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CTR HN 011620

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S(:IF.NTIFI(: AI/VIS(1RY It(/ARI1 to lhe Council for iohacco Research - t/.S A. KFNNIiIH MI: RRI1.1. LYN('i1, M 1), Sr' I)., 1.I. t7, C'hoirman ('honcrUor ond PrnJrsso. Emrrinus of Porhe'l.+Rr Medical ('olleRe of South C.rolina, ('harleston, South Carolina tNOWARI) B AN(N?RVONT, Sc D. Srirnri/Sc F dirn., f he )cwrnal of the Nationat ('ancer Institute Ilethcsda, Maryland RICHARD ). BIN(), M.D. ProJr,ror one ('hoirmon, Department of Medicine Wayne State l)niversity College of Medicinc, Iktroil, Michigan McKF.FN CATTF?LL, PN D., M.D. Prn/rssnr Fmrritw of PhsmaofoRv ('omell l)niversity Medical College. New York, New York I.FON O. JAC()BSON, M.D. Dean of the Diri,ion of Rioloticof .tclrncrs RrRerurrin Pro(rssor of Rioloticol.Scirncrs ()niversity of ('hk.g+, Illinois CLAYTON O. LOOSL1, Ph D., M D. //asfinR, Prn/rsror of M.Aicine mnA PorholnR y l/niversity of Southern C'alifornia School of Medicine I.vs Angeles, C.liforni. ('LARFNC'E COOK 1.ITT1.P, Sc D., 1.1. 11., 1.tt t 1) Scirnti/k l)irrcar, The Council for Tobacca Rrsearch - I I S A. Dirrctnr F.nrrrirus, Roscoe Is Jackson Memixial LaMiratory har Harbcn, Maine •STANLEY P. RF.IMANN, M 1)., Sc D. Dirrcror Emrrlrks, The Institute for Cancer Rc+earch Philadelphia. Pennsylvnni. WILLIAM F. RIENHOFF. 1.., M.D. Pro/rsso. Fmrrirus of SurRrry Johns Hopkins llniversity School of Medicine, Ilaltimore, Maryland SF1FLDt7N C. SOMMERS, M.D. Pro/rs,or of f arhofoRy Columbia l Inivenity College of Physicians & SurReons New York, New York RnBERT C. H(K'KI?fT, Ph I1. A»ociarr Stlrnrr/Sc l)irrcr,N 1 MORRISON RRADY, M 1) 1(NIN II KRFISFII'R, Ph 1). Amwiorr S(Irnrifir 1)irrrkrr As,(Niarr.~~irnri/S(~ l)rrrrfnr I I Stanley P. Reimann. M.D.. Sc.D. 1891-1968 Dr. Stanley Philip Reimann, a patho4ist and widely-published cancer speci.list, died on Wednesday, February 21. 1965. Dr. Reimann h.d served ns member of the Scientific Advisory Board to The Council for Tobacco Research-U.S.A. friooe 1954. As- sociated throughout the Tetus with the Uni- versiry of Pennsylvania. Crodn.te School of Medicine; llahnemann Medical Co11ege, and Lankenau Hospital. Dr. Reim.ne h.s.erved as president of the Amerk.n Association for Cancer Research and the American Sockty of Clinical Pathology. In 1925. Dr. Reimann founded the Institute for Cancer Research in Foa Chase. Pennsylvania, served as its tci- entific director from 1945-1956 and emeri- lus director. Believing that malignancy was a probkm of growth and teaching that the most eRective way to find a cure for cancer was to achieve an understanding of the pro- ccsses of growth. Dr. Reimann, through his life and writinRs, eserled a widespread in- fluence on cancer research. . VINC I N1 1: 1 ICnNfI, I)M1tI) l,tInn/,.44vv rore

TARLF OF c(1NTF.n7•S Inhoduction. . . . . . The ProRress of Research Abstracts of Reports . . Psycho-PhysiotoRical Studies Cardiovascular Studies . Carcinogenesis Studies . Studies at the ('cIlular ltvel FpidemiriloRy . . Pulntionary PhysiokrRy . NeurophysioloRy . . . . Chcmistry and Biochemistry 5 6 15 16 IB 33 r 36 39 41 46 49 Pharmacology and Psycho-Pharmacolo6Y . . . . . . . 52 Pregnancy Studies . . . . . . . . . . . . . . 54 ()ther Studies . . . . . . . . . . . . . . . . SS Recipien,s of Gr.nts . . 57 I introcluctiori I he Council came into being fourteen years ago (originally as the Tobacco Industry Research Committee) to sponsor financially a wide vari. ety of original independent research studies related to smokin6 and health. Other aRencies, both private and government, undertook also to support research in 1he same general arta. Thus, thett began a widespread ellort to gain more scientific knowkdge of a subject about which little was known. 1 he ramifscations of 7 he Council's research program have been and still are, quite e><tensive. Many scientists who have received and are receiving support from The Council have turned up knowledge and information of value in the ongoing eRort to uofve the riddks of cancer, heart disease, and other major ilments afllictirt mankind. Another benefit to both the general public and the scientific community of The Council's research program is perhaps more obscure but no less im- portant. The fact that reputabk, independent scientists at leading research or6anizations and institutions ree the need for more study is a clear indica- tion that the smokint and health situation is not as simple as some people would have us believe. The incidence of the various and suhdry diseases attributed by some to cigarette smoking would be a major public health problem even if smoking were not a worldwide custom and had never esisted. Many people who have never smoked now die and will continue to die from the same diseases as do those who do smoke. Many people who smoke do not die from the statistically implicated diseases. Whether smoking, as such, is ot is not involved in disease or death of certain individuals is still not the solution to the major problem. This solu- tion depends ors research which, it (s hoped, will lead to the detection nf thcne individuals who, with or witM.ut smokinR, face in cmmmum  greater riak of rkveMPinR or cr>sthactin` any of the diaascs which have hecume thc ma1or survival drreats tu m.nklnd. '1 here is increasing and significant evidence that cumple.. Rrnrtically, innate individual diflcrences In susceptibility and non-fusceprithrlity, whith aRr^,t the rate of aging and the imbalance of various organ and tissue lunc tions underlie and profawndly affect the three major f•ublic health laot.lenrs - eaneer, cardiovascular disease, and mental heallh. t 5

'I'hc I'ro ~9ress of Rcscarch The Council for Tobacco Research is and has been engaged in support- ing studies of thcne diseases that are currently the greatest causes of illness nd of death Of course, all these diseau-s occurred, and mtnl wete well known, hefore the use of cigarettes became prevalent, and they continue to occur among nommokers flence, any hypothetical or even real eRect of smoking could, at mcnt, he no more than a ctxNrihutory or ggravatinR factor in these dis- eases rather than an "all or nothinR" clouse of any. Fpidcmiolo6ical studies have been and still are the subject of debate by statisticians with respect to their rrliahility on tcchnical Rrounds. Addi- ticsnal research aimed al rectifying anme of their rkficiencies and clarifying rome of the curinui cnntradictirms an•I rcculiarities are nccdcd. It is a fact of histnry, nevrrlhelrss, tlrit theae rlnJrmudhiRi,.rl rerirrrts prnvidcd the im- petus for ahundant rcaeartir rrLrrurR in onr way -a another Iit °rnhiccrr rnd health" Ihal his auhsequently Lrrn undrrt.krn hir m.rny .crcntiua Ihit re- scarch has been sl.rrnsored by pwrrnnrrnt drparlmenta and by a number of voluntary hcalth aaociatir+ns and foundatruns rntludinR Ihc ('rruncil for Tobacco Research and the American Medical Aaarrciation Educalional and Research Ftwndaticxr. 7his was a logical development since a reco6nired - indeed, the major - rok of epidemiol..Rical research is to identify areas in which more minute and ettended studies of other kinds may be needed in the laboratory or clinic. Within the Iasl half century, notable progress has been made in the control of the Infectious disc.sts with a consequent great rise in life e><pecla- tion. T/x average infanl born In this country trday can e.ptct to live almost half again u Nrng as one born in 19(N) 'Ihis nxdical triumph has prnMluced a pnpulalion containing a larger prolxxticxr of older penons Ihan any herc tofore encountered In history. With this Increase in the older pnputatinn, disahility and death due to chrnnic nr drRenerative ailments such s cancer, disnrders of the heart and r.rterics, and chrrnnic respiratnry diseases have shown a rrfarive increase. 1 urther prnRrras in improving lifr e./tectancy must therefore cr+mc largely I I I from new methods for preventing or deferrin6 the development of such dis- eaaes, which characteristically have a slow and insidious onset. f:+tperts in these fields point out the complexities that are to be expected in the causation of such diseases. Their origin and development involve various degrces of host susceptibility or of resistance which are deep-seated in the constitutional or genetic nature+of each human individual. This "built in" susceptibility or resistance may then be•modified Importantly during the life span hy such factors n aging, sea, relative activity of the sever.l glands of internal secretion, and the individual characteristics of food absorption, utilizaticsn, storage and excretion. Daily life practicea such as eaercise, hours of tkep, use of coffce, tca, tobacco, akohol, and the common household dnrRs, eaptsures to all kinds of materials and substances on the job, psycho- N,6ical characteristicY, and the stresses that assail the psychrs-physioh,gical system, may play a role. So may also the numerous bacterial and virus infeclions, mild or acute, which all persons still eaperience even though these are much less often crippling or falal than formerly. Great bodies of date concerning such factors of internal and e><ternal envirnnmental oriRin, have been and are being collected in studies of cancer, cardirnascular diseases, chronic pulmonary diseases and general mortality. In such studies serious fallacies in perspective can result from over- interpretation of one-to-one correlations even though these may be valid mathematically. Hecause of the lack of multivariate analysis, emphasis on the single factor of smoking In a number of epidemiolnRical situalirrns involv- ing numerous unanalyzed factors may well have masked other Isrnsibly im- pnrtant factors and misstated or overstated any possible significance nl smoking. The pressing problem is therefore to bring the methods of multivariate analysis lo hear for weighting these various (acrors relalivcly, in a mathe- matical scnse, as contributors to the final evaluation of causation and devel- opment of a disease. The IaMaious classical method of multiple regression annlysis is now being superseded by new computer methods capable af handlinR a large number of variahles simultaneously and rapidly for "clusterinR Icndrncics." Such mrlMMls nerJ to he applied comprehensively hr many large awwlics uf dat* that have .Ircady t.een and will Le collected in thc srarch fnr tlurs to the elirduRy of tkgeneralive disease by epidendoluRical nredudh. I he Council is aiding in the development of such csxnlwler techniques and their application experimentally to certain bodies of dals that have been cnllrclcJ in its sfrinsr.red projects. There is also a great need for studies that will show how the many other 6 1 7

hahils and practices of life tend to he astt.ciated with smoking or nnnsrnoking. Only as wc develop a picture of how smukcrs nnd monsmrtkcrs di(Ter in such ways, will il become possible to distinguish between f+ncsihlc cf(ccts of smnk- ing per tr and the c/lccts of nthcr ssuuiatcd hahils in the causation o aRgra• vation of the various constitutirxral diseases. In this kind (if rcaarch also, computer techniques fnt multivariate analysis should he very helpful and tirne-saving (:(rrtcer of the I,trrrg In a sense, lung cancer carrks a particular emphasis in tohsrro and health investigatinns because of the reputcd "ttrcngth" (if its astix•ialion with cigarctte smoking nn monofactorial eridrminlr.gical sludics. Another reatnn is the rate at which this ditease is reported to have increased in incidence within recent decatks ~ T/Inr1a in Incrrlrnc• It ii certain that the rate of incrcace rrpnrtrd for this disease during recent dreadrs haa hern e>taggeratrd cttnvderahty by the progressively in- creasing skill of clinicians in diaRnnsis A number of autnfsy studies have shnwn that wherea. IunR car(inttma wat mnacd clinically as often as nine limri out of ten early in this century, il is presently dtaRnrncd clinically in eighty to ninety percent of casct Indeed, there are indicatitrnt now that Rcn- eral nwarencss of the diseate is leading ttr rrverdiaRntrtit Fven su, in tpite (if the fact that diagntnis has approached a high level (if efficiency, the curves of reported incidence have begun to show aigns of approaching a plateau rathcr than a continuing steep inerease. (anaai/icatlon ol /,unR Tumors Ilnman lung cancer tissues, still living afler surgical removal, are now being nbserved with respect to their behavior in standardired culture media. Such wide behavioral differences are bring seen in a single medium as to suggest that there are many mrxe differrnt tyftes snd Innhahly more di/lrrent cau.rt rlurn prrvirw.ty suspected hum the classilication uf fi.rd anJ slained sucth+ns on the bntis of yqtearance. f:.11 nml Tiaau. Culture Conj.r.nr• A tr.nfrrrnrr that Idacrel .Irtial rmPhaaia uitim thr hist~q~nthtrhtgicsl t h~nr .tn,l,,, r,1 n . rllt .u ,1 1-.ur , ul~ nr~ hv t irt ~m Rrrut :md nlher 1Rrnta i in rinrr, was heid March 6. 1967. In addition 10 staff and nxmbcrs of the Scientific Advistrry Board, the following Investigators participated: T. TIMnTIIY CR(KKFR, M.D., Professor of Mcdicine. Department of Internal Medicine. University of California Medical C'cntcr, San Francisco, C'alifornia. LFII-A DIAMOND, Ph.D.. The Wislar Institule, Philadelphia, Penn- sylvania. BERLE 1. NIFISF:N, A.B., Associate Specialist ((hmningy), Csncer Research Institute, University of California Medical ('enter, San Franciscn, California. I)ONAl f) M. PA('E:, Ph.D., 1lireclor of Cellular Research, 1)eparl- ment of Physiology and Pharmacok.Ry, llnivcrsily of the Psci/ic, Strkktcm, California. Rl1SSIa.1. P. SIIF:RWIN, M.D., flaslings Associate Professor of Path- ology. (lniversily of Southern California Schtxd of Medicine, Lrn Angcles, ('alifornia. f1ARHARA K. WATSON. Ph.D., Assistant Bacteriolo6ist, Massachu- sells (ieneral Hospilal, Boston, Massachusetts. (-IIARf I Y WAYMOUTH, Ph.l)., Senior Staff Scientist. The Jackson 1.aboralory, Bar Ilarbor, Maine. Cell and tissue culture studies hope for the in virro production and anal- ysis of such histopathological changes as are observed in the lungs of animals subjected to controlled eaposures to varioua agents. Subsequent direct obser- vations of the proliferative capacities of such tissues when replanted into the host animal may help relate microscopic appearance to tissue behavior. Stndira with (:iRerette Smoke (:ondenaotes F.><periments involving the painting of mouse-skins with cigarette smnke eondensates (t+ften erroneously called "lars°) have becn the chief basis for the view of srrme investigators that cigarette lmoke is to be regarded as a contact cucimogen for the human lung 1lowever. the relevance of auch ob servatirxrs lo the problem of human lung M quatinnable. First of all, there are greai differences between rodents and primates (mnnkeys and man ) in sus- cef•uhiitty to knitwn cau'inngens Secondly, the skits Is a very diflerent ussuc fram Ihe lung and shrrws very dlfkrent reqwinmcs In vatirrus irril.iting agents Thirdly, atntknaates of smoke collected by passing snrrrke thtouRh cnld tr:qK at very low ternperalures, such as --R(1^ eentigrade, •re not eyuivalrnr in either physical nr chemical properties tn whole smoke ('hemicnt and ifiyaical changes occur in smrtke, sonic rapidly, fGdluwing its formatinn in Ihc NnnntR mne nd these cnntinuc in Ihe condemate nfter etdtccrion M.'rrttver, .uch V

condens:,tes lack aIl Ihe Rasenus cnrnfwincnts of smnkc and some <+f tlrc vapras that arr not cnndcnacd nr that evalrrrate :rftcr colltctir+n Ihe rhysi<,-%I st.rtrs of whole smoke and of cnndensate ,re ohvir,usly quite dinerent Fin:rlly, ccr tiin srnnke comtituents are disprnprrrtionalcly cnncrnrratrd in the condcncite ITholeSmoke Irrhnlntion The cnntrnlled inhalation of whole fresh cigarette smoke by esl+rrinrental animals sccros to come much cltner to thc idcal of bringing thc riRht material, in the right form and right c<x+centratirnt into contact with the right nrRan, even though the wrnnR animal must still be employed Numtrrrus inhalati<.n studici were undertaken hy many invrsliR.t.rrs in the early days following p<rhlicatkxr of the reports linking cigarette smoking tn lung cancer 7 hrse added up to an impressive failure insofar as the af pear- ance of lung cancers was concerned I.itde account of this eRurt has been descrihcd in rrint, so that the estent of the work is relatively unknown tnJay, 7he Council has continued to sf.msnr such studies with cffnrt toward improvement of tcchniques lhese are now aPPrnachinR the point where a more cnmprchensive program can Le developed Among Ihc many other factnn which nced estensive sludy are Predi,lwninR factnrs in lung cancer Animal mrKlels for lung carcinnRrnrsis I ung clearance phenomena T7tr' (:arrli(rtursc•ulrrr I)i's(vrsr's Ath.roacleroaia There is broad agreement that the pr<xess of alherosclernsis tends in general lo predispcxe to ischemic diseascs of the heart and blood vessels "fhis gradual thickeninR and deReneratirrn of the vessrl walls occurs in all persons but 1 widely different rates A numher of diffcrent kinds nf evidcnce have cnmhincd to suRRrst that nicntine or smnkinR dtr not c<rnlributt tuward any acceltratinn of this prrxcss: ( 1) the fact that these diseases auc nrrt aplnr ciahFy more frequent anronR pipe and cigar snxrkers than anN+nR nonsn>,rkrts, 12 ) the inconclusive results In animal studies where nicotine was added to an athcrnRcnic dirt, ( 1) the occurrencr u/ angina /xti hrris no nxrre rdtrn In smokers than in nnrnm<+kers, and (, ) lNrfr mortrnr studies showing no siR nificantly incrrasrd Fwtvakncc of infarct~rns of the hrart anrnnR srn4rkers ()nr resrmlr rrfwwteal Mrrr m.wrrm stuily ha+, on the crmuary, found I snme relation between thickening uf arterial walls and ciRarette smrrkinR history Nevertheless, since so many other hahits and practiccs uf life tend to cluster with smoking, it cannot he concluded that Ihe smukinR per rr was resfxrnsihlc Further study of these life pallerns, (ir new and hrtter animal sludics as well as suitably controlled twin studies, may help to bring a dehnitc solulion. SmokinR and Ilyprrfenaion 'llsere is little evidence that smoking causes chronic hylrcrtrnsion ( i c, high M<wnl pressure ). AlthnuRh smoking ordinarily causes a snrall na in bhKrd pressure of a few minutes duration, many stu<lies shqrw Ihc restinR hhxxl pressures of habitual smokers to be lower generally Ihan thou of nun smokers. Nicotinc anrl SmokinR in Re/ntion to Blood Flnw A number of studies have shown that nicotine or smoking tend to in- crrarr the flow of bhrnd in mcnt of the vascular heds including thrne of the hcart, brain and skektal muscle. An e.ceptiun is blood flow in Ihe skin of the cutremitics. !'harmarnloRy of Nicotine There is a vast literature on the pharmacology of nicotine and ('ouncil projects have added a great deal to it. TIKw6h many transient eRects have been more fully described and mcasured in our proRram, no cvi<knce has emerged of any significant rnntritwtion by nicotine, at the levels smoktrs receive, to causatinn, aggravation of precipitatisxs of any cardiovascular di,. ease that conlrihutes significantly to mortality. (:Irrortir. I'ulntorrnry Uist•"trses Chronic anrl pr<Mressive diseases of the IunR, such as bronchitis, a,thma and emphyscrna are allractinR increasinR attentifNr as t'auses of disahility and drath ( linicians rclw)tt thal tuch aitments are htinR seen mone Ireyurutly and drry are appcarrnt nKrre often on dkath certiflcalcs as causrs rrf drnrlr 'I he rise in chnmk and proRressive Iwlmonauy disease, has f.rrn at tributed in part to the now frequent cure of acule lung infections by ann hiotics so that more people with damaged nr susceptilrle lungs are ahvr t4rlay than formerly. Alur, as has bccn pointed out, the conrlKrnent ut oldcr pcrq4c in the total population is greater than ever before in history. In this age puulr, and especially in males, these diseases are most frequent II

In this area, thc atatiatict are even more cnnfuud and tlf mrxe cluhiuus accuracy than they arc in the case td cancer ot cirdtuvacul:u diaca~rs, by reaafn fd laflhlcros tif diaRmnis and mlmenclatutc I he tcrm "cmphysema" his analumical dcfrnilinns and the patholfrpst uses the term Io Jescrit.e con- ditir,ns thal can he rrcr+Rnired under thc micrcncnPc, classified as to type antl tstimated in extcnt I he general /+ractitioncr, however, haa cnnrc to usc the Icrrn as hractically synnnymtws with a clinical relxItt of Jifficuhy in hrcathinR I here is an ahundant testimony that Persnns JiaRntviced clinically as havin6 scvere "crnllhyscma" often show little or none analr+nlicatly, when esamincd rrrfr mnrrr.rr ('c.nvcrxly. Patients who have hatl little breathing truuhk in life may show ctlcnsive snalnmical emlfhyaema at aulntsy In view of such variances in dcfinitinn and driRmsia, statcmcnts crln cerninR the estent kl whith "emphyxma" has incrcaud uver anv given perirwl as a cause fd death have limited meaning (:on f.rince on AIIirRfor enrl In.n.unnlnRir•nl Asp.rta nf ,SrnnkinR A cr+nfcrence on alkrRic and immnmiIrrRicil aslrcts nf Irlhaccn smi/kinR was held (in Mrrt h 1, 1967 In aJJitirm tu atifl and meml.ers ut the Scien tifK Atlvialty Hrurd, the IfdhlwrnR invrthgatnra LvUCil+atcd IIARRY S HI RNl(1N, M I), AttendinR AIIcrRist, Providence Ilfls- pital, WashinRtnn, I) (' RI('IIARI) S I'ARR, M 1) , IIc.u1, I)iviaifrn ut AIIcr6y. ImmunrlluRy and Rhrunuadr.Ry, Sc-rilqps ( hnrc and Rcscarch I fwndaUfln, la lulla, ('ahfcNnia PAUI-6(11.1)t1AHFR, 1) O S, Assfrciate Prufesanr nf Perir.dfrnuoInRy, Ilarvard SchtK-1 uf Dental MeJic'ine, Hrntun, Massachusctts 11AVIl) W. I At MAGI:, M 11., Prfdessor of Microhinhrgy and Asan- ciatc Ikan, (lniversity (if ('rlhrrado Schrwrl of MeJicinc, I)envcr, Cnlnradn. Ni(•(rcirrfr (rrifl [lle (;entr'fll N(rrlurrfs tiysrer/r Ihere is a recurrinR queatifln ,s Irr whether frrtain kinda /rl IKnplc eal.rcially need ur want to amf/ke wldrr the cnndrUrfns fd numlern life Ixr ause rrf a y/rcial need lor rrlief of Ierniun Is there any evrdrrKr that .utIr relief ia ctually Provided by snxrkinR7 In the past, dependence has had tf+ he Idaced largely upon Ihe suhjec- tive statements nl amflkers as tu+ why they like or nerd tf/ srnflke AmfrnR the fec-urfinR rrl"lrts arr such as Ihese ( I ) "It Rivea mr Illeasnre," (2) "1t gives me e I, r( kull nn, l hrll,t me Rrt R„u,R," 0) ..It tlcll,. rne tcl.rIt whcn I am lrflsc t I Sut h st.Hrrncnts raise the questions whether evidrncc tf/ chec k their imlvf+rt ttndd f.e larwidcd by any capcrimental methtnl. Stune answcrs rnay I+erhaPs hc furnishcd by psychological investi6atitrns and any PrranisinR alqpftl,ches along such Imcs shrwdd he cncouraRed. Anuther al-Pn+ach ia through the methods of psychn pharmacnhlRy, a relitivclv new licld nl science. Ity the study rif clcctrcxncephaln6rams it has been shown Ihat. Mrdr in animals and man, nict+tine has a hrief stimulatory or "arousal" effect r,n thc hrain, especially when this was nriRinally in a state of what might hc called telwrsc. When the hrain is in the kind trf stale aasnciatcd with aRitatitrn, nicre tine hat an effect ffn brain waves resembling Ilut uf wnx of the trYnquilinrs llrut paythupharmacohogy is PrnvidinR sume scientific auhatantiatirm If.r the seennnRly crrnlradainry suhjcctive testimony o( snmukcrs Nicutinc may M,th aruusc the lethargic and calm the agitated. Since direct electrical stimulalicxt of certain parts of the brain latKluces an effect that is pleasurabk, animal studies are being made tu determine whether nicotine alus stimulates the pkawre centers. Cechniyucs that Permit monkeys to inject themaelves with nicotinc at will, nrN only show that they find this a6reeahlc, but are shedJrnR light on the effects of envircrnmcnlal conditams on the anwwnls the animals will take sPr.ntanerwsly. In no case has any of the animals done damaRc tfl itsclf by srKh unreslriclcd self - adminislrati.n. Scvcral studies have also tapkxed thc eflects of nicotinc on the learning prtlcess in rals, usinR various rewards to stimulate the animals to learn their way through a mazc, press kvcra in snme pattern or avoid an electric shock by jumllinR (u a wooden Pok on signal. Several such caPcrimentt show Ihat nicu inc stimulates the karnin6 Process, mtxe particularly amflnR thc animalt that arc originally relatively slow learners. I Or(tl (,(ri!fily l irs(r(rr(•Ir lhe nral crvity is subjected Io direct contact with snulkc drrived fnrm Irilrs, tigira and ciy.aurttea mure quickly and in greater crfncen,ratif/ns Ihan Ithr IunRa I/ralnte thi., I1K irM irlrnt'e UI t"arlCrr Irf Ihe f•ra) t'hVlty 11.1% ahrrwrl nu vgnnc, ant intfrau iu ramfNrrrl, nr inciJrnce at n rarlirr rFr, flurruR Ihr dcc'arka in whk h/w cal+ila r.l>,aure tu t iRarctte sruoke haa ri.rn Rrr.rtly Ir is iml-Iul:mt to find Ihe esplanaliaxr for tfns /nti As rrpwlcd clsewhere, ('ouneil studies have shnwn that the nral riaurs rrf mice are far rnurc resistant tn certain carcinnRena than are Ihru akm. In nllce, liver dvnnRe ctlnsidetahly increasea the auacefaihitrty nf nce oral lisaues tn crrt.lin recrlRniled catcinrrRrnic suhN:rntes, 1,111 I'.I1ntinR nf Il I'

ciRarctle srnuke condensates inside the mouths of Iiver d.rnaReJ mice has not been f4dhrwed by appearance of any lumors. Much more study of the oral cavity is recommended by the fact thal il resemblcs the lung mcxe than does the tkin, yet is relatively arcetaihle. Since the saliva, oral structures and especially the oral Icucocytes al%o serve as a first line of defcnse against exlernal a`ents entering the lxK1y, they merit .Itenlion in their own riRht. The eRects of In vivn and in virr,r cwfa+ture of oral leucocyles to whole smoke and to smoke conatitucnts are LrinR sluJicd in recently inaugurated ('nuncil projects. Abstracts of Ilcports Pach recipient of agrant-in-aid from The Council for Tobacco Re- search - l/ S A. is responsible for the initial presentation or publication of the results of his rcsearch at scientific meelings or in appropriale scientific journals. Following are abstracts, .pprored by the authors, of reports on new eeperimcntd research acknowkdRing wpport from 7 he Council that have appeared in scien/ific journals since publication of the 19tS5-66 RryKUI uf the Scientific 1)ireclor. llrese atnlracts have been `rouped under the following beadinRs: 1. Psycho-PhysioloRical Studies. 11. ('ardinriscul.r Studies, 111. ('arcino genesis Sludies, IV. SluEiet at the Cellular E.evel, V. F.pidemioloRy, VI Pul- mon.ry Physiolo6y, VII. NeurophysioloRy, VIII. Chemistry and ifiuchem istr~ IX. PharmacokrRy and Psycho-Pharmacolo6y, X. Pregnancy Studies, and X1. Other Studies. A number of grantees of The Council for Tobacco Research - ll S A, participaled in The Third PeruRia Oradrennial International (bnfererwe on Cancer held at the l)nirersity of Peru6ia, June 21-29, 1965 "I.unR 1'umours In Animals; " the proceedings of this conferenoe, was published in lune, 1966, by the 1)ivision of Cancer Retearch, Peru6ia, Italy (iranlee cunlrihutions to the conference are as follows: "FPIDFMIOI.O(71C STUI)IES OF LUNO ('ANChR IN I)(x;S," by D. Cohen, J. S. Rcif and W. FI. Rhoiks. 'TEIP ROLE OF INFLUENZA VIRUS IN TIIE hFVFLOPMI?NI- 01: MALIONANT TRANSFORMATION IN V1TRO ANI) IN 1/11? RF.S- PIRATORY TRACT OF MICE. WITH AND WIT11Ol1I /iXPUSI/RF TO CIOARE3TTE SMOKP," by C. Ltr.chrcnDtrRn and R. I,cuchlenberRcr "TIIP RFLATIVF E?FFECTS OF SOME AIR POLL117 AN I SON 1111: HIIMAN RfSPIRAIORY EPIIIIELIl1M," by W. 1L (-ornrr and 1. F Muses. "1?III?('IS OF 1NIRAVI'.NOlIS ('AR(-IN(/(&N AND 1OIIA(ll) ('ONI)I-'NSAII! IN1F('IIONS 111'/IN 1111? IN('IINUN( I; 111. I IIN(i I I/Mr)RS IN A/lie MICE," by F. I/omDurRn anJ A. I reRcr "7l/MORS PRO1)l/('FI) IlY MEIFIYL(71(/1 AN I IIRIN1: . IN 1111: RIiSPIRAIORY 7RA('f Of IIIE W1111E 1'I-KIN 1)lt('K" hy R II Rirdon. I5 14

I. I',ycho-I'hy.it)(nRiral tifudir. "BIOL(Xill:'A1. ASPF("IS OF (1lJSTATIUN" fly Arnold R Kaplan, Phl), Laboratory of Medical Genetics, C'levcland Psychiatric Institute, Ohio. "Mutation in Population: Proceedings of a Sym(+rxium held in PraRue in August 9-1I, 1965;" pp 146-153, Cnechoslovak Academy of Sciences. Prague. 1966. Tris paper presents • sum2 and summation of early and recent studies of taste sensitivity. Differences in taste threshoklt have been found to be telaled to tnany facton. Including medkation, phases of the menstrual cTcle, preRnurc7, smoking habits, occurrence of duodenal (vs. gastric) ulcer, and dietary preferences. Tests In monoryRotk and dii,yRolx twins and In sibling pairs Iodkate that genetic factors ate invnlved in laste thresholds. ()tR.r Crantarr Natlooal Institwes o/ Ileakh "STVDIFS IN TASTT? ACl1rT'Y." By Arnold R. Kaplan. Phl), Iahoratory of Medkd (:cnetia, Ckvel.nd Psychiatric Institule, Uhio. Trchnicol Quartrrly 4/2:I3R-I44, April.lunc 1967. Intrapair thrcshold diflerences fnr hydrochloric acid, L-quinine sulfate, and PROP (6 n-ProPylthiouracil) were InvestiRated in pairs of one-egg twins, Iwocgg Iwlnt, and nnn twin siblinRa 'Ihere were no siRnificant differ- ersces in inttapair variations Irtween the two egg twin pairs and the non twin siblings. There werc, also, nr+ 1 rRnrhrant drllrrrnces hctwecn the nnc egg and two-egg twin ~airs for hydrrKhtruic uid and quinine, hut there was a very siRnifxant dilTcrcncx for PRUP Ihrrrfore, the innd.emrnt of genetic factors In etinkiRy of laste Ihre%hnlrl was rnH drmnnctrareJ for .nur ustrnR hydrochkxk acid or for bitter tavinR yurninc, hut was emphatically dcrnnn slrated for bitter tastinR PROP Sensitive tasten of quinine and PROP indicated relatively large numben of food dislikes and preference for relatively mild lastinR fcxids, compared to inscnsitive tasten, who indicated relatively few dislikes and preference for more strongly-IsstinR preparations. The sensitive tasters included a rela- tively high pro(+rxtiots of nonsrnokers, compared to the insensitive taslers, who inclurkd a relatively high proportion of hcav~ smokers l aste threshold was not found to be rclated to aRc or In uc when the dda were crrntrnikd lor difTerences In srsxokinR habits. The hcavr smokcrs, hnwever, shnwed rk- cre.ud lasle sensitivity asuxiated wilh lncrt.ud age Other factrxs InfluencinR taste sensitivity IrxlrHk (rh.us rd thr mrn stru.l cyck an.1 uker palhokrRy f)thrr Rrar.torr N.tion.l Institutes of Flcalth "ORAL.ITY, IMPUISIVITY AND ('1(IARF:1-T7? SMOKING IN MFN FIIRlIII'R FINI)tN(;S IN SUPPORI' OF A 11-1FORY." fly Martin A. lacnhi, Phl). I ukrn S Andcrsnn, Phl), T'mily (TrampaRne, MI), hath.niel I Karush, MI), Stephen 1. Richman, MD, and Peter H. KnapP, MI), T)ivision f Psychiatry, llostrm University School of Medicine, Massachuselts Thr Iournaf tr1 Nrrvnur and Mrnta! Distott 113/3:207-219, 1966 (()ranlee: Knapp) 76 college students and SR industrial workers, average age 26 years, served as subjects in this third of three studies designed to test shc hypothcsis that heavr cigarette smoking in men reflects part of a pattern r>< underlying oral craving defended against by active, impulsive behavior. T1u paid wd- unleer subjccts in this study look part in personal interviews after which they filled out a Parenl-(?rikl Ouestionnaire (P('V), • personalily inven- torr ( B11P1), and a form specially designed to directly test response set and social desirability. VoOunleen in the previous Investigations were unpaid and impersonally sent the completed forms by mail. The fint two studies revealed siRnificant differenocs between smokers and nonsmokers in the parental concepts of maternal conlrol, coldness and harshness, and in self-descriptions of defiance, impeluousness, thrill and dan6er-seekinR, neurotic emotional lability, and oral preoccupations In the last study, statistical comparison of mean scores for 54 cigarette smnkers and RO current nonsmokers supported the previous findings with the e.ceptiun of the maternal malevolence concept. On an individual prediction basis, overall 62.7 percent of the sample was correctly designated as either smokers or nonsmokers usinR this psy- chnloRic measure alone (chi square = 9.45, 1 df, P < 01 ) Presumably other factnn, such as sncin4ic and physiok>Rk, enter into the drlcrmina- lion of who will become a cigarette smoker and conlinue with the hahit, hut this theory seems significantly related to this outcome and accounts for an important portion of the variance. "AN ATLAS OF FIGURF? DRAWINGS: STUDIES ON '1 HT? PSY('llO- L(X;ICAI. CIIARA(TFRISIICS OF MEDICAI. Sftll)f;Nl'S -- I11." By Caroline Bedell Thomas, MI), lohns Hopkins University Schcw)1 of Medkine, Baltimore, Maryland. Published bythe Johns Hopkins Press, 1966 This third volume in the serks, Srudirs on rhr Psyr-lurloxical ('ha.a.vrr- lirict of Mrdiraf Srudrntt, presents the only compendium of fiRure drawinRs by healthy subjects to be hwnd in the psycholoRical lilcralure. The fiRmcs in this volume were an drawn by R)l) lohns 1lnpkins n.ed kal slurknts whrr were parlicipants In the krng term study of rhr 1'recurarrs of Ilylrerlcnslun .nd ('ourn.ry INscac, UrawinRs In thrs atla. .re Rr.rkd hy rkRrre of soqdristica/inn, and within sueh a RrnupinR .rc .rranRed .ccurd (nR In different parenlal hiiIrNies in regard to cc>.unary diseau and hylrrr tension, strnke, diabetes and obesity. Smoking habits and various nncer factors are also /,iven, •rkf a Strong Vocational Inlerrst "lcat is inclnrkd fur each suhjecl. Ihus, this Atlas provides a deflnilive drnuminsloa lur fiRure drawing studies involving healthy young adults of supcrinr inleiliRcnce OtArr Rrantnr.r Velerans Administration and the National lirart Institute Ih 17