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C II I A Scientific Perspective on the Cigarette Controversy I CT R- 1314 CTR Nfq 003338

Noic - Gatain of the quot.atioas in this booklet are from Gbvcrnmcat docu- ments and are in the public domaia. All otbcr qnotatioas btreia are indudcd by spcciai permission of the authots aad publications. No part of this documcat may be rcproduced for any advati:ing ot trade purpose. TOBACCO II.'DUSTRY RESEARCH COMMTITEE 5400 Empire State Building New York l, N. Y. I CTR- 1315 CaI-~ H ~`~ C.'.~ ~ ~~~~

Introduction No activiry in all the vast field of medical research is being carried on so intensively, in so many areas and at such cost as the effort to track down the causes and cure of cancer. With the whole world anxiously waiting for some word of success, any reported identification of,a cause of cancer arouses im- mediate and wide public interest. This has happened in the past year with the promotion of a theory by a number of research doctors that cigarette smoking may be in some way .li.nked with lung cancer. In papers read before scientific groups and published by medical journals, Doctors Ernest L. Wynder, Evarts A. Graham, and Alton Ochsner and others maintained that the sharp rise in lung cancer reported in this country was "compatible" with the greatly increased use of tobacco. A similar statistical association was suggested in England by Doctors Richard Doll and Bradford Hill. In addition to this alleged statistical association, considerable atten- tion was paid to reports of experiments in which Doctors Wynder and Graham had been able to. induce skin cancer on mice by application of cigarette tars. Some doctors have gone on record as accepting these views. But other d'utin¢uished medical authorities and trsearch s6entists have questioned the validity of the statistical methods and the conclusions drawn from laboratory experiments with mice. Among basic questions raised is how much of the apparent rise in lung cancer is real and how much is due to other reasons such as bester diagnosis and the aging population. These other authorities find no proof establishing that cigarette smok- ing is a cause of lung cancer. Especially significant is the stand taken by thc National Cancer Institute of the United States Government. In a report pub- lished in April, 1953, the NCI says: "Aside from the statistical significance and apparent realness of these associations there remains the question of whether -smoking is etio- loo cally related to lung cancer. Considerations are presented which ®~rR. 1316 ~~• ~.~ ' I9~ ~~'~•4 C303,

lead to the conclusion that the etiological (etiology: the science of causes of diseases) significance of these associations renmains un- established." Because of the wide publicity given statements made about tobacco by Doctors Wynder, Graham and Ochsner, many laymen and even physicians are unaware of the extent to which these statements have been qucstioned by other authorities. It is in the interest of science and of the public that these other views be brought to public att.ention, and it is for that purpose that this compendium is being published. The following pages contain the statements of many qualified cancer experts and organizations in the United States and overseas. The Tobacco Industry Research Committee does not suggest that these views represent the entire body of scientific opinion on the subject. Re- searchers the world over are studying dozens of theories in attempts to solve the mystery of cancer. At latest count them were more than 850 cancer research grants active in the United States alone, any one of which might pro- duce evidcnae to unlock the ucrets of bang cancer. As set forth in its public statement on January 4, 1954, the position of the group comprising the Tobacco Industry Research Committee is that they "accept an interest in people's health as a basic responsibility and paramount to every other consideration in their business." In that spirit, it is believed that no serious medical research, even though its results are inconclusive, should be disregarded or lightly dismissed. The important thing is to recognize the urgent need to explore every scientific avenue which could lead to discovery of the cause of lung cancer. The Tobacco Industry Research Committee has pledged its aid and assistance to the research effort into all phases of tobacco use and health. The joint eftort, of course, will be in addition to that already being contributed by individual companies. TOBACCO INDUSTRY RESEARCH COMMITTEE 5400 Empire State Building New York 1, New York ® CTR, 1317 CTR r1tq 0033,41

Comment on Current Theories Questions Role of Cigarette Many Compcrrabl e Correlations "Nosu o f Evidenre Conclusive" If uczssive cmoking plays a role in production of lung cancer, "ft teems to be a minor one," aacordi.ng to Dr. W. C. Hmcper, Chief of the C.anoaigcnic Stndies Sec6on, National Cancu Imtitute. Writiag in a 1953 iune of the Rhode Island Medicallournal, he uys: "It may be eooduded that the eridiag tvidence neither pnovea nor stroogly lndicates that tobacco amoking and tsP°cially cigar'rtu smoking ltipreuat a major or even prodomiaating causal factor in the production of canocn of the respiratory tract and are the main reason for the pbxaomenal tncrwse of pulmonary tumors during r eoent deada.. If czeessive amoking actually plays a rok in the production of lung anoer, it teem.s to be a minor one, if judged from the cvideace on hand."1 Prof. R D. Passey, Director of Cancer Re;search at England's University of Leeds, cautions "kt us be sure of our evidence." In a February, 1953, kuer to the British Medical Journal, he says: "In view of the present interrst in the relationship of smoking to lung cancet thers is undoubtedly a Lirge body of opinion, both professional and lay, which accepts, as though it bad brcn proved, that smoking ia the main cause of the rcorded iacrease in lung cancer, and no doubt there is considmble distress in the tommunity oo this aocount. In the ptaeat sute of our knowledge, is this anxiety really justified? . "It is easy to ull to mind other close sh •r•l carrelauons. F'kat catches the popular fancy is the .vay the rise in the Saba of cigarstte-stnnkiag goes Aand in hand with the tise ia lung cancer mortality. But in the bng history of our profession's attempts to elucidate the causes of canocr it has found maav correlations of a comparable nacure which bave in the end proved faise. .. "It may be that a proportion of lung canoers in mor, am induced by tobacco smoke; at the moment we do not know, but let us be sure of our evidence beforr we scare the public"= A public statement November 27, 1953, by the Damon Runyon Fund says that the evidence is not conclusive. "It is recognized that lung cancer is now more common than it was ooe or mo decades ago. Many avggestions as to the cause of this iacrcau have been made; the poaibk rdaz;onship of air pollution, rehiclc exhaust fumes, smok- ing and other faesoti have been aidefy meatiooed. Socae of tbesc surmises arc purely spaatlative, some are drawn from statistics, others derive from the experimental induction of eaneer in aaimals of these materials. Ho.rever, none of these factors has as yet induced in experimental animals lung cancer of the kind seen in maa None of this evidence is conclusive but does urge the need for carcfully controlJed research to secure the aaswer. ?hree questions arise .vhich require solution: tust, is tbere a ausal ydatioasdip: secoad, if so, what factors arc responsible; third, how can they be elim.inited?"s 3 I CTR. 1318 ~~I bN ~~~ ~ 1p1 F4 0 0

Unu,arranted Dr. Max Cutler, internationally noted cancer surgeon of Chicago, says, "I feel Conclusion strongly that the blanket sutements and conclusions which appea.red in the p~s that there is a direct and causative relation bttwecn smoking of dgarettes, and the number of cigarettes smoked, to cancer of the lung are absolutely ttnwananted.', During the last 30 years Dr. Cutler hu published two books and dozcns of medical papers on cancer. His ttnsoliciud stat4ment follows: "I feel strongly that the blankst atate:aeau and ooadusions which have ap- pcared in the press tLu there is a direct asd oautative relation between smoking of agarettes, and the ntsmber of eSgamtes smoked, to cancer of the lunp se absolutely tmwarranted "Medical liuraturt has atmxrous examples of aucb fallacious ooodusions which have been proved to be w-rong in the light of subsoquent experience. This whole question of cause and eQect deducted on a rtatirt;cal basis is wbjcct to the grc.atest fallacies. Ooe way I like to emphasize it is to uy that simply be- cause one jinds bult)rots a/tcr a r,Qin dors not numt thar It rained bullJrops." "To accept the conclusion that Aar been drawn oJ a direct causal relationslu'p between smolcinP and cancer of th-e lung simply because there ha,r been an increase in both, appears to mt scnscienti(ac and hazardous. "From all the avaIlable evideact, I think h is conttivable that in a very amall. probably intinitaimal peroeatage of sensitive individuals smoking may ultimauh prove to be one of ntsmerous oontnbuting facton in lung cancer. "Under aLese drarm:unoes, es ix wise to scare the public and crute wide- sprtiad anxiety among ras7lions of pdopie on the fiixasy evidence t>sat has been presented?••4 Facts and Faruies Need to be Sorted l:ced for a calm, objective appnisal of evideace is emphasized by Professor D. W. Sa:ithers, Director of Radiotherapy at Fagdand's Royal Cancer Hospital. In his report, entitled "Facu and Fancies About Cancer of the Lun_e." appeir- m£ in the June 6, 1953 Brirish Medical lournal, he says, -Lhe moment the word cancer is mcntioned to the public (of which doctors arc but a part) • emotion is aroused and any calm obiective view of the value of cvidcace preseatcd becomes most difficult." Follo%t.ing is complete tezt of his concltuiotss: '?be stutling rise io the recorded dcath rate from harg cznar: is in larae part due to dsange in numbers and age of the popukuiac and to improved dugnosis_ It is due in part to a sul iaa+rsse, but we are not yet in a position to say hoa rcat that rcal increase is. "7be size and the difficulty of this problem arc clear to us alL Although the bve-vear survival rate for the fortzmate few who are operable when they first rtacb hospital bas ri.en from nothing to betwraea 20 and 30% in 20 veus, and while much can be dooe with :-ray treument to ri.lieve asflering and some- times prolong tife for the leu fortunats ones who are, nevertbeteu, still in fairfy good general coodition, thcre are suTl thousands of these patients each year for whom no real attempt at treatment is being made. "$ince we all have to die, since some 90,000 people ax doiag so each vur with lung symptoms, and since this number is falling well, we should ask our- selves bow far we arc performing a useful service by helpiae to make a public issue of a comparatively small change within that group, which may be in larce • Prolrstor Smitherf partnrAetical staremenf. 4 1 0 TR• 131s L"-; TR 1,-Itq 00""~ ~~ ~

pan due to out owo method of recording. A'e should not be too readily swayed by thou who demand that the public be told 'tfle truth' wUe we are still attempting to sort the facts from the fancies for ourselves, espocially aince 'the truth' when told may not appear to them in at all the same Light as it does to us. Anthony Hope once wrote tlut 'telling the truth to people who misunderstand you is generally promoting a falsehood.' 'Tbe moment the word eancer is mentioned to the public (of which doctors are but a part) ethotion is aroused and any oalrn objective view of the value of evidence pressented becomes tnolt dit5cult. It is tmportant that the medicaI profesaioo take note of this dit6cult problem of lung eancer and bdp to deal .vith it more effidently, but it is also important that they do not maks mauers worse by mzrtly loi nmig in a«y and inereasing the alarm. A seau'ble view of the rrLs;oash.ip of smoking to this problem. for iasunce, tbrxild be and, after some .rtld cooameats in the Lay and medicil press, is noµ• be.ing prssented to the seaeral public-, but no comparable effort .oems to be joing mto an enduvour to persuade the attthor4ties to eleanse the air of ou: indusuial towns. As a profession which speaks so much and so rightly of the taeed to allay the cancer fear we should beware of putting eztrsvagant accounu of tuing ancer death rates and their cattses betore the publtc, espoctally when txuher the magnitude of the ooe nor the degree or responubiliry of the other Aas yet beea fully esubl.isbed."s More Accurate Interaatiowlly known in the field of cancer investigation, Dr. Qarenee Cook L.inle, Tests Needed Dircaor of the Roscoe B. Jackson Memorial Liborarory at Bar Harbor, Mainc, believes "If smoke in the lungs were a atue-fire caum of cancer, we'd all have had it long ago. 'Ibe cause is much more complicatcd than that." Dr. little's laboratory is credited with brecding a million laboratory mice per year. In connection with a rtctnt New York Town Hall progra..^i, Dr. Little stated: "In proving a eatue-and-e¢ect rrlationsIlip between any substaace and an,.c speci5c type of cancer in min. it is esxatial that a logical and rational approach to the problem and to the interptzution of data be employcd "From a Laboratory point of view, I do not feel that a de9nite eaux-and- effecr reiatioasLip between eigvme smoking and buman lung cancer bss berc eszablisbed ofl a basis thu meets the rsauircments of de-nl=css, extca ar.c specificity of dau which the seriousness and isaplieauoas of the problem de- scrve. Fttrther aad more amuau ezperimentii tttts and met4ods of ani!vss of the ma..^r scrars iamlwed should be derised and tttil'n.ed. For these rtssons I would trgrtt any undue alatm on the pan of the public at this time."G Statistical Associations "Etiological Significante ... Unestablished" Throe Natiotvtl Cancer Institute spoaali.su, Dr. A. G. Gt11um, Chief of Epidemi- ologv, and reseircb usociitcs J. Cotnfield and D. A_ Sadoavsky, in a 1953 repor, of the Institute's lourrtnf, have qnestiooea ttae relatioachip of tmoking to lun g cancer. Their report conta.ins the following observations; In this s±udv an association of about the aamt degree as that observed with cancer of the lung bss been shown between cancer of tbe Iarynz and eiga.rette smoking. A phenomenal increase in cancer of the larvn-L such as that rticorded for eancer of the lung. h.as not been observed in this eountrv. If the assocuuon betweeo eigarsae amol-ing and lung cancer is of euological signifi- 5 ® C1'R. 1320 ~ ~~~~ ~"`"`4 0t~~344

cance, some e.xplatution is needed as to wbv a corresponding increase in laryngeal cancer hat not followed an increase in dgarette contumption, .vitfl which this disease is also aaaociated. "Tbese data also provide oo evidence that age a.t onset of disease is intueaced by the qtuntities of cigarettu amoked. ... °1n the ume fashion these data provide no firm evidence that riuk increases with increase in duration of amoki6g. Wbea age was kept ootuunt no clear-cut ttcnd in this direction was apparent. ... "lt.rould tbercfore appear that though the asaociation bexw^een cigarrtts amok• iag and lung unoer aectna real. the aignificanee of this aaaociation rcmaiai tmestabliahed. . "Aaide hom the atitiaticat dgniscanoe and apparent nalnett of tbese aasocia- tioaa tbere remaina the question of wbether amoking is sooLoaicalty telated to lung cancer. Cocaideritioas are preaent.d ..hich {cad to the oondusion that the aiological signiticanoe of tbwe aaoeiations temaiaa uacaabliahed"r Clinical Data Experts at the Univer:ity of Tezas Scbool of Medicine have atndiad the atatirtical Questioned associatiotis employed in relating catnat to cigarctu amoking. Dr. Psul Briadley, Chairman of the Department of Psthobgy, Dr. R K Rigdon, Director of the Laboratory of Ezpcrimeatal Puhology, sad Mis. Hcka Kircbofi, Reaearcb Asso- ciate in Pathology, have reported on these ttudirs. Drs. Brind}ey and Rigdon, in a 1950 report in the Tesas State loional of Medicine have questiotud .vhetber there is an etioiogic factor in ltmg txaccr. They also ques- tion the basic data on frequency of lung ancxr, ciiiag "variuioa in the dinical data and the digercnce in these data and those ohuined from atru,pcies." Thcir observations: '7be distn'bvtion of the caae3 of cancer of the lung in the districts of Tezu as reported to the State Health Department does not tugltest to us any etiologic f.ctor as playing a aaigaibcant role in the production of putmonary nooplaffis. Furthermore, nothing significant as to the etiology is noted in our cascs studied at atrtopsy." . . . "Froc~ this study of primary car+cinoma of the lung at atuohsy tbere is in- auibcseat cvi,dence to prove that the frequency of this aa>plasm in all taalig- nsncies has maeaseC during the past twenty ytart. The: e is ao erideaae to xidica tha: canoG of the hmg is increasing in the feauk within this pcriod. One of thc factors contribusing to the confusion rdauve to the trtquency of cancer of the lung is the variuion in the clinical data aad the diffc:cace in these dau and those obtained from autopsies. A aecond factor contributing to this problem is the fi7une to separate data referable to these tvmors ia the white and P:ebro paticnt. In ataapty .eries the frequency of cancer of the lstngs may be eaab,ticbed moce readily by determining the percentage of tbese tumors in all neopiastua ratbe: than only the.a inddeacs in routine aatapsits."I Diagnostic Factor In a 1952 paper, published in the Spring Texar Reporu on Biolopy and Medicine, Dr. Rigdon and Mrs. Kirchoff question the theories advanced on the increase in lung cancer, and find that control of infectious diseases, iacrrased aging of the population and other factors are si.gnifiunt_ Quoting from this paper: 'There is etub a.ride variation in the eigaificance of the tbeories advanced to account for the increase in the frequency of eaneer of the lung that the data, in our opinion. do not justify the conclusion tbat cancer of the lung has actuall,v increased as a result of any one so far advanced. The eutistical diu presented 6 C ~9 ~~~ ~~~~~ ~~ 0 ~ ~

by some investigators relative to ciga.rme smoking are impteuive; bowever, there is such a wide variauon in control samples that, in our opinion. additioaal umpling is needed to warrant their eondusioas. There is no ngnificant eorrela- tion between the amount of tobacco eonsumed and the death rate for eancer of the lung in the United States. 7bere is, however, a si.gni6cant eorrelauon in the United States betwecn the population to physician ruio and the popala-uoo to bed ratio and the number of rrported deaths hotn cancer of the lung. Better diignoses, decrease in the number of dtaths from infocriow diseases by botb preveation and tberapy, and the incrcascd aging of the population seem to be more aignificant facton than any ooe or gxoup of araaogens to a.aaunt for the apparent iacrease in the frequency of earcinoma of the lung."s "Let's Rtvitw In a 1953 paper, publisbed in the Winter Ttxar Reports on Bioloty and Medicine, the Facts" Dr. Rigdon and Mrs. Kirchoff made a brvad analyus of the ttadctical d.ua that have been aimed at dgu'ette unolang. Their paper, entitled "Smok-ing aad Cancer of the Lung - Let'a Review the Facts," contains the following observations: "Regardleu of the fact that nome of the arocrps Save rery fe.w a.+a, we would like to empbaaiu tW in each of these three atudics the pcroeata.ge of individ- uals who smoked less than 15 eigareetes a day and did not have cancer of the lung is much higher than tfiat of the corrtspoadmg group who had bronchio- genic carcinoma. Fttrtbcrmore, aa far as we know the eases of ancer of the lung studied by Doll and Hill (1950) and Breslo.v (1951) were not proven by pathologic at•m±^a^^o„ wiu'k the sttady by McConnrv and araociata (1952) was based on proven eases of caaaer of the lung. Tbe lartrr investigaton eon- eluded that 5no aignificant difference aas found in the incidena of smoki^.g, or of the proportion of cigaretteamoYen, in the two groups' " "As you know, Dr. Ochmer has beea interested in amoking and cancer of the tung for sevcral ycars. Howtver, from a tiviea+ of his pubiiu:btu it would seeao th.at his opinion bas varied relative to this reiationsflip. In 1941 he pre- .cnted a graph showing the comparison of the duth rate per 100,000 popula- tion f:om eaocu of the lung with the production of tobacco aad automobiics in the United Stata during the period 1920 to 1936. Of automobiles and eance- of t9e 1uag. Oehine= and aasociaxes cooduded that the:e was no aigni~car:: rr_'ationship. but they did find an obvious paralJelism bctwecn the iacreascc produrtioo of tobacco and eanaer of the lung. In 1948 Ochsne.: and his grou. atated tba.t 'although we previously were of tLe opinion that the chronic irrita- tion resulting from excessive cigarette smoking was a factor, this cannot be proved However. the fact that tb~-e is a pa.rallelism be:ween the nurnber of dgaretta aold in tbe United Sutes and the iacreased incideace of bronchio- gcaic carcinnma is iaterating. . . . ln our s+ezies we have not be+ea abie to abow that tberc has been a higher incidtace of smokers than in the average popula- tion of a wbole.' Tbea in 1952 Oetisae: aaid. 'For some time two of us have boen eoav'snced that there is a cauui relatfonahip brrween the iacsta.sed inn- dcnce of broochiogenic carcinomi and the incrtased use of dgareua.' Ochsncr (1951) said thu Dr. Evaru Graham bas sa.id to bim, 'Ya, there is a p.raifelum bKt.+acn the increased iaadeace of broocbiogenic earciaoma and the sale of eigarettcs: but also there is a paralldixm betwocn tbe increascd iaeidcace of broocbiogcnic carcinoma and the aale of nylon aocl3ngs' " "ln suamary it may be said that in our opinion the data available today do not justity the eonclusions that the increase in the frcqueac,v of eancer of the lung is the rault of cigarette smoking. The siuemeat that carcinoma of tbe bronc5us has actually increased in frequency is in our opinion open to queseion. Furtber- more. adequate studies are not now available on the freouency of eigarette smokinR in the population. These factors would be necessary in establisLing a uusal relauonslLp between smoking and cancer of the lung."1o I 7 ® CTj• 139 2 CTR HN 001334G~

"Evid erue Gave Equivocal Results" "Hou, Much of the Rise Is Rea1": Dr. W. C. Hucper, Cancerigenic Reseascb Studies Scction Caief at the Federal Government's Cancer Control Branch, National Institutes of Hcaltl>, says the statis- tical relatioo is "in urgent aeed of supporting biologic evidence." In 1953 he re- ported in the Rhode lstand Medical lournal: "Ihe apparent lack of uniformity in the buman mauris.l analyzcd by the diderent atrtborities is turther demonstrated by the approciable differences in the sex disuibution of lung eanoers ttportad at differcat tiaoes, irom different regions a.nd by diSereat investigatots. The male to feana)e sex rario flucu,atu between 2:1 to 20:1 (Hueper). lt is noaewotthy, ho.ncver, that the tanitormly observed prcwaleaoe of luag cancer amona suales hu !n general become in recent years even tnore pronosrnoed than in former decadea. This observation rtrongly mIIitates ag>uaa a predoaniaant eanul role of cigarest.e amok.ing in the production of lung a.oocr. because an previow experience in the 8e1d of ocs,tpaioaal cancer lndscaees that Eivea the same type of umnoEenic expo:ure for both ases and at the aame time an iaa+asina eqttal¢.atioo of the iatensiry of exposure, tlura occurs a nama.ring of the gap in iacidcace rates of tbe two aex.es and not a.rideaing, which autsaIly exists. This iaterptxurion of the diverging sex related frequency trends is not fundameatagy alfected by the nut.eYaent thst the interval berwom the surt of toba,too smoking and the appearanu of a ltiag cancer is ber«eea 20 so 40 yean (Wytsder and Graharn; Ochaner, DcCamp and DeBakey, Schrtk. Baker and Ballard). Evta if .romen may not have indulged on a large scale in tobarco smoking wme thirty years a.go. there can be little doabt that the eiaaretu am+oking pabit has made during this pttiod much 6r+catcr suidies among women than among asea "ITte purely su~aca.l approach leading to the asutmptioa of the e:.is:cace of eausal relations bexwxa two ooiaeidestal rvcar.s and trbds is, thus, ia usgent need of supporting biologic evidcsce in man, since the avuZable ezperi- mental evidence gave equivocaJ rcatlts"it Ttte Metropolium life Iasurana Company during 1953 isstu.d a s,at_Wc= u',ing the data were far from concltu'rve. "In the present state of knowkdge it is difficult to aeeount for the recorded increase in the mortalirv and morbidirv fiom respiratory euncer. or even to deurmine ho.+ much of the ri.e is sraL Improved teth,niqucs for diiposu and the g'rca~ly io~ frequency of t3xir tsse have resulted in manv cases beine dr.ecscd and reported .vhie:, in the pasf, would have beea o+KZiooked. T3s applics espccially to diagnostic a-rays in medical and hospit.a) practice. Men- tion, too. tbou)d be made of the iaereax in the number of phyeicians with traiaing and eipericnce in this Sdd. Coatnbuting in a lesacz wac to the more freqcrere dacrnverrof anae-. of the respintory tract is the intrtaiing use of the broncboscope and of eytotosicxl e*aR+in•r;r,m of ltmg aer:etioas_ . . . The role of otber facxori, sucb as coal tar producu, excessive toba«ao amoking, and cpecific coflt•m=, ic stIIl far from conclusive.'u A Hospita1 A survey of lung cancer patients by Dr. E. D. Gagnon of the Cbest C7inic at Survey Montreal's Notre Dame Hospital tzvealed (as t=anslated from the French): "Since February, 19,49, brooc6oQulmonary cancer was observed in 120 men and S women admitstd to the tborscic dinic of the Notre-Dame Hospital in Mon- trca:. Of the 123 paticnts, 97 w,crs over SO yeirs; the oldru was 79 and the yotmgest 21. Fifty paticnts smoked more thsm 20 eigaretzes daOq and 10 did aot smoke. E.tiologica) factors discLLsxd in (medical) litersture are so numerous and so eontradictory that it is ianpouible for us to be sure of one etiological factor. Manv suttstiul analvses have teaded to incrirninate tobacco (esp. as cigarettes) but there arc just as many analyaes that negate tuch an euologv."ls 8 ! C TR- 1323 ~ c~~-~' ~` ~°1 ~~ 0 ~ ~ 47