Tobacco Documents Online

.r s-_ . ..~., .. . . Ryrintrd fro.n fAr Anhi(Kt of Pa/Aolopy Dtct,nbrr 1940, Vot. 70, ». 757-762 Ce.#yriyAr 1960, by .Amrric.a Alydira/ Auoriafio~ . .••. .. ~,.... ~fir.; a•rin lAl trri1Y : The Pathologic Anatom~f the Bronchial Tree an Lungs , t Altthodr Uftd foi o CooPrrati:x ` - rirG ~.r.!iG i:r r.:~•r ~t n w~ . s~anStt i'•rfek.r~f~ arrs fTANttY !t. tIIMANN, ~t.O. nl/."Ph/s how close a rciation there is betwr.a the use of tobacco, especially the'smoke.: of~, cigarettes, and the development of lung can';, cer. Statistical studies have rwt led ~to. unanimity of opinion nor have the results of , varied experimental studies. In both cnses,= disagreemcnt as to intcrpretabon is due usually to disputes about technics. There ii grncral agrexrnertt that there ire many vari;~ ~ 1404 The introduction •of tobacco into the Old'"'neglect of variables other than the ctwsea`r'~'- World from the New World started con=t ooes ~+ ra':r '• ,^"k' troversies which with exaccrbations and tr's7' The humin bronchial tree and the lungs ~ lapses continue on and oa. The tobacoo' " have' beea subjected to -examination for ~•:,' ~- habit has spread to all peoples; and there many` ycars When the microscope was . ._ hardly a country in which cl.imate and soii" added to thc' procedures of essminatioa,`.;e are suitable in which tobicco is not "grown'.` various differences from the :iormal wcrc: Pros and cons' were and are' argued:~ discovered by the use of this instrumeat scicntificaily, emotionally, sociologically and and were added to those recorded from the4i~:• mixtures of them. As in so many human 'gross aspects. Changes were t:lassified a.0~; habits and customs, emotions and sentiments';- degenerative, circulatory, or inflammatory;.~ play the larger part in the discussions. "The- others as the growth processes of hypcs= ~;•'-• I like' plasia, metaplasia and prctumor or tutnor use of tobacco is a nasty habit but it; '.czs said no doubt many years ago~t formation. Autolysis proceeds rapidly in', Statements of its efl'ect•on health cover the the tracheal and bronchial rnucosa, and the'. gamut of all organs and' organ systems.~ separation of true from artifact changes Ihring the last years, concomitant K-ith thcr remains difficult. The increasing use of increased incidencc of cancer of the lungs '' coal and petrolcum products in industry and special efforts have been direRed to discnver m~e heating, of tars and asphalts, and r the gruter amounts of exhaust gases liber-: k~ atcd frrnn gasoline and dicsel cngines cspo- , cially during the last 50 years, introduce new factors; other newer environmental conditions such as occur from various in= dustzies an also present. There is no doubt of the increase in the smoking of cigarettes; especially during and after the First Worid War with an added impetus during and following the second war. -. ablcs operating in tarrinoma of the lurig:~r, First base in epidemiological and physio-.:~ While science is objective, scientists arY not logical studies is knowledge of exactly what necessarily so, and emotions and sentiments are the anatomic changes in the bronchial ° color intaprctation and indeed may lead to, tree and lungs. Since different clrcvm-:•~~~' •~ Sutmitted for publiodon Feb. 22 1960. stancu prevail today than prevailed even F~nanciat support from grants of the Tobuco a few years ago, it was thought necessary lndustry• Rescarch C.ommittec through the Scien- to institute new studies of the lower respir-' ''. u6c Advisory Bovrd . ato tract so that this basic knowl llirector Erneritus• Institute for Cancc Resnrch ~ ~ cmtxr Scientific Advisory Board of the Tobacco could be put at the disposal of those lnttr-. •.' bt cmt x r Irvta~try Research C•ommittec ested in the epidemiologiul, the physiologi- ~ : . . V ': "4 '~~ ~.''. e_

c .Ltc-~~' : ARCN/YES OF PATHOLOGY cal, the ' etiological and the 'correlating Approximately f i f t c c n representative circumstances, quite apirt from the new areas from the trachea, main bronchi, scc-.•- j~,knowledget .that• might be gai~ d, f rrnn `d` ondary and scgrrxntal bronchi- inctuding'`~~'• progression sn thesc sita? V~r~; _ C~ ~f ~ lung tissut itself wtre to be sectioned and ~' _. Obviously, changes, if any, found in the stained for examination from each ijtti- above mentioned organs must be recorded 'wwn. The sites were to be subject to some-- , in large numbers of cases, since the number keway, for pathologists necessarily choose ?1,1'* of variables influencing changes are atuner- blocks from a specimen according to its >; ous. The suggestion K•as made that a group' appearance in the gross. Many pathologistsi ' of pathologists from various parts of the have pet technics and these rvue to be,i; . 4 ..;!:. . ~,~r country be asked to undertake a study of used in addition to the more or kss agrced;~ their individual postmortcm and surgical upon standard onu. For eumple, one`;:; ~;,: specimen findings and meet at stated times pathologist use ~ s the "Swiss roll" technici'~; tt thd discus thei s'ili ihih l liti bxam o presenem ansrunar-n wc aongnear srP cane e• 1:.~ n ties and differencu andLto attempt to ap ined in one section. ~ise their signi6cancti:~~ h'r At a second conference (May 14 ,~.~~~ :I, 1955) + j,.e.= P - i •~ ZY. T , ference were uteaded to 12 pathologtsts Lach of the pathologlsts brought rrprescn' of professorial rank and experieace from tative slides for their colleaguu to acamine.- f~,V: Accordingly, invitations to attend a con;n the gcrxral, techniu appeared adequate. various parts of the country. All re The classification of the lesions then came sponded • During the morning of Dec 6 to the fore The following six „.,.. categories i.-y{]d!~l11-11. f.1 _, -. 1954 t thfhh ': ~ ,.. ., skepticism asoe feasibility o suc were cosen:.. y a cooperative study was expressed by most.c..l. Nor,ru] 2 Hypcrylasu • : . .. of the participants. Difficulties of tech-, _?i 3 nic, distance between individtuls and .. ~"aniO1s °'euplasi'`:r . 4. Atyyinl rnehplasia '~ . ~- ~~ .r . various othcr possible handicaps wero~ S. Grarama in s;tu r mcntioned, including recoriciliation of no- . 6 Grcir,oraa ' menclature and differing interpretations. In- As in many pathologial discussions(as terestingly enough, and this is not the least well as in others), it .cv.s found that the . ` as each nomencl interesting facet of thc project,ature was more of an irritant than participant voiced his'opinior.s, objections were the actual lesions. biuch of the argU-.--i. were met, and before lunch'one of the fa- ment centered about names and not condi-~.: in;..,..,. vorite maxims of the late Dr. Charles Kct-". tions. Gradually, tix above prelirniaary ~' tering was illustrated: "\4hcn a number of classifications tempered in the heat of dis•,F.: -c sn,f people of different ointi" of view" sit ' cussion were adopted at the conference oa :.; " around a table and are 'm~itcd to discuss Dec. 2, 1955, though reluctantly by a few. ='..,.• 7:. . a subject without notes' of what is said, As usual disagreements arose mostly in the'~ ., t 50% of difficulties can be' talked away." borderline ases. , Before adjourning the morning session it- ln taking the histories of patients,effort'ti ~' was agreed that the program should be ~~s to be made to determine tobacco habits~ activated. The afternoon session was devoted -whether cigarettes, cigars or pipes wereg;} to technics. The gnal~ v,•as' to discover smoked, how rnany, and for how long;~: , what changes were present,- to rt•lut degre•e whether or not smoking had been given tup -$ after its indulgence for a stated time; and ° whether the patients or the family had expressed any opinion as to what happened if a person gave up smoking. Human testimony being what it is, it is obvious that complete d.ita, as above, cannot always - Yel. Jn, I)rr.. 1960 rf and in what incidence. E. B. Wilson, Ph.D., kindly agrecd to undertake statistical anal- . yses. ... . • . • . ~~ • They rerruin anonyrnovs TharScs arc cxtcnded for thcir chnrful and intcrested coopcration thro,gh the several rcars of the project. 126/7S8 / CT R- 1405 UF' ~ ~~``~ 00342 •r~

BRONCHIAL TREE AND LUNGS be obtained, but in auny cases sufficient opportunity to follow changes from begin- data could be acquired to' give a general nings to ends when they judiciously choose r vi.u- nf tl,• tihutinn Tn 1d[11tiAO tii t}li' fDCCYIDent for eY1ri11i]ltion- antt :~ f3,... srr 't oaupi interpreted cavtioust tsac usual i madon about s c Oa the othe7 k f' _ fo d ,~m ,. y. g , N ~~+,~ ~'~{ v . r . n un , ~ ~ ~ would ' , u mnch u the resideaa and like t ti us of dath be d bk b d y ~ , ons, an n e o a o o i,;. ' work in tuban,* suburban and/or tvral dis-~ $o, they cannot have a speamen both tmder'~ ' _ 000 the microscope and in the human bcin roxitnately 1 to tricts .vere'' noted• 'A , Pp g .~ ~ u se s ses soon came under 'rcview; later about' find'•out what would have happened had _ ; :; s;^s,,C 2,000 more were added. Of the many slides" they not obtained the specimen at the time ~l. :^ :.'.(."..: i S. 8,590 from males and 3,661 from fema.ks when they did. Attempting to project what were adjudged suitablc A popular method would have happened involves a prophecy of fixation was to inject the bmnchial'treer and, in the very nature of biological tnatt- ~ immediately after removal with fornulin rial, is haurdous. The above statements " " f r~`~ ' ~ prccacer and fti Slid hv th SOr6 aply to such pnophecics as as aixaveesatng lessanjpn . . ., "` intact mucosae were ruled out as were thox' "nrdnotna in situ" L poorly prescrved One' pathologist.' uudf~ ' There are two schools of thought in zeh- :~;.. develo ent of true invasive;'~' , larg ~ e whole mounts in scven selected casci.~ ytion._to the ?A~}' v r . , _ , ~ t j• ~ If the worst condition wzs widespread, canc•v: (1) that the process from the nor- ' it is equally likely to be found whether the' mal to cancer is a slow and gradual one, sections are large or small if the choice of'and (2) that the change is suddca _': • blocks is made in the There is general agreement among cancer c:ir;' ~ These experienced pathologists' are cog ." rescarch workcn that the behavior of carr- ~'. u ~' :, =-+,•,+C nizant of thc innumcnble variables involve eer ise to a changc of mtracrllular d d d -> y ,.... . ~_. .. . 1• _ ~ in this study Thty are ' to an individua~ • The chan nimics ared e can to the _' be corn r g ~- . , . p , J ~ '' convinccd that not only was the study potcncies within normal undifTerentuted or:•= 1= ` .'•.b,r. »:- ft~ worth while as far as it wcnt but, as always partially differentiated cells. All biological in any scientific investigation, many prob" experie•nce states that the potency of such krns hitherto either vague or not apparent- cells is greater than thcir ralization_ If a' came to the surface and a number have ccll'can do anything, it can do more than it '; - been crystallized into projects for further does. Therc is a point in the life of a cell 7' . ouu..a~y^. >. ,o aT rr., work. fi wbereat, from xvenl potencia, one ; hra3, Jr = r:• r~ .c~r r!ri'v - All realize fully that while pathologic- chosen to be exerted. This, called the point •:?•.:J tK~. ,•4 arutomic facts are at the basis of much of of determination, cannot be predicted by. 'r?'• :-gr•soti~Y1 7-, our knowledge of not only disease but also of looking at. a cell. It must be transplanted ;} the norrnal nevertheless the basic handicnps_' of watched so that it can show its true!" ' , . : of pa ology are constantly in their minds. colors frorn• its bchac-ior. Another bioloPi- :: Y•~. pathok>gists ser sperimens grossty as they cal truism' states that when the kind of ~~'' . ~:;kr~A '.r.., •. ~; are, and microscopically as they wcre at the " diff i l ti d eren at ergo has on a ce l is to un been instant when they were submerged in fixa= determined, it nccd not exert this potrncy„ tive solutions. Their deductions a poste- riori are of considerable worth because of immediate]y.. It can delay an hour, a day, {),;.., - ~ r )U,4 ~ the cumulative knowledge in the work of week or cvrn months or yars. The fac ' tors infiurncing this time art, broadly I nJ, ,", the master patholoe sts of the last century t:, .4... spaking within the environment of the _ 1C :: • .'.~1'.1 a1 .... Oo: and a half. in thc,z rnaterul they have the t The Kational lnstitutes of Health tuve be- cell. %Vhen the diagnosis "carcinoma in conc intere<ted in further investigations, and c«,•.. situ" is rrade, it is stated that the potency ferc.Kes were held in Salt Lake CGty, the hnt of the cells in this area have been changed on Dccembcr 1958. under the leadership of W. H.' to those of cancer but have not as yet been Carncs. M-D. Many of the original panel have ,lctcnninrd to rrmtintre the work and publish thcir exerted. Since it is impossible by visual i1wh,•iAval results. means to tell whether determination hac , o_~...--- _ .. . . ao~ w e • . . • 127/759 C °1, ~Z HN ()0•,3L1.- -6.4

I__ • . . . ARCHIVES OF PATHOLOGY emtn t ;.. .~ corne trultgrunt and us an e a ` t bditd ruenvasve cancercannoe pt•ece t ii with .accuracy. . •..f•.r• _c:-,:,. .. t~` . " :~Lr ~ . , es in tuzym ectra, e To discuss chan a g p ; f cv r1~~ur aal + ~r . , -..,~ .y the "deletion" and "addition" theories of arcinogenesis and others would lead us' too far afierd for this, a pathological study designed to use desmptive langtuge.sa'`' •••, But a pertinent qucstion when circum- _- - , . .. stances c}lanPe c'Oncerns the t>oisible re- •I : placement by others' of ceIls which have _' •.. taken place, i.e., whether or not the cells in a"urcinoma in situ" in truth have be- h b 2, lYfales haR ChGSe cnIIngeS ISfore oflen tl~ of norrrtal cells. The evidence states that femalcs, but both metaDlasn and hyperplasia do 'r~J :, the metaplastic cells have bee3 shed as, for ocasr freQnently 'at females. -.. tJ :._; y example, in the trachea of rabbits deficient 3. Ggzrette smoken in this study have fewer in vitamin A; the normal eyli.ndrical epi- norma1 sections than norssnsotcc:_ - 4 B h di •sion of t9- to a rou r, ocru v s tn Y f{. ~ :. i.:~r +. .rrr.:.:[r:~ r;. It was inevitable that Wilson and Burke,;: 7. ~~+~a in siru w•as less and Ieu frcyraently;s? ?' in their statistical analyses of the elassifin-•,. °dfin°"'a',ag"o'ed,in°"'a , was and also then usually o"ly when tions and interpretations made by the vari-:: presrnt ,,n In Janwry 1959, a year and a half after' { ous pathologists would pinpoint especially ` ~"' _ the last oonfcrence in June 1957, three of :~i. - the limitation of the methods under sun•ey. '~ pathologists agrced to reexamine their ~',, . This in itself is valuable, as any rtiexamina- own slides, the 40 that had been circulated ;. ` tion of fundamentals is bound to be, espe- : ~•'. ..i Appreciation is expressed to Dr. ~i Keshntr eially in a subject in ahich both individual j i: i._ .. for arnnging the necessary microscopes and expertence with its qualitative judgments jKtors for this part of the conferencrs and to tbe ' = i' and science are intermingled as in patho-. Bdlcvue Hospital of New York given the appearance of "carcinoma in situ." Evidence is presumptive on this would point because we cannot tell whatd have happened if the cells had not been" removed and placed under the microscopc. We know too little of the factors inhibiting and stimulattng the determination and fsil- fillrnettt of potencies. This applies to many situations including the relation of rneta- plasia to the future development of cancer. In metaplasia we know of various environ- _ I mental factors which eatue the ehange logic anatomy. The data used by Wilsoo •; . ~: and Burke were obtained in tbe five oon='~', :',: ferenccs which were held, nameFy, in ccmber 1954, May 1955, Dccr.mbers 1955; Dcccmber 1956, and June 1957. The 4ad'i-' vidual pathologists placed slides of own cboue alongside a microscope for others to examine; particular slides were then projected for attempts at agreement4 Needless to say, the borderline cases ro-', ceived the greater attelltion, and **n'nimiti was obtained in perhaps half. Between the last conferences, 40 slides were clsosca, y (SPR) from a number submitted by euh participant and tmiled to the partidpants m rot]tio4 Thely diagnoses and cotllment'f were turned over to Dr. Wilson and Burke. At the last conference (June 1957) the following tmtative oondusions wrre•1.0e ~ drawn as a compilation of impressions and~~ the prel'iminary sutistical res.tlts: 1. T•heTe is rw differrntt in the pcevalmx of ehanges• called hyperytasia or a+etaptasia• at axry.es^ }' ~ age aiwve 2.5 yeus. Less than 30% of aD easea'l studicd induding boch sexes and all ages, tndyS.sti; Khich when removed luds to restontion 15 sections with apparently normal tnucosae. : ,,• 128/760 Vol. )0, Dtt., 1960 / C1R• 14 0 l : g p thelrurn reappcars when vttarrun A is re-•7 y stored to the diet. "~ar~" (ttwse which may have a high death nte from lung d.nccr) and those in farrrung and +_ But, again, further discussion of the ~ ~ consistent excess of mctapiasia or kyper- many pertinent facets seems inaPProP-•iaseptasia appeared in any of the three srocrp& ,~- hcre. It remains to record briefiy some of S. Study of the occurmxz of inetapiasi.a or~„ the disagreements among the pathologists in~n hyperplasis by the sue of the largest city in .rhicba;-;i subsequent meetings, for they bear dizectly.. ~'e cases have evn rarded revealed no dH"mcc''ta(1 : r~ ~'~ D~ dnn a M~ ~w ~ l ,. , D on the advantages and limitations of the D from lung euxer than in those who died from •. pnctice of pathology. •~ ~~';~n~ri1Ni ~.~ other nncen or all other causes of death •.'=:;:~ ~' ix ~N ~•~ .~ +~~'~ ~ ~ °~~

4 ;-., .. --, .. . ' . ~ BRONCHIAL TREE AND LUNGS -` `' ~'""` r ! and a number of the others. There were :"' In two published papers and one in press three fiat dtsagreements on the 40. slides. by Wilson and Burke the statistical evalu- O h i i di m e = ' ~''~-'~` '' t er m nor( ') ugree cnts wr 1!~{; ar ti ation ofthedhd j? .. results a.n important metoo: 4i: d Mi Bkdd didlicds' < ~ gue away:ssure wonere, as: ooes are prescnte. *~x ~Ill'ti~r~ the atholo ists what th lt ld b~ • ~ ~ • th lid ' s : e i i e~~' p g e ruu s wou e , [ •~= e s e vere exam r ned some t m b h h l ' i d ` er y t pat o og e sts scparate and with~ t; Twelve e i d th l i f ' exp r ence pa rom o og sts ?r :~-.;: ,~ ~,: out bcnebt of invnedute discussion But u ' , nrio s s - T' .3 s 4~:: , parts of the United Statcs under- , `Z. ~~. 1. this question raises snany problems indcad, ~ a study of the pathologic anatomy of . ~ ! . .•, , i_ -.-: . u?] 1 the bronchial tree and lungs in specimens ogists but scicntists sociologists, and othu r obtaincd from routine autopsy services and f Morphologinl dauificatio ist o no a very d Tr , b a ~.~'rr_: - surgt exstonsx e o lect vszs tn nta- •• precise proccss. The patbologists differed ~ sit d 'd th s n es es k g , ~gti e an tnn ence m ese quite steadily and indeterminacy vPas the' organs in relation to are sex ~ . . . . occupation , place rule. Approximations betweea them wen' • , c:' s,~ +^ ~ of residence and work, use of tobaao,' • ~i:t~s ~: •;r f. ofc t 1 Th f f all `A < rn no f E ,, c ose e ree or- con u- ause of . death. The classifiations used ;-: '~.. , ; . encu probably dulled some of the differ-_ ~n normal, hyperplasia, squarnous meta-~e' • ences but bYno means removed tbein` _" plasii, atypical meuplasia, arcinoma ia completely. As another "test," a number situ,' carclnoma. About 3,000 cases were ~ of pathologists reexamined their own sT•idcs investigated yielding 8,590 slides from -V '• !Cr ~ ' a ycar or so later and found they diffe~ males and 3,661 slides from females ad- ' almost as much as they differed from one.' judged suitable. The bordu line uses pro-" j voked disa ecmrnts, man of which could , _ ,c,...;~~.: rT anot}xr. As a rernark on the practice of.~ gr y i bcta•een, now closer to physics, now closer From raw compilations the results are •• to sociology. Pathology has uncovered close equivocal. Rigid statistical appraisals have approxirnations in eer•ain fields, that is, ~~de and are published in separate` .: : close urunimity of diagnoses and interprc-: w~ • Again it has been shown that a ooopera- tations In others th a i ti e pprox ma ons are . tive study is needed in problems in which far from the base line. In the present nse, large amounts of data must be collected and ' it is apparent that quantitation is quite dif- in which basic procedures in a particutar are somewhat like the 'essay type' of exam- The Institute for Cancer Resarch, 7701 Bur- ficult. As Dr. Wilson remarks, "The data discipline can be collectively assessed. ' to examination papers by different, equallY.~::.; R£FEREhCES .1 ~ inations, wherein differing grades are given Wme Avc, Fox Chase (11). .._.. _.___.__ ___......~. , ~. v ....~.~.u a.w - . . ~ . - . individual examiners may change their grades upon subsequent reappraisal of the papers." "Multiple choice" examinations lend themselves more readily to agreement but have the disadvantages of not knowing how the student thinks and expresses him- self. _ ' Rnrtioww ~ .CTR• 140b pathology, it can be stated that they did,• not be reconctled. In addition to confu-.• ;.. much better than can be expected in a num- ences, selected slides were circulated and 5?_ ber of other subjects such as psychiatry or many pathologists reexamined their own r; i sociology. Physicists have constructed rnany slides a year or so after their original diag- laws lavc•s of great predictive power; sociologists, noses• Some of the Iiatitations of the prac- ~ vc few. Biol tice of pathologic anatomy are discussed . ry ogy and medeine ane in 1. Coulson, C. A.: Electronic Configuration and Carednogrnesis, in Greerutein J• P., ud Haddow, A, Editors: Advances in Cancer Rcsearcl, New York Aadcnic Press, Vol. 1, 1953, pp. 2-56. 2. Cawdry, E. V.: Epidermal Car•eirsogenesis. in Greerutun, J. P., srd Haddo.v, A, Editon: • Adrances in Cancer Researc}>, Vol. 1, pp. S&101. 3. Alexander. P.: The Reactions of Careir>ogens with Macromolecules• in Greerutein, J. p, &M • Srt•G : . 129/761 My~ti Vit"I 00-2A ~(3

•.~ . . • ..e.,. _ ~ ARCHlVES OF PATHOLOGY Haddow, A, Editon: Advancu in Cance.r Rr 11. Leuchtrnberger, C•: A CorrYlated Hir . acarc}, Vd. 2. DD. 2•72 • toio¢in,l. CytdoQical ard Cytocheaunl Study of ruti ti a d CM un] C t o G 1 d b B d T h B l 2 i- -- a761J n n . o u ~~,~ a Qer, . .. n t rac e roochn oo- Tra and l.tat8p of Tvl.a.: •' in Gransteu> Actirit J P Cua and E ~~'~~ "' ~ i d j C S ; ~~, ' y, , . , rr,Qen , .- c rpo.c t arttte to moke, Ach L1nio inte~nat , + ^ t' = : ` Tr - . 2/-,r~ -....~ Habda.r. A, Editon: Advams in Canm Re~ oootra tancttaa IS:G32~38, I959. ;~,*~~' usrch Vd. 2, pp. 73-127. .s:Un•: '- .l~' 12 ~. CtmninyEatsi. G. J, and Wirutanlry, D• PP ~uAr~tu= S. BcrmNturt I.: CaranoQeoais and Tt>mor Hyycrplasis and yfctayiasia in the Bronchial F.pi- = ~ " PathoQasesis, in Grecnstcir. J. P, and Haddow,' thditan, AntL Royal Cd1. SurYnocx, Frietand 2'4,~.- s~l~i~ A, Editors: Advanccs in Caneer Raeirc2ti Voi.' 123'r1J0, 1959. i!•-:~r.; 2, pp. 129-175. 13. Auerbach, O.; Gerr, G. B.; Formir>, DdL R: EcdoPy of LtrrtQ Cancer, in Gran Petrick T. G.; Smoiir> H. J.; lfudssarn G. E ~ •- ' ttein J. P., autd Haddoa, A, Editors : Advanccs I). Y, ar,c5 Stout A P.: Char~a in ; ~~y ~ in Canccr Rcsnrch Vot 3, pp. 1-SQ . ' Broochial Epitbtlitan in Relation to Staolvrig and 7. Pullmat~ A, and Pulltnat4 B.: Electronic i .~.~ Canccr of Lv:tY, New Enjiand J. Med. 25tS:9'l-104,"_ .1. Structarc and CarcirwQmic Activitia and Anorrntic 1957. Molecules. New Dcvdopmema, in Gmroteir4 J. P, J4. Aucrbnc}> 0, ct al.: Amtoasial Appronth~ )L and Haddo.v, A, Editon : Advances in CarKCr Ro-' to S of Stnoid and B c Carcinxcu," %.~ 7~ VoL 3, pp. 117-169. - ' farticr 91956. : ~~ty ;•,. . ~ r . 8 Rondoni, P.: Sonx AsDecu o( Carcrogehesis, ~ •. %_ y P' 15. Caratinjham, G. J. ; Nauay E, and waltv, '+• , , ' `.'; ;• in Grcatstd4 J• P, and Haddow•, A, Editors: .~ . ~sl~ar-t~+y.ru;: 14: Advances in Catsocr Rcsnrc4 Vd. 3. yp. 171-221: J B.: Tbe Freqtency ot Tt>aror-like Formatious._J. ; in Brnochiaiatic Ltmgt Thoraz 13:64-68 1958 ~" 9. Shitniria, M. H. : Pulmorury Ttcmors ia Es- -. pcrvnmta ll Animals, in Grernstcio, J. P, and 16. De Ha:r> P.: Pctmoaary Changes in Asian :. Haddow, A, Editors: Advances in Cancer Ro- Itsfluats~ Nederl- tijdschr. rerx~sk 103:721.72tS, anrcl, Voi. 3. pp. 223-267. .•., ,. . . ,..• 1959. `: 10 Leochtcnberaer, C. ; I•euchtenbcrger, R, and . 17. Krilcor>, E B, and Burke, Li. H.: Some`' • ~; Stztistical Obserntions on a Cooperativc Study Doola~ P. F.: A Correlated Histd cil Cyto tfyra'. ,....,, ; logical and Cytocheminl Study of the Tracheo- of Htanan Puit•nanry Pathology: I, Proc Nat r:+: 'r.... ;.t Brorxlal Tree and Lc•.gs of Mice Ezposed to And. Sc 43:1073-107$ 1957; 11, Proc. Nat Aad .'' Ci~arette Smok~ Carxer 2:~9Q50ti, 1958. --•' ' Sc ~5:389•393, 1959; III, to be published. t • J 7 b 9 II 1'17 - .1 -z0 •r'i~r 1.-'''`_t.- ?~ sf~i2t.+~ar: '-z~-,:7GtI Y, v; .. . . • " CCik a3.~ k T•.r.. ~:~, . ~¢rr .131 ~e >=r,{ a:us.,';,: 4C~'4 7 ~r. . ;r ~nlni ,inS:~'~b'vtf:'a + • fSl,. .a • ~~ tt_ .~:S~ay _'' &i; rDi m ,. . .. X ' ' v...• .:1• • 7 . . ''~.r.r. .r . .. t_. . T••rrr.~ . . . . . ')~ . ...:R• 5~~.•. ..•i.~ ~ , . 1LIt - ::.., . 130/762 ® P.i.t.d .•.! P.Ituh.1 iw U. D.tt.[ St.t.w a! Aw.r{.. I CTR- 140y C I R, H N 0 0 0 4," 1