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Vaccineswouldobviouslyprovidetheirgreatestbenefitinpreventinginfectionwithoncogenicvirusestransmittedhorizontallyafterbirth.However,eventhepossibleverticaltransmissionofhypotheticalneoplastic.agentsdoesnotruleoutapotentialbenefitfromvaccines.Nononcogenicvirusesmayfunctionasessentialcofactorsinexpressionofneoplasia,andimmunityagainstsuchsecondaryagentsmightpreventexpression·oftheneoplasticstate.Additionally,antibodyorcellular·immunitymaybeenhancedbyvaccinationwithhomologousvirusinvirus-dependent~ancer.ObviouslythisresearchinvestigationisoffundamentalimportancetothegoalsofSVCPandcanmakeuniquecontributionstothetotalprogram.ProposedCourse:The.investigatorswilldevoteinitialeffortstodevelopingmethodsforpropagation,purification,concentrationandspecificquantitationofcandidatevirusessuspectedorshowntocausecancerinman.Atthe·presenttime,investigationswillbefoc.useduponherpes-type(DNA)virusesand"B"and"C"type(RNA)particles.Parallelstudiestoevolveliveattenuated.andkilledvirusvaccinesinappropriateanimalmodelsystemsl.'i11beconducted.Particularattentionwillbegiventodeveloping·andapplyingoptimalmethodsforviralattenuation,viralinactivation,viralquantitation,vaccinesafetyassessment,andvaccinepotencyassay.DateContractInitiated:March1,1971
"Combinethesetwodiseases-felineIcukemiaandhepatitis-andyouhavetheimmunedeficiency"syndromctodaycallcdAIDS,saidCDChepatitisBchief.Dr.DonFrancisattheonsetofthepandemic.Asstatedintheabovecontract,Merckinvestigatorsdeveloped"methodsofpropagation.purification.concentration,andspecific·quantitation·ofcandidatevirusessuspectedorshowntocausecancerinman."Amongthesewasthe"KTstrainoffelineleukemiavirus(FLV)"concentratedto"IO~\'irusparticles/ml:'This"C'type(RNA)tui110rretrovirus.accordingtoleadingexpertOr.GeorgeTodaro.\vasanothermanmadevirusthatapparentlye\'olvedduring·similarcancervirushybridizationstudies,asinthecaseoftheRD
114
cat/humanmutant.and/orvaccineexperi-.mentsinvolvingcrossspt:ciestransfersofinfectiousparticles.Asstatedabove.inresponsetotheselaboratorystudies,authoritiesknewasearlyas1970that"non-oncogenic\'irusesrriayfunctionasessentialco-factorsinexprt:ssionof
.
neoplasia(cancer).andimmunityagainstsuchsecondaryagentsmightpreventexpressionoftheneoplasticstate,"Forthisreason.thesecancervinisandvaccinestudiesfocusedontheherpestype(DNA)viruses.especially
EB\'.
QS
infectiousco-factorstor~glllatcrctro\·iralcarcinogenesis~:l!ong\vithotherchc::mica!immunemodulators,E\·idcnce·isfim1lycstablishtd~therefore.thatthehepatitisB\'irusand\'accineresearch.conductedsimultaneullslvinN'iCandCentralAfricabet\Ve~n1970and1975undertheprecedin~Bi;neti~sandf\1crckcon-.tracts.invoh'inginfectedmonkeysandchill1panze~~usedforvaccineproduc.tion.wasextremelyriskyZlndcircumstantiallylinkedtotheAIDSpanckmic.Forprimarysourct:sandadditi()nalbackgroundregardingthisiml'DrLlntlh6is~cc:
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US-USSRAgreement.Af1emoranctllmof.Understandingforcooperationinthe'!
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ofthemicrobiology,irrrnunoloQY,andmolecularbiologyofcancerviruses.·'I~·firstsigned
on
November18,i~72.The11emorandumestablishedproceduresri~rjointstudiesthroughtheexchangeofinfonnation,.iTtaterialsandscienti;':betwecnthehiOcountries.
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Delegatesexpressedinterestinconductingcollaborativestudiesinthe.followingareas:(1)studiesofvirusesisolatedfromhumantisslJesin,;cl!cultureorinanimalsandtheirpossibleroleinthepathogenesisofh,",.ll1neoplasia;(2)continuationofstudiesonnon-humanprimatevirusesas'
[ill'"
relatetohumancancer;(3)studiesontheroleofvirusesintheindu(~i"'lofhumanbreasttumors,inc1udingcontinuationofstudiesonI1PMVandrcl,)"d
viruses;
(4)studiesoncocarcinngenesisuvirul/vi:'al,virol/cl:e:::icill.or:.;viral/hormonal;(~)characterizationofnucleicacid~andtheirroleill1.1'"inductionofanimalandhumancancers,particula;-lythedetectionoftra'1s·formingsequencesin.cellularnucleicacidsandmoleculargeneticstudie·.withDNAfromhumantumorcells;(6)studiesonviralproteinsasprobocforviral
gene
expressioninanimalsandhun\1ns;and(7)studiesononC"':",!,;virusesimportanttohUf1lJnecology.e.g.,thosederivedfrombovine.a:,i'III,Asagreed,thefifthm~etingoftheUS-USSRJointflorkingGroupon
Cancer
Virology,Co-ChairmenOr.J.B.lIoloneyandProfessorV.ltZhdanov,tookplaceattheNationalInstitutesofHealth,·Bethesda,r·:aryland,USA,onOctober26-28,1977.AtasymposiumheldonOctober27and28.membersofbothdelegationsandinvitedspeakerspresentedrecentst~diesincancer
virology.
Themainemphasisofthismeetingwasgiventoreviewingtheprogress'ofcurrentcooperativeeffortsandassessingtheproblcmofrecombinantDNAresearch.Or.r~ichaelCrawford(UniversityofKansas)presentedpreliminary'resultsofastudytodeterminetheroleofgeneticfactorsinanoutbreakofleukemiainbaboons.This\lork,conductedjointJ~:bylaboratories
in
theUSAandintheUSSR.isanexcellentexampleofthecooperativeresearcheffortssponsoredundertheUS-USSRAgreement.TheChairmenofbothSidesreportedontherecorrrnendationsmadeintheMemorandumofUnderstandingoftheJointCorrmitteeonf1a1ignantNe~p
1015
i,iheldinHoscow,USSR,September,1977.TherecollJ11endationsincluded:(1)discussing,indepth.cooperativestudiesonrecombinantDNAresearch,2)increasingtheprogrampartiCipationofotherUSSRinstitutions,inparticulartoincludetheInstituteofliolecularBiology,lioscow,(3)C~n·ductingexchangesofscientistsonlyundertheauspicesoftheCancerVirologyProgramunderthetopicofMaIi9nantNeoplasia,USA-USSRHea1thAgreement,and(4)encouragingtheuse'ofsmallworkinggroupmeetiogs
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subjects'ofintenseinterest...
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Title:C~ntorjal?~eserlation~nd:Jevel~!re'ntof
°ei2renc~·Grade
T:P'.orVirusesContractor'sPro;ec:~irec:ors:i;r.Charles~..~ldr;o
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~fficer'S
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Dr.
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Dr.
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~~~tives:To~iclcg;cal1lc~.!rac:eri~g
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historicallytracet.~eorigin
ofse1ec:e1
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Logisticshascontinued.Dat.!on
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Cire:tedDNApoly:::erase
offiverurfne!r.d~;Jrl"..ate
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anti;~nsugses~~s~'~ng
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squirrelronkeyr-etr:::yir~sand1'a5=n-Ffize~\l;)nkeyVir;s.The:entrac~'
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Ledem"..g.cC'minjt1NlCSth3,",igclI-t.:.:cn;,dued~e:lSC'r.~u~b~';Urrl\109biologic"1We3p<'ns.incluJing!e·A=iir.-dt:cingJ/1d.\ID1ik~
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iruses
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potentialcncmics.includingR'-I:>!i311ai->.duir:!!ill<CddWir.Dr.L~l!ert'<:n;(;l'"nila,iC'n.thcSenalcRicglcR~p<'n\'nL"eGuli
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Delegationfleetings:.November,1972November,1973Nay,1974l1ay,1975
June.
1976
October,1977September,1978flosCOli,USSRBethesda,USA(Subcol1'mittce).r~oscow,USSRBethesda,USASukhumi,USSRBethesda,USARi9a.latvianSSR
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Figure.16.5.US-USSRAgreementContinued
TOU.S.(continued)INSTITUTIONS·VISITEDDr.1.KryukovaGamaleyaInst.,.MoscowProf.S.M.KlimenkoIvanovskyInst.,MoscowDr.E.BagleyKievInst.ExperimentalandClinicalOncologyDr.Z.ButenkoKievInst.ExperimentalandClinicalOncolqgyDrS.A.Novakhatskiy·IvanovskyIhst.,MoscowDr.FelixFilatovIvanovskyInst.,MoscowDr.·L:B.Stepanova.Dr.O.B.KdrchakMoscowResearchInstitute.ofViralPreparationsProf.·I.F..SeitzPetrovInstituteofOncology,Leningrad
Dr.BorisLapir.
Director,Inst.for·ExperimentalPathologyandTherapy,Sukh~miFebruary,1976September,1976
.0
March,1977March,1977May,1977September.,1977November,1977April,1978September,1978M.D.AndersonHosp.(Dr.BO'ilen);MichiganCancerFdn(Dr.Rich);'NCIscientists;Rockefellerlnst.(Dr.Hanafusa)NC!scientists;Inst.CancerResearch(Dr.Blumberg).NCIscientists;F.HutchinsonCancerCtr(Dr.Hakomori);Sloari-KetteringInstitute(Dr.Sonnenberg)NCIscientists;laboratoriesofDrs.Spiegelman,~layyasi.W.Moloney,E.CronkiteUni'versityofChicago(Dr.B.Roizman)NCILaboratoryofViralCarcinogenesis,ViralOncologyProgram
NCI(Dr.Galll\);USC(Drs.
McA11ister
and
Vogt);UCLA·(Baluda);Sl~anKettering(Dr.Benc!ich)NCIscientists;SloanKetteringlnst.(Dr.Moore.Jankowsky);DeltaRegionalPrimateCtr(Dr.Gerone).
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.Dr.FelixP.Filatov,Se;liorScientifi~Researcner,IvanovskyInstitut~ofVirology,~·joscow,spenttl1ree-and-one-ha1fmonthsinthelaboratoryofDr.BernardRQizman~UniversityofChicago.Thepurposeofhi~exchangeyi~itwastogainexperiencein(~)preparativepurificationofHerJes
Theaboveagreementincludesapartiallistofresearchers.includingDr.RohertGall\1
\)f
theNC!.whotradedthemostadvancedmethodsandmaterialsinthefieldsofmolecularbiology.bacteriologyand\·irologyduringtheColdWar.InclutkJwasthe"brge-seakproductionofhumanyirus"tmnsferredtotheSovietsbyDr.Gallo.Mightthish:.m:beentheAIDSvirus'!·Additionally.besidespossibletreasonfortraJingbiologicalwcaponstechnicalknowledge.andtheweaponsthemselves.withtheRussians.thesedocumentsclearlyreflt;etthefunctioningof
Cl
glohalcryplocracythatsupen.:cdedthegc\)r\)liti~alp,)li·;.:icso!"theUnilcJSla\~'sCo\\.:rnm~nl.andknowlcugeorth~":\merican\,\,,"1,1pk.
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