrobestocarryoutprocessesthatNaturedidnotintend.Thisistobeexpected:theperformanceofmicrobesis“goodenough”fromanevolutionaryperspective.Microbesevolvedtoaddressthespecificneedsandchallengesoftheirnaturalenvironmentsnotthoseofindustrialfermentersandbioreactors.GeneTransferfromonesystemtoanothermaysoundeasybutinpracticeishardworkandrarelygeneratessufficientreward(i.e.,increasedyield)tojustifytheinvestmentmade.Theapplicationofautomationandartificialintelligence(e.g.,indesigningandbuildingplasmids)mayhelptoreducethetimeandcost—andimprovereturnoninvestment—inthefuture(Zhangetal.,2018). “Scaleupisproductspecific–weneedmoresyntheticbiologyintheproductionprocess” Plantsmakealternativeproductionplatforms.Improvementsinminingplantgenomesandthedevelopmentofeffectivetransientexpressionsystemshaveenabledlarge-scaleproductionof,forexample,vaccinesintobaccoplantsinjustafewweeks(Dirisalaetal.,2017;Emmanueletal.,2018).Directingtheproductionofsyntheticbiologicalmaterialstoplantchloroplastsalsoshowspromise(BoehmandBock,2019). Thephotosyntheticreducingpowergeneratedinplantchloroplastscanbeharnessedforthelight-drivensynthesisofbioactivemoleculessuchasdhurrin,whichprotectsplantsagainstinsects(Gnanasekaranetal.,2016). However,underlyingalltheseplatformsisaknowledgegapinourunderstandinginhownatureworks.Thismakesitveryhardtoapplythedesign/build/test/learncyclesusedinconventionalengineeringtotheproductionofsyntheticbiologicalmaterialswhatevertheproductionplatform(yeast,bacteria,plants,orhumancells)iftheplatformitselfisnotwell-understood(Sauroetal.,2006). Whatweneednowareinstrumentsabletomeasureandcharacterizeoutputs,assistedbyprogressinroboticsandautomation,andtheapplicationofmachinelearningapproachestoanalysethedatagenerated.Thiswillhelpustogeneratemorerobustmodelsofbiologicalsystems,sowecanimproveexperimentaldesignforfutureengineeringstrategies. “Wecando‘build’.‘Test’isthechallengewhenwewanttolearnfromtheiterativedesignprocess” Healthcare:ReimaginingMedicine Syntheticbiologyisdrivingsignificantadvancesinbiomedicine,whichwillleadtotransformationalimprovementsinhealthcare.Already,patientsarebenefitingfromso-calledCAR(forchimericantigenreceptor)technology,whichengineerstheimmunecells(T-cells)ofthepatienttorecognizeandattackcancercells(Juneetal.,2018). GeneticallyengineeredvirusesarebeingusedtocorrectdefectivegenesinpatientswithinheriteddiseasessuchasSevereCombinedImmuneDeficiency(SCID)orepidermolysisbullosa(Dunbaretal.,2018). Theabilitytoreprogrammesomaticcellsfrompatientsintoinducedpluripotentstemcellsisfurtheringourunderstandingoftheirdisease,reducingtheuseofanimalsinresearch,andpavingthewayforthedevelopmentofpersonalizedmedicinesandcelltherapies.Inprincipleatleast,wecouldengineerapatient'sowncellstomultiply,differentiateintodifferentcelltypesandevenself-assembleintonewtissues,orevenorgans,torepairthosedamagedthroughdiseaseorinjury(DaviesandCachat,2016;Satoshietal.,2018). Workonnewvectorsthatareabletodeliverlargegeneticloadstotargettissuesishelpingtoproducemoreefficienttherapeuticsandvaccinesthatwillhavefewersideeffectsandasmallerriskofresistance.Furthermore,optimizingantibodyorvaccineproduction,orexample,sothattheyareinanedibleformat(e.g.,plantbased),couldgreatlyreducethecostandincreasethespeedofvaccineproductioninanepidemic. “Wehavethetoolsbutneedthecreativitytomakestuffthatcan'tbemadewithoutsyntheticbiology” Inthenextfewyears,geneticallyengineeringpigstobevirusresistantandhavehuman-likeimmuneprofilescouldmakexenotransplantationaclinicalreality(Burkardetal.,2018).Engineeringthemicrobiomeisexpectedtoleadtothedevelopmentofsyntheticprobiotics(DouandBennett,2018). ThesyntheticbiologyinitiativeknownasHumanGenomeProject-write(HGP-write)hassetitssightsevenhigher,rallyingscientiststobuildentirehumanchromosomes(Boekeetal.,2016).Concernshavebeenraisedabouttheethicsofcreating“synthetichumans”andindeedthescientificandcommercialvalueofsuchaproject.Morerecently,HGP-writechampionshaveproposedamorefocusedprojecttobuildavirus-resistantchromosome,makingatleast400,000changestothehumangenometoremoveDNAsequencesthatvirusesusetohijackcellsandreplicate(Dolgin,2018). Oneofthemanyexcitingopportunitiesthatsyntheticbiologyoffersmedicineisintheproductionoftheranosticcelllinesthatcansenseadiseasestateandproduceanappropriatetherapeuticresponse(TeixeiraandFussenegger,2019).Severalobstaclesneedtobeovercometoachievethisgoal:first,toexpandtherangeofmoleculesthatcanberecognizedbycellular“sensors”asinputs;andsecond,tobetterunderstandthegeneticcontrolfactorsthatregulategeneexpressioninspaceandtimesowecanengineerbetteractivatorsystems. “Atpresentweneedpillsbecausewecan'tswallowachemistrykit” Metabolomicsissheddinglightonmanydiseasebiomarkers.Becausesomebiomarkersaresharedbetweenseeminglyunrelateddiseases,anaccuratediagnosiswillrequirethedetectionofmultiplemarkerstoprovideamoreunique“diseasefingerprint.”Workinwholecellandcellfreesystemstodevelopsensorsofmultipledisease-specificbiomarkerscouldassistinearlierdetectionofdiseaseandprognosticmonitoring. Toexpandtherangeofbiologicallydetectablemolecules,itispossibletodesignmetabolicpathwaysthattransformcurrentlyundetectablemoleculesofinterest(e.g.,hippuricacid,theprostatecancerbiomarker)intomoleculesforwhichsensorsalreadyexist(inthiscasebenzoicacid)(Libisetal.,2016). Cybergeneticsisanemergingfieldthatisdevelopingexperimentaltoolsforthecomputercontrolofcellularprocessesatthegenelevelinrealtime.Cybergeneticcontrolcanbeachievedbyinterfacinglivingcellswithadigitalcomputerthatswitchesonorofftheembedded“geneticswitch”usinglight(optogenetics)orchemicals(Gabrieleetal.,2018;Maysametal.,2019).Suchsystemscouldhelptomaintaincellularhomeostasisbymonitoringthestateofthebodyandtriggeringanappropriateresponseuponthedetectionofdysregulation;forexample,theycouldtriggerthereleaseofinsulinwhenbloodglucoselevelsriseasdetectedbyawirelessdiagnostictool(Yeetal.,2011). AdvancedMaterials:InspiredbyNature,ImprovedbySyntheticBiology Syntheticbiologyofferstheopportunitytocreateresponsiveandmultifunctionalmaterials(LeFeuvreandScrutton,2018).Theintegrationofbiochemicalcomponentsfromlivingsystemswithinorganiccomponentscanleadtonewmaterialsthatareabletosensetheenvironment(orinternalsignals)andchangetheirproperties.Thesefeaturescouldbeparticularlyusefulforimprovingprotectiveclothingorbuildingmaterials. Anissuewhenusingmicrobestoproducecompositematerialsisregulatingtheassemblyofthesematerialstoachievespecificdesiredproperties.Byunderstandinghowmicrobescommunicatewitheachother,itispossibletomakethemworkbettertogetherandcombinethemwithotherproductionsystemssothatthepropertiesofmaterialscanbetailoredforparticularfunctions. Interestingly,ratherthanmodifying,orimprovingexistingprotein-basedmaterials,analternativeapproachinvolvesusingcomputationaltechniquestodesigncompletelynovelproteinsthatself-assembleintopredictedshapes(Ljubetičetal.,2017).Such“programmable”proteinsopenupevenfurtheropportunitiesforsyntheticbiologynotonlyformaterialssciencebutalsoformedicineandchemistry. “Thetoolsarethere,wejustdon'tknowwhatwewanttomake” TacklingtheChallenges Regardlessoftheresearchareasinvolved,therearesomecommonchallengesforthecommunitytoaddress. DesignWiththeEndinMind Therewasconsensusthatwhiletheproductionofsmallmoleculesusingsyntheticallyengineeredcellsatthebenchisbecomingmoretractable,theseprocessesoftendonottranslatewellintomassproduction.Scalabilityneedstobeincorporatedintotheinitialdesignprocessbyincludingfeatures,forexample,thatreducetoxicityofthemoleculetotheproductionhostor“chassis”and/orbyintroducingmodificationsthatfavoritsextraction.Carefulconsiderationoftherightchassiscouldalsogreatlyimproveyieldsandsignificantlyreducecostofproduction. “Naturehasdevelopeditsownwaystoconcentrateandsolubilisechemicals…wearenotlearningfromthis” ExpandingtheHostRepertoire ThenumberofmicrobesthatarecurrentlyinusefortheproductionofsyntheticbiologicalmaterialsisonlyatinyfractionofthetotaldiversitythatexistsinNature;onlytenmicrobesare“domesticated”forindustrialuse.Toidentifythemostappropriatechassis,itisworthturningtonaturetoidentifyspeciesthathaveuniquemetabolicnetworkssuitedtohostparticulartypesofchemicalreactions.Forexample,thesoilbacteriumPseudomonasputida,whichhasadaptedtoharshenvironmentalconditions,isideallysuitedtohostredox-intensivereactions(PabloanddeLorenzo,2018).Atreasuretroveof,asyet,unexplorednaturalproducts,withnovelandbeneficialproperties,existintheplantkingdom.Inaddition,asnotedabove,plantsarenaturallyexcellentproductionhostsanditisnowpossibleto“plugandplay”combinationsofplantpathwaystogeneratenovelmolecules(SainsburyandLomonossoff,2014;EvangelosandO'connor,2016). DevelopingaUniversalProductionSystem Tocircumventtheproblemoftheimpactofdifferenthostchassisonsyntheticgenecircuits,researcherswouldbenefitfromauniversalsyntheticexpressionsystemthatpermitsthetestingofnewconstructs.Thiswouldaidintheidentificationofoptimalproductionplatformsanddecreasetheneedfororganism-specifictechnologies.CombiningthistechnologywithDNAeditingtechniques,suchasCRISPR/Cas9,willmaketheestablishmentofhostproductionplatformsandthegenerationofcomplexbiosyntheticproductseasierandfaster.Onearticulationofthiscouldbeincell-freeformats,inwhichtheessentialcellularmachineryisreconstitutedinvitroandusedasamanufacturingplatform(VillarrealandTan,2017;Kochetal.,2018). “Weneedtoreducetheburdenofsyntheticnetworksonendogenouscircuits” MovetoCell-FreeEnvironments Cell-freeenvironments,interfacedwithsemiconductors,offerapowerfulrouteforflexibleandcontrollableproductionsystems. Forexample,nanoparticlesmadeofsemiconductormaterialsorquantumdotscanbeusedtoenhanceenzymeactivityinacellfreeenvironmentwithaminimalsetofingredients.Multistepenzymaticpathwayscanbetetheredtonanoparticlesurfacesand,byavoidingthediffusioneffectthattakesplaceincells,reactionratescanbeincreased100-fold(Wangetal.,2017).Thisapproachcanbeusedtoaccessnon-naturalmaterialsandcircumventsthepotentialissueoftoxicityincells(aswellastheregulatoryissuesofgeneticallymodifiedcells). Researchonsiliconchipscontainingimmobilizedgenesandcelllysatesallowsdetailedexaminationofgeneexpressioninspaceandtime.WhenthecompartmentsinwhichDNA-drivenreactionstakeplacearelinked,withmaterialsflowingintoanddiffusingbetweenthecompartments,itispossibletorecreateoscillatingproteinexpressionpatternsandproteingradientsakintothoseobservedincells(Karzbrunetal.,2014).Geneexpressioninthese“artificialcells”canbecontrolledwithelectrodesthatpreventtheassemblyofproteinsbyribosomes.Bystandardizingoutputs,thisstrategyisimprovingthepredictabilityofengineeredgeneticcircuits. SystemsModeling,Standards,andMetrology Whateverthesystembeingexplored,arobustmodelofthatbiologicalsystemisneededifpredictablemodificationsofgeneticcircuitsaretobedesignedandimplementedwithanyconfidence.Tocreatesuchmodels,largesetsofdataarisingfrommeasuringmultipleparametersofcellbehaviorunderdifferentconditionsareessential(Fletcheretal.,2016). Thereisgreatexpectationthatimprovementsinhigh-throughputdatameasurementandcollectionsystemswillgenerateexactlythelargedatasetsneeded.Thesecanbeanalyzedusingartificialintelligenceoramachinelearningapproachtooptimizethedesignofsyntheticbiologicalproductsandmoveawayfromtheinefficienttrialanderrorprocess(Decoeneetal.,2018). Finally,agreementonstandardsofdesign,assembly,datatransfer,datameasurementandregulatoryrules,aswellasonthelanguagethatisused,willhelptoimprovetheinterdisciplinaryandinternationalcollaborationsthatarerequiredtodrivethefieldforward.Thisischallengingforacommunitywithsuchdiverseinterestsandperspectives,andwheredatasharing,curatingandqualitycontrolisnotcommonpractice. However,withoutsomeformofagreedstandards,manyoftheproductsandprocessesofsyntheticbiologywillnottranslatewelltoindustrialsettingsdependentonreproducibleprocessesandbeholdentoexactingregulatoryrequirements. Typically,academicresearchersaredrivenbyaneedtounderstandthecomplexityofnature(andpublishtheirworkinhighimpactjournals).Standardizationandscalingupproductionareimportant,buthavelessofanacademicpullthandiscoveringanewproduct.Accesstofunding,industrialpartnerships,andacademicrecognitionareexamplesofpotentialincentivesforcarryingoutthistypeofresearch. “Standardsrestrictflexibilitybutenableinteroperability” TacklingRisk Syntheticbiologyisanexampleofadual-usetechnology:itpromisesnumerousbeneficialapplications,butitcanalsocauseharm.Thishasledtofearsthatitcould,intentionallyorunintentionally,harmhumansordamagetheenvironment.Forexample,thereishugevalueinourabilitytoengineervirusestobemoreeffectiveandspecificshuttlesforgenetherapiesofdevastatinginheriteddisorders;however,engineeringvirusesmayalsoleadtothecreationofevenmoredeadlypathogensbythoseintentonharm. “Syntheticbiologyshouldberegardedasanextensionofearlierdevelopmentsandtechnologies” Somewouldarguethatsyntheticbiologyposesanexistentialriskandneedstobetreatedwithextremecaution.However,manynewtechnologicaladvancesacrossthedecadeshavemetsimilarconcerns.Theuncertaintyandremotepossibilityofsuchriskscouldhamperthedevelopmentofusefultechnology.Scientists,theirhostinstitutionsandfundingbodiesshould(andindeedalreadydo)considerwhethertheresearchplannedcouldbemisused.Measuresthatreducethelikelihoodofmisuseanditsconsequencesshouldbeimplementedandclearlycommunicated.Thesyntheticbiologycommunityneedstobeawareof,andrespondto,thesechallengesbyengaginginhorizonscanningexercisesaswellasopendialoguewithregulatorybodiesandthemedia. “Don'tavoidrisk–manageit” Beingmoreopenaboutrisks,andhowtheyarecontrolled,providesanopportunitytoshiftdiscoursetowardthebenefitsofsyntheticbiologyinaddressingurgentglobalneeds,suchastheproductionofbiofuels,foodsecurityandmoreeffectivemedicines,andpotentiallyimprovepublicacceptance. “Thequestionsshouldnotbe‘what’sthenextbigthingforsyntheticbiology'but‘whereisthegreatestunmetneed’.” Despitetheeffortsbyindividualcountriestoestablishsyntheticbiologyresearchroadmaps,broader,internationalagreementoncommonstandards(andredlines)acrossthefieldmayhelpestablishtrustandtoadvancethebestpre-competitiveresearchintousefulapplications. Meetingparticipantshighlightedtheimportanceoftraininginresponsibleresearchconductandethics.Givenstudents'futureroleasscienceambassadorsandinfluencers,theirtrainingshouldnotonlyconveyskillsandknowledgebutalsoawarenessandcriticalthinkingabouttheprospectsandpotentialfordualuseofsyntheticbiology.Allresearchersmustremainvigilantregardlessofthemanypressuresanddistractionsofrunningasuccessfulresearchlab;theymaynothavespecialisttraininginidentifyingtherisksofmisusebuttheyarethepeoplebestplacedtomaintaininformedoversightofrisks. Oneexampleofcurrentsyntheticbiologyresearchwithpotentialdualuseisgenedrivetechnology,whichcanbeusedtopropagateaparticularsuiteofgenesthroughoutapopulation.Thebenefitsofusinggenedrivetechnologyincludetheeradicationofdisease-carryinginsectpopulationsandtheeliminationofinvadingpestspeciesbutithasraisedconcernsabouttheunintendedecologicalimpactsofreducingoreliminatingapopulation(Callaway,2018;Collins,2018). Similarreleaseconcernssurroundresearchthatisharnessingtheabilityofpathogenstotargetparticulartissuesinthebodyorparticularchemicalsintheenvironment,whichcouldgreatlyaideffortstodelivertargetedtherapiesorclean-upcontaminatedsites.Todate,suchlarge-scalereleaseforenvironmentalbioremediationinterventionshasnotbeenpossible. “WeneedtomindthegapbetweenR&Dscaleupandcommunications….Onebadblogcankillacommercialproduct” Therewasconsensusthattheneedforregulationoverthiscommunityremainsimportant.Regulationneedstokeepuptospeedwiththeemergingtechnologiesandshouldfocusontheproductratherthantheprocessusedtocreateit(Taitetal.,2017).Unsuitableregulatoryframeworks(aswellasunfavorablepublicperception)coulddiscourageprivatesectorinvestmentinsyntheticbiology. Openandbalancedtwo-waycommunicationbetweenresearchers,funders,companiesandgovernmentsandthepublicwillbevital.Consumersandactivistsmayhavenointerestinthedifferencebetweenmakingachemical(e.g.,aflavororfragrance)syntheticallyandonemadeusinggeneticallymodifiedbacteriabuttheymayinstinctivelydistrustthelatter. ConclusionsandRecommendations Theshorttalkspresentedatthis2-daymeetingsuggestthatsyntheticbiologyisatthecuspofmanymajorbreakthroughsandthatitisperhapstimelytore-definethemeaningof“success”insyntheticbiology. Therearemanyhurdlestoovercomebutthepotentialforsyntheticbiologytodeliversolutionstomanyglobalchallenges—improvinghealthcare,limitingenvironmentaldamage,andcreatingawidevarietyofmoresustainableprocesses—isgreat. Meetingparticipantssuggestedthatasacommunitytheyshouldsupportthemeasureslistedbelowtohelpsyntheticbiologymovebeyondtheproof-of-conceptstageandtoensurethatpotentialrisksareminimizedanddialogwiththepubliccanbeoptimized. •Largerandlongerinvestmentinbetterbigdatamanagementandprocessing(ArtificialIntelligenceandMachineLearning)systems,andinfundamentalresearchonbiosystemsmodeling,chassisdevelopment,andgenomemining. •Supportstandardizationinitiatives;whilearguablynotattractiveacademically,thecommunityneedstoagreeandsupporteffortstowardcreatinginteroperabilityaroundbiosystemmodeling,andstandardsaroundDNAdesign(ifnotDNAbioparts).Withoutsomedegreeof“standardization”theabilitytopooldataandmodels,essentialforimprovingaccuracyandreproducibility,willbechallenging. •Thecreationandfunding(ideallyinternationally)ofa“GrandChallenge,”suchasthedevelopmentofgenericsensorsorthecreationofprotein-basedelectroniccomponents,couldhelpfocusthecommunitytowardatargetgoal. •Improvetheassessment,communication,andmanagementofriskandharmamongallaudiences. •EnsurethatearlycareerresearchersaretrainedinresponsibleresearchconductandethicsaswellasbeingcognizantofexistingrulesandregulationsaroundGM(regionallydependent)andtheissueofmisuseandharm. •Coordinatetheeffortsofacademia,governmentandindustrythroughfocusedmeetingsthatfosterinterdisciplinarycollaborationsaroundsharedobjectives. •Improveplatformsforknowledgesharingandrecognizethevalueoffailures. TheworkshophighlightedjusthowmuchmorewehavetolearnfromNatureitself.Syntheticbiologyisgivingusinsightsofthecriteriaandprocessesthatunderpinalllivingsystems;inturn,wecantakethisinsightanddesignanduseittobuilda“betterbiology.”However,weneedtotakethepublicwithusonthisjourney,createmeaningfulandconsidereddialogueabouttheworkwemaydoandtheimpactitmighthaveonourworld. Author'sNote ThemeetingwashostedbytheUKCenterforMammalianSyntheticBiology(theCenter),basedattheUniversityofEdinburgh.TheCenterisbuildingexpertiseincellengineeringtoolgeneration,whole-cellmodeling,computer-assisteddesignandconstructionofDNAandhigh-throughputphenotypingtoenablesyntheticbiologyformedicineandhealthcare.TheCentre'sresearchwillnotonlyadvancebasicunderstandingofmammalianbiologyandpathologybutalsogenerateproductsandservicesfornear-termcommercialexploitationbythepharmaceuticalanddrugtestingindustries,suchasdiagnostics,noveltherapeutics,protein-baseddrugs,andregenerativemedicines.TheCenterisfundedthroughtheResearchCouncil'sUK“SyntheticBiologyforGrowth”programmeandbytheBiologicalandBiotechnologySciencesResearchCouncil(BBSRC),theEngineeringandPhysicalSciencesResearchCouncilandtheMedicalResearchCouncil. AuthorContributions ThisisameetingreportandwasdraftedbyMH-FwithsupportfromMEandLF. ConflictofInterestStatement Theauthorsdeclarethattheresearchwasconductedintheabsenceofanycommercialorfinancialrelationshipsthatcouldbeconstruedasapotentialconflictofinterest. Acknowledgments WearegratefultoallcolleaguesthatcontributedtodiscussionsattheworkshopheldinEdinburghinMay2018andwhoseviewshelpedinformthisreport.WealsogratefullyacknowledgesponsorshipforthisworkshopfromtheOfficeofNavalResearchGlobalandtheUKCentreforMammalianSyntheticBiology(BBSRCGrantBB/M018040/1). 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Keywords:syntheticbiology,biosystem,futuretrendsanddevelopments,biodesignautomation,responsibleresearchandinnovation(RRI) Citation:ElKarouiM,Hoyos-FlightMandFletcherL(2019)FutureTrendsinSyntheticBiology—AReport.Front.Bioeng.Biotechnol.7:175.doi:10.3389/fbioe.2019.00175 Received:28May2019;Accepted:08July2019;Published:07August2019. Editedby:JeanMarieFrançois,UMR5504Laboratoired'IngénieriedesSystèmesBiologiquesetdesProcédés(LISBP),France Reviewedby:VijaiSingh,IndrashilUniversity,IndiaChrisJohnMyers,TheUniversityofUtah,UnitedStates Copyright©2019ElKaroui,Hoyos-FlightandFletcher.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense(CCBY).Theuse,distributionorreproductioninotherforumsispermitted,providedtheoriginalauthor(s)andthecopyrightowner(s)arecreditedandthattheoriginalpublicationinthisjournaliscited,inaccordancewithacceptedacademicpractice.Nouse,distributionorreproductionispermittedwhichdoesnotcomplywiththeseterms. *Correspondence:MeriemElKaroui,[email protected] COMMENTARY ORIGINALARTICLE Peoplealsolookedat SuggestaResearchTopic>