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Sebastian Seungs Quest to Map the Human Brain - The New York Times

http://nyti.ms/1zWvkOR

Magazine

SebastianSeungsQuesttoMapthe
HumanBrain
ByGARETHCOOK

JAN.8,2015

In2005,SebastianSeungsufferedtheacademicequivalentofanexistential
crisis.Morethanadecadeearlier,withaPh.D.intheoreticalphysicsfrom
Harvard,Seungmadeadramaticcareerswitchintoneuroscience,agamble
thatseemedtobepayingoff.HehadearnedtenurefromtheMassachusetts
InstituteofTechnologyayearfasterthanthenormandwasimmediately
namedafullprofessor,anunusualmovethatreflectedthesensethatSeung
wassomethingofasuperstar.Hislabwasunderwrittenwithgenerous
fundingbytheeliteHowardHughesMedicalInstitute.Hewasapopular
teacherwhotraveledtheworldZurichSeoul,SouthKoreaPaloAlto,
Calif.deliveringlecturesonhismathematicaltheoriesofhowneurons
mightbewiredtogethertoformtheenginesofthought.
AndyetSeung,amansonaturallyexuberantthathewasknownfor
stagingadhocdanceperformanceswithHarvardSquaresstreetmusicians,
wasgrowingincreasinglydepressed.Heandhiscolleaguesspenttheirdays
arguingoverhowthebrainmightfunction,butscienceofferednowayto
scanitfortheanswers.Itseemedlikedecadescouldgoby,Seungtoldme
recently,andyouwouldneverknowonewayoranotherwhetheranyof
thetheorieswerecorrect.
ThatNovember,SeungsoughttheadviceofDavidTank,amentorhe
metatBellLaboratorieswhowasattendingtheannualmeetingofthe
SocietyforNeuroscience,inWashington.Overlunchinthedowdydining

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roomofanearbyhotel,Tankadvisedaradicalcure.Aformercolleaguein
Heidelberg,Germany,hadjustbuiltadevicethatimagedbraintissuewith
enoughresolutiontomakeouttheconnectionsbetweenindividual
neurons.Butdrawingevenatinywiringdiagramrequiredherculean
efforts,aspeopletracedthecourseofneuronsthroughthousandsofblurry
blackandwhiteimages.Whatthefieldneeded,Tanksaid,wasacomputer
programthatcouldtracethemautomaticallyawaytomapthebrains
connectionsbythemillions,openinganewareaofscientificdiscovery.For
Seungtotackletheproblem,though,itwouldmeanabandoningthework
thathadpropelledhimtothetopofhisdisciplineinfavorofahighly
speculativeengineeringproject.
BackinCambridge,Seungspokewithtwoofhisgraduatestudents,
who,likeeveryoneelseinthelab,thoughttheideawasterrible.Overthe
nextfewweeks,asthethreeofthemtalkedandargued,Seungbecame
convincedthattheHeidelbergprojectwasboundtobemoreinteresting,
andultimatelylessrisky,thancontinuingwiththetheoreticalworkhehad
lostfaithin.Makesureyourpassportsareready,hesaidfinally.Weare
goingtoGermanynextmonth.
SeungandhistwostudentsspentagoodpartofJanuary2006in
Germany,learningthefinickywaysofhighresolutionbrainimageanalysis
fromWinfriedDenk,thescientistwhobuiltthedevice.Thethreereturned
toM.I.T.invigorated,butSeungsdecisionlooked,forquiteawhile,likean
actofcareersuicide.ColleaguesatM.I.T.whisperedthatSeunghadgone
offtherails,andinthemoresnobbishcirclesoftheoreticalneuroscience,
theengineeringprojectwasseenas,inSeungswords,toobluecollar.In
2010,theHughesinstitutepulledthemoneythatfundedhislab,andhe
hadtoscramble.Whenhiswifewentintolaborwiththeirdaughterinthe
middleofthenight,hewasworkingonagrantapplicationhewoundup
stayingawakefor36hoursstraight.(Science,Einsteinoncewrote,isa
wonderfulthingifonedoesnothavetoearnoneslivingatit.)Astheyears
passed,theadvancesoutoftheSeunglabweremetwithindifference,which
wasparticularlyhardonhisgraduatestudents.Everytimetheyhada
success,theyweredepressedaboutit,becauseeveryoneelsethoughtitwas

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dumb,Seungsaid.Itkilledme.
Lastspring,eightyearsafterheandhisstudentspackedacomputer
workstationintoapieceofluggageandheadedtoHeidelberg,Seung
publishedapaperintheprestigiousjournalNature,demonstratinghowthe
brainsneuralconnectionscanbemappedanddiscoveriesmadeusing
aningeniousmixofartificialintelligenceandacompetitiveonlinegame.
Seunghasalsobecometheleadingproponentofaplan,whichhedescribed
ina2012book,tocreateawiringdiagramofall100trillionconnections
betweentheneuronsofthehumanbrain,anunimaginablyvastand
complexnetworkknownastheconnectome.
Theracetomaptheconnectomehashardlyleftthestartingline,with
onlymodestfundingfromthefederalgovernmentandinitialexperiments
confinedtothebrainsoflaboratoryanimalslikefruitfliesandmice.Butits
anendeavorheavywithmoralandphilosophicalimplications,becauseto
mapahumanconnectomewouldbe,Seunghasargued,tocapturea
personsveryessence:everymemory,everyskill,everypassion.Whenthe
brainisntwiredproperly,itcanleadtodisorderslikeautismand
schizophreniaconnectopathiesthatcouldberevealedinthemap,
perhapssuggestingtreatments.Andifscienceweretogainthepowerto
recordandstoreconnectomes,thenitwouldbenaturaltospeculate,as
Seungandothershave,thattechnologymightsomedayenablearecording
toplayagain,therebyreanimatingahumanconsciousness.Themappingof
connectomes,itsmostzealousproponentsbelieve,wouldconfernothing
lessthanimmortality.
Lastyear,SeungwasluredawayfromM.I.T.tojointhePrinceton
NeuroscienceInstituteandPrincetonsBezosCenterforNeuralCircuit
Dynamics.Thesedays,Seung,whois48,hasanofficedownthehallfrom
hismentorTankattheinstitute,awhitebuildingwithstripsofwraparound
glazingthatopenedlastyearonthecampussforestedsouthernfringe.
OutsideSeungsfirstfloorwindowareathleticfields,whereafternoon
pickupgamesofsocceroccasionallylurehimaway.Afewboxesliearound,
halfunpacked.Nearasycamoreveneerbuiltindeskdesignedbythe

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buildingsarchitectsitsajumbojarofmixednutsfromCostco,ahabithe
pickedupfromhisfather,aprofessorofphilosophyattheUniversityof
Texas,Austin.Withconnectomemapping,Seungexplainedlastmonth,itis
possibletostartansweringquestionsthattheoristshavepuzzledoverfor
decades,includingtheonesthatpromptedhimtoputasidehisownworkin
frustration.Heisplanning,amongotherthings,toprovethathecanfinda
specificmemoryinthebrainofamouseandshowhowneuralconnections
sustainit.Iamgoingbacktosettleoldscores,hesaid.
In1946,theArgentinemanoflettersJorgeLuisBorgeswrotea
shortstoryaboutanempire,unnamed,thatsetouttoconstructaperfect
mapofitsterritory.Aseriesofmapsweredrawn,onlytobeputasidein
favorofmoreambitiousmaps.Eventually,Borgeswrote,the
CartographersGuildsstruckaMapoftheEmpirewhosesizewasthatofthe
Empire,andwhichcoincidedpointforpointwithit.Thefollowing
Generations,whowerenotsofondoftheStudyofCartographyastheir
Forebearshadbeen,sawthatthatvastmapwasUseless,and...deliveredit
uptotheInclemenciesofSunandWinters.
Withtime,Borgesscautionaryparablehasbecomeevenmorerelevant
forthewouldbecartographersoftheworld,Seungamongthem.
Technologicalprogresshasalwaysbroughtnovelwaysofseeingthenatural
worldandthusnewwaysofmappingit.Thetelescopewaswhatallowed
Galileotosketch,inhisbookTheStarryMessenger,afirstmapof
Jupiterslargestmoons.Theinventionofthemicroscope,sometimeinthe
late16thcentury,ledtoRobertHookesfamousdepictionofaflea,itsbody
armoredandspiked,aswellasthediscoveryofthecell,analienworldunto
itself.Todaythepaceofinventionandtherawpoweroftechnologyare
shocking:ANobelPrizewasawardedlastfallforthecreationofa
microscopewitharesolutionsoextremethatitseemstodefythephysical
constraintsoflightitself.
Whathasmadetheearly21stcenturyaparticularlygiddymomentfor
scientificmapmakers,though,istheprecipitousriseofinformation
technology.Advancesincomputershaveprovidedacheapmeanstocollect

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andanalyzehugevolumesofdata,andMooresLaw,whichpredictsregular
doublingsincomputingpower,hasshownlittlesignofflagging.Justas
importantisthefactthatmachinescannowdothegruntworkofresearch
automatically,handlingsamples,measuringandrecordingdata.Setupa
roboticsystem,feedthedatatothecloudandthemapwillpracticallydraw
itself.ItseasytoforgetBorgesscaution:Thequestionisnotwhethera
mapcanbemade,butwhatinsightsitwillbring.Willfuturegenerations
cherishacartographersworkorshaketheirheadsanddeliverituptothe
inclemencies?
TheurmapofthisbigscienceistheoneproducedbytheHuman
GenomeProject,astemtosternaccountingoftheDNAthatprovidesevery
cellsgeneticinstructions.Thegenomeprojectwascompletedfasterthan
anyoneexpected,thankstoMooresLaw,andhasbecomeanessential
scientifictool.Initswakehavecomeaproliferationofprojectsinthesame
veintheproteome(proteins),thefoldome(foldingofproteins)each
promisingacompletedescriptionofsomethingorother.(Oneonlinelisting
includestheantiome:Thetotalityofpeoplewhoobjecttothepropagation
ofomes.)TheBrainInitiative,theUnitedStatesgovernments12year,
$4.5billionbrainmappingeffort,isaconsciousechoofthegenome
project,butneuroscientistsfindthemselvesinafarmoretenuousposition
attheoutset.Thebrainmightbemappedinahostofways,andthe
initiativeispursuingmanyatonce.Infact,Seungandhiscolleagues,who
arereceivingsomeofthefunding,areworkingatthemarginsof
contemporaryneuroscience.Muchofthefieldsmostexcitingnew
technologyhassoughttotrackthebrainsactivitylikefunctionalM.R.I.,
withitsimagesofpartsofthebrainlightingupwhiletheconnectome
wouldmapthebrainsphysicalstructure.
Toexplainwhathefindssocompellingaboutthesubstanceofthe
brain,Seungpointstostoriesofneardeath.InMay1999,ayoungdoctor
namedAnnaBagenholmwasskiingdownaravineneartheArcticCirclein
Norwaywhenarocksnaggedherskis,spinningherhalfwayaroundand
knockingherontoherback.Shespedheadfirstdowntheslope,stillonher
skis,towardastreamcoveredwithice.Itwasasunnyday,unusuallywarm,

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andwhenshehittheice,shewentstraightthrough.Rushingmeltwater
balloonedherclothesanddraggedherfartherundertheice.Shefoundan
airpocket,andherfriendsfoughttofreeher,butthecurrentwastoostrong
andtheicetoohard.Theygrippedherfeetsotheywouldntloseher.
Bagenholmsbodywentlimp.Herheartstopped.
Bythetimeamountainrescueteamfreedher,pullingherbody
throughaholetheycutdownstream,shehadbeenunderformorethanan
hour.Atthatpointshewasclinicallydead.TherescueteambeganCPR,
winchedherupintoawaitinghelicopterandferriedhertoTromso
UniversityHospital,aonehourflight,herbodystillshowingnosignsof
life.Hertemperaturemeasured57degrees.Doctorsslowlywarmedher,
andsuddenlyherheartstarted.Shespentamonthinintensivecarebut
recoveredremarkablywell.Monthslater,Bagenholmreturnedtoworkand
wasevenskiingagain.
WhatpreservedBagenholmsmemoriesandabilities,overhours,ina
stateofclinicaldeath?Scientistsbelievethateverythought,every
sensation,isasetoftinyelectricalimpulsescoursingthroughthebrains
interconnectedneurons.Butwhenalittlegirllearnsaword,forexample,
herbrainmakesarecordbyalteringtheconnectionsthemselves.Whenshe
learnstorideabikeorsingHappyBirthday,anewconstellationof
connectionstakesshape.Asshegrows,everymemoryafriendsname,
thefeelofskisonvirginpowder,aBeethovensonataisrecordedthis
way.Takentogether,theseconnectionsconstituteherconnectome,the
brainspermanentrecordofherpersonality,talents,intelligence,
memories:thesumofallthatconstitutesherself.Evenafterthecold
arrestedBagenholmsheartandhushedhercracklingneuronalnettoa
whisper,theconnectomeendured.
Whatmakestheconnectomesrelationshiptoouridentitysodifficult
tounderstand,Seungtoldme,isthatweassociateourselfwithmotion.
Wewalk.Wesing.Weexperiencethoughtsandfeelingsthatbloominto
consciousnessandthenfade.PsycheisderivedfromtheGreektoblow,
evokingthevitalbreaththatdefineslife.Itseemslikeafallacytotalk

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aboutourselfassomewiringdiagramthatdoesntchangeveryquickly,
Seungsaid.Theconnectomeisjustmeat,andpeoplerebelatthat.
Seungtoldmetoimagineariver,theroilingwatersoftheColorado.
That,hesaid,isourexperiencefrommomenttomoment.Overtime,the
waterleavesitsmarkontheriverbed,wideningbends,tracingpatternsin
therockandsoil.Inasense,theGrandCanyonisamemoryofwherethe
Coloradohasbeen.Andofcourse,thatriverbedshapestheflowofthe
waterstoday.Therearetwoselvesthen,riverandriverbed.Theriverisall
tumultanddrama.Theriverdemandsattention.Yetitstheriverbedthat
Seungwantstoknow.
WhenSeungwasjustshyofhis5thbirthday,hisfathertookhimto
theirlocalbarbershop,ascreendoorjointinAustinwherethevending
machineservedCokeinbottles.WhileSeungsfatherwasgettinghishair
cut,thebarberstoppedandpointedoutanendearingscene:Little
Sebastianwaspretendingtoreadthepaper.No,hisfathersaid,Ithink
hesreallyreadingit.Thebarberwentovertoinvestigate,andsure
enough,theboywashappytoexplainwhatwashappeningthatdayinThe
AustinAmerican
Statesman.Seunghadtaughthimselftoread,inpartby
askinghisfathertocalloutstorenamesandstreetsigns.At5,hetoldhis
fatheramanwhoescapedNorthKoreaonhisownasateenagerthat
hewouldnolongerbeneedingtoysforChristmas.
Growingup,Seungsprimarypassionsweresoccer,mathematicsand
nonfiction(withanexceptionmadeforGreekmyths).Asateenager,hewas
inspiredbyCarlSagansCosmos.Hetookgraduatelevelphysicscourses
asa17yearoldHarvardsophomoreandwentdirectlyintoHarvardsPh.D.
programintheoreticalphysics.Duringa1989summerinternshipatBell
Laboratories,though,SeungfellunderthespellofagregariousIsraeli
namedHaimSompolinsky,whointroducedhimtoaproblemintheoretical
neuroscience:Howcananetworkofneuronsgeneratesomethinglikean
Aha!moment,whenlearningleadstosuddenunderstanding.This
broughtSeungtohisownAha!moment:Atthefuzzyborderbetween
neuroscienceandmathematics,hespiedanewscientificterrain,thrilling

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andlargelyunexplored,givinghimthesamefeelingphysicistsmusthave
hadwhentheatomfirstbegantoyielditssecrets.
Seungbecamepartofacadreofphysicistswhodeployedsophisticated
mathematicaltechniquestodevelopanideadatingbackasfarasPlatoand
Aristotle,thatmeaningemergesfromthelinksbetweenthingsinthis
case,thelinksbetweenneurons.Inthe19thcentury,WilliamJamesand
otherpsychologistsarticulatedmentalprocessesasassociationsfor
example,seeingaLabradorretrieverpromptsthoughtsofachildhoodpet,
whichleadstomusingsaboutafriendwholivednextdoor.Asthecentury
closed,theSpanishneuroscientistSantiagoRamnyCajalwascreating
illustrationsofneuronslong,slimstemsandspectacularbranchesthat
connectedtootherneuronswithlongstemsoftheirownwhenpeople
begantowonderwhethertheywereseeingthephysicalpathwaysof
thoughtitself.
Thenextturncameinmorerecentdecadesasacrossdisciplinary
groupofresearchers,includingSeung,hitonanewwayofthinkingthatis
describedasconnectionism.Thebasicidea(whichborrowsfromcomputer
science)isthatsimpleunits,connectedintherightway,cangiveriseto
surprisingabilities(memory,recognition,reasoning).Incomputerchips,
transistorsandotherbasicelectroniccomponentsarewiredtogetherto
makepowerfulprocessors.Inthebrain,neuronsarewiredtogetherand
rewired.Everytimeagirlseesherdog(waggingtail,chocolatebrownfur),
acertainsetofneuronsfirethischurnofactivityislikeSeungsColorado
River.Whentheseneuronsfiretogether,theconnectionsbetweenthem
growstronger,formingamemoryapartofSeungsriverbed,the
connectomethatshapesthought.Thenotionisdeeplycounterintuitive:Its
naturaltothinkofanetworkfunctioningasariversystemdoes,asetof
streamsthatcancarrymessages,butdownrightoddtosuggestthatthere
arepartsoftheriverbedthatencodeLabradorretriever.
Atypicalhumanneuronhasthousandsofconnectionsaneuroncan
beasnarrowasonetenthousandthofamillimeterandyetstretchfrom
onesideoftheheadtotheother.Onlyoncehavescientistsevermanagedto

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mapthecompletewiringdiagramofananimalatransparentworm
calledC.elegans,onemillimeterlongwithjust302neuronsandthe
workrequiredastunningdisplayofresolve.Beginningin1970andledby
theSouthAfricanNobellaureateSydneyBrenner,itinvolvedpainstakingly
slicingthewormintothousandsofsections,eachonethousandththewidth
ofahumanhair,tobephotographedunderanelectronmicroscope.
Thatwastheeasypart.Topullawiringdiagramfromthestackof
imagesrequiredidentifyingeachneuronandthenfollowingitthroughthe
sections,ataskakintotracingthefulllengthofeverystrandofpastaina
bowlofspaghettiandmeatballs,usingpensandthousandsofblurryblack
andwhitephotos.ForC.elegans,thisprocessaloneconsumedmorethana
dozenyears.WhenSeungstarted,heestimatedthatitwouldtakeasingle
tracerroughlyamillionyearstofinishacubicmillimeterofhumancortex
meaningthattracinganentirehumanbrainwouldconsumeroughlyone
trillionyearsoflabor.Hewouldneedalittlehelp.
In2012,SeungstartedEyeWire,anonlinegamethatchallengesthe
publictotraceneuronalwiringnowusingcomputers,notpensinthe
retinaofamouseseye.Seungsartificial
intelligencealgorithmsprocess
therawimages,thenplayersearnpointsastheymark,paintbynumbers
style,thebranchesofaneuronthroughathreedimensionalcube.The
gamehasattracted165,000playersin164countries.Ineffect,Seungis
employingartificialintelligenceasaforcemultiplierforaglobal,all
volunteerarmythathasincludedLorinda,aMissourigrandmotherwho
alsopaintswatercolors,andIliyan(a.k.a.@crazyman4865),ahighschool
studentinBulgariawhoonceplayedfornearly24hoursstraight.
Computersdowhattheycanandthenleavetheresttowhatremainsthe
mostpotentpatternrecognitiontechnologyeverdiscovered:thehuman
brain.
Ultimately,Seungstillhopesthatartificialintelligencewillbeableto
handletheentirejob.Butinthemeantime,heisworkingtorecruitmore
help.InAugust,SouthKoreaslargesttelecomcompanyannounceda
partnershipwithEyeWire,runningnationwideadstobringinmore

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players.Inthenextfewyears,Seunghopestogobiggerbyenticinga
companytoturnEyeWireintoagamewithcharactersandastorylinethat
peopleplaypurelyforfun.Thinkofwhatwecoulddo,Seungsaid,ifwe
couldcaptureevenasmallfractionofthementaleffortthatgoesintoAngry
Birds.
TheJaneliaResearchCampusfeaturesaserpentinelandscape
buildingconstructedintothesideofahillnorthwestofWashington.The
facility,fundedbytheHowardHughesMedicalInstitute,isnearly1,000
feetlong,andmostoftheexteriorwallsareglass,theunusualdesigna
resultofaviewpreservationstrictureputinplaceinperpetuitybythe
previousownersoftheland.Fromthetopofthehill,youcanseelittlesign
ofthe$500millionbuilding,exceptforapairofhummingsilverexhaust
silosandamodestglassentryway,allrisinginexplicablyfromafieldofwild
grasseswhereplovershavebeguntonest.
Overthesummer,IwenttoJaneliatomeetSeung,whoworeagray
poloshirt,blueshortsandapairofCrocs.Hewastheretotalkabout
possiblecollaborationsandlearnaboutthetechnologythatothersinthe
fieldaredeveloping.Inside,heintroducedmetoHaraldHess,an
acknowledgedgeniusatcreatingnewscientifictools.(Hesshelpedbuilda
prototypeinhislivingroomoftheextremeresolutionmicroscopethe
onethatearnedalongtimecolleagueaNobelthisyear.)Hessledusdowna
wide,arcingservicecorridor,theceilinghungwithexposedpipes,thewall
linedwithpalletsoffruitflyfood.Heunlockedadoorandthenushered
Seungintoaroomwithwhiteplasticcurtainshangingfromthe20foot
ceilings.HepartedonewithakshreeekofreleasingVelcroandsaid,Thisis
ouractofGod'proofroom.
Theroomcontainedapairofhulkingbeigedevices,labeledMERLIN
inblackletterseachpartofanewbrainimagingsystem.Thesystem
combinesslicingandimaging:Anelectronmicroscopetakesapictureofthe
brainsamplefromabove,thenabeamofionsmovesacrossthetop,
vaporizingmaterialandrevealingthenextlayerofbraintissueforthe
microscope.Itis,however,atemperature
sensitivebeast,saidShanXu,a

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scientistatJanelia.Iftheroomwarmsbyevenafractionofadegree,the
metalcanexpandimperceptibly,skewingtheionbeam,wreckingthe
sampleandforcingtheteamtostartover.Xuwasoncewithindaysof
completingamonthslongrunwhenaJulyheatwavecausedtheair

conditioningtohiccup.Alltheworkwaslost.Xuhassincedesigned
elaboratefailsafes,includingasystemthatcan(anddoes)wakehimupin
themiddleofthenightJaneliahasalsoinvestedseveralhundredthousand
dollarsinbackupclimatecontrol.Wevelearnedmoreaboututilitiesthan
youwouldeverwanttoknow,Hesssaid.
HereatJanelia,connectomesciencewillfaceitsmostdemandingtest.
GerryRubin,Janeliasdirector,saidhisteamhopestohaveacomplete
catalogofhighresolutionimages
ofthefruitflybraininayearortwoanda
completelytracedwiringdiagramwithinadecade.Rubinisaveteranof
genomemappingandsawhowtechnologicaladvancesenabledaproject
thatcriticsoriginallyderidedasprohibitivelydifficultandexpensive.Heis
bettingthatthestoryoftheconnectomewillfollowthesamearc.Ken
Hayworth,ascientistinHessslab,isdevelopingawaytocleanlycutlarger
brainsintocubeshecallsitthehotknife.Inotherlabs,JeffLichtmanof
HarvardandClayReidoftheAllenInstituteforBrainSciencearebuilding
theirownultrafastimagingsystems.Denk,Seungslongtimecollaboratorin
Heidelberg,isworkingonanewdevicetosliceandimageamousesentire
brain,avolumeordersofmagnitudelargerthanwhathasbeentriedto
date.Seung,meanwhile,isimprovinghistracingsoftwareandsettingup
newexperimentswithhismentorTankandRichardAxel,aNobel
laureateatColumbiatofindmemoriesintheconnectome.Still,Rubin
admitted,ifwecantdotheflyin10years,thereisnoprayerforthefield.
Attheendofalongday,SeungandIsatonapairofbluebar
stools,sharingsomepeanutsandsippingonbeersatJaneliasinhouse
wateringhole.Seungwasfeelingdaunted.EvenatJanelia,whichplansto
spendroughly$50millionandhassomeofthebesttoolbuildersonthe
planet,theconnectomeofafruitflylookstobeadecadeaway.Afruitfly!
Willhelivetoseethefirsthumanconnectome?Itcouldbepossible,he
said,ifweassumethatIexerciseandeatright.

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Yearsago,Seungofficiatedathisbestfriendswedding,andduringthe
invocationhetoldthegathering,Myfathersaysthatsuccessisnever
achievedinjustonegeneration.Ashehasgrownolderandhadachildof
hisown,hehasfelthisperspectiveshift.WhenSeungwasinhis20s,
scienceforhimwassolvingpuzzles,anextensionofthemathproblemshe
didforfunasachildaloneinhisroomonSaturdaysaftersoccer.Nowhe
findsgreatsatisfactioninencouragingyoungerscientists,inhelpingthem
avoiddeadendsthathehasalreadyexplored.Hewantstodosomething
thatwillallowthecommunitytoprogress,tobuildstrongfoundations,
steppingstonesthatthenextgenerationcanbesureof.
ThegroundsofJaneliahaveamonasticfeel,andwhiletalkingwith
Seung,IcouldnthelpthinkingofthepeoplewhobuiltEuropesgreat
cathedralsthecarpentersandmasonswholaboredknowingthatthe
workwouldnotbecompleteduntilaftertheirdeaths.Fromthebar,we
couldseethroughaglasswalltoapatiolinedwithsmoothriverrocksanda
fieldstonewall.Aspareshrubgardenwassetwithatricklingstainless
steel
fountain,illuminatedbyabankofsapphirelights.Idontknowhowmuch
Illaccomplishinmylifetime,Seungsaid.Butthebrainismysterious,
andIwanttospendmylifeinthepresenceofmystery.Itsassimpleas
that.
Asconnectomicshasgainedtraction,though,therearethefirsthints
thatitmaybeofinteresttomorethanjustmonkishacademics.In
September,ataBrainInitiativeconferenceintheEisenhowerbuildingon
theWhiteHousegrounds,itwasannouncedthatGooglehadstartedits
ownconnectomeproject.TomDean,aGoogleresearchscientistandthe
formerchairmanoftheBrownUniversitycomputersciencedepartment,
toldmehehasbeenassemblingateamtoimprovetheartificial
intelligence:fourengineersinMountainView,Calif.,andagroupbasedin
Seattle.Tobegin,Deansaid,Googlewillbeworkingmostcloselywiththe
AllenInstitute,whichistryingtounderstandhowthebrainofamouse
processesimagesfromtheeye.YetDeansaidtheyalsowanttoserveasa
clearinghouseforSeungandothers,applyingdifferentvariationsof
artificialintelligencetobrainimagerycomingoutofdifferentlabs,tosee

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whatworksbest.Eventually,Deansaid,hehopesforaGoogleEarthofthe
brain,weavingtogethermanydifferentkindsofmaps,acrossmanyscales,
allowingscientiststobeholdanentirebrainandthenzoomintoseethe
firingofasingleneuron,likelightninginathunderstorm.
Itspossiblenowtoseeavirtuouscyclethatcouldbuildthe
connectome.TheartificialintelligenceusedatGoogle,andinEyeWire,is
knownasdeeplearningbecauseittakesitscentralprinciplesfromtheway
networksofneuronsfunction.Overthelastfewyears,deeplearninghas
becomeapreciouscommercialtool,bringingunexpectedleapsinimage
andvoicerecognition,andnowitisbeingdeployedtomapthebrain.This
could,inthecomingdecades,leadtomoreinsightsaboutneuralnetworks,
improvingdeeplearningitselfthepremiseofanewprojectfundedby
Iarpa,ablueskyresearcharmoftheAmericanintelligencecommunity,
andperhapsonereasonforGooglesinterest.Betterdeeplearning,inturn,
couldbeusedtoacceleratethemappingandunderstandingofthebrain,
andsoon.
Evenso,theshadowofBorgesremains.Thefirstconnectomeproject
beganinthe1960swiththesameintuitionthatlaterdroveSeung:Sydney
Brennerwantedawaytounderstandhowbehavioremergesfroma
biologicalsystemandthoughtthathavingacompletemapofananimals
nervoussystemwouldbeessential.BrennersettledonthewormC.elegans
forsimplicityssakeitissmallandprospersinalaboratorydish.The
resultswerepublishedin1986atbooklength,takingovertheentiretyof
PhilosophicalTransactionsoftheRoyalSocietyofLondon,sciencesoldest
journal,theoutletforayoungIsaacNewton.Biologistswereelectrifiedand
stillsometimesrefertothat340pageeditionofthejournalasthebook.
Yetnearlythreedecadeslater,Brennersdiagramcontinuestomystify.
ScientistsknowroughlywhatindividualneuronsinC.elegansdoandcan
say,forexample,whichneuronsfiretosendthewormwrigglingforwardor
backward.Butmorecomplexquestionsremainunanswered.Howdoesthe
wormremember?Whatisconstantinthemindsofworms?Whatmakes
eachoneindividual?Inpart,thesedisappointmentswereaproblemof

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technology,whichhasmadeconnectomemappingsoonerousthatuntil
recentlynobodyconsidereddoingmore.Inscience,itisagreat
accomplishmenttomakethefirstmap,butfarmoreusefultohave10,ora
million,thatcanbecomparedwithoneanother.C.eleganswasaclassic
caseofbeingtoofaraheadofyourtime,saysGerryRubinofJanelia.
Thedifficultiesofinterpretingthewormconnectomecanalsobe
attributedtothefactthatithasbeenparticularlydifficulttoseetheworms
wiringinaction,tomeasuretheactivityofthewormsneurons.Without
enoughactivitydata,awiringdiagramisfundamentallyinscrutablea
problemakintotryingtoreadthehieroglyphsofancientEgyptbeforethe
RosettaStone,withitsparalleltextinancientGreek.Aconnectomeisnot
ananswer,butaclue,likeahieroglyphicstelepulledupfromthesand,
promisinginsightintoanempirebutsadlylackingakey.
In2000,PresidentBillClintonandPrimeMinisterTonyBlairof
Britainheldanewsconferencetoannounceacompletedraftofthehuman
genome,whichClintoncalledthemostwondrousmapeverproducedby
humankind.Themaphasindeedprovedfullofwondermodernbiology
wouldbeimpossiblewithoutitbutintheyearssince,ithasalsobecome
clearhowincompletethecartographyis.Thegenomeprojectidentified
roughly20,000genes,butcellsalsouseasystemofswitchesthatturn
genesoffandon,andthissystem,calledepigenetics,determineswhatwork
acellcandoandshapeswhatdiseasesapersonmightbeproneto.Recent
estimatesputthenumberofswitchesinthehundredsofthousands,
perhapsamillion.Aninternationalconsortiumisnowtryingtomapthe
epigenome,andnoonecansaywhenitwillbefinished.
EveMarder,aprominentneuroscientistatBrandeisUniversity,
cautionsagainstexpectingtoomuchfromtheconnectome.Shestudies
neuronsthatcontrolthestomachsofcrabsandlobsters.Intheserelatively
simplesystemsof30orsoneurons,shehasshownthatneuromodulators
signalingchemicalsthatwashacrossregionsofthebrain,omittedfrom
Seungsstaticmapcanfundamentallychangehowacircuitfunctions.If
thisistrueforthestomachofacrustacean,themindreelstoconsiderwhat

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maybehappeninginthebrainofamouse,nottomentionahuman.
Thehistoryofscienceisanarrativefullofcharactersconvincedthat
theyhadfoundthepathtounderstandingeverything,onlytohavethe
universeunveilaSisypheantwist.Physicistssoughtmattersbasicbuilding
blocksanddiscoveredatoms,butthenfoundthatatomshadtheirown
buildingblocks,whichhadtheirownpieces,whichhasbroughtus,today,
tostringtheory,thedisciplinesequivalentofalandwarinAsia.Afterthe
genomedeliveredupthetextofhumanitysgeneticcode,biologistsrealized
thatourgeneticmachineryissofilledwithfeedback,andlayersbuilton
layers,thattheirworkhadonlybegun.CriticsofSeungsvisiontherefore
seeitasnave,afaiththathecancrestthemountaininfrontofhimandnot
findmoreimposingpeaksbeyond.Ifwewanttounderstandthebrain,
Mardersays,theconnectomeisabsolutelynecessaryandcompletely
insufficient.
Seungagreesbuthasneverseenthatasanargumentforabandoning
theenterprise.Scienceprogresseswhenitspractitionersfindanswers
thisisthewayofglorybutalsowhentheymakesomethingthatfuture
generationsrelyon,eveniftheytakeitforgranted.That,forSeung,would
bemorethangoodenough.Necessary,hesaid,isstillaprettystrong
word,right?

GarethCookisaPulitzerPrizewinningjournalist.Hismost
recentarticleforthemagazinewasaboutautism.
AversionofthisarticleappearsinprintonJanuary11,2015,onpageMM27oftheSunday
Magazinewiththeheadline:MindGames.

2015TheNewYorkTimesCompany

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