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

Year and Subject of Investigation 1967 Galla RC. The Inhibitol'( Effect of Heme on Hom •• Formalion Possibl Mechanism lor th•• R••gulalion H••moglobin ./wma/ ••01 Clinicallnvesligation /967;46;1 of:124-132. GalloAC.

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

V"",-

Synthesis.

Mechanisms

lor

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

.1968 Gano pany S. Enr{TT1atic Abnormality Nalr. ~--- '"Id 3;218;465-466 ..•

Galla RC a,:,d Bre-itrnan TA.The Enzymatic" Mechanisms .Iar Oeoxy1hymidlne Synthesis in Human Leukocytes: Comparison of Deoxyrib=tf Dono<S. ./rxJrnaloI EJiob?i=aI CIIemisIry1968;243; 19:49364q4? . Gallo RC and Breitman TR~The Enzymatic Mechanisms for Deoxythymidine Synthesis in Human Leukocytes: Inhibition 01 D••oxythymidin •• Phosphol'(las •• byPurines. Joumal 018io/ogical Chemislrv1968·243·19:4!>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.

to HIV Synthesis

None.

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

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

Special in Human leuk.aemia.

Possible Relationship

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

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

·Human whit •• blood cell reproduction pendent enZYfT\&olinked mechanism~. 'ion of, one protein ..

am.t:~~~~~~:~~~a~

~i~i~~~:~~:!

~~~k~i~·:n~y~g'~~.i~:1

~~~~~~ds~~~~~ ducti on at this enzyme to prompt leukemia.

is largely regulaled by inde~ Bath activities are the func·

Further evidence that human white blood cell reproductfon

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

~~)(~~::'~~~~)O:nog~~~~o~~i~a~6~~d~~~ ~e~:S Ofe~)Nta~i.~e stimulated at inhibited by manipulating within the cells.

'"the function ~ne

p(otein~

isTargetY

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

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

Though the human Ireatmentleukocytes of childhood thisa larger study ptovides telated evidence1·0 that can beleukemia. inhibited to d"9ree by Ihe building blocks 01 RNA and DNA.

Same findings as cited. above

Same findings as ciled above

Transfer RNA (IRNA) compOl1enls from plants affects human lymph cells. 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.·

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

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

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

tor Be-

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.

1970

....

'ietreta F. Adamson RH and Galla RC. Uptake of Transfer Ribo-lucleic Acid by Notmal and Leukemk:' Cells. Proceedings 01 tI1e Na.

Upt~ke of foreign (bacten.al) tANA by m~mahan, leukem~a and norrnallmmature hu~an whlt.e blood cells I~ det~rmlned by an energy

Paper Tin-ks Galla nol only 10 Nalional Academy 01 Sciences al <he time contracted with them to develop immune deficiency ca~· ing biologIcal weapons. but also to Seniot NCI tes~atCh position In

>ooaIAca~yol.sc,6t?ces.1970;67;4:1943-19SQ.. 'Presented atthe .AT.O.lntemational on Uptake of Informative Molecules IVuVloq Cells. Mal.Symp.osium BelgIum. 1970.·

Indepe.~~ent. c3mer·'!'edlated, ~ech~nlsm . .P3p~r offe('S several poSSIbilities of what thIS mechanism might be.

-entry of foreign nucleic acids imo ceUs· to ettect Immuno.suppres-$ion--This at me time of10controversial Foct ~defense·teseatch. Oetnck sympoSIum. Papat alsoimpliesGallo'slink NATO'sapplied

alia RC and Longmore JL Asparaglnyl,'RNA and Reslslance of unne Leukaemlas to L.Asparaglnase Nat£!n!1910 227'1134.1136

L-AsparagInase synthetase (a Unique enzyme) plays a k!'y role In controlling the ~growth of 1Ur:'0rs By blockIng Ihls enzyme s actIVIty t~mors can be derepressed -{het! IS. made reSIS(isOI(0 cht::mo!hera·

SlUdy focuses 011key enzyme in whrte blood cells w!\i::I\ ~ repr;ssoo 'NIl! Induce 1€:'l.1k,:1~,I;. Jr.:J I)U1er cancers as w,=Uas make me eJlfpus.c.1 animal cells treatment re::>l$lant. ThLS work lays the fcund.iJuon fcr 0:.::.-

J~le~f\.Q

.. RC. RNA Dependent :1.110 RC. Yang SS and Tlng

f1NA Polymetase

Human Acule LeukaemlC Cells. Nah.Jre 1~70:22B:927-929.

oding Source/Biological

Weapons

Contractor;

~~~~~..9.!9..9~9~:

000

.~9.".!:!:f !09'~9)

"!v~

!'.PJ'!~~~.

Reverse ~fT'G3J

ot leukaemlc patients nOI at normal The enzyme an ANA templale Irombut mammalian cellsdonors. to synthesize DNA. can use

s:JC::srdl .cal~ .dngcarcerce:lproa..coon) and~j.;aefT1c.g€f)e.~fS· 't/~J'\1iJSCS HI :.It~as ~ ~ected T-4 l¥f\p'icCyte to pn::a..ce dcx:ioonal

Calif.: ~ Univ~.of Texas; 0

unon

Bionetics;

~ Bionetics Research

Labs;

§ Univ.ol

!fat\S(' ••'1(:(a.SEnr,'TTie id€:nt.fI<::d resp::coe-;e cy1CXiffCfEt1b.aDon,~ ti e .. d.av~t

,"".!-~4''''

•••. ~

dfor~

-:.

Af" ANA has dependentONA of RtJA viruses been lound inpojymerase IymphchlastsanalO<Justo {immature IOat white bloodturnOut cells}

~~f.ufc~lY.l1 (naf~i:(·

....

Uni~.01

ChicagO: 3 Yale U.·.'

cnD Study

Year and Subject of Investigation '97 o GIAIto HC I&n(t PUHlku

S. Tuulblo.

n,ls ¥I\ldr, the traNiler RNA rB~po":'lhlu IWUIY IlItlltO IdunUllod add In ht"nun Uaallt)~. Jllo(Jf1t' LI'lou:;1 'IUm boch nuu"nl Ql'wl [utlkltmlC t;HII•• MutU "podu~

cont.lnued nNA.

In Nuunul

Sf)O(;lu!to

'~"II'I1W' I Y"'Jlht.11Ilt,ullrl,AItHll;I/oI4ldtJ/lt.rll.lIl"*,yy

und IIIIIKOmic

IU/O.~J2.lUtl ~tu

Q)Ptlnrtyroavt fWllllnU'"IC:Al.I· •.1I!NA~II(IU~tllan~lI~ "INAwtlUlu

1971 .J

Oallo IU~. HAlln

ps.

/!.Uan. I'f. NQwhH1WA, "'lIull:~.

. OfllCx;lM;IWRA,11 I~QVaIQ" l1n1I.ulllIA ••• '" OIItJif1. N41l1l.N_w'Iit-t'f./VIU/I;:l:J.:l;I·m

lor prodUdlon of ~ U\tf I:IflUt;Ju~ ullHNA WCIIU

UlClcllllUllu:un

to HIV Synthesis

AtJPOrtfcX:UStfd(}ndtlflninQSPu(;lncwt6Ial'onslntRNA~espor'\SlbleI0l·~ nunnul cul\ulullu(julultJlV IIIud\wvsnI!i In 1"IdO~~IIC ctslls: SuenhOUinl}S

IIII1Y ~ltllillU I.I~

wot/ill

pltWl110 klll;'lwl~JUu

mudUlutl thy u.vlnrN)

..INIIIII '"IIIIJU.(

OIISCCWIIfY U'UNQIM IIAI\SCJlpIAIUI tu:tlvlty In 1"'111'" IVI)Q r. ~htln lIanod IIln«1 wilh 1Y1111,I"H" •• llV ad,I1,.u 11 aV'It11Alh: 'tNA.'Q,luQIKI I ,,1I.,.t (I d ,1:UI). 1ot*IIGml. ~I"" -IClIIII,jA(.~ lu IfI" 1\UI11I11 1 '\/'tu•••, !llu ull)NA pttllhH..lkltl

Aflll

Uowtln.lM

U.:i

tu whulu

a IUNA

IUllkulI\la

1III'IIXtu::U

IUnlucuJu

mi\111 nodtJ

to btJ.

OU'kI1Cd.r1C",j~

w\llputt\UJJeI ,

I'upctlt IIhalucllhllllypo (I' vll1l!1ltuiV C"AIJfI;.,mAtty rypaa ni cancota btI'iYdoe ImaAUlIlTllu '-I,wllY'III"IUIIIU IUau:IMIUla.latl()vtnll'UG1~1ldl I {IV CU\lIJua sAC/om. tStlyulelll"'UIII "'t )f\lV ""'1'" IIM;ltll,lil1U 1"1"l/ knuWlIIINA 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:~; :~~I~:~I~' c:r:a::~(:,U::~:: .•::~~;,:: 1~'7"~'~:~:1~ ;',~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 will plllluln ttlllllll, Ill, dl::.u~mu

ur I ""ItA'I

I'ypa (; VII\lal'II.Ut:.!aa 14'1

Possible' Relationship

Conclusions

vo,."

IIA,\&tIIIIJhtIlA)

whlt:h

t:an

utili/a

tlulh

Ill" MMJuIlI 11III (I $I, Yt.,IWn1lUh,

11/1uh 111.11 PI,,,,;llIftlll

U nIlMIM"V viII.

wu"

IIIII

"YlolluuwlR,

In t IIV

l-vhllJOCG

p.MIHUuO

hula

AI townl cuncanlual1C!f\l, 1t,,;IOQQUtl UNA ,y"lhDOII

""plu,Lly

t.:UIII.iJ,U

C1IhllfVlyt ,uklno.ina cyc;U(: ~'.O' nlCIf\tlplKXiphnln 11IIft! [hu 11110 uf Gall 1••••1161"" uf U"I1I1UI humulI

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

Gallo HC,

~IQ

.Puna

Enh"nrolM1 T'nnn'o~.\u~no

01 th""nn

comf\C1IUrtll.uu:Ry r~lllrlyrytA.d"fMIf6If\UCyd~G~.b ·MorWJt)l~K4)f"'lu 1J.;J/()/tI~tWJ/Jc.l(I;I/(.;:.;II"_"l$Itnllrc 1U/I,4',1.UI·IM. .. . _,

2U2.

.Av,,·

~~'.-~ ~;on~'ur ANA~~U~~US~;at lA In NOInlU1Iytll~:.l\OCy1~.~19/1;31;:l:~'

l .~.-.'.

IndtICUClf1 by"'!

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

t uvtlla

l..

VtJlwkla

IIIM11\Jf'MJ

'~r~II'I~:~y

1111111

brl!ona otfnc.:Uv. uQol110lA 1T10A1cnJlIUI1KIlIU1fI" tullt;ulllllnr.uUwllt;umu 111n wkMJold "law kllludANA cullt,01InplUralu II\lUII (;uU 1l1\U1I.I)NA GyrlIlIUuI. WU.U:iulul ulfUlltJIV IlIhlbllucJ but not IIYllthu~itl. 11", tJltlij nu.ay IJtf rUI ·"PtK:.Illc!\unont •..... ,

~I~;; ~~=ft~2~tt:~,~:I~:~~~LL~~~~"':::~:~~

~~~.~ ~~-~~~I~· phocyltt&:

a~~:~::~I~~:tll~~:I~~~ ::~~:;::I:t~I:~~IIII~::~ Nun. ·"IIP••' ••III .1 I,,"•••nl

~~~;~~~III\:;::;~

hnmlll1O.

itV und Oullo

HC:. Suftl~(JVk;

$pCJI:WCllloli

of Mulhytulud

5)'bhtllus. &xIJtJ(lIiSllY 1011; 10,11.2000· 20 13

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

I~~~~~~~:~~

'M1lch

wus-"dupordunl

Itl'y1ulud COI~ttl~flt

on thu SYlltlio~~ or ~.w !INA~ wllll;h t~ will! IfOn'ItJ !UUlOI:6 uotl CWtt;Ol VIHI~u:) ...

huun

~ftt~nce bY tRNA: c..o.uselmmuno-

~!~r~~~':~·II"~~:~~~~J~;~~:;I~, ':"~~;~AC~~:~~\~~~:~~~'~~

mo·

pI\ULiIu.:.t

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

SU/IIU ~

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

t_IIUIJIk;

1,,;1.111 IIIIU.~

•

u110vo ~lhJ.:£u(jdlUonul

fU\dlng

I"al

cl\fonic

IymphOCy1ic

•.

ItIlAt.aemio.

~~~:~,,~~~~~I~UrJr~I~~\I~~~f~~'~tJ~~~~~:JII::lj ~~~~tJ~~: I~:::;~~r: IllItllIllU In (-:rw' IU AI(J$ ullllV

IY"I(:.llor.:y10:t

$tM.H\ In

p.utlUflt:6

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

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

~::::I::::J ~II~II~~'~~ ~I~I~~;W:~\I~~,~Yt~~QII~~~II;~'~!;~~~:I~~~ '~I~~~pllxhlCU I1IU ol1ly unUhot:1lu:l dlw'\Ju:s In ~Ul1Itttl1I1\OI:6 unt!

UVQ.lluhlu to duh.t(.'1 1111.1 I\\IIIIUn T·lympt'ocy1tt 1111 V 1. 11.rtuvt,1ll)ptU.hoIl11111~,tlu"y unc1I11).lInd WUIUtuqulruclln HIV. CUllunlly, · VI1tI:'U=' thu I ItV (ullhhodlu~ 'NO'k,100uul'(IO() W(jIU pollt)(1h,>d tlf\d s.ofd

lallkuultlh1.1

0uIWom1 hl1I1\UI'n()lInw lymphohl!1:J~ (Immulllru IYll1pttcx:ytu:J)und hlllnun myulolll8 coll~ (CUJ1c.uU)tI~ uJlllbody fOlO1IoO p!U!.1II0 colts IIlun,dul:ltuuclln

o•.•t thu Ne.1 to ptcdu:~ th:t tQ:xj Ilbls \6tId 10 ~(ocIl ~V ".«%Ion:._ Ciullo Qnd h~lnku cOf1C".Judud hnl11lhls study conductod in lare 1969 or eat1y 1!J10 Ihut thoywuuld l1uu<llo hnlhUI ~"VUIW.l.lu 11\0 ftJl1ClIOc\U.! SoIIJ,urical1ca 01

WI;Irlt obsurvttd,Consaquttntly, IhUi uppulelll dulvet

I;jxpluinucllhot

by (~)

~~~ ~~;~~~:~I~:~~ ~~a'r:~~~~~:~~~~ ~~?O:~I~I:~N~~ ~~~\~~:~~~~ I:~~:s~r :~~d~ g~~:d'~1(~~x~I:,:~nC:~~II~~ In 'Mllltt

blood

cull

dd·

0I1tJ

way

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 ollhe ples~f\cu at '"mord hycJlophoolCgtOlips M ffidll'\yi groups 10tho IRNA (ltK)pl~tic (C.]t1Curous) ct./fls," rhlssuch UudIn will\ oyidtJnctl oted ohovtI of 1110Impollw1CU ollRNA nluu\yI~su UfI.lY'"US In U'\e Inc1uctton

;knowledgod

Funding

Source/Biological

Woapons

Contraclor:

Year and Subject of Investigation 1971 continued Galla RC, T/ansfst ANA and Transfer ANA Melhylalion in Growing and "Resting~ Adult and Embryonic TlSsues and in Various Oncogenic Systems. CilncgrRe$i1sn::n 1911; 31 :621-629.

Llllon

of leukaemia

Blonellcs;

(SV(O) and tfslabbshtJd ft1tf 010USdpafolkJ It.••. nol (poIYClfTto) vll\IS. Such 10rtNl expdflmunts; could havtJ thtt IOChnolor;Vand provided Elm~ deve!" opmQm 011 UV-uHUCJtJulyol~jmiDn Y;IUSdt,1$CUf\(--wraicnsimUilrlydt:llivtirs

horn 'oI1nlSes.

Blonetics

Study·

forolgn

Research

Labs;

Unlv.

Conclusions

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

DNAPolymerasa

of Oncogenic

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.

Possible

Article reviews and upclales know1edge regarding 1lie importance of reve/se transctiplase enzyme in cancer causing ANA tumor viruses.lmportant questions which Galla proposed be researched ;n.• duding: What are the detailed biochemical mechanisms for this enzyme?" and ~Does the enzyme in viruses from higher forms citter from that 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

~~::~:I

~A pNA pofymerasa h~s ~n lound in blood Iymph~laslS (immalure whrle blood ceUsj trom IndIViduals W1tnacu.t9 I.~karrua Ihat. unlike Iym·

70nal Academy

~~~A~,"NA

Source/BIological

Weapons

Contractor:

culls.

0 Univ.

Relationship

0/' Chicago;

A Yale

to HIV Synthesis

potyme/ases

'/om normal IfldtvlduaJs. Iranscnbes 70S

"Two DNApoIymerases purified Irom normal human IyrrchOC)19S (NHL) are distin9'J~~ from !he ~1ralreverse transcnp~es of aVian,[cntcken 1 my~OOIastos!s ViruS and mason-~zer monkey V\f\JS by ltIetr rafative affinity 101 select !emplates ...Critena fQ( distinguishing the activity of vi· ral rev81'S8 transcnprase are discussed.~ inducing .•...lhe ability of ""aI reverse II.anscnptases, but nOllhe cellular DNA poIymerases. to react with 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 an amli.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 1 ha RNA-dl!pcn· doe\! DNA poIymtrrase ffcm hUmdn acute 1E:\ .•Io.r::mtC.:eils 5a:DSJIHSall these cmena tor a rev03~e r/anscnplase

Litton

Bionelics;

catls induding

!he

None obvious in this sUl'T'CTlaryreport.

In this study, Galla and cowor1<el'S stuaed ·portions of ditfer801 viruses to determine if "'the tANA difference (in cancer c&l1s) be rEM:atedto the properties at neopjasia (cancer deve4oprnent) in general. or. more spacificalty, to the function 01 Iha DNA oncogenic (cancer causing) V\NS genome (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. ~ThIS work shows lhe analysis of different viral genes was 1Jnderway to dele/~ mine what effects each ml{11t have on delJek>ping cancer. They laponed U'leirdeSi/e to use !tis rlormaDcn on cancer ~ vitt:ses la Ii"1d a 0Jr9 far c.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.

f~~~~:r~~s:~~~%vV~~~~:f~~~r~= ......nth the abijity to p/odu:e vif\J.S-/elated

Smith RG and, Galla RC. DNA.Oependent DNA POlymetases I and 11 rom Normal Human~Blood Lympnocytes. Proceedings 01 tile Na~

'nding

blood

AI d'IIS VIruS.and the polyoma tumor) 'I1NS 1f'Itected S!mian (monkey) virus(mouse (5V40) parotJd the. murine (~at ar mouse)cens. satcom.a time changes in specific amino acidS within the ¥h'Iite bfood cells' ANA and DNA were,betng manu1acttJred in·lha lab and studied to detem'oine the related effects on Ihe immune cell SInx:tU/e and function. Combine ttlis research, and the available technology to isoiale and inject genes Irom different viruses to proauca a unique ANA ratrovirus. and GalkJ et. ~L, had all the requiremenls n~ to produce HIV. The. next ClJesbons are: 1) Did he i:i.nempt to combcne di1fe/enl viruses to Induce.s.pe.Otic carce<ousand mruna system anOf<llicr6. and 2) I so: v.t;cI1 speak: ~vic~raI~andCO<r€2':~.!!;_'!!!F.thehaveUS9dlDoea"' an AJDS Wui1 .

_________________________________________________

Iledg/"'-

while

0/ Tuxas;

DNA 10 synlheS4SIn and a build-up heavy Weight rANAdue a '"di~r.dercancerOUS 01 proteincells synthesis: Ttus isof i~dicaled .by reduced \he 3ssempiy station for building amino acids inlo' p/oteins--in young leukemic ce"s. (The amino acids ale. delivered by IRNA to the rRNA. Iha ribosomaI'aSS&fT'bfy Slation.') In this report, Galla questioned vd1ether awte tymphocytic leukema was associaled wilh a specific change in tyrosyl-tANA, and whether IympnosalComa. was related to a specific change in seryt-tRNA.-Similar 10the results with RNAviru_s-(ranstolTT\8d caUs, tne tumor derived from the polyoma (mouse parotid lumor) cells showed higher tRNA malhy1ase activity.

Wltt1lha ViruS genome function: anligeos and their effects.

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

la nOlmal

Uni •.

In this study, Galla used several virus-transfanned

~=t~,

of Scie/JC8s 1972; 69: 10:2879-2884.

Human acute leukemia likely involves a block in leukocyte maturation

•

Galla'-RNA

RNA

ut Calli.;

" 8ionetics

Research

Labs:

Until.

The 70S RNA virus is singMt stranded RNA retrovirus found in d1ickens 'NhiCh causes some pramlnenl features 01 AIDS, irduding white bk>od call dysfunctiOn. sarcomas, progressive

wasting. and deattl.

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 sexual uanmiss.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.S study s~;:iJ.: frJr :ham~I"'riS

of Ca Id,.

00'.•

Unlv.

at T~xas;

0 Un IV. of Chicago;

~ Yaia

""".

-1972 \1 Nand

('.u.UI) I tr:.~,Ulw:

h~nntlluwJ

<:0 1111nl " ••

•. fllMI hi r1NA

!lUIIIJ

~ynlplUkJ t \tJKI. IlIIm fhullul"'II,",uuua-

11ItUIM.M.toi

I'nly".,uuui Hun.lllv" I :;J;~J" :~:I~

cClndlll1ud

I UII(),".ldu"",

1t.af1nJltvu (INA

IIVl11'IacaII

wnall •••

J ko,

''''filIAl

NIIIH\QI 1y"~lhCJIJVtCf" .lIf1Iululotl with Ih ••• :" t;nl!c:NI''''Vlu'',""nlJU!uUul" ph~x."Ytaa. I )NA l'ulytllulAIMf

DNA Plu,'PPI1 Puly

1."'lun I~t".t

Ihet ftual\l" plnfl! dllllVtMIIUlI\u&.uil: "uh (l'IIA),hu! thla nul III Il\u IJIII.II".,I"h INuUII.lllum hl".lkll\ IklUlt lIul••1tyln It,I"

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 hll n\.l:u, kmIU.1I1\k; 1;0110.

·M;'U.

'Yha I)QIILaAy ptn1nucll)("ymDIAuc':l wflkJl amllllutJ III,uthucJuUQl;ltutZllk:1I

hlllnJINA IhuvhuQ'

t>OUfI

!tUUUf

/0111111111

. "AcontlmMJd G4:1",.;h IOf II"Uhodius 10 111U 11'I'iIlCHtW''t:u. :l1)uc:;/fUty Rlld<it!ft

IIIIUI)()4I1IIU Iu IIIVUl8 •• "'UI:;c;rlfJtnrMl IhQ 1cw.:1.MIUVII thlD ItJlKlft. IIItNld'!4J

'tNA lun\()f' vi· tu tiuvuh~I \hIt

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Possible Relationship to HIV Synthesis

Study Conclusions

Year and Subject of Investigation

q-,)

--..•.---.-----.

ut HNA

unt..l ONA

Bcld a ba5lc

cun ·UfUUUy Inctu.u:w Ihtl ratd rt1rUl.Juh Ihtt rtlvtt'~tt t'lln--

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blood the resuarchers manufactunng new itstrain 0' vi.uscells. hereC~arty. and checking to see It were chemotherapy could astop Iran ruproducing itsuU through 1I"1t3 r~val'S6 protein symhesis mechanism typt.. cal of RNA relro"iNses.. · ,

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

=Ie~~r~~~~~~~ O~~~i~-~~

L\ • sopenten ) Adenosh1e. a plont hormone (among a class 0' hormones called ey10kinins known to be a ·ciJus.ativa o!)tint in certain

Gallo RC, Hachl SM. Whang·P""9 J and O'Hopp S. N'·(.-\'-.'S<>I>'>nlenyl) AoonosJne: Thtt Rt.lQulo(ory Effacts 01 11 Cytoklllln 4nd Modified Nucle.o-Side From IRNA on H~jn\Oln Lymphocytos. 8-*OC1'v111C.:/ Et Bq:vt~ AL"td 1972: 261 :486 500. AcknowlouljfJd

Funding

Sourc~/Oiological

W8apon~

lymp!1050n:oma coils Ircm ca~"r pallonl. 0110",010 'our bme. a:; groal as thut In nannaJ Iymphocytes Iram !,oalthy humans. -aNA sy'ntho~is camot be ttle prima')' situ of adlon- ollhisdnJg which caus~ r~mUrkabty similar effects as phyto~omu.polutmin on ·stirnulated lymphoCy1es Ijl comparable concetltrallons.

t. LiHon

Conlt.uctor:

hill~~~I~II~O~~:~J~~~7:.1~~~~::·~::f~": ;~~f~~o:~~

~~~ts~'~r~'IIIA~~U~Of~~:"~~~~~~~~=~ ~~~

Blonalics:

Blonulics

Rasuurch

L8Uti~

Univ.

~~r~~~~~?~~e~~~~~o

strmulQte cancur call ('••••• Ision .. they appear ar this poiot 10 have -"ar~ rowed Ihttir anenttQn On 10the IRNA segments composad 0' ad900sine or lu1uI1YIic uods. 01

Cali/.;

Un;v.

Taxa.:

Univ.

Chicago;

6. Vala

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

es}. rt period." anscriplase nequivocally nto the host· ggests Ihat RNA ore toxic for es 01tumor botn mo, viruses n°[~~~r

r~:

reqUired for for formation of of the pro ..•• irus. the RNA lumor viruses, and cellS_by biochemical and immunological approaches. The enzyme is fresh human leukaemtc.blood cells than lor nOffilal blood cells. These used of !ha to National inhibit the Cancer effects Insllrule 0'teukemia rat and -thal The mouse NCt. leukaemia·sarcoma 1ha author3 -Nrate vi· rasarcoma. identification or methods for AIDS. Paper does provide "N';ilP:-.,.,S c~nltactor ~,~E:rr:k",nil \:,j ..1.150. ",,02r<;«1 is .::-,,,. is lIman and viral origin, .'cardycepin No apparent relation to the development of AIDS •.beginning lRNA ike viruses or 01 01IIJ:)lc<J1 experiment essential had iF'Jductlo~ been obtained from by Ihe exogenous ~Orug Development virus and corre-Brat'\Ch review article summarizes Gallo's research on the uI'\ique reinteresting acknowledgment: The antibiotic used in "The results of this study suggest that RNA-directed DNA polymerase assumed that the role of Ihe enzyme is to convert viral 70S ANA 10 [he with, the previous observation the same {Rifamycin antlbi~ and its link t.o cancar beatS no rela!ionship 10 the developmant 01 Pasteur Aeseach Institute isolated HIV trom the white blood caUs of HIV velop renUy or antibodies used othet to AIOS·like idenlify which HIV viruses. could help Gallo detect did, this discuss enzyme which is 10 curdetranscriptase has been lound in every RNA oncogenic it might virus.,.11 be interpreted is as rt;tverse This woO( transcripase advanced is the necessary use 01certain tor transformation anltbiotics in by an RNA effort tumour to fight menl 01 HIV o( other AIOS-Hka viruses. ;.continued RNA-Dependent DNA Polymerase inWeapons Viruses and Cells: Though this summary and update report on 'everse 1ranscnptase human duce Iheir leukamia. cancer Though itinfections. et19Cts. bears no HIV relationship anacks while to the blood de ..•• 'ceUs, elopshown to be required for leukaemia and sarcoma viruses pro-viruses. can from Reverse verse Galto the transcriptase Sludied DNA transcriplase. polymerases and discussed enzyme the at unique associated nannal produced enzyme -with HIV found a similar and in olher HIV complex ANA is hera tu· 01 having contributed tn the de ..•• elopment 01 chemotnerapies for can· discussed here. Itlreatment iscausing remarkable Ihat the type-C RNA turnor replical.e is published-ten years before Luc Monlagnier at the Besides RNA turnor Linon viruses Bionetics, can a dcx:umenled be stimulated U.S. la reproduce in mouse calls Derivatives 01 be Ihe distinguished antibiotic rifamycin sarcoma derived complex.' from bacteria were experim6nts. The Special Virus Cancer Program from Labo0.0,0. bi04ogic.a.1 weapmar viruses. Here the theory of how HIV and other such by the addition of adrenal carticosterolds and many olher hormones. The·late presence at an .RNA..(jependel1t DNA polymerase or reverse .,thal is leukocy1es, and causes ahere rare skin canca' known as Kaposi's d Funding Source/Biological Conlractor.: Littoo milt/3n~1 Blonetics: was shown ...; Bionetics to be an Inhlbtlor Research 01 .LabS; synthesis §viruses Univ, Calil.; 00 Merck and Co.; 0 Unlv. ot Chicago; ~ Yale U .. Co eps ·ratory in Vienna, Va. was mentioned as the supplier cfHaz1elon Aausher laucns contractor. being cited as lhe major funding source lor ltIasa bacteria best seller me Hot Zonswas Hazleton mentioned as an actual sup· ~_~~0~ui~;e~~i~e6~~~b:t~ ~~~.Si~~~:~ef?~~~~~~d

Study Conclusions

Possible Relationship to HIV Synthesis diseases with AIDS including a~leukemia-Iymphomanormal cells would also beto harmed along with cancer cells. demonstraled in soma human acute cells and its pres· ~~~~~~~~s~~~~d ~~~~~~i~~~~ plier atcame ANA tumor viruses. In fact. Preston alleged ttle deadly vi~ ·ca~ePin kemia viruses used inCo, this study. This is of noteworthy as Hazlelon's ,t:••. cej'Jti;d 1c1enccicA +~n~C~~Vj~~~r~~f~~a~~~I~n~COe~:~~~~~ fhe drug frem betwee:n ~Merck Gallo. and ih.,:. Co NC!. .leukemic Incc.rp and ,the Document J[~7,S:~~~fnss'v~~:' OOCUIT1cfil:r1blCi~ ~:rC"'IC.cS nuctlon far the dE#vt!lopm&nt of associated Merck and 01 ne .•••. pharmaceuficals. a s.p&Clal branch ofdav6Jc.ped !he t~CI r~spon~tr,le apparently ruses from either the Phillipines or Africa. 'Wllh ieder;),1 ~~t~~~~i~~~9Ar,:~y~'inG51~Ori~~t'i;:~i~~; i::and taxpayer 3_SSlslanC8, ~~~k~~~~CCH~~~~ cer as well as possibly AIDS patients. The authors did indicale !hat (a. crystallin.e antibiotic ~~n~~~~~ti~~~~~et~:~ ab!aine.d from the .iu,k Year and Subject Investigation

E~~~:~~,:

_______

Year and Subject of Investigation ~::~::;;:~::;:;;,:::::::::--------------:~-~--:--1973 conlinued

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

Possible Relationship to HIV Synthesis

Study· Conclusions

••- ••

The group lested "ANA from AD 114 virus, potentially an RNA tumour virus 01 human origin," 10 see if reverse Iranscription occurred to give rise to additional AD 114 virus. This study concluded that "the reverse transcriplaseof AD114 is nol closely related to any tested viral reverse transcriptase. 11is believed that the gs 1 antigen 01 tumour viruses is species specilic ... Unless it is shown that one spe. cies can produce only one type 01 9s 1 antigen, however, it can always differs be argued thal antigen RD114is lound a new withof aknown gs1 antigen that from the on cat the virus viruses feline origin. Also, il was noted that "only viruses which had been grown in Ihe orignal tumour cell and had never been purified as a cell free extract before the linal colleclion hybridized (Ihal is joined) strongly and specifically 10 cell DNA ..

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

"DNA polymerase activity in human acule leukemia is recovered lrom a cytoplasmic subcellular fraclion having a densily (1. 16-1. 17g1 011) characteristic of RNA tumor virus particles of animals ...lhe purilied enzyme uses synlhetic lemplate-primers with a specificily like RNA-dependent polymerase (reverse transcriptase/ of viruses and differenllrom DNA the major DNA polymerases of norma proliferalingleukocytes; and ... Ihe DNA synlhesized (within the cells) by RNAdependent DNA polymerase contained among ils sequences a high proportion (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 Ihe vasl maJonty 01 cytoplasmiC partlculate malenal, whIch had a den-· sity 011.16-1.17g/ml ... The presenl results stress the. importance of purification of the cyloplasmic particle 10 obtain a suitable DNA probe, [that is, a particle which can initiate the invasion of normal DNA by loreign viral RNA) ..

U--_";i;I·~nf~J..;i.t~

Many researchers believe that the AD114 virus evolv.~'1 from a cat virus to laler inlecl humans. This report stated Ihal: -:;,;me experiments have been reported which have led to the belid Ihat AD 114 is not a cat origin or is likely 10 be of human origin: ,Ill:;! as Gallo's research team argued in this paper, "il can always br, iH~JlJed thal the" HIV evolved as a simian virus with antigens Ifof81'"Jn proteins which prompt an immune response! that differ "Irom the antigen found on the viruses 01 known" monkey origin .. Also, Ihe group concluded Ihat"ANA lumour viruses mainlained in tissue [as opposed to a cellvirus line and in cullurel often for. do nol produce IheCUltufO pathology of the original give cause questioning the10indiscriminate use of the the group viruseswas tran:,Ierred trom one type of cell another." Apparently, ne,1 concerned about creating new viruses; rather Ihal the new virus':5 Itley created would nol mutate to other less deadly lorms bt.!for8 they could capture and study them thoroughly. Here in the Proceedings olthe NalionaIAcademyol,sr;timces. Gallo and co-workers proclaim they have isolated a virus-like particle Irom human acute (that is, quick acting) leukemic (white) 1,lo(;(j cells. ThiS particle they state has a specific density of 1.16-1.1"1 ~rnl. can be repeatedly recovered without being destroyed by phYSIcal handling. and has the capability of producing the principal rapidly progressing . cancers associated wilh.AIDS including leukemias, sarcomas, and carcinomas. In essence, Gallo and company announced isolating AIDS-like virus particles more than a decade before Luc Montagnier announced the discovery of lAV (HIVj. 11is also interesling to note that 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 rats WIth a Gross-Iype avian01(birdJ leukosis [IeukemiajmUrine virus,leukemlavlfus; slrain avian

... AvI.V (ANV). myelohlastosis

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

1974 .J

Similar 10 those reported previously

None more afJparent than above

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

"A clone containing Ihe full-Ienglh HTlV-1I1 proviral DNA was inserted Into a plasmid [a extrachromosomal hereditary determining replicating ·unit olher Ihan a gene from the cell nucleus] and used to transfecl cord blood T cells Irom normal newborn humans ... lhis molecular clone is infeclious ... and causes marked cytopathic [cell dealh) on T-cell cultures .. : ..

This ·paper along with Gallo's earlier publica lion (seE: G"ltaUher. Ting and Gallo, 1972) shows that Gallo nol only had the rnethods and materials needed 10 clone Luc Montagnier sLAV, I,ut also the capacity 10 develop a foreign germ capable 01 infecllng normal newborn human cells with the genetic material needE:d Ic, Ciwse marked !~!:nJ~~I.~.!'~AJQ_~_\l!!~s: ..... ... _._

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

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

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

1985 265.

•cknowledged

Funding

Source/Biological

Weapons

Contractor:

Ulton

Bionelics;

Bionetics

Research

labs;

As Slrecker 1986, lamily Ihis large group 01 rf:!,III ,8archers in· cluding Gallo reported found thein IITlV of retrovirusf)s dlitr but not identical to Ihe bovine leukaemia virus(SL V).

Univ.

01 Calif.;

( ..~~;'~~~t~I~-~i.1J.t.:;,;.It!~ •.,;,.(';.:...;.·: .~;:-;:: ...:h. ';;'~:.:'';.4.:''_.: •.•..•...~. :, ,.•..•....••.•.

00 Merck

and

Co.;

0 Univ.

of Cllici"J!Jo;

.:'1

.••:M:;:'t':(Jl ••·'71r•... _):.I.••.

.... .,~~~~~:ttVif:tit~W!1(,w~~·;.\~::~j"j,:..c:~~:i"'~:,,·~~;.~i\~~r!~.":~~~'r\~i;1JJ

-'-~:~~!~~~~~;

Yale U . •

In 1971, Gallo and co\vorkers reporteJthat a sim-i:m foamy virus (SFY)-a common contamin:lnt of monkey 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. For this reason, littk attempt to remove them --, from cancer virus cell cultures andvira! vaccines was made. ID

Rhesus ;\lonkey

SV40

-Q - -~

(~ 0--'

.)/y~- (G) ~

k:: .>

Viral Contaminants SFV and Othcr Likelv

Gallo's group at the NCI and Litton Bionetics also experimented with other simian and human cancer viruses (e.g.: SY40),IO·11 and developed recombinants (i.e .. mutants) Illl\;IUUing those that caused the prominent features of AIDS-WBC

dysfunction,

leukemias,

lymphomas, sarcomas, progressive wasting, 1~·IJ All this in the likely and humans. 10. retrovirus and ultimatecontaminants. death in cats, mice, ChiCke~s, presence A· '[ vw.n

1ofbl

ye 0

_-~ "(

other.. easily

mutated --- -

astOSIS ViruS /"" /""

•

,_/""-P~"-

-~j

'@ .f..-~:.,.., ~,-~---~

{--

.. ~f#:

FELV

1t"

r~t

F-·... ~

,', -

Finally.

these and other NCI d suc - h mutant .

..... mvestlgatorsmJecte

viruses into human WBCthem and tofetal tissue cultures to enable infect humans and even transmit these same diseases.15.16

the obser-

vation made ten years later by the CDC's chief AIDS researcher, Don Francis, who - noted the "laundry list" of feline leukemia-like diseases associated with AIDS.

AIDS? 7

AIDSlike ViruS

RD 11..1ca[ lcukcmia/sarcoma

• -

7i/':J R;\ . -\ founD In chicken

'" -

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-gene sequence that readily picks up other genes.

AMV

This work foreshadowed

R='iA sui[:J.bk for hum<ms . immunoddicic:ncy rc:tr0viru:>_

progress being made in the field or molecular

1l1e dramatic investi!!ate

group tions:

the relevance experts

considered this matter _

I. All biological

SOVIET CHE~nCAL A;";D BIOLOGICAL WEAPONS ~1t.SrKE5. The statements indicate that the Soviets have made extensi\"('~progi-ess in chemical and biological weapons. I would like you to pro\'ide for the record a statement which shows what they are doing in this area and with some indicatioh of their capabilities in this area. ;Vu. POOR. \Ve \vill be happy to provide that; (The information folJows:)

:::r

f'\J

psychologically for chemical ~d biological ":arfare than any othe.r nation .in the world. has L'nion placed isa great of emphaSIS on these systems 10 her military The She SO"iet belter deal equipped defensi'-ely. offensively, militarily, and machine. Ctilizing a wide spectrum of chemical munitions. the Soviets consider that chernicaltactical weapons would t-e used in conjunction with nuclear weapons 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 the battleiield. The Soviet soldier is well equipped defensively. He trains vigorously and for long periods of time utilizing his equipment. He looks upon chemical as a real possibility in any future conllic!. and respects his protective equipment. The research program in the SO\'jet CniGn for chemical warfare and biological agents has encompassed every facet from incapacitating to lethal effects. both offensively and defensivel\', (Additional classiiied information was supplied to the committee [including the testimony below].!

S~THETIC

BIOLOGICAL AGENTS

There are two things about the biological agent field I would like to mention, One is the possibility of technological surprise. Molecular biology is a field that is ad\'ancing \'ery rapidly and eminent biologists believe 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:)

of this field of science

and provided -

agents up to the present

biulo~y

to biological

us lu

It'll

warfare - :\ small

the following

time are representatives

ohser\'a-

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 any known disease-causIng organisms. MoslImportant of these IS, thall~":l\lB.!!~, be refractory to the immunological and then!JL~utic processes upon ,,-hich we aeiJe d to mall1tall1 our reTaTtve fre"ed(Ji111'fOm inrectI6'U:~-dlsease·.·-·" ' , 3. A researc

program

to cxp ore t e feaSiolli'tyoTiliis'cOtiTrbe

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

I \f

cOl11plCICU

Molecular

bil1logy

is a relatively new science. 1l1ere are not many highly competent scientists i_1lthe field, almost aJl are in university laboratories, and they are generally <Juequately - supported from sources other than 000. to initiate an adequate program through National Research Council (NAS-NRC).

However. it was considered possible the National Academy of Sciellces-

_5. The matter was discussed with the NAS-NRC and tentative plan~ \\TIC 111adc to 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 controversial 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 knowledge that such a weapon is possible, and an understanding of the ways it coulu be done, tl1ere is little that can be done to devise defensive measures. Should an enemy military

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

L. Poor, was printed on page 79 of the public record cited below. However, statements Defense. querilly

were deleted, The complete

by atlorney

the supplemental

Dr. MacArthur

testimony

Theodore

was, at the' time, the deputy director

was found initially by military investigator

Slrecker,

Ninety.Firsl

Before

a Subcommillee

Congress,

of the Commitlee

Part 5 Research,

day, July 1, 1969~ page 7\

'shinglon:

Development,

V.S. Government

Act (on page 129 of on page 124

of Defense Appropriations House

Test, and Evaluation,

above

of the Department

document was later published

on -Appropriations

Charles

Zears Miles and subse,

J.D., through the Freedom of Information

record). A copy of the original classified

Deadly Innocence by this author in 1994. Source: Department Hearings

Or. MacArthur's

for 1970,

of Represenlalives.

Dep!. of the Army_ TlIP~-

Printing Office, 1969.

IY\-

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

Bovine Leukemia Virus

./' /'

Strecker theorized that bioweapons researchers began by mixing bovine leukemia viruses-which they knew were T-cell attackers-with sheep ognizedvisna T-cell viruses-. destroyers. which They were thus rec-

C (~O

B VV

produced bovine visna viruses.

• I'\.

Virus

-t:!) .. Sheep

Visna Virus Next, in order to get these viruses to cross the species barrier and infect human cells, Strecker reported that researchers may· have cultured them with herpes viruses or hu~. man white blood cells. The .viruses· were thus repackaged. Herpes virus envelopes, for instance, then contained genes for BYV, which could have easily created a virus that did everything the AIDS virus did.

/V\-

0• -

Like .. Virus

~AIDS ?

Bovine leukemia virus RNA with reverse transcriptase 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.

s) ition 6ional

~. pc

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

Table

Funds obligated for A.I.D. activities and amount and p~rcentage for health, popula~ion and nutrition projects by country or other allocation, Africa Region, FY 1973 aridFY 1974. FY 1973

J",

II 1

-- -

,.. Allocation l~ I I I962. 2.0 3.0 26 22.6 8.3 45 9.0 80 11.1 41. 43.0 1 3.0 3 15 13.7 9.9 126 31.6 5.0 84 8.0 57 1533.3 301 111 3 55.0 3.0 11 & Nutrition 35 30 109 45.7 5路.0 107 9.1 2428.5 27 19 510 57.6 74 155 125 119 510 49 155 1114.8 75 5 Cameroon 115 Total 11, 700 65 830 . Percentage for 5,161 15,600 1,019 20,572 8,800 17 ,2. 188 0 0 21,433 12,200 3,592. 1,12.0 4,821 20,623 2,l.65 1,472 3,064 1,034 11,000 7,200 1,372 16,100 10,600 Hea1th,P~pu1ation Bo ts路 .路ana ..II IPopulation 162,143 Regional Central Africa Republic I Total

Health

_-----------------------------

-----------,-".-"----r.c::i....~;::;·:·

ilf

?:=:e~:

~€.:.=:es :::--.::J~ ~:;-::-;::-::~

:;::..::e:

,. ?:=~ ~::: .' ~.

':B::::';: ·..-es: A::~:a

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

Re~ion.]l S::.al:"cy.

Erad~c ..itlQn

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

,.1

. - -. -! CI..-: ..... ~5::=a:~: :~~:~c:~:~ _;:~:F:=:a:

j-=::,;:- .

'0';:.

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

'::.••

:~a~1~7~ Description:

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

;~~~~::

::2=:'g:-,:,: :.: as;:'·S:

···a'E

~=G!:~~X:~ :~e :: :~e ~:5: le:~a: ~~;~;ses knovn to ~an A!~~:a ~~::5 ;~~::X:=;:E:Y:~: :: :~:5~.5::i:~~~, :~e s=al:?cx ef

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

and

porticn

prcg:a~

~!~::~::~~~~·~i~~~~:;~~:~~~!~~::~~:::~:~~~:~~~~~~:~:~r::~1;a~~:l::litY a=c~~

::~~g~:~::~~5, '.

,. ::~E::::~

~~5 ~;~r:e= out fer A. I.D. bv Co~oci~ies were t~e :c~:E~ :~~ :~~=~=e ::~:~:: := :~~ ?~5 ~~:~: a ?A5A. pr~~i~e: :: A.:.). :~=:~g~ E~~~: ;~:~==e~:=~::~ :~e Crga~iza~1on for Ag;:~5~ ~a~or Eade~ic Diseases Ccc~era:ic= E=~ ::~7~~~E::=~i= :~E !~~~:

_~~~~:=;_

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~ zone covered by the" proposed co~trol program (a river bilsin area shared by "Dahomey, Ghana, Ivory Coast, Hali, NIger, Togo and Upper Volt;'). Fear of the disease has led to abandonment of e"xtenslve areas of fertile river valleys in the Volta Rive~ Basin. These valleys orB badly 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 technically feasible. Followini that conference the seven governments of the affected Volta River Basin area confirmed their desire to pnrtidp"v in 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 proposed program, convened a preliminary meeting In Paris of the particlp"t \:1;: African countries, .Interested dorior Governments, and concerned international agencies for purposes of organizing the programming and implementation of an international effort with regard to onchoc~:ciasis. Total costs for the twenty-year control program" are estJm"r",·! The to"tal cost for the first six years is estim.Jt."J at $120 mllUon. at $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 Uniterl Kingdom, th~ United States, the WHO,UNDP, and the World Bank. The total U.S. contribution to the six-year·phase of the program Is estimated at $8.2 million, or not to exceed 20 percent of total pregr~rn costs. The participating governmentA will provide the program ·with full support including priority consideration for socioeconomic development in the sectors freed from· onchocerciasis.

~:~~~~~a~~~:'~; ~~~~~I~;;:.~~~;~~~i::~~~i~~~~~~~~~:~~:~:~:~~:~~:;~:~e in" 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 :~~ ion years, late: ~~::·;ce: :: ::;;~ ::ea:, :.~ ::<:5: c:;",,::.les: Phase [I was

i~~ ~:~~~;'5 a ,,~<~~~~~~~<~: ~~:~a~~:-~ ~' ~~~\~~,/:~i;~~:. vaccinat ions ?~c5:~g :~: c:

~.~.

~ss~s:a~=: :~~~

t~19~1.

D~ring this

perioc L.S. ~~v:s~~~ _e:~ ~~ga~~~ :~ a::i~i::es ai=ec at br1~ging an orce~ly :=a~s:t~:~ c: :~e ~::;=a= ~~:~ ~eal:~ 5e~~:ces of the partic!?at:~! C~~~:::es. ':~e ;r=;e:: ~as in ~. 1974.

~=~::~ce~

about

~: ~;:

~; :"Jt,2,:

•..

=- ..

--==-~

::~a:=:

- ~..-::: .~:-~ :'::'':ga:e: 1.- :

FundJ.EE.:

A. I.D.

A. LD.

fY 1974 - $2,000,000 grant funds were obligated Total through 6/30/76 - $2,000;000

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

I \

by A. l.D.

-~•. _-

._-----"

-----

.•. '"-

-"¥"

CD •....

HEALTH,

Area

932-11-5 if)-D7 6~~B-1L-SQd-13i 932-11-580-166 932-11-580-359 932-11-580-373 932-11-570-374 932-11-580-358 698-11-580-189 698-11-580-346 932-11-570-360 _698-11-490-363 Project Number

-~egional Regional Regional Reg1"onal ::I~"; t:')na ~ /- Regional ~giQntll

popuunON AND NUTRITION AFRICA REGION FY 1973 - FY 1974

FY 1973

Contractor Loan No.

Tiele Labor

Project

Univ.

Teaching

of Population

Marketing

Research

Regional

Population

Regional

Dynamics

U. of N. Csrolina _AFR 797

1,605,000

1,775,000

600,000

500,000

Population Services Inc. AYR 827

245,000

Support

AAMC,

435,000-

Population

Planning

Pathfinder AFR-575

Fund

Regional

Population

Planning

Population AFR-629

Council

Maternal

and Child

Health

Family Planning Courses Training Institutes MC!! & FP Training

Extension

csd-117l

Univ. of Calif. (Santa Cruz), ORT AFR- 79 9

FY 1974 Funds

685,000

1,180,000

in Health

and Research

Meharrl AFR-373

Deve lopmor"

Med.

Col.

796,000

.. , j;, \

_________________________________________________

1_5

i.. ;"':j J

',.,

H.'~' : !

: ,''';';

Contractor

Ghana

Chad Gambia CI.IAR* C\lAR* Echiopla Ghana EChiopia Regional Kenya *Central Ghana CI.IAR*

Loan No.

615-11-580-141 66)-11-510-006 66 63S-11-5BO~200 641-11-580-064 )-11-5 30-170 625-11-510-908 625-11-550-B09 625-11-510-116 641-11-590-068 625-11-590-904 625-11-540-510 625-11-550-531 677-11-580-500 641-11-580-055 698-11-999-135 ~ect Numbe~ Howa~d

lIest Af~ica

Unive~sity

Cont~ol!Smallpox

Regional

Public

University

Health

Cente~

Strengthening Onchocerchiaaia Albe~t

80,000

Systems

1,011,000

2,000,000

45,000 335,000 224,000 740,000

4,800,000(1.) 340,000 15.000' 21,000

in MCH Care Activity

Danfa.Ru~al

Development!

Health

U.C.L.A.

A~R-697路

Planning

Population Rural

15,000 155,000 {L) 800,000 66)-H~OlJ<: 214,000

Special. Population

Family

1,000,000

Activity

Eradication

Training

436,000

Hoapital

'Population

Mala~ia

Sciences

Delivery

549,000

461,000

U. of Pittsburgh AFR-756

T~aining

Control

Schweitzer

Special

)5,000

E~adication

fo~ Health

Health

FY i974 Funds

Howard U. AFR-G-I077

Confe~ence

Region Meaales

197)

. Funds

ProKram

Health

Population

Support

Management

Services

Dynamics

FY 1973

Contractor Loa~

Proiect

Lesotho

632-11-580-500

Special

,Liberia

669-11-540-054

National

Medical

Libe~ia

669-11-540-110

Mate~nal

and Child

.a\Ji

612-11-580-500

Special

Population

Activity

49,000

Hauric.an1a

082-11-580-500

Special

Population

Activity

24,000

Mo~occo

608-:22-521-096

l.Iate~Supply

Morocco

608-11- 570-109

Demographic

Morocco

608':'11-580-112

Family

Ni ge r

698-11-580-500

Special

Nigeria

620-22-521-720

Nigeria

620-11-580-789

Family

R\Janda

696-11-580-500

Special

Population

Activity

Senegal

685-11-580-500

Special

Populatio~

Activlty

Nl1mbe~ Population

Activity DHEI.I/IHS PASA AFR 36-85

Cent er .

Health

Planning

Center

U. of N. Ca~oiina csd-2495

",;,j

Ho:::.:..

1,276,000

1;274,000

48,000

200,000

140,000

310,000

270,000 5,000

(1.) 620-H-004 Johus. Hopkin.

Training

路路!.';,!.'I

.:"tl.J I

830,000

11 ,000

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

19,OOO

19,000

Activity

.Ibadan \.laterSupply Health

11,000

(L)

Support

Population

1974

96,000

Training

608-H-040 Research

No.

Area

2~5,OO()

5 l ,000

- ~-.___ ..

...

._.. _-

_------_._.- .._._

..,--

..•.

-.... ,._-~... ,

---.----.

:.----.-.--

--- --..,

--------------.----- -----..

...--.

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!"11 DBlT ·'men!. Department of State for Fiscal Years 1973 and 1974. U.S. Government Printing Office, Washington, D.G. 1975 ( \

.._.._...

._J\ . .

...

.__~_.

.__...

.__u_._.

·.... -

~MITHSONIAN SCIE~CE !PROJECT NUMBER lOo

INFOR~ATION NOT U5e th

PROJECT

E:XCHANGE\

5DJ.ce)

U.S. DEPARTMENT OF HEALTH.PUBLIC EDUCATION) AND wELfARE HEALTH SERVICE NOTICE Of INTRAWURAL RESEARCH PROJECT

NUMBER

ZOl Al 00026-11 LID

I pE:.

. JD

COV ER EO

Cctober 1, 1977 through September 30, 1978

---

\..-

i T:Tl~

PRGJEC7 .

ch~r~cters

\~O

less)

I I

Laboratory

I.'WiES,

and Epiaemiolo~ic Studies of Viral Hepatitis Agents

lABCRATORY

I PROFESSIONAL

\ PI:

AND

INSTI7UTE

PERSJNNEL

E~jGAGEO

R.H. Purce11 Y. Moritsugu V. McAuliffe Y. Shi::lizu G. Hess J. Slusarczyk

! \ I !

AFFiliATIONS, ON THE

AND

TITLES

PRINCIPAL

INV.ESTIGATORS

AND

ALL

OTHE~

PROJECT

LLD, .NIAID LID, NIAID LID ,NIAID LID, NIALD LLD, NIAID LID, NIAID LLD, .NIAID

Head, Hepatitis Viruses Section Visiting Scientist . Research Associate Visiting Fellow Guest Worker Visiting Fellow

1. MathieseCl Guest.Worker Other: P. Holland, H. Alter (CC, ~lood Bank, NIH) I K. Soi~e (Delta PrimateCenter) J.L. Gerin (~~N Laboratory) \ I W. London (NINCDS)

erne)

M::>V"'""I::""cJ

COOPERATING

(if

UNlis

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

any)

None.

us7 BRAlICH Laboratory of Infectious Diseases SECT I ON

Hepatitis Viruses Section INSTITUTE

·ANO

LOCATION

NIAID, NIH, Bethesda, Maryland rOTAL

MANYEARS:

PROFESSIONAL:

99/12 :HECK

] (a ]

APPROPRIATE

)~HUMAN

(a. 1 )M

.OTHER:

51/12 60X(ES)

SUB .;ECTS

I NORS

36/12

0(.12)

:;UMMARY OF WORK (2QO

(b)

HUMAN

TISSUES

(c)

NEITHER

1NTERV I E\JS

words

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 application of the most appropriate methods, including active and passive immunization, chemotherapy and interdiction of spread of the viruses. Progress: The biophysical and biochemical characterization of hepatitis A viral antigen has begun, and studies of the immunopathology of hepatitis type A in non-hu"JJ.an primates, using defined pools of virus, are in progress. An inactivated subunit vaccine for hepatitis type B has been developed and is undergoing extensive tests of safety and efficacy in chimpanzees and ~an. A third hepatitis B antigen, ~ antigen, is being characterized and its relationshi? to infectivity is being explored. Eviden~e tha~ populacions of 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. .,~'~l'" "'''e "'~"s .,"'eP1'fre~·cg"'~zo(, '~"""cal s,-...c!.rnme ~"ne "'on' ""o . .. "e .... 1· lJ..-~ ha leen further defined and attempts to identify an etiologic agent intensifie~ through transmission s~udies in chimpanzees. -..'-

••••.

.••. .:

..,

,;:=.,";

.••

..-

.•.•..•••

"' •..

•.••.•.

1...1..

....•••.••

..;....1..

.• 1" .•••.

)urce: USDHEW. Virology: Volume Viralln/ections. :8, National Institutes of Health (NIH)4-Controlo/ 79-1834, 1979, p. 20-65.

1.:,

"-Jt:".

" ..

-.:-\,

•....

L ••

~'"-'-

.••

\,.--

MAID Task Force Report. Bethesda, MD: Public Health Ser·

RDTE TYPE CONTRACTS

FORT DETRICK NUMBER CONTRACTOR

Systems,

Merck New

Co.,

York

Inc.

Universi~y

Research Fnc1.'"'l. of Sta~e Univ. or New York Sr.a:J.fordResearch University

University

Jun 1960 Nov1962 Mar 1964 Sep 1964 May 1965 May 1965 Jun 1965 Mar 1966 Apr 1966 Jun 1962 Aug 1966 Nov 1966 Mar 1967 Nov 1967

Inc.

Inst.

TER1'1INATION

DATE May 1967 Sep1968 Sep 1953 Aug 1951 Jul 1953 Aug 1952 Oct 195~ Oct 1955 Dec 1965 Dec 1963 Feb1965 May 1966 Nov 1967 Nov 1968' Mar 1957 Sep 1963 Feb 1953 Jun 1953 Dec 1953 Jul1954 Mar 1954 Dec 1956

P-.pr 196:; Aug Oct

1965 196~

Oc t 19 65 . Ju11966' SeD 1965 Feb 196<. Nov 1965 Jan1965 Oct 1965 Jan 1966 Sep 1965 Apr 1966 Jul 1966 Jun196t. Dec 1966 Jan 1968 Mar 1967 Nov 1967

May Apr

1955 1960

Dec Jun

1955 1961

Nov Jan

1951_ 1954

Nov Jun

1959 1956

Oct 1952 Jun 1963 Jun-1969

Mar Jun Jul

1965 1967 1959

Mar

Je.:1 1966

1 8

of Texas

1966 1967

Apr 1950 Sep 1950 Mar 1951 Aug 1951 .~ug 1952 Oct 1954 Jul 1962 Mar 1963 Mar 1964 Jun 1965 Jun 1966 Dec 1967 Jul 1955 May 1956 Oct 1950 Jun 1951 Dec 1951 Jun 1952 Jun 1952 Dec 1953 Apr 1960 Aug 1962 Oct1963 Nov 1964 Mar 1966

of Chicago

Litton

Mar Jun

of California

Univ.

C{<{'l..JCONTRJl.CT DATE

CONTRACTS

Bion~tics Research Laboratories Univ.

of Virginia

1964

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

Jun 1970'

Jun 1965 Me.y 1957

A:Jr 1967 Feb 1969"

Oct

1954,

Jul 1959 Jul

10-~ .•..... :>

.....

.~'..lg 1953 Feb 1953 _~ug 1950 Ocr.

10-::: J 0_

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 lia:IJIJ~I ':'r":i,...~j ~rv:-,h!· -. ~:1••.•;~~-. ::::: .--.;-"''''' .•../1\ .•.... vI vJ,:l .••..•.••..•. h~\I.j:; ,j,.~ v :I\ •.• III\. .•••.• 1.')<4 _! •••.. u. T~ fi'J 1_ I., ••••.•••• ".'~' ,11 __ 11 v •...••...•..•.... ~_ "Cv tne ;]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. Denotes contractunder which Robert Galla and his colleagues may Congo Sess. 95-1, pp_ 80-100. have worked. !""

.••.•••

:::'

•••..•

-::.

v...J!

::> ••.

路

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 .

'EmergiTlg Viruses: ,'U1JS aruf 'Efjow

'I11cSpecia[ 'v'ims CtlTlca '1'n~lltJ:11

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

~blecular

Studies

In recent r.1Ont.'lsra;:id U\a;or ad\;ar.ces ha"'e !::eC!1made in the field of IOOlecular ~iolcg:.·. These :indir.gs· ha\'e direct· application to t.he s~:: ef :.'e relaticns;:iJ: of vi ruses to tlIlOOrs. 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 has provided 1:..~ebasis fer 1:..'1e::e·;elq:ment'·o: :-:e·~·.extre.'nely sensi tive :ne6od.s for the cetect:'en of or.co~enic vir.JSes or their "fingerprints." I::eeed, k;;c-';;leGgeof the fi.mdamental IOOlecular events ·~hic.'1 occ.:r durir.g \-ir.JS infection and subsequent cell tr-..nsfoT:;13tien provides ::-.e first tr.uy rational approac.~ to theraJ::--.. E:I:YFoCacti ·.i ties analogous to those of R';A turcr virolSes ha,,-e recent:·, been fOlmd in cells of h= leu\;e::rics. ·TI-oisoffers s:':~~g suvoortive evidence that '\iruses are associated ·~it.1 car.ccrs· in man.

.~ :(:)=

Immunological Stud ies ImmwlOlogic research has provided extremely scnsiti\T tcdUliqucs for detection and characterization of tumor vinlse5, viral cUllirt'l1s. and dlanges in surface membranes of tumor cells. Indeed. sllch efforts have' contributed to an understanding of the role of immunological mechanisms in host-tlDnor and Ilost ·vims interact, .,,: which provide an approach to the prevention and treatment of cancer. a.

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

ftpplied

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 fy , characterize and determine the vinlses. viral antigens. and membrane antigens of tWT10rcells. TI,is includes developmenl and appl ication of improved techniques with the sensit i vi ty and sped fid ty required to detect ce llular al terations induced. by twnor vin15es alone o.r as the result of interact ir'n with 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 Innnan cancer. Research will be intensified and expanded: (1)

To study cellular 'and to determine host recognition ttDnor vi ruses.

(2)

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

studies

As knowledge of tl-.e f-:r.d.a;:-oentalmlec.uar e\"ents in virus-cell interacticns is dc".-elcped,. the Progr;im ,,'ill apply this infor.naticn to t1:e st","dy'of human cancer

as fullm •.s: (1)

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

(2)

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

(3)

To de\-elcp a raticnal !::asis for therapy or prevention by 2xploring nricus ap?rnac.'1es to blocking of vi ral replication and/or tumorigenesis at the cellular and subcellular leyels. !ne tl:erauv could be directed at any or all of the stages of cell transfomaticn c€gi:mbg '~ith cell infection by a ttDror dr.J.S.

and humoral immunemechanisms their' relative significance in of and response to tumor and/or to

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

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

(

416 II~

(

./ [';(

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

(1) To relate candidate humanviruses to knownoncogenic agents .. (2) To identify and characterize interspecies viral antigens which are present in knownmammaliantumors, and therefore, could provide the basis for a formidable probe to detect human tUITOrviruses or viral antigens. (3) To launch large-scale seroepidemiological .which will define high risk populations.

surveys

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

antigens

Clinical studies will be directed toward understanding arid manipulation of i1mm..memechanisms in human cancer as a basis for: (1)· Development of vaccines from identified characterized human tumor virus (es).

and fully-

(2) Detennination of the· role of host irrrrn.meresponses in tumor recognition and rejection. (3) Application of (1) and (2) in the prevention and control of humancancer. research progresses, as follows:

AS·

increased emphasis on application. will be

Inmunodiagnosis and seroepidemiology . (2) Clinical studies on the role of irrrnunemechanisms ill hurnancancer (3) Immunotherapy (~) Vaccines(conventional or other)

(1)

Ultimately, these studies \oJOuldbe organized to coordinate and integrate the application of appropriate biochemical, immunological, and genetic methods of detection, prevention, and control of various types of humancancer .. 4.

Test Systems In vitro and in vivo (animal) test systems will be carefully selected to evaluate the work outlined L~ the previous research areas; specifically: (a) to determine the oncogenic potential of candidate humanviruses; Cb) ·to develop bioassay systems .. for testing viral, and viral/ch€mical carcinogens; (c) to begin vaccine (conventional or other) testing and irram.m.izationprograms; (d) to begin therapy testing programs; and (e) to explore special animal·tumor systems with particular relevance to human cancer. 30 Source: 1'1CIstaff. The Special Virus Cancer Program: Progress Report #8. Office of 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

I~\ZELTO:I LABORATORIES, r:;c. Title:

Studies

on t~e

Contrac~or's ?:oiect Officers

Proiec:

(:;ii!-;'~-:,)7ai 0:

::rialog::

Dr.

)

C.;~..::e:-

~i;~ae:

Title:

Study

of .Cell

Surface'

Alterations

U1rector:

Or,

Ind'uced

by RNA and

1':::.

Viruses.

Ch!~~3:S

D~. R~~e~.:A. ~~a~~~e: Objecti1Jes: To de~e::::::".e ·..·r.e::-:er and ~ilethEr t~ere i~ a~~ ?css~~:e and hu~a~ tancE~5.

)

INSTITUTE OF TilE CITY OF NEW YORK'---!l'~; ...

(NCI-E-, .-2028)

)~. ~r:!~~ ~. ;e~se~

J!rec:~::

(SC!):

':u:::":--.e

,LTII R~SEARCII

PUBLIC

Contractot's Project

.:::.:-:ce~ is caused b:' 'Jir'Jse~' ~:~:::g~':a::2:a:~c~s~i? bet~~e~' cani~e

:::-:.:: ;a:-.:':-,c

Project Officers

(NC!):

Dr. Or.

Thomas

Benjamin

George To<l"ro Roy KinanJ

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 of polyoma virus.

~:~~~t~~~~~~~~u~~:~~~~~~:~~~.~:,~: ~~~~::~::,~~~;:~~~a~~~~r~~:~~~~: ~~~ ::=~S~:~~:~:::~ :: ~ other

CC~5.

sar~c=a:c~s

S~::E£~;~:

~ani~e

carc~nc:::.a 'Jas a:::iie-;e:c '::: :'r.cc.;:a::::: passage

?fCVes

=a==.ar::

:: ·:c:.=.~:'=s :':-.~, ;:,:nti:1ucus :~~ :~~~; ~:.:: ;::':~~2'a ':a:~a~:e57ste= ~0r

?cssi~:e,

Major Findings: Eight cell lines including 3T3, 3Tl2 and sar",'I::.1 virus transfor~ed lines, have been transferred from Dr. Todaro'~ laboratory succ~ssfully and are being checked forpassible·spl~· Lion of ·variants .. This contract is new and no other results have b""\I obtained,

:~~:~~~~~:~~~~~~:;c~:~~~~:~~~~~:~:~.~t~=or

~~~;!~~~;:t:::~~;;::~~;;:~<':~~~:~~ Atte.!:Jpt5

ar<2 !Jf.cer,:a::

d=:-=:-::::'~.:

·_-:-.':::~.e:"

::-.;'~

::=:ce

urc

act~.' .•ated

',:":'JS

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

~:::~~~:e~::~ca~~~=~~ :~: ~~~~~=~~~:~~=:;.:~~~~:~:~~. ~::~~~ot~;~::c:~;~;c' leuke~ia ~iruEEs,

~~~

ac:~~a:~~ ~~:~5 ==:~~c:~:~.

T~o.viruses

appear

be prcs2~t.

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. ".,'Lh controls. Ul t inia tely. an understanding of the mechanism of ItN'I' I :1:'tic transformation 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, ;\" . '

~ffect o~ dcg cel15 i~fe::E~ ~i:~ ~!:~~e :~~~e=ia ~~rus. Eve~ a :~X~C le~Els, the re?:c~~c:i~n =~ :~i ~~=~S ~a5 ~ct eli~inated. ecal areas

(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 Litis problem and will foster collaboration .wi th other NCl and SVCI' '.,'rke!'s

~orpholo~ica: c~~~ge ~er2 =~se~:i~ ~~ :~e :a~~~e streptcavci~.

Proposed

Studies

~ere i~i:i2tE~

:c E~a:~i:: :~~ €~f!::

:~ c==bi~ed

ch~~ctherap?

a~d

::::O:~:~~~i~~~~~2:~~~~;~~~~~:~~O~~~~~:~'~;:: :~'~~~:~~~: ~~s~~~~~~i~:~, drug of

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

cells

expose

the

Date

Institute:

cani~e ~e~p:~s~s ~cr ~~~~e~ca cf ';~ra: asscciations is i~portant in 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 be investiga[ed_ !:1 '2c:1!,:-as: ~:' ::-.e c=.: .::r.:: '::Ices-c', -;::uses are nc:t re~ularly shed 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 presence Study

Course:

Contract

.Continuation Initiated:

t'o achieve

December

1971

of covert

viral

'infectiens

'ccntri~ut:::~

:-:e:~:as:::'c transfor:I1ations.

Current

Contract

Level:

$36,800

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, such

viral

Proposed Course: Re~i~ect~cn considered to u~ilize t~e :ac: viruses,

carcinoma" naturally

Date

~cre ccncent~ated ~ :~::~ ~:'~3 anc e'la!\1at·icr. cf i=;:u:-",~::-.e:-2;;-=·J occ~r~ing ~e~?la5~.

Contract

Current

:~~ ~:::~:

Annui:

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

:e':~l:'

S:OO,CCQ

UJ 1; ~"

:.~ :~i~

::es ::~ =~ :

labcrator!

beir.g

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

centrel

32~

the

objectives

de~"ri!,,~d.

.-Q oq,

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

CALIFORNIA, Title:

Comparative

Contra6tor's Project

UNIVERSITY

Officer

(NCI):

Dr. Leo K. Bustad.

Dr. Robert J. Huebner '1

Objectives: To further study the two simian Type C viruses (woolly monkey sarcoma and gibbon lymphosarcoma) which were first isolated in this laboratory. Major Findings: (1) Woolly Monkey Fibrosarcoma (SSV): (a) SSV-infected bonnet monkey cells, cultivated in roller bottles, are yielding significant amounts of SSV virus. Several other cell lines of human, bovine, and simian origin also support SSV replication. (b) Bovine cells infected with woolly monkey. sarcoma virus were inoculated ihto the· autochthonous host at 10- to 14-day intervals as.viable and freeze-thawed disrupted cells. Serum samples taken prior to. inoculation and 6 weeks later were tested for antibody against the woolly monkey sarcoma virus by immunodiffusion. A positive precipitin band developed with a serum sample taken 6 weeks post-inoculation. (c) Radioimmune precipitation assays using SSV replicated in bovine thymus cultures were positive for bovine anti-SSV antisera but negative for bovine anti-FeSV antisera, indicating that SSV-infected cultures are free of FeSV antigens and that SSV and FeSV do not possess common envelope antigens. (d) Cellular and cell-free materials from tissue culture were inoculated subcutaneously into two newborn cotton-topped marmosets. Nodules (7 to 13 mm diameter) developed at the site of inoculation within 12 to 14 days. However, nodules regressed within 3 weeks. One nodule detected 28 days after inoculation reached 1 cm in diameter and has remained that size for 4 months. Blood samples from each animal h~ve been examined monthly and no significant abnormalities haVe been noted. All inoculated monkeys are being held for continued observation ..

and human cell lines support low levels of SLY ·replicat i.1 (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)f' culture cells had a transient enlargement of ·the regional lymph 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 has revealed no abnormalities. All monkeys remain under ob,servation. Three of eight inoculated pigs were sacrificed 4 months after injection and found to have slightly 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 under observation.

I I

Si niflcance to 'Biomedical Research ·and.the Pro ram of tll" Institute: T e f1n ing at th1S aboratory 0 two Type C viruses 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~ harborin0 oncornaviruses. Since monk~ys and man are closely relatc~ phylogenetically, the proposed studies, which are orientcJ toward characterization of the primate viruses and seekjnq possible relation with human tumors, are of direct rele'!u!';.7P in establishing the etiology of human cancer. proposed Course: (1) Characterize in great~r detail the molecular components of t.he woolly 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.,v andgI1)bon lymphosarcoma viruses . (:3) Initiate serolog it: studies for the detection of antigenic components in spontaneous tumors of simian and human origin that may 1;." common to know simian RNA Type-C viruses. (4) continue efforts to isoiate oncogenic ~gents from spontaneous tum0"S of primates and complete limited studies on canine systems. (5) Complete studies on humoral ~ntibody response in cals to the leukemia-sarcoma virus complex. Date Contract

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

257

''J~~nl1;1

and Sarcoma Viral Studies

~r6ject Director:

Special 'VinLS Ca/w'

OF (NIIf-NCI-E-70-2048)

Leukemia

'If1£.

)

Current

Initiated:

Contract

Level:

November

16, 1969

$550,000

258

I'~

. _1,

436

,J:) ~ ~

)

SOUTHWEST Title: Antisera

FOUNDATION The

FOR

RESEARCH

production

projec~

Director:

Contracto~'s

AND EDUCA~

Simian

Viruses

Dr.

} (NIlI 69-9)

and

Homologous

Ka 1 t e r

S e y mo u r S.

MASSACHUSETTS

Project

Offi

cer

Dr.

(NCI ~

Ja~es

Title: Ob;ectives: To deter~i~e reagents (seed material another contractor. In diagnostic that may

laboratory emerge from

the quality and antisera) addition, the

in .a limited studies done

of simian packaged laboratory

capacity by other

virus reference ·for NCI by serves as a

for SVCp·

viral isolates contractors.

Ha;or Findings: The si~ian foamyvirus (FV) reagents tensively tested ~nd an atte~pt ~as made to determine a relationship exists bet~een the Mason-Pfizer monkey the foamyviruses. Assistance was given NC! personnel identification of HerDe9Vir~s saimiri, a WOOlly and in the study of other viruses isolated from plastic tissues. A~l seven fV types grew at lines indicating viability rabbit kidney cell cultures

were exwhether virus and in the

monkey primate

least on one of a variety of.theampouled stoc~s. supported the growth of

virus neo-

of cell Secondary all seven

types and wor~ing pools are in preparation on these cells. The Baboon Sub ••axillary Ly"';,h ~Iode cell (SMLN) culture has ~ost useful in vorking wit~ all the types except 5. proven This is a diploid cultUre now i~ its 10th subpassage. Cytopathology on these cells is rapid (6-8 days), reaching a maximum

two

~eeks

and

easy

read

beca~se

6 and

the

Significance Institute: characterizing (natural primate

Proposed and

serve

to SilFRE Date

Course: as

Contract

relationship

bet~een

M-PHV

to Bio~edical Research and the Program of the These reagents will be useful to investigators viruses isolated from neoplastic diseases

or induced] colonies.

that

Certify

diagnostic

occur

priMates,

t...'1e packaged laboratory

simian for

viral

and

for

monitoring

vir'us

reagents isolates referred

NCI. Initiatec:

June

15,

(NCI-E-71-21/.9)

Contractor's Project

of Leukeoda

Project

Officers

Director:

(NCI):

DNA Polymerase.

Dr. David B:J1t1more

Dr. George ToJaro Dr. Roy Kinard

Obiectives:

To characterize

and

reaction,

Virus

forwation

the enzyme. of

viral

RNA

The endogenous

reaction

i",101ves the copying

The initial

ffil..'chani·"

reaction

product

of the 60S-70S

RNA'

formed when the viri

",. 11\.

not

complementary

to other

RNAI S found in ret iculocytes

and

elsewiH'1

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 ~ us genetic information in human turnors.

1966

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

'.'.

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.

Course:

Continuation

D,.te Con,,-r~ct Initiated:

,;i

its

infection,

Proposed

product,

Ma or· Findings: Using polyr ibionuc leot ides as temp la tes, C,)"'p 1<','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.

with

slight

214

its during

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

to be no serologic ), 4, 6, 7.

OF TECHNOLOGY

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.

neu~ralization tes~ing indicated an ~nanticipat~d FV Cross 2-7 cross reaction and FV 6 and' 7 appear to be "aislabelled." There appears and FV 1, 2,

Studies

in the virion.

uniformity in appearance of the cell sheet. Working pools of 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 infection, producing CPE with roost susceptible to !oa~y~irus

FV. 1,

INSTITUTE

Cuff

~rent

C"Dtract

L,,",~:

May

I, 1971

$75,000 322

decrease

in budget.

A dl ~

fÂŁme.rging Viruses: xP1JS ami EEoUz .

Title:

Studies

Contractor's Project

on RNA-Dependent

Project

Officer

Director:

(NCI):

Dr.

DNA Dr.

George

Polymerase David

Baltimore

Todaro

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

Findings:

None

reported

yet,

this

is anew

contract.

Significance to Biomedical Research ind its Program of the Institute: The objectives above have highest prlority in the SVCP. The results may provide very sensitive techniques for finding cancer virus genetic information in human tumors. Proposed Date

440

Course:

Contract

Continuation

Initiated:

May

with

addition

1, 1971

of EM capability. 189

~Z".

'Fig. 23.5. Summary Report of Monkey Inoculation Studies •·Conducted by litton No~hwestUganda. FORMAT OF THE

REPORT

This review The studies are: A. B. C. D. E.

Bionetics and,' NCI Researchers· in

is divided

into

five .

types

of studies

plus

an Addendum.

MajorStudies Special Studies Other Active Studies Long-term Holding Studies Terminated Studies

A major study is the product of an ad hoc committee fonned within the Special Virus leukemia Program to investigate areas of significance. These are major group or collaborative efforts with emphasis on inoculation of human 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 of program was developed. The objectives were to provide for experimental manipulation, close observation and monitoring of a limited number of selected animals. These studies proceed according to more formal protocols which involve greater varieties of inoculation procedures, possible animal p,-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 and subsequent implementing of decisions .. Many of these may be considered preliminary 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 leukemic or tumor materials inoculated between 1962 and 1965. Section

E lists

all

The Addendum contains 1. 2.

completed reports

Spontaneous neoplasia Incidence of neoplasia manipulated elsewhere

studies. on two uninoculated

groups:

in the primate breeding colony; in animals experimentally and held at Bionetics.

Under Sections A through E,the studies are arranged alphabetically by in~estigator. Various codes are used to make the tables containing the information 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--is coded

by nurr.e'ral

(key

l.c).

The number 278

inoc~lated

and

the

numter

deaj

i'i 1:1

'!fie

Man-Made Ongill of

Ml1r6/l~111T1'/

'L!'I'!;,

'Ent£rging 'Viruses: ,'UtJJS and 'E/;ofa

ii :,

~: transferred

are

real

the

animals

the,til1'E

I~aterial

nurrtJers.

The

were

placed

dates on

present

the

tabulations

refer

study.

inoculated

a. 9i n Diasnosis ~ . Ori C :;' !~ D'L D 0,,In '!2S~O ;'L -CF ~ CA DC CSCL Enc CLL Chondr C-H Echo AlL AM ,Ill EL BL PI AI"OL BOl AT Bl S ;,d aw 7I'tYI ALL IAgt .o\rtxJ !'O l9 CC:-!j ,1,c2p Bac Au fIg Mo\

;. ,\125.10

Lymph , Mamm T Mening MH

Misc Misc ML

., ,Adenovirus Acenovirus

12 + S1;40 2 + SV-40

Acenovirus 2 + parainfluenza Adenoyi rus 7 AC:Jte leukemia Acute lymphocytic Acute lymphocytic Acute lymphocytic American Burkitt's Acute myelogenous

leukemia leukemia leukemia lymphoma leukemia

Acute myelogenous leukemia Acute rronocyti c 1 eukemi a Arthropod-borne vi rus Atypi ca I rronocy tos s

MSV MSV AV MSV L MSV MT Osteo S

+ influenza + parainfluenza

PI PIA

+ monocytic

Australia antigen Bacteri al agent Burkitt's lymphoma Bovine leukemia ' Condyloma acuminatum Con£enital cerebral Con tro 1 fami! i a 1 Chedi ak-Hi gas hi Olondrosarcoma

leukemia

Chronic lymphocytic l·eukemia 1 eukemi a Ol ron c myelogenous Cytomegalovi rus Concen ita 1 stem ce 11 1eukemi a Disease control Dawson's encephalitis Echovi rus 9

,Ii

I I

Erythroid

279,

Rau Vi RCS Reo', I Reo 3 Rhabd L RlJabdo RTC ,'S 520S40 SA 7 SCL

Sq S

(

the

liver

Lymphos a rcoma Lymphoma Marnna ry tumor Meningi t is Malignant'histiocytosis Miscellaneous leukemia Miscellaneous virus

Ma 1 gnan t lymphoma Multiple myeloma Moloney sarcoma virus Moloney sarcoma virus Moloney sarcoma vi rus Moloney sarcoma vi rus Osteosarcoma ' Papilloma Parai n fl uenza Pia mater control

+ arbovir'us + leukemia + monkey tumor

cell

Polycythemia Mycop 1 asma Rubella Rauscher vi rus Reticulum cell Reovi rus I ReOvi rus 3

(ulture

sarcoma

Rhabdomyosarcoma Rhabdomyosarcoma Rous transformed Sarcoma SV-20 + SV-40

leukemia

cells

Simian agent 7 Stem cell leukemia Squamous cell Simian virus Simian virus Simian virus

Th rombocy

sarcoma 5 20 40

topen

280

• = Possible Marburg predecessor

\ 45L.

L i posa rcoma Lympliocyti c I eukemi a Leukemoid reaction of

SV-S SV-20 5V-40

I!-

ii,I

le:Jkemia

Plyctm PPLO

• hyperplasia

L V

H. i;jenitalis H. simplex Hodgkfn's disease Herpes vi rus In fl uenza Infectious mononucleosis Kuru Leukemia

liposar L lymph lRL LS

pig

~ ~

Herp/G Herp/S HO

i I,

Glioblastoma H-l virus

Kuru L

ra b bit sinian

GB H-l

ovine

Eosinophilia Fib rosarcoma

Hian bo v ne (he!!1i ca 1 ecuine fel ine guir.ea human muri ne

Eosinp Fibro

./( ;

'Emergi1lfJ 'VinJ.$es:

,'uvs ami

'Ef;ow

Fink-Malmgren-Rauscher.

8/64.

- 9/65

! ,

Undiag

T~'Ii1r

'(eba

Thi.s human. leukemic

Trans fonned ce 115 Undi agnos ed Wilm's tUloor '(abavirus

products,

Source--coded.as

tissue culture b1cod plasma/serum tissue mince buffy coat chemical .asci tes

neoplasia

the

the abi 1 i ty manipulated

newborn

of fl"f~.h c~l I

monkey.

H AML

The major emphasis of this study was to detennine the SlJl'" pressive effects' of radiation upon primates and the subsequent enh,w':elllent or creation of a more favorable environment for neoplastic alter~l it'll,

spinal fluid bone m.arrow cu1 ture

'Iurreer of animals ~Iurrber of anirr.als

similar

to investigate as cultured and

EL H CHL HALL

follows. 3.

1 2 3 4 5 6 7 S:milk g 10 11

induce

desiqned well

9or2/67transfe~red 5a1 ted '11 2 i 625nocul Sou'rce Dead Irradiation Study, - 5/67 1nOClnNo. um

program was materials,as

The progra~ was under Ors. Rauscher, Landon.

inoculated. dead or transferred.

Inoculum

the direction of Drs: Reisinger and 80wser. with Stewart, 11010ney, Perry and Hart. collaborJt.il"j.

Source

No,

inoculated

Dead

transferred

, I,

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

cr-

BSA

Fig. 23.6. Bionetics Summary Report of Studies Code Named According to Researchers' Last Names Including MK-SVLP (ManakerlKotin-Special Virus Leukemia Program)

~or

*1 rradi

This study was established under the Special Virus Leukemia Program of the ~ICI to investigate human leukemic materials. human papilloma and infectious ~ncnucleosis in conjunction with the co-carcinogens benzo[a]pyrene and benzenthracene. The program was a product of the study group that included Dr.;. BrJan. FaH, Kotin, Manaker, Rauscher and Stevehson. This study has recently been terminated and the remaining animals are in the process of being transferred. 2 63 or L PI,.. 1I/o. 1 ~ource 11 11 Dead IS InocullZTl inoculated

9 trans ferred

H S+ I

rr .

rr.

MK-SVLP, 2/66

lymphoma ma teri a 1 in and benzo[a]pyrene ..

(

5 35 17

conjuncti

Control

on wi th

No.

the

co-ca re inogens

i nccul a ted

Dead or

ben zan th I"a 路:cne

trans

105 33

13 6

282

454

- 3/67

Source

. H Sq S

and this times in

This study was initiated by Drs. Manaker and Kotin in col1 aboration with an ad hoc corrrnittee of the SVlP. 'The prime objecti was the induction of neoplasia in primates using Burkitt and othcl:

1nocu 1 urn

of being terminated This is due to lag ..

8 8

ati on

H Bl H lymph H l 路SOIre studies strrnarized are in the process may not be r~flected in the total nurrbers. finalization of re~orts on selected studies

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

Studies

SF:oIRS. 10/65-3/66

M S+ I

SUMMARY OF STUDIES路 A.

H L+Irr.

fe r re~~

5 o

. I

._--\

I Perrj-P.2uscher, 7/66-10/68 4. 2. 3. 4.3. 3. O&S; H; S BL V 2. 7. disease S&H; l A; Marek's 8. 6. 3. 2. H; C; Benzo[a]pyrene Rau ViInoculum 4. 5. 8. 11; l Mise 6. 7. 1. 2. f 1.1.(terminated) This pragrar.t'dcs initiated by Dr. in collaboration with 1. O. C. Rauscher Special Studies Dr. Perry of aCI and Dr. Landon of Bionetics. Fresh whole blood from leukemic patients was inoculated directly intJ ~onkeys using multiple sites and voiur.€s as lar;e as Jossible.

" Z2

--1-

(', (' I) -Oe.,·1 .... ') j')'---'.--O· 1](, ,) Tr,lI~, 013 •.• 11"6/67-4/68 Z 177 I6/69 ('(' !~~tT(~d 64218373,5 ·8 37 26 landon-Rauscher-· Manaker-landon17 .) 20 38 862839513en, B. 12 11 10 16 Other !noc. Active Source Studies Manaker-Landon, 5/67 13 F. Fibro 12,F Lymph landon-O'Gara, S&M; S; Mise Rhab l H. Au Ag Feller, 7/66-11/66 Manm Gerber, 4/64 Ounke 1, 7170 S&H; Mise V levine. H; Bl S Witter, A; HV of TlTturkeys Melendez, 3/70 Adamson, 5/68 chelate Ri cka rd, 6/69 Kelly, C; MCA !3l Dilantin Spedi!LStudies (acti vc) landon, Fischinger-O'Connor, 7/70 ,Bryan-Jensen. Theil Pearson, 3171 1/69 S;; :MCA-Cu ~lamm Ablashi. 10/70· H. saimiri F; lymph Bl landon-laFontaine, Long-term Holding Studies Blumberg-london, Manaker, 8/64-10/69 H; ALL Sibinovic-Ulland, No. 8/69 BRAF, 6/70-7/70 Rauscher, 12/67 2/67 3/68 8/70 7/70

42 2Z 26 13 noD :10. 1 C:r.1 Scurce 12 incculated 6413 Cead G 012106 or transferred ?SG-~"e:nick, :;.:::::-,/50

"j;; i, 2'

, _,- C"\. - \

,:ii~' '~I !

~ "->

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

inccJlus

Source

1511 12 12 H 12 Reo

H Reo

:10.

ineC'Jlated

612157 or 015 Dead

trans

ferred

+ al H

.C~'1

H P H Her.J/S H Ad2P

H&5 AlS40 H R H Echo 9 C

,/,

11'

283 284

I I

(

• 'G--il'-1 --1-i----r-

-., .,"~ ! , 0SV-S ;;; L, :..:;E.:1er:J/S ClL. I 1noeul um 41 lS 1·1 11',11: l~ 1 1!! f,' I'n~d 13 3M; 18. ' ;.:; ;;; 0 ft:"L CSCL 09n 19 .Rhabdo [noc. Source 11 314Z'I~J Rhabdo 51 32 D,. 1 5 312 HI I: 1 1'1' 12. 421. ':!.S; :-:; SeL ;'.deno+S·I-~O S; 21 MSV J06G:3,"1 .:_ 11;MSV GB 241.\67J3 23 27438 .10. 56 '2 12 13 10 69153 761. S 25:; Contra ~ 5;Ma~aker-~auscher, 21 44 la De :20. D 0enoc. 15 8 72 01; 9/64 r 5/66211rIrradiation RCS Bowser, 8/65-11/66 . 4/67-5/67 'i; 14 19 5t-Mo 13 13SG')9/57-12/E9 lHO i Ene posarAV 23 .21 CML 20 16 H; BL ~S; ::l F; Fibro AML H; Undiag ALL 21. Rhabdo .A.LL R; ALS 14 11; ALL Graee-Horoscewiez, 'i; 5. .~.l M~L Terminated Trans ferrcd Studies 5L 6. M&S; ;;.Ml ~L 3. M; I24ado M; MSV 7. Sarma-Huebner, 9/69 Blumberg-Mo10ney, Hb.:i; ALL . •":J .1 ,2 Grace, "'e:r.~,:::, ~anaker-Stevens, 2/64-8/64 ~~/6~:-i; ~; :~; H; 9. ·~'i ~,1L BL [:'~ Gajdusek, Gross, 5/62-4/63 1/67 0HO Ene Shaeha 1oney, 8~ MSV 5/64-6/64 L-+MT Arbo Cohen, 3/68-1/69 4. AL CLL Bl AML Kuru F; ~ocre, MyL P,cuscher-L,:nccn, 9/5~ ~'; f;&H; n; 1l. BL L Osteo L1yr..ph lymph ALl?1 7/69-8/69 S[~'~alaria Rauscher-Reisinger6/66-10/66 3/69 Dreyer, H; 5/67 C; pI:C Gajdusek-Gibbs; 4/66-5/66 Gazdar-'Mo1 :,rc~:neJ, 1i1-oney, :'J';2J,/S:01e, Stewart, 4/62Aisenberg-Zameenik, Chirigos, O'Connor, one1'i2s ~rose Ccn trD H; 1H; ~~o 6/68 A; H; S Bl :-:; ~er;J/S Ir.2 '; ;'LL 2E5 c. :J t.. ,. L

rlo.

No.

286

H; EL

--'-,

Ib4

, 18/67 '.,2 436oney-He 32 31322. 916 322Raus . 9/65-5/66 Inoc. 271873 14 2rd'2 Deado rSource 77 18 10 ~03410 618 14 4A; 16 15 12 6 CF 268Skin Trans ferred Landan-Da rrowManaker-LandonH; Osteo 5 Nade 1che 3294531 S; SA CA Landon-Raus cher, M;BL L 5; LRL G; 5Control CL177'Z graft B; Non-inf Marton, 6/68S Jahnsan-Hul1 , r, SV-20 Huebner-Caates, Morris, CCHy ALL H; Howa rd-Notk ins, Landon-Valerio, Landon, 7/65Manaker-O'Connor, Morgan, 3/65 Ad Ki na che Liposar Molaney-Manaker, ~\a1 aney-Stewart, Mol rbe rt,r,. 1 Plyctm 99Raus M; L 1ymph DC Gawma globulin Rhabda M; S 5; Koprowski-Jensen, 13. 2/68-7/68 1/65-2/65 4/66-6/66 3/67-9/67 Darrow, 6/68-7/68 3/66 Stewart, 1/68

4C(~

No.

* = Nine monkeys ~-\

inoculated with Marburg-like viruses survived and apparently remained in the holdingfaciiities 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 20th and August 10th, 1967. John Landon, cited above, was Bionetics' Senior Project Directoraiong with Rabert Ting.

1Jr. ie1Jnan{

!. j

g. :Horowitz

I !

i !

Octolxr 28. 1996

I Dr. Robert C. Gallo Director. Institute for Human Virology 725 West Lombard Street Baltimore. MD 21201

I i

I I

Dear Bob:

Thank you very much for the interview you gave me on July 30. 1996. I found the very interesting, and am responding herein. First, I greatly appreciate your offer to help in determining the origin of human immunodeficiency viruses (HIVs). I understand that you must. however, limit your views partly for 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 routinely studied and recombined during the "Special Virus Cancer Program"-are as follows:

discussion

i I

! L

I I I II I I

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 the more homology the more recombination. However, neither the whole genome needs to be homologous noris there a requirement that the homologous regions be contiguous. Small stretches of even a few base pairs are all that is needed for recombination of type-C cancer viruses-the focus of substantial "Special Virus Cancer Program" research. HIV has been shown to evolve through 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 their labs. 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 me point out that the world of virology has known the lentiviruses for a long time. What about the bovine immunodeficiency virus? I do not need to tell you that there are a lot of organizational similarities between HIV and B IV. You mentioned Ray Gilden during our interview. I am currently preparing a paper that 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, perhaps by 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 acquired oncogenic potential." Gilden's warning obviously foreshadowed the AIDS pandemic. (See: Vi-

I I

. ruses, Evolution. and Cancer: Basic Considerations-International

I i

I i !

i i i i ! i I I

i II i

Conference of Compara-

tive 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 Litton Bionetics's labs. and HIV-l, this does not negate the probability that the SIVs and HIVs evolved from recombinant viral research. Having studied S V 40, you may recall how this and another very dissimilar virus-the human adenovirus-were found to combine. creating a potentially cc: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 <.:mcfseJ that contained as little as 6% of the original SV 40 genome.

p.a. Box402.. Rockport, MA 01966Âˇ Tele: ~546-6586

â&#x20AC;˘ Fax: ~-546-9226 â&#x20AC;˘ E-mail: tetra@tetrahedrolLOrg

.·-----------------1

r ·i

CJ t)

I tl

'f I,!

,. 1 ~

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, ,1 101 more 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 Ihen and time con$uming process, docu· testing the qabllity md function of new conllructl 11 a ,ainltabng menlecl e'.lde~,e ;ho\\ s ,his i; precisely" h~t '.\as done during the 19(Jr)s;rnd early 1970s by hinlogical weJpons' ,>:'nlr:lClOrs ';ee: Geissler E. B'"",!!i •."I.;,,d .J,'TlII \\ea"ollJ Tr,t/al·. London: Oxford Unil'C('lit,· Press. 1<;-~6 ',I IIh contnbutions QV Da\'id Baitinwre and Ra\ml'nd Zililllbs): . ·.-\Jdi!iQnail~· ;igmf"ant :.od 5uspic:oU5 IS Ihat Hli; doel nat lit Ihe I11Qld for nalurally ~';o"ed ';iruse\. Th~r~ :;' J !cne-.1f) pe,cent hcomolofous ·;irus-HIY·2-llhich mayor may nol halc r.:ea J ,rogeaimr of HI\'-!. Jnd il rm~· n'I'1 ha',e ·JriglOaled in monk~~s. HIV-2 is definilely nQt ell dogenOU$ to J.n~ !)f the ~~:,:e~ frr.'m '.\ hJt:h it hJ.5 ~en isnbred. Th~ '.\ord "endogenous" is meant here in Ihe classic.J1 ;ease. \\'h,,~ ~J= fir;r.' The fJct .hat ',>,eaow lind them in se\·cral monkeys and a group 01 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 suspecled hepl3.!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 not r.: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 that ans"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 the circumstantial ""d s.::e~uri: e', idence al hand. Do you hale any beneI' explanations'? You indicaled Ihal you ',\ere :wie IQ proqde a mQre "p/aulirle" iatrogenic theer; on Ihe origin of AIDS hut time did nOI rennil 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 cone oithern hale an', homrlo~.'·lo what is HIV, Therefore. none of Ihem 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 tQ HTIS-I and HTL\'-II, He~ce!.he name HTL\'-IIL As a malter of iactlhere was a publicalion in Scien •.e I see: Hcomcolcg: cof.-\IDS·JSsodated\·irus with genomes of human T-cellleukemia viruses. Arya SK, et al. 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 \'cry similar tQ HI\'s. HI\' ml1st b-e cconsidered unique l1y design. However, you know Ihal HIV is nOllotally unique. In \..,~. genera! lerms. HI\' is similar to Mth I~re C ""d t~pe 0 \'iruscs along with Ihe inclu~ion of regulatco<:' genes tYl'ic:1l of lenti\;",."es. Again. ~·Oll l11.1y·recall Ray Gilden's inslruction Qn this subject in Ihe "Comparison and Evolution 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.':

r J f

!t. I

mans and darify Ihe relalionShip belween SV40 and SV ~O-rclaled agents 10 chlonic dc~cnl'l'''':'''' ,','11 Iral nervous system disease in hI/mans, il appears 10 Ihis re\'icwer Ihal the lahoralnr)' malil,"I.:1I '11,'I SV40 involves same risks." Likewise, rcnecting on your work wilh human while hlond cells and typc·(' c:nhTI ',11'1'.,"

George Todaro (and Gallu), condudcd:

as pOlenlially

Bioha:",ris in Bit;;oercai Rem" •.;" Cold 'Spring HarNr LJMr:lIN).

--\

h:trids.

"L·r.tll s.omfa.:tcr;

studie;

e',Jlua"

the kng·tenn

(

agents."

wQrk "Endogenous type-C viruses in cell cultures. In: B;/lIr"wnIJ 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"I examples of cross species laborato·ry transfers, noted that since Ihese viruses grow so rcadil~ in cat cells, 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 ,,:rald Myers at Los Alamos reeenlly shared with my colleague, author Ed Haslam, Ihal mV mut:lIes r:1.,t,·r than anything he haS ever stl/died. In Ihis manner. HIV strelches Ihe bounds Qfnature. Thi<, ,:!'''plcd with 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'·. al1d like 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 !,,,",:I propertieslconsequences post infection in their present hosls. Objeeiion #3-"Obviously, you didn'! it was impossible la do intentionally, 1960s; and molecular techniques for unlil the late '70s and early 1980s. So The earliesl

cQntinned

say it was dQne intentionally, butjusl in c,\Se allyhl1d.' CH" ,aid. because the viruses exislcd in human heings at lea:.1 ,i,",' 11", gene cloning, doing the~e things in a laboralol)', did"'1 "'"" •. it's off by almo~t Iwenly years:'

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"'" when members of the National Ac:rdemy of Sciences-Nalional Research Council (NAS ..NRC) '"I",,",'d

197J, pp. %-11 J.) Regarding the dfects Qf SV~f) infection in hu-

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hazJrdous

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" •.• "

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Thcugh Gilden's .:onelusions '.'ere J",\>on long before the arri,·al of SOPhisticaled DNA sequencing techniqlJe$_ his p<'int is still "alid :!lid p3.f1icuIarly ai'rlicable 10 the queSlion here: Did IIIV e,·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: ad-S\'.1('

. "Because viruses can aller their hOlt ·range eilher hy 'adal'Ialion nr se!cctinn. II,,'se human hybrid cells wOllld appear to conslitute a potential biohalanl since. in Ihis silualion, 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~ 01 polentially ancogenic [cancer causing 1 viruses ... ,What is not clear is Ihe nalore "I Ihe 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 nncogenic potential and can produce tu mol's in a varicly of species is firmly eSlahlished It follows, then. that these viruses and the cells Ihat produce thcm rnu.51be trealed

"The relationship of liruSC's ;uch l.S "isna_ \f:L<en-Phizer. and mQuse MTV tl11.1mm.'1f)· I11mor virus) 10 IYpe C panicles C,,"nOI "" :L<sessed in qu""tilative terms. )·et t~ pre;ence of rc\er.e Ir.lJ1Script:l.\e md approximale morphQlogic similarity 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/lIde IIb.ll"' •.;i''''J. JJ1d aITuments of JitTerences are onl\· indicaters ofl'ariabilitv that arc difficult 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 stated this is. 11(1\\" do ;\t. Uto"o char lht ~ir:ljfJ (h0501 fur t11!rliys;J lire rerreStIl111ti\'e of Jdded] !h( spllitJ :rnm .\ 1,hh rhey· ',,'lrt iJt'hltt'd.7"·l~mphasis

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V.S. Department of Odense ofticials of their ability roproduce. through genetic engineering. a "new infective microorganism" that may ravage the human immune system. and leave people susceptible to infectious diseases and cancers. Obviously then. by 1968. shonly after you began work at the NC!. the NAS-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)

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I Objection #4-"rvlonkeys are infected with viruses rational informed person could argue othervvise."

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. : . We know [HIV] came from monkeys. ..

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:. The RelrtJviridae. op cit.)" were unconvinced HIV evolved from either monkeys left alone in the wild or from monkeys at all! This was made clear when the authors discussed only the "possible simian origin of HIY." And though evidence. they said, was mounting HlV evolved from monkey virus relatives. they entenained the possibility ancestral viruses may have fanned during the 1950s "as part of malaria experiments." (See page 59.) .. I agree that HlV appears to have evolved substantially from monkeys and/or monkey virus parts. But as these scientists. as well as Ray Gilden (see Gilden. op cit.) indicated. we can't ~ sure. My investigation confirms that much was done to monkeys and monkey viruses that might have contributed to HIV's development. ... Whereas I accept that S IV from the chimpanzee is the closest relative to HIV-I. and that HIV-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. or perhaps early' 1970s when iinmunedeficiency studies in New York City and Central Africa were in vo!!ue. - . Additional support for this iatrogenic theory comes from a series of letters/articles in the February 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. concluded S IV mac. the laboratory contaminant .identical to HIV-2. did not likely evolve from S IVagm or SlVmangabey. 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 John Martin reminded us in the foreword to Emerging Viruses: AIDS & Eboll.l. it was not uncommon to have experimental 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, and humans. Serum for the vaccine lots, containing 200.000 human doses. was obtained from the humans who received these viruses and. most assuredly. simian virus recombinants as well. By the way, these humans 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, greatly appreciate this dialogue with you on a subject that has been kept in the closet for a variety of understandable rea5ons. Since 1have your permission. I will incorporate your response in future work. and look forward to expanding common ground and reaching a scientific consensus regarding the origin of AIDS ..

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Yours in the Spirit of heals~,

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~ ...j 1.••I ~ r (,,/' ,1/(11 ";":...'..(). . .••... ~,: 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. Director Centers for Disease Control and Prevention Atlanta, GA30333

(CDC)

Dear Dr. S:J.tcher: Thank you for y·our invitation of Feb. 21, 1997 (that came by way of Minister of Health for 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 public n.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 my investigation 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 likewise invited me to visit the CDC for this purpose. We have yet to set a date for this meetin ...g . \-.

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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 misconception." 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 of animal viruses to humans. A growing body of scientific evidence indicates vaccine contaminants are most plausibly related to certain types of cancers, and contemporary epidemics 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, as opposed to politically correct pseudo-scientific speculations. is the theory that 1 have advanced 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-including those 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 contracts including, but not limited to NTH 69-2160)-to ;'pool" hepatitis B viruses that were used to develop a reponed 200,000 human doses of vaccine. Four subtypes of this