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06-06-17: A696-04: [3] T.75-84.4: Horowitz: NCIS Iatrogenic AIDS Docs: [3]T.75-76.1-77.1-77.2-78.1-78.2-78.3-78.4-79.1-79.1-80-80.1-81.1-81.2-81.3-81.4-81.5-82.1-82.2-82.3-82.4-82.5-83.1-83.2-84.1-84.2-84.3-84.4

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Page 1: 06-06-17: A696-04: [3] T.75-84.4: Horowitz: NCIS Iatrogenic AIDS Docs

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t.J ~ •• I ~, '.;::;'./,.., i •....•.- 7J = i ;"'; ~~ ;;. ~: ~: :: ~ ~: ;: ~ ~ ~: I :: ;.~.:~: ~ .~: ".,.4JI:: :IlrqIIPIO~,..1 .<:11 II .., I I ;:::I I O'i:" ;.:I';1'1 I II 0 I I h' I .,...; I I ell I: ?: : : : : ?'" 5 : :;j:: :: ~:. : ! : ! :~.~: .! ?':: :

.1 ("), I I I I ~~ t I •.•.••, I II I I I I I I I I U I I II I I I I I I I I I I II I I I I " I I I I II I I 1 I I I I I I I II I ',' I I I I I I I I I: : :.: : :: :: I:::• I I I I I" I I I I I I, I I I I I I I" I I I II I I I I I I I I I ."' II I I I I I I I I I I I I, I I I I I I I I ,- I -I II I I I I 'I I I I I I 1I I I I I I I I I I I I II I I I I I I I I I I I II I I I I I I I I I I I I

ig. 6.8... The Early Research of Dr. Robert Gallo at the National Cancer InstituteIOd Its ImRlications in Relation to the Theory of Synthetic HIV·. DeveloPJ"ent·

Year and Subject of Investigation1967

Galla RC. The Inhibitol'( Effect of Heme on Hom •• Formalion /n V"",­

Possibl •• Mechanism lor th•• R••gulalion of H••moglobin Synthesis../wma/ 01Clinicallnvesligation /967;46;1 :124-132.

GalloAC. P••rl'( Sand Br ••Hman TR. Th •• Enzymalic Mechanisms lor

Oeoxythymidine SynthesIs in Human Leukocy16S . .Joumal of B/oIog;'cal Chem/$Ity 1967;242;21 :505!!-5068.

.1968

Gano ~--- '"Id pany S. Enr{TT1atic Abnormality in Human leuk.aemia.Nalr. 3;218;465-466 ..•

Galla RC a,:,d Bre-itrnan TA.The Enzymatic" Mechanisms .IarOeoxy1hymidlne Synthesis in Human Leukocytes: Comparison ofDeoxyrib=tf Dono<S. ./rxJrnaloI EJiob?i=aI CIIemisIry1968;243; 19:4936-4q4? .Gallo RC and Breitman TR~The Enzymatic Mechanisms forDeoxythymidine Synthesis in Human Leukocytes: Inhibition 01D••oxythymidin •• Phosphol'(las •• byPurines. Joumal 018io/ogicalChemislrv1968·243·19:4!>43-4951.

Gallo RC. Pe"Y Sand Breitman TR. Inhibition of Human Leukocy1.Pyrimidine Deoxynucleoside Synthesis by Allopurinal and 5-Mercap­lopunne. 8iochefT1lCa/ Phamvcology1968; 17:2165-2191.

1969Galla RC and Perry S.Th •• Enzymalic Mechanisms torDeoxythymidine Synthesis in Human Leukocy1es: Comparison Be­tween Normal and Letikemic Leukocytes.

3allo RC. Whang-Peng J and Pe"Y S. Isopenlenyladenosine Slimu­ales and Inhibds Mitosis in Human Lymphocytes Trealed WIth Phy·ohemagglutinin. Saen=. 1969: 165:400-402.

Study Conclusions

Red blood ceil 'home' synthesis depends upon a leedback syslemthat is self·limiting.The ·possible site of negative feedback control" inred blood cell production is considered ...

Amino acid synthesis in. while blood ee4ls. and suOsequent ce4l repro­duction is r"9u1aled by special enzymes. These control taClOlS can berrodfied t>{ i10Iganic SIb;Iarces (e.g.••••••• ,•• or ~te).

Special enzymes ar•• altered in while blood cells ot leukemiapa-

~~~~~~ds~~~~~ ~~~k~i~·:n~y~g'~~.i~:1~i~i~~~:~~:!ducti on at this enzyme to prompt leukemia.

·Human whit •• blood cell reproduction is largely regulaled by inde~pendent enZYfT\&olinked mechanism~. Bath activities are the func·'ion of, one protein ..

Further evidence that human white blood cell reproductfon isTargetY

. :~~~~~~ti~~~~edg~~ee~~~~j~~~~~:i~i~~~a~~~a~~a!fect th •• synthesis of DNA and cell replicaliOl1.

The nucJeic acid base purtne plays a ro{e in the regulation of human'NtIite blood cell reproduction (whi<;h is large~y regulated by indepen·dent enzyme-ijnked mechanisms), but not as much as the pynmi·dine bases studied previously (and cited above).

Same findings as cited. above

Transfer RNA (IRNA) compOl1enls from plants affects human lymphcells. Stimulation or inhJbit!on orcell diviSion depends. on Ihe concen·trations of reagents used. tRNA components may be useful. in treat·ing cancets and '1'Ias potential immunosuppressive properties.·

Possible Relationship to HIV SynthesisNone.

MechanTs-ffiS for inhibiting white blood cell production. In AIDS (tIareis a teduction in the number 01 while blood cells from Ihe thymus(i.e .• T.lymphocytes) and tesulting immunosuppression.

~~~n~n~~:re~~:;~~~~:~~t~~r~a~~ am.t:~~~~~~:~~~a~(ion~ in the ptotein (genes) of white blood cells to create immunesystem dys1unction.

~~)(~~::'~~~~)O:nog~~~~o~~i~a~6~~d~~~~e~:SOfe~)Nta~i.~estimulated at inhibited by manipulating '"the function ~ne p(otein~within the cells.

DNA in human leukocytes can be inhibited by the addition 0(Y3.rtousreagems (including the "pooiinj:f at purine bases within the cell).Thismay cause ~DNA degradation and immune system dysfunction ..

Though telated 1·0 the Ireatment of childhood leukemia. this studyptovides evidence that human leukocytes can be inhibited to a largerd"9ree by Ihe building blocks 01 RNA and DNA.

Same findings as ciled above

Relates to human Iymphocytes (imf!lune cell) division control mec,ha·nisms as wen as immunosuppressIVe inlluence 01 tRNA. AIDS ViruSis RNA virus which causes immul)osupptession.

,"".!-~4'''' •••. ~ ....oding Source/Biological Weapons Contractor; t unon Bionetics; ~ Bionetics Research Labs; § Univ.ol Calif.: ~ Univ~.of Texas; 0 Uni~.01 ChicagO: 3 Yale U.·.'

1970 .... Paper Tin-ks Galla nol only 10 Nalional Academy 01 Sciences al <he'ietreta F. Adamson RH and Galla RC. Uptake of Transfer Ribo-- Upt~ke of foreign (bacten.al) tANA by m~mahan, leukem~a and nor- time 000 contracted with them to develop immune deficiency ca~·lucleic Acid by Notmal and Leukemk:' Cells. Proceedings 01 tI1e Na. rnallmmature hu~an whlt.e blood cells I~ det~rmlned by an energy ing biologIcal weapons. but also to Seniot NCI tes~atCh position In

>ooaIAca~yol.sc,6t?ces.1970;67;4:1943-19SQ.. 'Presented atthe Indepe.~~ent. c3mer·'!'edlated, ~ech~nlsm . .P3p~r offe('S several -entry of foreign nucleic acids imo ceUs· to ettect Immuno.suppres--.AT.O.lntemational Symp.osium on Uptake of Informative Molecules poSSIbilities of what thIS mechanism might be. $ion--This at me time of controversial Foct Oetnck sympoSIum. PapatIVuVloq Cells. Mal. BelgIum. 1970.· alsoimpliesGallo'slink 10NATO'sapplied~defense·teseatch.

alia RC and Longmore JL Asparaglnyl,'RNA and Reslslance of L-AsparagInase synthetase (a Unique enzyme) plays a k!'y role In SlUdy focuses 011key enzyme in whrte blood cells w!\i::I\ ~ repr;ssoounne Leukaemlas to L.Asparaglnase Nat£!n!1910 227'1134.1136 controlling the ~growth of 1Ur:'0rs By blockIng Ihls enzyme s actIVIty 'NIl! Induce 1€:'l.1k,:1~,I;. Jr.:J I)U1er cancers as w,=Uas make me eJlfpus.c.1

t~mors can be derepressed -{het! IS. made reSIS(isOI(0 cht::mo!hera· animal cells treatment re::>l$lant. ThLSwork lays the fcund.iJuon fcr 0:.::.-. J~le~f\.Q ~~~~~..9.!9..9~9~: . .~9.".!:!:f !09'~9) "!v~ ~~ ~~ !'.PJ'!~~~. -:.

.. Af" ANA dependentONA pojymerase analO<Justo IOat of RtJA turnOut Reverse !fat\S(' ••'1(:(a.SEnr,'TTie id€:nt.fI<::d resp::coe-;e for 4~ ~f.ufc~lY.l1:1.110RC. Yang SS and Tlng RC. RNA Dependent f1NA Polymetase viruses has been lound in Iymphchlasts {immature white blood cells} ~fT'G3J cy1CXiffCfEt1b.aDon,~ti e .. d.av~t d ~ ~ (naf~i:(·

Human Acule LeukaemlC Cells. Nah.Jre 1~70:22B:927-929. ot leukaemlc patients but nOI at normal donors. The enzyme can use s:JC::srdl ..dngcarcerce:lproa..coon) and~j.;aefT1c.g€f)e.~fS· 't/~ HI :.It~an ANA templale Irom mammalian cells to synthesize DNA. ~ cal~ ~ected T-4 l¥f\p'icCyte to pn::a..ce dcx:ioonal J'\1iJSCSas

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cnD

Year and Subject of Investigation Study Conclusions Possible' Relationship to HIV Synthesis

o n,ls ¥I\ldr, IdunUllod the traNiler RNA rB~po":'lhlu lor U\tf prodUdlon of AtJPOrtfcX:UStfd(}ndtlflninQSPu(;lncwt6Ial'onslntRNA~espor'\SlbleI0l·~ I'97 cont.lnued IWUIY IlItlltO add In ht"nun Uaallt)~. Jllo(Jf1t' LI'lou:;1 ~ I:IflUt;Ju~ ullHNA nunnul cul\ulullu(julultJlV IIIud\wvsnI!i In 1"IdO~~IIC ctslls: SuenhOUinl}S

GIAIto HC I&n(t PUHlku S. Tuulblo. nNA. Sf)O(;lu!to In Nuunul und IIIIIKOmic 'IUm boch nuu"nl Ql'wl [utlkltmlC t;HII•• MutU "podu~ WCIIU IIII1Y ~ltllillU I.I~ wot/ill pltWl110 klll;'lwl~JUu U.:i tu whulu a IUNA IUnlucuJu mi\111 nodtJ to btJ.

'~"II'I1W' I Y"'Jlht.11Ilt,ullrl,AItHll;I/oI4ldtJ/lt.rll.lIl"*,yy IU/O.~J2.lUtl ~tu Q)Ptlnrtyroavt •.1I!NA~II(IU~tllan~lI~ "INAwtlUlu UlClcllllUllu:un INIIIII '"IIIIJU.( mudUlutl thy u.vlnrN) 1III'IIXtu::U IUllkulI\la w\llputt\UJJeI OU'kI1Cd.r1C",j~fWllllnU'"IC:Al.I· .. ,

OIISCCWIIfY U'UNQIM IIAI\SCJlpIAIUI tu:tlvlty In 1"'111'" IVI)Q r. ~htln lIanod I'upctlt IIhalucllhllllypo (I' vll1l!1ltuiV C"AIJfI;.,mAtty rypaa ni cancota btI'iYdoeIIln«1 wilh 1Y1111,I"H" •• llV ad,I1,.u 11 aV'It11Alh: 'tNA. QIKI I ,,1I.,.t (I d ,1:UI). ImaAUlIlTllu '-I,wllY'III"IUIIIU IIM;ltll,lil1U IUau:IMIUla. I {IV CU\lIJua sAC/om. tStl-1ot*IIGml. ~I"" -IClIIII,jA(.~ lu IfI" 1\UI11I111 '\/'tu•••, !llu 'Q,lu ull)NA pttllhH..lkltl yulelll"'UIII "'t )f\lV '*"' ""'1'" 1"1"l/ knuWlIIINA latl()vtnll'UG1~1ldl conwl.u.

~~~jl::~~.~~~=;(1tI;~~:II'~~~~I~:}I:~:Q:::~1:11)~:::I:~:h,I:~:~~:Q(:: ::~:~:II:flll:~ }~~;IIIIIII:::'~'j:r~~'I~I;'~~~'lt~~~::.~_~M·J:I~:".~:~~:~:;(~~"~~~I~C:~;vo,." IIA,\&tIIIIJhtIlA) whlt:h t:an utili/a tlulh Ill" MMJuIlI 11III (I $I, Yt.,IWn1lUh, U nIlMIM"V viII. wu" 11/1uh 111.11PI,,,,;llIftlll In t IIV l-vhllJOCG p.MIHUuO hula

:~~I~:~I~'c:r:a::~(:,U::~::.•::~~;,:: 1~'7"~'~:~:1~t~ ;',~I,~~r,:,:~~~,~~'~~~i::~:~:;II~II~;I:~'~:':~lt:t~"~~~J'11,:;~~:y~~I~,:~~~~~~l~tI~::~,~f:~~I~~~I~:s~~~~~~~I''''ily Ilia I~W UOIIQlk:RlDlnllnl IIIII will plllluln "YlolluuwlR, ttlllllll, Ill, dl::.u~mut.:UIII.iJ,U ""plu,Lly

AI townl cuncanlual1C!f\l, C1IhllfVlyt ,uklno.ina cyc;U(: ~'.O' nlCIf\tlplKXiphnln1t,,;IOQQUtl UNA ,y"lhDOII 11IIft! [hu 11110 uf Gall 1••••1161"" uf U"I1I1UI humulI

IYUlphc)(:y1n. laaJ"If'ln,1U In ItllI _UIIII4CHII phytO"UlIILlUUhJIIUIII (PI lA) uIlIIwj(Ju plQll1 IlutlvfM' rud,.hU)(;A "11~hllf mn::Ufllrullnn •• Itf 1U1I\JllnL Ih ••U."lo ••1I1I la~II"lQa wun rHllnt!, (;y~Jh;:J ,O·A.MP "tuay hu ItrltJlLlllulnUlIlIIIIIIhul&1fty"

Gallo HC, ~IQ .Puna J. Enh"nrolM1T'nnn'o~.\u~no 01 th""nn hnmlll1O. ~~~;~~~III\:;::;~ '~r~II'I~:~ya~~:~::~I~~:tll~~:I~~~::~~:;::I:t~I:~~IIII~::~comf\C1IUrtll.uu:Ry r~lllrlyrytA.d"fMIf6If\UCyd~G~.b ·MorWJt)l~K4)f"'lu . .Av,,· brl!ona otfnc.:Uv. uQol110lA 1T10A1cnJlIUI1KIlIU1fI" tullt;ulllllnr.uUwllt;umu 111n1J.;J/()/tI~tWJ/Jc.l(I;I/(.;:.;II"_"l$Itnllrc 1U/I,4',1.UI·IM. wkMJold "law klllud cullt, In II\lUII (;uU 1l1\U1I.I)NA GyrlIlIUuI. WU. ulfUlltJIV.. IlIhlbllucJ but not ANA 01 plUralu IIYllthu~itl. 11", tJltlij nu.ay IJtf U:iulul rUI

. _, ·"PtK:.Illc!\unont •..... ,

~~~.~ ~~-~~~I~· ~~'.-~ ~;on~'ur ANA~~U~~US~;at ~I~;;l .~.-.'. ~~=ft~2~tt:~,~:I~:~~~LL~~~~"':::~:~~I~~~~~~~:~~phocyltt&: IndtICUClf1 by"'! lA In NOInlU1Iytll~:.l\OCy1~.~19/1;31;:l:~' 'M1lch wus-"dupordunl on thu SYlltlio~~ or ~.w !INA~ wllll;h t~ huun mo·2U2. Itl'y1uludCOI~ttl~flt will! IfOn'ItJ !UUlOI:6 uotl CWtt;Ol VIHI~u:) ...

;knowledgod Funding Source/Biological Woapons Contraclor:

I "ml1n tymphocytU8 (vnmlrwJ coil) conIrol mud"w'istl\3lS ~ftt~ncebY tRNA:AInS VilLlS Il1l1lJunc.l1~Ilus COlllfO~ IT)Ot.:hanism 10 ulhmalttly c..o.uselmmuno-

~!~r~~~':~·II"~~:~~~~J~;~~:;I~,':"~~;~AC~~:~~\~~~:~~~'~~~~~~pI\ULiIu.:.t 1,,;1.111IIIIU.~ • :. ._ •. _

SU/IIU ~ u110vo ~lhJ.:£u(jdlUonul fU\dlng I"al cl\fonic IymphOCy1ic ItIlAt.aemio.

~~~:~,,~~~~~I~UrJr~I~~\I~~~f~~'~tJ~~~~~:JII::lj~;::~~~~tJ~~:I~:::;~~r:t_IIUIJIk; IllItllIllU ullllV In (-:rw' IY"I(:.llor.:y10:t IU $tM.H\ In AI(J$ p.utlUflt:6

Nun. ·"IIP••' ••III .1 I,,"•••nl 1111111

Stu1y pmVlrtu:I Ihu rlr.il puhll:,.hod dvlrtUf\Cd 01 GallO's work In dtNe1op4ng· UI!II~)u(lIuS whicl1l;un dulvcl plOh1ulT1$ with IHNA in 'Mliht t)lood colts. ThISIO'llu:!lJnb thll hu:Jr.rustiUIU' \lIXJn wl\lcl\ Ih'lIodvunctld tI'Itf lecl\nok>{Jy la

pllxhlCU I1IU ol1ly unUhot:1lu:l UVQ.lluhlu to duh.t(.'1 1111.1 I\\IIIIUn T·lympt'ocy1ttVI1tI:'U='(1111 V 1. 11. unc1I11).lInd WUIUtuqulruclln 100uul'(IO() HIV. CUllunlly,· thu I ItV ullhhodlu~ rtuvt,1ll)ptU.hoIl11111~,tlu"y'NO'k, W(jIU pollt)(1h,>d tlf\d s.ofd

by (~) o•.•t thu Ne.1 to ptcdu:~ th:t tQ:xj Ilbls \6tId 10 ~(ocIl ~V ".«%Ion:._

0uIWom1hl1I1\UI'n()lInw lymphohl!1:J~ (Immulllru IYll1pttcx:ytu:J)und hlllnun Ciullo Qnd h~lnku cOf1C".Judud hnl11lhls study conductod in lare 1969 or eat1ymyulolll8 coll~ (CUJ1c.uU)tI~ uJlllbody fOlO1IoO p!U!.1II0 colts IIlun,dul:ltuuclln 1!J10 Ihut thoywuuld l1uu<llo hnlhUI ~"VUIW.l.lu11\0 ftJl1ClIOc\U.! SoIIJ,urical1ca01

~~~~~;~~~:~I~:~~~~a'r:~~~~~:~~~~~~?O:~I~I:~N~~~~~\~~:~~~~I:~~:s~r:~~d~g~~:d'~1(~~x~I:,:~nC:~~II~~:WI;Irlt obsurvttd,Consaquttntly, IhUi uppulelll dulvet In 'Mllltt blood cull dd· I;jxpluinucllhot 0I1tJ way 01 doing Iflis was to t.JStt\M\J.SOS 10 d,elivet!fle lor·

~~ir~~I~~~:~:~~~YB~~~~:~o"~~:~i!;~i:~~I~'~~~~~~:~~~~~P::~K:~I;~~~~r~~tal~~: ~ ••~ ~~~~j~~~;~:the tyrosyHRNA found lhe ples~f\cu at '"mord hycJlophoolCgtOlips such M (SV(O) and ft1tf 010USdpafolkJ It.••.nol (poIYClfTto)vll\IS. Such expdflmunts;ffidll'\yi groups 10tho IRNA ollhe (ltK)pl~tic (C.]t1Curous) ct./fls," rhls UudIn could havtJ tfslabbshtJd thtt IOChnolor;Vand provided Elm~ 10rtNl deve!"will\ oyidtJnctl oted ohovtI of 1110Impollw1CU ollRNA nluu\yI~su UfI.lY'"US opmQm 011 UV-uHUCJtJulyol~jmiDnY;IUSdt,1$CUf\(--wraicnsimUilrlydt:llivtirsIn U'\e Inc1uctton of leukaemia horn 'oI1nlSes. forolgn RNA la nOlmal while blood culls.

t Llllon Blonellcs; .J Blonetics Research Labs; § Unlv. ut Calli.; ~ Uni •. 0/ Tuxas; 0 Univ. 0/' Chicago; A Yale U.

-PhYtOht.f~·~OOIUIiI~~(Pt lA') !u.ulw InU1\W1!uukuumlclyrnpflul.,:ylu:JIn(ILK:U~

C1lmntilallva and ql.ollluUVd ChQ'\{)O~ In IRNA RlOlllytU:'U u11lyrlluS s1t1lUar InIMUII MJ(Jf1 1n nonnullymphocytuK, bul tllll MKll1uflC:U 01 tJvUlII:J uf Pt lAIflleunt;lIun 'MUt chrmuc Iyrnl)fItX;lyI(: It1tlkulllIU (C.11 ) 1Y1"I"ItIt;yt~ IUUlJlI~1tu Ollly-IIIII IlIduclllJlI b. duluyud .

ProCuln :iytalllaulo In cullo 1:6duptnMJuf11 nn'ltlGluIc udd:, • Iflu htclc (Jl.lllcllnQlJIucktt. o( DNA IJnU HNA.lhu lwo mu/or CUluUOltu~ 01 Ihu::io 'tU~Ull ~ pu·

~::::I::::J ~II~II~~'~~~I~I~~;W:~\I~~,~Yt~~QII~~~II;~'~!;~~~:I~~~'~I~~~dlw'\Ju:s In ~Ul1Itttl1I1\OI:6 unt! lallkuultlh1.1

1971

t uvtlla l..VtJlwkla itV und Oullo HC:. Suftl~(JVk; $pCJI:WCllloli of Mulhytulud~o IIIM11\Jf'MJ 5)'bhtllus. &xIJtJ(lIiSllY 1011; 10,11.2000· 20 13

Alddldc Ott Qnd GwlO AC. nH. Trw\ufuI HNA MuU1yiWiua 01 HI"'UlIl.YnI·phtH:ylUti: 11,0tJluYOtllndlK:tkJt1 by Pt IAlr11 ytnphoCy1ua FrofT\ puUunl1l WIU,\.1\1O'~(:I ympt1tx:y1Ic ""Ikomhl. ,,, .••"/1011;;)/;3:203 2OH ..

o

.J 1 Oallo IU~. HAlln ps. /!.Uan. I'f. NQwhH1WA, "'lIull:~. Uowtln.lM Aflll. OfllCx;lM;IWRA,11 I~QVaIQ" l1n1I.ulllIA ••• '" I'ypa (; VII\lal'II.Ut:.!aa ur I ""ItA'I

OIItJif1. N41l1l.N_w'Iit-t'f./VIU/I;:l:J.:l;I·m 14'1

Human acute leukemia likely involves a block in leukocyte maturation In this study, Galla used several virus-transfanned catls induding !he

due 10 a '"di~r.der 01 protein synthesis: Ttus is i~dicaled .by reduced S!mian (monkey) virus (5V40) the. murine (~at ar mouse) satcom.aDNA synlheS4SIn cancerOUScells and a build-up of heavy Weight rANA- VIruS.and the polyoma (mouse parotJd tumor) 'I1NS 1f'Itected cens. AI d'IIS

\he 3ssempiy station for building amino acids inlo' p/oteins--in young time changes in specific amino acidS within the ¥h'Iite bfood cells' ANAleukemic ce"s. (The amino acids ale. delivered by IRNA to the rRNA. and DNA were,betng manu1acttJred in·lha lab and studied to detem'oineIha ribosomaI'aSS&fT'bfy Slation.') In this report, Galla questioned vd1ether the related effects on Ihe immune cell SInx:tU/e and function. Combineawte tymphocytic leukema was associaled wilh a specific change in ttlis research, and the available technology to isoiale and inject genestyrosyl-tANA, and whether IympnosalComa. was related to a specific Irom different viruses to proauca a unique ANA ratrovirus. and GalkJ et.change in seryt-tRNA.-Similar 10the results with RNAviru_s-(ranstolTT\8d ~L, had all the requiremenls n~ to produce HIV. The. next ClJes-caUs, tne tumor derived from the polyoma (mouse parotid lumor) cells bons are: 1) Did he i:i.nempt to combcne di1fe/enl viruses to Induce.s.pe.-showed higher tRNA malhy1ase activity. Otic carce<ousand mruna system anOf<llicr6. and 2) I so: v.t;cI1 speak:

__ • ~vic~raI~andCO<r€2':~.!!;_'!!!F.thehaveUS9dlDoea"' an AJDSWui1Article reviews and upclales know1edge regarding 1lie importance of .reve/se transctiplase enzyme in cancer causing ANA tumorviruses.lmportant questions which Galla proposed be researched ;n.•duding: What are the detailed biochemical mechanisms for this en-zyme?" and ~Does the enzyme in viruses from higher forms citter fromthat of lower animaJs?"

A major difference in aspartyl·tANA (Asp..t~RNA) was demonstrated in.polyoma (mouse parotid lurnor) ~Us and SV 40 (simian monkey nJmor)c~ls. The "pat1em of Asp+ANA IS due to selecrive cellular gene ex·pres.sion.~ which "may be related to Ihe !unction at Ihe DNA oncogenic(cancer causing) virus genome (gene structurer in infected cells. In

~=t~,~~::~:If~~~~:r~~s:~~~%vV~~~~:f~~~r~=Wltt1lha ViruS genome function: ......nththe abijity to p/odu:e vif\J.S-/elatedanligeos and their effects.

In this study, Galla and cowor1<el'Sstuaed ·portions of ditfer801 virusesto determine if "'the tANA difference (in cancer c&l1s) be rEM:atedto theproperties at neopjasia (cancer deve4oprnent) in general. or. more spa­cificalty, to the function 01 Iha DNA oncogenic (cancer causing) V\NSgenome (genetic code) inserted;n the infected and transformed ce4s?They slated that '"by studying viral or cellular mutants at ceU·segregants ...whid\ have conditional variations in \I1rus--specific ceCular

· att~rations, it should be possible 10 mOre prec:isely Qetefl't'ine t1\e ~logICal significance ot lhe aspartyl-tANA vaMbon reported he/e. ~ThISwork shows lhe analysis of different viral genes was 1Jnderway to dele/~mine what effects each ml{11t have on delJek>ping cancer. They laponedU'leirdeSi/e to use !tis rlormaDcn on cancer ~ vitt:ses la Ii"1d a 0Jr9 farc.ar.:a<.bJt at 1I'is Orre tt'e; ~ !heir kr\ooMedge more taNaItlS aeaJrq

_________________________________________________ .varous ca_nce_"'_and~_ne_~w_Yl_ral~.spedes, ttlan lowatds arradcatrq 1\001.

Smith RG and, Galla RC. DNA.Oependent DNA POlymetases I and 11 ~A pNA pofymerasa h~s ~n lound in blood Iymph~laslS (immalure The 70S RNA virus is singMt stranded RNA retrovirus found in d1ickensrom Normal Human~Blood Lympnocytes. Proceedings 01 tile Na~ whrle blood ceUsj trom IndIViduals W1tnacu.t9 I.~karrua Ihat. unlike Iym· 'NhiCh causes some pramlnenl features 01 AIDS, irduding white bk>od

70nal Academy of Scie/JC8s 1972; 69: 10:2879-2884. ~~~A~,"NA potyme/ases '/om normal IfldtvlduaJs. Iranscnbes 70S call dysfunctiOn. sarcomas, progressive wasting. and deattl.

"Two DNApoIymerases purified Irom normal human IyrrchOC)19S (NHL)are distin9'J~~ from !he ~1ralreverse transcnp~es of aVian,[cntcken 1my~OOIastos!s ViruS and mason-~zer monkey V\f\JS by ltIetr rafativeaffinity 101 select !emplates ...Critena fQ( distinguishing the activity of vi·ral rev81'S8transcnprase are discussed.~ inducing .•...lhe ability of ""aIreverse II.anscnptases, but nOllhe cellular DNA poIymerases. to reactwith pumled singla-strancled 70S RNA templates: Also: "The impar­lance cl uSIng ngo/ousty punned 70S ANA cannot be overemphaslz€:<l.In Gar1y~xpenmf;f1IS. NHL Of'JA poIymerascs I and 11snowoo reacu'V,ry.•••,tn feline (cat) '6uk~mia "'H"\IS (FELV) 70S Rt~A ~110waver tt"IISWLl.S anamli.tC'1 !JI CClntalT'llnalu>n ~_A.U01 !he::>c dlstlnCjUl5h,tu) cn!€tna 'Ntll ~nal·ll~mCJfc<.;ntll..:W cJcl€:l1T1lno.luan 10 t>t:! mC)IJi:::.1.:. Id v .•ht:lu,t:( Cl.vltdl·hk.", (bvt;l::.e

transcnpl3sd is aSSOCJaledWIth ne-cpJasoc d~ease 1ha RNA-dl!pcn·doe\! DNA poIymtrrase ffcm hUmdn acute 1E:\.•Io.r::mtC.:eils 5a:DSJIHSallthese cmena tor a rev03~e r/anscnplase

Iledg/"'- 'nding Source/BIological Weapons Contractor: t Litton Bionelics; " 8ionetics Research Labs: § Until. of Ca Id,. 00' .• Unlv. at T~xas; 0 Un IV. of Chicago; ~ Yaia U.

Year and Subject of Investigation1971 continued

Galla RC, T/ansfst ANA and Transfer ANA Melhylalion in Growingand "Resting~ Adult and Embryonic TlSsues and in Various OncogenicSystems. CilncgrRe$i1sn::n 1911; 31 :621-629.

Galla'-- 'everse Tran~Ptase,lhe DNAPolymerasa of OncogenicRNA s. Nstllret97t;39;I:t94-198.

1972

Ganagher RE. Tong RC and Galla RC. A Common Change of As()arty1­tRNA in Polyama~ and SV..•~ Transformed Cells. B,ocl:tmlca Er.Biop/7y>ica Acta 19.72:2.72:500-582.

~obel1 MS. Smith RG and Galla RC. Vi/al and Cellular DNA Poly­nerase: Comparison 01 Activities with Synlhetic and Natural RNAemplifles. Sclsnca1972:176:798·800.

Study· Conclusions Possible Relationship to HIV Synthesis

None obvious in this sUl'T'CTlaryreport.

This lepan aJso indicates GaUa andco-wot1c:el'S were evaluating s.inQle

~~~~~.~~:g:2,e~g:S;;~f~ri:~~ ~~~~:t~~~~ocw:(~Ihe ~'aundry lisr" 01 feline leukamia·llke disei1s&s and the sexualuanmiss.abllity of AIDS. and remarked, ·Combine th6se two dtS-Oases­h:lune lt1u~emla and hepatltlS-:-and you have Ihe immlJr"18 d.;ficisnc'l"The posslblirtJ6S In relaaon [0 HIV synthesis 3S1dtne ImphcaDOI\S 01 tl\I.Sstudy s~;:iJ.: frJr :ham~I"'riS

Page 40: 06-06-17: A696-04: [3] T.75-84.4: Horowitz: NCIS Iatrogenic AIDS Docs

""".

--..•.---.-----. )-- q-,Year and Subject of Investigation Study Conclusions Possible Relationship to HIV Synthesis

'Yha I)QIILaAy ptn1nucll)("ymDIAuc':l hlllnJINA 11I1U0I vln.~u. uxt11t1lluctIII,uthucJuUQl;ltutZllk:1I wflkJl amllllutJ IhuvhuQ' ~IUYal:.Ju hlll1:M;llpha:wu-

:::I~:;~~.:~~I~~~~"'C~:~lttll;~'~I~I~lt~I:,~~;:'(tl~~:~;'~I:~~~~~:~~I~~~~tHOOP '"'D t>OUfI /0111111111 ~I HNA !tUUUf vlnnu-tU.hw.;lutl4.ld IIllhl:) 1..;111:.8

UIO ttlcrfu5k1Wll'O~vtn.ouo; MubUtl 111.:u' 'IM)llkuy 'Ilfl." vhtlU(M I'M I V)."vLuor! "iyttluhluufuCiht VhUD (AMV). ~mJ I tcauDlJlur Mullll" (IUVIIIU'U:aU)luukdf,'tIQ·vlru. (Hi V). M pM1V lu of IfllutUtd, :dnc:u It h, 11 p"mulu nNAvlnlA actnplud 10 I human coil Unu, NC-37. Th!!t. cull !lny wus Inllllllly

C;~~~,',r:~~~I':~:~~':J~I~~,~fl~:OI~~~'::=:c~I',~';~uK~~~k~~~:Ih" noOl' III humutllluuplutlllc culll:l. fhu dUlu ulnu dUll Itlllbt. ulud tlluRhUIty nt thu virul and nulluuurulty ou:un1l1U un/yt'kllI In IIIIU/I.I cMflulu

slrnnc10d ~NA lor IJrnfnln synlh~9ld wtdch moy t>tJ IrlCrou~wd c1wlllu!l·cnUy by Ihu IncUlt10rulkm ut IhYlUldyl~add unu udunyUc udd.'"HNA lurnor vtntStltS rupllc:utu vin Lt tUlntICrlill10n of pmvhul ONA .. 1hoUI:;.c;ovury 01 RNA'OOlkIfUJullt DNA potymuruw .•,:UJppu,t:j IIIU Icklll !l1Ut

thet ~U41Ultclulorn\idlun 01 HNA !UlnO' vhu~"" clln dlli:.llln un Inluc.::tod~~~~.}f,::,~~::~~~C~ij~~:V:~~::~I~~o<l~~:t~k;~~~;:V:J~~I~,1~~'IdU. (0 COf\sUhJynl of HNA) In ('noc.JS~IUIJ cuU IInU!lo· W115 ~()ckod Uy 11charnlcal (Cordyc~n3'·dtknyudo"osjntJ ,a known inhibllOf oll>Oly (A)(this hmn rttftJl"S to it chornleat potym~r OIIlUUf1y1k; add ~llch l:i u CutI'duns.ation product 0' adtmosintJ w1d phosphonc add; u nucltK)lI~ loundwithin all nucleic acids). '

M L\ • sopenten ) Adenosh1e. a plont hormone (among a class 0'

hormones called ey10kinins known to be a ·ciJus.ativa o!)tint in certain

f~~~~oT:~.~~~r~~~~:r~,~~;n~i~~~~a~~I~~~an~~~~ol~~

Gallo RC, Hachl SM. Whang·P""9 J and O'Hopp S. N'·(.-\'-.'S<>I>'>nlenyl) lymp!1050n:oma coils Ircm ca~"r pallonl. 0110",010 'our bme. a:; groalAoonosJne: Thtt Rt.lQulo(ory Effacts 01 11 Cytoklllln 4nd Modified Nucle.o-- as thut In nannaJ Iymphocytes Iram !,oalthy humans. -aNA sy'ntho~isSide From IRNA on H~jn\OlnLymphocytos. 8-*OC1'v111C.:/ Et Bq:vt~ camot be ttle prima')' situ of adlon- ollhisdnJg which caus~ r~mUrk­AL"td 1972: 261 :486 500. abty similar effects as phyto~omu.polutmin on ·stirnulated lympho-

Cy1es Ijl comparable concetltrallons.

AcknowlouljfJd Funding Sourc~/Oiological W8apon~ Conlt.uctor: t. LiHon Blonalics: .J Blonulics Rasuurch L8Uti~ § Univ.

1972 <:0 1111nl " •• I

=Ie~~r~~~~~~~~~r~~~~~?~~e~~~~~o O~~~i~-~~strmulQte cancur call ('•••••Ision .. they appear ar this poiot 10 have -"ar~rowed Ihttir anenttQn On 10the IRNA segments composad 0' ad900sineor lu1uI1YIic uods.

In Ihu nlH1vo !Sludy.. Gulln t:tl 01 round Ihul udunyllc Bcld a ba5lc(fludootkJU}(:0l11pol\tW11 ut HNA unt..l ONA cun ·UfUUUy Inctu.u:w Ihtl ratdur HNA lJltx ..1ud pruloin SYllt"u5~ hom UNA rt1rUl.Juh Ihtt rtlvtt'~tt t'lln--

~~(~~)~~~I~~I~(I~~~~'~~~ ::~~:lv~~\C~'~~:;'U~~~:~~~~hill~~~I~II~O~~:~J~~~7:.1~~~~::·~::f~":;~~f~~o:~~~~~ts~'~r~'IIIA~~U~Of~~:"~~~~~~~~=~~~~blood cells. C~arty. the resuarchers were manufactunng a new strain0' vi.us here and checking to see It chemotherapy could stop it Iranruproducing itsuU through 1I"1t3r~val'S6 protein symhesis mechanism typt..cal of RNA relro"iNses..· ,

nullu unll Tulnl cClndlll1ud Ihul . "AcontlmMJd G4:1",.;h IOf II"Uhodius 10null" •.•• hylHtdt'l JlUII,r. WUfrtUltln'· 111U 11'I'iIlCHtW''t:u. :l1)uc:;/fUty Rlld<it!ft

1:\1" hll~ 11' hll~nlh,u IIIIUI)()4I1IIU Iu IIIVUl8 •• "'UI:;c;rlfJtnrMl 'tNA lun\()f' vi·IIII)U8 IIIHM;lihu«111I thlD ItJlKlft. IIItNld'!4J IhQ 1cw.:1.MIUVII tu tiuvuh~I \hIt

11ItUIM.M.toi !:Ut!l1Ut)f1 ludv'kllllJ..' QIU.J ULlltb~du. ~hir.:h All)S IUfWUrchw,'1IhlllutJlllullhu WUlltll.tltI(j.1l!fl>tll, U&lllu.••ll".~~·

In ttll~ all.lI •••• OuRII o"cl t:u oMNk"" •••• )ulvnuflt..Mf¥rt'lth rtNf•.••v-.tmno..aIINA "'"" t;hk.;kulI vlnlQu. whil;h Wut" kUl.Jwl\ tu 1;8"0" IlJIuk..,.,'tIQIn IliahhlSQ 1h•.•y uca"u'I"uQy !111~;tut.llhv ".Inut., .lr~l1d.ul I \NA ~nlo IhQ hu·Ilun' wtlllu tJIIMMIt;:I.lI" hi /WJU if Ill" n«un",1 t)NA UC'uy""'. puu~,Qnl kllt\Q

""1'4I1It.ll:ytUIti wl1ukl ha nU" 10 wmk wUh thu vlua.! HNA 10 pttx).JCIII I·'&&IJkIlU:UVUIy lut-.ukKt 1)I(lhIMt·' hlr. !l.h.tly wU)wtt lIuat lJy·thCl DUlly IUIOI

~~~I~:I~~:1::~~"~IV(~:ltlnU~I'.I~'~~,~,t~~:~'7~~:~~:~;)f~:J~~~I'I~~'1:';';::~~IktllJnu If~ AIUH VhU8, ~. YIIU C1k1Y IUIW know, Iti· d •.'nu" ~tr&lndutJ

'tNAlllhuvhl'. whk~II1U1:lJIIIYwHIn Ihi.~ftlltr(. ~tt.Mt.kIGon U"\Jj'T11011mu,j\l.I·nlwllltuulUII tu Ih" l.;uU':to11IIIIIIUl ~)IOI"I"aynlhuoh' n•••.:hul'llI.m In On.M

. hi ~lft.h.;CI ~'I,Uh~.I, tlh.t Ita. lut"l)lft~u It~lItt

Ilulu, {lull,. mul 1:IIWlIIIIIII':I pldMltJIt tUI)Cutn16Mlla U~I1U ITKII""UY IUtlk •••111111 YlnI~UIi A:J wuJl us c;ha.;kull uf\d nMMISou vll\l:M.I:t 10 ItJCIi,llo,Ihulr 111'­

1t,II,;b IIfI1UunwJ humun DNA (.,uc.;tod I!,uh;tln soyUlhtJ::thlln whlh;t bloocJI:udu MUI1V IIlIlhll,III". 1I"lIuvlI Ih•• AI()~ VIIUSbtJu,:t D'UJJI .!t.11f1ltunUus toU1U uh1llun II1UfIJ\IJY vlnll' 'Nilh whk:h OuUo's lub wus ubo lNU.kino (Suehl~ui •.•1unlllillUU. 1IJ/1;1I11d {inlSo.M~,S4uinOUfundGUkJ~.1913t

In IJ,dclUol1, tt\d huwN.ln;hdf':l dC~drvd udUlUona.l tJVkJof"Co Iha1

~~J:;,~~~I'~ri,~~:~tJl~~::r~:~~~:~~~I~~~~c=,:r~:6w~~

IUc:lud ()NA Srn'huw~ whunutxllJd to thtl ~synlhulicONA-RN~'Yhrtd"·1111!:fu:.PIJr.1 (I Ihu tihu""II/II'K.1s 'hu ",II\IIlu (Jotull wt1~:h WUII( Inln .,nu­UIIUI\U IIkI U)fpIU~IOn oIlu.uign (In UliS CWHt mUllkoy 'W"1f\J3) RNA cohUlllun -M 111" t~()utJ cul~,

01 Cali/.; ~ Un;v. 01 Taxa.: 0 Univ. 01 Chicago; 6. Vala U.

I UII(),".ldu"", 1t.af1nJltvu (INA IIVl11'IacaII wnall ••• J ko, ''''filIAl 1."'lun I~t".t

1y"~lhCJIJVtCf" .lIf1Iululotl with Ihet ftual\l" plnfl! dllllVtMIIUlI\u&.uil: "uhIh ••• :" t;nl!c:NI''''Vlu'',""nlJU!uUul" (l'IIA),hu! nul III Il\u IJIII.II".,I"h ••1tylnph~x."Ytaa. I )NA l'ulytllulAIMf INuUII.lllum thla hl".lkll\ IklUlt lIul It,I"

·M;'U. 14NaCIIk: uJOI(NUa (If -",dluuily t)(;';:IIIII'IU, U.t'\JUIN."I~Y I1ltllldkuJ.lnUlu .I,"rubt IINA.- U"III. Utu -!tIS 11NA t"MII IINA 11$11"1' VIII'DUO,­

11\60 tl.lhtWli~IUQ 1111. ufll'ytl1aflc." 1I'1i IINA Ilh •..•:IUtJ I )NA IJltlyll"IUlrtlU'

(IINI:I'." 111U1••• ,lp4A:au) I(KIIUIII1 t;nm;u, 1:1t1l:.IIIU IINA v"":Ima I1ml hlln\.l:u, kmIU.1I1\k; 1;0110.

Wu AM, 11"0 HC, f.JtIHUI M unci Gulk) 14C.C:urdYt:upRllntut»I:llnrh:tlClnhI M"rlflfJ I ullkov1ru=- PlOtktc.;lItlf\ By ~ IOtkJ:!' tlu()xy",lclnu. Pn~'6'f/f.}If'!}:; uI/l1d N,.,hulJ,;IIA •.:,;lclcJmyvi ."x:mrlf.;(A>' lUrl..l.iU. t2.:JU;!O·3H~4

L\1Nand ('.u.UI) I tr:.~,Ulw: •. fllMI hi r1NA IINAtty'"lllln ~ynlplUkJ t \tJKI.h~nntlluwJ n""l1otlllMl hy RCu4kllllacll:llnt IlIIm fhullul"'II,",uuua­

._y N.'hJlfilMr"w!Iir"W10/~2·H)z·m~~·'7. ..

Hunllw :iN, :~f1l1h IIn, !lUIIIJ MM am' 0,,111111(: t~III1"~nlud NIIIH\QI

t 1111In1l111 IVlllllllOl:yt •.••, (;ul\lulll " HI1K)mtchu\Qu Hun.lllv" DNA Puly" 1I••••un" 1}lnll,.•;1 hum VI'nll-INA IIIfUIII:h~II)NA I'nly".,uuui Plu,'PPI1N'J,.U' Mltltnvl,-4..-.:tfilJtIlY ol.'W .•• a.¥4. ••• 1~t4!.UU.t I :;J;~J" :~:I~

"".. ,... "..':: ~.... : :?-:;.~...•.••

. Year and Subject of InvestigationStudy ConclusionsPossible Relationship to HIV Synthesis

1972

continued Derivatives 01 Ihe antibiotic rifamycin derived from bacteria wereReverse transcriplase. the unique enzyme found in HIV is hera..J +~n~C~~Vj~~~r~~f~~a~~~I~n~COe~:~~~~~ J[~7,S:~~~fnss'v~~:'

used to inhibit the effects 0' rat and mouse leukaemia·sarcoma vi·shown to be required for leukaemia and sarcoma viruses to pro--ruses preventing the fOfTnalion 0' cancer cells. ·:This suggests Ihat

duce Iheir cancer causing et19Cts. HIV anacks while blood 'ceUs,/IJ", Ntlw Biology 1972:236: 163-165 .

rt;tverse transcripase is necessary tor transformation by RNA tumour.,thal is leukocy1es, and causes a rare skin canca' known as Kaposi's.•muses.

sarcoma.

Certain rifamycin derivatives have been foun'd to be more toxic for

This woO( advanced the use 01certain anltbiotics in an effort to fight

..J~~t~~~~i~~~9Ar,:~y~'inG51~Ori~~t'i;:~i~~; ~~~k~~~~CCH~~~~

fresh human leukaemtc.blood cells than lor nOffilal blood cells. Thesehuman leukamia. Though it bears no relationship to the de ..••elop-

~articular antibiotics also inhibit the reverse transcriptases 01 botn

menl 01 HIV o( other AIOS-Hka viruses. it might be interpreted as

Laucocytes. Nall//'9 Naw Biology 1972:236: t 66·171.

. lIman and viral origin, .'having contributed tn the de ..••elopment 01 chemotnerapies for can·cer as well as possibly AIDS patients. The authors did indicale !hatnormal cells would also be harmed along with cancer cells./

The presence at an .RNA..(jependel1t DNA polymerase or reverseThough this summary and update report on 'everse 1ranscnptaseG

;. RNA-Dependent DNA Polymerase in Viruses and Cells:transcriptase has been lound in every RNA oncogenic virus.,.11 isand its link t.o cancar beatS no rela!ionship 10 the developmant 01Via •.. ,m the Current Slate. Blood1972;39;1 :117~137.

assumed that the role of Ihe enzyme is to convert viral 70S ANA 10HIV or othet AIOS·like viruses. Gallo did, discuss beginning 10 de-a DNA copy, allowing the viral genome to be inserted into the host·

velop antibodies which could help detect this enzyme which is cur-call,

renUy used to idenlify HIV infections.

-Reverse transcriptase. the DNA polymerase 01 type-C RNA tumor

This review article summarizes Gallo's research on the uI'\ique re-1973

viruses. can be distinguished from the DNA polymerases at nannalverse transcriptase enzyme associated -with HIV and olher ANA tu·

Gallo RC. Reverse Transcrip.lase and Neoplasia. Biomedicine

cellS_by biochemical and immunological approaches. The enzyme ismar viruses. Here the theory of how HIV and other such viruses

1973;18:446-452.

reqUired for formation of the pro ..••irus. the RNA lumor viruses, andreplical.e is published-ten years before Luc Monlagnier at the

hence. for inJection of cells by these viruses ...A revetse IranscriplasePasteur Aeseach Institute isolated HIV trom the white blood caUs of

related to the rev.grse transcriptase of ~pe.c RNA tumo, viruses·~~~~~~~~s~~~~d ~~~~~~i~~~~ ~~n~~~~~ti~~~~~et~:~(Iaukemia •.lymphoma .•sarcama complex. has been unequivocally demonstraled in soma human acute leukemic cells and its pres·discussed here. It is remarkable Ihat the type-C RNA turnor viruses

.~~~ee~~:n~~~I:~~~~~:~·~gb~(r~r I~u:;;:i~rc~~o~er~s~sfn°[~~~r r~:

Galto Sludied and discussed here produced a similar complex 01diseases associated with AIDS including a~leukemia-Iymphoma-rology and to molecular biology in general in a very short period."

sarcoma complex.'

Wu AM, Ting RCY and Gallo RC. RNA-Directed DNA Polymerase

"The results of this study suggest that RNA-directed DNA polymeraseBesides Linon Bionetics, a dcx:umenled U.S. 0.0,0. bi04ogic.a.1weap-and Virus-Induced Laukemia in Mice. Proceedings 01 t/1s National

is essential for iF'Jductlo~of teukemia by exogenous virus and corre--cns contractor. being cited as lhe major funding source lor ltIasaAcademy 01 SCii1nCtI$ 1973:70;5:1 298-1302.

late with, the previous observation thal the same {Rifamycin antlbi~· experim6nts. The Special Virus Cancer Program from Haz1elon Labo-otic! denvalives block viraltransfofTnation (in cell cultures}.

·ratory in Vienna, Va. was mentioned as the supplier cf Aausher lau-kemia viruses used in this study. This is noteworthy as Hazlelon's~_~~0~ui~;e~~i~e6~~~b:t~ ~~~.Si~~~:~ef?~~~~~~d E~~~:~~,:best seller me Hot Zonswas Hazleton mentioned as an actual sup·plier at ANA tumor viruses. In fact. Preston alleged ttle deadly vi~ruses came from either the Phillipines or Africa.

• Paran M. Gallo RC, Aichardson LS and Wu AM. Adrenal Conicos·

RNA turnor viruses can be stimulated la reproduce in mouse callsNo apparent relation to the development of AIDS •.like viruses or 01

teroids ~nhanca Production 01 Type·C Virus Induced by S·lodo •.2' ..by the addition of adrenal carticosterolds and many olher hormones.identification or lreatment methods for AIDS. Paper does provide

Oeoxyundine from Cultured Mouse Fibroblasts. Proceedings olll1e ca~ePin (a. crystallin.e antibiotic ab!aine.d from the bacteria

interesting acknowledgment: The cardycepin antibiotic used in [heNanonalAc.ildtlmy 01 :)'citlnctls 1973:70:8:2391-2395.

Co eps milt/3n~1was shown to be an Inhlbtlor 01RNA synthesisexperiment had been obtained from Ihe ~Orug Development Brat'\Ch

in ,RNA turner vin.lsas, ...

of !ha National Cancer Insllrule - The NCt. 1ha author3 -Nrate ra-

cej'Jti;d fhe drug frem ~Merck and Co . Incc.rp , Document ~:rC"'IC.cS,t:••.1c1enccicA iu,k betwee:n Gallo. ih.,:.NC!. and the OOCUIT1cfil:r1blCi~

L--.IIJ:)lc<J1"N';ilP:-.,.,S c~nltactor ~,~E:rr:k",nil \:,j ..1.150. ",,02r<;«1 is .::-,,,-

nuctlon of Merck and Co, to a s.p&Clal branch of !he t~CI r~spon~tr,lefar the dE#vt!lopm&nt 01 ne .•••.pharmaceuficals. dav6Jc.ped apparently'Wllh ieder;),1 i::and taxpayer 3_SSlslanC8,knolt'!

d Funding Source/Biological Weapons Conlractor.: t Littoo Blonetics: ...; Bionetics Research .LabS; § Univ, 01 Calil.; 00 Merck and Co.; 0 Unlv. ot Chicago; ~ Yale U ..

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_______ ~::~::;;:~::;:;;,:::::::::--------------:~-~--:--- ••- •• U--_";i;I·~nf~J..;i.t~ I

.y

~

.J

Year and Subject of Investigation1973 conlinued

Gillespie 0, Gillespie S, Galla RC, East JL and Dmochowski L. Ge­netic Origin 01 RD114 and Other RNA Tumour Viruses assayed byMolecular Hybridizatiqh. Nature New Biology 1973;224:52-54.

Gallo RC, Miller NR, Saxinger WC and Gillespie D. Primate RNATumor Virus-Like DNA Synthesized Endogenously by ANA-Depen­dent ON A Polymerase In Virus-like Particles Irom Fresh HumanAcule leukemlc Blood Cells. Proceedings National Academy 01Sciences 1973;70;11 :3219-3224.

1974

Wu AM and Gallo RC. Interaction between Murine Type-C VirusRNA-Directed DNA Polymerases and Rifamycin Derivatives.Biocnimica etBiopn)'slcaActa 1974;340;419-436

Study· Conclusions

The group lested "ANA from AD 114 virus, potentially an RNA tumourvirus 01 human origin," 10 see if reverse Iranscription occurred togive rise to additional AD 114 virus. This study concluded that "thereverse transcriplaseof AD114 is nol closely related to any testedviral reverse transcriptase. 11is believed that the gs 1 antigen 01tumour viruses is species specilic ...Unless it is shown that one spe-

. cies can produce only one type 01 9s 1 antigen, however, it can al­

ways be argued thal RD114is a new cat virus with a gs1 antigenthat differs from the antigen lound on the viruses of known felineorigin. Also, il was noted that "only viruses which had been grown inIhe orignal tumour cell and had never been purified as a cell freeextract before the linal colleclion hybridized (Ihal is joined) stronglyand specifically 10cell DNA ..

"DNA polymerase activity in human acule leukemia is recoveredlrom a cytoplasmic subcellular fraclion having a densily (1. 16-1. 17g1011) characteristic of RNA tumor virus particles of animals ...lhe puri­lied enzyme uses synlhetic lemplate-primers with a specificily like

RNA-dependent DNA polymerase (reverse transcriptase/ of virusesand differenllrom the major DNA polymerases of norma proliferal­ingleukocytes; and ... Ihe DNA synlhesized (within the cells) by RNA­dependent DNA polymerase contained among ils sequences a highproportion (50%) capable of hybridizing to ANA isolaled from a pri­mate Iype-C sarcoma virusandlor a murine sarcoma virus (thal is,a Kirsten (rat) sarcoma-feukemia virus complexj ...The DNA-synthe­sizing aclivily was recovered in a particle not disaggregaled [thal is,nol brok.en. apart or deStroyed) by physical m<;inipulalion unlike Ihevasl maJonty 01 cytoplasmiC partlculate malenal, whIch had a den-·sity 011.16-1.17g/ml ...The presenl results stress the. importance ofpurification of the cyloplasmic particle 10obtain a suitable DNA probe,[that is, a particle which can initiate the invasion of normal DNA byloreign viral RNA) ..

Similar 10 those reported previously

Possible Relationship to HIV Synthesis

Many researchers believe that the AD114 virus evolv.~'1 from a catvirus to laler inlecl humans. This report stated Ihal: -:;,;me experi­ments have been reported which have led to the belid Ihat AD 114is not a cat origin or is likely 10 be of human origin: ,Ill:;! as Gallo'sresearch team argued in this paper, "il can always br, iH~JlJed thalthe" HIV evolved as a simian virus with antigens Ifof81'"Jn proteinswhich prompt an immune response! that differ "Irom the antigenfound on the viruses 01 known" monkey origin ..

Also, Ihe group concluded Ihat"ANA lumour viruses main­

lained in tissue CUltufO [as opposed to a cell line in cullurel often donol produce Ihe pathology of the original virus and give cause for.

questioning the indiscriminate use of the viruses tran:,Ierred tromone type of cell 10another." Apparently, the group was ne,1 concernedabout creating new viruses; rather Ihal the new virus':5 Itley cre­ated would nol mutate to other less deadly lorms bt.!for8 they couldcapture and study them thoroughly.

Here in the Proceedings olthe NalionaIAcademyol,sr;timces. Galloand co-workers proclaim they have isolated a virus-like particle Iromhuman acute (that is, quick acting) leukemic (white) 1,lo(;(j cells. ThiSparticle they state has a specific density of 1.16-1.1"1 ~rnl. can berepeatedly recovered without being destroyed by phYSIcal handling.and has the capability of producing the principal rapidly progressing

. cancers associated wilh.AIDS including leukemias, sarcomas, andcarcinomas. In essence, Gallo and company announced isolatingAIDS-like virus particles more than a decade before Luc Montagnierannounced the discovery of lAV (HIVj. 11is also interesling to notethat 10 accomplish Ihis resull, Gallo and co-workers ""ported here.using severallypes of ANA tumorviruses including: ·SISV (NRK)­

simian (monkey) sarcoma virus grown in normal ral kidney (NAK)cells; MuSV {Kirslen (lypeJ)-a (ral/mousel sarcorna·leukemia vi·r.us complex 9rown in NAK cells which originated by repeated inlec·

lIon 01 rats WIth a Gross-Iype mUrine leukemlavlfus; ...AvI.V (ANV).avian (birdJ leukosis [Ieukemiaj virus, slrain avian myelohlastosis

(bone marrow cancerj; ...FeSV (Gardner), leline [cat! sarmma·leu·kemia virus, .. ." and several other RNA animal ViflISI::S ..

None more afJparent than above

As Slrecker reported in 1986, Ihis large group 01 rf: ,8archers in·cluding Gallo found the IITlV lamily of retrovirusf)s !,III dlitr but notidentical to Ihe bovine leukaemia virus(SL V).

1985Fisher AG, Collalti E, Ralner l, Gallo RC, Wong-Staal F. A molecu­lar clone 01 HTlV-1II with biological activity. Nature 1985;316;262­265.

Ratner l. Haselline W, Palarca R, livak KJ, Starcich A, and GalloRC el al. Complete nucleutide sequence 01 the AIDS virus, HTlV­Ill. Nature 1985;313;277-284 .

"A clone containing Ihe full-Ienglh HTlV-1I1 proviral DNA was in- This ·paper along with Gallo's earlier publica lion (seE: G"ltaUher. Tingserted Into a plasmid [a extrachromosomal hereditary determining and Gallo, 1972) shows that Gallo nol only had the rnethods andreplicating ·unit olher Ihan a gene from the cell nucleus] and used to materials needed 10 clone Luc Montagnier sLAV, I,ut also the ca-transfecl cord blood T cells Irom normal newborn humans ... lhis pacity 10 develop a foreign germ capable 01 infecllng normal new-molecular clone is infeclious ...and causes marked cytopathic [cell born human cells with the genetic material needE:d Ic, Ciwse markeddealh) on T-cell cultures .. : .. -'-~:~~!~~~~~;!~!:nJ~~I.~.!'~AJQ_~_\l!!~s: ..... ... _._

The complele genetic building block sequence 01 two human T-cellleukaemia Iype III (HTlV-/II) proviral DNAs are identilied and de'scribed.

•cknowledged Funding Source/Biological Weapons Contractor: t Ulton Bionelics; " Bionetics Research labs; § Univ. 01 Calif.; 00 Merck and Co.; 0 Univ. of Cllici"J!Jo; .:'1 Yale U .. .••:M:;:'t':(Jl ••·'71r•..._):.I.••. •

.... -

.,~~~~~:ttVif:tit~W!1(,w~~·;.\~::~j"j,:..c:~~:i"'~:,,·~~;.~i\~~r!~.":~~~'r\~i;1JJ ..~~;'~~~t~I~-~i.1J.t.:;,;.It!~•.,;,.(';.:...;.·:.~;:-;:: ...:h. ';;'~:.:'';.4.:''_.: •.•..•...~. :, ,.•..•....••.•. ,

( II.

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AIDS?7

AIDS­likeViruS

SV40

In 1971, Gallo and co\vorkers reporteJthat a sim­-i:m foamy virus (SFY)-a common contamin:lnt ofmonkey kidn~y cells used to m:lke vaccines-was the"only one" of 27 then known retroviruses. containing

-reverse transcriptase. that could not cause cancer in hu­mans. ID For this reason, littk attempt to remove them

--, from cancer virus cell cultures andvira! vaccines wasmade.

Rhesus ;\lonkey

0- RD 11..1ca[ lcukcmia/sarcoma R='iA sui[:J.bk for hum<ms .• - 7i/':J R;\ ..-\ founD In chicken immunoddicic:ncy rc:tr0viru:>_

'" - Viral shell or envdope proteins, produced in human WBC _cultures, functionally similar to HIV's GP [20s.

~ - Retroviral RNA from simian foamy virus with bel-genesequence that readily picks up other genes.

This work foreshadowed the obser­

vation made ten years later by the CDC'schief AIDS researcher, Don Francis, who

- noted the "laundry list" of feline leuke­mia-like diseases associated with AIDS.

(~ 0--'-Q .)/y~-~ -~ .> (G) -- k:: ~

/ SFV and Othcr Likelv-- Viral Contaminants

~ ~ -

'@ ~,--" ,_/""-P~"- -~j<> ~---~ -; - {--

" .. ~f#:Illl\;IUU- \ I FELV .f..-~:.,..,

ing those that caused the prominent features .

of AIDS-WBC dysfunction, leukemias, h 1t"lymphomas, sarcomas, progressive wasting, ~ r~tand ultimate death in cats, mice, ChiCke~s,

and humans. 10. 1~·IJ All this in the likely ,

presence of other easily mutated F-·...retrovirus contaminants. ,', - '

A· '[ 1 bl .. --- - • Finally. these and other NCIvw.n IV ye 0 astOSIS ViruS /"" ..... d - h . -/"" mvestlgatorsmJecte suc mutant

_ - ~ viruses into human WBC and fetal"( - AMV tissue cultures to enable them to in-fect humans and even transmitthese same diseases.15.16

Gallo's group at the NCI and LittonBionetics also experimented with other sim­ian and human cancer viruses (e.g.: SY40),IO·11and developed recombinants (i.e .. mutants)

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:::rf'\J

SOVIET CHE~nCAL A;";D BIOLOGICAL WEAPONS~1t.SrKE5. The statements indicate that the Soviets have made ex­

tensi\"('~progi-ess in chemical and biological weapons. I would like youto pro\'ide for the record a statement which shows what they are doingin this area and with some indicatioh of their capabilities in this area.

;Vu. POOR. \Ve \vill be happy to provide that;(The information folJows:)

1 The SO"iet L'nion is belter equipped defensi'-ely. offensively, militarily, andpsychologically for chemical ~d biological ":arfare than any othe.r nation .in theworld. She has placed a great deal of emphaSIS on these systems 10 her militarymachine. Ctilizing a wide spectrum of chemical munitions. the Soviets considerthat chernicaltactical weapons would t-e used in conjunction with nuclear weap-ons or separately. as the case may dict:He. The Soviet agent stockpiles include a\·ariet;· of agents and munitions capat-Ie of creating- a wide range of effects on thebattleiield. The Soviet soldier is well equipped defensively. He trains vigorouslyand for long periods of time utilizing his equipment. He looks upon chemical as areal possibility in any future conllic!. and respects his protective equipment. Theresearch program in the SO\'jet CniGn for chemical warfare and biological agentshas encompassed every facet from incapacitating to lethal effects. both offensivelyand defensivel\',

(Additional classiiied information was supplied to the committee [including thetestimony below].!

S~THETIC BIOLOGICAL AGENTS

There are two things about the biological agent field I would liketo mention, One is the possibility of technological surprise. Molecularbiology is a field that is ad\'ancing \'ery rapidly and eminent biologistsbelieve that \\'ithin a period of 5 to 10 years it would be possible to

produce a synthetic biological agent, an agenT that does not naturally~ and for which no natural unmunnycould have been acquired.

Mr. SIKES. Are \',;e doing any work in that field?Dr. ~1..•.cA.RTHL'R. \ .•••..e are not;]vir. SIKES. \Vhy not: Lack of money or lack of interest?Or. MACARTHl'R. Certainly not lack of interest.?\-Ir.SIKES. \\'ould you provide for ourrecords information on what

would be required. what the advantages of such a program would be,the time and the cost in\'o!\'ed?

Dr. ~I.'>"CARTHL·R, \Ve wi \I be \'ery happy to.(The information follo\\'5:)

\

1l1e dramatic progress being made in the field or molecular biulo~y It'll us lu

investi!!ate the relevance of this field of science to biological warfare - :\ small

group ~f experts considered this matter and provided the following ohser\'a-tions: - _ -

I. All biological agents up to the present time are representatives ofnalurally

occurring disease, and are thus known by scientists throughout the world, They

are easily available to qualified scientists for research. either for ollellsi\'e or

defensive purposes.2. _Within the next 5 to 10 years, it would probably be possible 10 mah.: _,I nc\\'

infective mi~roorganism. which c?uld differ i.n ceriain importan.laspl'lls from I \fany known disease-causIng organisms. MoslImportant of these IS, thall~":l\lB.!!~,

be refractory to the immunological and then!JL~utic processes upon ,,-hich weaeiJe d to mall1tall1 our reTaTtve fre"ed(Ji111'fOm inrectI6'U:~-dlsease·.·-·" ' ,

3. A researc program to cxp ore t e feaSiolli'tyoTiliis'cOtiTrbe cOl11plCICU

in approximately 5 years at a total cost of $10 million.4. It would be very difficult to establish such a program. Molecular bil1logy

is a relatively new science. 1l1ere are not many highly competent scientists i_1lthefield, almost aJl are in university laboratories, and they are generally <Juequately

- supported from sources other than 000. However. it was considered possible

to initiate an adequate program through the National Academy of Sciellces­National Research Council (NAS-NRC).

_5. The matter was discussed with the NAS-NRC and tentative plan~ \\TIC 111adcto initiate the program. However. decreasing funds in CB, growing criticism

of the CB program, and our reluctance to involve the NAS-NRC in slIch a con­

troversial endeavor have led us to postpone it for the past 2 years.

It is a highly controversial issue and there are many who belie\'e~u<;:I]research should not be undertaken lest it lead to yet anoTFier meliiod oGi1aSsiyc

:P\TII1g of larg~Q.Qp--uJa.ti.QJ.)1.Orithe otrrcrnand-;-;;vitnouitne'sure sc'lenti'lic knowl­

edge that such a weapon is possible, and an understanding of the ways it coulube done, tl1ere is little that can be done to devise defensive measures. Should an

enemy develop it there is little doubt that this is an important area of potelltial

military technological inferiority in which there is no adequate research pro-

gram. _

The above testimony of Acting Assistant Secretary of the Army for Research and Development. Charles

L. Poor, was printed on page 79 of the public record cited below. However, Or. MacArthur's above

statements were deleted, Dr. MacArthur was, at the' time, the deputy director of the Department 01

Defense. The complete testimony was found initially by military investigator Zears Miles and subse,

querilly by atlorney Theodore Slrecker, J.D., through the Freedom of Information Act (on page 129 of

the supplemental record). A copy of the original classified document was later published on page 124 Of IY\­

Deadly Innocence by this author in 1994. Source: Department of Defense Appropriations for 1970,

Hearings Before a Subcommillee of the Commitlee on -Appropriations House of Represenlalives.

Ninety.Firsl Congress, Part 5 Research, Development, Test, and Evaluation, Dep!. of the Army_ TlIP~-

day, July 1, 1969~ page 7\ 'shinglon: V.S. Government Printing Office, 1969. (,

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ql~Fig. 7.1. Theoretic Manufacture of AIDS-Like VirusesFrom Bovine Leukemia· and Sheep Visna Viruses

Bovine Leukemia \ .rVirus \ ./' /' -t:!) ..~ /' SheepI Visna Virus

~AIDS ?

Next, in order to getthese viruses to cross thespecies barrier and infecthuman cells, Strecker re­ported that researchersmay· have cultured themwith herpes viruses or hu~.man white blood cells. The

.viruses· were thus repack­aged. Herpes virus enve-lopes, for instance, thencontained genes for BYV,which could have easilycreated a virus that did ev­erything the AIDS virusdid.

~ ..LikeVirus

•I'\.

" ~

~.

Virus

Strecker theorized thatbioweapons researchers began by mix­ing bovine leukemia viruses-whichthey knew were T-cell attackers-with

sheep visna viruses-. which were rec- (~Oognized T-cell destroyers. They thus Cproduced bovine visna viruses. !BVV

/V\- Bovine leukemia virus RNA with reverse transcriptase0-Sheep visna virus RNA with reverse transcriptase• - Herpes virus DNA found in infected humans

Diagram depicts the theoretic manufacture of AIDS-like viruses according to Robert Strecxer, M.D.,

Ph.D., beginning with the bovine leukemia virus and sheep visna virus. Support for tr.;s theory was

presented by Fert Detr:ck, NCI researchers Gonda MA, Braun MJ, CEr-er SG, Kcst i,~.Sess Jr J'ff, !

Arthur LO, and VanDer Maalen 1v1J. Characterization and molecular Cloning of a tC'/ine !er:\!'/irus relate'.1 I

to human immunodeticiencyvirus. Nature 1987;330, 388-391.

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~. pc C v-. '")L\..J

~.

I Table 4Funds obligated for A.I.D. activities and amount and p~rcentagefor health, popula~ion and nutrition projects by country orother allocation, Africa Region, FY 1973 aridFY 1974.

FY 1973

HealthPercentage for

r

AllocationTotalPopulationHea1th,P~pu1ation

& Nutrition

& Nutrition

(thousands of dollars)I I

1 Total162,14320,57213.0I I Regional 15,6005,16133.0

IBots·...·ana 57I I Cameroon 80

J Central Africa Republic188

CWAR.P*17 ,2.001,472 9.0

Chad1091513.7

Daho!:ley

126

East Africa Regional

962.- I

.Ethiopia8,8004,82155.0I

Gabon

30- -I

Gambia

451533.3IGhana

21,4331,0345·.0IIvory Coas t

35- -I

Kenya12,2001552.0I

Lesotho

111119.9Liberia

16,1001,3729.1Ma 1a.•.•i

1554931.6Mali

27Mauritania

842428.5Mauritius

26Morocco

11,7005105.0

Niger

841922.6

Nigeria

10,600830 .8.0R.•.•anda

741114.8

Senegal6557.6

Seychelles

5Sierre Leone

75- ,..

So. Africa Reg. OSARAC20,6235103.0

Sudan11,000

S.•.•azi1and1074945.7

Tanzania7,2003,06443.0

Toga.119

Tunis ia2,l.651,01941. 3

Uganda1,12.012511.1

U?per Volta115

Zaire3,592.3018.3

Za:::::ia

l~J",

L--*Cen:ral ~~est: ;.~f:ic.2.. RC6ional

11

iI.

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~5::=a:~::~~:~c:~:~_;:~:F:=:a: :~a~1~7~

-----------,-".-"----r-

.c::i....~;::;·:· : ':B::::';: ·..-es: A::~:a Re~ion.]l?:=:e~: :;::..::e: ~€.:.=:es :::--.::J~ - S::.al:"cy. Erad~c ..itlQn

COUNTRY : Central West Africa Regional·Project Name: Onchoce"-clasis Control Pro~ramProject No. : 625-11~SI0-908Began : FISCAl Year 1976Estimated "Termination Date: Fiscul Ye,H 19RO

_----------------------------- ...--.-n....---. _._~__..~..

'0';:. '::.•• ! CI..-:. - -. - .....

~:;-::-;::-::~,. ­.' ~.

j-=::,;:- .

?:=~ ~:::'::=;-.::~:::;:

ilf

!i

,.1

!~!i

Description:

~:

'. , ._~~~~:=;_ ::~E::::~r

~"

Jes:::':::::.:

::-.:',; ;~~~~:: ···a'E ::2=:'g:-,:,: :.: as;:'·S: :: ··:es~ ;:-.c 'Ce~t:'al Africar.CCC~:=:E3:~ :~E E:~:::a:::~:: ;~e::~:Xa~: :~e :2~t:ol of ~e3s1es.

~=G!:~~X:~ :~e :: :~e ~:5:le:~a:~~;~;sesknovn to ~an and in

A!~~:a~~::5;~~::X:=;:E:Y:~: :: :~:5~.5::i:~~~, :~e s=al:?cx porticn

ef :he ;:c:~:: ~e~~~se~:5 a :.~. ::~::~~~:~:~ :: :~e global prcg:a~

~!~::~::~~~~·~i~~~~:;~~:~~~!~~::~~:::~:~~~:~~~~~~:~:~r::~1;a~~:l::litYa=c~~ ::~~g~:~::~~5,

~~5 ~;~r:e= out fer A. I.D. bvt~e :c~:E~ :~~ :~~=~=e ::~:~:: := :~~ ?~5 ~~:~: a ?A5A. Co~oci~ies were

pr~~i~e: :: A.:.). :~=:~g~E~~~: ;~:~==e~:=~::~ :~e Crga~iza~1on forCcc~era:ic= E=~ ::~7~~~E::=~i= :~E !~~~:Ag;:~5~~a~or Eade~ic Diseases

~:~~~~~a~~~:'~;~~~~~I~;;:.~~~;~~~i::~~~i~~~~~~~~~:~~:~:~:~~:~~:;~:~ein"par:ic:~at:~g ::~~:::=5~=~~::~ ~~~. ~E :e~~::eC.

:"jas~ .: :':-.c:'·,;,=~: ::.e ::..ass 5='; __~·:y. ·:a::':':-.a.:ion of the e.ntire

~~p~i~t ~~ :~~: ~;~" ~;:-.~~~~:~:.~: :.~: ~:.; :~;~~~:~~~;;: i~e::~;~5'J:~~ i :~~ ionyears, late: ~~::·;ce: :: ::;;~ ::ea:, :.~ ::<:5: c:;",,::.les: Phase [I was

i~~~:~~~;'5a,,~<~~~~~~~<~:~~:~a~~:-~ ~' ~~~\~~,/:~i;~~:.vaccinat ions

?~c5:~g :~: c: ~.~. ~ss~s:a~=: :~~~ i~ t~19~1. D~ring thisperioc L.S. ~~v:s~~~ _e:~ ~~ga~~~ :~ a::i~i::es ai=ec at br1~ging about

an orce~ly :=a~s:t~:~ c: :~e ~::;=a= ~~:~ ~eal:~ 5e~~:ces of the

partic!?at:~! C~~~:::es. ':~e ;r=;e:: ~as ~=~::~ce~in ~. 1974.

This program Is aimed at alleviating human "suffering and ,11

rehabilit"atlng the onchocerciasis infected areas. Onchocerciil';!s(river bllndne~s) affects over one million ~ersons in th~ zonecovered by the" proposed co~trol program (a river bilsin area sharedby "Dahomey, Ghana, Ivory Coast, Hali, NIger, Togo and Upper Volt;').Fear of the disease has led to abandonment of e"xtenslve areas offertile river valleys in the Volta Rive~ Basin. These valleys orBbadly needed for ~roductlon of stAple food supplies.

In July 1968 a conferenc~ convened by ~IO with the West Afrl,·~OCCCEand AID concluded that control of the disease was technicallyfeasible. Followini that conference the seven governments of theaffected Volta River Basin area confirmed their desire to pnrtidp"vin an onchocerciasis program.

A Preparatory Assistance Group prepared a plan of work to ~~hJ~~~control of the disease in the affected zone and to work out expccL~J

·costs andbeneHts of the scheme. At the end of June 1973, the" W.n\,!Bank and WHO, the fiscal and executing agencies for the proposedprogram, convened a preliminary meeting In Paris of the particlp"t \:1;:African countries, .Interested dorior Governments, and concernedinternational agencies for purposes of organizing the programmingand implementation of an international effort with regard to onchoc~:­ciasis. Total costs for the twenty-year control program" are estJm"r",·!at $120 mllUon. The to"tal cost for the first six years is estim.Jt."Jat $56 million. The Onchocerciasis 1976 Fund Agreement was promIJh,JI"" I. ";in which Initia.l funding of $7.5 million has been committed by Can;••.I:1.France, the Federal Republic of Germany, the Netherlands, the UniterlKingdom, th~ United States, the WHO,UNDP, and the World Bank. Thetotal U.S. contribution to the six-year·phase of the program Isestimated at $8.2 million, or not to exceed 20 percent of total pregr~rncosts. The participating governmentA will provide the program ·withfull support including priority consideration for socioeconomicdevelopment in the sectors freed from· onchocerciasis.

:"Jt,2,:

~;: •.. =- .. -

~;: - ~..-:::1.- :

--==-~ :: ::~a:=:.~:-~ :'::'':ga:e:

S:-,:':':,:'J:

A. I.D.

A. LD.FundJ.EE.:

fY 1974 - $2,000,000 grant funds were obligated by A. l.D.Total through 6/30/76 - $2,000;000

\

39I\:(

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- - --~•. _- ._-----" ----- .•. '"- ~ -"¥"

CD•....

,-

HEALTH, popuunON AND NUTRITIONAFRICA REGION

FY 1973 - FY 1974

Labor Project 1,605,000

Univ. Teaching of Population Dynamics U. of N. Csrolina_AFR 797 600,000

.. : ,''';';

500,000

1,775,000

FY 1974Funds

796,000

685,000

1,180,000

FY 1973

~

Meharrl Med. Col.AFR-373

, j;, \ i..J ;"':j ',., H.'~' : !

Population CouncilAFR-629

AAMC, csd-117l 435,000-

Pathfinder Fund

AFR-575

Univ. of Calif.

(Santa Cruz), ORTAFR- 79 9

Population Services 245,000Inc. AYR 827

ContractorLoan No.

MC!! & FP Training and Research

Deve lopmor"

Family Planning Courses in Health

Training Institutes

Maternal and Child Health Extension

Regional Population Planning

Regional Population Planning

Regional Population Support

Marketing Research

TieleArea Project Number

Regional

_698-11-490-363

-~egional

932-11-570-360

Regional

932-11-570-374

Regional

932-11-580-166

Regional

698-11-580-189

Regional

698-11-580-346

Regional

932-11-580-358

Regional

932-11-580-359

Reg1"onal

932-11-580-373

::I~";t:')na ~

6~~B-1L-SQd-13i

/- ~giQntll

932-11-5 if)-D7

_________________________________________________ ~ 1_5 _

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Meaales Cont~ol!Smallpox E~adication

University Cente~ fo~ Health Sciences

Strengthening Health Delivery Systems 436,000

549,000

)5,000

1,000,000

2,000,000

FY i974

Funds

461,000

15,000

4,800,000(1.)21,00015.000'

45,000

800,000

740,000

214,000

224,000

340,000155,000

335,000

80,000

1,011,000

FY 197)

. Funds

U.C.L.A. A~R-697·

Contractor

Loan No.

{L) 66)-H~OlJ<:

U. of PittsburghAFR-756

Howard U.

AFR-G-I077

Rural Health Management Services

Population ProKram Support

Population Dynamics

Special. Population Activity

Danfa.Ru~al Health Development!

Family Planning

Albe~t Schweitzer Hoapital

Mala~ia Eradication

Regional Public Health T~aining

Howa~d Unive~sity Confe~ence

Special 'Population Activity

Onchocerchiaaia Control

Training in MCH Care

~ ~ect Numbe~

Regional

698-11-999-135

CI.IAR*

625-11-510-116

CI.IAR*

625-11-540-510

CI.IAR*

625-11-550-531

CI.IAR*

625-11-590-904

CI.IAR*

625-11-510-908

C\lAR*

625-11-550-B09

Chad

677-11-580-500

Echiopla

66)-11-510-006

EChiopia

66 )-11-5 30-170

Gambia

63S-11-5BO~200

Ghana

641-11-580-055

Ghana

641-11-580-064

r--

Ghana641-11-590-068

Kenya

615-11-580-141

*Central lIest Af~ica Region

16

Area Proiect Nl1mbe~

Contractor

Loa~ No.

FY 1973

~FY 1974

~

Lesotho 632-11-580-500 Special Population Activity 11,000 19,OOO

,Liberia 669-11-540-054 National Medical Cent er . DHEI.I/IHSPASA AFR 36-85

1,276,000 1;274,000

Libe~ia 669-11-540-110 Mate~nal and Child Health Training 96,000

.a\Ji 612-11-580-500 Special Population Activity 49,000 48,000

Hauric.an1a 082-11-580-500 Special Population Activity 24,000

Mo~occo 608-:22-521-096 l.Iate~Supply 608-H-040 (L)

Morocco 608-11- 570-109 Demographic Research Center U. of N. Ca~oiina

csd-2495

200,000 140,000

Morocco 608':'11-580-112 Family Planning Support 310,000 270,000

Ni ge r 698-11-580-500 Special Population Activity 19,000 5,000

Nigeria 620-22-521-720 .Ibadan \.laterSupply (1.) 620-H-004

Nigeria 620-11-580-789 Family Health Training Johus. Hopkin. U. 830,000 2~5,OO()

R\Janda 696-11-580-500 Special Population Activity 11 ,000 5 l ,000

Senegal 685-11-580-500 Special Populatio~ Activlty

..:.,!:: 1 ",;,j Ho:::.:.. 1 .:"tl.J I

.::,! :...:H..:.al':h~ F.I.~i I,:··!.';,!.'I

17

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--------------.----- ..------ ...--.---.----. :.----.-.-- ---.., --- ..

.-.. ~-._...__ ._.._- .._------_._.- .._._ ..,-- ..•.-...., ,._-~...

IB

The above selected items show a wide array of conlraclors, including The Population Council of the City of New York, and related projecls, including several called "Special population ~clivily."

. The word "special," in intelligence circles, typically indicales "secret" or "covert" Source: Report on tIle Heallh Population and Nutrt/ion Activities 0/ /ITeAgency/or IfT/ema/IO!"11DBlT ·'men!.Department of State for Fiscal Years 1973 and 1974. U.S. Government Printing Office, Washington, D.G. 1975 ( \.._.._... . . . ._J . . ... .__~_. . .__... .__u_._. ·....-. \

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~MITHSONIAN SCIE~CE INFOR~ATION!PROJECT NUMBER lOo NOT U5e th i 5I

II

pE:. . JD COV ER EOI\..- --- -

i T:Tl~ OF PRGJEC7 \~O ch~r~cters or less)~ .I

I Laboratory and Epiaemiolo~ic Studies of Viral Hepatitis AgentsI

I.'WiES, lABCRATORY AND INSTI7UTE AFFiliATIONS, AND TITLES OF PRINCIPAL INV.ESTIGATORS AND

I PROFESSIONAL PERSJNNEL E~jGAGEO ON THE PROJECT

\ PI: R.H. Purce11 Head, Hepatitis Viruses SectionI Y. Moritsugu Visiting ScientistI .

! V. McAuliffe Research Associate\ Y. Shi::lizu Visiting Fellow

I G. Hess Guest Worker! J. Slusarczyk Visiting Fellow

1 1. MathieseCl Guest.Worker

I

\II

ZOl Al 00026-11 LID

Cctober 1, 1977 through September 30, 1978

ALL OTHE~

LLD, .NIAIDLID, NIAID

LID ,NIAIDLID, NIALDLLD, NIAIDLID, NIAIDLLD, .NIAID

PROJECT NUMBER

L. Barker, D. Lorenz,E.Tabor, R. Gerety (FDA)

Bank, NIH)

E:XCHANGE\ U.S. DEPARTMENT OF5DJ.ce) HEALTH. EDUCATION) AND wELfAREPUBLIC HEALTH SERVICE

NOTICE OfINTRAWURAL RESEARCH PROJECT

Other:

P. Holland, H. Alter (CC, ~loodK. Soi~e (Delta PrimateCenter)J.L. Gerin (~~N Laboratory)W. London (NINCDS)

T M::>V"'""I::""cJ erne)COOPERATING UNlis (if any)

None.

us7 BRAlICH

Laboratory of Infectious DiseasesSECT I ON

Hepatitis Viruses Section

INSTITUTE ·ANO LOCATION

NIAID, NIH, Bethesda, MarylandrOTAL MANYEARS: PROFESSIONAL:

99/12 51/12.OTHER:

36/12

:HECK APPROPRIATE 60X(ES)

] (a )~HUMAN SUB .;ECTS o (b) HUMAN TISSUES o (c) NEITHER

] (a. 1 )M I NORS 0(.12) 1NTERV I E\JS

:;UMMARYOF WORK (2QO words or less - underline key,",ords)

This project consists of concinuing studies of the chemistry, structure,

epidemiology, immunology and pathology of the human hepatitis viruses.The goal or such studies is the control of human viral hepatitis by applicationof the most appropriate methods, including active and passive immunization,

chemotherapy and interdiction of spread of the viruses. Progress: Thebiophysical and biochemical characterization of hepatitis Aviral antigen has begun, and studies of the immunopathology of hepatitis typeA in non-hu"JJ.anprimates, using defined pools of virus, are in progress. Aninactivated subunit vaccine for hepatitis type B has been developed and isundergoing extensive tests of safety and efficacy in chimpanzees and ~an. Athird hepatitis B antigen, ~ antigen, is being characterized and itsrelationshi? to infectivity is being explored. Eviden~e tha~ populacionsof he~a:~~~s B vi~~ses may cCQ:ai~ defec:i~le i~te~feri~g part~cles has b~e~-..'- - .••. .: .., ,;:=.,";uu'-.::.~.... )

... .-. '. '" ' .~ . a~a t~l~ :~~alng lS .oel~g.uclL~ZeG..~~ re~2~eG a~:2~?C3 [0 ~S.)~3~2."'''e"'~"s .,"'eP1'fre~·cg"'~zo(,'~"""cal s,-...c!.rnme~"ne "'on' ""o..."p "e .....,~'~l'"••••. l/ __ V_ .•• ..- .•.•..••• "' •.. ~_ •.••.•. 1...1.. .~ ....•••.•• ..;....1.. .• 1" .•••. 1· 1.:, , "-Jt:". " .. -.:-\, •.... lJ..-~ L •• ~'"-'- .•• \,.--

ha leen further defined and attempts to identify an etiologic agentintensifie~ through transmission s~udies in chimpanzees.

)urce: USDHEW. Virology: Volume 4-Controlo/ Viralln/ections. MAID Task Force Report. Bethesda, MD: Public Health Ser·:8, National Institutes of Health (NIH) 79-1834, 1979, p. 20-65.

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CONTRACTOR

FORT DETRICK RDTE

NUMBER OF

CONTRACTS

TYPE CONTRACTS

C{<{'l..JCONTRJl.CTDATE

TER1'1INATION

DATE

Bion~tics ResearchLaboratories

Univ. of California

Univ. of Chicago

Litton Systems, Inc.

Merck & Co., Inc.

New York Universi~y

Research Fnc1.'"'l.ofSta~e Univ. or NewYork

Sr.a:J.fordResearch Inst.

2

12

13

14

2

2

3

1

Mar 1966Jun 1967

Apr 1950Sep 1950Mar 1951Aug 1951.~ug 1952Oct 1954Jul 1962Mar 1963Mar 1964Jun 1965Jun 1966Dec 1967

Jul 1955May 1956Oct 1950Jun 1951Dec 1951Jun 1952Jun 1952Dec 1953Apr 1960Aug 1962Oct1963Nov 1964Mar 1966

Jun 1960Nov1962Mar 1964Sep 1964May 1965May 1965Jun 1965Mar 1966Apr 1966Jun 1962Aug 1966Nov 1966Mar 1967Nov 1967

May 1955Apr 1960

Nov 1951_Jan 1954

Oct 1952Jun 1963Jun-1969

Mar 1964

May 1967Sep1968

Sep 1953Aug 1951Jul 1953Aug 1952Oct 195~Oct 1955Dec 1965Dec 1963Feb1965May 1966Nov 1967Nov 1968'

Mar 1957Sep 1963Feb 1953Jun 1953Dec 1953Jul1954Mar 1954Dec 1956P-.pr 196:;Aug 1965Oct 196~Oc t 19 65 .Ju11966'

SeD 1965Feb 196<.Nov 1965Jan1965Oct 1965Jan 1966Sep 1965Apr 1966Jul 1966Jun196t.Dec 1966Jan 1968Mar 1967Nov 1967

Dec 1955Jun 1961

Nov 1959Jun 1956

Mar 1965Jun 1967Jul 1959

Je.:1 1966

A:Jr 1967Feb 1969"

University of Texas

University of Virginia

8 Oct 1951Oct 1952Sep 1955Jun 1957Fab 1951_~ug 1958Mav 1963J'..ln1968

Jun 1965

Me.y 1957

OctJulJul.~'..lgFeb_~ugOcr.Jun

1954,195910-~.•..... :> .....

19531953195010-:::J 0_1970'

Docume:lt recreated fromlibra0.1 micr::Jfiche. These For1 Detrick contracts were extracted frorT: twe:i'V-, ,......""';:. •••.:::.""'1~ •.• "':1 (" r'\.:"~~ .."~r !;_.:~"'S I~ A'1 ~~....\;v;_r 1.')<4 ,1 lia: ':'r":i,...~jT~ fi'J ~rv:-,h!· -. ~: ;~~-. :::::.--.;-"'''''.•../1\ .•.... !"" .••.••• :::' •••..• -::. vI vJ,:l .••..•.••..•.v...J! h~\I.j:; ,j,.~ v :I\ •.•III\. .•••.• J _! •••..1 IJIJ~I u. ::> ••. 1_ I., ••••.•••• ".'~' 1••.• ,11 __ 11 v •...••...•..•....~_"Cvtne ;]epailmeAt oi Deiense, 1377." Hearin:::s ~ei:)re the Suoc:;mmittee ::In He2i:h ana SCie::::rlc

ri'esearchto examine ,Army biological v'v'arfareresearch programs, March 8; 1977 a!ld May 23, 19-:-7.Congo Sess. 95-1, pp_ 80-100. t Denotes contractunder which Robert Galla and his colleagues mayhave worked.

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.:

· " ~~~

Fig. 22.t Special Virus Cancer Program Book Cover

'This book was removed by NCladministratorsfrom the Fort Oetrick library's catalog. It was discovered

by the author serendipitously in the basement of the University of North Carolina Oavis Library .

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'EmergiTlg Viruses: ,'U1JS aruf 'Efjow 'I11cSpecia[ 'v'ims CtlTlca '1'n~lltJ:11

Ultimately these studies will require an exhaustive effortto develop drugs, anti-en7.ymes, gene repressors or inhih i lorseffective at the roolecular level.

~blecular Studies 3. Immunological Stud ies

a. Basic studies

(2) To de~-elop highJ.:.· sensith-e methods for the detectionof virus or -.-irus actj-,-j ty in ht=.'1 cells.

As knowledge of tl-.e f-:r.d.a;:-oentalmlec.uar e\"ents invirus-cell interacticns is dc".-elcped,. the Progr;im ,,'illapply this infor.naticn to t1:e st","dy'of human canceras fullm •.s:

(3) To de\-elcp a raticnal !::asis for therapy or preventionby 2xploring nricus ap?rnac.'1es to blocking of vi ralreplication and/or tumorigenesis at the cellularand subcellular leyels. !ne tl:erauv could bedirected at any or all of the stages of celltransfomaticn c€gi:mbg '~ith cell infection by attDror dr.J.S.

a. Basic studies. Investigations of selected roodel systems,represent I11g twnors induced by Type C I Type B, and "erries­type vi ruses, will be extended to further ident ify ,characterize and determine the vinlses. viral antigens. andmembrane antigens of tWT10rcells. TI,is includes developmenland appl ication of improved techniques with the sensit i vi tyand sped fid ty required to detect ce llular al terationsinduced. by twnor vin15es alone o.r as the result of interact ir'nwith other environmental agents (e.g. chemicals, irradiation'.Efforts will be increased to develop similar immunological

.methods and diagnos t ie reagents for appl ication to Innnancancer. Research will be intensified and expanded:

(1) To study cellular and humoral immunemechanisms'and to determine their' relative significance inhost recognition of and response to tumor and/orttDnor vi ruses.

(2) To develop methods to enhance host response to. turnor or virus antigens.

ImmwlOlogic research has provided extremely scnsiti\T tcdUliqucsfor detection and characterization of tumor vinlse5, viral cUllirt'l1s.and dlanges in surface membranes of tumor cells. Indeed. sllchefforts have' contributed to an understanding of the role ofimmunological mechanisms in host-tlDnor and Ilost ·vims interact, .,,:which provide an approach to the prevention and treatment ofcancer.

b. Applied studies. Basic research will provide the fr3l1.el%rl·for Identification and characterization of viruses, viralantigens, and cell membrane alterations in hwnan cancers.Immunological methods and reagents will be developed andapplied:

Increasing emphasis will be directed toward research on sponta,v',,":or naturally occurring tumors in model systems relevant to humancancer. These studies would provide the basis for a rationalapproach to prevention (vacc.ines) and treatment (immunothcrapv)'of cancer.

To identi!'" and c.,",racteri:e si'1lilar enzymes orenzymatic activities ·~it.'1in nor.:-el and ~lignanthu.-nancell s .

(1)

The Progr= is prepar=:: :0 broade:J i:s activities foridentif;ing and cr.aractcd:i.-lg tI,e s;:ectrum of en;::mes(and other ~iators) r~red bv tur.cr viruses forreplication and trans~~tien.

b. ftpplied studies

In recent r.1Ont.'lsra;:id U\a;or ad\;ar.ces ha"'e !::eC!1made in thefield of IOOlecular ~iolcg:.·. These :indir.gs· ha\'e direct·application to t.he s~:: ef :.'e relaticns;:iJ: of vi ruses totlIlOOrs. There is e,,-:cer.ce ::-.a: ::-.e ge:-:eti( :1aterial (R'~-\)

. of the turrer \-ir'.1ses can di:ect t1:e s\Tlt::esis of new D~-\.The deroons'traticn &:.E.t R\.~.t\;..;or \i ruses c=ntaiil en:\T.1es

(polymerase, ligase) ••hie:' ::-.aybe requi ~d for \i ral' infect ion,interaction ;.-ith hest cell ge!1er.e, ar:d \'iral replication hasprovided 1:..~ebasis fer 1:..'1e::e·;elq:ment'·o: :-:e·~·.extre.'nelysensi tive :ne6od.s for the cetect:'en of or.co~enic vir.JSesor their "fingerprints." I::eeed, k;;c-';;leGgeof the fi.mdamentalIOOlecular events ·~hic.'1occ.:r durir.g \-ir.JS infection andsubsequent cell tr-..nsfoT:;13tien provides ::-.e first tr.uyrational approac.~ to theraJ::--.. E:I:YFoCacti ·.i ties analogousto those of R';A turcr virolSes ha,,-e recent:·, been fOlmd incells of h= leu\;e::rics. ·TI-oisoffers s:':~~g suvoortiveevidence that '\iruses are associated ·~it.1 car.ccrs· in man.

.~:(:)=

29

II~

(416 ( \

./ [';(

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·., "

'Etrt.erging rr/iru.ses: :J..l'DS and: f£vow.

(1) To relate candidate humanviruses to knownoncogenicagents ..

(2) To identify and characterize interspecies viral antigenswhich are present in knownmammaliantumors, and therefore,could provide the basis for a formidable probe to detecthuman tUITOrviruses or viral antigens.

(3) To launch large-scale seroepidemiological surveys.which will define high risk populations.

(~) To determine the presence of cross-reacting antigensin various humantUITOrs.

Clinical studies will be directed toward understanding arid manipulationof i1mm..memechanismsin humancancer as a basis for:

(1)· Development of vaccines from identified and fully­characterized human tumor virus (es).

(2) Detennination of the· role of host irrrrn.meresponsesin tumor recognition and rejection.

(3) Application of (1) and (2) in the prevention and controlof humancancer.

AS· research progresses, increased emphasis on application. will beas follows:

(1) Inmunodiagnosis and seroepidemiology .(2) Clinical studies on the role of irrrnunemechanisms ill

hurnancancer(3) Immunotherapy(~) Vaccines(conventional or other)

Ultimately, these studies \oJOuldbe organized to coordinate andintegrate the application of appropriate biochemical, immunological,and genetic methods of detection, prevention, and control of varioustypes of humancancer ..

4. Test Systems

In vitro and in vivo (animal) test systems will be carefullyselected to evaluate the work outlined L~ the previous researchareas; specifically: (a) to determine the oncogenic potentialof candidate humanviruses; Cb) ·to develop bioassay systems ..for testing viral, and viral/ch€mical carcinogens; (c) to beginvaccine (conventional or other) testing and irram.m.izationprograms;(d) to begin therapy testing programs; and (e) to explorespecial animal·tumor systems with particular relevance to humancancer.

30

Source: 1'1CIstaff. The Special Virus Cancer Program: Progress Report #8. Officeof the Associate Scientific Director for Viral Oncology (OASDVO). J. B. Moloney,Ed., Washington, D. C.: U. S. Government Printing Office, 1971, pp. 28-30.

418

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Objecti1Jes: To de~e::::::".e ·..·r.e::-:er :::-:.:: ;a:-.:':-,c .:::.:-:ce~ is caused b:' 'Jir'Jse~'and ~ilethEr t~ere i~ a~~ ?css~~:e ~:~:::g~':a::2:a:~c~s~i? bet~~e~' cani~eand hu~a~ tancE~5.

A conve~~ent, ~~a~::':a::'~a!:::~:::"::'.:y :=c~s assay ~ r feline ~i~~s ~asdevelo~~~ fer s:~~ie5 ~5~~g ~e::'~c::e·;~~=:'a~::':~5~E~ ?::e~pts,t= re~o~erdefact~~e ~i=~5~S ~=== :a~~~~ :~=~:E, ::ia:=~~:~::.:3CdR and I[~~ ~as

~:::~~~:e~::~ca~~~=~~:~:~~~~~=~~~:~~=:;.:~~~~:~:~~.~::~~~ot~;~::c:~;~;c'leuke~ia ~iruEEs, te ~~~ ac:~~a:~~ ~~:~5 ==:~~c:~:~. T~o.viruses appear tc

be prcs2~t.

Studies ~ere i~i:i2tE~ :c E~a:~i:: :~~ €~f!:: :~ c==bi~ed ch~~ctherap? a~d

::::O:~:~~~i~~~~~2:~~~~;~~~~~:~~O~~~~~:~'~;:::~'~~~:~~~:~~s~~~~~~i~:~,~ffect o~ dcg cel15 i~fe::E~ ~i:~ ~!:~~e :~~~e=ia ~~rus. Eve~ a :~X~C

drug le~Els, the re?:c~~c:i~n =~ :~i~~=~S ~a5 ~ct eli~inated. ecal areas

of ~orpholo~ica: c~~~ge ~er2 =~se~:i~ ~~ :~e :a~~~e cells expose te

streptcavci~.

.-Qoq,0'

Current Contract Level: $36,800

Date Contract Initiated: December 3. 1971

Proposed Course: .Continuation t'o achieve the objectives de~"ri!,,~d.

Significance to' Biomedical Research and the Prog~am of the Innlitute:The long range .goal of the research program of this laboratt1l'::---i·;;'---­an unders tand ing of how oncogenic vi ruses overcome cellu la r g r. ".,'Lhcontrols. Ul t inia tely. an understanding of the mechanism of ItN'I' I :1:'tictransformation by viruses will depend on progress in tWQ are",.;(1) the identification and characteriza~ion of those viral getll'functions which are essential to the tra'nsfol'mation process, ;\" ..'

(2) the determination of how and where these essential viraJ \,•.",',:interact with the cell and with factor.s which normally operatl·

in regulating cell growth, The proposed contract will allow.Dr. Benjamin to continue and extend his impressive work on Litisproblem and will foster collaboration .wi th other NCl and SVCI' '.,'rke!'s .

Project Officers (NC!): Dr. George To<l"roOr. Roy KinanJ

Major Findings: Eight cell lines including 3T3, 3Tl2 and sar",'I::.1virus transfor~ed lines, have been transferred from Dr. Todaro'~

laboratory succ~ssfully and are being checked forpassible·spl~· Lionof ·variants .. This contract is new and no other results have b""\I

obtained,

Objective~: To investigate the relationship between ~ell surr.t,~alterations induced by RNA ·viruses and thos~ induced by DNA v; nI''''';using several oncotna virus~s and non-transforming mutants ofpolyoma virus.

Contractot's Project U1rector: Or, Thomas Benjamin

Title: Study of .Cell Surface' Alterations Ind'uced by RNA and 1':::.Viruses.

, )PUBLIC LTII R~SEARCII INSTITUTE OF TilE CITY OF NEW YORK'---!l'~; ...(NCI-E-, .-2028))

I~\ZELTO:I LABORATORIES, r:;c. (:;ii!-;'~-:,)7ai

Title: Studies on t~e ::rialog:: 0: ':u:::":--.e C.;~..::e:-

Proiec: Officers (SC!): Dr. ~i;~ae: A. Ch!~~3:SD~. R~~e~.:A. ~~a~~~e:

Contrac~or's ?:oiect J!rec:~:: )~. ~r:!~~ ~. ;e~se~

~:~~~t~~~~~~~~u~~:~~~~~~:~~~.~:,~:~~~~::~::,~~~;:~~~a~~~~r~~:~~~~:~~~other sar~c=a:c~s CC~5. S~::E£~;~: ::=~S~:~~:~:::~::~ ~ani~e =a==.ar::

carc~nc:::.a 'Jas a:::iie-;e:c '::: :'r.cc.;:a::::: :: ·:c:.=.~:'=s :':-.~, I: ;:,:nti:1ucuspassage ?fCVes ?cssi~:e, :~~ :~~~; ~:.:: ;::':~~2'a ':a:~a~:e57ste= ~0r

~~~;!~~~;:t:::~~;;::~~;;:~<':~~~:~~:~~:~~~~~:~~~~~~:;c~:~~~~:~~~~~:~:~.~t~=orAtte.!:Jpt5 ar<2 !Jf.cer,:a:: :: d=:-=:-::::'~.: ·_-:-.':::~.e:" ::-.;'~ ::=:ce urc act~.' .•ated ',:":'JS

produc~i.cn,

Sl~nificance :0 3!c~e~~:al ~~5'2ar:~ ~~~ :~e ?~:z=a~ cf the Institute:

Study of cani~e ~e~p:~s~s ~cr ~~~~e~ca cf ';~ra: asscciations is i~portantin seve-:-al re.si=e:;:3. 3~;-..:e :Ol.:.=:.ci:-_$ .=.:-= ::1 C:'':SE ::::1tc.C't '-,ith .:ar.ine pets I

the possibili::: :;,at :::-?:: =..;;.:: :'h? -2::-;::se:: :c a C~::;:::E tt.:mcr vi:-us ::lust beinvestiga[ed_ !:1 '2c:1!,:-as: ~:' ::-.e c=.: .::r.:: '::Ices-c', -;::uses are nc:t re~ularlyshed by canine ~'';::10r c€:ls .. ';7'1 a:-.a::-!;C't:s 5:':·~.a.·:'·:C:1 e:<i!;ts in the nU:1an.

The dog ;novices 2:1 ex::el':c:1: ex?c::'=i:::ta: a:--.:'=.a1'·tc =eteL:!1ine t:,e presenceof covert viral 'infectiens 'ccntri~ut:::~ t: :-:e:~:as:::'c transfor:I1ations. Ifsuch viral relaticn5~i?~ to ca~ce~ :~ :~e ~~~ :a~ ~e firmly established)

the dog yil1 provide cpportuci:y :2 s:~~y ;~~ =~c~a~i5~s for trans~ission

of infection, virus~~cs~ relat~cns~~~s~ !~~ ~~'i:~3~~cnof control oeasures.

Ip. this res?ec:, t~.e cc-g -.;culd ::e ::-~:: :: :.-C ':-23!: =ccels for hlJ.Dan cancer,

Proposed Course: Re~i~ect~cn :~~ ~:::~:

considered to u~ilize t~e :ac: ::es ::~ =~viruses, a ~cre ccncent~ated ~ :~::~ ~:'~3carcinoma" anc e'la!\1at·icr. cf i=;:u:-",~::-.e:-2;;-=·J

naturally occ~r~ing ~e~?la5~.

:.~ :~i~ labcrator! is beir.g

: :~t=~si~e study 00 tu~or:E:a:~onships tq cani~e ma~ary

a~?roaches to centrel of

32~

~Date Contract !~i~!~:e~:~ay ~~, 'l~~?

Current Annui: :e':~l:' S:OO,CCQ

~-1;"L

UJ

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Project Officer (NCI): Dr. Robert J. Huebner

Contra6tor's ~r6ject Director: Dr. Leo K. Bustad.

Title: Comparative Leukemia and Sarcoma Viral Studies

,J:)~~

'If1£. Special 'VinLS Ca/w' ''J~~nl1;1)

Si niflcance to 'Biomedical Research ·and.the Pro ram of tll"Institute: T e f1n ing at th1S aboratory 0 two Type Cviruses associated with' tumors of different primate speGj,':;

is evidence. that the higher animals, including man, are.likely to be among the growing number of specie~ harborin0oncornaviruses. Since monk~ys and man are closely relatc~phylogenetically, the proposed studies, which are orientcJtoward characterization of the primate viruses and seekjnqpossible relation with human tumors, are of direct rele'!u!';.7Pin establishing the etiology of human cancer.

proposed Course: (1) Characterize in great~r detail themolecular components of t.hewoolly monkey fIbrosarcoma '1:1(;.

gibbon lymphosarcoma virus~s by analysis of enzymes,structural proteins and nucleic acid. (2) Deter,mine th,.~in vitro and in vivo biological activities of woolly monk.,vandgI1)bon lymphosarcoma viruses . (:3) Initiate serolog it: ­studies for the detection of antigenic components inspontaneous tumors of simian and human origin that may 1;."

common to know simian RNA Type-C viruses. (4) continueefforts to isoiate oncogenic ~gents from spontaneous tum0"Sof primates and complete limited studies on canine systems.(5) Complete studies on humoral ~ntibody response in calsto the leukemia-sarcoma virus complex.

and human cell lines support low levels of SLY ·replicat i.1 j"

(b) Transmission of the gibbon lymphosarcoma was tested i!''neonatal squirrel monkeys and pigs. Three of four newb·)i·!,squirrel monkeys inoculated with gibbon lymphosarcoma t i ::::I)f'culture cells had a transient enlargement of ·the regionallymph node draining the site of inoculation. No signs uJ'

neoplas ia have been. observed dur ing the 4 to .5mon ths [,):J ')',':­

ing challenge; regular examination of blood samples hasrevealed no abnormalities. All monkeys remain underob,servation. Three of eight inoculated pigs weresacrificed 4 months after injection and found to haveslightly enlarged mesenteric lymph nodes ;histopatholog it'diagnosis was 'lymphoid hyperplasia. No other -lesions W'?J.I.'

detected. Surviving pigs have showh no signs of neoplasj~in the 7 to 9 months. since inoculation and remain underobservation.

'1

II

I

II

)'Emerging 'llinLSes: JII'.DS afta 'E60[a

CALIFORNIA, UNIVERSITY OF (NIIf-NCI-E-70-2048)

Objectives: To further study the two simian Type C viruses(woolly monkey sarcoma and gibbon lymphosarcoma) which werefirst isolated in this laboratory.

Major Findings: (1) Woolly Monkey Fibrosarcoma (SSV):(a) SSV-infected bonnet monkey cells, cultivated in rollerbottles, are yielding significant amounts of SSV virus.Several other cell lines of human, bovine, and simian originalso support SSV replication. (b) Bovine cells infectedwith woolly monkey. sarcoma virus were inoculated ihto the·autochthonous host at 10- to 14-day intervals as.viable andfreeze-thawed disrupted cells. Serum samples taken priorto.inoculation and 6 weeks later were tested for antibodyagainst the woolly monkey sarcoma virus by immunodiffusion.A positive precipitin band developed with a serum sampletaken 6 weeks post-inoculation. (c) Radioimmuneprecipitation assays using SSV replicated in bovine thymuscultures were positive for bovine anti-SSV antisera butnegative for bovine anti-FeSV antisera, indicating thatSSV-infected cultures are free of FeSV antigens and thatSSV and FeSV do not possess common envelope antigens.(d) Cellular and cell-free materials from tissue culturewere inoculated subcutaneously into two newborn cotton-toppedmarmosets. Nodules (7 to 13 mm diameter) developed at thesite of inoculation within 12 to 14 days. However, nodulesregressed within 3 weeks. One nodule detected 28 daysafter inoculation reached 1 cm in diameter and has remainedthat size for 4 months. Blood samples from each animalh~ve been examined monthly and no significant abnormalitieshaVe been noted. All inoculated monkeys are being held forcontinued observation ..

')

(2) Gibbon Lymphosarcoma (SLV): (a) The cell line initiatedfrom the gibbon tumor tissue remains the best producer ofSLV, although bovine, African green monkey kidney (AGMK),

Date Contract Initiated: November 16, 1969

Current Contract Level: $550,000

257 258

I'~. _1,

436

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Title: The production of Simian Viruses and Homologous

Antisera

Dr. S e y mo u r S. Ka 1 t e r

)SOUTHWEST FOUNDATION FOR RESEARCH AND EDUCA~

Contracto~'s projec~ Director:

} (NIlI 69-9)

MASSACHUSETTS INSTITUTE OF TECHNOLOGY (NCI-E-71-21/.9)

Project Offi cer (NCI ~ Dr. Ja~es T: CuffTitle: Studies of Leukeoda Virus DNA Polymerase.

Ob;ectives: To deter~i~e the quality of simian virus referencereagents (seed material and antisera) packaged ·for NCI by

another contractor. In addition, the laboratory serves as a

diagnostic laboratory in .a limited capacity for viral isolates

that may emerge from studies done by other SVCp· contractors.

Contractor's Project Director: Dr. David B:J1t1more

Project Officers (NCI): Dr. George ToJaroDr. Roy Kinard

There appears to be no serologic relationship bet~een M-PHVand FV 1, 2, ), 4, 6, 7.

Cross neu~ralization tes~ing indicated an ~nanticipat~d FV

2-7 cross reaction and FV 6 and' 7 appear to be "aislabelled."

Proposed Course: Certify t...'1e packaged simian vir'us reagentsand serve as a diagnostic laboratory for viral isolates referred

to SilFRE by NCI.

Significance to Bio~edical Research and the Program of theInstitute: These reagents will be useful to investigators in

characterizing viruses isolated from neoplastic diseases

(natural or induced] that occur in priMates, and for monitoringprimate colonies.

Adl~

Obiectives: To characterize the enzyme. its product, its ffil..'chani·"

of reaction, and forwation of viral RNA during infection,

Ma ior· Findings: Using polyr ibionuc leot ides as temp lates, C,)"'p1<','1<"" , r·..

primer "as necessary to initiate DNA synthesis. Using poly(A) ".;

a template for the DNA polymerase, the amount of poly(dT) svntl,,'";i

was propoitional to the· amount of added template. The best prime,

were oligodeoxyrib6nucleotides such as oligo(~T) as a primer for

poly (A). Polyribonucleotides. were in general much better temp 1,,,".,

than polyribodeoxynucleotides.

Proposed Course: Continuation with slight decrease in budget.

The endogenous reaction i",101ves the copying of the 60S-70S RNA' ",.

in the virion. The initial reaction product formed when the viri 11\.

DNA polymerase copies the endogenous vIral RNA consists· of small

pieces of DNA attached to the 60S-70S RNA. The DNA can be re]e,,""'!from the bulk RNA by procedures which disrup.t hydrogen bc'nds. 1'h,'

density of ·the product is not that of a free DNA. but that of a

covalently-bonded DNA-RNA hybrid. This findIng, which was made b..,I:

with mouse leukemia virus and avian myeloblastosis virus, inclic,,""

that the primer for the endogenous reaction is an RNA molecule.

Significance to Biomedical Research and the Program of the lnst!~~l'

The characterization of the enzyme that produces DNA from ~he two.'!

viruses genetic material (RNA) has the highest priority in the ~;:'TP.

It may provide much more sensitive techniques for E~nding cancer IJj ~ usgenetic information in human turnors.

The globin messenger RNA or, more strictly, the 10S RNA from rab',;,

reticulocytes polyribosomes, was the best template for the DNA

polymerase found. Synthesis of DNA amounting to 30-807. of the ad'!··,;template was observed with this RNA. Actinomycin D inhIbited t\'"

reaction to about 507. indicating that half of the reaction invol·..',,!copying of RNA and the other half the copying of the complementar"DNA into a double-stranded DNA. In order to investigate the nat!lr.·

of the reaction product they studied its size ~nd its ability tp

hybridize specifically with 10S RNA .. They were able to demonstr.jt·'

that the product was completely complementary to 10S RNA and waA

not complementary to other RNAI S found in ret iculocytes and elsewiH'1 '.'.

This RNA may be of utility in many aspects of molecular cell hi,'\"1',':and a number of experi~ents have been initiated using it.

June 15, 1966

Ha;or Findings: The si~ian foamyvirus (FV) reagents were ex­tensively tested ~nd an atte~pt ~as made to determine whether

a relationship exists bet~een the Mason-Pfizer monkey virus and

the foamyviruses. Assistance was given NC! personnel in the

identification of HerDe9Vir~s saimiri, a WOOlly monkey virusand in the study of other viruses isolated from primate neo­

plastic tissues.

A~l seven fV types grew at least on one of a variety of cell

lines indicating viability of.theampouled stoc~s. Secondary

rabbit kidney cell cultures supported the growth of all seven

types and wor~ing pools are in preparation on these cells.

The Baboon Sub ••axillary Ly"';,h ~Iode cell (SMLN) culture has

proven ~ost useful in vorking wit~ all the types except 5.

This is a diploid cultUre now i~ its 10th subpassage. Cyto­pathology on these cells is rapid (6-8 days), reaching a

maximum in two ~eeks and is easy to read beca~se of the

uniformity in appearance of the cell sheet. Working poolsof types 1,2, 4, 6 and 7 have been prepared on SHLN cells

with titers_ of 2.0-3.0 10gs/0.1 ml. Vera cells were next

roost susceptible to !oa~y~irus infection, producing CPE withFV. 1, 2, 3, 6 and 7,

Date Contract Initiatec:

I'!:

,;i

214

Source: NCI staff. TlJeSpecla! V7rvsCancer Program: Progress Report #8. Office ofthe Asso­

ciate Scientrtic Dire<:tor for Viral OncDlogy (OASDVO). J. B. Moloney, Ed., Washington, D. C.:U. S. Government Printing OffiCe, 1970 and 1971. Page numbers are as shown.

D,.te Con,,-r~ctInitiated: May I, 1971

~rent C"Dtract L,,",~: $75,000

322

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f£me.rging Viruses: xP1JS ami EEoUz .

Title: Studies on RNA-Dependent DNA Polymerase

Contractor's Project Director: Dr. David Baltimore

Project Officer (NCI): Dr. George Todaro

Objectives: To characterize DNA polymerase and its product,to study its mechanism of reaction and .formation of viral RNAduring infection.

Major Findings: None reported yet, this is anew contract.

Significance to Biomedical Research ind its Program of theInstitute: The objectives above have highest prlority inthe SVCP. The results may provide very sensitive techniquesfor finding cancer virus genetic information in human tumors.

Proposed Course: Continuation with addition of EM capability.

Date Contract Initiated: May 1, 1971 189

440

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~Z".

'Fig. 23.5. Summary Report of Monkey Inoculation Studies•·Conducted by litton Bionetics and,'NCI Researchers· inNo~hwestUganda.

FORMAT OF THE REPORT

This review is divided into five types of studies plus an Addendum.The studies are: .

A. MajorStudiesB. Special StudiesC. Other Active StudiesD. Long-term Holding StudiesE. Terminated Studies

A major study is the product of an ad hoc committee fonned within theSpecial Virus leukemia Program to investigate areas of significance. Theseare major group or collaborative efforts with emphasis on inoculation ofhuman material and subsequent long-term holding. These studies extend from

,.--...Augus t 1964 to May 1967.

The special studies program was fonnally initiated in June 1969,although procedures of this type had. been employed since September 1968.With the shift in emphasis from gross tumor development to more sophis­ticated procedures involving inoculation and detection, a new type ofprogram was developed. The objectives were to provide for experimentalmanipulation, close observation and monitoring of a limited number ofselected animals. These studies proceed according to more formal protocolswhich involve greater varieties of inoculation procedures, possible animalp,-econditioning such as irrmunosuppression, or surgical manipulation,delayed hypersensitivity and more extensive and diverse monitoring.

Section C consists of current studies not of a special nature.These are programs with specified time limits for review, evaluation andsubsequent implementing of decisions .. Many of these may be consideredpreliminary investigations into previously undefined areas:

Section 0 includes those animals being maintained for extended time~periods. The rationale is based on known long latent periods in primary

lnimal tumor systems. In most of these, the inocula were human leukemicor tumor materials inoculated between 1962 and 1965.

Section E lists all completed studies.

The Addendum contains reports on two uninoculated groups:

1. Spontaneous neoplasia in the primate breeding colony;2. Incidence of neoplasia in animals experimentally

manipulated elsewhere and held at Bionetics.

Under Sections A through E,the studies are arranged alphabeticallyby in~estigator. Various codes are used to make the tables containing theinformation more meaningful. Origin of material is a capital letter(key l.a) and is associated with the disease type, which is also coded(key l.b). Information relative to source--the type of material IJsed--iscoded by nurr.e'ral (key l.c). The number inoc~lated and the numter deaj er

278

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i'i1:1

;1

ii:,~:

'Ent£rging 'Viruses: ,'UtJJS and 'E/;ofa'!fie Man-Made Ongill of Ml1r6/l~111T1'/ 'L!'I'!;,

(

45L.

transferred are real nurrtJers. The dates present in the tabulations refer

to the,til1'E the animals were placed on study.

1. I~aterial inoculated

• = Possible Marburg predecessor

./( ;.~

280

EosinophiliaFib rosarcoma

GlioblastomaH-l virus

H. i;jenitalisH. simplex

Hodgkfn's disease

Herpes vi rusIn fl uenzaInfectious mononucleosis

Kuru

Leukemia

Li posa rcomaLympliocyti c I eukemi aLeukemoid reaction of the liver

Lymphos a rcoma

LymphomaMarnna ry tumorMeningi t is

Malignant'histiocytosisMiscellaneous leukemiaMiscellaneous virus

Ma1ignan t lymphomaMultiple myeloma

Moloney sarcoma virusMoloney sarcoma virus + arbovir'us

Moloney sarcoma vi rus + leukemia

Moloney sarcoma vi rus + monkey tumorOsteosarcoma '

PapillomaParai n fl uenzaPia mater control cell (ulture

PolycythemiaMycop 1 asmaRubella

Rauscher vi rusReticulum cell sarcoma

Reovi rus IReOvi rus 3

Rhabdomyosarcoma + leukemia

RhabdomyosarcomaRous transformed cells

SarcomaSV-20 + SV-40

Simian agent 7Stem cell leukemia

Squamous cell sarcomaSimian virus 5Simian virus 20Simian virus 40

Th rombocy topen ia

I\

EosinpFibro

GBH-l

Herp/G

Herp/SHO

HV

IiM

Kuru

L

liposarL lymphlRL

LS

Lymph, Mamm T

MeningMH

Misc L

Misc V

MLMM

MSVMSV AV

MSV L

MSV MTOsteo SP

PIPIA C

PlyctmPPLOR

Rau ViRCS

Reo', IReo 3Rhabd L

• RlJabdoRTC

,'S520S40

SA 7

SCL

Sq SSV-SSV-20

5V-40T

i

I

279,

Hianbo v ine(he!!1i ca 1ecuinefel ine

guir.ea pighumanmuri neovinera b bit

sinian

,Adenovirus 12 + S1;40Acenovirus 2 + SV-40

Acenovirus 2 + parainfluenzaAdenoyi rus 7AC:Jte leukemia

Acute lymphocytic leukemiaAcute lymphocytic leukemia + influenza

Acute lymphocytic leukemia + parainfluenzaAmerican Burkitt's lymphomaAcute myelogenous leukemia

Acute myelogenous leukemia + monocytic leukemiaAcute rronocyti c 1 eukemi aArthropod-borne vi rusAtypi ca I rronocy tos is

Australia antigenBacteri al agentBurkitt's lymphomaBovine leukemia '

Condyloma acuminatum

Con£enital cerebral hyperplasiaCon tro 1 fami! i a 1Chedi ak-Hi gas hiOlondrosarcoma

Chronic lymphocytic l·eukemia

Ol ron ic myelogenous 1 eukemi aCytomegalovi rusConcen ita 1 stem ce 11 1eukemi a

Disease control

Dawson's encephalitisEchovi rus 9

Erythroid le:Jkemia

a. Ori 9i n

;.-C,~-:;' .!~0~S

b.

Diasnosis

,\125.10'!2S~O,1,c2p;,d 7;'LAlLALL I,Ill PIAM BL,InMo\ !'O lAI"OL.o\rtxJAT I'tYIAu fIgBac AgtBlBOlCACC:-!jCFC-HChondrCLLD'LawCSCLDCD EncEcho 9EL

~~

Iii,I!I

I

11

I!

I!­ii,II',0

11

".,"

t"

I,

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SUMMARYOF STUDIES·

c. Source--coded.as follows.

'Emergi1lfJ 'VinJ.$es: ,'uvs ami 'Ef;ow

A. ~or Studies

1. SF:oIRS. 10/65-3/66

2

52

32

2

1

123

88

.4

34

53517

16H 8L+Irr.*H 8L+Irr.+

BSA

H L+Irr. 2H S+ I rr . 3

M S+ I rr . 4

S lEl,2+Irr.l,A S-R+lrr. 1Irr.Irr.+8SA

1nOCln umSou'rceNo. i nocul a tedDead or transfe~red

H AML

2 6 5

HALL

2'11 9

H EL

2 5 5

H CHL

2 2 1

3.

Irradiation Study, 2/67 - 5/67

Inoculum Source No, inoculated Dead or transferred

*1 rradi ati on

The major emphasis of this study was to detennine the SlJl'"pressive effects' of radiation upon primates and the subsequent enh,w':elllentor creation of a more favorable environment for neoplastic alter~l it'll,The progra~ was under the direction of Drs: Reisinger and 80wser. withOrs. Rauscher, Landon. Stewart, 11010ney, Perry and Hart. collaborJt.il"j.

2. Fink-Malmgren-Rauscher. 8/64. - 9/65

Thi.s program was desiqned to investigate the abi 1 i ty of fl"f~.hhuman. leukemic materials,as well as cultured and manipulated c~l Iproducts, to induce similar neoplasia in the newborn monkey.

Trans fonned ce 115Undi agnos edWilm's tUloor'(abavirus

Tm Ce

UndiagiI T~'Ii1r

'(eba

1 tissue culture2 b1cod3 plasma/serum4 tissue mince5 buffy coat6 chemical7 .asci tesS:milkg spinal fluid

10 bone m.arrow11 cu1 ture

'Iurreer of animals inoculated.~Iurrber of anirr.als dead or transferred.

2.

,

Fig. 23.6. Bionetics Summary Report of Studies CodeNamed According to Researchers' Last Names IncludingMK-SVLP (ManakerlKotin-Special Virus Leukemia Program)

it

11t

rI!,

iiI

I, ~

It cr­u

This study was established under the Special Virus LeukemiaProgram of the ~ICI to investigate human leukemic materials. human papillomaand infectious ~ncnucleosis in conjunction with the co-carcinogensbenzo[a]pyrene and benzenthracene. The program was a product of the studygroup that included Dr.;. BrJan. FaH, Kotin, Manaker, Rauscher andStevehson. This study has recently been terminated and the remaining animalsare in the process of being transferred.

4. MK-SVLP, 2/66 - 3/67

This study was initiated by Drs. Manaker and Kotin in col-1aboration with an ad hoc corrrnittee of the SVlP. 'The prime objecti vcwas the induction of neoplasia in primates using Burkitt and othcl:

lymphoma ma teri a 1 in conjuncti on wi th the co-ca re inogens ben zan th I"a ·:cneand benzo[a]pyrene ..

1nocu 1urn Source No. i nccul a ted Dead or trans fe r re~~InocullZTl ~ourceI/o. inoculatedDead or trans ferred

H

P 1 11 6

H

L 1 IS 3

H

I,.. 1 11 3Contro 1

92

·SOIre studies strrnarized are in the process of being terminated and thismay not be r~flected in the total nurrbers. This is due to lag times infinalization of re~orts on selected studies ..

H Bl

H lymphH l

. H Sq SControl

105331813

6

1153o1

(

454( \

282 . I._--\

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I5. Perrj-P.2uscher, 7/66-10/68

This pragrar.t'dcs initiated by Dr. Rauscher in collaboration withDr. Perry of aCI and Dr. Landon of Bionetics. Fresh whole blood fromleukemic patients was inoculated directly intJ ~onkeys using multiple sitesand voiur.€s as lar;e as Jossible.

This s:t;d/ 'f/CS a ;Jroduct of t."e Pri~cte Study Group headed byDr. J. :·~lnick. ,The ;:r;'7'.arj ob~ecthe •.•••as tr:e iri',estigatioh of the pus­sible oncageni d ty of selected human prctotj~e vi rUSES in primates inconjunction with t.'le use of co-carcinogens. This study is in the processof being terminated '.;i th t.'le re~aining aniroa1s being transferred toOr.'f.'elnick. .

inoD 1 C:r.1Scurce:10. incculatedCead or transferred

H C"L

226 6

H ':'}'L212 0

n lSZ 4 0

HALL

2 13 0

r. C:"L

Z 6 0

H RCS

2 1 0

H HO

Z 3 1r. '\1 ~~c:;

Z 2 1H ~~L

2 2 0H C-;J

, 4 2H 3L

2 1 0

r. Ly~h

2 1 G

6.

?SG-~"e:nick, :;.:::::-,/50

B.Spedi!LStudies (acti vc)No.

Oe.,·1 ('('

Inoculum

Source!noc.Tr,lI~,!~~tT(~d

1.

Ablashi. 10/70· S; H. saimiri--1-Z2- .... j')'---'.---

2.

,Bryan-Jensen. 1/69 S; ~lamm T120 ('.)

3.

levine. 6/69 H; Bl138 (',)

4.Melendez, 3/70 S; H. saimiri116 (',

f

I5.Pearson, 3171 H; Bl116

6.

Ri cka rd, 6/69 F; lymph111

7.

Theil en, 6/69 F. Fibro113

8.

Witter, 7170 A; HV of turkeys18A; Marek's disease

18

Special Studies (terminated)1.

Ounke 1, 7170 H; Bl137

2.

landon, 7/70 S&H; Mise V126 1"

3.landon-laFontaine,

7/70

F; S13

4.Sibinovic-Ulland,

8/70C; Dilantin66

C.

Other Active Studies

1.

Adamson, 5/68 C; :MCA-Cu chelate637 •.• 1-

2.Blumberg-london,

3/68

H; Au Ag311

3.

Gerber, 4/64 H; Bl3,516 ](,

H; BL

72 "O&S; Mise V

212

O.

Long-term Holding Studies

1.

Feller, 7/66-11/66 H; Manm T85 I)

2.

Fischinger-O'Connor,8/69

,F ; Lymph16 ')

3.

Kelly, 6/67-4/68 C; MCA63 1C; Benzo[a]pyrene

610 I

4.

landon-O'Gara,

6/70-7/70

S; Mise l45 0

5.

landon-Rauscher-·

BRAF, 12/67

S&M; Rhab l417 7

6.

Manaker, 8/64-10/69 H; Bl116 13

11; l

21 1

H; S

18 1

H; Rau Vi

18 O·

S&H; Mise l

19 Z

7.

Manaker-Landon, 5/67H; ALL11 0

8.

Manaker-landon-

Rauscher, 2/67H; !3l1·8 7

:10. ineC'Jlated Dead or trans ferred

9

615

15

12

51

112

712

112

112

212

51

0

H Reo 1

H Reo :;

+ alH .C~'1H P

H Her.J/SH Ad2PH&5 AlS40H RH Echo 9C

inccJlus Source

1j

"j;; ,!i, _ C"\.2' ,- - \

,:ii~''~I ~! f) "->

I

,/,11'

II

283

( \284

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rlo.De ado r No.D,. HI 1'1'

[nocu1url

Source[noc.Trans ferrcd I noeul umSourceI noc.11',11: ; f,' I'n~d----. --1---1 Rauscher-Reisinger-H; BL----r-1i1---.,'G---

9.Ma~aker-~auscher, ; RCS . 018.

6/66-7/57

; ~L13 0 Bowser, 4/67-5/67Irradiation11

la.

~anaker-Stevens, ; 5L111 2 H; CML21 e

6/0-12:52

~S; ::l + ~'~alaria. .1 ,212 0 19 .Sarma-Huebner, 9/69F; Fibro13 l~

E; :'-L + Reo J,

,20.Shaeha t-Mo 1oney, M&S; MSV MT12

:~a1aria

23 0 8/65-11/66M; Rhabdo1la "c.

~, '~c1aria

219 14 21.Stewart, 4/62- 11; ALL156 ,"1

1l.

"'e:r.~,:::, ~~/6~- 'i; .~.l36 6!

6/68 H; AML16 I:.•. 'r'"

'i; [:'~113 9I A; S

432...• , ..... '; ;'LL

121 15 11; GB12

...!. 0

.\5 5I H; Bl

151 !!It, • :-:; ~er;J/S

144 : 1 H; CML12 "

:-i; Pea 1

13 :3 H; HO19 ~J

:-:; Ac2?

14 1 H; l i posar14 'I

"

'i; :1er:J/S·14 1 H; 0 Ene13 J, L

':!.S; ;'.deno+S·I-~O13 2 H; Undiag12 .,t..

!:

12.:,rc~:neJ, :'J';2- ~'; L1yr..ph112 8 S; SV-S13 :;

Ii~ ":J :-i; A.LL123 .21

.\'

L, :_

\

:..:; ClL.35 5 E.Terminated Studies

:-:; .~}~OL

J1. 1, Ccn trD 12313 1.Aisenberg-Zameenik, H; HO28 ')

11

~' ;;; CSCL33 2 5/64-6/64

~

;;; ft:"L320 15 2 .Blumberg-Mo10ney, • M; Rhabdo41

"3"'

;.:; lS14 1 6/66-10/66M; MSV L-12

,,:; ~LJ

3l' 0 3.Chirigos, 5/66- C; pI:C68 1

'.I

:-:; SeL17 4 3/69M; S16 G

:..:; Cc

35 2 M; Arbo12

,,; C'~L

1 .20 16 M; MSV AV12 ~~~; :~:1

J1 1 M; MSV12 1

~; ?

11 1 4.Cohen, 3/68-1/69 H; AL26 S

:..:; 3L.

714 5 H; Bl13 3

~~; 5

42 2 R; ALS37 G

ii; RCS

32 2 Contra 12~,.~~; ~,1,S'i

41 1 H; AML22 0

13.~~oione1'- r.2 i s i rose r-:~; ·~'i44 2 H; CLL22 0

3c"'se r, 5167 '

H; EL. 220

14.

~ocre, 9/5~ H; BL1'2 0 5.Dreyer, 9/64 H; .Ml12 ",.15.

O'Connor, J,/S:- f;&H; ALl?113 3 6.Gajdusek, 1/67 11; 0 Ene44 3

9/57

Hb.:i; ALL [13 3 7.Gajdusek-Gibbs;H; Rhabco

13 0 4/66-5/66H; Kuru48 4

16.

01e, 9/57-12/E9 n; Osteo S13 0 8~Gazdar-'Mo1 oney,5; Os tea 5

12 0 7/69-8/69F; Fibro43 0

17.

P,cuscher-L,:nccn, •5; Rhabdo 12 Z 9.Grace, 2/64-8/64 H; MyL11 1

12,'66-2170

~; ~,1L14 3 H; M~L110 n

r.; BL

713 0 H; ALL12 1

S; ~~e!ling

42 2 10.Graee-Horoscewiez,

~~; ~L

34 3 5/67H; BL16 ":J

H; HD

11 D 1l.Gross, 5/62-4/63 H; L lymph412 7

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, , .4C(~

No.

Deado rInoculum

SourceInoc.Trans ferred1Z.

Howa rd-Notk ins, H; Gawma globulin3Ib 16

.5/67-1/68 13.Huebner-Caates, H; Ad 7'13 3

8/64-3/68

H; Ad 1 Z16 4

A' S. 132, , M; S

1' 4 3

5&H; A12S40

12 0

14.Jahnsan-Hul1 , S; SV-2014 3

8/65-3/67

S; SA 7110 10

15.Ki na rd- Raus che r,

3/67-9/67A; S318 18

16.Koprowski-Jensen,

4/66-6/66H; Ad 71. 2 ' 2

17.Landon, 7/65- B; Non-inf214 9

5/70

Control1614

S; Rhabdo

17 7• 5; Rhabda 418 ~ 918.

Landan-Da rrow-

Stewart, 1/68

S; CCHy92 2

19.Landon-Raus cher,

2/68-7/68S; Plyctm28 6

20.Landon-Valerio, 8/675; LRL42 2

21.Manaker-Landon-

Darrow, 6/68-7/68Skin graft66

22.Manaker-O'Connor,

3/66H; BL1,2 2

23.Mol oney-He rbe rt, M; L42 2

4/67M; L 1ymph43 3

24.Molaney-Manaker, CF22

4/67H; BL12 0

25.~\a1aney-Stewart, H; DC12 2.

5/6 3- 7/ 6 3H; ALL11 1

H; CLL '

11 126.

Morgan, 3/65 H; CA43 327.

Morris, 9/65-5/66 5; SV-2017 7

5; 52054011 1

28.Marton, 6/68- H; Osteo 5112 6

9/69H; Liposar115 9

Con tro 186

H; Tm Ce14 2

H; Chondr.

11 0

E; ALS34 3

5; Bact Agt

41 029.

Nade 1- Raus che r,1/65-2/65

G; 5 CL53 3 .

287

~-\

* = Nine monkeys inoculated with Marburg-like viruses survived and apparently remained in theholdingfaciiities ef Bionetics in ~krthwest Uganda. These may have been transferred to EuropE:and/or infected other mor,kevs shipoed to Frankfurt, Marburc, and Belc;rade between Juty 20thand August 10th, 1967. John Landon, cited above, was Bionetics' Senior Project Directoraiongwith Rabert Ting.

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Octolxr 28. 1996

Dr. Robert C. Gallo

Director. Institute for Human Virology725 West Lombard StreetBaltimore. MD 21201

Dear Bob:

Thank you very much for the interview you gave me on July 30. 1996. I found thediscussion very interesting, and am responding herein.

First, I greatly appreciate your offer to help in determining the origin of humanimmunodeficiency viruses (HIVs). I understand that you must. however, limit your views partlyfor political expediency. and partly due to lack of any definitive knowledge.

In any case. my responses to your four specific objections to my thesis-that HIV-l.or its progenitors. could have evolved from laboratory experiments and subsequent human vac­cine contaminations (i.e .. hepatitis B and polio) with simian and type-C cancer viruses routinelystudied and recombined during the "Special Virus Cancer Program"-are as follows:

Objection #1- The viruses discussed lack the "homology" needed to recombine.

I will grant you that some degree of homology is needed for recombination, and themore homology the more recombination. However, neither the whole genome needs to be ho­mologous noris there a requirement that the homologous regions be contiguous. Small stretchesof even a few base pairs are all that is needed for recombination of type-C cancer viruses-thefocus of substantial "Special Virus Cancer Program" research. HIV has been shown to evolvethrough type-C like morphogenesis. (Salakian, Pet a1. I.Virology 70:3706-3715)

Moreover, random natural recombination is not the only issue. You may recall. given. your first hand knowledge of bench level virology during the late 1960s and early 19705. that

people who were really up on molecular virology at the National Institutes of Health (NIH)including the late Dr. George Khoury. Ed Scolnic, and others, recombined such viruses in theirlabs. Documents show many government and industry researchers, known -or unknown to you.were heavily involved in genetic engineering, in this time frame, preceding the discovery of HIY.

Additionally, some restriction enzymes were available before the discovery of HIV­1. Several enzymes were even publicly available to do gene cutting and pasting.

If you insist on homology of genomic organization, or nucleotide sequences. let mepoint out that the world of virology has known the lentiviruses for a long time. What about thebovine immunodeficiency virus? I do not need to tell you that there are a lot of organizationalsimilarities between HIV and B IV.

You mentioned Ray Gilden during our interview. I am currently preparing a paperthat discusses Gilden's warning in this regard. Following lengthy trials, concerning the homol­ogy of C-type cancer viruses, and the RD 114 cat/human viral recombinant, Gilden stated: "[A]new virus with no growth restrictions may be accidentally introduced in a new species, perhapsby vaccine, and these become epigenetic as opposed to a rarely seen endogenous virus. Possi- .bilities of recombinants are thus raised ... , which could have an extended or newly acquiredoncogenic potential." Gilden's warning obviously foreshadowed the AIDS pandemic. (See: Vi-

. ruses, Evolution. and Cancer: Basic Considerations-International Conference of Compara­tive Virology, 2nd, Mont Gabriel, Can., 1973. New York: Academic Press, 1974, pp. 235-256.)

Regarding the little genetic similarity between the viruses used in your and LittonBionetics's labs. and HIV-l, this does not negate the probability that the SIVs and HIVs evolvedfrom recombinant viral research. Having studied S V 40, you may recall how this and anothervery dissimilar virus-the human adenovirus-were found to combine. creating a potentiallycc:J.dly mutJ.IH-the ad-SV~O hybrid. In 1973. Andrew Lewis. at the ~I.-\ID (see: Biuhu::;urc!s in

Bio[oiica! Rt!seurch. Cold Spring H:J.rb()r Labor::nor,.;. 1973. pp. 911-1\3) sho'.vd th:.lt folk'xjr:;unexpected and unexpb.ined recombination of these grossly different viruses. hybrids <.:mcfseJthat contained as little as 6% of the original SV 40 genome.

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p.a. Box402.. Rockport, MA 01966· Tele: ~546-6586 • Fax: ~-546-9226 • E-mail: tetra@tetrahedrolLOrg .

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Thu(,. r~".\"·..;ral 'S-C4ucnlT~ n:~crnpling Ih\'(~ (~f r·ly~ \.::m(~r \'inl~cs may aprcar in 'tIV.:-el this Jcoes nol :1egJICIh~ ~)'islf,ility ,hal ,omc ..:q:l11~nt<;,'Ithe SI\\ Jod IIIV~may have comc froll!:"Cllaoor.Jtory 'recimens ... ' ,

Funhennore, molecular ,·irolo!!1 eOl:III, ,1 101more than hnmolo~olls recoml1,"ation. One

could rr.Jctic~ly construct n~\\ ,irus(s resiJut! Py resl(Ju~ ~slng Ih( general pancm of cSlahli~hl'd\·iruses ';iz, Ihe LTR, ~"!!.po;. em' and alllhe imcresling gencs Ipnnkled in. Though building and Ihentesting the qabllity md function of new conllructl 11 a ,ainltabng and time con$uming process, docu·menlecl e'.lde~,e ;ho\\ s ,his i; precisely" h~t '.\as done during the 19(Jr)s;rnd early 1970s by hinlogicalweJpons' ,>:'nlr:lClOrs ';ee: Geissler E. B'"",!!i •."I.;,,d .J,'TlII \\ea"ollJ Tr,t/al·. London: Oxford Unil'C('­lit,· Press. 1<;-~6 ',I IIh contnbutions QV Da\'id Baitinwre and Ra\ml'nd Zililllbs):

. ·.-\Jdi!iQnail~· ;igmf"ant :.od 5uspic:oU5 IS Ihat Hli; doel nat lit Ihe I11Qld for nalurally~';o"ed ';iruse\. Th~r~ :;' J !cne-.1f) pe,cent hcomolofous ·;irus-HIY·2-llhich mayor may nol halcr.:ea J ,rogeaimr of HI\'-!. Jnd il rm~· n'I'1 ha',e ·JriglOaled in monk~~s. HIV-2 is definilely nQt ell dog­enOU$ to J.n~ !)f the ~~:,:e~ frr.'m '.\ hJt:h it hJ.5 ~en isnbred. Th~ '.\ord "endogenous" is meant here inIhe classic.J1 ;ease. \\'h,,~ ~J= fir;r.' The fJct .hat ',>,eaow lind them in se\·cral monkeys and a group01 indi, iduals in ,'ne I'~:;:on ef .-\fri~J •Le. "high ri-k" Senegalese female prostitutes who, due 10 Iheir"risk:' ""d pam:',a"Qn m publi: healtlnesear.:h prograrn;, likely receil'ed Ihe moq suspecledhepl3.!il1l B '.3co:oe' makes cone.'er:, suspicious. This is like Ihe simian sareQma virus complex (SS V.SSa\· and SiSY, ',\hich J.xs nct ha'e my :emprable ,iru.ses in Ihe animal kingdam. There hris notr.:ea J second isclaticn 1'1' Ihat '. irus 'HI\'·: I' e:.

Where did HI\'·: and clher SlY; ccorr,e irrm' The ','.erld of ,·iroI02\' is slill waitin2 for thatans"er .. \Ia._ ElSe. ;niJr.ned me !:il Isolation ,we irom mcnkc\s mieCled ";;h human tissu;'s durino

laN-ratrr,' exrenmeOls. \1:. thecr;'l'f ;Iopp~' s,ie~ce 'e g .. conlaIninaled \'accines for HIV·I and Hlv':c. and cQntaminared mcnke~·; r.:ing rele.ased back inw Ihe wild 1'1'1' the other SIVs) !:>estexplains thecircumstantial ""d s.::e~uri: e', idence al hand. Do you hale any beneI' explanations'? You indicaled Ihalyou ',\ere :wie IQ proqde a mQre "p/aulirle" iatrogenic theer; on Ihe origin of AIDS hut time did nOIrennil you tr e_plaJl\ J a\lait any additirnal insights ~cu may be able to share:

Obje<:tiQn ~Z-Regarding the \ iruses r discusseJ as ha,ing t-cen recQml1ined by ~'our colleagues HI the:-;CI ""d Linon Bicone"cs. "nCI Jnl coneoithern hale an', homrlo~.'·lo what is HIV, Therefore. none ofIhem could ':Qntribute 10 an~' p3.f1'01' HI\· .... -.

It is a rmlter oi Fu~lic record Ihat 0nce ~TU rinnly r.:lie\·ed HIV w"' closely relaied tQHTIS-I and HTL\'-II, He~ce!.he name HTL\'-IIL As a malter of iactlhere was a publicalion in Scien •.eI see: Hcomcolcg: cof.-\IDS·JSsodated\·irus with genomes of human T-cellleukemia viruses. Arya SK, etal. S,'lence 19S.l::C5:9~--9:0) shQwing mcol«ular similarilY, Did ~ou e\'er withdraw that paper'

I ~=that since there are no kno\l n liruses in the e\'olutionary scheme that look \'crysimilar tQ HI\'s. HI\' ml1st b-e cconsidered unique l1y design. However, you know Ihal HIV is nOllotallyunique. In \..,~. genera! lerms. HI\' is similar to Mth I~re C ""d t~pe 0 \'iruscs along with Ihe inclu~ionof regulatco<:' genes tYl'ic:1l of lenti\;",."es.

Again. ~·Oll l11.1y·recall Ray Gilden's inslruction Qn this subject in Ihe "Comparison andEvolution of R:-;A Tumor \irus Components" Iln: linl5eJ, £<OI!lIl'>1I, II/lcl Cllllcer: Bmic Cm'.fider·arionJ-lnrenwriconal Conference Q[Comp<If<Uil e lira/MY. 2nd, \lonl Gabrie!. Can .. 197), New York:Academic Press. 197.1. FP. ~J5·2~6.':

"The relationship of liruSC's ;uch l.S "isna_ \f:L<en-Phizer. and mQuse MTVtl11.1mm.'1f)· I11mor virus) 10 IYpe C panicles C,,"nOI "" :L<sessed in qu""tilativeterms. )·et t~ pre;ence of rc\er.e Ir.lJ1Script:l.\e md approximale morphQlogicsimilarity of ImQns presenl a mQng ca...'<=far common ancestry hQweler remote,... Wc should ;tress here Ihat gmul''''gs such ,IJ '.'t're C" lire t1/<I1I-t1/lIdeIIb.ll"' •.­;i''''J. JJ1d aITuments of JitTerences are onl\· indicaters ofl'ariabilitv that arc diffi­

cult ior menio accQmmodate in simple classifical·iQn schemes,·., '-Once the abil­i!!· 10 make compari;Qns is granted. a ;econd major problem Qf critical signifi­,'L"-" 10 JJ1~' :utempt 10 discuss e\oluticn3.0 relaticomhips arises, Simply statedthis is. 11(1\\" do ;\t. Uto"o char lht ~ir:ljfJ (h0501 fur t11!rliys;J lire rerreStIl111ti\'e of

!h( spllitJ :rnm .\1,hh rhey· ',,'lrt iJt'hltt'd.7"·l~mphasis Jdded]

Thcugh Gilden's .:onelusions '.'ere J",\>on long before the arri,·al of SOPhisticaled DNAsequencing techniqlJe$_ his p<'int is still "alid :!lid p3.f1icuIarly ai'rlicable 10 the queSlion here: Did IIIVe,·o".., from laoor.ucor;· e._rerim<:nt5 in which .:h""ce or intentional encounlers occurred between dif· .ferent ';",se; or' fore'gn species ~ The ""swer. as your comments suggest. is very plousibly "yes:'despite t~ fact '~e may re unaware of the large;t cOnlribuling \;rusles),

Ha\1n2 srudied S\'Jr), IOU mal' a2ain re~all.-\ndre',\ Lewis's cQnelusionsm the NIAIDfsee:

Bioha:",ris in Bit;;oercai Rem" •.;" Cold 'Spring HarNr LJMr:lIN). 197J, pp. %-11 J.) Regarding thead-S\'.1(' h:trids. "L·r.tll s.omfa.:tcr; studie; e',Jlua" the kng·tenn dfects Qf SV~f) infection in hu-

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mans and darify Ihe relalionShip belween SV40 and SV ~O-rclaled agents 10 chlonic dc~cnl'l'''':'''' ,','11Iral nervous system disease in hI/mans, il appears 10 Ihis re\'icwer Ihal the lahoralnr)' malil,"I.:1I '11,'ISV40 involves same risks."

Likewise, rcnecting on your work wilh human while hlond cells and typc·(' c:nhTI ',11'1'.,"

George Todaro (and Gallu), condudcd: .

. "Because viruses can aller their hOlt ·range eilher hy 'adal'Ialion nr se!cctinn. II,,'sehuman hybrid cells wOllld appear to conslitute a potential biohalanl since. in Ihissilualion, one' has an endogenous virus of a speeie~ heing produced hy cells which,

at leasl in port, are hum3fl, These hybrid cells arc I1cing ~xlensively explored !:>y

gencticislS all over ih~ world who do nol realize that thcy conlain high litcr~ 01polentially ancogenic [cancer causing 1 viruses ... ,What is not clear is Ihe nalore "IIhe relalionship belwee" Ihe acquisilion of oncogenic p"tcntiall1y a cell and the

expression oflhat cell's endogenous type C viral information. Type C vinlses ea'"oncogenic information and can produce lumQrs (!cl/kernias, lymphomas and sar·comas) by eXQgenous infeclion: whether hQri7.0nlal spread (cell 10 cell and/nr ani·mal to animal) of exogenous Iype C virus is responsible for a signiticant portii,n of

nalurally occurring cancers in vertebrale~ is uncertain: Ihal Ihey can haw nnco­

genic potential and can produce tu mol's in a varicly of species is firmly eSlahlishedIt follows, then. that these viruses and the cells Ihat produce thcm rnu.51be trealed

as pOlenlially hazJrdous agents."

This is why I asked you in Vancouver whether YQUremain concerned Ihal YOl1rC;IIh' le

seJrch wilh cQlleagues at Litton Bionelies might have given rise lu AIDS viOlS prngenitors.A final poinl deserves mention here, HIV and other newly discnvered I'iruscs are .'1illll~ in~

to slabilize Ihemselves in Iheir respective hosls. A similar situation was d"cribed hy 1i,dall' r"~;lIdin.""the feline leukemia and sarcama viruses [that] mighl be derived from Olher ~pecies." (Se •• r,'d" •.•"wQrk "Endogenous type-C viruses in cell cultures. In: B;/lIr"wnIJ i" B;"/OIl;('(I/II"'«·/lrl'lr. A I kll,":!n.MN Oxman and R Pollack Eds, New York: CSHL, 197J. pp. 114-IJO.) Todaro, who ciled addlll"n"Iexamples of cross species laborato·ry transfers, noted that since Ihese viruses grow so rcadil~ in catcells, and spreads so "readily through the population, prQducing a high Icvel·of disc"ses, Ilh,'i, I',n·ence] represenls an apparenlly unnatural situatiQn among mammalian species:' Likewise. t ,,:raldMyers at Los Alamos reeenlly shared with my colleague, author Ed Haslam, Ihal mV mut:lIes r:1.,t,·rthan anything he haS ever stl/died. In Ihis manner. HIV strelches Ihe bounds Qfnature. Thi<, ,:!'''plcdwith the fact that no clase ancestors exist strongly suggesls HIV is nol natural hul ",an-mad,'.

Hopefully these extremely variable genQmes ma)' finally select a few stable ver<l"n'·. al1dlike innuenza, may senle dQwn 10 be mildly harmful to its prcsenl hasts (0 mutual advanta~c.

In cQnclusion, in the absence of orderly evolulion, uniquely high mutalionallendenri,". ;11101

its limely appearance Ihe decade following recombinant biotechnology initiation,lIlV was •.•.ry ,'n"i.bly designed and put together along Ihe lines afseveral well·known agenls wilh very adverse ill III !,,,",:Ipropertieslconsequences post infection in their present hosls.

Objeeiion #3-"Obviously, you didn'! say it was dQne intentionally, butjusl in c,\Se allyhl1d.' CH" ,aid.it was impossible la do intentionally, because the viruses exislcd in human heings at lea:.1 ,i,",' 11",1960s; and molecular techniques for gene cloning, doing the~e things in a laboralol)', did"'1 "'"" •.unlil the late '70s and early 1980s. So it's off by almo~t Iwenly years:'

The earliesl cQntinned iSQlates af HIV go back onl)' to 1976 (Mycrsand Pa.'I,,',· lI,.'RetrOl'iridae, New York: Plenum press, 1992, pg, 59). Regarding the reports claiming the carl":1 """.ence of HIV, I can anly say-"What wQn't people do IQ gel puhlishedT'

Recombinanl DNA lechnology was beginning 10 unfold. even in the pul1lic d(III1;';I1. hy 11",

. enrly 19705. YQU even repQrted a cellular eloning operation involving SV40 in a Iyn· I'"hl ,,·;11i,,"(Gallagher R, Ting R, and GaIlQ, RC. Bioclremicll er Oioplrv.finr lIerll 1972:272:570). Den";,,,\, "'.periments in phages and molecular biology using DNA manipulalion gQes hack IQ 1952,\\, •.: i'/'"C"lint/ r/,e ori!:ill "I Mo/em/"r Bio/,,!:y, Eds. Caira, J,. Slenl GS, and Watson J(). Cold Spnn~' II,nl'II'Press, 1972).

Please allQw me to ·refresh your memory Ihat a 1969 CtJll}ireHi"'If//l?cnml rill" lilllln

l3iQnetics as sixlh largesl U.S, Anny hiologieal weapons con fractoI', This is exaclly the 11"'" whenmembers of the National Ac:rdemy of Sciences-Nalional Research Council (NAS ..NRC) '"I",,",'d

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V.S. Department of Odense ofticials of their ability roproduce. through genetic engineering. a "newinfective microorganism" that may ravage the human immune system. and leave people susceptible toinfectious diseases and cancers. Obviously then. by 1968. shonly after you began work at the NC!. theNAS-NRC was aware of genetic engineering capabilities. and offered to help develop "synthetic bio- .logical agents" for germ warfare. (See Emerging Viruses: AIDS & Eblila. pp. 6-7)

Objection #4-"rvlonkeys are infected with viruses . : . We know [HIV] came from monkeys. Norational informed person could argue othervvise." ..

The later is not true. l. like other researchers inc!udingTodaro (re: feline leukemiavirus).Gerald ~lyers, and George Pavlakis. can argue otherwise.

Myers and favlakis. in "Evolutionary Potential of Complex Retroviruses (In:. TheRelrtJviridae. op cit.)" were unconvinced HIV evolved from either monkeys left alone in the wild orfrom monkeys at all! This was made clear when the authors discussed only the "possible simian originof HIY." And though evidence. they said, was mounting HlV evolved from monkey virus relatives. theyentenained the possibility ancestral viruses may have fanned during the 1950s "as part of malariaexperiments." (See page 59.) ..

I agree that HlV appears to have evolved substantially from monkeys and/or monkey virusparts. But as these scientists. as well as Ray Gilden (see Gilden. op cit.) indicated. we can't ~ sure. Myinvestigation confirms that much was done to monkeys and monkey viruses that might have contrib-uted to HIV's development. ...

Whereas I accept that S IV from the chimpanzee is the closest relative to HIV-I. and thatHIV-2 is much like SIV present in wild sooty mangabeys, these viruses are all relatively recent isolates,and may themsel yes have evolved from laboratory experiments conducted during the 1950s. 1960s. orperhaps early' 1970s when iinmunedeficiency studies in New York City and Central Africa were invo!!ue.

- . Additional support for this iatrogenic theory comes from a series of letters/articles in theFebruary 1988 issue of Nature wherein Essex and Kanki raised the "obvious possibility" that m:lcaques"beC:lme infected with SlY from another primate species in captivity." Yet. Kestler. et al. concludedS IV mac. the laboratory contaminant .identical to HIV-2. did not likely evolve from S IVagm orSlVmangabey. So if not from these primates, then where did SIVmac(HIV-2) come from?

"[ am aware ... of at least five. instances in other laboratories in the United States and

Europe where noninfected cell cultures became infected with HIV-l in the same containment hood."wrote Care! Mulder inNature. Thus. it remains highly plausible the original SlV evolved from labora­tory outbreaks of HIV-l. or some related virus. carried by monkeys or vaccines into the wild. As JohnMartin reminded us in the foreword to Emerging Viruses: AIDS & Eboll.l. it was not uncommon to haveexperimental animals. particularly ailing ones, released back into the wild.

So. how did the infectious agent HIV ,enter humans around 1970? Well, documents show. that in the late 1960s, and early 1970s. hepatitis B vaccine efforts concentrated in New York City and

Central Africa. The virus was pooled from live. heavily infected. chimpanzees~ Rhesus monkeys, andhumans. Serum for the vaccine lots, containing 200.000 human doses. was obtained from the humanswho received these viruses and. most assuredly. simian virus recombinants as well. By the way, thesehumans had received the earliest polio vaccines containing SV 40. simian foamy retroviruses. and more.The primate resource for this effort WOlS. as you mentioned. Litton Bionetics vis the U.S. Army.

In conclusion, igreatly appreciate this dialogue with you on a subject that has been kept inthe closet for a variety of understandable rea5ons. Since 1have your permission. I will incorporate yourresponse in future work. and look forward to expanding common ground and reaching a scientificconsensus regarding the origin of AIDS ..

Yours in the Spirit of heals~, r·~ ... ,1/(11 ..••...~,: j 1.••I ~ r (,,/' ";":...'..().

Leona.rd G. HOrOWItZ. 0.Y1.0 .. M.A .. M.P.H .

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March 14. 1997

Dr. David Satcher. M.D .. Ph.D.DirectorCenters for Disease Control and Prevention (CDC)Atlanta, GA30333

Dear Dr. S:J.tcher:

Thank you for y·our invitation of Feb. 21, 1997 (that came by way of Minister of Healthfor the Nation of Islam. Dr. Abdul Alim .Nluhammad·) to visitthe Centers for Disease·

~ontro.l and Pr~vention ~o discu:.s the issue of v?c~ine.contamination and ."other publicn.lth Issues of mutual Interest. name Iv the OrIgin of AIDS and Ebola viruses .... . ~

First. I gre:J.tly appreciate the opportunity to visit the CDC to present and discuss myinvestigation into the ori!2:in of AIDS and Ebob viruses. Last Fall. in the Bahamas. I met~ ~at length with vour Associate Director for Minoritv Health. Reubin \Varren. who like-

\-. <1-. ~ . ' •

wise invited me to visit the CDC for this purpose. We have yet to set a date for thismeetin g ....

Regarding your communication to Dr. Muhammad concerning the "misinformation. circulated that vaccines are the source by which the human immunodeficiency virus(HIV) was introduced into the human population, wherein you discuss "one such mis­

conception." the polio vaccine theory, Dr. N1uhammad asked me to reply to your com­ments.

For your information, you have apparently been misinformed. I challenge YOLl, or any;.-NI,Hinvestigator. to debate the scientific facts, the vast majority of which support the

_ntention that contaminatedvaccines have played a major role in the transmission ofanimal viruses to humans. A growing body of scientific evidence indicates vaccinecontaminants are most plausibly related to certain types of cancers, and contemporaryepidemics involving the human immune system including AIDS and chronic fatigue ..Regarding AIDS, the evidence shows that the most supported theory on AIDS's origin.that is, the only theory that takes into account all of the confirmed scientific facts, asopposed to politically correct pseudo-scientific speculations. is the theory that 1 haveadvanced in Emerging Viruses: AIDS & Ebola.

I advance the theory that HIV, and simian immunodeficiency virus (SIV) relatives,evol ved during the late. 1960s to mid 1970s as a result of vaccine trials-includingthose conducted by Saul Krugman and later Maurice Hillem~nat Merck pharmaceuti­cal company (under NIH contract number 71-2059). along with coinvestigators at the

\ CDC, FD.-\. and the ~:J.ticnal Institu«.; for All.-:rgics anJ. Infcctlt)U'i Discases (~L-\ID,.·as reported b'l Robcn Puree!! from NIAID. These invcstiQ;:.ll\)rs uscJheavliv cOr1wmi­

~.ed chimp~nzees, and rhesus monkeys, supplied by lhe~Army's sixth top' biulogicaJ~apons contractor-Litton B ionetics research lab (under NTH primate supply con­

tracts including, but not limited to NTH 69-2160)-to ;'pool" hepatitis B viruses thatwere used to develop a reponed 200,000 human doses of vaccine. Four subtypes of this