(Re)EngineeringBiologyAbstracts
April15-16,2016
CenterforPhilosophyofScience
Non-traditionalEngineeringofDesiredWeakEmergentPropertiesofSyntheticCells
MarkA.Bedau
Variouskindsofsyntheticcellsareproducedinsyntheticbiology.Top-downsynthetic
biologygeneticallymodifiessimplenaturalcellularlifeformstomake(partly)synthetic
cells.Bottom-upsyntheticbiologyusesnonlivingmaterialstomakesyntheticprotocells.
Bothformsofsyntheticbiologyengineersyntheticcellssothattheyhavecertaindesired
globalproperties.Thosepropertiesaretypicallyproducedbyverycomplexcausalwebs,
andsomecallthem“weak”emergentproperties(Bedau1997).Syntheticbiologyusesmany
methodsadaptedfromtraditionalengineeringtocreatedesiredemergentproperties,
includingEdisoniantrialanderror(Martinetal.2003),standardizedgeneticcomponents
(Mutaliketal.2013a,b),genomerefactoring(Temmeetal.2012),andsyntheticgenomes
(Gibsonetal.2010).Butitusesengineeringmethodsthatarenon-traditional.Onenontraditionalmethodisinvitro(directed)evolution,whichproducesdesiredgeneticmaterial
throughanartificialevolutionaryprocess(e.g.,Yokobayashietal.2002).Othermethods
applytoolsfromcontemporarymachinelearning(Cascheraetal.2011),andsimilarnontraditionalmethodscouldbeadaptedtosystemsbiologyandbio-medicalengineering.Both
methodsareespeciallyusefulforengineeringdesiredweakemergentproperties,becauseof
thecomplexcausalwebsunderlyingtheseproperties.Thenon-traditionalmethodsexplain
thecentralroleofsynthesisinsyntheticbiology.
WhyPhytobricks?:Howsyntheticbiologistsareengineeringplants
DominicBerry
Themajorityoflaboratoryworkwithinsyntheticbiologyhasbeendirectedtowardssinglecelledorganisms,butfromtheoutsetsynbiohaspromisedtorevolutionisethe
manipulationanddesignofmorecomplexorganisms.Inrecentyearseffortshavebeen
madetointegrateacadreofplantscientists,andthemostconspicuousaspectofthiswork
istheintroductionofanewiGEMtrackdedicatedentirelytoplantsyntheticbiology,which
willbelaunchedintimeforthe2016jamboree.TheiGEM(InternationalGenetically
EngineeredMachine)competitionisaninternationalstudentcompetitionthathasrun
annuallysince2003.Thegrowthofthelatter,whichtodayinvolvesthousandsofstudents
andhundredsofinstitutions,andtheintegrationofmorecomplexorganisms,aretakento
demonstratesynbio'sflourishing.
However,atthesametimeasplantscienceisbeingintegratedintosynbio,thereisalso
evidencethatplantscientistsaremaintainingadistinctidentityforthemselveswithin
syntheticbiology.Basedoninterviewswiththosescientistsresponsibleforcreatingthe
plantiGEMtrack,andlaboratoryobservationsofplantsynbioinpractice,thispaperis
dedicatedtoansweringthequestion:inafieldinspiredbyengineeringidealssuchas
modularityandorthogonality,whyPhytobricks?
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TheSyntheticMethodbetweenEngineeringandScience:Anewparadigmforthescientific
explorationofthefrontiersoflife?
LeonardoBichandLuisaDamiano
Thistalkwillfocusonthesyntheticmethod,anemergingapproachatthecrossroads
betweenengineeringandsciencethatdevelopspioneeringinsightsfromorganizational
biology,cyberneticsandsystemstheory.Thespecificityofthismethod,basedontheideaof
‘understandingbybuilding’,isthatitdirectlyinvolvesengineeringintothescientific
comprehensionofbiologicalprocessesthroughtheconstructionof‘syntheticmodels’:
‘functioningartefacts’thatincorporatescientifichypothesestoproducethephenomena
underinquiry,andcanbeusedasmeanstotesttheunderlyingtheories.
Inthispresentationwewillmarkoutthetheoretical,epistemologicalandmethodological
featuresofthisapproach,illustratinghowitcanbeconsideredcapabletogenerateanew
researchparadigmforbiology:newmethodologicalproceduresassociatedtonew
theoreticalandepistemologicalframeworks.Wewillsupportouranalysisbyfocusingon
casestudiesfromresearchonminimallife,i.e.,currentstudiesoncompartmentsinvolving
differentformsofsyntheticmodelling.Themaingoalsaretwo:
-Toidentifylimitsandpossibilitiesoftheseapplicationsofthesyntheticmethodthrough
comparisonswithothermethodologicalapproachesintegratingengineeringintobiology;
-Toestablishwhetherinthiscontextwecantalkofanewandpluralistresearchparadigm,
oratransitiontowardsit.
AnEngineeringParadigm:Whoseparadigm?
MiekeBoon
Astheorganizersofthisconferencesuggests,therearegoodreasonstotalkaboutan
engineeringparadigm,ratherthanconsideringthelife-sciencesasfundamentallydifferent
tootherexperimentalsciencesastheybringengineeringapproachestobiology.Inthis
paper,Iwillfocusontheparadigmofsciencemaintainedbyphilosophers.Thisparadigm
determineswhichproblems,ideas,approachesandanswersareconsideredrelevantand
adequateinthephilosophyofscience.Indeed,theshifttowardsanengineeringparadigmis
obviousfromchangesofconceptsemployedbyphilosopherswhentheytalkaboutthelife
sciences.Therecognitionbyphilosophersthatscientificpracticessuchasthelifesciences
incorporateengineeringapproaches,hasseveralofthetypicalcharacteristicsofachanging
paradigm.Thispaperaimstoanalyzethecontentandappropriatenessoftheemerging
engineeringparadigm,focusingontypicalKuhnianaspectssuchas:ontological
presuppositionsonthegeneralsubject-matterstudiedinexperimentalsciences;
fundamentalepistemologicalvalues;normativeideasontheaimsofscience;assumptions
onthecharacterofscientificknowledge;andparadigmexamplesofscience.Itwillbe
defendedthat,inmanycases,theengineeringparadigmismoreappropriatefor
understandingbothcontemporaryandhistoricalscientificpractices.
NatureasaToolbox:ANewLookattheConceptofLevelsofOrganization
DanielBrooks
Despiteitspervasiveness,theconceptof‘levelsoforganization’hasreceivedlittleattention
initsownright.InthispresentationIwillarguethat,contrarytorecentclaimsofits
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uselessness,the'levels'conceptcaneasilyberevealedasauniquelyeffectiveandflexible
conceptualtooltailoredtoperformawidehostofscientifictasks.Indeed,farfromany
reified“layer-cake”image,'levels'asdepictedinactualscientificusagearguablyrepresents
natureitselfasatoolbox,fromwhichscientistsarefreetoselectthepartswithwhichto
constructtheirsolutionstotheproblemstheyengageintheirinvestigations.
Thekeytothisapproachwillbeausage-basedreconstructionof'levels’thatrevealsa
fragmentaryconceptthatbalancesastrikingvariationinconceptualcontentbetween
instancesofusewitharemarkablyconservedandunifyingsignificanceattributedtoit
acrosstheseinstances.Thissignificance,capturedbythe“epistemicgoal”motivatingits
usage,isitsabilitytostructureexplanatoryproblems.Thisheuristic,usage-basedtreatment
oflevelsdoesnotdiminishtheconcept'sgeneralimportancetoscience,butratherallows
foritsusein,andusefulnessfor,scientificpracticetobebettercontextualizedtoparticular
tasksencompassingvaryingbreadthsofactivity.
CrashTestinganEngineeringFrameworkinNeuroscience:WhenDoestheIdeaof
RobustnessBreakDown?
MazviitaChirimuuta
InthispaperIdiscusstheconceptofrobustnessinneuroscience.SystemsbiologistKitano
(2004)definesrobustnessas,“apropertythatallowsasystemtomaintainitsfunctions
againstinternalandexternalperturbations.”Thus,inordertodeterminewhetherornota
systemisrobust,onemustspecifyitsfunction,andalsospecifythekindsofperturbationit
faces.Variousmeansformakingsystemsrobusthavebeendiscussedacrossbiologyand
neuroscience(e.g.copyredundancyandfail-safes).Itisobvious,butstillworth
emphasising,thatmanyofthesenotionsoriginatefromengineering.
Iwillarguethattheframeworkborrowedfromengineeringaidsneuroscientistsin(1)
operationalizingrobustness;(2)formulatinghypothesesabouthowthesystemachieves
robustness;and(3)showinghowrobustnessmaybepreciselyquantified.Furthermore,I
willarguethattheuseoftheengineeringframeworkinneurosciencegetsstretched,
perhapstobreakingpoint,whenappliedtosystemswhere(1)thereisnoprincipled
distinctionbetweenprocessesforrobustnessandprocesseswhichcontinuallymaintainthe
lifeofthecell;(2)whereperturbationsarearegularoccurrenceratherthananomalous
events;and(3)whereoneshouldnotconceiveofthesystemasseekingtomaintainasteady
state(O’Learyetal).
ReprogrammingandtheRepressilator
MelindaFagan
Syntheticbiologyistoutedbyproponentsasanovelapproachtostudyinglife.However,
somephilosophershavenotedsignificantcontinuitieswithexperimentalbiology(O’Malley
2009,Bechtel2011,KnuutilaandLoettgers2013).Thispaperbuildsontheirargumentsby
comparinganexemplarofsyntheticbiology,theRepressilator,toinducedpluripotentstem
celllines(iPSC)producedby“directreprogramming”–atraditionalexperimentalmethod.
Thisfocusedcomparisonexhibitssignificantcontinuitiesbetweensyntheticand
experimentalbiology.Thetwocasesinvolveverysimilaraims,biologicalmaterials,‘wet’
experimentalmethods,andresults.BoththeRepressilatorandreprogrammediPSCare
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engineeredsystemsconsistingofgeneticregulatorynetworksconstructedandinsertedinto
culturedcells,whichinducechangesincellphenotype.
Thesemethodologicalparallelsundercutthedistinctionbetweensyntheticandtraditional
biologyintermsof“forward-andreverse-engineering.”However,therearesomeimportant
differencesbetweenthetwocases.TheRepressilatorandcellreprogramming,Iargue,
differwithrespectto(i)thesourceoftranscriptionnetworkorganization,and(ii)theroles
ofpre-defined‘programs’inconstructingthesystemandgeneratingresults.Idiscusssome
broaderimplicationsoftheseresults,withemphasisonthesocialorganizationof
‘engineeringbiosciences.’
CrosscuttingBiologyandEngineeringviaFractals
LuisFavela
Fractalsareapotentiallyrichsourceoftheoriesandmethodsthatcanfacilitate
interdisciplinaryworkamongbiologistsandengineers.Fractalsarescale-free,self-similar
structures,wherebytheglobalstructureismaintainedatvariousscalesofspatialand
temporalobservation.Fractalmethodscanmathematicallyrevealstructureinvariability
thatisoftendisregardedasnoiseor“averagedaway”bytraditionallinearandadditive
statisticalanalyses.Assuch,phenomenacanbemisrepresentedifoutliersaretrimmedor
areunderstoodsolelyintermsoftheaverageofitsfeatures.Fractalanalysesare,atleastin
somecases,bettersuitedtocapturephenomenathatdonotconformtoGaussian
distributions.Engineershaveappliedfractalanalysestoworkonantennasignals,forceon
chainsandtheireffectonmaterials,Internettraffic,andurbanstructureplanning.
Biologistshaveappliedfractalanalysestoresearchontreeandbronchialtubebranching,
neurondendrites,breathing,andheartbeats.Asisevidentbythisbrieflistofexamples,
fractalconceptsandmethodsaresubstrateneutralandcanfacilitateunderstanding
regardlessofthematerialcompositionorcausalmechanismsrelatedtoaphenomenon.
Thesebenefitsmakefractalsagoodcontenderforfacilitatinginterdisciplinaryworkamong
biologistsandengineers.
ReconcilingSpecialtiesofEngineeringandBiology
ElihuGersonandAlokSrivastava
Participationofmultiplespecialtiesinasingleprojectraisespotentialproblemsof
cooperationthatmustbereconcilediftheprojectistocontinue.Participatingspecialties
facetrade-offsposedbytheneedtoaccommodateothers.Understandingthereconciliation
processinageneralwayrequiresdevelopingmeansforanalyzingthesetrade-offsthatare
notlimitedtoparticularcontexts.Wesuggesttwodimensionsofsuchcontexts.The
explicationspectrumliststhephasesaresearchprojectmightenteroverthecourseofits
life.Thetranslationspectrummarksthedistinctionsseparatingbasicresearchresultsfrom
productsorservicesingeneraluse.
Understandingthewaysinwhichdifferentspecialtiesinfluenceoneanotherdependsonthe
waysthatresearchersnegotiateandrevisetheirownapproachesastheylearnthelimits,
requirements,andpotentialofcomplementaryapproaches.Researchersemploymany
tacticstoaligntheirpositionsontheexplicationandtranslationdimensions.Twokindsof
reconciliationtacticseemtobeespeciallycommon:developingappropriatestandardsand
creatingcoordinationmechanisms.Thereconciliationtacticsusedareimprovedovertime,
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sothatjointresearchbecomesbetterintegratedandmorereliable.Weillustrateour
approachwithexamplesofstandardizationprocessesandcoordinationmechanismsdrawn
fromvariousintersectionsofbiologyandengineering.
TheMultifacetedPotentialofAffordance-basedReverseEngineeringinBiology
DominicHalsmer
Theconceptsofreverseengineeringandaffordanceshavebeencombinedtoproducea
fruitfulsynergywiththepotentialforadvancingsystemsbiology.Theideaofaffordances
hasfoundutility,notonlyindesignengineering,butalsoinaffordance-basedreverse
engineering(ARE).Inthiscontext,anaffordanceissomethingthatisprovidedtotheend
userofanengineereddevice,byvirtueofsomerelationshipbetweentheuserandthe
device.Inmorecomplexsystems,thisisextendedtoincludearelationshipbetweenpartsof
asystemthatplayaroleinultimatelyprovidingacapabilitytotheenduser.Thesepart-topartaffordancesarecriticalinanalyzingthedepthoffunctionalitythatcharacterizes
biologicalsystems,especiallyatthemicroscopiclevel.Researchersinevolutionarybiology
havealsofoundtheconceptofaffordancetobehelpfulinunderstandingtheevolutionary
process.Affordancescanassistinclarifyingtheprocessofnicheconstruction.Hence,it
seemsclearthatAREhasthepotentialtocontributeatboththemicroscopicand
macroscopiclevels.Furthermore,affordancesmerelyprovideastatementofcapabilitythat
persistsbecauseofkeybiologicalrelationships.Thus,itismetaphysicallyneutral,andas
such,moreinkeepingwiththeconcernsandlimitsofscience.
TheMachineAnalogyinSyntheticBiology
SuneHolm
Awidespreadandinfluentialcharacterizationofsyntheticbiologyemphasizesthat
syntheticbiologyistheapplicationofengineeringprinciplestolivingsystems.Furthermore,
thereisastrongtendencytoexpresstheengineeringapproachtoorganismsintermsof
whatseemstobeanontologicalclaim:organismsaremachines.InthepaperIinvestigate
theontologicalandheuristicsignificanceofthemachineanalogyinsyntheticbiology.I
arguethattheuseofthemachineanalogyandtheaimofproducingrationallydesigned
organismsdonotnecessarilyimplyacommitmenttotheidentityoforganismsand
machines.Theidealofapplyingengineeringprinciplestobiologyisbestunderstoodas
expressingrecognitionofthemachine-unlikenessofnaturalorganismsandthelimitsof
humancognition.Thepapersuggestsaninterpretationoftheidentificationoforganisms
withmachinesinsyntheticbiologyaccordingtowhichitexpressesastrategyfor
representing,understanding,andconstructinglivingsystemsthataremoremachine-like
thannaturalorganisms.
AbstractionandModelConstructioninSystemsandSyntheticBiology
TarjaKnuuttilaandAndreaLoettgers
Theprevalentviewonabstractionamongphilosophersofscienceisthatofomission.
Whereasidealizationsarethoughttointroducedistortionstoascientificrepresentation,
abstractionisunderstoodintermsofabstractingawayfromthedetailsofasystem.
Accordingtothistraditionamodelisahighlyselectivedepictionoftheunderlying
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mechanismofaphenomenon,orsomebasiccausalfactors,takingintoaccountonlythose
featuresthatmakeadifference.
Wearguethattheideaofabstractionasomissiondoesnotoftencapturewhatgoesonin
actualmodelconstruction.Fromtheperspectiveofmodelingheuristiconeshouldmakea
distinctionbetweencasesinwhichoneabstractsawayfrommostofthedetailsofa
phenomenonofinterestfromthosethatstartfromanabstractmathematicalmechanism
describingageneralpatternofinteractionoftenadaptedfromotherscientificdisciplines—
suchasphysicsandengineeringinthecaseofbiology.Wewillillustratethispointby
examininghowsystemsbiologistUriAlonhasmadeuseofoptimalityprinciplesin
modelinggeneregulatorynetworks.
UsingEvolutiontoEngineerMicrobiomes
NicolaeMorar&BrendanBohannan
Theconceptof‘engineering’,whichimpliestheapplicationofsciencetosolvingcertain
problemsinvolvedinthedesignofstructuresandsystemsthatrespondtohumanneeds,
hasbeenrecentlyattachedtobiology,genetics,andecology.Twospecificwaysof
engineeringbiologicalnetworkshaveemerged.Geneticengineeringconsistsofcreatingand
programingcellstoperformparticularfunctions,e.g.releasequantitiesofinsulinwhena
bodyneedsit.Incontrast,evolutionaryengineeringselectsforaparticularstateofa
property(e.g.aparticularfunction),wherechangesinthe‘parts’andtheirinteractionsare
occurringasaby-productofthisselection.Thesetwoformsofbiologicalengineeringare
underlinedbytwodifferentlogics.Whiletheformerfocusesonselectingunitsoflife,the
latterhighlightstheimportanceofevolutionaryconstraints.However,bothformsof
engineeringhaveunderplayedtwoimportantfactsaboutanimalsandplants:1)organisms
includeadiversecommunityofmicrobesthatcolonizethem&2)microbiomesarenot
passiveplayersbutcontributetohostfunctionandfitness.Theengineeringofbiological
systemscannolongeraffordtooverlooktheimportanceofmicrobialprocesses.Hence,our
question:couldthemanipulationofthemicrobiomeofanorganismhaveaneffectonhost
function,andthus,impacthostfitness?
TheEpistemologyof‘GoodEnough’:PragmatismandEngineeringKnowledgeinSynthetic
Biology
PabloSchyfter
Syntheticbiologyisafieldin-the-making,withoutanyconsensusidentity,ambitions,
practices,orprinciples.However,onecontingentadvocateafieldof‘authentic’engineering
withabiologicalsubstrate.Forthesepractitioners,settlingthefieldhingesondeliveringa
newengineeringmodelledonandcongruouswiththeold.
Asthesociologyofknowledgeandsciencestudieshavedemonstrated,epistemicsystems,
practicesandproductsresultfromcollectivepractice,andcontributetotheformationof
scientificandtechnologicalgroups.Assuch,thepursuitofengineeringstandingisinparta
pursuitofengineeringknowledge.
Sociologicalandphilosophicalstudiesofsyntheticbiologydemandanepistemologyof
engineeringknowledge.IpositthatpragmatistepistemologyfromtheworksofJohnDewey
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andWilliamJamescanserveinconcertwiththesociologyofknowledgetodevelopand
deliveranepistemologyofknowledge-makingandknowledge-useinengineering.
Engineeringknowledgeissomethingemployed,ratherthananendinitself.Pragmatism
arguesthattruthfulnessisusefulness,andthesociologyofknowledgeenablesempirical
studyofhowutilityisdefined,pursued,andevaluatedcollectively.Usingsyntheticbiology
asacasestudy,Idemonstratethevalueinthisepistemologicalpartnership,andthe
characterofengineeringknowledgeasknowledge‘goodenough’touse.
UnderstandingBiologicalSystemsthroughMathematicalModeling
EberhardO.Voit
Thehallmarkofbiologicalsystemsiscomplexity,whichistheconsequenceofenormous
numbersofmolecularcomponentsandnonlinearprocesses,non-intuitivesystem
responses,thresholdeffects,andemergingpropertiesthatoftencannotfullybeexplained.A
truecomprehensionofthiscomplexitywouldrequirecohesivetheories,whichhoweverdo
notexistatpresent.Afirststeptowardsuchtheoriesistheexplorationofcomplexsystems
withcomputationalmodels,whichcanaidourunderstandingofatleastcertainfeaturesof
suchsystems.Iwilldiscussthefollowingaspectsofbiologicalsystemsmodeling:
1.Modelsarenon-unique;somearemoreusefulthanothers,iftheyanswerpertinent
questions.
2.Modelsshouldbeinterlockingwithinbiologicallevels,butdifferingranularitybetween
them.
3.Eachlevelmayrequireuniquemodelingframeworks;othermodeltypesmayconnect
levels.
4.Modelsofbiologicalsystemscannotbeformulatedintermsoffirstprinciplesfrom
physics,becausetheirgoverningprocessesaretooconvoluted.
5.Allbiologicalmodelsaremesoscopic;thereisnofeasiblebottomortop.
6.Engineeringapproachesmaybeuseful,butrequirecaution,becausethesuperposition
principleseldomholdsinbiology.
Iwillanalyzetheseaspectsanddemonstratethemwithmodelsinthecontextof
schizophrenia.
FundamentalEngineeringPrinciplesofNaturalandArtifactualDesign
WilliamWimsatt
Severalfeaturesaredeeplyanchoredcharacteristicsofbothnaturalevolvedandartifactual
systems.Scaffoldingoccurswhenastructureorbehaviorisutilizedtomakepossible,
easier,orfastertheattainmentofagoal.Generativeentrenchmentisthebuildingof
dependentstructures,processesorbehaviors(SPB’s)onearlierSPB’sinawaythat
facilitatestheiradditionto(andscaffolding)anadaptivestructure.Thistherebymakesthe
primarySPB’smoreessential,theirlossmoresevereinitseffects,makingentrenched
elementsmoreconservativeinevolutionaryprocesses,andaffectingmoreandlesslikely
directionsofevolutionarychange.Scaffoldingandentrenchmentareendemictothe
evolutionofcomplexsystems,inbiology,intechnology,incognition,andin
culture.Robustnessistherelativeinsensitivityofsystemperformancetodifferent
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arrangementsorspecificationsormodificationsofitsparts.Modularityisalastdesign
principleofbiologicalandtechnologicalsystemsandfacilitatesindependentmodification
andrecombinationtocreatenewkindsofsystems.Theselasttwoproperties,however,are
realizedindifferentwaysinevolvedandartifactualsystems.Iconsidertheimplicationsof
thesecharacteristicsforarchitecturalsimilaritiesanddifferencesbetweennewlydesigned
engineeringartifactsandthosenaturalorartifactualsystemsthathaveundergonean
evolutionaryprocesses,andhowthesefundamentalarchitecturalpropertiesthemselves
evolve.
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