350 Year of Science

Home , Henri Testelin, Hippolyte Fizeau, Tempus fugit

37 La Lettre 38 de l’Académie des sciences SPRING-SUMMER AUTUMN-WINTER 2016

350 years of science

1666-2016: the solemn ceremony celebrating the 350 years of the Académie des Sciences was held under the Cupola of the Institut de France on 28 June 2016. Eight members of the Académie, from as many sections, brieﬂ y recounted the history of their disciplines, highlighting their important stages and paying tributes to the scientists who, whether they were French or from other countries, contributed the most to the progress, if not the revolution, that took place in their own disciplines. This special issue of La Lettre de l’Académie des Sciences presents the proceedings of this momentous one-day event dedicated to the history of science. 350 years Page Page Page Page Page Page Alain Aspect From Huygens’ wavestoEinstein’s photons:strangelights Anne-Marie Lagrange Planets andexoplanets Jacques Livage Chemistry, thescienceofmatter:tounderstandandcreate! Yvon LeMaho From thecelltoecosystems Jean-Pierre Changeux On thepathtodiscoveringhumanbeingsandtheirbrains Alain Fischer From empiricalmedicinetoprecision Pascale Cossart The newmicrobiology Catherine Bréchignac The marchofknowledge Cédric Villani Mathematics: tounderstandandpredict Gérard Berry Machines andinformation Draw mean Académie! Bernard Meunier Page Page Page Page Page

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5 Table of contents 6 37 38 La Lettre he askedColberttoengagethecreationof"AcadémieRoyaledesSciences". to makeyourkingdomabiggerandstrongerone. us abouttheworld,ourplanets,plants,animals,diseasesandalsomachinesthatshouldbecreated choice would be ChristiaanHuygens,amathematician andastronomer fromtheNetherland,admired by a scientistrecognizedbyhis pairinEuropeandabletoanimateanacademyof sciencesinParis. The his librarian,PierredeCarcavi, amathematicianwhohadbeentrainedbyPierre deFermat,torecruit It wasurgentfortheFrench royaltytoshowFrance’s precedenceontheContinent.Colbertappointed Europe: theRoyalSociety. and Englandhadrecentlycreatedascienti scientists suchasDescartesandPascal,whorespectively diedin1650and1662,hadnotbeenreplaced of the17 group ofscientistsabletodevelopmathematicsand physics–thislatterwordcovering,inthemiddle artistic creation,inall concerned withFrance’s in the "AcadémiedesSciences"hasbeentherefor350years! The youngKing,28yearsoldin1666,was In fact,therearenohistoricaldocumentsrecordinghowLouisXIVmadehisdecision.Onethingiscertain: Recruiting forexcellence th Century, notonlytoday’s physicsbutalsochemistry, naturalsciencesandmedicine. French ﬁ elds: architecture,painting,theatreandpoetry. Hisearlyreignwasstill lackinga ﬂ Draw mean Académie! uence, asisillustratedbyhissearchfornaturalbordersandsupport

© B.Eymann - Académie des sciences fi c society, in1660,immediatelytakinganimportantplace one isneeded,todealwithscience,scientiststelling language. in 1635;ittakesgoodcareofourbeautifulFrench “ The KinglistenedtotheLittlePrinceandsaidhim: and saidtohim: middle oftheocean.Suddenly, alittlevoicewokehimup the crowdofhiscourtiers,hefeltlikeacastawayin One evening,asLouisXIVwasfallingasleepawayfrom Researcher atCNRS President ofthe Académie desSciences,EmeritusSenior Bernard Meunier But Ialreadyhaveanacademy, whichmyfathermade ” The Kingwasconvinced. This wastheyear1666; ” “ I know Sire, please....drawmean Academy! ”, theLittlePrincesaid,“ but another ” © Ig0rZh - Fotolia fi would graduallygrowapassion foranatomyandbethe and Jean-BaptisteduHamel–anHellenistwho Pecquet (anatomist),NicolasMarchant(botanist) were addedClaudeBourdelin(chemist),Jean Louis Gayant(physician).BeforeDecember Cottereau duClos(physicianandchemist) for manyarchitectsovertheworld),Samuel the Louvre,whichhassincebeenaninspiration conceived thecolonnadesofeastfaçade (architect andCharlesPerrault’s brother–who la Chambre(physicianoftheKing),ClaudePerrault the famoustales. Also recruitedwere:MarinCureaude a manofletters,Colbert’s right-handmanandtheauthorof Observation section,withthehelpofCharlesPerrault,whowas In October1666,asecondsectionwascreated,theSciencesof sun. They producedareportthatreassuredColbertontheircapacitytoworktogether. Section, andstartedtomeetinthesummer1666observetwoeclipses,thatofmoon rst "Secrétaire del'Académie". balance. This all inEuropeandwhohadjustbeenelectedatthe who isstillknowntousforhisdoublepan Royal Societyin1663.ChristiaanHuygens Personne deRoberval–amathematician negotiated attractivetermsforhis fi rst groupformedtheMathematics Jean Picard(astronomer)andGilles Claude Perrault'sColonnades Bessy (mathematician),theabbot arrival inParis:anapartment Carcavi, BernardFréniclede the King’s libraryandanannual Buot (astronomer),Pierrede (astronomer), Jacques pension of6000pounds! of theLouvre Huygens, AdrienAuzout from ashortlist:Christiaan names wereselected The recruitmentofthe from May1666.Seven fi rst academiciansstarted

7 350 YEARS OF SCIENCE 8 37 38 La Lettre be seenatVersailles. This presentationbeforetheKingwasobjectofamagni This new Academy thusmetforthe the companydidnotdivideandthatallgatheredatassemblyonthesesamedays. shall workonphysics. As thereisagreatconnectionbetweenthesetwosciences,itwasdeemed Wednesdays andSaturdays.[...]OnWednesdays, oneshalldealwithmathematics,onSaturdays, " This conception they shouldbevoluntaryandassociatetheskillsofalltoventureoff intonewhorizons. lived through,likeanoldsongonesingsmoreorlessintunetofeelsafeforlackofideas;onthecontrary, own solutionwithinonesamediscipline.Interactionsbetweendisciplinary place smoothlyandnaturally, whenitisdeemednecessary, notforgettingthatmanyproblems together ontopicswhoseconsiderationrequiresstrongskills. The interactionbetween disciplinestakes should beanassemblyofveryhighlevelscientistsintheirowndiscipline,ordertoenablethemwork ﬁ This listofpersonalities,selectedfortheirexpertiseinrespective rst academicians,itismainlytheexpressionofaprincipleatfoundationourinstitution. An academy On this22December1666,ithasbeensettledinthecompanythatwouldmeettwiceaweek,on ﬁ nds itselfclearlyexpressedin thevery

© From B.Eymann - Académie des sciences that oneunderstands,followsthem, one wantsthings.Oneestablishesprinciples reign ofwordsandexpressionshaspassed, des Sciences"writtenbyBernarddeFontenelle:“ Things areclearfromthevery the Academy speakforthemselves:theworkingsessionsfollowed each examined andoftenrejected. it hadbeensoforalongtimeisnowre- received withoutcontradictionbecause bear moreweightthanreason,whatwas advances. Theauthorityhasceasedto and thencefromdoesithappenthatone What placeintheNation? science andthecountry. other ontopicschosenbytheacademicians,protecting theinterestsof fi rst timeon22December1666,intheKing’s library, rueVivienne. fi rst pageofthearchivesheldat the Academy: fi cent paintingbyHenri Testelin, whichmay fi ” The archivesof rst pageofthehistory"Académie fi eld,isnotonlyatributepaidtothe fi elds shouldnotbepassively The Bernard deFontenelle (1657 -1757) " fi nd their nd fi t that t

© Archives de l'Académie was itsheight:“ arts. Unfortunately, thisperiod oftheFrenchRevolutionwasnotconducivetosuchacreation. The Terror the creationofaninstitutegroupingdifferent academiesandaimingattheadvancementofscience were involvedinthe"Comitéd’instructionpublique", Talleyrand in1791andCondorcet1792proposed by theadjective“royal”,Conventiondecidedtosuppressallacademieson8 August 1793. As they of membersenjoyingitscomfort.Suchwasnotthecase.Itwentthroughdif years, the Academy couldhavefaltered,goneastray, forgotten itsraisond’être,becomeamerecoterie academies areboundbythedutytostayoncourse,“reasonagainstauthority”.Overaperiodof350 After suchagoodstart,fewwordstomentiontheresilienceof"AcadémiedesSciences":great work ofscientistswhowere committedtotheserviceofNation.Inalawon organizationofpublic The youngRepubliccame backfastenoughonthisdecision,takenin1793, and acknowledgedthe and culturalregression. Trying scienceisalwayspreferabletomaintaining ignorance. to getridofscienceandscientists.Very quickly, thesesocietiesfoundthemselvesonthepathtosocial scienti not forgetthattheevolutionofscienceislikeamedal:there isalwaysa was evenwrittenonthistheme.Eventoday, manypeoplequestionthevalueofscienti 1794. Evenifthesewordswerenotuttered,nodoubt some revolutioniststhoughtthemveryloud. A song fi c creation?We donothavefondmemoriesofthecountriesthat,atsomepointintheirhistory, tried The Republicdoesnotneedanyscientists Minutes ofthevery fi rst sessionofthe"Académiedessciences"(extract) ”, sowasitclaimedtohavebeensaidinMay fl ipside. Isthisanyreasontoreject fi cult times. Annoyed, indeed, fi cprogress.We do

9 350 YEARS OF SCIENCE 10 37 38 La Lettre and mathematicalsciences. This classbecamethe"AcadémiedesSciences"by theRoyalOrdinanceof dimension inthisInstituteconsistingof144members,dividedintothreeclasses,the against theperiodwhenworkstoppedat Academy, anditmaybenotedthereisaninternational correspondence withscienti et des Arts", aimedat“ instruction, approvedon25October1795,thethermidorianConventioncreatedan"InstitutdesSciences perfecting sciencesandartsbyunremittingresearch,thepublicationofdiscoveries, ﬁ c andforeignsocieties. ” Onemayfeelheretheremainsofafaintgrudge ﬁ rst beingphysical immediately placedbehind duHamel. A paintingby Henri Testelin (1616-1695) in red,withColbert tohisrightand,facinghim, theabbotduHamel;Christiaan Huygens,whoisrepresented full-face,is Colbert introduces themembersof"Académie desSciences"toLouisXIV :onemayrecognizetheKing atthecentre, Tempus fugit,memoria manet. see in2066. They willthenbeinasituationtosay:" The nextbigstepwillbethecelebrationof400years Academy, whichouryoungermemberswill 21 March1816. Two hundredyearslater, the Academy isstillthere,withthesametitle.

I rememberthe350yearsofouryoung Academy ."

11 350 YEARS OF SCIENCE 12 37 38 La Lettre progress inart,becausethere isnoprogressinaesthetics:beautyremainsasubjective value,apersonal painters toperfecttherepresentation oflandscapes;nevertheless,initself,thisis no progress. There isno however notsimilartoprogress. There isnodoubtthatthemasteryofperspectiveallowed Renaissance have displayedoncanvastheirbeliefs,environments, impressions, symbols,abstractions;suchhistoryis their abilitytomoveusthatmatters. True, paintinghasahistory. Oversuccessive periodsoftime,artists Dufy, KandinskyorFranzMark; betweenthem,noprogress.Evenifwedidnotknewtheirmeaning,itis The rockpaintingsthathavewithstoodtensofthousands yearstoreachusareasmovingpaintingsby As faraswemaytracebackhumanknowledge, whatprogresshasweachieved? is generallyquickerthanthedeductivemode. deduction. Itsometimesrelyonacombinationofthetwo. The comparativemode,oftencalled“intuitive”, by comparison–itthendrawsanalogiesfromalltheexperiencesstoredinitsmemoryortheoretical distinction re the know-how, whichisgroundedonempiricalknowledge,fromscience,basedtheory. This More thantwothousandyearshavepassedandthisre ﬂ ects theactivityofbrains,which,besidesemotion,works,toanswerquestions,either The marchofknowledge

© B.Eymann - Académie des sciences beginning of Aristotle’s use weesteemthemfortheirownsake this isouresteemforthesenses;apartfromtheir " for Science, Technology andInnovation Secrétaire perpétuelofthe Académie desSciences, Ambassador Catherine Bréchignac with theprimarycausesandprinciples. universal judgementisformed.Science[...]concerned when, frommanynotionsofexperience,asingle its experience. Hemakesadistinctiontherebetweenart,in which heexaminestheconstructionofknowledgefrom All mennaturallydesireknowledge. An indicationof fi rst senseofknow-how, andscience.“ fl ection remainsfullyrelevant. Aristotle dissociates fi rst bookof The Metaphysics ” Art isproduced .” Suchisthe , in © Classic Image - Alamy by FranzMarc in 1911 (ontheleft). Several tensof thousandsofyearsseparate the rockfrescoofChauvet Cave(ontheright)andBlue Horsepainted . whose moralremainstopical Rats The CouncilHeldbythe , afablebyLaFontaine, possibilities thatmoveusatdifferent scales. of wordsthattriggersemotion. There isindeedanin

© Albert Knapp - Alamy words, wordsthatexpress,suggest,thepower stone oftheother. climb overeachother. Theoneisnotthestepping confrontation betweenone’s sensitivityandawork anything inSophocles?[…]No.Poetsdonot of art,alandscape,moment,person. written in1864:« Nor shallprogressbementionedinliterature. reminded usinhisbook Homer’s IliadandOdyssey,Homer’s apoemby the sameintensity. This iswhatVictor Hugo by RimbaudorRilke,resonatewithinuswith Ronsard, afablefromLaFontaine,orverses ” Inliterature,whatmattersarethe Does Shakespearechange William Shakespeare ﬁ nt of nity , © Arnaud Frich/Centre National de la Préhistoire - Ministère de la Culture et de la Communication

13 350 YEARS OF SCIENCE 14 37 38 La Lettre electric circuits. At theendof19 current, whichwouldbringaboutthebirthof the electrostaticmachines,madetogenerate square ofthedistancebetweenthem. Then came the chargesandinverselyproportionalto electric charges.Suchaforceisproportionalto des Sciencesexplainingtheforcebetweentwo Coulomb presentedamemoiratthe Académie

in theearly2000s, wouldemergetheparadigm scales toreducethedimensions ofthetransistor would betherootofelectronics. Then, changing the UnitedStates,invented thetransistor, which researchers attheBell Telephone Company, in that makeupouruniverse.InDecember1947, would provetobeoneoftheelementaryparticles role oftheelectron,which,afewdecadeslater, J.J. Thomson demonstrated theexistenceand © Archives de l'Académie des sciences and Magnetism A platefromCharlesCoulomb's (1785) First MemoironElectricity th Century, An electrostatic machine attract eachother. In1785,Charles repel eachother;ofoppositesigns,they and “negative”.Ofthesamesign,they Benjamin Franklincalledthem“positive” or rubbingamber. Soonafterwards, whether itcamefromrubbingglass two kindsofelectricity, dependingon Du Faywho,inthe1730s,dissociated in theearly18 step tobetterunderstanditwasonlytaken for itselectrostaticproperties. The next meant “yellowamber”,whichwasknown in antiquity. The Greekword“electron” daily lives.Itwasdiscoveredveryearly has nowbecomeindispensableinour take theexampleofelectricity, which of whatwaspreviouslyacquired.Let’s must knowallthelinksofchainmade contribution toscienti and technologiesprogress:toadda they arecumulativethatsciences progress inscience.Itisbecause It ishowevercustomarytomention th CenturywithCharles ﬁ c knowledge, one knowledge, c

©Juulijs - Fotolia Science differs fromliteratureandarts.Scienti with asmuchprecision. relativity, wewouldhavedevelopedourGPSs to teamup.Inanycase,buildingongeneral as fast,ormaybewouldithavebeennecessary another wouldhavefoundrelativity, perhapsnot equal, interchangeable.HadEinsteinnotexisted, emerge. Menofscienceare,alllevelsbeing knowledge allowsadeeperunderstandingto breakthroughs materializewhentheacquired

tron orbits. about 100,000timessmallerthantheelec- A diagramofanatom:thecorediameteris ©CatherineBréchignac© Catherine Bréchignac An outlineofthe principleofoperationGPS ﬁ c Hugo. is constantlyremovingitself but approximationsofmoregeneraltheories.“ to gainmorecomprehension.Successivetheoriesare often associatedwithparadigmshiftsthatalwayslead not constructedinalinearwaybutitprogressessteps of one-electronelectronics.Suchcumulativescienceis ” wrote,onceagain,Victor

15 350 YEARS OF SCIENCE 16 37 38 La Lettre the worldfromoutside, whiletheotherismoreconcreteandconsidersitfrom theinside–because of thinkingcoexist,scienti by GeorgeWeiden prime importance.Inhisbook Education andeveryone’s involvementinre if onedoesnotwatchout,themassofnewscienti for whomscienti charlatans, ideologistsandimpostorsrush,usingapseudo-rational languagetotakeadvantageofthose make ittheirown,endangersthecohesionofoursocieties. Itcreatesanexpandingbreachintowhich a minorityofpeople,whohaveacquireddeepscienti how thesework,orsometimeswhattheirpurposeis,andyettheyusethem.Suchdiscrepancybetween enables themtocreateandproduceobjectsthatseemmagicalothers. The latterdonotunderstand centuries ago,still,theseancestralfearswerethesameforall.Buttoday, theknowledgethatsomehave from theshadowstohelpovercomefearsforwhatseemsmysteriousbecausenotunderstood.Some us. Suchprogress,however, doesnotexcludeperverseresults.Ignorancehasalwaysbroughtoutbeliefs This isthewayscienceprogresses,itscumulativenaturebeatingrhythmofirreversibilitythatdrives make thebestuseofknowledge. acquiring onediscipline.Itisthissegmentationofscience,indeed,thatweshouldconnectinorderto today, asnoneofuswouldbeabletoembraceeverythingandeveryonemustrestrictthemselves © www.neo-cortex.fr - Fotolia fi c knowledgeremainsanenigma.Likeaspringthatstretchesandeventuallybreaks fi eld andNicholsonLtd,London–, Claude Lévi-Straussinvitedustoletourtwoways fi c thinkingandsavage–theformeris moreabstractandconsiders La penséesauvage fl ecting ontheuseofsuchknowledgearemorethanever (PlonEd.,1962)– The SavageMind,translatedin1966 fi c knowledgecannotdrawawayfromoursocieties. fi c knowledge,andthevastmajority, whodoesnot in onebrain. Things arequitedifferent interdisciplinarity couldeasilygerminating gathered atthetimeandwhatwenowcall testi themselves, takingacriticalapproach. As the ancients,rediscoverknowledgeby to freethemselvesfromthedogmaof generation –andrightlysoatthetime Descartes usedtoadvisetheyounger of knowledge.Longgoneisthetimewhen us toadaptourselvestherapidincrease The cumulativenatureofscienceprompts Transmitting isurgent the scienti scientist couldacquireandassimilateall the centuryofEnlightenment,any it allbyoneself. Time ismissing.In let anyonebelievethatonecanrediscover (Plon Ed.,2014),itispointlesstodayto déshérités, oul’urgencedetransmettre fi ed byFrançois-XavierBellamyin fi c knowledgethathadbeen Les © Zacarias da Mata - Fotolia such atask. of howharshitis,wethankthemallthemorefortackling have acceptedtoundergoisadif from acertainideaofprogress. The exerciseourfellows Académie, thatthemarchofknowledgeisinseparable pages. Itremindsus,350yearsafterthecreationofour letting each through successiveaccumulation–thatweshallvisit, It isthisconstructionofscience–progressing fi eld carryusalongthroughthefollowing evolve, asmen’s emotionsevolve. fi cult one. Well aware stable overtime,becausetheydonotprogress–ormaybe creations we dowithit? That’s iswhereallartisticandliterary we cannotasksciencetoansweraloneallthe knowledge beinafewhundredyears,whatshall fi nd theirpotential,preciselybecausetheyare questions oursocietiesmustface.Itcannotdo discover. What willthestateofscienti so andsuchisnotitsrole. the anxietyassociatedwithwhatwewill ancestors. This producessomeanxiety: The unprecedentedincreaseinscienti apprehend theworlddifferently fromour and technologicalknowledgethathas has madeuschangeourworldview. We been takingplaceforthelasttwocenturies

17 350 YEARS OF SCIENCE 18 37 38 La Lettre It isreallytoLouisPasteur and RobertKochthatweowethebirthofmicrobiology inthelate19 which areimposednowadays! sions frombeingveri manufacturing technologywithothers,preventinghisobservations frombeingreproducedandhisconclu- Van Leeuwenhoek’s worklongremainedunknown,partlybecausethisscientisthadnotsharedhislense en 1680,the Académie desSciencesadmittedhimasCorresponding Memberin1699. correspondence thenfollowed,lastinguntilhisdeathin 1723. The RoyalSocietyelectedhimasa member teria. Herecordedhisobservationsinlettershesentto theRoyalSocietyasearly1673. An important binary way, thusgivingrise toidenticalunicellularorganisms:vanLeeuwenhoeckhadjustdiscoveredbac- cules”, smallorganismssometimesmoving. These unicellularlivingorganismswereabletodivideina liquids, suchaswaterfromthepondsofhisvillageandbroughthimtodiscoverwhathecalled“animal- had neverbeenreachedbefore. This ledhimtoobservethecontentsofblood,spermandmanyother quickly grewapassionformicroscopyandstartedmakinghimselflenses,ofqualitypowerthat copes –whichwerefarfromresemblingcurrentmicroscopestoascertainthequalityofhisfabrics.He It allstartedin1666Delft:thedraper Antonie vanLeeuwenhoek,then34yearsofage,usedmicros- An historicalperspective ﬁ ed. A thetime,researchpublications werenotsubjecttothesamerulesasthose The newmicrobiology

© B.Eymann - Académie des sciences forgetting theenvironment. our nutrition,medicineandmany will increasinglyin emerged; othersareabouttoappear. This revolution Indeed, inthelasttwentyyears,manynewconceptshave full “renaissance”,andevenundergoingarevolution. same timeasthe Académie desSciences.Itisnowin The disciplineofmicrobiologywasbornatexactlythe Institut Pasteur Secrétaire perpétuelofthe Académie desSciences,Professorat Pascale Cossart fl uence ourdailylives,including fi elds inbiology, not th Century. © From B.E From y mann - Académie des sciences des - Académie mann © Photo Researchers, Inc - Alamy generation hypothesisand,withtheirmanydisciples,identi therapeutics and,aboveall,prevention:vaccines. paved thewayfordevelopmentofvarioustoolsdiagnosis, nity formillenia,suchasplague,choleraortuberculosis. They agents responsiblefordiseasesthathadbeendevastatinghuma- These twoeminentscientistsde Antonie vanLeeuwenhoek(1632-1723) and thebeginningofmicrobiology fi nitively rejectedthe spontaneous fi ed the Replica ofLeeuwenhoek'smicroscope "Animalcules" detectedin human saliva,1675

19 350 YEARS OF SCIENCE 20 37 38 La Lettre great variabilityandtheiranalysis highlightedthebasisforbacterial published oneaftertheother. These bacterialgenomesdisplayed a complete sequencesofbacterial genomesofvariousspecieswere genomics enteredjustbeforethebeginningofthismillenium. The in realtime.Needlesstosaythat,helpthismolecular hunt, video microscopy–enabledmicrobiologiststoobserve infections of microscopy– the infectedhost.Very quickly, cellbiology anditsvarioustypes incredible varietyofstrategiestosubverttheimmune defensesof enter thecellsanddisseminateintissues,developing an be identi The virulencefactorsthatpathogenicbacteriaproducestartedto infectious diseasesbeganattheendof1980s. famous and itsapplicationsusingnon-pathogenbacteria,inparticularthe © Archivart - Alamy Escherichia coli ﬁ ed, aswellhowtoxinsactandsomebacteria ﬂ uorescence microscopy, electronicmicroscopy, , thatanewperiodintheunderstandingof the fathersofmicrobiology Louis PasteurandRobertKoch, the birthofmolecularbiology only withthediscoveryofDNA, course quiteempirical,anditis bacterial diseases,wasof diseases, andparticularly Their knowledgeoninfectious Éd., Paris,2016) last decades(P. Cossart, OdileJacob has dramatically changedduringthe To betterunderstandhowmicrobiology Robert Koch(1843-1910) Louis Pasteur(1822-1895)

© Juulijs - Fotolia © royaltystockphoto - Fotolia an endtothissituation,preventtheemergenceofnew resistanceandproducenewantibacterialagents. worldwide. Publicauthoritiesareonalertandstrong measures willbeneededatthegloballeveltoput become alarming:ifwedonotactnow, by2050suchdeathsmayeveryyearriseto10millionpersons resistance genes;theyarecalledmulti-resistant.Deathprediction presence ofapumpproteinexportingtheantibioticafterithasentered.Manybacteriahaveseveral bacteriophage mayhavedesastrous economicconsequences.Oneofthegreat breakthroughsofthese Antibiotic resistanceandthemondialpanic the abilitytoliveinmanyenvironments. bacteria, genomicfragmentsthatprovidenewproperties–inparticularofresistingtoantibioticsand adaptability: bacteriaareable,throughvariousmechanisms,toreceiveorgive,i.e.exchangewithother are indeedmadebyspeci have dramaticconsequences, forinstanceinthedairyindustry. Somedairyproducts,suchasyogurts, bacteriophages. These viralattackstakeplaceinany environmentbuttherearesituationswheretheymay Antibiotics arenottheonlyantibacterialagents.Innature, bacteriaare,asweattackedbyvirusescalled CRISPR/Cas9, thebacterialsystemthatrevolutionizes genetics Superbug antibioticresistantbacteria fi c bacteriaselectedforthearoma they bringtothe In 2016,indeed,onecannolongermentionbacterialinfectious antibiotic ineffective. Resistancemayalsostemfromthe diseases withoutmentioningantibiotics. These it, ortoalterthetargetofantibiotic,making compounds, whichstartedtobeusedonadaily able toaltertheantibioticandthusinactivate mentioned above,thatmakethebacteria basis inthe1950sandpredictedendof to? Ingreatparttothegenetransfers infectious diseases,have,togetherwith What aretheseresistancesdue fi vaccines, signi gures duetoantibioresistancehave mortality duetoinfectiousdiseases return tothepre-antibioticera. in developedcountries.Sadly, the dead ends,withaconspicuous fi now leadtodramatictherapeutic have becomesoseriousthatthey late 1960sandsuchresistances rst resistancesappearedinthe fi nal product. An attackbya fi cnl decreased cantly

21 350 YEARS OF SCIENCE 22 37 38 La Lettre before, incidentallyraisingatthesametimeimportant ethical issues. have neverbeenexplored therapeutic avenuesthat by modifyingthem,opening either bydeletingthemor studied inatargetedway, as itenablesgenestobe of revolutionizingbiology, technique isintheprocess was successfullydone. The of alllivingorganisms. This targeted way, thegenomes machinery toedit,ina to utilizethisbacterial quickly, emergedtheidea so impressivethat,very CRISPR/Cas9 systemis The ef only oneprotein,Cas9. associated proteins involves eitherseveralproteins,namelyCas( to destroyitandpreventtheinfection. This destruction meet thesamevirus,theyrecognizeitandareable Palindromic Repeats ( a locusoftheirgenomecalledCRISPR integrate asmallpartoftheviralDNA in the interactionofviruswithitsreceptor, may, rightaftertheinfection,thatis, When theyencounteravirus,mostbacteria and possessaveryef to immunizethemselvesagainstbacteriophages recent yearsisthediscoverythatbacteriaareable one ofthemlaysonasurface, inertoralive,adherestoit,multiplies,secretesa matrix whicheventually Rarely doesone One lastaspectofmicrobiology thathastobeconsideredisthenewconcept of“sociomicrobiology”. Bacterial communities Clustered RegularlyInterspacedShort fi ciency ofthe fi nd abacteriumwhichlivesalone: bacterialiveingroups,whichcanformassoon ). Ifthesebacteriathereafter ), or fi cient immunesystem. CRISPR CrRNA : CRISPR targeting RNA targeting :CRISPR CrRNA =CRISPR-associated Cas repeats palindromic short interspaced regularly =Clustered CRISPR © From Emmanuelle Charpentier, Planck Institute Max for Biology, Infection Berlin Bacteriophage attackingabacterium The CRISPR/Cassystem

© ktsdesign - Fotolia that inanorganism,amicrobiotaharboringgreatdiversityofspeciesissignalgoodhealthand us toremarkablyimproveourunderstandingofhowacrucialrolethis microbiota, formerlycalledthegut are beginningtobeextremelywell-documented:thesemicrobiota.Whohasn’theardoftheintestinal Other microbialassemblies,ofamuchlargersize,mayforminsymbiosiswithanylivingorganism,andthey which raisesseriousmedicalandindustrialconcerns. setting. Inthesebio some industrialstructures–suchaswaterpipesor, also,onsomeprosthesesorcathetersinthemedical bio structures asmallcommunity, protectedfromtheexternalenvironment,that is calledabio academicians, theytakeimportant decisionsonlyiftheyhaveaquorum! chance ofsucceedinganinfection andsubverttheimmunedefensesofinfected host.Bacteriaarelike bacterium onlyproducesitstoxinsifenoughbacteria of thesamespeciesarepresentandhaveagood fi lms maybefoundeverywhereinnature,butalsoonsomepartsofourbodies–teeth,particular fi lms, bacteriamaystayforseveralyears,shelteredfromantibioticsanddetergents, fl ora?Progressachievedingenomicsandtranscriptomicshasenabled The intestinalmicrobiota

© Gérard Eberl - Institut Pasteur fl ora plays.Itisnowwellestablished are Microbiota andbio and affect ourbehaviour. that maymigratetoourbrain and producescomponents protects usfrompathogens that ofourimmunesystem, in general,andparticular regulates ourdevelopment with age,thatthemicrobiota that suchdiversityreduces For instance,apathogen if thequorumisreached! of thegroupistoacttogether quorum sensing This phenomenoniscalled which theycanacttogether. close environmentandwith their sieblingspresentin to appreciatethenumberof receptors thatenablebacteria language, perceivedby other inaspeci same speciestalktoeach which themembersofa bona fi de societies,in : theobjective fi c chemical c fi l. Such lm. fi lms

23 350 YEARS OF SCIENCE 24 37 38 La Lettre the medical19 the World War II,70yearsago.S.Shryrock,an American expertinhumansciences, wrotein1947that Actually, thetherapeuticera ofmedicineonlystartedwithpenicillinandwouldriseonthedecline access totreatmentsforallisnotmerewords. possibly develop,providedthehumandimensionofmedicineremainssteadfastandconcept of areductionistapproach. Tomorrow, withtheintegrationofhealthdata,precisionapproacheswill he hadafterthewarwith directoroftheFrenchInstitutnationald'hygiène,François Jacobwrote,in the nextcentury. Medicalresearchhaddif expectancy, whichremained prettymuchstablefromprehistorytothebeginningof19 would tell,butalsoacruelone,asitstillremainedhardly ef because theyarescientistsbutforthemtobewith place, whowasreformingthe Académie, indicated:" opportunities forMolieretomocktheineffectiveness ofmedicine.Nearly150yearslater, PierreSimonLa- On theyearofcreation Académie des sciences, Dif ﬁ cult beginnings? th Centuryischaracterizedbytherapeuticnihilism,which isboundtolastuntilthehalfof to precisionmedicine From empiricalmedicine

© B.Eymann - Académie des sciences fi culty expandinginFrance. Forinstance,referringtoameeting progress ofmedicine,particularlythroughtheadoption biology (genetics,molecularbiology)contributedtothe (epidemiology), physics(imaging),chemistry(drugs)and Century, theupsurgeofsuchsciencesasmathematics curative medicinetoprogressivelyemerge.Inthe20th the introductionofexperimentalmethodbothallowed of medicineinhistime.Inthe19 Doctor inSpiteofHimself–,asatiricaldepictionthestate In 1666,Molierestaged Collège deFrance,Paris Descartes -UniversitéSorbonneParisCité), AP-HP, Inserm, Member ofthe Académie desSciences,InstitutImagine(Paris- Alain Fischer I donotplacedoctorsatthe Académie desSciences Le Médecinmalgrélui fi cient. Evidenceofthismaybefoundinlife " –aclearvisionofmedicine,asthefuture Le Médecinmalgrélui th Century, empiricismand wasoneofthemany th Century. – The Life expectanty ( 20 50 80 The 19 ciated toitwoulddropconsiderably, thusestablishingonsimpleobservationthefoundationsforhygiene. washed theirhandsafterdissectionandbeforedelivery, therateofpuerperalfeverandmortalityasso- Ignace PhilippeSemmelweis,whodidnotknowmicrobesexisted,understoodthatifdoctorsandmidwives the foundations. Thus, asearly1796,Jenneradministeredef Laennec, Bichat,Corvisart("theSchoolofParis")–intheearly19 dition ofmedicalempiricism,thequalityobservation–sharedby to makingsuresciencemetandfertilizedmedicine. The tra- A greatdealoftheanswerisno,formanyhavecontributed discovered microbes. and LouisPasteurRobert Koch Mendel de concept ofphysiology, whileGregor in themorbidstate vital phenomenainthehealthyand tries toreachtheimmediatecausesof sciences, (...)is(…)thesciencewhich tal medicine,likealltheexperimental mental Medicine Introduction totheStudyofExperi- by ClaudeBernardashewrote,in notion ofexperimentationintroduced obviously, howsigni rise inthe20 France, withthemajorcausesofincrease Evolution inlifeexpectancyduringthe350lastyears 1600 ǇĞĂƌƐͿ >ŝǀŝŶŐĐŽŶĚŝƟŽŶƐ Food th Centuryproducedtheessentialconceptsandmajordiscoveriesthatenabledmedicineto fi ned thelawsofgenetics th 1800 Century. Let’s mention, Ŷ ĚŝƟŽŶ (1865):“ .” Hecreatedthe Ɛ H Hygiène y fi cant wasthe g i è n V Vaccina Experimen- e a c c i n 1900 a Ɵ Ɵ WŚĂƌŵĂĐĞƵƟĐĂůƐ on o n Ɛ Ɛ An 2000 Claude Bernard byLéonLhermitte(oilpainting, 1889) painful? days ofmedicalresearchinFrancewere born but70yearsago,andthattheearly Does thismeanthatmedicinewasreally me; besides,geneticsdidnotinteresthim. The StatueWithin fi cient vaccines againstsmallpox;in1847, th Centurylaid : “ He coulddonothingfor Nayarit, 200B.C. - A.D. 500) fi Medical empiricism:Seated gure withsores(Mexico, ” © Photo Researchers, Inc - Alamy © LACMA

25 350 YEARS OF SCIENCE 26 37 38 La Lettre data replacedthe“opinion”inanalysisofcausesandconsequencesdiseases. became possibletomodelinfectiousandnon-infectiousdiseases. Thus, thequantitativeunderstandingof of variola.Sincethen,it ef of smallpox,orvariola)was variolation (theinoculation as 1760thatthemethodof he demonstratedasearly Daniel Bernoulli’s work example maybefoundin use ofmodels,whose diseases. Itimpliesthe that areresponsiblefor as itidenti central roleinmedicine Epidemiology playsa proved fruitful. reductionist standpointthat molecular level,froma chemistry and,obviously, biology. The latter, inthiscontext,madeitpossibletostudydiseasesatthe approach tomedicalissues,basedontheinputofsciences:mathematicsthencomputerscience,physics, As amatteroffact,theprogressmedicinesince1945stemmedfromdevelopmentscienti A scienti fi cientinreducingtherisk fi fi es thefactors c approachtowardsmedicine disrupted medicineastheyhaveallowedustolookinto theinteriorofbodyand gam’s fundamentalworkon nuclearmagneticresonance. These approacheshave Paul LauterbachandPeterMans tions dominatedbythemanyassetsofmagneticresonanceimaging,developed X-ray imageofahand,obtainedbyWilhelmRöntgenin1895,totheactualapplica- is nowever-presentinmedicine.Itwasamarvellousprogression,fromthe As forphysics,itmadepossible,inparticular, to developmedicalimaging,which fi rst 1 : Humanities and Social Sciences Social Chemistry Physics 1 - See AJ Valleron. CR Acad Sci Paris, Sciences de la vie 2000, 323 :429-33 323 2000, vie la de Sciences Paris, Sci Acad CR Valleron. AJ 1 -See Precision Medicine ^ǇƐƚĞŵŝĐĂƉƉƌŽĂĐŚ ^ĐŝĞŶƟĮĐĂƉƉƌŽĂĐŚ Experimenta fi eld (NobelPrize 2003)whobuilt Anatole Abra- Observa Empiricism Reduc Ɵ on Ɵ on Ɵ Ś onism © From B.E From Biology Computer Science Mathematics A historyofmedicalprogress ym m ann - Académie des sciences des -Académie ann 21 20 Paleolithic th > 1850 th century? century fi rst fi c © Arterra Picture Library - Alamy Wilhelm ConradRöntgen'swife Radiograph ofthehand sics hadmadepossible in the once again,toprogressphy- tics andcellbiology – thanks, molecular biology, gene- Biology, withtheriseof etc. analgesics, anesthetics, tensives, neuroleptics, infectives, anti-hyper- of activemolecules:anti- and diversityofclasses ting animpressivenumber for thelast70years,andcrea- tical industryhasbeenbooming As aconsequence,thepharmaceu- create chemicalmoleculesusedasdrugs. from theuseofnaturalsubstances,hadcometo sive. A newformofresearchwasborn,which,starting enzyme/substrate, ligand/receptor(PaulErlich)havebeendeci- The birthoforganicchemistryattheend19thCentury, theconceptsof medicine, whichshallbementionedfurtheron. organs. Nowcombinedwithalgorithmicscience,usingthemisakeyelementinthedevelopmentofdigital consider thevolumes,shapesandsomefunctionalaspects–whethernormalorpathologicalofall lopment ofahealthychildagedfrom5daysto3yearsold Brain imagingshowingthefunctionalregionsactivatedduringbraindeve-

27 350 YEARS OF SCIENCE 28 37 38 La Lettre

On thewhole,combiningtheseapproacheshasexpandedtherapeuticpalette: new hypertensiveoranticoagulantdrugs. the last20years.Let’s alsomentionthedevelopmentofanti-infectiveagentsagainstviruses,andthat example ofthepowerreductionistscienti whose usecontrolsthedisease(completeremission)and,sometimes,curesit. This isamostillustrative © Dan Race - Fotolia ● ●

cer (anti-PD1,-PDL1,-CTLA4 MAb). hopeless, asmetastaticmelanomaandsomeformsof lungcan- C20 MAb),orseveralcancerswhoseprognosisuntil thenwas sease (anti-TNFMAb)–orlethaldiseaseslymphomas (anti- chronic diseases–suchasrheumatoidarthritisorCrohn’s di- contributed tothedevelopmentofef increasingly well-toleratedmonoclonalantibodies(MAb) has drugs. Thus, thedevelopmentofmoreandelaborated Biotherapies takeanever-growingpartintheproductionofnew sible toimprovedrugavailibilityinsidethecell,inparticular. Thanks tothenanotechnologies,drugvectorizationmakesitpos- fi cient treatmentagainst fi c approachtomedicineaswehavebeenobservingitfor a familyofinhibitorsagainstthiskinase, resulted, by2000,inthedevelopmentof chronic myelogenousleukaemia. This of themostcommonformsleukaemia: to understandthephysiopathologyofone to anaberrantkinase–madeitpossible BCR tion ofafusiontranscriptbetweenthe with cancer. Forinstance,theidenti acquired geneticdisordersassociated be provided–andintheobservationof diagnoses andgeneticcounsellingto hereditary diseases–enablingprecise fi has proveddecisive,bothintheidenti- mechanisms ofdiseases.Studyinggenes resulting intheidenti nology, neurosciencesandphysiology, cularly feddevelopmentstudies,immu- elaboration ofmicroscopes–hasparti- cation ofmorethan3000monogenic and ABL genes–whichgivesbirth fi cation ofmany fi ca-

© Sebastian Kaulitzki - Fotolia © Cybrain - Fotolia © WavebreakMediaMicro - Fotolia in goodhealthhasincreased(4yearsgainedformenand3womenFrancebetween1990 of manydiseases,havebeenin and policies–hygienevaccinationsoastheeffective treatment especially improvementsinperinatalmedicine,preventivemeasures spectacular resultsarealsoduetosocialprogressbutmedicineand from 73to78yearsold,andinwomen8185old.Such France, between1990and2013,lifeexpectancyinmenthuspassed And theresultsareheretosee:lifeexpectancyisever-growing.In boosted byprogressinfundamental research,shouldtakethisintoaccount. allergic orautoimmunediseases, bacterialdiseasestriggeredbyantibioticresistance. Medicalresearch, behavioural evolutionsare atthesourceofsomeprogressingconditions:obesity, diabetes,addiction, or sensory(deafness,blindness)andwithmentalhealth conditions.Changesintheenvironmentand they raisearemorecomplex.Suchisthecase,inparticular, with diseasesthatareneurodegenerative Despite spectacularbreakthroughs,some The challengesoftomorrow’s medicine andhealth ● ●

enlarge thetherapeuticarsenal. ned (hereditarydiseases,someformsofleukaemia),mayeven combined withrobotics. on “augmentedreality”obtainedthroughtheuseofnewsoftware of progress,andsoisminimally-invasivesurgery, whichdraws implant inergonomicengineeringresearch–isanothersource The developmentofmedicaldevices–suchasasophisticated Cell andgenetherapies,forwhich fl uential. The implications ofsuchprogressaretwofold:thelifeexpectancy fi rst resultshavebeenobtai- fi elds ofmedicinehavelessprogressed,asthequestions society. economic challengeforour this situationisahealthand the ageingofpopulation, at least and closetohalfofthemhave suffer fromatleastonedisease age group,morethan75% Indeed, ofthe60-69yearsold or severalchronicdiseases. the populationliveswithone time, agrowingfractionof and 2013)but,atthesame fi ve. Combinedwith

29 350 YEARS OF SCIENCE 30 37 38 La Lettre cohabitation with4x10 access topreventionisvery diverse,etc. remain: therearelifeexpectancy differentials, lethal diseases arediagnosedatmoreorlessearlystages, How accessibleiscare?InFrance,despitearather ef caregivers), especiallyongraspingabetternotionof thedifferent ordersofmagnituderiskinvolved. line? Ef measures andpolicies,potentialforecasts,when healthisthematter?Whereshouldwedraw based onascienti Health isasocialissuewithanever-prominentplace; it isindirectcontactwiththeprogressofmedicine, human behavioursofthosefacinghealthissues. be crucialtounderstandtheindividualandcollective and socialsciencesreaponhealth,astheywill link upthefruitsofresearchthathuman A seriousissuewillbeourabilityto what mightbeprecisionmedicine. major medicaldecisiontoolin knowledge andbecomea drive progressinmedical sciences –shouldlogically development inalgorithmic of relevantdata–amajor The “intelligent”extraction metabolome, images,etc. epigenome, proteome, of information–genome, to variousbiologicalpieces which may, inturn,beassociated individuals’ electronicmedical data arebeingbuilt,ofteninvolvingthe healthy orsick,isborn. Thus, warehouses glycaemia, etc.). A systemicapproachtotheindividual, parameters inthecontextofanygivendiseases(cardiacrhythm, so as“connected”devicesaremoreandused,makingiteasiertoremotelyextractmanyrelevant Quite logically, thenumberandtypesofavailabledataforeachindividualincrease rapidly, allthemore quantify itandextractusefulelementsformedicinetobene as welltimeandindividualcollectivebehaviours–howisitpossibletograspthiscomplexity, to our 22000genes,themillionregulationelementsingenome,3x10 The complexityoflivingbeings,includinghumanbeing(whetheringoodhealthorill),asillustratedby 2 - O Nay, et al. Lancet 2016 , 387 :2236-49 ,387 2016 Lancet 2 -ONay, al. et fi cient publichealthpoliciesrequire quite sharphealthtrainingprogrammesforthepeople(and fi c approach.Manyquestionscallforananswer:howacceptablearepreventive 13 bacteriaintheintestineandmorethan10 fi les, 2 fi cient redistributionsystem,healthinequalities fi t frominever-changingenvironment? 15 viruseshastobetakenintoaccount, 13 cellsofourbody, our

© pandpstock001 - Fotolia A medicaldatawarehousewithrelevantextractionmodules mind historical viewoftheprogresshuman de Condorcet’s text–in prevent abuses.Inthiscontext,Nicolas part ofahumanvision,drawthelinesand order tomakeanyprogressinmedicinethe call foranin-depthethicalre drugs –isafactorweighingheavyontheriskthatinequalityofaccesstocaremayworsen.Suchissues The costofinnovativetreatments–asillustratedintherecentperiodtimebynewanticancer occupations. Norwoulditbedif climate, aliments,andthenatureofcertain well tothosegeneralmaladiesresultingfrom to transmissibleorcontagiousdisorders,as of medicine(…)mustintheendputaperiod manifest thattheimprovementofpractice causes." we shallhereafterdiscoverthemostremote every othermalady, ofwhich itisprobable that thishopemightbeextendedtoalmost EHR =electronichealthrecord Clinical databases EHR / , 1794–proveswidelyprophetic:" Knowledge databases and Sources

ontology Warehouse Data Outlines ofan ﬁ culttoprove ﬂ eto, in ection, Search engine Search Data miningalgorithm Security module It is Extract Transform Database E Load T L Nicolas deCondorcet (1743-1794) User interface Prognosis, treatment

31 350 YEARS OF SCIENCE 32 37 38 La Lettre “reasonable soul”,with“itsprincipalseatinthebrain”. the anatomyofthis“machine”anditsphysiologicalfunctions,onelevelafterother, uptothe muscles, nerves“smallandbigpipes”,soon–heattemptedtoestablishacausallinkbetween des Sciences,on26 April 1775,thatthecombustionofcharcoal released" Lavoisier, thefounderof modernchemistry, wasinterested incombustion.Hedemonstratedatthe Académie extinguishes the of matterfromatomshecalled"corpuscles In 1661,theIrishBoyle,asafollowertoDescartes’ mechanisticphilosophy, triedtoexplaintheproperties Step 1:thechemistryoflife knowledge onhumanbeingshasprogressed,fromthe chemistryoflifetothehigherfunctionsbrain. bodies. that burnscontinuouslyinitsheart,andwhichisofthesamenatureasthose principle ofmovementorlife,otherthanitsbloodandspiritswhichareagitatedbytheheat Here istheendofDescartes’ treatise:“ ” This propositionwillbethebackboneofmypresentationon the successivestepsbywhichour ﬂ ame ofacandle andkillstheanimalsplacedinsideit. human beingsandtheirbrains On thepathtodiscovering

© B.Eymann - Académie des sciences In thismachine(...)itisnotnecessarytoconceiveofanyother brains. Fromtheelementarystructuresofman’s body– research onthediscoveryofhumanbeingsandtheir text anticipates,despitetheinaccuracies,350yearsof Sciences washeld. Although un two yearsbeforethe which wouldonlybepublishedafterhisdeath,in1664, Descartes wroteabout1632the Collège deFranceandInstitutPasteur the UniversityofCalifornia,SanDiego,HonoraryProfessorat Member ofthe Académie desSciences,InternationalFacultyat Jean-Pierre Changeux " . Healsoobservedthatpumpingairfromaclosed vase fi rst sessionofthe Académie des fi xed" air, whichresultedfrom fi res thatoccurininanimate fi nished, thisprophetic Treatise onMan fi re , © Musée du Louvre, Dist. RMN-Grand Palais / Harry Bréjat fl is combustion concluded that“ being identical,Lavoisier pig: themeasurements or bytherespirationofaguinea- carbon producedeitherbya heat thatisreleasedperunitofgas calorimeter tomeasurethequantityof In cooperationwithLaplace,hebuiltthe chemical theorytotherespirationoflivingbeings. oxygen. A majorstepwastakenwhenLavoisierextendedhis the combinationofcarbonwithsomegas,mysteriousattime: information. pp 14-15).Thanksto Arnauld andBarbaraBrejondeLavergnéefortransmittingthis to RenéDescartesby Alexandre Marr( Pastel bySimonVouet, fromthecollectionsofLouvre.Identi discoveries thatwouldbemadeonthebrain. Descartes, inhisTreatise onMan observation madebyBoyle. painting, 1768–recaptures the pump –JosephWrightofDerby's An experimentonabirdwith theair ame ofacandle. ”, likethe respiration © The Artchives -Alam Artchives The In Times Literary Supplement fl ame (1664),anticipatedthe y fi cation ofthemodel , 13March2015,

33 350 YEARS OF SCIENCE 34 37 38 La Lettre

© Alamy that revolutionizedourunderstandingofheredity. Itwouldbefollowed,morerecently, bytheelucidationof diffraction. In1953,itwasthedoublestrandedDNA modeldescribedbyWatson, CrickandRosalindFranklin atomic level,ofthesemacromolecules.Various physicaltechniqueshavebeenused,includingX-ray Throughout the20 would playacentralrole. human beings–wouldbeunderstoodasvastandcomplexchemicalsystemsinwhichmacromolecules The relevantsetofenzymesandtheirsubstrateswereenough.Fromthenon,livingbeings–including fermentation couldbeobtainedinvitrofromanextractofyeast,theveryabsenceanylivingyeast. proteins. Finally, in1897,Buchnerdemonstratedthatthewholecomplexprocessesinvolvedalcohol it wasobservedthattheenzymescatalyzingchemicalreactionsconstitutelivingorganismswere desoxyribo- andribo-nucleicacids(DNA andRNA)–,sugarsforpolysaccharidessoforth.In1833, the linearcombinationof20aminoacids.Othermacromoleculesareformedfromnucleotides–suchas "macromolecules The repertoireofthemoleculesthatconstitutelivingbeingscompriseshigh-weightpolymers,or that vitalismhadfailed;themanyorganicsynthesesperformedsincethenhavecon inorganic substances? The chemicalsynthesisofureabyWhöler, in1825,broughta difference betweenorganiccompounds–producedbylivingbeingsand in thevitalisttheoriesthat,invokingmysteriousforces,claimeda debate thenshookthescienti produce fromtheseverychemicalradicals. A mostanimated called "polymers "chemical radicals resulted fromthecombinationofgroupsatomsthathecalled and proposedatheoryaccordingtowhichanychemicalreaction Fifty yearslater, approach theSwedishBerzeliusbuiltonLavoisier’s describe thespeci Francis Crick (1916-2004) " " the“organic”compoundsthatlivingbeings , includinginparticularproteins–anothertermBerzeliuscoinedwhichresultfrom th " fi . Heeveninventedtheterm"catalysis c accelerationofachemicalreactionand Century, andeventoday, researchhasbeendealing withthe fi c community. Couldonebelieve Tridimensional structureofDNA byX-raydiffraction " to Jons JacobBerzélius (1779-1848) fi ne structures,atthe fi rmed suchfailure. fi rst demonstration rst

© Leigh Prather - Fotolia © Georgios Kollidas - Fotolia © From B.Eymann - Académie des sciences Such wasmythesisworkatJacquesMonod’s laboratory. actions together. A changeintheconformationofproteincontrols couplingbetweendistinctsites. proteins, called“allosteric”actasbiologicalswitches,bindingregulatorysignalsand highlighted, onhaemoglobinandmyoglobin,thethree-dimensionfoldingofamino-acidproteinchain. Then Each humanbeinghasnowbecome“labeled”byhisorherDNA sequence.In1960,PerutzandKendrew the completechemicalsequenceof3.5billionbasepairs(whicharefourtypes)ahumanDNA. © Bruno Villoutreix -Inserm Villoutreix © Bruno hemoglobin byX-raydiffraction Tridimensional structure of (1914-2002) Max Perutz

© Alamy Specialized regulatory dinated withoneanother. another butrathercoor- independent fromone living systemsarenot tions thatcomposethe The chemicalreac- and key. protein justlikealock the ligandenters complex forms,inwhich they bindto:aspeci the smallmolecules the proteinstorecognize mechanism, enabling of thereconnaissance followed thedeciphering ﬁ c

35 350 YEARS OF SCIENCE 36 37 38 La Lettre

© From F. Delsuc. Nat Rev Genet. 2005 ; 6 : 361-75 Plantae EUKARYOTA BACTERIA organism isencodedbyagenetic sequenceofDNA moleculeandthatmutationsinsuchsequences areatthe mutations thatweretransmissible throughheredity. Molecular biologyhasestablishedthateachproteinof the are localizedonthechromosomes, ineachcellularnucleus.Heconsideredthey werelikelytobemodi that havebeencalled“genes” sincethen.Morgan,inthe1920s,demonstrated, withthe colour andformofthepeashecultivatedingarden ofhismonastery–whichheascribedtoinvisible“factors” 1866, Mendelacknowledgedtheexistenceofstableand transmissiblehereditarycharacteristics–suchasthe part, disappeared.Deathhasbecometheessentialcoginevolutionoflife.Unexpectedly, genetransfers Darwinian model. The studyoffossilshasshownthatspecies,orevenentiregroups,appearedandlater, ingreat the bene 59 yearslater, tookoverthetransformismthesisbutabandonedLamarck’s inheritanceofacquiredcharactersto revolutionary concept,theevolutionofspecies:speciesarenot speech ofhiscourseattheMuséumd’HistoireNaturelle,abandonedthisvisionworldtobene this harmonious“ “growing perfection”fromonetotheother. At thesummitwasseated“man”,thenCreatorabove,responsiblefor Linné and,inourcountry, withBuffon. These specieswereclassi Starting with Aristotle, thedescriptionofspeciesexpandedincenturyEnlightenmentswithSwedish beings. This microscopicdiversityisinlinewithabroaderdiversi embryo, notonlydocellsmultiply, buttheyalsodifferentiate intodistincttypes–muscular, hepaticandsoon. (“ in eachcell,insideawaterycytoplasm,circumscribedbymembranemadeoflipids.“ level isthecell,whichaccumulatesproteinsandnucleicacids.Withhigherorganisms,anucleustobefound The livingbeingisnotmerelyabagofenzymes:ithasshapeandanorganization. At themostelementary Step 2:cellbiologyandevolution bushy treeoflifeinwhichmanappearsonalateralbranch. Studying thegenetickinshipoflivingspecies(basedonribosomal RNA)revealsa Deinococcales Gram positive Every cell[stemsfrom]another High-GC, Cyanobacteria Chlamydiales Spirochaetes Land plants Amibozoa Proteobacteria fi Green algae Thermotogales t ofnaturalselectionasthedriveevolution. Two centuriesofbiologicalresearchwouldvalidatethis Aquificales Glaucophytes Mycetozoans Red algae Grampositive Pelobionts Diplomonads scala naturae Entamoeba Low-GC, Chloroplasts Excavata Euglenoids Mitochondria mycetales Plancto- Bacteria Jakobids Eukaryota ”. The tableis phytes Crypto- proteales Thermo- Archaea Chromalveolata Haptophytes ”), suggestedVirchow asearly1855.Duringthedevelopmentof Crenarchaeota Stramenopiles Alveolates Desulfurococcales fi xed andimmutable.UntilLamarck,on11 May1800,intheopening Opisthokonta Cercozoa Sulfolobales Radiolaria Rhizaria Choanoflagellates Fungi Metazoans Halobacteriales Thermococcales Methanococcales Methanosarcinales Thermoplasmatales Euryarchaeota Archaeoglobales fi cation, thediversi ARCHAEA fi ed withinahierarchyintableillustratingsome fi xed, they“transform”themselves.Darwin, HOMO fi cation ofthegeneralshapesliving development. As earlyas between evolutionand reveal unbreakablebonds discipline, genetics,would The developmentsofanew scale ofbeingsanymore. of placeatthesummit beings arenottakingpride on alateralbranch:human sapiens’ shape ofabush,where and irregular. Ittakesthe tree oflifebecomesuncertain very distantspecies,andthe occur betweensometimes Omnis cellulae fl y, thatthesegenes ancestors appear fi fi ed by ed Homo t ofa ” Neuron (SantiagoRamon yCajal,1894) changed istheorganization. vast physicochemicalsystemswhoseconstituentpartshavelittlechangedinthecourseofevolution.What has our brains. They arealsothetargetsofmanydrugs.Ournervoussystemsare,asrestourorganisms, present inbacteria,thesereceptorsimposeirreducibleconstraintsontheinformationprocessingperformedby chemical signalsintoelectricalsignals,receptorsarepartoftheallostericswitchesmentionedabove. Already signals –neurotransmitterstakeover, spreadinthesynapticspaceandbindtoreceptors. As theyconvert electric signalsthatareentirelyreducibletothetransportofelectrically-chargedions. At thesynapse,chemical physiological featuresofthenervecellarekeptfromprimitivespeciestohumanbeings. Axons propagate the membranesofnervouscellsarejuxtaposedatsynapses.Remarkablyenough,mainanatomicand of othercells. As RamonyCajalalreadysuggestedin1890,neuronsformdiscontinuousnetworkswhich prolongations, axonanddendrites,thatcomeintocontactwithhundredssometimestensofthousands communication andcoordinationbetweenthedifferent partsoftheorganism.It individualisesitselfbythemany The neuronappearedveryearlyinthecourseofevolution,withhydraandjelly lineages intheorganism,andnotablythatofnervouscell,neuron. receptor The basic components ofthebrain: the nervouscell, synapseand moleculeofthe acetylcholine neurotransmitter withits made in1961,specializedgenesequences,called"regulatory themselves atthesametimeduringdevelopment. Tallying withthemasterfuldemonstrationJacobandMonod origin ofmanydiseasesinhumankind.Besides,itisafactthatallthegenesourchromosomesdonotexpress , ilmtrmcoee nanometer micrometer 0,1 millimeter

© molekuul.be © Jean Cartaud " sequences,controlthediversi Fine structure(atomicresolution)ofaneurotransmitterreceptor Allosteric transitition ofareceptorlike like thenicotinicacetylcholinereceptor the acetylcholinereceptor ﬁ sh. Itensuresfast ﬁ cation ofcell

37 350 YEARS OF SCIENCE 38 37 38 La Lettre computational modelling. Another revolutionisunderway:itstemsfromSocrates’ " with them,severaldisciplinesmustconverge:brainimaging,electrophysiology, psychophysicsand whether consciouslyornon-consciously. obtained whilevisualprocessesaretakingplace, this neuronalspacetomakeoutthebrainimages being involvedinemotions.Itispossiblewithin parietotemporal andcingulatecortices,thelatter space. Suchanetworkinvolvestheprefrontal, and contributetobuildingthisconscious between thesedifferent territoriesofthebrain long axonsmightcreateinterconnections and Ihavesuggestedthatneuronswithvery exterior eventsandinnermemories.Dehaene the “globalandunitary”synthesisofperceived physical spacesofourbrains. There, takesplace shared byallhumanbeings,developincommon idea behinditisthatconsciousprocesses, Eminent scientistshaveembarkedonthispath,suchasJouvetorBuser, CrickorEdelman. The strong Descartes’ " All thesefunctions,de awareness, ourabilitytoconsiderothersasoneself,symboliclife,withspokenandthenwrittenlanguage. in micetonearly100billionhumans. At thesametimes,newpsychologicalfunctionsappeared:self- Left/right hemisphericasymmetrydeveloped. The numberofbrainneuronsincreased,from50million especially thesurfaceofcerebralcortexandmorespeci The brainevolveddramaticallyanddifferentially, bothinsizeandcomplexity. Brainsizeincreased, Step 3:theevolutionofbrainandoriginculture work, thatthisplanisdetermined byanetwork especially throughNüsslein-Volhard’s pioneer is onthefrontpartofthis plan. We nowknow, of animalspecies. The centralnervous system there wasaunityofplanintheorganisation Saint-Hilaire suggestedatour Académie that such cognitivefunctions.In1830,Geoffroy increase instructuralcomplexityentailedby modi Everyone mightwonderwhatcriticalgenetic No mysteries,butstillalottodiscover! fi cations have ledtotheastounding Cogito ergosum fi ned as“cognitive”,nowfallwithinthescopeofscienti "! conscious way individual readingawordin conscious ornon- Functional magneticresonance imagingofa fi cally itsfrontpart:theprefrontalcortex. Reading inanon-consciousway Reading inaconsciousway Know thyself fi c method. To deal " andeven

© From Dehaene S, et al. Nat Neurosci 2001 ; 4 : 752-8 are doing representative capacityinordertoknowwhatyou Here isindeedwhatGünther Anders tellsus:“ drive mankindtolosepartofitshumanity? This isfarfromcertain. Would thisphysicalistapproach– person” withhis/her“ Vygotsky, thefeaturesofhis/herphysical,socialandculturalenvironment. Thus developsthe“human rules, remaininscribed,asitwere,inthebrain. The brainofeachindividual“internalizes”,accordingto groups fromoneanother. “Culturalpathways”,suchasthosetakenbywriting,reading,orevenethical intense synapticplasticity, culturesdevelop,passfromonegenerationtotheotheranddistinguishsocial individuals. As wehavesuggestedwithCourrègeandDanchin,“ process, whichis“Darwinian”butnotgenetic.Somevariabilityevenoccursbetweengeneticallyidentical network, whetheritbespontaneousortriggeredbytheenvironment,regulatesthissynapticselection phases withthestabilisationofsomeconnexionsandeliminationothers. The activityofthe interactions. Then phasesofsynapticexuberanceoccurwithmaximalvariability, followedbyselection this period,fundamentallearningtakesplace,suchastheacquisitionofwalking,languageorsocial More thanhalfofthesynapsesadultbrain,orderonemillionbillions,formafterbirth.During maturation afterbirthisexceptionallylongcomparedtootherspecies–itlastsmorethan At birth,humancubshavebrainsthatweigh the brain. Another liesintheprocessofpostnataldevelopment. evolution mayresultfrommutationsinsomecriticalregulatorysequencesthatcontrolthedevelopmentof of thebrainthusincreasesmuchfasterthancomplexitygenome.One humans, thetotalsequencesofcodinggenesonlydiffers by1.2%! The anatomicandfunctionalcomplexity of genesthatcodeforproteinsfrommicetohumans–about25000and,betweenchimpanzeesand contains about6000genesagainst13forthedrosophila,thereishowevernovariationinnumber genome, however, hascreatedonemoreparadox. As amatteroffactindeed,ifthegenome yeast These genesplayindeedaroleinthebiogenesisofbrain. The recentdeciphering ofthecomplete in the of regulatorygenes,called“homeotic”genes. Their mutationsbringaboutspectacularchanges,suchas, sustainable environment... Seuil Ed.,1990 institutions it, a“ that willopenaccessto,asRicoeurput is forustoinvent,withourbrains,afuture leave uswithaheavyethicalresponsibility. It us toprogressintheknowledgeofwhatweare, 1999 ). The dispositionsofour brains, thatenable good lifewithandforothers,injust fl y, thesubstitutionofanantennaforaleg. ” (In ” (In Nous, Soi-même commeunautre, ) and,Ishouldadd,ina habitus fi ls d’Eichmann,RivagesEd., ” associatedtoeachindividual’s story. fi rst CartesianandthenDarwinian– © coo ki fi Extend your ecu ve timeslessthanthebrainofanadult,andperiod tt e r -F o t o li a to learniseliminate fi rst hypothesisisthatthis ”. Duetothis fi fteen years. fteen

39 350 YEARS OF SCIENCE 40 37 38 La Lettre sail thouforthtoseekand context, animalbiodiversityprovestobeanamazingsourceofbiomedicalinnovation.Now, Voyager, “ and howitwasrelevantto devotevirtuallyalltheresourcesofresearchto standard animalmodel: of theNational Academy ofSciences theUnitedStatesof America (PNAS,2009),asked thenwhether have, preventingtheproliferation ofcancercells. The editorialwrittenby JMSedivy, intheProceedings than amouse.Now, wehavediscoveredthatitisprovidedwitha mechanism, whichthemousedoesnot Less photogenicthanitsfellowcreaturefromDamaraland, itmaylive32years,whichis16timeslonger But let’s getbacktothefamily ofmole-rats. All havehighlifeexpectancy, includingthenakedmole-rat. took thalidomide. is beingused.Becausethiswasoverlooked,tragicfoetal malformationsoccurredafterpregnantwomen all sortsofso-called"mechanistic"approaches.Butthe keyissueistherelevanceofanimalmodelthat and, beingsmall,isquitecheap.We nowhaveawholerangeofgeneticallyengineeredmice,designedfor research, itisundoubtedlyanexoticanimal.Indeed,the"standard"modelmouse:breedsrapidly nor amole–itbelongstofamilyofanimalsclosetheguineapig.Butasmodelanimalforbiomedical First stop:theKalahariDesert,withastrangeanimal,Damaralandmole-rat.Infact,itisneitherrat, Classical modelsVSexotic The situationisinsomeways reminiscentoftheoldjokedrunklookingforhis keysunderthestreet ﬁ nd… From thecelltoecosystems

© B.Eymann - Académie des sciences and howto by whichwetrytounderstandhowourorganismsfunction question of“animalmodels”. This iswhatwecallanimals spans fromthecelltoecosystemsisconsider One waytoexplorethehuge Centre University ofStrasbourg,alsoaf Researcher atCNRS,InstitutpluridisciplinaireHubert-Curien, Member ofthe Académie dessciences,EmeritusSenior Yvon LeMaho fi ghtmoreef fi cientlyagainstdiseases.Inthis fi liated attheMonacoScienti fi eld forinvestigation that fi c © Andrew Young The mole-rat,herefromDamaraland,anexoticanimalmodel there isstillalotofexcess fat,verylowcalorie in thetreatmentofsevereobesity, evenwhen their musclemasswhenthey fast.Indeed, as somebats,experience a reductionof other animals,withafewexceptionssuch only animalsabletodoso:men,asany of itshibernation.Bearsareamongthe urinate ordefecateforthe5to6months proteins, whichexplainswhyitdoesnot muscles andallitsothervaluablebody exclusively usesitsownfat:itsaves in thishibernationfastingisthatthebear the bearhibernates.Whatisextraordinary rate thatreducesto5or6beatsperminutewhen show thatitsheartbeatsabout60perminute-a is thehibernatingbear. Echocardiographyperformedonthebear may onlybestudiedinnature. Thus, oneof themostremarkablemodelanimals Research onmole-ratsisconductedinthelaboratory, butmechanismsdevelopedbysomeexoticanimals human health. determine whatelementsledtheseanimalstodeveloptumours,inorderpossiblylearnlessonsfor have justbeendiscoveredinanimalskept American zoos.Itwillobviouslybeveryinterestingto thought thatthenakedmole-ratwaspreservedfromcancer, buttumours questions maysimplynotbefoundunderit the keystosomereallyinteresting(andimportant) model systemssureshineapowerfullight,but lamp. Thecurrentlymainstreambiological (Southof Africa) Kalahari Desert .” However, we

41 350 YEARS OF SCIENCE 42 37 38 La Lettre

© Solvin Zankl - Alamy the synthesisofitsmoleculemade,ithasbeenshownwasveryeffective against twoofthemainagents food withthepresenceofasmallantibacterialandantifungalprotein.Onceitsstructureestablished 38° C.WiththesupportofFondationdeFrance,wehavebeenabletoassociatethisabilitypreserve marine preyitkeepsintactduringthosetwoorthreeweeksintoitsstomachdespiteatemperatureof37- further south.Itisremarkablethatthemalethenabletokeepsitschickaliveforaweek,feedingitwith effects arefeltasfartheSouthernOcean,andmaythusdriveitspreyeven further away, over200km may howevernotcomebackintime,especiallybecauseofthewarmingassociatedwithElNiño,whose during thelast2or3weeks,withfemalethencomingbackonhatchingtimetofeedchick. The female with incubation,forwhichtheytaketurnsondryland.Usually, itisthemalethat performstheincubation king penguinincubatingitsegg.Maleandfemalefeedat300to400kmoffshore; fastingisthusassociated Another exampleofaphysiologicalmechanisminterestthatcanonlybestudiedinnatureisthe mechanism inthetreatmentofsevereobesity. of muscles,andnotablyheartmuscle.We thereforeseehowdesirableitisto elucidateandmimicthis diets maynotbeextendedbeyondacertainperiodoftimebecausetheywouldresultincriticalloss digests it.Buthowshouldwegoaboutstudyingananimalinitsenvironment? cause reproductiontofail.Ifapenguinstopsincubating,itkeepingitsfoodinstomachand of theincubation,insatisfactoryasepsisconditions,andwithout,course,disturbinganimals is comparabletothatofoureyes–unlikemostantibiotics.Now, bacterialresistancetoantibioticshas Moreover, thisproteinisveryeffective insalineenvironments–thesalinityofpenguin's stomach of nosocomialinfections, miniaturization. few decadesincomputingandelectronic progress thathasbeenachievedinthelast it wasmadepossiblebytheconsiderable undisturbed observationisaveryrecentone: their waysoflifeandbehavioursthrough The approachentailingthedescriptionof their onlyremainsbroughtfromexpeditions. For centuries,animalshavebeenstudiedfrom environment Adapting researchtothenatural al. JBiolChem (left, controlsample;right,withpenguinpeptide).FromThouzeauC, the growthofmicroorganisms–here, Spheniscin, apeptideproducedbythestomachofkingpenguin,alters 2003;278:51023-8. Staphylococcus aureus Aspergillus fumigatus andthepathogenicfungusresponsibleforaspergillosis. et

© Philippe Bulet content atthedifferent stages microsamples ofgastric new methodstocollect been enough.Ittookinnovate structure, itwouldnothave such amoleculeandits biology requiredtoidentify Even withalltheexpertisein ﬁ antimicrobial agentsableto there isadramaticlackof public healthconcern,and become anemergingmajor ght eyeinfections.

43 350 YEARS OF SCIENCE 44 37 38 La Lettre abandonment. At Kerguelen, wehavealreadylaunchedtheoperationalphase. that wouldmakethemleave theirlocationinthecolony-thuscausingitsdisruption, withtheriskofegg signi equipping kingpenguinswithcardiacmonitorsofthetype thatisusedforjogging,wedonotobservethe territory againsttheroverinsamewayastheydo theirfellowsthatcommuteintothecolony. By the ideaofusingrovers,thatistosayremote-controlled vehicles.Incubatingkingpenguinsdefendtheir Inspired inthisbytheexplorationofMars,andwithmeans providedbythe Total Foundation,wehavehad each animalthiswayisoutofthequestionasresulting disturbancewouldbephenomenal. in thecolonywithamanualRFIDreadercontaining activation-sensorantenna.However, approaching theory, itcouldbepossible toidentifyandlocatetheindividualswearingelectronictagsbyrovingaround identi of thecolonyPossessionIsland,inCrozet Archipelago, allowingkingpenguinstobeautomatically of thePaul-EmileVictor PolarInstitute,antennashavebeenburiedonthreepassagepointsinalargearea antenna takesdownthenumbercorrespondingtolabel.It’s been18yearssince,withintheframework battery. Powerissuppliedbyanantennawhenthe"labelled"animallessthan50cmfromit;inreturn, This extrememiniaturizationofelectronicRFIDtagsismadepossiblebecausetheyoperatewithoutany 16%. The chicksurvivalafterthreeyearsishalvedwhenithasbeenwearinga band. the reproductivesuccessofbandedindividualsreducedfrom40%intenyears,andtheirsurvival enabled ustohighlighttheimpactofa hindrance. Thanks totheBettencourt-SchullerFoundation,thistechnology, evenbeforebeingmarketed, tags oflessthanonegramimplantedundertheskin,tohaverealcontrolanimalswithnohydrodynamic 1990s, theinventionby Texas InstrumentsofRFID-radiofrequencyidenti resulting hydrodynamichindrancetothemovementofseaanimalcausednoinjury?Ittook,inearly that wereeasytoreadfromacertaindistancewithbinoculars.Buthowwemakesurethe have usedforalongtime,inpenguins,metalbandplacedon To identifyeachindividualanimalandlocateitwithoutdisturbingisnotsimple.Forthisto be done,we fi cant increase intheheartbeatratethatre fi ed onenteringorleaving. This, however, doesnotenableustolocatethemwithinthecolony. In fl ipper bandonthekingpenguin:comparedtocontrolindividuals, fl ects stress caused bythepresenceofhumans-stress

© IPEV/IPHC locate thepenguins A band,orevenbetteranelectronictag,helps fl ipper ofeachpenguinwith numbers fi cation -whichuseselectronic © Julien Courtecuisse/CNRS-IPHC © Julien make arewithinthevocalization spectrumofthepenguins.Newmethodologicalinnovation isneeded. until thepresentday, activatetherobotsmaynotbeused becausethesoundsthey which itisfornowunabletomove. Another hurdle:theservomotors that, working inStrasbourgonthearticulationofits are currentlyunderwayinthecolony, whileengineersare sent totheDumontd'UrvilleStation,in Adélie Land. Tests Strasbourg. Itwascompletedinmid-Januaryandthen Foundation, a Centre, andonceagainwiththesupportof Total Hubert-Curien deStrasbourgandtheMonacoScienti we havecreatedwiththeInstitutpluridisciplinaire project wasborn:withintheinternationallaboratory they aresaidtobe“tobogganing”. This is howournew on theirstomachswiththehelpof 100 km/hin Adélie Land.However, adultscanbeseenmoving position andmakeitmove,asthespeedofwindoftenexceeds obstacle toit:itisimpossiblemaintaininanupright a fakeadultemperorpenguin. There isabig It wasthereforenecessarytobuild when therearesmallchicks. used intheperiodoftime such arovermayonlybe it cancarry. Moreover, scienti to thenumberof chick isalimitation disguise ofasmall of aroverunderthe place. Butthesize identi distance forelectronic approached attheright penguin allowstobe with afakelittlechick,the However, if theroverisdisguised energy expenditureinthepolarcold. huddling tightlywithitsfellowsandthusreducing when incubatingitseggorchick,asthiswouldpreventitfrom With theemperorpenguin,allturnedouttobemorecomplicated.Indeed,itdoesnotdefendanyterritory fi cation totake fi c instruments c fi rst prototypehasbeendesignedin fl ippers andlegs: fl ippers andlegs, fi c 2014; 11: 1242-4). chick rover(LeMaho, vocalize tocommunicatewiththefake Adult andchickemperorpenguinseven et al.NatMethods

45 350 YEARS OF SCIENCE 46 37 38 La Lettre be, impactthereproductivesuccessandsurvivalofpenguins. a population,howclimatevariations,astheydeterminewhereandabundanttheirmarinepreymay have beeninplacefor18yearswithkingpenguins,itwillbeeventuallypossibletoknow, onthescaleof especially intothoserelatedtovariationsintheclimate. Thanks totheelectronicmonitoringsystemsthat Studying animalsintheirnaturalenvironmentsalsoprovidesmoreinsightintoenvironmentalchanges, Precious information that areyetunknownand,atthesametime,betterunderstandourenvironment. unexplored minesofinformationthatenableustohighlight,fromthecellecosystems,mechanisms In additiontothestandardmouseandratmodels,so-called"exotic"animalmodelsarestilllargely its livingenvironmentvaryatdifferent depths. particular, fortheoliveridleyseaturtleinGuyana,ordertomeasurehowsalinityandtemperatureof Argos beacons,datamaybegatheredontheecosystemsinwhichtheylive. This hasbeendone,in In return,whenwildanimalsareequippedwithdataacquisitionsystemscoupledcarefullydesigned "Adult" roverin acolonyofemperorpenguins in Adélie Land(austral winter2016)

47 350 YEARS OF SCIENCE 48 37 38 La Lettre For chemistry, thescienceofmatter, therewasstillafundamentalquestiontoanswerintheearly17 analyzing mineralwater:itwaspartofmedicineandpharmacology. physician toLouisXIV. At thetime,chemistrywasmostlyaboutextractingactiveprinciplesfromplantsor was reallyachemist:theformeranapothecarytoDukeofOrleans,andlatterordinary appointed twochemists,ClaudeBourdelinandSamuelCottereauduClos. As amatteroffact,neither universal language -chemicalnomenclature -thatwouldbeusedbychemists worldwide!Shortlyafterwards, phenomena. The publicationofthe Elementary Treatise ofChemistry, in 1789,markedthebirthofa "phlogiston" theory, supersededbyLavoisierwhenhe highlightedtheroleoxygenplayedincombustion 18 earth –amodelthatalchemistswouldapplytotheirown ambition,transformingmetalsintogold...Inthe whereas Empedocles, Aristotle andPlatoassertedthatitwasmade offourelements:water, air, antiquity werestillpredominating.Democritusclaimed thatmatterwascomposedoftinygrains(atoms), century: whatismatter, whatisitmadeof? The hypothesespropoundedby theGreekphilosophersof science onlyroseinthelate17 Curiously enough,although"chemicalarts"hadbeenpractisedsinceearliestantiquity, chemistryasa Chemical Arts th Century, ErnstStahl,toexplaincombustion,wasstill resorting totheelementof" to understandandcreate! Chemistry, thescience ofmatter: th century. As soonasitwascreated,in1666,the Académie desSciences

© B.Eymann - Académie des sciences development ofallmodernelectronics. to theformationofsilicon,whichisatorigin and iron. Today, high-temperaturesilicareductionleads gone fromthe Age ofstonetothatcopper, thenbronze stage wasreachedinourdevelopment.Indeed,wehave achieved inextractingmetalsfromtheirores,another role inthehistoryofhumanity. Witheveryprogress Chemistry, theartoftransformingmatter, playedakey Collège deFrance Member ofthe Académie desSciences,HonoraryProfessoratthe Jacques Livage fl ame": itwasthe fi re and re th essential contributions analyticalchemistrymade inthe18 The periodictable ofelements,publishedby DmitriMendeleevin1869,illustrates the time, only adozenchemical elements (inblue)were known. in theperiodictablepublishedbyRussianchemistMendeleev1869. This classi (Berzelius). About sixtychemicalswerethusdiscoveredoverthefollowingtwocenturies. They werelisted task: theydiscoveredchromiumandberyllium(Vauquelin), boron(Thénard),bromine(Balard)andsilicon to befoundinorderknowatlastwhatmatterwasmadeof. Analysis thusbecamethechemists’ lead, copper, sulphurandcarbon. There stillremainedahundredotherelements elements hadbeenidenti theory. birth ofthemodernatomic water vapour!Itwasthe oxygen, carbondioxideand of fourgases:nitrogen, that airwasmadeofamixture published in1808,heshowed System ofChemicalPhilosophy, atom andthemolecule.InhisNew drawing adistinctionbetweenthe John Daltoncon an atomwas.Intheearly18 accepted, butitstillremainedtoknowwhat elementary compoundsofmatterwas The conceptofatomsasthe to synthesis From analysis fi rmed Democritus’ model, fi ed, suchasgold,silver, mercury, th century, onlyadozen th century. However, atthat John Dalton'stableofatomicsymbols

© Paul Stringer - Juulijs - Fotolia the elementsthatwouldbe some miracle,coincidewith spaces, whichwould,by necessary toleaveblank be discovered.Itwasthus many elementswerestillto and properties.Moreover, was onlyde by NielsBohr. Eachelement being onlydescribedin1913 were stillunknown,thelatter and thestructureofatoms were. At thetime,electrons chemists ofthe19 clever andsharp-eyedthe fi cation revealshow fi ned byits mass th century fi rst

49 350 YEARS OF SCIENCE 50 37 38 La Lettre

© Pictorial Press Ltd - Alamy what thechemicalindustry has beenabletoachieve. Solvay process. Technically ambitiousandclever, theimplementationoftheseprocesses isamodelof opened thepathwayfororganicchemistry. force". MarcelinBerthelot'swork, Berthelot, showedthatitwaspossibletosynthesizeanorganiccompoundwithoutresortingthe"vital nature, butalsotocreatenewmolecules. The synthesisofureabyWohler, thenthatofacetyleneby the mostcreativepartofchemistry, synthesis.Chemistswerebecomingable notonlytounderstand understood whatmatterwasmadeof.Inreturn,theycouldcombinetheelementsinordertodevelop With analysis,chemists the atomictheory! Marcelin Berthelot,violentlyopposed accepted: somechemists,suchas of atomswasnotyetuniversally Incidentally, theveryexistence constitute allmatterintheuniverse. that nomorethansometensofatoms scienti was probablyoneofthegreatest later discovered! The periodictable William HenryPerkin fi c discoveriesever:itshowed (1838-1907) Chemistry wasasciencebutitalsoanindustry, which,relyingonthe synthetic dyetobemade(Perkin,1856). industry era:hereismauveine,the The synthesisofdyeslaunchedthechemical fi new synthesesperformedinthelaboratory, wouldbeagreatcontribution nally Organic ChemistrybasedonSynthesis Marcelin Berthelot(1827-1907) fi rst

© Bruno Villoutreix - Inserm , publishedin1860,triumphantly years afterwardsbythe process, replaced50 soda usingtheLeblanc ping themanufactureof nic chemistrywasdevelo- At thesametime,inorga- 1865. BASF tobecreated,in and companiessuchas organic industrytorise Nobel Prize–enabledthe indigo byBaeyer, the1905 – mauveinebyPerkin, The synthesisofdyes of the19thCentury. to theindustrialrevolution

© Archives de l'Académie des sciences transforming matterto became moreskilledat developments. Chemists countered considerable chemical synthesisen- With suchnewdata, examples ofit. were mostsigni Crick, 1962NobelPrize) double helix(Watson and bel Prize)andoftheDNA insulin (Sanger, 1958No- tions ofthestructure matter.determina- The microscopy, scanningtunnelingmicroscopy, etc.– providedamuch At thesametime,analysistoolsandcharacterizationtechniques-X-raydiffraction, NMR,electron (Karplus, LevittandWarshell, 2013). methods, thatallowthebehaviourofapopulationseveralhundredthousandatomstobemodelled Prizes, the chemistry wouldplayanever-increasingrole.ItbecamepredictiveandberewardedwithtwoNobel molecules (Pauling,1954NobelPrize;Ken'ichiFukuiandHoffmann, 1981NobelPrize). Theoretical possible toprovideaquantitativedescriptionofchemicalbondingandtheelectronicproperties The quantumdescriptionoftheelectronsshednewlightontheirbehaviourswithinmatter. Itbecame medicine, energy, andevenweapons. radiochemistry, withallitsimpactsonthe and MarieCuriemarkedthebeginningof elements -poloniumandradiumbyPierre geochemistry, etc. The discoveryofradioactive chemistry, physicalchemistry, biochemistry, organometallic chemistry, computational appeared: catalysis,solidstatechemistry, and diversi a rapidevolution.Itconspicuouslydeepened course ofthe20 characterization techniquesimprovinginthe With quantumtheoriesdevelopingand In the20 th fi fi ed atthesametime.Newdisciplines rst onebeingforquantummethods(PopleandKohn,1998)theothermultiscale century, chemistrydiversi th Century, chemistryexperienced fi cant fi elds of elds fi es es The Watson-Crick modelofthestructure DNA Pierre (1859-1906)etMarie(1867-1934)Curie fi ner pictureofthestructure

51 350 YEARS OF SCIENCE synthesize increasingly more complex molecules. Vitamin B12,

La Lettre in this respect, is quite exemplary. This molecule, which is vital to us, is synthesized naturally by microorganisms - bacteria, fungi, 37 38 a

li algae. It was an object of investigation for numerous studies, o t o

- F leading to four Nobel Prizes. Isolated in 1948, its structure was be l. elucidated in the early 1960s. Its synthesis, published in 1973, uu k e l o was achieved through the use of the Woodward-Hoffman rules © m that describe chemical bonding in terms of molecular orbital Vitamin B12 molecule symmetry.

Chemical synthesis had made it possible to move from atoms to molecules, and now to supramolecular chemistry, in which the molecules assemble into increasingly complex structures (Cram, Pedersen and Lehn, 1987 Nobel Prize). The issue was no longer to study the properties of a given molecule,

Supramolecular chemistry deals © DR with the complex combinations that but to consider the synergy their molecules form with one another: associations created. This blur- here, a cryptate, for whose discovery the Member of the Académie des red the borders between organic sciences Jean-Marie Lehn was Jean-Marie Lehn awarded the Nobel Prize in Chemistry and inorganic chemistry. Organo- in 1987. metallic compounds, coordination 52 complexes and organic-inorganic o hybrids developed, in which metal o o o o atoms are associated to organic K+ NNK+ ligands. o o o o o

During the second half of the 20th century, inorganic chemistry turned to the study of structure-properties relationships. Such research, primarily conducted on crystals, in close interaction with physicists, have led to the development of materials with remarkable physical properties - spintronics, semiconductors, magnetism, superconductivity, photovoltaics, etc. Quite memorable was the revolution brought about in 1986 by the synthesis of superconducting ceramics (Berdnoz and Muller,

© From B.Eymann - Acaadémie des sciences chemist, theCO of catalysis. which reliesonprogressmade inthe This isapromisingavenue ofresearch, of CO that wouldusethephotoreduction develop "bio-inspired"chemistry Couldn’t weimitatenatureand for lifetodeveloponEarth. cellulose, etc.–thatarenecessary organic molecules–sugars,starch, with watertoformoxygenandthe action ofthesun’s radiation,itreacts Through photosynthesisandunderthe capture, storageandrecyclingofCO liquid crystals,emulsionsandenhancedoilrecovery. chemists andphysicists(deGennes,1991NobelPrize),broughtaboutimportantprogressinthe and diversifying. At thesametime,studieson"softmatter",with,hereagain,closecooperationbetween achieving greatindustrialsuccess.Fromstructuralpolymerstofunctionalpolymers,theyarestillthriving chemistry (Staudinger, 1953NobelPrize)broughtthedevelopmentofanewrangematerialsquickly syntheses performedonplasticmaterials,suchasnylonduringWorld War II.Researchinmacromolecular needs, lednaturalproductiontobereplacedwithchemicalsynthesis.Suchworkwasattherootof Polymer chemistryexpandedrapidlyaftertheFirstWorld War. Rubberproduction,spurredbymilitary collaboration betweenchemistsandphysicists. 1987 NobelPrize).Mostofthenewmaterialsincurrentdevelopmentindustryarederivedfromsuch dioxide, CO to theproductionofgreenhousegases,suchascarbon Global warmingisoneofthemajorconcernsourtimes.Itlinked chemistry", whicharerootedintheobservationoflivingbeings. of "softchemistry","greenoreven"bio-inspired its inspirationfrombiologicalprocesses. There arementions often opposedtonaturalproducts,drawsanincreasingpartof development. The synthesisofchemicalproducts,whichare concerned withsociety'sneedsandbeinlinesustainable It isoftensaidthat"chemistryeverywhere":itshouldthusbe 21 st Century:chemistryandsustainabledevelopment 2 intoCO, 2 . Whatrolemaychemistryplayinthe 2

moleculeisessentialtolife. HCOOH orCH 3 OH? 2 ? Forthe fi eld whole organic matteressential forlife. through photosynthesis, reactswithwaterto producethe CO 2 isagreenhouse gas,butitisalsoamolecule which, fi eld of eld fi rst © From Jakinnboaz - Fotolia © emaria - Fotolia

53 350 YEARS OF SCIENCE 54 37 38 La Lettre

© Catherine Bréchignac - Académie des sciences the pastdecade. research, inwhichchemistry playsanessentialrole;theirperformanceshavebeen greatlyimprovedover solve theproblemsraisedbyproductionandstorage ofelectricity. Batteriesarenowunderintense the batteryinventedbyVolta, stackingcopperandzincdiscs.Building batteriesisawaytosimultaneously elements; allittakesthenistocapturetheseelectrons todirectlyproduceelectricity:suchisthesecretof into electricity. Any simplechemicalredox reaction,though,impliesatransferofelectronsbetweentwo converted –withaverylowyieldintoelectricity. We donotknowhowtodirectlyconvertnuclearreactions developed inFranceinvolvesophisticatedreactions to generateheatthentransformed,thatissay Energy transitionaimsto ﬂ performed inchemicaldyes.Hereagain,chemistryoffers newsolutionsandpaves thewayformuchmore crystals toconvertphotonsintoelectrons.Buttherearealsocellsinwhichsuchatransformationis Solar energymayalsobeusedtogenerateelectricity. Conventionalphotovoltaicdevicesusesemiconductor exibility inmolecularelectronics(Heeger, MacDiarmidandShirakawa,2000NobelPrize). Solar powerplantinSeville ﬁ nd newformsofrenewableenergy. The nuclearpowerplantscurrently © Archives de l'Académie des sciences © Dr_Kateryna - Fotolia development ofmodernsociety. life, itwillplayakeyrole inthe universe andtheappearance of involved intheformation ofthe earth science,etc.Justasitwas biology, medicine,pharmacology, different disciplines– physics, chemistry buildsbridgesbetween A versatilemolecularscience, against parasiticdisease.Inbothcases,chemistrywasdirectlyinvolved. Nobel PrizeofMedicinerewardedworkconductedontheroleartemisininandavermectinin Chemistry hasthusbeenawardedtothediscoveryofDNA repairmechanisms,while,thesameyear, the against breastandlungcancer. Incidentally, chemistryandmedicineoftenmerge. The 2015NobelPrizein Pierre Potier (1934-2006) of cancerchemotherapy. his colleagues,wasarevolutionintheworld Académie desSciencesPierrePotierand Taxotère ® , synthesizedbyMemberofthe Chemistry isnotonlyinterestedindiscoveringnewdrugs,italsoinvolved in drugdelivery. The introductionofnanotechnology inpharmacology helps developnanoparticlesthatcanbeusedasvectorstotransport contributing tothedevelopmentofnanomedicine. active principlesattheveryheartofacell.Incasecancer, progress isbeingmade,bothindiagnosisandtherapy, thus the drugisonlydeliveredinitstarget–canceroustumour–, thus avoidingthewell-knownsideeffects ofchemotherapy. Swift inside thetumor itself. In medicine,chemistry usesnanoparticlesas vectorstotransportdrugs

© Bruno Villoutreix - Inserm active compoundtobeidenti Yvette has allowed anevenmore recherche scienti the French removed. Researchconductedat a greatnumberoftreestobe Taxotere become themostusedofallproducts marketing authorizationin1995,has the productionof Taxol improve cancerdrugs.Unfortunately, the yewtree,signi as Taxol synthesis ofactivemoleculessuch role inthe Chemists alsoplayafundamental ® ® , derivedfromthebarkof –which,sinceitreceived Centre nationaldela fi eld ofhealth. The fi que fi cnl helped cantly inGif-sur- ® required fi e – ed fi ght

©©F From S ervi er médi édical lgraph hes

55 350 YEARS OF SCIENCE 56 37 38 La Lettre study ofsomeknownexamplestobegin. considered butitwouldtakeuntiltheendof20 growing. The possibilitythatplanetswereorbitingstarsotherthanthesun–exoplanetswas as wellinphysics,chemistryandgeology. The observableuniversekeptonenrichingitselfand increasing precisionthankstoprogressachievedinspyglasses,telescopesandotherinstruments, Samos inthe3 with theuniversallawsofphysics,whichthuscorroborated theintuitionexpressedby Aristarchus of and Newton,wouldnowplaceEarth,thentheplanets, inorbitaroundthesun,movingaccordance made inthe Ptolemy), hadbeenplacingEarthatthecenterof world graduallylostgroundasprogresswasbeing workplace oftheastronomer membersoftheRoi-Soleil’s Académie. created, suchasthe would cherish. The appetite forsciencegrew, secularstructuresinwhich scientistswouldgatherwere In the16 The placeofEarthintheUniverse th and17 ﬁ eldsofcelestialmechanicsandgravitation. The worksofCopernicus,thenKepler, Galileo rd CenturyB.C.Sciencecouldnowgainitsindependence fromreligion–anidead’Alembert th Centuries,thetheologicalandphilosophicalconceptionsthat,sinceantiquity(Aristotle, Académie desSciences Planets andexoplanets

© B.Eymann - Académie des sciences in1666and,oneyearlater, the were observed,identi the sunanditsplanets.Stars,comets,nebulae,galaxies the sun,itbecamepossibletoexamineformationof once ithadbeenrecognisedasoneoftheplanetsorbiting speci has considerablychanged.OnceEarthhadlostthe During thelastcenturies,ourunderstandingofworld CNRS, Institutdeplanétologieetd’astrophysiqueofGrenoble Member ofthe Académie desSciences,SeniorResearcherat Anne-Marie Lagrange fi c statusthegeocentricsystemprovideditand th Centuryforanytobedetectedandthedetailed fi ed,catalogued,studiedwithever- Observatoire deParis asthe © Granger Historical Picture Archive - Alamy © Photo Researchers, Inc - Alamy theory ofgeneralRelativity accounted for. 1920s asLemaîtreandHubble did,whichEinstein’s establishing theexpansion of theUniverseduring the galaxiesmovedaway fromeachotherandin effect, indeed,wouldbe decisiveinshowingthat with referencetoanobserverlocatedonEarth. This effect madeitpossibleto measure thespeedofstars and, later, starsandgalaxies. The Doppler-Fizeau of Andreas Cellarius (1660). on theright).TheHarmoniaMacrocosmica and theheliocentricsystem(Copernicus, geocentric system(Ptolemy, ontheleft) Two systemsdescribingtheworld: An imagefrom the HubbleUltraDeepField © R. Williams (STScI), équipe HDF-S, et NASA/ESA et HDF-S, équipe (STScI), Williams © R. of theatmospheressun,planets,solarsystem became possibletostudythechemicalcomposition Fraunhofer inventedthespectroscopeandit 1670, andallowedforitsspeedtobemeasured. that Huygenshadputforwardforconsiderationin provided supportforthewave-likenatureoflight works of Young, Fresnel,FoucaultandMaxwell In the19 useful preambletophysicallyunderstandthem. with ever-increasingprecision,whichwasavery allowed MessierandHerscheltoclassifythestars compiled, becamemoreanddetailed. They way oftheobservationreportsthatnaturalists catalogues ofthestarsandnebulae,muchin with ever-growingprecisionandsensitivity. The Astronomers builttelescopestoprobethesky was theageofourplanet. diameters, Buffon calculatedthat10millionyears of thecoolingtimemetalspheresfromvarious some thousandyearsago.Drawingonthestudy around thesunorthatitwasnotformedinsixdays of thetime.ItisestablishedthatEarthrevolves and astronomers(Cassini,Lalande,LaCaille) geologists (Hutton,Cuvierand,later, Brongniart) (Buffon, Lamarck),geographers(Von Humboldt), explain theobservationsofgreatnaturalists Earth, seaorsky, andtheorieswouldfollowto feed atasteforscienti The CenturyoftheEnlightenmentwouldresolutely th Century, thetheoreticalandexperimental fi c exploration,whetheron

57 350 YEARS OF SCIENCE 58 37 38 La Lettre (Shapley, Ross,Hubble). Milky Way hasbecomebutagalaxyamonghundredsofthousandotherswithintheexpandingUniverse the MilkyWay, ourGalaxy, whichcompriseshundredsofbillionstarsmoreorlesscomparabletoours. The At theendofsuchprogress,ithasbeenestablishedthatsunanditstrainplanetsareinmotion radioactivity countingtechniques,at1andthen4billionyearsduringthe interstellar mediumwithheavierelements(Burbidge). The ageofEarthwasestimated, bymeansofnatural became knowntooccurwithinthestarswhich,atendoftheirevolution,wereacknowledgedenrich the others,itsenergyderivingfromreactionsofnuclearfusion(Perrin,Eddington).Nucleosynthetis and 1950,providethebasesforanexplanationoforiginselements. The sun thenbecameastarlike Nuclear physicsandthestudyofradioactivity(Becquerel,Rutherford,Curiecouple)would,between1850 The suninside the MilkyWay (artistview) ﬁ rst halfofthe20 th Century.

© Caltech et NASA be sharplyre of themoderntheorysolarsystemformation. This scenariowould rotating gascloudinwhichplanetswouldform.Hethuslaidthefoundation Laplace propoundedthetheoryofPrimitiveNebula,acontractingand debris fromthesun,tearedoff whenacometcollidedwithit.In1785, the otherhand.Buffon suggestedthatEarthandtheotherplanetsare Century with,notably, Buffon ontheonehand,andKantLaplace understood :itisnotpossible to steps describedhereare still ill- of millionyears.Some of the from planetesimalsinsometens rocky planetswouldformdirectly planets. Closertothesun, accrete enoughgastoformgiant cores wouldthenveryquickly of thefuturesolarsystem;such Earth masses,inthecoldpart agglomerate intocores,ofafew Those planetesimalsthenwould grains oftheinterstellarmedium. from thegasandsub-micronic wide (planetesimals,comets) icy elementsofsomekilometers predicts theformationofrockyor of theobjectsinsolarsystem that explainsbesttheproperties system formation. The scenario the majorstepsofsolar in ansimpli We alsoowethemtothedevelopmentofcomputerswhichhavemadeitpossiblesimulate–although and tolaboratoryexperimentsdesignedreproducethoroughlystudysomeoftheprocessesinvolved. observation tools,tospaceexploration,progressintermsofrockdating as Jupiter. We owetheseimprovementstoprogressachievedinground planets: therockyplanets,suchasEarth,andgiantgas and theprocessesleadingtoemergenceoftwogreatgroups in whatregardstheinitialphysicalconditionsinsideprotosolarnebula of God. The to thinkaboutanoriginthatdidnotneedtheinterventionofhand Once thesunandEarthfreedfromtheirspeci The formationofthesolarsystem fi ed way, obviously– fi ned anddetailedinthecourseof20 fi rst trulyscienti fi c theoriesappearedinEuropethe18 planets. are thebuildingblocksoftelluric planetsandthesolidcoresofgiant bodies andstructuresinthedisks. Thesolidscalledplanetisimals of aprotostarandprotoplanetary disk,andformationofbigsolid molecular cloudandtheformation ofthePrimitiveNebula:formation A sketchoftheformationsolarsystem, fromthecollapseofa fi c status,itbecamepossible th Century, especially th

Georges-Louis LeclercdeBuffon Pierre-Simon deLaplace (1749-1827) (1707-1788)

59 350 YEARS OF SCIENCE 60 37 38 La Lettre Twenty yearsafterthose obtained inthe2000sthrough sophisticatedtechnologicaldevelopments. quite commonthereafter. The of theirproximitytostars),whichhoweverproved existence ofsuch“HotJupiters”(“hot”because The theoriesofthetimedidnotexpect closer toitsstarthanJupiterthesun. it wasorbitingonehundredtimes comparable tothatofJupiterbut planet, itsmasswasindeed explosion; asforthesecond is theremnantofastellar around apulsar, which was aplanetrevolving planets. The from theexpected fact quitedifferent were asamatterof exoplanets discovered of thetime. The to detectwiththeresources such planetsweretoodif planet ofthesolarsystem.But analogous toJupiter, thebiggest had startedbysearchingforplanets found beforethe1990s.Howcome? Astronomers one planetormoreorbitingaroundthem.However, noplanetwas of indirectdetection,intendedtoidentifysmallperturbationsthestarsinducedbypresence ten yearslater, launchedthehuntforextrasolarplanets.Suchawasbasedattimeonmethodology announcement, in1963,thataplanetaroundthestarofBarnardhadbeendiscovered,althoughdisproved an openquestionuntiltheendof20 of othersystemsformedaccordingtothesamelaws.Whetherworldsexisted,however, remained Now thatthesunhadbecomeonestaramongbillionothers,itwaslegitimatetospeculateonexistence Exoplanets chemical conditionsinwhichthesolarsystemformed. to simulatethemandbecauseonlyscarcedirectinformationisavailableonthephysical,dynamic reproduce theminlaboratoryconditions,becauseourcomputationalresourcesarenotpowerfulenough fi rt one rst fi rst fi rst discoveries,morethan3000exoplanets havealreadybeenidenti fi cult fi rst imagesofexoplanets were th Century, asadequateobservationtoolswerelacking. The probably due to planetary evaporation (artist view). probably duetoplanetaryevaporation(artistview). in 3.5days,haveanextendedenvelopeofatomichydrogen constellation Pegasus.Thisexoplanet,whichorbitSitsstar Osiris, agiantplanetnearthestarHD209458,in fi nally fi ed; many

©ESA, Alfred Vidal-Madjar (Institut d'Astrophysique de Paris, CNRS, France) and NASA science

await confirmation. Their characterization already reveals a vast range of masses (ranging from a few Earth of masses to several Jupiter masses), radii and orbital properties (planets with inclined or retrograd orbits, or very remote ones), some of which

have no equivalent in the solar years system. Such a diversity may not 350 be explained without considering the existence of several planet formation scenarios. Moreover, it appears that the individual and dynamic histories of young © ESO- A.-M. Lagrange extrasolar planet systems may be very complex, even more than The exoplanet β Pictoris b is a giant gas planet orbiting at about 9 au the history of the solar system: (1 au = the distance between Earth and the sun, which is 150 million kilometres) from its star (here represented as a star at the centre of the indeed, the orbit of an exoplanet, image). On the left, the image of the discovery of exoplanet β Pictoris b in November 2003 (light dot on the upper-left side of the image) ; on the once the planet is formed, may right, 6 years later (in the bottom-right of the image). be considerably altered due to interactions with the protoplanetary disk (which may account for the existence of “Hot Jupiters”) or with other objects present in the system (which may explain why there are exoplanets with inclined or retrograde orbits).

The variety of architectures of the extrasolar planet systems is probably the most surprising result obtained 61 in exoplanetology so far. It is probable that the interiors and atmospheres of the exoplanets, which we have only started to probe, will also prove very diverse. The proprieties of the forming atmospheres result from the capture of the gas present in the Primitive Nebula but also from outgassing that occurs on the forming planets, and from potential external inputs (asteroids, comets) and complex and multiple physico-chemical processes. Their evolution depends on many factors (volcanism, light gases escape, stellar radiation, etc.) – as many circumstances that are difficult to foretell and variable parameters that make it very tricky to formulate any prediction. Since the atmospheres play fundamental roles on the conditions in which life appears and develops, considerable efforts, in particular with the James Webb Space Telescope, the successor to the Hubble Space Telescope, and with the future Extremely Large Telescopes, will be devoted in the years and decades to come to probing the atmospheres of giant, and then telluric, exoplanets.

© Science Photo Library - Alamy Given thatclose–notmentioning Whether Earthshouldplay apotentialroleasreferencemodelisindeedvery centralquestion.So that isdifferent fromthesun? case oftheatmosphere anexoEarthbearingadifferent physico-chemicalhistory, andorbitingastar to explainitbysimplephysicalouchemicalabioticprocesses. However, isthiscriterionstillvalidinthe presence ofdioxygeninouratmosphereresultsindeed fromphotosynthesisanditwouldnotbepossible derives fromit)inanatmospherethatwouldmoreover haveproprietiesquitesimilartothoseofEarth. The on ananalogywithourplanet,onepreferredcriterion isthepresenceofdioxygen(andozone,which What signaturesoflifearetobelookedforontheexoplanets? This questionishighlycomplex.Drawing atmosphere (greenhouseeffect). asteroids, magnetic or evennecessary, roleforlifetodevelop, including:theproprietiesofsunitself,moon,comets, appear onourplanet. Yet itisprobablynotsuf to beonthesurface. The presenceofliquidwaterisassumedtobeanecessaryconditionforlife a preferenceisgiventotelluricplanetslocatedatsuchdistancetheirstarsasallowliquidwater is toidentifywhichexoplanetsaremost atmospheres thatwillprobablyallowforthe The PrimitiveEarth(artistview) fi eld ofEarth,internactivityourplanet(volcanism,outgassing),compositionthe in situ fi t forthedevelopmentoflife.Drawingonananalogywith Earth, –explorationsareimpossible,itisthedetailedstudyof fi rst signsoflifetobedetectedonexoplanets. The fi cient. Otherfactorsindeedmayhaveplayedanimportant, fi rst step rst differ fromthoseofEarth. experiments, originalandcoherentscenariosontheformationdevelopmentoflife,inconditionsthat formulate, onthesolebasisoftheoreticalconsiderationsandwithhelpsimulationslaboratory is ourabilitytoapprehendthevarietyofatmospheresonexoplanets,imagineotherpossibilitiesand systems whosediversityappearsgreatereveryday. we mustrememberitisbutonecase,andnotnecessarilyarepresentativeone,amongpopulationof The solarsystem,inthiscontext,isavaluableandindispensableelementofcomparison,eventhough establish theprobableexistenceoflifeonanotherplanetappearstobeaverylongtermobjective. will probablybetheonlywaytodetectsignaturesoflife.However, inthepresentstateofknowledge,to has beeninvestigated. The atmospheresoftheexoplanetsalsoremainwidelyunexploredandtheirstudy, for instance,ifsystemsanalogoustothesolarsystemexistandonlycloseneighbourhoodofsun The huntforexoplanetsisnotover:wehaveexploredallthediversityofsystems–doknow, observe thereisawidevarietyofexoplanetsandwemayhaveonlycaughtglimpsesyetsuchvariety. The pieces inaverywideUniverse. The questionwhetherotherworldsexistisnow raisedinscienti brought aboutasharplynewperspectiveonEarthandthesolarsystem,thatareregardednowastiny now calledphysics,geophysics,chemistry, lifesciencesand,morerecently, computersciencehave The explosionofknowledgethatoccuredduringthe350lastyears,emergencevariousdisciplines A grainofsandinaverywideUniverse be theonlyway todetectsignaturesoflife. the presenceof oxygenthatderivedfromlife on Earth.Thestudyoftheatmospheres ofexoplanetswillprobably The spectrumof theEarthdiffersfromthatof thetwoothertelluricplanets Mars andVenus, inparticulardueto fi rst extrasolarplanetsystemswereonlydiscoveredrecently, inthe1990s. After 20yearsofstudy, we fi c terms. c

63 350 YEARS OF SCIENCE 64 37 38 La Lettre land, tospendtheretherestofhislife. Colbert’s deathandtherevocationofEditdeNantes–eventsthatledhimtoreturnhisnative of thetremendousprestige conferreduponNewton,whohadmanagedtoexplain themotionsofplanets ignored bymostscientistsfor morethanacentury. Ifthey adoptedthecorpuscularmodel,itwasbecause Despite itsvalue,Huygens’ wavemodel,describedinfulldetail 1690inhis 1678 thatawavemodeloflightwouldmeetthisrequirement, whileNewton’s corpuscularmodeldidnot. phenomenon ofdoublerefractionthatisobservedwith somecrystals,suchascalcite.Hediscoveredin But Huygenswaslookingforamodelthatwouldaccount forallknownphenomenaandinparticularthe of lightareacceleratedperpendicularlytotheinterface, andthetrajectoryisthereforeclosertonormal. such aswaterorglass.Newtonexplaineditbyinvoking theattractionofdensermedium:particles understand whytherefractedraycomesclosertonormal whenitpassesfromairtoadensermedium, fact thatarayoflightisre by DescartesandSnell.Itiseasytounderstandthatabouncingcorpusclegoodmodeldescribethe problem wasto In 1672,HuygensdiscoveredNewton’s workonthecorpuscularmodeloflight. At thetime,major Emergence ofawavemodellight ﬁ nd amodelthatwouldjustifythelawsofre ﬂ ected inasymmetricalwaywith respecttothenormal,butchallengeis photons: strangelights From Huygens’ wavestoEinstein’s

© B.Eymann - Académie des sciences to comeandsettleinPariswherehewoulddwelluntil in mechanics,mathematicsandastronomy. Heaccepted Pascal andFermat,alreadyproducedmajorresults and raisedintheNetherlands,hadstudiedDescartes, most eminentofthem,ChristiaanHuygens,bornin1629 the timetojoin Académie dessciences.Oneofthe 350 yearsago,Colbertinvitedthegreatscientistsof École polytechnique Researcher atCNRS,ProfessortheInstitutd’optiqueand Member ofthe Académie desSciences,EmeritusSenior Alain Aspect ﬂ ection andrefractionindependentlyformulated Treatise onLight , was ©©M Morpharh t - Fotolia

© gallica.bnf.fr - Bibliothèque nationale de France Christiaan Huygens(1629-1695) studied inremarkableexperiments. interference anddiffraction, thattheycarefully one abletoaccountforthephenomenaof developed thewavemodeloflight,asonly in England,and Augustin Fresnel,inFrance, more thanonecenturybefore Thomas Young, through hislawofuniversalgravitation.Ittook in contrasttoNewton's corpusculartheory. that thespeedoflightisslower inthedensermediumthanair, in hisTreatise onLight(1690),accountsforrefraction provided Huygens’ wavemodel,expressedin1678anddescribed infull Incident ray Incident Mirror Normal to thepoint ELCINREFRACTION REFLECTION θ θ of incidence 1 2 = θ θ 2 1 Reflected ray Reflected the questionoflightbeamre Christiaan Huygenssoonlookedinto refraction. Incident ray Incident Glass Air n 2 sin Normal to thepoint θ θ of incidence 1 2 = θ n 2 1 Refracted ray Refracted sin Index ofmediumn Index ofmediumn ﬂ eto and ection θ 1

2 1

65 350 YEARS OF SCIENCE 66 37 38 La Lettre

© Archives de l'Académie des sciences Siméon DenisPoisson,one ofthe even ina Fresnel questionedtheir hero, and theywouldnotadmitthat based onNewton’s mechanics, scientists, whoseworkswere Académie, though,wereeminent wave model.Manymembersofthe treatment, basedonaconvincing his workinEngland. Sciences. Inparallel,Thomas Young conducted model atacontestlaunchedbythe Académie des In France, Augustin Fresneldevelopedthewave zone, fringesareobserved,thatis,alternatingshadowsandlight.Fresnel,ayoungbrilliantmind other words,onthefactthat,inzoneoftransitionbetweenshadowascreenandanilluminated 1819 wastheyear, andthe Académie desScienceshadsponsoredacontestonthediffraction oflight,in which introducesmembersofthe Académie whoweremost...bright. Young andFresnelhad to Wave VScorpusculartheories ﬁ eld otherthanmechanics. Augustin Fresnel (1788-1827) ﬁ ght toimposethismodel,asevidencedbythestoryofPoisson’s brightspot, educated oftheÉcolepolytechnique,andwhowasastudent of themember Académie Arago, presenteda memoir describinghisexperimentsandgiving the problemacompletemathematical Thomas Young (1773-1829)

theory, calledthe“systemofundulations”. All ittakes,heexplained,isacomparisonbetweenthespeed argument betweenNewton’s corpusculartheory, then calledthe“systemofemission”,andFresnel’s wave him again–oncemoreplayedakeyrolein1838whenheproposedcrucialexperimenttosettlethe theory remainedactiveinthesubsequentyearsuntilanewepisodewouldcleardebate. Arago – Newton’s opticsshouldberejected.Onecannotfailtonotice,indeed,thatthefollowersofcorpuscular and waswaitingonlytowelcomehimatthe Académie, whilebeingatthesametimenotreallyconvinced John Worrall), PoissonwasdazzledbytheeleganceandmathematicalconsistencyofFresnel’s theory, theory wasfarfrombeingsomassive. As amatteroffact,explainedforexampleDominiquePestre(citing Some historiansofscienceclaimthatthestoryhasbeenembellishedandconversiontowave soon admittinghimasanewmember. the Académie thenshiftedinfavourofthewavetheory, awardingFresneltheprizeofcompetitionand amazement ofPoissonandtheNewtonians,brightspotwasindeedobserved. The storyhasitthat © FALKENSTEINFOTO - Alamy Siméon DenisPoisson (1781-1840) Fresnel wave-theoryoflight feature playedanimportantroleinthesuccessof shade. Theobservationofthatcounter-intuitive the existenceofabrightspotinmiddle The Poisson’s brightspot:Fresneltheorypredicts be abrightspotbehindthescreen,atplacewherecommonsensetellsus the axisofacircularobstaclethatblockslight,theorypredictstherewill surprising consequenceofFresnel’s equations:ifalightsourceisplacedon die-hard Newtoniansandasophisticatedmathematician,discovered Ball Screen Shade conducted, and,tothe experiment shouldbe Arago decidedthatan still remembers: the historyofphysics surprising turnthat the eventstooka absurd? This iswhen Fresnel’s theoryis Does itnotshowthat utter darknessreigns.

67 350 YEARS OF SCIENCE 68 37 38 La Lettre

© Observatoire de Paris, Dominique Monseigny © Archives de l'Académie ries doprevailonlywhentheirdetractorshavepassed? then surrenderedorpassed–isitnotasayingthatnewtheo- reality ofthefacts in declaringthesystemofemissionincompatiblewith medium. The light isdelayedasitpassesthroughthemostrefractive is only35pageslonganditplainlyconcludes:" Huygens andFresnel,lightgoesslowerinthedensermedium. light accelerateswhenitpenetratesadensermedium;onthecontrary, according tothewavetheoryof of lightinairandarefractivemediumsuchaswater. Oneremembers,indeed,that,inNewton’s theory, Measuring the speed oflightbetweentheObservatoire deParisandMontmartre, in2005 Hippolyte Fizeau (1819-1896) thesis ofthefuturemember Academy ﬁ nal conclusionofthisworkthusconsists ." The lastfollowersofthewavetheory In 1849,FizeaumeasuredthespeedoflightbetweenMontmartreandMont- the speedoflightinairandwater. The Valérien, nearParis. The websiteoftheObservatoiredeParispresentsa meter. Hecouldthendirectlycompare remarkable explanationoftheseexperiments,whichwererepeatedin2005 rement overadistanceofonlyone and wasabletorealizethemeasu- with alaserbeam.In1850,Foucault improved theexperimentalset-up Always,

© https://www.bibnum.education.fr/sites/default/fi les/ foucault-texte.pdf fi itself [...]isanelectromagnetic disturbanceintheformofwavespropagatingthrough theelectromagnetic speed issoclosetothatoflightitseemswehavegood reasontoconcludethatlight waves propagatingataspeedMaxwellcalculated. And heconcluded:“ their noveltywasimpressive:somesolutionsofthe equationsindicated for throughexperimentalobservation.InthecaseofMaxwell’s equations, into them;theyhaveunexpectedsolutionswhosetraces maybelooked any truephysicaltheory, equations implymorethanwhathasbeenbuilt that wereknownatthetimein 1864. Hehadwrittenequationsenablingtodescribethe wholesetoffacts It wasthegreatScottishgeniusJamesClerkMaxwellwhogaveanswer, in this question:whatisthenatureofquantitythatvibratesasitpropagates? we maycontinuetouseitwithoutmakinganychangeit.Butin1818,Fresnelstilllackedtheanswer they areequippedwiththemarvellousFresnellenses. As forhistheoryofwaveoptics,itissoperfectthat that hecontributedtoconceivethemasanengineerofthecorpsePontsetChaussées,and should bepointedoutthatthetheoretician Augustin Fresnelwasalsothefatherofallmodernlighthouses, In thesetimesofdebateandsometimesoppositionbetweenfundamentalresearchapplications,it eld according tothelawsofelectromagnetism fi elds ofelectricity andmagnetism.In .” Huge Fresnellensinalighthouse This James ClerkMaxwell (1831-1879)

69 350 YEARS OF SCIENCE 70 37 38 La Lettre a keyrole. Century physics:relativity, obviously, butalsoquantumphysics,intheemergenceofwhichhewouldplay described as“verydense”,wouldleadEinsteintolaythefoundationsoftworevolutions20 theory ofheatandlight.PhilosophicalMagazineSeries above thedynamicaltheoryofheatandlight”(LordKelvin. scientist Michelsonreportedlyputit?Surelynot.In1900,thegreatKelvincaughtsightoftwo“clouds physics, andistherenothingforphysicistsbuttore theory towhichnophenomenonseemsbeableescape.Isittheendoftheoreticalresearchin they aretransversalwaves,asFresnel’s waves,andwecandescribethesewaves withacomprehensive and magnetic The casethusseemssettled:lightisnowknowntobeanelectromagneticwave,inotherwords,electric the wavemodel?Howcould onemakethiscorpuscularmodelcompatiblewith Maxwell’s description or doublerefraction,as Young andFresnelshowedthey could onlybeconsistentlyexplainedthrough The corpuscularmodelwas backontrack.Butthen,howcouldoneaccountfor interferences, diffraction 1949 ;21:343). His SeventiethBirthday. Rev ModPhys memoirs (R.A.Millikan. my expectations effect –acon Einstein's predictionsonthephotoelectric Millikan' experimentscon awarding himthePrizein1922after the attentionofNobelCommittee, 1911. Yet itwasthisarticlethatcaught the Prussian Academy ofsciencesin would howeverleadtohiselectionat a negativecommentinthereportwhich appreciated ofall,ascanbeseenfrom that time,thisarticleiscertainlytheleast Among theworksEinsteinpublishedat was theenergyofejectedelectrons. electron collisionandthusdeducedwhat under theeffect oflight–asaphoton- model, Einsteininterpretedthephotoelectriceffect –inotherwordstheejectionofelectronsfrommatter constant introducedbyPlanckin1900. Today, thesequantaoflightarecalledphotons.Drawingonthis is formedofgrains,theLichtQuanten,withaveryspeci Einstein’s The wave-particleduality fi rst articleonquantumphysicswaspublishedin1905.Itpropoundsadrastichypothesis:light fi elds vibratinginharmony, perpendicularlytothedirectionofpropagation. That istosay fi rain “ rmation ”, saidMillikaninhis Albert Einsteinon contrary toall fi rmed

© Bygone Collection - Alamy con theory oflight,allowinghimtomakepredictionsonthephoto-electric effect With Albert Einstein (1879-1955),1905markstherevivalofcorpuscular fi rmed byexperimentsofRobertMillikan(1868-1953)in1915. fi ne theirmeasurements,asthe American optics 61901;2:1-40).Suchtwoclouds,whichKelvin fi c energyandmomentum,dependingonthe Nineteenth centurycloudsoverthedynamical th

the mathematician 1932; suchquestionsledhimtodiscoveropticpumpingwithJeanBrossel.“ the questionsoffutureNobellaureate Alfred Kastler, then ahigh-schoolprofessorinBordeaux battalions. Butthewave-corpuscledualityoflightstillremainedquitemysterious,asisapparentfrom tradition oftheirpredecessors,wouldtakeaneminentstandthere,supplyingour Académie withimportant throughout theworld. to exertaradiantin School ofQuantumOptics thus enabledtheFrench clari at CollègedeFrance,ashe years to a professorwhowashardputtoanswerit,despitehishugecapacities.Itwouldtakeme Thirty twoyearslater, asastudentinuppersixthattheLycée of Agen, Iaskedthesamequestionsto séances delaSociétédessciencesphysiquesetnaturellesBordeaux remains anunresolvedmystery... with abstractformulas.To him,thedualitybetweenwaveaspectsandcorpuscleoflight arguments andconcluded:“ in 1909.Einsteindevelopedthereaseriesof conference ofGermanphysicsthatheldinSalzburg fi and providedamasterfulanswertoitonhis admirer ofMaxwell,couldnotignorethequestion of lightasanelectromagneticwave?Einstein, over the20 With wave-particleduality, modernquantumphysicswasborn.Opticswouldcontinueprogressingall wave-particle duality, thistimenotforlightbutmaterialparticles. years beforeLouisdeBrogliewouldexpressthis is bothwaveandcorpuscle.Itwouldtakefourteen argument, Einstein’s conclusionwasthesame:light not beseenasincompatible (wave structureandquantumstructure)…should illustrate thefactthattwostructuralproperties rst appearanceatascienti fi ed suchquestionsand fi nd, asmanyofmycontemporaries,illuminatinganswersatClaude Cohen-Tannoudji’s course th © DR Century, notablywiththeinventionoflaser, andtheFrenchscientists,perpetuating Claude Cohen-Tannoudji ”, Alfred Kastlerwrote,“ fl uence I onlywantedtobrie .” At theendofeach fi c conference,the ” (Lespropriétéscorpusculairesdelalumière,In Claude Cohen-Tannoudji, courseatCollègedeFrance,1979 question: couldwedowithouttheconceptofphoton,atleast inthe Fruitful questioning:"Objectofthiscourse:totry[…] answerthefollowing it continuestoworrythephysician,whoshallnotbecontent fl y Princeton Universitypress,2014" and in" Darrigol andBrunoJech.SeuilÉditionsduCNRS" selected andpresentedbyFrançoiseBalibar, Olivier choisies (Frenchtranslations), Tome 1:Quanta. Texts theory ishighlightedin" The majorroleofEinsteinintheemergencequantum Einstein andtheQuantum, A. DouglasStone, , 1931-1932,pp32-58) If thissynthesissatis Albert Einstein,Œuvres Procès-verbaux des . fi fteen more fteen fi eld ofoptics?". fi es ,

71 350 YEARS OF SCIENCE 72 37 38 La Lettre Until themiddleof20 support. completed thebedrocktriangleandmadeitpossibletoconnectmenoneanotherwithoutanymaterial one formofenergyintoanother;thewholegreatindustrialrevolutionthatappearedin18 Mechanical machines,andthenelectricones,usedenergytotransportworkonmatter, oralsoconvert airplane, machine-tool,etc. of successiveindustrialrevolutions,fromthemotortocomputer, includingthetrain,automobile, “algebra” derivesfrom Al Jabr, whichisthenameof histreatiseonsolvingequationsthroughcalculation. writing. The veryword“algorithm”comesfromthename ofthegreatPersianscientist Al Khw algorithmic methodsareancient, datingfurtherbackintimethanmechanics, mathematics andeven we nowliveonatetrahedron andnotonatriangleanymore.Letitbementioned, incidentally, thatthe information andthealgorithmsthatmanipulateitnow playamuchwiderrole,tosuchanextentthat standard materialsupportssuchasbooks,blackboards andpiecesofchalk.Withmoderncomputing, calculations, architecturesandplansallpertaintothe for natureandimprovemachinesbymeansofsuperior architecturesandplans.Measures,models, phenomena asthebalanceofforces,friction,combustion andradiation,leadingtoconceivebettermodels a verycentralrole.Progressindeedconstantlybuilton evermoreprecisemeasurementsofsuchnatural Matter andenergyformedthebedrockofsciencetechnologyuntilmiddle19 th Century, informationwas not reallyanexplicitnotion,althoughitalreadyplayed Machines andinformation

© B.Eymann - Académie des sciences optimization ofallsortsmachinesthatareatthecore by acommonthoughtandaction:theinvention were onlyborninthe20 old. Modernappliedmathematicsandcomputerscience Académie dessciencesareobviouslynot350years of the control theoryandsignalprocessing:allthosedomains Mechanics, appliedmathematics,computerscience, de France Member ofthe Académie desSciences,ProfessorattheCollège Gérard Berry Mechanics andComputerScienceSection ﬁ eld ofinformation,storedandtransmittedvia th Century. Yet theyaremoved ā th rizm th Century. Century ofthe ī , while © From B.Eymann - Académie des sciences

© Maurice Nivat pressure vessels. The development ofperfect elastic bodies,thebehaviourofstrainedbeamsand in 1821.Poissonthenstudiedtheequilibriumof generaltheoryofelasticity Caucher andNavier’s Mechanics extendedtodeformablesolidswith the introductionofafundamentalnotion:entropy. way forthesecondprincipleofthermodynamicsand cycle ofworkproduction.Hisintuitionspavedthe mechanical energyandintroducedthenotionof Carnot understoodtheconversionofheatin industrial revolution. Then, in1824,Sadi adequately regulated,createdthe which wasreliablebecauseit 1788. In1765,Watt’s steamengine, treatise, served asabasisforLagrange’s Traité dedynamique steam. D’Alembertpublishedhis Al Khw of thewordalgorithm ā rizm Mécanique analytique ī (c.783-c.850),attheorigin in1743,which , in fi rst fl uid Papin experimentedonthedrivingforceof developed thependulumclockandhe fundamental principleordynamics.Huygens Galileo andDescartes,Newtonlaidoutthe and calculationwereestablishedby Once the Mechanical scienceevolution pressure cooker digester (1679),anancestorofthe Denis Papin(1647-1713)andhis fi rstconnectionsbetweenmechanics

73 350 YEARS OF SCIENCE 74 37 38 La Lettre

© John Frost Newspapers - Alamy machines, fromPascaltoBabbage… were alsoolderattemptsto buildcalculating on, mechanographicmachines. Butthere of logarithmictables,sliderulesand,later and tedious,performedbyhandwithhelp just mentioned,calculationwaslengthy During thewholeperiodoftimewehave required very complex calculations, and then in required verycomplexcalculations,andthenin construction oftheEiffel Tower, amonumentthat mechanics wasbrightlyillustratedin1889bythe and Lagrangethecalculusofvariations.Progressin Cauchy holomorphicanalysisandfunctions,Euler Newton andLeibnizcreatedthedifferential calculus, from mathematicians,asthoseresearchersworebothhats. In thosetimes,itwasquitedif wavelet analysis,whichisfarmoreprecise. by thecomputerimplementationofFastFourier Transform, orFFT. Itwasextendedmorerecentlyby ﬁ instrument forstudyingwavesandvibrationsinmechanics,acousticsallthe from signals,FourierSpectral Analysis, whichwasextendedbyWienerin1930,becamethekey Laplace andFouriertransformswerefromthesameperiodoftime.Extractingfundamentalinformation 19 mechanics, initiatedbyEuler, d’AlembertandtheBernoullis,wastakenoverbyNavierStokesin rst Fourieranalysers/synthesizers,whichweremechanicalandthenelectronic,replacedin1965 th Century, whomodeledviscousstressandwrotetheirfamousequations. Pascal machine invented in1642byBlaise The Pascaline, anadding/substracting ﬁ cult to distinguish scientists in mechanics cult todistinguishscientistsinmechanics French aeronauticindustry. demonstrating thestillunfailingstrengthof far moreef over theChannel.Hisairplaneandenginewere 1909 whenLouis © The EiffelTower elevator in1889

G ran fi cient thanhiscompetitors’,thus g er Historical Picture Archve -Alam Archve Picture Historical er Blériot fi made the elds ofphysics. The fi y rst

ﬂ ight

© The Print Collector - Alamy Alan Turing computerproject. The Automatic Computing Engine(ACE)istheprototype ofthe by asurprisingandstilltopicaldiscovery:thedif But itwasnotuntiltheendofWorld War IIthatthe been contradicted. any formalismofeffective computationtocomewouldalsobeequivalentthem –athesisthathasnever languages, andshowedithasthesameexpressivepoweras Turing machines.Hestatedthethesisthat Church introducedthe at theverymomenthede impossibility tocomputein universal machinesabletocomputefromaprogramthatisrecordedonthetapenextitsdata,and any knowncalculation;hethenestablishedtwofundamentalresults,theexistenceof shifted. Turing the characterthatisbeingreadmustbereplacedbyanotherortape may bewritten,aread/writeheadandmechanismthatdecideswhether Turing presentshismachines,composedofatapeonwhichcharacters of thecomputabilitytheoryby Alan Turing in1936.Inavisionaryarticle, Modern informationandcomputationscienceswerebornfromtheinvention Information sciencedevelopment fi rst showedthattheseextremelysimplemachinescouldperform λ -calculus, alogicallanguagestillusedasthebasisformodernprogramming fi fi ned thenotionofcalculability, didhesetitslimits. The sameyear, Alonzo nite timewhetheragivenmachinewillornotstopondata. Thus, fi culty towriteanddevelopprogramsgiventhegap fi rst computerswerebuilt,immediatelyfollowed fi rst computerbuiltinthe UK,developedin1950from (1912-1954) Alan Turing

75 350 YEARS OF SCIENCE 76 37 38 La Lettre

© Keystone Pictures USA / Alamy of appliedmathematics. to theuseofnumericalanalysissolvemoreandcomplexequationsbypromotingallforms industrial sides. And Jacques-LouisLions’ exceptional personalityhonouredourcompanybygivingrise it hasbeenwellillustratedbyourfellowPierreFaurreonbothitsresearchand and controllingphysicalsystems.MaxwellWienerwereitspioneers, same time,processcontrolwasbornasanewsciencedevotedtoanalyzing processing, optimizationofmajornetworkssuchastheInternet,etc. At the ﬁ telephone lines,thistheoryhasbecomeofmajorimportanceinmany at understandingandoptimizingthetransportationofinformationonnoisy to ClaudeShannontherevolutionoftheoryinformation.Firstaimed At thebeginningof1950s,otherconceptualrevolutionsoccurred.We owe always inthesoftware,noonbarecircuitboard. improved, there–orbyusingsoftwareabletoconfersomeformofintelligencecomputers:strengthis how tobypassthisdif bugs arefailuresfromtheprogrammers,notprogramsthemselves. Turing himselfwonderedthen computers, whichareunabletomakemistakesbutlackcommonsenseandintuition.Incomputerscience, that separatesmen,whoareintuitivebutslowandnotveryrigorousdespitetheirefforts, andhyperfast elds: telecommunications, soundandimagecompression,generalsignal Claude Shannon (1916-2001) ﬁ culty, eitherbymathematicallyprovingthatprogramsarecorrect–andwehave

© happystock - Fotolia Processing suchthisdatadeluge iskeyforthefuture. It issaidthat,overthelasttwoyears,moredatahas beenproducedthansincethebirthofmankind. because measurementsandexperimentshaveinduced progressinall of datatobeprocessedisexpandingatevenfastera speed,whetherbecauseofhumaninteractionor as allsortsofcomputerizedobjectswillconnect.Butthe amount connects billionmachinesandwillstillgrowenormously so muchastoformtheactualInternet,which connected tooneanotherandnetworked, Computers havebeenprogressively rescue! and mighttakeover–physiciststothe technologies are circuits etchedontosiliconwafers.Other needed toleavetheworldofelectronic and development.Sofar, wehavenever production factoriesaswellresearch heaviest intheworldtermsofcosts industry ofcircuitshasbecomethe though itproducestinyobjects,the physical butmostofalleconomic:even weaker, though,forreasonscertainly computers. This exponentiallawisgetting transistors insidethemicrochipsoftoday’s 4004 in1971,andthentothebillionsof in 1946tothe2250transistorsofIntel from the17500vacuumtubesofENIAC years. Indeed,therewasquiteamove per surfaceunitmoreorlesseverytwo industry todoublethenumberoftransistor expresses theconcerteddecisionof the implementationofMoore’s law, which the inventionofintegratedcircuitand with theuseoftransistorandthen booming atthebeginningof1970s The industryofcomputersreallystarted Informatics intheindustrialera ﬁ nally beingliberated The ElectronicNumericalIntergrator Intel Analyser andComputer(ENIAC) ® Core ™ i7-5960XProcessor ﬁ elds ofscienceandmedicine.

77 350 YEARS OF SCIENCE 78 37 38 La Lettre

© Oleksandr Delyk - Fotolia multilingual translationuse only fewlinguisticconcepts,wedograspanotionofhow faritremainspossible translation, andtheanalysis ofscienti fi power tobeavailable.Deep neuralnetwork-basedlearningnowcausesgreat disruption inasvarious older ideasburstout:theyweretriggeredbyarti which wecannotdowithoutanymore,orthesystematic useofprobabilityinalgorithmics.Recently, machines withinthenetworks.We thensawdrasticallynewideascomeout,suchasWeb searchengines, man-machine interfacesandthestandardizationof communicationprotocolsef We witnessedthecreation ofdatabaseswiththeirfastindexingmechanisms,thedevelopmentmodern techniques forprogramcorrectness. programming languages,whichledtomorecompactandsaferlanguagesformalveri our fellowMarcel-PaulSchützenbergerhasillustratedhimself,thenregardingtheformalsemanticsof of programminghasgraduallyimproved, and optimizesthem.Sincethesameperiodoftime,ourunderstandingmathematicalfoundations Algorithmic complexity, atheorywhichwasborninthe1970s,studiesperformancesofalgorithms internal reasonsastheconceptionandproductionofcircuits,networks,softwareoperatingsystems. fl a rolethatisascentralthepowerincreaseofcomputers.Incomputerscience,algorithmshave In today’s digitalworld,computerscienceandappliedmathematicshaveplayedkeeponplaying elds asGogame,the recognitionoffacesorobjectsinimages,speechrecognition, automaticlanguage ourished, drivenbymoreanddiverseapplications(images,sounds,videos,etc.)butalsosuch fi c data. Ifwebearinmindthatthenewandef fi rst asregardssyntax,withthe theoryoflanguagesinwhich fi cial intelligencebuthadtowaitforveryhighcomputing fi cety connecting ciently fi cient methodsof fi cation © Frédéric Alauzet/Inria is onlystartingtoamazeus. information, asauniquelever that to us,nowcomesthepowerof are variousandquitewellknown power ofphysicallevers,which knows? –thebrain. After the populations andeventually–who cells, organs,organisms, progressive modelsofproteins, of theliving,forwhichwedraw to thein-depthunderstanding formation andevolutionofgalaxies of naturalphenomena,fromthe understanding ofthemostcomplex now takingaprominentpartinour and toolsofinformationscienceare Finally, thealgorithmicconcepts drives theobjectsdependingontheirinteractionswithenvironment. The image providedhereconcerns computer models,whichalsomakeitpossibletosimulatetheeffects ofthecontroltheory-based softwarethat computer-aided designisreplacingpaperdocumentsandphysicalprototypeswiththree-dimensional turbulence thatlieatthecoreofmodernmechanicsandrequirelargecomputersimulations.Moregenerally, computer scienceareincreasinglyentwinedintooneanother. Suchisdirectlythecaseintheoriesof It isimportanttopointoutthat,inthe21 and practice. computer security, wherecrafthasreacheditslimits:itnowrequiresscience,at the highestlevelsoftheory for progresstogo. Yet essential A modelingofairplanewaketurbulence fi elds arestillill-understood. The mostcriticalofthemiscertainlythat st Century, mechanics,appliedmathematics,controltheoryand robotics, 3Dprinting,etc. Control (CNC)machines, Computer Numerical Other examplesinclude has distinguishedhimself. colleague PaulGermain airplane, a the aerodynamicsofan fi eld inwhichour

79 350 YEARS OF SCIENCE 80 37 38 La Lettre was inhisthirtiesandhad been educatedat The Hague, ParisandLondon.Hisworkonthependulum Now, atthetime,inParis,mostacclaimed mathematicianwastheDutchmanChristiaan Huygens, who over, farfromsuspectinghewouldbecome the merchant, NicolausBernoulli, wasraisinghissonJacobinthehopethathewould take thefamilybusiness the intellectualexplorationthatwouldmakehimoneof mostuniversalspiritsofhistimes.InBasel,arich from Leipzig,GottfriedLeibniz,hadjustbecomeDoctor oflaw;herefusedateachingpositiontocontinue epidemic, heworkedon–amongothertopicsanew theoryofgravitation. A somewhatyoungerstudent and Barrow, hehadalsoreadFermatandDescarteswithenthusiasm. Forcedoutofclassbyaplague of Cambridge,astudentnamedIsaacNewtonwas making thebestimpression:in Those whowereabouttofollowthestepsofthese giants wouldnotbelessbright. At theUniversity nature –asamatteroffact,physics. outside, ontheotherhand,inaperpetualstruggletodescribe,understandandpredictphenomenaof on theonehand,withstudyofmathematicalconceptsandobjectsinthemselves,towards each andeveryoneofthem,therewasthisdoublemovementmathematicalideas:towardstheinside, variations, decipheredthelawsofopticsandacousticsevenbuilt and analysis,builtbridgesbetweengeometryalgebra,initiatedthecalculusofprobability Gone wereMersenne,Descartes,Pascal,Fermat:theyhadlaidthefoundationsfortheoryofnumbers to understandandpredict Mathematics:

© B.Eymann - Académie des sciences take overinthefourcornersofEurope. passed away, yetanextraordinaryonewaspreparingto generation ofboldandprolixmathematicianshadjust of algebra”,wasachievedhardlyfortyyearsearlier. A the translationofwritingsDiophantus,“thefather Greek sciencerediscoverywasstillrecent;forinstance, des Scienceswasfoundedin1666. The movementof It wasinastateofmathematicalfrenzythatthe Académie (UPMC, CNRS),Paris Claude-Bernard Lyon 1,DirectoroftheInstitutHenri-Poincaré Member ofthe Académie desSciences,ProfessorattheUniversity Cédric Villani fi rst ofthemostfamous dynastyofmathematiciansever. fi rst calculatingmachines.In fl uenced byWallis following freetranslation:" the mathematicianVladimir Arnold suggestedthe involvente, " encoded theLatinandhardlylessmysterioussentence That ishowNewton,atrueamateurofmysteries,had with eachother: to Leibniz,inatimewhentheywerenotsocross Here isafamousexcerptfromletterNewtonwrote from thiscountry. resumed anditwouldeventuallydriveHuygensaway more dramatically, inFrance,religious persecution which GreatBritainwouldsuffer fortwolargecenturies; preamble totherelativeisolationinmathematicsfrom Leibniz onthe the ferociousquarrelthatopposedNewtonand be quanti allowing thevariationsoffunctionsto major applicationsinmodernanalysis, calculus, averypowerfultoolwith in As emblematicwasthebirthof most in would makeitsauthoroneofthe Such anambitiousprogramme our knowledgeoftheworld. mathematical foundationsunderlying title foretells,aimsatdevelopingthe a workpublishedin1687that,asits Philosophiae NaturalisPrincipiaMathematica Emblematic ofthisperiodwasNewton’s most importantofthehistoryscience. only themcouldfullyappreciate;withinafewdecades,theywouldproduceseveraltreatisesthatcountamongthe one another, joinforces,tearoneanothertopieces,challengeandsometimesinsultinlettersalmost Data aequationequotcunque revolution thatwouldbreakoutinthissecondhalfofthe17 Huygens, Newton,Leibniz,theBernoullis:thosewouldbecomemostfamousheroesofmathematical chosen amongColbert’s very clock wasarevolutioninhowwemeasuretime,althoughthatonlyoneofthefeatsbroughthimtobe fi nitesimal, differential andintegral fl uential menofalltimes. fi ed. And no lessemblematicwas fl uxiones invenire;etviceversa fi rst paternityofdifferential calculus–a 6accdae13eff7i3l9n4o4qrr4s8t12ux It isusefultosolvedifferential fi rst recruitsatthe Académie desSciences. fl une quantitates uentes , ", forwhich .

th Century. Strongpersonalitieswhowouldin one ofthe mostin (1687) wouldmake IsaacNewton(1642-1727) Philosophiae Naturalis PrincipiaMathematica ﬂ uential menofalltimes. ﬂ uence

81 350 YEARS OF SCIENCE 82 37 38 La Lettre famous cycloid,i.e.thecurve describedbya its energy? The solutionwasnootherthanthe make itsoscillationperiod independent from pendulum byawell-chosencurve,soasto is itpossibletoconstrainthemotionofa then hadapurelymathematicalquestion: such avariationlimitedaccuracy. Huygens of pendulumoscillationstobuildclocks, motion. Whenitcametousingtheregularity but variesaccordingtotheamplitudeof oscillation perioddoesnotdependonmass, Italian remarked,andrightlyso,thatthe really observed,withGalileo. The illustrious apparently, onlycirca1600didtheystarttobe been there,underoneformortheother;yet, the endofathread.Pendulumshavealways object, thependulum:amasssuspendedat of the17 stories thathavebeeninitiatedbyourheroes Let’s consideroneofthoseinnumerable unexpected developments,andinvolvedtheparallelefforts ofanever-growingnumberscientists. and transmitusawealthofinformation.Eachsteptheway, though,wasfraughtwithobstaclesand 12 generationstosendahumanbeingonthemoon;andtwomoreformachinelandcomet mathematizing themotionsofplanets;yet,oncedifferential equationsdiscovered,itwouldtakelessthan everything wouldgoveryfast.Ninetygenerationshadpassedsince Thales and hisdisciplesdreamtof problem couldnowbetranslatedintomathematics.Fromthenon, sum ofgravitationalforcesisequaltomasstimesacceleration–the two planets? Thanks todifferential equationsandNewton’s law–the be devastatedbyamajorcataclysm,suchascollisionbetween whether thesolarsystemwillstayasweknowitor, onthecontrary, the equationsthatdescribemotionsofstars,isitpossibletopredict One famousexampleofitisthestabilitysolarsystem:knowing The differentialcalculus:promiseskept important stepevertakeninphysics? problems basedontendenciesandvariations.Did Albert Einsteinhimselfnotdeclarethiswasthemost unprecedented revolution,inasmuchasitmadepossibletotranslateintoequationsallsortsofphysical equations”. Nowadays,suchsecretsmayseemchildishbuttheinventionofdifferential calculuswasan th Century. Itstartedwithafamiliar Sabatelli, circa 1840) hanging lampinthePisaCathedral (FrescobyLuigi Galileo (1564-1632)observing theoscillationofa

©©s stormtorm- FoFotoliatolia © Archives de l'Académie universel unit,themetre. on thewakeofFrench RevolutiontomeasuretheEarthandthusprovide theworldwithatruly controversial forhalfaCentury, untilafamousmeasurementcampaigninLaplandthatthe Académie the Earth,subjecttoacentrifugalforce,isslightly Huygens andNewtondeducedfromthistrivialobservationthat pendulum tickedabitslowerinCayennethanParis. "élève académicien"in1666,discoveredthathis Jean Richer, whohadbeenrecruitedas saying itslastword.In1673,theastronomer However, the pendulumwasfarfrom one secondperhour. precision clock,withanerrorinferiorto Huygens tobuildthe be rigorouslyinvariant. This enabled remarkably, theoscillationperiodwill a trajectorythatisitselfcycloidal;and, cycloidal shape,thenthemassdescribes pendulum isconstrainedbytwo“cheeks”of marked pointonarollingwheel.Indeed,if Lapland and thecampaignto Maupertuis (1698-1759) Pierre LouisMoreaude ﬁ rst mechanical rst

© Bibliotheque de l'Institut de France Maupertuis, Paris,1744 by theabbotOuthierand Journal ofthecampaign, ﬂ attened atthepoles:atheorythatwouldremain Louis XIV. presents hispendulumclockto Christiaan Huygens(1629-1695) Delambre etMéchainmade chapter wastheheroiceffort Earth, whosemostdramatic of thepreciseshape sea. The otheristhediscovery to takeprecisebearingsat calculation oftimedifference, made itpossible,throughthe one secondpermonthand that wouldnotlosemorethan chronometer, arealwonder moment wasHarrison’s 1765 clocks, whosemostcolorful technology ofprecision scienti lie theseedsoftwogreat Thus, withinthispendulum Maupertuis. des Sciencesentrustedto ﬁ c epics.Oneisthe

83 350 YEARS OF SCIENCE 84 37 38 La Lettre differential equations,whichshednewlightonNewton’s mechanics. dynamical systems,HenriPoincaréintroducedavastprogrammeofqualitativestudyonthesolutions the sametimealgebrawasusedtodemonstratethatsomeproblemsarenotsolvable.Withhistheoryof the notionofset. The theoryofcomplexfunctionsprovidedforasystematicresearchsolutions,whileat well asalgebraandtheveryconceptofnumber;non-Euclideangeometrywasfounded,topology, and Dirichlet, Riemann,Weierstrass, Cantor, Poincaré,tonamebutafewofthem. Analysis wasrede Century, conceptswererefounded,oneaftertheother, byGauss,Legendre,Cauchy, Jacobi, Abel, Galois, regunt numeri” oscillations ofmembranes,andwithFourier, thepropagationofheat. mottoputsit:“ As Fourier’s as thedisplacementandrearrangementofmatteratleastexpense,withSophieGermain, with Laplace,thestatistical ﬁ sought toconquertheungraspable

© Archives de l'Académie des sciences nally wonrecognition.WithCondorcet, then,itwastimetoexplorevotesandsystemsofdecision, Mathematical refoundationsandrevolutions other, problems wouldwindupintomathematicalhands.Inthe18 conceptual revolutions,becamemorenumerousinthefollowingdecadesandcenturies.Oneafter Adventures likethese,withtheirshareofsurprisingobservations,unexpecteddevelopmentsand To bemoreef Henri Poincaré (1854-1912) –even fi cient, thedisciplinealsohadtoimproveitsownstructureandtools. Throughout the19 fi re isruledbynumbers,equations. fl uctuations ofstochasticevents,andwithMonge,suchoperationalproblems fl uids; ittookalmostonecenturybeforetheNavier-Stokesequations th Century, Euler, Bernoulliandd'Alembert fi Et ignem ned, as ned, th

differential equations–de science wasthesystematicstudyof fi operations. Interestinglyenough,oneofthe machines abletoperformanymathematical Shannon ontoimaginecomputers,aslogical eventually spurredVon Neumann, Turing and Gödel andothers,suchanabyssofperplexity 1+1=2!), andtotheworksofHilbert,Church, nearly 400pages,totheeventualproofthat Whitehead (avolumeofwhichendsup,after Principia Mathematica does thismean:“1+1=2”? A sourcetothe a solutionandthosethatdonot? And what a proof,whicharetheproblemsthathave the discipline–whatisareasoning, in logic,questioningtheveryfoundationsof amazing ofsuchscienti mathematical expression.Butthemost fi physics, quantummechanicsandeven Baire, LebesgueandKolmogorov. Statistical probability theory, wererefoundedbyBorel, its trainofrevolutions.Measuretheory, and 20 to themathematicaldevelopmentof It isimpossiblehereformetopaytribute topic. emerged. Ishallmentiononly one,whichis so manyothers,hundreds ofnewtopics Thurston, Varadhan, Wiles,Perelmanand Solovay, Malliavin, Gromov, Langlands, Hörmander, Carleson,Nash,DeGiorgi, Hironaka, Itô,Serre,Gel'fand,Schwartz, Chern, Grothendieck,Cohen,Leray, Cartan, Hardy, Ramanujan, Littlewood, Noether, Banach,Wiener, Riesz, Atiyah, feats achievedbythegreatBourbaki,Weil, richest ofall.Besidethenewconceptual The beginningofthe20 rstmotivationofthesepioneerscomputer nance: allreceivedtheirownpersonalized th Century, whichmayhavebeenthe writtenbyRusselland fi c stormstookplace th Centuryalsohad fi nitely auniversal Andrei Kolmogorov (1903-1987)

85 350 YEARS OF SCIENCE 86 37 38 La Lettre Lagrange, PoincaréandKolmogorov–tothisquestion,wemaynowcon Hamiltonian systems,symplecticschemesandthecontributionsofsuchsacredmonstersasLaplace, of work,theintroductionlinearalgebra,dynamicalsystems,probabilitytheory, chaostheory, perturbed Thus, tothequestionraisedbyNewton–Issolarsystemstable?afterthreehundredand to understandandpredictthephenomena,withissometimesful Newton andhiscolleagues,isfaraway;yettheirquestionsarestillours,soasunremittingdesire acknowledged; theyhavebeenpraisedandreviled,bytimescalledcriminals. The timeofcraft, ballet ofconferences,symposiaandemails. The rolesofmathematicianswithin theindustryhasbeen journals, mostofthetimeincollaborationwithothers;theygatheralloverworld,arelentless research systemsandpublishingmorethanever–probablytoomuchinhundredsofspecialized And mathematiciansmaynowbecountedbyhundredsofthousand,operatingwithinhighlyorganized mathematical literatureonthistopicistensofthousandpageslong. describing andpredictingthestatisticalevolutionofagasthatexperiencesunceasingcollisions;today, the dear tome:in1933, Torsten Carlemanconductedthe the lostorbitofasteroidCeres,thento turns. Indeed,whenGaussmanagedto novel, withitsshareofironictwistsand this longstory, whichisnotunlikeagreat themes entwinedineachotherthroughout Prediction andunpredictabilityaretwo conceptual monsters:chanceandthein problem, wearefacedwithtwowell-known unreachable precision.Ultimately, inNewton’s ruled byasetofprobabilities,forlackanin possible todobetter:theoutcomeofuniverseis quanti This “perhaps”isnothingweshouldbeashamedof,asitmay fi ed inprobabilityterms,andasweknowitisnot fi fi nite. nd fi nite,

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© Photo Researchers, Inc - Alamy © nirutft - Fotolia our world. observe inour Academies, andin ever, attheimageofwhatwe widely blendtogether, nowmorethan gravitational wavedetectors.Disciplines grids, orevenanalyzingmeasurestakenby that coordinatetheelectricsupplyofintelligent heart developedbyourfellow Alain Carpentier, those adventures ofourtime,aswiththealgorithmsthatfeedarti © From B.E From y mann - Académie des sciences des - Académie mann sciences, tosomeofthegreattechnological the measurementoftime,letussaythat proud toparticipate,inharmonywithother fi cial the programmeinitiatedbyHuygens The mathematicalscienceisthus to beunderstoodandpredicted. progressed tosuchanextent,with every scienti © D'aprèèsès php otootoo B.B EymEyEymymannannnn been translatedintoequations that thebestmodernclocks rumor –allandmorehave growth ofatumor, ora would notvarymorethan in one secondinabillion forecasts, electrical years. one-week weather Above all,heartbeats, fl ux inourneurons,the fi c opportunity, c

87 350 YEARS OF SCIENCE 88 37 38 La Lettre whole rangeofscienti the mostprestigiousscientistsoftheirtimein 88 correspondingmembers by its259members,138foreignassociatesand an advisoryroletothedecision-makers.Enriched independent institution,the Académie performs of PresidenttheFrenchRepublic. As an of a‘PublicLegalEntity’ undertheprotection Académie desSciencestodayhasthestatus Originally undertheprotectionofKing, ● ● ● ● ●

de l’Académie des sciences and Recommendations. Notes Advice Reports, committees, thematic Standing and advisor: Performingcooperation. Bilateral networks, Interacademic collaboration: Fostering international the role ofscienti anTransmitting knowledge: Public expert teaching: Scienti science Promoting andmedals, Prizes Scienti scienti the Encouraging programme, Archives. letter, Twinning MPs with scientists Museums. andtraining, education science for committee Standing atteaching school, fi fi Website, c sessions, Biannual andcolloquia, c conferences Five missions Five fi c disciplinesincludingthe 1 a forward-lookinginstitution The Academie desSciences, Comptes Rendus Comptes —whorankamong fi c community: community: c . fi c 1 - As of 1 September 2016 1September of 1 -As Académie’s expertise. committees whicharethe cornerstonesofthe but theyworkinmultidisciplinary standing elected fromtheeightsectionsof Académie, acting asdecisionaidtools.Membersarepeer- reports, advicenotesandrecommendations,all most emergingones—,the Académie composes

© Institut de France sciences —the Since thefoundingofvery applications. the developmentofscienceandits to thequestionssocietymayhaveon up-to-date andappropriateanswers future andallowingittoalwaysprovide keeping the Académie focusedonthe years old. This isaworthwhileassetin newly electedmembersarelessthan55 adopted intheearly2000s,halfof As providedbythenewstatutes Académie essential partnerforinternationalscienti global issues.Itsrenownand350year-longexpertisestillmaketheFrench Académie desSciencesan play intheirowncountries,theseacademies,linkedinteracademicnetworks,expressopinionson expanded, 1603 —,thenumberofnationalacademiesrapidly fi rst inEuropeandthenworldwide.Inadditiontotherolethey Accademia DeiLincei fi rst academyof , inRome, fi c diplomacy. c

89 350 YEARS OF SCIENCE

Head of publication Catherine Bréchignac

Directory Catherine Bréchignac Pascale Cossart Alain-Jacques Valleron

Editorial Board Alain Aspect Gérard Berry Catherine Bréchignac Jean-Pierre Changeux Pascale Cossart Alain Fischer Anne-Marie Lagrange Yvon Le Maho Jacques Livage Bernard Meunier Cédric Villani

Editor in Chief Emmanuelle Chollet

Art director Natacha Oliveira

Translation Nicolas Rigaud

Printing Boudard Imprimeur

ISSN 2102-5398

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