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JUNE 2020 Profiteering from health and ecological crises in Africa The Target Malaria project and new risky GE technologies

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Page 1: Profiteering from health and ecological crises in Africa · food sovereignty and agroecology in Africa, with a focus on biosafety, seed systems and agricultural biodiversity. The

PO Box 29170, Melville 2109, South Africawww.acbio.org.za

J U N E 2 0 2 0

Profiteering from health and ecological crises in Africa

The Target Malaria project and new risky GE technologies

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AFRICAN CENTRE FOR BIODIVERSITY – Profiteering from health and ecological crises in Africa

ContentsAbbreviations 3Keyfindings 4Aboutthispaper 5Introduction 5Keyactorsof“discovery”researchandfunding 6Populationsuppression–TheGates-fundedTargetMalariaProject 6

Phase I update 6Phase II update 10Phase III – in the (near?) future: Gene drive mosquitoes 12

Genedrivepopulationreplacementstrategies 14Work underway at the University of California 14Strong public relations and big regulatory push onto Africa 14Biotech’s investment in developing a “consensus pathway” 15Paratransgenesis 16

GM fungus designed to kill mosquitoes 16GM bacteria designed to secrete anti-malaria parasite proteins 17

Genome editing 18RNAi-based pesticides for mosquito control 18Locust infestations – the next GE target? 18US military “biodefence” projects target African crops 19

Conclusion 21References 23

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Acknowledgements

TheACBthanksSashaMentz-LagrangeandDrEvaSirinathsinghjiforwritingthisresearchpaper,aswellasMariamMayetandLinziLewis(bothfromtheACB)forvaluablecontributionsandinputs.TheACBgratefullyacknowledgesthefinancialsupportofseveraldonors.Theviewsexpressedinthispapermaynotnecessarilyreflecttheviewsofourdonors.

TheAfricanCentreforBiodiversity(ACB)isaresearchandadvocacyorganisationworkingtowardsfoodsovereigntyandagroecologyinAfrica,withafocusonbiosafety,seedsystemsandagriculturalbiodiversity.Theorganisationiscommittedtodismantlinginequalitiesandresistingcorporate-industrialexpansioninAfrica’sfoodandagriculturesystems.

www.acbio.org.za

POBox29170,Melville2109,Johannesburg,SouthAfrica.Tel:+27(0)114861156

©TheAfricanCentreforBiodiversity

ThispublicationislicensedunderaCreativeCommonsAttribution-NonCommercial-NoDerivatives4.0InternationalLicense.Thispublicationmaybesharedwithoutmodificationfornon-commercialuseprovidedtheAfricanCentreforBiodiversityisacknowledgedasthesource.Priorwrittenagreementisnecessaryforanycommercialuseofmaterialordataderivedfromthispublication.

ResearchedandwrittenbySashaMentz-LagrangeandDrEvaSirinathsinghjiProofing:LizSpargLayoutandcover:AdamRumball,SharkbuoysDesigns

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Abbreviations ACB AfricanCentreforBiodiversityBecA–ILRI BioscienceseasternandcentralAfrica–InternationalLivestock ResearchInstituteBMFG BillandMelindaGatesFoundationCBD ConventionforBiologicalDiversityCRISPR ClusteredregularlyinterspacedshortpalindromicrepeatsCSIRO AgricultureandFoodBusinessUnitoftheCommonwealthScientificand IndustrialResearchOrganisationDARPA USDefenceAdvancedResearchProjectsAgencyDEFRA UKDepartmentforEnvironment,FoodandRuralAffairsFNIH FoundationfortheNationalInstitutesofHealthGDO GenedriveorganismGE GeneticengineeringGMO GeneticallymodifiedorganismHEGAAs HorizontalenvironmentalgeneticalterationagentsIC IslandConservationIITA InternationalInstituteofTropicalAgricultureILSI InternationalLifeScienceInstituteLR LandcareResearchMRC MalarialResearchCompanyNBA NationalBiosafetyAuthorityNCSU NorthCarolinaStateUniversityNEPAD NewPartnershipforAfrica’sDevelopmentNIH USNationalInstitutesofHealthNWRC USDepartmentofAgriculture’sNationalWildlifeResearchCenterOECD OrganisationforEconomicCo-operationandDevelopmentPR PublicrelationsR&D ResearchanddevelopmentRNAi RNAinterferenceTAMU TexasA&MUniversityUA UniversityofAdelaideUNCST UgandaNationalCouncilforScienceandTechnologyUSDA USDepartmentofAgricultureVCTR Vector-BasedControlofTransmission:DiscoveryResearchWHO WorldHealthOrganizationZAAB ZambiaAllianceforAgroecologyandBiodiversity

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Key findings• Variousnovelformsofsecond-generation

geneticengineering(GE)technologies,suchasgenedrivetechnologies,genomeediting,paratransgenesisandcisgenesisareincreasingthescope,scale,depthandflexibilityofinterventionsthatcanbeperformedbythebiotechindustry,includingGEwildpopulationsandecosystems.

• Researchanddevelopment(R&D)projectsarelargelyfinancedbyEuropeanandNorthAmericaninstitutions;theBillandMelindaGatesFoundation(BMGF);andtheUSmilitaryresearcharm,theUSDefenceAdvancedResearchProjectsAgency(DARPA).

• Africaisexperiencingseveralhealthandfoodcrises,whichareaggravatedbybiodiversityloss,climatechangeandthecoronavirus(SARS-CoV-2)pandemic.Themalariaandlocustinvasioncrisesfeatureamongthose“ancient”crisesthattheGEindustryisseekingtoexploitinabidtoforceAfricaintoadoptingthesetechnologies.

• Thebiotechnologyindustryisheavilyinvestinginpublicrelations(PR)andlobbyingmachinerytoputinplacepermissiveregulationsandsecureacceptanceofthesesecond-generationbiotechnologiesfocusedonwildinsectpopulations.

• TheNewPartnershipforAfrica’sDevelopment(NEPAD)issupportinggenedrivecapacitybuildinginitiativesonthecontinent,notablywiththesupportfromtheOpenPhilanthropyProject.

• TheOpenPhilanthropyProjectandtheBMGFhavegrantedsignificantfundingtotheFoundationfortheNationalInstitutes

ofHealth(FNIH),whichinturnhasbeenrelyingontheInternationalLifeScienceInstitute(ILSI)inAfricatodeliveronitsmandatetopavethewayforfieldtestingofgenedrivemosquitoes,notablythroughtheelaborationofpermissiveregulatoryframeworks.

• ILSIisheavilyfundedbyindustryandservesasapseudo-scientificfront-group,despiteits“publicgood”façade.

• Current“discovery”researchthatisfocusedonwildinsectpopulations,fortheallegedadvancementofhealthinAfrica,pertainstothecontrolorsuppressionofmosquitoesthattransmitmalaria.BurkinaFaso,Mali,Uganda,GhanaandZambiaaretargetedcountriesofthis“discovery”research.

• GEresearchthatlooksatinsectcontrolinthecontextoffoodsecurityisfocusedoncontrollinglocustpopulations,whileDARPAisalsospearheadingresearchoninsectstodeliverageneticallyengineeredvirusthatwill“improve”cropgrowthundertheauspicesofthe“InsectAllies”project.

• AhistoricalreviewofmalariaeradicationsuccessstoriesinAfricashowsthattraditionalmethodscanbesuccessfulineradicatingthiskillerdisease.If,inthelightofnewdiscoveriesrelatedtohowtransmissionisevolving,novelapproachestocontrolmalariaarewarranted,applicationsthatarebasedonshiftingecosystemsandthatentailunprecedentedenvironmentalandhumanhealthrisksshouldbeunequivocallyrejectedbyAfricangovernmentsandsociety.Africanecosystemshavealreadyreachedtippingpoints;whatweneedistoprotectourbiodiversityandsupportdomesticstrategiestocombatmalariathatarefocusedonbolsteringhealthcaresystemsandfixingpublicinfrastructure.

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About this paperAnewwaveofsecond-generationgeneticengineering(GE)strategiesarebeingusedtoreinvigoratetheGEpushontheAfricancontinent,withdiverseprojectsbeingtargetedatprovidingtechnofixsolutionstomalariaandlocustinfestations.ThispapercomesatanopportunetimetoquestiontheGEtechnologiesbeingpromotedto“rescue”Africafromitshealthandfoodsystemcrises.Inthiscontextofclimate,ecologicalandhealthcrises,thefirstgeneeditingtechnologyknownasclusteredregularlyinterspacedshortpalindromicrepeats(CRISPR)testforcoronaviruswasgranted“emergency-useauthorisations”intheUnitedStates1.Thisillustrateshowsecond-generationGEtechnologiesovercomeregulatoryhurdleswhenemergenciesstrike.

Thesafety,ethicalandpoliticalimplicationsofecosystem-wideGEprojectshaveraisedsustainedcallsforextremeprecautionandmoratoria,inlightoftheunprecedentedscaleofsuchprojectsandadverseimpacts,andthemurkyplayersthatliebehindthework,includingtheUSmilitary.

Introduction DevelopmentofnovelGEtechnologies,suchasgenedrivetechnologies,genomeediting,paratransgenesisandcisgenesisareprovidingnewavenuesforthebiotechmachinerytoincreasethescope,efficiency,scaleandflexibilityoforganismsthatcanbetargetedforengineering,includingecosystem-wideengineeringbygenedrivetechnologies.

Itisnowwellestablishedthatindustrialfarmingpracticesaredirectdriversoftheverycrisestheyclaimtosolve(IPBES2019).Industrialisedfoodsystemshavecausedinequality,povertyandclimatechange,andareaprimarycauseofbiodiversitylossand

erosioninAfrica,whichisreachingalarminglevels.

Further,governmentsaroundtheworldhaveallowedagribusiness,theprimaryprofiteersfromtheglobalindustrialfoodsystem,toexternaliseadverseenvironmentalimpactssuchaspollution(airpollutionandco-morbiditiesthataremakingpeoplesusceptibletosuccumbingtoCOVID-19),andviraloutbreaksontoanimals,people,andhealthcaresystems.

Wantondeforestationoverthepasttwodecadescanbelinkedto31percentofviraloutbreakssuchasEbola,ZikaandNipahvirus(WorldEconomicForum2020).TheSARS-CoV-2coronaviruspandemichasbroughtintostarkreliefhowthelossofeco-landscapeshasobliteratedthenaturalprotectivefunctionsthatecosystemsplayinkeepingviralloadsatbay(Wallace2020).

However,thedisturbanceofnaturalequilibriathroughdeforestationnotonlyopensthechannelsofcontagionforpandemicsofzoonoticorigin,butisalsolinkedtootherhumaninfectiousdiseasessuchasmalaria(Walshetal.1993).TheissueofmalariainAfricacanberethoughtinthelightoftheexosystemicshiftstriggeredbyhumanactivity.Populationslivingwithinornearfragmentedforestshaveamuchhigherriskofinfectionduetoincreasedcontactwithvectorsatforestedgesandthereducedbiodiversityinthearea.Researchhasshownthathuman-vectorcontactinnewlycreatedforestedgesledtoincreasedriskofmalariaincommunitiesinSouthAmerica(Chen2015),andprojectionsindicatethatintensificationofagricultureandirrigationineastandwestAfricawillundermineeradicationeffortsbycreatingapropitiousenvironmentformalaria(WHO2020).

ThispaperbuildsontheAfricanCentreforBiodiversity(ACB)’sworkonGEtechnologiesinAfrica(ACB2018b;ACB2019a),andprovidesacritiqueofcurrentprojectsintendedforrolloutinanumberofAfricancountriesandtheplayersbehindthem,in

1. TheCRISPR-baseddiagnostickitwasdevelopedbySherlockBiosciences,abiotechnologyresearchcompanybasedinCambridge,Massachusetts.ItusesCRISPRtodetectasnippetofSARS-CoV-2geneticmaterialinanose,mouthorthroatswab,orinfluidfromthelungs.Ifthevirus’sgeneticmaterialisfound,aCRISPRenzymegeneratesafluorescentglow.Thetestcanreturnresultsinaboutanhour,accordingtothecompany(Guglielmi2020).

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6thehopethattheseriskyprojectsdonotbecomeentrenchedinourhealthandfoodsystems.WefocusspecificallyonGEwildinsectpopulations,whichareintendedtoeitherprovidehealthcaresolutionsonthecontinentorprotectfoodsecurity.

GEresearchfocusedonhealthcaresolutionsinvolvesthecontrolorsuppressionofmosquitoesthattransmitmalaria,withBurkinaFaso,Mali,Uganda,GhanaandZambiabeingkeytargetcountries.GEresearchlookingatinsectcontrolinthecontextoffoodsecurityisaimedatcontrollinglocustpopulations,whichhasrecentlyimpactedoneightcountriesinEastAfricawhenlocustsdecimatedentirefieldcropsuponswarming.Further,wealsolookatinsectsthataretodeliveraGEvirusthatwill“improve”cropgrowth(accordingtothe“InsectAllies”project).AlthoughatfirstglancethisisnotdirectedatAfrica,itnonethelessconcernsAfricancrops,suchasrice,cassava,cowpeaandfruittrees.

Key actors of “discovery” research and funding R&DofnewtechnologiesinAfricafocusingoninsectpopulationsislargelycarriedoutbyaconsortiacomprisedofAmericanandEuropeanuniversitiesandresearchinstitutions.Theseareeuphemisticallycalled“discoverylaboratories”(Carballar-Lejarazú&James2017)–withpartnershipsbrokeredwithvariousAfricanresearchinstitutionstorollout“biotechnologyinnovations”.

TheseconsortiaareusuallypresentedasbeingofequalpartnershipwithpublicresearchcounterpartsinAfrica,topromotethenotionof“nationalownership”andstaveoffcriticismofforeigninterference.ThebiggestfundersoverallincludetheUSMilitary’sDefenceAdvancedResearchProjectAgency(DARPA)andtheBillandMelindaGatesFoundation(BMGF)(ETCGroup&HeinrichBöllFoundation2018)(seeTable1).

Population suppression – The Gates-funded Target Malaria ProjectTargetMalaria,aresearchconsortiumledbyImperialCollegeLondon,whichreceivescorefundingfromtheBMGF,isthemostadvancedGEmosquitoandgenedriveproject.Itistoutedasbeingabletohavethefirstgenedriveapplicationforrelease.TheprojectistargetingfourAfricancountries:BurkinaFaso,Mali,UgandaandGhana.

Theprojecthasbeendesignedtoconductthreephasesoftransgenicmosquitoreleases,withthefirsttwophasesinvolvingtransgenicmosquitoesandthefinalphase,thereleaseofgenedrivemosquitoes.Theprojectaimstopresentresponsible,phasedreleaseswhereinformationfromphasesIandIIcaninformthefinalgenedrivereleaseinphaseIII.However,thereappeartobelimitedrelationshipsbetweenthetraitsinthethreephases.

Phase I update

Thefirstphasewasconductedin2019,involvingthereleaseof6400GE(transgenic)(non-genedrive)mosquitoesengineeredtobeinfertile,intwovillagesinBurkinaFaso(ACB2018a).

GatheringinformationonTargetMalaria’sreleasesandfutureplannedreleasesisextremelydifficult,astheprojecthasthusfarbeenshroudedinsecrecyandlittleinformationhasbeendisclosedontheTargetMalariaofficialwebsite.ThewebsitesaysthefollowingaboutthePhaseIrelease:“TheteamwillcontinuetomonthlymonitorthemosquitopopulationinthereleasevillageofBanauntilJuly(2020a),2(itisaone-yearmonitoringprotocol).ThenextstepwillbetosubmitanapplicationtotheNationalRegulatoryAgencyforasecondconstruct”(TargetMalaria2020a).

2. Ouraddition

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7Table 1. Select investments in second-generation technologies with a current or hypothesised future focus on Africa

Funder Research institution or consortium

Programme name

Focus Current or potential applicability for Africa

Value (US$)

DARPA 3consortiaofUSuniversities

InsectAllies(2016–2020)

Preventcropfailuredrivenbyclimatechangeandpathogensbyusinginsectstodeliverageneticallyengineeredvirusthatwill“improve”cropgrowthbyalteringwhichgenestheplantsexpress.

PotentialfutureapplicationsinAfricaareplausiblegiventhefocusoncropsofanagronomicsignificanceinAfrica.

45million(Kupfer-schmidt2018)

DARPA NA “SafeGenes”programme

Theprogramme’semphasisison“protecting(military)servicemembersfromaccidentalorintentionalmisuseofgenomeeditingtechnologies”.Theintentistherefore“todeveloptoolsandmethodologiestocontrol,counter,andevenreversetheeffectsofgenomeediting–includinggenedrives–inbiologicalsystemsacrossscales”(DARPAn.d.).

AlthoughatfirstglancethisisnotdirectedatAfrica,itnonethelessconcernsAfricancrops,suchasrice,cassava,cowpeaandfruittrees.

65million(Haridy2017)

BMGF TargetMalariareceivescorefundingfromBMFGandfromtheOpenPhilanthropyProjectFund.Additionalfundingtoresearchlabscomesfrom:DEFRA,theEuropeanCommission,MalarialResearchCompany(MRC),NIH,theUgandanMinistryofHealth,WellcomeTrust,UgandaNationalCouncilforScienceandTechnology(UNCST)andDARPA(TargetMalarian.d.(c))

TargetMalaria Potentialdeploymentofgenedrivetechnologiestohelpeliminatemalariainsub-SaharanAfrica.

CurrentlyunderwayinBurkinaFaso,Mali,Uganda.

75million

BMGF NA FNIH

ToacceleratetheplanningandpreparationfortheapplicationofgenedrivetechnologytothecontrolofmalariatransmissioninAfrica.

Africafocus. 9.43million

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Funder Research institution or consortium

Programme name

Focus Current or potential applicability for Africa

Value (US$)

BMGF PirbrightInstitute

Todevelopengineeredhigh-thresholdmosquitogenedrivesforcontrolofmalaria-transmittingmosquitoestolaboratoryproof-of-concept.

AssumedapplicabilitytoAfrica.

3.5million

OpenPhilanthropyProject

NA NEPAD/AfricanUnion

Developregulatorycapacityfornovelvectorcontrolapproaches,includinggenedrivemosquitoes.

SupportingregulatorybodiesinareasrelatedtotransgenicmosquitoesisaprerequisitetoensuretheadoptionsofgenedrivesbyAfricangovernments.

2.35million

BMGF IfakaraHealthInstitute(DaresSalaam)

TodemonstratesuccessfulcolonisationandgeneticallycharacteriseAnophelesfunestusasthemajordriverofmalariatransmissioninEasternandSouthernAfricansettings,toinformpotentialnovelapproachestolarge-scalemalariacontrolandeliminationefforts.

EasternandSouthernAfricanfocus.

2million

BMGF

NA EmergingAgInc.

Toincreaseawareness,understandingandacceptanceofpossiblegenedriveapplicationsforpublicgoodpurposes.Providescommunications,stakeholderengagementandstrategicsupporttoOutreachNetworkforGeneDriveResearch,whichincludesTargetMalaria.

Africafocus. 1.6million

OpenPhilanthropyProject

FNIH

“Tosupportdevelopmentofaconsensuspathwayforfieldtestingmodifiedmosquitoeswithdrivingtransgenes”(FNIHn.d.).

Africafocus. 1.22million

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Funder Research institution or consortium

Programme name

Focus Current or potential applicability for Africa

Value (US$)

FNIH UniversityofMaryland,USA

GMfungusparatransgenesis(thetoxinisderivedfromthevenomoftheAustralianBlueMountainsfunnel-webspider)testedina“mosquitosphere”financedbytheFNIH.

Soumousso,BurkinaFaso.

Unspecifiedamount

CSIRO, IC, LR, NCSU, NWRC, TAMU, UA, USNationalScienceFoundation(toNCSU;NSFIGERTgrant#000166685),andTheSeaverInstitute(toIC)

SevenorganisationsfromAustralia,NewZealandandtheUSA:3universities(NCSU,TAMU,UA);3governmentresearchorganisations(CSIRO,LR,NWRC)andthenon-profitgroupIslandConservation

GeneticBiocontrolofInvasiveRodents(GBIRd)programme

Todevelopmultiplegenedrivesystemsinmicewithlong-termgoalofreleaseofgenedriveconstructedmiceonanislandtotesteradicationofthewild,invasivemousepopulation(Campbelletal.2019)

FocusonUS/AustraliaandNZ–noreleaseyet;potentialapplicabilitytoAfricaassumedinthelongterm,dependingon“robustness”ofregulatoryframeworks.

Unspecifiedamount

TataTrusts(notUSbutwhononethelessspendtheirfundsonUSresearch)

UniversityofCalifornia,Riverside

Engineeringmosquitoessotheyareunabletocarrythemalariaparasite.WorkonmalarialvectorsforAsiaandonAnopheles gambiae(Africanvector)

“Functional”genedriveAnopheles gambiaecouldbereadyby2023.(JamesA,pers.com.heldon30October2019.)Thetargetedmosquito,Anopheles stephensi,wasspottedinEastAfrica,implyingthattheresearchoriginallyfocusedonSouthEastAsiacouldfinditsfutureapplicabilityinAfrica.

NationalInstitutesofHealth

ILSIandOECD

ILSIassignedtobuildcapacityintheenvironmentalriskassessmentofgenedrives.ElaborationofanAnopheles gambiaebiologydocumentforEthiopiainearly2019(ILSIn.d.)

FocusonGDOcapacitybuildinginAfrica.

Unspecifiedamount

Unclearsourceoffunding

MalariaResearchInstitute,JohnsHopkinsBloombergSchoolofPublicHealth

CRISPR/Cas9gene-editingtechnologytorendermosquitosmalaria-resistantbyremovingaso-calledhostfactorgene.

SupportsandfundstheZambia-basedMachamosquitocentre

Unspecifiedamount

Source:AdaptedfromETCGroup&HeinrichBöllFoundation2018

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10ItisanticipatedthatthefindingsfromthisphaseIresearchwouldbeincorporatedintothedossierthattheconsortiumintendedsubmittingfortheregulatoryapprovalofphaseII.However,basedonourresearch,itappearsasifTargetMalariamayhaveappliedforpermissiontorepeatthereleaseofsimilarGMmosquitoesastheyhadduringphaseI,ostensiblyduetofailuresconcerningthereleasenothavingyieldedtherequiredordesiredresults.Indeed,problemswerealreadypreviouslyreportedconcerningthebreedingofinsufficientnumbersfortherelease(ACB2018a).

Atthetimeofwriting,anewapplicationforarepeatedreleasehadnotbeengranted,asnoreportfromthefirstreleasewassubmittedtotheNationalBiosafetyAuthority(NBA)inBurkinaFaso.Withoutpublicaccesstothisinformation,itremainsunknownwhataspectsofthereleasefailed.CivilsocietyinBurkinaFasolamenttheirresponsivenessstemmingfromtheNBA,whichwasrepeatedlyapproachedforinformationandaccountability.Inearly2020,theACBwrotealetterincludingdetailedquestionstothedirectoroftheBurkinabeNationalBiosafetyAgency.Thisrequestforinformationwasrebukedwithastatementthattheagencyreservedinformationdisclosureto“peopleresidingontheterritory”.(OfficialcorrespondencereceivedbytheACBresearchteam).

Itishighlyquestionablewhethertheinformationanddatageneratedfromthereleasecanbeconsideredrelevantforfuturephases.Genedriveproponent,KevinEsveltfromMassachusettsInstituteofTechnologyMediaLab,isreportedasbeingextremelyapprehensiveoftheGMmosquitorelease,voicingfearsthatitcouldderailtheTargetMalariaprojectandimperilthetechnology(ETCGroup&HeinrichBöll2018).

Phase II update

PhaseIIentailsreleasesoffurtherGM(non-genedrive)mosquitoes,thistimedesignedtoproducepredominantlymaleoffspring(malebias),tosupposedlyreducepopulationnumbers.ThestrainthoughttobereleasediscalledtheAg(PMB)1strain(Galizietal.2014).

ThemalebiasmechanismusedinphaseIIwasoriginallybeingenvisagedasoneoftwostrategiesthatcanbeconvertedintoagenedrivemechanismfortheultimategenedrivereleases.Theotherstrategyistomakefemalesinfertile.However,technicalchallengesregardingtheabilitytoconvertthismalebiasmolecularstrategyintoagenedriveexist.TheTargetMalariawebsiteindicatesthat:“Progressontheself-limitingmalebiasispromising,howeveritisstillunderdevelopment”(TargetMalarian.d.(a)).Ifindeednomale-biastraitisdeployedforgenedrives,itraisesquestionsregardinghowrelevantthisphaseIIreleasewouldbeininforminggenedrivereleasesgoingforward.Itispertinenttonotethatwhileinitiallaboratorystudiesshowedhighratesofmalebias,asubsequentstudyperformedinlargecagesdesignedtomorecloselymimicwildenvironmentsshowedthattherewasupto20percentreductioninmalebias,to73–80percent(Facchinellietal.2019).Thisillustratesjusthowineffectivethemalebiastraitcouldbe,oncereleasedintothewild.Further,howtheseGMmosquitoeswillbehaveinthewildisunknown.

Nonetheless,itappearsthatTargetMalariahavedeemedthemale-biasmosquitoesreadyforfieldrelease(Facchinellietal.2019).TargetMalariaislikelytojustifythephaseIIreleaseasameanstoassesstheperformanceofmalebiasinthewild.Ifthesexdistortionratiolevelinthewilddiffersfromthatobservedinthelaboratory,theymayattempttothenalterthegenedriveconstruct.ThismayalsoinformTargetMalariaonhowmanymosquitoeswouldhavetobereleasedinphaseIIIandhowfrequently.

ItisunclearwhatthetimelinewouldbeforthissecondphaseinBurkinaFaso,thoughitseemsthataphaseIIreleaseisunlikelyiftheprojectintendsrepeatingthereleaseofthephaseIGMmosquitoes.TargetMalariawereaskedforinformationbutdidnotgivetimelinesforanyfuturereleasesordeclarewhetherphaseIImosquitoeshavealreadybeenimportedintoanycountries.

ItiscurrentlyunclearhowmanymosquitoeswouldbereleasedduringphaseII.Iftheintentionistoreducepopulationnumbers,a

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Target Malaria in Mali

WithregardtotheprojectinMali,asyettherehasbeennoreleaseofGMmosquitoes,butTargetMalariaimportedGMmosquitoes/eggsinSeptember2019.Thisappearstohaveoccurred“aftertheMalianGovernmentauthorisedtheexperiments”,thusenabling“extensivework”forthegroupinitsinsectary,whilsttheTargetMalariaentomologyteamstudiestheinteractionbetween“thetargetedspeciesandtheirendorsement”(TargetMalaria2020a).

Workinthelaboratoryseemstohavereachedanadvancedphase.DiscussionswithlocalstakeholdersindicatethattheprojectmaywellskipphaseI(arguablybasedontheinformationanddatageneratedfromthephaseIreleaseinBurkinaFaso),andgostraightforreleaseofthephaseIIGMmosquitoes.

Nevertheless,theconsortiumisfacingmajorregulatoryhurdlesinMali,as,atthetimeofwriting,theMinistryofEnvironmenthadnotissuedanyofficialcommunicationrelatingtothecompositionoftheBiosafetyNationalCommittee,asenvisagedinthebiosafetyregulations(COPAGEN2018).Civilsocietyorganisationshavestronglymobilisedagainsttheconsortium’sworkinthecountry.ThisregulatorydimensionmaywellexplainwhyTargetMalariaindicatesthatfirsttrialswillnothappeninthenextfiveyearsanditwilltakeabouttenyearsforthepotentialrolloutofanygenedrivemosquitoes.

Thearthropodcontainmentlevel2insectaryopenedinBamakoiswheretheteamisworkingonGMsterilemalemosquitoes(TargetMalaria2020).TheinfrastructureputinplaceiscapturedinapromotionalvideomadebyTargetMalaria3,whichraisesconcernsaboutthelackofstringencyofcontainmentmeasurestoensurethattherearenoaccidentalreleases.Robustandsoundbiosafetyguidelinesshouldbecraftedandimplementedtoregulatecontaineduseexperiments,topreventaccidentalreleasesofallgeneticallymodifiedorganisms(GMOs).Ithasbeenproposedthatforgenedrivemosquitoes,containmentmeasuresmustbesimilartothoserequiredforpathogensinhighsecurityconditions(TWN2019).Nevertheless,duetothepotential“highinvasiveness”ofgenedriveorganisms(GDOs),modellingpredictsthataccidentalreleasesofjusttwoGDOswillallowfortheirpotentialestablishmentintheenvironment(Nobleetal.2018).ThemeasurescurrentlyinplaceintheMaliinsectary,suchasdoubledoorsandtheuseoffanstoblowmosquitoesawayfromdoorsarewoefullyinadequate(TWN2019).

3. Seehttps://targetmalaria.org/welcome-to-our-insectary-in-mali/

Credit:wlablack/Shutterstock.com

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one-offreleasewouldlikelynotsuffice,withrepeatedweeklyreleasesbeingrequiredtoachieveanysignificantreduction,ifatall.However,somelimiteddatamaybeobtainedfromsinglereleases,suchasassessingtheextentofmalebiasandhowthetransgenesbehaveandmovethroughthepopulation,aswellasmorebasicinformationonbreedingandtransportprotocolsandsurvival.

Phase III – in the (near?) future: Gene drive mosquitoes

ItiscurrentlynotknownwhatgenedriveswouldultimatelybeaimedfortrialreleaseinAfrica.However,femaleinfertilitystrainsappearmoreadvancedinthedevelopmentandproofofprincipleversionspublishedtodate(Kyrouetal.2018).AustinBurt,professorofevolutionarygeneticsatImperialCollege,Londonisreportedtohavesaidtheir“currentplan(was)tohaveadossier(orapplication)

forfieldtestingreadytosubmitin2025”(Weiss2019).TargetMalaria’ssecondpotentialgenedrivestrategytoconvertthemale-biastraitofphaseIImosquitoesintoagenedrivehasfacedtechnicaldifficultiesandnowappearsunlikelytocometofruition.However,anewTargetMalariastudyreportsthedevelopmentofagenedrivethatcombinesthemale-biastraitsofthephaseIIGMmosquitoes,andtheCRISPR-basedfemaleinfertilitytrait(Simonietal.2020).

RelevantsitesforgeneticcontroltrialsincludetheSseseislands(Bergeyetal.2019;Lukinduetal.2018).Genedrivedevelopersaresuggestingthatislandlocationsare“geographicallyconfined”,andassuch,suitableforfieldtrialreleases.However,thisisnotinaccordancewiththeinternationalregulatorydiscourses,includingthosetakingplaceundertheaegisoftheConventionforBiologicalDiversity(CBD).Theexpertgroups

Target Malaria in Uganda and Ghana

TheresearchinUgandaisinanearlystage,withTargetMalariaindicatingthattheyarecurrently“focusingonentomologicalmosquitocollectionsfromfieldsitesonislandswithinLakeVictoriaandmainlandsites”(UgandaVirusResearchInstituten.d).Anewarthropodcontainmentlevel2insectariumwasreportedlyopenedinJuly2019attheUgandaVirusResearchInstitute,Entebbe,whereTargetMalariaisworkingonlocalwildmosquitoes(TargetMalaria2020a).ResearchinGhanaalsoseemstobeatanearlystage,whereanewinsectarylibraryisreportedlybeingconstructedattheUniversityofGhana(TargetMalaria2020a).

Credit:Pecold/Shutterstock.com

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onsyntheticbiology,wheregenedrivesarebeingdiscussed,acknowledgethatislandscannotbeconsideredcontained.ThisisimplicitlyacknowledgedbyTargetMalariaanditscollaborators(Jamesetal.2018),astheymakesuggestionsforremediationintheeventofadverseeffects,namelytheneedformasspesticidespraying.Thisisindeedludicrous,consideringthattherationaleforgenedrivesistocontrolmalariabecauseinsecticidesareunsuccessfulateradicatingmosquitopopulations,andthatinsecticideresistanceiswidespreadandontherise.Crucially,Sseseislandsarealsoinhabitedbypeople;apre-requisiteformosquitogenedrivereleasesasmosquitoesfeedoffhumans(Beisel&Boëte2013),raisinggraveconcernsabouthumanexperimentationandthehighlyunethicalnatureofsuchintendedreleases.

Intheend,thepurportedintentofgenedrivereleasesistoobviatethenecessityofrepeatedreleasesandtheheavycoststhatthisentails.TheACBhasexplainedinpreviousresearch(ACB2019b)howOxitec‘s4

releasesofGMmosquitoesinPanamaandMalaysiaintheearly2010swashaltedduetoconcernsaboutcosts,lackofeffectivenessandunacceptablerisksposed.InMalaysia,trialswereabandonedfollowingasmallopenreleaseexperimenttomeasureflyingdistancesandsurvivalrates.In2014,releasesof300000GMmosquitoesinPanamacostUS$620000,whichcomestomorethanUS$2permosquito(TVNNoticias2014).

However,itisunlikelythatinphaseIIIaonce-offreleasewouldtakeplace.TheTargetMalariateamiscurrentlyworkingouttheoptimalreleasefrequency,butitseemstheyareconfidentthattherewillbeafewreleases.Thesereleaseswillnotresultinfulleradication,butinsuppressingpopulationstosuchanextentthatitwouldbreakthecycleofmalaria.TargetMalaria’spublicationsusingcomputermodellingtopredictefficacyhavesuggestedthatregularreleasesoverseveralyearsmaybenecessary,andeventhesimultaneousreleaseofmultipledifferentversions(North,Burt&Godfray2019;Eckhoffetal.2017).Ifsuchregularreleasesareindeed

4. OxitecisaUK-basedcommercialcompanythatproducesGMmosquitoesandotherinsects.Since2009,OxitechasconductedexperimentalopenreleasesofGMmosquitoesintheCaymanIslands,Malaysia,BrazilandPanama.IthasalsoconductedasmallexperimentalreleaseofGMdiamondbackmoths(apestofcabbagesandothercrops)intheUS.OnlyreleasesinBrazilcontinueatthepresenttime(ACB2019b).

Gene drives

Thegoalofgenedrivesistobeabletogeneticallyengineerentirewildpopulationsoforganisms.ThisisachievedbyinsertingGEtoolsinsidetheorganismssothattheseorganismscarryoutGEoforganismsinthewild,ateverysucceedinggeneration,bypassingontheengineeredtraittooffspring–whereas,usingexistingGEtools,onlyhalfofalloffspringmayinheritthemodification.Genedrivesarethusdesignedtospreadandpersistintheenvironment,withtherebeingnopossibilityorabilitytorecallthemorpreventtheirspreadacrossborders.Suchtechnologiesraiseunprecedentedbiosafety,ethical,politicalandsocietalrisks.GenedrivereleaseswerehotlydebatedbythePartiestotheCBDinNovember2018,wherestrictconditionswereplacedonenvironmentalreleases.AtrecentCBDmeetings,thetechnicalexpertworkinggroupalsoacknowledgedchallengestocurrentriskassessment,recommendingnewguidancebedevelopedinordertodealwithsuchrisks.Fundamentalconcernsofpotentialtrialreleasesrelate,interalia,toGMmosquitotrialsbeingabletoco-existwithotherconventionalmalariacontrolstrategies.Inorderforgenedrivemosquitoestoestablishthemselvesintheenvironmentandspread,theyrelyonthewillingnessofhumanstobebitten,andthusareindirectcontradictionwithcurrentmethodsthataimtopreventhumanexposure(Beisel&Boëte2013).

Therearetwomainstrategiesbeingdevelopedforgenedriveapplicationsformalaria:populationsuppression,wheretheintentionistoeradicatepopulationnumbers(explainedinphaseIIIoftheTargetMalariaproject);andpopulationreplacement,wheretheintentionistomodifythemosquitoinordertorenderitunabletotransmitmalaria.

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14required,itbegsthequestionregardingthepurportedcost-effectivenessofagenedriveapproachincomparisontoexistingGMmosquitoapproaches,which,inthepast,havebeenrejectedbygovernments,duetothehighcostsofrepeatedreleasesthatrequireongoingwork,suchascontinuousbreedingoftheGMmosquitoes.

AccordingtoAustinBurt,professorofevolutionarygeneticsatImperialCollege,theircurrentplanistohaveadossier(orapplication)forfieldtestingreadytosubmitin2025(Weiss2019).

Gene drive population replacement strategies Work underway at the University of California

Thefirstproof-of-principlepopulationmodificationgenedrivemosquitowasdevelopedbyresearchersattheUniversityofCalifornia,Irvine,wheretheAnopheles stephensiimosquitowasmodifiedtoresisttransmissionofmalaria.Anopheles stephensi isanimportantvectorofmalariainSouthAsia(Sarkar2018).

TheresearchatIrvineUniversityofCaliforniatargetsAnopheles stephensi5apredominantlyAsianvector,andtheAnopheles gambiae,amajorAfricanvector.Inapaperpublishedin2017,theresearchersclaimthattheir“advancesmadeitpossibletodemonstratetheproof-of-principlethatmoleculargenetictechniquescouldbeusedtomakemosquitoesthatareincapableoftransmittinghumanmalariaparasites”(Carballar-Lejarazú&James2017:426).

Contactedonthisresearchin2019,ProfessorJamesexplainedthattheywere“combining(the)developmentofapopulationmodificationstrainwithalongsmallcageexperimentandthat(theywere)preparing

themanuscriptontheresultsnow.Thedrivecomponentworksverywellandwehavetotesttheantimalarialeffectorgenes.Weexpecttohaveafunctional‘product’withinthreeyears,butitsapplicationdependsontheoutcomesofsocialandregulatoryreview”(JamesA,pers.com.30October2019.)

Thework,however,hassincebeenpublishedandshowntoresultinpopulationcrashesinlaboratoryexperiments,becauseofknowledgegapspertainingtothegenethatwastargetedfordisruption(Phametal.2019).Thesefindingshighlightthedisconnectionbetweenthetheoreticalpromisesandtherealityofcurrentdevelopments,lackofknowledgeanduncertainties.Itexposesthehubrissurroundingthetechnicalandtechnologicalinabilitytoclearlycontrolordefinedistinctgenedrivemechanismsandapproaches.

FurtherworkisbeingundertakentodevelopAnopheles gambiaeGDOsatIrvine,althoughthisisyettobepublished.Suchastrategyappearstobeyetanotherpopulationmodificationapproach,butpublisheddemonstrationiscurrentlylacking.Nevertheless,developersarealreadyactivelyresearchingandscoutingforpotentialtrialreleasesites,includingtheComorosIslandsandSãoToméandPríncipe(Marsdenetal.2013;Plataformamedia2019).

Strong public relations and big regulatory push onto Africa

Researchersandconservationistsareseekingtoeradicateinvasivespeciesthroughgene-drivemodifiedorganismsintheGeneticBiocontrolofInvasiveRodents(GBIRd)programme.GenedrivepromotersseetheGBIRdprogrammeaspivotaltoovercomingpublicresistancetothetechnology(BoëteC,ResearcheratMontpellierEvolutionInstitute,pers.com.26October2019).Inotherwords,conservationandhealthcarearetheTrojanhorsesofabiggergenedriveagenda.Oncethepublicis“conquered”bythetechnology,thetechnologywillbeabletoentertherealmoffoodproduction.KevinEsvelt,oneof

5. WorthnotingisthattheAnopheles stephensispecieswasfoundtoinvadeAfrica–itisapparentlybeingfoundinEthiopia/DjiboutiandtheRepublicoftheSudan.TheWorldHealthOrganisationhaswarnedthatthespreadofAn. stephensiconstitutesamajorpotentialthreattomalariacontrolandeliminationinAfricaandsouthernAsia(WHO2019).

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15theforerunnersofgenedrivetechnologies,toldtheETCGroupin2016that“agriculturalapplicationsshouldwaitonpublichealthandconservationapplicationssimplybecausethebenefitsarenotascleartoordinarycitizensandwewillnotrepeattheGMOmess”(ETCGroup&HeinrichBöll2018:8).HiddenfrompublicviewistheUSmilitaryinterestingenedrivetechnologies,withDARPAbeingthebiggestfunderofgenedriveresearchintheworld(GeneDriveFilesn.d.).Thepotentialdual-usenatureofgenedrivesthusraisesurgentquestionsregardingtheirapplicationforbioweaponpurposes.

Biotech’s investment in developing a “consensus pathway”

Lending“support”totheregulatorydimensionhasbecomeakeypriorityfortheresearchcommunityandphilanthropicorganisationsfundingthisresearch.MostoftheworkdoneinthisregardstemsfromUS-fundedprogrammes.

WhatwillinterestthereaderishowtheAfricanUnion’sNewPartnershipforAfrica’sDevelopment(NEPAD),whichhasopenlystateditssupportforthedevelopmentofgenedrivesinAfrica,issupportinggenedriveregulatorycapacitybuildinginitiativesonthecontinent.

Tobeginwith,theOpenPhilanthropyProject(afoundationstartedbyacofounderofFacebook)awardedUS$2.3milliontoNEPADtosupportregulatorybodiesinareasrelatedtotransgenicmosquitoes,whichisviewedasaprerequisitetoensuretheadoptionsofgenedrivesbyAfricangovernments(TeemJetal.2019:1).Thisfoundation,togetherwiththeBMGF,havegrantedsignificantfundingtotheFNIH(anot-forprofitorganisationestablishedbytheUSCongressfocusedonbiomedicalresearch)to“supportdevelopmentofaconsensuspathwayforfieldtestingmodifiedmosquitoeswithdrivingtransgenes”(OpenPhilanthropygrant)and“toacceleratetheplanningandpreparationfortheapplicationofgenedrivetechnologytothecontrolofmalariatransmissioninAfrica”(BMGFgrant)(FNIH.n.d.).ThisillustrateshowthePRandlobbyingmachineryhavebeensetinmotiontoputinplacepermissiveregulationsonthecontinent

andsecurepublicacceptanceofthesetechnologies.

Inordertodeliveronitsmandate,theFNIHhasbeenworkingwiththeInternationalLifeScienceInstitute(ILSI)inAfrica.ILSIhasalsobeenattheforefrontoftheNEPADAgency’seffortstobuildgenedrivecapacityonthecontinent.NEPADhasrequestedtheILSIResearchFoundationto“assistinsettingtheagendaforthescientificprogramsandguideparticipantsthroughaproblemformulationexercisetoinformfutureworkonriskassessment”(TeemJetal.2019:1).Thisresultedintheorganisationhostingaseriesoffourconsultativemeetingsbetween2016and2018,focusingonbuildingcapacityinproblemformulationaroundgenedrivetechnologies.Thesefour-dayworkshops,heldinAccra(Ghana),Nairobi(Kenya),Gaborone(Botswana)andLibreville(Gabon)werereportedlyaimedatinitiating“discussionsconcerningtheprocessesbywhichenvironmentalriskassessmentsshouldbeconductedforgenedrivemosquitoes”inAfrica(TeemJetal.2019:1).TheresultsfromthispublicationarealsofeedingintotheCBDdiscussionsthatwilldeterminehowandifGDOswillberiskassessedundertheguidanceoftheConvention.TheILSIreportonthesemeetingsdescribeshowtheseworkshops“involvedadiversegroupofparticipantsrepresentingregionalhumanhealthandenvironmentalagenciesinAfricaaswellaslocalandinternationalscientistsandothergovernmentofficials.Theworkshopparticipantswerechosenbasedontheirinvolvementwithbiotechnology,malariacontrolandscientifictechnologydevelopmentinAfrica,withostensiblynoknownbiasregardinggenedrivetechnology(eitherinfavouroragainst)”(TeemJetal.2019:2).

Despitewantingtosoundunbiased,whatisstrikinginthesediscussionsisthelackofinvolvementofanyUnitedNationsorganisations,notablytheWorldHealthOrganization(WHO),whooneassumeswouldhaveaninterestintakingpartinsuchmeetings,especiallyoneconvenedbytheAfricanUnion.Probedonthisissue,theorganiserswereeitherevasiveorindicatedthatthelikesoftheWHOhadnotexpressedanyinterest(BoëteC,Researcherat

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MontpellierEvolutionInstitute,pers.com.26October2019).Althoughparticipantlistsarenotavailable,itishighlyunlikelythatthesemeetingsincludedexpertsfromthepublichealthsector,expertsinecologyandcivilsociety.

LikemanysuchUS-basedputative“philanthropicandindependentorganisations”,ILSIisheavilyfundedbyindustry.IfILSIopenlyacknowledgesthis6,itdeniesthatsuchfundingcanleadtoanyformofinfluenceandthatthis“tripartitemodel”isthebestmeanstoinformthepublicmorebroadlyandbenefitthe“publicgood”.TheworkdonebyILSIwasrecentlyanalysedandshowntoserveasoneofmanypseudo-scientificfront-groups,pushingindustryfavourablepositionstopolicymakersandinternationalbodies,undertheguiseofaneutralscientificendeavour(Steeleetal.2019).

Paratransgenesis

ParatransgenesisisatechniquethatinvolvestheGEofoneorganismtoexerteffectsonadifferentorganism.ItservesasausefultoolfordevelopersastherearelimitedspeciesthatareamenabletoGEforvarioustechnicalandbiologicalreasons.Developersarethususingparatransgenesisapproachesasanalternative,technicallysimplermeanstoexerteffectsontargetorganismssuchasmalaria.TheGEofmicro-organismssuchasfungiandbacteriaalsooffersasimplerandeasiermethodtogeneticallyengineerinsectssuchasmosquitoes.

GM fungus designed to kill mosquitoesResearchbeingconductedattheUniversityofMaryland,incollaborationwiththeBurkinabeInstitutdeRechercheenSciencesdelaSanté/CentreMuraz,Bobo-Dioulasso,onGMfungusparatransgenesisapproacheshasalreadyprogressedtoadvancedstages.A2019publicationdescribesexperimentsperformedin2015–17inBurkinaFasoin

6. https://globalizationandhealth.biomedcentral.com/articles/10.1186/s12992-019-0478-6#ref-CR14

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17enclosuressurroundedsolelybymosquitonetting(Lovettetal.2019).Theinformationprovidedinthispublicationdoesnotsatisfylegalrequirementsforcontaineduse.Thestructureinquestion,calledthe“MosquitoSphere”,7islocatedinthevillageofSoumousso.Itisaroughly6550square-footscreened-instructure,builttosimulatea“nearnaturalenvironment”.Thesphereiscomposedofsixseparatecompartments,fourofwhichcontaintraditionalWestAfricanhouses,alongwithnativeplantsandbreedingsitesformosquitoes.

TheGMfunguswasmodifiedtoexpressaspidertoxinfromtheBlueMountainsfunnelwebspider,atoxinthathasbeenunder-characterisedforpotentialriskstohumanhealth.Experimentswereapprovedas“semi-field”trialexperiments,atestingphasethatisnotmentionedintheBurkinabebiosafetylaw.Indeed,thereisnosuchconceptinacceptedbiosafetyparlanceorregulation,callingintoquestionthelegalityofthisexperiment.

Releasesintothe“semi-field”trialconditionsalsoraiseconcernsaboutpotentialescapeoftheGMfungus.Thereappeartobenomeasuresinplaceforresearcherstowearprotectiveclothing;orfortheearthtobecoveredtopreventGMfungalsporesfromestablishing;orothercontainmentmeasuresthatshouldhavebeeninplace.Theresearchersclaimthetechnologyisnowclosetofieldreadyandprogressedsufficientlyforfieldapplication(Lovettetal.2019),thoughnoinformationappearstobecurrentlyavailableonwhereanopenfieldmaytakeplace.

GM bacteria designed to secrete anti-malaria parasite proteins AdditionalparatransgenesisvectorcontrolstrategieshavebeenunderdevelopmentbytheJohnsHopkinsBloombergSchoolofPublicHealth’sMalariaResearchInstitute.GMbacteria(anon-pathogenicSerretia Spbacteria)fromvectormosquitoeshavebeendevelopedandwerepublishedin2017.TheaimofthisworkistousegutGMbacteriatosecreteanti-malariaparasiteproteinsthatinhibititsdevelopment(Wangetal.2017).

Asanextstageoftheresearch,theintentionistotestthegeneticallymodifiedmosquitoesandbacteriatoassessthemoutsidethelabina“natural”environment.ThemosquitowasthereforeintendedforexporttoinsectariesinZambia,whereJohnsHopkinsBloombergSchoolofPublicHealthhasrecentlybuilta“mosquitohouse”atMachainordertoproceedtothenextphaseoftestingthemosquitoesinlargerspacesthatmorecloselyreflectenvironmentalconditions(JohnsHopkinsBloombergSchoolofPublicHealthn.d.).

In2018,theZambianNBAgaveitsapprovalfortheimportationandresearchona“geneticallyengineeredsyntheticbacteriafromvectormosquitoes”(NationalBiosafetyAgencyofZambia2018)buttheprojectappearstohavebeenhaltedin2018duetoUSregulatoryhurdleswithregardtoexportingtransgenicorganismsfromtheUS.Suchexportationrequiresexportapproval,whichwasnotobtainedforthiswork.Theprojecthasthusbeendelayedforareportedthreeyears.Itappearsthattheworkmaymovetocountriesalreadypursuingtransgenicmalariawork,suchasthoseinvolvedintheTargetMalariaproject,namely,BurkinaFaso,Ghana,MaliandUganda(ZambiaAllianceforAgroecologyandBiodiversity(ZAAB)Secretariat,pers.com.February2020).

TargetingtheTsetseflywithparatransgenesisTsetsefliesareanothertargetfornewGEtechnologies.However,tsetsefliesarenotamenabletoGE,duetothenatureoftheirviviparous(givebirthtoliveyoung)reproductivesystem.TsetseflyparatransgenesisapproachesappeartobeattheearlystagesofR&D,withsuggestionsbeingmadetogeneticallyengineergutbacteriatodisrupttrypanosometransmissiontohumans,whichleadstotrypanosomiasisandChagasdisease.Noproof-of-principlestudiesappeartohavebeenpublisheddemonstratingtheuseofsuchbacteria,butstudieshavebeenperformedtoidentifypotentialbacterialspeciesthatcouldbethetargetforfuturemodifications(DeVooghtetal.2018).The

7. The“MosquitoSphereisvisiblehere:https://www.eurekalert.org/multimedia/pub/222526.php

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18workhasbeenperformedbyresearchersattheInstituteofTropicalMedicineAntwerp(Belgium),fundedbytheEuropeanResearchCouncilandajointFoodandAgricultureOrganization(FAO)/InternationalAtomicEnergyAgency(IAEA)project.

Genome editing

JohnsHopkinsBloombergSchoolofPublicHealth’sMalariaResearchInstituteisaninstitutionthathasbeenattheforefrontofgeneeditingresearch,focusingonmosquitoes.Theirspecificresearchfocuseson“CRISPR/Cas9gene-editingtechnologytorendermosquitoesmalaria-resistantbyremovingaso-calledhostfactorgene”(Dimopoulos,ascitedinJohnsHopkinsBloombergSchoolofPublicHealth.n.d.).GenomeeditingisanewGEtechnologythattargetsspecificregionsofDNAformodification,unlikestandardexistingGEthatreliesoninsertingDNAintorandom,unchosenlocationsinanorganism’sgenome.

WorkhasbeenpublishedshowingthetargetingoftheFREP1geneandtheresearchisfocusedondeletingitinAnopheles gambiaemosquitoes(seebelow),inordertomakethemosquitoesresistanttomalariainfection.SupportforthisresearchwasprovidedbytheNationalInstituteofAllergyandInfectiousDiseases,theBloombergPhilanthropies,Centre national de la recherche scientifique(CNRS),theFrenchNationalInstituteofHealthandMedicalResearch(Inserm),theUniversityofStrasbourg,theFrenchNationalResearchAgencyandtheJohnsHopkinsMalariaResearchInstitute(Dongetal.2018).

ZambiahasinrecentyearsbeenundertremendouspressuretorelaxitsrobustBiosafetyActof2007,includingashiftawayfromtheprecautionaryprincipleandremovingprovisionsonliabilityandredressinordertoenableexperimentationwithGMOs(ACB2017;Mutamba2018).Inlate2019,Zambia’sGMOregulatorhadgrantedlicencestofourcompaniestoimportproductscontainingGMOs,despitestrongdomesticresistance(Shilangwa2019).

RNAi-based pesticides for mosquito control

TheuseofRNAinterference(RNAi)productsisbeingenvisagedformosquitocontrol,withpotentialapplicationsinAfrica.ResearchpublicationshavedemonstratedusingRNAiinproductssuchaspesticides(Bonaetal.2016)orforreversingpesticideresistanceinAedes aegypti(Chenetal.2019)andAnopheles stephensispecies(Negrietal.2019),thelatterbeingpresentinAfrica.FieldtrialsofRNAitreatedlarvaehavealsoalreadybeentestedinBrazilonAedesmosquitospecies,whereRNAiwasusedinordertoinducesterility,asanalternativetoradiation,whichisnormallypractisedforSterileInsectTechnique.Currently,theredoesnotappeartobeanyapplicationsbeyondtheresearchphaseonAfricanmosquitospecies.

Locust infestations – the next GE target?

The2020locustinfestationsoftheEastAfricanregionhavepromptedcallsbyGEproponentsfortheuseofGEMetarhiziumfungusasasolution.Unsurprisingly,theGMpromotingCornellAllianceforSciencemediawebsite,fundedbytheBMGF,hasrecentlycalledforsuchapproaches(AllianceforScience2020).Non-GMfungalpesticidesarealreadycommercialisedforsuchuses,butthewebsitepromotesGEapproachestomakethemmoreeffective.ThisrepresentsthesametypeoftechnologytrialledinBurkinaFaso(seeabove).

ChinesemediahasalsoreportedthatChinesefactoriesarealreadyproducingthousandsoftonnesofMetarhiziumforexport,reportingthat“Metarhiziumisagenusoffungiwithnearly50species–somegeneticallymodified–thatisusedasabiologicalinsecticidebecauseitsrootsdrillthroughtheinsects’hardexoskeletonandgraduallypoisonsthem”(SCMP,2020).However,noofficialinformationonanyGMfungusproductorregulatoryapprovalsappearstobecurrentlyavailabletoverifythesereports.TheInternationalInstituteofTropicalAgriculture(IITA)isalsopushingconventionalGMcropsasasolutiontothelocustinvasionplaguingtheHornofAfrica(Sangiga2020).Suchmediareportsserveas

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aforewarningthattheGMindustrywilltrytotakeadvantageofthiscrisisinordertoprofitfromit,andrushthroughregulatoryapprovalsforGMstrategiesaspurportedsolutions.

Thesearealarmingtrends,especiallyastherelationshipbetweenclimatechangeandtheunprecedentedlocustcrisisplaguingEastAfricahasbeenestablished(UnitedNationsEnvironmentProgramme2020).Locustswarmsareknowntobemoreactiveinhotterconditions,buttheycanalsobetriggeredbywetterthanusualconditions.FromOctobertoDecember2019,theHornofAfricaexperiencedupto400percentnormalrainfall,whichbroughtonmassiveswarmseatingtheirwaythroughcrops,inaregionthatisalreadyfoodinsecure.Itisfearedsuchphenomenamightbecomemorefrequentwithachangingclimate.

US military “biodefence” projects target African crops

Environmentalengineeringapplicationsarebeingdevelopedintheuseofvirusestodelivergenomeeditingmachinerydirectlytoorganisms.Termed“horizontalenvironmentalgeneticalterationagents”(HEGAAs),theyarefundedbytheUSmilitaryresearcharm,

DARPA.UndertheauspicesoftheInsectAlliesproject,thestatedgoalontheirwebsite8istodevelop“countermeasuresagainstpotentialnaturalandengineeredthreatstothefoodsupplywiththegoalsofpreservingtheUScropsystem”.Citedexamplesofthreatsincludeclimatechangeissues,suchasdroughtandflooding,pathogensandfrost,aswellas“threatsintroducedbystateandnon-stateactors”(DARPA2016).AsunderlinedbyawebsitealertingtothedangersoftheInsectAlliesprogramme,“whatmakestheDARPAInsectAlliesprogramuniquecomparedtoallearlierGMvirusprogramsisthatitistheveryfirstprogramtoproposeorfundthedevelopmentofHEGAAviruses.ThesehavethecapacitytoperformGEintheenvironment(thismightalsoincludeseedsifthetargetspeciesisaplant)”(TWN2019;Evolbion.d.).

TheDARPAworkplanpublishedin2016,however,describesitsaimsasgoingbeyondmodifyingtheUScropsystem,toincludecropsof“globalagriculturalimportance(includingrice,cassava,cowpea,treefruits,etc.)”(DARPA2016).Infact,theoriginalcallforfundingexplicitlystatesthattheDARPAresearchexcludesworkonsocalled“modelplants”(suchastobacco)andshouldonlyfocusonagronomiccrops.

8. https://www.darpa.mil/program/insect-allies

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20DARPAstatesthatsuchatechnologyprovidesanalternativetopesticideapplication,slashandburn,selectivebreedingandquarantinethatwouldbeemployedforrapidlyemergingthreats.Thefocusoncropssuchasrice,cassavaandcowpea,whicharestaplecrops,keytofoodsecurityinAfrica,combinedwiththementionofasolutiontoslashandburn,raisesalarmbellsasitclearlypointstothepotentialapplicationofsuchtechnologyontheAfricancontinent(butothersoutherncontinentsaswell).

TheapplicabilityoftheInsectAlliesapproachwasexplicitlystatedbyBlakeBextine(DARPAprogrammemanagerforInsectAllies),whoina2019articlewasreportedtounderlinehowusefulinsectalliescouldbeincombattingpestslikethefallarmyworm(Spodoptera frugiperda).Heisfurtherquotedassayingthat“theseproblems(thatis,thefallarmyworm)canpopupveryquicklyandsometimes(inan)unforeseenmanner”(Partan&Goldstone2018).Thishintsatthefactthatdevelopersinherentlyassume(andhope)thatanemergencysuchasthefallarmywormoutbreak,whichobviouslyposesafoodsecuritythreat,wouldwarrantsuchbiotechsolutions,leadingtooverridingregulatoryobstructionsquickerthanusual.ThisechoesatechniquethatwasdescribedbyNaomiKleininherbooktheShockDoctrine,whichdepictshowshocksofanykind(cataclysm/economiccrisis)havehistoricallycreatedfertilegroundforprivatesectorenterprisestoappropriatespacesandoverhaulsocieties.

ScientificexpertshavepublishedconcernsonthelimitedscopeprovidedbyHEGAAstoenhanceUSagriculture(Reevesetal.2018).Instead,InsectAlliesprovidesafarmorerealisticopportunityfordual-useapplications,developingtargetablebioweapons.Indeed,itisfarmorefeasibletodestroygenesandthuskillorganismsthanitistoinsertoreditgenesinordertomodifyacomplextraitsuchasdroughttolerance(Maoetal.2008).Reeves’(2018)commentonthisisthat:“It’sveryhardtoimagineyouwouldn’tverymuchearlierdeveloptheknowledgenecessarytodevelopbiologicalweapons,whichcouldeitherkillgrowingplantsorsterilisegrowingplants”(Partan&Goldstone2018).Thelogisticsofthistechnologyasanagriculturaltoolisalsocomplex,requiring

rapidresponsestothreatsthatwouldrequireglobalinfrastructure,suchasinsectaries,continuousbreedingprogrammes,andcorrectdevelopmentofvirusesforeachupcomingthreat.

Usinginsectstospreadgenomeeditingmachinerytowildorganismsremovesallpredictabilityforcontrollingdispersalinagriculturalsettings,whereavarietyoffarmingpracticestendtoco-exist.Thisprojectalsoraisesgraveconcernsoverthecontrollability,persistenceandtemporal-spatialspreadofinsectvectors,theirassociatedvirusesandtheresultantgeneticmodificationsintheopenenvironment.

WhendecryptingwhichinstitutionswereinvolvedasDARPAInsectAlliescontractors,researchersinvestigatingthedangersofInsectAlliesidentified,amongothers,theVirusesandInsectsasPlantEnhancementResources(VPER)programme(theirinvolvementinDARPAwasannouncedin2017).TheconsortiumincludestheBoyceThompsonInstitute,IowaStateUniversity,theUniversityofMinnesotaandUniversityofCaliforniaDavis(meanttohostthefinalphaseofthetesting“intightlycontrolledgreenhouses”).Thisresearchcomponentfocusesonmaize,withthetargetinsectsmentionedbeingaphidsandleafhoppers,withareportedbudgetof$10.3million.Twootherconsortia,composedofAmericanuniversities,arecarryingoutsimilarresearch,withafocusonmaizeandtomatoes(Evolbion.d.).

InsectAlliesistocometoaclosein2020.SinceDARPAisafundingagency,itsroleisnottoconcretiseitsresearchintoaproduct;theonuswillbeonanotheragency,company,ornon-governmentalorganisationtopickuponthetechnology,andaccordingtoDARPA’sspokesman,theirhopeisthattheUnitedStatesDepartmentofAgriculture(USDA)willtakeoverfromthere(Partan&Goldstone2018).TheACBhasextensivelydocumentedhowtheUSDAhasbeeninstrumentalinpushingthebiotechnologyagendainAfrica,startingwithGMOsinthe1990s.Thereislittledoubtthat,shouldtheUSDAtaketheleadonconcretisingthisresearchintoprojects,Africawouldverymuchbeonthemap.

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ConclusionSecond-generationGMOsarebeingfiercelypromotedascuttingedge‘innovations’toaddresshealthandecologicalcrisesonthecontinent.Therealityhowever,isthatthetechnologiesbeingpromotedemanatefromtheverysystemsthathavecaused/aggravatedthecrises.Forexample,philanthro-capitalistactorssuchastheGatesFoundationarefundingthesetechnologieswhileatthesametimeinvestingdirectlyinchemicalcorporations,agribusiness,weaponsproducersandfood/retailindustriesthatarecreatingtheproblemstheypurporttoaddress(ShawandWilson,2019).

Systemsofextractionforprofitandwantonplunderarenotnovel,butarerootedincolonial,capitalistsystemsbuiltoffhumanandenvironmentalexploitationthathasbroughtustoourcurrentdaycrisesofgrosseconomicinequalities,environmentaldestructionandcollapsinghealthcaresystems.AswitnessedwithSARS-CoV2,neoliberalapproachestohealthintheUKandUShaveresultedinsomeoftheslowest,mostineffectiveandfatalresponsestothepandemicintheworld(Dalglishetal.2020).Scientistsandpractitionersinvolvedinsecond-generationGEresearchconstruegeneticengineeringresearchinthefieldofhealthasthebestmannertosecureconsentandovercomepublicresistancetogeneticcontroltechnologies(Boëte2019,pers.Com).Inotherwords,healthcareisoneoftheTrojanhorsesofbiggerandmoreambitiousGEtechnologyagendas,withthepromotersofsecond-generationtechnologiesbeingextremelycautiousnottorepeatthesame“mistakes”madebyMonsantoetal,(whentheyaggressivelyforcedfirstgenerationGMOsontotheworld)(EsveltascitedinETC&HeinrichBöll2018:8).

Whatisbeingoverlooked,isthatAfrican(andother)scientificsystemsprovideahugeamountofmedicalknowledgethathasandcontinuestogetappropriatedandfunnelledintobiomedicalandpharma-basedapproachestohealthcare.

ThecurrentCOVID-19crisisisfracturingthemyththatglobalhealthexpertiseistobefoundprincipallyinNorthAmericaand

Europe.AsrecognisedintheBritishmedicaljournalThe Lancet:“COVID-19isgivingthelietoprevailingnotionsofexpertiseandsolidarity.TheglobalhealthmodelisbasedinlargepartontechnicalassistanceandcapacitybuildingbytheUS,theUK,andotherrichcountries,whoseresponsehasbeen“scleroticanddelayedatbest”(Dalglishetal.2020).TheBritishmedicaljournalfollowssuitinarecenteditorial(Kickbuschetal.2020),statingthat“Covid-19hastaughtusthathealthisthebasisofwealth,thatglobalhealthisnolongerdefinedbyWesternnationsandmustalsobeguidedbyAfricaandAsia”(Kickbuschetal.2020),withtheWestneedlesslylosinglivesasaresultofhubrisandfailuretolearnfromothernations.

Asearlyas2008,DrArataKochi,formerDirectoroftheWHOMalariaProgramme,releasedamemoinwhichhecomplainedaboutthestrongholdexertedbytheBMGFonmalariaresearch,pointingoutthatthedebateisbeingstifledandresearchisbiasedinfavourofnewtechnologyandnewdrugs(DonaldandMcNeil2008).Thereisdemonstrableevidencethattraditionalmethodsforaddressingmalariaonthecontinentoverthepasttwodecadeshavebeenhighlyeffectiveincurbingmalaria-attributedfatalities.InsecticidetreatednetshavebeenreportedtooutweighanyotherinterventionsinpreventingmalariatransmissioninAfrica,accountingforanestimated68percent(62-72percent)ofthedeclineswitnessedby2015.Indoorresidualsprayingandartemisinin-basedcombinationtherapyhavefurthercontributedsignificantlytoreducingprevalenceandincidencewheretheyhavebeenimplementedatscale(Bhattetal2015).ThisisnotsomethingTargetMalariaandtheBMGFwouldlikethegeneralpublictobeawareof.ItalsoseemsthatsolutionsthatarebasedonNature’sownweaponrycouldofferlessriskyprospectstocurbthedisease,withthediscoverythatnaturallypresentbacteriainKenyanmosquitoesareabletopreventmosquitoesfrombeinginfectedwiththeparasiteinlaboratorysettings(HerrenJKetal.2020).Assetoutinthispaper,imperialistprojectsarenotinterestedinbetteringthelivesofAfricans.Anyreleaseofgenedrivemosquitowouldservethesolepurposeofcreatingaprecedentforothersuchsimilar

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technologicalapplicationselsewhereintheworldandinothersectors.Furthermore,theforeseenrecrudescenceoflocustinvasionsintheHornAfricawillbeexploitedtopushGMcropsondepletedcountriesinEastAfrica.Philantro-capitalistventuresaresettoprofitfromthemanyhealthandecologicalcrisesinAfricafordecadestocome.

Asalreadyexperienced,GEtechnologiesaredoomedforfailure.Theserepresentinessence‘epistemiccolonisation’(Navdanya,2020)anddenythediversityofknowledgethatisrequiredtosustainbiodiversityandsustainablefoodproduction.Westernsciencehaslongbeenusedtojustifyimperialistprojects,aswellasprovidethenecessarytoolsfortheirapplication,allthewhiledenigratingandsimultaneouslyappropriatingotherscientificsystemsintheprocess.

Mostimportantly,ourAfricanleadersneedtoplayapioneeringroleincurbingecosystemsdestructionandcollapseandbiodiversityerosionandlossonthecontinent.(IPBES2019).Thiscallforavertingtheecologicalcrisisisnotdrivenbyapure“conservationist”vision;itisinextricablytiedtohumanhealth.ThecurrentCovid-19crisishasverybluntlyshownthatthedisruptionofthebufferrolesthathasbeentraditionally

playedbyforestrysystemsmeansthatpotentialviraltransmissionfromwildlifeisnolongercontained(Wallace2020).Theupsettingofequilibriathatnatureprovidesthroughdeforestationisalsolinkedtootherhumaninfectioussuchasmalariaandleishmaniasis(Walshetal.1993).Populationslivingwithinornearfragmentedforestshaveamuchhigherriskofinfectionduetoincreasedcontactwithvectorsatforestedgesandthereducedbiodiversityofthearea(Chen2015).Resourcescouldbefarbetterspentifdedicatedtoalleviatingtherealissuesofoverrelianceonecosystems,deepeninginequalities,derelictinfrastructureandlackofsanitation,whichifaddressed,wouldmakeamuchgreaterdentinchangingmalariaendemicityinsub-SaharanAfricathantheriskyanddangerouscolonialprojectssupportedbytheGatesFoundationandforcedontoAfricabyactorssuchasTargetMalaria.

Aswithfirst-generationGMOs,second-generationGMOswillcontinuetodivertattentionandinvestmentawayfromsovereignsystemicsolutionstocombatecological,economicandhealthcrises.Suchsolutionscanprosperfromacleanbreakfromthefailedpromisesoffirst-andsecond-generationGMOsandtheirunderlying,failedideologies.

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Profiteering from health and ecological crises in Africa

The Target Malaria project and new risky GE technologies