If we want to accelerate progress in tackling cancer and other non-infectious diseases, decoding the informationinourgenesprovidesimportantnewwaysforward.WhenthefirstdraftDNAsequenceofthe human genome was shared with the world in 2003 it promised to open the door to a new future of preventativemedicine.Manyofthoseinvolvedlookedforwardtoaworldwhereanyindividual’sgenetic riskfactorscouldbeaccuratelycalculatedatthemomentofbirth,includingpredictionsabouthowthose riskswouldinteractwithlifestyleanddiet.Butrealizingthisaimisverychallenging,bothscientifically andethically.
That’spartlybecauseoflife’sprofoundcomplexity.Fewhumancharacteristicsbehaveliketheclear-cut characters of the pea seedlings that Mendel studied in his garden. The diseases that are caused in a similar way, by defective versions of single genes, include Huntington’s disease, cystic fibrosis and haemophilia. Together these diseases cause a great deal of suffering and pain, but they each affect relativelysmallnumbersofpeople.Mostcommondiseasesanddisorders,includingheartdisease,cancer and Alzheimer’s disease, by contrast, have more multi-factorial triggers. They are caused by the combinedinfluencesofmanyindividualgeneswhichoperateandinteractwitheachotherandwiththe environmentsweliveinincomplicatedandhard-to-predictways.Wearestartingtounraveltheintricate chainsofcauseandeffectthatintertwineournatureandournurture,butallprogressishard-wonand slow.
This is an area where understanding Life as Information comes to the fore. Researchers are now amassing extremely large collections of data – some of them containing gene sequences, lifestyle information and medical records gathered from up to millions of different people. But making sense of suchlargedatasetsisdifficult.Theinteractionsbetweengenesandenvironmentaresocomplexthatthe researchers who study them are stretching the limits of presently available techniques, including new approachessuchasmachinelearning.
Usefulinsightsareemerging,though.Itisnowpossibletousegeneticprofilingtoidentifypeoplewith an elevated risk of suffering heart disease, or becoming obese, for example. These can be used to give adviceaboutlifestyleanddrugtreatmentsthatistailoredtoindividuals.Thisisgoodprogress,butasthe ability to make accurate predictions from our genomes gets better, we must think hard about how this knowledgeshouldbestbeused.
Accurategeneticpredictorsofillhealthposeparticulardifficultiesformedicalsystemsthatarefunded by personal health insurance. Without strict controls on how gene information can be used, individuals could find themselves being deemed uninsurable and denied care, or charged unaffordably high
insurancepremiumsthroughnofaultoftheirown.Therearenosuchproblemswithmedicalsystemsthat provide care that is free at the point of delivery, since they will be able to use advances in genetic predisposition to predict, diagnose and treat disease more easily. That said, this is not always easy knowledge to live with. If genetic science advanced to the point where it could make a reasonably accuratepredictionofwhenandhowyouaremostlikelytodie,wouldyouwanttoknow?
Then there is deciphering the genetic factors that influence non-medical factors, such as general intelligenceandeducationalattainment.Aswelearnmoreaboutgeneticdifferencesbetweenindividuals, genders and populations, we must make sure these insights are never used as the basis for discrimination.
Advancing in parallel with the ability to read genomes is the ability to edit and rewrite them. An enzymecalledCRISPR-Cas9isapowerfultoolthatfunctionslikeapairofmolecularscissors.Scientists canuseittomakeveryprecisecutsinDNA,inordertoadd,deleteoraltergenesequences.Thisiswhat is referred to as gene-editing, or genome-editing. Biologists have been able to do this in simple organisms,suchasyeast,sincearound1980,whichisoneofthereasonsthatIhaveworkedwithfission yeast, but CRISPR-Cas9 vastly improves the speed, accuracy and efficiency with which DNA sequences can be edited. It also makes it much easier to edit the genes of many more species, including human beings.
Intime,wecanexpectnewtherapiesbasedongene-editedcells.Researchersarealreadymakingcells thatareresistanttospecificinfections,suchasHIV,orusingthemtoattackcancers,forexample.Butfor thetimebeing,itisextremelyrecklesstoattempttoedittheDNAofearlystagehumanembryos,which wouldresultingeneticchangesinallthecellsofthepersonborn,andthoseofanychildrentheymight haveinthefuture.Atpresentthereisariskthatgene-basedtherapiesmightaccidentallychangeother genesinthegenome.However,evenifonlythedesiredgeneisedited,thosegeneticchangescouldalso cause hard-to-predict and potentially dangerous side effects. We simply don’t yet understand our genomes well enough to know for sure. There may come a time when this procedure is deemed safe enoughtofreefamiliesfromcertaingeneticdiseases,likeHuntingdon’sorcysticfibrosis.Butusingitfor more cosmetic purposes, like creating babies with enhanced intelligence, great beauty, or high athletic abilityisanothermatteraltogether.Thisareaentailsoneofthemostthornyoftoday’sethicalconcerns abouttheapplicationofbiologytohumanlife.Butalthoughtalkofusinggeneeditingtomakedesigner babiesismostlyhotairatpresent,manyparents-to-bewillhavetocontemplatesomechallengingissues in the years and decades to come, as scientists develop more powerful abilities to predict genetic influences,modifygenesandmanipulatehumanembryosandcells.Alltheseissuesneedtobediscussed bysocietyasawhole,andtheyneedtobediscussednow.
At the other end of life, advances and developments in cell biology are providing ways to treat degenerative diseases. Take stem cells, for example: these are cells that the body maintains in an immature state, rather like those present in an early embryo. The key property of stem cells is their abilitytodividerepeatedly,toproducenewcellsthatcanthengoontoadoptmorespecializedproperties.
Agrowingfetusorababycontainslargenumbersofstemcells,sincetheyhaveaconstantrequirement fornewcells.Butstemcellsalsopersistinmanydifferentpartsoftheadultbodylongafterithasstopped growing.Manymillionsofyourbody’scellsdieorareshedeveryday.That’swhyyourskin,yourmuscles, theliningofyourgut,theedgesofthecorneasinyoureyes,andmanyothertissuesofyourbodycontain populationsofstemcells.
Inrecentyearsscientistshaveworkedouthowtoisolateandculturestemcellsandtopushthemto developintospecificcelltypes–nerve,liverormusclecells,forexample.Itisalsonowpossibletotake fully mature cells from a patient’s skin and treat them in such a way that they turn back the developmentalclock,revertingtoastemcellstate.Thisraisestheexcitingprospectthatitmightoneday bepossibletotakeaswabfrominsideyourcheekandusethecellstogeneratealmostanyothercellin your body. If scientists and doctors can fully master these techniques, and can establish that they are safe,theycouldpotentiallyrevolutionizetreatmentofdegenerativediseaseandinjuriesandrevolutionize transplant surgery. It might even become possible to reverse currently incurable conditions of the nervoussystemsandmuscles,likeParkinson’sdiseaseormusculardystrophy.
Thisprogressispartofwhathasinspiredboldpredictions,manyofthememanatingfromfirmsbased inSiliconValley,ofafast-approachingfutureinwhichitwillbepossibletoarrestorevenreverseageing.
It is important to keep these claims grounded in practical reality. Personally, I will not be opting to cryopreservemybrainorbodywhenmytimeisup,inanticipationofahighlyunlikelyfuturetimewhenI might b
e resuscitated, rejuvenated and kept alive into perpetuity. Ageing is the end product of the combined damage, death and pre-programmed shutdown of a body’s cells and organ systems. Even for those in fine health, skin becomes less elastic, muscles lose tone, the immune systems becomes less responsive,andthepoweroftheheartgraduallyweakens.Thereisnosinglecauseforallthisanditis, therefore,veryunlikelythattherecanbeastraightforwardfix.ButIhavelittledoubtthedecadesahead willseelifeexpectancycreepingonupwardsand–importantly–thequalityoflifeimprovinginoldage.
Wewillnotliveforever,butwecouldallbenefitfromevermorerefinedtreatmentsthatusecombinations ofstemcells,noveldrugsandgene-basedtherapies,aswellashealthylifestylepractices,toreviveand regeneratemanypartsofelderlyandailingbodies.
Theapplicationofbiologicalknowledgehasnotonlyrevolutionizedourabilitytomendbrokenbodies, it has allowed humankind as a whole to flourish. Beginning around 10,000 BCE, the world’s population leapedupwardswhenourancestorsstartedfarming.Theydidn’tseeitthiswayatthetime,butthiswas achievedbyourhumanancestorsapplyingtheprinciplesofartificialselectiontodomesticateanimalsand
plants.Amuchlargerandmorereliablesupplyoffoodwasthereward.
Comparedtotheprehistoricalsurge,theworld’spopulationhasgrownevenmoredramaticallywithin mylifetime:ithasnearlytripledsinceIwasbornin1949.Thatmeansnearly5billionextramouthsthat must be fed each day, with all that extra food being produced on roughly the same area of agricultural land. The Green Revolution, which started in the 1950s and 60s, was key to making this possible. This involved developments in irrigation, fertilizers, pest control and, most importantly, the creation of new strainsofstaplefoodcrops.Incontrasttobreedersthroughouthistory,thescientistsinvolvedwereable to leverage all that had been gleaned about genetics, biochemistry, botany and evolution towards the production of novel plant varieties. It was astonishingly successful and generated new crops with significantly higher yields. This hasn’t been an entirely cost-free exercise, however. Some of today’s intensivefarmingpracticeshaveadamagingeffectontheland,farmers’livelihoods,andonotherspecies thatsharetheenvironmentwithfoodcrops.Theamountoffoodwastedeverydayisascandalthatmust alsobesolved.Butwithoutthatmajorinjectionofbiologicalknowledgeintofarmingpracticelastcentury, millionsmorewouldstarveeveryyear.
The global population continues to grow today. As it does, there is increasing concern about the damagehumanactivitydoestothelivingworld.Lookingahead,wefacethestarkcombinedchallengeof ekingoutyetmorefoodfromtheland,whilstalsotryingtoreduceourenvironmentalimpact.Ithinkwe willneedtogobeyondthemethodsthatdrovelastcentury’sagriculturalrevolutionanddeviseevenmore efficientandcreativewaysofproducingfood.
Butunfortunately,sincethe1990s,attemptstocreategeneticallymodified(GM)strainsofplantsand livestock with enhanced properties have often been blocked. Frequently this has had little to do with scientific evidence and understanding. I have seen debates about the safety of GM foods constantly derailedbymisunderstanding,misplacedlobbyingandtheinjectionofmisleadinginformation.Consider thecaseofgoldenrice,whichhasbeengeneticallyengineeredtoincorporateabacterialgeneintooneof the rice plant’s chromosomes, which makes it produce large quantities of vitamin A. There are an estimated 250 million preschool children across the world who are deficient in vitamin A, which is a significantcauseofblindnessanddeath.Goldenricemightprovideadirectwaytohelp,yetithasbeen attacked repeatedly by environmental campaigners and non-governmental organizations (NGOs) who haveevenvandalizedfieldtrialssetupspecificallytotestitssafetyanditseffectontheenvironment.
Isitreallyacceptabletodenytheworld’spoorestaccesstoinventionsthatcouldhelptheirhealthand food security, especially if that denial is based on fashion and ill-informed opinion rather than sound science?ThereisnothingintrinsicallydangerousorpoisonousaboutfoodstuffsmadeusingGMmethods.
Whatreallymattersisthat all plants and livestock should be similarly tested for their safety, efficiency andpredictedenvironmentalandeconomicimpact,regardlessofhowtheyhavebeenmade.Weneedto considerwhatthesciencehastosayaboutrisksandbenefits,uncolouredbyeithercommercialinterests ofcompanies,theideologicalopinionsofNGOs,orthefinancialconcernsofboth.
In the coming decades, I think that we will have to use genetic engineering techniques more. This couldbeanareawheretherelativelynewbranchofscienceknownas syntheticbiology could make an impact.Syntheticbiologistsseektogobeyondthemorefocusedandincrementalapproachestraditionally usedingeneticengineering,towritemoreradicalchangestoorganisms’geneticprogramming.
The technical challenges here are substantial, and there are questions about how we control and containthesenewspecies,butthepotentialrewardscouldbesignificant.That’sbecauselife’schemistry isfarmoreadaptableandefficientthanmostchemicalprocessespeoplehavebeenabletocarryoutin labs or factories. With GM and synthetic biology we could reorganize and repurpose life’s chemical brilliance in powerful new ways. It should be possible to use synthetic biology to create nutritionally enhancedcropsandlivestock,butitcouldbeappliedmorebroadlythanthat.Itcouldseeuscreatingre-engineered plants, animals and microbes that produce entirely new types of pharmaceuticals, fuels, fabricsandbuildingmaterials.
Novelengineeredbiologicalsystemsmightevenhelptackleclimatechange.Thescientificconsensusis clear that our planet has entered a phase of accelerating global warming. This is a grave threat to our futureandtothatofthewiderbiospherethatwearebutonepartof.Anincreasinglyurgentchallengeis toreducetheamountofgreenhousegasesthatweemitandreducetheextentofwarming.Ifwecouldre-engineer plants to carry out photosynthesis even more efficiently than they do, or make it work at an industrial scale, outside the confines of living cells, it might be possible to make biological fuels and industrialfeedstocksthatarecarbonneutral.Scientistsmayalsobeabletoengineernovelplantvarieties that can thrive in marginal environments, for example in degraded soils or areas that are prone to drought, that previously have not supported cultivation. Such plants could be used not only to feed the worldbut also todraw down andstore carbon dioxide tohelp manage climatechange. They could also formthebasisoflivingfactoriesthatworkinsustainableways.Insteadofrelyingonfossilfuels,itmight be possible to produce biological systems that will feed more effectively off waste, by-products and sunlight.
In parallel with these engineered life forms, another goal would be to increase the total area of the planet’s surface that is covered by naturally occurring photosynthesizing organisms. This is not such a straightforwardproposalasitmightfirstseem.Tomakeameaningfulimpactitneedstobeimplemented atamassivescale,andalsothereneedstobeconsiderationoftheissueoflong-termcarbonstorageonce the plants have died or been harvested. It could involve more forests, cultivating algae and seaweed in the oceans, and encouraging the formation of peat bogs. But making any intervention work effectively and quickly enough will stretch our understanding of ecological dynamics to its limits. The ongoing,
widespread, and largely unexplained decline in insect numbers is a case in point. Our future is tied to insectspecies,sincetheypollinatemanyofourfoodcrops,buildsoils,andmorebesides.
Progr
essinalltheseapplicationsrequiresbetterunderstandingoflifeandhowitworks.Biologistsof alldisciplines–molecularandcellularbiologists,geneticists,botanists,zoologists,ecologistsandbeyond
–allneedtoworkalongsideoneanothertohelpensurehumancivilizationcontinuestoflourish,together with,ratherthanattheexpenseof,therestofthebiosphere.Foranyofthistosucceedweneedtoface up to the scale of our ignorance. Despite the great progress we have made in understanding how life works,ourpresentunderstandingispartial,sometimesverymuchso.Ifwewanttointerferewithliving systemsconstructively–andsafely–toachievesomeofourmoreambitiouspracticalgoals,westillhave muchtolearn.
Thedevelopmentofnewapplicationsshouldalwaysmoveforwardhandinhandwitheffortstolearn moreabouthowlifeworks.AstheNobelprizewinningchemistGeorgePorteronceputit:‘Tofeedapplied sciencebystarvingbasicscienceislikeeconomizingonthefoundationsofabuildingsothatitmaybe builthigher.Itisonlyamatteroftimebeforethewholeedificecrumbles.’Butbythesametokenitisself-indulgent of scientists not to recognize that useful applications should be generated wherever possible.
Whenweseeopportunitiestousethatknowledgeforthepublicgoodwemustdoso.
Thiscreatesfreshquestionsandfurtherproblems,however.Howdoweagreeonwhatwemeanbythe
Paul Nurse - What Is Life Page 11