CHAPTERSEVEN

ADVENTURESINBODYBUILDING

WhenIwasn’toutinthefieldcollectingfossils,muchofmygraduatecareerwasspentstaringintoamicroscope,lookingathowcellscometogethertomakebones.Iwouldtakethedevelopinglimbofasalamanderora

frog,andstainthecellswithdyesthatturndevelopingcartilageblueandbonesred.Icouldthenmaketherestofthetissuesclearbytreatingthelimbwithglycerin.Thesewerebeautifulpreparations:theembryoentirelyclearandallthebonesradiatingthecolorsofthedyes.Itwaslikelookingatcreaturesmadeofglass.Duringtheselonghoursatthemicroscope,Iwasliterally

watchingananimalbeingbuilt.Theearliestembryoswouldhavetinylittlelimbbudsandthecellsinsidewouldbeevenlyspaced.Then,atlaterstages,thecellswouldclumpinsidethelimbbud.Insuccessivelyolderembryos,thecellswouldtakedifferentshapesandtheboneswouldform.EachofthoseclumpsIsawduringtheearlystagesbecameabone.Itishardnottofeelawestruckwatchingananimal

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assembleitself.Justlikeabrickhouse,alimbisbuiltbysmallerpiecesjoiningtomakealargerstructure.Butthereisahugedifference.Houseshaveabuilder,somebodywhoactuallyknowswhereallthebricksneedtogo;limbsandbodiesdonot.Theinformationthatbuildslimbsisnotinsomearchitecturalplanbutiscontainedwithineachcell.Imagineahousecomingtogetherspontaneouslyfromalltheinformationcontainedinthebricks:thatishowanimalbodiesaremade.Muchofwhatmakesabodyislockedinsidethecell;in

fact,muchofwhatmakesusuniqueisthere,too.Ourbodylooksdifferentfromthatofajellyfishbecauseofthewaysourcellsattachtooneanother,thewaystheycommunicate,andthedifferentmaterialstheymake.Beforewecouldevenhavea“bodyplan”—letalonea

head,brain,orarm—therehadtobeawaytomakeabodyinthefirstplace.Whatdoesthismean?Tomakeallofabody’stissuesandstructures,cellshadtoknowhowtocooperate—tocometogethertomakeanentirelynewkindofindividual.Tounderstandthemeaningofthis,let’sfirstconsider

whatabodyis.Then,let’saddressthethreegreatquestionsaboutbodies:When?How?AndWhy?Whendidbodiesarise,howdidtheycomeabout,and,mostimportant,whyaretherebodiesatall?

HABEASCORPUS:SHOWMETHEBODY

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Noteveryclumpofcellscanbeawardedthehonorofbeingcalledabody.Amatofbacteriaoragroupofskincellsisaverydifferentthingfromanarrayofcellsthatwewouldcallanindividual.Thisisanessentialdistinction;athoughtexperimentwillhelpusseethedifference.Whathappensifyoutakeawaysomebacteriafromamat

ofbacteria?Youendupwithasmallermatofbacteria.Whathappenswhenyouremovesomecellsofahumanorfish,sayfromtheheartorbrain?Youcouldendupwithadeadhumanorfish,dependingonwhichcellsyouremove.Sothethoughtexperimentrevealsoneofthedefining

featuresofbodies:ourcomponentpartsworktogethertomakeagreaterwhole.Butnotallpartsofbodiesareequal;somepartsareabsolutelyrequiredforlife.Moreover,inbodies,thereisadivisionoflaborbetweenparts;brains,hearts,andstomachshavedistinctfunctions.Thisdivisionoflaborextendstothesmallestlevelsofstructure,includingthecells,genes,andproteinsthatmakebodies.Thebodyofawormorapersonhasanidentitythatthe

constituentparts—organs,tissues,andcells—lack.Ourskincells,forexample,arecontinuallydividing,dying,andbeingsloughedoff.Yetyouarethesameindividualyouweresevenyearsago,eventhoughvirtuallyeveryoneofyourskincellsisnowdifferent:theonesyouhadbackthenaredeadandgone,replacedbynewones.Thesameistrueofvirtuallyeverycellinourbodies.Likeariverthatremainsthesamedespitechangesinitscourse,watercontent,evensize,weremainthesameindividualsdespitethecontinual

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turnoverofourparts.Anddespitethiscontinualchange,eachofourorgans

“knows”itssizeandplaceinthebody.Wegrowinthecorrectproportionsbecausethegrowthofthebonesinourarmsiscoordinatedwiththegrowthofthebonesinourfingersandourskulls.Ourskinissmoothbecausecellscancommunicatetomaintainitsintegrityandtheregularityofitssurface.Untilsomethingoutoftheordinaryhappens,like,forinstance,wegetawart.Thecellsinsidethewartaren’tfollowingtherules:theydonotknowwhentostopgrowing.Whenthefinelytunedbalanceamongthedifferentparts

ofbodiesbreaksdown,theindividualcreaturecandie.Acanceroustumor,forexample,isbornwhenonebatchofcellsnolongercooperateswithothers.Bydividingendlessly,orbyfailingtodieproperly,thesecellscandestroythenecessarybalancethatmakesalivingindividualperson.Cancersbreaktherulesthatallowcellstocooperatewithoneanother.Likebullieswhobreakdownhighlycooperativesocieties,cancersbehaveintheirownbestinterestuntiltheykilltheirlargercommunity,thehumanbody.Whatmadeallthiscomplexitypossible?Forourdistant

ancestorstogofromsingle-celledcreaturestobodiedones,astheydidoverabillionyearsago,theircellshadtoutilizenewmechanismstoworktogether.Theyneededtobeabletocommunicatewithoneanother.Theyneededtobeabletosticktogetherinnewways.Andtheyneededtobeableto

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makenewthings,suchasthemoleculesthatmakeourorgansdistinct.Thesefeatures—thegluebetweencells,thewayscellscan“talk”toeachother,andthemoleculesthatcellsmake—constitutethetoolkitneededtobuildallthedifferentbodiesweseeonearth.Theinventionofthesetoolsamountedtoarevolution.

Theshiftfromsingle-celledanimalstoanimalswithbodiesrevealsawholenewworld.Newcreatureswithwholenewcapabilitiescameabout:theygotbig,theymovedaround,andtheydevelopedneworgansthathelpedthemsense,eat,anddigesttheirworld.

DIGGINGUPBODIES

Here’sahumblingthoughtforallofusworms,fish,andhumans:mostoflife’shistoryisthestoryofsingle-celledcreatures.Virtuallyeverythingwehavetalkedaboutthusfar—animalswithhands,heads,senseorgans,evenbodyplans—hasbeenaroundforonlyasmallfractionoftheearth’shistory.Thoseofuswhoteachpaleontologyoftenusetheanalogyofthe“earthyear”toillustratehowtinythatfractionis.Taketheentire4.5-billion-yearhistoryoftheearthandscaleitdowntoasingleyear,withJanuary1beingtheoriginoftheearthandmidnightonDecember31beingthepresent.UntilJune,theonlyorganismsweresingle-celledmicrobes,suchasalgae,bacteria,andamoebae.Thefirstanimalwithaheaddidnotappearuntil

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October.ThefirsthumanappearsonDecember31.We,likealltheanimalsandplantsthathaveeverlived,arerecentcrashersatthepartyoflifeonearth.Thevastnessofthistimescalebecomesabundantlyclear

whenwelookattherocksintheworld.Rocksolderthan600millionyearsaregenerallydevoidofanimalsorplants.Inthemwefindonlysingle-celledcreaturesorcoloniesofalgae.Thesecoloniesformmatsorstrands;somecoloniesaredoorknob-shaped.Innowayarethesetobeconfusedwithbodies.Thefirstpeopletoseetheearliestbodiesinthefossil

recordhadnoideawhattheywerelookingat.Between1920and1960reallyoddfossilsstartedpoppingupfromallaroundtheworld.Inthe1920sand1930s,MartinGurich,aGermanpaleontologistworkinginwhatistodayNamibia,discoveredavarietyofimpressionsofwhatlookedlikeanimalbodies.Shapedlikedisksandplates,thesethingsseemedunremarkable:theycouldhavebeenprimitivealgaeorjellyfishlivinginancientseas.In1947,anAustralianmininggeologistnamedReginald

Sprigghappeneduponalocalitywheretheundersidesoftherockscontainedimpressionsofdisks,ribbons,andfronds.WorkingaroundanabandonedmineintheEdiacaraHillsofSouthAustralia,Sprigguncoveredacollectionofthesefossilsanddescribedthemdutifully.Overtime,similarimpressionsbecameknownfromeverycontinentoftheworldexceptAntarctica.Sprigg’screaturesseemedstrange,butfewpeoplereallycaredaboutthem.

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ThereasonforthecollectivepaleontologicalyawnwasthatthesefossilswerethoughttocomefromtherelativelyyoungrocksoftheCambrianera,whenmanyanimalfossilswithprimitivebodieswerealreadyknown.Sprigg’sandGurich’sfossilssatrelativelyunnoticed,anassemblageofnotterriblyexciting,ifweird,impressionsfromaperiodalreadywellrepresentedinthemuseumcollectionsoftheworld.Inthemid-1960s,MartinGlaessner,acharismatic

Austrianex-patlivinginAustralia,changedallthat.Aftercomparingtheserockstothoseinotherpartsoftheworld,Glaessnershowedthatwithoutadoubtthesefossilswere15millionto20millionyearsolderthanoriginallythought.Theywerenodullcollectionofimpressions—rather,Gurich,Sprigg,andotherswereseeingtheearliestbodies.

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Atimescaleforeventsinthehistoryoflife.Noticetheextremelylongperiodoftimeduringwhichtherewerenobodiesonearth,onlysingle-celledorganismslivingaloneorincolonies.

Thesefossilscamefromtheperiodknownasthe

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Precambrian,whosenameliterallymeans“BeforeLife.”Ourunderstandingoftheantiquityoflifehadjustexploded.Paleontologicalcuriositiesbecamescientificjewels.ThePrecambriandisks,ribbons,andfrondsareclearly

theoldestcreatureswithbodies.Aswe’dexpectfromotherearlyanimalfossils,theyincluderepresentativesofsomeofthemostprimitiveanimalsontheplanettoday:spongesandjellyfish.OtherPrecambrianfossilslooklikenothingknown.Wecantellthattheyareimpressionsofsomethingwithabody,buttheirpatternsofblobs,stripes,andshapesmatchnolivingcreature.Onemessagefromthisisveryclear:creatureswithmany

cellsbegantopopulatetheseasoftheplanetby600millionyearsago.Thesecreatureshadwell-definedbodiesandweren’tjustcoloniesofcells.Theyhavepatternsofsymmetrythat,insomecases,resemblethoseoflivingforms.Asforthosethatcannotbecompareddirectlywithlivingforms,differentpartsoftheirbodiesneverthelesshavespecializedstructures.ThisimpliesthatthePrecambrianorganismshadalevelofbiologicalorganizationthatatthetimewasutterlynewontheplanet.Evidenceofthesechangesisseennotonlyinthefossil

bodiesbutalsointherocksthemselves.Withthefirstbodiescomethefirsttrackways.Etchedintherocksarethefirstsignsthatcreatureswereactuallycrawlingandsquirmingthroughtheooze.Theearliesttrackways,smallribbon-shapedscrapesintheancientmud,showthatsomeofthesecreatureswithbodieswerecapableofrelatively

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complicatedmotions.Notonlydidtheyhavebodieswithidentifiableparts,buttheywereactuallyusingthemtomoveinnewways.Allofthismakestotalsense.Weseethefirstbodies

beforeweseethefirstbodyplans.Weseethefirstprimitivebodyplansbeforeweseethefirstbodyplanswithheads,andsoon.Liketheimaginaryzoowewalkedthroughinthefirstchapter,therocksoftheworldarehighlyordered.Aswesaidatthebeginningofthissection,weareafter

thewhen,how,andwhyofbodies.ThePrecambriandiscoveriestellusthewhen.Toseethehow,andultimatelythewhy,weneedtotakeaslightlydifferenttack.

OUROWNBODYOFEVIDENCE

AphotocouldnevercapturejusthowmuchofourbodiesistobefoundwithinthosePrecambriandisks,fronds,andribbons.Whatcouldwehumans,withallourcomplexity,eversharewithimpressionsinrocks,particularlyonesthatlooklikecrinkledjellyfishandsquashedrollsoffilm?Theanswerisprofoundand,whenweseetheevidence,

inescapable:the“stuff”thatholdsustogether—thatmakesourbodiespossible—isnodifferentfromwhatformedthebodiesofGurich’sandSprigg’sancientimpressions.Infact,thescaffoldingofourentirebodyoriginatedinasurprisinglyancientplace:single-celledanimals.

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Whatholdsaclumpofcellstogether,whethertheyformajellyfishoraneyeball?Increatureslikeus,thatbiologicalglueisastoundinglycomplicated;itnotonlyholdsourcellstogether,butalsoallowscellstocommunicateandformsmuchofourstructure.Theglueisnotonething;itisavarietyofdifferentmoleculesthatconnectandliebetweenourcells.Atthemicroscopiclevel,itgiveseachofourtissuesandorgansitsdistinctiveappearanceandfunction.Aneyeballlooksdifferentfromalegbonewhetherwelookatitwiththenakedeyeorunderamicroscope.Infact,muchofthedifferencebetweenalegboneandaneyerestsinthewaysthecellsandmaterialsarearrangeddeepinside.Everyfallforthepastseveralyears,Ihavedrivenmedical

studentscrazywithjusttheseconcepts.Nervousfirst-yearstudentsmustlearntoidentifyorgansbylookingatrandomslidesoftissueunderamicroscope.Howdotheydothis?Thetaskisalittlelikefiguringoutwhatcountryyouare

inbylookingatastreetmapofasmallvillage.Thetaskisdoable,butweneedtherightclues.Inorgans,someofthebestclueslieintheshapeofcellsandhowtheyattachtooneanother;itisalsoimportanttobeabletoidentifythestuffthatliesbetweenthem.Tissueshaveallkindsofdifferentcells,whichattachtooneanotherindifferentways:someregionshavestripsorcolumnsofcells;inothers,cellsarerandomlyscatteredandlooselyattachedtooneanother.Theseareas,wherecellsarelooselypacked,

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areoftenfilledwithmaterialsthatgiveeachtissueitscharacteristicphysicalproperties.Forinstance,themineralsthatliebetweenbonecellsdeterminethehardnessofbone,whereasthelooserproteinsinthewhitesofoureyesmakethewalloftheeyeballmorepliant.Ourstudents’abilitytoidentifyorgansfrommicroscope

slides,then,comesfromknowinghowcellsarearrangedandwhatliesbetweenthecells.Forus,thereisadeepermeaning.Themoleculesthatmakethesecellulararrangementspossiblearethemoleculesthatmakebodiespossible.Iftherewerenowaytoattachcellstooneanother,oriftherewerenomaterialsbetweencells,therewouldbenobodiesontheearth—justbatchesofcells.Thismeansthatthestartingpointforunderstandinghowandwhybodiesaroseistoseethesemolecules:themoleculesthathelpcellssticktogether,themoleculesthatallowthemtocommunicatewithoneanother,andthesubstancesthatliebetweencells.Tounderstandtherelevanceofthismolecularstructure

toourbodies,let’sfocusindetailononepart:ourskeleton.Ourskeletonisapowerfulexampleofhowtinymoleculescanhaveabigimpactonthestructureofourbodyandexemplifiesgeneralprinciplesthatapplytoallthebody’sparts.Withoutskeletons,wewouldbeformlessmassesofgoo.Livingonlandwouldnotbeeasyorevenpossible.Somuchofourbasicbiologyandbehaviorismadepossiblebyourskeletonthatweoftentakeitforgranted.Everytimewewalk,playpiano,inhale,orchewfoodwehaveour

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skeletontothank.Agreatanalogyfortheworkingsofourskeletonisa

bridge.Thestrengthofabridgedependsonthesizes,shapes,andproportionsofitsgirdersandcables.Butalso,importantly,thestrengthofthebridgedependsonthemicroscopicpropertiesofthematerialsfromwhichitismade.Themolecularstructureofsteeldetermineshowstrongitisandhowfaritwillbendbeforebreaking.Inthesameway,ourskeleton’sstrengthisbasedonthesizesandshapesofourbones,butalsoonthemolecularpropertiesofourbonesthemselves.Let’sgoforaruntoseehow.Aswejogalongapath,our

musclescontract,ourback,arms,andlegsmove,andourfeetpushagainstthegroundtomoveusforward.Ourbonesandjointsfunctionlikeagiantcomplexofleversandpulleysthatmakeallthatmovementpossible.Ourbody’smovementsaregovernedbybasicphysics:ourabilitytorunisinlargepartbasedonthesize,shape,andproportionsofourskeletonandtheconfigurationofourjoints.Atthislevel,welooklikeabigmachine.Andlikeamachine,ourdesignmatchesourfunctions.Aworld-classhighjumperhasdifferentboneproportionsfromachampionsumowrestler.Theproportionsofthelegsofarabbitorafrog,specializedtohopandjump,aredifferentfromthoseofahorse.Now,let’stakeamoremicroscopicview.Popasliceofa

femurunderthemicroscope,andyouwillimmediatelyseewhatgivesboneitsdistinctivemechanicalproperties.The

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cellsarehighlyorganizedinplaces,particularlyontheouterrimofthebone.Somecellssticktogether,whereasothersareseparated.Betweentheseparatedcellsarethematerialsthatdefinethestrengthofbone.Oneofthemistherock,orcrystal,knownashydroxyapatite,whichwediscussedinChapter4.Hydroxyapatiteishardthewayconcreteis:strongwhencompressed,lessstrongiftwistedorbent.So,likeabuildingmadeofbricksorconcrete,bonesareshapedsoastomaximizetheircompressivefunctionsandminimizetwistingandbending,somethingGalileorecognizedintheseventeenthcentury.Theothermoleculefoundbetweenourbonecellsisthe

mostcommonproteinintheentirehumanbody.Ifwemagnifyit10,000timeswithanelectronmicroscope,weseesomethingthatlookslikearopeconsistingofbundlesoflittlemolecularfibers.Thismolecule,collagen,alsohasthemechanicalpropertiesofarope.Ropeisrelativelystrongwhenpulled,butitcollapseswhencompressed;thinkofthetwoteamsinatug-of-warrunningtowardthemiddle.Collagen,likerope,isstrongwhenpulledbutweakwhentheendsarepushedtogether.Boneiscomposedofcellsthatsitinaseaof

hydroxyapatite,collagen,andsomeother,lesscommonmolecules.Somecellssticktogether;othercellsfloatinsidethesematerials.Thestrengthofboneisbasedoncollagen’sstrengthwhenpulled,andonhydroxyapatite’sstrengthwhencompressed.Cartilage,theothertissueinourskeleton,behaves

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somewhatdifferently.Duringourjog,itwasthecartilageinourjointsthatprovidedthesmoothsurfaceswhereourbonesglidedagainstoneanother.Cartilageisamuchmoreplianttissuethanbone;itcanbendandsmushasforcesareappliedtoit.Thesmoothoperationofthekneejoint,aswellasmostoftheotherjointsweusedduringourjog,dependsonhavingrelativelysoftcartilage.Whenhealthycartilageiscompresseditalwaysreturnstoitsnativeshape,likeakitchensponge.Duringeachstepofourrun,ourentirebodymassslamsagainstthegroundatsomespeed.Withouttheseprotectivecapsatourjointsourboneswouldgrindagainstoneanother:averyunpleasantanddebilitatingoutcomeofarthritis.Thepliabilityofcartilageisapropertyofitsmicroscopic

structure.Thecartilageatourjointshasrelativelyfewcells,andthesecellsareseparatedbyalotoffillingbetweenthem.Aswithbone,itisthepropertiesofthisinterstitialfillingthatlargelydeterminethemechanicalpropertiesofthecartilage.Collagenfillsmuchofthespacebetweencartilagecells

(aswellasthecellsofourothertissues).Whatreallygivescartilageitspliancyisanotherkindofmolecule,oneofthemostextraordinaryinthewholebody.Thiskindofmolecule,calledaproteoglycancomplex,givescartilagestrengthwhensqueezedorcompressed.Shapedlikeagiantthree-dimensionalbrush,withalongstemandlotsoflittlebranches,theproteoglycancomplexisactuallyvisibleunderamicroscope.Ithasanamazingpropertyrelevantto

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ourabilitiestowalkandmove,thankstothefactthatthetiniestbrancheslovetoattachtowater.Aproteoglycan,then,isamoleculethatactuallyswellsupwithwater,fillingupuntilit’slikeagiantpieceofJell-O.Takethispieceofgelatin,wrapcollagenropesinandaroundit,andyouendupwithasubstancethatisbothpliantandsomewhatresistanttotension.This,essentially,iscartilage.Aperfectpadforourjoints.Theroleofthecartilagecellsistosecretethesemoleculeswhentheanimalisgrowingandmaintainthemwhentheanimalisnot.Theratiosamongthevariousmaterialsdefinemuchof

themechanicaldifferencesamongbone,cartilage,andteeth.Teethareveryhardand,predictably,thereislotsofhydroxyapatiteandrelativelylittlecollagenbetweenthecellsintheenamel.Bonehasrelativelymorecollagen,lesshydroxyapatite,andnoenamel.Consequently,itisnotashardasteeth.Cartilagehaslotsofcollagenandnohydroxyapatite,andisloadedwithproteoglycans.Itisthesoftestofthetissuesinourskeleton.Oneofthemainreasonsourskeletonslookandworkastheydoisthatthesemoleculesaredeployedintherightplacesintherightproportions.Whatdoesallthishavetodowiththeoriginofbodies?

Onepropertyiscommontoanimals,whethertheyhaveskeletonsornot:allofthem,includingclumpsofcells,havemoleculesthatliebetweentheircells,specificallydifferentkindsofcollagensandproteoglycans.Collagenseemsparticularlyimportant:themostcommonproteinin

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animals,itmakesupover90percentofthebody’sproteinbyweight.Bodybuildinginthedistantpastmeantthatmoleculeslikethesehadtobeinvented.Somethingelseisessentialforbodies:thecellsinour

boneshavetobeabletosticktogetherandtalktooneanother.Howdobonecellsattachtooneanother,andhowdodifferentpartsofboneknowtobehavedifferently?Hereiswheremuchofourbodybuildingkitlies.Bonecells,likeeverycellinourbodies,sticktoone

anotherbymeansoftinymolecularrivets,ofwhichthereisavastdiversity.Somebindcellsthewaycontactcementholdsthesolesofshoestogether:onemoleculeisfirmlyattachedtotheoutermembraneofonecell,anothertotheoutermembraneofaneighboringcell.Thusattachedtobothcellmembranes,theglueformsastablebondbetweenthecells.Othermolecularrivetsaresoprecisethattheybind

selectively,onlytothesamekindofrivet.Thisisahugelysignificantfeaturebecauseithelpsorganizeourbodiesinafundamentalway.Theseselectiverivetsenablecellstoorganizethemselvesandensurethatbonecellssticktobonecells,skintoskin,andsoon.Theycanorganizeourbodiesintheabsenceofotherinformation.Ifweputanumberofcells,eachwithadifferentkindofthistypeofrivet,onadishandletthecellsgrow,thecellswillorganizethemselves.Somemightformballs,otherssheets,asthecellssortoutbythenumbersandkindsofrivetstheyhave.Butarguablythemostimportantconnectionbetween

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cellsliesinthewaysthattheyexchangeinformationwithoneanother.Theprecisepatternofourskeleton,infactofourwholebody,ispossibleonlybecausecellsknowhowtobehave.Cellsneedtoknowwhentodivide,whentomakemolecules,andwhentodie.If,forexample,boneorskincellsbehavedrandomly—iftheydividedtoomuchordiedtoolittle—thenwewouldbeveryuglyor,worse,verydead.Cellscommunicatewithoneanotherusing“words”

writtenasmoleculesthatmovefromcelltocell.Onecellcan“talk”tothenextbysendingmoleculesbackandforth.Forinstance,inarelativelysimpleformofcell-to-cellcommunication,onecellwillemitasignal,inthiscaseamolecule.Thismoleculewillattachtotheoutercovering,ormembrane,ofthecellreceivingthesignal.Onceattachedtotheoutermembrane,themoleculewillsetoffachainreactionofmoleculareventsthattravelsfromtheoutermembranealltheway,inmanycases,tothenucleusofthecell.Rememberthatthegeneticinformationsitsinsidethenucleus.Consequently,thismolecularsignalcancausegenestobeturnedonandoff.Theendresultofallthisisthatthecellreceivingtheinformationnowchangesitsbehavior:itmaydie,divide,ormakenewmoleculesinresponsetothecuefromtheothercell.Atthemostbasiclevel,thesearethethingsthatmake

bodiespossible.Allanimalswithbodieshavestructuralmoleculeslikecollagensandproteoglycans,allofthemhavethearrayofmolecularrivetsthatholdcellstogether,andallofthemhavethemoleculartoolsthatallowcellsto

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communicatewithoneanother.Wenowhaveasearchimagetounderstandthehowof

bodyorigins.Toseehowbodiesarose,weneedtolookforthesemoleculesinthemostprimitivebodiesontheplanet,andthen,ultimately,increaturesthathavenobodyatall.

BODYBUILDINGFORBLOBS

Whatdoesthebodyofaprofessorsharewithablob?Let’slookatsomeofthemostprimitivebodiesalivetodaytofindtheanswer.Oneofthesecreatureshasthedubiousdistinctionof

almostneverbeingseeninthewild.Inthelate1880s,astrangelysimplecreaturewasdiscoveredlivingontheglasswallsofanaquarium.Unlikeanythingelsealive,itlookedlikeamassofgoo.TheonlythingwecancompareitwithisthealiencreatureintheSteveMcQueenmovieTheBlob.RecallthattheBlobwasanamorphousglopthat,afterdroppinginfromouterspace,engulfeditsprey:dogs,people,andeventuallysmalldinersinlittletownsinPennsylvania.TheBlob’sdigestiveendwasonitsunderside:weneversawit;weonlyheardtheshrieksofcreaturescaughtthere.ShrinktheBlobdowntobetween200and1,000cells,abouttwomillimetersindiameter,andwehavetheenigmaticlivingcreatureknownasaplacozoan.Placozoanshaveonlyfourtypesofcells,whichmakeaverysimplebodyshapedlikeasmallplate.Itisa

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realbody,though.Someofthecellsontheundersurfacearespecializedfordigestion;othershaveflagella,whichbeattomovethecreaturearound.Wehavelittleideaofwhattheyeatinthewild,wheretheylive,orwhattheirnaturalhabitatis.Yetthesesimpleblobsrevealsomethingterrificallyimportant:withasmallnumberofspecializedcells,theseprimitivecreaturesalreadyhaveadivisionoflaboramongtheirparts.Muchofwhatisinterestingaboutbodiesalreadyexists

inplacozoans.Theyhavetruebodies,albeitprimitivelyorganizedones.InsearchingthroughtheirDNAandexaminingthemoleculesonthesurfaceoftheircells,wefindthatmuchofourbodybuildingapparatusisalreadythere.Placozoanshaveversionsofthemolecularrivetsandcellcommunicationtoolsweseeinourownbodies.Ourbodybuildingapparatusisfoundinblobssimpler

thansomeofReginaldSprigg’sancientimpressions.Canwegofurther,toevenmoreprimitivekindsofbodies?Partoftheanswerliesinapieceofclassickitchenware:thesponge.Atfirstglance,spongesareunremarkable.Thebodyofaspongeconsistsofthespongematrixitself;notalivingmaterial,itisaformofsilica(glassymaterial)orcalciumcarbonate(ahardshell-likematerial)withsomecollageninterspersed.Rightoffthebat,thatmakesspongesinteresting.Recallthatcollagenisamajorpartofourintercellularspaces,holdingcellsandmanytissuestogether.Spongesmaynotlookit,buttheyalreadyhaveoneoftheearmarksofbodies.

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Intheearly1900s,H.V.P.Wilsonshowedjusthowamazingspongesreallyare.WilsoncametotheUniversityofNorthCarolinaasitsfirstprofessorofbiologyin1894.TherehewentontotrainacadreofAmericanbiologistswhoweretodefinethefieldofgeneticsandcellbiologyinNorthAmericaforthenextcentury.Asayoungman,Wilsondecidedtofocushislife’sresearchon,ofallthings,sponges.Oneofhisexperimentsrevealedatrulyremarkablecapabilityoftheseapparentlysimplecreatures.Heranthemthroughakindofsieve,whichbrokethemdowntoasetofdisaggregatedcells.Wilsonputthenowcompletelydisaggregated,amoeba-likecellsinadishandwatchedthem.Atfirst,theycrawledaroundonthesurfaceofthedish.Then,somethingsurprisinghappened:thecellscametogether.First,theyformedredcloudyballsofcells.Next,theygainedmoreorganization,withcellsbecomingpackedindefinitepatterns.Finally,theclumpofcellswouldformanentirenewspongebody,withthevarioustypesofcellsassumingtheappropriatepositions.Wilsonwaswatchingabodycometogetheralmostfromscratch.Ifwewerelikesponges,thentheSteveBuscemicharacterwhogetsmincedinthewoodchipperintheCoenbrothers’movieFargowouldhavebeenjustfine.Infact,hemighthavebeeninvigoratedbytheexperience,ashiscellsmighthaveaggregatedtoformmanydifferentversionsofhim.Itisthecellswithinspongesthatmakethemusefulin

understandingtheoriginofbodies.Theinsideofthespongeisusuallyahollowspacethatcanbedividedinto

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compartments,dependingonthespecies.Waterflowsthroughthespace,directedbyaveryspecialkindofcell.Thesecellsareshapedlikegobletswiththecuppartfacingtheinsideofthesponge.Tinyciliaextendingfromtherimofthegobletbeatandcapturefoodparticlesinthewater.Alsoextendingfromthegobletpartofeachofthesecellsisalargeflagellum.Theconcertedactionoftheflagellaoftheselittlebeatercellsmoveswaterandfoodthroughtheporesofthesponge.Othercellsontheinsideofthespongeprocesstheparticlesoffood.Stillotherslinetheoutsideandcancontractwhenthespongeneedstochangeitsshapeaswatercurrentschange.Aspongeseemsafarcryfromabody,yetithasmanyof

themostimportantpropertiesofbodies:itscellshaveadivisionoflabor;thecellscancommunicatewithoneanother;andthearrayofcellsfunctionsasasingleindividual.Aspongeisorganized,withdifferentkindsofcellsindifferentplacesdoingdifferentthings.Itisafarcryfromahumanbodywithtrillionsofpreciselypackagedcells,butitsharessomeofthehumanbody’sfeatures.Mostsignificantly,thespongehasmuchofthecelladhesion,communication,andscaffoldingapparatusthatwehave.Spongesarebodies,albeitveryprimitiveandrelativelydisorganizedones.Likeplacozoansandsponges,wehavemanycells.Like

them,ourbodiesshowadivisionoflaboramongparts.Thewholemolecularapparatusthatholdsbodiestogetherisalsopresent:therivetsthatholdcellstogether;thevarious

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devicesthathelpcellssignaltooneanother;andmanyofthemoleculesthatliebetweencells.Likeusandallotheranimals,placozoansandspongesevenhavecollagen.Unlikeus,theyhaveveryprimitiveversionsofallthesefeatures:insteadoftwenty-onecollagens,spongeshavetwo;whereaswehavehundredsofdifferenttypesofmolecularrivets,spongeshaveasmallfractionofthatnumber.Spongesaresimplerthanweandhavefewerkindsofcells,butthebasicbodybuildingapparatusisthere.Placozoansandspongesareaboutassimpleasbodies

getnowadays.Togoanyfurther,wehavetosearchforthethingsthatbuildourbodiesincreaturesthathavenobodiesatall:single-celledmicrobes.Howdoyoucompareamicrobetoananimalwitha

body?Arethetoolsthatbuildbodiesinanimalspresentinsingle-celledcreatures?Ifso,andiftheyarenotbuildingbodies,whataretheydoing?Themoststraightforwardwaytobegintoanswerthese

questionsinvolveslookinginsidethegenesofmicrobestosearchforanysimilaritiestoanimals.Theearliestcomparisonsbetweenanimalandmicrobialgenomesrevealedastrikingfact:inmanysingle-celledanimals,muchofthemolecularmachineryforcelladhesion,interaction,andsoonisjustnotthere.Someanalysesevensuggestedthatmorethaneighthundredofthesekindsofmoleculesarefoundonlyinanimalswithbodieswhiletheyareabsentinsingle-celledcreatures.Thiswouldseemtosupportthenotionthatthegenesthathelpcellsuniteto

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makebodiesarosetogetherwiththeoriginofbodies.Andatfirstglance,itseemstomakesensethatthetoolstobuildbodiesshouldariseinlockstepwithbodiesthemselves.ThestoryturnedupsidedownwhenNicoleKing,ofthe

UniversityofCaliforniaatBerkeley,studiedtheorganismscalledchoanoflagellates.King’schoiceofsubjectwasnoaccident.FromworkonDNA,sheknewthatchoanoflagellatesarelikelytheclosestmicroberelativesofanimalswithbodies,placozoans,andsponges.ShealsosuspectedthathiddeninthegenesofchoanoflagellatesareversionsoftheDNAthatmakeourbodies.NicolewasaidedinhersearchbytheHumanGenome

Project,anenterprisethathassucceededinmappingallthegenesinourbodies.WiththesuccessoftheHumanGenomeProjectcamemanyothermappingstudies:we’vehadtheRatGenomeProject,theFlyGenomeProject,theBumblebeeGenomeProject—thereareevenongoingprojectstosequencethegenomesofsponges,placozoans,andmicrobes.Thesemapsareagoldmineofinformationbecausetheyenableustocomparethebodybuildinggenesinmanydifferentspecies.TheyalsogaveNicolethegenetictoolstostudyherchoanoflagellates.Choanoflagellateslookremarkablylikethegoblet-shaped

cellsinsideasponge.Infact,foralongtime,manypeoplethoughtthattheywerejustdegeneratesponges—spongeswithoutalltheothercells.Ifthiswerethecase,thentheDNAofchoanoflagellatesshouldresemblethatofabizarresponge.Itdoesn’t.WhenpartsoftheDNAof

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choanoflagellateswerecomparedwithmicrobeandspongeDNA,thesimilaritytomicrobeDNAturnedouttobeextraordinary.Choanoflagellatesaresingle-celledmicrobes.Thegeneticdistinctionbetween“single-celledmicrobe”

and“animalwithbody”completelybrokedownthankstoNicole’sworkonchoanoflagellates.Mostofthegenesthatareactiveinchoanoflagellatesarealsoactiveinanimals.Infact,manyofthosegenesarepartofthemachinerythatbuildsbodies.Afewexamplesrevealthepowerofthiscomparison.Functionsofcelladhesionandcellcommunication,evenpartsofthemoleculesthatformthematrixbetweencellsandthemolecularcascadesthatferryasignalfromoutsidethecelltotheinside—allarepresentinchoanoflagellates.Collagensarepresentinchoanoflagellates.Thevariouskindsofmolecularrivetsthatholdcellstogetherarealsopresentinchoanoflagellates,althoughtheyaredoingslightlydifferentjobs.

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Choanoflagellates(left)andsponges(right).ChoanoflagellatesevengiveNicolearoadmapfor

comparingourbodybuildingapparatustothatofothermicrobes.Thefundamentalmolecularstructurethatmakescollagensandproteoglycanaggregatesisknownfromanumberofdifferentkindofmicrobes.Streptococcusbacteria—commoninourmouths(and,onehopes,rareinotherplaces)—haveontheircellsurfaceamoleculethatisverysimilartocollagen.Ithasthesamemolecular

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signature,butdoesnotaggregatetoformropesorsheetsascollagensdoinanimals.Likewise,someofthesugarsthatmakeupproteoglycancomplexesinsideourcartilageareseeninthewallsofdifferentkindsofbacteria.Theirfunctionsinbothvirusesandbacteriaarenotparticularlypleasant.Theyareassociatedwiththewaysthattheseagentsinvadeandinfectcellsand,inmanycases,becomemorevirulent.Manyofthemoleculesthatmicrobesusetocauseusmiseryareprimitiveversionsofthemoleculesthatmakeourownbodiespossible.Thissetsupapuzzle.Inthefossilrecord,weseenothing

butmicrobesforthefirst3.5billionyearsofearthhistory.Then,suddenly,overaspanofperhaps40millionyears,allkindsofbodiesappear:plantbodies,fungalbodies,animalbodies;bodieseverywhere.Bodieswerearealfad.But,ifyoutakeNicole’sworkatfacevalue,thepotentialtobuildbodieswasinplacewellbeforebodieseverhitthescene.Whytherushforbodiesaftersuchaverylongtimewithnobodiesatall?

APERFECTSTORMINTHEORIGINOFBODIES

Timingiseverything.Thebestideas,inventions,andconceptsdon’talwayswin.Howmanymusicians,inventors,andartistsweresofaraheadoftheirtimethattheyfloppedandwereforgotten,onlytoberediscoveredlater?WeneedlooknofurtherthanpoorHeronofAlexandria,who,

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perhapsinthefirstcenturya.d.,inventedthesteamturbine.Unfortunately,itwasregardedasatoy.Theworldwasn’treadyforit.Thehistoryoflifeworksthesameway.Thereisa

momentforeverything,perhapsevenforbodies.Toseethis,weneedtounderstandwhybodiesmighthavecomeaboutinthefirstplace.Onetheoryaboutthisisextremelysimple:Perhaps

bodiesarosewhenmicrobesdevelopednewwaystoeateachotheroravoidbeingeaten?Havingabodywithmanycellsallowscreaturestogetbig.Gettingbigisoftenaverygoodwaytoavoidbeingeaten.Bodiesmayhavearisenasjustthatkindofdefense.Whenpredatorsdevelopnewwaysofeating,prey

developnewwaysofavoidingthatfate.Thisinterplaymayhaveledtotheoriginofmanyofourbodybuildingmolecules.Manymicrobesfeedbyattachingandengulfingothermicrobes.Themoleculesthatallowmicrobestocatchtheirpreyandholdontothemarelikelycandidatesforthemoleculesthatformtherivetattachmentsbetweencellsinourbodies.Somemicrobescanactuallycommunicatewitheachotherbymakingcompoundsthatinfluencethebehaviorofothermicrobes.Predator-preyinteractionsbetweenmicrobesofteninvolvemolecularcues,eithertowardoffpotentialpredatorsortoserveasluresenticingpreytocomeclose.Perhapssignalslikethesewereprecursorstothekindsofsignalsthatourowncellsusetoexchangeinformationtokeepourbodiesintact.

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Wecouldspeculateonthisadinfinitum,butmoreexcitingwouldbesometangibleexperimentalevidencethatshowshowpredationcouldbringaboutbodies.ThatisessentiallywhatMartinBoraasandhiscolleaguesprovided.Theytookanalgathatisnormallysingle-celledandletitliveinthelabforoverathousandgenerations.Thentheyintroducedapredator:asingle-celledcreaturewithaflagellumthatengulfsothermicrobestoingestthem.Inlessthantwohundredgenerations,thealgarespondedbybecomingaclumpofhundredsofcells;overtime,thenumberofcellsdroppeduntiltherewereonlyeightineachclump.Eightturnedouttobetheoptimumbecauseitmadeclumpslargeenoughtoavoidbeingeatenbutsmallenoughsothateachcellcouldpickuplighttosurvive.Themostsurprisingthinghappenedwhenthepredatorwasremoved:thealgaecontinuedtoreproduceandformindividualswitheightcells.Inshort,asimpleversionofamulticellularformhadarisenfromano-body.Ifanexperimentcanproduceasimplebody-like

organizationfromano-bodyinseveralyears,imaginewhatcouldhappeninbillionsofyears.Thequestionthenbecomesnothowcouldbodiesarise,butwhydidn’ttheyarisesooner?Answerstothispuzzlemightlieintheancient

environmentinwhichbodiesarose:theworldmaynothavebeenreadyforbodies.Abodyisaveryexpensivethingtohave.Thereare

obviousadvantagesofbecomingacreaturewithalarge

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body:besidesavoidingpredators,animalswithbodiescaneatother,smallercreaturesandactivelymovelongdistances.Bothoftheseabilitiesallowtheanimalstohavemorecontrolovertheirenvironment.Butbothconsumealotofenergy.Bodiesrequireevenmoreenergyastheygetlarger,particularlyiftheyincorporatecollagen.Collagenrequiresarelativelylargeamountofoxygenforitssynthesisandwouldhavegreatlyincreasedourancestors’needforthisimportantmetabolicelement.Buttheproblemwasthis:levelsofoxygenontheancient

earthwereverylow.Forbillionsofyearsoxygenlevelsintheatmospheredidnotcomeclosetowhatwehavetoday.Then,roughlyabillionyearsago,theamountofoxygenincreaseddramaticallyandhasstayedrelativelyhigheversince.Howdoweknowthis?Fromthechemistryofrocks.Rocksfromaboutabillionyearsagoshowthetelltalesignatureofhavingbeenformedwithincreasingamountsofoxygen.Couldtheriseinoxygenintheatmospherebelinkedtotheoriginofbodies?Itmayhavetakenthepaleontologicalequivalentofa

perfectstormtobringaboutbodies.Forbillionsofyears,microbesdevelopednewwaysofinteractingwiththeirenvironmentandwithoneanother.Indoingso,theyhitonanumberofthemolecularpartsandtoolstobuildbodies,thoughtheyusedthemforotherpurposes.Acausefortheoriginofbodieswasalsoinplace:byabillionyearsago,microbeshadlearnedtoeateachother.Therewasareasontobuildbodies,andthetoolstodosowerealreadythere.

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Somethingwasmissing.Thatsomethingwasenoughoxygenontheearthtosupportbodies.Whentheearth’soxygenincreased,bodiesappearedeverywhere.Lifewouldneverbethesame.

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