‘Abeautifullywrittenexplorationofperhapsthemostimportantquestioninscience.IfeltIwasbeinggivenrareaccessto atrulydeepunderstandingofacomplexandprofoundsubject.ThisisthebestintroductiontomodernbiologyI’veread.’
BrianCox
‘Inthisvibrant,livelybook,SirPaulNurse,discovererofsomeofthecrucialgenesthatcontrolthedivisionofcells,takesa deepdiveintobiologybyilluminatingfiveoftheessentialcharacteristicsof“life”.Thewritingissospiritedand knowledgeable–andthefivesectionssofullofwondrousrevelations–thatIcouldnotputitdown.Thisisabookthatwill inspireagenerationofbiologists.’
SiddharthaMukherjee
‘Amasterfuloverviewofbiologythatdrawstogetherbigideas,luminousdetailsandpersonalinsights.Youemergewitha moreprofoundsenseofwonderaboutthediversity,complexityandinterconnectednessoflivingorganisms.It’sthe biggestquestioninbiology.AndthisbookrepresentsthebestanswerI’veeverseen.PaulNurseisararelife-form–a Nobel-winningscientistandabrilliantcommunicator.’
AliceRoberts
‘PaulNurseisaboutasdistinguishedascientistastherecouldbe.Heisalsoagreatcommunicator.Thisbookexplains,in awaythatisbothclearandelegant,howtheprocessesoflifeunfold,anddoesasmuchassciencecantoanswerthe questionposedbythetitle.It’salsoprofoundlyimportant,atatimewhentheworldisconnectedsocloselythatanynew illnesscansweepfromnationtonationwithimmensespeed,thatallofus–includingpoliticians–shouldbeaswell-informedaspossible.Thisbookprovidesthesortofclarityandunderstandingthatcouldsavemanythousandsoflives.I learnedagreatdeal,andIenjoyedtheprocessenormously.’
PhilipPullman
‘PaulNurseprovidesaconcise,lucidresponsetoanage-oldquestion.Hiswritingisnotjustinformedbylongexperience, butalsowise,visionaryandpersonal.Ireadthebookinonesitting,andfeltexhilaratedbytheend,asthoughI’drunfor miles–fromtheauthor’sowngardenintotheinteriorofthecell,backintimetohumankind’smostdistantancestors,and throughthelaboratoryofadedicatedscientistatworkonwhathemostlovestodo.’
DavaSobel
Lifeisallaroundus,abundantanddiverse,itisextraordinary.Butwhatdoesitactuallymeantobealive?
Nobelprize-winnerPaulNursehasspenthiscareerrevealinghowlivingcellswork.Inthisbook,hetakesupthechallenge ofdefininglifeinawaythateveryreadercanunderstand.Itisasharedjourneyofdiscovery;stepbystepheilluminates fivegreatideasthatunderpinbiology.Hetracestherootsofhisowncuriosityandknowledgetorevealhowscienceworks, bothnowandinthepast.Usinghispersonalexperiences,inandoutofthelab,heshareswithusthechallenges,thelucky breaks,andthethrillingeurekamomentsofdiscovery.
Tosurvivethechallengesthatfacethehumanracetoday–fromclimatechange,topandemics,lossofbiodiversityand foodsecurity–itisvitalthatweallunderstandwhatlifeis.
ToAndyMartynoga(Yog),friendandfather
andmygrandchildren:
Zoe,Joseph,OwenandJoshua
andtheirgeneration
whowillneedtocareforLifeonourplanet
CONTENTS
TitlePage
Dedication
Introduction
1.TheCell
Biology’sAtom
2.TheGene
TheTestofTime
3.EvolutionbyNaturalSelection
ChanceandNecessity
4.LifeasChemistry
OrderfromChaos
5.LifeasInformation
WorkingasaWhole
ChangingtheWorld
WhatisLife?
Acknowledgements
AbouttheAuthor
Copyright
INTRODUCTION
Itmayhavebeenabutterflythatfirststartedmethinkingseriouslyaboutbiology.Itwasearlyspring;I wasperhapstwelveorthirteenyearsoldandsittinginthegardenwhenaquiveringyellowbutterflyflew over the fence. It turned, hovered and briefly settled – just long enough for me to notice the elaborate veinsandspotsonitswings.Thenashadowdisturbeditandittookflightagain,disappearingoverthe oppositefence.Thatintricate,perfectlyformedbutterflymademethink.Itwasbothutterlydifferentto meandyetsomehowfamiliartoo.Likeme,itwassoobviouslyalive:itcouldmove,itcouldsense,itcould respond,itseemedsofullof purpose.Ifoundmyselfwondering:whatdoesitreallymeantobealive?In short,whatislife?
Ihavebeenthinkingaboutthisquestionformuchofmylife,butfindingasatisfactoryanswerisnot easy.Perhapssurprisingly,thereisnostandarddefinitionoflife,althoughscientistshavewrestledwith thisquestionacrosstheages.Eventhetitleofthisbook, WhatisLife?, hasbeenshamelesslystolenfrom a physicist, Erwin Schrödinger, who published an influential book of the same name in 1944. His main focus was on one important aspect of life: how living things maintained such impressive order and uniformity for generation after generation in a universe that is, according to the Second Law of Thermodynamics,constantlymovingtowardsastateofdisorderandchaos.Schrödingerquiterightlysaw thisasabigquestion,andhebelievedthatunderstandinginheritance–thatiswhatgenesareandhow theyarepassedonfaithfullybetweengenerations–waskey.
In this book I ask the same question – What is life? – but I do not think that only deciphering inheritancewillgiveusacompleteanswer.InsteadIwillconsiderfiveofbiology’sgreatideas,usingthem asstepsthatwecanclimb,oneatatime,togetaclearerviewofhowlifeworks.Theseideashavemostly beenaroundforsometime,andaregenerallywellacceptedforexplaininghowlivingorganismsfunction.
But I will draw these different ideas together in new ways, and use them to develop a set of unifying principlesthatdefinelife.Hopefullytheywillhelpyouseethelivingworldthroughfresheyes.
I should say, right at the start, that we biologists often shy away from talking about great ideas and grandtheories.Inthisrespectweareratherdifferentfromphysicists.Wesometimesgivetheimpression thatwearemorecomfortableimmersingourselvesindetails,cataloguesanddescriptions,whetherthat’s listingallthespeciesinaparticularhabitat,countingthehairsonabeetle’sleg,orsequencingthousands of genes. Perhaps it is nature’s bewildering, even overwhelming, diversity that makes it seem hard to seek out simple theories and unifying ideas. But important overarching ideas of this kind do exist in biology,andtheyhelpusmakesenseoflifeinallitscomplexity.
ThefiveideasIwillexplaintoyouare:‘TheCell’,‘TheGene’,‘EvolutionbyNaturalSelection’,‘Lifeas Chemistry’ and ‘Life as Information’. As well as explaining where they came from, why they are important, and how they interact, I want to show you that they are still changing and being further developedtoday,asscientistsallovertheworldmakenewdiscoveries.Ialsowanttogiveyouatasteof whatit’sliketobeengagedinscientificdiscovery,soIwillintroduceyoutothescientistswhomadethese advances, some of whom I knew personally. I will also tell you stories of my own experiences of doing research in the laboratory, the ‘lab’, including the hunches, the frustrations, the luck and the rare but wonderful moments of genuinely new insight. My aim is for you to share in the thrill of scientific discoveryandtoexperiencethesatisfactionthatcomesthroughagrowin
gunderstandingofthenatural world.
Humanactivityispushingourclimateandmanyoftheecosystemsitsupportstotheedgesof–oreven beyond–whattheycanbear.Tomaintainlifeasweknowit,wearegoingtoneedalltheinsightswecan getfromstudyingthelivingworld.Thatiswhyintheyearsanddecadesahead,biologywillincreasingly steerthechoiceswemakeabouthowpeoplelive,areborn,fed,healedandprotectedfrompandemics.I will describe some of the applications of biological knowledge and the difficult trade-offs, ethical uncertaintiesandthepossibleunintendedconsequencesthattheycangiveriseto.Butbeforewecanjoin thegrowingdebatesthatsurroundthesetopics,wefirstneedtoaskwhatlifeisandhowitfunctions.
Weliveinavastandawe-inspiringuniverse,butthelifethatthrivesrighthereinourtinycornerof thatgreaterwholeisoneofitsmostfascinatingandmysteriousparts.Thefiveideasinthisbookwillact likestepsthatwewillmoveup,progressivelyrevealingprinciplesthatdefinelifeonEarth.Thiswillalso helpusthinkabouthowlifeonourplanetmighthavefirstgotstartedandwhatlifemightbelikeshould weeverencounteritelsewhereintheuniverse.Whateveryourstartingpoint–evenifyouthinkthatyou knowlittleornothingaboutscience–bythetimeyouhavefinishedthisbook,mygoalisforyoutohavea bettersenseofhowyou,me,thatdelicateyellowbutterflyandallotherlivingthingsonourplanetare connected.
Itismyhopethat,together,wewillbeclosertounderstandingwhatlifeis.
1.THECELL
Biology’sAtom
IsawmyfirstcellwhenIwasatschool,notlongaftermyencounterwiththeyellowbutterfly.Myclass hadgerminatedonionseedlingsandsquashedtheirrootsunderamicroscopeslidetoseewhattheywere madefrom.Myinspirationalbiologyteacher,KeithNeal,explainedthatwewouldseecells,thebasicunit of life. And there they were: neat arrays of box-like cells, all stacked up in orderly columns. How impressiveitseemedthatthegrowthanddivisionofthosetinycellswereenoughtopushtherootsofan oniondownthroughthesoil,toprovidethegrowingplantwithwater,nutrientsandanchorage.
As I learned more about cells, my sense of wonder only grew. Cells come in an incredible variety of shapes and sizes. Most of them are too small to be seen with the naked eye – they are truly minute.
Individual cells of a type of parasitic bacteria that can infect the bladder could line up 3,000-abreast acrossaone-millimetregap.Othercellsareimmense.Ifyouhadaneggforbreakfast,considerthefact that the whole of its yolk is just one single cell. Some cells in our bodies are also huge. There are, for example,individualnervecellsthatreachfromthebaseofyourspineallthewaytothetipofyourbig toe.Thatmeansthosecellscaneachbeaboutametrelong!
Startling as all this diversity is, what is most interesting for me is what all cells have in common.
Scientistsarealwaysinterestedinidentifyingfundamentalunits,thebestexamplebeingtheatomasthe basic unit of matter. Biology’s atom is the cell. Cells are not only the basic structural unit of all living organisms,theyarealsothebasicfunctionalunitoflife.WhatImeanbythisisthatcellsarethesmallest entitiesthathavethecorecharacteristicsoflife.Thisisthebasisofwhatbiologistscall celltheory:tothe bestofourknowledge,everythingthatisaliveontheplanetiseitheracellormadefromacollectionof cells.Thecellisthesimplestthingthatcanbesaid,definitively,tobealive.
Celltheoryisaboutacenturyandahalfold,andithasbecomeoneofbiology’scrucialfoundations.
Giventheimportanceofthisideaforunderstandingbiology,Ifinditsurprisingthatithasnotcaughtthe public imagination more than it has. This might be because most people are taught in school biology classestothinkofcellsasmerebuildingblocksformorecomplexbeings,whentherealityismuchmore interesting.
Thestoryofthecellbeginsin1665withRobertHooke,amemberofthenewlyformedRoyalSocietyof London,oneofthefirstscienceacademiesintheworld.Asissooftenthecaseinscience,itwasanew technology that triggered his discovery. Since most cells are too small to see with the naked eye, their discoveryhadtowaitfortheinventionofthemicroscopeintheearlyseventeenthcentury.Scientistsare oftenacombinationoftheoristandskilledartisan,andthiswascertainlytrueofHooke,whowasequally comfortable exploring the frontiers of physics, architecture or biology as he was inventing scientific instruments. He built his own microscopes, which he then used to explore the strange worlds hidden beyondthereachofthenakedeye.
OneofthethingsHookelookedatwasathinsliceofcork.Hesawthatthecorkwoodwasmadeupof rowafterrowofwalledcavities,verysimilartothecellsintheonionroottipsIsawasaschoolboy300
yearslater.HookenamedthesecellsaftertheLatinword cella,meaningasmallroomorcubicle.Atthat time Hooke did not know that the cells he had drawn were in fact not only the basic component of all plants,butofalllife.
NotlongafterHooke,theDutchresearcherAntonvanLeeuwenhoekmadeanothercrucialobservation when he discovered single-celled life. He spotted these microscopic organisms swimming in samples of pondwaterandgrowingintheplaquehescrapedfromhisteeth:anobservationthatdisturbedhim,since he was rather proud of his dental hygiene! He gave these tiny beings an endearing name, that we no longer used today, ‘animalcules’. Those he found flourishing between his teeth were, in fact, the first bacteriaeverdescribed.Leeuwenhoekhadstumbledacrossanentirenewdomainofminutesingle-celled lifeforms.
We now know that bacteria and other sorts of microbial cells (‘microbe’ is a general term for all microscopic organisms that can live as single cells) are by far the most numerous life forms on Earth.
They inhabit every environment, from the high atmosphere to the depths of the Earth’s crust. Without them,lifewouldcometoastandstill.Theybreakdownwaste,buildsoils,recyclenutrientsandcapture from the air the nitrogen that plants and animals need to grow. And when scientists look at our own bodies,theyseethatforeachandeveryoneofour30trillionormorehumancells,wehaveatleastone microbialcell.You–andeveryotherhumanbeing–arenotanisolated,individualentity,butahugeand constantlychangingcolonymadeupofhumanandnon-humancells.Thesecellsofmicroscopicbacteria andfungilive onusand inus,affectinghowwedigestfoodandfightillnesses.
But before the seventeenth century, nobody had any idea that these invisible cells even existed, let alonethattheyworkedaccordingtothesamebasicprinciplesasallothermorevisiblelifeforms.
During the eighteenth century and into the beginning of the nineteenth century, microscopes and microscopic techniques improved, and very soon scientists were identifying cells from all manner of different creatures. Some began to speculate that all plants and animals were built from collections of thoseanimalculesthatLeeuwenhoekhadidentifiedseveralgenerationsbeforethem.Then,afteralong
gestation, the cell theory was finally fully born. In 1839 the botanist Matthias Schleiden and zoologist TheodoreSchwann,summarizedworkfromthemselvesandmanyotherresearchers,andwrote‘wehave seenthatallorganismsarecomposedofessentiallylikeparts,namelyofcells’.Sciencehadreachedthe illuminatingconclusionthatthecellisthefundamentalstructuralunitoflife.
Theimplicationsofthisinsightdeepenedfurtherwhenbiologistsrealizedthateverycellisalifeform initsownright.ThisideawascapturedbythepioneeringpathologistRudolfVirchow,whenhewrotein 1858 ‘that every animal appears as a sum of vital units, each of which bears in itself
the complete characteristicsoflife’.
What this means is that all cells are themselves alive. Biologists demonstrate this most vividly when theytakecellsfromthemulticellularbodiesofanimalsorplantsandkeepthemaliveinglassorplastic vessels, often flat-bottomed vessels called Petri dishes. Some of these cell lines have been growing in laboratoriesaroundtheworldfordecadesonend.Theyletresearchersstudybiologicalprocesseswithout needingtodealwiththecomplexityofwholeorganisms.Cellsareactive;theycanmoveandrespondto theenvironment,andtheircontentsarealwaysinmotion.Comparedtoawholeorganism,likeananimal oraplant,acellmayseemsimple,butitisdefinitelyalive.
There was, however, an important gap in cell theory, as originally formulated by Schleiden and Schwann.Itdidnotdescribehownewcellscameintobeing.Thatgapclosedwhenbiologistsrecognized thatcellsreproducebydividingthemselvesfromonecellintotwo,andconcludedthatcellsareonlyever made by the division of a pre-existing cell in two. Virchow popularized this idea with a Latin epigram:
‘ Omniscellulaecellula’,thatis,allcellscomefromcells.Thisphrasealsohelpedtocountertheincorrect idea,stillpopularamongstsomeatthetime,thatlifearisesspontaneouslyfrominertmatterallthetime–
itdoesnot.
Celldivisionisthebasisofthegrowthanddevelopmentofalllivingorganisms.Itisthefirstcritical step in the transformation of a single, uniform fertilized egg of an animal into a ball of cells and then, eventually,intoahighlycomplexandorganizedlivingbeing,anembryo.Itallbeginswithacelldividing andproducingtwocellswhichcantakeondifferentidentities.Theentiredevelopmentoftheembryothat thentakesplaceisbasedonthissameprocess–repeatedroundsofcelldivision,followedbythecreation ofanevermoreelaboratelypatternedembryo,ascellsmatureintoincreasinglyspecializedtissuesand organs.Thismeansthatalllivingorganisms,regardlessoftheirsizeorcomplexity,emergefromasingle cell. I think we would all respect cells a little more if we remembered that every one of us was once a singlecell,formedwhenaspermandaneggfusedatthemomentofourconception.
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