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Sleep and Dreams

Georges M. Halpern, MD, DSC

With Yves P. Huin

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Morpheus,thesonofSleep (ύπνος),andtheGodofDreams.Thenamesignifiesthefashionerormolder,becauseheshapedorformedthedreamswhichappearedtothesleeper.(Ov.Met.xi.635.)HewastheleaderoftheOneiroi(Oνειροι),thepersonifiedspirits(δαίμων)ofdreams.Hewasamessengerofthegodswhoappearedinthedreamsofkings inhumanguise.Hence,onethirdofour life(sometimesmore;attimes,muchless)wetakerefugeinthearmsofaGod–aminorone,butstill…

Sleepanddreamshavebeenpuzzlinghumansforever.Intercessors(magi,priests,pythias,shamans,exorcists,fortune-tellers,psychics,andnowneuroscientists)haveofferedmeaningstailoredtotheevents,thepatsy,thezanyoftheday.Wearestillfacingabigblackbox,oraseriesofRussiandolls-likemazes.

Themajorquestionsthatimmediatelyriseare:WhatisSleep?andthenWhydoweneedSleep?

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What Is Sleep?

Silence is the sleep that nourishes wisdom - Francis Bacon

TheWikipediaentrywasrevisedandupdatedon27December2017.Itislongandcomprehensive–asyoucanexpect-butitbrings,inlaylanguage,awealthofsolidinformation:

Sleep is a naturally recurring state of mind and body, characterized by alteredconsciousness,relativelyinhibitedsensoryactivity,inhibitionofnearlyallvoluntarymuscles, and reduced interactions with surroundings. It is distinguished fromwakefulnessbyadecreasedability toreact tostimulibut ismoreeasily reversedthanthestateofbeingcomatose.Sleepoccursinrepeatingperiods,inwhichthebodyalternatesbetweentwodistinctmodesknownasnon-REMandREMsleep.

AlthoughREMstandsfor"rapideyemovement",thismodeofsleephasmanyotheraspects,includingvirtualparalysisofthebody.Awell-knownfeatureofsleepisthedream,anexperiencetypicallyrecountedinnarrativeform,whichresembleswakinglifewhileinprogress,butwhichusuallycanlaterbedistinguishedasfantasy.

Duringsleep,mostofthebody'ssystemsareinananabolicstate,helpingtorestoretheimmune,nervous,skeletal,andmuscularsystems;thesearevitalprocessesthat

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maintainmood,memory, and cognitiveperformance, andplay a large role in thefunctionoftheendocrineandimmunesystems.

Theinternalcircadianclockpromotessleepdailyatnight.Thediversepurposesandmechanismsofsleeparethesubjectofsubstantialongoingresearch.Theadventofartificiallighthassubstantiallyalteredsleeptiminginindustrializedcountries.

MichelValentinMarcelJouvet(16November1925–3October2017)wasProfessorat the Collège de France –a colleague and friend of my father Bernard- and aProfessorofExperimentalMedicineattheUniversityofLyon.HewastheDirectoroftheResearchUnitINSERMU52(MolecularOnirology)andoftheAssociatedUnitUA1195oftheCNRS(StatesofVigilance-Neurobiology).

Hedescribedtheelectroencephalogramsignsofcerebraldeathin1959,andin1961categorized sleep into two different states: telencephalic (slow wave) sleep andrhombencephalicsleep(paradoxicalsleep,knownasREMsleepinEnglish-languagewritingsonthesubject).

IntheParadoxofSleep(MITPress,1999)Jouvetproposedthespeculativetheorythatthe purpose of dreaming is a kind of iterative neurological programming thatworkstopreserveanindividual'spsychologicalheredity,thebasisofpersonality.

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Hewaselectedin1977totheFrenchAcademyofSciences;in1991hewasawardedtheprestigiousPrixmondialCinoDelDuca.Hisworks,andthoseofhisteam,havebroughtaboutthediscoveryofparadoxicalsleepandtoitsindividualizationasthethirdstateoffunctioningofthebrain(1959),tothediscoveryofitsphylogenesis,ofitsontogenesisanditsmainmechanisms.

In 1959 Michel Jouvet conducted several experiments on cats regarding muscleatonia (paralysis) during REM sleep. Jouvet demonstrated that the generation ofREMsleepdependsonanintactpontinetegmentumandthatREMatoniaisduetoaninhibitionofmotorcentersinthemedullaoblongata.CatswithlesionsaroundthelocuscoeruleushavelessrestrictedmusclemovementduringREMsleep,andshowavariety of complex behaviors, including motor patterns suggesting that they aredreamingofattack,defenseandexploration.

Michel Jouvet: Polygraphs of Cats dreaming

Jouvet was the researcher who first developed the analeptic drug Modafinil(ProvigilÒ).

Asmentionedabove,themostpronouncedphysiologicalchangesinsleepoccurinthebrain.Especiallyduringnon-REMsleep,thebrainusessignificantlylessenergyduringsleepthanitdoesinwaking.Inareaswithreducedactivity,thebrainrestores

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itssupplyofadenosinetriphosphate(ATP),themoleculeusedforshort-termstorageandtransportofenergy.(Rememberthatinquietwakingthebrainisresponsiblefor20% of the body's energy use; this reduction has a noticeable impact on overallenergyconsumption.)

Sleep increases the sensory threshold: sleeping persons perceive fewer stimuli.However,theycangenerallystillrespondtoloudnoisesandothersalientsensoryevents.

Duringslow-wavesleep,humanssecreteburstsofgrowthhormone(children“grow”during sleep!). All sleep, even during the day, is associated with secretion ofprolactin.

MeasurementsindicatorsofsleepincludeEEGofbrainwaves,electrooculography(EOG) of eye movements, electromyography (EMG) of skeletal muscle activity.Simultaneous collection of these measurements: polysomnography, can beperformed in a sleep laboratory. Sleep researchers also use simplifiedelectrocardiography(EKG)forcardiacactivityandactigraphyformotormovements.

AsMichelJouvetdemonstrated, sleepisdividedintotwobroadtypes:non-rapideyemovement(non-REMorNREMsleep)andrapideyemovement(REMsleep);non-REM and REM sleep are so different that physiologists identify them as distinctbehavioralstates.Non-REMsleepoccursfirstandafteratransitionalperiodiscalledlowwavesleepordeepsleep.Duringthisphase,bodytemperatureandheartratefall,and the brain uses less energy. REM sleep (also known as paradoxical sleep), asmallerportionoftotalsleeptimeandthemainoccasionfordreams(ornightmares),is associatedwith desynchronized and fast brain waves, eyemovements, loss ofmuscletone,andsuspensionofhomeostasis.

ThesleepcycleofalternateNREMandREMsleeptakesanaverageof90minutes,occurring4–6timesinagoodnight'ssleep.

TheAmericanAcademyofSleepMedicine(AASM)dividesNREMintothreestages:N1,N2,andN3,thelastofwhichisalsocalleddeltasleeporslow-wavesleep.Thewholeperiodnormallyproceedsintheorder:N1→N2→N3→N2→REM.REMsleepoccurs as a person returns to stage 2 or 1 from a deep sleep. There is a greateramountofdeepsleep(stageN3)earlierinthenight,whiletheproportionofREMsleepincreasesinthetwocyclesjustbeforenaturalawakening.

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Awakening can mean the end of sleep, or simply a moment to survey theenvironmentandreadjustbodypositionbeforefallingbackasleep.Sleeperstypicallyawaken soon after the end of a REM phase or sometimes in themiddle of REM.Internalcircadianindicators,alongwithsuccessfulreductionofhomeostaticsleepneed,typicallybringaboutawakeningandtheendofthesleepepisode.Awakeninginvolvesheightenedelectricalactivationinthebrain,beginningwiththethalamusandspreadingthroughoutthecortex.

Duringanight'ssleep,asmallportionisusuallyspentinawakingstate.Asmeasuredbyelectroencephalography,youngfemalesareawakefor0–1%ofthelargersleepingperiod;youngmalesareawakefor0–2%.Inadults,wakefulnessincreases,especiallyinlatercycles.Onestudyfound3%awaketimeinthefirstninety-minutesleepcycle,8%inthesecond,10%inthethird,12%inthefourth,and13–14%inthefifth.MostofthisawaketimeoccurredshortlyafterREMsleep.Today,manyhumanswakeupwithanalarmclock.(Somepeople,however,canreliablywakethemselvesupataspecifictimewithnoneedforanalarm.Disclosure:Iamoneofthese).Manysleepquitedifferentlyonworkdaysversusdaysoff,apatternwhichcanleadtochroniccircadiandesynchronization.Manypeopleregularlylookattelevisionandotherscreensbeforegoingtobed,afactorwhichmayexacerbatethismasscircadiandisruption.Scientificstudiesonsleephaveshownthatsleepstageatawakeningisanimportantfactorinamplifyingsleepinertia.

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Sleeptimingiscontrolledbythecircadianclock(ProcessC),sleep-wakehomeostasis(ProcessS),andtosomeextentbyindividualwill.-[Foranin-depthexplorationofthe circadian rhythms, please readmy essayTheTimes of Time, available on thiswebsite.]

Thelongeranorganismisawake,themoreitfeelsaneedtosleep("sleepdebt").ThisdriverofsleepisreferredtoasProcessS.Thebalancebetweensleepingandwakingisregulatedbyaprocesscalledhomeostasis.

ProcessSisdrivenbythedepletionofglycogenandaccumulationofadenosineinthe forebrain that disinhibits the ventrolateral preoptic nucleus, allowing forinhibitionof theascending reticularactivating system.Sleepdeprivation tends tocause slower brainwaves in the frontal cortex, shortened attention span, higheranxiety,impairedmemory,andagrouchymood.Conversely,awell-restedorganismtends to have improved memory and mood. Neurophysiological and functionalimagingstudieshavedemonstratedthatfrontalregionsofthebrainareparticularlyresponsivetohomeostaticsleeppressure.Sleepdebtdoesshowsomeevidenceofbeing cumulative. Subjectively, however, humans seem to reach maximumsleepinessafter30hoursofwaking.

One neurochemical indicator of sleep debt is adenosine, a neurotransmitter thatinhibitsmanyofthebodilyprocessesassociatedwithwakefulness.Adenosinelevelsincrease in the cortex and basal forebrain during prolonged wakefulness anddecrease during the sleep-recovery period, potentially acting as a homeostaticregulator of sleep. Coffee and caffeine temporarily block the effect of adenosine,prolongsleeplatency,andreducetotalsleeptimeandquality.

A considerable amount of sleep-related behavior, such as when and how long aperson needs to sleep, is regulated by genetics. Monozygotic (identical) but notdizygotic (fraternal) twins tend to have similar sleep habits. Neurotransmitters,molecules whose production can be traced to specific genes, are one geneticinfluenceonsleepthatcanbeanalyzed.Andthecircadianclockhasitsownsetofgenes.GeneswhichinfluencesleepincludeABCC9,DEC2,andvariantsnearPAX8andVRK2.Myowngene(seeref.UCSF)inheritedfrommyfather,allowsmetowakeup(very!)earlywhereverIam,andfunctiondecentlywellwith4-6hoursofsleep.

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Thequalityofsleepmaybeevaluated fromanobjectiveandasubjectivepointofview.Objectivesleepqualityreferstohowdifficultitisforapersontofallasleepandremaininasleepingstate,andhowmanytimestheywakeupduringasinglenight.Poor sleepqualitydisrupts the cycleof transitionbetween thedifferent stagesofsleep. Subjective sleep quality in turn refers to a sense of being rested andregeneratedafterawakingfromsleep.Homeostaticsleeppropensity(theneedforsleep as a function of the amount of time elapsed since the last adequate sleepepisode)mustbebalancedagainstthecircadianelementforsatisfactorysleep.Alongwithcorrespondingmessagesfromthecircadianclock,thistellsthebodyitneedstosleep.Apersonwhoregularlyawakensatanearlyhourwillgenerallynotbeabletosleep much later than his/her normal waking time, even if moderately sleep-deprived.Thetimingiscorrectwhenthefollowingtwocircadianmarkersoccurafterthemiddleofthesleepepisodeandbeforeawakening:maximumconcentrationofthehormonemelatonin,andminimumcorebodytemperature.

Humansleepneedsvarybyageandamongstindividuals,andsleepisadequatewhenthere is no daytime sleepiness or dysfunction. Moreover, self-reported sleepduration is only moderately correlated with actual sleep time as measured byactigraphy,andthoseaffectedwithsleepstatemisperceptionmaytypicallyreporthavingsleptonlyfourhoursdespitehavingsleptafulleighthours.Researchershavefoundthatsleeping6–7hourseachnightcorrelateswithlongevityandcardiachealthinhumans,thoughmanyunderlyingfactorsmaybeinvolvedinthecausalitybehindthisrelationship.

Sleep difficulties are furthermore associated with psychiatric disorders such asdepression,alcoholism,andbipolardisorder.Upto90%ofadultswithdepressionwere found to have sleep difficulties. Dysregulation found on EEG includesdisturbances in sleep continuity, decreaseddelta sleep and alteredREMpatternsregardinglatency,distributionacrossthenightanddensityofeyemovements.

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We NEED Sleep! The human organism physically restores itself during sleep, healing itself andremovingwastewhichbuildsupduringperiodsofactivity.Thisrestorationtakesplacemostlyduringslow-wavesleep,duringwhichbody temperature,heart rate,andbrainoxygenconsumptiondecrease.

Thebrain,especially,requiressleepforrestoration,whereasintherestofthebodytheseprocessescantakeplaceduringquiescentwaking.Inbothcases,thereducedrate of metabolism enables countervailing restorative processes. While awake,metabolismgeneratesreactiveoxygenspecies,whicharedamagingtocells.Insleep,metabolic rates decrease, and reactive oxygen species generation is reducedallowingrestorativeprocessestotakeover.

Thesleepingbrainhasbeenshowntoremovemetabolicwasteproductsatafasterratethanduringanawakestate;sleephelpsfacilitatethesynthesisofmoleculesthathelp repair and protect the brain from these harmful elements generated duringwaking.Anabolichormones suchas growthhormonesare secretedpreferentiallyduring sleep. The concentration of the sugar compound glycogen in the brainincreases during sleep and is depleted through metabolism during wakefulness.Woundhealinghasbeenshowntobeaffectedbysleep.

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It has been shown that sleep deprivation affects the immune system: sleep lossimpairs immune functionand immunechallengealters sleep, and sleep increaseswhitebloodcellcounts.

Sleepenhancesmemory,withproceduralmemorybenefiting from late,REM-richsleep,andexplicitmemorybenefitingfromearly,slowwave-richsleep.

Duringsleep,especiallyREMsleep,peopletendtohavedreams:elusivefirst-personexperiences,which,despitetheirfrequentlybizarrequalities,seemrealisticwhileinprogress.Dreamscanseamlesslyincorporateelementswithinaperson'smindthatwouldnotnormallygotogether.Theycanincludeapparentsensationsofalltypes,especiallyvisionandmovement.

SigmundFreudpostulated that dreams are the symbolic expressionof frustrateddesires that have been relegated to the unconscious mind, and he used dreaminterpretationintheformofpsychoanalysisinattemptingtouncoverthesedesires.

Counterintuitively, penile erections during sleep are not more frequent duringsexual dreams than during other dreams. The parasympathetic nervous systemexperiences increasedactivityduringREMsleepwhichmaycauseerectionof thepenisorclitoris. Inmales,80%to95%ofREMsleep isnormallyaccompaniedbypartialtofullpenileerection,whileonlyabout12%ofmen'sdreamscontainsexualcontent.

DreamsarecausedbytherandomfiringofneuronsinthecerebralcortexduringtheREMperiod;thisexplainstheirrationalityofthemindduringREMperiods,astheforebrainthencreatesastorytoreconcileandmakesenseofthenonsensicalsensoryinformationpresentedtoit.Thisalsoexplainstheoddnatureofmanydreams.

Using antidepressants, benzodiazepines (and derived sleep-inducers),acetaminophen, ibuprofen, or alcoholic beverages potentially suppresses dreams,whereasmelatonincanencouragethem.

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Is Caffeine Bad –or even Good? Asmentionedabove,caffeineinterferes(interacts)withadenosineinthebrain,butalsoinmuscles(e.g.heart)-andalmosteverywhereinourbody.

It’swell-knownthatcaffeinecan,inextremecases,bedeadly.About10gramsofthestuffwillkillmostpeople.Butatypicalcupofcoffeehaslessthan100milligrams—orjust0.1gram—ofcaffeine.Inotherwords,onewouldneedtodrink100cupsofcoffee in rapid succession to (possibly) hit the deadly dose. For people withoutunderlying medical conditions, it’s exceptionally hard to die from drinkingcaffeinatedbeveragesbecauseofhow(relatively)littlecaffeinetheycontain.

ThisissomethingKingGustavIIIofSwedenfoundoutinthe18thcentury,whenheconductedanexperimenttoseewhetherteaorcoffeekillsfaster.Bothtestsubjectslivedwellintooldage,faroutlivingKingGustav-andtheresearchersconductingtheexperiment.

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There’s little scientific evidence suggesting that evenhighamountsof caffeinatedbeveragescancauseheartarrhythmias.A2016studyfoundthatpatientsathighriskforarrhythmiascouldimbibe500mgofcaffeineinafive-hourspanwithoutraisingtheirriskofirregularheartbeat.

Scientists andmedical professionals concerned about caffeine generally focus onenergy drinks, since they’re wildly popular but contain lots of ingredients thatinteract in unknownways, or on combinations of caffeine and alcohol,which getpeopledrunkerevenastheycontinuetofeelsober.Butwhileenergydrinksmaybea relatively new concoction, coffee and tea and other traditional caffeinatedbeverages are not. And there’s extensive research showing it’s wrong to suggesttypicalcaffeineconsumptionisdangerous.

When you drink a caffeinated beverage, the chemical immediately dissolves andspreadsthroughallthefluidsinyourbody.Thecaffeinecrossesintothebrainwithinminutes,whereitlatchesontoproteinsthatnormallyreceiveadenosine,achemicalthatmakesyoudrowsy.

Caffeine blocks adenosine receptors in the brain

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Caffeinereachesitspeakbloodconcentrationbetween45and60minutesafteryoudrink it.As timegoeson,your liverdegrades thecaffeine inyourblood,meaningthere’slessandlesstoelbowouttheadenosinemoleculesthatmakeyoutired.So,beforetoolong,youstarttogetsleepyagain.Inthreetofivehours,abouthalfthecaffeinefromthatcupofmorningjoewillhavedegraded;itmightfeelliketimeforarefill.

In addition, your brain receptors for adenosine are linked with receptors fordopamine,the“feel-good”chemical.Coffeemakesyouchippernotjustbecauseit’sfightingoffdrowsiness;butalso,becauseitmakesiteasierfordopaminetodoitsjob,whichinturnincreasesyourfeelingsofpleasure.Butdopamineisalsothekeyingredienttoaddiction;drugslikecocaineandamphetaminefloodpartsofthebrainwithittohijackthebrain’srewardsystem—thementalcircuitryofmotivation.Aftergetting flooded with those feelings of pleasure, you’ll naturally seek those goodfeelings repeatedly.Motivation is important to keeping you alive, likewhen yourbrainismakingyoueat.Butit’snotsogoodwhenit’smakingyousnortjustonemorelineat04:00amwhenthebaristryingtoclose.

Ifyoufocusjustondopamine,caffeinelookssortoflikeveryweakcocaine.It’sclearcaffeinehasreinforcingeffects;drinkingcoffeemakesyouwanttodrinkmorecoffee.Whatisn’tcleariswhetherit’strulyaddictive.It’sacontentioustopic.If“caffeine-usedisorder”weretobecomearecognizeddiagnosis,itwouldappearalongsideopioid-usedisorder, tobacco-usedisorder, andother oftendeadly addictions. This could“minimize the severity of other substance-use disorders,” says Maggie Sweeney, apsychiatryinstructoratJohnsHopkinsUniversity.Othersagree.“Itreallytrivializesotherknownaddictions,suchassmoking—weknowthoseareclearaddictions,“saysMarilynCornelis,anassistantprofessoratNorthwesternUniversity.“Ifweweretoasksomeonetocutoutsmokingandtheygavethatupforaweek,theymightstillcraveit….Coffee’salittledifferent.Youcanthinkaboutsomeonecuttingbackontheircoffee,andtheycoulddoitforamonth.Idon’tthinkthey’regoingtogocrazyiftheywalkintoaroomwithabunchofcoffeedrinkers.”

Addiction is typicallyunderstood tobe the resultofexposure toa substance thatincreasesdopamineinbrainstructures.Caffeinemakesthebrainmoresensitivetodopamine,butitdoesn’tincreaselevelsofthechemicalinthebrain.In2015,aUSNationalInstitutesofHealthteamundertookanexperimentonhumansandfound

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nodopamineincrease.Forsomescientists,thisisclearevidencethatcaffeineisnotaddictive.

AstridNehlig,aresearchdirectoratINSERM(FrenchNationalInstituteofHealthandMedicalResearch),pointsoutthataddictionsnegativelyimpactpeople’s lives,butcaffeinegenerallydoestheopposite.“Yougetdependentoncaffeine,butwhydoyoulikecaffeine?”saysNehlig.“Becauseitwakesyouup,it increasesyourwell-being,inaddition to helping you be productive, etc. And it’s also very often drank in socialconditions.Youmeetwithpeople;youhaveacoffee.So,it’salsopartofakindofritual.”

Caffeine’s short-termbenefitsareobvious.Butstudiesshowcoffeedoes farmorethanhelpyoufocusandimproveyourmood.Forexample,lifelongcoffeedrinkersare less likely to have Alzheimer’s, Huntington’s, and Parkinson’s diseases. Inaddition, if you consume caffeine in the morning, it can help maintain circadianrhythms, keeping your body’s 24-hour internal clock consistent. When yourcircadianrhythmsgetoutofwhack,you’reatriskforallsortsofsleepdisorders,aswellasweightgainandmentalhealthissues.(Ofcourse,caffeine’sabilitytoaffectyourbody’sinternalclockisalsowhyitmightbebadtoconsumecaffeineatnight.)

Infact,someresearcherssuggestweshouldbedrinkingthreeorfourcupsofcoffeeaday,ifwewanttoreapthefullbenefitsofcaffeinewithoutlosingsleeporfeelingagitated.Thatsaid,everyonehandlescaffeinedifferently;forsomepeoplefourcupsinadaymightkeepthemupallnight.This,itturnsout,iscodedintoyourgenes.Inthe past few years, researchers have identified specific variations in the humangenomethatenablecertainpeopletometabolizecaffeinefaster.Thatexplainswhyeveryone’s experience with caffeine is different, and why any one-size-fits-allrecommendation for caffeine is misguided. “For someone who can’t metabolizecaffeine very quickly…one or two cups of coffee per day…might be equivalent tosomeone[else]drinkingeightcupsaday,”saysCornelis.Ina2016study,researchersdiscoveredthatpeoplewhodrinkthemostcoffeearealsothepeoplewhosebodieshavethegeneticcodetobreakcaffeinedownfaster.Inotherwords,thestudysamplepopulationwasalreadydoingagoodjobself-regulatingtheirintake.Thissuggestscaffeineisn’tdangerousformostpeople,sincewenaturallysticktoourlimits.So,whenyougetjitteryorhavetroublesleeping,you’llsimplytakethatasasigntodrinkabitlessinthefuture.Andmeanwhile,you’llbegettingthedailybenefitsofcaffeine,and perhaps even building up your body’s defenses against neurodegenerative

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disease.Inaddition,it’sveryuncommonforpeopletohavetroublecuttingbackoncaffeine,iftheydoitgradually—say,foregoingthatsixthcupofcoffee,givingtheirbodyaweektore-equilibratetofivecups,thenundergoingthesameexperiencetogetdowntofourcupsadayandsettlingthere.Theonecaveatisthatthisresearchappliestothewaymostadultsconsumecaffeine—namely,drinkingcoffeetofightdrowsinessorwithdrawal-likesymptoms.

Childrenoftenreactverydifferentlytothedrug,likelyduetoseveralfactors:theirbrains are still developing; they’re consuming different types of caffeinatedbeverages; and they’redrinking them fordifferent reasons. JenniferTemple, nowdirectoroftheStateUniversityofNewYork-Buffalo’sNutritionandHealthResearchLaboratory, discovered that young people, ages 8-17, consume caffeine lessconsistentlythanadults,butmoreimportantly,theyconsumeitforentirelydifferentreasonsthanadults:“It’slessaboutcombatingfatigueandmoreaboutthingslike,‘Iuseittostudyforatest,orIuseittobebetteratplayingvideogames,orIuseittofeelhigh,’”Templesays.“Theyusealanguagethat’smuchmoreaboutperformance-enhancementormood-elevation,whereas in adults, the language… ismuchmorecenteredonwithdrawalreversal-‘soIwakeupinthemorning,Idon’twanttogetaheadache,Idon’twanttofeelsluggish,I’lldrinkmycoffee.’”Templesaysthere’snoevidencethatsmall-to-moderatedosesofcaffeinearedangerousfor8-17-year-olds,butshegenerallyrecommendschildrenavoidcaffeineentirely,becausetheydon’tneedittobefunctionalday-to-day,anditcaninterferewiththeirsleep.

Butmillions–maybebillions-ofpeopleconsumecoffeedaily,canaffordit,enjoyitandfindnosignificantadverseeffect.Nordoscientistsorhealthprofessionals.

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Why do we NEED Sleep?

“To die, to sleep - To sleep, perchance to dream - ay, there's the rub,

For in this sleep of death what dreams may come...”

William Shakespeare. Hamlet

The precise benefits of sleep are still mysterious, and for many biologists, theunknownsaretransfixing.Evensimplejellyfishmustrestlongerafterbeingforcedto stayup; there’s aneed tomakeup lost sleep,whichhasbeen seennot just injellyfishandhumans,butacrosstheanimalkingdom.

Whywefeeltheneedforsleepisseenbymanyaskeytounderstandingwhatitgivesus.Biologistscallthisneed“sleeppressure”:stayuptoolate,buildupsleeppressure.But like “darkmatter,” this is aname for somethingwhosenaturewedonot yetunderstand. Themore timewe spend thinking about sleep pressure, themore itseemslikeariddlegameoutofTolkien:Whatbuildsupoverthecourseofwakefulness,anddispersesduringsleep?Isitatimer?Amoleculethataccrueseverydayandneedstobeflushedaway?Whatisthismetaphoricaltallyofhours,lockedinsomechamberof the brain,waiting to bewiped clean every night? In otherwords, “What is thephysicalsubstrateofsleepiness?”

Biologicalresearchintosleeppressurebeganmorethanacenturyago.Insomeofthemostfamousexperiments,HenriPiéron,aFrenchscientistkeptdogsawakeformorethan10days.Then,hesiphonedfluidfromtheanimals’brains,andinjecteditintothebrainsofnormal,well-restedcanines,whichpromptlyfellasleep.Therewassomethinginthefluid,accumulatingduringsleepdeprivation,thatmadethedogsgounder.Thehuntwasonforthisingredient,thishypnotoxin,asPiéroncalledit,wouldreveal why animals grow drowsy, as he wrote in Le Problème Physiologique duSommeil(MassonEd.,Paris,1912).

Ifyouneededproofthatsleep,withitspeculiarmany-stagedstructureandtendencytofillyourmindwithnonsense,isn’tsomepassive,energy-savingstate,considerthatgoldenhamstershavebeenobservedwakingupfromboutsofhibernation-tonap.Whatever they’re getting from sleep, it’s not available to them while they’re

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hibernating.Eventhoughtheyhavesloweddownnearlyeveryprocessintheirbody,sleeppressurestillbuildsup.“WhatIwanttoknowis,whataboutthisbrainactivityis so important?” says Kasper Vogt, one of the researchers gathered at the newInternational Institute for IntegrativeSleepMedicine(IIIS)atTsukubaUniversity,nearTokyoNaritaairport,Japan.Hegesturesathisscreen,showingdataonthefiringofneuronsinsleepingmice.“Whatissoimportantthatyouriskbeingeaten,noteatingyourself,procreation...yougiveallthatup,forthis?”

UniversityofTsukuba,Japan,IIISThesearchforthePiéron’shypnotoxinwasnotunsuccessful.Thereareahandfulofsubstances clearly demonstrated to cause sleep -including as we discussed- amoleculecalledadenosine,whichappearstobuildupincertainpartsofthebrainsofwakingrats,thendrainawayduringslumber.Adenosineisparticularlyinterestingbecauseoftheadenosinereceptorsthatcaffeineseemstoworkon.Whencaffeinebindstothem,adenosinecan’tbindtothesestructures,whichcontributestocoffee’santi-drowsinesspowers.Butworkonhypnotoxinshasnotfullyexplainedhowthebodykeepstrackofsleeppressure.Forinstance,ifadenosineputsusunderwhenwetransitionfromwakefulnesstosleep,wheredoesitcomefrom?“Nobodyknows,”remarks Michael Lazarus, a researcher at the Tsukuba Institute who studies

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adenosine.Somepeoplesayit’scomingfromneurons,somesayit’sanotherclassofbraincells.But there isn’taconsensus.Atanyrate, “this isn’taboutstorage,”saysMasashi Yanagisawa, the Institute director. In other words, these substancesthemselvesdon’t seemtostore informationabout sleeppressure.Theyare justaresponsetoit.

Masashi Yanasigawa

Sleep-inducingsubstancesmaycomefromtheprocessofmakingnewconnectionsbetween neurons. Chiara Cirelli and Giulio Tononi, sleep researchers at theUniversityofWisconsin,suggestthatsincemakingtheseconnections,orsynapses,iswhatourbrainsdowhenweareawake,maybewhattheydoduringsleepisscalebacktheunimportantones,removingthememoriesorimagesthatdon’tfitwiththeothers,ordon’tneedtobeusedtomakesenseoftheworld.“Sleepisawayofgettingridofthememoriesinawaythatisgoodforthebrain,”Tononispeculates.

Another grouphas discovered a protein that enters little-used synapses to causetheirdestruction,andoneofthetimesitcandothis iswhenadenosinelevelsarehigh.Maybesleepiswhenthiscleanuphappens.OnegroupattheTsukubainstitute,ledbyYuHayashi,isdestroyingaselectgroupofbraincellsinmice,aprocedurethatcanhavesurprisingeffects.DeprivingmicespecificallyofREMsleepbyshakingthem

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awakerepeatedly justas they’reabout toenter it (abit likewhathappens to theparentsofcryingbabies)causesseriousREMsleeppressure,whichmicemustmakeupforintheirnextboutofslumber.Butwithoutthisspecificsetofcells,micecanmissREMsleepwithoutneeding to sleepmore later.Whether themicegetawaytotallyunscathed is anotherquestion—the team is testinghowREMsleepaffectstheir performance on cognitive tests—but this experiment suggests that wheredreamingsleepisconcerned,thesecells,orsomecircuittheyarepartof,maykeeptherecordsofsleeppressure.

Yanagisawahimselfhasalwayshadatasteforepicprojects,likescreeningthousandsof proteins and cellular receptors to see what they do. In fact, one such projectbroughthimintosleepscienceabout20yearsago.Heandhiscollaborators,afterdiscoveringaneurotransmittertheynamedorexin,realizedthatthereasonthemicewithout it kept collapsing all the time was that they were falling asleep. Thatneurotransmitter turned out to be missing in people with narcolepsy, who areincapableofmakingit,aninsightthathelpedtriggeranexplosionofresearchintothecondition’sunderpinnings.Infact,agroupofchemistsattheInstituteatTsukubaiscollaboratingwithadrugcompanyinaninvestigationofthepotentialoforexinmimicsfortreatment.

These days, Yanagisawa and his collaborators are working on a vast screeningprojectaimedat identifyingthegenesrelatedtosleep.Eachmouseintheproject,exposedtoasubstancethatcausesmutationsandfittedwithitsownEEGsensors,curlsupinanestofwoodchipsandgivesintosleeppressurewhilemachinesrecorditsbrainwaves.Morethan8,000micesofarhaveslumberedunderobservation.

When a mouse sleeps oddly -when it wakes up a lot, or sleeps too long- theresearchersdigintoitsgenome.Ifthereisamutationthatmightbethecause,theytry toengineermice that carry it, and thenstudywhy it is themutationdisruptssleep. Many very accomplished researchers have been doing this for years inorganismslikefruitflies,makinggreatprogress.Butthebenefittodoingitinmice,whichare extremely expensive tomaintain compared to flies, is that they canbehookeduptoanEEG,justlikeaperson.

Afewyearsago,thegroupdiscoveredamousethatjustcouldnotseemtogetridofitssleeppressure.ItsEEGssuggesteditlivedalifeofsnoozyexhaustion,andmicethathadbeenengineeredtocarryitsmutationshowedthesamesymptoms.“This

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mutanthasmorehigh-amplitudesleepwavesthannormal.It’salwayssleep-deprived,”saysYanagisawa.ThemutationwasinagenecalledSIK3.Thelongerthemutantsstayawake,themorechemicaltagstheSIK3proteinaccumulates.TheresearcherspublishedtheirdiscoveryoftheSIK3mutants,aswellasanothersleepmutant, inNaturein2016.Whileitisn’texactlyclearyethowSIK3relatestosleepiness,thefactthat tagsbuildupon theenzyme, likegrainsofsandpouring to thebottomofanhourglass,hastheresearchersexcited.“Weareconvinced,forourselves,thatSIK3isoneofthecentralplayers,”saysYanagisawa.

As researchers probe outward into themysterious darkness of sleepiness, thesediscoveriesshineaheadofthemlikeflashlightbeams,lightingtheway.Howtheyallconnect, how theymay come together into a bigger picture, is still unclear. Theresearchersholdouthopethatclaritywillcome,maybenotnextyearorthenext,butsometime, sooner than you might think. On an upper floor at the InternationalInstituteforIntegrativeSleep,micegoabouttheirbusiness,wakinganddreaming,inrowafterrowofplasticbins.Intheirbrains,asinallofours,islockedasecret.

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The End of Sleep? IntheApril10,2013,ofAeonMagazine,thescience-writerJessaGamble,authorofThe Siesta and the Midnight Sun: HowWe Measure and Experience Time (2011),pennedaremarkableessayonNew,EmergingTechnologiesthatcouldradicallyreduceourneedtosleep.ThischapterisaneditedversionoftheAeonpiece.

Work, friendships,exercise,parenting,eating, reading—there justaren’tenoughhoursintheday.Tolivefully,manyofuscarvethoseextrahoursoutofoursleeptime.Thenwepayforitthenextday.Athirstforlifeleadsmanytopineforadrasticreduction,ifnotelimination,ofthehumanneedforsleep.Littlewonder:iftherewereawidespreaddisease that similarly deprivedpeople of a third of their consciouslives, the search for a curewould be lavishly funded. It’s the Holy Grail of sleepresearchers,andtheymightbeclosingin.

Aswithmosthumanbehaviors,it’shardtoteaseoutourbiologicalneedforsleepfromtheculturalpracticesthatinterpretit.Thepracticeofsleepingforeighthoursonasoft,raisedplatform,aloneorinpairs,isatypicalforhumans.Manytraditionalsocietiessleepmoresporadically,andsocialactivitycarriesonthroughoutthenight.Groupmembersgetupwhensomethinginterestingisgoingon,andsometimestheyfallasleep inthemiddleofaconversationasapolitewayofexitinganargument.Sleepingisuniversal,butthereisgloriousdiversityinthewaysweaccomplishit.

Differentspeciesalsoseemtovarywidely intheirsleepingbehaviors.Herbivoressleepfarlessthancarnivores-fourhoursforanelephant,comparedwithalmost20hoursforalion-presumablybecauseittakesthemlongertofeedthemselves,andvigilance is selected for. As omnivores, humans fall between the two sleeporientations.Circadianrhythms,thebody’smasterclock,allowustoanticipatedailyenvironmentalcyclesandarrangeourorgan’sfunctionsalongatimelinesothattheydo not interfere with one another.Our internal clock is based on a chemicaloscillation,afeedbacklooponthecellularlevelthattakes24hourstocompleteandisoverseenbyaclumpofbraincellsbehindoureyes(nearthemeetingpointofouropticnerves).Evendeepinacavewithnoaccesstolightorclocks,ourbodieskeepan internalscheduleofalmostexactly24hours.This isolatedstate iscalled ‘free-running’,andweknowit’sdrivenfromwithinbecauseourbodyclockrunsjustabit

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slow.Whenthereisnolighttoresetit,wewakeupafewminuteslatereachday.It’sadeeplyengrainedcyclefoundineveryknownmulti-cellularorganism,asinevitableastherotationoftheEarth—andthecorrespondingday-nightcycles-thatshapedit.

Oneofthemostvaluableoutcomesofworkonsleepdeprivationistheemergenceofclear individual differences -groups of people who reliably perform better aftersleeplessnights,aswellasthosewhosufferdisproportionately.Thedivisionisquitestark and seems based on a few gene variants that code for neurotransmitterreceptors, opening the possibility that itwill soon be possible to tailor stimulantvarietyanddosagetogenetictype.

Aroundtheturnofthismillennium,thebiologicalimperativetosleepforathirdofevery24-hourperiodbegantoseemquaintandunnecessary.Justasthebirthcontrolpill had uncoupled sex from reproduction, designer stimulants seemed poised toremoveusyetfurtherfromthearchaicrequirementsoftheanimalkingdom.

Theexecutivefunctionsofthebrainareparticularlyvulnerabletosleepdeprivation,andpeoplewhoaresleep-deprivedarebothmorelikelytotakerisks,andlesslikelyto be able tomake novel or imaginative decisions, or to plan a course of action.Designerstimulantssuchasmodafinil[inventedbyMichelJouvet]andarmodafinil(marketedasProvigilÒandNuvigilÒ)bringtheseareasbackonlineandarehighlyeffectiveatcounteringthenegativeeffectsofsleeploss.Overthecourseof60hoursawake,a400mgdoseofmodafinileveryeighthoursreinstatesrestedperformancelevelsineverythingfromstaminaforboringtaskstooriginalityforcomplexones.Itstaves off the risk propensity that accompanies sleepiness and brings bothdeclarativememory (facts or personal experiences) andnon-declarativememory(learnedskillsorunconsciousassociations)backuptosnuff.

It’s impressive, but also roughly identical to the restorative effects of 20 mg ofdextroamphetamineor600mgofcaffeine(theequivalentofaroundsixcoffeecups).Thoughcaffeinehasashorterhalf-lifeandmustbetakeneveryfourhoursorso,itenjoystheadvantagesofbeingubiquitousandcheap.

Foranycollegestudentwhohaspulledanall-nighterguzzlingenergydrinkstofinishanessay, itshouldcomeasnosurprisethatdesignerstimulantsenableextended,focusedwork.Amorechallengingtest,forapersonwiredonamphetamines,would

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be to successfully navigate a phone call from his or her grandmother. It is verydifficult todesignastimulant thatoffers focuswithout tunneling -that is,withoutlosing the ability to relate well to one’s wider environment and therefore makesociallynuanceddecisions.Irritabilityandimpatiencegrateonteamdynamicsandsocial skills,but suchnuancesareusuallymissed indrugstudies,where theyareusually treated as unreliable self-reported data. These problems were largelyignoredintheearlyenthusiasmfordrug-basedwaystoreducesleep.

They came to light in an ingenious experimental paradigm designed at thegovernment agency Defence Research and Development Canada. In 1996, thedefensepsychologistMartinTaylorpairedvolunteersandgaveeachmemberoftheduoamap.Oneofthetwomapshadaroutemarkedonitandthetaskwasfortheindividual who had the marked map to describe it accurately enough for theirpartnertoreproduceitontheirmap.Meanwhile,theresearcherslistenedinontheverbaldialogue.Controlgroupvolunteersoftenintroducedalandmarkonthemapbyaquestionsuchas:‘Doyouseetheparkjustwestoftheroundabout?’Volunteerson the stimulant modafinil omitted these feedback requests, instead providingbrusque,non-questioninstructions,suchas:‘ExitWestattheroundabout,thenturnleftatthepark.’Theirdialogueswereshorterandtheyproducedlessaccuratemapsthancontrolvolunteers.Whatismore,modafinilcausesanoverestimationofone’sown performance: those individuals onmodafinil not only performedworse, butwerelesslikelytonoticethattheydid.

Onereasonwhystimulantshaveprovedadisappointmentinreducingsleepisthatwestilldon’tunderstandenoughaboutwhywesleepinthefirstplace.Morethanahundred years of sleep deprivation studies have confirmed the truism that sleepdeprivation makes people sleepy. Slow reaction times, reduced informationprocessingcapacity,andfailuresofsustainedattentionareallpartofsleepiness,butthemostreliableindicatorisshortenedsleeplatency,orthetendencytofallasleepfasterwhenlyinginadarkroom.Anexasperatinglyrecursiveconclusionremainsthatsleep’sprimaryfunctionistomaintainourwakefulnessduringtheday.

Since stimulants have failed to offer a biological substitute for sleep, the newwatchword of sleep innovators is ‘efficiency’, whichmeans in effect reducing thenumber of hours of sleep needed for full functionality. The Defense AdvancedResearchProjectsAgency(DARPA)-theresearcharmoftheUSmilitary-leadsthe

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wayinsqueezingafullnight’ssleepintofewerhours,byforcingsleepthemomentheadmeetspillow,andbyconcentratingthatsleep intoonly themostrestorativestages.Soldiersonactivedutyneedtofunctionattheircognitiveandphysiologicalbest,evenwhentheyaregettingonlyafewhours’sleepina24-hourcycle.

Nancy Wesensten, a psychologist for the Center for Military Psychiatry andNeuroscience at theWalter Reed Army Institute of Research in Maryland, has amissiontofindwaystosustainsoldieroperationsforlonger,fightingtheeffectsofacuteorchronicsleepdeprivation.Shehasarguedthatindividual’ssleepshouldberegardedasanimportantresource,justlikefoodorfuel.WorkingwiththeMarinecorps, Wesensten is not trying to create a super warrior who can stay awakeindefinitely. Shedoesnot even seeherself trying to enhanceperformance, as shealreadyconsidershersubjectstheeliteoftheelite.Everyonemustsleepeventually,butthetheatreofwarrequiressoldierstostayawakeandalertforlongstretchesatatime.

WhereastheUSArmyandAirForcehavealonghistoryofadoptingstimulants—

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pioneeringmodafinilapplicationsanddextroamphetamineusein24-hourflights—the Marines generally will not accept any pharmacological intervention. LikeWesensten,ChrisBerka,theco-founderofAdvancedBrainMonitoring(ABM),oneofDARPA’s research partners, says that she is cautious about the usefulness ofstimulants,‘Everysooften,anewstimulantcomesalong,anditworkswell,andthere’sa lotof interest,and thenyoudon’thearanythingmoreabout it, because ithas itslimitations.’

SomefailedAirForcemissionshavedrawnattentiontothedangersofamphetamine-inducedparanoia.Lessthanadecadeaftera1992AirForcebanonamphetamines,‘gopills’werequietlyreintroducedtocombatpilotsforlongsortiesduringthewarinAfghanistan.On17April2002,MajorHarrySchmidt,whohadtrainedasatopgunfighterpilot,wasflyinganF-16fighterjetoverKandahar.Canadiansoldiersbelowhim were conducting an exercise, and controllers told Schmidt to hold his fire.Convinced he was under attack, the speed-addled pilot let loose and killed fourCanadiansoldiers.Thefriendlyfire incidentresultedinacourtmartial,but inthemedia,itwasthedrugsthatwereontrial.

Withmilitarypersonnelinmind,ABMhasdevelopedamaskcalledtheSomneoSleepTrainerthatexploitsoneortwo-hourwindowsforstrategicnapsinmobilesleepingenvironments.Screeningoutambientnoiseandvisualdistractions,themaskcarriesaheatingelementaroundtheeyes,basedonthefindingthatfacialwarminghelpssendpeopletosleep.Italsocarriesabluelightthatgraduallybrightensasyoursetalarmtimeapproaches,suppressingthesleephormonemelatoninforalessgroggyawakening.

ForMarinesatCampPendletonnearSanDiego(California),fourhoursofsleeporlessisoneoftherigorsofbothbasicandadvancedtraining.Asacharacter-buildingstressor,nightafternightofprivationisapersonalendurancetestbut,asWesenstenhasargued,itrunscountertoothergoalsoftheirtraining,suchaslearninghowtohandlegunssafely,andthenrememberingthatinformationinamonth’stime.Berkaagrees.‘Wedemonstratedcumulativeeffectsofchronicsleepdeprivation,evenpriortodeployment, and itwashavingan impact on learningandmemory,’ she explained,after ABM had brought brain-monitoring devices into the camp for 28 days ofmeasurement.‘Itwasdefeatingthepurposeoftrainingfornewskillsets,andcommandacknowledged thiswas important.’ It’snot cheap toequipdozensof traineeswith

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nightgogglesandtrainthemtodistinguishfoesfromfriends—allthewhilepayingoutsalaries.

Darknessanddietarewaysofpracticing ‘sleephygiene’,orasuiteofbehaviorstooptimizeahealthyslumber.

TheSomneomaskisonlyoneofmanyattemptstomaintainclarityinthemindofasoldier.Anotherinitiativeinvolvesdietarysupplements.Omega-3fattyacids,suchasthosefoundinmarineoils,sustainperformanceover48hourswithoutsleep-aswellasboostingattentionandlearning-andMarinescanexpecttoseemoreofthenutritionalsupplementmakingitswayintorations.Thequestionremainswhethermeasuresthatblockshort-termsleepdeprivationsymptomswillalsoprotectagainstitslong-termeffects.Ascanoftheliteraturewarnsusthatyearsofsleepdeficitwillmakeusfat,sickandstupid.Agrowinglistofailmentshasbeenlinkedtocircadiandisturbanceasariskfactor.

BoththeSomneomaskandthesupplements-inotherwords,darknessanddiet-areways of practicing ‘sleep hygiene’, or a suite of behaviors to optimize a healthyslumber.Thesecanbring theeffectofa truncatednight’s restup to theexpectednorm -eight hours of satisfying shut-eye.But proponents of human enhancementaren’tsatisfiedwithnormal.Alwayspushingtheboundaries,sometechno-pioneerswillgotoradicallengthstoshrugofftheneedforsleepaltogether.

AmongthesenewplayersisFisher,thepresidentofFisherWallaceLaboratoriesofMadisonAvenueinNewYork,whoacquiredthepatentforatranscranialstimulationdevicefromthebrothersSaulandBernardLiss,bothelectricalengineersfromtheMassachusettsInstituteofTechnology.Heseesthebodyasacollectionofmaterials,somemoreconductiveandothersmoreresistanttoelectricity. ‘Theneedtopiercebone and skull means we need a higher carrier frequency, which is the 15,000 Hzfrequency.That’scombinedwith500Hzand15Hz,’Fishersays. ‘Ittookeightto12yearstoderivethosevalues.Thebodyisinfluencedbyfrequenciesbetweenzeroand40Hz.’ThosesearchingforatreatmentforinsomniaareFisher’sbiggestandfastest-growingmarket.Someonewithintractableinsomniawilltryjustaboutanythingtogetsomesleep.

Transcranialdirect-currentstimulation(tDCS)isapromisingtechnologyinthefieldofsleepefficiencyandcognitiveenhancement.Alternatingcurrentadministeredto

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thedorsolateralprefrontalcortexthroughthethinnestpartoftheskullhasbeneficialeffects almost as mysterious as electroconvulsive therapy (ECT), its amnesia-inducingancestor.

Negativeeffectsonthebrainhavenotyetbeenobserved,andtheFDAhasapprovedsomedevices,suchastheFisherWallaceStimulator,forunsupervisedhomeuse,butlong-termeffectsarestillunknown.TheneurologistSoroushZaghiandhisteamatHarvardMedicalSchoolareonthetrailofhow,exactly,theseclinicaloutcomesareachieved.Oncethisisestablished,potentialdangerswillbeeasiertolookfor.

Usingaslightlydifferenttechnique-transcranialmagneticstimulation(TMS),whichdirectly causes neurons to fire- neuroscientists at Duke University could induceslow-waveoscillations,theonce-per-secondripplesofbrainactivitythatweseeindeepsleep.Targetingacentralregionatthetopofthescalp,slow-frequencypulsesreachtheneuralareawhereslow-wavesleepisgenerated,afterwhichitpropagatestotherestofthebrain.WhereastheSomneomaskisdesignedtosenditswearersintoalightsleepfaster,TMSdevicesmightbeabletolaunchusstraightintodeepsleepattheflipofaswitch.Fullcontrolofoursleepcyclescouldmaximizetimespentinslow-wavesleepandREM,ensuringfullphysicalandmentalbenefitswhilecuttingsleep time in half. Your four hours of sleep could feel like someone else’s eight.Imaginebeingabletoreadanextrabookeveryweek-thetimeaddsupquickly.

Thequestioniswhetherthestrangenessoftheideawillkeepusfromacceptingit.Ifsocietyrejectssleepcurtailment,itwon’tbeabiologicalissue;rather,theresistancewillbecultural.Thewaragainstsleepisinextricablylinkedwithdebatesoverhumanenhancement, because an eight-hour consolidated sleep is the ultimate cognitiveenhancer.Sleepinessandalackofmentalfocusareindistinguishable,andmanyofthepharmaceuticallybasedcognitiveenhancersonthemarketworktocombatboth.Ifonlyitwerepossiblefortherestorativefunctionsthathappenduringsleeptooccursimplyduringwakinghours instead…Onereasonwhyweneedtoshutdownourconscious selves to perform routinemaintenance is that our visual system is sogreedy.Glucosemetabolismisazero-sumgame,andfunctionalMRIstudiesshowaradicallydifferentpatternofglucosemetabolismduringsleep,withdistinctregionsactivatedeitherinactiveorsleepstatesbutnotinboth.Assoonaswecloseoureyesforsleep,alargeproportionofavailableenergyisfreedup.Justasmostplanesmustbegroundedtorefuel,wemustbeasleeptorestoreourbrainsforthenextday.A

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radical sleep technology would permit the equivalent of aerial refueling, whichextendstherangeofasingleflight(orwakingday).

Such attempts are likely to meet with powerful resistance from a culture thatassumesthat‘natural’is‘optimal’.Perceptionsofwhatiswithinnormalrangedictatewhatsortofhumanperformanceenhancementismedicallyacceptable,abovewhichethics review boards get cagey. Never mind that these bell curves have shiftedradically throughouthistory.Our contemporary sleephabitsarenot inany sensenatural,andancestralhumansleepingpatternswouldbeverydifficulttointegrateintomodernlife.

Humanenhancementisnowbeingdrivenbymilitaryimperatives,atleastintheUS,because civilian society ismore conservative in its approach.Dedicateddivisionssuch as the US Air Force’s Human Effectiveness Directorate try tomake humansbetteratwhattheydonaturally.It’samissedopportunityforasociety-widepushtounderstandandreduceourneedtopowerthebraindownforhourseveryday.Everyhourwesleepisanhourwearenotworking,findingmates,orteachingourchildren;ifsleepdoesnothaveavitaladaptivefunctiontopayforitsstaggeringopportunitycost,itcouldbe‘thegreatestmistaketheevolutionaryprocessevermade’,inthewordsofAllanRechtschaffen,thepioneeringsleepresearcherandprofessorofpsychiatryattheUniversityofChicago.

As biologistsmap the details of the human genome, they are looking for geneticmarkersthatcodecertainbehaviorsandtendencies.Onegenetheyhopetolocateisthe“sleepgene”–ifitexists.Certaingenes,suchasCLOCKBMAL1,areknowntoplayanimportantroleinthebody’scircadianrhythm.Butanothergene–DEC2-mightbethesecret to lightsleeping.Mutations toDEC2significantlyreduce theamountofsleeptimethat’srequiredforthehumanbody.Themilitaryis,asexpected,amajorconsumerforsuchgenetictechnology:SEALsandGreenBeretscouldbeable,aftergene therapy, to soldier on for days at a time during operations. They wouldaccomplishmissionswithoutdrowsiness,disorientationandslowerreflexes.

In her award-winning Beggars trilogy of the 1990s, the American science fictionwriterNancyKresspositedaworld inwhichgeneticmodificationhasbecomederigueur.Oneof these ‘genemods’ -cookedupbygifted children let loose in a lab-eliminates sleep and evenbucks the sci-fi conventionof dire side effects, insteadendowingthefortunateSleeplesswithbonusesofgreaterintelligenceandemotional

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stability.Thesideeffectsare,instead,societal-theunevenlydistributedtechnologybecomesthebasisofasocialschism,inwhichaperpetuallyproductiveeliterulesasleep-dependent majority of Livers. Kress presciently anticipated the ethicalimplications of our emerging era ofwhat the neuroscientist RoyHamilton of theUniversityofPennsylvaniahasdubbed‘cosmeticneuroscience’,orthetailoringofourancientbrainstosuitourmoderndemands.

Should technologies such as tDCS prove safe and become widely available, theywould represent an alternate route to human longevity, extending our consciouslifespanbyasmuchas50percent.Manyofuscherishthetimewespendinbed,butwedon’tconsciouslyexperiencemostofoursleepinghours-iftheywerereducedwithoutextrafatigue,wemightscarcelynoticeadifferenceexceptforallthoseopen,newhoursinournighttimeexistence.Lifespanstatisticsoftenadjustfortimespentdisabled by illness, but they rarely account for the ultimate debilitation: lack ofconsciousness.Nowalifelivedat150percentmightbewithinourgrasp.

Arewebraveenoughtochooseit?

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The Future of Sleep Futuristsareaccustomedto launchingheadfirst intosomeverycomplexsubjects,buteventhemosthigh-mindedandenthusiasticofprognosticatorsmaytakeapasswhenitcomestodealingwiththefutureofsleep.It’sjustthatwehumans-thoseinthedevelopedworldatleast-maintainsuchacomplicatedrelationshipwithsleep.Wearetaughtthatweneedit,seemtoloveitwhilewe'reengagedinitandspendourwakinghoursmoaningtoeachotherabouthowmuchmoreofitwedesire.Butthenwedoeverythinginourpowertodelayitsnaturalonseteachnight.

Psychologiststellusthatmuchofthatstruggleisclassicallyexistential;havingtodowith the subconscious realization that our time among the living is finite, soweattempt to make the most of the hours we’re fully conscious. Much more of it,however,mustdowiththeallureoftechnologythatbeganwiththeintroductionofartificial lighting about100 years ago and continues toplagueus. In fact,we arecurrently inthethroesofamajordownwardspiral,asallmannerofblinkingandbuzzinggadgetskeepusworking,worryingandwatching.

“Sleepinalotofwaysiskindoflikerebootingyourcomputer,onlyit’san8-hourprocessofrebootingyourbody,”saysThomasFrey.“Butcanwedothatfaster,quickerandmore frequently in the future?" In doing so humans are sidestepping a biologicimperative, sleeping less than ever before in history despite enjoying a longerlifespanthanallpreviousgenerationsthatroamedtheEarth.Morethanonethirdofusarenotgettingenoughsleep,reportstheCDC(CenterforDiseaseControl),withmostofusenjoyingjustsixhourspernightofsuchrecuperativetime.

But if technologyistoblameforthecurrent imbalance,mightwealsoutilize it tousherinacorrectivesleep-filledfuture?

Ian Peterson, a renowned physicist and futurist, thinks so. In a 2011 report, heenvisionedaworldwheretechnologygearedtowardsleepwouldrevolutionizeourbedroom environment. Much of what Peterson imagined is on its way to beingrealized: “smart” pajamas, bed clothing andmattresses outfittedwith sensors tomeasure brain-body data -especially our responses to pressure, light and

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temperature -that will then be fed tomechanical beds; thermostats and lightingfixtures which adjust themselves on the fly to create and maintain a highlypersonalizedoptimalsleepexperience;butwhowillneedthese,orjustbuyanyofthem?

Ifallofthatseemsabitfarfetched,considertheFitbityou’rewearingnow—theonethat’s invisiblytetheredtoasmartphoneappthat’salreadymonitoring,recordingandsharingyourpersonalhealthdata.Consider,too,theburgeoning“smarthome”industrywhoseaffordableandeasilyoperatedhardwareandappsallowustoadjustthelighting,temperatureandsecurityfeaturesofourhomesfromanywhereintheworld. And consider that somewhere around 2023 approximately one trillionhyperlinked sensorswill have been implanted in our everyday surroundings. By2036thefigurejumpstoonehundredtrillion…

Allthesedatashouldbecontrollingsomething,sowhynotusethemtostudyandimprovesleep?

Whynot,indeed,sayfuturistsJackUldrichandThomasFrey.Bothmenseethefutureofsleepasinexorablylinkedtobigdataandthesupercomputersthatwillemployartificial intelligence to provide new insights on sleep that take us well beyondPeterson’s safe and sensible environmental modifications. “By then, the real

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vanguardwillbeaquestionofhowtousesleeptofurthereducation,figuringouthowtoget therestweneedwhilealsousingsleepasareallyproductive time.”Therealfutureofsleep,itseems,islocatedjustoffthetranshumanisthighway.

Obtaininganykindofreliableroadmapforsuchatripisthedifficultpartfornow,particularly ifyou’reexpectingeitherUldrichorFrey toofferoneup.As futuristswho seem comfortably planted at the conservative end of their profession’sspectrum, they’re reluctant to pinpointing their ideas along any hypotheticaltimeline.One reason for this reluctance is that somanywill take it forprophecy.Anotheristhat“therearejusttoomanyvariables,”saysFrey.“Computingthatkindofexponential growth canmesswith yourhead in lots ofways.”Maybewe’ll becomeaccustomedtotaking“braincations,”oneswhereourdreamsgobeyondthewildestexpectationsofvirtualrealityenthusiasts.

Ultimately,thenewsleepwillcomedownto“personalizedoptimization,”meaningitwillbecustomizedtoanindividual’sspecificbiologyandbrainfunctioningandbeutilized formore than just rest.Perhapssleepwillbeused tohealemotionalandphysicalwounds,toearnadiplomaoreventolearnanewlanguage.“Wearealreadyusingbrainscanningtechnologytogetveryfuzzypicturesofdreams,”saysUldrich.“Soitwillbecomeamatterofhowweuseittoalteroursleepexperience.Inotherwords,aretheDisneyPixarreleasesofthefarfuturenotmeantforamoviescreenbutinsteadmeantforourdreams?WhendoesDreamworksreallybecomedreamworks?”

Transhumanistsarenotaloneintheirdesiretopushthelimitsofwhatisnatural.Asmentionedabove,biggovernmentagencieslikeDARPAwanttocreatehyperawakesoldiersandfighterpilotswhonolongersuffertheafflictionofsleep.ForthoseliketranshumanistZoltanIstvan,optimizationisdefinedasnothinglessthan“curingthedisease”ofsleep.Sucharadicalnotionistobeexpectedgiventhatthewholepointoftranshumanismistotranscendhumanitywiththeaidoftechnology-tounitemanandmachine,ifnecessary,inwaysthatpushevolutiontothenextlevelasrapidlyaspossible.Totranshumanists,andmaybeeventoourpostSingularityprogeny,thehuman requirement for sleep, the equivalent of roughly one third of a person’slifetime,canonlyimpedetransformation.

Transhumanistsarenotaloneintheirdesiretopushthelimitsofwhatisnatural.Infact,asyouslumberedlastnight,anastoundingnumberofresearchscientistsandtechnicians in labsaround theworldwerebusysearching fora cure.And they’re

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gettingbetteratit.Thesciencemayonlybeinitsinfancybutalreadythere’sthe“go-pill”modafinil, thatstavesoff thedebilitatingeffectsof sleep-related fatigue foralimitedduration.Transcranialbrainstimulation(TCBS)andimplantsarealsointheworks, asmentioned in a previous section. Both can operatewith the swipe of asmartphoneapp,zappingyouintoatrance-likestatethatlastsjustminutesbutisincrediblyrefreshing.Iftestresultsaretobebelieved,thejoltisasproductiveandrestfulasanhours-longsiesta.“Ifwecanspeedupthebraintolearnquicker,canwealsospeedituptosleepfaster?That’scounterintuitivebutslowingthebraindowntosleepbettermaynotbetherightdirectionatall.”

Afarsmallerpercentageofus-thosewithdeeppocketsandasenseofdaring-willgettoexperiencesleepoptimizationtothemax.Thatfrantictimeinthefuturewherewe can begin routinely speeding the brain through its sleep cycle, taking FDA-approvedpillsassleepworkarounds,andevensuccessfullygeneticallyengineeringhumans who require less sleep may be a major tipping point. Ultimately, saysUldrich,“Humanitymayevolveintotwodifferentspecies:onethatfavorstheslower,naturalevolutionaryprocessandanother–theKurzweilianbranch-thatwillembraceanenhancedevolutionaryprocess.”

Tobeclear,Uldrichassuresusthat“muchofEarth’spopulationwillcontinuetosleepverymuch theway italwayshas,”probablyevenbetter.But thenet result for the“sleep optimized,” Uldrich and Frey agree, is that they will likely become moreproductive,energeticandcreative,andthiswillundoubtedlyprovidethemwithacompetitiveadvantagein life.“TheanalogyIusetodescribethesplit, thoughnotaperfectone,istheAmishlivingamidtherestoftheworld,”addsUldrich.“Roughlytwocenturies ago they essentially said to society, ‘Look, you can continue to embracetechnology.Wedon’tjudgeyouforitbutwejustdon’tlikewhatit’sdoingtoourfamiliesandcommunities,sowerejectit.Andwehopeyou’lljustletusliveinpeace.’Ithinkwewillseeverybright,intelligentpeoplewhowillcometoadifferenceofopiniononthematter.ButIdon’tthinkthereisarightorwronganswer.”

If there’s a cautionary note to consider, it should dowith the risk of unintendedconsequences.Or,asFreyputsit:“Lotsofthingsthatcangowrongwhenyouchangesomefundamentaltenantofthehumancondition.Let’ssaywehadsomeinstantsleepdevice,butaftertenyearsofusingitpeopleturnedintopsychopathickillers-well,youseewherethat’sheading,right?”“Forwhateverreason,wehumansevolvedbasedona

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circadianrhythm,somaybeweshouldjustrespectthewisdomofevolutionbeforewepushittoitslimits,”Uldrichconcludes.“Havingsaidthat,however,pushinglimitsisjust what evolution is. We conduct experiments to see if we can become moreproductive, creative, healthier and happier -andmaybe even to offer a new humanexperience.Butwemustrecognizethatmostofthemaregoingtofail.Wehavetokeepthatinmindandsimplysay,‘Thisisthewaylifeplaysout.’”

Thatmaybetrue,butmaybein50yearswe’llbeaskingeachotheraboutwhensleepbecamesocomplicated.

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Sleep and the Light at the End of a Tunnel

Thedreamsandcurrent(butnotyetverifiable)predictionsoffuturistsareexciting–justasthelatestStarWarsmovie.Butifwewanttolookatprogressandtherealisticfutureofuncoveringmoreamongthemysteriesofsleep,thereisoneplacethatisbuiltonsolidtradition,anddeliversregularbreakthroughs:StanfordUniversity,inNorthernCalifornia.

TheStanfordSleepMedicineCenter, the firstone in theUSAwhen itopened,hasplayedacriticalroleinthedevelopmentofthefieldofsleepmedicine.

TheCenterwasfoundedbyDr.WilliamC.DementandDr.ChristianGuilleminault(myformercolleagueattheSalpétrièreinParisinthelate1950s)in1970andhasbeenthesiteofnumerousadvancesinsleepeversince.

Today the Stanford Center for Sleep Sciences andMedicine is an internationallyrenownedsleepcenterrecognizedforoutstandingpatientcareandinnovativesleepmedicineresearch.In2009,theStanfordSleepMedicineCentermovedtoastate-of-the-art facility in the new StanfordMedicine Outpatient Center in Redwood City

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(California).Thesleepcenterhas14clinicalbeds,fouradditionalbedsdedicatedtoresearch and treats more than 5,000 adults and children each year, includingpatientsfromallovertheworld.

The Stanford Sleep Medicine Center works to improve coordination among thevarious specialties involved in treating patients. Its faculty includes specialists inobstructivesleepapnea,insomnia,narcolepsy,pediatricsleep,parasomnias,restlesslegs syndrome, and other sleep disorders. The clinical staff is comprised ofpsychologists,psychiatrists,neurologists,pulmonaryspecialists,andpediatricians.Inaddition,allworkcloselywithsleepapneasurgeons,dentists,andorthodontists,whospecializeinthetreatmentofsleepdisorders.TheCenterhasmorethan100doctors, research faculty, staff, and students who are devoted to the study andtreatmentofsleepandsleepdisorders.

As the birthplace of sleep medicine, the center has a long history of importantcontributionstothefieldofsleepmedicine.TheSleepCenterspansacrossmultiplescientificandmedicalspecialties.Researchinterestsrangefromseekingthegenesassociatedwithsleepdisorderstostudyingtheneurologicalandchemicalsystemsthat regulate sleep andwaking. It hosts several basic research labs ranging fromgenetics to neurobiology, as well as an active clinical research department withprojectsinareassuchasinsomnia,narcolepsy,obstructivesleepapnea,comparativeeffectivenessanddiseaseregistry.

TheSleepCenteratStanford’sunmatchedreputationisduetothevisionarywork,dedication,tirelessenergy,creativityandwarmconnectionwithallwhoapproachhim,ofWilliamC.Dement.

Thisshortvideoisarguablyawell-deservedhomage:https://youtu.be/UWkeI45kbNU

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Acknowledgements

Thisessayisstuffedandpaddedwith(toomany)references.Themajorones–thatIplundered,oftenverbatim-arelisted.Iconcludedbycomingbackhome:weliveontheWesternedgeofStanfordUniversitycampus,andIvisititsDepartmentsoften;Ibegforforgiveness.

YvesP.Huin,besideshisdevotion, friendshipandwebmaster’sskills,hasbeenanastuteeditor.

References • https://en.wikipedia.org/wiki/Morpheus_(mythology)

• https://en.wikipedia.org/wiki/Sleep

• https://en.wikipedia.org/wiki/Michel_Jouvet

• https://www.ucsf.edu/news/2009/08/4281/first-human-gene-implicated-regulating-length-human-sleep

• https://en.wikipedia.org/wiki/Dream

• https://qz.com/1172398/people-have-spent-centuries-trying-to-prove-caffeine-is-dangerous-but-the-science-suggests-otherwise/

• https://www.theatlantic.com/science/archive/2018/01/the-mystery-of-sleep-pressure/549473/

• https://aeon.co/essays/technology-to-cut-down-on-sleep-is-just-around-the-corner

• https://vanwinkles.com/what-will-sleep-be-like-in-the-future

• https://www.washingtonpost.com/news/innovations/wp/2014/05/20/7-reasons-why-the-future-of-sleep-could-be-wilder-than-your-wildest-dreams/?utm_term=.e98bc49d8fa7

• http://sleep.stanford.edu/about/history.html

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Illustration Credits • https://www.newscientist.com/gallery/dreams-art/

• https://www.pinterest.com/pin/44473115046524955/

• https://www.wikiart.org/en/henri-rousseau/the-sleeping-gypsy-1897

• https://www.nytimes.com/2017/10/11/obituaries/michel-jouvet-who-unlocked-rem-sleeps-secrets-dies-at-91.html?_r=0

• https://sommeil.univ-lyon1.fr/articles/jouvet/la_recherche/fig1b.php

• http://awakeningartsacademy.com/

• https://rsconnett.deviantart.com/art/Dreams-and-Nighmares-158643565

• https://commons.wikimedia.org/wiki/File:Gustavo-III,-Rey-de-Suecia_1777-by-Roslin.JPG

• https://medicalxpress.com/news/2012-11-caffeine-effect-brain-adenosine-receptors.html

• https://wpi-iiis.tsukuba.ac.jp/access/

• https://wpi-iiis.tsukuba.ac.jp/research/member/detail/masashiyanagisawa/

• https://www.thedailybeast.com/from-appomattox-to-afghanistan-portraits-of-american-gis

• https://vanwinkles.com/what-will-sleep-be-like-in-the-future

• https://www.britannica.com/topic/Stanford-University