Your Inner Fish - Weeblymtbio.weebly.com/.../your_inner_fish_-_neil_shubin.pdfCHAPTER ONE FINDING...

CONTENTS

TitlePageDedicationPreface

ONEFindingYourInnerFish

TWOGettingaGripTHREEHandyGenes

FOURTeethEverywhereFIVEGettingAhead

SIXTheBest-Laid(Body)PlansSEVENAdventuresinBodybuilding

EIGHTMakingScentsNINEVisionTENEars

ELEVENTheMeaningofItAll

EpilogueNotes,References,andFurtherReading

AcknowledgmentsCopyright

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TOMICHELE

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PREFACE

Thisbookgrewoutofanextraordinarycircumstanceinmylife.Onaccountoffacultydepartures,IendedupdirectingthehumananatomycourseatthemedicalschooloftheUniversityofChicago.Anatomyisthecourseduringwhichnervousfirst-yearmedicalstudentsdissecthumancadaverswhilelearningthenamesandorganizationofmostoftheorgans,holes,nerves,andvesselsinthebody.Thisistheirgrandentrancetotheworldofmedicine,aformativeexperienceontheirpathtobecomingphysicians.Atfirstglance,youcouldn’thaveimaginedaworsecandidateforthejoboftrainingthenextgenerationofdoctors:I’mapaleontologistwhohasspentmostofhiscareerworkingonfish.Itturnsoutthatbeingapaleontologistisahuge

advantageinteachinghumananatomy.Why?Thebestroadmapstohumanbodieslieinthebodiesofotheranimals.Thesimplestwaytoteachstudentsthenervesinthehumanheadistoshowthemthestateofaffairsinsharks.Theeasiestroadmaptotheirlimbsliesinfish.Reptilesarearealhelpwiththestructureofthebrain.Thereasonisthat

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thebodiesofthesecreaturesareoftensimplerversionsofours.Duringthesummerofmysecondyearleadingthecourse,

workingintheArctic,mycolleaguesandIdiscoveredfossilfishthatgaveuspowerfulnewinsightsintotheinvasionoflandbyfishover375millionyearsago.Thatdiscoveryandmyforayintoteachinghumananatomyledmetoexploreaprofoundconnection.Thatexplorationbecamethisbook.

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CHAPTERONE

FINDINGYOURINNERFISH

Typicalsummersofmyadultlifearespentinsnowandsleet,crackingrocksoncliffswellnorthoftheArcticCircle.MostofthetimeIfreeze,getblisters,andfindabsolutelynothing.ButifIhaveanyluck,Ifindancientfishbones.Thatmaynotsoundlikeburiedtreasuretomostpeople,buttomeitismorevaluablethangold.Ancientfishbonescanbeapathtoknowledgeaboutwho

weareandhowwegotthatway.Welearnaboutourownbodiesinseeminglybizarreplaces,rangingfromthefossilsofwormsandfishrecoveredfromrocksfromaroundtheworldtotheDNAinvirtuallyeveryanimalaliveonearthtoday.Butthatdoesnotexplainmyconfidenceaboutwhyskeletalremainsfromthepast—andtheremainsoffish,noless—offercluesaboutthefundamentalstructureofourbodies.Howcanwevisualizeeventsthathappenedmillionsand,

inmanycases,billionsofyearsago?Unfortunately,therewerenoeyewitnesses;noneofuswasaround.Infact,nothingthattalksorhasamouthorevenaheadwas

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aroundformostofthistime.Evenworse,theanimalsthatexistedbackthenhavebeendeadandburiedforsolongtheirbodiesareonlyrarelypreserved.Ifyouconsiderthatover99percentofallspeciesthateverlivedarenowextinct,thatonlyaverysmallfractionarepreservedasfossils,andthatanevensmallerfractionstillareeverfound,thenanyattempttoseeourpastseemsdoomedfromthestart.

DIGGINGFOSSILS—SEEINGOURSELVES

IfirstsawoneofourinnerfishonasnowyJulyafternoonwhilestudying375-million-year-oldrocksonEllesmereIsland,atalatitudeabout80degreesnorth.MycolleaguesandIhadtraveleduptothisdesolatepartoftheworldtotrytodiscoveroneofthekeystagesintheshiftfromfishtoland-livinganimals.Stickingoutoftherockswasthesnoutofafish.Andnotjustanyfish:afishwithaflathead.Oncewesawtheflatheadweknewwewereontosomething.Ifmoreofthisskeletonwerefoundinsidethecliff,itwouldrevealtheearlystagesinthehistoryofourskull,ourneck,evenourlimbs.Whatdidaflatheadtellmeabouttheshiftfromseato

land?Morerelevanttomypersonalsafetyandcomfort,whywasIintheArcticandnotinHawaii?Theanswerstothesequestionslieinthestoryofhowwefindfossilsandhowweusethemtodecipherourownpast.

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Fossilsareoneofthemajorlinesofevidencethatweusetounderstandourselves.(Genesandembryosareothers,whichIwilldiscusslater.)Mostpeopledonotknowthatfindingfossilsissomethingwecanoftendowithsurprisingprecisionandpredictability.Weworkathometomaximizeourchancesofsuccessinthefield.Thenweletlucktakeover.Theparadoxicalrelationshipbetweenplanningand

chanceisbestdescribedbyDwightD.Eisenhower’sfamousremarkaboutwarfare:“Inpreparingforbattle,Ihavefoundthatplanningisessential,butplansareuseless.”Thiscapturesfieldpaleontologyinanutshell.Wemakeallkindsofplanstogetustopromisingfossilsites.Oncewe’rethere,theentirefieldplanmaybethrownoutthewindow.Factsonthegroundcanchangeourbest-laidplans.Yetwecandesignexpeditionstoanswerspecific

scientificquestions.Usingafewsimpleideas,whichI’lltalkaboutbelow,wecanpredictwhereimportantfossilsmightbefound.Ofcourse,wearenotsuccessful100percentofthetime,butwestrikeitrichoftenenoughtomakethingsinteresting.Ihavemadeacareeroutofdoingjustthat:findingearlymammalstoanswerquestionsofmammalorigins,theearliestfrogstoanswerquestionsoffrogorigins,andsomeoftheearliestlimbedanimalstounderstandtheoriginsofland-livinganimals.Inmanyways,fieldpaleontologistshaveasignificantly

easiertimefindingnewsitestodaythanweeverdidbefore.Weknowmoreaboutthegeologyoflocalareas,thanksto

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thegeologicalexplorationundertakenbylocalgovernmentsandoilandgascompanies.TheInternetgivesusrapidaccesstomaps,surveyinformation,andaerialphotos.Icanevenscanyourbackyardforpromisingfossilsitesrightfrommylaptop.Totopitoff,imagingandradiographicdevicescanseethroughsomekindsofrockandallowustovisualizethebonesinside.Despitetheseadvances,thehuntfortheimportant

fossilsismuchwhatitwasahundredyearsago.Paleontologistsstillneedtolookatrock—literallytocrawloverit—andthefossilswithinmustoftenberemovedbyhand.Somanydecisionsneedtobemadewhenprospectingforandremovingfossilbonethattheseprocessesaredifficulttoautomate.Besides,lookingatamonitorscreentofindfossilswouldneverbenearlyasmuchfunasactuallydiggingforthem.Whatmakesthistrickyisthatfossilsitesarerare.To

maximizeouroddsofsuccess,welookfortheconvergenceofthreethings.Welookforplacesthathaverocksoftherightage,rocksoftherighttypetopreservefossils,androcksthatareexposedatthesurface.Thereisanotherfactor:serendipity.ThatIwillshowbyexample.Ourexamplewillshowusoneofthegreattransitionsin

thehistoryoflife:theinvasionoflandbyfish.Forbillionsofyears,alllifelivedonlyinwater.Then,asofabout365millionyearsago,creaturesalsoinhabitedland.Lifeinthesetwoenvironmentsisradicallydifferent.Breathinginwaterrequiresverydifferentorgansthanbreathinginair.

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Thesameistrueforexcretion,feeding,andmovingabout.Awholenewkindofbodyhadtoarise.Atfirstglance,thedividebetweenthetwoenvironmentsappearsalmostunbridgeable.Buteverythingchangeswhenwelookattheevidence;whatlooksimpossibleactuallyhappened.Inseekingrocksoftherightage,wehavearemarkable

factonourside.Thefossilsintherocksoftheworldarenotarrangedatrandom.Wheretheysit,andwhatliesinsidethem,ismostdefinitelyordered,andwecanusethisordertodesignourexpeditions.Billionsofyearsofchangehaveleftlayeruponlayerofdifferentkindsofrockintheearth.Theworkingassumption,whichiseasytotest,isthatrocksonthetopareyoungerthanrocksonthebottom;thisisusuallytrueinareasthathaveastraightforward,layer-cakearrangement(thinktheGrandCanyon).Butmovementsoftheearth’scrustcancausefaultsthatshiftthepositionofthelayers,puttingolderrocksontopofyoungerones.Fortunately,oncethepositionsofthesefaultsarerecognized,wecanoftenpiecetheoriginalsequenceoflayersbacktogether.Thefossilsinsidetheserocklayersalsofollowa

progression,withlowerlayerscontainingspeciesentirelydifferentfromthoseinthelayersabove.Ifwecouldquarryasinglecolumnofrockthatcontainedtheentirehistoryoflife,wewouldfindanextraordinaryrangeoffossils.Thelowestlayerswouldcontainlittlevisibleevidenceoflife.Layersabovethemwouldcontainimpressionsofadiversesetofjellyfish-likethings.Layersstillhigherwouldhave

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creatureswithskeletons,appendages,andvariousorgans,suchaseyes.Abovethosewouldbelayerswiththefirstanimalstohavebackbones.Andsoon.Thelayerswiththefirstpeoplewouldbefoundhigherstill.Ofcourse,asinglecolumncontainingtheentiretyofearthhistorydoesnotexist.Rather,therocksineachlocationonearthrepresentonlyasmallsliveroftime.Togetthewholepicture,weneedtoputthepiecestogetherbycomparingtherocksthemselvesandthefossilsinsidethem,muchasifworkingagiantjigsawpuzzle.Thatacolumnofrockshasaprogressionoffossilspecies

probablycomesasnosurprise.Lessobviousisthatwecanmakedetailedpredictionsaboutwhatthespeciesineachlayermightactuallylooklikebycomparingthemwithspeciesofanimalsthatarealivetoday;thisinformationhelpsustopredictthekindsoffossilswewillfindinancientrocklayers.Infact,thefossilsequencesintheworld’srockscanbepredictedbycomparingourselveswiththeanimalsatourlocalzoooraquarium.Howcanawalkthroughthezoohelpuspredictwherewe

shouldlookintherockstofindimportantfossils?Azoooffersagreatvarietyofcreaturesthatarealldistinctinmanyways.Butlet’snotfocusonwhatmakesthemdistinct;topulloffourprediction,weneedtofocusonwhatdifferentcreaturesshare.Wecanthenusethefeaturescommontoallspeciestoidentifygroupsofcreatureswithsimilartraits.AllthelivingthingscanbeorganizedandarrangedlikeasetofRussiannestingdolls,withsmaller

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groupsofanimalscomprisedinbiggergroupsofanimals.Whenwedothis,wediscoversomethingveryfundamentalaboutnature.Everyspeciesinthezooandtheaquariumhasaheadand

twoeyes.Callthesespecies“Everythings.”Asubsetofthecreatureswithaheadandtwoeyeshaslimbs.Callthelimbedspecies“Everythingswithlimbs.”Asubsetoftheseheadedandlimbedcreatureshasahugebrain,walksontwofeet,andspeaks.Thatsubsetisus,humans.Wecould,ofcourse,usethiswayofcategorizingthingstomakemanymoresubsets,buteventhisthreefolddivisionhaspredictivepower.Thefossilsinsidetherocksoftheworldgenerallyfollow

thisorder,andwecanputittouseindesigningnewexpeditions.Tousetheexampleabove,thefirstmemberofthegroup“Everythings,”acreaturewithaheadandtwoeyes,isfoundinthefossilrecordwellbeforethefirst“Everythingwithlimbs.”Moreprecisely,thefirstfish(acard-carryingmemberofthe“Everythings”)appearsbeforethefirstamphibian(an“Everythingwithlimbs”).Obviously,werefinethisbylookingatmorekindsofanimalsandmanymorecharacteristicsthatgroupsofthemshare,aswellasbyassessingtheactualageoftherocksthemselves.Inourlabs,wedoexactlythistypeofanalysiswith

thousandsuponthousandsofcharacteristicsandspecies.Welookateverybitofanatomywecan,andoftenatlargechunksofDNA.Thereissomuchdatathatweoftenneed

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powerfulcomputerstoshowusthegroupswithingroups.Thisapproachisthefoundationofbiology,becauseitenablesustomakehypothesesabouthowcreaturesarerelatedtooneanother.Besideshelpingusrefinethegroupingsoflife,hundreds

ofyearsoffossilcollectionhaveproducedavastlibrary,orcatalogue,oftheagesoftheearthandthelifeonit.Wecannowidentifygeneraltimeperiodswhenmajorchangesoccurred.Interestedintheoriginofmammals?GotorocksfromtheperiodcalledtheEarlyMesozoic;geochemistrytellsusthattheserocksarelikelyabout210millionyearsold.Interestedintheoriginofprimates?Gohigherintherockcolumn,totheCretaceousperiod,whererocksareabout80millionyearsold.Theorderoffossilsintheworld’srocksispowerful

evidenceofourconnectionstotherestoflife.If,diggingin600-million-year-oldrocks,wefoundtheearliestjellyfishlyingnexttotheskeletonofawoodchuck,thenwewouldhavetorewriteourtexts.Thatwoodchuckwouldhaveappearedearlierinthefossilrecordthanthefirstmammal,reptile,orevenfish—beforeeventhefirstworm.Moreover,ourancientwoodchuckwouldtellusthatmuchofwhatwethinkweknowaboutthehistoryoftheearthandlifeonitiswrong.Despitemorethan150yearsofpeoplelookingforfossils—oneverycontinentofearthandinvirtuallyeveryrocklayerthatisaccessible—thisobservationhasneverbeenmade.

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Whatwediscoveronourwalkthroughthezoomirrorshowfossilsarelaidoutintherocksoftheworld.

Let’snowreturntoourproblemofhowtofindrelatives

ofthefirstfishtowalkonland.Inourgroupingscheme,thesecreaturesaresomewherebetweenthe“Everythings”andthe“Everythingswithlimbs.”Mapthistowhatweknowoftherocks,andthereisstronggeologicalevidencethattheperiodfrom380millionto365millionyearsagois

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thecriticaltime.Theyoungerrocksinthatrange,thoseabout360millionyearsold,includediversekindsoffossilizedanimalsthatwewouldallrecognizeasamphibiansorreptiles.MycolleagueJennyClackatCambridgeUniversityandothershaveuncoveredamphibiansfromrocksinGreenlandthatareabout365millionyearsold.Withtheirnecks,theirears,andtheirfourlegs,theydonotlooklikefish.Butinrocksthatareabout385millionyearsold,wefindwholefishthatlooklike,well,fish.Theyhavefins,conicalheads,andscales;andtheyhavenonecks.Giventhis,itisprobablynogreatsurprisethatweshouldfocusonrocksabout375millionyearsoldtofindevidenceofthetransitionbetweenfishandland-livinganimals.Wehavesettledonatimeperiodtoresearch,andsohave

identifiedthelayersofthegeologicalcolumnwewishtoinvestigate.Nowthechallengeistofindrocksthatwereformedunderconditionscapableofpreservingfossils.Rocksformindifferentkindsofenvironmentsandtheseinitialsettingsleavedistinctsignaturesontherocklayers.Volcanicrocksaremostlyout.Nofishthatweknowofcanliveinlava.Andevenifsuchafishexisted,itsfossilizedboneswouldnotsurvivethesuperheatedconditionsinwhichbasalts,rhyolites,granites,andotherigneousrocksareformed.Wecanalsoignoremetamorphicrocks,suchasschistandmarble,fortheyhaveundergoneeithersuperheatingorextremepressuresincetheirinitialformation.Whateverfossilsmighthavebeenpreservedin

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themhavelongsincedisappeared.Idealtopreservefossilsaresedimentaryrocks:limestones,sandstones,silt-stones,andshales.Comparedwithvolcanicandmetamorphicrocks,theseareformedbymoregentleprocesses,includingtheactionofrivers,lakes,andseas.Notonlyareanimalslikelytoliveinsuchenvironments,butthesedimentaryprocessesmaketheserocksmorelikelyplacestopreservefossils.Forexample,inanoceanorlake,particlesconstantlysettleoutofthewaterandaredepositedonthebottom.Overtime,astheseparticlesaccumulate,theyarecompressedbynew,overridinglayers.Thegradualcompression,coupledwithchemicalprocesseshappeninginsidetherocksoverlongperiodsoftime,meansthatanyskeletonscontainedintherocksstandadecentchanceoffossilizing.Similarprocesseshappeninandalongstreams.Thegeneralruleisthatthegentlertheflowofthestreamorriver,thebetterpreservedthefossils.Everyrocksittingonthegroundhasastorytotell:the

storyofwhattheworldlookedlikeasthatparticularrockformed.Insidetherockisevidenceofpastclimatesandsurroundingsoftenvastlydifferentfromthoseoftoday.Sometimes,thedisconnectbetweenpresentandpastcouldnotbesharper.TaketheextremeexampleofMountEverest,nearwhosetop,atanaltitudeofoverfivemiles,lierocksfromanancientseafloor.GototheNorthFacealmostwithinsightofthefamousHillaryStep,andyoucanfindfossilizedseashells.Similarly,whereweworkintheArctic,temperaturescanreachminus40degreesFahrenheitinthe

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winter.Yetinsidesomeoftheregion’srocksareremnantsofanancienttropicaldelta,almostliketheAmazon:fossilizedplantsandfishthatcouldhavethrivedonlyinwarm,humidlocales.Thepresenceofwarm-adaptedspeciesatwhattodayareextremealtitudesandlatitudesatteststohowmuchourplanetcanchange:mountainsriseandfall,climateswarmandcool,andcontinentsmoveabout.Oncewecometogripswiththevastnessoftimeandtheextraordinarywaysourplanethaschanged,wewillbeinapositiontoputthisinformationtouseindesigningnewfossil-huntingexpeditions.Ifweareinterestedinunderstandingtheoriginoflimbed

animals,wecannowrestrictoursearchtorocksthatareroughly375millionto380millionyearsoldandthatwereformedinoceans,lakes,orstreams.Ruleoutvolcanicrocksandmetamorphicrocks,andoursearchimageforpromisingsitescomesintobetterfocus.Weareonlypartlyonthewaytodesigninganew

expedition,however.Itdoesusnogoodifourpromisingsedimentaryrocksoftherightageareburieddeepinsidetheearth,oriftheyarecoveredwithgrass,orshoppingmalls,orcities.We’dbediggingblindly.Asyoucanimagine,drillingawellholetofindafossiloffersalowprobabilityofsuccess,ratherlikethrowingdartsatadartboardhiddenbehindaclosetdoor.Thebestplacestolookarethosewherewecanwalkfor

milesovertherocktodiscoverareaswherebonesare“weatheringout.”Fossilbonesareoftenharderthanthe

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surroundingrockandsoerodeataslightlyslowerrateandpresentaraisedprofileontherocksurface.Consequently,weliketowalkoverbarebedrock,findasmatteringofbonesonthesurface,thendigin.Sohereisthetricktodesigninganewfossilexpedition:

findrocksthatareoftherightage,oftherighttype(sedimentary),andwellexposed,andweareinbusiness.Idealfossil-huntingsiteshavelittlesoilcoverandlittlevegetation,andhavebeensubjecttofewhumandisturbances.Isitanysurprisethatasignificantfractionofdiscoverieshappenindesertareas?IntheGobiDesert.IntheSahara.InUtah.InArcticdeserts,suchasGreenland.Thisallsoundsverylogical,butlet’snotforget

serendipity.Infact,itwasserendipitythatputourteamontothetrailofourinnerfish.Ourfirstimportantdiscoveriesdidn’thappeninadesert,butalongaroadsideincentralPennsylvaniawheretheexposurescouldhardlyhavebeenworse.Totopitoff,wewerelookingthereonlybecausewedidnothavemuchmoney.IttakesalotofmoneyandtimetogotoGreenlandorthe

SaharaDesert.Incontrast,alocalprojectdoesn’trequirebigresearchgrants,onlymoneyforgasandturnpiketolls.Thesearecriticalvariablesforayounggraduatestudentoranewlyhiredcollegeteacher.WhenIstartedmyfirstjobinPhiladelphia,thelurewasagroupofrockscollectivelyknownastheCatskillFormationofPennsylvania.Thisformationhasbeenextensivelystudiedforover150years.ItsagewaswellknownandspannedtheLateDevonian.In

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addition,itsrockswereperfecttopreserveearlylimbedanimalsandtheirclosestrelatives.Tounderstandthis,itisbesttohaveanimageofwhatPennsylvanialookedlikebackintheDevonian.Removetheimageofpresent-dayPhiladelphia,Pittsburgh,orHarrisburgfromyourmindandthinkoftheAmazonRiverdelta.Therewerehighlandsintheeasternpartofthestate.Aseriesofstreamsrunningeasttowestdrainedthesemountains,endinginalargeseawherePittsburghistoday.Itishardtoimaginebetterconditionstofindfossils,

exceptthatcentralPennsylvaniaiscoveredintowns,forests,andfields.Asfortheexposures,theyaremostlywherethePennsylvaniaDepartmentofTransportation(PennDOT)hasdecidedtoputbigroads.WhenPennDOTbuildsahighway,itblasts.Whenitblasts,itexposesrock.It’snotalwaysthebestexposure,butwetakewhatwecanget.Withcheapscience,yougetwhatyoupayfor.Andthenthereisalsoserendipityofadifferentorder:in

1993,TedDaeschlerarrivedtostudypaleontologyundermysupervision.Thispartnershipwastochangebothourlives.Ourdifferenttemperamentsareperfectlymatched:Ihaveantsinmypantsandamalwaysthinkingofthenextplacetolook;Tedispatientandknowswhentositonasitetomineitforitsriches.TedandIbeganasurveyoftheDevonianrocksofPennsylvaniainhopesoffindingnewevidenceontheoriginoflimbs.Webeganbydrivingtovirtuallyeverylargeroadcutintheeasternpartofthestate.Toourgreatsurprise,shortlyafterwebeganthesurvey,

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Tedfoundamarvelousshoulderbone.WenameditsownerHynerpeton,anamethattranslatesfromGreekas“littlecreepinganimalfromHyner.”Hyner,Pennsylvania,isthenearesttown.Hynerpetonhadaveryrobustshoulder,whichindicatesacreaturethatlikelyhadverypowerfulappendages.Unfortunately,wewereneverabletofindthewholeskeletonoftheanimal.Theexposuresweretoolimited.By?Youguessedit:vegetation,houses,andshoppingmalls.

AlongtheroadsinPennsylvania,wewerelookingatanancientriverdelta,muchliketheAmazontoday.ThestateofPennsylvania(bottom)withtheDevoniantopographymappedaboveit.

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AfterthediscoveryofHynerpetonandotherfossilsfromtheserocks,TedandIwerechampingatthebitforbetter-exposedrock.Ifourentirescientificenterprisewasgoingtobebasedonrecoveringbitsandpieces,thenwecouldaddressonlyverylimitedquestions.Sowetooka“textbook”approach,lookingforwell-exposedrocksoftherightageandtherighttypeindesertregions,meaningthatwewouldn’thavemadethebiggestdiscoveryofourcareersifnotforanintroductorygeologytextbook.OriginallywewerelookingatAlaskaandtheYukonas

potentialvenuesforanewexpedition,largelybecauseofrelevantdiscoveriesmadebyotherteams.Weendedupgettingintoabitofanargument/debateaboutsomegeologicalesoterica,andintheheatofthemoment,oneofuspulledtheluckygeologytextbookfromadesk.Whilerifflingthroughthepagestofindoutwhichoneofuswasright,wefoundadiagram.Thediagramtookourbreathaway;itshowedeverythingwewerelookingfor.Theargumentstopped,andplanningforanewfield

expeditionbegan.Onthebasisofpreviousdiscoveriesmadeinslightly

youngerrocks,webelievedthatancientfreshwaterstreamswerethebestenvironmentinwhichtobeginourhunt.ThisdiagramshowedthreeareaswithDevonianfreshwaterrocks,eachwithariverdeltasystem.First,thereistheeastcoastofGreenland.ThisishometoJennyClack’sfossil,averyearlycreaturewithlimbsandoneoftheearliestknowntetrapods.ThenthereiseasternNorthAmerica,

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wherewehadalreadyworked,hometoHynerpeton.Andthereisathirdarea,largeandrunningeast–westacrosstheCanadianArctic.Therearenotrees,dirt,orcitiesintheArctic.Thechancesweregoodthatrocksoftherightageandtypewouldbeextremelywellexposed.TheCanadianArcticexposureswerewellknown,

particularlytotheCanadiangeologistsandpaleobotanistswhohadalreadymappedthem.Infact,AshtonEmbry,theleaderoftheteamsthatdidmuchofthiswork,haddescribedthegeologyoftheDevonianCanadianrocksasidenticalinmanywaystothegeologyofPennsylvania’s.TedandIwerereadytopackourbagstheminutewereadthisphrase.ThelessonswehadlearnedonthehighwaysofPennsylvaniacouldhelpusintheHighArcticofCanada.Remarkably,theArcticrocksareevenolderthanthe

fossilbedsofGreenlandandPennsylvania.Sotheareaperfectlyfitallthreeofourcriteria:age,type,andexposure.Evenbetter,itwasunknowntovertebratepaleontologists,andthereforeun-prospectedforfossils.

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Themapthatstarteditall.ThismapofNorthAmericacaptureswhatwelookforinanutshell.ThedifferentkindsofshadingreflectwhereDevonianagerocks,whethermarineorfreshwater,areexposed.Threeareasthatwereonceriverdeltasarelabeled.Modifiedfromfigure13.1,R.H.DottandR.L.Batten,EvolutionoftheEarth(NewYork:McGraw-Hill,1988).ReproducedwiththepermissionofTheMcGraw-HillCompanies.

Ournewchallengesweretotallydifferentfromthosewe

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facedinPennsylvania.AlongthehighwaysinPennsylvania,weriskedbeinghitbythetrucksthatwhizzedbyaswelookedforfossils.IntheArcticweriskedbeingeatenbypolarbears,runningoutoffood,orbeingmaroonedbybadweather.Nolongercouldwepacksandwichesinthecaranddrivetothefossilbeds.Wenowhadtospendatleasteightdaysplanningforeverysingledayspentinthefield,becausetherockswereaccessibleonlybyairandthenearestsupplybasewas250milesaway.Wecouldflyinonlyenoughfoodandsuppliesforourcrew,plusaslendersafetymargin.And,mostimportant,theplane’sstrictweightlimitsmeantthatwecouldtakeoutonlyasmallfractionofthefossilsthatwefound.CouplethoselimitationswiththeshortwindowoftimeduringwhichwecanactuallyworkintheArcticeveryyear,andyoucanseethatthefrustrationswefacedwerecompletelynewanddaunting.Entermygraduateadviser,Dr.FarishA.Jenkins,Jr.,from

Harvard.FarishhadledexpeditionstoGreenlandforyearsandhadtheexperiencenecessarytopullthisventureoff.Theteamwasset.Threeacademicgenerations:Ted,myformerstudent;Farish,mygraduateadviser;andIweregoingtomarchuptotheArctictotrytodiscoverevidenceoftheshiftfromfishtoland-livinganimal.ThereisnofieldmanualforArcticpaleontology.We

receivedgearrecommendationsfromfriendsandcolleagues,andwereadbooks—onlytorealizethatnothingcouldprepareusfortheexperienceitself.Atnotimeisthis

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moresharplyfeltthanwhenthehelicopterdropsoneoffforthefirsttimeinsomegodforsakenpartoftheArctictotallyalone.Thefirstthoughtisofpolarbears.Ican’ttellyouhowmanytimesI’vescannedthelandscapelookingforwhitespecksthatmove.Thisanxietycanmakeyouseethings.InourfirstweekintheArctic,oneofthecrewsawamovingwhitespeck.Itlookedlikeapolarbearaboutaquartermileaway.WescrambledlikeKeystoneKopsforourguns,flares,andwhistlesuntilwediscoveredthatourbearwasawhiteArcticharetwohundredfeetaway.Withnotreesorhousesbywhichtojudgedistance,youloseperspectiveintheArctic.TheArcticisabig,emptyplace.Therockswewere

interestedinareexposedoveranareaabout1,500kilometerswide.Thecreatureswewerelookingforwereaboutfourfeetlong.Somehow,weneededtohomeinonasmallpatchofrockthathadpreservedourfossils.Reviewersofgrantproposalscanbeaferociouslot;theylightonthiskindofdifficultyallthetime.AreviewerforoneofFarish’searlyArcticgrantproposalsputitbest.Asthisrefereewroteinhisreviewoftheproposal(notcordially,Imightadd),theoddsoffindingnewfossilsintheArcticwere“worsethanfindingtheproverbialneedleinthehaystack.”IttookusfourexpeditionstoEllesmereIslandoversix

yearstofindourneedle.Somuchforserendipity.Wefoundwhatwewerelookingforbytrying,failing,and

learningfromourfailures.Ourfirstsites,inthe1999field

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season,werewayoutinthewesternpartoftheArctic,onMelvilleIsland.Wedidnotknowit,butwehadbeendroppedoffontheedgeofanancientocean.Therockswereloadedwithfossils,andwefoundmanydifferentkindsoffish.Theproblemwasthattheyallseemedtobedeep-watercreatures,notthekindwewouldexpecttofindintheshallowstreamsorlakesthatgaverisetoland-livinganimals.UsingAshtonEmbry’sgeologicalanalysis,in2000wedecidedtomovetheexpeditioneasttoEllesmereIsland,becausetheretherockswouldcontainancientstreambeds.Itdidnottakelongforustobeginfindingpiecesoffishbonesaboutthesizeofaquarterpreservedasfossils.

Ourcamp(top)lookstinyinthevastnessofthelandscape.Mysummerhome(bottom)isasmalltent,

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usuallysurroundedbypilesofrockstoprotectitfromfifty-mile-per-hourwinds.Photographsbytheauthor.

Therealbreakthroughcametowardtheendofthefield

seasonin2000.Itwasjustbeforedinner,aboutaweekbeforeourscheduledpickuptoreturnhome.Thecrewhadcomebacktocamp,andwewereinvolvedinourearly-eveningactivities:organizingtheday’scollections,preparingfieldnotes,andbeginningtoassembledinner.JasonDowns,thenacollegeundergraduateeagertolearnpaleontology,hadn’treturnedtocampontime.Thisisacauseforworry,aswetypicallygooutinteams;orifweseparate,wegiveeachotheradefinitescheduleofwhenwewillmakecontactagain.Withpolarbearsintheareaandfiercestormsthatcanrollinunexpectedly,wedonottakeanychances.Iremembersittinginthemaintentwiththecrew,theworryaboutJasonbuildingwitheachpassingmoment.Aswebegantoconcoctasearchplan,Iheardthezipperonthetentopen.AtfirstallIsawwasJason’shead.Hehadawild-eyedexpressiononhisfaceandwasoutofbreath.AsJasonenteredthetent,weknewwewerenotdealingwithapolarbearemergency;hisshotgunwasstillshouldered.Thecauseofhisdelaybecameclearashisstillshakinghandpulledouthandfulafterhandfuloffossilbonesthathadbeenstuffedintoeverypocket:hiscoat,pants,innershirt,anddaypack.Iimaginehewouldhavestuffedhissocksandshoesifhecouldhavewalkedhomethatway.Alloftheselittlefossilboneswereonthesurfaceofasmallsite,nobiggerthanaparkingspotforacompact

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car,aboutamileawayfromcamp.Dinnercouldwait.Withtwenty-fourhoursofdaylightintheArcticsummer,

wedidnothavetoworryaboutthesettingsun,sowegrabbedchocolatebarsandsetoffforJason’ssite.Itwasonthesideofahillbetweentwobeautifulrivervalleysand,asJasonhaddiscovered,wascoveredinacarpetoffossilfishbones.Wespentafewhourspickingupthefragments,takingphotos,andmakingplans.Thissitehadallthemakingsofpreciselywhatwewerelookingfor.Wereturnedthenextdaywithanewgoal:tofindtheexactlayerofrockthatcontainedthebones.ThetrickwastoidentifythesourceofJason’smessof

bonefragments—ouronlyhopeoffindingintactskeletons.TheproblemwastheArcticenvironment.Eachwinter,thetemperaturesinkstominus40degreesFahrenheit.Inthesummer,whenthesunneversets,thetemperaturerisestonearly50degrees.Theresultingfreeze-thawcyclecrumblesthesurfacerocksandfossils.Eachwintertheycoolandshrink;eachsummertheyheatandexpand.Astheyshrinkandswellwitheachseasonoverthousandsofyearsatthesurface,thebonesfallapart.Confrontedbyajumbledmassofbonespreadacrossthehill,wecouldnotidentifyanyobviousrocklayerastheirsource.Wespentseveraldaysfollowingthefragmenttrails,diggingtestpits,practicallyusingourgeologicalhammersasdiviningrodstoseewhereintheclifftheboneswereemerging.Afterfourdays,weexposedthelayerandeventuallyfoundskeletonuponskeletonoffossilfish,oftenlyingoneontopofanother.We

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spentpartsoftwosummersexposingthesefish.

Thisiswherewework:southernEllesmereIsland,inNunavutTerritory,Canada,1,000milesfromtheNorthPole.

Failureagain:allthefishwewerefindingwerewell-

knownspeciesthathadbeencollectedinsitesofasimilarageinEasternEurope.Totopitoff,thesefishweren’tverycloselyrelatedtoland-livinganimals.In2004,wedecidedtogiveitonemoretry.Thiswasado-or-diesituation.TheArcticexpeditionswereprohibitivelyexpensiveand,short

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ofaremarkablediscovery,wewouldhavetocallitquits.Everythingchangedoveraperiodoffourdaysinearly

July2004.Iwasflippingrockatthebottomofthequarry,crackingicemoreoftenthanrock.IcrackedtheiceandsawsomethingthatIwillneverforget:apatchofscalesunlikeanythingelsewehadyetseeninthequarry.Thispatchledtoanotherblobcoveredbyice.Itlookedlikeasetofjaws.Theywere,however,unlikethejawsofanyfishIhadeverseen.Theylookedasiftheymighthaveconnectedtoaflathead.Onedaylater,mycolleagueSteveGatesywasflipping

rocksatthetopofthequarry.Steveremovedafist-sizerocktorevealthesnoutofananimallookingrightoutathim.Likemyice-coveredfishatthebottomofthepit,ithadaflathead.Itwasnewandimportant.Butunlikemyfish,Steve’shadrealpotential.Wewerelookingatthefrontend,andwithlucktherestoftheskeletonmightbesafelysittinginthecliff.Stevespenttherestofthesummerremovingrockfromitbitbybitsothatwecouldbringtheentireskeletonbacktothelabandcleanitup.Steve’smasterfulworkwiththisspecimenledtotherecoveryofoneofthefinestfossilsdiscoveredtodateatthewater–landtransition.Thespecimenswebroughtbacktothelabathomewere

littlemorethanboulderswithfossilsinside.Overthecourseoftwomonths,therockwasremovedpiecebypiece,oftenmanuallywithdentaltoolsorsmallpicksbythepreparatorsinthelab.Everydayanewpieceofthefossil

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creature’sanatomywasrevealed.Almosteverytimealargesectionwasexposed,welearnedsomethingnewabouttheoriginofland-livinganimals.Whatwesawgraduallyemergefromtheserocksduring

thefallof2004wasabeautifulintermediatebetweenfishandland-livinganimals.Fishandland-livinganimalsdifferinmanyrespects.Fishhaveconicalheads,whereastheearliestland-livinganimalshavealmostcrocodile-likeheads—flat,withtheeyesontop.Fishdonothavenecks:theirshouldersareattachedtotheirheadsbyaseriesofbonyplates.Earlyland-livinganimals,likealltheirdescendants,dohavenecks,meaningtheirheadscanbendindependentlyoftheirshoulders.Thereareotherbigdifferences.Fishhavescalesallover

theirbodies;land-livinganimalsdonot.Also,importantly,fishhavefins,whereasland-livinganimalshavelimbswithfingers,toes,wrists,andankles.Wecancontinuethesecomparisonsandmakeaverylonglistofthewaysthatfishdifferfromland-livinganimals.

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Theprocessoffindingfossilsbeginswithamassinarockthatisgraduallyremovedovertime.HereIshowafossilasittravelsfromthefieldtothelabandiscarefullypreparedasaspecimen:theskeletonofthenewanimal.Photographinupperleftbyauthor;otherphotographscourtesyofTedDaeschler,AcademyofNaturalSciencesofPhiladelphia.

Butournewcreaturebrokedownthedistinction

betweenthesetwodifferentkindsofanimal.Likeafish,ithasscalesonitsbackandfinswithfinwebbing.But,likeearlyland-livinganimals,ithasaflatheadandaneck.And,whenwelookinsidethefin,weseebonesthatcorrespondtotheupperarm,theforearm,evenpartsofthewrist.Thejointsarethere,too:thisisafishwithshoulder,elbow,andwristjoints.Allinsideafinwithwebbing.Virtuallyallofthefeaturesthatthiscreatureshareswith

land-livingcreatureslookveryprimitive.Forexample,the

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shapeandvariousridgesonthefish’supper“arm”bone,thehumerus,lookpartfishandpartamphibian.Thesameistrueoftheshapeoftheskullandtheshoulder.Ittookussixyearstofindit,butthisfossilconfirmeda

predictionofpaleontology:notonlywasthenewfishanintermediatebetweentwodifferentkindsofanimal,butwehadfounditalsointherighttimeperiodinearth’shistoryandintherightancientenvironment.Theanswercamefrom375-million-year-oldrocks,formedinancientstreams.

Thisfiguresaysitall.Tiktaalikisintermediatebetweenfishandprimitiveland-livinganimal.

Asthediscoverersofthecreature,Ted,Farish,andIhad

theprivilegeofgivingitaformalscientificname.Wewantedthenametoreflectthefish’sprovenanceintheNunavutTerritoryoftheArcticandthedebtweowedtothe

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Inuitpeopleforpermissiontoworkthere.WeengagedtheNunavutCouncilofElders,formallyknownastheInuitQaujimajatuqangitKatimajiit,tocomeupwithanameintheInuktitutlanguage.MyobviousconcernwasthatacommitteenamedInuitQaujimajatuqangitKatimajiitmightnotproposeascientificnamewecouldpronounce.Isentthemapictureofthefossil,andtheelderscameupwithtwosuggestions,SiksagiaqandTiktaalik.WewentwithTiktaalikforitsrelativeeaseofpronunciationforthenon-Inuktitut-speakingtongueandbecauseofitsmeaninginInuktitut:“largefreshwaterfish.”Tiktaalikwastheleadstoryinanumberofnewspapers

thedayafterthefindwasannouncedinApril2006,includingabove-the-foldheadlinesinsuchplacesasTheNewYorkTimes.Thisattentionusheredinaweekunlikeanyotherinmynormallyquietlife.Thoughformethegreatestmomentofthewholemediablitzwasnotseeingthepoliticalcartoonsorreadingtheeditorialcoverageandtheheateddiscussionsontheblogs.Ittookplaceatmyson’spreschool.Inthemidstofthepresshubbub,myson’spreschool

teacheraskedmetobringinthefossilanddescribeit.IdutifullybroughtacastofTiktaalikintoNathaniel’sclass,bracingmyselfforthechaosthatwouldensue.Thetwentyfour-andfive-year-oldsweresurprisinglywellbehavedasIdescribedhowwehadworkedintheArctictofindthefossilandshowedthemtheanimal’ssharpteeth.ThenIaskedwhattheythoughtitwas.Handsshotup.Thefirstchildsaid

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itwasacrocodileoranalligator.Whenqueriedwhy,hesaidthatlikeacrocodileorlizardithasaflatheadwitheyesontop.Bigteeth,too.Otherchildrenstartedtovoicetheirdissent.Choosingtheraisedhandofoneofthesekids,Iheard:No,no,itisn’tacrocodile,itisafish,becauseithasscalesandfins.Yetanotherchildshouted,“Maybeitisboth.”Tiktaalik’smessageissostraightforwardevenpreschoolerscanseeit.Forourpurposes,thereisanevenmoreprofoundtakeon

Tiktaalik.Thisfishdoesn’tjusttellusaboutfish;italsocontainsapieceofus.ThesearchforthisconnectioniswhatledmetotheArcticinthefirstplace.HowcanIbesosurethatthisfossilsayssomething

aboutmyownbody?ConsidertheneckofTiktaalik.AllfishpriortoTiktaalikhaveasetofbonesthatattachtheskulltotheshoulder,sothateverytimetheanimalbentitsbody,italsobentitshead.Tiktaalikisdifferent.Theheadiscompletelyfreeoftheshoulder.Thiswholearrangementissharedwithamphibians,reptiles,birds,andmammals,includingus.TheentireshiftcanbetracedtothelossofafewsmallbonesinafishlikeTiktaalik.

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Tracingarmbonesfromfishtohumans.Icandoasimilaranalysisforthewrists,ribs,ears,and

otherpartsofourskeleton—allthesefeaturescanbetracedbacktoafishlikethis.ThisfossilisjustasmuchapartofourhistoryastheAfricanhominids,suchasAustralopithecusafarensis,thefamous“Lucy.”SeeingLucy,wecanunderstandourhistoryashighlyadvancedprimates.SeeingTiktaalikisseeingourhistoryasfish.Sowhathavewelearned?Ourworldissohighlyordered

thatwecanuseawalkthroughazootopredictthekindsoffossilsthatlieinthedifferentlayersofrocksaroundtheworld.Thosepredictionscanbringaboutfossildiscoveriesthattellusaboutancienteventsinthehistoryoflife.Therecordofthoseeventsremainsinsideus,aspartofour

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anatomicalorganization.WhatIhaven’tmentionedisthatwecanalsotraceour

historyinsideourgenes,throughDNA.Thisrecordofourpastdoesn’tlieintherocksoftheworld;itliesineverycellinsideus.We’llusebothfossilsandgenestotellourstory,thestoryofthemakingofourbodies.

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CHAPTERTWO

GETTINGAGRIP

Imagesofthemedicalschoolanatomylabareimpossibletoforget.Imaginewalkingintoaroomwhereyouwillspendseveralmonthstakingahumanbodyapartlayerbylayer,organbyorgan,allasawaytolearntensofthousandsofnewnamesandbodystructures.InthemonthsbeforeIdidmyfirsthumandissection,I

readiedmyselfbytryingtoenvisionwhatIwouldsee,howIwouldreact,andwhatIwouldfeel.Itturnedoutthatmyimaginedworldinnowaypreparedmefortheexperience.Themomentwhenweremovedthesheetandsawthebodyforthefirsttimewasn’tnearlyasstressfulasI’dexpected.Weweretodissectthechest,soweexposeditwhileleavingthehead,arms,andlegswrappedinpreservative-drenchedgauze.Thetissuesdidnotlookveryhuman.Havingbeentreatedwithanumberofpreservatives,thebodydidn’tbleedwhencut,andtheskinandinternalorganshadtheconsistencyofrubber.Ibegantothinkthatthecadaverlookedmorelikeadollthanahuman.Afewweekswentbyasweexposedtheorgansofthechestandabdomen.Icame

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tothinkthatIwasquitethepro;havingalreadyseenmostoftheinternalorgans,Ihaddevelopedacockyself-confidenceaboutthewholeexperience.Ididmyinitialdissections,mademycuts,andlearnedtheanatomyofmostofthemajororgans.Itwasallverymechanical,detached,andscientific.ThiscomfortableillusionwasrudelyshatteredwhenI

uncoveredthehand.AsIunwrappedthegauzefromthefingers—asIsawthejoints,fingertips,andfingernailsforthefirsttime—Iuncoveredemotionsthathadbeenconcealedduringthepreviousfewweeks.Thiswasnodollormannequin;thishadoncebeenalivingperson,whousedthathandtocarryandcaress.Suddenly,thismechanicalexercise,dissection,becamedeeplyandemotionallypersonal.Untilthatmoment,Iwasblindtomyconnectiontothecadaver.Ihadalreadyexposedthestomach,thegallbladder,andotherorgans;butwhatsanepersonformsahumanconnectionatthesightofagallbladder?Whatisitaboutahandthatseemsquintessentially

human?Theanswermust,atsomelevel,bethatthehandisavisibleconnectionbetweenus;itisasignatureforwhoweareandwhatwecanattain.Ourabilitytograsp,tobuild,andtomakeourthoughtsrealliesinsidethiscomplexofbones,nerves,andvessels.Theimmediatethingthatstrikesyouwhenyouseethe

insideofthehandisitscompactness.Theballofyourthumb,thethenareminence,containsfourdifferentmuscles.Twiddleyourthumbandtiltyourhand:ten

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differentmusclesandatleastsixdifferentbonesworkinunison.Insidethewristareatleasteightsmallbonesthatmoveagainstoneanother.Bendyourwrist,andyouareusinganumberofmusclesthatbegininyourforearm,extendingintotendonsastheytraveldownyourarmtoendatyourhand.Eventhesimplestmotioninvolvesacomplexinterplayamongmanypartspackedinasmallspace.Therelationshipbetweencomplexityandhumanity

withinourhandshaslongfascinatedscientists.In1822,theeminentScottishsurgeonSirCharlesBellwrotetheclassicbookontheanatomyofhands.Thetitlesaysitall:TheHand,ItsMechanismandVitalEndowmentsasEvincingDesign.ToBell,thestructureofthehandwas“perfect”becauseitwascomplexandideallyarrangedforthewaywelive.Inhiseye,thisdesignedperfectioncouldonlyhaveadivineorigin.ThegreatanatomistSirRichardOwenwasoneofthe

scientificleadersinthissearchfordivineorderwithinbodies.Hewasfortunatetobeananatomistinthemid-1800s,whentherewerestillentirelynewkindsofanimalstodiscoverlivinginthedistantreachesoftheearth.Asmoreandmorepartsoftheworldwereexploredbywesterners,allsortsofexoticcreaturesmadetheirwaybacktolaboratoriesandmuseums.Owendescribedthefirstgorilla,broughtbackfromexpeditionstocentralAfrica.Hecoinedthename“dinosaur”foranewkindoffossilcreaturediscoveredinrocksinEngland.Hisstudyofthesebizarrenewcreaturesgavehimspecialinsights:he

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begantoseeimportantpatternsintheseemingchaosoflife’sdiversity.Owendiscoveredthatourarmsandlegs,ourhandsand

feet,fitintoalargerscheme.Hesawwhatanatomistsbeforehimhadlongknown,thatthereisapatterntotheskeletonofahumanarm:oneboneintheupperarm,twobonesintheforearm,abunchofninelittlebonesatthewrists,thenaseriesoffiverodsthatmakethefingers.Thepatternofbonesinthehumanlegismuchthesame:onebone,twobones,lotsablobs,andfivetoes.Incomparingthispatternwiththediversityofskeletonsintheworld,Owenmadearemarkablediscovery.Owen’sgeniuswasnotthathefocusedonwhatmadethe

variousskeletonsdifferent.Whathefound,andlaterpromotedinaseriesoflecturesandvolumes,wereexceptionalsimilaritiesamongcreaturesasdifferentasfrogsandpeople.Allcreatureswithlimbs,whetherthoselimbsarewings,flippers,orhands,haveacommondesign.Onebone,thehumerusinthearmorthefemurintheleg,articulateswithtwobones,whichattachtoaseriesofsmallblobs,whichconnectwiththefingersortoes.Thispatternunderliesthearchitectureofalllimbs.Wanttomakeabatwing?Makethefingersreallylong.Makeahorse?Elongatethemiddlefingersandtoesandreduceandlosetheouterones.Howaboutafrogleg?Elongatethebonesofthelegandfuseseveralofthemtogether.Thedifferencesbetweencreatureslieindifferencesintheshapesandsizesofthebonesandthenumbersofblobs,fingers,andtoes.Despite

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radicalchangesinwhatlimbsdoandwhattheylooklike,thisunderlyingblueprintisalwayspresent.

Thecommonplanforalllimbs:onebone,followedbytwobones,thenlittleblobs,thenfingersortoes.

ForOwen,seeingadesigninthelimbswasonlythe

beginning:whenhelookedatskullsandbackbones,indeedwhenheconsideredtheentirearchitectureofthebody,he

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foundthesamething.Thereisafundamentaldesignintheskeletonofallanimals.Frogs,bats,humans,andlizardsarealljustvariationsonatheme.Thattheme,toOwen,wastheplanoftheCreator.ShortlyafterOwenannouncedthisobservationinhis

classicmonographOntheNatureofLimbs,CharlesDarwinsuppliedanelegantexplanationforit.Thereasonthewingofabatandthearmofahumanshareacommonskeletalpatternisbecausetheysharedacommonancestor.Thesamereasoningappliestohumanarmsandbirdwings,humanlegsandfroglegs—everythingthathaslimbs.ThereisamajordifferencebetweenOwen’stheoryandthatofDarwin:Darwin’stheoryallowsustomakeveryprecisepredictions.FollowingDarwin,wewouldexpecttofindthatOwen’sblueprinthasahistorythatwillberevealedincreatureswithnolimbsatall.Where,then,dowelookforthehistoryofthelimbpattern?Welooktofishandtheirfinskeletons.

SEEINGTHEFISH

InOwenandDarwin’sday,thegulfbetweenfinsandlimbsseemedimpossiblywide.Fishfinsdon’thaveanyobvioussimilaritiestolimbs.Ontheoutside,mostfishfinsarelargelymadeupoffinwebbing.Ourlimbshavenothinglikethis,nordothelimbsofanyothercreaturealivetoday.Thecomparisonsdonotgetanyeasierwhenyouremovethefin

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webbingtoseetheskeletoninside.Inmostfish,thereisnothingthatcanbecomparedtoOwen’sonebone–twobones–lotsablobs–digitspattern.Alllimbshaveasinglelongboneattheirbase:thehumerusintheupperarmandthefemurintheupperleg.Infish,thewholeskeletonlooksutterlydifferent.Thebaseofatypicalfinhasfourormorebonesinside.Inthemid-1800s,anatomistsbegantolearnof

mysteriouslivingfishfromthesoutherncontinents.OneofthefirstwasdiscoveredbyGermananatomistsworkinginSouthAmerica.Itlookedlikeanormalfish,withfinsandscales,butbehinditsthroatwerelargevascularsacs:lungs.Yetthecreaturehadscalesandfins.SoconfusedwerethediscoverersthattheynamedthecreatureLepidosirenparadoxa,“paradoxicallyscaledamphibian.”Otherfishwithlungs,aptlynamedlungfish,weresoonfoundinAfricaandAustralia.AfricanexplorersbroughtonetoOwen.ScientistssuchasThomasHuxleyandtheanatomistCarlGegenbaurfoundlungfishtobeessentiallyacrossbetweenanamphibianandafish.Localsfoundthemdelicious.Aseeminglytrivialpatterninthefinsofthesefishhada

profoundimpactonscience.Thefinsoflungfishhaveattheirbaseasinglebonethatattachestotheshoulder.Toanatomists,thecomparisonwasobvious.Ourupperarmhasasinglebone,andthatsinglebone,thehumerus,attachestoourshoulder.Inthelungfish,wehaveafishwithahumerus.And,curiously,itisnotjustanyfish;itisafishthatalsohaslungs.Coincidence?

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Asahandfuloftheselivingspeciesbecameknowninthe1800s,cluesstartedtocomefromanothersource.Asyoumightguess,theseinsightscamefromancientfish.Oneofthefirstofthesefossilscamefromtheshoresof

theGaspéPeninsulainQuebec,inrocksabout380millionyearsold.Thefishwasgivenatongue-twistername,Eusthenopteron.Eusthenopteronhadasurprisingmixoffeaturesseeninamphibiansandfish.OfOwen’sonebone–twobones–lotsablobs–digitsplanoflimbs,Eusthenopteronhadtheonebone–twobonespart,butinafin.Somefish,then,hadstructureslikethoseinalimb.Owen’sarchetypewasnotadivineandeternalpartofalllife.Ithadahistory,andthathistorywastobefoundinDevonianagerocks,rocksthatarebetween390millionand360millionyearsold.Thisprofoundinsightdefinedawholenewresearchprogramwithawholenewresearchagenda:somewhereintheDevonianrocksweshouldfindtheoriginoffingersandtoes.Inthe1920s,therocksprovidedmoresurprises.Ayoung

Swedishpaleontologist,GunnarSave-Soderbergh,wasgiventheextraordinaryopportunitytoexploretheeastcoastofGreenlandforfossils.Theregionwasterraincognita,butSave-SoderberghrecognizedthatitfeaturedenormousdepositsofDevonianrocks.Hewasoneoftheexceptionalfieldpaleontologistsofalltime,whothroughouthisshortcareeruncoveredremarkablefossilswithbothaboldexploringspiritandapreciseattentiontodetail.(Unfortunately,hewastodietragicallyof

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tuberculosisatayoungage,soonafterthestunningsuccessofhisfieldexpeditions.)Inexpeditionsbetween1929and1934,Save-Soderbergh’steamdiscoveredwhat,atthetime,waslabeledamajormissinglink.Newspapersaroundtheworldtrumpetedhisdiscovery;editorialsanalyzeditsimportance;cartoonslampoonedit.Thefossilsinquestionweretruemosaics:theyhadfish-likeheadsandtails,yettheyalsohadfullyformedlimbs(withfingersandtoes),andvertebraethatwereextraordinarilyamphibian-like.AfterSave-Soderberghdied,thefossilsweredescribedbyhiscolleagueErikJarvik,whonamedoneofthenewspeciesIchthyostegasoderberghiinhonorofhisfriend.

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Thefinsofmostfish—forexample,azebrafish(top)—havelargeamountsoffinwebbingandmanybonesatthebase.Lungfishcapturedpeople’sinterestbecauselikeustheyhaveasingleboneatthebaseoftheappendage.Eusthenopteron(middle)showedhowfossilsbegintofillthegap;ithasbonesthatcomparetoourupperarmandforearm.Acanthostega(bottom)sharesEusthenopteron’spatternofarmboneswiththeadditionoffullyformeddigits.

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Forourstory,Ichthyostegaisabitofaletdown.True,itisaremarkableintermediateinmostaspectsofitsheadandback,butitsaysverylittleabouttheoriginoflimbsbecause,likeanyamphibian,italreadyhasfingersandtoes.Anothercreature,onethatreceivedlittlenoticewhenSave-Soderberghannouncedit,wastoproviderealinsightsdecadeslater.Thissecondlimbedanimalwastoremainanenigmauntil1988,whenapaleontologicalcolleagueofmine,JennyClack,whoweintroducedinthefirstchapter,returnedtoSave-Soderbergh’ssitesandfoundmoreofitsfossils.Thecreature,calledAcanthostegagunnaribackinthe1920sonthebasisofSave-Soderbergh’sfragments,nowrevealedfulllimbs,withfingersandtoes.Butitalsocarriedarealsurprise:Jennyfoundthatthelimbwasshapedlikeaflipper,almostlikethatofaseal.Thissuggestedtoherthattheearliestlimbsarosetohelpanimalsswim,notwalk.Thatinsightwasasignificantadvance,butaproblemremained:Acanthostegahadfullyformeddigits,witharealwristandnofinwebbing.Acanthostegahadalimb,albeitaveryprimitiveone.Thesearchfortheoriginsofhandsandfeet,wristsandankleshadtogostilldeeperintime.Thisiswheremattersstooduntil1995.

FINDINGFISHFINGERSANDWRISTS

In1995,TedDaeschlerandIhadjustreturnedtohishouse

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inPhiladelphiaafterdrivingallthroughcentralPennsylvaniainanefforttofindnewroadcuts.WehadfoundalovelycutonRoute15northofWilliamsport,wherePennDOThadcreatedagiantcliffinsandstonesabout365millionyearsold.Theagencyhaddynamitedthecliffandleftpilesofbouldersalongsidethehighway.Thiswasperfectfossil-huntinggroundforus,andwestoppedtocrawlovertheboulders,manyofthemroughlythesizeofasmallmicrowaveoven.Somehadfishscalesscatteredthroughout,sowedecidedtobringafewbackhometoPhiladelphia.UponourreturntoTed’shouse,hisfour-year-olddaughter,Daisy,camerunningouttoseeherdadandaskedwhatwehadfound.InshowingDaisyoneoftheboulders,wesuddenly

realizedthatstickingoutofitwasasliveroffinbelongingtoalargefish.Wehadcompletelymisseditinthefield.And,asweweretolearn,thiswasnoordinaryfishfin:itclearlyhadlotsofbonesinside.Peopleinthelabspentaboutamonthremovingthefinfromtheboulder—andthere,exposedforthefirsttime,wasafishwithOwen’spattern.Closesttothebodywasonebone.Thisoneboneattachedtotwobones.Extendingawayfromthefinwereabouteightrods.Thislookedforalltheworldlikeafishwithfingers.Ourfinhadafullsetofwebbing,scales,andevenafish-

likeshoulder,butdeepinsidewerebonesthatcorrespondedtomuchofthe“standard”limb.Unfortunately,wehadonlyanisolatedfin.Whatweneededwastofindaplacewherewholebodiesofcreaturescould

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berecoveredintact.Asingleisolatedfincouldneverhelpusanswertherealquestions:Whatdidthecreatureuseitsfinsfor,anddidthefishfinshavebonesandjointsthatworkedlikeours?Theanswerwouldcomeonlyfromwholeskeletons.

Ourtantalizingfin.Sadly,wefoundonlythisisolatedspecimen.StipplediagramusedwiththepermissionofScottRawlins,ArcadiaUniversity.Photobytheauthor.

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Forthatfind,wehadtosearchalmosttenyears.AndIwasn’tthefirsttorecognizewhatwewerelookingat.Thefirstweretwoprofessionalfossilpreparators,FredMullisonandBobMasek.Preparatorsusedentaltoolstoscratchattherockswefindinthefieldandtherebyexposethefossilsinside.Itcantakemonths,ifnotyears,forapreparatortoturnabigfossil-filledboulderlikeoursintoabeautiful,research-qualityspecimen.Duringthe2004expedition,wehadcollectedthree

chunksofrock,eachaboutthesizeofapieceofcarry-onluggage,fromtheDevonianofEllesmereIsland.Eachcontainedaflat-headedanimal:theoneIfoundiniceatthebottomofthequarry,Steve’sspecimen,andathirdspecimenwediscoveredinthefinalweekoftheexpedition.Inthefieldwehadremovedeachhead,leavingenoughrockintactaroundittoexploreinthelabfortherestofthebody.Thentherockswerewrappedinplasterforthetriphome.Openingthesekindsofplastercoveringsinthelabismuchlikeencounteringatimecapsule.BitsandpiecesofourlifeontheArctictundraarethere,asarethefieldnotesandscribbleswemakeonthespecimen.Eventhesmellofthetundracomeswaftingoutofthesepackagesaswecracktheplasteropen.FredinPhiladelphiaandBobinChicagowerescratching

ondifferentbouldersatthesamegeneraltime.FromoneoftheseArcticblocks,BobhadpulledoutaparticularsmallboneinabigfinoftheFish(wehadn’tnameditTiktaalikyet).Whatmadethiscube-shapedblobofbonedifferent

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fromanyotherfinbonewasajointattheendthathadspacesforfourotherbones.Thatis,thebloblookedscarilylikeawristbone—butthefinsintheblockthatBobwaspreparingweretoojumbledtotellforsure.ThenextpieceofevidencecamefromPhiladelphiaaweeklater.Fred,amagicianwithhisdentaltools,uncoveredawholefininhisblock.Attherightplace,justattheendoftheforearmbones,thefinhadthatbone.Andthatboneattachedtofourmorebeyond.Wewerestaringattheoriginofapieceofourownbodiesinsidethis375-million-year-oldfish.Wehadafishwithawrist.

ThebonesofthefrontfinofTiktaalik—afishwithawrist.

Overthenextmonths,wewereabletoseemuchofthe

restoftheappendage.Itwaspartfin,partlimb.Ourfishhadfinwebbing,butinsidewasaprimitiveversionofOwen’sonebone–twobones–lotsablobs–digitsarrangement.JustasDarwin’stheorypredicted:attherighttime,attherightplace,wehadfoundintermediatesbetweentwoapparently

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differentkindsofanimals.Findingthefinwasonlythebeginningofthediscovery.

TherealfunforTed,Farish,andmecamefromunderstandingwhatthefindidandhowitworked,andinguessingwhyawristjointaroseinthefirstplace.Solutionstothesepuzzlesarefoundinthestructureofthebonesandjointsthemselves.WhenwetookthefinofTiktaalikapart,wefound

somethingtrulyremarkable:allthejointsurfaceswereextremelywellpreserved.Tiktaalikhasashoulder,elbow,andwristcomposedofthesamebonesasanupperarm,forearm,andwristinahuman.Whenwestudythestructureofthesejointstoassesshowonebonemovesagainstanother,weseethatTiktaalikwasspecializedforaratherextraordinaryfunction:itwascapableofdoingpush-ups.Whenwedopush-ups,ourhandslieflushagainstthe

ground,ourelbowsarebent,andweuseourchestmusclestomoveupanddown.Tiktaalik’sbodywascapableofallofthis.Theelbowwascapableofbendinglikeours,andthewristwasabletobendtomakethefish’s“palm”lieflatagainsttheground.Asforchestmuscles,Tiktaaliklikelyhadtheminabundance.Whenwelookattheshoulderandtheundersideofthearmboneatthepointwheretheywouldhaveconnected,wefindmassivecrestsandscarswherethelargepectoralmuscleswouldhaveattached.Tiktaalikwasableto“dropandgiveustwenty.”

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Afull-scalemodelofTiktaalik’sbody(top)andadrawingofitsfin(bottom).Thisisafininwhichtheshoulder,elbow,andproto-wristwerecapableofperformingatypeofpush-up.

Whywouldafisheverwanttodoapush-up?Ithelpsto

considertherestoftheanimal.Withaflathead,eyesontop,andribs,Tiktaalikwaslikelybuilttonavigatethebottomandshallowsofstreamsorponds,andeventofloparoundonthemudflatsalongthebanks.Finscapableofsupportingthebodywouldhavebeenveryhelpfulindeedforafishthatneededtomaneuverinalltheseenvironments.ThisinterpretationalsofitswiththegeologyofthesitewherewefoundthefossilsofTiktaalik.Thestructureoftherocklayersandthepatternofthegrainsin

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therocksthemselveshavethecharacteristicsignatureofadepositthatwasoriginallyformedbyashallowstreamsurroundedbylargeseasonalmudflats.Butwhyliveintheseenvironmentsatall?What

possessedfishtogetoutofthewaterorliveinthemargins?Thinkofthis:virtuallyeveryfishswimminginthese375-million-year-oldstreamswasapredatorofsomekind.Somewereuptosixteenfeetlong,almosttwicethesizeofthelargestTiktaalik.ThemostcommonfishspecieswefindalongsideTiktaalikissevenfeetlongandhasaheadaswideasabasketball.Theteetharebarbsthesizeofrailroadspikes.Wouldyouwanttoswimintheseancientstreams?Itisnoexaggerationtosaythatthiswasafish-eat-fish

world.Thestrategiestosucceedinthissettingwereprettyobvious:getbig,getarmor,orgetoutofthewater.Itlooksasifourdistantancestorsavoidedthefight.Butthisconflictavoidancemeantsomethingmuch

deepertous.Wecantracemanyofthestructuresofourownlimbstothefinsofthesefish.Bendyourwristbackandforth.Openandcloseyourhand.Whenyoudothis,youareusingjointsthatfirstappearedinthefinsoffishlikeTiktaalik.Earlier,thesejointsdidnotexist.Later,wefindtheminlimbs.ProceedfromTiktaaliktoamphibiansallthewayto

mammals,andonethingbecomesabundantlyclear:theearliestcreaturetohavethebonesofourupperarm,ourforearm,evenourwristandpalm,alsohadscalesandfinwebbing.Thatcreaturewasafish.

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Whatdowemakeoftheonebone–twobones–lotsablobs–digitsplanthatOwenattributedtoaCreator?Somefish,forexamplethelungfish,havetheoneboneatthebase.Otherfish,forexampleEusthenopteron,havetheonebone–twobonesarrangement.ThentherearecreatureslikeTiktaalik,withonebone–twobones–lotsablobs.Thereisn’tjustasinglefishinsideofourlimbs;thereisawholeaquarium.Owen’sblueprintwasassembledinfish.Tiktaalikmightbeabletodoapush-up,butitcouldnever

throwabaseball,playthepiano,orwalkontwolegs.ItisalongwayfromTiktaaliktohumanity.Theimportant,andoftensurprising,factisthatmostofthemajorboneshumansusetowalk,throw,orgraspfirstappearinanimalstenstohundredsofmillionsofyearsbefore.Thefirstbitsofourupperarmandlegarein380-million-year-oldfishlikeEusthenopteron.Tiktaalikrevealstheearlystagesintheevolutionofourwrist,palm,andfingerarea.Thefirsttruefingersandtoesareseenin365-million-year-oldamphibianslikeAcanthostega.Finally,thefullcomplementofwristandanklebonesfoundinahumanhandorfootisseeninreptilesmorethan250millionyearsold.Thebasicskeletonofourhandsandfeetemergedoverhundredsofmillionsofyears,firstinfishandlaterinamphibiansandreptiles.Butwhatarethemajorchangesthatenableustouseour

handsorwalkontwolegs?Howdotheseshiftscomeabout?Let’slookattwosimpleexamplesfromlimbsforsomeanswers.

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Wehumans,likemanyothermammals,canrotateourthumbrelativetoourelbow.Thissimplefunctionisveryimportantfortheuseofourhandsineverydaylife.Imaginetryingtoeat,write,orthrowaballwithoutbeingabletorotateyourhandrelativetoyourelbow.Wecandothisbecauseoneforearmbone,theradius,rotatesalongapivotpointattheelbowjoint.Thestructureofthejointattheelbowiswonderfullydesignedforthisfunction.Attheendofourupper-armbone,thehumerus,liesaball.Thetipoftheradius,whichattacheshere,formsabeautifullittlesocketthatfitsontheball.Thisball-and-socketjointallowstherotationofourhand,calledpronationandsupination.Wheredoweseethebeginningsofthisability?IncreatureslikeTiktaalik.InTiktaalik,theendofthehumerusformsanelongatedbumpontowhichacup-shapedjointontheradiusfits.WhenTiktaalikbentitselbow,theendofitsradiuswouldrotate,orpronate,relativetotheelbow.Refinementsofthisabilityareseeninamphibiansandreptiles,wheretheendofthehumerusbecomesatrueball,muchlikeourown.Lookingnowatthehindlimb,wefindakeyfeaturethat

givesusthecapacitytowalk,onewesharewithothermammals.Unlikefishandamphibians,ourkneesandelbowsfaceinoppositedirections.Thisfeatureiscritical:thinkoftryingtowalkwithyourkneecapfacingbackward.AverydifferentsituationexistsinfishlikeEusthenopteron,wheretheequivalentsofthekneeandelbowfacelargelyinthesamedirection.Westartdevelopmentwithlittlelimbs

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orientedmuchlikethoseinEusthenopteron,withelbowsandkneesfacinginthesamedirection.Aswegrowinthewomb,ourkneesandelbowsrotatetogiveusthestateofaffairsweseeinhumanstoday.Ourbipedalpatternofwalkingusesthemovementsof

ourhips,knees,ankles,andfootbonestopropelusforwardinanuprightstanceunlikethesprawledpostureofcreatureslikeTiktaalik.Onebigdifferenceisthepositionofourhips.Ourlegsdonotprojectsidewayslikethoseofacrocodile,amphibian,orfish;rather,theyprojectunderneathourbodies.Thischangeinposturecameaboutbychangestothehipjoint,pelvis,andupperleg:ourpelvisbecamebowlshaped,ourhipsocketbecamedeep,ourfemurgaineditsdistinctiveneck,thefeaturethatenablesittoprojectunderthebodyratherthantotheside.Dothefactsofourancienthistorymeanthathumansare

notspecialoruniqueamonglivingcreatures?Ofcoursenot.Infact,knowingsomethingaboutthedeeporiginsofhumanityonlyaddstotheremarkablefactofourexistence:allofourextraordinarycapabilitiesarosefrombasiccomponentsthatevolvedinancientfishandothercreatures.Fromcommonpartscameaveryuniqueconstruction.Wearenotseparatefromtherestofthelivingworld;wearepartofitdowntoourbonesand,aswewillseeshortly,evenourgenes.Inretrospect,themomentwhenIfirstsawthewristofa

fishwasasmeaningfulasthefirsttimeIunwrappedthefingersofthecadaverbackinthehumananatomylab.Both

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timesIwasuncoveringadeepconnectionbetweenmyhumanityandanotherbeing.

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CHAPTERTHREE

HANDYGENES

WhilemycolleaguesandIwerediggingupthefirstTiktaalikintheArcticinJuly2004,RandyDahn,aresearcherinmylaboratory,wassweatingitoutontheSouthSideofChicagodoinggeneticexperimentsontheembryosofsharksandskates,cousinsofstingrays.You’veprobablyseensmallblackeggcases,knownasmermaid’spurses,onthebeach.Insidethepurseoncelayaneggwithyolk,whichdevelopedintoanembryonicskateorray.Overtheyears,Randyhasspenthundredsofhoursexperimentingwiththeembryosinsidetheseeggcases,oftenworkingwellpastmidnight.Duringthefatefulsummerof2004,RandywastakingthesecasesandinjectingamolecularversionofvitaminAintotheeggs.Afterthathewouldlettheeggsdevelopforseveralmonthsuntiltheyhatched.Hisexperimentsmayseemtobeabizarrewaytospend

thebetterpartofayear,letaloneforayoungscientisttolaunchapromisingscientificcareer.Whysharks?WhyaformofvitaminA?

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Tomakesenseoftheseexperiments,weneedtostepbackandlookatwhatwehopetheymightexplain.Whatwearereallygettingatinthischapteristherecipe,writteninourDNA,thatbuildsourbodiesfromasingleegg.Whenspermfertilizesanegg,thatfertilizedeggdoesnotcontainatinyhand,forinstance.Thehandisbuiltfromtheinformationcontainedinthatsinglecell.Thistakesustoaveryprofoundproblem.Itisonethingtocomparethebonesofourhandswiththebonesinfishfins.Whathappensifyoucomparethegeneticrecipethatbuildsourhandswiththerecipethatbuildsafish’sfin?Tofindanswerstothisquestion,justlikeRandy,wewillfollowatrailofdiscoverythattakesusfromourhandstothefinsofsharksandeventothewingsofflies.Aswe’veseen,whenwediscovercreaturesthatreveal

differentandoftensimplerversionsofourbodiesinsidetheirown,awonderfullydirectwindowopensintothedistantpast.Butthereisabiglimitationtoworkingwithfossils.Wecannotdoexperimentsonlong-deadanimals.Experimentsaregreatbecausewecanactuallymanipulatesomethingtoseetheresults.Forthisreason,mylaboratoryissplitdirectlyintwo:halfisdevotedtofossils,theotherhalftoembryosandDNA.Lifeinmylabcanbeschizophrenic.ThelockedcabinetthatholdsTiktaalikspecimensisadjacenttothefreezercontainingourpreciousDNAsamples.ExperimentswithDNAhaveenormouspotentialto

revealinnerfish.Whatifyoucoulddoanexperimentin

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whichyoutreatedtheembryoofafishwithvariouschemicalsandactuallychangeditsbody,makingpartofitsfinlooklikeahand?Whatifyoucouldshowthatthegenesthatbuildafish’sfinarevirtuallythesameasthosethatbuildourhands?Webeginwithanapparentpuzzle.Ourbodyismadeup

ofhundredsofdifferentkindsofcells.Thiscellulardiversitygivesourtissuesandorganstheirdistinctshapesandfunctions.Thecellsthatmakeourbones,nerves,guts,andsoonlookandbehaveentirelydifferently.Despitethesedifferences,thereisadeepsimilarityamongeverycellinsideourbodies:allofthemcontainexactlythesameDNA.IfDNAcontainstheinformationtobuildourbodies,tissues,andorgans,howisitthatcellsasdifferentasthosefoundinmuscle,nerve,andbonecontainthesameDNA?TheanswerliesinunderstandingwhatpiecesofDNA

(thegenes)areactuallyturnedonineverycell.Askincellisdifferentfromaneuronbecausedifferentgenesareactiveineachcell.Whenageneisturnedon,itmakesaproteinthatcanaffectwhatthecelllookslikeandhowitbehaves.Therefore,tounderstandwhatmakesacellintheeyedifferentfromacellinthebonesofthehand,weneedtoknowaboutthegeneticswitchesthatcontroltheactivityofgenesineachcellandtissue.Here’stheimportantfact:thesegeneticswitcheshelpto

assembleus.Atconception,westartasasinglecellthatcontainsalltheDNAneededtobuildourbody.Theplanforthatentirebodyunfoldsviatheinstructionscontainedin

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thissinglemicroscopiccell.Togofromthisgeneralizedeggcelltoacompletehuman,withtrillionsofspecializedcellsorganizedinjusttherightway,wholebatteriesofgenesneedtobeturnedonandoffatjusttherightstagesofdevelopment.Likeaconcertocomposedofindividualnotesplayedbymanyinstruments,ourbodiesareacompositionofindividualgenesturningonandoffinsideeachcellduringourdevelopment.

GenesarestretchesofDNAcontainedineverycellofourbodies.

Thisinformationisaboontothosewhoworkto

understandbodies,becausewecannowcomparetheactivityofdifferentgenestoassesswhatkindsofchangesareinvolvedintheoriginofneworgans.Takelimbs,forexample.Whenwecomparetheensembleofgenesactiveinthedevelopmentofafishfintothoseactiveinthedevelopmentofahumanhand,wecancataloguethegeneticdifferencesbetweenfinsandlimbs.Thiskindofcomparisongivesussomelikelyculprits—thegenetic

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switchesthatmayhavechangedduringtheoriginoflimbs.Wecanthenstudywhatthesegenesaredoingintheembryoandhowtheymighthavechanged.Wecanevendoexperimentsinwhichwemanipulatethegenestoseehowbodiesactuallychangeinresponsetodifferentconditionsorstimuli.Toseethegenesthatbuildourhandsandfeet,weneed

totakeapagefromascriptfortheTVshowCSI:CrimeSceneInvestigation—startatthebodyandworkourwayin.Wewillbeginbylookingatthestructureofourlimbs,andzoomallthewaydowntothetissues,cells,andgenesthatmakeit.

MAKINGHANDS

Ourlimbsexistinthreedimensions:theyhaveatopandabottom,apinkysideandathumbside,abaseandatip.Thebonesatthetips,inourfingers,aredifferentfromthebonesattheshoulder.Likewise,ourhandsaredifferentfromonesidetotheother.Ourpinkiesareshapeddifferentlyfromourthumbs.TheHolyGrailofourdevelopmentalresearchistounderstandwhatgenesdifferentiatethevariousbonesofourlimb,andwhatcontrolsdevelopmentinthesethreedimensions.WhatDNAactuallymakesapinkydifferentfromathumb?Whatmakesourfingersdistinctfromourarmbones?Ifwecanunderstandthegenesthatcontrolsuchpatterns,wewillbe

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privytotherecipethatbuildsus.Allthegeneticswitchesthatmakefingers,armbones,

andtoesdotheirthingduringthethirdtoeighthweekafterconception.Limbsbegintheirdevelopmentastinybudsthatextendfromourembryonicbodies.Thebudsgrowovertwoweeks,untilthetipformsalittlepaddle.Insidethispaddlearemillionsofcellswhichwillultimatelygiverisetotheskeleton,nerves,andmusclesthatwe’llhavefortherestofourlives.

Thedevelopmentofalimb,inthiscaseachickenwing.Allofthekeystagesinthedevelopmentofawingskeletonhappeninsidetheegg.

Tostudyhowthispatternemerges,weneedtolookat

embryosandsometimesinterferewiththeirdevelopmenttoassesswhathappenswhenthingsgowrong.Moreover,weneedtolookatmutantsandattheirinternalstructuresandgenes,oftenbymakingwholemutantpopulations

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throughcarefulbreeding.Obviously,wecannotstudyhumansintheseways.Thechallengeforthepioneersinthisfieldwastofindtheanimalsthatcouldbeusefulwindowsintoourowndevelopment.Thefirstexperimentalembryologistsinterestedinlimbsinthe1930sand1940sfacedseveralproblems.Theyneededanorganisminwhichthelimbswereaccessibleforobservationandexperiment.Theembryohadtoberelativelylarge,sothattheycouldperformsurgicalproceduresonit.Importantly,theembryohadtogrowinaprotectedplace,inacontainerthatsheltereditfromjostlingandotherenvironmentaldisturbances.Also,andcritically,theembryoshadtobeabundantandavailableyear-round.Theobvioussolutiontothisscientificneedisatyourlocalgrocerystore:chickeneggs.Inthe1950sand1960sanumberofbiologists,including

EdgarZwillingandJohnSaunders,didextraordinarilycreativeexperimentsonchickeneggstounderstandhowthepatternoftheskeletonforms.Thiswasaneraofsliceanddice.Embryoswerecutupandvarioustissuesmovedabouttoseewhateffectthishadondevelopment.Theapproachinvolvedverycarefulmicrosurgery,manipulatingpatchesoftissuenomorethanamillimeterthick.Inthatway,bymovingtissuesaboutinthedevelopinglimb,SaundersandZwillinguncoveredsomeofthekeymechanismsthatbuildlimbsasdifferentasbirdwings,whaleflippers,andhumanhands.Theydiscoveredthattwolittlepatchesoftissue

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essentiallycontrolthedevelopmentofthepatternofbonesinsidelimbs.Astripoftissueattheextremeendofthelimbbudisessentialforalllimbdevelopment.Removeit,anddevelopmentstops.Removeitearly,andweareleftwithonlyanupperarm,orapieceofanarm.Removeitslightlylater,andweendupwithanupperarmandaforearm.Removeitevenlater,andthearmisalmostcomplete,exceptthatthedigitsareshortanddeformed.Anotherexperiment,initiallydonebyMaryGasselingin

JohnSaunders’slaboratory,ledtoapowerfulnewlineofresearch.Takealittlepatchoftissuefromwhatwillbecomethepinkysideofalimbbud,earlyindevelopment,andtransplantitontheoppositeside,justunderwherethefirstfingerwillform.Letthechickdevelopandformawing.Theresultsurprisednearlyeverybody.Thewingdevelopednormallyexceptthatitalsohadafullduplicatesetofdigits.Evenmoreremarkablewasthepatternofthedigits:thenewfingersweremirrorimagesofthenormalset.Obviously,somethinginsidethatpatchoftissue,somemoleculeorgene,wasabletodirectthedevelopmentofthepatternofthefingers.Thisresultspawnedablizzardofnewexperiments,andwelearnedthatthiseffectcanbemimickedbyavarietyofothermeans.Forexample,takeachickenembryoanddabalittlevitaminAonitslimbbud,orsimplyinjectvitaminAintotheegg,andlettheembryodevelop.IfyousupplythevitaminAattherightconcentrationandattherightstage,you’llgetthesamemirror-imageduplicationthatGasseling,Saunders,and

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Zwillinggotfromthegraftingexperiments.Thispatchoftissuewasnamedthezoneofpolarizingactivity(ZPA).Essentially,theZPAisapatchoftissuethatcausesthepinkysidetobedifferentfromthethumbside.Obviouslychicksdonothaveapinkyandathumb.Theterminologyweuseistonumberthedigits,withourpinkycorrespondingtodigitfiveofotheranimalsandourthumbcorrespondingtodigitone.

MovingalittlepatchoftissuecalledtheZPAcausesthefingerstobeduplicated.

TheZPAdrewinterestbecauseitappeared,insomeway,

tocontroltheformationoffingersandtoes.Buthow?SomepeoplebelievedthatthecellsintheZPAmadeamoleculethatthenspreadacrossthelimbtoinstructcellstomakedifferentfingers.Thekeyproposalwasthatitwastheconcentrationofthisunnamedmoleculethatwasthe

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importantfactor.InareasclosetotheZPA,wherethereisahighconcentrationofthismolecule,cellswouldrespondbymakingapinky.Intheoppositesideofthedevelopinghand,fartherfromtheZPAsothatthemoleculewasmorediffused,thecellswouldrespondbymakingathumb.Cellsinthemiddlewouldeachrespondaccordingtotheconcentrationofthismoleculetomakethesecond,third,andfourthfingers.Thisconcentration-dependentideacouldbetested.In

1979,DenisSummerbellplacedanextremelysmallpieceoffoilbetweentheZPApatchandtherestofthelimb.TheideawastousethisbarriertopreventanykindofmoleculefromdiffusingfromtheZPAtotheotherside.Summerbellstudiedwhathappenedtothecellsoneachsideofthebarrier.CellsontheZPAsideformeddigits.Cellsontheoppositesideoftendidnotformdigits;iftheydid,thedigitswerebadlymalformed.Theconclusionwasobvious.SomethingwasemanatingfromtheZPAthatcontrolledhowthedigitsformedandwhattheylookedlike.Toidentifythatsomething,researchersneededtolookatDNA.

THEDNARECIPE

Thatprojectwaslefttoanewgenerationofscientists.Notuntilthe1990s,whennewmoleculartechniquesbecameavailable,wasthegeneticcontrolfortheZPA’soperationunraveled.

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Amajorbreakthroughhappenedin1993,whenCliffTabin’slaboratoryatHarvardstartedhuntingforthegenesthatcontroltheZPA.TheirpreywasthemolecularmechanismsthatgavetheZPAitsabilitytomakeourpinkydifferentfromourthumb.Bythetimehisgroupstartedtoworkintheearly1990s,anumberofexperimentsliketheonesI’vedescribedhadledustobelievethatsomesortofmoleculecausedthewholething.Thiswasagrandtheory,butnobodyknewwhatthismoleculewas.Peoplewouldproposeonemoleculeafteranother,onlytofindthatnonewasuptothejob.Finally,theTabinlabcameupwithanovelnotion,andoneveryrelevanttothethemeofthisbook.Looktofliesfortheanswer.Geneticexperimentsinthe1980shadrevealedthe

wonderfulpatternofgeneactivitythatsculptsthebodyofaflyfromasingle-celledegg.Thebodyofafruitflyisorganizedfromfronttoback,withtheheadatthefrontandthewingsattheback.Wholebatteriesofgenesareturnedonandoffduringflydevelopment,andthispatternofgeneactivityservestodemarcatethedifferentregionsofthefly.Tabindidn’tknowitatthetime,buttwoother

laboratories—thoseofAndyMacMahonandPhilIngham—hadalreadycomeupwiththesamegeneralideaindependently.Whatemergedwasaremarkablysuccessfulcollaborationamongthreedifferentlabgroups.OneoftheflygenescaughttheattentionofTabin,McMahon,andIngham.Theynotedthatthisgenemadeoneendofabodysegmentlookdifferentfromtheother.Flygeneticists

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namedithedgehog.Doesn’tthefunctionofhedgehogintheflybody—tomakeoneregiondifferentfromanother—soundlikewhattheZPAdoesinmakingthepinkydifferentfromthethumb?Thatparallelwasnotlostonthethreelabs.Soofftheywent,lookingforahedgehoggeneincreatureslikechickens,mice,andfish.Becausethelabgroupsknewthestructureofthefly’s

hedgehoggene,theyhadasearchimagetohelpthemsingleoutthegeneinchickens.Eachgenehasadistinctivesequence;usinganumberofmoleculartools,theresearcherscouldscanthechicken’sDNAforthehedgehogsequence.Afteralotoftrialanderror,theyfoundachickenhedgehoggene.Justaspaleontologistsgettonamenewspecies,

geneticistsgettonamenewgenes.Theflygeneticistswhodiscoveredhedgehoghadnameditthatbecausetheflieswithamutationinthegenehadbristlesthatremindedthemofalittlehedgehog.Tabin,McMahon,andInghamnamedthechickenversionofthegeneSonichedgehog,aftertheSegaGenesisvideogame.Nowcamethefunquestion:WhatdoesSonichedgehog

actuallydointhelimb?TheTabingroupattachedadyetoamoleculethatwouldsticktothegene,enablingthemtovisualizewherethegeneisactiveinthelimb.Totheirgreatsurprise,theyfoundthatonlycellsinatinypatchofthelimbhadgeneactivity:theZPA.Sothenextstepsbecameobvious.Thepatternsof

activityintheSonichedgehoggeneshouldmimicthoseof

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theZPAtissueitself.Recallthatwhenyoutreatthelimbwithretinoicacid,aformofvitaminA,yougetaZPAactiveontheoppositeside.Guesswhathappenswhenyoutreatalimbwithretinoicacid,thenmapwhereSonichedgehogisactive?Sonichedgehogbecomesactiveonbothsides—pinkyandthumb—justastheZPAdoeswhenitistreatedwithretinoicacid.KnowingthestructureofthechickenSonichedgehog

gaveotherresearchersthetoolstolookforitineverythingelsethathasfingers,fromfrogstohumans.EverylimbedanimalhastheSonichedgehoggene.Andineverysingleanimalthatwehavestudied,SonichedgehogisactiveintheZPAtissue.IfSonichedgehoghadn’tturnedonproperlyduringtheeighthweekofyourowndevelopment,thenyoueitherwouldhaveextrafingersoryourpinkyandthumbwouldlookalike.Occasionally,whenthingsgowrongwithSonichedgehog,thehandendsuplookinglikeabroadpaddlewithasmanyastwelvefingersthatalllookalike.WenowknowthatSonichedgehogisoneofdozensof

genesthatacttosculptourlimbsfromshouldertofingertipbyturningonandoffattherighttime.Remarkably,workinchickens,frogs,andmicewastellingusthesamething.TheDNArecipetobuildupperarms,forearms,wrists,anddigitsisvirtuallyidenticalineverycreaturethathaslimbs.HowfarbackcanwetraceSonichedgehogandtheother

bitsofDNAthatbuildlimbs?Isthisstuffactiveinbuildingtheskeletonoffishfins?Orarehandsgeneticallycompletelydifferentfromfishfins?Wesawaninnerfishin

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theanatomyofourarmsandhands.WhatabouttheDNAthatbuildsit?EnterRandyDahnwithhismermaid’spurses.

GIVINGSHARKSAHAND

RandyDahnenteredmylaboratorywithasimplebutveryelegantidea:treatskateembryosjustthewayCliffTabintreatedchickeneggs.Randy’sgoalwastoperformalltheexperimentsonskatesthatchickenbiologistshadperformedonchickeneggs,fromSaundersandZwilling’stissuesurgeriesallthewaytoCliffTabin’sgeneexperiments.Skatesdevelopinaneggwithakindofshellandayolk.Skatesevenhavebigembryos,justaschickensdo.Becauseoftheseconvenientfacts,wecouldapplytoskatesmanyofthegeneticandexperimentaltoolspeoplehaddevelopedtounderstandchickens.Whatcouldwelearnbycomparingthedevelopmentofa

sharkfintothatofachickenleg?Evenmorerelevant,whatcouldwelearnaboutourselvesfromallthis?Chickens,asSaunders,Zwilling,andTabinshowed,area

surprisinglygoodproxyforourownlimbs.EverythingthatwasdiscoveredbySaundersandZwilling’scuttingandgraftingexperimentsandbyTabin’sDNAworkappliestoourownlimbsaswell:wehaveaZPA,wehaveSonichedgehog,andbothhaveagreatbearingonourwell-being.Aswesaw,amalfunctioningZPAoramutationinSonic

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hedgehogcancausemajormalformationsinhumanhands.Randywantedtodeterminehowdifferenttheapparatus

isthatbuildsourhands.Howdeepisourconnectiontotherestoflife?Istherecipethatbuildsourhandsnew,ordoesit,too,havedeeprootsinothercreatures?Ifso,howdeep?Sharksandtheirrelativesaretheearliestcreaturesthat

havefinswithaskeletoninside.Ideally,toanswerRandy’squestion,youwouldwanttobringa400-million-year-oldsharkfossilintothelaboratory,grinditup,andlookatitsgeneticstructure.Thenyou’dtrytomanipulateitsfossilembryostolearnwhetherSonichedgehogisactiveinthesamegeneralplaceasinourlimbstoday.Thiswouldbeawonderfulexperiment,butitisimpossible.WecannotextractDNAfromfossilssoold,and,evenifwecould,wecouldneverfindembryosofthosefossilanimalsonwhichtodoexperiments.Livingsharksandtheirrelativesarethenextbestthing.

Nobodywouldeverconfuseasharkfinwithahumanhand:youcouldn’taskfortwomoredifferentkindsofappendages.Notonlyaresharksandhumansverydistantlyrelated,butalsotheskeletalstructuresoftheirappendageslooknothingalike.NothingevenremotelysimilartoOwen’sonebone–twobones–lotsablobs–digitspatternisinsideashark’sfin.Instead,thebonesinsideareshapedlikerods,longandshort,thinandwide.Wecallthemboneseventhoughtheyaremadeofcartilage(sharksandskatesareknownascartilaginousfish,becausetheirskeletonsneverturnintohardbone).IfyouwanttoassesswhetherSonic

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hedgehog’sroleinlimbsisuniquetolimbedanimals,whynotchooseaspeciesutterlydifferentinalmosteveryway?Inaddition,whynotchoosethespeciesthatisthemostprimitivelivingfishwithanykindofpairedappendage,whetherfinorlimb?Sharksfitbothbillsperfectly.Ourfirstproblemwasasimpleone.Weneededareliable

sourcefortheembryosofsharksandskates.Sharksproveddifficulttoobtainwithanydegreeofregularity,butskates,theircloserelatives,wereanothermatter.Sowestartedwithsharksandusedskatesasoursupplyofsharksdwindled.Wefoundasupplierwhowouldshipuseverymonthortwoabatchoftwentyorthirtyeggcaseswithembryosinside.Webecameavirtualcargocultaswewaitedeachmonthforourshipmentofpreciouseggcases.WorkbyTabin’sgroupandothersgaveRandyimportant

cluestobeginhissearch.SinceTabin’sworkin1993,peoplehadfoundSonichedgehoginanumberofdifferentspecies,everythingfromfishtohumans.Withtheknowledgeofthestructureofthegene,RandywasabletosearchalltheDNAoftheskateandsharkforSonichedgehog.Inaveryshorttimehefoundit:asharkSonichedgehoggene.ThekeyquestionstoanswerwereWhereisSonic

hedgehogactive?,and,evenmoreimportant,Whatisitdoing?TheeggcaseswereputtouseasRandyvisualizedwhere

andwhenSonichedgehogisactiveinthedevelopmentofskates.HefirststudiedwhetherSonichedgehogturnsonat

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thesametimeinskatefindevelopmentasitdoesinchickenlimbs.Yes,itdoes.Thenhestudiedwhetheritisturnedoninthepatchoftissueatthebackendofthefin,theequivalentofourpinky.Yesagain.NowhedidhisvitaminAexperiment.Thiswasthemillion-dollarmoment.Ifyoutreatthelimbofachickenormammalwiththiscompound,yougetapatchoftissuethathasSonichedgehogactivityontheoppositeside,andthisresultiscoupledwithaduplicationofthebones.Randyinjectedtheegg,waitedadayorso,andthencheckedwhether,asinchickens,thevitaminAcausedSonichedgehogtoturnonintheoppositesideofthelimb.Itdid.Nowcamethelongwait.WeknewthatSonichedgehogwasbehavingthesamewayinourhandsandinskates’andsharks’fins.Butwhatwouldtheeffectofallthisbeontheskeleton?Wewouldhavetowaittwomonthsfortheanswer.Theembryosweredevelopinginsideanopaqueeggcase.

Allwecouldtellwaswhetherthecreaturewasalive;theinsideofthefinwasinvisibletous.Theendresultwasastunningexampleofsimilarity

amongus,sharks,andskates:amirror-imagefin.Thedorsalfinsduplicatedtheirstructuresinawonderfulfront-to-backpattern,thesamekindwesawwithexperimentsinlimbs.Limbsduplicatealimbstructure.Sharkfinsduplicateasharkfinstructureasdoskates.Sonichedgehoghasasimilareffectineventhemostdifferentkindsofappendageskeletonsfoundonearthtoday.OneeffectofSonichedgehog,youmayrecall,istomake

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thefingersdistinctfromoneanother.AswesawwithrespecttotheZPA,whatkindofdigitdevelopsdependsonhowclosethedigitistothesourceofSonichedgehog.Anormaladultskatefincontainsmanyskeletalrods,whichalllookalike.Couldwemaketheserodsdifferentfromoneanother,likeourdigits?RandytookasmallbeadimpregnatedwiththeproteinmadebySonichedgehogandputitinbetweentheseidenticalskeletalrods.ThekeytohisexperimentisthatheusedmouseSonichedgehog.Sonowwehavearealcontraption:askateembryowithabeadinsidethatisgraduallyleakingmouseSonichedgehogprotein.Wouldthatmouseproteinhaveanyeffectonasharkoraskate?Therearetwoextremeoutcomestoanexperimentlike

this.Oneisthatnothinghappens.ThiswouldmeanthatskatesaresodifferentfrommicethatSonichedgehogproteinhasnoeffect.Theotherextremeoutcomewouldpresentastunningexampleofourinnerfish.Thisoutcomewouldbethattherodsdevelopdifferentlyfromoneanother,demonstratingthatSonichedgehogdoessomethingsimilarinskatesandinus.Andlet’snotforgetthatsinceRandyisusingtheproteinfromamammal,itmeansthatthegeneticrecipewouldbereally,reallysimilar.Notonlydidtherodsenduplookingdifferentfromone

another,theyrespondedtoSonichedgehog,muchasfingersdo,onthebasisofhowclosetheyweretotheSonichedgehogbead:thecloserrodsdevelopedadifferentshapefromtheonesfartheraway.Totopmattersoff,itwasthe

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mouseproteinthatdidthejobsoeffectivelyintheskates.

Normalfins(left)andRandy’streatedfins.Thetreatedfinsshowedamirror-imageduplicationjustaschickenwingsdid.PhotographscourtesyofRandallDahn,UniversityofChicago.

The“innerfish”thatRandyfoundwasnotasinglebone,

orevenasectionoftheskeleton.Randy’sinnerfishlayinthebiologicaltoolsthatactuallybuildfins.Experimentafterexperimentoncreaturesasdifferentasmice,sharks,andfliesshowsusthatthelessonsofSonichedgehogareverygeneral.Allappendages,whethertheyarefinsorlimbs,arebuiltbysimilarkindsofgenes.Whatdoesthismeanfortheproblemwelookedatinthefirsttwochapters—the

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transitionoffishfinsintolimbs?ItmeansthatthisgreatevolutionarytransformationdidnotinvolvetheoriginofnewDNA:muchoftheshiftlikelyinvolvedusingancientgenes,suchasthoseinvolvedinsharkfindevelopment,innewwaystomakelimbswithfingersandtoes.Butthereisadeeperbeautytotheseexperimentson

limbsandfins.Tabin’slabusedworkinfliestofindageneinchickensthattellsusabouthumanbirthdefects.RandyusedtheTabinlabdiscoverytotellussomethingaboutourconnectionstoskates.An“innerfly”helpedfindan“innerchicken,”whichultimatelyhelpedRandyfindan“innerskate.”Theconnectionsamonglivingcreaturesrundeep.

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CHAPTERFOUR

TEETHEVERYWHERE

Thetoothgetsshortshriftinanatomyclass:wespendalloffiveminutesonit.Inthepantheonoffavoriteorgans—I’llleaveittoeachofyoutomakeyourlist—teethrarelyreachthetopfive.Yetthelittletoothcontainssomuchofourconnectiontotherestoflifethatitisvirtuallyimpossibletounderstandourbodieswithoutknowingteeth.Teethalsohavespecialsignificanceforme,becauseitwasinsearchingforthemthatIfirstlearnedhowtofindfossilsandhowtorunafossilexpedition.Thejobofteethistomakebiggercreaturesintosmaller

pieces.Whenattachedtoamovingjaw,teethslice,dice,andmacerate.Mouthsareonlysobig,andteethenablecreaturestoeatthingsthatarebiggerthantheirmouths.Thisisparticularlytrueofcreaturesthatdonothavehandsorclawsthatcanshredorcutthingsbeforetheygettothemouth.True,bigfishtendtoeatlittlerfish.Butteethcanbethegreatequalizer:smallerfishcanmunchonbiggerfishiftheyhavegoodteeth.Smallerfishcanusetheirteethtoscrapescales,feedonparticles,ortakeoutwholechunksof

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fleshfrombiggerfish.Wecanlearnalotaboutananimalbylookingatitsteeth.

Thebumps,pits,andridgesonteethoftenreflectthediet.Carnivores,suchascats,haveblade-likemolarstocutmeat,whileplanteatershaveamouthfullofflatterteeththatcanmacerateleavesandnuts.Theinformationalvalueofteethwasnotlostontheanatomistsofhistory.TheFrenchanatomistGeorgesCuvieroncefamouslyboastedthathecouldreconstructananimal’sentireskeletonfromasingletooth.Thisisalittleoverthetop,butthegeneralpointisvalid;teethareapowerfulwindowintoananimal’slifestyle.Humanmouthsrevealthatweareall-purposeeaters,for

wehaveseveralkindsofteeth.Ourfrontteeth,theincisors,areflatbladesspecializedforcutting.Therearmostteeth,themolars,areflatter,withadistinctivepatternthatcanmacerateplantoranimaltissue.Thepremolars,inbetween,areintermediateinfunctionbetweenincisorsandmolars.Themostremarkablethingaboutourmouthsisthe

precisionwithwhichwechew.Openandcloseyourmouth:yourteethalwayscometogetherinthesameposition,withupperandlowerteethfittingtogetherprecisely.Becausetheupperandlowercusps,basins,andridgesmatchclosely,weareabletobreakupfoodwithmaximalefficiency.Infact,amismatchbetweenupperandlowerteethcanshatterourteeth,andenrichourdentists.Paleontologistsfindteethwonderfullyinformative.Teeth

arethehardestpartsofourbodies,becausetheenamelincludesahighproportionofthemineralhydroxyapatite—

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highereventhanisfoundinbones.Thankstotheirhardness,teethareoftenthebest-preservedanimalpartwefindinthefossilrecordformanytimeperiods.Thisislucky;sinceteetharesuchagreatcluetoananimal’sdiet,thefossilrecordcangiveusagoodwindowonhowdifferentwaysoffeedingcameabout.Thisisparticularlytrueofmammalhistory:whereasmanyreptileshavesimilarteeth,thoseofmammalsaredistinctive.ThemammalsectionofatypicalpaleontologycoursefeelsalmostlikeDentistry101.Livingreptiles—crocodiles,lizards,snakes—lackmuch

ofwhatmakesmammalianmouthsunique.Acrocodile’steeth,forexample,allhaveasimilarblade-likeshape;theonlydifferencebetweenthemisthatsomearebigandotherssmall.Reptilesalsolackthepreciseocclusion—thefitbetweenupperandlowerteeth—thathumansandothermammalshave.Also,whereaswemammalsreplaceourteethonlyonce,reptilestypicallyreceivevisitsfromthetoothfairyfortheirentirelives,replacingtheirteethcontinuallyastheywearandbreakdown.Averybasicpieceofus—ourmammalianwayofprecise

chewing—emergesinthefossilrecordfromaroundtheworldthatrangesfrom225millionto195millionyearsago.Atthebase,intheolderrocks,wefindanumberofreptilesthatlooksuperficiallydog-like.Walkingonfourlegs,theyhavebigskulls,andmanyofthemhavesharpteeth.Theretheresemblancestops.Unlikedogs,thesereptileshaveajawmadeupofmanybones,andtheirteethdon’treallyfitwelltogether.Also,theirteetharereplacedin

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adecidedlyreptilianway:newteethpopinandoutthroughouttheanimals’lives.Gohigherintherocksandweseesomethingutterly

different:theappearanceofmammalness.Thebonesofthejawgetsmallerandmovetotheear.Wecanseethefirstevidenceofupperandlowerteethcomingtogetherinpreciseways.Thejaw’sshapechanges,too:whatwasasimplerodinreptileslooksmorelikeaboomeranginmammals.Atthistime,too,teetharereplacedonlyonceperlifetime,asinus.Wecantraceallthesechangesinthefossilrecord,especiallyfromcertainsitesinEurope,SouthAfrica,andChina.Therocksofabout200millionyearsagocontainrodent-

likecreatures,suchasMorganucodonandEozostrodon,thathavebeguntolooklikemammals.Theseanimals,nobiggerthanamouse,holdimportantpiecesofusinside.Picturescannotconveyjusthowwonderfultheseearlymammalsare.Forme,itwasarealthrilltoseecreatureslikethemforthefirsttime.WhenIenteredgraduateschool,Iwantedtostudyearly

mammals.IchoseHarvardbecauseFarishA.Jenkins,Jr.,whomwemetinthefirstchapter,wasleadingexpeditionstotheAmericanWestthatsystematicallyscouredtherocksforsignsofhowmammalsdevelopedtheirdistinctabilitiestochew.Theworkwasrealexploration;Farishandhisteamwerelookingfornewlocalitiesandsites,notreturningtoplacesotherpeoplehaddiscovered.Farishhadassembledatalentedgroupoffossilfinderscomprising

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stafffromHarvard’sMuseumofComparativeZoologyandafewfree-lancemercenaries.ChiefamongthemwereBillAmaral,ChuckSchaff,andthelateWillDowns.Thesepeopleweremyintroductiontotheworldofpaleontology.Farishandtheteamhadstudiedgeologicalmapsand

aerialphotostochoosepromisingareaswheretheymightfindearlymammals.Then,eachsummer,theygotintheirtrucksandheadedoffintothedesertsofWyoming,Arizona,andUtah.BythetimeIjoinedthem,in1983,theyhadalreadyfoundanumberofimportantnewmammalsandfossilsites.Iwasstruckbythepowerofpredictions:simplybyreadingscientificarticlesandbooks,Farish’steamcouldidentifylikelyandunlikelyplacestofindearlymammals.Mybaptisminfieldpaleontologycamefromwalkingout

intheArizonadesertwithChuckandBill.Atfirst,thewholeenterpriseseemedutterlyrandom.Iexpectedsomethingakintoamilitarycampaign,anorganizedandcoordinatedreconnaissanceofthearea.WhatIsawlookedliketheextremeopposite.Theteamwouldplunkdownonaparticularpatchofrock,andpeoplewouldscatterineveryconceivabledirectiontolookforfragmentsofboneonthesurface.Forthefirstfewweeksoftheexpedition,theyleftmealone.I’dsetofflookingforfossils,systematicallyinspectingeveryrockIsawforascrapofboneatthesurface.Attheendofeachdaywewouldcomehometoshowoffthegoodieswefound.Chuckwouldhaveseveralbagsofbones.Billwouldhavehiscomplement,usuallywithsomesortoflittleskullorotherprize.AndIhadnothing,my

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emptybagasadreminderofhowmuchIhadtolearn.Afterafewweeksofthis,Idecideditwouldbeagood

ideatowalkwithChuck.Heseemedtohavethefullestbagseachday,sowhynottakesomecuesfromtheexpert?Chuckwashappytowalkwithmeandexpoundonhislongcareerinfieldpaleontology.ChuckisallWestTexaswithaBrooklynflourish:cowboybootsandwesternvalueswithaNewYorkaccent.Whileheregaledmewithtalesofhispastexpeditions,Ifoundthewholeexperienceutterlyhumbling.First,Chuckdidnotlookateveryrock,andwhenhechoseonetolookat,forthelifeofmeIcouldn’tfigureoutwhy.Thentherewasthereallyembarrassingaspectofallthis:ChuckandIwouldlookatthesamepatchofground.Isawnothingbutrock—barrendesertfloor.Chucksawfossilteeth,jaws,andevenchunksofskull.Anaerialviewwouldhaveshowntwopeoplewalking

aloneinthemiddleofaseeminglylimitlessplain,wherethevistaofdustyredandgreensandstonemesas,buttes,andbadlandsextendedformiles.ButChuckandIwerestaringonlyattheground,attherubbleandtalusofthedesertfloor.Thefossilswesoughtweretiny,nomorethanafewincheslong,andourswasaverysmallworld.Thisintimateenvironmentstoodinextremecontrasttothevastnessofthedesertpanoramathatsurroundedus.Ifeltasifmywalkingpartnerwastheonlypersonontheentireplanet,andmywholeexistencewasfocusedonpiecesofrubble.ChuckwasextraordinarilypatientwithmeasIpestered

himwithquestionsforthebetterpartofeachday’swalk.I

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wantedhimtodescribeexactlyhowtofindbones.Overandover,hetoldmetolookfor“somethingdifferent,”somethingthathadthetextureofbonenotrock,somethingthatglistenedliketeeth,somethingthatlookedlikeanarmbone,notapieceofsandstone.Itsoundedeasy,butIcouldn’tgraspwhathewastellingme.TryasImight,Istillreturnedhomeeachdayempty-handed.Nowitwasevenmoreembarrassing,asChuck,whowaslookingatthesamerocks,camehomewithbagafterbag.Finally,oneday,Isawmyfirstpieceoftoothglisteningin

thedesertsun.Itwassittinginsomesandstonerubble,butthereitwas,asplainasday.Theenamelhadasheenthatnootherrockhad;itwaslikenothingIhadseenbefore.Well,notexactly—Iwaslookingatthingslikeiteveryday.ThedifferencewasthistimeIfinallysawit,sawthedistinctionbetweenrockandbone.Thetoothglistened,andwhenIsawitglistenIspotteditscusps.Thewholeisolatedtoothwasaboutthesizeofadime,notincludingtherootsthatprojectedfromitsbase.Tome,itwasasgloriousasthebiggestdinosaurinthehallsofanymuseum.Allofasudden,thedesertfloorexplodedwithbone;

whereonceIhadseenonlyrock,nowIwasseeinglittlebitsandpiecesoffossileverywhere,asifIwerewearingaspecialnewpairofglassesandaspotlightwasshiningonallthedifferentpiecesofbone.Nexttothetoothweresmallfragmentsofotherbones,thenmoreteeth.Iwaslookingatajawthathadweatheredoutonthesurfaceandfragmented.Istartedtoreturnhomewithmyownlittle

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bagseachnight.NowthatIcouldfinallyseebonesformyself,whatonce

seemedahaphazardgroupeffortstartedtolookdecidedlyordered.Peopleweren’tjustscatteringrandomlyacrossthedesert;therewererealthoughunspokenrules.Rulenumberone:gotothemostproductive-lookingrocks,judgingbywhateversearchimageorvisualcuesyou’vegainedfrompreviousexperience.Rulenumbertwo:don’tfollowinanybody’sfootsteps;covernewground(Chuckhadgraciouslyletmebreakthisone).Rulethree:ifyourplumareaalreadyhassomebodyonit,findanewplum,orsearchalesspromisingsite.Firstcome,firstserved.Overtime,Ibegantolearnthevisualcuesforotherkinds

ofbones:longbones,jawbones,andskullparts.Onceyouseethesethingsyouneverlosetheabilitytofindthem.Justasagreatfishermancanreadthewaterandseethefishwithin,soafossilfinderusesacatalogueofsearchimagesthatmakefossilsseemtojumpoutfromtherocks.Iwasbeginningtogainmyownvisualimpressionsofwhatfossilboneslooklikeindifferentrocksandindifferentlightingconditions.Findingfossilsinthemorningsunisverydifferentfromfindingthemintheafternoon,becauseofthewaythelightplaysalongtheground.Twentyyearslater,IknowthatImustgothrougha

similarexperienceeverytimeIlookforfossilssomeplacenew,fromtheTriassicofMoroccototheDevonianofEllesmereIsland.I’llstruggleforthefirstfewdays,almostasIdidthosedayswithChuckinArizonatwentyyearsago.

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ThedifferenceisthatnowIhavesomeconfidencethatasearchimagewillkickineventually.ThewholegoaloftheprospectingIdidwithChuckwasto

findasitewithenoughbonestomarkafossil-richlayerthatwecouldexpose.BythetimeIjoinedthecrew,Farish’steamhadalreadydiscoveredsuchazone,apatchofrockaboutahundredfeetlongthatcontainedskeletonafterskeletonofsmallanimals.Farish’sfossilquarrywasinsomeveryfine-grained

mudstone.Thetricktoworkingonitwastorealizethatthefossilswerecomingfromonethinlayer,nomorethanamillimeterthick.Onceyouexposedthatsurface,youhadaverygoodchanceofseeingbones.Theyweretiny,nomorethananinchortwolong,andblack,sotheylookedalmostlikeblacksmudgesagainstthebrownishrock.Thelittleanimalswefoundincludedfrogs(someoftheearliest),leglessamphibians,lizardsandotherreptiles,and,importantly,someoftheearliestmammals.Thekeypointisthattheearlymammalsweresmall.Very

small.Theirteethwerenotmuchmorethan2millimeterslong.Tospotthem,youhadtobeverycarefuland,moreoften,verylucky.Ifthetoothwascoveredbyacrumbofrockorevenbyafewgrainsofsand,youmightneverseeit.Itwasthesightoftheseearlymammalsthatreally

hookedme.I’dexposethefossillayer,thenscantheentiresurfacethroughmy10-powerhandlens.I’dscrutinizethewholethingonmyhandsandknees,withmyeyeandhandlensonlyabouttwoinchesfromthesurfaceoftheground.

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Thusengrossed,I’doftenforgetwhereIwasandaccidentallytrespassonmyneighbor’sspotonlytohaveabagofdirtdumpedonmyheadasasharpremindertokeeptomyspace.Occasionally,though,I’dhitthejackpotandseeadeepconnectionforthefirsttime.Theteethwouldlooklikelittleblades,withcuspsandroots.Thecuspsonthoselittleteethrevealedsomethingveryspecial.Eachtoothhadacharacteristicpatternofwearatthefacewhereupperandlowerteethfittogether.Iwasseeingsomeofthefirstevidenceofourpatternofprecisechewing,onlyinatinymammal190millionyearsold.ThepowerofthosemomentswassomethingI’llnever

forget.Here,crackingrocksinthedirt,Iwasdiscoveringobjectsthatcouldchangethewaypeoplethink.Thatjuxtapositionbetweenthemostchild-like,evenhumbling,activitiesandoneofthegreathumanintellectualaspirationshasneverbeenlostonme.ItrytoremindmyselfofiteachtimeIdigsomewherenew.Returningtoschoolthatfall,Idevelopedtheexpedition

bugbig-time.Iwantedtoleadmyownexpeditionbutlackedtheresourcestodoanythingbig,soIsetofftoexplorerocksinConnecticutthatwereabout200millionyearsold.Wellstudiedduringthenineteenthcentury,theyhadbeenthesettingforanumberofimportantfossildiscoveries.IfiguredthatifIhitthosesamerockswithmyhandlensandmywonderfullysuccessfulearlymammalsearchimage,I’dfindlotsofgoodies.Irentedaminivan,grabbedacaseofcollectingbags,andsetoff.

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Yetanotherlessonlearned:Ifoundnothing.Backtothedrawingboard,ormoreprecisely,thegeologylibraryatschool.Ineededaplacewhere200-million-year-oldrockswere

wellexposed:inConnecticuttherewereonlyroadcuts.Theidealplacewouldbealongthecoast,wherewaveactionwouldprovidelotsoffreshlybrokenrocksurfacetolookat.Lookingatamapmademychoiceclear:upinNovaScotia,TriassicandJurassicrocks(roughly200millionyearsold)layalongthesurface.Totopitoff,thetouristliteratureabouttheareaadvertisedtheworld’shighesttides,occasionallyoverfiftyfeet.Icouldn’tbelievemyluck.Icalledtheexpertontheserocks,PaulOlsen,whohad

juststartedteachingatColumbiaUniversity.IfIwasexcitedaboutfossil-findingprospectsbeforeItalkedtoPaul,Iwasfrothingafterward.Hedescribedtheperfectgeologyforfindingsmallmammalsorreptiles:ancientstreamsanddunesthathadjusttherightpropertiestopreservetinybones.Evenbetter,hehadalreadyfoundsomedinosaurbonesandfootprintsalongastretchofbeachnearthetownofParrsboro,NovaScotia.PaulandIhatchedaplantovisitParrsborotogetherandscanthebeachforlittlefossils.ThiswaswonderfullygenerousonPaul’spartbecausehehaddibsontheareaandwasundernoresponsibilitytohelpmeout,letalonecollaborate.IconsultedwithFarishonmyemergingplans,andhenot

onlyofferedmoneybutsuggestedthatItakethefossil-findingexperts,BillandChuck.Money,Bill,Chuck,Paul

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Olsen,excellentrocks,anddecentexposures—whatmorecouldyouwant?Thefollowingsummer,Iledmyveryfirstfossilexpedition.OffIwentinarentedstationwagontothebeachesof

NovaScotiawithmyfieldcrew,BillandChuck.Thejoke,ofcourse,wasonme.WithBillandChuckalong,whobetweenthemhadmoreyearsoffieldexperiencethanIhadbirthdays,Iwastheleaderinnameonly.Theycalledthefossil-findingshots,whileIpaidthedinnerbills.TherocksinNovaScotiawereexposedinabsolutely

gorgeousorangesandstonecliffsalongtheBayofFundy.Thetideswouldgoinandoutabouthalfamileeachday,exposingenormousflatsoforangebedrock.Itwasn’tlongbeforewestartedtofindbonesinmanydifferentareas.Smallwhiteflecksofbonewerecomingoutalongthecliffs.Paulwasfindingfootprintseverywhere,evenintheflatsopenedbythemovingtideseachday.

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PaulOlsenfindingfootprintsinthetidalflatsofNovaScotia.Athightide,thewaterwouldcomeallthewaytothecliffsatleft.Thearrowheadpointstoaspotwhere,ifwetimedourtripwrong,wewouldbestuckonthecliffsforhoursatatime.Photographbytheauthor.

Chuck,Bill,Paul,andIspenttwoweeksdigginginNova

Scotia,findingbits,flakes,andfragmentsofbonesstickingoutoftherocks.Bill,beingthefossilpreparatorofthegroup,continuallywarnedmenottoexposemuchofthebonesinthefieldbutrathertowrapthemupstillcoveredinsandstonesothathecouldtracethebonesinthelaboratoryunderamicroscopeinmorecontrolledconditions.Wedidthis,butI’lladmittobeingdisappointedwithwhatwebroughthome:justafewshoeboxesofrocks,withsmallchipsandflakesofbonesshowing.Aswedrovehome,Irecallthinkingthateventhoughwehadn’tfoundmuch,ithadbeenagreatexperience.ThenItookaweek’svacation;ChuckandBillreturnedtothelab.WhenIreturnedtoBoston,ChuckandBillwereoutto

lunch.Somecolleagueswerevisitingthemuseumand,havingcaughtsightofme,cameuptoshakemyhand,offercongratulations,andslapmeontheback.Iwasbeingtreatedlikeaconqueringhero,butIhadnoideawhy;itseemedlikeabizarrejoke,asiftheyweresettingmeupforsomebigcon.TheytoldmetogotoBill’slabtoseemytrophy.Notknowingwhattothink,Iran.UnderBill’smicroscopewasatinyjaw,notmorethan

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halfaninchlong.Initwereafewminuteteeth.Thejaw’sownerwasclearlyareptile,becausetheteethhadonlyasinglerootatthebase,whereasmammalteethhavemany.ButontheteethweretinybumpsandridgesthatIcouldseeevenwiththenakedeye.Lookingattheteethunderthemicroscopegavemethebiggestsurprise:thecuspshadlittlepatchesofwear.Thiswasareptilewithtooth-to-toothocclusion.Myfossilwaspartmammal,partreptile.Unbeknownsttome,Billhadunwrappedoneofour

blocksofrock,seenafleckofbone,andprepareditwithaneedleunderthemicroscope.Noneofushadknownitinthefield,butourexpeditionwasahugesuccess.AllbecauseofBill.WhatdidIlearnthatsummer?First,Ilearnedtolistento

ChuckandBill.Second,Ilearnedthatmanyofthebiggestdiscoverieshappeninthehandsoffossilpreparators,notinthefield.Asitturnedout,mybiggestlessonsaboutfieldworkwereyettocome.ThereptileBillhadfoundwasatritheledont,acreature

knownfromSouthAfricaaswellasnowfromNovaScotia.Thesewereveryrare,sowewantedtoreturntoNovaScotiathenextsummertofindmore.Ispentthewholewintertensewithanticipation.IfIcouldhavechippedthroughthewintericetofindfossils,Iwouldhavedoneit.Inthesummerof1985,wereturnedtothesitewherewe

hadfoundthetritheledont.Thefossilbedwasjustatbeachlevel,wherealittlepieceofthecliffhadfallenoffseveralyearsbefore.Wehadtotimeourdailyvisitjustso:thesite

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wasinaccessibleathightidebecausethewatercameuptoohigharoundapointwehadtonavigate.I’llneverforgetthatfirstdayofexcitementwhenweroundedthepointtofindourlittlepatchofbrightorangerock.Theexperiencewasmemorableforwhatwasmissing:mostoftheareawehadworkedtheyearbefore.Ithadweatheredawaythepreviouswinter.Ourlovelyfossilsite,containingbeautifultritheledonts,wasgonewiththetides.Thegoodnews,ifyoucouldcallitthat,wasthatthere

wasalittlemoreorangesandstonetoscanalongthebeach.Mostofthebeach,inparticularthepointwehadtogoaroundeachmorning,wasmadeupofbasaltfroma200-million-year-oldlavaflow.Wewerepositivenofossilscouldbefoundthere,foritisvirtuallyaxiomaticthattheserocks,whichwereoncesuperhot,wouldneverpreservefossilbone.Wespentfiveormoredaystimingourvisitstothesitesbythetides,pawingawayattheorangesandstonesbeyondit,andfindingabsolutelynothing.Ourbreakthroughcamewhenthepresidentofthelocal

LionsClubcamebyourcabinonenightlookingforjudgesforthelocalbeautycontest,tocrownParrsboro’sMissOldHomeWeek.Thetownalwaysreliedonvisitorsforthisoneroustask,becauseinternecinepassionstypicallyrunhighduringtheevent.Theusualjudges,anelderlycouplefromQuebec,werenotvisitingthisyear,andthecrewandIwereinvitedtosubstitute.Butinjudgingthebeautycontestandarguingoverits

conclusion,westayedupwaytoolate,forgotaboutthenext

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morning’stides,andendeduptrappedaroundabendinthebasaltcliffs.Forabouttwohours,wewerestuckonalittlepromontoryaboutfiftyfeetwide.Therockwasvolcanicandnotthetypeonewouldeverchoosetosearchforfossils.Weskippedstonesuntilwegotbored,thenwelookedattherocks:maybewe’dfindinterestingcrystalsorminerals.Billdisappearedaroundacorner,andIlookedatsomeofthebasaltbehindus.AfteraboutfifteenminutesIheardmyname.I’llneverforgetBill’sunderstatedtone:“Uh,Neil,youmightwanttocomeoverhere.”AsIroundedthecorner,IsawtheexcitementinBill’seyes.ThenIsawtherocksathisfeet.Stickingoutoftherocksweresmallwhitefragments.Fossilbones,thousandsofthem.Thiswasexactlywhatwewerelookingfor,asitewith

smallbones.Itturnedoutthatthevolcanicrockswerenotentirelyvolcanic:sliversofsandstonecutthroughthecliff.Therockshadbeenproducedbyanancientmudflowassociatedwithavolcaniceruption.Thefossilswerestuckintheancientmuds.Webroughttonsoftheserockshome.Insideweremore

tritheledonts,someprimitivecrocodiles,andotherlizard-likereptiles.Thetritheledontswerethegems,ofcourse,becausetheyshowedthatsomekindsofreptilesalreadydisplayedourmammaliankindofchewing.Earlymammals,suchasthoseFarish’steamuncovered

inArizona,hadveryprecisepatternsofbiting.Scrapesonthecuspsofanuppertoothfitagainstmirrorimagesofthesescrapesonalowertooth.Thesepatternsofwearare

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sofinethatdifferentspeciesofearlymammalscanbedistinguishedbytheirpatternsoftoothwearandocclusion.Farish’sArizonamammalshaveadifferentpatternofcuspsandchewingthanthoseofthesameagefromSouthAmerica,Europe,orChina.Ifallwehadtocomparethesefossilstowerelivingreptiles,thentheoriginofmammalianfeedingwouldappeartobeabigmystery.AsI’vementioned,crocodilesandlizardsdonothaveanykindofmatchingpatternofocclusion.Hereiswherecreaturesliketritheledontscomein.Whenwegobackintime,torocksabout10millionyearsolder,suchasthoseinNovaScotia,wefindtritheledontswithanincipientversionofthiswayofchewing.Intritheledonts,individualcuspsdonotinterlockinapreciseway,astheydoinmammals;instead,theentireinnersurfaceoftheuppertoothshearsagainsttheoutersurfaceofthelowertooth,almostlikeascissors.Ofcourse,thesechangesinocclusiondidnothappeninavacuum.Itshouldcomeasnosurprisethattheearliestcreaturestoshowamammaliankindofchewingalsodisplaymammalianfeaturesofthelowerjaw,skull,andskeleton.

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AtritheledontandapieceofitsupperjawdiscoveredinNovaScotia.JawfragmentillustratedbyLazloMeszoley.

Becauseteethpreservesowellinthefossilrecord,we

haveverydetailedinformationabouthowmajorpatternsofchewing—andtheabilitytousenewdiets—aroseovertime.Muchofthestoryofmammalsisthestoryofnewwaysofprocessingfood.Soonafterweencountertritheledontsinthefossilrecord,westartseeingallsortsofnewmammalspecieswithnewkindsofteeth,aswellasnewwaysofoccludingandusingthem.Byabout150millionyearsago,inrocksfromaroundtheworld,wefindsmallrodent-sizemammalswithanewkindoftoothrow,onethatpavedthewayforourownexistence.Whatmadethesecreaturesspecialwasthecomplexityoftheirmouths:thejawhaddifferentkindsofteethsetinit.Themouthdevelopedakindofdivisionoflabor.Incisorsinthefrontbecamespecializedtocutfood,caninesfurtherbacktopunctureit,andmolarsintheextremebacktoshearormashit.Theselittlemammals,whichresemblemice,haveafundamentalpieceofourhistoryinsideofthem.Ifyoudoubtthis,imagineeatinganapplelackingyourincisorteethor,betteryet,alargecarrotwithnomolars.Ourdiversediet,rangingfromfruittomeattoTwinkie,ispossibleonlybecauseourdistantmammalianancestorsdevelopedamouthwithdifferentkindsofteeththatcanoccludeprecisely.Andyes,initialstagesofthisareseenintritheledontsandotherancientrelatives:theteethinthe

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fronthaveadifferentpatternofbladesandcuspsthanthoseintheback.

TEETHANDBONES—THEHARDSTUFF

Italmostgoeswithoutsayingthatwhatmakesteethspecialamongorgansistheirhardness.Teethhavetobeharderthanthebitsoffoodtheybreakdown;imaginetryingtocutasteakwithasponge.Inmanyways,teethareashardasrocks,andthereasonisthattheycontainacrystalmoleculeontheinside.Thatmolecule,knownashydroxyapatite,impregnatesthemolecularandcellularinfrastructureofbothteethandbones,makingthemresistanttobending,compression,andotherstresses.Teethareextrahardbecausetheirouterlayer,enamel,isfarricherinhydroxyapatitethananyotherstructureinthebody,includingbone.Enamelgivesteeththeirwhitesheen.Ofcourse,enamelisonlyoneofthelayersthatmakeupourteeth.Theinnerlayers,suchasthepulpanddentine,arealsofilledwithhydroxyapatite.Therearelotsofcreatureswithhardtissues—clamsand

lobsters,forexample.Buttheydonotusehydroxyapatite;lobstersandclamsuseothermaterials,suchascalciumcarbonateorchitin.Also,unlikeus,theseanimalshaveanexoskeletoncoveringthebody.Ourhardnesslieswithin.Ourparticularbrandofhardness,withteethinsideour

mouthsandbonesinsideourbodies,isanessentialpartof

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whoweare.Wecaneat,moveabout,breathe,evenmetabolizecertainmineralsbecauseofourhydroxyapatite-containingtissues.Forthesecapabilities,wecanthankthecommonancestorwesharewithallfish.Everyfish,amphibian,reptile,bird,andmammalontheplanetislikeus.Allofthemhavehydroxyapatite-containingstructures.Butwheredidthisallcomefrom?Thereisanimportantintellectualissueatstakehere.By

knowingwhere,when,andhowhardbonesandteethcameabout,wewillbeinapositiontounderstandwhy.Whydidourkindofhardtissuesarise?Didtheycomeabouttoprotectanimalsfromtheirenvironment?Didtheycomeabouttohelpthemmove?Answerstothesequestionslieinthefossilrecord,inrocksapproximately500millionyearsold.Someofthemostcommonfossilsinancientoceans,500

millionto250millionyearsold,areconodonts.Conodontswerediscoveredinthe1830sbytheRussianbiologistChristianPander,whowillreappearinafewchapters.Theyaresmallshellyorganismswithaseriesofspikesprojectingoutofthem.SincePander’stime,conodontshavebeendiscoveredoneverycontinent;thereareplaceswhereyoucannotcrackarockwithoutfindingvastnumbersofthem.Hundredsofkindsofconodontsareknown.Foralongtime,conodontswereenigmas:scientists

disagreedoverwhethertheywereanimal,vegetable,ormineral.Everybodyseemedtohaveapettheory.Conodontswereclaimedtobepiecesofclams,sponges,

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vertebrates,evenworms.Thespeculationendedwhenwholeanimalsstartedtoshowupinthefossilrecord.Thefirstspecimenthatmadesenseofeverythingwas

foundbyaprofessorofpaleontologyrummagingthroughthebasementattheUniversityofEdinburgh:therewasaslabofrockwithwhatlookedlikealampreyinit.Youmightrecalllampreysfrombiologyclass—theseareveryprimitivefishthathavenojaws.Theymaketheirlivingbyattachingtootherfishandfeedingontheirbodilyfluids.Embeddedinthefrontofthelampreyimpressionweresmallfossilsthatlookedstrangelyfamiliar.Conodonts.Otherlamprey-likefossilsstartedtocomeoutofrocksinSouthAfricaandlaterthewesternUnitedStates.Thesecreaturesallhadanexceptionaltrait:theyhadwholeassemblagesofconodontsintheirmouths.Theconclusionbecameabundantlyclear:conodontswereteeth.Andnotjustanyteeth.Conodontsweretheteethofanancientjawlessfish.Wehadtheearliestteethinthefossilrecordforover150

yearsbeforewerealizedwhattheywere.Thereasoncomesdowntohowfossilsarepreserved.Thehardbits,forexampleteeth,tendtogetpreservedeasily.Softparts,suchasmuscle,skin,andguts,usuallydecaywithoutfossilizing.Wehavemuseumcabinetsfulloffossilskeletons,shells,andteeth,butpreciousfewgutsandbrains.Ontherareoccasionswhenwefindevidenceofsofttissues,theyaretypicallypreservedonlyasimpressionsorcasts.Ourfossilrecordisloadedwithconodontteeth,butittookus150

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yearstofindthebodies.Thereissomethingelseremarkableaboutthebodiestowhichconodontsbelonged.Theyhavenohardbones.Theseweresoft-bodiedanimalswithhardteeth.Foryears,paleontologistshavearguedaboutwhyhard

skeletons,thosecontaininghydroxyapatite,aroseinthefirstplace.Forthosewhobelievedthatskeletonsbeganwithjaws,backbones,orbodyarmor,conodontsprovidean“inconvenienttooth,”ifyouwill.Thefirsthardhydroxyapatite-containingbodypartswereteeth.Hardbonesarosenottoprotectanimals,buttoeatthem.Withthis,thefish-eat-fishworldreallybeganinearnest.First,bigfishatelittlefish;then,anarmsracebegan.Littlefishdevelopedarmor,bigfishobtainedbiggerjawstocrackthearmor,andsoon.Teethandbonesreallychangedthecompetitivelandscape.Thingsgetmoreinterestingstillaswelookatsomeof

thefirstanimalswithbonyheads.Aswemoveupintimefromtheearliestconodontanimals,weseewhatthefirstbony-headskeletonslookedlike.Theybelongedtofishcalledostracoderms,areabout500millionyearsold,andarefoundinrocksallovertheworld,fromtheArctictoBolivia.Thesefishlooklikehamburgerswithfleshytails.Theheadregionofanostracodermisabigdiskcovered

byashieldofbone,lookingalmostlikearmor.IfIweretoopenamuseumdrawerandshowyouone,youwouldimmediatelynoticesomethingodd:theheadskeletonisreallyshiny,muchlikeourteethorthescalesofafish.

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Aconodont(left)andanostracoderm(right).Conodontswereoriginallyfoundisolated.Then,aswholeanimalsbecameknown,welearnedthatmanyofthemfunctionedtogetherasatoothrowinthemouthsofthesesoft-bodiedjawlessfish.Ostracodermshaveheadscoveredwithabonyshield.Themicroscopiclayersofthatshieldlookliketheyarecomposedoflittletooth-likestructures.ConodonttoothrowreconstructioncourtesyofDr.MarkPurnell,UniversityofLeicester,andDr.PhilipDonoghue,UniversityofBristol.

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Oneofthejoysofbeingascientististhatthenaturalworldhasthepowertoamazeandsurprise.Here,inostracoderms,anobscuregroupofancientjawlessfish,liesaprimeexample.Ostracodermsareamongtheearliestcreatureswithbonyheads.Cuttheboneoftheskullopen,embeditinplastic,popitunderthemicroscope,andyoudonotfindjustanyoldtissuestructure;rather,youfindvirtuallythesamestructureasinourteeth.Thereisalayerofenamelandevenalayerofpulp.Thewholeshieldismadeupofthousandsofsmallteethfusedtogether.Thisbonyskull—oneoftheearliestinthefossilrecord—ismadeentirelyoflittleteeth.Teethoriginallyarosetobitecreatures;later,aversionofteethwasusedinanewwaytoprotectthem.

TEETH,GLANDS,ANDFEATHERS

Teethnotonlyheraldawholenewwayofliving,theyrevealtheoriginofawholenewwayofmakingorgans.Teethdevelopbyaninteractionoftwolayersoftissueinourdevelopingskin.Basically,twolayersapproacheachother,cellsdivide,andthelayerschangeshapeandmakeproteins.Theouterlayerspitsoutthemolecularprecursorsofenamel,theinnerlayerthedentineandpulpoftheinsideofthetooth.Overtime,thestructureofthetoothislaiddown,thentweakedtomakethepatternsofcuspsandtroughsthatdistinguisheachspecies.

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Thekeytotoothdevelopmentisthataninteractionbetweenthesetwolayersoftissue,anoutersheetofcellsandaninnerlooselayerofcells,causesthetissuetofoldandmakesbothlayerssecretethemoleculesthatbuildtheorgan.Itturnsoutthatexactlythesameprocessunderliesthedevelopmentofallthestructuresthatdevelopwithinskin:scales,hair,feathers,sweatglands,evenmammaryglands.Ineachcase,twolayerscometogether,fold,andsecreteproteins.Indeed,thebatteriesofthemajorgeneticswitchesthatareactiveinthisprocessineachkindoftissuearelargelysimilar.

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Teeth,breasts,feathers,andhairalldevelopfromtheinteractionsbetweenlayersofskin.

Thisexampleisakintomakinganewfactoryorassembly

process.Onceplasticinjectionwasinvented,itwasusedinmakingeverythingfromcarpartstoyo-yos.Teetharenodifferent.Oncetheprocessthatmakesteethcameintobeing,itwasmodifiedtomakethediversekindsoforgans

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thatliewithinskin.Wesawthistakentoaverygreatextremeintheostracoderms.Birds,reptiles,andhumansarejustasextremeinmanyways.Wewouldneverhavescales,feathers,orbreastsifwedidn’thaveteethinthefirstplace.Thedevelopmentaltoolsthatmaketeethhavebeenrepurposedtomakeotherimportantskinstructures.Inaveryrealsenseorgansasdifferentasteeth,feathers,andbreastsareinextricablylinkedbyhistory.Athemeofthesefirstfourchaptersishowwecantrace

thesameorganindifferentcreatures.InChapter1wesawthatwecanmakepredictionsandfindversionsofourorgansinancientrocks.InChapter2wesawhowwecantracesimilarbonesallthewayfromfishtohumans.Chapter3showshowtherealheritablepartofourbodies—theDNAandgeneticrecipethatbuildsorgans—canbefollowedinverydifferentcreatures.Here,inteeth,mammaryglands,andfeathers,wefindasimilartheme.Thebiologicalprocessesthatmakethesedifferentorgansareversionsofthesamething.Whenyouseethesedeepsimilaritiesamongdifferentorgansandbodies,youbegintorecognizethatthediverseinhabitantsofourworldarejustvariationsonatheme.

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CHAPTERFIVE

GETTINGAHEAD

ItwastwonightsbeforemyanatomyfinalandIwasinthelabataroundtwointhemorning,memorizingthecranialnerves.Therearetwelvecranialnerves,eachbranchingtotakebizarretwistsandturnsthroughtheinsideoftheskull.Tostudythem,webisectedtheskullfromforeheadtochinandsawedopensomeofthebonesofthecheek.SothereIwas,holdinghalfoftheheadineachhand,tracingthetwistedpathsthatthenervestakefromourbrainstothedifferentmusclesandsenseorgansinside.Iwasenrapturedbytwoofthecranialnerves,the

trigeminalandthefacial.Theircomplicatedpatternboileddowntosomethingsosimple,sooutrageouslyeasythatIsawthehumanheadinanewway.Thatinsightcamefromunderstandingthefarsimplerstateofaffairsinsharks.Theeleganceofmyrealization—thoughnotitsnovelty;comparativeanatomistshadhaditacenturyormoreago—andthepressureoftheupcomingexamledmetoforgetwhereIwas.Atsomepoint,Ilookedaround.ItwasthemiddleofthenightandIwasaloneinthelab.Ialso

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happenedtobesurroundedbythebodiesoftwenty-fivehumanbeingsundersheets.Forthefirstandlasttime,Igotthewillies.Iworkedmyselfintosuchalatherthatthehairsonthebackofmyneckrose,myfeetdidtheirjob,andwithinananosecondIfoundmyselfatthebusstop,outofbreath.ItgoeswithoutsayingthatIfeltridiculous.Iremembertellingmyself:Shubin,you’vebecomehard-core.Thatthoughtdidnotlastlong;IsoondiscoveredIhadlockedmyhousekeysinthelab.Whatmademesohard-coreisthatheadanatomyis

deeplymesmerizing,infact,beautiful.Oneofthejoysofscienceisthat,onoccasion,weseeapatternthatrevealstheorderinwhatinitiallyseemschaotic.Ajumblebecomespartofasimpleplan,andyoufeelyouareseeingrightthroughsomethingtofinditsessence.Thischapterisaboutseeingthatessenceinsideourownheads.And,ofcourse,theheadsoffish.

THEINNERCHAOSOFTHEHEAD

Headanatomyisnotonlycomplicatedbuthardtosee,since,unlikeotherpartsofthebody,thetissuesoftheheadareencapsulatedinabonybox.Weliterallyhavetosawthroughthecheek,forehead,andcraniumtoseethevesselsandorgans.Havingthusopenedahumanhead,wefindaclumpofwhatlooksliketangledfishinglines.Vesselsandnervesmakecuriousloopsandturnsastheytravelthrough

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theskull.Thousandsofnervebranches,muscles,andbonessitwithinthissmallbox.Atfirstglance,thewholearrayisabewilderingmess.Ourskullsaremadeupofthreefundamentalparts:think

plates,blocks,androds.Theplatescoverourbrain.Patthetopofyourhead,andyouarefeelingthem.Theselargeplatesfittogetherlikejigsaw-puzzlepiecesandformmuchofourcranium.Whenwewereborn,theplateswereseparate;theopenspacesbetweenthem,thefontanelles,arevisibleininfants,occasionallythrobbingwiththebraintissueunderneath.Aswegrow,thebonesenlarge,andbythetimewereachtheageoftwotheyhavefused.Anotherpartofourskullliesunderneaththebrain,

formingaplatformthatholdsitup.Unliketheplate-likebonesatthetop,theseboneslooklikecomplicatedblocksandhavemanyarteriesandnervesrunningthroughthem.Thethirdkindofbonemakesupourjaws,somebonesinourears,andotherbonesinourthroats;thesebonesstartdevelopmentlookinglikerods,whichultimatelybreakupandchangeshapetohelpuschew,swallow,andhear.Insidetheskullareanumberofcompartmentsand

spacesthathousedifferentorgans.Obviously,thebrainoccupiesthelargestofthese.Otherspacescontainoureyes,partsofourears,andournasalstructures.Muchofthechallengeinunderstandingheadanatomycomesfromseeingthesedifferentspacesandorgansinthreedimensions.Attachedtothebonesandorgansintheheadarethe

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musclesweusetobite,totalk,andtomoveoureyesandwholehead.Twelvenervessupplythesemuscles,eachexitingthebraintotraveltoadifferentregioninsideourhead.Thesearethedreadedcranialnerves.

Plates,blocks,androds:thethemeforskulls.Everyboneinourheadcanbetracedtooneofthesethings.

Thekeytounlockingthebasicsoftheheadistoseethe

cranialnervesasmorethanajumble.Indeed,mostofthemreallyaresimple.Thesimplestcranialnerveshaveonlyonefunction,andtheyattachtoonemuscleororgan.Thecranialnervethatgoestoournasalstructures,theolfactory,hasonejob:totakeinformationfromournasaltissuestoourbrain.Someofthenervesthatgotooureyesandearsarealsosimpleinthisway:theopticnerveisinvolvedwithvision;theacousticnerveworksinhearing.Aboutfourothercranialnervesonlyservemuscles—

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workingtomovetheeyesinsidetheorbits,forexample,ortomovetheheadaroundontheneck.Butfourofthecranialnerveshavegivenmedical

studentsfitsfordecades.Forgoodreason:thefourhaveverycomplexfunctionsandtaketortuouspathsthroughtheheadtodotheirjobs.Thetrigeminalnerveandthefacialnervedeservespecialmention.Bothexitthebrainandbreakupintoabewilderingnetworkofbranches.Muchlikeacablethatcancarrytelevision,Internet,andvoiceinformation,asinglebranchofthetrigeminalorfacialnervecancarryinformationaboutbothsensationandaction.Individualfibersforsensationandactionemanatefromdifferentpartsofthebrain,areconsolidatedincables(whatweendupcallingthetrigeminalandfacialnerves),thenbreakupagain,sendingbranchesalloverthehead.Thetrigeminal’sbranchesdotwomajorthings:they

controlmuscles,andtheycarrysensoryinformationfrommuchofourfacebacktoourbrain.Themusclescontrolledbythetrigeminalnerveincludethoseweusetochewaswellastinymusclesdeepinsidetheear.Thetrigeminalisalsothemajornerveforsensationintheface.Thereasonaslaptothefacehurtssomuch,beyondtheemotionalpain,isbecausethetrigeminalcarriessensoryinformationfromtheskinofourfacebacktoourbrain.Yourdentistalsoknowsthebranchesofyourtrigeminalnervewell.Differentbranchesgototherootsofourteeth;asinglejabofanestheticalongoneofthesebranchescandeadenthesensationofdifferentpartsofourtoothrow.

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Thefacialnervealsocontrolsmusclesandrelayssensoryinformation.Asitsnameimplies,itisthemainnervethatcontrolsthemusclesoffacialexpression.Weusethesetinymusclestosmile,tofrown,toraiseandloweroureyebrows,toflareournostrils,andsoon.Theyhavewonderfullyevocativenames.Oneofthemajormusclesthatweuseinfrowning—itmovesthecornersofourmouthdown—iscalledthedepressorangulioris.Anothergreatnamebelongstothemuscleweusetofurrowourbrowinconcern:thecorrugatorsupercilli.Flareyournostrilsandyouareusingyournasalis.Eachofthesemuscles,likeeveryothermuscleoffacialexpression,iscontrolledbybranchesofthefacialnerve.Thingslikeanunevensmileorasymmetricallydroopingeyelidsareasignthatsomethingmightbewrongwiththefacialnerveononesideofaperson’sface.YouareprobablybeginningtoseewhyIwasstayingup

solatetostudythesenerves.Nothingaboutthemseemstomakeanysense.Forexample,boththetrigeminalandthefacialnervessendtinybranchestomusclesinsideourears.Whydotwodifferentnerves,whichinnervateentirelydifferentpartsofthefaceandjaw,sendbranchestoearmusclesthatlieadjacenttooneanother?Evenmoreconfusing,thetrigeminalandfacialalmostcrisscrossastheysendbranchestoourfaceandjaw.Why?Withsuchoddlyredundantfunctionsandtortuouspaths,thereseemstobenorhymeorreasontotheirstructure,muchlesstohowthesenervesmatchupwiththeplates,blocks,androds

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thatmakeupourskull.Inthinkingaboutthesenerves,Iamremindedofmyfirst

dayshereinChicagoin2001.Ihadbeengivenspaceforaresearchlaboratoryinahundred-year-oldbuildingandthelabneedednewutilitycables,plumbing,andairhandling.Irememberthedaywhenthecontractorsfirstopenedthewallstogetaccesstotheinnardsofthebuilding.TheirreactiontotheplumbingandwiringinsidemywallwasalmostexactlylikeminewhenIopenedthehumanheadandsawthetrigeminalandfacialnervesforthefirsttime.Thewires,cables,andpipesinsidethewallswereajumble.Nobodyinhisrightmindwouldhavedesignedabuildingfromscratchthisway,withcablesandpipestakingbizarreloopsandturnsthroughoutthebuilding.Andthat’sexactlythepoint.Mybuildingwasconstructed

in1896,andtheutilitiesreflectanolddesignthathasbeenjerry-riggedfurtherwitheachrenovation.Ifyouwanttounderstandthewiringandplumbinginmybuilding,youhavetounderstanditshistory,howitwasrenovatedforeachnewgenerationofscientists.Myheadhasalonghistoryalso,andthathistoryexplainscomplicatednerveslikethetrigeminalandthefacial.Forus,thathistorybeginswithafertilizedegg.

THEESSENCEINEMBRYOS

Nobodystartslifewithahead:spermandeggcome

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togethertomakeasinglecell.Betweenthemomentofconceptionandthethirdweekthereafter,wegofromthatsinglecelltoaballofcells,thentoaFrisbee-shapedcollectionofcells,thentosomethingthatlooksvaguelylikeatubeandincludesdifferentkindsoftissues.Betweenthetwenty-thirdandtwenty-eighthdaysafterconception,thefrontendofthetubethickensandfoldsoverthebody,sotheembryolooksasifit’salreadycurledupinthefetalposition.Theheadatthisstagelookslikeabigglob.Thebaseofthisglobholdsthekeytomuchofthebasicorganizationofourheads.Fourlittleswellingsdeveloparoundtheareathatwill

becomethethroat.Ataboutthreeweeksweseethefirsttwo;theothertwoemergeaboutfourdayslater.Eachswellinglooksquitehumbleontheoutside:asimpleblob,separatedfromthenextbyalittlecrease.Whenyoufollowwhathappenstotheblobsandcreases,youbegintoseetheorderandbeautyofthehead,includingthetrigeminalandfacialnerves.Ofthecellsinsideeachblob,knownasarches,somewill

formbonetissueandothersmuscleandbloodvessels.Thereisacomplexmixofcellsinsideeacharch;somecellsdividedrighttherewhileothersmigratedalongwaytoenterthearchitself.Whenweidentifythecellsineacharchaccordingtowheretheyendupintheadult,thingsstarttomakealotofsense.Ultimately,thefirstarchtissuesformtheupperand

lowerjaws,twotinyearbones(themalleusandincus),and

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allthevesselsandmusclesthatsupplythem.Thesecondarchformsthethirdsmallearbone(thestapes),atinythroatbone,andmostofthemusclesthatcontrolfacialexpression.Thethirdarchformsbones,muscles,andnervesdeeperinthethroat;weusethesetoswallow.Finally,thefourtharchformsthedeepestpartsofourthroat,includingpartsofourlarynxandthemusclesandvesselsthatsurrounditandhelpitfunction.Ifyouweretoshrinkyourselftothesizeofapinheadand

travelinsidethemouthofthedevelopingembryo,youwouldseeindentationsthatcorrespondtoeachswelling.Therearefouroftheseindentations.And,likethearchesontheoutside,cellsontheindentationsformimportantstructures.ThefirstelongatestoformourEustachiantubeandsomestructuresintheear.Thesecondformsthecavitythatholdsourtonsils.Thethirdandfourthformimportantglands,includingtheparathyroid,thymus,andthyroid.WhatI’vejustgivenyouisoneofthebigtricksfor

understandingthemostcomplicatedcranialnervesandlargeportionsofthehead.Whenyouthinktrigeminalnerve,thinkfirstarch.Facialnerve,secondarch.Thereasonthetrigeminalnervegoestoboththejawsandtheearisthatallthestructuresitsuppliesoriginallydevelopedinthefirstarch.Thesamethingistrueforthefacialnerveandthesecondarch.Whatdothemusclesoffacialexpressionhaveincommonwiththemusclesintheearthatthefacialnervesupplies?Theyareallsecondarchderivatives.Asforthenervesofthethirdandfourtharches,theircomplexpaths

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allrelatetothefactthattheyinnervatestructuresthatarosefromtheirrespectivearches.Thosethirdandfourtharchnerves,amongthemtheglossopharyngealandvagus,followthesamepatternastheonesinfront,eachgoingtostructuresthatdevelopedfromthearchtheyareassociatedwith.

Ifwefollowthegillarchesfromanembryotoanadult,wecantracetheoriginsofjaws,ears,larynx,andthroat.Bones,muscles,nerves,andarteriesalldevelopinsidethesegillarches.

Thisfundamentalblueprintofheadshelpsusmakesense

ofoneoftheapocryphaltalesinanatomy.In1820,sothestorygoes,JohannesGoethewaswalkingthroughtheJewishcemeteryinViennawhenhespottedthedecomposingskeletonofaram.Thevertebraewereexposedandabovethemlayadamagedskull.Goethe,inamomentofepiphany,sawthatthebreaksintheskullmade

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itlooklikeagnarledmessofvertebrae.ToGoethe,thisrevealedtheessentialpatternwithin:theheadismadeupofvertebraethatfusedandgrewavaulttoholdourbrainsandsenseorgans.Thiswasarevolutionaryideabecauseitlinkedheadsandbodiesastwoversionsofthesamefundamentalplan.Thenotionmusthavebeeninthedrinkingwaterintheearly1800sbecauseotherpeople,amongthemLorenzOken,allegedlycameupwithvirtuallythesameideainasimilarsetting.GoetheandOkenwerebothpickingupsomethingvery

profound,althoughtheycouldnothaveknownitatthetime.Ourbodyissegmented,andthispatternismostclearlyseeninourvertebrae.Eachvertebraisablockthatrepresentsasegmentofourbody.Theorganizationofournervesisalsosegmental,correlatingcloselywiththepatternofthevertebrae.Nervesexitthespinalcordtosupplythebody.Thesegmentalconfigurationisobviouswhenyoulookatthelevelsofthespinalcordthatareassociatedwitheachpartofourbody.Forexample,themusclesinourlegsaresuppliedbynervesthatexitfromlowerpartsofthespinalcordthanthosethatsupplyourarms.Headsmaynotlookit,buttheyalsocontainaverydeepsegmentalpattern.Ourarchesdefinesegmentsofbones,muscles,arteries,andnerves.Lookintheadult,andyouwon’tseethispattern.Weseeitonlyintheembryo.Ourskullsloseallovertevidenceoftheirsegmental

originsaswegofromembryotoadult.Theplate-likebonesofourskullsformoverourgillarches,andthemuscles,

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nerves,andarteries,whichallhadaverysimplesegmentalpatternearlyon,arerewiredtomakeouradultheads.Knowingsomethingaboutdevelopmentcanhelpus

predictwheretolookforwhatismissinginchildrenwhohavecertainbirthdefects.Forexample,childrenbornwithfirstarchsyndromehaveatinyjawandnonfunctioningearswithnomalleusorincusbone.Missingarestructuresthatnormallywouldhaveformedfromthefirstarch.Thearchesaretheroadmapformajorchunksofthe

skull,fromthemostcomplicatedcranialnervestothemuscles,arteries,bones,andglandsinside.Thearchesarealsoaguidetosomethingelse:ourverydeepconnectionwithsharks.

OURINNERSHARK

Thetake-homemessageofmanyalawyerjokeisthatlawyersareanespeciallyvoraciouskindofshark.Teachingembryologyduringoneoftherecurringvoguesforthesejokes,Irememberthinkingthatthejokeisonallofus.We’reallmodifiedsharks—or,worse,thereisalawyerinsideeachofus.Aswe’veseen,muchofthesecretofheadsliesinthe

arches,theswellingsthatgaveustheroadmapforthecomplicatedcranialnervesandkeystructuresinsidethehead.Thoseinsignificant-lookingswellingsandindentationshavecapturedtheimaginationofanatomists

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for150years,becausetheylooklikethegillslitsinthethroatregionsoffishandsharks.Fishembryoshavethesebulgesandindentations,too.In

fish,theindentationsultimatelyopenuptoformthespacesbetweenthegillswherewaterflows.Inus,theindentationsnormallysealover.Inabnormalcases,gillslitsfailtocloseandremainopenaspouchesorcysts.Abranchialcyst,forexample,isoftenabenignfluid-filledcystthatformsinanopenpouchinsidetheneck;thepouchiscreatedbythefailureofthethirdorfourtharchtoclose.Rarely,childrenarebornwithanactualvestigeofanancientgillarchcartilage,alittlerodthatrepresentsagillbarfromthethirdarch.Intheseinstances,mysurgicalcolleaguesareoperatingonaninnerfishthatunfortunatelyhascomebacktobiteus.Everyheadoneveryanimalfromasharktoahuman

sharesthosefourarchesindevelopment.Therichnessofthestoryliesinwhathappensinsideeacharch.Here,wecanmakeapoint-by-pointcomparisonbetweenourheadsandthoseofsharks.

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Thegillregionofadevelopinghumanandadevelopingsharklookthesameearlyon.

Lookatthefirstarchinahumanandashark,andyou

findaverysimilarstateofaffairs:jaws.Themajordifferenceisthathumans’firstarchalsoformssomeearbones,whichwedonotseeinsharks.Unsurprisingly,thecranialnervethatsuppliesthejawsofhumansandsharksisthefirstarchnerve,thetrigeminalnerve.Thecellsinsidethesecondgillarchdivide,change,and

giverisetoabarofcartilageandmuscle.Inus,thebarofcartilagebreaksuptoformoneofthethreebonesofourmiddleear(thestapes)andsomeothersmallstructuresatthebaseoftheheadandthroat.Oneofthesebones,calledthehyoid,assistsusinswallowing.Takeagulp,listentomusic,andthankthestructuresthatformfromyoursecondarch.Inashark,thesecondarchrodbreaksuptoformtwo

bonesthatsupportthejaws:aloweronethatcompares

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withourhyoidandanupperonethatsupportstheupperjaw.Ifyouhaveeverwatchedagreatwhitesharktrytochompsomething—adiverinacage,forexample—youhaveprobablynoticedthattheupperjawcanextendandretractasthesharkbites.Theupperboneofthissecondarchispartoftheleversystemofbonesthatrotatetomakethatpossible.Thatupperboneisremarkableinanotherway,too.Itcompareswithoneofthebonesinourmiddleear:thestapes.Bonesthatsupporttheupperandlowerjawsinsharksareusedinustoswallowandhear.Asforthethirdandfourtharches,wefindthatmanyof

thestructuresweusetotalkandswalloware,insharks,partsoftissuesthatsupportthegills.Themusclesandcranialnervesweusetoswallowandtalkmovethegillsinsharksandfish.

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Atfirstglance,ourcranialnerves(bottomright)appeardifferentfromthoseofashark(bottomleft).Butlookcloselyandyouwillfindprofoundsimilarities.Virtuallyallofournervesarepresentinsharks.Theparallelsgodeeperstill:equivalentnervesinsharksandhumanssupplysimilarstructures,andtheyevenexitthebraininthesameorder(topleftandright).

Ourheadmaylookincrediblycomplicated,butitisbuilt

fromasimpleandelegantblueprint.Thereisapatterncommontoeveryskullonearth,whetheritbelongstoashark,abonyfish,asalamander,orahuman.Thediscovery

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ofthispatternwasamajoraccomplishmentofnineteenth-centuryanatomy,atimewhenanatomistswereputtingembryosofallkindsofspeciesunderthemicroscope.In1872,theOxfordanatomistFrancisMaitlandBalfourfirstsawthebasicplanofheadswhenhelookedatsharksandsawthebulges,thegillarches,andthestructuresinside.Unfortunately,hediedsoonafterinamountaineeringaccidentintheSwissAlps.Hewasonlyinhisthirties.

GILLARCHGENES

Duringthefirstthreeweeksafterconception,wholebatteriesofgenesareturnedonandoffinourgillarchesandthroughoutthetissuesthatwillbecomeourfuturebrain.Thesegenesinstructcellstomakethedifferentportionsofourhead.Thinkofeachregionofourheadasgainingageneticaddressthatmakesitdistinctive.Modifythisgeneticaddressandwecanmodifythekindsofstructuresthatdevelopthere.Forexample,ageneknownasOtxisactiveinthefront

region,wherethefirstgillarchforms.Behindit,towardthebackofthehead,anumberofso-calledHoxgenesareactive.EachgillarchhasadifferentcomplementofHoxgenesactiveinit.Withthisinformation,wecanmakeamapofourgillarchesandtheconstellationofgenesactiveinmakingeach.Nowwecandoexperiments:changethegeneticaddress

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ofonegillarchintothatofanother.Takeafrogembryo,turnoffsomegenes,makethegeneticsignalssimilarinthefirstandsecondarches,andyouendupwithafrogthathastwojaws:amandibledevelopswhereahyoidbonewouldnormallybe.Thisshowsthepowerofthegeneticaddressesinmakingourgillarches.Changetheaddress,andyouchangethestructuresinthearch.Thepowerofthisapproachisthatwecannowexperimentwiththebasicdesignofheads:wecanmanipulatetheidentityofthegillarchesalmostatwill,bychangingtheactivityofthegenesinside.

TRACINGHEADS:FROMHEADLESSWONDERSTOOURHEADEDANCESTORS

Whystopatfrogsandsharks?Whynotextendourcomparisontoothercreatures,likeinsectsorworms?Butwhywouldwedothiswhennoneofthesecreatureshasaskull,muchlesscranialnerves?Noneofthemevenhasbones.Whenweleavefishforworms,wegettoaverysoftandheadlessworld.Bitsofourselvesarethere,though,ifyoulookclosely.Thoseofuswhoteachcomparativeanatomyto

undergraduatesusuallybeginthecoursewithaslideofAmphioxus.EverySeptember,hundredsofAmphioxusslidesappearonscreensincollegelecturehallsfromMainetoCalifornia.Why?Rememberthesimpledichotomybetweeninvertebratesandvertebrates?Amphioxusisaworm,an

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invertebrate,thatsharesmanyfeatureswithbackbonedanimalssuchasfish,amphibians,andmammals.Amphioxuslacksabackbone,butlikeallcreatureswithbackbones,ithasanervecordthatrunsalongitsback.Inaddition,arodrunsthelengthofitsbody,paralleltothenervecord.Thisrod,knownasthenotochord,isfilledwithajelly-likesubstanceandprovidessupportforthebody.Asembryos,wehaveanotochord,too,butunlikeAmphioxus’s,oursbreaksupandultimatelybecomespartofthedisksthatliebetweenourvertebrae.Ruptureadiskandthejelly-likesubstanceofwhatwasonceanotochordcanwreakhavocwhenitpinchesnervesorinterfereswiththeabilityofonevertebratomovealongthenext.Whenweinjureadisk,averyancientpartofourbodyplanisrupturing.Thanksalot,Amphioxus.

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Theclosestrelativestoanimalswithheadsarewormswithgillslits.ShownareAmphioxusandareconstructionofafossilworm(Haikouella)over530millionyearsold.Bothwormshaveanotochord,anervecord,andgillslits.ThefossilwormisknownfromoverthreehundredindividualspecimensfromsouthernChina.

Amphioxusisnotuniqueamongworms.Someofthebest

examplesarenotintheoceansoftodaybutinancientrocksofChinaandCanada.Buriedinsedimentsover500millionyearsoldaresmallwormsthatlackheads,complexbrains,orcranialnerves.Theymaynotlooklikemuch,beingsmallsmudgesintherock,butthepreservationofthesefossilsis

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incredible.Whenyoulookunderamicroscope,youfindbeautifullypreservedimpressionsthatdisplaytheirsoftanatomyinfinedetail,occasionallyevenwithimpressionsofskin.Theyshowsomethingelsewonderful,too.Theyaretheearliestcreatureswithnotochordsandnervecords.Thesewormsaretellingussomethingabouttheoriginofpartsofourbodies.Butthereissomethingelsewesharewiththeselittle

worms:gillarches.Amphioxus,forexample,hastheminabundance,andassociatedwitheacharchisalittlebarofcartilage.Likethecartilagesthatformourjaws,ourearbones,andpartsofourvoicebox,theserodssupportthegillslit.Theessenceofourheadgoesbacktoworms,organismsthatdonotevenhaveahead.WhatdoesAmphioxusdowiththegillarches?Itpumpswaterthroughthemtofilteroutlittleparticlesoffood.Fromsohumbleabeginningcomesthebasicstructuresofourownhead.Justasteeth,genes,andlimbshavebeenmodifiedandtheirfunctionsrepurposedovertheages,so,too,hasthebasicstructureofourhead.

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CHAPTERSIX

THEBEST-LAID(BODY)PLANS

Weareapackageofabouttwotrillioncellsassembledinaverypreciseway.Ourbodiesexistinthreedimensions,withourcellsandorgansintheirproperplaces.Theheadisontop.Thespinalcordistowardourback.Ourgutsareonthebellyside.Ourarmsandlegsaretothesides.Thisbasicarchitecturedistinguishesusfromprimitivecreaturesorganizedasclumpsordisksofcells.Thesamedesignisalsoanimportantpartofthebodies

ofothercreatures.Likeus,fish,lizards,andcowshavebodiesthataresymmetricalwithafront/back,top/bottom,andleft/right.Theirfrontends(correspondingtothetopofanuprighthuman)allhaveheads,withsenseorgansandbrainsinside.Theyhaveaspinalcordthatrunsthelengthofthebodyalongtheback.Alsolikeus,theyhaveananus,whichisattheoppositeendoftheirbodiesfromthemouth.Theheadisontheforwardend,inthedirectiontheytypicallyswimorwalk.Asyoucanimagine,“anus-forward”wouldn’tworkverywellinmostsettings,particularlyaquaticones.Socialsituationswouldbeaproblem,too.

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Itismoredifficulttofindourbasicdesigninreallyprimitiveanimals—jellyfish,forexample.Jellyfishhaveadifferentkindofbodyplan:theircellsareorganizedintodisksthathaveatopandbottom.Lackingafrontandback,aheadandtail,andaleftandright,jellyfishbodyorganizationappearsverydifferentfromourown.Don’tevenbothertryingtocompareyourbodyplanwithasponge.Youcouldtry,butthemerefactthatyouweretryingwouldrevealsomethingmorepsychiatricthananatomical.Toproperlycompareourselveswiththeseprimitive

animals,weneedsometools.Justaswithheadsandlimbs,ourhistoryiswrittenwithinourdevelopmentfromeggtoadult.Embryosholdthecluestosomeoftheprofoundmysteriesoflife.Theyalsohavetheabilitytoderailmyplans.

THECOMMONPLAN:COMPARINGEMBRYOS

Ienteredgraduateschooltostudyfossilmammalsandendedupthreeyearslaterstudyingfishandamphibiansformydissertation.Myfallfromgrace,ifyouwanttocallitthat,happenedwhenIstartedtolookatembryos.Wehadalotofembryosinthelab:salamanderlarvae,fishembryos,evenfertilizedchickeneggs.I’droutinelypopthemunderthemicroscopetoseewhatwasgoingon.Theembryosofallthespecieslookedlikelittlewhitishbatchesofcells,no

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morethananeighthofaninchlong.Itwasexcitingwatchingdevelopmentprogress;astheembryogotbigger,theyolk,itsfoodsupply,gotsmallerandsmaller.Bythetimetheyolkwasgone,theembryowasusuallybigenoughtohatch.Watchingtheprocessofdevelopmentbroughtabouta

hugeintellectualtransformationinme.Fromsuchsimpleembryonicbeginnings—smallblobsofcells—camewonderfullycomplexbirds,frogs,andtroutcomprisingtrillionsofcellsarrangedinjusttherightway.Buttherewasmore.Thefish,amphibian,andchickenembryoswerelikenothingIhadeverseenbeforeinbiology.Theyalllookedgenerallyalike.Allofthemhadaheadwithgillarches.Allofthemhadalittlebrainthatbeganitsdevelopmentwiththreeswellings.Allofthemhadlittlelimbbuds.Infact,thelimbsweretobecomemythesis,thefocusofmynextthreeyears’work.Here,incomparinghowtheskeletondevelopedinbirds,salamanders,frogs,andturtles,Iwasfindingthatlimbsasdifferentasbirdwingsandfroglegslookedverysimilarduringtheirdevelopment.Inseeingtheseembryos,Iwasseeingacommonarchitecture.Thespeciesendeduplookingdifferent,buttheystartedfromagenerallysimilarplace.Lookingatembryos,italmostseemsthatthedifferencesamongmammals,birds,amphibians,andfishsimplypaleincomparisonwiththeirfundamentalsimilarities.ThenIlearnedoftheworkofKarlErnstvonBaer.Inthe1800s,somenaturalphilosopherslookedto

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embryostotrytofindthecommonplanforlifeonearth.ParamountamongtheseobserverswasKarlErnstvonBaer.Borntoanoblefamily,heinitiallytrainedtobeaphysician.Hisacademicmentorsuggestedthathestudychickendevelopmentandtrytounderstandhowchickenorgansdeveloped.Unfortunately,vonBaercouldnotaffordincubatorsto

workonchickens,norcouldheaffordmanyeggs.Thiswasnotverypromising.Luckyforhim,hehadanaffluentfriend,ChristianPander,whocouldaffordtodotheexperiments.Astheylookedatembryos,theyfoundsomethingfundamental:allorgansinthechickencanbetracedtooneofthreelayersoftissueinthedevelopingembryo.Thesethreelayersbecameknownasthegermlayers.Theyachievedalmostlegendarystatus,whichtheyretaineventothisday.Pander’sthreelayersgavevonBaerthemeanstoask

importantquestions.Doallanimalssharethispattern?Arethehearts,lungs,andmusclesofallanimalsderivedfromtheselayers?And,importantly,dothesamelayersdevelopintothesameorgansindifferentspecies?VonBaercomparedthethreelayersofPander’schicken

embryoswitheverythingelsehecouldgethishandson:fish,reptiles,andmammals.Yes,everyanimalorganoriginatedinoneofthesethreelayers.Significantly,thethreelayersformedthesamestructuresineveryspecies.Everyheartofeveryspeciesformedfromthesamelayer.Anotherlayergaverisetoeverybrainofeveryanimal.Andsoon.Nomatterhowdifferentthespecieslookasadults,as

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tinyembryostheyallgothroughthesamestagesofdevelopment.Tofullyappreciatetheimportanceofthis,weneedto

lookagainatourfirstthreeweeksafterconception.Atthemomentoffertilization,majorchangeshappeninsidetheegg—thegeneticmaterialofthespermandeggfusesandtheeggbeginstodivide.Ultimately,thecellsformaball.Inhumans,overaboutfivedays,thesingle-cellbodydividesfourtimes,toproduceaballofsixteencells.Thisballofcells,knownasablastocyst,resemblesafluid-filledballoon.Athinsphericalwallofcellssurroundssomefluidinthecenter.Atthis“blastocyststage”therestilldoesnotappeartobeanybodyplan—thereisnofrontandback,andcertainlytherearenotyetanydifferentorgansortissues.Onaboutthesixthdayafterconception,theballofcellsattachestoitsmother’suterusandbeginstheprocessofconnectingtoitsothatmotherandembryocanjoinbloodstreams.Thereisstillnoevidenceofthebodyplan.Itisafarcryfromthisballofcellstoanythingthatyou’drecognizeasanymammal,reptile,orfish,muchlessahuman.Ifwearelucky,ourballofcellshasimplantedinour

mother’suterus.Whenablastocystimplantsinthewrongplace—whenthereisan“ectopicimplantation”—theresultscanbedangerous.About96percentofectopicimplantationshappenintheuterine(orfallopian)tubes,nearwhereconceptionhappens.Sometimesmucusblockstheeasypassageoftheblastocysttotheuterus,causingit

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toimplantimproperlyinthetubes.Ectopicpregnancycancausevarioustissuerupturesifnotcaughtintime.Inreallyrarecases,theblastocystisexpelledintothemother’sbodycavity,thespacebetweenhergutsandbodywall.Inevenrarercases,theseblastocystswillimplantontheoutsideliningofthemother’srectumoruterusandthefetusdevelopstofullterm!Althoughthesefetusescansometimesbedeliveredbyanabdominalincision,suchimplantationisgenerallyverydangerousbecauseitincreasestheriskofmaternaldeathbybleedingbyafactorof90,ascomparedwithanormalimplantationinsidetheuterus.Inanyevent,atthisstageofdevelopmentweare

extremelyhumble-lookingcreatures.Aroundthebeginningofoursecondweekafterconception,theblastocysthasimplanted,withonepartoftheballembeddedinthewalloftheuterus,andtheotherfree.Thinkofaballoonpushedintoawall:thisflatteneddiskbecomesthehumanembryo.Ourentirebodyformsfromonlythetoppartofthisball,thepartthatismushedintothewall.Thepartoftheblastocystbelowthediskcoverstheyolk.Atthisstageofdevelopment,welooklikeaFrisbee,asimpletwo-layereddisk.HowdoesthisovalFrisbeeendupwithvonBaer’sthree

germlayersandgoontolookanythinglikeahuman?First,cellsdivideandmove,causingtissuestofoldinonthemselves.Eventually,astissuesmoveandfold,webecomeatubewithafoldedswellingattheheadendand

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anotheratthetail.Ifweweretocutourselvesinhalfrightaboutnow,wewouldfindatubewithinatube.Theoutertubewouldbeourbodywall,theinnertubeoureventualdigestivetract.Aspace,thefuturebodycavity,separatesthetwotubes.Thistube-within-a-tubestructurestayswithusourentirelives.Theguttubegetsmorecomplicated,withabigsacforastomachandlongintestinaltwistsandturns.Theoutertubeiscomplicatedbyhair,skin,ribs,andlimbsthatpushout.Butthebasicplanpersists.Wemaybemorecomplicatedthanwewereattwenty-onedaysafterconception,butwearestillatubewithinatube,andallofourorgansderivefromoneofthethreelayersoftissuethatappearedinoursecondweekafterconception.Thenamesofthesethreeall-importantlayersare

derivedfromtheirposition:theouterlayeriscalledectoderm,theinnerlayerendoderm,andthemiddlelayermesoderm.Ectodermformsmuchoftheouterpartofthebody(theskin)andthenervoussystem.Endoderm,theinsidelayer,formsmanyoftheinnerstructuresofthebody,includingourdigestivetractandnumerousglandsassociatedwithit.Themiddlelayer,themesoderm,formstissueinbetweenthegutsandskin,includingmuchofourskeletonandourmuscles.Whetherthebodybelongstoasalmon,achicken,afrog,oramouse,allofitsorgansareformedbyendoderm,ectoderm,andmesoderm.

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Ourearlydays,thefirstthreeweeksafterconception.Wegofrombeingasinglecelltoaballofcellsandendupasatube.

VonBaersawhowembryosrevealfundamentalpatterns

oflife.Hecontrastedtwokindsoffeaturesindevelopment:featuressharedbyeveryspecies,andfeaturesthatvaryfromspeciestospecies.Featuressuchasthetube-within-a-tubearrangementaresharedbyallanimalswithabackbone:fish,amphibians,reptiles,birds,andmammals.Thesecommonfeaturesappearrelativelyearlyindevelopment.Thefeaturesthatdistinguishus—biggerbrainsinhumans,shellsonturtles,feathersonbirds—arise

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relativelylater.VonBaer’sapproachisverydifferentfromthe“ontogeny

recapitulatesphylogeny”ideayoumighthavelearnedinschool.VonBaersimplycomparedembryosandnotedthattheembryosofdifferentspecieslookedmoresimilartoeachotherthandotheadultsofthosespecies.The“ontogenyrecapitulatesphylogeny”approachchampioneddecadeslaterbyErnstHaeckelmadetheclaimthateachspeciestrackeditsevolutionaryhistoryasitproceededthroughdevelopment.Accordingly,theembryoofahumanwentthroughafish,areptile,andamammalstage.Haeckelwouldcompareahumanembryotoanadultfishoralizard.ThedifferencesbetweentheideasofvonBaerandHaeckelmightseemsubtle,buttheyarenot.Inthepastonehundredyears,timeandnewevidencehavetreatedvonBaermuchmorekindly.Incomparingembryosofonespeciestoadultsofanother,Haeckelwascomparingapplestooranges.Amoremeaningfulcomparisonisonewherewecanultimatelyuncoverthemechanismsthatdriveevolution.Forthat,wecompareembryosofonespeciestoembryosofanother.Theembryosofdifferentspeciesarenotcompletelyidentical,buttheirsimilaritiesareprofound.Allhavegillarches,notochords,andlooklikeatubewithinatubeatsomestageoftheirdevelopment.And,importantly,embryosasdistinctasfishandpeoplehavePanderandvonBaer’sthreegermlayers.

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Atfourweeksafterconception,weareatubewithinatubeandhavethethreegermlayersthatgiverisetoallourorgans.

Allofthesecomparisonsleadustotherealissueatstake.

Howdoestheembryo“know”todevelopaheadatthefrontendandananusattheback?Whatmechanismsdrivedevelopmentandmakecellsandtissuesabletoformbodies?Toanswerthesequestionsrequiredawholenew

approach.RatherthansimplycomparingembryosasinvonBaer’sday,wehadtofindanewwayofanalyzingthem.Thelatterpartofthenineteenthcenturyusheredintheera,

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whichwefirstdiscussedinChapter3,whenembryoswerechopped,grafted,split,andtreatedwithvirtuallyeverykindofchemicalimaginable.Allinthenameofscience.

EXPERIMENTINGWITHEMBRYOS

Biologistsattheturnofthetwentiethcenturyweregrapplingwithfundamentalquestionsaboutbodies.Whereintheembryodoestheinformationtobuildthemlie?Isthisinformationcontainedineverycellorinpatchesofcells?Andwhatformdoesthisinformationtake—isitaspecialkindofchemical?Beginningin1903,theGermanembryologistHans

Spemannbegantoinvestigatehowcellslearnedtobuildbodiesduringdevelopment.Hisgoalwastofindwherethebody-buildinginformationresides.ThebigquestionforSpemannwaswhetherallthecellsintheembryohaveenoughinformationtobuildwholebodies,orwhetherthatinformationisconfinedtocertainpartsofthedevelopingembryo.Workingwithnewteggs,whichwereeasytoobtainand

relativelyeasytofiddlewithinthelab,Spemanndevisedacleverexperiment.Hecutoffastrandofhisinfantdaughter’shairandmadeaminiaturelassooutofit.Babyhairisremarkablestuff;soft,thin,andpliant,itmadetheidealmaterialfortyingupatinyspheresuchasanewtegg.Spemanndidexactlythattoadevelopingnewtegg,

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pinchingonesideofffromtheother.Manipulatingthenucleiofthecellsabit,helettheresultingcontraptiondevelopandwatchedwhathappened.Theembryoformedtwins:twocompletesalamandersemerged,eachwithanormalbodyplanandeachentirelyviable.Theconclusionwasobvious:fromoneeggcancomemorethanoneindividual.Thisiswhatidenticaltwinsare.Biologically,Spemannhaddemonstratedthatintheearlyembryosomecellshavethecapacitytoformawholenewindividualontheirown.Thisexperimentwasonlythebeginningofawholenew

phaseofdiscovery.Inthe1920sHildeMangold,agraduatestudentin

Spemann’slaboratory,startedtoworkwithsmallembryos.Thefinecontrolshehadofherfingersmadeherabletodosomeincrediblydemandingexperiments.AtthestageofdevelopmentwithwhichMangoldworked,thesalamanderembryoisasphereaboutasixteenthofaninchindiameter.Sheloppedoffatinypieceoftissue,smallerthanapinhead,fromonepartoftheembryoandgrafteditontotheembryoofanotherspecies.WhatMangoldtransplantedwasn’tjustanypatch,butanareawherecellsthatweretoformmuchofthethreegermlayersweremovingandfolding.Mangoldwassoskilledthatthegraftedembryosactuallycontinuedtodevelop,givingherapleasantsurprise.Thegraftedpatchledtotheformationofawholenewbody,includingaspinalcord,back,belly,evenahead.

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Justbymovingasmallpatchoftissueintheembryo,Mangoldproducedtwins.

Whyisallthisimportant?Mangoldhaddiscovereda

smallpatchoftissuethatwasabletodirectothercellstoformanentirebodyplan.Thetiny,incrediblyimportantpatchoftissuecontainingallthisinformationwastobeknownastheOrganizer.Mangold’sdissertationworkwasultimatelytowinthe

NobelPrize,butnotforher.HildeMangolddiedtragically(thegasolinestoveinherkitchencaughtfire)beforeherthesiscouldevenbepublished.SpemannwontheNobelPrizeinMedicinein1935,andtheawardcites“hisdiscoveryoftheOrganizeranditseffectinembryonicdevelopment.”Today,manyscientistsconsiderMangold’sworktobe

thesinglemostimportantexperimentinthehistoryofembryology.AtroughlythesametimethatMangoldwasdoing

experimentsinSpemann’slab,W.Vogt(alsoinGermany)wasdesigningclevertechniquestolabelcells,orbatchesofthem,andthusallowtheexperimentertowatchwhathappensastheeggdevelops.Vogtwasabletoproducea

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mapoftheembryothatshowswhereeveryorganoriginatesintheegg.Weseetheantecedentsofthebodyplaninthecellfatesoftheearlyembryo.Fromtheearlyembryologists,peoplelikevonBaer,

Pander,Mangold,andSpemann,wehavelearnedthatallthepartsofouradultbodiescanbemappedtoindividualbatchesofcellsinthesimplethree-layeredFrisbee,andthegeneralstructureofthebodyisinitiatedbytheOrganizerregiondiscoveredbyMangoldandSpemann.Cut,slice,anddice,andyou’llfindthatallmammals,

birds,amphibians,andfishhaveOrganizers.Youcanevensometimesswaponespecies’Organizerforanother.TaketheOrganizerregionfromachickenandgraftittoasalamanderembryo:yougetatwinnedsalamander.ButjustwhatisanOrganizer?Whatinsideittellscells

howtobuildbodies?DNA,ofcourse.AnditisinthisDNAthatwewillfindtheinnerrecipethatwesharewiththerestofanimallife.

OFFLIESANDMEN

VonBaerwatchedembryosdevelop,comparedonespeciestoanother,andsawfundamentalpatternsinbodies.MangoldandSpemannphysicallydistortedembryostolearnhowtheirtissuesbuildbodies.IntheDNAage,wecanaskquestionsaboutourowngeneticmakeup.Howdoourgenescontrolthedevelopmentofourtissuesandour

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bodies?Ifyoueverthoughtthatfliesareunimportant,considerthis:mutationsinfliesgaveusimportantcluestothemajorbodyplangenesactiveinhumanembryos.Weputthiskindofthinkingtouseinthediscoveryofgenesthatbuildfingersandtoes.Nowwe’llseehowittellsusaboutthewaysentirebodiesarebuilt.Flieshaveabodyplan.Theyhaveafrontandaback,atop

andabottom,andsoon.Theirantennae,wings,andotherappendagespopoutofthebodyintherightplace.Exceptwhentheydon’t.Somemutantflieshavelimbsgrowingoutoftheirheads.Othershaveduplicatewingsandextrabodysegments.Theseareamongtheflymutantsthattelluswhyourvertebraechangeshapefromtheheadendtotheanalendofthebody.Peoplehavebeenstudyingabnormalfliesforovera

hundredyears.Mutantswithoneparticularkindofabnormalitygotspecialattention.Theseflieshadorgansinthewrongplaces—alegwhereanantennashouldhavebeen;anextrasetofwings—orweremissingbodysegments.Somethingwasmessingwiththeirfundamentalbodyplan.Ultimately,thesemutantsarisefromsomesortoferrorintheDNA.RememberthatgenesarestretchesofDNAthatlieonthechromosome.Usingavarietyoftechniquesthatallowustovisualizethechromosome,wecanidentifythepatchofthechromosomeresponsibleforthemutanteffect.Essentially,webreedmutantstomakeawholepopulationwhereeveryindividualhasthegeneticerror.Then,usingavarietyofmolecularmarkers,we

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comparethegenesofindividualswiththemutationtothosewithout.Thisallowsustopinpointtheregionandthelikelystretchofchromosomeresponsibleforthemutanteffect.Itturnsoutthataflyhaseightgenesthatmakesuchmutants.ThesegeneslienexttooneanotherononeofthelongDNAstrandsofthefly.Thegenesthataffecttheheadsegmentslienexttothosethataffectthesegmentsinthemiddleofthefly,thepartofthebodythatcontainsthewings.ThesebitsofDNA,inturn,lieadjacenttotheonesthatcontrolthedevelopmentoftherearpartofthefly.Thereisawonderfulordertothewaythegenesareorganized:theirpositionalongtheDNAstrandparallelsthestructureofthebodyfromfronttoback.Nowthechallengewastoidentifythestructureofthe

DNAactuallyresponsibleforthemutation.MikeLevineandBillMcGinnis,inWalterGehring’slabinSwitzerland,andMattScott,inTomKauffman’slabinIndiana,noticedthatinthemiddleofeachgenewasashortDNAsequencethatwasvirtuallyidenticalineachspeciestheylookedat.Thislittlesequenceiscalledahomeobox.TheeightgenesthatcontainthehomeoboxarecalledHoxgenes.Whenthescientistsfishedaroundforthisgenesequenceinotherspecies,theyfoundsomethingsouniformthatitcameasatruesurprise:versionsoftheHoxgenesappearineveryanimalwithabody.

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Hoxgenesinfliesandpeople.Thehead-to-tailorganizationofthebodyisunderthecontrolofdifferentHoxgenes.Flieshaveonesetofeighthoxgenes,eachrepresentedasalittleboxinthediagram.Humanshavefoursetsofthesegenes.Infliesand

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people,theactivityofagenematchesitspositionontheDNA:genesactiveintheheadlieatoneend,thoseinthetailatanother,withgenesaffectingthemiddleofthebodylyinginbetween.

Versionsofthesamegenessculptthefront-to-back

organizationofthebodiesofcreaturesasdifferentasfliesandmice.MesswiththeHoxgenesandyoumesswiththebodyplaninpredictableways.Ifyoumakeaflythatlacksageneactiveinamiddlesegment,themidsectionoftheflyismissingoraltered.Makeamousethatlacksoneofthegenesthatspecifiesthoracicsegments,andyoutransformpartsoftheback.Hoxgenesalsoestablishtheproportionsofourbodies—

thesizesofthedifferentregionsofourhead,chest,andlowerback.Theyareinvolvedinthedevelopmentofindividualorgans,limbs,genitalia,andguts.Changesinthembringaboutchangesinthewaysourbodiesareputtogether.Differentkindsofcreatureshavedifferentnumbersof

Hoxgenes.Fliesandotherinsectshaveeight,miceandothermammalsthirty-nine.Thethirty-nineHoxgenesinmiceareallversionsoftheonesthatarefoundinflies.ThissimilarityhasledtotheideathatthelargenumberofmammalianHoxgenesarosefromaduplicationofthesmallercomplementofgenesinthefly.Despitethesedifferencesinnumber,themousegenesareactivefromfronttobackinaverypreciseorderjustastheflygenesare.Canwegoevendeeperinourfamilytree,findingsimilar

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stretchesofDNAinvolvedinmakingevenmorefundamentalpartsofourbodies?Theanswer,surprisingly,isyes.Anditlinksustoanimalsevensimplerthanflies.

DNAANDTHEORGANIZER

AtthetimewhenSpemannwontheNobelPrize,theOrganizerwasalltherage.Scientistssoughtthemysteriouschemicalthatcouldinducetheentirebodyplan.Butjustaspopularculturehasyo-yosandTickleMeElmodolls,sosciencehasfadsthatwaxandwane.Bythe1970s,theOrganizerwasviewedaslittlemorethanacuriosity,acleveranecdoteinthehistoryofembryology.Thereasonforthisfallfromgracewasthatnoonecoulddecipherthemechanismsthatmadeitwork.ThediscoveryofHoxgenesinthe1980schanged

everything.Intheearly1990s,whentheOrganizerconceptwasstilldecidedlyunfashionable,EddieDeRobertis’slaboratoryatUCLAwaslookingforHoxgenesinfrogs,usingtechniqueslikeLevineandMcGinnis’s.Thesearchwasbroadanditnettedmanydifferentkindsofgenes.Oneofthesehadaveryspecialpatternofactivity.ItwasactiveattheexactsiteintheembryothatcontainstheOrganizer,anditwasactiveatexactlytherighttimeofdevelopment.IcanonlyimaginewhatDeRobertisfeltwhenhefoundthatgene.HewaslookingattheOrganizer,andthereintheOrganizerwasagenethatseemedspecificallytocontrolit

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orbelinkedtoitsactivityintheembryo.TheOrganizerwasback.Organizergenesstartedpoppingupinlaboratories

everywhere.Whiledoingadifferentkindofexperiment,RichardHarlandatBerkeleyfoundanothergene,whichhecalledNoggin.NoggindoesexactlywhatanOrganizergeneshould.WhenHarlandtooksomeNogginandinjecteditintotherightplaceinanembryo,itfunctionedexactlyliketheOrganizer.Theembryodevelopedtwobodyaxes,includingtwoheads.AreDeRobertis’sgeneandNoggintheactualbitsofDNA

thatmakeuptheOrganizer?Theanswerisyesandno.Manygenes,includingthesetwo,interacttoorganizethebodyplan.Suchsystemsarecomplex,becausegenescanplaymanydifferentrolesduringdevelopment.Noggin,forexample,playsaroleinthedevelopmentofthebodyaxisbutisalsoinvolvedwithahostofotherorgans.Furthermore,genesdonotactalonetospecifycomplicatedcellbehaviorslikethoseweseeinheaddevelopment.Genesinteractwithothergenesatallstagesofdevelopment.Onegenemayinhibittheactivityofanotherorpromoteit.Sometimesmanygenesinteracttoturnanothergeneonoroff.Fortunately,newtoolsallowustostudytheactivityofthousandsofgenesinacellatonce.Couplethistechnologywithnewcomputer-basedwaysofinterpretinggenefunctionandwehaveenormouspotentialtounderstandhowgenesbuildcells,tissues,andbodies.Understandingthesecomplexinteractionsbetween

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batteriesofgenesshedslightontheactualmechanismsthatbuildbodies.Nogginservesasagreatexample.Nogginalonedoesnotinstructanycellintheembryoaboutitspositiononthetop–bottomaxis;rather,itactsinconcertwithseveralothergenestodothis.Anothergene,BMP-4,isabottomgene;itisturnedonincellsthatwillmakethebottom,orbellyside,ofanembryo.ThereisanimportantinteractionbetweenBMP-4andNoggin.WhereverNogginisactive,BMP-4cannotdoitsjob.TheupshotisthatNoggindoesnottellcellstodevelopas“cellsonthetopofthebody”instead,itturnsoffthesignalthatwouldmakethembottomcells.Theseoff-oninteractionsunderlievirtuallyalldevelopmentalprocesses.

ANINNERSEAANEMONE

Itisonethingtocompareourbodieswiththoseoffrogsandfish.Inarealsenseweandtheyaremuchalike:weallhaveabackbone,twolegs,twoarms,ahead,andsoon.Whatifwecompareourselveswithsomethingutterlydifferent,forexamplejellyfishandtheirrelatives?Mostanimalshavebodyaxesdefinedbytheirdirection

ofmovementorbywheretheirmouthandanuslierelativetoeachother.Thinkaboutit:ourmouthisontheoppositeendofthebodyfromouranusand,asinfishandinsects,itisusuallyinthedirection“forward.”Howcanwetrytoseeourselvesinanimalsthathaveno

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nervecordatall?Howaboutnoanusandnomouth?Creatureslikejellyfish,corals,andseaanemoneshaveamouth,butnoanus.Theopeningthatservesasamouthalsoservestoexpelwaste.Whilethatoddarrangementmaybeconvenientforjellyfishandtheirrelatives,itgivesbiologistsvertigowhentheytrytocomparethesecreaturestoanythingelse.Anumberofcolleagues,MarkMartindaleandJohn

Finnertyamongthem,havedivedintothisproblembystudyingthedevelopmentofthisgroupofanimals.Seaanemoneshavebeenremarkablyinformative,becausetheyarecloserelativesofjellyfishandtheyhaveaveryprimitivebodypattern.Also,seaanemoneshaveaveryunusualshape,onethatatfirstglancewouldseemtomakethemworthlessasaformtocomparetous.Aseaanemoneisshapedlikeatreetrunkwithalongcentralstumpandabunchoftentaclesattheend.Thisoddshapemakesitparticularlyappealing,sinceitmighthaveafrontandaback,atopandabottom.Drawalinefromthemouthtothebaseoftheanimal.Biologistshavegiventhatlineaname:theoral–aboralaxis.Butnamingitdoesn’tmakeitmorethananarbitraryline.Ifitisreal,thenitsdevelopmentshouldresemblethedevelopmentofoneofourownbodydimensions.Martindaleandhiscolleaguesdiscoveredthatprimitive

versionsofsomeofourmajorbodyplangenes—thosethatdetermineourhead-to-anusaxis—areindeedpresentintheseaanemone.And,moreimportant,thesegenesare

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activealongtheoral–aboralaxis.Thisinturnmeansthattheoral–aboralaxisoftheseprimitivecreaturesisgeneticallyequivalenttoourhead-to-anusaxis.Oneaxisdown,anothertogo.Doseaanemoneshave

anythinganalogoustoourbelly-to-backaxis?Seaanemonesdon’tseemtohaveanythingcomparable.Despitethis,Martindaleandhiscolleaguestooktheboldstepofsearchingintheseaanemoneforthegenesthatspecifyourbelly-to-backaxis.Theyknewwhatourgeneslookedlike,andthisgavethemasearchimage.Theyuncoverednotone,butmanydifferentbelly-to-backgenesintheseaanemone.Butalthoughthesegeneswereactivealonganaxisintheseaanemone,thataxisdidn’tseemtocorrelatewithanypatterninhowtheadultanimal’sorgansareputtogether.

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Jellyfishrelatives,suchasseaanemones,haveafrontandabackaswedo,abodyplansetupbyversionsofthesamegenes.

Justwhatthishiddenaxiscouldbeisnotapparentfrom

theoutsideoftheanimal.Ifwecutoneinhalf,however,wefindanimportantclue,anotheraxisofsymmetry.Calledthedirectiveaxis,itseemstodefinetwodistinctsidesofthecreature,almostaleftandaright.Thisobscureaxiswasknowntoanatomistsbackinthe1920sbutremainedacuriosityinthescientificliterature.Martindale,Finnerty,andtheirteamchangedthat.Allanimalsarethesamebutdifferent.Likeacakerecipe

passeddownfromgenerationtogeneration—withenhancementstothecakeineach—therecipethatbuildsourbodieshasbeenpasseddown,andmodified,foreons.Wemaynotlookmuchlikeseaanemonesandjellyfish,buttherecipethatbuildsusisamoreintricateversionoftheonethatbuildsthem.Powerfulevidenceforacommongeneticrecipefor

animalbodiesisfoundwhenweswapgenesbetweenspecies.Whathappenswhenyouswapabody-buildinggenefromananimalthathasacomplexbodyplanlikeourswithonefromaseaanemone?RecallthegeneNoggin,whichinfrogs,mice,andhumansisturnedoninplacesthatwilldevelopintobackstructures.InjectextraamountsoffrogNogginintoafrogegg,andthefrogwillgrowextrabackstructures,sometimesevenasecondhead.Inseaanemoneembryos,aversionofNogginisalsoturnedonat

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oneendofthedirectiveaxis.Now,themillion-dollarexperiment:taketheproductofNogginfromaseaanemoneandinjectitintoafrogembryo.Theresult:afrogwithextrabackstructures,almostthesameresultasifthefrogwereinjectedwithitsownNoggin.Now,though,aswegobackintime,weareleftwithwhat

lookslikeahugegap.Everythinginthischapterhadabody.Howdowecompareourselveswiththingsthathavenobodiesatall—withsingle-celledmicrobes?

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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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CHAPTEREIGHT

MAKINGSCENTS

Intheearly1980s,therewastensionbetweenmolecularbiologistsandpeoplewhoworkedonwholeorganisms—ecologists,anatomists,andpaleontologists.Anatomists,forexample,wereseenasquaintlyout-of-date,hopelesslyentrancedbyanantiquatedkindofscience.Molecularbiologywasrevolutionizingourapproachtoanatomyanddevelopmentalbiology,somuchsothattheclassicaldisciplines,suchaspaleontology,seemedtobedeadendsinthehistoryofbiology.Iwasmadetofeelthat,becauseofmyloveoffossils,IwasgoingtobereplacedbyoneofthosenewautomatedDNAsequencers.Twentyyearslater,I’mstilldigginginthedirtand

crackingrocks.I’malsocollectingDNAandlookingatitsroleindevelopment.Debatesusuallybeginaseither-orscenarios.Overtime,all-or-nothingpositionsgivewaytoamorerealisticapproach.Fossilsandthegeologicalrecordremainaverypowerfulsourceofevidenceaboutthepast;nothingelserevealstheactualenvironmentsandtransitionalstructuresthatexistedduringthehistoryof

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life.Aswe’veseen,DNAisanextraordinarilypowerfulwindowintolife’shistoryandtheformationofbodiesandorgans.Itsroleisparticularlyimportantwherethefossilrecordissilent.Largepartsofbodies—softtissues,forexample—simplydonotfossilizereadily.Inthesecases,theDNArecordisvirtuallyallwehave.ExtractingDNAfrombodiesisincrediblyeasy,soeasy

youcandoitinyourkitchen.Takeahandfuloftissuefromsomeplantoranimal—peas,orsteak,orchickenliver.Addsomesaltandwaterandpopeverythinginablendertomushupthetissue.Thenaddsomedishsoap.Soapbreaksupthemembranesthatsurroundallthecellsinthetissuethatweretoosmallfortheblendertohandle.Afterthat,addsomemeattenderizer.ThemeattenderizerbreaksupsomeoftheproteinsthatattachtoDNA.Nowyouhaveasoapy,meat-tenderizedsoup,withDNAinside.Finally,addsomerubbingalcoholtothemix.You’llhavetwolayersofliquid:soapymushonthebottom,clearalcoholontop.DNAhasarealattractiontoalcoholandwillmoveintoit.Ifagoopywhiteballappearsinthealcohol,you’vedoneeverythingright.ThatgoopistheDNA.Youarenowinapositiontousethatwhiteglopto

understandmanyofthebasicconnectionswehavewiththerestoflife.Thetrick,onwhichwespendcountlesshoursanddollars,comesdowntocomparingDNA’sstructureandfunctionindifferentspecies.Hereisthecounterintuitivebit.ByextractingDNAfromanytissue,saytheliver,ofdifferentspecies,youcanactuallydecipherthehistoryof

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virtuallyanypartofourbody,includingoursenseofsmell.LockedinsidethatDNA,whetheritcomesfromliver,blood,ormuscle,ismuchoftheapparatusweusetodetectodorsinourenvironment.RecallthatallourcellscontainthesameDNA;whatdiffersiswhichbitsofDNAareactive.Thegenesinvolvedinthesenseofsmellarepresentinallofourcells,althoughtheyareactiveonlyinthenasalarea.Asweallknow,odorselicitimpulsesinourbrainsthat

canhaveaprofoundimpactonthewayweperceiveourworld.Awhiffmightleadustorecalltheschoolroomsofourchildhoodorthemustycozinessofourgrandparents’attic,eachoccasionbringinglong-buriedfeelingstothesurface.Moreessentially,smellscanhelpustosurvive.Thesmelloftastyfoodgetsushungry;thesmellofsewagemakesusfeelill.Wearehardwiredtoavoidrotteneggs.Wanttosellyourhome?Itwouldbefarbettertohavebreadbakingintheoventhancabbageboilingonthestovetopwhenprospectivebuyerscomeby.Wecollectivelyinvestvastsumsinoursenseofsmell:in2005theperfumeindustrygenerated$24billionofbusinessintheUnitedStatesalone.Allofthisatteststohowdeeplyembeddedoursenseofsmellisinsideofus.Itisalsoveryancient.Oursenseofsmellallowsustodiscriminateamongfive

thousandtotenthousandodors.Somepeoplecandetecttheodormoleculesinagreenbellpepperataconcentrationoflessthanonepartpertrillion.Thatislikepickingoutonegrainofsandfromamile-longbeach.Howdowedothat?Whatweperceiveasasmellisourbrain’sresponsetoa

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cocktailofmoleculesfloatingintheair.Themoleculesthatweultimatelyregisterasanodoraretiny,lightenoughtobesuspendedintheair.Aswebreatheorsniff,wesucktheseodormoleculesintoournostrils.Fromthere,theodormoleculesgotoanareabehindournosewheretheyaretrappedbythemucousliningofournasalpassages.Insidethisliningisapatchoftissuecontainingmillionsofnervecells,eachwithlittleprojectionsintothemucousmembrane.Whenthemoleculesintheairbindtothenervecells,signalsaresenttoourbrain.Ourbrainrecordsthesesignalsasasmell.Themolecularpartofsmellingworkslikealock-and-key

mechanism.Thelockistheodormolecule;thekeyisthereceptoronthenervecell.Amoleculecapturedbythemucousmembranesinournoseinteractswithareceptoronthenervecell.Onlywhenthemoleculeattachestothereceptorisasignalsenttoourbrain.Eachreceptoristunedtoadifferentkindofmolecule,soaparticularodormightinvolvelotsofmoleculesand,accordingly,lotsofreceptorssendingsignalstoourbrains.Thebestanalogyforsmellcomesfrommusic:achord.A

chordismadeupofseveralnotesactingtogetherasone.Inthesameway,anodoristheproductofsignalsfromlotsofreceptorskeyedtodifferentodormolecules.Ourbrainperceivesthesedifferentimpulsesasonesmell.

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Molecules(enlargedmany,manytimes)fromaflowerwaftthroughtheair.Thesemoleculesattachtoreceptorsinsidetheliningofournasalcavities.Oncethemoleculesattach,asignalissenttoourbrain.Eachsmelliscomposedofmanydifferentmoleculesattachingtodifferentreceptors.Ourbrainintegratesthesesignalsasweperceiveasmell.

Asinfish,amphibians,reptiles,mammals,andbirds,

muchofoursenseofsmellishousedinsideourskull.Liketheotheranimals,wehaveoneormoreholesthroughwhichwebringairinside,andthenasetofspecialized

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tissueswherethechemicalsintheaircaninteractwithneurons.Wecantracethepatternsoftheseholes,spaces,andmembranesfromfishtomanandfindageneralpattern.Themostprimitivelivinganimalswithskulls,jawlessfishsuchaslampreysandhagfish,haveasinglenostrilthatleadstoasacinsidetheskull.Watergoesintothisblindsac,anditistherethatsmellingtakesplace;themaindifferencefromusbeingthatlampreysandhagfishextractodorsfromwaterinsteadofair.Ourclosestfishrelativeshaveanarrangementsomewhatlikeours:thewaterentersanostrilandultimatelygoestoacavitylinkedwiththemouth.FishlikelungfishorTiktaalikhavetwokindsofnostrils:anexternaloneandaninternalone.Inthis,theyarealotlikeus.Sitwithyourmouthclosedandbreathe.Airentersanexternalnostrilandtravelsthroughyournasalcavitiestoenterthebackofyourthroatviainternalpassageways.Ourfishancestorshadinternalandexternalnostrils,too,andtonobody’ssurprisethesearethesamefishthathavearmbonesandotherfeaturesincommonwithus.Oursenseofsmellcontainsadeeprecordofourhistory

asfish,amphibians,andmammals.Amajorbreakthroughinunderstandingthisoccurredin1991whenLindaBuckandRichardAxeldiscoveredthelargefamilyofgenesthatgiveusoursenseofsmell.

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Nasalopeningsandtheflowofodormoleculesfromjawlessfishtoman.

BuckandAxelusedthreemajorassumptionstodesign

theirexperiments.First,theycameupwithareasonedhypothesis,basedonworkdoneinotherlaboratories,aboutwhatthegenesthatmakeodorreceptorsmighthavelookedlike.Experimentsshowedthatodorreceptorshaveacharacteristicstructurewithanumberofmolecularloopsthathelpthemconveyinformationacrossacell.Thiswasabigclue,becauseBuckandAxelcouldthensearchthegenomeofamouseforeverygenethatmakesthisstructure.Second,theyassumedthatthegenesforthesereceptorshadtohaveaveryspecificactivity—theyshouldbeactiveonlyinthetissuesinvolvedwithsmell.This

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makessense:ifsomethingisinvolvedinsmelling,thenitshouldberestrictedtothetissuesspecializedforthatpurpose.Third—andthislastwasabigassumption—AxelandBuckreasonedthattherewasn’tonlyoneorevenasmallnumberofthesegenes,therehadtobelotsofthem.Thishypothesiswasbasedonthefactthatmanydifferentkindsofchemicalscanstimulatedifferentsmells.Iftherewasaone-to-onematchbetweeneachchemicaltypeandareceptor/genespecializedforit,thentherehadtobemany,manygenes.But,giventhedatatheyhadatthetime,thisneedn’thavebeentrue.BuckandAxel’sthreeassumptionswereborneout

perfectly.Theyfoundgenesthathadthecharacteristicstructureofthereceptortheywerelookingfor.Theyfoundthatallofthesegeneswereactiveonlyinthetissuesinvolvedinsmelling,theolfactoryepithelium.Andfinally,theyfoundahugenumberofthesegenes.Itwasahomerun.Then,BuckandAxeldiscoveredsomethingtrulyastounding:fully3percentofourentiregenomeisdevotedtogenesfordetectingdifferentodors.Eachofthesegenesmakesareceptorforanodormolecule.Forthiswork,BuckandAxelsharedtheNobelPrizein2004.FollowingBuckandAxel’ssuccess,peoplestartedfishing

aroundforolfactoryreceptorgenesinotherspecies.Itturnsoutthatsuchgenesarealivingrecordofsomemajortransitionsinthehistoryoflife.Takethewater-to-landtransition,over365millionyearsago.Therearetwokindsofsmellinggenes:oneisspecializedforpickingupchemical

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scentsinthewater,theotherspecializedforair.Thechemicalreactionbetweenodormoleculeandreceptorisdifferentinwaterandair,hencetheneedforslightlydifferentreceptors.Aswe’dexpect,fishhavewater-basedreceptorsintheirnasalneurons,mammalsandreptileshaveair-basedones.Thisdiscoveryhelpsusmakesenseofthestateofaffairs

inthemostprimitivefishaliveontheplanettoday—thejawlessfishsuchaslampreysandhagfish.Itturnsoutthatthesecreatureshave,unlikemoreadvancedfishandmammals,neither“air”nor“water”genes;rather,theirreceptorscombinebothtypes.Theimplicationisclear:theseprimitivefisharosebeforethesmellinggenessplitintotwotypes.Jawlessfishrevealanotherveryimportantpoint:they

haveaverysmallnumberofodorgenes.Bonyfishhavemore,andstillmoreareseeninamphibiansandreptiles.Thenumberofodorgeneshasincreasedovertime,fromrelativelyfewinprimitivecreaturessuchasjawlessfish,totheenormousnumberseeninmammals.Wemammals,withoverathousandofthesegenes,devoteahugepartofourentiregeneticapparatusjusttosmelling.Presumably,themoreofthesegenesananimalhas,themoreacuteitsabilitytodiscerndifferentkindsofsmells.Inthislight,ourlargenumberofodorgenesmakessense—mammalsarehighlyspecializedsmellinganimals.Justthinkofwhateffectivetrackersdogscanbe.Butwheredoallourextraodorgenescomefrom?Did

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theyjustpopoutoftheblue?Howthisexpansionhappenedseemsobviouswhenwelookatthestructureofthegenes.Ifyoucomparetheodorgenesofamammalwiththehandfulofodorgenesinajawlessfish,the“extra”genesinmammalsareallvariationsonatheme:theylooklikecopies,albeitmodifiedones,ofthegenesinjawlessfish.Thismeansthatourlargenumberofodorgenesarosebymanyroundsofduplicationofthesmallnumberofgenespresentinprimitivespecies.Thisleadsustoaparadox.Humansdevoteabout3

percentofourgenometoodorgenes,justlikeeveryothermammal.Whengeneticistslookedatthestructureofthehumangenesinmoredetail,theyfoundabigsurprise:fullythreehundredofthesethousandgenesarerenderedcompletelyfunctionlessbymutationsthathavealteredtheirstructurebeyondrepair.(Othermammalsdousethesegenes.)Whyhavesomanyodorgenesifsomanyofthemareentirelyuseless?Dolphinsandwhales,ofallcreatures,offeraninsightto

helpusanswerthisquestion.Likeallmammals,dolphinsandwhaleshavehair,breasts,andathree-bonedmiddleear.Theirmammalianhistoryisalsorecordedintheirsmellinggenes:lackingfish-likewater-specializedgenes,cetaceanshavemammalianair-specializedgenes.ThemammalianhistoryofwhalesanddolphinsisevenwrittenintheDNAoftheirodorperceptionapparatus.Butthereisaninterestingpuzzle:dolphinsandwhalesnolongerusetheirnasalpassagestosmell.Whatarethesegenesdoing?

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Theformernasalpassagehasbeenmodifiedintoablowhole,whichisusedinbreathing,notinsmelling.Thishashadaremarkableeffectonthesmellinggenes:allofacetacean’sodorgenesarepresent,butnotoneisfunctional.Whathashappenedtothesmellgenesofdolphinsand

whalesalsohappensinmanyotherspecies’genes.Mutationscropupingenomesfromgenerationtogeneration.Ifamutationknocksoutthefunctionofagene,theresultcanbedangerous,orevenlethal.Butwhathappensifamutationknocksoutthefunctionofagenethatdoesnothing?Thereisalotofmathematicaltheorythatsaystheobvious:suchmutationswilljustsilentlygetpassedonfromgenerationtogeneration.Thisisexactlywhatappearstohavehappenedindolphins.Theirsmellgenesarenolongerneeded,giventheblowhole,sothemutationsthatknockedouttheirfunctionjustaccumulateovertime.Thegeneshavenouse,buttheyremainpresentintheDNAassilentrecordsofevolution.Buthumansdohaveasenseofsmell,sowhyhaveso

manyofourodorgenesbeenknockedout?YoavGiladandhiscolleaguesansweredthisquestionbycomparinggenesamongdifferentprimates.Hefoundthatprimatesthatdevelopcolorvisiontendtohavelargenumbersofknocked-outsmellgenes.Theconclusionisclear.Wehumansarepartofalineagethathastradedsmellforsight.Wenowrelyonvisionmorethanonsmell,andthisisreflectedinourgenome.Inthistrade-off,oursenseofsmellwasdeemphasized,andmanyofourolfactorygenes

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becamefunctionless.Wecarryalotofbaggageinournoses—or,more

precisely,intheDNAthatcontrolsoursenseofsmell.Ourhundredsofuselessolfactorygenesareleftoverfrommammalancestorswhoreliedmoreheavilyonthesenseofsmelltosurvive.Infact,wecantakethesecomparisonsdeeperstill.Likephotocopiesthatlosetheirfidelityastheyarerepeatedlycopied,ourolfactorygenesgetmoredissimilaraswecompareourselvestosuccessivelymoreprimitivecreatures.Ourgenesaresimilartoprimates’,lesssimilartoothermammals’,lesssimilarstilltoreptiles’,amphibians’,fishes’,andsoon.Thatbaggageisasilentwitnesstoourpast;insideournosesisaveritabletreeoflife.

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CHAPTERNINE

VISION

OnlyonceinmyentirecareerhaveIfoundtheeyeofafossilcreature.Iwasn’tinthefieldonanexpedition,IwasinthebackroomofamineralshopinasmalltowninnortheastChina.MycolleagueGaoKeqinandIwerestudyingtheearliestknownsalamanders,beautifulfossilscollectedfromChineserocksabout160millionyearsold.WehadjustfinishedacollectingtriptosomesitesGaoknewabout.Thelocationsweresecret,becausethesesalamanderfossilshaveseriousmonetaryvalueforthefarmerswhotypicallyfindthem.Whatmakesthemspecialisthatimpressionsofthesofttissue,suchasgills,guts,andthenotochord,areoftenpreserved.Privatecollectorslovethembecausefossilsofthisqualityareexceedinglyrare.Bythetimeweendedupatthemineralshop,GaoandIhadalreadycollectedanumberofreallybeautifulancientsalamandersofourownfromhissites.Thisparticularmineraldealerhadgottenhishandson

oneofthebestsalamanderfossilsofalltime.Gaowantedustoseeitandspentthebetterpartofadaytryingtowork

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thedeal.Thewholevisithadaterrificallyillicitfeel.Gaospentseveralhourssmokingcigaretteswiththegentleman,speakingandgesturinginChinese.Clearlytherewassomebarteringgoingon,butnotknowingChineseIhadnoideawhatofferswerebeingputonthetable.Afterlotsofheadshakingandultimatelyabighandshake,Iwaspermittedtogotothebackroomandlookatafossilonthedealer’sdesk.Itwasastunningsight:thebodyofalarvalsalamander,nomorethanthreeincheslong.Init,Icouldseeimpressionsofthewholeanimal,allthewaydowntothelittleshellsitateasitslastmeal.And,forthefirstandonlytimeinmycareer,Iwasstaringattheeyeofanancientfossilanimal.Eyesrarelymakeitintothefossilrecord.Aswe’veseen,

thebestcandidatesforpreservationasfossilsarethehardpartsoftheanimals—bones,teeth,andscales.Ifwewanttounderstandthehistoryofeyes,thenwecanuseanimportantfacttoouradvantage.Thereisaremarkablediversityoforgansandtissuesthatanimalsusetocapturelight,fromsimplephotoreceptororgansininvertebrateanimalstothecompoundeyesofvariousinsectsandourowncamera-typeeye.Howdoweputthisvariationtouseinunderstandinghowourabilitytoseedevelopedovertime?Thehistoryofoureyesisalotlikethatofacar.Takea

ChevyCorvette,forexample.Wecantracethehistoryofthemodelasawhole—theCorvette—andthehistoryofeachofitsparts.The’Vettehasahistory,beginningwithitsorigins

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in1953andcontinuingthroughthedifferentmodeldesignseachyear.Thetiresusedonthe’Vettealsohaveahistory,asdoestherubberusedinmakingthem.Thissuppliesagreatanalogyforbodiesandorgans.Oureyeshaveahistoryasorgans,butsodoeyes’constituentparts,thecellsandtissues,andsodothegenesthatmakethoseparts.Onceweidentifythesemultiplelayersofhistoryinourorgans,weunderstandthatwearesimplyamosaicofbitsandpiecesfoundinvirtuallyeverythingelseontheplanet.Muchoftheprocessingoftheimagesweseeactually

happensinsideourbrains:theroleoftheeyeistocapturelightinawaythatitcanbecarriedtothebrainforprocessingasanimage.Oureyes,likethoseofeverycreaturewithaskullandbackbone,arelikelittlecameras.Afterlightfromtheoutsideenterstheeye,itisfocusedonascreenatthebackoftheeyeball.Lighttravelsthroughseverallayersasittraversesthispath.Firstitpassesthroughthecornea,athinlayerofcleartissuethatcoversthelens.Theamountoflightthatenterstheeyeiscontrolledbyadiaphragm,calledtheiris,whichdilatesandcontractsbytheactionofinvoluntarymuscles.Thelightthenpassesthroughthelens,which,asacameradoes,focusestheimage.Tinymusclessurroundthelens;asthesemusclescontract,theychangethelens’sshape,thusfocusingimagesfromnearandfar.Ahealthylensisclearandmadeupofspecialproteinsthatgiveititsdistinctiveshapeandlight-gatheringproperties.Theseproteins,knownaslenscrystallins,areexceptionallylong-lived,

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allowingthelenstocontinuefunctioningasweage.Thescreenonwhichallofthelightisprojected,theretina,isloadedwithbloodvesselsandlightreceptors.Theselightreceptorssendsignalstoourbrainthatwetheninterpretasimages.Theretinaabsorbsthelightviasensitivelight-gatheringcells.Therearetwotypesofsuchcells:oneisverysensitivetolight,theotherlessso.Themoresensitivecellsrecordonlyinblackandwhite;thelesssensitivecellsrecordincolor.Ifwelookaroundtheanimalworld,wecanassesswhetheranimalsarespecializedfordaylightornightbylookingatthepercentagesofeachtypeoflight-sensingcellintheireyes.Inhumansthesecellsmakeupabout70percentofallthesensorycellsinourbody.Thatisaclearstatementabouthowimportantvisionistous.Ourcamera-likeeyeiscommontoeverycreaturewitha

skull,fromfishtomammals.Inothergroupsofanimalswefinddifferenteyes,rangingfromsimplepatchesofcellsspecializedtodetectlight,toeyeswithcompoundlensessuchasthosefoundinflies,toprimordialversionsofourowneye.Thekeytounderstandingthehistoryofoureyesistounderstandtherelationshipbetweenthestructuresthatmakeourcamera-eyeandthosethatmakealltheotherkindsofeyes.Todothis,wewillstudythemoleculesthatgatherlight,thetissuesweusetosee,andthegenesthatmakethewholething.

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Eyescomeintofocus:fromprimitivelight-capturingdevicesininvertebratestoourcamera-typeeyewithalens.Aseyesevolve,visualacuityincreases.

LIGHT-GATHERINGMOLECULES

Thereallyimportantworkinthelight-gatheringcellshappensinsidethemoleculethatactuallycollectslight.

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Whenthismoleculeabsorbslight,itchangesshapeandbreaksupintotwoparts.OnepartisderivedfromvitaminA,theotherfromaproteinknownasanopsin.Whentheopsinbreaksoff,itinitiatesachainreactionthatleadstoaneuronsendinganimpulsetoourbrain.Weusedifferentopsinstoseeinblackandwhiteandincolor.Justasaninkjetprinterneedsthreeorfourinkstoprintincolor,weneedthreelight-gatheringmoleculestoseeincolor.Forblack-and-whitevision,weuseonlyone.Theselight-gatheringmoleculeschangeshapeinthe

light,thenrechargeinthedarkandgobacktotheirnormalstate.Theprocesstakesafewminutes.Weallknowthisfrompersonalexperience:gofromabrightplaceintoadarkroomanditisvirtuallyimpossibletoseefaintobjects.Thereasonisthatthelight-gatheringmoleculesneedtimetorecharge.Afterafewminutes,visioninthedarkreturns.Despitethestunningvarietyofphotoreceptororgans,

everyanimalusesthesamekindoflight-capturingmoleculetodothisjob.Insects,humans,clams,andscallopsalluseopsins.Notonlycanwetracethehistoryofeyesthroughdifferencesinthestructureoftheiropsins,butwehavegoodevidencethatwecanthankbacteriaforthesemoleculesinthefirstplace.Essentially,anopsinisakindofmoleculethatconveys

informationfromtheoutsideofacelltotheinside.Topulloffthisfeat,itneedstocarryachemicalacrossthemembranethatencirclesacell.Opsinsuseaspecializedkindofconductorthattakesaseriesofbendsandloopsas

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ittravelsfromtheoutsidetotheinsideofthecell.Butthistwistedpaththereceptortakesthroughthecellmembraneisnotrandom—ithasacharacteristicsignature.Whereelseisthistwistedpathseen?Itisidenticaltopartsofcertainmoleculesinbacteria.Theveryprecisemolecularsimilaritiesinthismoleculesuggestaveryancientpropertyofallanimalsextendingallthewaytooursharedhistorywithbacteria.Inasense,modifiedbitsofancientbacterialieinsideourretinas,helpingustosee.Wecaneventracesomemajoreventsinthehistoryof

oureyesbyexaminingopsinsindifferentanimals.Takeoneofthemajoreventsinourprimatepast,thedevelopmentofrichcolorvision.Recallthathumansandourclosestaperelatives,theOldWorldmonkeys,haveaverydetailedkindofcolorvisionthatreliesonthreedifferentkindsoflightreceptors.Eachofthesereceptorsistunedtoadifferentkindoflight.Mostothermammalshaveonlytwokindsofreceptorsandsocannotdiscriminateasmanycolorsaswecan.Itturnsoutthatwecantracetheoriginofourcolorvisionbylookingatthegenesthatmakethereceptors.Thetwokindsofreceptorsmostmammalshavearemadebytwokindsofgenes.Ofourthreereceptor-makinggenes,twoareremarkablylikeoneofthoseinothermammals.Thisseemstoimplythatourcolorvisionbeganwhenoneofthegenesinothermammalsduplicatedandthecopiesspecializedovertimefordifferentlightsources.Asyou’llremember,asimilarthinghappenedwithodorreceptorgenes.

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Thisshiftmayberelatedtochangesinthefloraoftheearthmillionsofyearsago.Ithelpstothinkwhatcolorvisionwaslikelygoodforwhenitfirstappeared.Monkeysthatliveintreeswouldbenefitbecausecolorvisionenabledthemtodiscriminatebetteramongmanykindsoffruitsandleavesandselectthemostnutritiousamongthem.Fromstudyingtheotherprimatesthathavecolorvision,wecanestimatethatourkindofcolorvisionaroseabout55millionyearsago.Atthistimewefindfossilevidenceofchangesinthecompositionofancientforests.Beforethistime,theforestswererichinfigsandpalms,whicharetastybutallofthesamegeneralcolor.Laterforestshadmoreofadiversityofplants,likelywithdifferentcolors.Itseemsagoodbetthattheswitchtocolorvisioncorrelateswithaswitchfromamonochromaticforesttoonewitharicherpaletteofcolorsinfood.

TISSUES

Animaleyescomeintwoflavors;oneisseenininvertebrates,theotherinvertebrates,suchasfishandhumans.Thecentralideaisthattherearetwodifferentwaysofincreasingthelight-gatheringsurfaceareaineyetissue.Invertebrates,suchasfliesandworms,accomplishthisbyhavingnumerousfoldsinthetissue,whileourlineageexpandsthesurfaceareabyhavinglotsoflittleprojectionsextendingfromthetissueliketinybristles.A

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hostofotherdifferencesalsorelatetothesedifferentkindsofdesigns.Lackingfossilsattherelevantphaseofhistory,itwouldseemthatwewouldneverbeabletobridgethedifferencesbetweenoureyesandthoseofinvertebrates.Thatis,until2001,whenDetlevArendtthoughttostudytheeyesofaveryprimitivelittleworm.Polychaetesareamongthemostprimitivelivingworms

known.Theyhaveaverysimplesegmentedbodyplan,andtheyalsohavetwokindsoflight-sensingorgans:aneyeand,buriedundertheirskin,apartoftheirnervoussystemthatisspecializedtopickuplight.Arendttookthesewormsapartbothphysicallyandgenetically.Knowledgeofthegenesequenceofouropsingenesandthestructureofourlight-gatheringneuronsgaveArendtthetoolstostudyhowpolychaetesaremade.Hefoundthattheyhadelementsofbothkindsofanimalphotoreceptors.Thenormal“eye”wasmadeupofneuronsandopsinsliketheeyeofanyinvertebrate.Thetinyphotoreceptorsundertheskinwereanothermatteraltogether.Theyhad“vertebrate”opsinsandcellularstructureevenwiththelittlebristle-likeprojections,butinprimitiveform.Arendthadfoundalivingbridge,ananimalwithbothkindsofeyes,oneofwhich—ourkind—existedinaveryprimitiveform.Whenwelooktoprimitiveinvertebrates,wefindthatthedifferentkindsofanimaleyessharecommonparts.

GENES

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Arendt’sdiscoveryleadstoyetanotherquestion.Itisonethingforeyestosharecommonparts,buthowcaneyesthatlooksodifferent—suchasthoseofworms,flies,andmice—becloselyrelated?Fortheanswer,letusconsiderthegeneticrecipethatbuildseyes.Attheturnofthetwentiethcentury,MildredHogewas

recordingmutationsinfruitflieswhenshefoundaflythathadnoeyeswhatsoever.Thismutantwasnotanisolatedcase,andHogediscoveredthatshecouldbreedawholelineofsuchflies,whichshenamedeyeless.Later,asimilarmutationwasdiscoveredinmice.Someindividualshadsmalleyes;otherslackedwholeportionsoftheheadandface,includingtheireyes.Asimilarconditioninhumansisknownasaniridia;affectedindividualsaremissinglargepiecesoftheireyes.Intheseverydifferentcreatures—flies,mice,andhumans—geneticistswerefindingsimilarkindsofmutants.Abreakthroughcameintheearly1990s,when

laboratoriesappliednewmoleculartechniquestounderstandhoweyelessmutantsaffectedeyedevelopment.Mappingthegenes,theywereabletolocalizethebitsofDNAresponsibleforthemutations.WhentheDNAwassequenced,itturnedoutthatthefly,mouse,andhumangenesresponsibleforeyelessnesshadsimilarDNAstructuresandsequences.Inaveryrealsense,theyarethesamegene.Whatdidwelearnfromthis?Scientistshadidentifieda

singlegenethat,whenmutated,producedcreatureswith

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smalleyesornoeyesatall.Thismeantthatthenormalversionofthegenewasamajortriggerfortheformationofeyes.Nowcamethechancetodoexperimentstoaskawholeotherkindofquestion.Whathappenswhenwemesswiththegene,turningitonandoffinthewrongplaces?Flieswereanidealsubjectforthiswork.Duringthe

1980s,anumberofverypowerfulgenetictoolsweredevelopedthroughworkonflies.Ifyouknewagene,oraDNAsequence,youcouldmakeaflylackingthegeneor,thereverse,aflywiththegeneactiveinthewrongplaces.Usingthesetools,WalterGehringstartedplayingaround

withtheeyelessgene.Gehring’steamwasabletomaketheeyelessDNAactiveprettymuchanywheretheywanted:intheantenna,onthelegs,onthewings.Whenhisteamdidthis,theyfoundsomethingstunning.Iftheyturnedontheeyelessgeneintheantenna,aneyegrewthere.Iftheyturnedontheeyelessgeneonabodysegment,aneyedevelopedthere.Everywheretheyturnedonthegene,theywouldgetaneweye.Totopitalloff,someofthemisplacedeyesshowedanascentabilitytorespondtolight.Gehringhaduncoveredamajortriggerintheformationofeyes.Gehringdidn’tstopthere;hebeganswappinggenes

betweenspecies.Theytookthemouseequivalentofeyeless,Pax6,andturneditoninafly.Themousegeneproducedaneweye.Andnotjustanyeye—aflyeye.Gehring’slabfoundtheycouldusethemousegenetotriggertheformationofanextraflyeyeanywhere:ontheback,onawing,nearthemouth.WhatGehringhadfoundwasamasterswitchfor

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eyedevelopmentthatwasvirtuallythesameinamouseandafly.Thisgene,Pax6,initiatedacomplexchainreactionofgeneactivitythatultimatelyledtoanewflyeye.Wenowknowthateyeless,orPax6,controls

developmentineverythingthathaseyes.Theeyesmaylookdifferent—somewithalens,somewithout;somecompound,somesimple—butthegeneticswitchesthatmakethemarethesame.Whenyoulookintoeyes,forgetaboutromance,creation,

andthewindowsintothesoul.Withtheirmolecules,genes,andtissuesderivedfrommicrobes,jellyfish,worms,andflies,youseeanentiremenagerie.

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CHAPTERTEN

EARS

Thefirsttimeyouseetheinsideoftheearisaletdown:therealmachineryishiddendeepinsidetheskull,encasedinawallofbone.Onceyouopentheskullandremovethebrain,youneedtochipwithachiseltoremovethatwall.Ifyouarereallygood,orverylucky,you’llmaketherightstrokeandseeit—theinnerear.Itresemblesthekindoftinycoiledsnailshellyoufindinthedirtinyourlawn.Theearmaynotlooklikemuch,butitisawonderful

RubeGoldbergcontraption.Whenwehear,soundwavesarefunneledintotheoutsideflap,theexternalear.Thesoundwavesentertheearandmaketheeardrumrattle.Theeardrumisattachedtothreelittlebones,whichshakealongwithit.Oneoftheseearbonesisattachedtothesnail-shellstructurebyakindofplunger.Theshakingoftheearbonecausestheplungertogoupanddown.Thiscausessomegelinsidethesnailshelltomovearound.Swishinggelbendsnerves,whichsendasignaltothebrain,whichinterpretsitassound.Nexttimeyouareataconcert,justimagineallthestuffflyingaroundinyourhead.

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Thisstructureallowsustodistinguishthreepartstotheear:external,middle,andinner.Theexternalearisthevisiblepart.Themiddlecontainsthelittleearbones.Finally,theinnerearconsistsofthenerves,thegel,andthetissuesthatsurroundthem.Thesethreecomponentsofearsenableustostructureourdiscussioninaveryconvenientway.

Ofthethreepartsofourear—theouter,middle,andinner—theinnerearisthemostancientandthepartthatcontrolsthenerveimpulsessenttothebrain.

Thepartoftheearwecansee,theflaponwhichwehang

ourglasses,isarelativelynewevolutionaryadditiontobodies.Confirmthisonyournexttriptotheaquariumorzoo.Howmanysharks,bonyfish,amphibians,andreptileshaveexternalears?Thepinna—theflapoftheexternalear—isfoundonlyinmammals.Someamphibiansandreptileshavevisibleexternalears,buttheyhavenopinna.Oftenthe

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externalearisonlyamembranethatlookslikethetopofadrum.Theeleganceofourconnectiontosharksandbonyfishis

revealedwhenwelookinsideourears.Earsmightseemanunlikelyplaceforahuman-sharkconnection,especiallysincesharksdon’thaveears.Buttheconnectionisthere.Let’sstartwiththeearbones.

THEMIDDLEEAR—THETHREEEARBONES

Mammalsareveryspecial.Withhairandmilk-producingglands,wecaneasilybedistinguishedfromothercreatures.Itsurprisesmostpeopletolearnthatsomeofthemostdistinctivetraitsofmammalslieinsidetheear.Thebonesofthemammalianmiddleeararelikethoseofnootheranimal:mammalshavethreebones,whereasreptilesandamphibianshaveonlyone.Fishhavenoneatall.Wheredidourmiddleearbonescomefrom?Someanatomy:recallthatourthreemiddleearbonesare

knownasthemalleus,incus,andstapes.Aswe’veseen,eachoftheseearbonesisderivedfromthegillarches:thestapesfromthefirstarch,andthemalleusandincusfromthesecondarch.Itisherethatourstorybegins.In1837,theGermananatomistKarlReichertwaslooking

atembryosofmammalsandreptilestounderstandhowtheskullforms.Hefollowedthegillarchesofdifferentspeciestounderstandwheretheyendedupinthevariousskulls.As

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hedidthisagainandagain,hefoundsomethingthatappearednottomakeanysense:twooftheearbonesinthemammalscorrespondedtopiecesofthejawinthereptiles.Reichertcouldnotbelievehiseyes,andhismonographrevealshisexcitement.Ashedescribestheear-jawcomparison,hisprosedepartsfromthenormallystaiddescriptionofnineteenth-centuryanatomytoexpressshock,evenwonderment,atthisdiscovery.Theconclusionwasinescapable:thesamegillarchthatformedpartofthejawofareptileformedearbonesinmammals.Reichertproposedanotionthatevenhecouldbarelybelieve—thatpartsoftheearsofmammalsarethesamethingasthejawsofreptiles.ThingsgetmoredifficultwhenwerealizethatReichertproposedthisseveraldecadesbeforeDarwinpropoundedhisnotionofafamilytreeforlife.Whatdoesitmeantocallstructuresintwodifferentspecies“thesame”withoutanotionofevolution?Muchlater,in1910and1912,theGermananatomist

ErnstGaupppickeduponReichert’sworkandpublishedanexhaustivestudyontheembryologyofmammalianears.Gauppprovidedmoredetailand,giventhetimes,interpretedReichert’sworkinanevolutionaryframework.Gaupp’sstorywentlikethis:thethreemiddleearbonesrevealthetiebetweenreptilesandmammals.Thesingleboneinthereptilianmiddleearisthesameasthestapesofmammals;botharesecond-archderivatives.Theexplosivebitofinformation,though,wasthatthetwoothermiddleearbonesofmammals—themalleusandtheincus—

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evolvedfrombonessetinthebackofthereptilianjaw.Ifthiswasindeedthecase,thenthefossilrecordshouldshowbonesshiftingfromthejawtotheearduringtheoriginofmammals.TheproblemwasthatGauppworkedonlyonlivingcreaturesanddidn’tfullyappreciatetherolethatfossilscouldplayinhistheory.Beginninginthe1840sanumberofnewkindsoffossil

creatureswerebecomingknownfromdiscoveriesinSouthAfricaandRussia.Oftenabundantlypreserved,wholeskeletonsofdog-sizeanimalswerebeingunearthed.Astheywerediscovered,manyofthemwerecratedandshippedtoRichardOweninLondonforidentificationandanalysis.Owenwasstruckthatthesecreatureshadamélangeoffeatures.Partsoftheirskeletonlookedreptile-like.Otherparts,notablytheirteeth,lookedlikemammals.Andthesewerenotisolatedfinds.Itturnsoutthatthese“mammal-likereptiles”werethemostcommonskeletonsbeinguncoveredatmanyfossilsites.Notonlyweretheyverycommon,thereweremanykinds.IntheyearsafterOwen,thesemammal-likereptilesbecameknownfromotherpartsoftheworldandfromseveraldifferenttimeperiodsinearthhistory.Theyformedabeautifultransitionalseriesinthefossilrecordbetweenreptileandmammal.Until1913,embryologistsandpaleontologistswere

workinginisolationfromoneanother.Atthistime,theAmericanpaleontologistW.K.Gregory,oftheAmericanMuseumofNaturalHistory,sawanimportantlinkbetween

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Gaupp’sembryosandtheAfricanfossils.Themostreptilianofthemammal-likereptileshadonlyasingleboneinitsmiddleear;likeotherreptiles,ithadajawcomposedofmanybones.SomethingremarkablewasrevealedasGregorylookedatthesuccessivelymoremammalianmammal-likereptiles,somethingthatwouldhaveflooredReicherthadhebeenalive:acontinuumofformsshowingbeyonddoubtthatovertimethebonesatthebackofthereptilianjawgotsmallerandsmaller,untiltheyultimatelylayinthemiddleearofmammals.Themalleusandincusdidindeedevolvefromjawbones.WhatReichertandGauppobservedinembryoswasburiedinthefossilrecordallalong,justwaitingtobediscovered.Whywouldmammalsneedathree-bonedmiddleear?

Thislittlelinkageformsaleversystemthatallowsmammalstohearhigher-frequencysoundsthananimalswithasinglemiddleearbone.Theoriginofmammalsinvolvednotonlynewpatternsofchewing,aswesawinChapter4,butnewwaysofhearing.Infact,thisshiftwasaccomplishednotbyevolvingnewbonesperse,butbyrepurposingexistingones.Bonesoriginallyusedbyreptilestochewevolvedinmammalstoassistinhearing.Somuchforthemalleusandincus.Where,though,does

thestapescomefrom?IfIsimplyshowedyouanadulthumanandashark,you

wouldneverguessthatthistinybonedeepinsideahuman’searisthesamethingasalargerodintheupperjawofafish.Yet,developmentally,thesebonesarethe

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samething.Thestapesisasecond-archbone,asisthecorrespondingboneinasharkandafish—thehyomandibula.Butthehyomandibulaisnotanearbone;recallthatfishandsharksdonothaveears.Inouraquaticcousins,thisboneisalargerodthatconnectstheupperjawtothebraincase.Despitetheapparentdifferencesinthefunctionandshapeofthesebones,thesimilaritiesbetweenthehyomandibulaandthestapesextendeventothenervesthatsupplythem.Thekeynerveforthefunctioningofbothbonesisthesecond-archnerve,thefacialnerve.Wethushaveasituationwheretwoverydifferentboneshavesimilardevelopmentaloriginsandpatternsofinnervation.Isthereanexplanationforthis?Again,welooktothefossils.Aswetracethe

hyomandibulafromsharkstocreatureslikeTiktaaliktoamphibians,wecanseehowitgetssmallerandsmaller,ultimatelyshiftingpositionfromtheupperjawtoplayaroleinhearing.Thenamechanges,too.Whenitisbigandsupportingthejaw,wecallitahyomandibula;whenitissmallandfunctionsinhearing,itisknownasastapes.Thisshifthappenedwhenthedescendantsoffishbegantowalkonland.Hearinginwaterisdifferentfromhearingonland,andthesmallsizeandpositionofthestapesmakesitidealforpickingupvibrationsinair.Thenewabilitycameaboutbymodifyingtheupperjawboneofafish.

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Wecantracebonesfromgillarchestoourears,firstduringthetransitionfromfishtoamphibian(right),andlaterduringtheshiftfromreptiletomammal(left).

Ourmiddleearcontainsarecordoftwoofthegreat

transformationsinthehistoryoflife.Theoriginofourstapes,anditstransformationfromajawsupportboneto

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anearbone,beganwhenfishstartedtowalkonland.Theotherbigeventtookplaceduringtheoriginofmammals,whenbonesatthebackofareptilejawbecameourmalleusandincus.Nowlet’sgofurtherinsidetheear—totheinnerear.

THEINNEREAR—GELSMOVINGANDHAIRSBENDING

Movethroughtheexternalear,godeeperinside,pasttheeardrumandthreemiddleearbones,andyouendupdeepinsidetheskull.Hereyouwillfindtheinnerear—tubesandsomegel-filledsacs.Inhumans,asinothermammals,thebonytubestakethesnail-shellshapethatissostrikinglyapparentintheanatomylab.Theinnerearhasdifferentpartsdedicatedtodifferent

functions.Onepartisusedinhearing,anotherintellinguswhichwayourheadistilted,andstillanotherinrecordinghowfastourheadisacceleratingorstopping.Incarryingouteachofthesefunctions,theinnerearworksinroughlythesameway.Theseveralpartsoftheinnereararefilledwithagelthat

canmove.Specializednervecellssendhairlikeprojectionsintothisgel.Whenthegelmoves,thehairsontheendsofthenervecellsbend.Whenthesehairsbend,thenervecellssendanelectricalimpulsetothebrain,whereitisrecordedassound,position,oracceleration.

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Eachtimeyoutiltyourhead,thetinyrocksonthefluid-filledsacsmove.Indoingso,theybendnerveendingsinsidethesacsandcauseanimpulsetobesenttoyourbrainsaying“Yourheadistilted.”

Toenvisionthestructurethattellsuswhereourheadis

inspace,imagineaStatueofLibertysnowglobe.Thesnowglobeismadeofplasticandfilledwithgel.Whenyoushakeit,thegelmovesandthe“snow”fallsonLadyLiberty.Nowimagineasnowglobemadeofaflexiblemembrane.Pickitupandtiltit,andthewholethingwillflopabout,causing

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thegelinsidetoswisharound.This,onamuchsmallerscale,iswhatwehaveinsideourears.Whenwebendourheads,thesecontraptionsfloparound,causingtheusualchainofevents:thegelinsideswishes,thehairprojectionsonthenervesbend,andanimpulseissentbacktoourbrains.Inus,thiswholesystemismadeevenmoresensitiveby

thepresenceoftinyrock-likestructuresontopofthemembrane.Aswebendourheads,therocksaccentuatethefloppingofthemembrane,causingthegeltomoveevenmore.Thisincreasesthesensitivityofthesystem,enablingustoperceivesmalldifferencesinposition.Tiltyourhead,andlittlerocksinsideyourskullmove.Youcanprobablyimaginehowtoughitwouldbetolive

inouterspace.Oursensorsaretunedtoworkintheearth’sgravity,notinagravity-freespacecapsule.Floatingaround,oureyesrecordingoneversionofupanddown,ourinnerearsensorstotallyconfused,itisalltooeasytogetsick.Spacesicknesshasbeenarealproblemfortheseveryreasons.Thewayweperceiveaccelerationisbasedonyetanother

partofourinnerear,connectedtotheprevioustwo.Therearethreegel-filledtubesinsidetheear;eachtimeweaccelerateorstop,thegelinsidethetubesmoves,causingthenervecellstobendandstimulateacurrent.Thewholesystemweusetoperceivepositionand

accelerationisconnectedtooureyemuscles.Themotionofoureyesiscontrolledbyeightsmallmusclesattachedto

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thesidewallsoftheeyeball.Themusclescontracttomovetheeyeup,down,left,andright.Wecanmoveoureyesvoluntarilybycontractingthesemuscleseachtimewedecidetolookinanewdirection;butsomeofthemostfascinatingpropertiesofthesemusclesrelatetotheirinvoluntaryaction.Theymoveoureyesallthetime,withoutoureventhinkingaboutit.Toappreciatethesensitivityofthiseye-musclelink,

moveyourheadbackandforthwhilelookingatthepage.Keepyoureyesfixedinoneplaceasyoumoveyourhead.Whathappenedduringthisexperiment?Youreyes

stayedfixedonasinglepointwhileyourheadmoved.Thismotionissocommonplacethatwetakeitforgranted,butitisincrediblycomplex.Eachoftheeightmusclesinbotheyesisrespondingtothemovementofthehead.Sensorsinyourhead,whichI’lldescribeinthenextsection,recordthedirectionandvelocityofyourhead’smovement.Thesesignalsarecarriedtothebrain,whichthensendsoutsignalstellingyoureyemusclestofire.Thinkaboutthatthenexttimeyoufixyourgazeasyourheadismoving.Thissystemcanmisfire,andmisfireshavemuchtotellusaboutourgeneralwell-being.

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Everytimeweaccelerate,fluidintheinnerearswishes.Theswishistransformedintoanerveimpulsethatissenttothebrain.

Aneasywaytounderstandtheinnerear–eyeconnection

istointerferewithit.Onewayhumansdothisistoimbibetoomuchalcohol.Drinkingtoomuchethanolleadsustodosillythingsbecauseourinhibitionsarelowered.Drinkingwaytoomuchgivesusthespins.Andthespinsoftenpredictalousymorningahead,hungover,withmorespins,

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nausea,andheadache.Whenwedrinktoomuch,weareputtinglotsofethanol

intoourbloodstream,butthefluidinsideoureartubesinitiallycontainsverylittle.Astimepasses,however,thealcoholdiffusesfromourbloodintothegeloftheinnerear.Alcoholislighterthanthegel,sotheresultofthediffusionisliketheresultofpouringalcoholintoaglassofoliveoil.Justastheoilmovesaroundintheglassasthealcoholenters,sothegelinsideourearswirls.Theconvectionwreakshavocontheintemperateamongus.Ourhaircellsarestimulatedandourbrainthinkswearemoving.Butwearenotmoving;weareslumpedinacornerorhunchedonabarstool.Ourbrainhasbeentricked.Theproblemextendstooureyes.Ourbrainthinksweare

spinning,anditpassesthisinformationtooureyemuscles.Theeyestwitchinonedirection(usuallytotheright)aswetrytotrackanobjectmovingfromsidetoside.Ifyoupropopentheeyesofsomeonewhoisstonedrunk,youmightseethisstereotypicaltwitch,callednystagmus.Policeknowthiswell,andoftenlookfornystagmusinpeoplewhomtheyhavestoppedfordrivingerratically.Massivehangoversinvolveaslightlydifferentresponse.

Thedayafterthebinge,yourliverhasdonearemarkablyefficientjobofremovingthealcoholfromyourbloodstream.Tooefficient,forwestillhavealcoholinthetubesinourears.Thatalcoholthendiffusesfromthegelbackintothebloodstream,andindoingsoitoncemoresetsthegelinmotion:thespinsagain.Takethesameheavy

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drinkerwhoseeyesyousawtwitchtotherightthenightbeforeandlookathimduringthehangover.Hiseyesmightstilltwitch,butintheoppositedirection.Wecanthankoursharedhistorywithsharksandfishfor

this.Ifyouhaveevertriedtocatchatrout,thenyouhavecomeupagainstanorganthatislikelyanantecedenttoourinnerear.Aseveryfishermanknows,troutholdonlyincertainpartsofastream,typicallyspotswheretheycangetthebestmealwhileavoidingpredators.Oftensuchplacesareintheshadeandintheeddiesofthestream’scurrent.Greatplacesforbigfishtoholdarebehindbigrocksorfallenlogs.Trout,likeallfish,haveamechanismthatallowsthemtosensethecurrentandthemotionofthewateraroundthem,almostlikeasenseoftouch.Withintheskinandbonesofthefish,arrangedinlines

thatrunthelengthofthebodyandhead,aresmallorganswithsensoryreceptors.Thesereceptorslieinsmallbundlesfromwhichtheysendsmallhair-likeprojectionsintoajelly-filledsaccalledaneuromastorgan.IthelpstothinkofthesnowglobeStatueofLibertyagain.Aneuromastorganislikeatinyoneofthese,withnervesprojectinginside.Whenthewaterflowsaroundthefish,itdeformsthissmallsac,therebybendingthehair-likeprojectionsofthenerve.Muchlikethewholesysteminourears,thisapparatusthensendsasignalbacktothebrainandgivesthefishasenseofwhatthewaterisdoingaroundthem.Sharksandfishcandiscernthedirectioninwhichthewaterisflowing,andsomesharkscanevendetect

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distortionsofthewater,suchasareproducedbyotherfishswimmingnearthem.Weusedaversionofthissystemwhenwemovedourheadwithafixedgaze,andwesawitgoawrywhenweproppedopentheeyesoftheinebriatedindividualatthestartofthissection.Iftheancestorwehaveincommonwithsharksandfishhadusedsomeotherkindofinnereargel,sayonethatdoesnotswirlwhenalcoholisadded,wewouldneverspinwhendrunk.Ifyouthinkofourinnerearsandneuromastorgansas

versionsofthesamething,youwouldnotbefaroff.Bothcomefromthesamesortoftissueduringdevelopment,andtheyshareasimilarstructure.Butwhichcamefirst:neuromastsorinnerears?Heretheevidencegetssketchy.Ifyoulookatsomeoftheearliestfossilswithheads,creaturesabout500millionyearsold,you’llfindlittlepitsintheirexternalarmorthatsuggesttheyhadneuromastorgans.Unfortunately,wedonotknowmuchabouttheinnerearsofthesecreaturesbecausethepreservationofthatareaoftheheadiswanting.Untilmoreevidencerollsin,weareleftwithoneoftwoalternatives:eitherourinnerearsarosefromneuromastorgansortheotherwayaround.Bothscenarios,attheircore,reflectaprinciplewe’veseenatworkinotherpartsofthebody.Organscancomeaboutforonefunction,onlytoberepurposedovertimeforanynumberofnewuses.Inourownears,thereoccurredanexpansionoftheinner

ear.Thepartofourinnereardevotedtohearingis,asinothermammals,hugeandcoiled.Moreprimitivecreatures,

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suchasamphibiansandreptiles,haveasimpleuncoiledinnerear.Clearly,ourmammalianforebearsobtainedanewandbettertypeofhearing.Thesameistrueforthestructuresthatperceiveacceleration.Wehavethreecanalstorecordaccelerationbecauseweperceivespaceinthreedimensions.Theearliestknownfishwiththesecanals,akindofjawlessfishlikeahagfish,hasonlyone.Then,inotherprimitivefish,weseetwo.Finally,mostmodernfish,andothervertebrates,havethree,likeus.Wehaveseenthatourinnerearhasahistorythatcanbe

tracedtotheearliestfish.Remarkably,theneuronsinsidethegelofourearshaveanevenmoreancienthistory.Theseneurons,calledhaircells,havespecialfeatures

thatareseeninnootherneuron.Withfinehair-likeprojections,consistingofonelong“hair”andaseriesofsmallerones,theseneuronsliewithafixedorientationinourinnerearandinafish’sneuromastorgan.Recently,peoplehavesearchedforthesecellsinothercreatures,andhavefoundthemnotonlyinanimalsthatdonothavesenseorganslikeoursatallbutalsoinanimalsthathavenoheads.TheyareseenincreatureslikeAmphioxus,whichwemetinChapter5,thathavenoears,eyes,heads,orskulls.Haircells,then,werearounddoingotherthingsbeforeoursenseorgansevenhitthescene.

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Aprimitiveversionofpartofourinnerearisembeddedintheskinoffish.Smallsacs—theneuromasts—aredistributedaroundthebody.Whentheybend,theygivethefishinformationabouthowtheflowofwaterischanging.

Allthisisrecordedinourgenes,ofcourse.Ifhumansor

micehaveamutationthatknocksoutagenecalledPax2,theinnerearfailstoformproperly.Pax2isactiveintheearregionandappearstostartachainreactionofgeneactivitythatleadstothedevelopmentoftheinnerear.GofishingforthisgeneinmoreprimitiveanimalsandwefindPax2activeintheheadand,loandbehold,intheneuromasts.

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Thespinningdrunkandthefish’swater-sensingorganshavecommongenes:evidenceofacommonhistory.

JELLYFISHANDTHEORIGINSOFEYESANDEARS

JustlikePax6,whichwediscussedearlierinconnectionwitheyes,Pax2inearsisamajorgene,essentialforproperdevelopment.Interestingly,alinkbetweenPax2andPax6suggeststhatearsandeyesmighthavehadaveryancientcommonhistory.Thisiswheretheboxjellyfishentersourstory.Well

knowntoswimmersinAustraliabecausetheyhaveparticularlypoisonousvenom,thesejellyfisharedifferentfrommostothersinthattheyhaveeyes,morethantwentyofthem.Mostoftheseeyesaresimplepitsspreadoverthejellyfish’sepidermis.Othereyesonthebodyarestrikinglysimilartoourown,withakindofcornea,alens,evenanervousstructurelikeours.JellyfishdonothaveeitherPax6orPax2:theyarose

beforethosegeneshitthescene.Butintheboxjellyfish’sgenesweseesomethingremarkable.ThegenethatformstheeyesisnotPax6,aswe’dexpect,butasortofmosaicthathasthestructureofbothPax6andPax2.Inotherwords,thisgenelookslikeaprimitiveversionofotheranimals’Pax6andPax2.Themajorgenesthatcontroloureyeandearcorrespond

toasinglegeneinmoreprimitivecreatures,suchas

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jellyfish.You’reprobablythinking,Sowhat?Theancientconnectionbetweenearandeyegeneshelpstomakesenseofthingsweseeinhospitalclinicstoday:anumberofhumanbirthdefectsaffectboththeeyesandtheinnerear.Allthisisareflectionofourdeepconnectionstoprimitivecreatureslikethestingingboxjellyfish.

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CHAPTERELEVEN

THEMEANINGOFITALL

THEZOOINYOU

Myprofessionalintroductiontoacademiahappenedintheearly1980s,duringmycollegeyears,whenIvolunteeredattheAmericanMuseumofNaturalHistoryinNewYorkCity.Asidefromtheexcitementofworkingbehindthescenesinthecollectionsofthemuseum,oneofthemostmemorableexperienceswasattendingtheirraucousweeklyseminars.Eachweekaspeakerwouldcometopresentsomeesotericstudyonnaturalhistory.Followingthepresentation,oftenafairlylow-keyaffair,thelistenerswouldpickthetalkapartpointbypoint.Itwasmerciless.Onoccasion,thewholethingfeltlikeahumanbarbecue,withtheinvitedspeakerasthespit-roastedmaincourse.Frequently,thesedebateswoulddevolveintoshoutingsessionswithallthehighdudgeonandoperaticpantomimeofanoldsilentmovie,completewithshakenfistsandstompedfeet.HereIwas,inthehallowedhallsofacademe,listeningto

seminarsontaxonomy.Youknow,taxonomy—thescience

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ofnamingspeciesandorganizingthemintotheclassificationschemethatweallmemorizedinintroductorybiology.Icouldnotimagineatopiclessrelevanttoeverydaylife,letaloneonelesslikelytoleademinentseniorscientistsintoapoplexyandthelossofmuchoftheirhumandignity.Theinjunction“Getalife”couldnothaveseemedmoreapt.TheironyisthatInowseewhytheygotsoworkedup.I

didn’tappreciateitatthetime,buttheyweredebatingoneofthemostimportantconceptsinallofbiology.Itmaynotseemearth-shattering,butthisconceptliesattherootofhowwecomparedifferentcreatures—ahumanwithafish,orafishwithaworm,oranythingwithanythingelse.Ithasledustodeveloptechniquesthatallowustotraceourfamilylineages,identifycriminalsbymeansofDNAevidence,understandhowtheAIDSvirusbecamedangerous,andeventrackthespreadoffluvirusesthroughouttheworld.TheconceptI’mabouttodiscusssuppliestheunderpinningformuchofthelogicofthisbook.Oncewegraspit,weseethemeaningofthefish,worms,andbacteriathatlieinsideofus.Thearticulationoftrulygreatideas,ofthelawsofnature,

beginswithsimplepremisesthatallofusseeeveryday.Fromsimplebeginnings,ideasliketheseextendtoexplainthereallybigstuff,likethemovementofthestarsortheworkingsoftime.Inthatspirit,Icansharewithyouonetruelawthatallofuscanagreeupon.Thislawissoprofoundthatmostofustakeitcompletelyforgranted.Yet

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itisthestartingpointforalmosteverythingwedoinpaleontology,developmentalbiology,andgenetics.Thisbiological“lawofeverything”isthateveryliving

thingontheplanethadparents.Everypersonyou’veeverknownhasbiologicalparents,

asdoeseverybird,salamander,orsharkyouhaveeverseen.Technologymaychangethis,thankstocloningorsomeyet-to-be-inventedmethod,butsofarthelawholds.Toputitinamorepreciseform:everylivingthingsprangfromsomeparentalgeneticinformation.Thisformulationdefinesparenthoodinawaythatgetstotheactualbiologicalmechanismofheredityandallowsustoapplyittocreatureslikebacteriathatdonotreproducethewaywedo.Theextensionofthislawiswhereitspowercomesin.

Hereitis,inallitsbeauty:allofusaremodifieddescendantsofourparentsorparentalgeneticinformation.I’mdescendedfrommymotherandfather,butI’mnotidenticaltothem.Myparentsaremodifieddescendantsoftheirparents.Andsoon.Thispatternofdescentwithmodificationdefinesourfamilylineage.Itdoesthissowellthatwecanreconstructyourfamilylineagejustbytakingbloodsamplesofindividuals.Imaginethatyouarestandinginaroomfullofpeople

whomyouhaveneverseenbefore.Youaregivenasimpletask:findouthowcloselyrelatedeachpersonintheroomistoyou.Howdoyoutellwhoareyourdistantcousins,yoursuper-distantcousins,yourgreat-grandunclesseventy-five

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timesremoved?Toanswerthisquestion,weneedabiologicalmechanism

toguideourthinkingandgiveusawaytotesttheaccuracyofourhypothesizedfamilytree.Thismechanismcomesfromthinkingaboutourlawofbiology.Knowinghowdescentwithmodificationworksiskeytounlockingbiologicalhistory,becausedescentwithmodificationcanleaveasignature,whichwecandetect.Let’stakeahypotheticalhumorless,quiteunclown-like

couplewhohavechildren.Oneoftheirsonswasbornwithageneticmutationthatgavehimaredrubbernosethatsqueaks.Thissongrowsupandmarriesaluckywoman.Hepasseshismutatednosegenetohischildren,andtheyallhavehisredrubbernosethatsqueaks.Now,supposeoneofhisoffspringgetsamutationthatcauseshimtohavehugefloppyfeet.Whenthismutationpassestothenextgeneration,allofhischildrenarelikehim:theyhavearedrubbernosethatsqueaksandhugefloppyfeet.Goonegenerationfurther.Imaginethatoneofthesekids,theoriginalcouple’sgreat-grandchild,hasanothermutation:orangecurlyhair.Whenthismutationpassestothenextgeneration,allofhischildrenwillhaveorangecurlyhair,arubbernosethatsqueaks,andgiantfloppyfeet.Whenyouask“Whoisthisbozo?”you’llbeinquiringabouteachofourpoorcouple’sgreat-great-grandchildren.Thisexampleillustratesaveryseriouspoint.Descent

withmodificationcanbuildafamilytree,orlineage,thatwecanidentifybycharacters.Ithasasignaturethatwe

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immediatelyrecognize.LikeanestedsetofRussiandolls,ourhypotheticallineageformedgroupswithingroups,whichwerecognizebytheiruniquefeatures.Thegroupof“fullbozo”great-great-grandchildrenisdescendedfromanindividualwhohadonlythesqueakynoseandthehugefloppyfeet.Thisindividualwasinagroupof“proto-bozos,”whoaredescendedfromanindividualwhohadonlytherubbernosethatsqueaks.This“pre-proto-bozo”wasdescendedfromtheoriginalcouple,whodidn’tlookovertlyclown-like.

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Thebozofamilytree.Thispatternofdescentwithmodificationmeansthatyou

couldeasilyhavehypothesizedthebozofamilytreewithoutmetellingyouanythingaboutit.Ifyouhadaroomfullofthevariousgenerationsofbozos,youwouldhaveseenthatallclownkinareinagroupthatpossessesasqueakynose.Asubsetofthesehaveorangehairandfloppy

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feet.Nestedwithinthissubsetisanothergroup,thefullbozos.Thekeyisthatthefeatures—orangehair,squeakynose,bigfloppyfeet—enableyoutorecognizethegroups.Thesefeaturesareyourevidenceforthedifferentgroups,orinthiscasegenerations,ofclowns.Replacethisfamilycircuswithrealfeatures—genetic

mutationsandthebodychangesthattheyencode—andyouhavealineagethatcanbeidentifiedbybiologicalfeatures.Ifdescentwithmodificationworksthisway,thenourfamilytreeshaveasignatureintheirbasicstructure.Sopowerfulisthistruththatitcanhelpusreconstructfamilytreesfromgeneticdataalone,asweseefromthenumberofgenealogicalprojectscurrentlyunderway.Obviously,therealworldismorecomplexthanoursimplehypotheticalexample.Reconstructingfamilytreescanbedifficultiftraitsarisemanydifferenttimesinafamily,iftherelationshipbetweenatraitandthegenesthatcauseitisnotdirect,oriftraitsdonothaveageneticbasisandariseastheresultofchangesindietorotherenvironmentalconditions.Thegoodnewsisthatthepatternofdescentwithmodificationcanoftenbeidentifiedinthefaceofthesecomplications,almostlikefilteringoutnoisefromaradiosignal.Butwheredoourlineagesstop?Didthebozosstopatthe

humorlesscouple?DoesmylineagestopatthefirstShubins?Thatseemsawfullyarbitrary.DoesitstopatUkranianJews,ornorthernItalians?Howaboutatthefirsthumans?Ordoesitcontinueto3.8-billion-year-oldpond

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scum,andbeyond?Everybodyagreesthattheirownlineagegoesbacktosomepointintime,butjusthowfarbackistheissue.Ifourlineagegoesallthewaybacktopondscum,and

doessowhilefollowingourlawofbiology,thenweshouldbeabletomarshalevidenceandmakespecificpredictions.Ratherthanbeingarandomassortmentofcreatures,alllifeonearthshouldshowthesamesignatureofdescentwithmodificationthatwesawamongthebozos.Infact,thestructureoftheentiregeologicalrecordshouldn’tberandom,either.Recentadditionsshouldappearinrelativelyyoungrocklayers.JustasIamamorerecentarrivalthanmygrandfatherinmyfamilytree,sothestructureofthefamilytreeoflifeshouldalsohaveitsparallelsintime.Toseehowbiologistsactuallyreconstructour

relatednesstoothercreatures,weneedtoleavethecircusandreturntothezoowevisitedinthefirstchapterofthebook.

A(LONGER)WALKTHROUGHTHEZOO

Aswe’veseen,ourbodiesarenotputtogetheratrandom.Here,Iusetheword“random”inaveryspecificsense;Imeanthatthestructureofourbodiesisdefinitelynotrandomwithrespecttotheotheranimalsthatwalk,fly,swim,orcrawlacrossthisearth.Someanimalssharepart

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ofourstructure;othersdonot.Thereisordertowhatwesharewiththerestoftheworld.Wehavetwoears,twoeyes,onehead,apairofarms,andapairoflegs.Wedonothavesevenlegsortwoheads.Nordowehavewheels.Awalkinthezooimmediatelyshowsourconnectionsto

therestoflife.Infact,itwillshowthatwecangroupmuchoflifeinthesamewaywedidwiththebozos.Let’sgotojustthreeexhibitsatfirst.Startwiththepolarbears.Youcanmakealonglistofthefeaturesthatyousharewithpolarbears:hair,mammaryglands,fourlimbs,aneck,andtwoeyes,amonglotsofotherthings.Next,considertheturtleacrosstheway.Therearedefinitelysimilarities,butthelistisabitshorter.Yousharefourlimbs,aneck,andtwoeyes(amongotherthings)withtheturtle.Butunlikepolarbearsandyou,turtlesdon’thavehairormammaryglands.Asfortheturtle’sshell,thatseemsuniquetotheturtle,justasthewhitefurwasuniquetothepolarbear.NowvisittheAfricanfishexhibit.Itsinhabitantsarestillsimilartoyou,butthelistofcommonalitiesisevenshorterthanthelistforturtles.Likeyou,fishhavetwoeyes.Likeyou,theyhavefourappendages,butthoseappendageslooklikefins,notarmsandlegs.Fishlack,amongmanyotherfeatures,thehairandmammaryglandsthatyousharewithpolarbears.ThisisbeginningtosoundliketheRussiandollsetof

groups,subgroups,andsub-subgroupsthatappearedinthebozoexample.Fish,turtles,polarbears,andhumansallsharesomefeatures—heads,twoeyes,twoears,andsoon.Turtles,polarbears,andhumanshaveallthesefeatures,

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andtheyalsohavenecksandlimbs,featuresnotseeninfish.Polarbearsandhumansformanevenmoreelitegroup,whosemembershaveallofthesefeaturesandalsohairandmammaryglands.Thebozoexamplegivesusthemeanstomakesenseof

ourwalkthroughthezoo.Inthebozos,thepatternofgroupsreflecteddescentwithmodification.Theimplicationisthatthefull-bozokidssharedamorerecentrelativethantheydowiththekidswhohaveonlyasqueakynose.Thatmakessense:theparentofthesqueaky-nosedkidsisthegreat-greatgrandparentofthefullbozos.Applyingthissameapproachtothegroupsweencounteredduringourzoowalkmeansthathumansandpolarbearsshouldshareamorerecentancestorthantheydowithturtles.Thispredictionistrue:theearliestmammalismuchmorerecentthantheearliestreptile.Thecentralissuehereisdecipheringthefamilytreeof

species.Or,inmoreprecisebiologicalterms,theirpatternofrelatedness.ThispatternevengivesusthemeanstointerpretafossilsuchasTiktaalikinlightofourwalkthroughthezoo.Tiktaalikisawonderfulintermediatebetweenfishandtheirland-livingdescendants,buttheoddsofitbeingourexactancestorareveryremote.Itismorelikeacousinofourancestor.Nosanepaleontologistwouldeverclaimthatheorshehaddiscovered“TheAncestor.”Thinkaboutitthisway:WhatisthechancethatwhilewalkingthroughanyrandomcemeteryonourplanetIwoulddiscoveranactualancestorofmine?Diminishingly

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small.WhatIwoulddiscoveristhatallofthepeopleburiedinthesecemeteries—nomatterwhetherthatcemeteryisinChina,Botswana,orItaly—arerelatedtometodifferentdegrees.IcanfindthisoutbylookingattheirDNAwithmanyoftheforensictechniquesinuseincrimelabstoday.I’dseethatsomeofthedenizensofthecemeteriesaredistantlyrelatedtome,othersarerelatedmoreclosely.Thistreewouldbeaverypowerfulwindowintomypastandmyfamilyhistory.ItwouldalsohaveapracticalapplicationbecauseIcouldusethistreetounderstandmypredilectiontogetcertaindiseasesandotherfactsofmybiology.Thesameistruewhenweinferrelationshipsamongspecies.Therealpowerofthisfamilytreeliesinthepredictionsit

allowsustomake.Chiefamongtheseisthatasweidentifymoresharedcharacteristics,theyshouldbeconsistentwiththeframework.Thatis,asIidentifyfeaturesfromcells,DNA,andalltheotherstructures,tissues,andmoleculesinthebodiesoftheseanimals,theyshouldsupportthegroupingsthatweidentifiedduringourwalk.Conversely,wecanfalsifyourgroupingsbyfindingfeaturesinconsistentwiththem.Thatis,ifthereexistmanytraitssharedbyfishandpeoplethataren’tseeninpolarbears,ourframeworkisflawedandneedstoberevisedorjettisoned.Incaseswheretheevidenceisambiguous,weapplyanumberofstatisticaltoolstoassessthequalityofthecharacteristicssupportingthearrangementsinthefamilytree.Ininstanceswherethereisambiguity,the

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genealogicalarrangementistreatedasaworkinghypothesisuntilwecanfindsomethingconclusivetoallowustoeitheracceptorrejectit.Somegroupingsaresostrongthat,forallintentsand

purposes,weconsiderthemfact.Thefish–turtle–polarbear–humangrouping,forexample,issupportedbycharacteristicsfromhundredsofgenesandvirtuallyallfeaturesoftheanatomy,physiology,andcellularbiologyoftheseanimals.Ourfish-to-humanframeworkissostronglysupportedthatwenolongertrytomarshalevidenceforit—doingsowouldbelikedroppingaballfiftytimestotestthetheoryofgravity.Thesameholdsforourbiologicalexample.Youwouldhavethesamechanceofseeingyourballgoupthefifty-firsttimeyoudroppeditasyouwouldoffindingstrongevidenceagainsttheserelationships.Wecannowreturntotheopeningchallengeofthebook.

Howcanweconfidentlyreconstructtherelationshipsamonglong-deadanimalsandthebodiesandgenesofrecentones?Welookforthesignatureofdescentwithmodification,weaddcharacteristics,weevaluatethequalityoftheevidence,andweassessthedegreetowhichourgroupsarerepresentedinthefossilrecord.Theamazingthingisthatwenowhavetoolstoprobethishierarchy,usingcomputersandlargeDNAsequencinglabstoperformthesameanalysesyouperformedduringyourwalkthroughthezoo.Wenowhaveaccesstonewfossilsitesaroundtheworld.Wecanseeourbodies’placeinthenaturalworldbetterthanweevercould.

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FromChapter1throughChapter10,wehaveshownthatdeepsimilaritiesexistbetweencreatureslivingtodayandthoselongdeceased—ancientworms,livingsponges,andvariouskindsoffish.Now,armedwithknowledgeofthepatternofdescentwithmodification,wecanbegintomakesenseofitall.Enoughfunatthecircusandzoo.It’stimetogetdowntobusiness.Wehaveseenthatinsideourbodiesareconnectionstoamenagerieofothercreatures.Somepartsresemblepartsofjellyfish,otherspartsofworms,stillotherspartsoffish.Thesearen’thaphazardsimilarities.Somepartsofusareseenineveryotheranimal;othersareveryuniquetous.Itisdeeplybeautifultoseethatthereisanorderinallthesefeatures.HundredsofcharactersfromDNA,innumerableanatomicalanddevelopmentalfeatures—allfollowthesamelogicasthebozoswesawearlier.Let’sconsidersomeofthefeatureswe’vealreadytalked

aboutinthebookandshowyouhowtheyareordered.Witheveryotheranimalontheplanet,weshareabody

composedofmanycells.Callthisgroupmulticellularlife.Wesharethetraitofmulticellularitywitheverythingfromspongestoplacozoanstojellyfishtochimpanzees.Asubsetofthesemulticellularanimalshaveabodyplan

likeours,withafrontandaback,atopandabottom,andaleftandaright.TaxonomistscallthisgroupBilateria(meaning“bilaterallysymmetricalanimals”).Itincludeseveryanimalfrominsectstohumans.

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Asubsetofmulticellularanimalsthathaveabodyplanlikeours,withafrontandaback,atopandabottom,andaleftandaright,alsohaveskullsandbackbones.Callthesecreaturesvertebrates.Asubsetofthemulticellularanimalsthathaveabody

planlikeours,withafrontandaback,atopandabottom,andaleftandaright,andthathaveskulls,alsohavehandsandfeet.Callthesevertebratestetrapods(animalswithfourlimbs).Asubsetofthemulticellularanimalsthathaveabody

planlikeours,withafrontandaback,atopandabottom,andaleftandaright,thathaveskulls,andthathavehandsandfeet,alsohaveathree-bonedmiddleear.Callthesetetrapodsmammals.Asubsetofthemulticellularanimalsthathaveabody

planlikeourswithafrontandaback,atopandabottom,andaleftandaright,thathaveskullsandbackbones,thathavehandsandfeet,andthathaveathree-bonedmiddleear,alsohaveabipedalgaitandenormousbrains.Callthesemammalspeople.

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Ahumanfamilytree,allthewaybacktojellyfish.Ithasthesamestructureastheoneforthebozos.

Thepowerofthesegroupingsisseenintheevidenceon

whichtheyarebased.Hundredsofgenetic,embryological,andanatomicalfeaturessupportthem.Thisarrangementallowsustolookinsideourselvesinanimportantway.Thisexerciseisalmostlikepeelinganonion,exposing

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layerafterlayerofhistory.Firstweseefeatureswesharewithallothermammals.Then,aswelookdeeper,wefindthefeatureswesharewithfish.Deeperstillarethosewesharewithworms.Andsoon.Recallingthelogicofthebozos,thismeansthatweseeapatternofdescentwithmodificationdeeplyetchedinsideourownbodies.Thatpatternisreflectedinthegeologicalrecord.Theoldestmany-celledfossilisover600millionyearsold.Theearliestfossilwithathree-bonedmiddleearislessthan200millionyearsold.Theoldestfossilwithabipedalgaitisaround4millionyearsold.Areallthesefactsjustcoincidence,ordotheyreflectalawofbiologywecanseeatworkarounduseveryday?CarlSaganoncefamouslysaidthatlookingatthestarsis

likelookingbackintime.Thestars’lightbeganthejourneytooureyeseonsago,longbeforeourworldwasformed.Iliketothinkthatlookingathumansismuchlikepeeringatthestars.Ifyouknowhowtolook,ourbodybecomesatimecapsulethat,whenopened,tellsofcriticalmomentsinthehistoryofourplanetandofadistantpastinancientoceans,streams,andforests.Changesintheancientatmospherearereflectedinthemoleculesthatallowourcellstocooperatetomakebodies.Theenvironmentofancientstreamsshapedthebasicanatomyofourlimbs.Ourcolorvisionandsenseofsmellhasbeenmoldedbylifeinancientforestsandplains.Andthelistgoeson.Thishistoryisourinheritance,onethataffectsourlivestodayandwilldosointhefuture.

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WHYHISTORYMAKESUSSICK

Mykneewasswollentothesizeagrapefruit,andoneofmycolleaguesfromthesurgerydepartmentwastwistingandbendingittodeterminewhetherIhadstrainedorrippedoneoftheligamentsorcartilagepadsinside.This,andtheMRIscanthatfollowed,revealedatornmeniscus,theprobableresultoftwenty-fiveyearsspentcarryingabackpackoverrocks,boulders,andscreeinthefield.Hurtyourkneeandyouwillalmostcertainlyinjureoneormoreofthreestructures:themedialmeniscus,themedialcollateralligament,ortheanteriorcruciateligament.Soregularareinjuriestothesethreepartsofyourkneethatthesethreestructuresareknownamongdoctorsasthe“UnhappyTriad.”Theyareclearevidenceofthepitfallsofhavinganinnerfish.Fishdonotwalkontwolegs.Ourhumanitycomesatacost.Fortheexceptional

combinationofthingswedo—talk,think,grasp,andwalkontwolegs—wepayaprice.Thisisaninevitableresultofthetreeoflifeinsideus.Imaginetryingtojerry-rigaVolkswagenBeetletotravel

atspeedsof150milesperhour.In1933,AdolfHitlercommissionedDr.FerdinandPorschetodevelopacheapcarthatcouldget40milespergallonofgasandprovideareliableformoftransportationfortheaverageGermanfamily.TheresultwastheVWBeetle.Thishistory,Hitler’splan,placesconstraintsonthewayswecanmodifytheBeetletoday;theengineeringcanbetweakedonlysofar

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beforemajorproblemsariseandthecarreachesitslimit.Inmanyways,wehumansarethefishequivalentofa

hot-rodBeetle.Takethebodyplanofafish,dressituptobeamammal,thentweakandtwistthatmammaluntilitwalksontwolegs,talks,thinks,andhassuperfinecontrolofitsfingers—andyouhavearecipeforproblems.Wecandressupafishonlysomuchwithoutpayingaprice.Inaperfectlydesignedworld—onewithnohistory—wewouldnothavetosuffereverythingfromhemorrhoidstocancer.Nowhereisthishistorymorevisiblethaninthedetours,

twists,andturnsofourarteries,nerves,andveins.Followsomenervesandyou’llfindthattheymakestrangeloopsaroundotherorgans,apparentlygoinginonedirectiononlytotwistandendupinanunexpectedplace.Thedetoursarefascinatingproductsofourpastthat,aswe’llsee,oftencreateproblemsforus—hiccupsandhernias,forexample.Andthisisonlyonewayourpastcomesbacktoplagueus.Ourdeephistorywasspent,atdifferenttimes,inancient

oceans,smallstreams,andsavannahs,notofficebuildings,skislopes,andtenniscourts.Wewerenotdesignedtolivepasttheageofeighty,sitonourkeistersfortenhoursaday,andeatHostessTwinkies,norwerewedesignedtoplayfootball.Thisdisconnectbetweenourpastandourhumanpresentmeansthatourbodiesfallapartincertainpredictableways.Virtuallyeveryillnesswesufferhassomehistorical

component.Theexamplesthatfollowreflecthowdifferentbranchesofthetreeoflifeinsideus—fromancienthumans,

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toamphibiansandfish,andfinallytomicrobes—comebacktopesterustoday.Eachoftheseexamplesshowthatwewerenotdesignedrationally,butareproductsofaconvolutedhistory.

OURHUNTER-GATHERERPAST:OBESITY,HEARTDISEASE,ANDHEMORRHOIDS

Duringourhistoryasfishwewereactivepredatorsinancientoceansandstreams.Duringourmorerecentpastasamphibians,reptiles,andmammals,wewereactivecreaturespreyingoneverythingfromreptilestoinsects.Evenmorerecently,asprimates,wewereactivetree-livinganimals,feedingonfruitsandleaves.Earlyhumanswereactivehunter-gatherersand,ultimately,agriculturalists.Didyounoticeathemehere?Thatcommonthreadistheword“active.”Thebadnewsisthatmostofusspendalargeportionof

ourdaybeinganythingbutactive.Iamsittingonmybehindatthisveryminutetypingthisbook,andanumberofyouaredoingthesamereadingit(exceptforthevirtuousamonguswhoarereadingitinthegym).Ourhistoryfromfishtoearlyhumaninnowaypreparedusforthisnewregimen.Thiscollisionbetweenpresentandpasthasitssignatureinmanyoftheailmentsofmodernlife.Whataretheleadingcausesofdeathinhumans?Fourof

thetoptencauses—heartdisease,diabetes,obesity,andstroke—havesomesortofgeneticbasisand,likely,a

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historicalone.Muchofthedifficultyisalmostcertainlyduetoourhavingabodybuiltforanactiveanimalbutthelifestyleofaspud.In1962,theanthropologistJamesNeeladdressedthis

notionfromtheperspectiveofourdiet.Formulatingwhatbecameknownasthe“thriftygenotype”hypothesis,Neelsuggestedthatourhumanancestorswereadaptedforaboom-bustexistence.Ashunter-gatherers,earlyhumanswouldhaveexperiencedperiodsofbounty,whenpreywascommonandhuntingsuccessful.Theseperiodsofplentywouldbepunctuatedbytimesofscarcity,whenourancestorshadconsiderablylesstoeat.Neelhypothesizedthatthiscycleoffeastandfaminehad

asignatureinourgenesandinourillnesses.Essentially,heproposedthatourancestors’bodiesallowedthemtosaveresourcesduringtimesofplentysoastousethemduringperiodsoffamine.Inthiscontext,fatstoragebecomesveryuseful.Theenergyinthefoodweeatisapportionedsothatsomesupportsouractivitiesgoingonnow,andsomeisstored,forexampleinfat,tobeusedlater.Thisapportionmentworkswellinaboom-bustworld,butitfailsmiserablyinanenvironmentwhererichfoodsareavailable24/7.Obesityanditsassociatedmaladies—age-relateddiabetes,highbloodpressure,andheartdisease—becomethenaturalstateofaffairs.Thethriftygenotypehypothesisalsomightexplainwhywelovefattyfoods.Theyarehigh-valueintermsofhowmuchenergytheycontain,somethingthatwouldhaveconferredadistinctadvantageinour

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distantpast.Oursedentarylifestyleaffectsusinotherways,because

ourcirculatorysystemoriginallyappearedinmoreactiveanimals.Ourheartpumpsblood,whichiscarriedtoourorgansvia

arteriesandreturnedtotheheartbywayofveins.Becausearteriesareclosertothepump,thebloodpressureinthemismuchhigherthaninveins.Thiscanbeaparticularproblemforthebloodthatneedstoreturntoourheartfromourfeet.Bloodfromthefeetneedstogouphill,sotospeak,uptheveinsofourlegstoourchest.Ifthebloodisunderlowpressure,itmaynotclimballtheway.Consequently,wehavetwofeaturesthathelpthebloodmoveup.Thefirstarelittlevalvesthatpermitthebloodtomoveupbutstopitfromgoingdown.Theotherfeatureisourlegmuscles.Whenwewalkwecontractthem,andthiscontractionservestopumpthebloodupourlegveins.Theone-wayvalvesandtheleg-musclepumpsenableourbloodtoclimbfromfeettochest.Thissystemworkssuperblyinanactiveanimal,which

usesitslegstowalk,run,andjump.Itdoesnotworkwellinamoresedentarycreature.Ifthelegsarenotusedmuch,themuscleswillnotpumptheblooduptheveins.Problemscandevelopifbloodpoolsintheveins,becausethatpoolingcancausethevalvestofail.Thisisexactlywhathappenswithvaricoseveins.Asthevalvesfail,bloodpoolsintheveins.Theveinsgetbiggerandbigger,swellingandtakingtortuouspathsinourlegs.

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Needlesstosay,thearrangementofveinscanalsobearealpaininthebehind.Truckdriversandotherswhositforlongstretchesoftimeareparticularlypronetohemorrhoids,anothercostofoursedentarylives.Duringtheirlonghoursofsitting,bloodpoolsintheveinsandspacesaroundtherectum.Asthebloodpools,hemorrhoidsform—anunpleasantreminderthatwewerenotbuilttositfortoolong,particularlynotonsoftsurfaces.

PRIMATEPAST:TALKISNOTCHEAP

Talkingcomesatasteepprice:chokingandsleepapneaarehighonthelistofproblemswehavetolivewithinordertobeabletotalk.Weproducespeechsoundsbycontrollingmotionsofthe

tongue,thelarynx,andthebackofthethroat.Allofthesearerelativelysimplemodificationstothebasicdesignofamammalorareptile.AswesawinChapter5,thehumanlarynxismadeupmostlyofgillarchcartilages,correspondingtothegillbarsofasharkorfish.Thebackofthethroat,extendingfromthelastmolartoothtojustabovethevoicebox,hasflexiblewallsthatcanopenandclose.Wemakespeechsoundsbymovingourtongue,bychangingtheshapeofourmouth,andbycontractinganumberofmusclesthatcontroltherigidityofthiswall.Sleepapneaisapotentiallydangeroustrade-offforthe

abilitytotalk.Duringsleep,themusclesofourthroatrelax.

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Inmostpeople,thisdoesnotpresentaproblem,butinsomethepassagecancollapsesothatrelativelylongstretchespasswithoutabreath.This,ofcourse,canbeverydangerous,particularlyinpeoplewhohaveheartconditions.Theflexibilityofourthroat,sousefulinourabilitytotalk,makesussusceptibletoaformofsleepapneathatresultsfromobstructionoftheairway.Anothertrade-offofthisdesignischoking.Ourmouth

leadsbothtothetrachea,throughwhichwebreathe,andtoouresophagus,soweusethesamepassagetoswallow,breathe,andtalk.Thesethreefunctionscanbeatodds,forexamplewhenapieceoffoodgetslodgedinthetrachea.

FISHANDTADPOLEPAST:HICCUPS

Thisannoyancehasitsrootsinthehistorywesharewithfishandtadpoles.Ifthereisanyconsolationforgettinghiccups,itisthat

ourmiseryissharedwithmanyothermammals.Catscanbestimulatedtohiccupbysendinganelectricalimpulsetoasmallpatchoftissueintheirbrainstem.Thisareaofthebrainstemisthoughttobethecenterthatcontrolsthecomplicatedreflexthatwecallahiccup.Thehiccupreflexisastereotypedtwitchinvolvinga

numberofmusclesinourbodywall,diaphragm,neck,andthroat.Aspasminoneortwoofthemajornervesthatcontrolbreathingcausesthesemusclestocontract.This

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resultsinaverysharpinspirationofair.Then,about35millisecondslater,aflapoftissueinthebackofourthroat(theglottis)closesthetopofourairway.Thefastinhalationfollowedbyabriefclosureofthetubeproducesthe“hic.”Theproblemisthatwerarelyexperienceonlyasingle

hic.Stopthehiccupsinthefirstfivetotenhics,andyouhaveadecentchanceofendingtheboutaltogether.Missthatwindow,andtheboutofhiccupscanpersistforanaverageofaboutsixtyhics.Inhalingcarbondioxide(bybreathingintotheclassicpaperbag)andstretchingthebodywall(takingabiginhalationandholdingit)canendhiccupsearlyinsomeofus.Butnotall.Somecasesofpathologicalhiccupscanbeextremelyprolonged.Thelongestuninterruptedhiccupsinapersonlastedfrom1922to1990.Ourtendencytodevelophiccupsisanotherinfluenceof

ourpast.Therearetwoissuestothinkabout.Thefirstiswhatcausesthespasmofnervesthatinitiatesthehiccup.Thesecondiswhatcontrolsthatdistinctivehic,theabruptinhalation–glottisclosure.Thenervespasmisaproductofourfishhistory,whilethehicisanoutcomeofthehistorywesharewithanimalssuchastadpoles.First,fish.Ourbraincancontrolourbreathingwithout

anyconsciouseffortonourpart.Mostoftheworktakesplaceinthebrainstem,attheboundarybetweenthebrainandthespinalcord.Thebrainstemsendsnerveimpulsestoourmainbreathingmuscles.Breathinghappensinapattern.Musclesofthechest,diaphragm,andthroat

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contractinawell-definedorder.Consequently,thispartofthebrainstemisknownasa“centralpatterngenerator.”Thisregioncanproducerhythmicpatternsofnerveand,consequently,muscleactivation.Anumberofsuchgeneratorsinourbrainandspinalcordcontrolotherrhythmicbehaviors,suchasswallowingandwalking.Theproblemisthatthebrainstemoriginallycontrolled

breathinginfish;ithasbeenjerry-riggedtoworkinmammals.Sharksandbonyfishallhaveaportionofthebrainstemthatcontrolstherhythmicfiringofmusclesinthethroatandaroundthegills.Thenervesthatcontroltheseareasalloriginateinawell-definedportionofthebrainstem.Wecanevenseethisnervearrangementinsomeofthemostprimitivefishinthefossilrecord.Ancientostracoderms,fromrocksover400millionyearsold,preservecastsofthebrainandcranialnerves.Justasinlivingfish,thenervesthatcontrolbreathingextendfromthebrainstem.Thisworkswellinfish,butitisalousyarrangementfor

mammals.Infish,thenervesthatcontrolbreathingdonothavetotravelveryfarfromthebrainstem.Thegillsandthroatgenerallysurroundthisareaofthebrain.Wemammalshaveadifferentproblem.Ourbreathingiscontrolledbymusclesinthewallofourchestandbythediaphragm,thesheetofmusclethatseparatesourchestfromourabdomen.Contractionofthediaphragmcontrolsinspiration.Thenervesthatcontrolthediaphragmexitourbrainjustastheydoinfish,andtheyleavefromthebrain

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stem,nearourneck.Thesenerves,thevagusandthephrenicnerve,extendfromthebaseoftheskullandtravelthroughthechestcavitytoreachthediaphragmandtheportionsofthechestthatcontrolbreathing.Thisconvolutedpathcreatesproblems;arationaldesignwouldhavethenervestravelingnotfromtheneckbutfromnearerthediaphragm.Unfortunately,anythingthatinterfereswithoneofthesenervescanblocktheirfunctionorcauseaspasm.Iftheoddcourseofournervesisaproductofourfishy

past,thehiccupitselfislikelytheproductofourhistoryasamphibians.Hiccupsareuniqueamongourbreathingbehaviorsinthatanabruptintakeofairisfollowedbyaclosureoftheglottis.Hiccupsseemtobecontrolledbyacentralpatterngeneratorinthebrainstem:stimulatethisregionwithanelectricalimpulse,andwestimulatehiccups.Itmakessensethathiccupsarecontrolledbyacentralpatterngenerator,since,asinotherrhythmicbehaviors,asetsequenceofeventshappensduringahic.Itturnsoutthatthepatterngeneratorresponsiblefor

hiccupsisvirtuallyidenticaltooneinamphibians.Andnotinjustanyamphibians—intadpoles,whichusebothlungsandgillstobreathe.Tadpolesusethispatterngeneratorwhentheybreathewithgills.Inthatcircumstance,theywanttopumpwaterintotheirmouthandthroatandacrossthegills,buttheydonotwantthewatertoentertheirlungs.Topreventitfromdoingso,theyclosetheglottis,theflapthatclosesoffthebreathingtube.Andtoclosetheglottis,

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tadpoleshaveacentralpatterngeneratorintheirbrainstemsothataninspirationisfollowedimmediatelybyaclosingglottis.Theycanbreathewiththeirgillsthankstoanextendedformofhiccup.Theparallelsbetweenourhiccupsandgillbreathingin

tadpolesaresoextensivethatmanyhaveproposedthatthetwophenomenaareoneandthesame.Gillbreathingintadpolescanbeblockedbycarbondioxide,justlikeourhiccups.Wecanalsoblockgillbreathingbystretchingthewallofthechest,justaswecanstophiccupsbyinhalingdeeplyandholdingourbreath.Perhapswecouldevenblockgillbreathingintadpolesbyhavingthemdrinkaglassofwaterupsidedown.

SHARKPAST:HERNIAS

Ourpropensityforhernias,atleastforthoseherniasnearthegroin,resultsfromtakingafishbodyandmorphingitintoamammal.Fishhavegonadsthatextendtowardtheirchest,

approachingtheirheart.Mammalsdon’t,andthereinliestheproblem.Itisaverygoodthingthatourgonadsarenotdeepinourchestandnearourheart(althoughitmightmakerecitingthePledgeofAllegianceadifferentexperience).Ifourgonadswereinourchest,wewouldn’tbeabletoreproduce.Slitthebellyofasharkfrommouthtotail.Thefirstthing

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you’llseeisliver,alotofit.Theliverofasharkisgigantic.Somezoologistsbelievethatalargelivercontributestothebuoyancyoftheshark.Movetheliverawayandyou’llfindthegonadsextendingupneartheheart,inthe“chest”area.Thisarrangementistypicalofmostfish:thegonadslietowardthefrontofthebody.Inus,asinmostmammals,thisarrangementwouldbea

disaster.Malescontinuouslyproducespermthroughoutourlives.Spermarefinickylittlecellsthatneedexactlytherightrangeoftemperaturestodevelopcorrectlyforthethreemonthstheylive.Toohot,andspermaremalformed;toocold,andtheydie.Malemammalshaveaneatlittledeviceforcontrollingthetemperatureofthesperm-makingapparatus:thescrotum.Asweallknow,themalegonadssitinasac.Insidetheskinofthesacaremusclesthatcanexpandandcontractasthetemperaturechanges.Musclesalsolieinourspermcords.Hence,thecoldshowereffect:thescrotumwilltuckclosetothebodywhenitiscold.Thewholepackagerisesandfallswithtemperature.Thisisallawaytooptimizetheproductionofhealthysperm.Thedanglingscrotumalsoservesasasexualsignalin

manymammals.Betweenthephysiologicaladvantagesofhavinggonadsoutsidethebodywall,andtheoccasionalbenefitsthisprovidesinsecuringmates,thereareampleadvantagesforourdistantmammalianancestorsinhavingascrotum.

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Openasharkandyoufindahugeliver(top).Pushtheliverasideandyouseegonads,whichextendrelativelyclosetotheheart,astheydoinotherprimitivecreatures.PhotoscourtesyofDr.StevenCampana,CanadianSharkResearchLaboratory.

Theproblemwiththisarrangementisthattheplumbing

thatcarriesspermtothepenisiscircuitous.Spermtravelfromthetestesinthescrotumthroughthespermcord.Thecordleavesthescrotum,travelsuptowardthewaist,loopsoverthepelvis,thengoesthroughthepelvistotravelthroughthepenisandout.Alongthiscomplexpath,thespermgainseminalfluidsfromanumberofglandsthat

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connecttothetube.Thereasonforthisabsurdrouteliesinour

developmentalandevolutionaryhistory.Ourgonadsbegintheirdevelopmentinmuchthesameplaceasashark’s:upnearourlivers.Astheygrowanddevelop,ourgonadsdescend.Infemales,theovariesdescendfromthemidsectiontolieneartheuterusandfallopiantubes.Thisensuresthattheeggdoesnothavefartotraveltobefertilized.Inmales,thedescentgoesfarther.Thedescentofthegonads,particularlyinmales,createsa

weakspotinthebodywall.Toenvisionwhathappenswhenthetestesandspermaticcorddescendtoformascrotum,imaginepushingyourfistagainstarubbersheet.Inthisexample,yourfistbecomesequivalenttothetestesandyourarmtothespermaticcord.Theproblemisthatyouhavecreatedaweakspacewhereyourarmsits.Whereoncetherubbersheetwasasimplewall,you’venowmadeanotherspace,betweenyourarmandtherubbersheet,wherethingscanslip.Thisisessentiallywhathappensinmanytypesofinguinalherniasinmen.Someoftheseinguinalherniasarecongenital—whenapieceoftheguttravelswiththetestesasitdescends.Anotherkindofinguinalherniaisacquired.Whenwecontractourabdominalmuscles,ourgutspushagainstthebodywall.Aweaknessinthebodywallmeansthatgutscanescapethebodycavityandbesqueezedtolienexttothespermaticcord.Femalesarefartougherthanmales,particularlyinthis

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partofthebody.Becausefemalesdonothaveagianttuberunningthroughit,theirabdominalwallismuchstrongerthanaman’s.Thisisagoodthingwhenyouthinkoftheenormousstressesthatfemalebodywallsgothroughduringpregnancyandchildbirth.Atubethroughthebodywalljustwouldn’tdo.Men’stendencytodevelopherniasisatrade-offbetweenourfishancestryandourmammalpresent.

Thedescentofthetestes.Duringgrowth,thetestes

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descendfromthegonads’primitivepositionhighupinthebody.Theyenduplyinginthescrotum,whichisanoutpocketofthebodywall.Allofthisleavesthebodywallofhumanmalesweakinthegroinarea.

MICROBIALPAST:MITOCHONDRIALDISEASES

Mitochondriaexistinsideeverycellofourbodies,doingaremarkablenumberofthings.Theirmostobviousjobistoturnoxygenandsugarsintoakindofenergywecanuseinsideourcells.Otherfunctionsincludemetabolizingtoxinsinourliversandregulatingdifferentpartsofthefunctionofourcells.Wenoticeourmitochondriaonlywhenthingsgowrong.Unfortunately,thelistofdiseasescausedbymalfunctioningmitochondriaisextraordinarilylongandcomplex.Ifthereisaprobleminthechemicalreactionsinwhichoxygenisconsumed,energyproductioncanbeimpaired.Themalfunctionmaybeconfinedtoindividualtissues,saytheeyes,ormayaffecteverysysteminthebody.Dependingonthelocationandseverityofthemalfunction,itcanleadtoanythingfromweaknesstodeath.Manyoftheprocessesweusetolivereflectour

mitochondria’shistory.Thechainreactionofchemicaleventsthatturnssugarsandoxygenintousableenergyandcarbondioxidearosebillionsofyearsago,andversionsofit

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arestillseenindiversemicrobes.Mitochondriacarrythisbacterialpastinsideofthem:withanentiregeneticstructureandcellularmicrostructuresimilartobacteria,itisgenerallyacceptedthattheyoriginallyarosefromfree-livingmicrobesoverabillionyearsago.Infact,theentireenergy-generatingmachineryofourmitochondriaaroseinoneofthesekindsofancientbacteria.Thebacterialpastcanbeusedtoouradvantagein

studyingthediseasesofmitochondria—infact,someofthebestexperimentalmodelsforthesediseasesarebacteria.Thisispowerfulbecausewecandoallkindsofexperimentswithbacteriathatarenotpossiblewithhumancells.OneofthemostprovocativestudieswasdonebyateamofscientistsfromItalyandGermany.Thediseasethattheystudiedinvariablykillstheinfantswhoarebornwithit.Calledcardioencephalomyopathy,itresultsfromageneticchangethatinterruptsthenormalmetabolicfunctionofmitochondria.Instudyingapatientwhohadthedisease,theEuropeanteamidentifiedaplaceintheDNAthathadasuspiciouschange.Knowingsomethingaboutthehistoryoflife,theythenturnedtothemicrobeknownasParacoccusdenitrificans,whichisoftencalledafree-livingmitochondrionbecauseitsgenesandchemicalpathwaysaresosimilartothoseofmitochondria.JusthowsimilarwasrevealedbytheEuropeanteam.Theyproducedthesamechangeinthebacteria’sgenesthattheysawintheirhumanpatient.Whattheyfoundmakestotalsense,onceweknowourhistory.Theywereabletosimulatepartsofa

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humanmitochondrialdiseaseinabacterium,withvirtuallythesamechangeinmetabolism.Thisisputtingamany-billion-yearpartofourhistorytoworkforus.Theexamplefrommicrobesisnotunique.Judgingbythe

NobelPrizesawardedinmedicineandphysiologyinthepastthirteenyears,IshouldhavecalledthisbookYourInnerFly,YourInnerWorm,orYourInnerYeast.Pioneeringresearchonflieswonthe1995NobelPrizeinmedicineforuncoveringasetofgenesthatbuildsbodiesinhumansandotheranimals.Nobelsinmedicinein2002and2006wenttopeoplewhomadesignificantadvancesinhumangeneticsandhealthbystudyinganinsignificant-lookinglittleworm(C.elegans).Similarly,in2001,elegantanalysesofyeast(includingbaker’syeast)andseaurchinswontheNobelinmedicineforincreasingourunderstandingofsomeofthebasicbiologyofallcells.Thesearenotesotericdiscoveriesmadeonobscureandunimportantcreatures.Thesediscoveriesonyeast,flies,worms,and,yes,fishtellusabouthowourownbodieswork,thecausesofmanyofthediseaseswesuffer,andwayswecandeveloptoolstomakeourliveslongerandhealthier.

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EPILOGUE

Asaparentoftwoyoungchildren,Ifindmyselfspendingalotoftimelatelyinzoos,museums,andaquaria.Beingavisitorisastrangeexperience,becauseI’vebeeninvolvedwiththeseplacesfordecades,workinginmuseumcollectionsandevenhelpingtoprepareexhibitsonoccasion.Duringfamilytrips,I’vecometorealizehowmuchmyvocationcanmakemenumbtothebeautyandsublimecomplexityofourworldandourbodies.Iteachandwriteaboutmillionsofyearsofhistoryandaboutbizarreancientworlds,andusuallymyinterestisdetachedandanalytic.NowI’mexperiencingsciencewithmychildren—inthekindsofplaceswhereIdiscoveredmyloveforitinthefirstplace.Onespecialmomenthappenedrecentlywithmysonat

theMuseumofScienceandIndustryinChicago.We’vegonethereregularlyoverthepastthreeyearsbecauseofhisloveoftrainsandthefactthatthereisahugemodelrailroadsmackinthecenteroftheplace.I’vespentcountlesshoursatthatoneexhibittracingmodellocomotivesontheirlittletrekfromChicagotoSeattle.Afteranumberofweeklyvisits

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tothisshrineforthetrain-obsessed,NathanielandIwalkedtocornersofthemuseumwehadfailedtovisitduringourtrain-watchingventuresoroccasionalforaystothefull-sizetractorsandplanes.Inthebackofthemuseum,intheHenryCrownSpaceCenter,modelplanetshangfromtheceilingandspacesuitslieincasestogetherwithothermemorabiliaofthespaceprogramofthe1960sand1970s.IwasunderthepresumptionthatinthebackofthemuseumIwouldseethetriviathatdidn’tmakeittothemajorexhibitsupfront.Onedisplayconsistedofabatteredspacecapsulethatyoucouldwalkaroundandlookinside.Itdidn’tlooksignificant;itseemedwaytoosmallandjerry-riggedtobeanythingreallyimportant.Theplacardwasstrangelyformal,andIhadtoreaditseveraltimesbeforeitdawnedonme:herewastheoriginalCommandModulefromApollo8,theactualvesselthatcarriedJamesLovell,FrankBorman,andWilliamAndersonhumanity’sfirsttriptothemoonandback.ThiswasthespacecraftwhosepathIfollowedduringChristmasbreakinthirdgrade,andhereIwasthirty-eightyearslaterwithmyownson,lookingattherealthing.Ofcourseitwasbattered.Icouldseethescarsofitsjourneyandsubsequentreturntoearth.Nathanielwascompletelydisinterested,soIgrabbedhimandtriedtoexplainwhatitwas.ButIcouldn’tspeak;myvoicebecamesochokedwithemotionthatIcouldbarelyutterasingleword.Afterafewminutes,Iregainedmycomposureandtoldhimthestoryofman’striptothemoon.ButthestoryIcan’ttellhimuntilheisolderiswhyI

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becamespeechlessandemotional.TherealstoryisthatApollo8isasymbolforthepowerofsciencetoexplainandmakeouruniverseknowable.Peoplecanquibbleovertheextenttowhichthespaceprogramwasaboutscienceorpolitics,butthecentralfactremainsascleartodayasitwasin1968:Apollo8wasaproductoftheessentialoptimismthatfuelsthebestscience.Itexemplifieshowtheunknownshouldnotbeasourceofsuspicion,fear,orretreattosuperstition,butmotivationtocontinueaskingquestionsandseekinganswers.Justasthespaceprogramchangedthewaywelookatthe

moon,paleontologyandgeneticsarechangingthewayweviewourselves.Aswelearnmore,whatonceseemeddistantandunattainablecomeswithinourcomprehensionandourgrasp.Weliveinanageofdiscovery,whenscienceisrevealingtheinnerworkingsofcreaturesasdifferentasjellyfish,worms,andmice.Wearenowseeingtheglimmerofasolutiontooneofthegreatestmysteriesofscience—thegeneticdifferencesthatmakehumansdistinctfromotherlivingcreatures.Couplethesepowerfulnewinsightswiththefactthatsomeofthemostimportantdiscoveriesinpaleontology—newfossilsandnewtoolstoanalyzethem—havecometolightinthepasttwentyyears,andweareseeingthetruthsofourhistorywithever-increasingprecision.Lookingbackthroughbillionsofyearsofchange,everythinginnovativeorapparentlyuniqueinthehistoryoflifeisreallyjustoldstuffthathasbeenrecycled,recombined,repurposed,orotherwisemodifiedfornew

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uses.Thisisthestoryofeverypartofus,fromoursenseorganstoourheads,indeedourentirebodyplan.Whatdobillionsofyearsofhistorymeanforourlives

today?Answerstofundamentalquestionsweface—abouttheinnerworkingsofourorgansandourplaceinnature—willcomefromunderstandinghowourbodiesandmindshaveemergedfrompartscommontootherlivingcreatures.Icanimaginefewthingsmorebeautifulorintellectuallyprofoundthanfindingthebasisforourhumanity,andremediesformanyoftheillswesuffer,nestledinsidesomeofthemosthumblecreaturesthathaveeverlivedonourplanet.

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NOTES,REFERENCES,ANDFURTHERREADING

CHAPTERONEFINDINGANINNERFISH

Ihaveincludedamixofprimaryandsecondarysourcesforthoseinterestedinpursuingthetopicsinthebookfurther.Foraccountsthatuseexploratorypaleontologicalexpeditionsasavehicletodiscussmajorquestionsinbiologyandgeology,seeMikeNovacek’sDinosaursoftheFlamingCliffs(NewYork:Anchor,1997),AndrewKnoll’sLifeonaYoungPlanet(Princeton:PrincetonUniversityPress,2002),andJohnLong’sSwimminginStone(Melbourne:FreemantlePress,2006).Allbalancescientificanalysiswithdescriptionsofdiscoveryinthefield.ThecomparativemethodsthatIdiscuss,includingthe

methodsusedinourwalkthroughthezoo,arethemethodsofcladistics.AsuperboverviewisHenryGee’sInSearchofDeepTime(NewYork:FreePress,1999).Basically,Ipresentaversionofthethree-taxonstatement,thestartingpointforcladisticcomparisons.AgoodtreatmentwithbackgroundsourcesisfoundinRichardForeyetal.,“TheLungfish,theCoelacanthandtheCowRevisited,”inH.-P.

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SchultzeandL.Trueb,eds.,OriginoftheHigherGroupsofTetrapods(Ithaca,N.Y.:CornellUniversityPress,1991).Thecorrelationbetweenthefossilrecordandour“walk

throughthezoo”isdiscussedinseveralpapers.Asampling:Benton,M.J.,andHitchin,R.(1997)Congruencebetweenphylogeneticandstratigraphicdatainthehistoryoflife,ProceedingsoftheRoyalSocietyofLondon,B264:885–890;Norell,M.A.,andNovacek,M.J.(1992)Congruencebetweensuperpositionalandphylogeneticpatterns:Comparingcladisticpatternswithfossilrecords,Cladistics8:319–337;Wagner,P.J.,andSidor,C.(2000)Agerank/claderankmetrics—sampling,taxonomy,andthemeaningof“stratigraphicconsistency,”SystematicBiology49:463–479.Thelayersoftherockcolumnandthefossilscontained

thereinarebeautifullyandcomprehensivelydiscussedinRichardFortey’sLife:ANaturalHistoryoftheFirstFourBillionYearsofLifeonEarth(NewYork:Knopf,1998).ResourcesforvertebratepaleontologyincludeR.Carroll,VertebratePaleontologyandEvolution(SanFrancisco:W.H.Freeman,1987),andM.J.Benton,VertebratePaleontology(London:Blackwell,2004).Fortheoriginoftetrapods:CarlZimmerreviewedthe

stateoftheartinthefieldinhishighlyreadableandwell-researchedAttheWater’sEdge(NewYork:FreePress,1998).JennyClackhaswrittenthedefinitivetextonthewholetransition,GainingGround(Bloomington:IndianaUniversityPress,2002).Thebibleofthistransition,Clack’sbookwillbringanovicetoexpertstatusquickly.

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OuroriginalpapersdescribingTiktaalikappearedintheApril6,2006,issueofNature.Thereferencesare:Daeschleretal.(2006)ADevoniantetrapod-likefishandtheoriginofthetetrapodbodyplan,Nature757:757–763;Shubinetal.(2006)ThepectoralfinofTiktaalikroseaeandtheoriginofthetetrapodlimb,Nature757:764–771.JennyClackandPerAhlberghadaveryreadableandcomprehensivecommentarypieceinthesameissue(Nature757:747–749).Everythingaboutourpastisrelative,eventhestructure

ofthisbook.Icouldhavecalledthisbook“OurInnerHuman”andwrittenitfromafish’spointofview.Thestructureofthatbookwouldhavebeenstrangelysimilar:afocusonthehistoryhumansandfishshareinbodies,brains,andcells.Aswe’veseen,alllifesharesadeeppartofitshistorywithotherspecies,whileanotherpartofitshistoryisunique.

CHAPTERTWOGETTINGAGRIP

Owenwasbynomeansthefirstpersontoseethepatternofonebone–twobones–lotsablobs–digits.Vicq-d’Azyrinthe1600sandGeoffroySt.Hilaire(1812)alsomadethispatternpartoftheirworldviews.WhatdistinguishedOwenwashisconceptofthearchetype.Thiswasatranscendentalorganizationofthebody,reflectingthedesignoftheCreator.St.Hilairewassearchinglessforanarchetypicalpatternhiddeninallstructurethanfor“lawsofform”that

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governtheformationofbodies.AnicetreatmentoftheseissuesisinT.Appel,TheCuvier-GeoffroyDebate:FrenchBiologyintheDecadesBeforeDarwin(NewYork:OxfordUniversityPress,1987),andE.S.Russell,FormandFunction:AContributiontotheHistoryofMorphology(Chicago:UniversityofChicagoPress,1982).ArecentvolumeeditedbyBrianHallisone-stop

shoppingforinformationonlimbdiversityanddevelopmentandcontainsanumberofimportantpapersondifferentkindsoflimbs:BrianK.Hall,ed.,FinsintoLimbs:Evolution,Development,andTransformation(Chicago:UniversityofChicagoPress,2007).UsefulreferencesforexploringtheshiftfromfinsandlimbsinmoredetailincludeShubinetal.(2006)ThepectoralfinofTiktaalikroseaeandtheoriginofthetetrapodlimb,Nature757:764–771;Coates,M.I.,Jeffery,J.E.,andRuta,M.(2002)Finstolimbs:whatthefossilssay,EvolutionandDevelopment4:390–412.

CHAPTERTHREEHANDYGENES

Thedevelopmentalbiologyoflimbdiversityhasseenanumberofreviewsandprimarypapers.ForareviewoftheclassicliteratureseeShubin,N.,andAlberch,P.(1986)Amorphogeneticapproachtotheoriginandbasicorganizationofthetetrapodlimb,EvolutionaryBiology20:319–387;andHinchliffe,J.R.,andGriffiths,P.,“ThePre-chondrogenicPatternsinTetrapodLimbDevelomentand

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TheirPhylogeneticSignificance,”inB.Goodwin,N.Holder,andC.Wylie,eds.,DevelopmentandEvolution(Cambridge,Eng.:CambridgeUniversityPress,1983),pp.99–121.Saunders’sandZwilling’sexperimentsarenowclassic,sosomeofthebestaccountsarenowseeninthemajortextbooksindevelopmentalbiology.TheseincludeS.Gilbert,DevelopmentalBiology,8thed.(Sunderland,Mass.:SinauerAssociates,2006);L.Wolpert,J.Smith,T.Jessell,F.Lawrence,E.Robertson,andE.Meyerowitz,PrinciplesofDevelopment(Oxford,Eng.:OxfordUniversityPress,2006).ForthefirstpaperdescribingSonichedgehog’srolein

limbpatterning,gotoRiddle,R.,Johnson,R.L.,Laufer,E.,Tabin,C.(1993)SonichedgehogmediatesthepolarizingactivityoftheZPA,Cell75:1401–1416.Randy’sworkonSonicsignalinginsharkandskatefinsis

inDahn,R.,Davis,M.,Pappano,W.,Shubin,N.(2007)Sonichedgehogfunctioninchondrichthyanfinsandtheevolutionofappendagepatterning,Nature445:311–314.Subsequentworkfromthelabontheoriginoflimbs,atleastfromageneticperspective,iscontainedinDavis,M.,Dahn,R.,andShubin,N.(2007)Alimbautopodial-likepatternofHoxexpressioninabasalactinopterygianfish,Nature447:473–476.Thestunninggeneticsimilaritiesinthedevelopmentof

flies,chickens,andhumansisdiscussedinShubin,N.,Tabin,C.,Carroll,S.(1997)Fossils,genes,andtheevolutionofanimallimbs,Nature388:639–648;andErwin,D.andDavidson,E.H.(2003)Thelastcommonbilaterian

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ancestor,Development129:3021–3032.

CHAPTERFOURTEETHEVERYWHERE

Theimportanceofteethtoanunderstandingofmammalsisevidentinthemanytreatmentsinthefield.Dentalstructureplaysaparticularlyimportantroleinunderstandingtheearlyrecordofmammals.ExtensivereviewsarefoundinZ.Kielan-Jaworowska,R.L.Cifelli,andZ.Luo,MammalsfromtheAgeofDinosaurs(NewYork:ColumbiaUniversityPress,2004);andJ.A.Lillegraven,Z.Kielan-Jaworowska,andW.Clemens,eds.,MesozoicMammals:TheFirstTwo-ThirdsofMammalianHistory(Berkeley:UniversityofCaliforniaPress,1979),p.311.Farish’smammalfromArizonaisanalyzedinJenkins,F.

A.,Jr.,Crompton,A.W.,Downs,W.R.(1983)MesozoicmammalsfromArizona:Newevidenceonmammalianevolution,Science222:1233–1235.ThetritheledontswefoundinNovaScotiaaredescribed

inShubin,N.,Crompton,A.W.,Sues,H.-D.,andOlsen,P.(1991)Newfossilevidenceonthesister-groupofmammalsandearlyMesozoicfaunaldistributions,Science251:1063–1065.Arecentreviewontheoriginofteeth,bone,andskulls,in

particularthenewevolutiongleanedfromconodontanimals,isfoundinDonoghue,P.,andSansomI.(2002)Originandearlyevolutionofvertebrateskeletonization,MicroscopyResearchandTechnique59:352–372.A

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thoroughreviewoftheevolutionaryrelationshipsamongconodontsandtheirsignificanceisinDonoghue,P.,Forey,P.,andAldridge,R.(2000)Conodontaffinityandchordatephylogeny,BiologicalReviews75:191–251.

CHAPTERFIVEGETTINGAHEAD

Awonderfullycomprehensiveanddetailedtreatmentofthedetailsofskullstructure,development,andevolutionisfoundinathree-volumeset:TheSkull,JamesHankenandBrianHall,eds.(Chicago:UniversityofChicagoPress,1993).Thisisamulti-authorupdateofoneoftheclassicvolumesonheaddevelopmentandstructure:G.R.deBeer,TheDevelopmentoftheVertebrateSkull(Oxford,Eng.:OxfordUniversityPress,1937).Detailsofheaddevelopmentandstructureinhumanscan

befoundintextsonhumananatomyandembryology.Forembryology,seeK.MooreandT.V.N.Persaud,TheDevelopingHuman,7thed.(Philadelphia:Elsevier,2006).ThecompanionanatomytextisK.MooreandA.F.Dalley,ClinicallyOrientedAnatomy(Philadelphia:LippincottWilliams&Wilkins,2006).FrancisMaitlandBalfour’sseminalworkisencapsulated

inBalfour,F.M.(1874)Apreliminaryaccountofthedevelopmentoftheelasmobranchfishes,Q.J.Microsc.Sci.14:323–364;F.M.Balfour,AMonographontheDevelopmentofElasmobranchFishes,4vols.(London:Macmillan&Co.,1878);F.M.Balfour,ATreatiseonComparativeEmbryology,

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2vols.(London:Macmillan&Co.,1880–81);M.FosterandA.Sedgwick,TheWorksofFrancisMaitlandBalfour,withanintroductorybiographicalnoticebyMichaelFoster,4vols.(London:Macmillan&Co.,1885).AsuccessoratOxford,EdwinGoodrich,producedoneoftheclassicsofcomparativeanatomy,StudiesontheStructureandDevelopmentofVertebrates(London:Macmillan,1930).Balfour,Oken,Goethe,Huxley,andotherswere

addressingtheproblemknownasheadsegmentation.Justasthevertebraedifferinaregularprogressionfromfronttoback,sotheheadhasasegmentalpattern.Aselectionofclassicandrecentresources(allwithgoodbibliographies)topursuethisfieldfurther:Olsson,L.,Ericsson,R.,Cerny,R.(2005)Vertebrateheaddevelopment:Segmentation,novelties,andhomology,TheoryinBiosciences124:145–163;Jollie,M.(1977)Segmentationofthevertebratehead,AmericanZoologist17:323–333;Graham,A.(2001)Thedevelopmentandevolutionofthepharyngealarches,JournalofAnatomy199:133–141.Arecentoverviewofthegeneticbasisofgillarch

formationisfoundinKuratani,S.(2004)Evolutionofthevertebratejaw:comparativeembryologyandmoleculardevelopmentalbiologyrevealthefactorsbehindevolutionarynovelty,JournalofAnatomy205:335–347.Examplesoftheexperimentalmanipulationofonegillarchintoanother,usinggenetictechnologies,includeBaltzinger,M.,Ori,M.,Pasqualetti,M.,Nardi,I.,Riji,F.(2005)Hoxa2knockdowninXenopusresultsinhyoidtomandibular

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homeosis,DevelopmentalDynamics234:858–867;Depew,M.,Lufkin,T.,Rubenstein,J.(2002)SpecificationofjawsubdivisionsbyDlxgenes,Science298:381–385.Acomprehensive,well-illustrated,andinformative

resourceforearlyfossilrecordsofskulls,heads,andprimitivefishisreviewedinP.Janvier,EarlyVertebrates(Oxford,Eng.:OxfordUniversityPress,1996).ThepaperdescribingHaikouella,the530-million-year-oldwormwithgills,isChen,J.-Y.,Huang,D.Y.,andLi,C.W.(1999)AnearlyCambriancraniate-likechordate,Nature402:518–522.

CHAPTERSIXTHEBEST-LAID(BODY)PLANS

Theoriginofbodyplanshasbeenthesubjectofanumberofbook-lengthtreatments.Foronewithanexceptionalscopeandbibliography,gotoJ.Valentine,OntheOriginofPhyla(Chicago:UniversityofChicagoPress,2004).TherehavebeenseveralbiographiesofvonBaer.Ashort

oneisJaneOppenheimer,“Baer,KarlErnstvon,”inC.Gillespie,ed.,DictionaryofScientificBiography,vol.1(NewYork:Scribners,1970).Formoredetailedtreatments,seeAutobiographyofDr.KarlErnstvonBaer,ed.JaneOppenheimer(1986;originallypublishedinGerman,2nded.,1886).SeealsoB.E.Raikov,KarlErnstvonBaer,1792–1876,trans.fromRussian(1968),andLudwigStieda,KarlErnstvonBaer,2nded.(1886).Alltheseresourceshavelargebibliographies.SeealsoS.Gould,OntogenyandPhylogeny(Cambridge,Mass.:HarvardUniversityPress,

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1977),foradiscussionofvonBaer’slaws.SpemannandMangold’sexperimentsarediscussedin

embryologytextbooks:S.Gilbert,DevelopmentalBiology,8thed.(Sunderland,Mass.:SinauerAssociates,2006).AmoderngeneticperspectiveontheOrganizeriscontainedinDeRobertis,E.M.(2006)Spemann’sorganizerandselfregulationinamphibianembryos,NatureReviews7:296–302,andDeRobertis,E.M.,andArecheaga,J.TheSpemannOrganizer:75yearson,InternationalJournalofDevelopmentalBiology45(specialissue).ForaccesstothehugeliteratureonHoxgenesand

evolution,thebeststartingreferenceisSeanCarroll’srecentbookEndlessFormsMostBeautiful(NewYork:Norton,2004).ArecentreviewandinterpretationofthewaysthatgenesallowustounderstandthecommonancestorofbilaterallysymmetricalanimalsisinErwin,D.,andDavidson,E.H.(2002)Thelastcommonbilaterianancestor,Development129:3021–3032.Anumberofinvestigatorsarguethatagenetic“flip”

betweenthebodyplanofananthropodandthebodyplanofahumanhappenedsometimeinthedistantpast.ThisideaisdiscussedinDeRobertis,E.,andSasai,Y.(1996)AcommonplanfordorsoventralpatterninginBilateria,Nature380:37–40.HistoricalperspectiveonSt.Hilaire’sviews,aswellasothercontroversiesintheearlyyearsofcomparativeanatomy,arefoundinT.Appel,TheCuvier-GeoffroyDebate:FrenchBiologyintheDecadesBeforeDarwin(NewYork:OxfordUniversityPress,1987).Data

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fromacornwormsdoesnoteasilyfitthismodel,andsuggeststhatinsometaxathemapbetweengeneactivityandaxisspecificationmayhaveevolved.Forthiswork,seeLowe,C.J.,etal.(2006)Dorsoventralpatterninginhemichordates:insightsintoearlychordateevolution,PLoSBiologyonlineaccess:http://dx.doi.org/journal.0040291.Theevolutionofthegenesthatdeterminethebodyaxes

isreviewedinMartindale,M.Q.(2005)Theevolutionofmetazoanaxialproperties,NatureReviewsGenetics6:917–927.Bodyplangenesincnidarians(jellyfish,seaanemones,andtheirrelatives)arediscussedinaseriesofprimarypapers:Martindale,M.Q.,Finnerty,J.R.,Henry,J.(2002)TheRadiataandtheevolutionaryoriginsofthebilaterianbodyplan,MolecularPhylogeneticsandEvolution24:358–365;Matus,D.Q.,Pang,K.,Marlow,H.,Dunn,C.,Thomsen,G.,Martindale,M.(2006)Molecularevidencefordeepevolutionaryrootsofbilateralityinanimaldevelopment,ProceedingsoftheNationalAcademyofSciences103:11195–11200;Chourrout,D.,etal.(2006)MinimalprotohoxclusterinferredfrombilaterianandcnidarianHoxcomplements,Nature442:684–687;Martindale,M.,Pang,K.,Finnerty,J.(2004)Investigatingtheoriginsoftriploblasty:“mesodermal”geneexpressioninadiploblasticanimal,theseaanemoneNemostellavectensis(phylum,Cnidaria;class,Anthozoa),Development131:2463–2474;Finnerty,J.,Pang,K.,Burton,P.,Paulson,D.,Martindale,M.Q.(2004)Deeporiginsforbilateralsymmetry:HoxandDppexpressioninaseaanemone,Science304:1335–1337.

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CHAPTERSEVENADVENTURESINBODYBUILDING

Threekeyarticlesreviewtheoriginsandevolutionofbodiesandofferanintegrativeperspectiveongenetics,geology,andecology:King,N.(2004)Theunicellularancestryofanimaldevelopment,DevelopmentalCell7:313–325;Knoll,A.H.,andCarroll,S.B.(1999)Earlyanimalevolution:Emergingviewsfromcomparativebiologyandgeology,Science284:2129–2137;Brooke,N.M.,andHolland,P.(2003)Theevolutionofmulticellularityandearlyanimalgenomes,CurrentOpinioninGeneticsandDevelopment13:599–603.Allthreepapersarewellreferencedandofferagoodintroductiontothetopicsofthechapter.Forstimulatingtreatmentsoftheconsequencesofthe

originofbodiesandofothernewformsofbiologicalorganization,seeL.W.Buss,TheEvolutionofIndividuality(Princeton:PrincetonUniversityPress,2006),andJ.MaynardSmith,andE.Szathmary,TheMajorTransitionsinEvolution(NewYork:OxfordUniversityPress,1998).ThestorybehindtheEdiacariananimalsiscovered,with

references,inRichardFortey’sLife:ANaturalHistoryoftheFirstFourBillionYearsofLifeonEarth(NewYork:Knopf,1998),andAndrewKnoll’sLifeonaYoungPlanet(Princeton:PrincetonUniversityPress,2002).Theexperimentthatyielded“proto-bodies”from“no-

bodies”isdescribedinBoraas,M.E.,Seale,D.B.,Boxhorn,J.(1998)Phagotrophybyaflagellateselectsforcolonialprey:Apossibleoriginofmulticellularity,EvolutionaryEcology

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12:153–164.

CHAPTEREIGHTMAKINGSCENTS

TheUniversityofUtahhasaneffectivewebsite,Learn.Genetics,thatprovidesawonderfullysimplekitchenprotocolforextractingDNA.TheURLishttp://learn.genetics.utah.edu/units/activities/extraction/.Theevolutionoftheso-calledodorgenesor,more

precisely,olfactoryreceptorgeneshasalargeliterature.BuckandAxel’sseminalpaperisBuck,L.,andAxel,R.(1991)Anovelmultigenefamilymayencodeodorantreceptors:amolecularbasisforodorrecognition,Cell65:175–181.Comparativeaspectsofolfactorygeneevolutionare

treatedinYoung,B.,andTrask,B.J.(2002)Thesenseofsmell:genomicsofvertebrateodorantreceptors,HumanMolecularGenetics11:1153–1160;Mombaerts,P.(1999)Molecularbiologyofodorantreceptorsinvertebrates,AnnualReviewsofNeuroscience22:487–509.Olfactoryreceptorgenesinjawlessfisharediscussedin

Freitag,J.,Beck,A.,Ludwig,G.,vonBuchholtz,L.,Breer,H.(1999)Ontheoriginoftheolfactoryreceptorfamily:receptorgenesofthejawlessfish(Lampetrafluviatilis),Gene226:165–174.ThedistinctionbetweenaquaticandterrestrialolfactoryreceptorgenesisdescribedinFreitag,J.,Ludwig,G.,Andreini,I.,Rossler,P.,Breer,H.(1998)Olfactoryreceptorsinaquaticandterrestrialvertebrates,

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JournalofComparativePhysiologyA183:635–650.Humanolfactoryreceptorevolutionisdiscussedina

numberofpapers.Thisselectionreflectstheissuesdiscussedinthetext:Gilad,Y.,Man,O.,Lancet,D.(2003)Humanspecificlossofolfactoryreceptorgenes,ProceedingsoftheNationalAcademyofSciences100:3324–3327;Gilad,Y.,Man,O.,andGlusman,G.(2005)Acomparisonofthehumanandchimpanzeeolfactoryreceptorgenerepertoires,GenomeResearch15:224–230;Menashe,I.,Man,O.,Lancet,D.,Gilad,Y.(2003)Differentnosesfordifferentpeople,NatureGenetics34:143–144;Gilad,Y.,Wiebe,V.,Przeworski,M.,Lancet,D.,Paabo,S.(2003)Lossofolfactoryreceptorgenescoincideswiththeacquisitionoffulltrichromaticvisioninprimates,PLoSBiologyonlineaccess:http://dx.doi.org/journal.pbio.0020005.Thenotionofgeneduplicationasanimportantsourceof

newgeneticvariationtracestotheseminalworkofOhnoalmostfortyyearsago:S.Ohno,EvolutionbyGeneDuplication(NewYork:Springer-Verlag,1970).ArecentreviewoftheissuethatcontainsadiscussionofbothopsinsandolfactoryreceptorgenesisfoundinTaylor,J.,andRaes,J.(2004)Duplicationanddivergence:theevolutionofnewgenesandoldideas,AnnualReviewsofGenetics38:615–643.

CHAPTERNINEVISION

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Opsingenesintheevolutionofeyeshavebeendescribedinanumberofpapersinrecentyears.ReviewsofthebasicbiologyandtheconsequencesofopsingeneevolutionincludeNathans,J.(1999)Theevolutionandphysiologyofhumancolorvision:insightsfrommoleculargeneticstudiesofvisualpigments,Neuron24:299–312;Dominy,N.,Svenning,J.C.,Li,W.H.(2003)Historicalcontingencyintheevolutionofprimatecolorvision,JournalofHumanEvolution44:25–45;Tan,Y.,Yoder,A.,Yamashita,N.,Li,W.H.(2005)Evidencefromopsingenesrejectsnocturnalityinancestralprimates,ProceedingsoftheNationalAcademyofSciences102:14712–14716;Yokoyama,S.(1996)Molecularevolutionofretinalandnonretinalopsins,GenestoCells1:787–794;Dulai,K.,vonDornum,M.,Mollon,J.,Hunt,D.M.(1999)TheevolutionoftrichromaticcolorvisionbyopsingeneduplicationinNewWorldandOldWorldprimates,Genome9:629–638.DetlevArendtandJoachimWittbrodt’sworkon

photoreceptortissueswasoriginallydescribedinapaperfromtheprimaryliterature:Arendt,D.,Tessmar-Raible,K.,Synman,H.,Dorresteijn,A.,Wittbrodt,J.(2004)Ciliaryphotoreceptorswithavertebrate-typeopsininaninvertebratebrain,Science306:869–871.Anassociatedcommentaryappearedwiththepiece:Pennisi,E.(2004)Worm’slight-sensingproteinssuggesteye’ssingleorigin,Science306:796–797.AnearlierreviewbyArendtprovidesthelargerframeworkthatheusestointerpretthediscovery:Arendt,D.(2003)Theevolutionofeyesand

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photoreceptorcelltypes,InternationalJournalofDevelopmentalBiology47:563–571.FurthercommentarycanbefoundinPlachetzki,D.C.,Serb,J.M.,Oakley,T.H.(2005)Newinsightsintophotoreceptorevolution,TrendsinEcologyandEvolution20:465–467.StillmorecommentaryonArendtandWittbrodt’sworkbyBerndFritzschandJoramPiatigorskyappearedinalaterissueofScience,withacomment-replythatdiscussedthenotionthattheoriginofeyesmaybeextremelyancient,andtracedtoaverydeepbranchofourevolutionarytree.ThistextcanbefoundinScience(2005)308:1113–1114.AreviewofWalterGehring’sworkonPax6andits

consequencesforeyeevolutioniscontainedinapersonalaccount:Gehring,W.(2005)Newperspectivesoneyedevelopmentandtheevolutionofeyesandphotoreceptors,JournalofHeredity96:171–184.Papersthatlookatthedifferentpossiblerelationships

betweenconservedeyeformationgenesandtheevolutionofeyeorgansincludeOakley,T.(2003)Theeyeasareplicatinganddivergingmodulardevelopmentalunit,TrendsinEcologyandEvolution18:623–627,andNilssonD.-E.(2004)Eyeevolution:aquestionofgeneticpromiscuity,CurrentOpinioninNeurobiology14:407–414.Therelationshipbetweenthelensproteinsinoureyes

andthoseoflarvalseasquirtsisdiscussedinShimeld,S.,Purkiss,A.G.,Dirks,R.P.H.,Bateman,O.,Slingsby,C.,Lubsen,N.(2005)Urochordateby-crystallinandtheevolutionaryoriginofthevertebrateeyelens,CurrentBiology15:1684–

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1689.

CHAPTERTENEARS

ThegeneticsofinnerearevolutionisdiscussedinBeisel,K.W.,andFritzsch,B.(2004)Keepingsensorycellsandevolvingneuronstoconnectthemtothebrain:molecularconservationandnoveltiesinvertebrateeardevelopment,BrainBehaviorandEvolution64:182–197.EardevelopmentandthegenesbehinditarediscussedinRepresa,J.,Frenz,D.A.,VandeWater,T.(2000)Geneticpatterningofembryoniceardevelopment,ActaOtolaryngolica120:5–10.Thetransformationofthehyomandibulaintothestapes

isreviewedincomprehensivebook-lengthtreatmentsoftheevolutionofprimitivefishortheoriginofland-livinganimals:J.Clack,GainingGround(Bloomington:IndianaUniversityPress,2002);P.Janvier,EarlyVertebrates(Oxford,Eng.:OxfordUniversityPress,1996).Itisalsodiscussedinrecentresearchpapers,includingClack,J.A.(1989)Discoveryoftheearliestknowntetrapodstapes,Nature342:425–427;Brazeau,M.,andAhlberg,P.(2005)Tetrapod-likemiddleeararchitectureinaDevonianfish,Nature439:318–321.Theoriginofthemammalianmiddleearisdiscussed

fromtheperspectiveofascientifichistorianinP.Bowler,Life’sSpendidJourney(Chicago:UniversityofChicagoPress,1996).Keyprimarysourcesinclude:Reichert,C.(1837)UberdieVisceralbogenderWirbeltiereimallgemeinenund

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derenMetamorphosenbeidenVogelnundSaugetieren,Arch.Anat.Physiol.Wiss.Med.1837:120–222;Gaupp,E.(1911)BeiträgezurKenntnisdesUnterkiefersderWirbeltiereI.DerProcessusanterior(Folii)desHammersderSaugerunddasGonialederNichtsäuger,AnatomischerAnzeiger39:97–135;Gaupp,E.(1911)BeiträgezurKenntnisdesUnterkiefersderWirbeltiereII.DieZusammensetzungdesUnterkiefersderQuadrupeden,AnatomischerAnzeiger,39:433–473;Gaupp,E.(1911)BeiträgezurKenntnisdesUnterkiefersderWirbeltiereIII.DasProblemederEntstehungeines“sekundären”KiefergelenkesbeidenSäugern,AnatomischerAnzeiger,39:609–666;Gregory,W.K.(1913)Critiqueofrecentworkonthemorphologyofthevertebrateskull,especiallyinrelationtotheoriginofmammals,JournalofMorphology24:1–42.Majorliteratureontheoriginofthemammalianjaw,

chewing,andthethree-bonedmiddleearincludesCrompton,A.W.(1963)Theevolutionofthemammalianjaw,Evolution17:431–439;Crompton,A.W.,andParker,P.(1978)Evolutionofthemammalianmasticatoryapparatus,AmericanScientist66:192–201;Hopson,J.(1966)Theoriginofthemammalianmiddleear,AmericanZoologist6:437–450;Allin,E.(1975)Evolutionofthemammalianear,JournalofMorphology147:403–438.TheevolutionaryoriginofPax2andPax6andthe

evolutionarylinkofearsandeyestoboxjellyfishisdiscussedinPiatigorsky,J.,andKozmik,Z.(2004)Cubozoanjellyfish:anevo/devomodelforeyesandothersensory

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systems,InternationalJournalforDevelopmentalBiology48:719–729.Linksofsensoryreceptormoleculestodifferent

moleculesinbacteriaarediscussedinKung,C.(2005)Apossibleunifyingprincipleformechanosensation,Nature436:647–654.

CHAPTERELEVENTHEMEANINGOFITALL

Themethodsofphylogeneticsystematicsarediscussedinanumberofsources.KeyprimaryliteratureincludestheclassicworkofWilliHennig,publishedoriginallyinGerman(GrundzügeeinerTheoriederphylogenetischenSystematik[Berlin:DeutscherZentralverlag,1950])andtranslatedintoEnglishmorethanadecadelater(PhylogeneticSystematics,trans.D.D.DavisandR.Zangerl[Urbana:UniversityofIllinoisPress,1966]).Methodsofphylogeneticreconstruction,whichformthe

basisforthechapter,arediscussedindetailinP.Forey,ed.,Cladistics:APracticalCourseinSystematics(Oxford,Eng.:ClarendonPress,1992);D.Hillis,C.Moritz,andB.Mable,eds.,MolecularSystematics(Sunderland,Mass.:SinauerAssociates,1996);R.DeSalle,G.Girbet,andW.Wheeler,MolecularSystematicsandEvolution:TheoryandPractice(Basel:BirkhauserVerlag,2002).Acomprehensivetreatmentofthephenomenonof

independentevolutionofsimilarfeaturesisinM.SandersonandL.Hufford,Homoplasy:TheRecurrenceof

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SimilarityinEvolution(SanDiego:AcademicPress,1996).Toseethetreeoflifeandthedifferenthypothesesforthe

relationshipsbetweenlivingcreatures,visithttp://tolweb.org/tree/.Thenotionthatourevolutionaryhistoryhasmedical

implicationshasbeenthesubjectofseveralgoodrecentbooks.Forcomprehensiveandwell-referencedtreatments,seeN.Boaz,EvolvingHealth:TheOriginsofIllnessandHowtheModernWorldIsMakingUsSick(NewYork:Wiley,2002);D.Mindell,TheEvolvingWorld:EvolutioninEverydayLife(Cambridge,Mass.:HarvardUniversityPress,2006);R.M.NesseandG.C.Williams,WhyWeGetSick:TheNewScienceofDarwinianMedicine(NewYork:Vintage,1996);W.R.Trevathan,E.O.Smith,andJ.J.McKenna,EvolutionaryMedicine(NewYork:OxfordUniversityPress,1999).TheapneaexampleIderivedfromdiscussionswithNino

Ramirez,chairmanoftheDepartmentofAnatomyattheUniversityofChicago.ThehiccupexampleisderivedfromStraus,C.,etal.(2003)Aphylogenetichypothesisfortheoriginofhiccoughs,Bioessays25:182–188.Thehuman-bacterialgeneswitchusedinthestudyofmitochondrialcardioencephalomyopathywasoriginallydiscussedinLucioli,S.,etal.(2006)IntroducinganovelhumanmtDNAmutationintotheParacoccusdenitriticansCOX1geneexplainsfunctionaldeficitsinapatient,Neurogenetics7:51–57.

ONLINERESOURCES

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Anumberofwebsitesandblogscarryaccurateinformationandareupdatedfrequently.

http://www.ucmp.berkeley.edu/ProducedbytheMuseumofPaleontologyattheUniversityofCalifornia–Berkeley,thisisoneofthebestonlineresourcesonpaleontologyandevolution.Itiscontinuouslyupdatedandrevised.

http://www.scienceblogs.com/loom/ThisisCarlZimmer’sblog,awell-written,timely,andthoughtfulsourceofinformationanddiscussiononevolution.

http://www.scienceblogs.com/pharyngula/P.Z.Myers,aprofessorofdevelopmentalbiology,writesthisaccessible,informative,andcutting-edgeblog.Thisisarichsourceofinformation,wellworthfollowing.

BothZimmer’sandMyers’sblogsareathttp://www.scienceblogs.com,asitethatcontainsanumberofexcellentblogsalsoworthfollowingforinformationandcommentaryonrecentdiscoveries.BlogsrelevanttothethemeofthisbookatthatsiteincludeAfarensis,TetrapodZoology,EvolvingThoughts,andGeneExpression.

http://www.tolweb.org/tree/TheTreeofLifeProjectprovidesaregularlyupdatedandauthoritativetreatmentoftherelationshipsamongallgroupsoflife.LiketheUCMP

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pageatBerkeley,italsoincludesresourcesforlearningabouthowevolutionarytreesaremadeandinterpreted.

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ACKNOWLEDGMENTS

Alltheillustrations,exceptwherenoted,arebyMs.KalliopiMonoyios(www.kalliopimonoyios.com).Kapireaddraftsofthemanuscriptandnotonlyimprovedthetextbutdesignedartthatmatchedit.Ihavebeentrulyfortunatetoworkwithsomeonewithsomanytalents.ScottRawlins(ArcadiaUniversity)generouslygavepermissiontousehiselegantrenderingofSauripterusinChapter2.TedDaeschler(AcademyofNaturalSciencesofPhiladelphia)graciouslyprovidedhissuperbphotosofthegreatTiktaalik“C”specimen.ThanksareduetoPhillipDonoghue(UniversityofBristol)andMarkPurnell(UniversityofLeicester)forpermissiontousetheirrenderingoftheconodonttootharray,McGraw-HillforpermissiontousethetextbookfigurethatstartedthehuntforTiktaalik,andStevenCampanaoftheCanadianSharkResearchLaboratoryforthephotosofsharkorgans.Oneofthegreatestdebtsstudentsofanatomyhaveisto

thepeoplewhodonatetheirbodiessothatwecanlearn.Itisarareprivilegetolearnfromarealbody.Sittingthroughlonghoursinthelab,onefeelsaveryprofoundconnection

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tothedonorswhomaketheexperiencepossible.Ifeltthatconnectionagainwhilewritingthisbook.TheideasIpresentherearerootedinresearchI’vedone

andinclassesI’vetaught.Colleaguesandstudentstoonumeroustoname—undergraduates,medicalstudents,andgraduatestudents—haveplayedaroleinthethinkingthatwentintothesepages.IoweagreatdebttothecolleaguesIhaveworkedwith

overtheyears.TedDaeschler,FarishA.Jenkins,Jr.,FredMullison,PaulOlsen,WilliamAmaral,JasonDowns,andChuckSchaffhaveallbeenpartofthestoriesItellhere.WithoutthesepeopleIwouldhavehadnoreservoirofexperienceonwhichtodraw,norwouldIhavehadasmuchfunalongtheway.MembersofmylaboratoryattheUniversityofChicago—RandallDahn,MarcusDavis,AdamFranssen,AndrewGillis,ChristianKammerer,KalliopiMonoyios,andBeckyShearman—allinfluencedmythinkingandtoleratedmytimeawayfromthebenchasIwrote.Colleagueswhogavetheirtimetoprovideneeded

backgroundorcommentsonthemanuscriptincludeKamlaAhluwalia,SeanCarroll,MichaelCoates,RandallDahn,MarcusDavis,AnnaDiRienzo,AndrewGillis,LanceGrande,ElizabethGrove,NicholasHatsopoulos,RobertHo,BettyKatsaros,MichaelLaBarbera,ChrisLowe,DanielMargoliash,KalliopiMonoyios,JonathanPritchard,VickyPrince,CliffRagsdale,NinoRamirez,CallumRoss,AviStopper,CliffTabin,andJohnZeller.HaythamAbu-Zaydhelpedwithmanyadministrativematters.Myownteachers

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ofanatomyintheHarvard–MITHealthSciencesandTechnologyprogram,FarishA.Jenkins,Jr.,andLeeGehrke,stimulatedaninterestthathaslastedovertwentyyears.Keyadviceattheinceptionoftheproject,andinspiration

throughout,camefromSeanCarrollandCarlZimmer.TheWellfleetPublicLibrary(Wellfleet,Massachusetts)

providedacomfortablehome,andmuch-neededretreat,whereIwrotesignificantpartsofthebook.AbriefstintattheAmericanAcademyinBerlinputmeinanenvironmentthatprovedcriticalwhenIwascompletingthemanuscript.Mytwobosses,Dr.JamesMadara,M.D.(CEO,University

ofChicagoMedicalCenter,VicePresidentforMedicalAffairs,DeanandSaraandHaroldThompsonDistinguishedServiceProfessorintheBiologicalSciencesDivisionandthePritzkerSchoolofMedicine),andJohnMcCarter,Jr.(CEO,TheFieldMuseum),supportedthisprojectandtheresearchbehindit.Ithasbeenatruepleasuretoworkwithsuchinsightfulandcompassionateleaders.IhavebeenfortunatetoteachattheUniversityof

ChicagoandtohavehadtheopportunitytointeractwiththeleadershipofthePritzkerSchoolofMedicinethere.Thedeans,HollyHumphreyandHalinaBruckner,graciouslywelcomedapaleontologisttotheirteam.ThroughinteractingwiththemIcametoappreciatethechallengesandimportanceofbasicmedicaleducation.IthasbeenagreatpleasuretobeassociatedwithThe

FieldMuseuminChicago,whereIhavehadtheopportunitytoworkwithauniquegroupofpeoplededicatedto

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scientificdiscovery,application,andoutreach.ThesecolleaguesincludeElizabethBabcock,JosephBrennan,SheilaCawley,JimCroft,LanceGrande,MelissaHilton,EdHorner,DebraMoskovits,LauraSadler,SeanVanDerziel,andDianeWhite.Iamalsogratefulforthesupport,guidance,andencouragementIhavereceivedfromtheleadersoftheCommitteeonScienceoftheBoardofTrusteesatTheFieldMuseum,JamesL.AlexanderandAdeleS.Simmons.Iamindebtedtomyagent,KatinkaMatson,forhelping

meturnanideaintoaproposalandforadvicethroughouttheprocess.IfeelprivilegedtohaveworkedwithMartyAsher,myeditor.Likeapatientteacher,hegavemeanurturingcombinationofadvice,time,andencouragementtohelpmefindmyway.ZacharyWagmancontributedtothisprojectincountlesswaysbybeingfreewithhistime,keeneditorialeye,andgoodcounsel.DanFrankmadeinsightfulsuggestionsthatstimulatedmetothinkaboutthestoryinnewways.JolantaBenalcopyeditedthetextandimprovedthepresentationimmeasurably.IamverygratefultoEllenFeldman,KristenBearse,andtheproductionteamfortheirhardworkunderatightschedule.Myparents,GloriaandSeymourShubin,alwaysknew

thatIwouldwriteabook,evenbeforeIdid.Withouttheirfaithinme,IdoubtthatIeverwouldhaveputawordonpaper.Mywife,MicheleSeidl,andourchildren,Nathanieland

Hannah,havebeenlivingwithfish—bothTiktaalikandthis

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book—forthebetterpartoftwoyears.MichelereadandcommentedoneverydraftofthistextandsupportedlongweekendabsenceswhileIwrote.Herpatienceandlovemadeitallpossible.

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Copyright©2008byNeilShubin

Allrightsreserved.PublishedintheUnitedStatesby

PantheonBooks,adivisionofRandomHouse,Inc.,NewYork,andinCanadabyRandomHouseofCanadaLimited,

Toronto.PantheonBooksandcolophonareregisteredtrademarksof

RandomHouse,Inc.AllillustrationsbyKalliopiMonoyiosunlessotherwise

noted.

LibraryofCongressCataloging-in-PublicationData

Shubin,Neil.Yourinnerfish:ajourneyintothe3.5-billion-yearhistory

ofthehumanbody/ByNeilShubin.—1sted.p.cm.

Includesbibliographicalreferences.eISBN:978-0-307-37716-6

1.Humananatomy—Popularworks.2.Humanevolution—Popularworks.I.Title.

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http://www.pantheonbooks.com

TableofContentsTitlePageDedicationPrefaceONEFindingYourInnerFishTWOGettingaGripTHREEHandyGenesFOURTeethEverywhereFIVEGettingAheadSIXTheBest-Laid(Body)PlansSEVENAdventuresinBodybuildingEIGHTMakingScentsNINEVisionTENEarsELEVENTheMeaningofItAllEpilogueNotes,References,andFurtherReadingAcknowledgmentsCopyright

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TableofContents

TitlePage 2Dedication 4Preface 5ONEFindingYourInnerFish 7TWOGettingaGrip 39THREEHandyGenes 61FOURTeethEverywhere 81FIVEGettingAhead 108SIXTheBest-Laid(Body)Plans 129SEVENAdventuresinBodybuilding 154EIGHTMakingScents 185NINEVision 197TENEars 209ELEVENTheMeaningofItAll 229Epilogue 263Notes,References,andFurtherReading 267Acknowledgments 289Copyright 294

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