Document ykK5RY0NQGOb9MzvLDw3KvqY4

MEMORANDUM /pUUNTiFPSo jEXHIBIT Case: Date: February 6, 1955 Pag** 1 4Ir.H. 3H8a8i8ner Subject: American Cancer Society Sponsored Conference * * e* Daricia on LtlQS C****** and Heart Disease with Particular * ft* Emphasis on Tobacco as a Potential Causative Ager: (Princeton Meeting) Program arranged by Dr* Kerry Weaver of the ___ American Cancer Society f>4day7 January 26, 1955 - A.M* sorning session was devoted to consideration of the possible role played by pollutants such as coal tar and soot, diepoxides, engine exhausts, ionising [radiation, etc* in the increased incidence of long cancer, The general consensus opinion was that is terms of the public at large, as opposed to certain apetic-occupational groups, that the coal tar and engine exhaust derivatives were jjjaitae only ones which might have major significance* There was no unanimity of ^pinion as to what portion of the increase might be attributed to the action of th*ee agents* Siftiday, F.M. Afternoon session. session was devoted to a discussion of the chemical composition of smoke and Efpactionation program with respect to 37k-Benzpyrene. Dr. Fieser presented his Stark indicating that this ccspouai was probably not present in the amounts which |bad been reported t? the English group, If it was present at all* He reported ' erthat compounds giving similar fluorescent spectra, but partially different uitraiSviolet absorption spectra were present* Dr* Dickey of Tennessee-Eastman Co. grind Dr* Wright of the University of Toronto concurred is this evaluation* Fieser presented his work on the isolation of tobacerol from tobacco and ?suggested that it might be a precursor for tbs formation of aliphatic or aromatic .^carcinogens* Dr* -Wright reported that ha had isolated the amounts of 5 mgs. per .15 gas* which was highly fluorescent,was an acid* and was ffsensitive to alkali in the presence of air. ^rDr* Frankecburg of American Cigar Co. discussed the chemistry of cigar tobacco, ^stressing (a) the variation of alkaloid content from strain to strain and year to year, (b) some of the changes occurring in the composition of the tobacco leaf *`u a result of fermentation* He presented no evidence on the composition of cigar moke. Dr* Stephano presented some material which purported to show that if the .tempera ture of the smoka bitting the tongue was lt-S degrees above room temperature, that the smoker decreased the volume of the puff and usually shortly thereafter put out the cigarette* He claimed that all machines used to smoke cigarettes were grossly Inadequate to give combustion conditions similar to those which hold in normal smoking. He felt that puffs every 20 seconds were too frequent. (Keith Carman vho eat next to Dr. Stephano the next morning, timed Stenhano'e smoking habits sad found that he smcked a cigarette on ths average of 5? minutes and that his puff averaged higher than two per minute). Dr. Newman of Ohio State stated that he did not believe that the rate of puffing or volume of puff would alter the combustion process significantly and lead to changes in the compos!tion of the smoke. o-vt /gET .Kessler. WV-03050 MEMORANDUM f: S. Stevens l, Bass tf. Kainer Case: Date: February 5, 1955 ^2?*: 2 Subject: American Cancer Society Sponsored Cooferer.ee on Lung Cancer and Heart disease with Particular Emphasis on Tobacco as a Potential Causative Agent Program arranged by Dr. Harry Weaver of the American Cancer Society Friday Afternoon Session (cooVd) 2; Hr. Saaaer, Research Director of American Tobacco Ccsnpsny reported some of their f studies which indicated nicotine ecid*--. and aldehydes in the smoke, were very positive to the smoking conditions and did not increase or decrease uniformly one component night increase $0% whereas another only 10% and vice versa). Dr. Hobbs presented his data os the composition of the gas phase and reported that v. be could account for more than $5% (?) of its cosposition. V Dr. Wright who is preparing fractions for test by Wyader, is using Imperial Cigarette Company cigarettes which do not contain any flavoring materials. He is & using "aagnesol" for a chromatographic fractionation. Dr. Shear mentioned the .... desirability determining the carcinogenic activity of cigarette smoke prepared in the absence of particulate matter in the air which is known to contain carcinogenic 41 materials. Dr. Keasler stated that this was being done at Arthur D. Little, Inc. ** Friday Evening - Bio Assay gjfDr. Tbolan presented her work on the cultivation of human embryonic lung tissue In T^tfae cheek pouch of the blaster and subcutaneously in the rat. Rats were irradiated and treated with cortisone; the hamsters treated with cortisone alone. Vaanijjig &, females were used in both cases. The rats were employed as a reservoir host and 3^ the hamsters for experimental work. The embryonic material was obtained from V Sweden. Usually 36 hours later, the tissue was implanted In the rat. The tissue j^wa* minced and approximately 3 mg.'-portions were implanted and left for 1U to 16 If day*. The tissue was then transferred to the hamster. It was found meet effective Jfet insert the tissue by the use of a needle to cut down on lnfeotioi. Takes were M* of the order of 95% to 100%* The embryonic lung increased in mass by a factor of %20 in four months. The hamsters were treated with cortisone with an initial dose ^ of 3 age. and subsequent doses of 1 mg. per week. The first human tissue was <*. received ca October ?th and has increased in amount from 25 to 500 mgs. In con* trast to the behavior of the embryonic lung in the aqueous humor of the rabbit's eye, this material in the hamster's cheek pouch rapidly takes on adult morphology /l3 to U days). The lobule* are filled with a fluid of untoewn tempositicn. *8*. Tissue implants in the cheek pouch of the hamster can be inspected regularly and * are accessible for local treatment with potential carcinogens. Problems which may *?ise in the future in terms of evaluating any response to these agents are: . I) The uncertainty of the effects of cortisone. 2) The abnormal stromal-parer.^ccyaal cell relationship. It does appear to be a promising technique to gain 'information on the susceptibility of human tissues to suspected carcinogenic agents. . Sthfir Bio assay procedures were discussed, but the consensus was that the production of neoplasia was still the only reliable guide for carcinogenicity. The possibility of using paranecim was discussed, as this organism had been reported seme years *6o by Mottram to be inhibited by photo-oxidation products of aromatic tydrocarbon arctnogens. Vs"torlej .ha-alar MEMORANDUM ;v'*Basa HU gaiie? Dace: February 6, 1955 Page: 3 Subject: American Career Society 'Sponsored Conference on Lung Cancer and Heart*' disease 'with Particular Emphasis on tobacco as & Potential*Causative Agent Program arranged by Dr. Harry Weaver of the American Cancer Society *, * Januaryp 29 presented the: result of his forward epidemiologic study* in tems of '5. rw& ltog cancer, . coronary disease and longevity. The material was essen- siteat-reported .by- him. in San Francisco, last June. J.r ***2 : Vender reported on the experimental approach to the problem of cigarettes and {cancer, ant stressed-that be vaa uel^g. the atti^cf the .npuse as .a. means of taring caroicogycia activity cigarette, smoke .and that he did. not consider! / sdnctlOD'of cancer In 'this species, to'.constitute proof that cigarette azaoke"' foinogenic/to oBU"r He presented his .fractionation scheme which did not fr'freer-thp' slide presented to the Pharmaceutical Manufacturers Association tpeceaber* th U. v. ,;** t s-,gv. e-'coor?.; * .. :<^mdsr>reportel^bat Svisa-aice^aremore susceptible than C?7 and CAP..;, ;He' oaed-that cigar tare appear to be lees icttye-than cigarette .tars. BA , j:Basuremfihts. cf .sebaceous-.gland-activity anduepideraal. thickness in asssy- *i frectdoasi** the acidic .andibaai* fraction* produced."predominantly a * .trplaaia and'.the neutral fractions, pre^oainantly decreased sebaceous, gland Tu^by.* The Tseutrairfraction appear*-to*be lass active.than the total tar. in {term test for carcinogenicity. He reported that Er.'Sugiura using cigarette i* obtained from Dr^Wynder, : h*d produced 3 papillomas out ,of 60 mice, the i-being arbund? months;-. ., - , vlansler,.at the request of. Dr.,Weaver, discussed some of the pharmacologic fUrs: involved in the, actions'of tobacco- sacking on the cardiovascular system,1 basing the- need for. more information pf. the-actions'on coronary flow and the1 tuotlon of arteriosclerotic lesions following chronic exposure end pointing j*that-that availably evidence,, in^tbs latter-situation is practically worthless. ,i%" *r n*v. .. .* ... Utcrday afternoonr JamiAry 29 %. *>. w v ' % Kelson atiempted'tlo Summarize the significant points that had been brought din lha. discuseJjOB a$d it ws_ his conclusion that cigarette smoldag is a factor i'tia*present'''increase of" lung cancer/ WtJ how important a factor is'-not imown. > pointed1 out the" difficulty of resolving 'the- interplay of other' factors in the gJteg^cancer^sBiidflg problem 'pyepidemiologic'methods, and suggested that a with* v^vvel-type experiment would be in order. He also stressed the differences .qrtgp end nsral areas .and jd^ced^ emphasis on the need for more information * .ea.c*ai"tar`and petroleiaa products as air pollutants^ hDi'the discussion whicht followed,! Ancel' Keys cobbjnte'd to'the *.effect'that he 'still1 questioned the sigolf - icanc# of the epidemiologic findings'la terms 'o't* coronary disease. He mentioned in various countries, changes in ccrcnary disease and lung cancer did not go parallel. Ke also mentioned the difficulties of studying this prctlers exoen- $.. J v.)v.ecjslex r MEMORANDUM ' * r..1'/ /i< a. 5te.v?M k *,Bas3.;s L> *-** Date: February 6, 1955 Page: ^ Subject: American Cancer Society Sponsored Conference on I.ung'.Cancer and Heart disease with Particular Emphasis- on. Tobacco as a Potential Causative Agent /..Program apranged by Dr. Harry Weaver of the l- ..?- American Cancer Society ___ -U nsriai** I*,. Schrek: reported on a. study in progress which indicates the correlation between lung cancel^d'snoicijag'^-and reported a slight correlation for coronary disease, ge'streeyedrtfc* "point bat of the various things they had studied, infectious dis<jaa*/mte;'; that everything,correlated positively with smoking, with the excep- tiSn-'of^dlabeta** Sf * 1** - . s j&d'^w^Aotuarian'of1Metropolitan Life,. commented. on the fine job Hammond .and fiora &*tf~done in tbeir-epidemiologic study* fce&pointed outs (a) the. information obtained rald'be mch aoW reliable if they had a longer period of. observation, and (b) he thought that the study was biased in ten&s of favoring decreased correlation for he, older age groups. ,*/' "J; " > . >- t ' * .< Haairaeaed ti^e^probability 'that a significant proportion of the reported increase l&.lnngrcajicer Bay be due,toInsproved diagnosis and reporting* He also questioned ti# significance ^of any'estimates as to Hhe proportionate role -that cigarst smoking aight^pliy^ia^this process* ;;Ea Sneatiohedthat he had recently surveyed 500 death claims'-of people .whohad.taken.out insurance In the 1920*3 and mentioned that, in toi littit^s8e^es,'oaly1i.diaeflsefl appeared to be*correlated with, smoking5 these were lung cancer, cancer of,the^buccal-cavity, coronary disease-and diodenai ulcere. -- 'a >* Dr; Cl&aensen' from Copenhagen, reported on the incidence of lung cancer in remark, lid'pointed cut that the^urban. area^ curves were about ten (10)vyears ahead of the jural"ftreaa> and-noted that.the birth rate increasea,,were relatively separated by insane paric*! of time* In a study, of the incidence of lung cancer'as a function of the- economic' level, the conclusion was, that the people who lived In the poorer &*ighberhpos,hdd a higher incidence of lung cancer* Dr*. Higdon from Texas pointed out the' difficulty of. determining whether lung cancer vaa squamous br^adenbcarcinbaatous and stated that his experience, many lung tumors contained areas which resemble both types. Hence' the. smaller the area examinedV the sore<certain the opinion of the pathologist. ............. . <c.-n *- * ......... hr* Glesaettsea. agreed :v4th Br. fiigdoa. ^hat .this'`introduced a problem, particularly ** the squasttusttype has been.characterized.as the 3igaret cancer8;'' &r* Higdon reported .o&:.a.nev..study underway ihvolFing 12,000 cases. Re presented tabular data shoving variations of gmokiag^b*blts with* age and educational level. S' ... . -,r - Dr.' GiHia-B presented^data to* show, that,..if. there had been' a h% error in the diagnosis of Jung caneer over, the years., which was* gradually corrected, that the- total reported increase-in lung cancer could be. explained by this degree of improvement1'in diagnosis. a-.Charles. Kessler /grer