第27章

Thecontroversyoverspontaneousgeneration，which，thankstoPasteurandTyndall，hadjustbeenbroughttoatermination，madeitclearthatnobacteriumneedbefearedwhereanantecedentbacteriumhadnotfoundlodgment；Listerisminsurgeryhadnowshownhowmuchmightbeaccomplishedtowardspreventingtheaccessofgermstoabradedsurfacesofthebodyanddestroyingthosethatalreadyhadfoundlodgmentthere。Asyet，however，therewasnoinklingofawayinwhichacorrespondingonslaughtmightbemadeuponthoseothergermswhichfindtheirwayintotheanimalorganismbywayofthemouthandthenostrils，andwhich，aswasnowclear，arethecauseofthosecontagiousdiseaseswhich，firstandlast，claimsolargeaproportionofmankindfortheirvictims。Howsuchmeansmightbefoundnowbecametheanxiousthoughtofeveryimaginativephysician，ofeveryworkingmicrobiologist。

Asithappened，theworldwasnotkeptlonginsuspense。Almostbeforethepropositionhadtakenshapeinthemindsoftheotherleaders，Pasteurhadfoundasolution。GuidedbytheempiricalsuccessofJenner，he，likemanyothers，hadlongpractisedinoculationexperiments，andonFebruary9，1880，heannouncedtotheFrenchAcademyofSciencesthathehadfoundamethodofsoreducingthevirulenceofadiseasegermthatwhenintroducedintothesystemofasusceptibleanimalitproducedonlyamildformofthedisease，which，however，sufficedtoprotectagainsttheusualvirulentformexactlyasvacciniaprotectsagainstsmall-pox。Theparticulardiseaseexperimentedwithwasthatinfectiousmaladyofpoultryknownfamiliarlyas"chickencholera。"InOctoberofthesameyearPasteurannouncedthemethodbywhichthis"attenuationofthevirus，"ashetermedit，hadbeenbroughtabout——bycultivationofthediseasegermsinartificialmedia，exposedtotheair，andhedidnothesitatetoasserthisbeliefthatthemethodwouldprove"susceptibleofgeneralization"——thatistosay，ofapplicationtootherdiseasesthantheparticularoneinquestion。

Withinafewmonthshemadegoodthisprophecy，forinFebruary，1881，heannouncedtotheAcademythatwiththeaid，asbefore，ofhisassociatesMM。ChamberlandandRoux，hehadproducedanattenuatedvirusoftheanthraxmicrobebytheuseofwhich，asheaffirmedwithgreatconfidence，hecouldprotectsheep，andpresumablycattle，againstthatfatalmalady。"Insomerecentpublications，"saidPasteur，"Iannouncedthefirstcaseoftheattenuationofavirusbyexperimentalmethodsonly。Formedofaspecialmicrobeofanextrememinuteness，thisvirusmaybemultipliedbyartificialcultureoutsidetheanimalbody。Thesecultures，leftalonewithoutanypossibleexternalcontamination，undergo，inthecourseoftime，modificationsoftheirvirulencytoagreaterorlessextent。Theoxygenoftheatmosphereissaidtobethechiefcauseoftheseattenuations——thatis，thislesseningofthefacilitiesofmultiplicationofthemicrobe；foritisevidentthatthedifferenceofvirulenceisinsomewayassociatedwithdifferencesofdevelopmentintheparasiticeconomy。

"Thereisnoneedtoinsistupontheinterestingcharacteroftheseresultsandthedeductionstobemadetherefrom。Toseektolessenthevirulencebyrationalmeanswouldbetoestablish，uponanexperimentalbasis，thehopeofpreparingfromanactivevirus，easilycultivatedeitherinthehumanoranimalbody，avaccine-virusofrestraineddevelopmentcapableofpreventingthefataleffectsoftheformer。Therefore，wehaveappliedallourenergiestoinvestigatethepossiblegeneralizingactionofatmosphericoxygenintheattenuationofvirus。

"Theanthraxvirus，beingonethathasbeenmostcarefullystudied，seemedtobethefirstthatshouldattractourattention。Everytime，however，weencounteredadifficulty。

Betweenthemicrobeofchickencholeraandthemicrobeofanthraxthereexistsanessentialdifferencewhichdoesnotallowthenewexperimenttobeverifiedbytheold。Themicrobesofchickencholeradonot，ineffect，seemtoresolvethemselves，intheirculture，intoveritablegerms。Thelatteraremerelycells，orarticulationsalwaysreadytomultiplybydivision，exceptwhentheparticularconditionsinwhichtheybecometruegermsareknown。

"Theyeastofbeerisastrikingexampleofthesecellularproductions，beingabletomultiplythemselvesindefinitelywithouttheapparitionoftheiroriginalspores。Thereexistmanymucedines(Mucedinae？)oftubularmushrooms，whichincertainconditionsofcultureproduceachainofmoreorlesssphericalcellscalledConidae。Thelatter，detachedfromtheirbranches，areabletoreproducethemselvesintheformofcells，withouttheappearance，atleastwithachangeintheconditionsofculture，ofthesporesoftheirrespectivemucedines。Thesevegetableorganismscanbecomparedtoplantswhicharecultivatedbyslipping，andtoproducewhichitisnotnecessarytohavethefruitsortheseedsofthemotherplant。

Theanthraxbacterium，initsartificialcultivation，behavesverydifferently。Itsmycelianfilaments，ifonemaysodescribethem，havebeenproducedscarcelyfortwenty-fourorforty-eighthourswhentheyareseentotransformthemselves，thoseespeciallywhichareinfreecontactwiththeair，intoveryrefringentcorpuscles，capableofgraduallyisolatingthemselvesintotruegermsofslightorganization。Moreover，observationshowsthatthesegerms，formedsoquicklyintheculture，donotundergo，afterexposureforatimetoatmosphericair，anychangeeitherintheirvitalityortheirvirulence。IwasabletopresenttotheAcademyatubecontainingsomesporesofanthraxbacteriaproducedfouryearsago，onMarch21，1887。Eachyearthegerminationoftheselittlecorpuscleshasbeentried，andeachyearthegerminationhasbeenaccomplishedwiththesamefacilityandthesamerapidityasatfirst。Eachyearalsothevirulenceofthenewcultureshasbeentested，andtheyhavenotshownanyvisiblefallingoff。Therefore，howcanweexperimentwiththeactionoftheairupontheanthraxviruswithanyexpectationofmakingitlessvirulent？

"Thecrucialdifficultyliesperhapsentirelyinthisrapidreproductionofthebacteriagermswhichwehavejustrelated。Initsformofafilament，andinitsmultiplicationbydivision，isnotthisorganismatallpointscomparablewiththemicrobeofthechickencholera？

"Thatagerm，properlysocalled，thataseed，doesnotsufferanymodificationonaccountoftheairiseasilyconceived；butitisconceivablenotlesseasilythatifthereshouldbeanychangeitwouldoccurbypreferenceinthecaseofamycelianfragment。Itisthusthataslipwhichmayhavebeenabandonedinthesoilincontactwiththeairdoesnottakelongtoloseallvitality，whileundersimilarconditionsaseedispreservedinreadinesstoreproducetheplant。Iftheseviewshaveanyfoundation，weareledtothinkthatinordertoprovetheactionoftheairupontheanthraxbacteriaitwillbeindispensabletosubmittothisactionthemyceliandevelopmentoftheminuteorganismunderconditionswheretherecannotbetheleastadmixtureofcorpusculargerms。Hencetheproblemofsubmittingthebacteriatotheactionofoxygencomesbacktothequestionofpresentingentirelytheformationofspores。Thequestionbeingputinthisway，wearebeginningtorecognizethatitiscapableofbeingsolved。

"Wecan，infact，preventtheappearanceofsporesintheartificialculturesoftheanthraxparasitebyvariousartifices。

Atthelowesttemperatureatwhichthisparasitecanbecultivated——thatistosay，about+16degreesCentigrade——thebacteriumdoesnotproducegerms——atanyrate，foraverylongtime。Theshapesoftheminutemicrobeatthislowestlimitofitsdevelopmentareirregular，intheformofballsandpears——inaword，theyaremonstrosities——buttheyarewithoutspores。Inthelastregardalsoitisthesameatthehighesttemperaturesatwhichtheparasitecanbecultivated，temperatureswhichvaryslightlyaccordingtothemeansemployed。Inneutralchickenbouillonthebacteriacannotbecultivatedabove45degrees。

Culture，however，iseasyandabundantat42to43degrees，butequallywithoutanyformationofspores。Consequentlyacultureofmycelianbacteriacanbekeptentirelyfreefromgermswhileincontactwiththeopenairatatemperatureoffrom42to43

degreesCentigrade。Nowappearthethreeremarkableresults。

Afteraboutonemonthofwaitingtheculturedies——thatistosay，ifputintoafreshbouillonitbecomesabsolutelysterile。

"Somuchforthelifeandnutritionofthisorganism。Inrespecttoitsvirulence，itisanextraordinaryfactthatitdisappearsentirelyaftereightdays’cultureat42to43degreesCentigrade，or，atanyrate，theculturesareinnocuousfortheguinea-pig，therabbit，andthesheep，thethreekindsofanimalsmostapttocontractanthrax。Wearethusabletoobtain，notonlytheattenuationofthevirulence，butalsoitscompletesuppressionbyasimplemethodofcultivation。Moreover，weseealsothepossibilityofpreservingandcultivatingtheterriblemicrobeinaninoffensivestate。Whatisitthathappensintheseeightdaysat43degreesthatsufficestotakeawaythevirulenceofthebacteria？Letusrememberthatthemicrobeofchickencholeradiesincontactwiththeair，inaperiodsomewhatprotracted，itistrue，butaftersuccessiveattenuations。Arewejustifiedinthinkingthatitoughttobethesameinregardtothemicrobeofanthrax？Thishypothesisisconfirmedbyexperiment。Beforethedisappearanceofitsvirulencetheanthraxmicrobepassesthroughvariousdegreesofattenuation，and，moreover，asisalsothecasewiththemicrobeofchickencholera，eachoftheseattenuatedstatesofvirulencecanbeobtainedbycultivation。Moreover，since，accordingtooneofourrecentCommunications，anthraxisnotrecurrent，eachofourattenuatedanthraxmicrobesis，forthebetter-developedmicrobe，avaccine——thatistosay，avirusproducingaless-malignantmalady。What，therefore，iseasierthantofindintheseavirusthatwillinfectwithanthraxsheep，cows，andhorses，withoutkillingthem，andultimatelycapableofwardingoffthemortalmalady？Wehavepractisedthisexperimentwithgreatsuccessuponsheep，andwhentheseasoncomesfortheassemblingoftheflocksatBeauceweshalltrytheexperimentonalargerscale。

"AlreadyM。Toussainthasannouncedthatsheepcanbesavedbypreventiveinoculations；butwhenthisableobservershallhavepublishedhisresults；onthesubjectofwhichwehavemadesuchexhaustivestudies，asyetunpublished，weshallbeabletoseethewholedifferencewhichexistsbetweenthetwomethods——theuncertaintyoftheoneandthecertaintyoftheother。Thatwhichweannouncehas，moreover，theverygreatadvantageofrestingupontheexistenceofapoisonvaccinecultivableatwill，andwhichcanbeincreasedindefinitelyinthespaceofafewhourswithouthavingrecoursetoinfectedblood。"[8]

Thisannouncementwasimmediatelychallengedinawaythatbroughtittotheattentionoftheentireworld。Thepresidentofanagriculturalsociety，realizingtheenormousimportanceofthesubject，proposedtoPasteurthathisallegeddiscoveryshouldbesubmittedtoadecisivepublictest。HeproposedtofurnishadroveoffiftysheephalfofwhichweretobeinoculatedwiththeattenuatedvirusofPasteur。Subsequentlyallthesheepweretobeinoculatedwithvirulentvirus，allbeingkepttogetherinonepenunderpreciselythesameconditions。The"protected"sheepweretoremainhealthy；theunprotectedonestodieofanthrax；

soreadthetermsoftheproposition。Pasteuracceptedthechallenge；heevenpermittedachangeintheprogrammebywhichtwogoatsweresubstitutedfortwoofthesheep，andtencattleadded，stipulating，however，thatsincehisexperimentshadnotyetbeenextendedtocattletheseshouldnotberegardedasfallingrigidlywithinthetermsofthetest。

Itwasatesttotrythesoulofanyman，foralltheworldlookedonaskance，preparedtoderidethemakerofsopreposterousaclaimassoonashisclaimshouldbeprovedbaseless。NoteventhefameofPasteurcouldmakethepublicatlarge，layorscientific，believeinthepossibilityofwhatheproposedtoaccomplish。Therewastimeforalltheworldtobeinformedoftheprocedure，forthefirst"preventive"

inoculation——orvaccination，asPasteurtermedit——wasmadeonMay5th，thesecondonMay17th，andanotherintervaloftwoweeksmustelapsebeforethefinalinoculationswiththeunattenuatedvirus。Twenty-foursheep，onegoat，andfivecattleweresubmittedtothepreliminaryvaccinations。Then，onMay31

st，allsixtyoftheanimalswereinoculated，aprotectedandunprotectedonealternately，withanextremelyvirulentcultureofanthraxmicrobesthathadbeeninPasteur’slaboratorysince1877。Thisaccomplished，theanimalswerelefttogetherinoneenclosuretoawaittheissue。

Twodayslater，June2d，attheappointedhourofrendezvous，avastcrowd，composedofveterinarysurgeons，newspapercorrespondents，andfarmersfromfarandnear，gatheredtowitnesstheclosingscenesofthisscientifictourney。Whattheysawwasoneofthemostdramaticscenesinthehistoryofpeacefulscience——ascenewhich，asPasteurdeclaredafterwards，"amazedtheassembly。"Scatteredabouttheenclosure，dead，dying，ormanifestlysickuntodeath，laytheunprotectedanimals，oneandall，whileeachandevery"protected"animalstalkedunconcernedlyaboutwitheveryappearanceofperfecthealth。Twentyofthesheepandtheonegoatwerealreadydead；

twoothersheepexpiredundertheeyesofthespectators；theremainingvictimslingeredbutafewhourslonger。Thusinamannertheatricalenough，nottosaytragic，wasproclaimedtheunequivocalvictoryofscience。Naturallyenough，theunbelieversstrucktheircolorsandsurrenderedwithoutterms；theprincipleofprotectivevaccination，withavirusexperimentallypreparedinthelaboratory，wasestablishedbeyondthereachofcontroversy。

Thatmemorablescientificbattlemarkedthebeginningofanewerainmedicine。Itwasaforegoneconclusionthattheprinciplethusestablishedwouldbestillfurthergeneralized；thatitwouldbeappliedtohumanmaladies；thatinallprobabilityitwouldgrapplesuccessfully，soonerorlater，withmanyinfectiousdiseases。Thatexpectationhasadvancedrapidlytowardsrealization。Pasteurhimselfmadetheapplicationtothehumansubjectinthediseasehydrophobiain1885，sincewhichtimethathithertomostfatalofmaladieshaslargelylostitsterrors。

ThousandsofpersonsbittenbymaddogshavebeensnatchedfromthefatalconsequencesofthatmishapbythismethodatthePasteurInstituteinParis，andatthesimilarinstitutes，builtonthemodelofthisparentone，thathavebeenestablishedallovertheworldinregionsaswidelyseparatedasNewYorkandNha-Trang。

SERUM-THERAPY

IntheproductionoftherabiesvaccinePasteurandhisassociatesdevelopedamethodofattenuationofavirusquitedifferentfromthatwhichhadbeenemployedinthecaseofthevaccinesofchickencholeraandofanthrax。Therabiesviruswasinoculatedintothesystemofguinea-pigsorrabbitsand，ineffect，cultivatedinthesystemsoftheseanimals。Thespinalcordoftheseinfectedanimalswasfoundtoberichinthevirus，whichrapidlybecameattenuatedwhenthecordwasdriedintheair。Thepreventivevirus，ofvaryingstrengths，wasmadebymacerationofthesecordsatvaryingstagesofdesiccation。Thiscultivationofaviruswithintheanimalorganismsuggested，nodoubt，bythefamiliarJennerianmethodofsecuringsmall-poxvaccine，wasatthesametimeastepinthedirectionofanewtherapeuticprocedurewhichwasdestinedpresentlytobecomeofall-absorbingimportance——themethod，namely，ofso-calledserum-therapy，orthetreatmentofadiseasewiththebloodserumofananimalthathasbeensubjectedtoprotectiveinoculationagainstthatdisease。

Thepossibilityofsuchamethodwassuggestedbythefamiliarobservation，madebyPasteurandnumerousotherworkers，thatanimalsofdifferentspeciesdifferwidelyintheirsusceptibilitytovariousmaladies，andthatthevirusofagivendiseasemaybecomemoreandmorevirulentwhenpassedthroughthesystemsofsuccessiveindividualsofonespecies，and，contrariwise，lessandlessvirulentwhenpassedthroughthesystemsofsuccessiveindividualsofanotherspecies。Thesefactssuggestedthetheorythatthebloodofresistantanimalsmightcontainsomethingdirectlyantagonistictothevirus，andthehopethatthissomethingmightbetransferredwithcurativeeffecttothebloodofaninfectedsusceptibleanimal。Numerousexperimentersallovertheworldmadeinvestigationsalongthelineofthisalluringpossibility，theleadersperhapsbeingDrs。

BehringandKitasato，closelyfollowedbyDr。RouxandhisassociatesofthePasteurInstituteofParis。DefiniteresultswereannouncedbyBehringin1892regardingtwoimportantdiseases——tetanusanddiphtheria——butthemethoddidnotcomeintogeneralnoticeuntil1894，whenDr。Rouxreadanepoch-makingpaperonthesubjectattheCongressofHygieneatBuda-Pesth。

InthispaperDr。Roux，afteradvertingtothelaborsofBehring，Ehrlich，Boer，Kossel，andWasserman，describedindetailthemethodsthathadbeendevelopedatthePasteurInstituteforthedevelopmentofthecurativeserum，towhichBehringhadgiventhesince-familiarnameantitoxine。Themethodconsists，first，ofthecultivation，forsomemonths，ofthediphtheriabacillus(calledtheKlebs-Loefflerbacillus，inhonorofitsdiscoverers)

inanartificialbouillon，forthedevelopmentofapowerfultoxinecapableofgivingthediseaseinavirulentform。

Thistoxine，aftercertaindetailsofmechanicaltreatment，isinjectedinsmallbutincreasingdosesintothesystemofananimal，carebeingtakentograduatetheamountsothattheanimaldoesnotsuccumbtothedisease。Afteracertaincourseofthistreatmentitisfoundthataportionofbloodserumoftheanimalsotreatedwillactinacurativewayifinjectedintothebloodofanotheranimal，orahumanpatient，sufferingwithdiphtheria。Inotherwords，accordingtotheory，anantitoxinehasbeendevelopedinthesystemoftheanimalsubjectedtotheprogressiveinoculationsofthediphtheriatoxine。InDr。Roux’sexperiencetheanimalbestsuitedforthepurposeisthehorse，thoughalmostanyofthedomesticatedanimalswillservethepurpose。

ButDr。Roux’spaperdidnotstopwiththedescriptionoflaboratorymethods。IttoldalsoofthepracticalapplicationoftheserumtothetreatmentofnumerouscasesofdiphtheriainthehospitalsofParis——applicationsthathadmetwithagratifyingmeasureofsuccess。Hemadeitclearthatameanshadbeenfoundofcopingsuccessfullywithwhathadbeenoneofthemostvirulentandintractableofthediseasesofchildhood。Henceitwasnotstrangethathispapermadeasensationinallcircles，medicalandlayalike。

PhysiciansfromallovertheworldflockedtoParistolearnthedetailsoftheopensecret，andwithinafewmonthsthenewserum-therapyhadanacknowledgedstandingwiththemedicalprofessioneverywhere。Whatithadaccomplishedwasregardedasbutanearnestofwhatthenewmethodmightaccomplishpresentlywhenappliedtotheotherinfectiousdiseases。

Effortsatsuchapplicationswereimmediatelybeguninnumberlessdirections——had，indeed，beenunderwayinmanyalaboratoryforsomeyearsbefore。Itistooearlyyettospeakoftheresultsindetail。Butenoughhasbeendonetoshowthatthismethodalsoissusceptibleofthewidestgeneralization。Itisnoteasyatthepresentstagetosiftthatwhichistentativefromthatwhichwillbepermanent；butsogreatanauthorityasBehringdoesnothesitatetoaffirmthattodaywepossess，inadditiontothediphtheriaantitoxine，equallyspecificantitoxinesoftetanus，cholera，typhusfever，pneumonia，andtuberculosis——asetofdiseaseswhichintheaggregateaccountforastartlingproportionofthegeneraldeath-rate。ThenitisknownthatDr。

Yersin，withthecollaborationofhisformercolleaguesofthePasteurInstitute，hasdeveloped，andhasusedwithsuccess，anantitoxinefromthemicrobeoftheplaguewhichrecentlyravagedChina。

Dr。Calmette，anothergraduateofthePasteurInstitute，hasextendedtherangeoftheserum-therapytoincludethepreventionandtreatmentofpoisoningbyvenoms，andhasdevelopedanantitoxinethathasalreadygivenimmunityfromthelethaleffectsofsnakebitestothousandsofpersonsinIndiaandAustralia。

Justhowmuchofpresentpromiseistentative，justwhatarethelimitsofthemethods——thesearequestionsforthefuturetodecide。But，inanyevent，thereseemslittlequestionthattheserumtreatmentwillstandastheculminatingachievementintherapeuticsofourcentury。Itisthelogicaloutgrowthofthoseexperimentalstudieswiththemicroscopebegunbyourpredecessorsofthethirties，anditrepresentsthepresentculminationoftherigidlyexperimentalmethodwhichhasbroughtmedicinefromaleveloffancifulempiricismtotheplaneofarationalexperimentalscience。

IX。THENEWSCIENCEOFEXPERIMENTALPSYCHOLOGY

BRAINANDMIND

Alittleoverahundredyearsagoareformmovementwasafootintheworldintheinterestsoftheinsane。Aswasfitting，themovementshoweditselffirstinAmerica，wheretheseunfortunateswerehumanelycaredforatatimewhentheirtreatmentelsewherewasworsethanbrutal；butEnglandandFrancequicklyfellintoline。TheleaderonthissideofthewaterwasthefamousPhiladelphian，Dr。BenjaminRush，"theSydenhamofAmerica"；inEngland，Dr。WilliamTukeinauguratedthemovement；andinFrance，Dr。PhilippePinel，single-handed，ledtheway。Movedbyacommonspirit，thoughactingquiteindependently，thesemenraisedarevoltagainstthetraditionalcustomwhich，spurningtheinsaneasdemon-hauntedoutcasts，hadcondemnedtheseunfortunatestodungeons，chains，andthelash。Hithertofewpeoplehadthoughtitotherthanthenaturalcourseofeventsthatthe"maniac"shouldbethrustintoadungeon，andperhapschainedtothewallwiththeaidofanironbandrivetedpermanentlyabouthisneckorwaist。Manyanunfortunate，thusmanacled，washeldtothenarrowlimitsofhischainforyearstogetherinacelltowhichfulldaylightneverpenetrated；

sometimes——ironbeingexpensive——thechainwassoshortthatthewretchedvictimcouldnotrisetotheuprightpostureorevenshifthispositionuponhissqualidpalletofstraw。

InAmerica，indeed，therebeingnoMiddleAgeprecedentstocrystallizeintoestablishedcustoms，thetreatmentaccordedtheinsanehadseldomorneversunktothislevel。Partlyforthisreason，perhaps，theworkofDr。RushatthePhiladelphiaHospital，in1784，bymeansofwhichtheinsanecametobehumanelytreated，eventotheextentofbanishingthelash，hasbeenbutlittlenoted，whiletheworkoftheEuropeanleaders，thoughbelongingtolaterdecades，hasbeenmadefamous。Andperhapsthisisnotasunjustasitseems，forthestepwhichRushtook，fromrelativelybadtogood，wasafareasieronetotakethantheleapfromatrocitiestogoodtreatmentwhichtheEuropeanreformerswereobligedtocompass。InParis，forexample，Pinelwasobligedtoaskpermissionoftheauthoritieseventomaketheattemptatliberatingtheinsanefromtheirchains，and，notwithstandinghisrecognizedpositionasaleaderofscience，hegainedbutgrudgingassent，andwasregardedasbeinghimselflittlebetterthanalunaticformakingsomanifestlyunwiseandhopelessanattempt。Oncetheattempthadbeenmade，however，andcarriedtoasuccessf