Paul Nurse - What Is Life

by Understand Biology In Five Steps (pdf)

  ‘publicgood’?Ifnewcancertherapiesarehugelyexpensive,whoshouldgetthemandwhoshouldnot?

  Should advocating vaccine refusal without adequate evidence, or the misuse of antibiotics, be criminal offences? Is punishment for certain criminal behaviours right if they are strongly influenced by an individual’sgenes?IfgermlinegeneeditingcanridfamiliesofHuntingdon’sdisease,shouldtheybefree touseit?Cancloninganadulthumaneverbeacceptable?Andiftacklingclimatechangemeansseeding theoceanswithbillionsofgeneticallyengineeredalgae,shoulditbedone?

  These are but a handful of the increasingly urgent and often intensely personal questions that our advancing understanding of life pushes us to ask. The only way to find acceptable answers is through constant,honestandopendebate.Scientistshaveaspecialroletoplayinthesediscussionsbecauseitis theywhomustexplainclearlythebenefits,risksanddangersofeachstepforward.Butitissocietyasa wholethatmusttaketheleadinthediscussions.Politicalleadersmustbefullyengagedwiththeseissues.

  Toofewofthemtodaytakesufficientnoticeofthehugeimpactscienceandtechnologyhaveonourlives andeconomies.

  Butthetimeforpoliticsis afterthesciencenot before.Theworldhasseentoooftenhowthingscango horribly wrong when the reverse is true. During the Cold War, the Soviet Union was able to build a nuclear bomb and send the first human into space. But work on genetics and crop improvements were severely damaged, because, for ideological reasons, Stalin backed the charlatan Lysenko who rejected Mendelian genetics. People starved as a consequence. More recently, we have witnessed the delays in action brought about by climate change deniers, who have ignored or actively undermined scientific understanding. Debates about the public good need to be driven by knowledge, evidence and rational thinking,andnotbyideology,unsubstantiatedbeliefs,greedorpoliticalextremes.

  Butmakenomistake,thevalueofscienceitselfisnotupfordebate.Theworldneedsscienceandthe advancesitcanoffer.Asself-aware,ingeniousandcuriosity-drivenhumans,wehaveauniqueopportunity touseourunderstandingoflifetochangetheworld.Itisuptoustodowhatwecantomakelifebetter.

  Not only for our families and local communities, but also for all the generations to come, and for the ecosystemsthatweareaninextricablepartof.Thelivingworldaroundusnotonlyprovidesushumans withanendlesssourceofwonder,italsosustainsourveryexistence.

  WHATISLIFE?

  Thisisabigquestion.TheanswerIgotatschoolwassomethingliketheMRSGRENlist,whichstates that living organisms exhibit M ovement, R espiration, S ensitivity, G rowth, R eproduction, E xcretion and N utrition. It is a neat summary of the sorts of things that living organisms do, but it is not a satisfying explanation of what life is. I want to take a different approach. Based on the steps we have taken to understand five of biology’s great ideas, I will draw out a set of essential principles that we can use to define life. These principles will then allow us to get deeper insight into how life works, how it got started,andthenatureoftherelationshipsthatbindtogetheralllifeonourplanet.

  Of course, many others have attempted to answer this question. Erwin Schrödinger emphasized inheritanceandinformationinhisprescient1944book WhatisLife? Heproposeda‘codescript’forlife, whichwenowknowiswritteninDNA.Butheendedhisbookbymakingasuggestionthatalmostborders onvitalism:hearguedthattoreallyexplainhowlifeworks,wemightneedanewandasyetundiscovered typeofphysicallaw.

  A few years later the radical British-Indian biologist J. B. S. Haldane wrote another book, also called WhatisLife? ,inwhichhedeclared,‘Iamnotgoingtoanswerthisquestion.Infact,Idoubtifitwillever bepossibletogiveafullanswer.’Hecomparedthefeelingofbeingalivetotheperceptionofcolour,pain or effort, suggesting that ‘we cannot describe them in terms of anything else’. I have sympathy for Haldane’sview,butitdoesratherremindmeoftheUSSupremeCourtJudgeJusticePotter,who,in1964, definedpornographybysaying,‘IknowitwhenIseeit.’

  TheNobelprizewinninggeneticistHermannMullerwasnotsohesitant.In1966heoffereda‘stripped down’definitionofalivingthingassimply‘thatwhichpossessestheabilitytoevolve’.Mullercorrectly identifiedDarwin’sgreatideaofevolutionbynaturalselectionascoretothinkingaboutwhatlifeis.Itis amechanism–infact,theonlymechanismweknowof–thatcangeneratediverse,organized,purposeful livingentitieswithoutinvokingasupernaturalCreator.

  TheabilitytoevolvethroughnaturalselectionisthefirstprincipleIwillusetodefinelife.Asshownin thechapteronnaturalselection,itdependsonthreeessentialfeatures.Toevolve,livingorganismsmust reproduce,theymusthaveahereditarysystem,andthathereditarysystemmustexhibitvariability.Any entitythathasthesefeaturescanandwillevolve.

  Mysecondprincipleisthatlifeformsarebounded,physicalentities.Theyareseparatedfrom,butin communicationwith,theirenvironments.Thisprincipleisderivedfromtheideaofthecell,thesimplest thingthatclearlyembodiesallthesignaturecharacteristicsoflife.Thisprincipleinvokesaphysicalityof life, which excludes computer programs and cultural entities from being considered as life forms, even thoughtheycanappeartoevolve.

  My third principle is that living entities are chemical, physical and informational machines. They construct their own metabolism and use it to maintain themselves, grow and reproduce. These living machines are co-ordinated and regulated by managing information, with the effect that living entities operateaspurposefulwholes.

  Together, these three principles define life. Any entity which operates according to all three of them canbedeemedtobealive.

  Theextraordinaryformofchemistrythatunderpinslifeneedsmoreelaborationforafullappreciation ofhowlivingmachineswork.Acentralfeatureofthatchemistryisthatitisbuiltaroundlargepolymer molecules,formedmainlyfromlinkedatomsofcarbon.DNAisoneofthemanditscorepurposeistoact as a highly reliable long-term store of information. To this end, the DNA helix shields its critical information-containingelements–thenucleotidebases–atthecoreofthehelix,wheretheyarestable andwell-protected.SomuchsothatscientistswhostudyancientDNAhavebeenabletosequenceDNA obtainedfromorganismsthatlivedanddiedaverylongtimeago,includingDNAfromahorsethathad beenfrozeninpermafrostfornearlyamillionyears!

  ButtheinformationstoredintheDNAsequenceofthegenescannotremainhiddenandinert.Itmust betransformedintoaction,togeneratethemetabolicactivitiesandphysicalstructuresthatunderpinlife.

  The information held in chemically stable and rather uninteresting DNA needs to be translated into chemicallyactivemolecules:theproteins.

  Proteinsarealsocarbon-basedpolymers,butincontrasttoDNA,mostofthechemicallyvariableparts ofproteinsarelocatedonthe outsideofthepolymermolecule.Thismeansthattheyinfluencethethree-dimensionalshapeoftheproteinandalsointeractwiththeworld.Thisisultimatelywhatallowsthemto perform their many functions, building, maintaining and reproducing the chemical machine. And unlike DNA,ifproteinsaredamagedordestroyed,thecellcansimplyreplacethembybuildinganewprotein molecule.

  Icannotimagineamoreelegantsolution:differentconfigurationsoflinearcarbonpolymersgenerate both chemically stable information storage devices and highly diverse chemical activities. I find this aspectoflife’schemistrybothutterlysimpleandcompletelyextraordinary.Thewaylifecouplescomplex polymerchemistrywithlinearin
formationstorageissuchacompellingprinciplethatIspeculatethatitis notonlycoretolifeonEarth,butisalsolikelytobecriticalforlifewhereverelseitmaybefoundinthe

  universe.

  Thoughweandallotherknownlifeformsdependoncarbonpolymers,weshouldnotbelimitedinour thinkingaboutlifebyourexperienceoflife’schemistryonEarth.Itispossibletoimaginelifeelsewhere in the cosmos that uses carbon in different ways, or life that is not built on carbon at all. The British chemistandmolecularbiologistGrahamCairns-Smithproposedinthe1960saprimitivelifeformbased onself-replicatingparticlesofcrystallineclay,forexample.

  Cairns-Smith’simaginedclayparticleswerebasedonsilicon,apopularchoiceofsciencefictionwriters when they imagine otherworldly life forms. Like carbon, silicon atoms can make up to four chemical bondsandweknowtheycanformpolymers:thesearethebasisofsiliconsealants,adhesives,lubricants and kitchenware. In principle, silicon polymers might be large and varied enough to contain biological information.However,despitesiliconbeingfarmoreabundantonEarththancarbon,lifehereisbasedon carbon.Thatmightbebecauseundertheconditionsfoundonthesurfaceofourplanetsilicondoesnot form chemical bonds with other atoms as readily as carbon does, and it does not therefore produce enoughchemicaldiversityforlife.Itwouldbefoolish,though,toruleoutthepossibilitythatsilicon-based life, or for that matter life based on other chemistries altogether, might thrive in different conditions foundelsewhereintheuniverse.

  Whenthinkingaboutwhatlifeis,itistemptingtodrawasharpdividinglinebetweenlifeandnon-life.

  Cellsareclearlyaliveandallorganismsmadefromcollectionsofcellsarealivetoo.Butthereareother life-likeformsthathaveamoreintermediatestatus.

  Virusesaretheprimeexample.Theyarechemicalentitieswithagenome,somebasedonDNA,others onRNA,whichcontainsgenesneededtomaketheproteincoatthatencapsulateseachvirus.Virusescan evolvebynaturalselection,thuspassingMuller’stest,butbeyondthatthingsarelessclear.Inparticular, viruses cannot, strictly speaking, reproduce themselves. Instead, the only way they can multiply is by infectingthecellsofalivingorganismandhijackingthemetabolismoftheinfectedcells.

  Sowhenyoucatchacold,virusesenterthecellsthatlineyournoseanduseyournosecell’senzymes and raw materials to reproduce the virus many times. So many viruses are produced, in fact, that the infectedcellinyournoseruptures,releasingthousandsofcoldviruses.Thesenewvirusesinfectnearby cellsandgetintoyourbloodstreamtoinfectcellselsewhere.Itisahighlyeffectivestrategyforavirusto perpetuateitself,butmeansthattheviruscannotoperateseparatelyfromthecellularenvironmentofits host.Inotherwords,itiscompletelydependentonanotherlivingentity.Youcouldalmostsaythatviruses cycle between being alive, when chemically active and reproducing in host cells, and not being alive, whenexistingaschemicallyinertvirusesoutsideacell.

  Somebiologistsconcludethattheirstrictdependenceonanotherlivingentitymeansthatvirusesare nottrulyalive.Butit’simportanttorememberthatalmostallotherformsoflife,includingourselves,are alsodependentonotherlivingbeings.

  Yourfamiliarbodyisinfactanecosystemmadeupofamixtureofhumanandnon-humancells.Our own30trillionorsocellsareoutnumberedbythecellsofdiversecommunitiesofbacteria,archaea,fungi andsingle-celledeukaryotesthatliveonusandinsideus.Manypeoplecarrywiththemlargeranimals too,includingavarietyofintestinalwormsandthetinyeight-leggedmitesthatliveonourskinandlay their eggs in our hair follicles. Many of these intimate, non-human companions depend heavily on our cells and bodies, but we also depend on some of them too. For example, bacteria in our guts produce certainaminoacidsorvitaminsthatourcellscannotmakeforthemselves.

  And we should not forget that every single mouthful of the food we eat is produced by other living organisms. Even many microbes, such as the yeast I study, are completely dependent upon molecules usuallymadebyotherlivingorganisms.Theseincludeglucoseandammoniaforexample,thatareneeded formakingcarbon-andnitrogen-containingmacromolecules.

  Plantsappeartoberathermoreindependent.Theycandrawcarbondioxideoutoftheairandwater from the earth, and use the energy of the sun to synthesize many of the more complex molecules they need, including carbon polymers. But even plants rely on bacteria found in or near their roots that capture nitrogen from the atmosphere. Without them they cannot make the macromolecules of life. In fact,thisissomethingthat,sofarasweknow,noeukaryotecandoforitself.Thatmeansthereisnota singleknownspeciesofanimal,plantorfungusthatcangenerateitsowncellularchemistryentirelyfrom scratch.

  So perhaps the most genuinely independent life forms – the only ones with some claim to be fully independent and ‘free-living’ – are some that might at first seem rather primitive. These include the microscopiccyanobacteria,oftencalledblue-greenalgae,thatcanbothphotosynthesizeandcapturetheir own nitrogen, and the archaea that get all their energy and chemical raw materials from volcanically activehydrothermalventsdeepbelowthesea.Strikingly,theserelativelysimpleorganismshavenotonly survivedforfarlongerthanwehave,buttheyarealsomoreself-reliantthanweare.

  The deep interdependency of different life forms is also reflected in the fundamental make-up of our cells.Themitochondriathatproducetheenergyourbodiesneedwereonceentirelyseparatebacteria–

  onesthathadmasteredtheabilitytomakeATP.Throughsomeaccidentoffatethattookplacearound1.5

  billionyearsago,someofthesebacteriatookupresidenceinsideanothertypeofcell.Overtime,thehost cells became so dependent on the ATP made by their bacterial guests that the mitochondria became a permanentfixture.Thecementingofthismutuallybeneficialrelationshipprobablymarkedthebeginning of the entire eukaryote lineage. With a reliable supply of energy, the cells of eukaryotes were able to becomebiggerandmorecomplex.This,inturn,precipitatedtheevolutionoftoday’sexuberantdiversity ofanimals,plantsandfungi.

  This all demonstrates that there is a graded spectrum of living organisms that ranges from wholly dependentviruses,throughtothemuchmoreself-sufficientcyanobacteria,archaeaandplants.Iwould argue that these different forms are all alive. That’s because they are all self-directed physical entities that can evolve by natural selection, although they are also all dependent to varying degrees on other livingorganisms.

  Fromthisbroaderperspectiveonlifegrowsaricherviewofthelivingworld.LifeonEarthbelongstoa single, vastly interconnected ecosystem, which incorporates all living organisms. This fundamental connectedness comes not only from their deep interdependency, but also from the fact that all life is genetically related through its shared evolutionary roots. This perspective of deep relatedness and interconnectednesshaslongbeenchampionedbyecologists.Ithasitsoriginsinthethinkingoftheearly nineteenth-century explorer and naturalist Alexander von Humboldt, who argued that all life is bound togetherbyaholisticwebofconnections.Unexpectedasitmaybe,thisinterconnectivityiscoretolife, andshouldgiveusgoodreasontopauseandthinkmoredeeplyabouttheimpacthumanactivityhason therestofthelivingworld.

  Theorganismsthatliveonthemanybranchesoflife’ssharedfamilytreeareastonishinglyvaried.But thatvarietyisoutshonebytheirfargreaterandmorefundamentalsimilarities.Aschemical,physicaland informational machines, the basic details of their operations are the same. For exampl
e, they use the same small molecule, ATP, as their energy currency; they rely on the same basic relationships between DNA,RNAandprotein;andtheyuseribosomestomaketheirproteins.FrancisCrickarguedthattheflow of information from DNA to RNA to protein was so fundamental to life that he called it the ‘Central Dogma’ofmolecularbiology.Somehavesincepointedoutminorexceptionstotherule,butCrick’skey pointstillstands.

  Thesedeepcommonalitiesinlife’schemicalfoundationspointtoaremarkableconclusion:lifeasitis onEarthtodaystarted justonce.Ifdifferentlifeformshademergedseveraltimesindependently,andhad survived,itisextremelyunlikelythattheirdescendantswouldallconducttheirbasicoperationsinsucha similarway.

  If all life is part of the same vast family tree, what kind of seed did that tree grow from? Somehow, somewhere, a very long time ago inanimate and disordered chemicals arranged themselves into more ordered forms that could perpetuate themselves, copy themselves and eventually gain the all-important ability to evolve by natural selection. But how did this story, which is eventually our story too, actually start?

  TheEarthwasformedalittleover4.5billionyearsago,atthedawnofoursolarsystem.Forthefirst half a billion years or so, the surface of the planet was too hot and unstable to have allowed the emergence of life as we know it. The oldest unambiguously identified fossil organisms yet found lived around 3.5 billion years ago. That gives a window of a few hundred million years for life to get up and running.That’s a longerexpanse of timethan our minds canreadily comprehend, butis rather a small fraction of the total history of life on Earth. For Francis Crick, it seemed too improbable that life could havestarted here onEarth in thetime available. That’s whyhe suggested thatlife must have emerged elsewhere in the universe and been delivered here in either a partially or fully formed state. But this rather evades, instead of answers, the crucial question of how life might have started from humbler beginnings.Today,wecangiveacredible,ifpresentlyunverifiable,accountofthatstory.