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TAIt1.E (/F /:Q1NTF:N'I'S PaRe Introduclion . . . . . . . . . . . . . . . . . . 5 Research FindinRs and Studie~ . . . . . . . . . . . . . /t Abstracls uf Reports Sludics at the Cellilar l.evel . . . . . . . . . . Itt Pulmonary Physiolosy and Anatomy . . . . . . . . . 22 Cardiovascular Studies . . . . . . . . . . . . . 23 Psycho physiokgical Studies . . . . . . . . . . . 11 Tobacco Chemistry and Diiuhemislry . . . . . . . . ]b Pharmacology . . . . . . . . . . . . . . . 411 Other SI udies . . . . . . . . . . . . . . . . 41 Review . . . . . . . . . . . . . . . . . . 41 Recipients Of (7rants . . . . . . . . . . . . . . . . 44 m A B

S/:IF:NTIFij(: AnvilSOttY I?U1ARi1/ to the Tobacco Industry Research ('ommittee KfiNNl31 I I MI?RRIf.L LYN('FI, M D., Sc• I) , LL I) ,('hair,nan ( hiwrrR,.r rrnd 1'rn/rr.vrr nl 1'athrdoRy McJlcal ('c,11cPe of South Carolina ( harlcdnn, South Carolina RI(•IIARh ) I1ING, M D. /'n,frctor and ('hairmon. Department of Medicine Wayne State I Iniversity Colkse of Medicine 1)ctrnil, Michigan McK f:FN ('Al-1 FiI.L, Pu F) , M f). !'r(-frtuir F.mrrituv r,( f'harmat-nGrty ('iwncll I /nivcrsiry Medical ('n11cRe New Yrnk, N Y. l.f(1N () lA(•OHSON, M I) 1'r Irrc N nnd ('hairman Department of Medicine ltniversily cd ('hicasn ttirr( n,r, ArRc+nne Cancer Rtesearch ftospilal ( hicaRlr, Illinois PAIII. KOl IN. M 1). ('arcinnRcnesis Studies 1lranch N:rliunal ('ancer Institute FSethcuQa. Maryland ('I.ARf:N('U. ('(N)K l.fi'11.E, Sc 1) , 1 1. 1) , 1.trr I). Sf irnrifir fl~rrrtur, lnhaccu Industry Rcacarch ('rnnmiltre Ihrrrr,r f- rrrrrifut. Ruscoc 11 lacksnn Memprial LalN,ratnry Har Ilartw,r, Maine STANI.FiY P. RFIMANN. M D., Sc•.f). 1)irrct,w Emrrnur, l he Institute for Cancer Research Philadelphia, Pennsylvania WII.I.IAM F. RIFNIIOFF. 1a., M.f). 1'rn/rttrrr Emrritut Ir/ SurRtry Jnhns flnpkins Universily Schoxil of Medicine Itahimore, Maryland EDWIN I) WILSON, Pn 1) . LL I) 1'rnfrru,r Fmrritut r,/ Viral.Sfnriclic.t Ilarvanl Ilniversity ('amhriJge, Massachusetts f(ctltt {( I(' IRx'KI I"1, I'rr t) 1 AI(1RR1CON IIRAIIY, M 1) .1 "n'Lrfr 1 h,r,h,r 4 lli,, I,Ifr .Cf Irnrl/'ir f lfrn ron Introd«ctiori During the past year the Tobacco Industry Research Committec has continued and extended its suppcxt of research. 'f he major direction con- tinues to f.e intn sonre of the many clinical and eaperimcntal factcas that ttill need to be itknlificd, investiRated and evaluatcd in ccrnsideratiun of the origin of lung cancer, cardiuvascular diseases, and othcr cuml.lex constitutiunal ilments. While these research atudies have increased our factual km+wlcJRe, they have at the same time continued to makc clear and tu eml,has'vc the great and critical gaps in that knnwkdse. They have cun/irnrcd tlre sr,und ness of the position hcld and expressed by the T.1 R('. This position is that there dues nol exist tlre esscntial e.f.crimental and clinical knowkdse with which science can even dclinc or idcrntify thc multiple factors or influences that may contribute to thc origin and lrrrrRress of these diseases. This statcmcnt hokls good ls a Reneraliraticm. II also apPlies with even greater siFnificance to jud6mentl concerning the causes cd Ihesc diseaus in any individual human being. 1 here have hecn and will cc,nlimrc to be speculations and opinions on the causes, Dur it it a rrfultrr uf .uirrrti/Ir fact rhar, in our prr.rrnt ttatr of knuNdrdgr, nu nnr An„ws the „ncwrrc R.prrirrrv .Srnd1.. Inconclusive Reported epidenriological findinRs, resultinR (n,m siuril:rr turvcys that use yucslinnnaires and inlerviews, indicate certain ":rcaKi:rti~~nc" tx•Iwccn the incidence of Ihcse dixases antl one or mure cnvironmcnt.rl /actort, includinR tc,hacco uce, especially when that p:rrliculor faclur ic .inyh-J ~,ut fcx study. The mcthoMhdopy crf such auvcys :urd uL,r Iht intr//~rcl,ru~~n nf Ihcir reported findinFs have been caimincd and t'rilit'ircd hy t t -nypctcnl ~leus ticians artd cPidrrninlnRists 5

It is not turprisinR that cvery timc anothcr -mnvcy of this typc ia crm- ducted unJcr cnnditums that are hnridly simil:rr, the aame Rcncr:rl rcwlts are ohtaincd f luwcvcr, the rerrrrnnn of :rn inJircct or uns:rlictactrrry ~cicn- tific pnccdure does not add to the reliability of the data rrllcctcd by previnus enorts of the same type. Reviews and reports cnntinue to appear, bascd mrxtly on sl:rtictically- orientcd survcys llre unquestioning, unreserved enrlrrrscmcnt, as nrncluave, of each such rerHitive report, which contains no ncw ur original d:rta hut amnunts to a statement of opinion, is a disservice lu Irue scientilic rcsearch. l his places an obstacle in the path of accurate recnRnitinn and analysis of the problems that remain before tts. As stated, great gaps exist In knowkdge of the causes of cancer and of cardinvascular diseases. These result in a IarRe degree from Ihe lack of adequate nd coMrolkd nxthoKls of bioa><say of suspected processes cx suhstances, and from the absence of contrrdkd clinical studies fully utitirinR availahle biochemical tests of metabolic and hormonal changes and tkvehrp- men,s under diflerent physicat, physiokrRical, and mcnlal environments, /mproo.m.nt oJ R..enrch SouRAr The T I R('. is continuing its activities in supporting scientific studies nd in c<mductinR confcrences of scientists in order to rklineate mcthrals (d imptovinR research in these directions. As ideas and opportunities for the est:rhlkhrncnl (if ncw rcacirch undertakings are defined, studies will he initiated and crmtinurd for wlrrl- ever pericd Js nccessary to scdve the rnany complex prrrblrrnc that uni- versally are recognized as lying ahead. It is hoped that it may sr>trn f.c (+o•.ihle for var:<rus intcredcd orpnni- zations, now conducting or supfwrrting research indcfiendcnlly crf onc arr other, to coopcrate in organizing prnFrams of mrrre srrphi.tic:rted and potentially more significant studies aimed at filling the gaps in our knowl- edge. This should kad to proRress more intelligently than doxc explrriting exclusively any one over-simplificd hyfx,thesis of specific environmental causation, or of sekctive emphasis nn any one factor statistically asauialcJ with certain causes of death. !Yn Slmpl. "MnRIc RulfrP" E:l.t. The need for a broader, rnure milurc and mme diversifirrl I1rofram of research was evident in results of some invcstiR:rtinns rrf+ratcd durinK 1962. Uuring thal year, scientific work contimrcd trr auplxrrl the view that the quest for a sinRle, simple "magic bullet" to explain the causes or pm- vide the cure for cancer and of heart diseases is unrealistic and probably futile lhe interaction of many constitutional and envirrmrnental factras and influences, some of which still may be undetecled, is becoming incicas- ingly evident. For this reason alone--the fact that research indicates a possible in- volvement for these many factors and inffuences-it is at present scientific- ally unwise and indeed may he harmful to attribute a simple, definitive, causative role to any one of them, or to attempt to assign them relative degrees of imporlance. The smoking of tobacco continues to be one of the subjects requiring study in the lung cancer probkm, as do many other agents and influences in modern living Science does not yet know enough abtwt any auapected factors to judge whether they may operate aione, whether they may of.erate in conjunction with others, or whether they may affect or tre affected by factors of whose existence science is not yet aware. Indeed, it is not known whether these factors actually are "causative" in any real sense. "' 6 7 r~

Ile scarcli I~ indings arid Studies flurinR 1962 the Scientific Advitory Board to T I R C made Rrants for a number or new prnjectt and awarded grant renewals for c(rntinuinR wnrk in the broad areas of laboratory experimentation, clinical invcttiRa- tions, and epidemi(.h.Ry Progress of the research is partly reflcc:cd in pal.crt puhlished by recipients of grants. Since the 1961 Rcpnrt, hll addi- tional repats have been published, bringing the tntal to date t(r 2112. Abstracts of the new papers appear elsewhere in this Report, and may be consulted for delails on pr(>Rress of research. All Rrants awarded by the Board are for studies that prornise Irr ad- vance the Board's objective of stimulating research that will prrwluce help- ful knowledge atarut what is Involved in the problems of lung cancer, coronary discau, and other ailntcnls. Viruaes and Cancer World wide scientific inlerest.in Ihe viral theory of carcinr•Rcnetit is obvious and powirtR Considerable attention was given to this subject at the Vlllth Internatitmal ('ancer ('t)nRrctt held the summer of 1962. Some 50 papers relatcd to Ihe patihihty r+f a viral etiology of cancer were presentcd, cnmparcd with only four p:q+crs on that topic at Ihc ('ancer ('onRrrst held only fnur yeart prcvurutly 'lhit inrrcattd intcrctt in and attrntion trr virus cancer rctcarch it indicative or Ihc r:rl.irl chanRct that can take place in retcarch ctmcrrtt irrnccrninR canccr. Vinrtes have been thuwn to in(luce a varicty of canccrt in several nimal sprcics In 1962 there were rcpatt Ih;rt human adcnrrvnutes known to cause resriral(xy ailmentt snih as coldt, when injeclcd into c.{.cri- ntental animalt, had resuited in Ihc dcvel(lI+mcnt of ('anccrt in thc animalt As with other aRcncics, the *1 1 R('s rctcarch Rrants in Ihis field have been increasing in recent years One T:1 R(' - supprrlcd study is seckinR lu dctcrnrine whcncer injected vital aRentt, either alone ur in cornhinatinn with variout environ- mental factors, will result in meatrnahle clfc(is on the IrachcnF,r(mchial tree and pulrnnnary littuct of lahoaatrrry aninrait 'Ihit wrrtk :rltn will Ix cxtcnrlcd In intlndr titurrt in nryan cullure nnnthrr tludy in prnRrett invnlvet Ihc qurttion of any rnlcrrrlnlrrl rulr thyt inflrrrnra virus rnteetnrnt, r.hnure tu ( IR.llrttr trn.rke nnd r.lhrr /er tort may havr in Ihc rlrvrlnhmcnt nf fwlmnnary anrl hronrdrial Icv.rnt in rnr((• Ihia (•.urrcul.rr .IU.ly it an retrntii.n r.f work that Ir.r% Lrrn tul.I•.arrJ Inr .rvn.rl yr.u~ rnru rlv r.urrl.orrl hiN.,I~,F•y r ylr.l,.ry, uml r yrr.Y hr nrr.lry or thr u.r. h rJ.r.m hr.J Irrr .urrl Irmrt r,l r~l. nnrcnt.rl mmnr.Jt I Also under way is  project involving the use of chemical agents in virus-free animals to see whether it is possible to clucidate Ihc rclahunship, if any, between viral and chemical carcinogenesis Cell Studies Of vital imptrtance to virtually all esperimental scientific endeavnr is work involving the cell. For years the T.I.R C. has been supporting hasic cell research, aiming primarily at the training of more experienced workers and at the development of more reliable and accurate techniyues. While previous interest lended to concentrate upon the morph(doRy of cells and morpholrrical changes, the emphasis has now been shifted In the area of the metaholitm and behavior of «lls in resl+onse to varirnn Ireatmentt Studies now in progress aim al describing basic dillerences between normal and ahnormal, or cancer, cells in virro, rcRardkss of how the cells may be affected by the challenge of some external asent. Of course. In a sense a normal cell in a culture medium is not exactly "normal" because It has been removed from the medium of its natural host. In (wx laboratory scientists found that continuous ultraviolct irradia- lion of the nucleus of a living cell produces damage to the nucleus Smrilar damage was found to occur with the use of certa•Kr chemical aRents. One imporsant implication of this particular work is the possibility or developing and prrfectin6 a more rapid and accurate bi(iassay methad. A series of agents, among them polycyclic hydrocarbons, are now being tested in the hope of developing a semi-quantitative biuassay for relative carcinogenic Ixrlenlial or activity of a multitude of suhstances. On April 21, 1962. the Scientific Advisory floard sponsored a con- ference on cell differentiation at the (nstitute for ('ancer Research, Phila- delphia. Among the topics discussed at the jnfnrmal session were the lac- tors within cells kadin6 to and guiding diRerentiatian, and the inlluences on cells of various environmental factors, ('hemical recrmstitutiun of un- differentiated tn differentiated cells received Altentiun l)itcuttcJ were crllu lar and tissue p+lentialt, influence of chromosomes and Rencs, varirrut frrnns of "mutalion," urprniration of tissues, and other topics. In addition to sta0 members and memtxrs of Ihe SAIf, the /ullrrwinR were present: 11R /()/1N 1' HONNI R. /'rIn(rlon U.dvrr.ity, 1'rin(cton, N I I/R IN)N W FAW('Y.1•1, It.rv.rJ Univrr.ily, ('amhrldRr, M.,t t)R ('l 11-1//R1/ W GtIRNFV, ttnrvrr.lty o/ ('hic.g.r, ('hr,.p,, tlt 1)R At 1 N117 1' MIRCKY, Rr-Ir/rtlrr In.fitutr. New V.vll t)R /(//tN NtINNCIRt)M, Wrunrr (irrn Intrllulr, \t.h~huhn, S..rJrn 1)R. F. (' SIt Wi1R1), ('urnrll Ilnivcrsity, Irh.ca. N Y 9 x

I rnrn Ihc InttUtnte f++r (•anccr (tctcarth A(ARI! Ila 81 RARI/1N(1• I'h I) 11 R()t•(t-, I t R/: FI), Ph 1) l 11()MAS 1 KING. 1 h 1). A I IMA 1)F UAINF, Fil 1)ir , Rctcarch I cllnw MARIIN 1. NI'MhR, Phl). RUI)I:R T P. PF RRY, Ph 1). (:I'ORUI? RUI)KIN, Ph 1). lA('K S('HUf.TZ. Ph f) l IMOf IIY R. TAI PUT, )R , fN f). ('ar(liot+a+(•trlnr 41'erdi(•s Surl.r.rt of cardiovascular retearch conlinucs U+ he an imf+++rt:urt f+art of Ihe Advitury Ilr+ard's recearch prr+gram. T hit it a cuntl+licatcd and carn- pfet fic•hl and cncrrmpatses, of neccccity, a variety of sfa•cific tr+piu:t Work cr+n/inucs tm a T I R(' cupp+rlcd pn+iccl which it ceckin6 to dcterminc if cnvirrmmental factrul have any effect on the dcvctnpmcnt r+l athcrr+sclcn+tit at revealed by autofny atudict uf accidcnt viclirnt traincd interviewers are suckinR to Icirn all they can :rhr+ut Ihc victim's life -hit dicl, hit smoking and t+thcr hahitt ti+ c+nnl+.uc ++r cnnnccl thic inh+rma- liun if I+rntihle wrlh the aut .lay +I it + In Ihe tarnc Rcncril fu Id .+ I I k t t r+nir r h r, it 1-rrr• 1 lindmr Ih:rl durinR tmc+king thcre w:)c a r+.c in •- I.ouN .++r,/. (I I A ) m 17 palicntt with hcalrrl myr+cir+lr.+l rnl.+r+r-n 1r, h.l A Icv.rr n•c w:rc found durinR smr+kinR in I(6 n++n +„r++n:+rv I+.rncpt., :nn1 thc tc.c:+rther suRfesaccl that the Frcatcr FTA rctP+~ncc in rlre cunm:rry P:Nic•nlc rccaltcd fmnr a Rrcatcr rclcicc of catechr+limine after nicutinc slimul.rtir+n I F+it chf- ference in reap+nte, if ct+nfirmcd, may reflect a cunuitulir+nal Jillcrcncc hc- twcen furumt who are prcdiya+ccd lu cc)rcmary diaatc and thu.c whu arc md It it, (+f cr+urtc, nul known what Ihc cRcctt may t.c• rd rerx-titivc ricct in the f.IrHKI Icvclt r,f FFA, whic h actu:rlly are a vital fHtily fuct I'mvt murtcm cr+mparicnnt nf Ihc degree nl athcr~+cclcrntis in the curnn:rry aricrics r+f tnu+kcrc and nr+nvrtukcrs have thuwn no tiFnilic:+nt dillcrcncct Anirn:+l cxf.r•rimcntt tarried rwt under Ihe I I R ( ' f+n+pram have :+Icn thr+wn nr+ clcar rtilTcrcncct in Ihe dcRrce d alth+ r++cclcn+cic in chulcttcr+d Icd animalt ++f tevcr.J tf+ccict at a cnnscyucncc +d chronic nitutinc irrit:rtnm SnrnLlrnR an+f Itt.rnrl Flow Of iinf-rt.ince in the c:+rJir+vaccul:+r ficl+l ic a rcccarch f+n+jcct that a nl.l t tn in+ aij•,'tr Ih(• cllt +t I+f r„I~.++tn tnwkinP rm tkclct:+l muctlc i blood fluw. I hcrc has been conflicting evidence on Ihit suhject in Ihc few ftudiet exittinR in the mcdical Iileralure. Working undcr  T.f R.C. Rranl, two Ilc+ston investiRah+rs uced the disappearance rate of a radioactive iscNope fronm skeletal nroscle as a measure of its nutritive blood flow. (N 17 normal subjecls studicd. 14 showed an increasc in skektal muuk nutritive blood flow as measured by the radioiccllupe disappearance rate during cigarette tmnkinR dccf,ite srnall changes in total calf blood flow and the usual decreases in skin tempera- ture. 1 he mechanitm of such an increase slill remains unknown According Io the scienlitls, lhis wc)rk reveals constancy of the increase and suRResls hat inhalation is not a factor. The investigators reported that evidently an inlact nervous tupply to Ihe limb is unnecessary since three of four sympatheclnmired limhs also +howed an increased disappearance rale during smoking AttuminR that skin blood flow docs not decrease in sympalhectomircd limht during smok- inR. Ihey said, the increased disappearance rate does not represent a simPlc shifl of hkKxl from the vasc)constricted skin to the musck. Nlrotlne ond Cor6on A/onorJde The Scientific Advisory Roard has alNl aulhorired a study to sce whether determination of inelaholites of nicotine or of carbon mum+otide in the blood s(ream will Rive more accurate infrrrmalir.n nn the ealenl to which cigarette users inhale the smoke. Nicotine is ahsorbed in some dc- Rree in the buccal cavity and lo a greater degree folNlwinR dccp inhalalion uf unoke. Carbon monoaitk, on the other hand, is reputcd Iu be absurfxd only on deep inhalation. Perfection of such ntNhods may permit mnre accurate dclermination of true physir+luRkal smoke eRpt+ture front cigar- eltes, pipes and cigars than yucstinnnaires on .mrlkinR hahi/s and Ihe depth of inhalation, and thus may raise correlation sludicc to a new level of reliability. T'he methrxlt dcveh+pcd in this ttudy will be utcd by the invettiRatras lu help intcrt.'rct resulls of anulher project on Ihe relatir+nchip hclwccn steroid levels in hrxly ftuids and various forms nf hr.ul ditcate aml crrl:+in lyres of maliRnant tumors. Thit latter prr+ject is tu he tulqw+rred by a federal agency. An invcstip,atinn hat hccn inaufuratrd with rcFarJ tr+ c.uh+.n rni+n r+tidc The amr+untt r+f carM+m mtim+aiJe that can f.c :rhsr+ncerl cv+•n rtur.nl-h very heavy smr+kino have been shr+wn Ir+ lie well f.ch+w Ihc tr+tic Icvcl S+nrc the Iracct uf carbon munotidc Prcccnt in ciy-arcUC smr+kc arc rcl.+uvcly cnnslanl. Ihit ttutly will seek lu dctcrniinc whclFher hI(NMI Ievl'Ic r+/ c:uh+~tY henu+Rluhin, whith can be dcrcrrninc•J very atcuratcly, will rcnrtt thr 1I

dilfcrt•nccs Ixtwccn Ihe amr+unl of trm,kc cr+nlict with Ihe alvcr,li invulved in scvcral dil)crcnt lrrtntt of Inu,kinR Work also is hcinR sulqxrrtcd wilh the r,hicctive (d learning sonic- thing about Ihe eflrcls r.f nicrrtine tin the cerel.r.rl crrt'ulatirrn A Icchniyue of anRioRraphy has been developed whereby it is possible 1n take what amrnrnts to x ray "movies" of the hkxxl flow in thc cranial vt•sa:+It includ- inR the srt-c:rlled "circle of Willis," the structural didrihutir.n syatcm that mnnitnrs regional cerehral arterial flow. This technique has alrearly shown its value in diagnosis of circulatory obstrvclion. 'I his and other studies are supplcmentary to previuus inrlicatinns that nicrrlinc may have stimulating nr, in some ways, tranyuitirinR ellccls (in the central ncrvr,us systcm. Cnnf.renr• on ('.rrbrnl F: f'.rf. of Nirorlne A conference on the eflccts of nicotine on the central nervous system was held by Ihe Scirntific Advisory floard in New York un Sept 2R, 1962. Wurk under way in Ihis area and sqccifrc topics in need of furlhcr research were discussed by prantces and others investigating this particular fich). In addilirm lo mcnmtx•rs (if Ihe T I R(' tlafl and of the Itoard, the following were present: I)R A K ARMITA6F, KinR's l',dlrRc Iln.pit:rl Medical Schrxil, lon- t)on. FnRl:,nd. I)R lil)WARI) I" I)OMINO, Thc Ilniversity of MithiRan Mrdical Schrxd, Ann Ar)xx. I)R. FSKII. 11ANSSON, Onivcrtily of California Medical ('rnter, Ios AnRrlr. DR FHPI? ('(1RT1S 11Ot F Ar.n T)R. CIIARI IiS H(X'KMAN. Medical ('olleRc of VirRinia, RKhmond DR PAlll. S I ARSON, Medical ('ollef;c of Virginia. Richrnund DR FhW/1Rh W. PFI.IKAN, Iltnton University Schcx,l nf Mrdicinc hR FI C - SARF.t I I, (7ricaRo Medical Schtxtl, ('hicaRo. III 1)R CARI C. SFLTZFR, Ilarvard Ilnivrrsity, (brnhridRe, Mats DR f)tIANF (: WENZII , Univrrvty of Kans.., I awrrn.e Studlr. In rlhe clrrufnrory Arcn New sludies now heinR supl-+rtcd in the Rrntr:tl cirt'uL.tlr+ry area are cnnt'crnerl with vasuular retlwmtcs Irt Ir-haccn tnutkinR in Iratirms with vascul:n th.ra~e, thr relcatr 0 c.1trr hrrlaminrt hrnn Ihe iau)alyd hrart. Ihr rll. , 1 - ,/ ni~ ,,,u,r ,nJ rr t,,- .I .,,1• r,n, r„n .,n,u,r I,'.cl, in Il,r nrrvrmt i A study was undertaken to investigate thc contn•versia yucslion whether I)uerRcr's disease and general peripheral vaa-ular disease are scparate clinical cntities. Research done un+kr a T I R(' Rr:rnt led the atnMas lo cr,nchrde that they are. The study investigated Ihc IlucrRer syndrt+mc in Palicnts, most nf whom were heavy smokcrs, in Ihc Orient, whcrc it was fnund Io occur with relatively high freyuency in Japan and Korca among f,crsuns of low socio-economic class, and in the l)nhed Stairs It was found that those already afflicted with the BucrRer syndrun+e were scnsilive to tubacco, but there was no implication that a similar sensi- Iivily occurs in persons with general peripheral vascular disease Multiple factors of undetermined etiology seem to he involved. Work in this particular field is continuing with a study of IluerRer's disease among various Jewish ethnic groups in Israel Sonic scientists have reported that, for some still unknown reason, the disease pixars to afflict male Jews more than those of any other race. Of interest in coronary research are the several studies that have been previously refxxted on the relationship between the incidence of heart disease and stress One survey covered 1O,(100 physicians, dentisat, and lawyers subdivided 3ccording to the relative stressfulness of their special- ties. Its author, a cardiovascular sixcialist, reported that emotional stress arf+eared to he an important accekratin6 factor in alhcroRenesis when the diet is relatively high in animal fat. Other researchers have relxxled finding an association between coronary disease and emotional stress anti strain. The investigator is alxrut to underlake a similar sludy with stock market workers under a T.I.R.C. grant. SmokinR nnel Prof.in Metnbo/iam It has long been known that young animals esposed lo tohacco smoke or treated chronically with nicotine, gain weight at a lower rate than nnn-e><posed controls. If pnNcin access is adequate, survival nf the animals is not impaired. followinR rclx,rls from F.nRlantl that rats to esfx,sed eRcrNe rmue nitrogen than crtnttrds during the dutation of the cRfxrsurc, an invcslipatinn was heRtm In determine whether an analaRttus cRect call be trhservcd in healthy, younR hrnnan suhjecls Cin.Nr an.f /'.v. An l'Av.iulntlrnl Fnrfnra Of cnntinuinR inlcrctt to Ihe S, icmifit' Atlvisury Ilrrird anrl tn r,thcrs is the rclalivrly unc.ph,rcrl prulhlcros of Ihc varyinR ;tnd Jttlrrin/. t h.rr.r, Irr itlics nf Ix•rqdr `rnrtrr. Irtythn/r,Pical and Irhyti„Irq•.u:rr an,l thr h,.urnK of such ddlcrrntct r,n di.c:r.r Prrrli.lrrtilirm I1

It is now rccnRniretl fnvn a number of studics here and abroad that thcre are mcasurihle or dclectahk dillcrences hr,th among people whr, arnr,kc in v•rrious ways antl betwcen thosc whrr tlo anrl Ihnae whrr do not vnn,ke. auFpevting that smr,kinR practices rney in part rcllert cnnslitu- Iir,nal f:rctr,rs that may influence different disease predileclions One ttudy of male patients at chest clinics reported that thc rersrrn- ality traits of IunR cancer patients diflered significantly front thnse nf cancer-free l+ersnns. A T I R(' -supf+nrled study of a biologically nd culturally homm Rencous group of Italian-American factory wnrkers, almost all born in this cr,untry. found that the kaner individuals smoke significantly mrrre than the str,ut or fat, hut not muscular, nnes. ('ontrary to other previnus rerur,s, the sn+okcrs in this Rsoup were no less maxuline in phytiyue, no more acuve, and cr,nenrned nco more akohrd than nnnsmr,kcra Anothcr cOntinuinR study is seeking to determine ur define lite prc curson of hyfxrtention and coronary artery diseate in a itroup of medical schrw,l students Reports already have indicated that a familial factor is involved A prosrective phase oP this long term prnject is the analysis of figure drawings obtained from the students It is believed that thcce fiRurc drawinRs may provide a simple, eflective, psychrdnRicat screeninR device for Ihe personality appraital r,f normal suhjccts Also continuing is a stu ly of the psych<dr,Rical, cullnral and hcilth ehiracrttictics of aging tmr,kcrs and nr,ncnurkcrs Another invcvtipatinn just beginning will scek lo exansine lite e><tcnt Of and cunaitutinnal haait frx diflcrences in taale untitivitict, and their I,r,ttihlc cnrrcl:rtir,n with any cnn.titutinnal prcdit)xrtitiun to palhrdr,Ric cuntlitiont, with dillcrrnccs in smr,kiriR practices and with frKK1 dillikes Also RettinR under way ic a sludy inur pcycholoRical influenees uitrrn the translation of motives into action with smr+kinR behavior as an inslance. Cls.mJrtry enrl R1orR.mlrrry 1 fre Scientific Advisory Board awarded a grant to scienticls . I Ntath Carolina State College to measure the levels of arsenic ahaurfitiun by tohacco plants in relation tn soil cnnlent of the element and U, tstimate the residual levels of arsenic in the soils used for tohacco RruwinR in varir,us parts nf the state. 71rt study frnrnd that anenic in snils tanPrd /Yr,m I/rr S f,.rtt l+er millir,n (l,l,m ), with an average for all areas rrf the state of 7 X hl,rn 'llris value ii clo+c lu the 4 pf+tn ref,<,rted by 1 1: (;rravca in 1101 1 1„r a vitlvn soil anrl thus +uyPrs/t that there has l.ten n.. nleTlnral,Ie inr rcaae frr,m the I,rrvinu1 u, nf ar.rnitnl ini,c(tuidea in IFhr ar%enic c.mlrnrs r,f auil in wln, h " i. Rrt"n '1hc invcstiRators reported arsenic in the cured Ic.rf uf luh:ntn Kr„wn in these srnfs was from 0.5 to 3.55 ppm, with an avcraFc (r,r all Icaf tamldcs of 1.5 ppm Also under T I R C. support is a study designcd Irr sce whether various annrunts of trace metals, including atsenic and nickel, when added to tobacco, will have any effect on the incidence of pulnron:rry ademmras in Strain A mice that inhale the smnke front such tobacco ('ontrhl .tudics will administer the same metals by other routcs. Another supported project will attempt to identify individual poly- phenolie compwnds in cigarette smoke and to estimate their amrwnts Where feasible, these comfaronds will be prepared for future or concurrent studies on their metabolism and possibk effect on human I,cings. I:PJrIt•mJol..Rltnl Aren A study is now untier way into the influence of certain envimmuental factors in the genesis of neoplastic disease in tuberculosis patients and in children. Tlrc work is being done by four California scientists who received a grant from T.I.R.C. to augment their eurrent project uf testing Ihe hypo- thesis that medical uses of radiation are associated with an increase in the incidence of kukemia or other malignancies. The T.I.R C.-supprsrted project will seek to study the incidence of lung cancer or other cancer in tuberculosis patients with a dcsiRn that would atcertnin the relalionship, if any, between lung cancer in .uch p:rticros and three facUxs-tuberculosis, cmokinR habits, and radiation eagxrture Alur under way in Massachusetts is an epirkmirdugical IunR cancer study designed to check a previous investigation. lhc invcsliRaturs fr,und in earlier woJk that there apf+eared to he a statistical corrclatirm between lung cancer and cigarette smokinF, respiratory illness, heavy crmvuml,tion of akuhol, and uuttlocsr oeeupaliun They said that whilc thc st:uimic:d correlation between lung cancer and cigarette smoking was slnml;cst, lite data !uggeated that a threshold in consumption had to he I+asacd befrue a linear relationship occurred. The dala further shawcd, they rryNnlcd, th:rl the same level of cigarette use with rrddirirrn of pipe or rihnr trnokinR dinrin• ished the disease associatinn, a tesult dillictilt to intcrpret LunR Phy.J.rfnRy Certain phnses rd lite aclual mcchanical wnrk rd lite hum:rn 1unr. renrrin a mystery lo icience (hte .uch rhase is irubn„n:uy clr.u.mce exactly how drKs lite IunR remove inhaled f,articks A stu.ll m,w undrr way in this suhjrcl deal. with the pIragoeytes fuund rn the I,ulmr,nary alveoli. IS 1.1

lhe work heRan with Ihe cnncept (if nrraturinR the ovcrall IunR clear- anct• capacity <d healthy, intact rahhilt RaJrrraclivc srlvt•r nKlidc• I I11, ( whi(h it alco used by mete<nulr+Fitts to secd chrudt for larrlut lirm td rain) was inanKluced into the IunRs of the rabbits by a m n inhal:rlirrn pmcedure lhc rnuvenunt of the radioactive element was then traced with sensitive measuring equipment. It was f<wnd that eventually all of the 1-111 was engulfed by the alveolar phagocytes and carricd Irt Ihc alimcn- tary canal whence it was e><creted. The current phase of the study erKompasses the inhalation nf whole cigarette smr+ke following introduction of the 1- 1)1 in order to rlc,t•rmine the overall eflecl on clearance rates and the relalive rates by alternative routes. Other nimals are to he used in the projrct in adrlitirrn In the rahhil, and druRs that aflect the flow (if mucous iltn arr tn hr invcar~atcJ, as well as the ef/cclt (if other inhakd Rascs and acrnsuk. Afrv..fl Srurlir.t fn Pufrnr.nory F:nrphr.rma Recent ditcnvery that a powerful surfactant tnhstance lint•t the alverdi has gone far toward etplaininR Arc hitherto mysterious physic'aI character- istict of these structures and their cehavira durinR espansiun and contrac- titm Morerwer, the effects t+f Ihn apcnt and the crrnscyuencct of its tlcfic'icncy tupFctl that a hirchcmit•rl appr<tach to the invt•.Ul;:rrirrn (if the etinlupy <d rrnphy%ema may now ht• within rcach A prr-jccl hat t.ccn cf,rmtrncd in which lunp tittu.•t rrhluinr•d at curp.ery nd at lrutr,fxy are heing studred 11 will attcmpt 1<t ruca.ruc the rctative activity of thit tutfactant rccrrvcrcJ frrrrn lunpt allliclcd with carcinr+ma, ernphytcma, and hrnnchiccta%is I Ilrnt will hc ru:rJt• tn dr<r nninc whcthcr tobacco sm<tke inhalalinn :dlccts Itte activity rd this surfactanl, and furthcr study of its chemittry will fx undertaken. A report by a T.1 R('. grantee in 1962 said that bronchial distutb- .nces may pnxlucc an ohstructive airway mechanitm IcarlinR to air trap- ping as well as indirectly inllucncc surlace tentit,n phcnnmen:r in the lunF or impair clearance (if entrapped pollutants In this way. Ihc rc(Kxl sairl, ertxion (if the alveolar nrcnrhranc is initiated I A comparative study of the effects of 7-mcthylchnlanthrcne and ciR- arettc smuke cunJt•n<ate applied to the oral tissues (if Swr.s nucc in wMth liver danrape has hecn previously induced. T he purificaliun and structure tkterminatit,n of the cfdor<rgcnic acid Isomen. Mechanisms of the psychotropic effects of nicotine. Fellrrwrhip ProRrarn In 1962. as in every previous year since 1955, the T.I R C , upon recr.ntrnendation of the SAD, pxovitkd funds (ur the granting of fellow- ships lo the nation's accredited medical and osteopathic scht>,dt Nearly (.(K) young men and women have so far received fellowships. 1)eans uf the schools choose the fellows, and the studenlt, working with their faculty advisors, determine the subjects they wish to study dur- inR sunrnxr or othcr ufl term time. '1'he felltrwship pnrRrans secks tu stimo- lale interest in basic research amtxrR medical schrMd ctudents and any subject of study may be sekcted by fellows, without regard In its relcvanc; to tobacco use or effects. Sunrnrnry 'I his narrative section seeks only Itu indicate hriclly srnne uf the rmorc recent findings and trcnds. More compkte delailt will he frrnntl in previrrut Annual Reports antf in the abstracts they contain Work in ruany <rl thctc ficlds is continuing to receive support. In closins, it seems appropriate to reiterate the hasic belief umlrrlyinR the Advisory 1loard's pcxilion, which was fully e>tpresscd in the floard's report two years ago. Tlrat report ctrocluded w~th lhit paragraph'. "As the tobacco industry continues its suppnrt of the scarch for truth and knowlcdge, it must rcctsRnisc, is is always the case in true scientific research. there can he no promise of a quick antwer. '1 lie inqxtrt:rnt thiuR is to keep on adding to knrrwlcdqe until the accurnuLNivc factt pruvide the hasis fta a srrund cunclutirm " nthrr /'r..)rrfr Antt.nR the other prnjccts, whir h arc unJcr way in institulions tT tn thrnuphtrut thc c<runhy, arc'. A sludy rtf the rlatal In<I ph.uVnl•cal h.rr Irrral Ilnra rrr ~mrrk'rt• rurn m n U. u r tmrrkrrs nnd fnrrnrr snurkcrt I hr .rn. l r-Ui~6~1•nLrr rnr. irr Inincvy lunt• t'inim% :r. iIctcrnunrd (r.mi I-ntmn1h ui nl,.rrv.iW~n~ I7 I 6