Paul Nurse - What Is Life

by Understand Biology In Five Steps (pdf)

  ThischallengewascompoundedbythefactthatmostofthestrainsIlabouredtoidentifywereoflimited interest because they all contained subtly different mutations of the same gene, which I had by then called wee1.

  Then,onewetFridayafternoon,Ispottedanother weemutant.ThistimemyPetridishwasdefinitely contaminated:thedish,andtheabnormallysmallyeastcellsthathadcaughtmyeye,werecoveredbythe longtendrilsofaninvadingfungus.Iwastiredandknewthatgettingridofsuchacontaminatingfungus wasalongandtedioustask.Inanycase,Iassumedthisnewstrainwouldmostlikelycontainyetanother mutantformofthesamegene, wee1.IthrewthewholePetridishintotherubbishbinandwenthomefor mytea.

  LaterthateveningIfeltguiltyaboutwhatIhaddone.Whatif thismutantwasdifferentfromtheother 50weemutants?BythenitwasaparticularlydarkandwetEdinburghnight,butIgotbackonmybicycle androdebackupthehilltothelab.OverthenextfewweeksImanagedtoisolatethenewweemutant away from the invading fungus. And then – to my sublime pleasure – it turned out that this wasn’t yet

  another variant of the wee1 gene. It was a completely new gene and, ultimately, the key that unlocked howthecellcyclewascontrolled.

  Icalledmynewgenecelldivisioncycle2,or cdc2forshort.Lookingback,IsometimeswishI’dgiven thiscentralpartofthecellcyclepuzzleamoreelegant,oratleastamorememorablename!Notleast sinceyou’regoingtohearrathermoreabout cdc2laterinthisbook.

  Withthebenefitofhindsight,allofthiswasreallyquitesimple,bothtodoandtothinkabout.Luckwas veryimportanttoo:boththeaccidentalfindingofthefirstweemutant,whichIwasnot even searching for,andthequirkoffatethatmeantthe‘failed’experimentIretrievedfromtherubbishbinwastheone thateventuallyledmetothecentralplayerincellcyclecontrol.Simpleexperimentsandthinkingcanbe surprisingly illuminating in science, especially when combined with a good measure of hard graft, hopefulness,and,ofcourse,theoccasionalluckybreak.

  IdidmostoftheseexperimentswhenIwasajuniorscientist,withayoungfamilyathome,workingin thelabofProfessorMurdochMitchisoninEdinburgh.HeprovidedthespaceandequipmentIneededto domyexperiments,aswellasanendlesssupplyofadviceandcommentonwhatIwasdoing.Despiteall hisinput,hewouldnotletmeincludehimasanauthoronanyofmypapersbecausehedidnotthinkhe hadcontributedenough.Itwasnottrue,ofcourse.Itisgenerositylikethatwhichhasbeenmyprincipal experience of doing science, but it gets less attention than it should. Murdoch was an interesting man.

  Generous, as I have said, somewhat shy, and utterly consumed by his research. He cared little about whether others were interested in what he was doing; he marched to the beat of his own drum. If Murdochwasstillaround,hemightnothaveapprovedofmysinglinghimoutlikethishere,butIwantto give him full credit for showing me why the best research is both intensely individual and utterly communal.

  Lifecannotexistwithoutgenes:eachnewgenerationofcellsandorganismsmustinheritthegenetic instructionstheyneedtogrow,functionandreproduce.Thismeansthatforlivingthingstopersistinthe long term, genes must be able replicate themselves very precisely and carefully. Only that way can the DNAsequencesbekeptconstantthroughmultiplecelldivisions,sogenescanwithstandthe‘testoftime’.

  Cellsachievethiswithimpressiveexactitude.Weseetheresultofthisallaroundus.TheDNAsequence ofthehugemajorityofthe22,000genesthatcontrolyourcellsisalmostcompletelyidenticaltothoseof allotherpeopleonthisplanettoday.Theyarealsolargelyindistinguishablefromthoseofourancestors who hunted, gathered and swapped stories around campfires in the depths of pre-history, tens of thousands of years ago. Altogether, the mutations that differentiate your inborn characteristics from mine,andbothofusfromourprehistoricancestors,adduptoatinyfraction–lessthanonepercent–of yourtotalcomplementofDNAcode.Thisisoneofthebigdiscoveriesoftwenty-firstcenturygenetics:our genomes,eachthreebillionDNA‘letters’long,areverysimilar,acrossgenders,ethnicities,religionsand socialclasses.Thisisanimportantequalizingfactthatsocietiesacrosstheworldshouldappreciate.

  Wecannotdisregardthosescatteredvariationsthatweallcarryinourgenes,however.Althoughinthe smallminorityoverall,theycanhaveabigeffectonourindividualbiologyandlifehistory.Someofthese variantsaresharedbetweenmeandmydaughtersandgrandchildren,andtheyexplainsomeaspectsof ourresemblanceasafamily.Othergenevariantsareuniquetoeachofus,andarepartofwhatmakesus intodistinctindividuals,byinfluencingourphysicalappearance,ourhealthandourwaysofthinking,in eithersubtleornotsosubtleways.

  Geneticsiscentraltoallourlives,shapingoursenseofidentityandoutlookontheworld.Lateinmy life,Idiscoveredsomethingrathersurprisingaboutmyowngenetics.Igrewupinaworking-classfamily; myfatherworkedinafactoryandmymotherwasacleaner.Mybrothersandsisterallleftschoolwhen theywerefifteen,soIwastheonlyonewhostayedonatschooland,later,wentontouniversity.Ihada happyandwell-supported,ifsomewhatold-fashioned,childhood.Myparentswereratherolderthanthose ofmyfriends,andIusedtoquipthatitwaslikebeingbroughtupbymygrandparents.

  ManyyearslaterIappliedfora‘GreenCard’soIcouldtakeupresidenceintheUSAandstartmynew jobasPresidentoftheRockefellerUniversity,inNewYork.Tomysurprise,myapplicationwasrejected.

  TheUS Department ofHomeland Security saidit was because theversion of thebirth certificate I had usedallmylifedidnotlistthenamesofmyparents.Irritated,Iwroteoffforthefullversionofmybirth certificate.TheshockcamewhenIopenedtheenvelopecontainingthatnewcertificate.Whatitshowed wasthatmyparentswerenotmyparents–theyreally were my grandparents. My mother was actually my sister. It turned out that she had got pregnant at seventeen and, since illegitimacy was considered rather shameful at that time, she had been sent to her aunt’s home in Norwich, which is where I was born.WhenwereturnedtoLondon,mygrandmother,wantingtoprotectherdaughter,pretendedtobe my mother, and brought me up. The great irony on discovering all this was that although I am a geneticist,Ididnotknowmyowngenetics!Infact,becauseeveryonewhomighthaveknownhassince died, I still don’t know who my father is: there is just a dash on my birth certificate where his name shouldbe.

  Allindividuals are bornwith a relativelysmall number of novelgenetic variants thattend to arise at randomandarenotsharedwitheitheroftheirbiologicalparents.Aswellascontributingtowhatmakes individualorganismsunique,theseheritabledifferencesalsoexplainwhylivingspeciesarenotstaticand unchanging over long periods of time. Life is constantly experimenting, innovating and adapting as it changestheworldandtheworldchangesaroundit.Forthistobepossible,genesmustbalancetheneed to preserve information by staying constant, with the simultaneous ability to change, sometimes substantiallyso.Thenextideashowsushowthatthiscancomeaboutand,asaresult,howlifebecameso bewilderinglydiverse.

  Thatideaisevolutionbynaturalselection.

  3.EVOLUTIONBYNATURALSELECTION

  ChanceandNecessity

  Theworldisteemingwithanextraordinarydiversityoflifeforms.Theyellowbutterflythatstartedthis book was a brimstone, an early harbinger of spring. With its delicate yellow wings, it is a beautiful exampleoftheamazinglydiversegroupofanimalsthatwecallinsects.

  I like insects, particularly beetles, which were a hobby of mine when I was a teenager. There is an astonishingvarietyofbeetles–
somescientiststhinkthereareoveronemilliondistinctspeciesofthem throughout the world. Growing up in England, I marvelled at armour-plated ground beetles scurrying aroundunderstones,beetlesthatglowedatnight,redandblackladybirdseatingaphidsinthegarden, powerful water beetles swimming in ponds and weevils in the flour packet. Beetles present us with a cacophonyofdiversity;theyareamicrocosmofthediversityofalllife.

  Life in all its different forms can at times seem overwhelming: we share our world with countless animals,birds,fish,insects,plants,fungiandanevenlongerrosterofdifferentmicrobes,eachappearing tobewelladaptedtotheirownparticularlifestyleandenvironment.Nowonderthatformillenniamost peoplethoughtthatallthisdiversitymusthaveresultedfromtheeffortsofadivineCreator.

  Creationmythsaboundinmostcultures.TheJudaeo-ChristianmythofGenesis,ifreadliterally,claims life was created within just a few days. The pervasive idea, that individual species had each been fashionedbyaCreator,ledthetwentiethcenturygeneticistJ.B.S.Haldanetolookatthehugediversity ofbeetlesandquipthatwhoeverGodis,‘Hehasaninordinatefondnessforbeetles.’

  Duringtheeighteenthandnineteenthcenturies,thinkersbegantocomparetheintricatemechanisms oflivingthingswiththoseofthecomplexmachinesbeingdesignedandconstructedduringtheIndustrial Revolution.Thesecomparisonsoftenreinforcedreligiousbeliefs:howcouldsuchintricacyhavecometo bewithouttheinputofasupremelyintelligentdesigner?

  One colourful example of this kind of reasoning came from the Reverend William Paley in 1802. He askedyoutoimaginethatyouwereoutwalkingandfoundawatchonthepath.Ifyouopenedthewatch and examined its complex mechanism, clearly designed for the purpose of tracking time, it would, he argued, convince you that the watch was made by an intelligent Creator. According to Paley, the same logicmustapplytointricatelivingmechanisms.

  We now know that complex life forms endowed with a sense of purpose can be generated without a designerofanykind,andthatisduetonaturalselection.

  Natural selection is the intensely creative process that has produced us – and the extraordinary diversityoflivingformsthatsurroundsus–fromthemillionsofdifferentmicrobespeciestothefearsome jaws of the stag beetle, the 30-metre tentacles of the lion’s mane jellyfish, the fluid-filled traps of the carnivorouspitcherplantandtheopposablethumbsofthegreatapes,includingourselves.Withoutever deviating from the laws of science or invoking supernatural phenomena, evolution by natural selection has generated populations of increasingly complex and diverse creatures. Over aeons of time, different species have risen to prominence, their forms changing beyond recognition, as they have explored new possibilitiesandinteractedwithdifferentenvironmentsandotherlivingcreatures.Allspecies–including ourown–areinastateofperpetualchange,eventuallybecomingextinctordevelopingintonewspecies.

  Formethisstoryoflifeisjustasfullofwonderasanyofthecreationistmyths.Whereasmostofthe religiousstoriespresentuswithcreativeactsthatarefamiliar,evensomewhatmundane,anddurationsof timethatwecanreadilyunderstand,evolutionbynaturalselectionpushesustoimaginesomethingmuch more at the edge of our comfort zone, but also more magnificent. It is a wholly undirected and incrementalprocess,butwhenitisembeddedintheinconceivablyvastdurationoftime,whatscientists sometimescall‘deeptime’,itbecomesthemostsupremelycreativeforceofall.

  ThetoweringfigureinevolutionisCharlesDarwin,thenineteenth-centurynaturalistwhotravelledthe world in the tiny Royal Naval ship HMS Beagle, collecting specimens of plants, animals and fossils.

  Hungrily,Darwingatheredobservationsthatsupportedtheideaofevolutionandcameupwithabeautiful mechanism–naturalselection–thatexplainedhowitworked.Hesharedallofthisinhis1859book On theOriginofSpecies.Ofallthegreatideasofbiology,thisisprobablythebestknown,ifnotalwaysthe bestunderstood.

  Darwinwasnotthefirsttosuggestthatlifeevolvedovertime.Ashenotesin OntheOriginofSpecies, Aristotlehadarguedthatbodypartsofanimalsmightappearordisappearoverlongperiodsoftime.The late eighteenth-century French scientist Jean-Baptiste Lamarck took this further, arguing that different specieswerelinkedtogetherinchainsofrelatedness.Heproposedthatspecieschangegraduallythrough theprocessofadaptation,withtheirformrespondingtoshiftsintheenvironmentandchangesintheir habits.Famously,hearguedthatgiraffesdevelopedtheirlongnecksbecause,witheachgeneration,they stretched upwards to reach leaves higher up on trees, and somehow, the results of that exertion were passed on to their offspring, who would have slightly longer necks. Lamarck’s ideas are sometimes belittledtodaybecausehedidnotgetthedetailsoftheprocessofevolutionright,buthedeservesgreat credit for providing one of the first comprehensive accounts of the phenomenon of evolution, if not its cause.

  Lamarck was certainly not alone in speculating about evolution. Even in Charles’s own family, his colourful grandfather, Erasmus Darwin, was another early and enthusiastic supporter of evolution. He had a motto inscribed on his coach which read ‘ E conchis omnia’, that is ‘everything from shells’, advertisinghisbeliefthatalllifedevelopedfrommuchsimplerancestors,suchastheapparentlyformless blob of a mollusc inside its shell. However, he had to remove it after the Dean of Lichfield Cathedral accused him of having ‘renounced his Creator’. Erasmus obliged, since he was also a successful doctor andunderstoodthat,hadhenotdoneso,hewouldhavebeenindangeroflosinghismorerespectable, and therefore wealthier, patients. He was also considered at the time to be a distinguished poet, expoundinghisviewsonevolutioninversesfromhispoem TheTempleofNature:

  ‘Firstformsminute,unseenbysphericglass

  Moveonthemud,orpiercethewaterymass;

  These,assuccessivegenerationsbloom,

  NewPowersacquireandlargerlimbsassume;

  Whencecountlessgroupsofvegetationspring

  Andbreathingrealmsoffin,andfeet,andwing.’

  His reputation as a poet may not have survived, perhaps understandably, but his reputation as a scientist has. However, his lines anticipated aspects of the ideas elaborated by his better-known grandson.

  Charles Darwin was more scientific and systematic in his approach to evolution, and his means of communicationweremoreconventional,confininghimselftoproseratherthanverse.Heamassedhuge amountsofobservationaldatafromthefossilrecordandhisstudiesofplantsandanimals,bothathome and abroad. He organized it all to provide strong evidence for the view, shared by Lamarck, his grandfather and others, that living organisms do evolve. But Darwin did more than that when he proposednaturalselectionasa mechanismforevolution.Hejoinedupallthedotsandshowedtheworld howevolutioncouldactuallywork.

  Theideaofnaturalselectionisbasedonthefactthatpopulationsoflivingorganismsexhibitvariations, and when these variants are caused by genetic changes, they will be inherited from generation to generation. Some of these variants will affect characteristics that make certain individuals more successful in producing offspring. This enhanced reproductive success means that the offspring possessingthesevariantswillmakeupagreaterproportionofthepopulationinthenextgeneration.In thecaseofthegiraffe’slongneck,wecaninferthattherandomappearanceandaccumulationofvariants thatsubtlyalteredtheskeletonandmusclesoftheneckallowedsomeofthegiraffe’sancestorstoreach slightly higher branc
hes, eat more leaves and gain more nutrition. Eventually, those that could do so provedmoreresilientandmorecapableofproducingyounggiraffes,sotheherdsofgiraffesroamingthe savannahsofAfricagraduallybecamedominatedbyindividualswithlongernecks.Thisprocessisknown as natural selection since constraints imposed by all manner of natural factors, such as competition for food or mates or the presence of diseases and parasites, ensure that some individuals fare better and thereforereproducemorethanothers.

  ThesamemechanismwasputforwardindependentlybythenaturalistandcollectorAlfredWallace.It’s less widely known that both of them followed speculations about natural selection made earlier in the century,inparticularbytheScottishagriculturalistandlandownerPatrickMatthewinhis1831bookon naval timber. Nevertheless, Darwin was the first to present the whole idea in a convincing, comprehensiveandenduringlycompellingway.

  Humans have actually been hijacking the same process for thousands of years, using it to breed organisms possessing particular characteristics. This is called artificial selection, and Darwin actually developed his ideas about natural selection by observing the way pigeon fanciers selected particular individualstobreedtoproduceawiderangeofpigeonvarieties.Artificialselectioncanproducedramatic results.Itishowwetransformedwildgreywolvesintoman’sbestfriend,creatingdogbreedsthatrange from the tiny Chihuahua to the towering Great Dane. It’s also how the wild mustard plant gave rise to broccoli,cabbage,cauliflower,kaleandkohlrabi.Thesetransformationshavetakenplaceoverarelatively modestnumberofgenerations,givingaglimpseofthegreatpoweroftheevolutionaryprocesswhenitis allowedtorunitscoursenaturallyovermillionsofyears.