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IIrc Lt,l, t, Itt Irntl entl I,rcii hyr111, 1 tht• nunrrtnn, cl:ntt•nl, rn.r6 cr1 in I+rr~Jut ntg Iung t•rrt.cr rnJ It+ 1rn •rlc tShc lrnl r+r Irn1, +m„t vtrlni 1.rIJ1 trr rntctrul,lr..It In Ilu, I.t,1, 11+r rnlcrc,t, t,l 1he Inil,lrt, Ihi mctltt•rI IIr. 'tr„urrt, Ihc vt+lttntary ht••Illlr af•,rn.tt'+, Ihi luviturnt•nt Jrlr.nllninl, :rn,111ri Ir,l+.rttt, imluttry. .r. will rt rrlhcr 110100 Urcv tlrat ntjy f+r tt,ntctncJ, ati c„cnlr.rlly irlcnttc:rl In tlcvtIr•I,rnl, •r ri,carch I+rlrKrrm un Ihi, teutm.J Iuunrl.rtt„tt. tt 1te, I+ct•n rrt nl•ruii J. ul trmr.c. Ih:tt thcrc is a vrxilirmn, uuuunly tlial •rJtrK.ltr. 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I.r rn..u y I'rogress iit Rescarcfi '1his sciuun is dcvrtuJ lu a Jiscussitm nf thc majra lines of rescarth cfftttt hcinK sul+pr+ttcJ by the T I R C. •Ilre rcxarch prugram has a Iwo fnlJ purlwrsc Onc is the aJvanccntcnt u( ntcdicel and scicnttfic undc[sland ing tt( cancer anJ hcarl Jiscase, particularly. The nther is nrlentetl to yucstit,ns t1cN hrvc lxcn raiseJ Cunccrning thc pos.ible title of trrhaiit) in thcse unJ Itthcr htnnan ailmcnts. l. Itl11fC F,xperimentut Keyeurch •lite SucntOii /1Jvisttry Huar1l has cunlinucJ ilc atlivc wtcrca in thtcc Fhrt+•rJ Itni. u,( tcscatch that nr.d Jevclt+ptncnl anJ catcmtnn It r. hnlK•J th.tt .uch (atbecdurc wdl Cunltdrulc stcatlhly aurl ctrrt,lnri lively It+w•ntls Ittc c.t•IhlLslrutent ttl a snunP ubundatittn u/ c, Itcnmcnl:J resccuih un llti ctinlttgy uf cttmtilutian:tl Jiscascs Such a hwnJ•tut+n is an csscnU:tl clentcnt in tltc lin:tl st+Iulttm t+f Ihr prnhlcm. t+( rantrul nr causalinn tt( such Jiscascs IY+ JiviLrlaucut nrust ptcicJc anJ will Vt•ncr•ttc lhe tyl,e u( yuanUlattvc stuJics wl+itlt atc an a),.ulutc I)rcrctluivitc ttn e.acl 1nt+wtcJge. 'thc thrcr {rncs t,( rescatt:h tucntit+ttcd ate ( I ) (•.utinnl•rn+itty ,nd ICtu,tss:ty, 12 ) I ts.uc ('ullure; ( J/ 1'sychu physiult)gical fak arn llrc+c will hc hticily dt.iu+u•J in urdcr. 1• 1 A111'IN(N:F:NI(:1•1'Y ANt/ I{1/1AtiSAY ti•ftll/lla When thc .t•+Uttiial rsstx'rtlir+n stuJies t+n lunl; c:+nicr iniidin.c anJ cig.trctlc snurArnl; wctc lit.t puhlt,hcJ, thc siulplc+l anJ ntn,t t+hvittu. Ihcuty pur.ucJ w.t% that Inlh:tccu snutkc nul;hl cttntain ttnc ttr nu+re suh.tencis lnuwn tt+ tictcn.c tt+ be,iatiint,tcnit It+ anitn:tls Arn+„nh sr+.h su1„1•+nct•s wcre xt+tne lurlynuilrar hyJrrxathuns lhat laeviuu,ly Irrtl Ivcn sclrer.tlcJ Itt+nt ct+:t1 t•rr end t4rntllicA by elhcuti.ls. It was lul•iial. Ihcrcftttc, (trr invc,u};atars Itt tntJrtl•,Lc t Itcuucal :+nal ysicut Itrh,icu,tur,lc wrlh thc viry scnvttivc nrntlcrn tcchnirfucv nf t'lurtrn•r trrly:y+aic .rlt,rr•runn anJ sl+ct•trr+mrttic mclhnJs tt( ic)rnltlia•tnnn Suth imc.ul•elinrt. h•IVC hccn ttndcr way in .cvcr;tl Lthnr.tttrtict (ru a mrntl-ct r+f yr•lrn anJ .r tirl.rrn .umrnnl t+f .1t,rA t•rAing is ntrw (+ut•.rhlc Iltt• u,c „I tl,t,c u+,,,lt•tn tcrhimitres has rc.ultrtl tn tilltrtt. I,y In,lc hrnrtrn/ rnvr,lr/•.rlnr, rr/ Ihr tlrict ti.rn nl ,iver•rl la•lynnt Ir•n hyJrra .rrlrr.ns In rrl•.rrtilr •.nn~lr 1J.nrr r,1 Ih„i I+e, :ntuelly hrrn t,nLNt'r1 Ir„rtt 1.,1,.atn srmrltt• tn •t vrahlc rlu.rnltly Ih.'y hevi nnly ht•cn rrlcnlnccJ y+cttrrl•t.rlrh I1 Ih

ir.rlly rrt hrl!hly tnntrntr.rlctl fr./cltnns nf .nrrr4r ttmrlcn.Jtr lhc InvcNu RJtnr4 rt•Iurr1 111.111 tile rmmittc yn.rnuttcs itlcnLrltc,l arc fJr Ircluw tile 1nnd. t,/Inr,wnlnuhrl-l,el :tcllvlty rrn i.licrnnanlJl JnrrnJls Ihus, a I,rrrhlinr is inllruviJ hy Ihc c.lrcmc u'n.rtivtty nf thcvc rnrxlcrn anJlylla JI Ictllni,yucs ( Inly t few ycers al;rr, :I snnllJr scJrth wrrulrl hJvc rcturncJ ncl,Jtivc IinJmgs :rnJ loh:rttu srnrdc wrwlJ h:lvc hccn rcrt)rlcd /rcc rrnm Ihc.c hyJrlKJrhIqIC As n1011ers stJrltl'. Irlvc51/plllls are Irccd with tile prr.hlcm trf rntcrprelinK the signiftcance of the in1in11rsntrJl Ireccs uf such rclxrrtcJ suhslanccs '1 Fhe problcnl gains in intl,/rrl:tncc whcn cr,nsiJ- cr•turm is given fn Ihc lacl th:rl simllar hyJrtxarhuns have hccn iJcnlilicd in r,fhcr crrmmrrn cnvirtrnmcntal al;cnts, int'Iuding nnt only tuy air hut smnnF; Ihe hakcJ, rn:rsted, hn,ilcd and r+lherwiu crx)kcJ (rxxl pruJucls In Sil,trrntx r, I'lSR, an AuslrrllJn cancer authority rclx,rtcd 111.11 tile hiJllnl; rrl .t.rrth unJcr tcrtaln cnnJuirms pr/wlutcJ Iraccs nf hvArrx'arhr,m sirnrl•n Irr Uw.c rrl+nrtrrl ulcnUlttJ Irt snr,rkc tnndcns.rtcs frum hurntrl trdbJCCn Prr.I,L rn. r/ Ifi,rrri.ny I lru., ncw I,r„hlcnl% I)evc tx'rn r:rrwd rrf hrnJ.%:ty and t:trtinul.,cntcily tests nn livrnl-, Jrunt.rls Out'%luons ptcvinlct) fur Jllcnlion /nilurli Ihe rC- IJlilrn. hclw,in rLr..rrc Icvil.• rLr..rl:c inlcrv:rls :rnJ 110.11 clnl sc nl Unlc; tile Iauldrm rrl IlrrcvhrrlJ., Ihc Iur.al.lc t'unntl.rlrvr cllctlv nf nrlnulc dnses; :rnd thc t,unlrtct rnl.ntLr/n,n. rrl nulr.rtrnl. Irrrnuotrng, inlydnUnl! JnJ aug. mcnUnl; JI'rnls I IrC.t I~r,~l.liin% rrl Iqrr.r.~.ry Jn,l c.rrclnul•ini.is J(c nl l,rr,.ul irnlxal In tile wh.di I1r1,1 rrl Iri.rllh nrvc.lrl•,.rlr.•n ,rm1 1tnl",.i Ihc nccrl Inr nrutIt Ih,rstt Jnrl sy'%ICrrt.rl_II wotl Ititnl•ruirrl/- tlrrs nicd, Iht' S.Itnlrlit Arlvrr,ny It,r,ud tilrnn.,rlcrl .1 tun fcrtntc rrn Ilri snlr/rtl on A1,ry t/, 1'/SH In :rrl,llti.1n In ntcnrlrcn n( tile Ifr,JrJ• Ih,rsc ,u1, nrlinK wcrc I1H /IUW \klt 11 AN11t kVlrNl. t lu./, I.,hur.,r„ry ur HnJ„ry. N.,u,.n.J 1 .n„r In.nrnle. Ilrrl,c.d.,. M.n,l.,n4 ItH I HI Ir (. HUl K, \t.i 1',r,k AI, ,•n,l In,rn„IC. 11„rl,h. Nrw y',.rl Itk (: 'l)1 I 1 A 1•(/k 1 A. Ih•r.r„n nt /lu,,,h-t;y, lI,e 1 Ln.,g,. MrJ.,el GL,,..1. ( hn.,~n, Ill,n,nv /Nk I HI 1/1 klr 1 1 kl N( II IrH 1V.n1 II H I 111 \trlN, 11„J,U,ncr.rl Iln,l~~gy Cnrr,•n. N.,rronel t en tr, In.nr~~ir II,r1,r.J.r, M.uyl,,nJ I)H I lll Illrs II(IKIIIttH(,1 K, I•rrvJ,nl, Ilw kr.r.,nL In.)nurr, lm , 1.uul, iJ)r hu.rU. Ilk w r Ilt'l 1'1 K. 1 I,r,l 1 n.v„nurcnt.J N.,rr„n.,l (..n Irlt r 11 ~ul 1`, 1 1~t N•,I 1 H It,l, ,rm, ni n/ 1'I~ ~ „~l,•r~y .~~,•1 I•I••n I 1)K (, IItIHKrttt(:11\ 111II11 K.1..,rr.,rc Ifu..r,n n, r I~,,r);: „( kc.c.u.h N I 1 • L IJK ..r ,.rn„rt. Ilcd,r.,l.,_ A1•,rlt.,u,l 1 ItwtN II ,nII/lrk/'11y kan...% r.,r:. k,,..,t Ir I.,a1.un IUr rn. .r r.,l I.dn,,.,rur 1. Il.u I l.n bur 111 ,rnc . 11k Itl NI \PIIN .\ KI)IIIN. Il,p,,,r„~~rn ..1 /',d,h, IIc,Jrh ,,oJ 1•rc.rnrr.[ ht I Itk ,, arn,. Il.itl„r tlurvir.ny l,J/r/!i ul Pi6Jr.mr. II...,, \11/ \H I 111 \1 \\11f,1V, A.v.t,,nl llnt,rnr• Neha,n,J ( ~utrr lu,rrnnlr 14,6r.,L,. K1.,u/1.,uJ • I)k Iv11rHK11' 1 1111 Ak, ( href, I,rM1ur.dury uf <'A.mK-~I 1'Irarm:ri,d„aY, N.,u„n.J l.n.vr 1n.ululc• Ilklla.,l.r, f.1..rt1~nJ ( hc crmfcrt•n.c rc.ullcJ in .clling ulp ccrl:tin r,h/ccUvcs Suhscyucnlly, an S A 11 Suhtrtnnnnlcc rfn Iliu.tss:ry anJ (:Ircinrr;!cnc.ls w:rs alqx,utlrtrtl lu wtrrl :ICllvrly fur J hasii IattEr.nn un su.h I,rr,lrlcrus Ihc hr.1 .crics l ncw Icsls r. Ixml~ I,Lrnncd currrnlly al thc Illn Rc.c.uch Imtrlulc rd (':rnl hruh'r, hl:r.. It rN hrya•J 111.11 Ihr.c will It•arl tr, nryar•virl rnctltnJ. ul raling wltJ,rnrrs .rnJ nnUurrs l,n ril,ruvc c:urinng.cttit' atli.rly rn sl,rnrlnrJlrcd Jnlnl.rl .rrh.tr.ur. i1s 1, wcll lnrrwn, .cvt•r,ll Lrhur:tlttrics Ir,IVC rcl,raltrl IhJ1 tile I,cr srslcnl :tJrnrnr.lr,ru„n rd srntr{,c tv,nJin.:rIcs iu hc,lvy J„v.rl•c. rrn Ihc .lnlt nf .cn.nivc .rn/nr.tl. .Ir:rlns 11.1% rc.ullctl nt rr'.:r.itrn.ll ut.rhrn:rnt Inutnrs nn vnJll I,crirnl.ll•cs rr1 tile Ic.l ,rnlnt:rl. Nuw :Irnunl' Ihr.r n r,nc Lrlarr.rlrrry ptnrlt wh,r.r .lutly w:rs prrnancJ hy Ihc SircnWic Arlvr.,rry Ilrr,url Suth exl,crnurnt,J uh.rrv:/uun.l,ruvirlc a ufininnnn tci Illnnun.lurrn trn tile qlu•s Itnn td cllril. u/ Inh,rtrt, .nnrlc rrnrlir ntrnu:rl crrntlut,rn. r,n tile rt•.laralrrry .y.tr,n rrl lu•ut AI ht'.1, IhcY :Ililic:lr lu Sli'nily wh.u rn,r.l ntv..ul•.rl,rr. tun ccrli L:r It.ldr l.rul,rl•tc atlrvny nl Iht' Int,rl tt,ntlcn.Jli lur I,Jtlrtul•rr It. .ucv ul I,ct rhi .tr,un, rrl anun.rl~ tirrrrrR.• Inlud.rli..n 1'r•.h A'r•I;ruir•r• r\II ,rnnfr,rl ctl,rtnnint. unrrlvluF• rhrrtl rnh,tl.rli„n nf srnuAc Ir.rvc Lrllitl hr Irr,vhr.i I.rnnthnl•ini. i:ut/n,rur,l, ,rnrl rvin .rrr,J.t tun,lrn..rli. tnlr,rJn... l rnl„ Ihc 11,14 hi rrhrnnt hr,rl Ircc. 1.1 nrtnrr.rl. )n h..rvy rln.,rl•i. (r•rvr lerlrrl I„ rnrlrrcc Iln, ninl,le.ot luth rt.ull, rnrl,h.nvc Ihr nicJ lur drritl t'.I,irrnrrnt.rl tr,ntl..rrr.,,u. dnurnl. t„nrl..u.rl,lr Ir..rn'. ul v:nuru. .)urnrel .I.rtrrs ,rml t.lrrt).rlly nl hrrrn.rn htnrr. %rn,: hmir.rn cvl,irrmrnl~ wllh la,lrrrl t.u,ntul•,n t.rnn d Li tnnlrrul,l. lt,l Ihr rrtir.c Iq,rr,lnr: .rl.lrier 1„ Irr rn lrt.,l„1 .\ ntnrrl~, l l.rr I,r.lr.n.rlr,ml 11.1%, Irc.'n rnyd,rttJ Ir•r 611.111) ~t.u. Inr Ur.rlnunt nl hrrruin Nlin ,Ir.,,rJrr. t.ilh,rnl c,.r rrtr.rllnl• •uty rr,.,/•nvi.l ..r r,lr,nl„I t ert )nnl•t mt .n Ir, rtt I lu. nlrtn. Ihr Ir,,..rlulrly „1 ,rlunr,il I, .1. ,t rllr .m h nl,.l.rn,i. •r. .r „I .nhr,tnn• Ihr nurtIr rrri,lr,1 rrr.,nr. r, I,., , r, I,n,ii.rr, •110 rn„n„ • 1„ , r, . I'r, 11.11411 ,r 1 1, .1 I,.,,, .,,It ~Ir,mn n„ r,JL ,u. Irllrr, n. r nr .l,n .u..t 1•Irl•rl,lt Iq Irr nn„ .ui~l hmn.rn b,nri. ,tlu.Ir ru.ry 10, ,.rl,.,l•I, nl ni„r, I,n,r..,6.rr IH

(/n Illt wIr„Ic• II :II,IKeh tht'rt' 11.1% ht't'n .111 unlu,lillrJ Jrt•/rc' /,1 clnl,ll,l,it nn Ihc aorttc(H Ihal a.I,illht :1(;rnl In .tl',rnls in thr I,.,tluul,tlr (+tt.l,c tt( .nn,ke ntiF'ttl lti a (,ttlut In ll,e .1(,It.trrnl rr1,,W,n.ln(, l,ctwa'in snu,ktng .m,l huln:rn hrl,nah„grmr t'./riimnu•I V,Irunl. I,rr,lw,,.l1, /„t Inr.t sutcs rrlrtin(; tl+ snu,ktn(; Ihel (,I,tce IYIIl rcti•Intc un Ilti, tnntcl+l trt (,rr- m,lllnc an,l t,lnlcclur:ll tn thc Iw,int n( i(res(aln,tlnllly. 2• •rl„I/F: c111.TIIltF: ti•(Ii1111'ti Ihr us.ut• ctllwrc pr//(;rrnl i> n,lw well lut,lrr w,ly in Iltltc ltntsat,ily ccl+h'ts 1f h,,., t.lkca (hc /uttul thlcfly of (wt,t tl,K'1,Ir.tl (rlL,w+hl(, a(,l,nrnt rncnts 11) (urnt+ll ,lx't l./lltc,! Iraln/n(; ut Ille arl .Inrl „li ntr ,d u,stlr tulunc nr sl(rn I'Invi,i„n i, ntadt /1,1 ahtw rtt.ttk ulx,n IunaLuurnl,ll (1r,drlrnt, uN wt'll •,s Itrr,IJrlu% hc.lrlny; yx t lht ,,lly ulw,n Il,c .,I Inrnten 1un(; m.I1tn.,S I„ t h.tllrnl c Irn ,mc I.,I,nr,llmy, nnnn.ll dn,nl.,1 .tn,l hurn,u, 11,111! U,.ut• ,Ir.lrll+ Ih.lvc m,w tx•rn m.llnt.,mr,l I„r n,.rny nt„nlh, nr tvrr,r, tfirr,nn„utt,. th.tltl•i, h.tvt' Ix'cn ut„crvcd n,mulrly II frcyutnl Inlrrv.lh, .nul Ih. rt'v(w,n,t% t„ v.lrnnuv thellinl;c\ ere n„w bt(•ntnm(; In hc „l"crvcJ i\n„lhrr 1ab,n.tl„ty i, .las tcnllrUny c11n1( ulxln mtl,t„tctl aultutr rt/rth,wl, wtlh :I vlcw lu „I.I.trnmg e tK'llt'r vnrvlv.ll r.llr ,rm.,nh tnlhnc,l at11. A cnnlirtn,c 1„ ,is,rw I,t„).,r•. I a,l,.,,tl•,' ,nI.,I,,,.,Umn. .InJ ,cl nt'w r,1,tls w,ts IttI,I „n I'r,K I1, , .,n, rn1" t1, „1 II„' 11,i,iril, fltc („IluwUtl; .n,.l ,..,t, I•,..aul I/K I)K Uk 1)k ('lltl ll• r Iwtl'1 k r lu,. , .1 I',•d..... ,.I " , , sn.. rl 1... .r,.., 1 .4 hrr d MnL,-r Il-n. N- \.•.t (,1/1K/.1 11 (,I Y. Ilnr,l•., I,un,t IL,v.,ll I k,.,.,r,1~ 1~L~n tury, As,,....rr /'r,da..a nl \n,K,ry Ihp.ni,miil „1 `...,/rry (fir II„(.t,nI llnraralyr'xh,.,l „1 Mr,Larnt. I/.,h„ru.r[, MrrYl,,m) A11k1' V KI I I/, Iht luhn, 1luplun S.h,xd ,d Atrdramr, Ilrll.ru,.,r, RI.,yIrnJ Iw/NAl Il M/'A/ I'. Wu(cs..•r rn0 ( hrrnn.,u, Ur~rrln,rnl u1 1'hy Ilk (/K UK UK 1)I( s,.duKy. 11,rr.l,u, h,.li/ult• (or /( rllul.u ktsr.,r.h, ILt tlnlva-ni/y ,f N[Ma.kr, I rnt„In, Nrhrrsla AI t( I. /1 I 11/1'1, Iht l/n,rtr+ily uf Nthrr.lr, I lntuln, Nrln,..~r MASAIIIKO Al11lt1ANI, I/svur (ulluri I.rharrlu,y. Ikprrlrnrnl /il Analnmy. Iht tlnrvrrsity ut It..+ MrrJlul (:atvr,wn Ir...s Y/1 NAKANI5111, liswt ( uhu,t 1 rMnrt,uy. Ilrp.nlrnrnl „/ .4r,r 1,,,ny, lht tln,vcrslly u/ lr[rs MaJrtrl 11r.,n.h, (:rlva,bm. I,.r. ( 11AK111' WTYMI)lltll. S/..(1 Sai,nn+1. k,~.a„r II Iral.,~„ M,,,,u I,.d I rhu„7mY, Hrt Il.,tx,t, Mrrnr !sIIIAK I M tl SS(IMS. AMSlslrnl l)r.rtlnr, Nr/1,u,,.,l (bn.cr In.l,lult, 1)K Hrlhr.dr, M.I,yt.nd K/11111 KINI~ K S^NFIIKII. Ir..ur M n ~ 1tr,JaRY. N.trnn.A (.narr 1n,utut<, N.,t„unrl lu.iriutas u( Il.~llh, It,16tsJ., Mar)t.nj S ( 11111'l1Y',11/1//1:11'A1. Itl •1 1It( II Ih, I~It.r„I,~)•r..,) In. .1,11,1r. nt.,,1-.r,l ,n :t ,ttr.lN ,.1 a~, f r use have .rfrratly htcn Inuchcd u(wrn I hesr in.luJr (hc (;t/rI uf suhl4tlIng lhc teasun. (,tr ,nlt,kinK III sl,me tSr,rnlyUvc an,rly+rs in trrnro „( huul,ln ncctls unJrr nllw/crrn cunthliuns trf (llc. It is inlpurlont ltl lratn jusl wlw snw,kcs antl wt+t, dt,es nul in telatiun lu Inyehrd,tl:y, (thysarh,(~y, /eru1K•ra nlrnl ;.ntl „w I,tl •Itl/uslolenl, and tu dcatadr: (,attc(ns ltl sulatktub I,chevr,n Such drstrlltunn may I,e aplyliul lu yrarng I><rs/rns whu are jua br(;uuunA Ihts l,r.trutc Itu tlrlcrnunc wlwt klntl af J sCICf11lN1 Ixcuts I1 utay t+c rp phrJ 1/, nlutc mature sluukcrs /u dclcrnunc hl/w Ihc cvululu,n tll thcrr sn,nkink; p,luclns lrav IYCCn tclalrtt lu Iheit (»ychulltl;ltrl and I,hy,rut„gn rl nl:tkc up :utQ lihclr lric c><(k•ricnt'rs. Ihe l,hcannlene acclwllpanying Ihe crssatil/n of srnuklnl; alicr h.nh h,/hllualiun nray ht tlt'sirlhahle in Irrnls of Ihe tcspltn,cs, tc.ullu,llucntv and tcaclluln, (u ,Icl,laveuun Sinltlatly, Ihc drllcrcnt'r> arnuw)(; /n,hvnlurls in IILe ra,r /,r surtcss wnll whiih Ihry can u11c/ 1hcu Irratltccs ,Illc-t lua(; c.(kncntrs ntay IK• Imftutuve. 71hc („y,h„6,f;ttal anll (,hyslullr(;icrl tharaclctrslms 1,( pctst,n. wlut have Ihvcd tu cxtrrmc old agc as Ilcavy snwtkcrs, wllhuul ill cilr((s. Inry pruvc 111 t,e /,f spt't:i.ll rnlcrrst. 'Iwn I,il„1 studlrs Jrawin6 up/tn Jal;l alrrally acrunlul•rtcJ In /tlllcr researth Itr,yrtts wrre s(wtn.atrtl scvctal yeat% attt and havc n+tw rc- sut(cd in sugl;cslivc (Irclmlirlary rc(wnts hy I)rs. (•Llrk Ilcalh Hr111 ( ha/Ics McAtlltur. 'ft) srl up sprcilic Itlans anJ guals as wcl( as Iu dl,russ thc lct'hniyucs av:111:II,IC (,/t altal'k ulN/ll IhCse llllht:uh Iyr/l1YlCllls, \t'vcral IlllUtlllal rUllnlt t:lble tIrnfc(cntrs h,tve Iwcn s(w)nsured by Ihc Iluartl 'Ihe fitst uf t11rx was held on tirlllcmhrr 6, 1957, ;In,l inclu,lc,l Ihr fulll/wing (x'rtunv utht•r Ihan mcnlbers u/ Ihe lSI1;uJ Ilk 1 kNtil /: /II IIK, An.,x,,dr Ihulo..ur of /'sy,laduKY, I)hrralw .,f 1 hnra,,t Irrrnu,R I'roKn,ul, tlnrvtrsrlY uf I/lrh, $rll I.,1[ / nY, Illrf, I1k 111/;1 NI- M III 1//d111 K(:, 1'/,.an,/nr I'.),lhuln,,./, 1 uur hrrah, ( rhl.nuir I/K 111 NKl' I 1/n11N('I-Y, Prtvidrn/, I~ducrliunrl I[.ImK C,ru,c, 1'1u,.t 1nn Nrw /, ncY 11K knl I'll W.1111// (:IKAKI1, Wufcssur nf Nrur,•phYal,l,.4y. Mcnl.l 11r.,llh Kr+a•.nah Inslrlnlt, Ilnrvrrs[/y ,d Mlahr~.,n, Ann ^,bur, Mah 1/H IH)N1111 W M.,.KINNtIN, I'rol,..ur u/ 1'sY.h,d,.KV. Un,v,~,,,lr „/ I rl,/,nn..r (1n ~,IUr, Inll/tult uf I'tr...n..hlY M.,+.m[nl rml Ita...u.l, IIr,1rl, y, 1 ,'Ir/,nnrr - Ilk 1',% (11 /'11K 11 K, I1:parlrnrnl u/ 1'+yahulu6'Y. I/nrvrr.,lY .,1 U,.,h %r11 I rtr / dy, 111.01 Uk 1) I/ 141I111, I)uc,lnr, 1'sy,Lal,.p.~l ti.rtnar. (h.n,,,n lNh,a ,.1 N..v..l 141 ...,ra h. W.,.hrnt) (1tK kINAIrt I1(,11ik/ I:r..Au.,lr \.L,..I of Il,,.u.r.. AJo,..,,.,, ttK 11/'.1 I IUtllll K, n.v.a„I. Itsl,,.,,14., M„u„ s„Ir, \, h,..d .,/ I1. rl,h, At.u.u,. ..A1,u,., ,,.,..

I/k ( I AkK W IIIA111- Pr..fe.,nr n/ A/tJitrnt. Iluctrur u/ Ile+llh Ser •,ar, 1,41, I/nt.er,dy. MnlhuJ, A/.,,+ahuarl. Ilk (/11k1I C M,AKIIIIIR, Psy,h,d,yrvl r,l rht llnrvervey /Ie+Ilh Strvµr. 11. +rJ llniveruly. ( •rnfvrJ1e, Mau,hn.ent ItH I Ak1II IfJIIII 11111 '1IlI1MAS, Atuxr+lt Pr.Je,tu. ul McJ,.rnc, Ilht Iol,n, /lnplrnt Un,versrry, N.Inowrc. M+tyLnJ A sccunJ confcrcnce un lenurry 24, I'1SA, included thc ftAlnwinR Icrstlns: llk //1\1 1IIH11/IK, Aswcialt Proltsvot ol Phy,nduarcat tiy[trr,c, I.m •ct.iry ul Mrnnt.uld kho.d of Public IIt+IdA, Mutnc+ryJrv, M.nne,.rr+ l)k I)IAN I1)AVII'S, AJrmnivl.a/or for Rt,c+t.h nn I un{ (+n,tt, An,rnt.,n (.nttr $ocrtly, Ntw Y.wl, N Y 11k IIAHIfIN I1 IUNIS, Ui.nt,rn ol MeJi,+l Phy.rcv, llnrver.uy of 1+I if,ant., Itrtlclty, Cah/„rm• I)k M/'r1W/I1 1AWION, Attnlanl 1)vttru., Psythul..p,.l Sc.-tt, N,un.r,.wn Sl+le Ilu..r/.l, Nu.rna.wn, Pennalv+n,a IIH 1 11.1k1/ C tv1,AK1II'IR. t'snbnh,rr,l lo Iht I/n,ver.nv 11,0111 , )rr , . Il+r.+r,l Ilru vtrvlY. ( IIH IIlkt 1' Hlt 1111K, 1luttt..r. /'.ythut~r,./.,rr,+l l.br.r+l,n), ILr I,du„ IAqdu,. Mt•hcal C.b,nJ, H+Ihuwrt, M.uyl+nJ Ilk K'1111AR1 II SIII I ININ, tht.,l,n, (.dlrlit u/ 1'hy.ar.n. .nJ \ur r„mt, I ohm,fnr llmvtrsrly. Ncw YrwY. N Y I)H II 1) SMI1I1, 1)uhlnr, P.)vhnlupaal S.,tn,c. 1lrvrvun, I)fl,.t o/ N.,v+l krw.rth, Wa,hrnKtun. tf ('. Ilk kI NA1/) 1A(:Il/kl, l~r+Ju+tr ti.htt,l uf 1luvne+t AJnun,.n..ri„n, Il.,rv..rJ Ilnrversiry, <+ruMrJKt, 1•I+v.ethu.t/h 'Ihc+c (trn/crcntcs and a still lurlhcr sc..n,n of a slnall suh cunnnnlcc t,n (ktr.l.cr 17, I'lS1{, hevc In,MluccJ J 1,1•rn ctIn,l,rl.mg cnntrclc ul,jrc- Uves Ihe lir,itd nrrw f)Lrns tit a.uv:tle scvct,rl nrw sluJlcs of :ucunlu- Ia/cJ d:rta in Ihc hnltc tl/ t,hl•rininl; :Itl.huun:ll tlut's Ih.d nl:ty I,It,vc inl fwrl:tnt in thc untlcr.t:mJing ul lltc wldcshrc•,J hum.ln nscs uf luhaccn 11. Crrrfliuru+l'rrlrrr llt'+t'rrrt•lr Hf6CJrlI1 inlt, the eltects t+f nrct+line :trul +nulking t,n Ihe c:uJiuvascular systcln has rcccived consiJcrehle Iht,ughl anJ attcnliun frunl Ihe ticicnlific /\Jvisuly Ittlard In addition to gr:lnts ruatJc slxcilically for rcacarch lanjccts nn this suthjccl, a numhcr of rNhtrs, such as Ihe granls In Ilc:lth, lirtliek anJ Keys, cr,nccrn IHqlnl,/lilln sludlcs Iflal inclutlc in . It,rmrlitrn un Ihc InciJcncc t,f corunary thr:lrl Jr,c.l,c in rclelirrn hr smtrking (rnfw,rt.lnl aJilrlitrns Irr rnt'thc:rl knuwli,lhc t,f Iaclrrrs allcctinl; Ihc hcarl anJ tlrcvl,luun Ilavc alrc•nly hrcn nl•ulc :1+ :1 rc.ult of Ihrs rc.r:uch In tunnt•tl)nn wllll .mnkinl!, in It.rrlriul.lr, tht• hnJrrlF,. h•IVt I+rt,tlrrccJ tvtJrnic Ih.rl r% cnnlrayy tu .,,nlc nllt•n yuulrJ t,l,lninns drrivcJ Irtau sln,lii, meJr Ivu.r t,r tlrvcby,rncnt nf In,Lty', Ic,linulnr+ I„r +uth w„rk I)r ^1. Krtn t ( nrfrN /(.•rie•u• Ptrarnr.•.1 1)r (',Illcll he% crtna•ntcd lu I,<rntil his rcvrcw tu lie int InJrJ ,1. Ihr. stcutrn r,f Ihc Annn,ll 12clwlrl It shntdJ I.c nu1rJ /h,ll hc tlr.ru..cs Ihc prngrca of st,n/e wnrk rhal h•IS ntrl yet I><cn Irnhlr.hcJ Illc rclnwm.lcr rd Ihr. c,rrJluvauular .cctinn is I)r. ('a11tll's revicw. (:rr.lh;.r h,ls undcrl:lkcn a cunlprncirn.ivc s1uJy t)f the iardruvJUUl.tt anJ rc.l,ir.ttt,ry cllccl. r/l nicnlinc incluJlynl; eight hJrJ111c1cL] td attH,n 'Ihe ncl cllccl un tllc circulaUun is cumlllcK hccausc uf thc u/.lny sucs uf :rclitln lhe resulls inJl.;uc Ihat the initial clfecls t/f nitntlnc ar1J Ihn.c prtNluccJ hy .nl,lll duxs :uc tluc lu sliuluLuinn uf chnlnwtcccl,lr,rs rn Ihc alntic •rnJ c:uuriJ Mahcs, whose allcrcnl% rcllctly cau.c hyl.rlrnc.t, hyl,cr Icmu.n :Iml I:rrhyi.IrJrj Pvlca.utclurnh uf Ihc h1ut.J 11rtw llut,ut•,h rbc fcmta.ll •rrlrry rn Jnhs .rml 4.11% I/rtwlJcd cvnlcncc t.f th.urhas .r.t,nJ.uy tu 1•I1ct Is r,n I,Lr„tl prc..rrrc wi111 ntl rnarlctl Cllt•cls wlut h cuulJ t•t• a1lrllhuteJ lu a thanl•r ln Ihc rr.l.t:rllcC t.f Ihc vascuLtr I,ctl Anr,lh,r Intr/ccl Irnvnlving thtr Ilh:urn:lc(.lugy ul nltullnc i. 16.11 of I'r•h4un, wlrn rs stutlyrnp Ihc struclurc-aclivlly rcl.ltit.n,hyl t,l cutn/,nunJ. whlch I,ruJucc Illciy clfccls Ily :tclinl; al Ihtt s.lulc silc :r% n/iuunt• llrs 41.11.1 are ctln,ut.nl wltlr thi hylwlth.va Ih:U nictltlna and t'crtaln tuhcr bLKklnl; ahcnts tlcut•:Isc Ir.ul.nussu,o Ihrt/ugh dlc .ulrt•rlur ccrvlial I;.Inf'lu,n ut Ihr cat Ly inlcrlt:rrng wllh llhc rclc•.r.c uf :tcclylthulrnc /rulu Iht: l,lrh,ul/;hulut ncrvc Icrrnin:ll ~ l1'irufin'• .uvf ffJ..... f 1'rrsrla Sint'c nrctdmc, ill atnlc suhlcct. :11 Ic.ul, r.ruscs .r launytl Jrry, of ,km Icnll,cr:lturc, inJlc:tlUnl; c'un.lriiu,m tll' thc sul,crluial vc+.cls. It 11.1% I,t•cn ctmunr,nly ;rsvurrlt•tl Ihal nlhcr vauul,rr IKd. Itarllcil,•Ilc sinuLuly Il.rw cvcr, Ihrs is nr/t Iruc nl nr,lny tllhcr Jrul;s; in lacl. Ihrrc rs rnrlrc Itl,cly In hc d rCilf,r,K':II rcl.ulun.llilt hclwet•n Ihc vasculet ttmc t,t thc tlrcl, :ut,l sulK•r/icl.ll vcsscl. If Ih,s wcre ntrt llrc ta.c, /1 wtu/1J rc.ull rn a.h.rnl,i in lllc cJl,erny of Ihc v:lsrular systcrn ncccs.rl,lring crrnc.Irr.nJml: ch,rn/:r. in c,uth:rc r,ullarl Sl,riiel :Illt'ntiurl 11:1c thCrt'lure hct•r1 I!ivcn /u Ihc s1uJy of Ihc cllc:r. trl nlcrHmc Inl .fk•c/ht' v:rstuL1r IK•tl. AR.t/ftir•n/r.l 11.0% tn.,Jc tnca,lucn,rnla of Iht• cllicl of nrcullnc t,n Ihe hltuwl fL,w Ihruul•h Iltt• .Im end musclcs in nt•rn Kcsult% nLt.tincJ Ihruul;h Ihc usr t,l I,Irlh).nr„1•/.rl h tr,luu,lni,, .,nrl Ihi Ilina•1 Ilhcnn,,.lttlrl1 ncirll., mtht,ut• 111•rl Ihr .b-w inlr•rvcnrnrs nrlr,tu,n ,rf nr,ulnlw rlnrc.tas hhr,pl Il„w tn Ihr lln ,nJ int rc:ra•s if Ir.rn•.,rnlly rrl rr,lrn/• .l, 1, 1.,1 18111,4 Ir Snl,lt.,r 1 I,.r .i ,r,,,. l .r •r,i,lv Irn, h, . n r., J, e,.,rl,rlJr 1„ 1,.,v.,,.,1 In lln. ,, 1,•.rr rl .1,,,.,1.1 h,n„1, J Il,.ir ,,, I.,nl• .il., .r. I') Iv NI.r.rnr...n. /.vttl,r ,,n,l 1.11,1„ nli, in„ r I,,,I,I,JrrJ .luJi, ,.ur ILr I,L-.J Il,,,t in,l „Juu,r In Il,r h.,nJ .u,J I•,r, .u.„

which In"viJc Sd1111JCtury rvrJrntc thet tllr veu' Kttn.trttlur rr.l>.rn.r frunt srnrtkinF th.rractcrislic td tltr skrn vcsu:lk td thc h.rntl rs mrl sh.rrrd hy Ihr vcacls sul+ltlying Ihc tuustlcs trt lltc ftuc:unt In thc l.tltcr. Ihcrc was citFtrr nu resltitnsc or a sntatl intrcase in hh>,rJ Iltlw 'lltr etfctl uf smuking t/n Ihe Ixrrpheral trrtul.ttiun ha% hrrn stuJred by frrunJ using ntultr lcchnical pruccdures (skirt tcnt1lt•ralllrr, digital plclhysnutl;ralthy, raJtu srwlium skin elearance and A-V thlfcrcnce in O, satur.lulm and Ltclic aciJ). A significant rctlutuun in Ikrilthcril skin tcntrcraturc• raJitt srxlium clearance and vcnuus oxygen salurariun was observed after cigarette srnuking. 1his was asstkiatctl wilh an incrcasc in /tulst rate antl markctl individual varlahrllty with Jiy;tlal plclhyvmuKralthy 1 hcre were no siRnifit'ant changes ttbsctvet) fulluwtng sh rln +nud rnl; .Srrrlnn has 1,uhfishcd his study trf Ilte clfctl rtf chcwing tuh.rrttt nn thc ttitulnlnm• rrl..nting an intrre.c tn -Pulse r.ltc antl blttt14l Itrcvsurc, a dctlr.tsc tn skn tcrnltcralurr anJ thangcs in Ihc h:rlh.lK,ntht•t.relth, changrs whlth arc atlrthutctl lu Ihc nktNinc ahsrutxtl dmtnl; Ihc thcwm); n/ I4A..Itttr (• omlter•rhlc sludres are no•w Itetng carried uut 4111 Ihc ellrtls rtf I•tlx and t/g.tr tn trkrng Srntrl,.•..' l'nrrnta Ftn.ntl l)iflrrrnt llh.rnrtlr h.n ttuJtr l Iltr tutul.tlnry rt'.I-n.c lu til;.uctti .nuoktng ill hralllty ntalr Inrdit.tl stu lrnt. wh.t It.tt,iluelly mJull~i hy nm.un td Ihr IrJIIoINa/t11.~1'I.Iph .um1 othrr litordrttl•,% l hc rr,ttll% h.rvr Itct n.ut.tlyicd wllh rilt•rin.r 141 Ihc vy.tnht, tli.t.l..ltC antl ItnlSi Ilres.ulr.• hr.rtl rJlc, strt+kc vnhltnt dn.l c.trJt.rt- outltul I hc (den r% Itt turrrL.tli Ilic I.tllt•rn~ of t'trtul.rtnry atttvrly wtlh ulhcr th.rr;rtlrrruts tlf Ihe inJntJuel Ihe results shtrw that slntrkirtg results in a vil,nnccanl nlt•en ri.c rn %y.tulti and tli.rstullc fvcssurc, hcart r:rle antl crrJi;lt: rtutput antl a f.ill in slrnkc vulumc. Pulse tur..ure wjs little atlccleJ I he results were reprrxluctblc anJ Ihc petlrrn ch:rractcriaic lur Ihe intliviJual She has af.u provlJrtl csulcnce that smukcrs as a tlass are tt/ a tltllcrcnt ctat.tttuUun;rl tylx tltan nnn- smtrkcrs, in Ihel the parcnts td srttodcrs arc rnttrc Ircyuently allt•tted hy hcarl tll.case than the parcnts rtf ntnt srnttkrrs Il'n.rJ 11.1% lucdsurcd Ihr ve.utnnstntlur clfirls td sntukinl; nt rcl,rtir+n lu Ihc trntlxralu/c of Ihc cnvirttnmrnl dnd dhstinrntc (r.tnt Ioharttt uant. a Itlrthy.rntrr/.ltlnc Iethn.yue :rlytlit-J to Ihr It.•l antl anklc Ihe smtrkinK of Iw tIF,.Irllr. rcvullctl in a ritlutlnut in hltwtJ fltrw tn nc.rly all rxlxrt nlcnlv ;rvcr.rpinl• 22"S• Ixing little :tllcttrJ hy alt.trurncr or runm Icrnlrrr alr rr \ntnlu r, Itr wlutrd Ic%t v.r~rK• n.lrithnn 111.111 ttMrhnl! Illc tnvrrttn mtnt Ir.nn K 1' I.. r.N'1 In (urthrr Ir.t% tn Jrtrrnonr wht~lhrr Iht.r %Urnult .tl,.. tllrt I tl, t• int ri.r.rtt Itl-rd Ilow 111.11 rullnwv .t prrual trl r.'.rn,tvc hY1xI emia, it wus dcrnttnstralctl that tstkly ct>tlling wa% a rnurc t unslslcnl sttntulus thin srrttrking twu ti6arciles in reducing reaclive Ily/tclrr/lla, rnd thrt Ihc two slinluh ntay have adtlitive effects. (:.pcriulcnls on paticnts wrth syrn pathcc4mtirctl Iruths showed no decrease in rcaclive hypcrctnia bltHxl fltlw durinK snulking, producing evitlence that the slimuli in normal pcr- suns were ntrdiatcd Ihruugh the sympathetic nervous system. l;*t A tlran, whtt was assrxialcJ with the rtxtve wotk, sludtrtl aFso llte effect u/ nicutine on the peripheral veins. Rapid inlravenuus atlruinislra liun resultcd in constriction of Ihe veins bul, since this was acauultanicJ by pain and hyfxrvenlilatiun, cor»/ricliun may have !><en sct'untl.try. lhts appeared Ut bc ca)nfirmctl by tests which showcd that htut+tl shillctl out uf the furearrn vcins in each instance during hypervcn(ileliun whllc hrcallung air 'Ihis sulxcas that peripheral venuus cttnslriclian rnay serve lu intrrasc thc avalLlhtllly u/ hltalJ lu Ihe lrcatt duting dccp brcalhrng Nu F,(IrN trn llrnin llluurl Flute II'rthilrr is tluing work on the effects of cigarclte suwkmg ttn Ihe huwan hrarn Measurements rre being nt•atlc on Ihc crrchr:J hluttt) Iluw, cerebral mctalndivrn, bltwttl gases, btartl pll, clcctrtKardalgrams, arlrnal pulse Inc+sure curvcs and elcclrtxnccphalugrarns OIhrr Ih;rn an incrrasr in Ihc pnlu ratc •antl an inlerruittent flaltening rtf Ihe clectrttrncrph.rlic rct'tln/ings, nu sil;ndicant changes have thus lar Ixen fntmtl lurtrbttm is evaluating elcclrurelintlgraphy in cumparison wilh trlhcr Irchniyues fur he stutly u/ the circulation of the brain and retina. A rtunthcr of grants have been given for Ihe stuJy ol chan);cs in Ihc curunary cilcutatian resulting from nicutine and smttking /lu/Arrnrhrrl ha+ sluJreel the cllecl of nicu(ine rrn Ihe cumnary clrcuLurun in rrlatnrn to the rtsygcn rcyuircmenls of the hcart in hulh dugs and rllarl. I):Ita h.rvc txcn uht:tinctl, indicatin6r that inqwrlanl changcs arr Inttttut't•d ttnly wnh rclativcly hi/;h drtscs uf nicutine eyuivalcnl to that nht,nnitl by Ihr nJrela tutn ttf ft+ur cil;arcUCs Nicotine resultctl in an incrcascJ car.li.rc oullrut with :r currc.lwmtling increase in curunary artcry (tluutl suthcit•nt Iu mrt•1 /hc int:rr;nctl utygcn tlcntanJ "lhe average nle.tn cttrunary vinuu% binttJ urrygrn Icn.rmi was .hghtly rcdurctl 1hc studtcs rtf llrnK are in atvccntcnl with Ihe :dnrvc I).rta wt•rr r.lr lainrd thruu)•h eudiec t'.tthcteriiata n nn Ihr rllicl tt/ ct/-.uil,r .nurlml• un lllc cortrn:try hltMtd Iltlw antl urn myrt.'arrhal ntcl.rhulivnt td Itrurlicn nttrrnal hunr. n vtrhlt•tts 'Ihc rt•sults .htrwctl an inirr.r.c in tn/un.try Lha.J tlnw .11141 n 1.111 rn ttnrur.try vaaul.tr rc.r.t.tntr, alttrtg wtult .rn rno l..tu tn nlrl.thuhan I l r I,L ttJ Ituw kil l f~.rt c.rntl lu l.tl ly ctt t'ctlrJ Ithel nictlrrl f,tr Iht• t•tti.. cni/l•y rtltcnJthui ()Ihrr t'tl.ilunintv tlr.rl lutn".ntly wlllt il 2S

tl w tk.rlu/, ntnts l•f ntclhl,tl, tn ,IUJy Ihc 1tc.trl if I,.tucnt, wtlh t..r„n.ny dt,r,t,c III Ihc ctficrmtrnt, ul ftrllrr Inlre.url1n.try rrlctt.tl Inlrttuut, uf rut„Unr (11111 1 u;kg ) In tlnf•, mirra.ctl t:l,run.try (tl.n.ll If.tw wtrhr.ut irnlrc.r.inl; I.Ila,.l l,ri„n1c lrt Iti.ul r.ttc I 1~(i ,hl,wid dil+rt•„n,n .lnlt tn- vir,ntn uf I w.tvr Ihr,c rllctth atc :thldt,ht•t/ hy "11'A. ') lhcrc i, cvt lrnic th,tt the rt-tiltn ld ccrt.lm tlruls ,ut It a, rrl;..nr,vinc is n,t,dtlird hy thc /'tcsenre t,f artetitnvclerlt.,r, t,f thr ct'rl,nary arlcrtes 11ti, I+rl,l,lctn is hilnl; sluJicd by 7ntvrll in r:tl•I,tl, nt:ttlc Jiltirrt,t'Irrlllic by hif•,h chwlc,lcrt,l llicts In the mrnnal i,ltlaltJ hiert l,cr/u,u,n wtllt nrctl title rcwlls in a f.rtcf dacrcaw in (It)w 1ttlltrwcJ by a mltrc I,rulun)'rd ln crca,c in l.rrfu,n,n rate lhe I:utcr pltesc is ah,cnl III Ihc alhrttt,tlcrl,uc htarl this Jlllrrcnte, rf it lKCUrs rn rnan hutn ,ntnktnl•,• r, nf uhvtuus itnlw+rLtnlc Itr l•ur luuhlcm 1('rn;rf 11.1% unllrrw:ty .1 s1uJy rnf Ihi .hrmmt' cllt-t1, nf ntl.,rtnr nn thnlc,lrr.ll mclal>,th,rn, u,tnl, t;tht,ll, r.n .1 hy!h th.di,lcr.,l Jtil ('h.utltt•, IK•ynnlt Ihl„c tKCUrrtnl•, wtth rull,unc .0h,ni ur tlLUli,trr.J 111 .ni, Ict1,rArtl ln /,rrlnntn.rry c~lKnntrnls, rntlullc 1I ) m uc.t,iJ ntt,rt.tlrly. ('.) Arvcl,q,n,rnt td Ir,itms un I,aws, anJ (1) 1•rc.ucr tlillt,utnn ,f thnlc,tcrul in tltc ,.Irra Intl irt,, (4) I;rr,tlcr ilctu Kerlhtt- gral,luc anJ l+.ttltnlnKic cvitlcntc ld t.rrth:rc invulvcmt•nt anJ f,cnl+hcral v;tttul.v ch.ntl;r, Wult .1 vtcw nl dr,trtbinf; thr n.tlur.P ub,/„ry r,l a.,rLit an l tl,rl,n.try ~tlu tu,clcrl„It. Il.•lnr.rn is ,IUJytnl; .tulnl„y (.t,r, l.l acl tJrnt.tl Jr.ttlt dnd Ilu„c wtlh stnf•Ir rl,i,,,.lrv l,l aittlc nty.K.trdt.tl Inlertlii,n Ihr J.t.t :uc In tic arn:Jy),cJ hy l.u c, ,cA. ahc, Irrtnt tl,nl .'au,i ul tli alh, a„nt t.tlcJ clm dtunn, ,uth av hylk•rtcrr,ittn, unJ vlKi.,l hi,ll,ry . Cuf: hrr);rr (unntl I S N"', st•n,tlFvlrly tu It,l,.tl ttt r> tr.it I Ihr ,.trnc f.crtcnt.tl;c .t, ntitJintc ltf allrrpy in girtcr.tl I,n1,ul.tti,m Il.h.ttitr ,yrlnl' Itttns wirc frntr Innc, mrlrc (rcllurnt in /huve havtng hlt,ilrvc ,kut tt,ts A hil;h it,ncl.tItnn w.t, nt,lyd I,tlwcrrt fr.,vtivc skrn Ic,tc an/l ahnurrnal lrcn phcr.tl v.l,tul.tr rc,l,tmw, af,cr ,nu,ktny; I'n,ittvc rC.ttlinn, wcri lut-hcr in ,ml,krrs th.rn ut nt,n stnl,kcrc :rnJ 1,nrticuLuly htl;h III p.ttirnts wtllr tltrrnuht, .Inl•,itti, l,hltlcrans lll. (.(r.rfrFr' tntrl 1lrrrrrG'rrrrl 1'1t•t•r f i.t,trii .tn.l IIV/MIcnJI ulcct are tll It.nticuLlr inriri•l rrt ril.tttl,n w Ihr u,r l,f I~,1•elrl, Ihc,c arc atrwml., ,ttntcnls tu wlntlr a,tr ,nl ,Ielnuc.J a,,,M ietu~n wtlh Il,l,.rcclt u,e he, fK•en rclwrrlt' I I,y ,.,tnr ilnJrntn.6,l•IC.tI ullir ,IuJri, Iltirr el„l t, a cltnical u:t,lhuttn :unnng tn.utv I~hvat1.,11% 01.11 p.,Urnl, ,lu~ul~l hr i-ttut'd tn ,r.•I„nu.kml-,• .,Itl,nut•Fh Iht' Ir...ltla~n .il,l.r.,t• /i. 1,'J Idt11t'r 1r-l,It.Hl~.li.ry r'l, itnur'llA l'vt.lrf,~t' `,u, r tl„ if tili ir ,. •mn ,.It.,t t•l-Itrt ,nt0rr,t„nJ Il,nn ..tnti r t•Ii J.tl;y, ul, t'r• tlt,r.l,r, h•rvc latwrllt•d an rnlirc,tUnl; t.l,c Itlr t ~Irinntinl. l csf,h,r.ut.,n nl Iltr h.t,u ulwtn wlnth s1:Wslrtal ,t„l.tr.tln,n l,1 tlu, 1ut.l llt.ly ri,t I ht• Sl linltht Atlvuuty Illr:utl h:t, w(.rr ,Itlm,nrcd IFhrrt mvc,ltl el.n, in thc ultir fIrIJ .rnll several sluthcs have mrw IKCn crmtlrlrtctl anll 1,111) fitllcJ I)t 1'hilt/t ('lrulrrr has rcpurtcJ Ihc c/lctts uf crg.trctlc ann.krny; lm latticnlc wtth dutwlrn.tl IJccr as cump.rrctl wrlh Ihc clfcct% rrn ficrmm, wnhuul an ult:cr hr,lnry Vulumcs uf 6aslric sccrcUltn, hyJrlty;rn tun clm ccntraliun, "frcc rt:ul,'• "lic cunccntrauun anJ uutlwl, urulrcl„in, I,Lt,tur I><psinlt},Cn, dlal,IvcJ ga,lric mueine, vi,elnity uf g:uttic juitc, inlrel-.t,lnc bjlllHtn frrc.vurc :rnd inlraga+lric Irmlxralure have I>'<cn mcasurrJ Ihc lwcral/ rcvull uf Ihc,e sludres was that nn srgnilic;lnl dlllrrcncr~ wrrc /nunJ In any ttf Ihcsc re.pun,es as belwecn nltrru:rl Itcrams and ultct vulims In na„t i.rlcf-unl•v, smltkinl; ju,( (rcfurc ur dutml; nlca,urrnlcnls pruvrdill nu al;nncA, aul .hantic in crlhcr nttrnr.tls ur ultcr /r.urrnh 1'Lt,m.r fx•Irvn,q,rn w.t, .111 cuaplilw, Ivinl; dctrca,cd in atntcnrr.twtn Ilr .1 ,m.Jl bul sl.ui,uc•:Illy ,r),ntlicanl Ikl;rcc tluring IkrilrJs uf aml,kin}; Currrlariun. H.•rnnin (lnri pfninrd Ihcsc lindinf,s, Ihcreflrte, lad curnlrlctely Ilt cRld.un Ihc .I.tlr,ll.al as+tk'ialiun thctwccn ulicr and snlukmg un a I+hyaulltgtc.tl ha,v, I•:uhir ulccr is inllucctl hy still untlixlu,eJ fac/las, rnhcr Ihan thusc sulJletl• t-r else thc ;t„lk'i:tuun is invehtl, ur rc,ls ultun snme uthcr It.t.r. ;rllul;clhrr lhc willra><;td intptc,sinn that ulcer eliuhrgy i, p.nUcul:uly inllucntrJ by cnullitln.tl nr f1,ythn,nruauc fnilttro, IcrtJs Ilr r,ri,c a/~:ttn Iht• yuc,lum whcthcr Ihlr,c whlr :Irr ulcer rrlrnc lm accuunl ld .untc clrrncul uI cl.nvr luuunal m:dc ulr are uutrc Incely Ih:rn ulhcrs In Ilnd sld.ttr tn ,nu.krr•1; '1 hu i, tu sul•I;c,l thal ultcr and Jrvire Itt srnukt• nlay h.lvc j rlluun.m c.tu,r t.tlhir Ilctn ,1.rnd in Ihc rcl.tultn uf cau,c :rnt/ rl/c.t I hc Ityl,..lfhc.r, c,l,tii.llly tt•.t,mrTdc in rt•,Itcct lu Ihl, It.ult.ul.u Jr,r.t,c .~nJ Irnd, lu ,Inlt invc,Itf;.lnun again uult thc p,ychulnl,lcal 1r.t1rn A,utul.n inlctlucl.uutn lrf Iltr a„lK'ialiltn Ik•twccn snu,kinl; :utd l,llttr ,h,t•.t,i, I,.r., lll tt,ur,t•. IK•in 1)uI Iluw.lrJ Irul in ltlhcr~c:r,c, stull alyti.u, ut.ur tunlcr. 'u1;d. Ih url~h UII lnf,tt':rlly tt•nahlc. ('Ilnic.rl tc1~1~11, Ir•ni,t, rncvcrthclca. rn inJlc.tlinl., 111.11 ul.cr P.lttintv wlur :ui cuml,cllcJ lu ,ru1t ,rnl.kml; shltw hrtlcr Iti.dutl relr, Ilt.,n Ilnr.i alluwcd /tt tl.ntlnui III vrcw ul Iht• ,I:dus III uttuul Idty,tul.qrt.tl rr,l,.nt i mrn,urcntrnl, .n tnJu.dcJ. Ilu, lacwnt.thly rtll.Fldr ld„rr%.rtnm rrni.un. .1 rny,trry 1. 2 ]

I i rn 1• /1 bst racts of Reporl s I-•Ith rcctplrnt uf a Tuhricu Intluslry Rc+c:rrc-h ('unurrutrc );runt is rc+J1unvhlc for lftc initial prr+cn(rtiun trr pulblii:trrtut of tllr rc,ulls t.l 1u+ rrscarch in si'icnufhc mccttngs of in al+prupri.dc sttrnlific jtrurn.rt+ Ftdluwing arc ahstracls, alrptuvetJ hy Ihc authnrs, uf rc+cerih rr(Nrrls thal have alqrc•arctl in scit:nlific journals (inclutJlnl; two stMm to hr Iruh- hshcd), wrth cknuwlctJgcntcnt of sup/>,rrt frtm. Utr 7 I F{ (' Ahstracts of earllcr pa(+crs by grantees which appearetl in Ihc 1957 Rcl+txt of the $cienldic Ilirectur are listed at the end of thit scctiun '1 he n:,nte uf the scicnri+t lo whtrnr the T I R(' grant was alat)c is given in parcntlrescs at Ihc cntl of cath upcning Itaragral,h. Ihrsc ah+rracts have Irccn grtruluJ unJrr +ri hc.rt)rngs I('.uttt•r Rcscarth; 2 Illrrn,rn I.ung Sludres; 1 Ilrrrl antl ('trcuLtturn, -1 (irslrtr inlc+tln.ll, S I'.yt hnlrrgit .11 Slutllcs; and 6 ful..tct tr ('hcttu+lr y 1. Canre•r llr'+r•trrt•h "A StIRVFY ()I (')MPOIINIIS / UF{ A('1IVI I1' IN '111F SI/PPI(FS- SIl)N (11 M(/IISI= SI IIA('I OIIS (i1 ANI)S" Ily I 111tn li IttK k :"nJ Ilrltnln Mtr•in, 1{ r+wrll I'drA f\trrntrrt.tl In,lrtntc. Ilullelu, N Y(-u.urr . Kr•trurr It. Vnl I H, Nu H, lr.rgr+ 1(K ) H'! ~, Si pIrnrl.ir I9SH 1 I I RC gr.tntcc (lrK k / I'urpu.. u/.turly Srh.ltctw+ F•,Lrntl Ir+h h.rvc Fr,rn uu'J by v.rritru+ rr- scatncCr+ to as+ay Ihc Iwrlcncy trf lnrrwn antJ su+l+t•ttctl sl.rrt t.uunnl;rns Ixc.rusc they can bc t'unlplctcd wtrlnn a sbtrrl unrr u,t ntudcretc cRlwntJrturc of anunrls antJ m.ltcrial If rcllahlc, Ihc ass.rys wunltl grcetly rrJutc Ihc lirne fcyuirctl ftrr the /rectiunautm uf trutlc tnatcrtels cau+nrl; sLtn Ilmmof + irt nrrtc hy I+mlarintrnb cllcctrvc fruttitrns 1hrs invcstil;.ttirm w.rs unJcr- takrn In Ir:rrn n+tac alxrut Ihc nalurc of sih:urtrus gl,tntl supl+rr,.urn threrul;h slutly td the activity of a vrriety u/ ctnnlHtundk of krnnwrn tn suslxctt-tl carcintrl;rnicity or wlrh prmnuttrtg. inrhaung ur hrrtcntt:tun); arritm in carcinrrgrnc+is Pror.durr: -1 wn IhutJs trf the h.tcks of Swiss nlitc al-ctl SS (rS tlays wcrc shevcJ Iry clcctric tfiltl+cr. On thc ftrlluwing Ihrcr t1ay% ruth :mrm.rl w:rs trretctJ twice tl.uly with (/2 nrl uf Ihc tc+l strluuuns hy alluwlng Iltc hynld Ir+ flr+w• frtrnt a(tilrctlc nntu thc trnlt•r trf the t'hlq+rd .rrr.t A Int:rl of 1111 rnrnlwrund+ was cnll+lr+yrd in thr+c c>tl'<'rinrrnts lhc anrnt.rl+ were s.t,rrficctl 4 dtyt aflcr the latl .tlr/dn'atrun antl nu.rtr,ctrlut• ,tu.ly trf Irrr I+.trrtl +lirlrs w.rs rn.ldc lh¢ rcl.tlrvc srh.rcctrus 1'I.rnJ sulrluc++u.n rntlr. nf c•u Ih tmnlunrnrl was t)clcrnrrnrtl Firt.lirtK.: Ihrrlrrn trf /hc t'r-nr/wrunrl+ tr+tr,l Ihml en indrt rrf 111111) trr mrrrr, Il. h.r l rtl.rtrvtlY srn.rll rnrlttr+, enrt /•1 h.rJ nn mr.r,ut.l,l .ntrvrtv ~r I~.ir r r~n+ )'I.rn~l +ul.l.tr++iun w.r+ turtln r nrt r,..uy mrr ,ulln r. nr .~, .r ttrlrrrn n/ +krn t.rrtrnr~l•r~nr: .rttrvrly 1Fhc Irntcnt c.rrtinn)'tn 1).') 1 tlrntcthyll,eni( t) acriAine had vcry weak suppresst,r at (rvlly, whrlc t tnlthrt nlc was rnutlcr.ttcly active Ihuugh not a skrn t'arctntrl;cn. Sumc cuntpuuntl+ may cause Icss suppressiun in cunccnlra(cJ suluUt,ns IJt.rn thry t1I, Irum a tJrlnte unc Suh(rit to Ihcsc Irmuatiuns, schaceutu glantl trsls can trr trl grrrt veluc lur Ihe stuJy of crrt:inngrncsis. A scctrod applrcautrn of wch Irsts Iics in Jclcrntinatiun of supprrNsur activity per unit uf weight atuJ per unit of chrumuphure at vrrruus w•tvr Irn);ths -Iltr tccluuyue can l,e enrpluyetl fur crude nralcnals whrch h.rvc h.rtk);tuuntl absurfrlrun preventing e.ata idtuldicatiun. An cxernldc trl Ihis aplrhiautm is tlrrnunsttalrJ by Ihe case of 2 hacliuns tlcrivctl Irttut crg.trcttc suruke cttntJcnsale. One cuntainetl 41( units trf suppresstrr actrvny, antl when tltlutrtl 25(N) tintcs had an optical density of O 6 al 100 nullr miirtrns, Ihr ratiu of activhy to uplic'al density falling well wilhrn Ih¢ rang,: uf (trur strun);ly active byJrtkarlwtn carcinugens. I he tclhcr cuntaurcJ ahuul 4(I(/ units of supl,rrssur •aclivity rnd, when dilulrJ al I(1(11/ lu 1, IIJII arl UlrtIt-JI tlrnspy u/ .75; it is clcar frurn the ralUU rd aclivtty (u ul,lt.al drn+rly Ih.tl ncrthir bcnipyrene nur Ikntanlhr.rcene cuu1J h.lve .rtitrunlctl (rrt :tll td the suly)rrsst,r activity (,f Ihis fracliun. '1 hc nnnng antl Jusc sihrJulcs u+rJ by (hr authurs are largely arhilrary. 'Ihry wcrr tlrsrl;nrJ lu I,rrmil thr ruaainturn reslwnx Itour ciKatc(le smtrkc cuntlrn+alc "('AR('INIt(iFNI(' A('7IVI'IY OF ('I(:AR131'I1i SMOK1: ('ONUI N SA') li I 1i11rtl uf 'Iraurna and Rcmute X-IrrJtlWtlUn " fly I MI U(i 11ut n •rntJ (irumta• F Mtwrptt, Roswell I'ark Mcrnurial In+ututc, 11uIL.Ju, N Y ( f'rcp:trctl fur puhhcauttn )('I' I K('. grantee: I1t,ik ) 1'urp.r..../ srudy: Strtne eRperirncnlers have rclstrrlitl pruJucutrn n/ turutrrs hy alqrltcal/un of cigarette srnuke cnndrnsale tu nwuse +lins whrlr ulht•rs havc nut uhtainctl any malignancies.'Ihctc havr hrcn iniun+istcuitcs Jht) alntmf, .tuthcs rrleting irritrtit+n to carcinugenic Int.ir+.rs I ht•sc rR (K•ritnrnh were ctrnduclyd In drtt'nninc whelhrr Ihe tllvrrgrnl tesultn ctrulJ h:tvc ht•rn dnc It, nnnnr drilrrcuccs in LaintrnK Irthnryurt, ;,nA al,tr In drtcrntntr whcnccr sccuntl:rry al;cnts wuu1J ruaAc scrccnrng Icsh naur senvrlrvr 1'ru.•rdurr: ('rgerctre srntrkc cundcn+atr w.ts IauthrtcJ In a rn.tnrltrhl tylrr stnrdrnp nt.tthrrtr rn wlnch a IS cc 2-sriund lut(1 w.rs lalin trntc every mtnulc unril thc hutts wcrc ahuut 23 ntm Inng, I hr t trnJrmcJ was w.r+hrtl frtrm Ihe cnllcclion Il.r+ks weekly wllh acrtnnc, antJ a 2(1'sttluUtrn in I S ru1 of aicltrnc was nltluinctl tnchrtLnl! ahr,ul •1 g uf snntlc tlt+ldlelt• Ix•f c.trnat td ctr.arrltcs 1h,s w:r+ rtlrnrrtictl a+ srduturn Swi+s /rntelc nutr wcrc dtvided rn(u R grtrulrs lur I ~Lcrintint A.t+ IrdLrws 1 1(/ rnlic +h.rvitl .,n altrrn.tlc Altrnd:ty% lust Itturr Itr It.rrntrnl- , wuh A 11 111 mttc rrc.rlrtl av ehtrvc, Irut p.urtlcd wrtlt atrtnnc, 111 (It nutr sh.tvcd 111r lir+t I rul.ry td r.nh rrtunlh .uttl tuH Iremtt•tl wrrlr ••n" tnud tlrr (trllrrwtrng A1rrnJ.ty, IV 1/1 tuiir +hdvitl wlrt'n it alqrr.utrl nrtr+,.nv ,nl. jr. trvrly, 1'•rrntrrl wrth "A" V III tnu t' rulda rl 'enh +.rnJlr.rl : r I t.m. + wr.-kly lu,l Inrur Lr I..nntrnl: wttlt'•A" VI III tnntttrl, Ir..rt..l Irtr \' I-r Ir.turl.rl wrtlr .nt~rnnr, \'ll 1/1 muc 1h.rf wrrt• nivrr +Ir.tvrJ It.rtntrrl wrllr "A"\'III 11) un+he+rtl rnltc 1tr.uirl wnh att•trrrtr 111(. rrunr Ir.r, A,..I

Ihc rnitc wcre shJvitl with an clcctnc clyqxr, anll "parrlllul;" wJ1 t.uncJ rwt hy d+,sca t+f 0 25 nil uf sulutu+n a(+phctl with a synngc and Itrrwrng evcnty nvcr thc cnure shavcJ arce All anrntJls were pJintcd I1/ Urnes a week ca'cIN (irnu(+ IV nrtcc, whitlr were pJintcd S ttn+cs a week lr+ Lrrwlutc strluunn "b", a bcpt:ute cxUrct of Ihe cr+nJcnscJ tJr was trcatetl trl remt+vc nttu(nte arld other hescs anrl then rnaJe up to a final vt,lunrc uf 1 rnl r+f acetone sr+lutitro xr uriKinal teru+n of ttgrrrttcs 'Ilus is fivc tnncs dtc cr+nccnttaliun of ulSution "A". I'xl+crintcnlil rnite were JtvirlrJ intu 5 gruups for [inperintcnt 11 as ktlluws. IX: 5f/ nan Irralllated Swiss frmelc mice, painted with "U"; X: 65 irrarliateJ Swiss frnralc nucc, painted wtlh "H"; X I: 39 irradiated Swiss femalr mice, painteJ wit t ace- lunc as contruls fur X; XI1: 45 irradiated ('111 mJle rnrtc, 1larntrJ willt "II"; XII1: 19 irraJrated CJII males, painted with acetone as cuntrols h+r XII A single irrJdiaion Jux of 25(HI r was JcltvcreJ to a I square crn arce ut skin when thc animals were 55 days old; lltc IIV1. was (1 1 nrm AI PJinunP wJS drmc live times a wcck and all Ihc animals were shavcd as nccArd lu krrl+ Ihc Il:ur alattl. AII rd Ihc .nrnr,lls of htNh ct(xrirncnls wcrc Ireutlcd tunlrnwur.ly unhl they rlrrJ tit were rnrnihund 'Itre skirt lesiuns wcrc eaantrncd nrrcrr+sir+l+t tJlly wrthuul knr+wleJge of Ihe e>t(krrrnental grrrul+s hr+rn wltith tl+ry t'urue FindinRrr In Swi.s mice paintcd with cigarette sntnlc cunJrnsJtc, hcnign and melrlm.rnt .kut trnu-rrs wcrr IarrJucid in all grr+ulls rc(;errllc.. tul cr+rnttJcnt irnl,rlu+n 'lhc JJIa ,nJi.Jtc th:tt yu:+lilJhve Jtlfcrcnics in rc- sults Jnu+nl! I,il'ruJrruic+ I+rr+hal•ly Jre nrrt tluc In ccrlam sl+ccihrJ Jtllrr- cnres rn +Lrn (t.rmlrnl; Irthnryrrrt hut nr.ry t.c Jnc tu tlrllrrintcs in muutr str.iks t•nrld.+v.J No lunrnr. Jt.OL,LrJ u+ Jny ../ thr trmu-•l nntr Skin cJnccr. drvtl .l.+d rn 7 1.1 .... 1, + V n n: I..rn,Il..rl r+J/, rn Is (•r,mp \'11 nurt• ( nrvcr .hevrrl l. rn 2)'r.mfr IV rnr, r(.t, nt J..Iir n n. t r.,.It v 1..rnJ tn I eJth rd I,rr+rrl+ I(t)r.r+rrl h+ wcc11,,1 enJ 1•rrmlr 111 ( h.rv~J nnuuhl~ 1 rnrtt• In Swt%s fcnr.rlr .lnrl ('111 rn.rlr ntrtr, mtrn.t• urJrh.rtn- r.l .r tmell arc:+ intrrJ+id Iltr mrnal+vny rd dntenl JrrJt nl .lrn Il+ I+.lrnlrnl•, wrth rrt, arctic smuke tnnJrnwle In tlu. Ca.c R irrJtlhatrnn a1111Jrt•Itlly attl'lI a% a sy.timic intuJlmR agent tit carunn}rnc.is. 'Ihc Swiss fcnrJlc rutrc were ntuth nuore sin.itivc to Ihe ct+mhincd treatnrrnt than tlre ('311 rn:tlcs Skin canccrs dcvclr,pcJ in 17 tirtrup X mice, in 2 Fruup IX nticc, and in I gruu(1 X II mrrute lhe data sLpgrsl that the dr+ta(;e rale crnl+lr+yctl in Frl+rrintcnt A w:rs IIIJ1lIrI1JI Mrcc r+f gruuh IV whith were painted r+nly 5 timcs a week Revc :t rctlw+nte sinulJr tit IhJt rd rninr:+ls pJrntid Il/ tinres a wcrk 'ft+tJl tunu+r yrrld is cr+rnl+.rr:+hle in 311 prr+up+ N'hilc thc nunnc-s nf r.irrinrrntJs varied (rrm+ rrnc Rrr+ull tu anuthrr. Iltt• nuntlK•n arc tra+ sntJll 1~+ w:rrr:ntl drJwinl, cr+ntlutarnt It allht•.trs that Ihc qnPub.rtrvc dillrrcnccs nh.rrvcrl arnnnl; I.rlmu;tlmics Jrc nrrt tluc In sm:Jl rlrllcrcnrc+ in thr urithr+J uf 1Jr al,lrlrtatrnn Il+r Int•.cnt dLrIJ Icnrl tr+ rrrnrirh.r.iir Ihr irn(urrlJru rhllrrintr. ur st•rnitrvrty of .rr.rnr. in c,o(x•nmint rlr.~1•n :utrl rn rntr rl+rt•t,runn of rc.ultt In rhr +.nt• ./ .r Nr.,l t.nrinr.l•rn, rhlllrcntct rn . n.rtrvrly en„ur/' rnne .ullv .ti .n,, nut~l~l .. . ..•... I li,r .r~r.n.Ut rlivr .Ir11. rrni. , m r.lr, rnw nr .1 r. l l., i1r, ~,it•. .i tfh 0 . r" rr1 rl. A+' r ia..l, n..~lr r. .. v,i iA nr,.rnr, .~, of r i skin t:utinrrl-rn 11 has ht•cn (xanlcd r+ut n+any trnrcv 111.11 Jrtirn:rl etl+cri rncnt.tlirm tJrutnt I,c uscd as a srrlc rnc:r.ure tit Ilrr hJiJrJ tu humJnt .rv sr+ciJtcd with an cnvirrrnrnentJl agent 'Ihit i+ I1.utrrulJrly Irur rn Ihi (srr.rnl scrirs uf ccl+rrirucnls "A ('(K1tI I.AM1) IIISfUI (1(iI('AI., ('Y I(1LO(iI('AI., ANI) ('Y 1(1 ('I IIiMI('Al. S I ttl)Y OF '1111i I RA('111:UIIRON('IIIAI. I' 121T. ANI> I.I1N(iSOI MI('I: I:XI'OSI:I)'IU('1(:Altlil"11i SMOKli. I Itrr+nthdis wtllt Atyl+icJl 1'I+ilhclc.rl ('hen6rs in Mitc F.IwseJ Ul (ll;areuc Snn+kr" Dy ('tr tl tr 1.(ur ntt NaI racl It, Rutwrt t l.t ur rrtrNUl Itt,t K, P1 1), and PAut I•. 1),N/t IN, A1 S, with /he tcthnical ata.tJncc rd I'AiMlr tA SuarfrK, Inttitutc of 1'Jthuhrl;y. Wrstcrn kcurvr (Inivcr.ily, ('Icvclnnd, OItir+ l',uu rr, Vrd. I I, Nrr 1, pel;cs 49(1 5(Ih, May lune, 1'158 ( 1 I 1l (' gr:uttic: ('irilic I curhlcnlKrl,cr ) Yurp..., .I/.ru,ly: In view uf the rnany cumplcR anJ unknuwn (JClurs IhJt rney hc tit uula+rlJncc in Ihe Jcvch+l+rnenf tit t:anccr in ntJn• rt was Jccirl..l trl invc.trl;Jtc thc inicrdcprndcncc tit ci6arcllc .uwkinl, JnJ 11111 nwn:rry cantcr tit thc c><(><rimrnlal uniucrl hy syacrn:rtrc .IuJy nl tltc clfcit rrn dtr trathctlhrunchial Ircc, no atudics tit Ihis chJraclcr havrng ht•cn rrl+urlcJ in thc litrraturc. 1'r...rdurr: (irr+ula of Ient:de ('1'r albino nrite (rrlu.rJ in wirc cal!es whh lrNNI and w:ncr in a nKmt u( cunstanf tcm(xratlur, whirc ntl .vnnkiny. wJ. .d6rwrd, were c><Ilrttcd lu fhc sntukc t+f up trr R ci(t:+rctlcs rlJdy in a s/1ccLtl th:mrfrcr, whtlc cunlrul rnicc were IudgcJ in :r sintilar ch:trnhcr withuut ciu'•uclle +nrr+ke e><(+rlsure, all uthcr crlnditirln% ul Ihc tett tn•inl• idcnutJl I lie tmukc was r1I1f:1111etI frllllt c/l!:Ireltct, nulonltJ tun a whcel in the .nurkrnl; ch.rnncer, and 61;h1cJ at rcyuircd intcrvul. I alxrimrntJl :+nJ rn:tfilunl; cr+nlrrd luicc wrrt killctl at selected intcrvJl. in .udrr lu .tudy a1ICrJUrrrts in thr Irachculhrunchinl Irce. FindinK.: 'h'I+in linf c.lwr.ed tit Ihe snulkc, 1}tc mice wcrc vt•ry ruuth cothed :uul :rttrn+l+tcd 1r+ esr:yk Irum Ihe snulke. Ir-rit:rlirln td the cychJ, anJ nJ+al rnutu.a wai n(ten nrHeJ, anJ srtmclirrncs thr wht.ker% were hr.t '11tc+c ctft•ih du:+ll/a•arrJ un h:JrituJlitln lTte ntit•c lu.l wril;hl nr Jul mH intvc:r.c tit wcil;ht whcthcr the drllcrence in wci(•ht hctwt•cn Ihc ti.l :rnJ crrntrr+l mtcc wa; rluc Itt h•ss ftwKl intake t'annrH hc Jrt'rrlrJ, nr+ nuui Irun:rl .lutlhr. havinl' hccn rn:rdc Ilt.hrLytrJl .m,l t'yh+lut;ital ch:ln),rs in Ihe hrrmthi rrf Ihe etl+rr.rJ ntitc can I.c JrvuliJ /r+r crrnvcnicnrr rnlrt 3 main Itrr+ulr. I I/ nrr .i/YUIr cJnl t Ir.mlIct, (2 1 hront hrtia wrllh ntfld (ttulifrr:rlivc r I+ithrlr.rl t'h:rnlIrt; ( 1) Irrnnr hrti. with nrJrAcJ, rdtrn atylticcJ, 1wrdifrr.rlivc th.url-r. (If ' 1 i. I+rr.rJ n+iir, 11 h.nl F.runthiti. Jnrl Ih •hr+wcJ rnultihK:ll th:rur•r% n+ rlrr hrrmt Inr. Mrnr Ih.+n f+Jlf Ihc rnir r whFh hrnnilhitrt 11.1.1 Inri rd i1nthrir.d rlytlrLrtt.t rn rn.rnY rry+rcls tiuniler tn wl+Jt wuuld I+t• r.rllrJ t.ut+n"nr.r nr trlu tn m.vl ( )Idv ?.hnwid .rluenwn. trll mrLrldJtr.r f)f /r nu. r Ilr. t Jr l n,.l h.rvr I,rr.ur lirn.. 7 h.rrt :+ lrr.+ tvt•A aJt m.m.+lurrt Irun .r id rlr. ( nn N.. lu.n~.tuu. w.r, f..uml .rn+nn/' tl+r rrurlrnl rnrti. .uul n..nr ul rlrr 'I m.rl.hrJ tnntr .1. .li ...tJ nrylnvn .( ncl- rl+nhchJl hnrnl' . ll

Otlrr1111J11vc rnirruspcc'trlrllhultlructtic studics on ct•Ils frtlnl c.Ilt+scJ ntlle wltll c1lrlrprratlVcly shght histul/athtllugical chrngrs showed a gradurl incrcase in siic, protein cuntcnt, and dry mrss, whtlc the 1)NA ctnltcnl rcmrincd ctanlrnt; crlls Of epithcltel areas with pruldcratiun, on Ihc tllhcr hanJ, showed a grrtltrrl intreaie in I)NA content in rJdiut/n to the in crease in sitc, protein content and dry mass. "A ('OItFtIiLA l F h IIISIOLOGICAL, CY7Ol.(HiI('A1., ANI) ('Y IU- ('Il1;Ml('AL Sltll)Y OF '1lIE? SI:V()ENCE OF I:VI:NIS IN '1111? I1RON('IIIAL IiFI11IFLIt)M FNOM MICE F.XI'OS1:I) 7O ('1(i/tR- F.1-11: SMOKF. II StuJies on the Fate of Atypical Lpithchal ('hanges in thc Ilrunt hi front Mice EsptucJ tu ('igarcttc Snwke." l1y ('et ta te 1_rtrt rl r rnaru(:r m, I'N I) , Rutltlt r I.rur NrrNnt KcrR, M 1)., Wtt t IAkI Irn11t/N, 1'IrI), anJ 1'Alatl-IA SnArrrll, Institule t/f Pathtdugy, Western Reserve Ilnlvcrsrly, ('tcvelanJ, Ohiu I'rescntcJ at lite Scvcnth Inlrrnau.-nrl ('anccr ('tlnl;ress, I unJun, lingland, )uly 1958. ( I I R C. granacc: ('ct lite 1 cuchtcnllctgcr ) 1'urpu.r o/ audy: In view of dle statistical findings indicating a possi- ble rclatiumhip txtwccn cigarette srnt)king and human lung cantcr, anJ sincc Ihc great rnajurtty of these ari.e in lite brunchial Ircc, an cxpcri- nlrrltal study of lite seyucnce of evenls in lite branthial epithchum of rmce after etlxnure to cll;arrl(c srntlke wrs unJcrtaken Iruril a hrstulul;ical, cytu- Inglcal, and cytlxllcrlltCJl point nf view. Prorrdurr: Gtt/u/1S uf Icmale ('Ft rnice al three nttlnths uf a);c were utptr+eJ tu cigarette snulke in a chumtx•r which Ix•rnuts Ihe ht/u,rng of bulh lite exlwlseJ and cunttul mrce at fhe same Intue unJcr Ihc s:unr strnJ- arJiieJ cunJitillns, lite only e><ceptit+rt being Ihat lite ttlntrtrl miie rrcclveJ no smnke '1he test nlire received snwke ffum clgarrllcs t'onsumeJ at re- yuirctl intcrvals At ccrtain periods aftcr cRptlsure, e>tllcrtrnenlal mice anJ Ulcir t'l)nutlls were sacrificcJ artd hhrcks were taken Irllm lite srmc sitcs of Ihc trachcr/brunthial and lung Iissues. FindinR.: Whcn nutc were etl>,1scJ Jrity to tire stntlke frnm 4 tu 6 eiKarcttes for a Lericxl of two rntmlhs ur hinger, marked t'hanges were Gwnd in tire hrunchial ellithellurn 1he mice developed irt Ihe ruaprrity of cases a hronchitis which JillcrcJ frum Ih:rt whiih llccurs in nlitc altrr viral infrctitln, where Ihe striking fcatures are Jegcneralive chrnFes of thc eptlhchum anJ cells 'lhc hrunchius following cif;:trcltc smokc cRllu,ure was asuwiatcJ wilh matkcd, often atypicrl, Ilrtlldrrativc Ilrtx'c+scs of Illc lining cllithchum; there a{1fleareJ Itr lre a step wi.e scyucnt'e 'rf allcr,luoms frtrm a nrntnal restinK cprthchutn to a swtlllcn tlnc• ttr a prllli/rrrtivc nnc, anJ finrlly lu rn alyf/ltat hyf.efplasllc tlne; and s(nnc dyspLr.uc thrngrs whith irc tnmistrru wilh the Jcsil;nrtinn "carcinumr m.vru" No n)v.l.ivc carclntxncts hrve hcen It1unJ in any of lite rniie which hrd hren rtl/t/.rJ tu Ihc stnokr td ul, ttl I SIN) cit•rrcllcs tlvrr a Lcritx) tll nc:lrly Iwn yrrr. ! ln lt,r .,Ih~~r h..n. l nl n.a r whi, I1 w~'rr t•cl.u.r. I to t il•.uttlr %onukc r. 1...1 , I..it., t..,.„ ,t.l. o.,l I,- I„ n, iill n-uin il. I I I I strcml;ly tuggcstinR rcversihility of Ute changes in Ihc ca.cs lllrxrvcd sn far 111cre scctut•J to tlc a gradual desyuamation uf lite atyprcal cprt))cllum fulltlwcJ by restnr•rti/m to the normal one. ('utrclrtcd wrth Ihe histological and cytuchcruical changes, (hcrc were gradual cyttlihcmical alterations in the bronchial epithclium, the earltest change being an increase in protein which precedes the ccllular changcs anti which is ft11111wcJ by an increase in the !)NA content. These altcratrnns are also reversible when e.plnute to cigarette stnuke is atuppcd. "1f1U1.lKilC'Al. ASSAY OF 1'OSSII)l.E CANCER PRO1)1/('ING FA(' 1ORS IN ('1(lARl:l-E1: SMUKN 7AR." lly II. R. I'KAt r-'11wr.tAS, M l) , Medical College nf Slluth ('arulina, ('harlestun. ( E'rcparcJ fur publication 2) urp uar o/ .rrufy: 'llle varying results in the testing uf cigarette snulkc ntlcns:rtcs un lite skin rnf lahoratory nlice tepurteJ irt lite Iitcralurc in Jtcate tlle ncc.l fur thluuugh studics of the role of a Lrge numllcr of JI.'crcnl strmulr in rxllcrimcrual cartinlrgenesis PrurrJure: ('rgarcttc smoke concentrates were applicJ to lite cervix anJ upper vagrrlal area Itf mure than 2(M) UIIA I mice. As cunlruls, lite sulvcnt used tu dissolve lite c<ncenlrates, 2O-melhylchnlanlhrene, anJ physical Irauma produced by rotation of a euttun4ippeJ applicator, were tested. FindinK.: Preliminary data on tumor yields were J(11f%. fur rnrte painted twice weekly with cigarette smoke concentrates and 25% hlr those paintcd three times a week. '1'be solvent alone produced 6(1'76 results with painting twice weekly artJ none three times a week. 1he methylchul:rnthtcnc resulu totaled 6U'% with twice weekly painting. With the cll1tt/n applrcatur Itic- tinn, tuntor yield was 42 g% on twice weekly and 25^/• with three times weekly. The cellular respcrose of the mouse may be so sensitive as tu invalidate or renJcr yuc+tiunahle Ihe use of the nwuse as a reliable indicator of car- cinugenic putcncy of various substances. Certainly it wuu1J appear thal traurna rnua br kept at a minimum and Ihe tar itscll ptlaihly uscJ in whnle Lttm rathcr Ihan being dissolved in a sulvent, which rllpcars as ptllent as mcthyltht/lanthrcne if used long enuugh. "SOLltltl.li I IVI'R It I'RO-1•I:INS 1)IIRING Illil'AlO('AI(('INO(iFN- I•SIS I)Y AMINOAYO UYIS ANI) 2 A('Ii1Yl AMINOI 1 IIUI(IiNI? IN 'l Ill; IZAl'." Ily SAM StlMrrp, l:nltt v M Y1111N(J, Jrlll fhMAkrl yN (; Or r, Instilute fur (':Inccr Re%carch anJ I.ankenau Iltlslllt.tl I(e+carch In.titwe, 1'hilatlrlllhia, 1'cnn.ylvania ('urn rr Krsrurr h, Vol I H, Nu 1, Il.rt cs 11 dh, ):ulurry I')S!i ( I I It (' grantce: Strrtd I I'urpu.rn/.rudy: Invcstigaliuns Jr:J/ng with 1hr car.rnr~t;cncsr. Iry aminrlartl Jyrs, 2 rtclylrrninuftuutcne, anJ hyJrtxarhuu. hrve rmh.rtrd Ihat l)inJinK tlf rnct.rfwllitcs uf Ihc%c ctlrnlwunJs Itn thc Irrtllrtns tlf I.ul•t't ur/crns i. a nrtr%..uy hut ntlt a suthtit'nt rryw.ilc lur Ihr tlt vrltyllncnr ul nrtqplr+lr thu., pr.-trm hnuhnt, trtun n1N tmly wuh Jrnvarivrs 1 t.n cintlprrnc tlyrs . nJ /iyJrur:uh ns. I-ul .tfat willl a niln t rrt int l•t ni/ .v.l Jvi ou Ihvllr x.tl-n 1 v/Jrntt• u1"l .upl•cvtril Ihrt Iht• v"liildc In,0riii. ..1 {I

file 1arl;cl Ivl;.ln5 nlry f.c cau,ally Intulvcll In thcu t'.Irtmtll;rnt'Sr5 IhuS, file h I,rl,lilrn nl r.11 hvcr ttnt I/niy tnnt.lin Ihr l,ulk /d tht' St,luhlc hlnlnJ .tnt JycS, bllt :nc thcmxIvcS altn.ttl t•nurt•ly ah.cnl Irunl th rc5ulh.tnl Ilvcr lumlv, I/.u.lllchnl; Ihc ah5cntc 1,1 La,unJ tlyct in file lunlnr I urthl: r ctltlt,t- •,tn,n Ilf file /n1JIt.ItrJ Ilrl/trn) Iltlcrlnn nllah.lnlan InvUItCJ w.rt (llcrcll,rr nCt i ,..I r y 1'ra.r.•.flf..•: AJult ral5 uf h1,11h 5ctt'S wrrc IrJ 'Hl hhrrum Jt.U11cJ w;llt'r InJ a 5cmi \ynthrlrt Jtrt cuntanlnlg 12t.l.cln antl I (I ntl. rllw Il.lvrn, Ag A nunlhcr uf Jycs uf Jrflcrcnl cart/nnginli l,tllin.lc5 nr ntmc wirr .I/IJ:d In Ihc Jltl fur varyind Inrilltl% anll r I;rllult 1,1 tllnlr„I ra15 wcrr frtl Ihc •,bltvr Jrct wnh/lut Jye 1 hC fhcll.rllK ert rrlul•cn, 2 .Iti lyl.lnlul I,Ilulninr, w.lt ,115u fCll in a Ivarn Jlt'1 lu tn:Jc r.lt% anJ trnufl.ucJ witlr a tllrrt't1+ImJrrll; t/tnltlll Jirl 111 Ji5lrllgui5h Ihc rllctt% ri5111t1r11; ffltnl file tartrn/,l;cnic f,rlrct5 fr/1ul Ih/,sc Id rel;cnCraUvr I-.ruwth, ),rr ,r, r.ll. It( hl/tll 5cec5 wcrc Il.lrlt,rlly ht'Ir./1rcI1,nliirJ, they wcre ..ItrlhtiJ :II thc cnJ t,f file IIurJ J.ly, whirt file gr/rwlll ydtc 1,1 Ilver n-I;rni r,lu•In 1N nl.l.nrl.11 I hc vlluhlr (ivit I,flrlrm. Irtun Illt• r.lt. wiri 151/1.IIrJ .rrlll etl.•'1ic,l t•Itylrly,hurr llt.llly, enJ tllr II f,/ntirnt wcrc ri.ultctl /urlllir /nl,l .rt tuhtnltllll,nrnlt I,y .In I,r tl•rlt.ll Ict I1nIt1Ui I IrIrlfllgr: I Ili I,/I,Irtf15 1,/ Iwl1 \IIIt 1.11fi11,/1/1t'lll\, h, ;Irltl \Il/w• It tllll Lnnt,l I-,n/nJ Jtr, frlun file teltlnnl•rnit Ilr n,m c.trtrrlul•.trnc tlyt'. I eth :Ir., r.lrtln,11-tn 11I file 5u-r1C. I,rl,lllqi,l .1 tllvuhC:tf11 n1lJC./\l /rl file .,InUUnI d Il,r 51,Iw I1 I,r•Ilcrn., hul Illi .li/l n•,n t.lrclnl,l•in JIJ n„t InJntr Iltl. rt'tl,,,na, Jryu/i Illc en.ll I•,al. I,rnJu,Intn nl (t)(5 h/nln,l III Ihl'.c lun It'rllt Irtlinll~ nl Ihr Irvt•r t.lr,lm,l•rn, 2.Itrt)le/nntullunrini nlt,ri Ill.ut J/,uhlt J file Ir„nrllrl nl .1„w tt I,rnlt In. I ivcr 111•rncr.llunl, Jtc Intlt lly. :Inll Jrtrr.l.r.l 1,•.0 Intel,c. /•tr I/. III,I rl„I el,l,t'.,r 1„ I,r I.lu..llly /n.,,l.cll m Ihl. rc•.Iwn.c I llt rc .Il,l,r.u t„ I,i Iw„ ( nrn irl'Int. hnr. /,I c.IJint r. ft'I.tllfll•. In I,r„et ln I,nurl,l .1/,1 II)i. In,l h I,r„et nl.. 111.11 ,II,I,I 11 Illt' II)In. /hiaN tl/.ll Illc n/r"raldi Ir.nl l„nn.ll,•n 1„ Ihi .vll ,Itr rnJllttnl In.t'r lulnln rr.nlt, Irlnn Jrlt'lu,n tlf t..rnlr.ll It.rr I•1„Irln. Ily tlnlunuwJ rt In,alrc Irl :tv„ t ert rn„I~cnt Ilthrr l.nnr....: Il.lrnl,n Rllntl,n Ittiluurl.ll I unJ (nf ('•lntrr {(i.curtll antl i\Inirilen ('.Iruir S„tlt'ty I (. llrrlrrrnr l.rrrlF; ,ti(rrrfrr.r (l(iA I(1: 1 11 SAtOKF Ilti I I 11 ('1 ON I'III 11()Nr11t1' I IIN('IIUN N11 -1\IIKI MI NIS" liv Ill-Kl,t I Atl,lrlt, N11), ./nll N•rttlvnl 1 K11/P11AN, A1 1) ,U.u/lln /(t'tl.rr.lIt,ry I.tlntr.llury• I lnnt'r.llt „1 ti„nlhrnl ('.Ihfl,rnl i tit hn•,I ,nf AlrJit Inr. I I,. Atl/•rli , (Irhl••rtun AIrJr, nr, ,\'ul ?fl(• NI, 1, ? 1 1 !'11, ftl.uth I')SH ( I I It (' I•r.ultci C\ll,llr) I I'11r)rnu. u/ twlt : A vcfy lnl•h trlt lilCllt C uf t 1/•Jn'lli ~Innl, ulr h:l. 11t'1•n fLdill t„nlnn,nly ul lllc ht.h,fy Id (t.ll1cflt\ wltll 't'VCrc' l'Ull,llt+l'111.1 \a11Y11 thcri 15 ttu .rl,l,./rrnt t:nLC flnr ehr 11,n-IILImn, 5nt 11 .n f\I,It.uli Il, rtrlt.ltn11• Iln~l. nr .1 fhl,l„Iv t,l sntrlc t In,uul I,ulln/m.,ry tl/.r.l•.I• I h,' nt lulty Ihr I I, /, u( nl,l, , Yltr ..I1,. II In ,.I,Iln.rll .I•. I.I wllt IIH 1.1 I,.Illt nl \h•y11,1 •II,I, ~,nulnl/• Pru.rdurr: 1?ath uf 125 nlrrt and 16 wunlen suhlctls aged ftum 24 tu 711 was given a c/nnpICte pulnuntary evaluauun wbtle al resl anJ altcr cr- ercl5c, cxtcl/t far Ihrcc subjech with hcarl J/5ea5e arid nne n/nnl.l suhlctt. SIUJrCS wl:re t11/talneJ un 9 prtienls, all but 2 wllh sevcre Itulnwn.uy enlphy5cnla, in the supine pt/5iliun aftCr snnrking twu cll;arettes; sume rn haled Jt:cldy, ulfters harJly at all. In another test a smoking devite wrs useJ so thut snu+ke would he inhalCJ with each breath. 50 suhjCits were aluJlcJ Juring the 5nluking uf une cigarette, of whom 23 IIaJ insvgnihcanl, 8 mltJcrale, and 11) sevcrc tx vcry severe ernphy5ema. Pulnu,nary cunl pliancc rncuturcmcnts wcre uhtaineJ on 41 subjecls IlHrcxl gas cuthangc nlcasurClul:nts hcfurc and aflcr smuking were obtained un a gruup ul 5(/ euhlecl5, 19 with insignificant. 16 nltklrrate, and 15 with sCVCrc ur very sevCrC crlnlthySentJ, using Iwrn CJ{ercise tests (Itr cllnl(laralive purlMbes. Fir.rlinK.: I lie usr rH file 5mllking Jcvice Ilrrt bruught nutfc wntkc inlu file Iungs than urJlnrry snniking pnNluceJ consistcnl significrnt Jrcrca5rs in artcrlal hlrntJ utyl;cn salur.luun and in arlCriul Ir(/: in tn1.5t 5uhlCtti wull 5r•vcrc ur vcry srvcrc Cnlphyscrna. ht nurrttal sublccls :InJ 1h115c wuh a rnl.Jcratc Jt•l;rce of entllhysenu nu significant ch.nges in b11Mrd gas c. ehan);e tctultcJ Nu sigrrilicrnl changcs in hhxxl gas cnthangc werC nltlrJ aller file sluuking tu( two cigarenes, either with Ihe suhjccl ;rl rest Ilr aftcr e.rr.ne A Jr.rca5e in uxyhcn uplake Iw'curretl when IrcaJmdl C.rrtltc w:ls JImC ,ftcr srullking twu cigarcllcs, and IhC venUlatinn vulumc was aISU J/:trcaSCJ, lur/hably at't'uunling fur part nf the utygin Jrcrrax. 1'utmt,n:lry cltnlrlr,lncc rucasurewenls after 5nlllkutl; tlne flgJtelle were cuntl,trntly •rnJ signilicantly JcercaseJ in n11+51 sul.lrth -nunn.l) as well as th/lsc wllh Itnlnwn:uy cmphysrma l'he c1.15Iic wlak //1 brcatlung was inircau'J in Ihc nlajtaity of cJscs. (n twu ca5c5 in w•hlch aulllcs wctC Jtme altcr Ihe sublcits st+lppCJ snwking, tunc for threc uutnths anJ nnc file twll yrars, sll•.rnliirnl rcduclions in rcSiJual air wcrc nutc.l Ihr ic sult5 intlit.l/c/l thal Ix•r\uns willl scvere or vcry sa•vrtC cnylhy5rma wttlJd hc bcut•r 1111 to slnp smuking. "O1151'HVA'I'IONS ('ON(TRN1N(i "1111i IIKON(•I11 1(fl A 1'IVI: '1O SMOKIN(i ANI) ISNVIF(()NMIiNI'." Ity 11. R. I'It.ttl IlnrnIn%, MI) 1)i(tarlrnint ul I':Ilh/dngy, Mcdrtal ('ullt•ge uf !iuulh (•nruhn./, ('h•uli.tun 7 ri-S/urc /Nnhrtul luurnul ( Vul;irnia, Nllrth ( arulin:r. Snuth ('.utdln.t ), V.,I 5, NII 1, pel;cs 21 -21, May 1957 I'urpn....f .rNU/y: Intrca5ing knttwlt:Jl;e Id Ihe cvltluti/m anJ hfr hl5 (tfry 1,( nl.lny nc/,platn/s indlcatc5 Ihat inv.151ve catrintlula (rcllucntly 15 /11rtrJc'J hy cluthCli.11 ah/11Mr11JI/ty It suth thanl;cs nughl lie Jclt•rlid In Ihr hrunthlel ure in v:unlu5 I;rrdu:.tiun5 ut Jcl,fct'S tcl adv,/ntcm.rH, thrn slully w//uIJ ItruvlJC v,IhJ lu.lninl.'ic sulllwlrl ftlt IIIC cvulutlun Id Ilrun, h,~ gt•n1c t'.turtnllnc1 unllcr file inllurrltc /d v:uiuu5 slimuli l'rlrr.•Jurr': Ihc 1).I,.Irlnrinlt I11 I'elfjlllol'y nf 12 in.uluW,n. In wltllIy scll.lr.tlcll I,nrl. ul file Ilnrlt'J SLItiS I,hldmiJ (ri.h huln.ut lun/ , Ir„- autol,.n•t, T I '.rt ul,n. I,f Illr hrllnl ht.ll w.•rc t.lll n.It I„/,Ilnr 1.. a.I.In,l.v/hrr,1 I,I.,n It/r .r11Jy, ut,l i1.uhr11.11 th.ntl!t't an,l I,Ihr1 1•rr/rl,I/II t1•11.1 wt'rt' r('tl,rtiCJ I Iltl,rrl[•. I,f Iht- Ir.llil'rttl' SJtt/lkllll; h.lhll~, nl t III,,,tl•nn. a' i1 i5