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EVOLVINGTOMORROW

ADVANCEPRAISEFORTHEBOOK

“Cutterpresentsuswithawonderfullystimulatingbook.Ratherthansimplyyetanother basicintroductiontoevolutionaryprocesseswithsomehighlightsofpromisesfrom moderngeneticengineering,theauthorelegantlyweavesinpersonalnarratives,naturalhistoryexamples,andinspiringthoughtexperiments.Whowouldn’twanttoreada step-by-stepaccountofhowtobuildadragon,forexample?Importantly,healsohas thereaderconsiderconsequencesofindiscriminateapplicationsofgeneticengineering, suchastheeffectsofourownbiasesandassumptionsaroundnormativity.”

MohamedNoor,ProfessorofBiologyandInterimViceProvost forAcademicAffairs,DukeUniversity.

“EvolvingTomorrow guidesreadersonanawe-inspiringjourneythroughthespectacularpotentialofmodernDNAtechnologies.WenowpossessGod-likepowersbeyond anythinghumanshavehadbefore.WecouldendmalariabytweakingtheDNAof mosquitoestomakethemgoextinct.Wecouldbringbacktheanimalswe’vewiped offthefaceoftheEarth,likemammoths,woollyrhinos,andcavelions.Wemayevenbe abletocreatefire-breathingdragons.Butshouldwe?Cutterexploresthesethemes,and others,asheseesthemonthefrontlinesofDNAscience,presentingthemclearlyin thecontextofevolutionarybiology.Thisbookisamust-readforanyonecuriousabout thepotentialofgenetictechnologiestocontroltheveryfateofnature,itself.Andifyou happentobesomeonewhowantstobuildadragonfromscratch,thenit’sagoodbook foryou,too!”

DanielRiskin,AdjunctProfessor,UniversityofTorontoMississauga, TVHost,andProducer.

“AsherCutterarmsthereaderwitharobustunderstandingoftheevolutionaryprocess andthenasksthemtoapplythisknowledgetoconsiderhowwe,humans,areanewkind ofevolutionaryforce. EvolvingTomorrow isanexcellentprimerforanyonehopingto understandhowtoday’sbiotechnologies-andthewaywechoosetousethem-havethe powertochangealloflifeonEarth.”

BethShapiro,Professor,UniversityofCalifornia,SantaCruz.Authorof Howto CloneaMammoth and LifeAsWeMadeIt.

“Cutterhaswrittenahighlyenjoyableandthought-provokingbookabouttheways inwhichtimelessbiologicalprocessesandevermorepowerfulhumantinkeringare, together,shapingtheevolutionaryfuture.Amustreadforanyonewhocaresaboutthe futureofhumanityandtherestoflife.”

RobDunn,Professor,NorthCarolinaStateUniversity.

EvolvingTomorrow

GeneticEngineeringandtheEvolutionaryFuture oftheAnthropocene

DepartmentofEcology&EvolutionaryBiology,UniversityofToronto

GreatClarendonStreet,Oxford,OX26DP, UnitedKingdom

OxfordUniversityPressisadepartmentoftheUniversityofOxford. ItfurtherstheUniversity’sobjectiveofexcellenceinresearch,scholarship, andeducationbypublishingworldwide.Oxfordisaregisteredtrademarkof OxfordUniversityPressintheUKandincertainothercountries

©AsherD.Cutter2023

Themoralrightsoftheauthorhavebeenasserted Allrightsreserved.Nopartofthispublicationmaybereproduced,storedin aretrievalsystem,ortransmitted,inanyformorbyanymeans,withoutthe priorpermissioninwritingofOxfordUniversityPress,orasexpresslypermitted bylaw,bylicenceorundertermsagreedwiththeappropriatereprographics rightsorganization.Enquiriesconcerningreproductionoutsidethescopeofthe aboveshouldbesenttotheRightsDepartment,OxfordUniversityPress,atthe addressabove

Youmustnotcirculatethisworkinanyotherform andyoumustimposethissameconditiononanyacquirer

PublishedintheUnitedStatesofAmericabyOxfordUniversityPress 198MadisonAvenue,NewYork,NY10016,UnitedStatesofAmerica BritishLibraryCataloguinginPublicationData Dataavailable

LibraryofCongressControlNumber:2022952187

ISBN978–0–19–887452–2

DOI:10.1093/oso/9780198874522.001.0001

Printedandboundby CPIGroup(UK)Ltd,Croydon,CR04YY

LinkstothirdpartywebsitesareprovidedbyOxfordingoodfaithand forinformationonly.Oxforddisclaimsanyresponsibilityforthematerials containedinanythirdpartywebsitereferencedinthiswork.

Formymostpreciousexperimentsinevolution,BeatrixandOona,andallthekin oftheirgeneration:Fletcher,Lucy,Damon,Jasper,EddieArlene,Hildegard,andArlo.

Part2Evolutionaryfutures

Preface

Icanpromiseyouthatlifetoday,despitemillenniaofprofoundevolutionarychange,will continuetoevolvetomorrow.Someofthatevolutiontospecies’featureshasnothingto dowithhumanity.Someofitarisesasanincidentalbyproductofourexistence.And someevolutionresultsdirectlyfromintentionalinterventionbypeople.Thisbookwill scrutinizehowallofthatevolutionarychangecanhappen,howmodern-daygenetic engineeringcaninfluenceit,andwhatconsequencesoftheseforceswecanexpectto seeinthefutureoftheAnthropoceneera.

Part1ofthisbook, Theheartsofnature,exploreshowlivingorganismschangeover time.Overthesefirst10chapters,we’llunearthnature’sevolutionaryforcesandhow theseforcesinterplaywithgenetics.Part1explainstheintricaciesofgeneticbiotechnologieslikeCRISPR-Cas9genomeediting,andhowCRISPR-Cas9,whenusedtomake genedrives,nowpermitshumanstomodifythegenomesofeverysingleindividualinany speciesofourchoosing.Imakethecasethatthiskindofgeneticengineering,“genetic welding,”unleashedintothewild,willpresentanewforceofevolution.Ishowjusthow fastevolutioncanproceedtochangeaspecies,andwe’lllearnwhatitisthatmakesa speciesaspeciesinthefirstplace.Iinfusetheconceptualpointswithincredibletalesof organismalbiology:ofmelanicsquirrelsandblanchedmice,oftomatoesandtheopsin genesthatletussee,ofcrocodilesandskunkmusk,ofchimericsexandofthevirtues ofchickens.Idrawonmyownexperienceoflivingonthreecontinentsandconducting researchinthelabandinthefieldoftropicalhabitatsoverthepastfewdecades.

Part2, Evolutionaryfutures,shiftsattentiontowardtheapplicationsandimplications ofusingevolutionaryforces,andgeneticengineering,tomanipulateorganismsandto createnewspecies.We’llwalkthroughtheecosystemconsequencesofspeciesgainand lossinourcurrentAnthropoceneera.We’lldeliberatetheins-and-outsofde-extinction withaurochsandwoollymammoths,ofrewildingwithwisent(Europeanbison)and chestnuts,of“pest”controloverinvasivespecieslikehippos,allasmodernlarge-scale incarnationsofecologicalrestoration.We’llponderthefigurativedragonsthatwewould needtoconfrontinapplyinggeneticweldingtocreateandintroducenewspeciesinto ecosystems.Fromtheviewofgenetics,humansarejustanotheranimal.Inconsidering theethicalsoupofgeneticengineeringofourownspecies,Ihighlightlessonsfrombody modificationandinvitrofertilization,identifyingthepotentialforgeneticweldingof humangenomestounleashwhatIterm guerrillaeugenics.Isharemyowninternalconflictsinthesemultifacetedethicaldiscussions.We’lllaybarethecompetingandoften internallyinconsistentviewsofwhatis“wild”andwhatpeopledesirefrom“nature,” theoft-neglectedconsiderationsthatarecrucialindecidinghowhumansshoulddeploy orpreventevolutionaryengineeringandgeneticweldinginecosystems.Whatwedecide

todoasaglobalsocietywillshapethekindofevolutionarychangethatwillaccumulate intheworldoftomorrowandthroughoutthenextmillennia.

Inpreparing EvolvingTomorrow,I’vehadthegoodfortuneofgoodcolleaguesand goodsupports.Forexpertconsultationonmyblue-moonquestions,Iamgrateful tothekindandquickmindsofSpencerC.H.Barrett,JohnCalarco,BelindaChang, MarcT.J.Johnson,LukeMahler,ShelbyRiskin,F.HelenRodd,NjalRollinson,and StephenWright.IalsobenefitedfromGrahamCoop’slucidinsightsintogeneticsdeliveredonaverysnowyeveningforthe2019DarwinDaylectureattheUniversityof Toronto.ThanksalsogotoAshleyReynoldsforassistancewiththeteachingcollectionofmammalbonesintheDepartmentofEcology&EvolutionaryBiology.Iam fortunateforthefavorandencouragementofcarefulandthoughtfulreadersofdraft versionsofchapters.Inparticular,I’mgratefultoBelindaChang,ZoeClarke,Steven Coyne,BeatrixCutter,OonaCutter,MarcT.J.Johnson,NicoleMideo,ShelbyRiskin, Yee-FanSun,JasonWeir,andStephenWright.ThankyoualsototheEvolutionary GeneticsDiscussionGroupandthemembersofmyresearchteamattheUniversityof Toronto,fordiscussionofearlyversionsofchapters,includingEniolayeBalogun,Maia Dall’Acqua,DanielFusca,KarlGrieshop,VedikaJha,KatjaKasimatis,ElseMikkelsen, ChristineRehaluk,RebeccaSchalkowski,MaríaTocora,AthmajaViswanath,Sabrina Zaidi,andLinyiZhang.I’mveryappreciativeofmyproductioneditor,KatieLakina, forkeepingitallinorder.I’mindebtedtomyeditor,IanSherman,atOxfordUniversity Press,forhisencouragementandfrankadviceinworkingfromtheproposalthroughto bookfinalization,andtothecollectionofthoughtfulanonymousreviewersoftheinitial bookproposalwhosharedexceptionalconstructivefeedback.Oneaccidentalblessing oftheCOVID-19pandemicisthatitgiftedmetheluxuryofwritingthisbookfrom homewhilesurroundedbyfamily.Iamcontinuallygratefulfortheloveandsupportof Yee-Fan,Oona,andBeatrix,inallthosemomentswhenIneededitmost.

Mygrowthasascientistwasshapedbyalongtrainofbiologicalmentorswhotook greatcareinguidingmydevelopment,startingfromwhenIwasateenager.Thankyou, LeoP.Kenney,NortonH.Nickerson,SaraM.Lewis,StephenH.Levine,MichaelP. Ghiglieri,ChristopherA.M.Reid,LeticiaAvilés,SamuelWard,DeborahCharlesworth, andBrianCharlesworth.WhileIamsoverygratefulforthepersonalcontributionsof theseindividualpeopletomyparticularscientificdevelopment,mydebtrunsdeeper: totheentirecommunityoftheworld’sscientists,pastandpresent.Theopensharingof theirfindingsanddata,aswellastheblossomingandfadingofideasacrossthedecades asrecordedinthescientificliterature,madethisbookpossibleandallthemoreenjoyable towrite.Theinquisitivenessandrigorofscientificresearchersindisciplinesofallstripes hasgiveneveryoneofusthiscurrentunderstandingoftheworld.

InwritingthisbookinToronto,Ontario,Igratefullyacknowledgethislandthat isnowhometodiversepeoplesasthetraditionalterritoryoftheMississaugasofthe Credit,theAnishnabeg,theChippewa,theHaudenosaunee,theWendatpeoples,and theirancestors.

Abbreviations

BRCA1: Breastcancergene1,foundinhumangenomeswithmutatedgenevariants thatconferahighlikelihoodofdevelopingbreastorovariancancerinone’s lifetime.

Cas9: CRISPR-associatedprotein9,encodedbygenesfoundinbacteriaand archaeathatisinvolvedindefenseagainstphagevirusesandthathasbeen co-optedinbiotechnologyforgenomeediting.

CCR5: C-Cchemokinereceptortype5gene,foundinhumangenomeswitha mutatedgenevariantassociatedwithresistancetoinfectionbythehuman immunodeficiencyvirus(HIV).

ClvR: Cleaveandrescuegenedrive,akindofgeneticallyengineeredselfishgenetic elementsystemthatactstoincreaseitsabundanceinapopulationasit transmitsitselffromgenerationtogeneration.

CRISPR: Clusteredregularlyinterspersedshortpalindromicrepeats,regionsofbacterialandarchaealgenomesthatencodealibraryofphageviralDNAto targetaspartoftheirimmunesystem,portionsofwhichgetexpressedto formguideRNAstoworkinconcertwithCas9proteinstocutinvadingviral DNA,asystemthathasbeenco-optedforbiotechnologicaluseingenetic engineering.

dCas9: deadCRISPR-associatedprotein9,ageneticallymodifiedversionofCas9 proteinthatdisablestheabilitytocutDNA.

DMI: Dobzhansky-Mullerincompatibility,adetrimentalinteractionbetween genesthatgetsrevealedwheninterspecieshybridsdevelop.

DNA: Deoxyribonucleicacid,thechemicalresponsibleforstoringheritablematerialinanimals,plants,fungi,bacteria,archaea,andDNA-basedviruses.

GDO: Genedriveorganism,ageneticallymodifiedorganismthatencodesa syntheticgenedriveinitsgenome.

GE: Geneticallyengineered,synonymforgeneticallymodifiedbyvirtueof alterationsofthegenomethroughdirectedmolecularbiologytechniques, typicallyinvolvingtransgenicDNA.

GFP: Greenfluorescentprotein,aproteinfoundnaturallyinthegenomesofsome jellyfishspeciesthathasbeenco-optedforuseinexperimentalmolecular biologyduetoitsabilitytoemitlightwhenexposedtoUVillumination.

GMO: Geneticallymodifiedorganism,anorganismwhosegenomeincludes changesfromgeneticengineering,usuallyoftransgenicorigin.

Abbreviations

GPCR: G-protein-coupledreceptor,akindofproteinthatispartofalargefamily ofproteinsinanimalgenomesthatlocalizetocellmembranesandoften havefunctionsrelatedtotransductionofinformationintothecell,including sensationoflightorodor.

HDR: Homologydirectedrepair,ahighlyaccuratecellularmechanismthatfixes damagedDNAbyusingasimilarsequenceofDNAasthetemplatefor repair,usuallyusingahomologouschromosomeundernaturalcircumstancesbutthatcanalsouseatemplateofDNAprovidedbyaresearcher whenconductinggenomeediting.

HGT: Horizontalgenetransfer,themovementofgeneticmaterialfromonespecies toanotherspecies,usuallyinthecontextofnaturalmicrobialmechanisms ofDNAexchange.

HHGE: Heritablehumangenomeediting,geneticengineeringappliedtohuman cellsthatwillleadtotransmissionofthegeneticchangesacrossgenerations.

IUCN: InternationalUnionforConservationofNature,anongovernmentalorganizationwithobserverstatuswithintheUnitedNationsandexpertisein environmentalissues.

IVF: Invitrofertilization,amedicalandveterinarytechniqueforhumansand othermammalstofacilitatefusionofgametesinaPetridishoutsidethebody forsubsequenttransfertothewombofahostfemaletoenablegestationof theresultingembryoandfetus.

MC1R: Melanocortin-1receptorprotein,atypeofproteinencodedingenomesof mammalsandothervertebrateswithakeyroleinthepathwayresponsible forproductionofmelaninpigments.

mRNA: Messengerribonucleicacid,theintermediarymoleculethatresultsfrom transcriptionofageneinthegenomethatwillthengettranslatedintoa protein.

MRSA: Methicillin-resistant Staphylococcusaureus,apathogenicbacteriumresponsibleforstaphinfectionsthatisnottreatablebymanyantibiotics.

NHEJ: Nonhomologousendjoining,amechanismofDNArepairthatisproneto introduceinsertionordeletionchangestotheDNAsequenceinthecourse offixingbreaksinDNA.

PGC: Primordialgermcell,akindofstemcellthatwillenabledevelopmentof spermcellsoreggcellsintheadultorganism.

PGD: Preimplantationgeneticdiagnosis,agenetictestperformedonaparticular geneatanearlystageofembryogenesisbeforeinsertingtheembryointoa wombviaIVF.

PGS: Preimplantationgenomicscreen,geneticanalysisoftheentiregenomeofan earlystageembryobeforeIVFtransferintoawomb.

Abbreviations xv

RNA: Ribonucleicacid,akindofbiomoleculethatcancontainheritableinformation(asforRNAviruses),serveasanintermediateinthetransmissionof heritableinformationinthecourseofproducingproteins(asformRNA),or functionasabioactivecomponentofcellstoinfluenceexpressionofgenesor othercellularactivities(suchasguidingCas9proteinstogenomiclocations, inthecaseofguideRNAs).

RNAi: Ribonucleicacidinterference,anexperimentaltechniquethatenablesa researchertoinhibittheexpressionofagene.

SCNT: Somaticcellnucleartransfer,akeyexperimentalprocedureusedtoclone mammalsthatinvolvesinsertionofthecellnucleusandDNAfromabody cellsuchasaskincellintoanenucleatedeggcell.

TARE: Toxin-antidoterecessiveembryogenedrive,aparticulartypeofgenetically engineeredselfishgeneticelementthatiscapableofincreasingitsabundance inthegenomesofapopulationfromonegenerationtothenext.

UV: Ultravioletlight,aformofelectromagneticradiationwithawavelength between10nmand400nm,thatisnotvisibletohumansbutcanbevisibletootherorganismswithappropriateshort-wavelength-sensitiveopsin proteins.

AbouttheAuthor

AsherD.CutterisaprofessorofEcologyandEvolutionaryBiologyattheUniversity ofToronto,Canada.AformerFulbrightScholar,CuttertrainedatTuftsUniversity, JamesCookUniversity,theUniversityofArizona,andtheUniversityofEdinburgh. Heauthoredthetextbook APrimerofMolecularPopulationGenetics,aswellasnearly 100scientificarticlesonthetopicsofgenomeevolution,populationgenetics,speciation,andthebiologyof Caenorhabditis nematoderoundworms.RaisedintheBoston, Massachusetts,area,CutterlivesinTorontowithhisfamily.

Part1 Theheartsofnature

Natureintheraw,andcooked

WanderingthelongbeachoftheGoldCoastofAustraliaononesunnyJulyafternoon,a shiftoflightcaughtmyeyeinthethinskimofsurfonthesand.Leaningdown,Icouldn’t seemuch,justanovalshimmeragainstthetansand.WhenIcuppedmyhandstohold apalmfullofwaterandsandgrains,however,IdiscoveredsomethingthatI’dnever encounteredbefore:anutterlytransparentfish-shapedcreature.Aslongasmypalm waswide,itsflat-sidedbodysportedapigmenteddarkeyeoneachsideofitshead,and itwriggledsedatelybetweenmyfingers.Itwasabsolutelystunning.Ilaterlearnedthat thiscreatureiscalledaleptocephaluslarva,thejuvenileformofamarineeel.Itwas entirelytransparentandalive,andthewispybonesofitsskeletonwereonlyjustvisible asfaintpalecreases,asifencasedinthickwetcellophane.

Iwasamazed.Ihadonlyseensuchincredibletransparencyinbonelesscreatureslike jellyfishandnematoderoundworms.Or,inthechemicallypreservedfishinjarsthat IpreppedattheSmithsonianNationalMuseumofNaturalHistoryonesummerasa student.I’dclearedandstainedtheirdeadpiscinebodiestomakevisibletheirskeleton ofcrimsonbonesandceruleancartilage,courtesyofalizarinandalcianstains,theother tissuesrenderedtransparentfromarecipeofchemicalacidsandbasesandenzymes. Notonlyhadtheexistenceof living transparentvertebrates—asee-throughliveanimal withabackbone!—somehowevadedallofmypriorexperience,buttheunexpectedness oftheencounterinnatureinthepalmofmyhandwasamarvel(Figure 1.1).

Asabiologist,perhapsIshouldnotbesurprisedthatIamconstantlysurprised.I am,though.I’msurprisedandamazedbythemultitudeofshapes,sizes,colors,and behaviorsoforganismsthatIcomeacrossyearinandyearout,ofanimalsandplants andcrittersthatareneither.

Inthedaytodayofmybiologicalresearch,though,itisstringsofDNAthatIthink aboutmost.Ithinkaboutthespace-timeofgenetics,oftheswirlofthedoublehelixofa chromosomeasthesequenceofchemicallettersonitsrungsgoontomutateandevolve. IthinkabouthowtheDNAsequencesthattrailacrossmycomputerscreenencodethe ongoingtugofdistinctandancientforcesofevolution,arecordofwhathasevolved andofcluestowhereevolutionwillgonext.Ithinkaboutwhatexperimentswemight conducttoalterthoseDNAsequences,tocreatesomethingnewtotestthelimitsofour understandingofbiologicalprinciples.JustasIcan’thelpbutmarvelatanewpersonal discoveryonabeach,Imarvelattheprospectofmeldinggeneticengineeringwiththe forcesofevolution.

Figure1.1 Transparentleptocephaluslarvaofamarineeel(Queensland,Australia),oneofthe marvelsofthelivingworldthatalreadyexists. Photobytheauthor.

Inthelaboratory,wecancreateextraordinarycreatures.Inthelaboratory,wecan usegeneticengineeringtochangeacreature’sDNAsothatitexpressescharacteristicsit neverhadbeforeorthatnocreatureeverhadbefore.Inmylab,wehavewormslikenone foundinnature:wormswithgenesthatmakethemglowgreenorredoryellowwhen youshineaUVlampontothem.Thisfactteasesabiggeridea,anigglingquestionabout lifebeyondthelab.Wouldthegreatoutdoorsalsobenefitfromnewlyevolvedcreatures, populationsofnewandextraordinaryspecies,whatwemightcallhyperexoticspecies, producedwithevolutionaryengineeringtobesoremarkablethattheworldhadnever beforeseentheirlikeness?

Ididn’talwaysthinkabouttheDNAofgenomesandhowtomessaboutwiththem. Ioncewasalittlecountryboywhosatamongtheovergrownpokeweedinthesunny gardenofmyparents’backyard,smooshingtheirbrilliantberriesandfollowingtheslow trailsofinsectsalongtheirstems.IoncewasakidwhoroamedtheNewEnglandforest thatringedmychildhoodhomeattheendofadirtroad,snatchingbullfrogsinswampy

pondsandspyingthepinksac-likeflowersofladyslipperorchids—Cypripediumacaule boorishlyrenamedas“scrotumplants”—thatsproutedfromtherustyduffofpineneedlesinspring.EvenasIgotolder,throughuniversity,itwastheouterlivesintheliving worldthatIspenttimewith.Irubbedelbowswiththeplantsandanimalsofvernalpools andbogsandmangroveswamps,Ipeepedinonthesexlivesofbeetles,Isoughtoutthe signsoflifeinEocenefossilleavesandtheantsofAustraliantropicalrainforests.

AfterItransplantedmylifefromNewEnglandtoArizonaforatime,Ibegantolearn moreabouttheinnerlivesinthelivingworld.AttheendofthatfirstyearIlivedinTucson,1999,forthefirsttimeintheworld,thefirstanimalgotitsentiregenomesequenced. It’salittlesquiggleofacreatureknownasanematoderoundworm,oftenreferredtoas C.elegans.Whenyouwatchthroughtheeyepiecesofamicroscopeastheseminiature animalsswervesinuouslywithquietdetermination,youunderstandhowtheygottheir name: elegans derivesfromtheLatinfor elegant.Also,theyaretransparent.Iwashooked. Intheensuingyearsthathavenowturnedintodecades,they’vetaughtmehowDNA makesanorganismdevelopandhowDNAchanges,howtoengineergeneticchanges, andhowthosechangesmakeanorganismdevelopdifferentlyandbehavedifferently. Ididn’tgiveuponouterlivesthough.Understandingevolutionmeanspayingattentiontoboththeunseenandtheseen,bothDNAandthemagnificentdiversityofforms andspeciesallaroundus.ForaYankeeNewEnglander,theurbanincarnationofthe SonoranDesertofArizonashowedmeanalienlandscape.Ibeganapricklypeargarden inmyTucsonbackyard.Iexploitedtheastoundingbiologicalfeatthatmanyplants,and evensomeanimals,areabletodo:togrowanentirelynewindividualfromabrokenoffpieceofanother.Transplantingthetrimmingsofdiversevarietiesof Opuntia cactus thatIscavengedinthealleysaroundmyTucsonneighborhood—palegreenandpurple cladodepads,1 cladodescoveredinlongwhitishoryellowishspikes,enormousemeraldgreencladodesnearlydevoidofspines,cladodesnearlybrownwiththedenseclusters oftawnyprickles—theresoongrewaspinydisplayoflivingplant-paddlebiodiversity unlikeanythingI’dexperiencedinmyhometownoutsideofBoston.Theyweremyintownhomagetothesaguaro,those10-m-tall(33-foot-tall)botanicaliconsthatstoodin legionsthroughoutthefoothillsofthemountainsthatringedtheedgeofthecity.

Onsomeofmycacti,tinywhitefluffballspockedthesurface.Theylookedlikeclusters ofQ-tiptopsthat,atfirst,Ithoughtmightbeafungalinfection.Afterapokeproduced asmearofshockingpurple-redbrilliance,Irealizedthattheymustbecochinealbugs, acreatureI’dheardaboutonlyinstories.Cochineal Dactylopiuscoccus arethosemagnificentso-calledscaleinsects,parasitesof Opuntia pricklypear,thatproducecopious quantitiesofcarminicacidasadefenseagainstpredators.Humansharvestthatcarminic acidtomaketheintenseredcolorofcarminedye,a.k.a.naturalred#4oringredient E120.YoumightalsoknowcarminefromtheingredientlistofallmannerofFDAapprovedcosmeticsandfoodstuffs,fromlipsticktohotdogs,store-boughtstrawberry jamtotheredveneerofimitationcrab.

Doyoueverhappenuponnatureintherawtofindsomethingunexpectedinthe wild?Somethingbeautifulorinexplicable,itmightevenbesomethingtiny,something thatcompelsasmileoragasporalaugh?Thewovendetailofabird’snestdangling onabranch,theflashofthefirstfirefly’slightonasummerevening,fossilshellsspied

inarockonacliffside,atransparentanimalcaughtinthesurfonthebeach.Thereare truewondersinthisworldrightnow,everyminute.Theyhaveouterwondersandinner wonders,encodedinDNA.Perhapsweshould—orperhapsweshouldnot—gooutof ourwaytomakemorewondrousanimals.Couldwe?Howwouldwe?And,again, should we?

Evolution,geneticengineering,ecosystems,bioethics,andthestateoftheworld— we’llneedtosiftthroughallofthesethingstoanswerthosequestions.

1.1 Thenatureofchange

Theworldisawashinchange.Decadeoverdecade,theclimateacrosstheglobehas grownhigheraveragetemperaturesandgreaterextremesoftemperature.Comparedto preindustrialperiods,theairhas50%morecarbondioxide,andtheoceansare30% moreacidic,achievinglevelsunprecedentedoverthepast65millionyears.2 Wedid that.Entirespecieshavegoneextinctatsuchanastoundingratethatsomesaythat weareamidstthesixth-greatestmassextinctioneventthatourplanethaseverexperienced.Estimatesputtheworldonapaceofnearly1000speciesextinctionsaccumulating globallyeachyear,arate1000timeshigherthanitwasprehistorically.3 Population declinesandextinctionshitsometypesoforganisms,andsomeplaces,harderthan others.Invertebrates,largeanimals,amphibians,andtheIndo-Pacificareespecially hard-hit.4 Wedidthat,too.Andatthesametime,nonnative,invasivespeciesofanimalsandplantsarriveontheshores,islands,andwaterwaysofdistantlandsanddistant lakes,rivers,andseas.Thisspreadingoflifealongsidehumanmovementtakesaway lives,too,throughextinctionsmediatedbypredation,competition,andpathogenicity.5 Yes,wealsodidthat.Wehavecometodependonsomeofthosenonnativespecies, however,forfoodorothergoods.Theyfilltheagriculturalspacethatnowoccupies over41%oftheworld’sland.6 Human-manufacturedmaterial,frombuildingstosoda bottlestothemicroplasticflecksthatinfiltratethetissuesofseeminglypristinearcticwildlife,7 nowexceedthecombinedmassofalllivingthingsonplanetEarth,all 1.1trillionmetrictonsofit.8 Westupefyinglydidthat.Theseingloriousmarkersof changethatleavegeologicallyindelibletracksontheplanetarethehallmarksofthe Anthropoceneera.9

TheAnthropoceneisthehere-and-nowepochdefinedbyhumanity’sprofoundinfluenceonchangingtheshapeofthenaturalworld.I’velistedsomeofthedirectmaterial changes,mostofwhichyouhaveprobablyheardaboutfromnewsheadlines.Youcan relatetotheircausesorconsequencesinsomepartofyourday-to-daylife.Buttheyalso impactthenaturalworldindirectly:shiftsinwaysbothsubtleandprofoundtotheecologicalinteractionsthatorganismshavewithoneanotherandwiththeenvironmentsthey livein.Thesekindsofimpactscauseshiftstothenaturalselectionpressuresthatsculpt theevolutionofthosespeciesthatmanagetopersist,thatmanagetoevadeextinction. Humanscausedallthischangeinaboutonemilliondays.Theknock-oneffectson ecosystemsandevolutionofindividualspecies,however,willfollowthelawsoflifethat haveruledtheplanetforroughly3700millionyears.10 Humansnudge,orpunch,the

scalesofthewild,tippingbalances.Butalltheusualprocessesstillapplyinhownature responds:nutrientuptakeandrelease;predation;competitionbetweenorganismsfor resources,forsunandspaceandfoodandmates;under-the-hoodevolutionaryprocesses likemutationandnaturalselectionandgeneticdrift.Allthesethingsstilloperateinthe samefundamentalwayinresponsetoallthemanhandling.Withonepotentialexception. Mankind,orinthiscasewomankind,giventhe2020awardingoftherelevantNobel PrizeinChemistrytoEmmanuelleCharpentierandJenniferDoudna,11 hasdevised biotechnologywiththecapacityforhumanstobendthoselawsoflife.

Theideaofbendingthelawsoflifemaymakeyounervous.Theideaofcarvingthe DNAofwildorganismswithtoolsofgeneticengineeringmayeveninspireinyoua feelingofhorroratthehubris.Beforeindignityjumpsuptoohigh,however,takestock ofthefactthatwe’vebeenshapingtheDNAofanimalsandplantsandmicrobesfor millennia.Humancreationofdomesticatedanimalsandplantsaretheobviouscases— thehorseandhoganddog,theBrusselssproutandNashipearandfreestonepeach. Homosapiens isalsoanecosystemengineerparexcellence,meaningthatoursuccessesin makingtheworldmoretoourlikingalsomodifiestheworldfortheinnocentbystanders. OurAnthropoceneexploitspushtheforcesofevolution,drivingchangeinresponse tonewenvironmentalconditions,habitatperturbation,eliminationoffellowspecies,or creatingoverlapamongspeciesthathadneverbeforeencounteredoneanother.The evolutionaryresponsesintheoutdoorsare,perhaps,slowenoughforusindividuallyto acclimateto,toacceptasanewnormal.Thisacclimationishowshiftingbaselinesare born,fromonegenerationtothenext,casualacceptanceofwhatisprofoundlydifferent fromthegenerationbefore.

Whattodo?Oneoptionforcivilizationistocontinuetoacclimate.Thiskindof proposalisnotnecessarilyasapatheticasitmightseem.Forexample,byproactively establishinglargeregionsforrewilding,wecouldletecologicalandevolutionaryprocessesproceedinapassiveandnoninterventionistwaytopromotebiologicaldiversity andholisticecosystemfunctionality.ThenewsoutoftheUnitedKingdom,thesedays, seemschockfullofreportsofformerpasturelandlefttoseeditselfintoforestwithout thenibblingoflargeherdsofsheepandcattle.Itthenbecomesaquestionofpatience. Wehumans,however,arenotknownforourpatience.

AnotherwingofthoughtholdsthatthesymptomsofEarth’sillsaresodirethatthe curerequiresactivetreatment,notsimplebedrest.Thatis,humansoughttotakeaheavy handinestablishingfunctioningecosystems.Tohelpkeepthemostcatastrophiceffects ofrapidclimatechangeatbay,forexample,wecouldpartakeofsolargeoengineering— alteringatmosphericchemistrytoblockoutthesun—asatemporarychemicalparasol fortheplanet.Perhapsweevenoughttomodelnatureonthestructureandcompositionofecologicallandscapespriortowidespreadhumanimpacts,so-calledPleistocene trophicrewilding.Thisplancouldintroduceexistingspeciesintoenvironmentsinwhich theirecologicalanalogsareextinct,intentionallychangingthebiotawithacascadeof ecologicalconsequences.Thisplancouldalsointroducegeneticallyengineeredspecies, perhapsspeciesresurrected—asfortheso-calledde-extinctionofmammoths—oreven brand-newspeciesevolveddenovowiththeaidofbiotechnologicaltools.

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