未来病原体研究的框架

Researchonbioriskmanagementtomakeresearchwithpandemicriskmoresafe,secure,andresponsibleTherearesignificantdifferencesacrosslaboratoriesandcountriesinthemeasuresadoptedtomanagebiorisks(Koblentzetal.2023).Limiteddataexisttosupportwhetherthesedifferencesresultinameasurableimprovementinsafetyandsecurityorwhetherresourcesarebeingwastedonunnecessaryandcostlyequipment(RittersonandCasagrande2017).Historically,biosafetyandbiosecurityimprovementshavealwaysaddedontoexistingequipment,procedures,oradministrationbecausetherewerenodatasuggestingwhichspecificimprovementswereparticularlyeffective.Asdatatoinformbioriskmanagementarelacking,thefrequencyandconsequencesofaccidentsareunknown;well-informedkeydecisionscannotbemadeintheabsenceofadequateevidence.Similarly,itisdifficulttounderstandthemeansbywhichoutsidersaremostlikelytogainaccesstoalaboratoryorhowtheycouldmisusepathogens.Ifrobustdatawereavailable,stakeholderscouldidentifywhichbioriskmanagementmeasuresweretrulyworththeinvestment,enablingstakeholderstospendonlywhatisneededonsafetyandsecurityandtherestonresearch.Researchonbioriskmanagementisurgentlyneededtoimproveeffortsateliminatingandmitigatingassociatedrisks(Palmer,Fukuyama,andRelman2015).Suchresearchcouldgenerateusefulknowledgeto(1)preventlaboratoryaccidentsandmistakes(astheresearchcommunitygeneratesrealdataonwhichpracticesaresafe,whicharerisky,andunderwhichconditions)and(2)reducethechancethatmaliciousactorscanaccessknownandpotentialpandemicpathogens.Researchdatacouldinformchangestoaprotocol,policiesforaccesscontrol,themovementofequipmentwithinalaboratory,thetrainingreceivedbykeypersonnel,oraredesignofariskyexperimentalapproach.Biosafetyandbiosecuritystudiescouldhelpinformwherenewlaboratoriesofvarioustypesshouldbebuilt.Naturally,properbiosecurityandbiosafetyprecautionsentailmorethansoundlaboratoryinfrastructureandpractices.Contextmatters.Whatworksinonesettingorcountrymaynotfitwithpracticesoravailableresourceselsewhereandrunningsimulations,whilevaluable,maynotconsiderthefullspectrumofpossibilityregardingsafetyandsecurityrisks.Psychosocialandbehavioralresearchmayalsoshedimportantlightonhowdifferentactors(e.g.,laboratoryworkers)interactwithlaboratoryinfrastructureandrespondtogovernancestructuresandpolicies.ResearchtoimprovebiosafetymanagementTheWHO’sLaboratoryBiosafetyManualinformsbestpracticesforsafelyhandlingbiologicalagentsinlaboratoriesandcoversarangeoftopics,includingpersonalprotectiveequipment,biosafetycabinets,riskassessment,decontamination,andwastemanagement(WHO2020).Originallypublishedin1983,itisnowinitsfourthedition.TheLaboratoryBiosafetyManualisviewedbythescientificandpractitionercommunityasthegoldstandardforbiosafetyanditisinwideuse.Nonetheless,accidentsoccurandthereisconsiderablebenefitinbetterunderstandingthecauses.Forexample,recentlypublishedresearchdemonstrateshowfrequentlysnap-capmicrocentrifugetubes,whicharecommonlyusedtostoreandmixbiologicalsamples,splashwhenopened(Wynekenetal.2023a).Thefrequencyofsplashesfromthesetubesnomatterhowtheyareopenedsuggeststhatlaboratoriesshouldsubstitutetheseortakeadditionalmeasurestoreducesplashingandimmediatelyimplementthesesolutionstoreducerisk.Alaboratorysimulatorinwhichresearchersareobservedmanipulatingsmallvolumesoffluidandrunningmockassayscouldbeusedtocompiledataonthefrequencyofspills,splashes,andaccidents.Researchersarecompletingthefirststudiesofthistype(Wynekenetal.2023b;Wynekenetal.2023a),whichmaybegintoanswerkeyquestionssuchas:Howoftendoresearchersspill?Whatfactors(e.g.,trainingandexperience)reducethis?Importantly,thisinitialresearchhasdemonstratedthatstudiesdonebyvolunteersinmocklaboratoriesreplicatesimilaraccidentratesinrealclinicallaboratoriesthatwereconductingblindedstudiesoferror.Acriticalfindingofthisresearchisthatevenexperiencedlaboratoryresearchersoftendonotknowwhenorwhereaspilloccurred.Thisunderscorestheoften-repeatedadviceofbiosafetyprofessionalstodecontaminatetheentireworkspaceaftereveryexperiment,notjustafteraspill.Additionally,researchersarecollectingdataonthefrequency,size,andpatternofcontaminationofthebiologicallaboratoryworker;thiscriticalfirststepwillguidestudiesonhowbesttoreduceriskfromcontamination.Datageneratedbybiosafetyresearchcanalsoboostcompliancewithsaferbutinconvenientpractices.Moregenerally,basicdataarelackingforhowresearchersinlaboratoriesareexposedtoinfectiousmaterialthroughspills,splashes,andcontamination.Unlikeinotherindustries,inwhichmechanicalfailuresalonecancausecatastrophe,inbiologicallaboratories,researchersinitiateorexacerbatemostaccidents;forexample,researchersmayspillinfectiousmaterialand/orrespondinappropriatelybyviolatingquarantineorcontaminatingthemselvesduringcleanup.Inclinicalsettings,accidentalinfectionsoftenoccurwhenprotectivegear(e.g.,gloves,masks,coats,etc.)isremovedaftersterileprocedures(Mummaetal.2018).Itissuspected,butunproven,thatmanyinstancesofinfectionorcontaminationinlaboratorysettingshappeninasimilarmanner.Studiesthatdocumenthowfrequentlylaboratoryresearcherscontaminatetheirhandswhentakingoffgloves(orbreachtheirglovesduringresearch)couldimprovepracticesandprocedures.Forexamples,studiesthatcomparetheuseofasinglepairofgloveswiththeuseoftwooverlappingpairsofglovescoulddemonstratetheeffectivenessofoneortheotherstrategytoeithersolidifyornegatetheuseoftwooverlappingpairsofgloves.Similarly,studiesonwhenrespiratoryprotectionshouldbewornandwhattypeofprotectionisneededunderdifferentconditionscouldusefullyguidepracticesandprocedures.Forexample,avarietyofroutineprocedures,includingcentrifugationandflowcytometryorcellsorting,cangenerateandexposelaboratoryworkerstoaerosolsifthepropercontainmentisnotusedorifthedeviceisnotconfinedtoabiosafetyhood.Ingeneral,ifprotectivegearworkswellinmostsituationsbutnotwhencarelessorinexperiencedresearcherswearand/orremoveit,additionalinvestmentsintrainingandoversight/proficiencytestingwouldbewarranted.ResearchtoimprovebiosecuritymanagementFailuresinbiosecuritycanoccurwhenleadershipisinadequate,oversightinstitutionsdonothavetheneededexpertiseorpropermeanstoassesstheireffectiveness,ororganizationalstructuresandriskmanagementprocessesareslowtorecognizeconsequentialadvancesinscienceandtechnology(Palmer,Fukuyama,andRelman2015).Biosecurityischallengingtoinvestigateempirically,butobservationalresearchandcontrolledstudiescanbeveryuseful.Observationalstudiesintraininglaboratoriescanmeasurethefrequencyofsimilarfailures(e.g.,unauthorizedaccess,failuretoreportworrisomebehavior,ordatabasesecurityglitches).Controlledstudiescanalsomeasureboththerateofnon-compliancewitharuleandtherateatwhichresearchershidetheirnon-compliance.Withoutasignificanteffort,studiescouldgathermorebiosecuritydatageneratedintheday-to-dayconductofresearchortraining.Aresearchagendashouldalsoseektoexaminetheextenttowhichreleasinginformationaboutresearchwithpotentialpandemicpathogensmaycreateso-called“informationhazards(Relman2014).”Maliciousactorsmaymisusepublishedinformationandthereforeresearchers,funders,andjournalsshouldconsiderwhetherinformationcontrolsareappropriate.Insummary:Thereisanevidentneedtoimprovecurrenteffortsateliminatingandmitigatingbiosafetyandbiosecurityrisks.Researchersandtheirinstitutions,aswellasfundersandgovernments,shouldfundstudiesthatwillproviderobustempiricalevidenceaboutthenatureofbiosafetyandbiosecuritychallengesandtheeffectivenessofpotentialmitigationstrategies.Suchdatawouldenablemoreeffectiveriskreductionpractices.Bioriskmanagementdatacouldinformharm–benefitstudiestodetermineexactlyhowlaboratoriesworkingwithknownandpotentialpandemicpathogens,includinginresearchwithpandemicrisks,shouldbeorganizedandmanagedwithoutunnecessarilydivertingfundingthatcouldbeinvestedintheresearchitself.Notonlywillthisimprovebioriskmanagement,butusingnewevidencetoeliminatewastefulmeasureswouldmakelaboratoriesmoreefficientandsustainable.Atthesametime,bioriskmanagementpracticesshouldbereviewedtoeliminatethosewithoutevidenceofaddedvalueortoreplacemoreburdensomepracticeswithlessburdensomeones.