26 THE STUFF OF LIFE
IFYOURTWOparentshadn’tbondedjustwhentheydid—possiblytothesed,possiblytothenanosed—youwouldn’tbehere.Andiftheirparentshadn’tbondedinapreciselytimelymanner,youwouldn’tbehereeither.Andiftheirparentshadn’tdonelikewise,andtheirparentsbeforethem,andsoon,obviouslyandindefinitely,youwouldn’tbehere.
Pushbackwardsthroughtimeandthesearaldebtsbegintoaddup.GobackjusteightgeionstoaboutthetimethatCharlesDarwinandAbrahamLinwereborn,andalreadythereareover250peopleonwhosetimelycouplingsyourexistencedepends.
tiher,tothetimeofShakespeareandtheMayflrims,andyouhavehan16,384aorsearlyexgiicmaterialinawaythatwould,eventuallyandmiraculously,resultinyou.
Attwentygeionsago,thenumberofpeopleprocreatingonyourbehalfhasrisento1,048,576.Fivegeionsbeforethat,andtherearehan33,554,432menandwomenonwhosedevotedcouplingsyourexistencedepends.Bythirtygeionsago,yourtotalnumberofforebears—remember,thesearen’tcousinsandauntsandotherialrelatives,butonlyparentsandparentsofparentsinalineleadiablytoyou—isoveronebillion(1,073,741,824,tobeprecise).Ifyougobacksixty-feions,tothetimeoftheRomans,thenumberofpeopleonwhosecooperativeeffortsyoureventualexistencedependshasrisentoapproximately1,000,000,000,000,000,000,whichisseveralthousandtimesthetotalnumberofpeoplewhohaveeverlived.
Clearlysomethinghasgwithourmathhere.Theamayiyoutolearn,isthatyourlineisnotpure.Youcouldn’tbeherewithoutalittlei—actuallyquitealotofi—albeitatageicallydiscreetremove.Withsomanymillionsofaorsinyourbackground,therewillhavebeenmanyoccasionswheivefromyourmother’ssideofthefamilyprocreatedwithsomedistantcousinfromyourfather’ssideoftheledger.Infact,ifyouareinapartnershipnowwithsomeonefromyourownradtry,thecesareexcellentthatyouareatsomelevelrelated.Indeed,ifyoulookaroundyouonabusorinaparkorcaféoranycrowdedplace,mostofthepeopleyouseeareveryprobablyrelatives.WhensomeoneboaststoyouthatheisdesdedfromWilliamthequerorortheMayflrims,youshouldaonce:“Me,too!”Iliteralandfualsenseweareallfamily.
Wearealsounilyalike.pareyehanyotherhumanbeing’sandonaveragetheywillbeabout99.9pertthesame.Thatiswhatmakesusaspecies.Thetinydifferehatremaining0.1pert—“roughlyoneidebaseihousand,”
toquotetheBritishgeicistaNobellaureateJohnSulstoendowuswithourindividuality.Muchhasbeenmadeiyearsoftheunravelingofthehumangenome.Infact,thereisnosuchthingas“the”humangenome.Everyhumangenomeisdifferent.Otherouldallbeidentical.Itistheendlessrebinationsenomes—eaearlyidentical,butnotquite—thatmakeuswhatweare,bothasindividualsandasaspecies.
Butwhatexactlyisthisthingwecallthegenome?Andwhat,etothat,aregenes?
Well,startwithacellagain.Ihecellisanucleus,andinsideeaucleusaretheosomes—forty-sixlittlebundlesofplexity,ofwhichtwenty-threeefromyourmotheray-threefromyourfather.Withaveryfewexceptions,everycellinyourbody—99.999pertofthem,say—carriesthesameplementofosomes.(Theexceptionsareredbloodcells,someimmuemcells,andeggandspermcells,whichforvarianizationalreasonsdon’tcarrythefullgeicpackage.)osomesstitutethepletesetofinstrusnecessarytomakeandmaintainyouandaremadeoflongstrandsofthelittlewonderchemicalcalleddeoxyribonucleicacidorDNA—“themostextraordinarymoleculeoh,”asithasbeencalled.
Dsforjustonereason—tocreatemoreDNA—andyouhavealotofitinsideyou:
aboutsixfeetofitsqueezedintoalmosteverycell.EagthofDNAprisessome3.2billioersofg,enoughtoprovide103,480,000,000possiblebinations,“guaraobeuniqueagainstallceivableodds,”inthewordsofChristiandeDuve.That’salotofpossibility—aonefollowedbymorethanthreebillionzeroes.“Itwouldtakemorethahousandaverage-sizebooksjusttoprintthatfigure,”notesdeDuve.Lookatyourselfinthemirrorandreflectupothatyouarebeholdihousandtrillioncells,andthatalmosteveryohemholdstwoyardsofdenselypactedDNA,andyoubegintoappreciatejusthowmuchofthisstuffyoucarryaroundwithyou.IfallyourDNAwerewovenintoasinglefirand,therewouldbeenoughofittostrettheEarthtotheMoonandbaotowicebutagainandagain.Altogether,acctoonecalculation,youmayhaveasmuchastwentymillionkilometersofDNAbundledupinsideyou.
Yourbody,inshort,lovestomakeDNAandwithoutityoucouldn’tlive.YetDNAisnotitselfalive.Nomoleculeis,butDNAis,asitwere,especiallyunalive.Itis“amoive,chemicallyimoleculesinthelivingworld,”inthewordsofthegeicistRichardLewontin.Thatiswhyitberecoveredfrompatchesoflong-driedbloodorsemeninmurderiigationsandcoaxedfromthebonesofaNeaals.Italsoexplainswhyittookstistssolongtoworkouthowasubstanystifyinglylowkey—so,inaword,lifeless—couldbeattheveryheartoflifeitself.
Asaky,DNAhasbeenaroundlohanyoumightthink.Itwasdiscoveredasfarbackas1869byJohannFriedrichMiescher,aSwissstistwattheUyofTübingeninGermany.Whiledelvingmicroscopicallythroughthepusinsurgicalbandages,Miescherfoundasubstancehedidn’treizeandcalleditnu(becauseitresidedinthenucleiofcells).Atthetime,Miescherdidlittlemorethasexistenuclearlyremainedonhismind,fortwenty-threeyearslateriertohisuncleheraisedthepossibilitythatsuchmoleculescouldbetheagentsbehindheredity.Thiswasaraordinaryinsight,butonesofarinadvaheday’sstificrequirementsthatitattraoattentionatall.
Formostofthehalfturytheonassumptionwasthatthematerial—nowcalleddeoxyribonucleicacid,orDNA—hadatmostasubsidiaryroleinmattersofheredity.Itwastoosimple.Ithadjustfourbasipos,calledides,whichwaslikehavinganalphabetofjustfourletters.Howcouldyoupossiblywritethestoryoflifewithsucharudimentaryalphabet?(TheahatyoudoitinmuchthewaythatyoucreateplexmessageswiththesimpledotsanddashesofMorsecode—bybiningthem.)DNAdidn’tdoanythingatall,asfarasanyonecouldtell.Itjustsatthereinthenucleus,possiblybindingtheosomeinsomewayoraddingasplashofacidityonandorfulfillingsomeothertrivialtaskthatnoonehadyetthoughtof.Thenecessaryplexity,itwasthought,hadtoexistinproteinsinthenucleus.
Therewere,however,twoproblemswithdismissingDNA.First,therewassomuchofit:
twoyardsinnearlyeverynucleus,soclearlythecellsesteemeditinsomeimportantway.Ontopofthis,itkeptturningup,likethesuspeamurdermystery,inexperiments.Intwostudiesinparticular,oneinvolvingthePneumonococcusbacteriumandanotherinvolvingbacteriophages(virusesthatibacteria),Drayedanimportacouldonlybeexplainedifitsroleweremoretralthanprevailingthoughtallowed.TheevidencesuggestedthatDNAwassomehowinvolvedinthemakingofproteins,aprocessvitaltolife,yetitwasalsoclearthatproteinswerebeingmadeoutsidethenucleus,wellawayfromtheDNAthatposedlydiregtheirassembly.
NoonecoulduandhowDNAcouldpossiblybegettingmessagestotheproteins.Theansknow,wasRNA,orribonucleicacid,whichactsasaninterpreterbetweewo.ItisanotableoddityofbiologythatDNAandproteinsdon’tspeakthesamelanguage.Foralmostfourbillioheyhavebeenthelivingworld’sgreatdoubleadyettheyaomutuallyinpatiblecodes,asifonespokeSpanishaherHindi.
TounicatetheyneedamediatorintheformofRNA.Wwithakindofchemicalclerkcalledaribosome,RNAtranslatesinformationfromacell’sDNAintotermsproteinsderstandandactupon.
However,bytheearly1900s,whereweresumeourstory,wewerestillaverylongwayfromuandingthat,orindeedalmostanythiodowiththefusedbusinessofheredity.
Clearlytherewasaneedforsomeinspiredandcleverexperimentation,andhappilytheageproducedayoungpersonwiththediligendaptitudetouakeit.HishomasHuntMan,andin1904,justfouryearsafterthetimelyrediscoveryofMendel’sexperimentswithpeaplantsandstillalmostadecadebefenewouldevenbeeaword,hebegantodoremarkablydedicatedthingswithosomes.
osomeshadbeendiscoveredby1888andweresocalledbecausetheyreadilyabsorbeddyeandthuswereeasytoseeuhemicroscope.Bytheturnofthetwehturyitwasstronglysuspectedthattheywereinvolvedinthepassingonoftraits,butnooneknewhow,orevenreallywhether,theydidthis.
Manchoseashissubjectofstudyatiny,delicateflyformallycalledDrosophilamelanogaster,butmoreonlyknownasthefruitfly(orvinegarfly,bananafly,efly).Drosophilaisfamiliartomostofusasthatfrail,colorlessihatseemstohaveapulsiveurgetodrowninourdrinks.Aslaboratoryspesfruitflieshadcertaitractiveadvaheycostalmostnothingtohouseandfeed,couldbebredbythemillionsinmilkbottles,wentfromeggtoproductiveparenthoodintendaysorless,andhadjustfourosomes,whichkeptthingsvelysimple.
Woutofasmalllab(whichbecameknowablyastheFlyRoom)inSchermerhornHallatbiaUyinNewYork,Manandhisteamembarkedramofmeticulousbreedingandcrossbreedinginvolvingmillionsofflies(onebiographersaysbillions,thoughthatisprobablyanexaggeration),eachofwhichhadtobecapturedwithtweezersandexaminedunderajeweler’sglassforanytinyvariationsiance.Forsixyearstheytriedtoproducemutationsbyaheycouldthinkof—zappingtheflieswithradiationandX-rays,rearingtheminbrightlightanddarkness,bakingthemgentlyinovens,spinningthemcrazilyirifuges—butnothingworked.Manwasonthebrinkofgivingupwhenthereoccurredasuddenaablemutation—aflythathadwhiteeyesratherthantheusualredones.Withthisbreakthrough,Manandhisassistantswereabletogeeusefuldeformities,allowirackatraitthroughsuccessivegeions.Bysuchmeanstheycouldworkoutthecorrelatioweenparticularcharacteristidindividualosomes,eventuallyprovingtomoreorlesseveryone’ssatisfathatosomeswereattheheartofiance.
Theproblem,however,remaihelevelofbiologitricacy:theenigmatiesahatposedthem.Theseweremuchtrickiertoisolateanduand.Aslateas1933,whenManwasawardedaNobelPrizeforhiswork,manyresearchersstillweren’tvihatgeneseveed.AsMahetime,therewasnosensus“astowhatthegenesare—whethertheyarerealorpurelyfictitious.”Itmayseemsurprisingthatstistscouldstruggletoacceptthephysicalrealityofsomethingsofualtocellularactivity,butasWallace,King,andSanderspointoutinBiology:TheSceofLife(thatrarestthing:areadablecollegetext),weareinmuchthesamepositiontodaywithmentalprocessessuchasthoughtandmemory.Weknowthatwehavethem,ofcourse,butwedon’tknowwhat,ifany,physitheytake.Soitwasfortheloimewithgeheideathatyoucouldpluefromyourbodyandtakeitawayforstudywasasabsurdtomanyan’speersastheideathatstiststodaymightcaptureastraythoughtandexamiunderamicroscope.
Whatwascertainlytruewasthatsomethingassociatedwithosomeswasdiregcellreplication.Finally,in1944,afterfifteenyearsofeffort,ateamattheRockefellerInstituteinManhattan,ledbyabrilliantbutdiffidentadiannamedOswaldAvery,succeededwithanexceedinglytrickyexperimentinwhiinnocuousstrainofbacteriaermalyiiousbycrossingitwithalienDNA,provingthatDNAwasfarmorethanapassivemoleculeandalmostcertainlywastheactiveagentiy.TheAustrian-bornbiochemistErwinChargafflatersuggestedquiteseriouslythatAvery’sdiscoverywasworthtwoNobelPrizes.
Unfortunately,Averyosedbyoneofhisowncolleaguesattheinstitute,astrong-willedanddisagreeableproteihusiastnamedAlfredMirsky,whodideverythinginhispowertodiscreditAvery’swork—including,ithasbeensaid,lobbyihoritiesattheKarolinskaInstituteinStonottogiveAveryaNobelPrize.Averybythistimewassixty-sixyearsoldandtired.Uodealwiththestressandtroversy,heresignedhispositionandneverwentnearalabagain.Butotherexperimentselsewhereoverwhelminglysupportedhisclusions,andsoontheracewasontofiructureofDNA.
Hadyoubeeingpersonintheearly1950s,yourmoneywouldalmostcertainlyhavebeenonLinusPaulingofCaltech,America’sleadi,tocrackthestructureofDNA.
PaulingwasunrivaledierminingthearchitectureofmoleculesandhadbeenapiohefieldofX-raycrystallography,ateiquethatwouldprovecrucialtintotheheartofDNA.Inanexceedinglydistinguishedcareer,hewouldwintwoNobelPrizes(forchemistryin1954andpea1962),butwithDNAhebecamevihatthestructurelehelix,notadoubleone,andneverquitegotontherighttrastead,victoryfelltoanunlikelyquartetofstistsinEnglandwhodidn’tworkasateam,ofteonspeakingterms,andwereforthemostpartnovithefield.
Ofthefour,theoaventionalboffinwasMauriceWilkins,entmuchoftheSedWorldWarhelpingtodesigomib.Twooftheothers,RosalindFranklinandFrancisCrick,hadpassedtheirwaryearswonminesfortheBritishgover—Crickofthetypethatblowup,Franklinofthetypethatproducecoal.
ThemostunventionalofthefoursomewasJamesWatson,anAmeriprodigywhohaddistinguishedhimselfasaboyasamemberofahighlypopularradiramcalledTheQuizKids(andthuscouldclaimtobeatleastpartoftheinspirationforsomeofthemembersoftheGlassfamilyinFrannyandZooeyandotherworksbyJ.D.Salinger)andwhohadeheUyofChicagoagedjustfifteen.HehadearnedhisPh.D.bytheageoftwenty-twoandwasnowattachedtothefamousdishLaboratoryinCambridge.In1951,hewasagawkytwenty-three-year-oldwithastrikinglylivelyheadofhairthatappearsinphotographstobestrainingtoattachitselftosomepowerfulmagjustoutofframe.
Crick,twelveyearsolderandstillwithoutadoctorate,waslessmemorablyhirsuteandslightlymoretweedy.InWatson’satheispresentedasblustery,nosy,cheerfullyargumentative,impatientwithanyoneslowtoshareanotion,andstantlyindangerofbeingaskedtogoelsewhere.herwasformallytrainedinbiochemistry.
TheirassumptionwasthatifyoucoulddetermiheshapeofaDNAmoleculeyouwouldbeabletosee—correctly,asittur—howitdidwhatitdid.Theyhopedtoachievethis,itwouldappear,bydoingaslittleossiblebeyondthinking,andnomoreofthatthanwasabsolutelynecessary.AsWatsoncheerfully(ifatouchdisingenuously)remarkedinhisautobiographicalbookTheDoubleHelix,“Itwasmyhopethatthegenemightbesolvedwithoutmylearningary.”Theyweren’tactuallyassigoworkonDNA,andatonepointwereorderedtostopit.Watsonwasostensiblymasteriofcrystallography;CrickposedtobepletingathesisontheX-raydiffraemolecules.
AlthoughCridWatsonenjoynearlyallthecreditinpopularatsforsolvieryofDNA,theirbreakthroughwascruciallydepeonexperimentalworkdoheirpetitors,theresultsofwhichwereobtained“fortuitously,”ifulwordsofthehistorianLisaJardine.Faraheadofthem,atleastatthebeginniwoacademicsatKing’sCollegeinLondon,WilkinsandFranklin.
TheNewZealand–bornWilkinswasaretiringfigure,almosttothepointofinvisibility.A1998PBSdotaryonthediscoveryofthestructureofDNA—afeatforwhichhesharedthe1962NobelPrizewithCridWatson—maooverlookhimentirely.
ThemostenigmaticcharacterofallwasFranklin.Inaseverelyunflatteringportrait,WatsoninTheDoubleHelixdepictedFranklinasawomanwhowasunreasonable,secretive,icallyuncooperative,and—thisseemedespeciallytoirritatehim—almostwillfullyunsexy.Heallowedthatshe“wasnotunattractiveandmighthavebeenquitestunninghadshetakenevenamildiinclothes,”butinthisshedisappointedallexpectations.Shedidn’tevenuselipstick,henotedinwonder,whileherdresssense“showedalltheimaginationofEnglishblue-stogadolests.”
1However,shedidhavethebestimagesiehepossiblestructureofDNA,achievedbymeansofX-raycrystallography,theteiqueperfectedbyLinusPauling.
Crystallographyhadbeenusedsuccessfullytomapatomsincrystals(hence“crystallography”),butDNAmoleculeswereamuchmorefinickyproposition.OnlyFranklinwasmanagingtogetgoodresultsfromtheprocess,buttoWilkins’sperennialexasperationsherefusedtoshareherfindings.
IfFranklinwasnotwarmlyforthingwithherfindings,sheotbealtogetherblamed.FemaleacademicsatKing’sinthe1950sweretreatedwithaformalizeddisdainthatdazzlesmodernsensibilities(actuallyanysensibilities).Howeverseniororaplished,theywerenotallowedintothecollege’ssenioronroombutinsteadhadtotaketheirmealsinamoreutilitarianchamberthatevenWatsoncededwas“dingilypokey.”Ontopofthisshewasbeingstantlypressed—attimesactivelyharassed—toshareherresultswithatrioofmenwhosedesperatioapeekatthemwasseldommatchedbymagingqualities,likerespect.“I’mafraidwealwaysusedtoadopt—let’ssayapatronizingattitudetowardher,”Cricklaterrecalled.Twoofthesemenwerefromapetinginstitutionahirdwasmoreorlessopenlysidingwiththem.Itshouldhardlyeasasurprisethatshekeptherresultslockedaway.
ThatWilkinsandFranklindidalongwasafactthatWatsonandCrickseemtohaveexploitedtotheirbe.AlthoughCridWatsorespassingratherunashamedlyonWilkins’sterritory,itwaswiththemthatheincreasinglysided—notaltogethersurprisinglysinceFranklinherselfwasbeginningtoaadecidedlyqueerway.AlthoughherresultsshowedthatDNAdefinitelywashelishape,sheinsistedtoallthatitwasnot.ToWilkins’spresumeddismayandembarrassment,inthesummerof1952shepostedamooticearoundtheKing’sphysicsdepartmentthatsaid:“Itiswithgreatregretthatwehavetoannouhedeath,onFriday18thJuly1952ofD.N.A.helix....ItishopedthatDr.M.H.F.
Wilkinswillspeakinmemoryofthelatehelix.”
TheouteofallthiswasthatinJanuary1953,WilkinsshowedWatsonFranklin’simages,“apparentlywithoutherknowledgeorsent.”Itwouldbeaatementtocallitasignifithelp.YearslaterWatsoncededthatit“wasthekeyevent...itmobilizedus.”ArmedwiththeknowledgeoftheDNAmolecule’sbasicshapeandsomeimportasofitsdimensions,WatsonandCrickredoubledtheirefforts.Everythingnowseemedtogotheirway.AtonepointPaulingwasenroutetoaferenEnglandatwhichhewouldinalllikelihoodhavemetwithWilkinsandlearnedenoughtocorrectthemisceptionsthathadputhimonthewronglineofinquiry,butthiswastheMcCarthyeraandPaulingfoundhimselfdetaiIdleortinNewYork,hispassportfiscated,onthegroundsthathewastooliberaloftemperamenttobeallowedtotravelabroad.CridWatsonalsohadthenolessvegoodfortuPauling’ssonwaswatthedishandilykeptthemabreastofanynewsofdevelopmentsabacksathome.
Stillfagthepossibilityofbeingtrumpedatanymoment,WatsonandCrickappliedthemselvesfeverishlytotheproblem.ItwasknownthatDNAhadfourchemical1In1968,HarvardUyPressceledpublicationofTheDoubleHelixafterCridWilkinsplainedaboutitscharacterizations,whichthescehistorianLisaJardinehasdescribedas"gratuitouslyhurtful."ThedescriptionsquotedaboveareafterWatsonsoftenedhisents.
pos—calledadenine,guaosine,andthiamine—andthatthesepairedupinparticularways.Byplayingwithpiecesofcardboardtotheshapesofmolecules,WatsonandCrickwereabletoworkouthowthepiecesfittogether.FromthistheymadeaMeo-likemodel—perhapsthemostfamousinmodernsce—sistingofmetalplatesboltedtogetherinaspiral,andinvitedWilkins,Franklin,aoftheworldtohavealook.
Anyinformedpersoncouldseeatotheyhadsolvedtheproblem.Itwaswithoutquestionabrilliantpieceofdetectivework,withorwithouttheboostofFranklin’spicture.
TheApril25,1953,editionofNaturecarrieda900-wordarticlebyWatsonandCricktitled“AStructureforDeoxyriboseNucleicAcid.”ApanyingitwereseparatearticlesbyWilkinsandFranklin.Itwasafultimeintheworld—EdmundHillarywasjustabouttoclambertothetopofEverestwhileElizabethIIwasimmilytobeedqueenofEngland—sothediscoveryofthesecretoflifewasmostlyoverlooked.ItreceivedasmallmentionintheNewsidwasignoredelsewhere.
RosalindFranklindidnotshareintheNobelPrize.Shediedofovariancerattheageofjustthirty-sevenin1958,fouryearsbeforetheawardwasgranted.NobelPrizesarenotawardedposthumously.TheceralmostcertainlyaroseasaresultoficoverexposuretoX-raysthroughherworkahavehappened.Inhermuch-praised2002biographyofFranklin,BrendaMaddoxhatFranklinrarelyworealeadapronandoftensteppedcarelesslyinfrontofabeam.OswaldAveryneverwonaNobelPrizeeitherandwasalselyoverlookedbyposterity,thoughhedidatleasthavethesatisfaoflivingjustlongenoughtoseehisfindingsvindicated.Hediedin1955.
WatsonandCrick’sdiscoverywasn’tactuallyfirmeduntilthe1980s.AsCricksaidinoneofhisbooks:“Ittookovertwenty-fiveyearsforourmodelofDNAtogofrombeingonlyratherplausible,tobeingveryplausible...andfromtheretobeingvirtuallycertainlycorrect.”
Evenso,withthestructureofDNAuressiicswasswift,andby1968thejournalScecouldrunanarticletitled“ThatWastheMolecularBiologyThatWas,”
suggesting—ithardlyseemspossible,butitisso—thattheweicswasnearlyatanend.
Infact,ofcourse,itwasonlyjustbeginning.EvennowthereisagreatdealaboutDNAthatwescarcelyuand,whysomuchofitdoesn’tactuallyseemtodoanything.
y-sevenpertofyourDNAsistsofnothingbutlongstreteaninglessgarble—“junk,”or“non-gDNA,”asbiochemistsprefertoputit.Onlyhereandtherealongeachstranddoyoufiionsthattrolandaalfuns.Thesearethecuriousandlong-elusivegenes.
Genesarenothingmore(haninstrustomakeproteins.Thistheydowithacertaindullfidelity.Inthisseheyareratherlikethekeysofapiano,eachplayingasieandnothingelse,whichisobviouslyatriflemonotonous.Butbihegenes,asyouwouldbinepianokeys,andyoucreatechordsandmelodiesofinfinitevariety.
Putallthesegeogether,andyouhave(totihemetaphor)thegreatsymphoenownasthehumangenome.
Aiveandmoreonwaytardthegenomeisasakindofinstruanualforthebody.Viewedthisway,theosomesbeimagihebook’schaptersandthegenesasindividualinstrusformakingproteins.Thewordsinwhichtheinstrusarewrittenarecalleds,aersareknownasbases.Thebases—thelettersofthegeicalphabet—sistofthefouridesmentionedapageortwoback:
adehiamine,guanine,andcytosietheimportanceofwhattheydo,thesesubstancesarenotmadeofanythiic.Guanine,forinstahesamestuffthataboundsin,andgivesitso,guano.
TheshapeofaDNAmolecule,aseveryoneknows,isratherlikeaspiralstaircaseortwistedropeladder:thefamousdoublehelix.Theuprightsofthisstructurearemadeofatypeofsugarcalleddeoxyribose,andthewholeofthehelixisanucleicacid—hehename“deoxyribonucleicacid.”Therungs(orsteps)areformedbytwobasesjoiningacrossthespacebetween,andtheybineinonlytwoways:guanineisalairedwithcytosihiaminealwayswithadeheorderinwhichtheselettersappearasyoumoveupordowntheladderstitutestheDNAcode;loggingithasbeenthejoboftheHumanGenomeProject.
NowtheparticularbrillianceofDNAliesinitsmannerofreplicatioistimetoproduewDNAmolecule,thetwostrandspartdownthemiddle,likethezipperonajacket,andeachhalfgoesofftoformanewpartnership.Becauseeaucleotidealongastrandpairsupecificotheride,eachstrandservesasatemplateforthecreationofagstrand.IfyoupossessedjustorandofyourownDNA,youcouldeasilyenoughrestructthematgsidebywoutthenecessarypartnerships:
ifthetopmorandwasmadeofguahenyouwouldknowthatthetopmogstrandmustbecytosine.Workyourwaydowntheladderthroughalltheidepairings,auallyyouwouldhavethecodeforanewmolecule.Thatisjustpensinnature,exceptthatnaturedoesitreallyquickly—inonlyamatterofseds,whichisquiteafeat.
MostofthetimeourDNAreplicateswithdutifulaccuracy,butjustoccasionally—aboutoimeinamillioergetsintothewrongplace.Thisisknownasasingleidepolymorphism,orSNP,familiarlyknowntobiochemistsasa“Snip.”GenerallytheseSnipsareburiedichesofnongDNAandhaveablesequehebody.
Butoccasionallytheymakeadiffereheymightleaveyoupredisposedtosomedisease,butequallytheymightfersomeslightadvantage—moreprotectivepigmentation,forinst松语文学www.16sy.coM免费小说阅读
Pushbackwardsthroughtimeandthesearaldebtsbegintoaddup.GobackjusteightgeionstoaboutthetimethatCharlesDarwinandAbrahamLinwereborn,andalreadythereareover250peopleonwhosetimelycouplingsyourexistencedepends.
tiher,tothetimeofShakespeareandtheMayflrims,andyouhavehan16,384aorsearlyexgiicmaterialinawaythatwould,eventuallyandmiraculously,resultinyou.
Attwentygeionsago,thenumberofpeopleprocreatingonyourbehalfhasrisento1,048,576.Fivegeionsbeforethat,andtherearehan33,554,432menandwomenonwhosedevotedcouplingsyourexistencedepends.Bythirtygeionsago,yourtotalnumberofforebears—remember,thesearen’tcousinsandauntsandotherialrelatives,butonlyparentsandparentsofparentsinalineleadiablytoyou—isoveronebillion(1,073,741,824,tobeprecise).Ifyougobacksixty-feions,tothetimeoftheRomans,thenumberofpeopleonwhosecooperativeeffortsyoureventualexistencedependshasrisentoapproximately1,000,000,000,000,000,000,whichisseveralthousandtimesthetotalnumberofpeoplewhohaveeverlived.
Clearlysomethinghasgwithourmathhere.Theamayiyoutolearn,isthatyourlineisnotpure.Youcouldn’tbeherewithoutalittlei—actuallyquitealotofi—albeitatageicallydiscreetremove.Withsomanymillionsofaorsinyourbackground,therewillhavebeenmanyoccasionswheivefromyourmother’ssideofthefamilyprocreatedwithsomedistantcousinfromyourfather’ssideoftheledger.Infact,ifyouareinapartnershipnowwithsomeonefromyourownradtry,thecesareexcellentthatyouareatsomelevelrelated.Indeed,ifyoulookaroundyouonabusorinaparkorcaféoranycrowdedplace,mostofthepeopleyouseeareveryprobablyrelatives.WhensomeoneboaststoyouthatheisdesdedfromWilliamthequerorortheMayflrims,youshouldaonce:“Me,too!”Iliteralandfualsenseweareallfamily.
Wearealsounilyalike.pareyehanyotherhumanbeing’sandonaveragetheywillbeabout99.9pertthesame.Thatiswhatmakesusaspecies.Thetinydifferehatremaining0.1pert—“roughlyoneidebaseihousand,”
toquotetheBritishgeicistaNobellaureateJohnSulstoendowuswithourindividuality.Muchhasbeenmadeiyearsoftheunravelingofthehumangenome.Infact,thereisnosuchthingas“the”humangenome.Everyhumangenomeisdifferent.Otherouldallbeidentical.Itistheendlessrebinationsenomes—eaearlyidentical,butnotquite—thatmakeuswhatweare,bothasindividualsandasaspecies.
Butwhatexactlyisthisthingwecallthegenome?Andwhat,etothat,aregenes?
Well,startwithacellagain.Ihecellisanucleus,andinsideeaucleusaretheosomes—forty-sixlittlebundlesofplexity,ofwhichtwenty-threeefromyourmotheray-threefromyourfather.Withaveryfewexceptions,everycellinyourbody—99.999pertofthem,say—carriesthesameplementofosomes.(Theexceptionsareredbloodcells,someimmuemcells,andeggandspermcells,whichforvarianizationalreasonsdon’tcarrythefullgeicpackage.)osomesstitutethepletesetofinstrusnecessarytomakeandmaintainyouandaremadeoflongstrandsofthelittlewonderchemicalcalleddeoxyribonucleicacidorDNA—“themostextraordinarymoleculeoh,”asithasbeencalled.
Dsforjustonereason—tocreatemoreDNA—andyouhavealotofitinsideyou:
aboutsixfeetofitsqueezedintoalmosteverycell.EagthofDNAprisessome3.2billioersofg,enoughtoprovide103,480,000,000possiblebinations,“guaraobeuniqueagainstallceivableodds,”inthewordsofChristiandeDuve.That’salotofpossibility—aonefollowedbymorethanthreebillionzeroes.“Itwouldtakemorethahousandaverage-sizebooksjusttoprintthatfigure,”notesdeDuve.Lookatyourselfinthemirrorandreflectupothatyouarebeholdihousandtrillioncells,andthatalmosteveryohemholdstwoyardsofdenselypactedDNA,andyoubegintoappreciatejusthowmuchofthisstuffyoucarryaroundwithyou.IfallyourDNAwerewovenintoasinglefirand,therewouldbeenoughofittostrettheEarthtotheMoonandbaotowicebutagainandagain.Altogether,acctoonecalculation,youmayhaveasmuchastwentymillionkilometersofDNAbundledupinsideyou.
Yourbody,inshort,lovestomakeDNAandwithoutityoucouldn’tlive.YetDNAisnotitselfalive.Nomoleculeis,butDNAis,asitwere,especiallyunalive.Itis“amoive,chemicallyimoleculesinthelivingworld,”inthewordsofthegeicistRichardLewontin.Thatiswhyitberecoveredfrompatchesoflong-driedbloodorsemeninmurderiigationsandcoaxedfromthebonesofaNeaals.Italsoexplainswhyittookstistssolongtoworkouthowasubstanystifyinglylowkey—so,inaword,lifeless—couldbeattheveryheartoflifeitself.
Asaky,DNAhasbeenaroundlohanyoumightthink.Itwasdiscoveredasfarbackas1869byJohannFriedrichMiescher,aSwissstistwattheUyofTübingeninGermany.Whiledelvingmicroscopicallythroughthepusinsurgicalbandages,Miescherfoundasubstancehedidn’treizeandcalleditnu(becauseitresidedinthenucleiofcells).Atthetime,Miescherdidlittlemorethasexistenuclearlyremainedonhismind,fortwenty-threeyearslateriertohisuncleheraisedthepossibilitythatsuchmoleculescouldbetheagentsbehindheredity.Thiswasaraordinaryinsight,butonesofarinadvaheday’sstificrequirementsthatitattraoattentionatall.
Formostofthehalfturytheonassumptionwasthatthematerial—nowcalleddeoxyribonucleicacid,orDNA—hadatmostasubsidiaryroleinmattersofheredity.Itwastoosimple.Ithadjustfourbasipos,calledides,whichwaslikehavinganalphabetofjustfourletters.Howcouldyoupossiblywritethestoryoflifewithsucharudimentaryalphabet?(TheahatyoudoitinmuchthewaythatyoucreateplexmessageswiththesimpledotsanddashesofMorsecode—bybiningthem.)DNAdidn’tdoanythingatall,asfarasanyonecouldtell.Itjustsatthereinthenucleus,possiblybindingtheosomeinsomewayoraddingasplashofacidityonandorfulfillingsomeothertrivialtaskthatnoonehadyetthoughtof.Thenecessaryplexity,itwasthought,hadtoexistinproteinsinthenucleus.
Therewere,however,twoproblemswithdismissingDNA.First,therewassomuchofit:
twoyardsinnearlyeverynucleus,soclearlythecellsesteemeditinsomeimportantway.Ontopofthis,itkeptturningup,likethesuspeamurdermystery,inexperiments.Intwostudiesinparticular,oneinvolvingthePneumonococcusbacteriumandanotherinvolvingbacteriophages(virusesthatibacteria),Drayedanimportacouldonlybeexplainedifitsroleweremoretralthanprevailingthoughtallowed.TheevidencesuggestedthatDNAwassomehowinvolvedinthemakingofproteins,aprocessvitaltolife,yetitwasalsoclearthatproteinswerebeingmadeoutsidethenucleus,wellawayfromtheDNAthatposedlydiregtheirassembly.
NoonecoulduandhowDNAcouldpossiblybegettingmessagestotheproteins.Theansknow,wasRNA,orribonucleicacid,whichactsasaninterpreterbetweewo.ItisanotableoddityofbiologythatDNAandproteinsdon’tspeakthesamelanguage.Foralmostfourbillioheyhavebeenthelivingworld’sgreatdoubleadyettheyaomutuallyinpatiblecodes,asifonespokeSpanishaherHindi.
TounicatetheyneedamediatorintheformofRNA.Wwithakindofchemicalclerkcalledaribosome,RNAtranslatesinformationfromacell’sDNAintotermsproteinsderstandandactupon.
However,bytheearly1900s,whereweresumeourstory,wewerestillaverylongwayfromuandingthat,orindeedalmostanythiodowiththefusedbusinessofheredity.
Clearlytherewasaneedforsomeinspiredandcleverexperimentation,andhappilytheageproducedayoungpersonwiththediligendaptitudetouakeit.HishomasHuntMan,andin1904,justfouryearsafterthetimelyrediscoveryofMendel’sexperimentswithpeaplantsandstillalmostadecadebefenewouldevenbeeaword,hebegantodoremarkablydedicatedthingswithosomes.
osomeshadbeendiscoveredby1888andweresocalledbecausetheyreadilyabsorbeddyeandthuswereeasytoseeuhemicroscope.Bytheturnofthetwehturyitwasstronglysuspectedthattheywereinvolvedinthepassingonoftraits,butnooneknewhow,orevenreallywhether,theydidthis.
Manchoseashissubjectofstudyatiny,delicateflyformallycalledDrosophilamelanogaster,butmoreonlyknownasthefruitfly(orvinegarfly,bananafly,efly).Drosophilaisfamiliartomostofusasthatfrail,colorlessihatseemstohaveapulsiveurgetodrowninourdrinks.Aslaboratoryspesfruitflieshadcertaitractiveadvaheycostalmostnothingtohouseandfeed,couldbebredbythemillionsinmilkbottles,wentfromeggtoproductiveparenthoodintendaysorless,andhadjustfourosomes,whichkeptthingsvelysimple.
Woutofasmalllab(whichbecameknowablyastheFlyRoom)inSchermerhornHallatbiaUyinNewYork,Manandhisteamembarkedramofmeticulousbreedingandcrossbreedinginvolvingmillionsofflies(onebiographersaysbillions,thoughthatisprobablyanexaggeration),eachofwhichhadtobecapturedwithtweezersandexaminedunderajeweler’sglassforanytinyvariationsiance.Forsixyearstheytriedtoproducemutationsbyaheycouldthinkof—zappingtheflieswithradiationandX-rays,rearingtheminbrightlightanddarkness,bakingthemgentlyinovens,spinningthemcrazilyirifuges—butnothingworked.Manwasonthebrinkofgivingupwhenthereoccurredasuddenaablemutation—aflythathadwhiteeyesratherthantheusualredones.Withthisbreakthrough,Manandhisassistantswereabletogeeusefuldeformities,allowirackatraitthroughsuccessivegeions.Bysuchmeanstheycouldworkoutthecorrelatioweenparticularcharacteristidindividualosomes,eventuallyprovingtomoreorlesseveryone’ssatisfathatosomeswereattheheartofiance.
Theproblem,however,remaihelevelofbiologitricacy:theenigmatiesahatposedthem.Theseweremuchtrickiertoisolateanduand.Aslateas1933,whenManwasawardedaNobelPrizeforhiswork,manyresearchersstillweren’tvihatgeneseveed.AsMahetime,therewasnosensus“astowhatthegenesare—whethertheyarerealorpurelyfictitious.”Itmayseemsurprisingthatstistscouldstruggletoacceptthephysicalrealityofsomethingsofualtocellularactivity,butasWallace,King,andSanderspointoutinBiology:TheSceofLife(thatrarestthing:areadablecollegetext),weareinmuchthesamepositiontodaywithmentalprocessessuchasthoughtandmemory.Weknowthatwehavethem,ofcourse,butwedon’tknowwhat,ifany,physitheytake.Soitwasfortheloimewithgeheideathatyoucouldpluefromyourbodyandtakeitawayforstudywasasabsurdtomanyan’speersastheideathatstiststodaymightcaptureastraythoughtandexamiunderamicroscope.
Whatwascertainlytruewasthatsomethingassociatedwithosomeswasdiregcellreplication.Finally,in1944,afterfifteenyearsofeffort,ateamattheRockefellerInstituteinManhattan,ledbyabrilliantbutdiffidentadiannamedOswaldAvery,succeededwithanexceedinglytrickyexperimentinwhiinnocuousstrainofbacteriaermalyiiousbycrossingitwithalienDNA,provingthatDNAwasfarmorethanapassivemoleculeandalmostcertainlywastheactiveagentiy.TheAustrian-bornbiochemistErwinChargafflatersuggestedquiteseriouslythatAvery’sdiscoverywasworthtwoNobelPrizes.
Unfortunately,Averyosedbyoneofhisowncolleaguesattheinstitute,astrong-willedanddisagreeableproteihusiastnamedAlfredMirsky,whodideverythinginhispowertodiscreditAvery’swork—including,ithasbeensaid,lobbyihoritiesattheKarolinskaInstituteinStonottogiveAveryaNobelPrize.Averybythistimewassixty-sixyearsoldandtired.Uodealwiththestressandtroversy,heresignedhispositionandneverwentnearalabagain.Butotherexperimentselsewhereoverwhelminglysupportedhisclusions,andsoontheracewasontofiructureofDNA.
Hadyoubeeingpersonintheearly1950s,yourmoneywouldalmostcertainlyhavebeenonLinusPaulingofCaltech,America’sleadi,tocrackthestructureofDNA.
PaulingwasunrivaledierminingthearchitectureofmoleculesandhadbeenapiohefieldofX-raycrystallography,ateiquethatwouldprovecrucialtintotheheartofDNA.Inanexceedinglydistinguishedcareer,hewouldwintwoNobelPrizes(forchemistryin1954andpea1962),butwithDNAhebecamevihatthestructurelehelix,notadoubleone,andneverquitegotontherighttrastead,victoryfelltoanunlikelyquartetofstistsinEnglandwhodidn’tworkasateam,ofteonspeakingterms,andwereforthemostpartnovithefield.
Ofthefour,theoaventionalboffinwasMauriceWilkins,entmuchoftheSedWorldWarhelpingtodesigomib.Twooftheothers,RosalindFranklinandFrancisCrick,hadpassedtheirwaryearswonminesfortheBritishgover—Crickofthetypethatblowup,Franklinofthetypethatproducecoal.
ThemostunventionalofthefoursomewasJamesWatson,anAmeriprodigywhohaddistinguishedhimselfasaboyasamemberofahighlypopularradiramcalledTheQuizKids(andthuscouldclaimtobeatleastpartoftheinspirationforsomeofthemembersoftheGlassfamilyinFrannyandZooeyandotherworksbyJ.D.Salinger)andwhohadeheUyofChicagoagedjustfifteen.HehadearnedhisPh.D.bytheageoftwenty-twoandwasnowattachedtothefamousdishLaboratoryinCambridge.In1951,hewasagawkytwenty-three-year-oldwithastrikinglylivelyheadofhairthatappearsinphotographstobestrainingtoattachitselftosomepowerfulmagjustoutofframe.
Crick,twelveyearsolderandstillwithoutadoctorate,waslessmemorablyhirsuteandslightlymoretweedy.InWatson’satheispresentedasblustery,nosy,cheerfullyargumentative,impatientwithanyoneslowtoshareanotion,andstantlyindangerofbeingaskedtogoelsewhere.herwasformallytrainedinbiochemistry.
TheirassumptionwasthatifyoucoulddetermiheshapeofaDNAmoleculeyouwouldbeabletosee—correctly,asittur—howitdidwhatitdid.Theyhopedtoachievethis,itwouldappear,bydoingaslittleossiblebeyondthinking,andnomoreofthatthanwasabsolutelynecessary.AsWatsoncheerfully(ifatouchdisingenuously)remarkedinhisautobiographicalbookTheDoubleHelix,“Itwasmyhopethatthegenemightbesolvedwithoutmylearningary.”Theyweren’tactuallyassigoworkonDNA,andatonepointwereorderedtostopit.Watsonwasostensiblymasteriofcrystallography;CrickposedtobepletingathesisontheX-raydiffraemolecules.
AlthoughCridWatsonenjoynearlyallthecreditinpopularatsforsolvieryofDNA,theirbreakthroughwascruciallydepeonexperimentalworkdoheirpetitors,theresultsofwhichwereobtained“fortuitously,”ifulwordsofthehistorianLisaJardine.Faraheadofthem,atleastatthebeginniwoacademicsatKing’sCollegeinLondon,WilkinsandFranklin.
TheNewZealand–bornWilkinswasaretiringfigure,almosttothepointofinvisibility.A1998PBSdotaryonthediscoveryofthestructureofDNA—afeatforwhichhesharedthe1962NobelPrizewithCridWatson—maooverlookhimentirely.
ThemostenigmaticcharacterofallwasFranklin.Inaseverelyunflatteringportrait,WatsoninTheDoubleHelixdepictedFranklinasawomanwhowasunreasonable,secretive,icallyuncooperative,and—thisseemedespeciallytoirritatehim—almostwillfullyunsexy.Heallowedthatshe“wasnotunattractiveandmighthavebeenquitestunninghadshetakenevenamildiinclothes,”butinthisshedisappointedallexpectations.Shedidn’tevenuselipstick,henotedinwonder,whileherdresssense“showedalltheimaginationofEnglishblue-stogadolests.”
1However,shedidhavethebestimagesiehepossiblestructureofDNA,achievedbymeansofX-raycrystallography,theteiqueperfectedbyLinusPauling.
Crystallographyhadbeenusedsuccessfullytomapatomsincrystals(hence“crystallography”),butDNAmoleculeswereamuchmorefinickyproposition.OnlyFranklinwasmanagingtogetgoodresultsfromtheprocess,buttoWilkins’sperennialexasperationsherefusedtoshareherfindings.
IfFranklinwasnotwarmlyforthingwithherfindings,sheotbealtogetherblamed.FemaleacademicsatKing’sinthe1950sweretreatedwithaformalizeddisdainthatdazzlesmodernsensibilities(actuallyanysensibilities).Howeverseniororaplished,theywerenotallowedintothecollege’ssenioronroombutinsteadhadtotaketheirmealsinamoreutilitarianchamberthatevenWatsoncededwas“dingilypokey.”Ontopofthisshewasbeingstantlypressed—attimesactivelyharassed—toshareherresultswithatrioofmenwhosedesperatioapeekatthemwasseldommatchedbymagingqualities,likerespect.“I’mafraidwealwaysusedtoadopt—let’ssayapatronizingattitudetowardher,”Cricklaterrecalled.Twoofthesemenwerefromapetinginstitutionahirdwasmoreorlessopenlysidingwiththem.Itshouldhardlyeasasurprisethatshekeptherresultslockedaway.
ThatWilkinsandFranklindidalongwasafactthatWatsonandCrickseemtohaveexploitedtotheirbe.AlthoughCridWatsorespassingratherunashamedlyonWilkins’sterritory,itwaswiththemthatheincreasinglysided—notaltogethersurprisinglysinceFranklinherselfwasbeginningtoaadecidedlyqueerway.AlthoughherresultsshowedthatDNAdefinitelywashelishape,sheinsistedtoallthatitwasnot.ToWilkins’spresumeddismayandembarrassment,inthesummerof1952shepostedamooticearoundtheKing’sphysicsdepartmentthatsaid:“Itiswithgreatregretthatwehavetoannouhedeath,onFriday18thJuly1952ofD.N.A.helix....ItishopedthatDr.M.H.F.
Wilkinswillspeakinmemoryofthelatehelix.”
TheouteofallthiswasthatinJanuary1953,WilkinsshowedWatsonFranklin’simages,“apparentlywithoutherknowledgeorsent.”Itwouldbeaatementtocallitasignifithelp.YearslaterWatsoncededthatit“wasthekeyevent...itmobilizedus.”ArmedwiththeknowledgeoftheDNAmolecule’sbasicshapeandsomeimportasofitsdimensions,WatsonandCrickredoubledtheirefforts.Everythingnowseemedtogotheirway.AtonepointPaulingwasenroutetoaferenEnglandatwhichhewouldinalllikelihoodhavemetwithWilkinsandlearnedenoughtocorrectthemisceptionsthathadputhimonthewronglineofinquiry,butthiswastheMcCarthyeraandPaulingfoundhimselfdetaiIdleortinNewYork,hispassportfiscated,onthegroundsthathewastooliberaloftemperamenttobeallowedtotravelabroad.CridWatsonalsohadthenolessvegoodfortuPauling’ssonwaswatthedishandilykeptthemabreastofanynewsofdevelopmentsabacksathome.
Stillfagthepossibilityofbeingtrumpedatanymoment,WatsonandCrickappliedthemselvesfeverishlytotheproblem.ItwasknownthatDNAhadfourchemical1In1968,HarvardUyPressceledpublicationofTheDoubleHelixafterCridWilkinsplainedaboutitscharacterizations,whichthescehistorianLisaJardinehasdescribedas"gratuitouslyhurtful."ThedescriptionsquotedaboveareafterWatsonsoftenedhisents.
pos—calledadenine,guaosine,andthiamine—andthatthesepairedupinparticularways.Byplayingwithpiecesofcardboardtotheshapesofmolecules,WatsonandCrickwereabletoworkouthowthepiecesfittogether.FromthistheymadeaMeo-likemodel—perhapsthemostfamousinmodernsce—sistingofmetalplatesboltedtogetherinaspiral,andinvitedWilkins,Franklin,aoftheworldtohavealook.
Anyinformedpersoncouldseeatotheyhadsolvedtheproblem.Itwaswithoutquestionabrilliantpieceofdetectivework,withorwithouttheboostofFranklin’spicture.
TheApril25,1953,editionofNaturecarrieda900-wordarticlebyWatsonandCricktitled“AStructureforDeoxyriboseNucleicAcid.”ApanyingitwereseparatearticlesbyWilkinsandFranklin.Itwasafultimeintheworld—EdmundHillarywasjustabouttoclambertothetopofEverestwhileElizabethIIwasimmilytobeedqueenofEngland—sothediscoveryofthesecretoflifewasmostlyoverlooked.ItreceivedasmallmentionintheNewsidwasignoredelsewhere.
RosalindFranklindidnotshareintheNobelPrize.Shediedofovariancerattheageofjustthirty-sevenin1958,fouryearsbeforetheawardwasgranted.NobelPrizesarenotawardedposthumously.TheceralmostcertainlyaroseasaresultoficoverexposuretoX-raysthroughherworkahavehappened.Inhermuch-praised2002biographyofFranklin,BrendaMaddoxhatFranklinrarelyworealeadapronandoftensteppedcarelesslyinfrontofabeam.OswaldAveryneverwonaNobelPrizeeitherandwasalselyoverlookedbyposterity,thoughhedidatleasthavethesatisfaoflivingjustlongenoughtoseehisfindingsvindicated.Hediedin1955.
WatsonandCrick’sdiscoverywasn’tactuallyfirmeduntilthe1980s.AsCricksaidinoneofhisbooks:“Ittookovertwenty-fiveyearsforourmodelofDNAtogofrombeingonlyratherplausible,tobeingveryplausible...andfromtheretobeingvirtuallycertainlycorrect.”
Evenso,withthestructureofDNAuressiicswasswift,andby1968thejournalScecouldrunanarticletitled“ThatWastheMolecularBiologyThatWas,”
suggesting—ithardlyseemspossible,butitisso—thattheweicswasnearlyatanend.
Infact,ofcourse,itwasonlyjustbeginning.EvennowthereisagreatdealaboutDNAthatwescarcelyuand,whysomuchofitdoesn’tactuallyseemtodoanything.
y-sevenpertofyourDNAsistsofnothingbutlongstreteaninglessgarble—“junk,”or“non-gDNA,”asbiochemistsprefertoputit.Onlyhereandtherealongeachstranddoyoufiionsthattrolandaalfuns.Thesearethecuriousandlong-elusivegenes.
Genesarenothingmore(haninstrustomakeproteins.Thistheydowithacertaindullfidelity.Inthisseheyareratherlikethekeysofapiano,eachplayingasieandnothingelse,whichisobviouslyatriflemonotonous.Butbihegenes,asyouwouldbinepianokeys,andyoucreatechordsandmelodiesofinfinitevariety.
Putallthesegeogether,andyouhave(totihemetaphor)thegreatsymphoenownasthehumangenome.
Aiveandmoreonwaytardthegenomeisasakindofinstruanualforthebody.Viewedthisway,theosomesbeimagihebook’schaptersandthegenesasindividualinstrusformakingproteins.Thewordsinwhichtheinstrusarewrittenarecalleds,aersareknownasbases.Thebases—thelettersofthegeicalphabet—sistofthefouridesmentionedapageortwoback:
adehiamine,guanine,andcytosietheimportanceofwhattheydo,thesesubstancesarenotmadeofanythiic.Guanine,forinstahesamestuffthataboundsin,andgivesitso,guano.
TheshapeofaDNAmolecule,aseveryoneknows,isratherlikeaspiralstaircaseortwistedropeladder:thefamousdoublehelix.Theuprightsofthisstructurearemadeofatypeofsugarcalleddeoxyribose,andthewholeofthehelixisanucleicacid—hehename“deoxyribonucleicacid.”Therungs(orsteps)areformedbytwobasesjoiningacrossthespacebetween,andtheybineinonlytwoways:guanineisalairedwithcytosihiaminealwayswithadeheorderinwhichtheselettersappearasyoumoveupordowntheladderstitutestheDNAcode;loggingithasbeenthejoboftheHumanGenomeProject.
NowtheparticularbrillianceofDNAliesinitsmannerofreplicatioistimetoproduewDNAmolecule,thetwostrandspartdownthemiddle,likethezipperonajacket,andeachhalfgoesofftoformanewpartnership.Becauseeaucleotidealongastrandpairsupecificotheride,eachstrandservesasatemplateforthecreationofagstrand.IfyoupossessedjustorandofyourownDNA,youcouldeasilyenoughrestructthematgsidebywoutthenecessarypartnerships:
ifthetopmorandwasmadeofguahenyouwouldknowthatthetopmogstrandmustbecytosine.Workyourwaydowntheladderthroughalltheidepairings,auallyyouwouldhavethecodeforanewmolecule.Thatisjustpensinnature,exceptthatnaturedoesitreallyquickly—inonlyamatterofseds,whichisquiteafeat.
MostofthetimeourDNAreplicateswithdutifulaccuracy,butjustoccasionally—aboutoimeinamillioergetsintothewrongplace.Thisisknownasasingleidepolymorphism,orSNP,familiarlyknowntobiochemistsasa“Snip.”GenerallytheseSnipsareburiedichesofnongDNAandhaveablesequehebody.
Butoccasionallytheymakeadiffereheymightleaveyoupredisposedtosomedisease,butequallytheymightfersomeslightadvantage—moreprotectivepigmentation,forinst松语文学www.16sy.coM免费小说阅读
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