EvolvingTomorrow
GeneticEngineeringandtheEvolutionaryFuture oftheAnthropocene
AsherD.Cutter
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.
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.
ItisthislastpossibilitythatIwouldlikeustodwellon,topokeat.Whatwouldittake andwhatwoulditmeantoshapetheevolutionaryoriginsofnewcreaturesandtoset themlooseinthewild?Indoingso,wecouldbendthelawsoflifeandwecouldadda newevolutionaryforceintotheworld,aforcethatIcallgeneticwelding.
Thefossilrecordandthelivingworldshowusexoticcreatures.Ifwesetourminds andmusclesandmoneytoit,thefuturecouldunveilthemostexoticcreaturesofthemall. YouandImaygivetheAnthropoceneanewhallmark:populationsofnewandextraordinaryspecies.SuchhyperexoticswouldsetloosethedragonsoftheAnthropocene,both figurativelyandliterally.
1.2 Evolvingtomorrow
Asabiologist,Imaketradeinlivingphysicalsystems.So,let’sfirsttalkabouttheideaof human-mediatedevolutionofextraordinarycreaturesinacorporealsense.Despitethe bountyofexoticcreaturesinnature,technicallyspeaking,couldwecreatesomething new?Somethingthatmorecompletelycapturesthephysicalessenceofwhatitistobe entirelynovel?CouldwecreatesomethingthatistheepitomeoftheAnthropocene?To answerthisquestion,wewillneedtodigintowhatweareasking.
First,whatcharacteristicsmightweshape?Thepossibilitiesabound:sizeandcolor andlocomotion,aswellasfeaturesofphysiologyanddevelopmentandbehaviorandthe senses.Thesearethekeycharacteristicsofallanimals,howtheyinteractwitheachother andwiththerestoftheworld.Wecanexplorethediversityofoptionsthatcurrentlyexist orresurrectfeaturesthatweknowtohaveexistedfromextinctremains,tohelpdefine theso-calledmorphospaceofwhatispossible.Dippingintothisanimalmorphospaceis alsoadipintoameltingpotofinspiration.Wewillexploreindepththebodyandsoulof whatittakestobeacreatureinthenextchaptersasweprepareamentalmapforwhat ittakestobeanevolutionaryengineerofextraordinaryspecies.
Second,weneedtosetourtoolsonthetable.Someofthesetoolsareancienttools,the toolsofevolution.Humansaremoreadeptinusingevolutionarytoolsthanyoumight think.Consider,forexample,themagnificentvarietyofdogbreedsthatbringjoyand comfort,theextraordinaryproductivityofmaizeandriceplantsthatdeliverabountyof carbs,thephenomenalmilkyieldandmuscledensityofdocilecattlethatfindtheirway tosupermarketshelvesnearyou.Humansshapedgeneticchangesinthesespeciesover thecourseofdomestication,guidingtraitsthroughaprocesscalledartificialselection, theincarnationofnaturalselectiondirectedbypeople.
Evolutionrequiresthatwehaveapopulationoforganismswithgeneticheterogeneity withinit.Themoreabundantandvariablethepopulation,themorerawmaterialthere isforselectiontochiselandchipaway.Whatyoumightnotalsorealizeisthatevolution ishappeningallaroundus,allthetime.Thatevolutioncanhappenfastenoughforus towatchit,andfastenoughtomoldit.
Othertoolsarenewtools,thetoolsofbiotechnologyandgeneticengineering.One classofsuchmoderntoolsarebluntbuteffective.Forexample,weknowhowtoinduce
geneticchangewithchemicalmutagensasacrudebutpotentmeanstoanend.Other toolsactwithgreatprecision,includingaspectrumofapplicationstogeneeditingusing CRISPR-Cas9techniques.Ifyouareunfamiliarwiththetangleofkeyboardcharacters thatspells“CRISPR-Cas9,”thentakeheart,asalaterchapterwillcoverwhatyouneed toknow.Thisboxofmoleculartools,co-optedfromthecellularmachinerythatbacteriaevolvedasacounterstrikeagainstviralattacks,canletusmanipulateorremove individualDNAletters,orwholegenes,aswellasinsertnovelgenesorgeneregulators atpreciselocationsingenomes.
Genomeediting,onitsown,whetherwithCRISPR-Cas9orothertechniques,introducesnovelgeneticvariantsintoDNA.Initsmostbasicsense,thisisnearlyidentical towhatmutationdoesortowhatgeneflowdoeswhenmigrantsfromoneplaceinterbreedwithresidentsofanotherlocale.Humaningenuity,however,hasledresearchers tomeldgenomeeditingwithourunderstandingofhowtheforcesofevolutionoperate.Thisblendingofevolutionaryprincipleswithbiotechnologicaltoolsnowgivesa waytopropagatethroughoutanentirewildspeciesanygivennovelDNAvariantconstructedbygeneticengineering.Inthecontrolledconfinesofthelab,theyarecalledgene drives.Deployedintonature,weshallseehowgenedrivesarethefoundationforgenetic welding,anewforceofevolution.
Wewillunpackthisslateoftoolsthatwehaveatourdisposal,fromthetoolsofevolutiontothetoolsofbiotechnology.Bycombiningthesetools,wehavetheopportunity tobecomemoreskillfulevolutionaryengineerswiththecapacitytodirecttheevolution ofwildorganismsoutsidetheconfinesofthelaboratory,oreventodirecttheevolution ofnewspeciesaltogether.We’llseehowthesetoolsoperate,bycreatingandharvesting geneticdifferencesandthenalteringtheabundanceofthosegeneticchangesintheface ofconstraintsandlimitations.Ishumanityinapositiontocreatebiologicallyhyperexotic entities,newspecieswithuniquecharacteristics,aliving-and-breathinghallmarkofthe Anthropocene?Moresothaneverbefore.
Thecreationbyhumansofrobustpopulationsofextraordinarynewspeciesthrough evolutionaryengineeringwould,asitturnsout,createsomethingelseonthesly,beforehand,whetherwelikeitornot.Itcreatesfigurativedragons,themonstersthatinhabit everycornerofourimagination,theconcerns,suspicions,andworries.
Theprospectofdisruptingthenaturalorderoflivingthings,understandably,stirs uneaseinallofourhearts.Forsome,thisworrystemsfromreligioussensibility.Itcomes fromthesensethatgeneticengineeringorperturbingnaturalsystemsisakintoplaying godand,consequently,blasphemousandimmoral.Forothers,likeme,theapprehensionissecular.Theconcernsarerootedmoreinasensethatthereisintrinsicvaluein lettingnaturegoaboutitsbusinesswithoutunduehumanintervention.FortheStarTrek aficionados,thisisthelogicofthePrimeDirective.12 Peoplefeeltheseviewsintheirgut, aswellasintheirmind,sometimestranslatingintorawemotion.Whateverthebasis,the senseisthatmessingwithDNAisjustplainwrong—nomatterthatwe’vebeenmessing withDNAinotherwaysformillennia.And,ofcourse,humansarejustanotherkindof animal.Geneticmanipulationofourowngenomescouldbeundertaken,inprinciple,in
exactlythesamewayasforanyotherkindofanimal.Anyapplicationofbiotechnology mustconfrontthesefigurativedragonssoberlyandwithnuance,aswewilldoinlater chapters.
Weshouldalsoanticipateasecondrealmofapprehensioninanyattempttocreatenew species.Itdealswiththepoliticalandeconomicviewsthatpeoplehold.Whilesomefolks ascribetoanything-goescapitalism,othersareleeryofstrictlyfinancialprofit-driven motivesandtheirnegativeknock-oneffectstosociety.Forexample,corporatepatents overgeneticallymodifiedorganismsandmonopoliesoverbiologicalentitiesrepresent moralaffrontstomanypeople.Whenpublicfundsareinvested,theynecessarilycome withtheopportunitycostofnotinvestinginsomethingelsethatmightbenefitsociety.Thistensioninsocietyaboutwhattodevotetaxdollarsto,orwhatnotto,forms afundamentalaxisofstrifebetweenpoliticalviews.Wemustconsiderinearnestsuch legitimatedifferencesinperspective.Deepspendingbygovernmentsonafocusedissue oftencomeswithformidablelong-termbenefits:thinkhowtheApollomissions,tosend spacecrafttotheMoon,sparkednewinnovationsandentrepreneurialspin-offs.Yet, italsoechoestherationalizationsofcolonialismandtheravagesthatitexactedonthe partsofourglobalsocietythatwieldlesspower.Thepoliticsandeconomicsofbiologicaladventurismisfraughtwithcompetingperspectivessuchasthesethatdemand thoughtfulpublicdebate.
Lifeisfullofrisks,butweallvaryinhowillateasewefeelfromanygivenrisk. TheCOVID-19pandemictaughtusafastlessoninhowindividualrisktolerancevaries frompersontopersonaswecametonavigatenewsocialnormswithfriendsandfamily andcoworkers.13 Aforayintothebiologicalunknownalsohasrisks.Thekeyriskisthat welosecontrolinawaythatcascadeswithdetrimentaleffectonthenaturalworldor onsociety,tomorroworforthenextgenerationorforthenextmillennium.Afterall, biologicalsystemsarepredisposedtotakingonalifeoftheirown,evolutiondriving theirdestinyinunexpectedways.Anexoticorganismmayproveinvasive,anewkudzu, fireant,orcanetoadwritlarge.Theymaydisruptecosystems,driveotherspeciesto extinction,orintroducediseasesthatdevastatewildlifeorevenhumanhealth.14
Wehumanshavegoodexperience,asaninvasivespeciesourselves,withdrivinganimalsandplantstoextinction.Moa,groundsloths,andaurochscometomind,justto nameafewlargeexamples.Nonnativespeciesmaychangethefaceoflandscapesor imposenovelselectionpressuresonotherspecies,ortheymayexactfinancialimpacts— ontourism,ecologicalremediationefforts,andmedicalcosts.Therealsoarerisks, sometimesevenworse,ofdoingnothing.Wemust,asasociety,assesshowtolerant oraversewearetojudgetherisk-rewardtrade-offindecision-making,todosomething ornot.
Natureisfullofexotics.Withallthispre-existingwonderintheworld,itisfairtoask: Whybothertoembarkonabiologicalmissiontocreateyetanotherexoticspecies,even ifitissouniquethattheworldhasneverencountereditbefore?
Wehumansareacuriousspecies.Whenshownamapoftherealmofknowledge, theedgecallstoustoresolvetheboundarywithunderstanding.Inthescribblethat notes“herebedragons,”weseeaconjecture,ahypothesisworthtesting.Ourhistoryof
explorationprovesit,fromgeographicmigrationoutofAfricatotherestoftheworld, fromsurfacetosubmarinetoouterspace.Ourhistoryofingenuityprovesit,too.The goal,andtheresult,oftheApolloMoonmissionswasnotsimplytosethumanfootprints ontheMoonandtoreturn.Itwasmoreambitiousandsuccessfulthanthat.TheApollo Moonmissionssoughtscientificexplorationinitsownrightandtoestablishnewinsights andtechnologiesalongthewaytodoso.StartingwithNASA’sArtemisMoonMission V,plansareafoottoevenbegincolonizingothercelestialbodies.15
Let’senvisionamissionthatmakesagrandbiologicaltwintoNASA’sApolloand ArtemisMoonprojects,anArtemismissionhereonEarth.Artemiswas,afterall,the goddessofwildanimalsandwilderness,thetwinsisterofApollo,bornoutofwedlockfromtheancientunionofthesecond-generationTitan,Leto,andhercousinZeus. Wewouldneedtomeldtheancientwiththecutting-edge.Wewouldtakelife’sanalogs ofslide-rulesandquantumcomputing:theclassicforcesofevolutionandbiotechnologieswithgeneticwelding.AbiologicalArtemisagendaonEarthmightspawn heretoforeundiscoveredinsightsintogenomeediting,novelbiotechnologies,biological controlofinvasiveorganisms,restorationofdisruptedecosystems,reclamationofpreAnthropocenefoodwebs,newmedicalinventions,fertilityinterventions,deciphering ofheretoforeunknowndevelopmentalandphysiologicalmechanismsofanimalsand plants,andwhoknowswhatelse.Scientificcuriosityandexplorationthroughbasic researchhasproducedanastoundingfoundationofknowledge.16 Agrandvisionlets ustestandexpandthelimitsofourknowledge,totestwhetherourideasabouthowthe worldworksholdupinpracticewhenwestretchthemtotheedgeofthemap.
Toempoweragrandbiologicalvisionofcreation,toevolvenewandextraordinary speciestoinhabittheworldoftomorrow,infusedwiththetoolsofbiotechnology,we mustconfrontfigurativedragonsaswellastechnicalobstacles.Introducingnewspecies intoagivenspotintheworlduncorksatesttubeforecosystemstorespondto.Species innovelcircumstancescanimpartunexpectedandunintendedconsequences.Wewill observehowecosystemsmatteralongsideevolutionarychange.Wewilldeliberatethe minefieldofethicaltanglesassociatedwithevolutionaryengineeringofthenaturalworld, andtheprospectofgeneticengineeringofourselves.Wewillconsiderhowchangebegets morechange,whichwemayperceiveasgood,bad,orindifferent.Wewillseehowevolutionneverstops,exceptwithextinction,andhowextinctioncan,itself,leaveunexpected andunintendedconsequences.
Notes
1. Acladodeisthatfleshypadofapricklypearcactus.Botanicallyspeaking,it’saflattenedstem andnotaleaf,despitebeingthemainlocationofphotosynthesis.
2. Humanactivitieshaveincreasedglobalaveragetemperatureby1.0 ◦C(1.8 ◦F)since1850, puttingtoday’sglobaltemperatureaverageabovethatfromanytimeinthepast100,000years. Masson-Delmotte,V.,etal.2018.Globalwarmingof1.5 ◦C:AnIPCCspecialreportonthe impactsofglobalwarmingof1.5 ◦Cabovepre-industriallevelsandrelatedglobalgreenhouse
