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CONFIDENT/AL: : • MINNESOTA TOBACCO LITIGAT/ON EVALUATION OF THE 1969 SUP~[:EMENT TO THE 1967 PUBLIC HEA.LTH SERVICE REVIEW - THE HEALTH CONSEQUENCES OF SMOKI NG The 1969 Supplement,1 as did its predecessors, seeks to convey the impression that most basic questions concernino~ smoking and health have been answered. However, the gradu~(lly accumulating scientific evidence fails to support that impression. Moreover, it remains true that ~esearch has not provided answers to such funda- mental questions as (i) whether any fngred~ent as found in cigarette smoke can be demonstrated to cause cancer or cardiovascular, re- splratory or other disease in humans, or (il) whether any physio- loEfeal process C~echanism9 can be demonstrated th=ou~h which exposure to cigarette smoke results in death, illness or disability. ° Unfortunately, the 1969 Supplement does not fairly reflect . ~hls state of knowledge. Rather, it is characterized, as was its predecessors, by the ~ailure of the data cited to support the conclusions expressed. " The 1969 Supplement claims that no negative evidence has developed to refute the ~ud~ments of previous years ~nd that those previous f~n.din~s have been confirmed by the studies made subsequent to rheim release.3 In contrasted these claims, the followin~ b~ef review of the pertinent scientific material will show that the 1969 Supplement continues to manifest a bias against smoking and PRIVILEGED AND CONFIDENTIAL ,Pcoduced as reqmr." ed by the Coutt~',s ~,~arch 7, 1998 Ordex is • . TIMN 0151876 State of Minnesota,-et aL v. Philip Morxis~ et Court File No.: C-1-94-8565 ,..

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION" continues to provide a selective rather than a scientific evaluation of only some of the available knowledge. To avoid over-extendin~ this review, it will be illustrative rathe~ than exhaustive. As this review t~aces the Supplement through it's consider- ation of several of the major disease areas with which smokin~ claimed to be associated, a majom consideration ap~lleable in all areas should be kept in m~nd. Despite the ~heto~le of the 1969 Supplement, of its pmedeeessors and of othe~ anti-smoking pro- nouncements, research directed at the question of smok/n~ and health all too often done with tSe sin~le~minded purpose of implieatin~ smok~n~ -- has up to now failed to produce answers or explanations for any of the follow~ng questions and problems: [i) Why do most heavy smoke=s not develop these diseases?' (li) Why do non-smokers often develop these diseases? [i~i) Why do women have a much lower incidence of these diseases, regardless of smokin~ habits? (iv) Why. are there w£de variations in incidence f~om country t0 couni-~y and among different ~aeial g~oups within Indlv~dual countr£es, regardless of smok£ng habits? [v) Why is it not possible ~o~pr6duce~these diseases experimentally in animals, using c~are~Te smoke in a manner ~easonably simulatin~ ium~n~smoking? (Vl) Why is i~ tha~no consistent d~se-~esponse • relationships can be demonstrated between the use of ei~arei-~es and these diseases? PRMLEGEDAND Cn~r~ -~ Produced ~,~,,-IDENTI~L " . I TIMN 0151877 as requ~ed by the Cou~ s March ~, 1998 O~er State of Minn4so/a, ef al. ~ Philip Morris, et aL

CONFIDENTIAL: ME~SOTA TOBACCO LITIGATION Cvii) What are the relationships to the development of these diseases of the many other factors found to be associated with t~em? .[viii) What are the mechanisms through which these diseases develop and how can smoking be shown to plhy a ~ole ~n those processes? Ce~talnly the 1969 Supplement provides no answers to any of these questions and 'no solutions to any .of these problems. The continued failure to provide substantial scientific information w~th respect to these problems suggests that the hypothesis that smoking causes these diseases should remain suspect. Further, the consistent failure to develop pmuof to convic~ smokin~ should compel the conclusion that the Publie Health Servi~ would be well advbsed to cease its effomts to gloss ove~ ~aps ~n knowledge by sweepbn~ statemen~ of unsupportable conclusions and should, instead, devote ~ts efforts to an expansbon of research into @~i~ possible -~potheses, both causal and otherwise. SmokSnK and Card$ova~eular D~seases In April 1969, the Surgeon General reaffirmed to Congress h~s previous statement that smokin~ had not been proved to be a cause';of heart disease.~ His view was concurred in by the representa- ~s'did the Sumgeon General) with the eoncluslons of Dr. Carl Seltzer of Ha~vard in his January 1968 review in theJournal of the American

CONFIDENTIAL: " MINNESOTA TOBACCO LITIGATION Medical Association~ Without the slightest reference to this con- co,dance of viewpoint, and without the slightest citation of intervening new evidence to support its contradictory statement, the 1969 Supplement flatly assemts that smokin~ "is a significant mlsk factom thateon£ributes t0 the development of coronary heart disease.''8 This unqualified assemtion of causality is in conflic~ not ohly with the conclusions of the Surgeon General and the Heart Association as expressed to Confess just thmee months before the Sup~lement's date, but also with the scientific evidence available, as[outlined ~n this Evaluation and its pmedecesso~s and as other- wise ~epo~ted in the medical and scientific literature. As even %his brief evaluation of that evidence makes plain, the search for mechar~sms or chains of causation has. p~oduced only theories and possibilities? not factually demonstrated pathoEen~tic developments. No new evidence to suppomt the sweepin~ claims of the 1959 Supplement is to be found in the section dealin~ with epidemio- lo~ic~l studies. Indeed,. the dearth of new ~nformation of consequence -~n this area ~s sugEested by the over-emphasis ~iven to the study by Hammond9 That study was based upon reports obtained by question- na~me from individuals, not fmom their doctors, and causes of death taken from death certlficates~1 There is no showin~ ~hat the difflculti~s of dealing with such data havebeen overcome, and so . _~epetltion of lonE~eco~nizs~.met~od01£g~?al em~ors. . can scarcely be expected to lead to enlightenment. Curiously, Hammond's data indicates that the coronary heart disease mate is lower forsmokers of forty oP mo~e c~arettes daily Ptodu6~d ds req~ed by t~ Courib~.~:~r~h ~ ~998 Order m .... :.: ........... ~'-e~-Minnesot~ et M2 ~ Philip Morris, et aL ....... Court Erie No.:-C1-94.8565 - " "

CONFIDENTIAL: ~SOTA TOBACCO LITIGATION £n. eertain age groups in each sex than it is fo~ smokers of twenty to thirty cigarettes daily in those eategori~s~2 This raises question as to the claimed showing of dose-~esponse. Unfortunately, but as might be expected, the inconsistency to be e~aluated here is not discussed in the Supplement. Similarly, the Supplement mentions but does not discuss the findlnE of the Thomne paper~3thaZ attack mates of non-fatal coronary heart disease are lowe~ &n smokers often to nineteen cigarettes per day than they a~e in smokers of one to nine cigarettes per day. Typical of its selective approach and bias, the 1969 Supplement does not discuss the Thomne paper's findinE of an association ~e~ween short stat-ure and increasedmisk of coronary mombidity. The paper, however, does-d~scuss this at len~h, p~ntin~ tO the possibility of insulin hypoactivity affectin~ the action of ~rowth hormones, in turn affectin~ lipid om suEar ~etabolisms, which are associated with coronary disease risks. The genotypi~ possib~l£tles here are nowhere considered in the "1969 Supplement. No~ is mention made of.the finding that non- participants in sports had the same ~isks as cigarette smokers. The Supplement affords similar non-conside~atlon ~upplemental citation and no discussion) to the finding of Bassettl~hat the significant dif~eTences in coronary heart disease between Hawaiians ....... and.Japanese men_~n..~awal! we~e_~% m~lpte~ ~9 any differences., in s~king histories. Sevemal othe~'studies reportin~ failures to find

CONFIDENTD~: MINNESOTA TOBACCO LITIGATION association or correlation of smoking wi~h cardiovascular diseases and f~ndlng associations of other factors with th~se diseasesl7either appear in the Supplemental B~blio~aphy or are omiZted entirely. 'Bu~ the Supplement's conclusions and text reveal not the slizhtest hint of this very importan~ fact, i.e., that epidemlolo~ical sln/dies have had inconsistent results, with~many showin~ no relaZion- ship be~een smokin~ and heart disease. Rather, the Supplement, by selective discussion, conveys the false ~pression of consistently shown association. . In its eagerness to emphasize the various associations he~een smok~n~ and coronary hea?~ d~sease appea~ing &n %he data of analyses of ~he impac% of behavioP t~e$O~ii) ignores ~he&m findings conf~mmin~ the genemal fail~e to find a si~if~can~ly incmeased Pi~k Patio fop angina pecto~is in smoker~and (l~i) ignores the fa~l~e to f~d a s~iflcant association be~een eigame%~e smokin~ and %he ~cidenee of i~lent o~ cl~n~cally ~Peco~n~zed myocamd~al ~ . .. 22 n~are~on. O~e searehe~ ~h~ Supplemen~ in va~n ~o~ discussion ~ndeed, eve~ reeo~i~ion of ~he highly s~i£~ea~ observations, • ha~ ~he coronary he~r~ d~sease ra~e~ in ~he hea~ smokers o~ perso~- ali~ ~ype: B were similar ~o or lowe~ ~han ~ho~e o~ ~he non-smoke~ 2~ ex-smokers o~ personality ~ype A. ~nd only in ~he Supplemental Biblio- s~d~ which found ~o enee in smok~nff babi~ be~een ~hose who d~ed o~ coronary hear~ disease and ~hose who died of no~-eoronar~ causes. Mos~ ~mpor~an~ly, however, 0151 SI

CONFIDENTIAL: .... MINNESOTA TOBACCO LITIGATION the 1959 Supplement makes no mention of the point emphasized by 25 Jenkins and Rosenman: ".. The demonstration of statistical association does Sot indicate a causal relationship or define the physiological om biochemical mechanisms by which smoking might engender an increased risk of myocardial ~nfarction or advanced mortality rates from acute i~farctio~ . . . proof of a causal relationship between smoking and eomonary atherogenesis has been lacking despite a substantial number of investigations." In furtherance of its constant emphasis uponassociation • 2 27 as if it were cause, the Supplement ~escribes Dr. Mulcahy as having observed an association between smoking and disease in an Irish population. Not described is his statement that "It is impossible to deny the association between cigamette smoking and CHD, but it would be advantageous to establish whether this association is a causal one. "' 29 The Supplement's stubborn refusal to treat evidence 30 scientifically is revealed hy its discussion ofCederlof's recent twin study in the United States. RecoEnition of the fact that this is a continuation of an extensive line of studies, begun in Sweden and pointing to the conclusion that cigarette smoking may not he causally related to coronary heamt disease, is nowhere to be found in the Supplement. Rather, the Supplement here chooses to question the validity of data obtained by questionoaive, in .... stamk contmas~ to its. ready-acceptance of such data in other studies fayorin~ lib cohelusions. _More importantly, the Supplement suggests that theme may be an~nder-estimation of the immediate effect of ctbTrent clgarei-~e smokin~ because recent ex-smokems are included

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION ~n the same category as smoke~s. The Supplement's theory appears • o be that the inclusion of recent ex-smokems will include people who have a lowe~ Fate of d~sease and 'therefore weight the s~udy ~n favom of smo~n~. Th~s spee~at~on should ~e eonZ~asted w~tb 32 %he Supplemen%'s quotation elsewheme f~om Ha~ond's s~dy, wheme. the suggestion is ~de that the hi~he~ disease ~a~e of ~eeent ex-smokems~ is due %0 the fac~ tha~ Zhey a~e people who a=e fomeed %o stop smok~n~ because of the~m illnesses. The ~mportant consideration fo~ the moment ~s not whethe~ om why ex-smokevs have mome om less d~sease, ThaZ ~s a ma~em which can and should be %he s~eet of meseameh. But the comparison %he Supplement's tmeatment of the ~'o s~ations does s~ow ~he s~gle ~nded approach of the ~lle H~alth Semvice, ~.e., ~n each s~%ua%~on %o a~opt %he ~nte~pmeta~ions and, ~ndeed, speculations nee~ssa=y to ~l~eate smoking, even ~f thaz means %he adoption of d~ame%~ically opposed ~n~e~p~etat~ons and speculations of dlffe~t s~dles. Another mevealing note fmom the Suppl~ent's t~ea~ent of The ~in' studies: The particular study in questlo~3deals with angina pecto~is, which has been ratheP consistently shown to be no~ 3% associated w~h clgamette smoking. Rather than meco~nize this, 35 howevem, %he Supplement can only state that the "melationsh~p" ~e~een Ssok~ a~d~ ~A~~~%-0-9~ "ha~ 'not been clamified." 36 '-Th~s equivocation should be ~ead in l~ht of the conclusion of the .. ' - ....... .......

CONFIDENTIAL: 1VHNNESOTA TOBACCO LITIGATION • - ................. ............... 37 Cederlof paper, consistent with many studies in this field, t.hat "it was not possible to reproduce the association ~etween smoking and certain cardiovascular symtoms) when studying monozygotie smoking discordant twin pairs." The Supplement's discussion of atherosclerosis continues 40 to display its bias. Thus, Strong's work is a~ain referred to, but wizhout recognition of the author's own negation of any inference of causation. In similar v~in, the work of Saeket~ is embraced. ~2 But the Supplement does no'~ credit the investigator's own statemen~ that other variables had not been thoroughly examined. Nom does it consider whether, in light of a Russian finding, Saekett's population was as representative as he thought it was. Saekett had meported that his population of persons admitted to a cancer hospital was not biased or uncharacteristic because no r'elat~onship between cancer and. atheroselerotie disease had been reported in the literature. However, Vihert has reported his U.S.S.R. study, which indicated that subjects with lun~ cancer had more atherosclerosis than subjects with cancer of the stomach or "healthy" people. And, not unexpectedly, the:Supplement is devoid of discussion of the important point about aZherosclerosis made by Kannel in eommentln~ on Sackett's w6rk:%5 ' " the relationship between this pmoeess [athero- s~l~r~sis] and coronary artery disease is not perfect, .................... and coronary artery disease, is our ma~o~ concern." "No~ is reference made to Kannel's statement of the autopsy study on 85 subdeets from the Framingham investigation, in which theme

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION was a failure to find any relation between smoking and uncomplicated coronary atherosclerosls in Those not dying of coronary heart disease. The comment by Kannel, which puts the whole matter in pemspecTive, was ignored by the Supplement:q~ "No one can d£spute the statistical association be%~¢een mortality from coronary heart disease and smoking, nor the fact That the intensity af smoking is related to The risk of mortality from This disease. However, tSe present time, we don'T know if that relationship ~s causal." The experimental work~ealin~ with single massive in- ~ected doses of n~cotine is of questionable pertinence at 5esT, despite %he Suppl~ent's e~hasis on it. Nothin~ has yet appea~ed which would mela~e the effee~ o9 such a dose ~o the effects, ~f any, of %he &n%emmi~tent small doses of nicotine characteristic of h~an smok~nE habits. Indeed, Whelan's studies~ no~ mentioned -- would suEEes% %hat no such ~ela~ionsh~p exists. In ~his conneeZlon, S~pplement does no~ mention the Ha~ka~ mev~ew, which pointed ou~ ~ha~ :51 ."Extensive investigation of the pharmacological action of nicoZ~ne and ~obacco smoke ~ experimental animals as well as man, failed to show any evidence ~hat e~hem of ~hese s~sZances pmoduce in~umy to ~he nodal vaseulam appa~a~s." The qua!~Zy of the section of th~o~us fommat~on ~s revealed by its assemt~on ~hat ci~ame~e smok~E causes an -- __ ~ f~ee~fa~ty acids through stimulation of~"ca~echolam~ne melease.52 This ~gno~es ~he demonstrations ~hat incmeases ~n f~ee-fa~y a~ids occasioned by cigarette smok~nE occum only ~n a fasting, sTa%~B As ~he work of Solof~has shown, an ~nc~ease in • . ~o~__,u~2~~ ~,,.,,~.~.~ " ........................

CONFIDENTIAL: ' free-fatty acids is not a response to normal cigarette smoking. ~ 55 The Supplement's choice of Diatenfass's side5%f the debate on whether high blood viscosity precedes clinical mani- festations of myocardial infarction would be irrelevant, were it not for the unwarranted speculation that f011ows'to the effect . that high blood viscosity is somehow brought about by the increase ~n carboxyhaemo~lobin which has been reported by some observems i~ ciEare%te smokers. Here, the Supplement chooses to speculate about the work of Dintenfass ~ather than to rely upon the 57 • observation of Solvsteen, that blood viscosity isnot c~anEed hy high concentrations of carbon monoxide..This unscientific eholce :. cannot be explained by unawareness of Solvsteen's work, since the 'Supplemental Biblio~Taphy includes a citation ~f the article. Because Solvsteen noted that the eambon monoxide tension applied wa~ much higher than that of the blood of smokers, the pertinence of his observation is manifest. Of course, in order to follow its blood viscosity specu- latlon, The Supplement has to assume that 6iEher viscosity and thrombus formation is the cause of ~he heart a~tack. This, however, ~s quite contrary to the current view expressed by Spain[8 His view, based upon observation ~ather than speculation, is that thrombus formation may well be the result, rather than the caus____~e, of the ho~ after The onset of the attack and the~frequency of incidence of thrombl thereafter rises wi~h increased survival time. PeOduced . . ............... . S o£ edbyt2NDCoNFlh_ " " .... :TIMN 0151886

.... CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION In support of its assertion that "platelet adhesiveness is increased by smok~nE, probably secondary to the release of catecholamines,'~he Supplement can find only the speculations of last year's Supplement as a ~efemence. It thus ~Enores the " Jenkins and Rosenman study cited earlier, perhaps because the 62 conclusion is contrary: '~Ithou~h smokin~ may enhance pla~elet adhesiveness, critical analysis of available s~dies have f~iled to confirm that smoking causes any significant ehan~es in blood coa~ulabil~ty." The Supplement's unwill~n~ness to mecognize that association is not causation is again shownin its treatment of ~he wor~%f Stables, which indicated that patients with myocardial Infirets had mean hematoc~it levels siEn~ficantly hi~her than those of con~mols. Unmentioned is Stables eo~ent tha~ his s~udy did not'answer t~e question whethem the association is an et~olo~&cal 65 .i one, A eameful readin~ of the section on carbon monoxide shows ~hat last year's hypotheses have not been established by any of the matemial reported in the ~nter~m. Therefore, the possibility that smokfn~ has somethin~ to do w~th increased carboxyhaemo~lob~n levels ' which in turn has somethin~ to dO with ca~diovasoula~ d~sease, memains an u~suppo~ted speculation. On the rare occasions when the ~q~5i~f~d~~ ~-~-~-~~er~~v~ of ~act~ather than o~ ~eculation~ ~t Ss not always correct. ~hus~ it's cla~ra that smoking causes carboxyhaemoglobin levels o~ ~ive to ten percen~ . :TI N 0151887 • ......................

~ p CONFIDENTIAL: _, MINNESOTA TOBACCO LITIGATION. 67. flies in the face of the observation tha~ many cigarette smokers have levels of less than five percent. The basic point is that the whole area of carbon monoxide remains one fov research. E%~h such basicquestions as (i) whethem smoking increases levels, or (ii) whethem there is an acclimatization pmoeess, om (iii) ~hether levels that are ~llghtly increased [the most that smoking could be postulated to do ) have any significance fg~'~ealth, are'all questions~which remain unanswered. Indeed, only the spareest preliminary information h~s as ye~ been repomted. Observations -- not speculations -- fmom the s~udies of Seaver~Sand Cumphey6~ave indicated that cemtain individuals can be exposed to heavy concentrations of carbon monoxide foe substantial pemiods (as compared to the exposure of cigarette smoke=s) without experiencing ill effects. Accordingly, the approach taken to the ~a~bon monoxide question should be open-minded, with =ecognltion of the continuing need to answem the questions raised by Curphey ~n National Cancer InstiZute Monograph "If mome CO is present in the blood of the smoker, does it p~oduee either functional om structural pathological changes? Are such changes demonstrable by symptomatic, el~nieal, or laboratory evidence, and can they, ~herefome, ~e assumed to be detrimental ~o ~he heal=h or well being of %he smokem . . ." Most notably absent from the 1969 Supplemen@ is eonside~- __a.%~Qn_of.%h@=~r~¢ually_a~e~;~g_9,vi~@nce support~n~ the hypothesis that smoking habits express constitutional d±ffeeences and that these differences, not smoking, are at the root of the 8tateo~.~re~ b~ ,~O CO~.~ . .l~- ~TIMN 0151888

MINNESOTA TOBACCO LITIGATION problem. Several studies reported contributions in this area, encompassing observations on brain wave patterns~2anxiety factors,7B personality traits~Whehavioral patternsT~nd somatotype.76Damon"s s~udyT~f somatotype showed that in general men who would develop comonary heart disease could be diser~mlnated from those who would not by body type. His report included confirmation by the National Heart Institute of his results. Significantly, these results were found to be independent of Cigarette smoking. I~ .is not sumprisin~, then. that Hut~hison concluded78 %hat the evidence on whether smoking causes cardiovascular disease was not adequate to eonsidem the issue closed. It is lamentable %hat the 1989 Supplement not only came to~he opposite conclusion but also refused to even reco~nlze the conflicting evidence or the ~ossibility of a conclusion contrary To its own. • Smoking and Chronic Obstructive Broncho- PulmonarV Disease The 1969 Supplement follows the 1968 Supplement in failing to discuss, much less answer, the "crucial" question posed by the 1967 Report.79 "This crucial question must be answeee~d affirmatively • before an inference can be made that smoking directly causes pulmonary emphysema: Does ~nhaled Tobacco smoke have a direct toxic effect on the a!vlola~ tissue in %he lun~ paPench~a ~hich is impomtant in the patho- Eenesls of pulmonamy emphysema? A~ present it cannot .............. be. ,answered. Ae~o~d~nEly, the P~lie Health Semv~ce, ~n it~ 1968 publ~ at~on "A Special Repom~ on Emphysema'~ told ~on~ess that: 81

CONFIDENTIAL: MINNF OTA TOBACCO LITIGATION "The cause or causes of emphysema ave not now known." and that~2 ' "Since there are no clear-cut leads as to the cause or causes of emphysema, no quick solution to the problem • can be anticipated." Entlr~ly consistent with this viewpoint, the Surgeon General %old ConKTess ~n April 1969 that no causal relationship had been established between pulmonary emphgsema and cigarettes.83 Dr. John L. G0mpertz, P~esident of ~he National Tuberculosis and Respiratory Disease Association, agreed~Wand Dr. Robert BrowninE, a member of the Boardof D/rectors of that Association, pointed out that emphysema was "an area on which . . . we have not any valid statistics ye~ available.'~5 Just three months later, in contrast to these candid statements and without new evidence to justify an9 chan~e in ~iese concl~sions, the 1959 ~uppAement,maEes sweepin~ assertions of causality of chronic bronehopulmonary diseases by smoking. At the outset, one significant point of departure taken • 87 by the 1969 Supplement should be noted. In both the 1967 Report 88 and the 1958 Supplement, the Publ~e Health Service considered the research findings on chronic bronehltis and emphysema together. The still val~d reason for doin~ so, set forth in the 1@67 Report, is the difficulty of distinEuishin~ between these diseases~9 The 1959 Supplemelt does not assert that criteria for the differential definition of chronic bronchitis and emphysema have been established. Nevertheless, the Supplemen~0does purport to treat these diseases " " ' 0151890

CONFm mlAL: .... MINNESOTA. TOBACCO LITIGATION separately. ' .......... - -. : ~ This arbitrary separate treatment should not obscure the po~Xnt that a conclusion of causation .cannot be substantiated con- cemninE either chronic bronchitis or emphysema, when the evidence admittedly cannot establish causation fo~ emphysema and knowledg, e is Xnsuffielent to tell the two apart. Review of the studies cited as "reconfirming' the Supplement's flat assertion of causation of chronic bronchitis shows that the difficulties of establishing causation in this area 92 have not been surmounted. All told, only eight studies are cited. 93 Of these, just one comes from the United States. The. Supplement's use9o~f ~hat study95as confirming its con- clusion is exemplary of its unscientific attitude. The primary objective of ~he study was the prognosis of chronic bronchitis. No data or tables were presented; and reservations were expressed a~out diagnosis because the information was obtained 5y questionnaire to the patient himself.6 The Supplement ignores the suggestion that differences in ventilary capacity may be due to a genetic:difference.97A difference which is genetic in origin could, of coumse, have significance for "" etiology. Indeed~ the author himself discussed thi~ possibility in a statement98submltted to Congress in April i969, almost a yeam after • - .... publication .~f. the eited report.- As Dr. Brinkman told Con~Tess:99 "Besides a hi,hem incidence of lun~ cancer, there ~ . ' are many other differences between smokers and non-smoke~s : ~ accident proneness, absenteeism, and disability are more eo Tt¢. -=.o % eo# i , " ,. , 0151891

CONFIDENTIAL: . lV~WNESOTA TOBACCO LITIGATION Of heart disease, stroke, bronchitis, emphysema, cancer of the bladder and peptic ulcer, are all more common in the sm0kin~ population. While some people have attributed all these diffemenees solely to c~arette smoking, it would appear more likely "that there are basic physlolo~ieal, psychological and geneZle differences between smokers and non-smokers which makes the smokin~ population mome prone to develop various d~seases and to follow certain social pat-terns which distinguish them from the non-smoking population." In contrast to the Supplement'S em~oneous equa~n~ of . causation and association, Dr. Brinkman concluded:100 '~ghile it iS reeoEnlzed'that there is a s~atistieal association between clga=ettes and various lun~ diseases, including lung Cancer, .~ronehitis and emphysema, I hope i have been able .. to illustrate some Of the difficulties in aceeptin~ cigarettes as the actual cause of these diseases. Besides other research, we need more electron m~croscopy studies of the bronchial response to • various substances so we can identify any chan~es which a~e specific to c~arette'smoke. With the advent of new reseamch tools, such as the scanning m~croscope, which allows a th~ee-dimension~l vfsual- ization of the sumfaee of the hmonehus, more knowledge can ~e expected. Until much more knowledge is acquired, • a ~ud:~ment as to whether or not cigarette smokin~ causes diseases is premature." Nor can convinein~ reconfirmationfor a causation con- clusion ~e found ~n the seven foreign amtieles Sited. Fom example, on~0~f th~ ~wo English studies c£ted dia:~nosed '%ronchitis" by amount of sputum productCon alone. It specifically found "no effect of smoking on chest illnesses independent o~ sputum produo- 103 10~ ~ion." In the other EnEllsh s~udy, the most significant findinE, ..... not mentioned in. the.1969. Supplement, fs.that bronchitis is more than ~w~ce as common in occupations ~nvolv~nE heavy exposume to heavy

And, in s/milar vein, the Italian studly0~ound the most sIEnlficant factors to be high temperature diffemential and dust exposume. With the small numbers involved, and no ~ndication whether the high risk occupational groups contained higheP propoPtions of smoke=s, any conclusions as to cigarette smoking drawn from this s~udy would he extremely suspect. The Dutch s~dy involved an ~oup with an extremely high p~evalence of bronch~Zis and, again, small n~ems. The Swedish stud~08 was a ~estionnai~e study, with self-expressed ~ese~var~ons s~ilar to those of Dr. B~i~an abou~ the limitations on ~he data obta~ed. The controversial nature of • he diagnostic c~te~a used was mentioned by ~he authors, but ~ema~s ~entioned in the Supplement. S~lamly un=entioned a~e The Supplemen~ noted that differences in forced expiratory vol~e and peak expiratory flow• ~a~es wi~h increased ~obacco consump- .... iii t~on were repomted by the South African study. But it failed note that no statist~cally si~f~cant differences in FEV were ~o~d be~een smoke~s a=d ~on-smoke~s before a~e ~i ~ha~ ~he d~fferences noted in PEFR fom Those ovem age 55 involved only 55 ll3 s~ects and were signiflcan~ only ~t ~he I~ level, and that d~ffe=ences noted in ~EV for those over age 55 involved only 53 llg s~ect8. To ~he ex%en~ that d~ffe~ences were shown, this~dy d~ffe~s f~om ~he above mentioned Swedig~.~.~ZL which ~noluded the ... f~nd~n~ of n6 diffemence in maximal explmaZomyflow be~een ~roups of smokems, ex-smokems and non-smokems. But n~ discussion of these eonfl&ct~n~ f~nd~nEs appea~s ~n %he 1969 Suppl~ent. Instead, the CO~E~:TOBACCO : ; TIMN 0151893 ~OTA LITIGA~ON~8 .....

unjustifiable impression is left that there is an entirely self- consistent body of evidence meconfirming the sweeping conclusions stated. Not only do the very stud£es cited to confirm and support the impression in fact demonstrate its error, but also, several Qther studies have shown that claimed differences between smokers and non-smokems as to vamious ~espiratory function vaiues cannot be demonstrated. And, of course, the reservations expressed by the investigators themselves should be given even gTeater weight when it is reco~c~nized that the 1969 Supplement fails to cite a single experimental finding insupport of its conclusions on bronchitis. .The Supplement's uncmitieal acceptance of every scrap of material antithetical to cigarettes and hypocritical ~ejeetion of anything to the contrary of its view leads it to a most curious conflict in its dlscussion of the prevalence of chron£c obstructive .. b~onchopulmonary disease. It suggests that this disease is under- reported, c~iticizes the view that it may be only more accurately "reported and'bases its argument on the speculation that la~ge-scale smokinE cessation would ngt show effects for some time to come. Howevem, it then oites a si-udy which emphasizes the difficulty of assessing the effects of cessation of smoking, and whose authom stated as to cessation that "I~is difficul~ to.prove a beneficial The Supplemen~2~urther--- confuses this field by misciting a si-udy by Mitchell. The cited study was concerned with the clinical

CO ENT/AL: picture of emphysema and its ~elat~onship ~o autopsy findings. It did not deal with ~der-reporting of b~onehopulmona~y disease, although the Supplemen~ says £t d~d. A different stud#~y Mitehell ~y have ~een the one the Supplement had £n mind. However, that study concluded that the £nc=ease £n death due to bmonehitis and emphysema =epo=ted in the United States is att=~butable in part ~o the fact that mo~e people l&ve to the age at which these diseases s%m~ke and ~ pa~t to ~proved diagnosis'--factors which cannot be said %o £mpl~cate eiga=e~es. Not a hint of eont~ovemsy om disagmeemenr clouds the Supplement's fae£1e asse=%ion that smoking ~s the most ~mpomtant agent ~n the development of pulmong=y emphysema ~ man. Not the - slightest explanation for *he change "in view taken f~om that of the ': " Surgeon Genera~ ~usZ th=ee months before is offe=ed. Nor a=e the many sZud£e#~knowledging that ~he cause of emphysema is u~nown and indicating the difficulty of its dia~os£s mentioned. Thus. 126 "~not~eed, fom example, ~s Homowitz's a=tiele ,meview~ng the field -and observing that "theme have been n~ne intemnat~onal eonfe=enees a~ouZ emphysema~ Aspen, Col0mmdo and Zheme ~s no a~eement as to ,~27 i~s cause. . Conf=onted by a~ezman s conclusion that inade~ate ~wledge .eonee=~ng :he etiolo~ of e~hysema makes an etiologic ... elassifieatlon ~sat~sfae~o=y' d by ~he. ~mk o~ .St=awb=~dge'_ which suggests %has e~hysema is caused by an a%=ophy of the vascular system ~o ' " • very diffleult %o a~t=~ute ~o e~ga~et~e smo~n~ -- ~he Supplement

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION ' van only speculate that several mevhanisms m~y be involved and %hat two suggested theories may be applicable but not mutually exozusive. Far from supporting this speculation, howevem, the sum total of the literature -- only pa==ially and selectively cited in the Supplement -- points to theaccuracy of Adelman's assessment that oumknowledge of the etiology of emphysema is •£nadequate. Thus, the eite~Peters study recognized the possibility of a third variable,, either of personality om cons%iZut£onal omig~n~ wh£eh causes one to smoke and ~o have diffement " " " physxolo~ze parameters of the lungs. Findings of the authoms, not mentioned in the Supplement, included a finding of no significant difference between one-second fomcedexpirato~y volumes of smokers.and non-smoke~s and one of no s~gnifieant difference in vital capacity. In the lattem connection, the authors noted %hat Andemson and Fem~is had reported young smokers 135 to have a larger v~tal oapaeity than non-smokers. The constitutional theory is given additional s~bstanee • . 136 '- ~y the sruaies ~eportin~ that chronic obstructive lun~ disease is ~elated to an ~nherited ~ene deficiency and consequent deficiency in alpha antltripsin. But the Supplement's~sin~le-minded emphasis ~pon smoking pmeeludes it from consideration of such alternate • h~otheses. ~n simila~ slngle-minded fashion, the 1969 Supplement .................................................. • ~elies on a ~eport of exper~m.ents with ~ But it does not dis- eus~ the authom's recognition of the diffem~nees in the struetume of the ~espi~a~o~y system of dlffe~ent animals -- differences he

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION eons~deres sufficient to suggest that experiments in one may have no relation to the other. This "~" reco~n~lon is confirmed hy 139 McLauEhlin who, in an article cited in the Supplement~4stated:l~110 "Great caution should 5e exercfsed in t~he choiceI of an experimental animal for pulmonary studies if they are to be applied to man. This is especially so if %he dog, eat., or monkey are to be used, in view of , Their marked anatomical differences from man." Indeed, the Supplemen~ cites observations of Me~u~hlin and of with mespec~ to spontaneous e~hysema and s~ilam diseases in the horse~ an an~al with a I~ anatomy s~i~r to man. But these point the way to caution ~ ass~n~ %hat ci~amette smoke or othe~ exogenous factors a~e necessarily ~nv01ved ~n causation. The same &s t~ue of Boatman's ohsemvation of a p~monamy d~sease, s~la~ %o emphysema in man, oceummin~ spon~aneousl~ in rabSitsl~s. The Supplement mentions ~he results mepo~ted by F~eeman on exposure of ra~s to h~h concentrations of n~%moKen d~ox&de -- ram ~iEhe~ ~han ~hose %o which cigarette smokems expose Zheim lungs. But no mention i8 made of Fmeeman's f~nd~n~ that mats exposed to moderate amounts:of n~%~o~en dioxide ~cew normally and l~ved normal l~fespans wi~h ne~he~ a~mflow mesistanee no~ dynamle eo~l~anee ,d~ffem&ng f~om ~hose of eonZ~ols. The lackof adequate etiologic ~nowledze as ~o e~hysema 150 ~s shown ~y the Supplement's section on "othem studies". Heme, a d~verse ~oup of ~heo~ies agd s~eculatlons ~s repo~ted, with no attempt ~o draw to~ether the ~rela~ed thmeads. In each instance, %he d~sc~sion ~s put ~n speculative te~ms such as "may predispose"; "can interfere"; "may be melated"; "may be inhibited'"; "Zheomizes",

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION J.5 The material cited in the discussion ~o~ cil~astasis does not ~ndieate any new infommation of note, but does contain Dalhamn's eoncluslon, not mentioned in the Supplement, that it ~s ~mpomtant, when evaluatinE bioloE~cal effects of tobacco smoke, to use methods which appPox~mate acZual smok~nE conditions~52 The Supplement does not even purport to apply this evaluation ~o the matePial it discusses. And, of co~se, measured by th~s cmlteP~on, vi=~ally all of the woPk in th~s field would he fo~d wantonE. The" need fom caution ~s fu~them shown 5y such s~d~es as ~hat of La~S~ot c~ted in the Supplement. He =epomted that mats exposed to c~Ea~ and cigarette smoke f~ve days a week fom six weeks had nommal e~lia ~ntaet thmouEhout the ai~ays, w~th no evidence of s~ous metaplasia om of h~onchieetas~s. The Eene~al condition of t~e" ~ats appea~ed to he l~t~le affected ~y hiEh doses of both and e~Ea~ette smoke. Caution ~ ~ntempmetin~ the results of achte s~d~es ~s d~etated by the woPk of ~ahl~SWHe found that the acute effect he obsemved f~om applyinE ciEamette s~oke to clam E~lls soon dissipated and the Eills me~Pned ~o normal cil~a~ action. These studi~5~end credence to the observation made ~n the 1068 Supplement, not ~epe~ted in the 1969 Supplement, that "the ma~n to deZe~m~ne to what extent the ~n vitmo studies can ~elate to the ~n v~vo studies ~n annals and ~ man.'~2~he 157 worn eite~ suEEests

CONFIDENT/AL: _.- : MINNESOTA TOBACCO LITIGATION " that ~here may well be no ~elationsh~p at all. Indeed, the whole quesZ~on of lunE clearance is much more ~n need of additional research than of assertion of sweepinE and unsupportable conelus&ons. Thus, uuensin~er used radio-aetlvely labelled plasti~ spheres to measure cleamanee from the pu~ona~y ai~ays of smokems and non-smokems. He fo~d that the~e was no ~ela~onsh~p be~een smok~n~ h&s~omy and ~icheal-l~ clearance. Xndeed, he noted Zhat some 6f ~he heavies~ smoke~s had the best clearance ~a%es. 159 S~la~ly, Haddad found that patfents s~ud~ed du~in~ c~ga~ette cons~pt~on as well as d~in~ ciEaret~e dep~ivatlon showed no si~ifican~ difference in clearance in ~he ~o cases. He concluded that his sZudy could not confirm a partic~ar mechanism by which cigarette smoke inhalation had been expected ~o slow clearance ~a~es . ' Consistent with these s~dies is the f~nd~nE of Lippmann, That smok~n~ histomy did not seem to affect the clearance of ~ad~o- active particles fPom %he l~Es. Q~nlan's wo~ ~s of pam~iculam s~ficance fom evaluation of ~h~ many experiments where conditions dono~ ~easonably app~ox~a%e h~n smok~nE habits. He s~died the mucohiliamy f~ction in smokems and non-smokems, f~ndln~ no d~ffemence ~n ~mans~t rates be~een the .-.~.__~o. He did no~e, however, tha~..the~e was a s~ificant difference ~n ~a~e when the h~d~y was varied. Vamiat~on in h~dity is an obvious consequence of such vam~ations ~n expem~en%al exposume as P~E smoke dimee~iy Into t~e tmachea. Thus, Qu~lan's womk su~Kests 0151899

CONFIDENTIAL: lVIINI~SOTA TOBACCO LITIGATION that experiments'which do not very closely approximate human exposure and the conditions of human exposure should be treated w~th caution. It is. precisely that caution, however, which is not exhibited.throughout the 1969 Supplement's selective consideration of anti-cigarette fragments. This selectivity can -- and in the 1959 Supplement does -- create a wholly unjhstified impression %hat the problems of the etiology of chronic obstructive broncho- pulmonary disease are solved. However, from even as brief a review as this one, the salient fact that ememges is the failure to vide answers for the questions of causation' .Sm°kinK. . and C~n~er The 1969 Supplementdoes not claim that any major new evidence has appeared ~ith respect to smoking and cancer. Rather, i~ limits its claim to the assertion that various studies have "added to the weight of the evidence linking smoking and cancer."162 But even this" comparatively limited claim is without foundation ~n the material cited or otherwise reported during the period covered:: by the Supplement. All too frequent discrepancies between the Supplement's statements and the data are present right from the outset of the discussion of epidemiolo~ic studies. Thus, the Supplement states that "epidemiolo~ical information on cigarette smoking and lung cancer, similar to that which has been collected in the United States and Western European countries, is n6w. bein~ reported from Eastern Europe and Africa aswell.~6%ut the sum total of such

CONFIDENTIAL: I ~ MINNESOTA TOBACCO LITIGATION "~nformation" cited consists of just two me~ger reports.16~ne, 165 Gelfand's study of lung cancer among Rhodesian Africans, covered jUSt 32 lung cancer patients and 32 controls matched by age and back~Tound. But "regular smokers" included those smoking only one c~garette a day for a year, 17 of the 32 lung cancers were in people between the ages of 41 and 50 -- much earlier than the average age of dla~nosls in the United States -- and the light smokers had a Emeater number of lung cancers than the heavier smokers. The only other study cited in support of this statement 165 was so far afield that even the Supplement cited it in the section on oral cancer rather than in the section on lung cancer. That . 167 was a Russian study, by 0rlovskiy, which cited no data. It merely. noted that, in one geographical area with solcalled "pre-cancerous "" diseases of the respiratory organs" appearing f~equently in men, 81% of the men interrogated were smokers, while in another area, with the lowest incidence of respiratory disease, practically no one smoked. Thus, not only is the report one of a crudest possible " "relationship," but even that is not a relationship with lung cance'~~. MissinE from the Supplement is discussion or citation of ,169 Hill s stu,dy of cancer in Jamaica. That study found lung cancer to ., , ~ . ].70 ~e relatively uncommon and smoking common. Brunel's limited s~udy ~n Dakar, also missing from the Supplement, reported the role of '" ;" ~' ' , 171 tobacco as "negligible." Denk s uneited study of i00 German vintners' als.o....reported no correlation be%-ween smoking and lun~ 172 ~ancer incidence. A similar observation was made by Shim~zu as to A-bomb survivors in Hiroshima. And the geo~Taphic di,~crepancies -- . l,e~- " . " " -~-6- TIM__N 0151901 ~roduced ~ re- • ~G~1) A~ tare o/~ ~:_Y e Co,~-,,~ • "" ~'~mesota, i~~ ~'- ' ~ ~"~.~bT. ,~-- .... ' ...... " ........

CONFIDENTIAL: • • MINNESOTA TOBACCO LITIGATION 173 17~ .. noted in the sin/dy of Pedersen and the reviews of Wagner and 175 Skinner are not noted in the Supplement. Once again, whsn all the evidence is considered, no pattern consistent with smokin~ causa- tion emerges, 177 • 17 The Supplement K~eyber~'s-'s'tudy, as if it were new data. In fact, this study was discussed ~n, and in important part discounted by, the Surgeon General's Adv ry Committee Report178 of 196W. Aceomdlngly, it should be suffielen~, in lieu of detailed • analysis, simply to point out that (i) K~eybe~g's study admittedly 'is weighted toward epidermoid carcinoma {because the material con- sisted of far more su~gleal than autopsy specimens) and [ii) that most of the analysis of the data is based upon the assumption that "the sole difference between the smoker and the non-smoker of today is .smoking. ~h~s assumption, of e0umse, is not established by, Kr'eybemg's (o~ anyone else's) data and is contravened by many studi~Y "The extreme to which the Supplemen~'s and Kreyberg's .s~ngle-minded emphasis upon smokinE to the exclusion of all else .- has driven them Es shown by their assertion that, if smoking wePe "" el~mlnated,, lung cancer in Europe today wouldpresent the same patterns of ~noidenee, sex ratio and histological tyPe as were =' true ~0 years ago.18OThus conveniently swept aside is ~he large . • ~ 181 . 182. body of evidence suggesting ~hat u~Dan~'zarion, occupation ans other 13~-: ._ .factoms-~ave d~stlnct possible moles in the development of lunE @%= . ca.ncer, quite apart from any postulated role fo~ ci~are.ttes. ~'°d~, " ~, ' 8~ ,18 ,,

SOI"A TOBAcco h~h fo~ ~he smokers ~ho 'drooped' ~he ~g~e~e~ of~ ~h~ ~p ~h~e •hey smoked.~8~he Supplemen~'s speculation ~hat d~ooping ~s "a habit . which ~y ~esul% in %he del~ve~y of a gmeate~' dose of smoke is ~ontmas% ~o B~ett's cautionary s~at~en~ that "to elucidate whethe~ • ~moop~ng involved a ~eatem meas~e of i~al~ compared with the .. memoval of %he cigame~e afte~ each p~f would need special ~nves- . ~ga~on, fo~ which this s~dy was no~ designed."188 . . " ,189 In ~%s d~ouss~on of ~oss s s~dy of ~sks of .l~g caner amonE f~item c~amette smoke~s and non-filTem ciEa~e~te smokems, the 8upplementl~nnot resist speculatin~ as %o ~he si~ificanee of "ta~" content. Bu~ the a~ost complete lack of meanin~ul data in %his a~ea leads even the Supplement to the ~ud~n~ ~eco~ition that mome exact eompaP~sons of misks must await fum%hem ~s~dies. Such s~dies of course, ~st ~ake accoun~ of mymiad factors no~ even hinted at ~n %he Supplemen~'s d~scussion, such as Zhe chamacte~istics of the peopl~ who switch f~om non-filters to filtems vis a vis those who do not swltch~, and the chan~es in o~hem habits ~ha~ may accompany om ' follow upon ~he switch. 191 The Supplement pursues ~he ~lic Health Se~v~ce's con- ~nuinE and often self-con~adieto~y ques~ fo~ an explanation of ~he male-female ~atio by ci%~E Lomba~d'~9~tudy a~d claim~n~ a positive eommelaZion of smoking with epide~moid cancer ram g~ea~e~ than ~hat " w~th adenoca~cinoma. Th~s ~uns exactly eont~imy Zo the posit~on %akin by %he Surgeon General's Advisomy Committee in 196W as ~o ~he

. MINNESOTA TOBACCO LITIGATION d. PAFFENBARGER, R.S., Jr., THORNE, M.C., W~G, A.L. Ch~on-~e d~sease in fo~mer college students. VIII. Characteristics in youth preduposing to hypertension in later years. American Journal of EpidemioloEy 88 (i) : 25-32, 1968. f. FRIEDMAN, M., ROSENMAN, R.H., STRAUSS, R'.~, WURM, M., KESITCHEK, The melationship of behavior pattern A to the state of the eoronar~ vasculature. A study of fifty-one autopsy subjects.. Amemlean Journal of Medicine 4~{~): 525-537, Apmil 1968, g. PAUL, 0., Mac MILLAN, A., MoKEAN~ H., PARK, H. Sucrose intake and coronary heart disease. Lancet 2(7577): 1049-I051, November 1968. "" h. CHIANG, op..c~t, fn. 16.d., above. ~. EPSTEIN~ Y.H.~ YRANCIS, T., Jr.~ HAYNER~ N.S., JOHNSON', B.C.~ KJELSBERG~ M.O.~ NAPIER~ J.A.~ OSTRANDER, L.D., Jr.~ PAYNE~ M.W.~ • DODGE, H.J. Prevalence of chronic diseases and distribution of selected physiological variables in a total community', Teeumseh, Michigan. American Journal of Epidem/oloEy 81: 307, 1965. J. CHIANG, B.N., PERL~N, L.V., OS~RANDER, L.D., Jr., EPSTEIN, F.H. ' Relationship of p~emature systoles to coronary hea~ disease and • . sudden death ~n the Tecumseh epidemiologic study. Annals of Internal 'Medicine 70 (6) : i159-i168, 1969. k.KASKELL, W. ~ FOX, S. Exercise and heart disease. Post Graduate Medicine g[3): 177-182, 1968. 1. WARDWELL, W. Socio-environmental antecedent to comonary hea~t-diseas'e in eighty-seven white males. Social Science of Medicine ~ (2): 165-168, 1968. m. GERTLER, M., WELSH, J.J., WHITER, H.H. Early diaEnosis of coronamy disease and stroke. New York State Journal of Medicine 66 (21): 2765-2771, November 19~6. n. OSCEERWITZ~ M., KRASNOFF, S., MORETTi, L., SYME, S. The relat~on- • ship of myorcardial infarction to parental mortality and longevity. Journal of Chronic Diseases 21: 3~i-3~8, 1968. .... b& CHIANG, B.M., PERLMAN, L.V., EPSTEIN, F.H. Overweight and hyperten- sion: A review. Circulation 39 (3): ~03-W22, March 1969. JENKINS, C.A.~ ROSEEq~IN, R.H.~ ZYZ/~NSKI, S.J. C_~garette smokinE. Its relationship to coronamy disease and related risk factors in .%he Western Collaborative Group Study. Cimculation 38 (6): ll~0-1155, Decembem 1968. " .......... ~.. Produced as reqmred by the ~"~- -, F_ IDENTIAL. ' ..: . State o~ --, n,Mi""esot~- ,-ourt ~ Me.rch . et ~L .z. Philip Mor~is,-etT" 1998 aLOrder :n ~.. ~ Cottrt File N~,~: C1-94-8565

, MINNESOTA TOBACCO L~TIGATION 'of constitutional differentiation, rather than of a cigaret~e causa~£on mechanism. S~dies ~o da~e have fa~led ~o show c~ga~e~te smoking elevates cholesterol levels. "" The b~ief discussion of pu~ona~y e~ol0~ is, at best, 203_. ~p~ec~se. -xne so-called "finally malignan~ cells,"2~ph~ase used 205 %o descm~e ~he Valaitls obse~vaZions, appeaPed in people who did no~ have eancem of ~he l~s. The n~evs ~nvolved, mo~eovem, ame stated by the Supplement in t~rms of "W.8~ of %he smoke~s and 0~9~ 206 of %he non-smokems." In fact, of 3,123 smoke~s s~died, 95.~ ~eg~s~e~ed n~ga%ive, W.5M atypical, 0.29~ suspicious and only 0.~ positive. The 0.~ positive translates into ~ust three smokers, of whom weme dia~osed as havin~ carcinoma ~ situ -- not caneem of %he lung. The third was diagnosed as" havin~ a pne~on~tis of the migh~ loweP lobe, which cleared up followin~ an¢~io~ic tmea~ment. As ~he s~dy noted wi~h mespect ~o %he ~o camclnomas ~n 207 si~, ~here was "no evidence of invasion." This contmas%s with the 208 "fmankly maliEnant" descmiption of the Supplement, which constantly fails ~o dis%~ish be~een cancem and vam~ous so-called "pre-cancerous" 209 . lesions. ~hus, ~n deso~ibln~ Aue~bach's s~u~y of such lesions 2~0 la~y~, ~he Supplement ~a~Is to no~e the author's caution ~ha~ the Temm was not meant "to ~ply that the lesion would necessamilv have become ~nvas~ve ~f the s~jeet had lived.'~l~nd not discussed, buZ ---buPied ~ the S~pplemen~al B~lio~aphy, is a~ ~st~a~ st~d~ich Pepo~ted no siEn~ficant differences in ~he lamynxes of smoke~s and .. 213 Rgn-smokems -- exactly the opposite of Aue~baeh's ~epo~t. Similarly e. "S re~e. #~ A ~,~ • " . . ,"--' .... . :..

CONFIDENTIAL: MINNESOTA TOBACCO LI_TIGATION bu~ied ~s the fla~ statement 0f Dr. Mu~21&at "The causes of cance~ • Of ~he lazTnx remain unknown."215 • " ': , 216 NO% even cited by the Supplement is Einhoz'n s study of 1:he s~nificanee of leukoplakia in o~al cancer. ~.inhorn found , an eight t/rues h~ghe~ f~equeney of malf&~nant ~/mo~s in non-%obaceo ~e~s wt~h le~oplakia th~n in Zobaeeo users wi~h le~oplakta. ~e "The le@opl~kia ~ toS~ee0 users seems no~ %o '~e Of ~eat precancerous s~fieance; in only one of 250 • cases d&d o~al eam~noma develop in the first 5 yeams. vl e-a'eneI% m~t be se=iously considemed whethem this pme- justifies the suffemin~ often inflicted on ~nvete~ate smokers ZhDou~h the d~scovemy of le~oplakia. It is also questionable to what ~xtent this p~evalenee, m~Eht be meduced by pmohibition of smoking." " , 218 The Supplement s %~ical. I~ ~efe~s ~o ~he s~dy as showin~ a "~elationship of ~obaeoo chewing ~o omal and omalpharyngeal cancem in a d~s~m~ct ~n India." 220 I~ does not mefem %o his statement tha~: 221 '~nothe~ ~omtant finding amusing fmom ~his s~dy %he absence of any association wi~&h ~he habit of smokin~ .tobacco. No ~ereased ~isk was observed amon~ da~ly smokems." 2~ an association In assertinE ~hat James has "demonstrated"223 smoking and cance~ of ~he bladdem, %he .~upplemen~ neglects be~een %o mention that only 91 cases spread ovem a 21-yea~ pemiod ame involved. It also fails to note that ~he s~dy included 2W pemsons w~%h a second pm~ma~y eameinoma ~n othe~ sites, many of which a~e ....... ~o~-e~e-~~e~otely ~u~e6t~d b9" anyone as being ~elated to sm0kin~. The poss~lity of a eonst~ional detemminant would .seem worthy of eonsidemat&on he~e, but the •Supplement fails ~o discuss ~.

CONFIDENT/AL: -MINNESOTA TOBACCO LITIGATION • Th~s possib~l~y, "~ha'~ "oonoom~:ant variation be~een ~tal~y f~om any cause and smoking may be due ~o a mutual assoc~atlon with another variable," is among the several points ~qo~ized by F~a~eni as limiting inte~etat~on of h~s s~dy. Bu% none of ~hese po~ts are mentioned, ~ch less discussed, by The Supplement ~~5 . In eontras~ ~o %he .Supplement's cla~ ~hat Wynder~e- l~na~y s~dy showed a "s~f~cant assoc~at~6~ . . . be~een clovers smoking and~ide~mo~d c~nce~ of ~he ~idney,'~]ynde~ h~elf ~ecently sta~ed in a le~e~ ~o the Tobacco Ins~i~te that "~he~e a~e ~iI ~oo few cases mean~gful statistical analys~s and this data ~s be~nz included for yo~ information only." 228 ~he. Surgeon Gene~al's Advisory Co~iZtee Report of 196~ has failed • o identify any new carcinogens ~ ~obacco smoke, detailed discussion of ~he ca~clnogenicity sec~ion iS unnecessary. No,cla~ of implica- Tion of a culpable ~n~edien% o~ ingmed~ents is made 5y the Supplement. " ~l~hgUgh ~he Suppl~ent---discusses "~he cell eultume womk of the Leuehte~e~ge~s, i= does nor even Cite their; comprehensive ~eview ~ ~he need fo~ experimental ~hala~ion s~dies. Consisten~ wi~h th~s_.~eview, the exper~ental, si~arion ~S s~ed up by Wynde~ and Hoffman'233s admission "that clga~et~e smoke ~s a cause of squamous- cell l~g eance~ has yet ~o he experimentally dstablished." -32-

---

CONFIDENTIAL: _MINNESOTA ..... TOBACCO LITIGATION "' AS to another, the Supplement ~eco~nizes possible bias2.~7Aecordingly, only %we s~udles are left in which an increase in fetal and nee-natal momtal~ty is meported. " Analysis of these ~wo papers indicates that the Supplement's tmeatment of this subdect should have been even mome cautionamy than £twas: "" ~ The Russel~mgaterial lumps ~oge~he~ abor~ion~, still-bi~ths and nee-natal deaths in one index of "unsuccessful ou~come.'~5~his • - is a methodological e~mom which makes the papem deficient ~na most /mpomtant respect, because the study of abortions presents many dlffieult problems and is quite unrelated to the problem here under ~ study. Further di#ficul%ies are in part indicated by the fact that ~ the rate obtained by Russell for abort-ion, st~ll-birth and nee-natal ., ~ ~eaths combined ~s approximately ~, whereas all a~a~lable data'~ ~ndicat~ tha~ abortions alone constituteapproximately'iS% of all • pmegnancles. [As a comparison, the only other cited study ~e~o~ting a significant increase in nee-natal and fetal m~.~tality ~that of Mulcahey~%~ows a ~ate of 16.1~for nee-natal deaths, still-births "and abortions combined.] Further, the method of selection is open ~ ~.~ • to serious criticism, partlculavly because it includes, by the author's ~.o" ~ o~n statement, a select~on of cases which threatened, to abomt. B~ushed aside by the Supplement is th~ finding the authors • 252 likely to be hypertensive tha~ women who do not smoke. This would seem to point to basic differences between smokers and non-smoke~s o, which a~e independent of the act of smokinE. I~ also casts light • ' .iTIMN0151909

• :: CO~FIDE~,,-,- :~ MINNESOTA TOBACCO LITIGATION" upon the finding, emphasized by the 'Supplement, that women with hyper~enslon who smoke have a large proportion of "unsuccessful 253 = . p~e~ancie~." S~nce ~he blood p~essu~e of smoke~s ~s no~mally lowem %han that of non-smoke~s, hiKh blood p~/ssu~e in a smoke~ would ~ndlca%e a s~eepe~ ~se and Chemefore a mome serious eond~¢ion than it would in a non-smoke~. The othem s~ud~ha~ of Mulcahey, has The same deficiency of l~pinE abomtions, s¢ill-bim~hs and neo-na~al deaths. Also, £s not clea~ whethem %he study was done pmospectively o~ ~etmo- spec~vely. In the lat~e~ event, of coumse, £nte~pme~a~£on of ~esults would be mo~e l~mi%ed. In any event, ~t~s inte~estinE to compare the ~elatlvely ~est~ained findin~ of the authors ~ha~ "~he p~oport~on of neo-natal deaths, "st~ll-bi~ths and abo~t~ons ; • ~S somewhat higher among smokers" with the st=ongee sZatement ~he~ cogent section and in" the Supplement t~'at "they discovered a s~gnifican% ~ncmease in the ~nc~dence of neo-na%al dea~hs~ still- 256 ,, birth, and spontaneous abortion. "~. In v~ew of the Supplement~s consistent selectivity, ~t is perhaps not. sumprising that it quoZes extensively fmom these studie~J~hamactemized as ~hey .~e ~y questionable methodolo= and ~elatlvely small nu~ers of cases. On the other hand, ~t E~ves no mention o~ only Passing cogent to the very large and well ~ecog- ..... 258 .... nized .studies in %he field, .such .as_~hose of Unde~ood ~ased on over These s~dies show no increase in neo-na%al morality of ~nfants of

MINNESOTA TOBACCO LITIGATION~ ' smoke~s compared to Those of non-smokers. Both ~epo~t that low b~rth weight infants of smoking mothers survive much bette~ Than. .low birth weight infants of non-smoke~s. While the paper of 260 Yevushalmy does not deal with The subjecT, that of Underwood 261 also finds no difference in still-birth. • In considering This subjecT, it is ~ortanT To~em~mbe~ ~ha~ the ~se in mo~Tel$Cy w~ich could be expected from an increase ~~ in ~he proportio~ of low birth weigh~ infants is not minor. It ' can be calculated that the observed increase in number of low ~.~ birth weight infants born to smoking mothers should p~oduce an ~~, mesult &s to follow fPom The low-birth weight condition. Therefore, O~ an increase in neo-naTal mortality caused by smokln~, if it ex£sted, ~'~ could not be easily overlooked. The fact that the large-scale, ~ -.~ wel~ conceived studies did not find differences in perinatal ~ ~N mortality between infants of smoking and of non-smoking mothers ~°~" ~ - should have been sufficien~ indication that such differences do • not exist. ~owever.thaT may be, the few small studies selected ~ fo~ quotation in the Supplemen~ canno~ be sa~d~o p~ove the contrary o~ even ~o maise s~s%antial question -- because of thei~ notable defects in des~ and analysis. .................... Conclusion - " Th~s bmief ~eview shows thst ~he 1969 Supplement's eoncluslons on smok~nE and health a~e not ~ust~fied. U~o~tunately,

CONFIDENTIAL: lVlINNESOTA TOBACCO LITIGATION ~he Supplemen~ asse~s unsuPpo~1:able conclusions withou~ ~eeoEniz~ng • the .fact %hat ~esea~ch has not p~ovided the data needed to answer the many open questions of causation. ,.. PRIVILEGEDAND CONFIDENTIAL .:.., Produced as required by the Court's March 7, 19.98 ord~ in ~ . ..~: " Corot File No.: C1-94-8565 .. "' .............. iTIMN0151912

CONF/DENTIAL: .. MINNSSOTA__ . TOBACCO LITIGATION i. U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. 1969 Supplement to the 1967 Public Health Service Review. U.S. Department of Health, Education~ and Welfare, Public Health Service Publication No.1696-2 (Supplement), 1969. 2. 1969 ~upplement, at p. ~. 3. I~id. " ~. Hearings on Cigarette Lahelin~ and ~dvez~cising Be~.ore the House Committee on Interstate and Foreign Comme_rce, 91st Cong., ist Sess., Pt. l, at p. 91. .' .5. I_~d. at pp. 508, 510, 526. ", 6. Id. at p. 5~5. ' 7. SELTZER~ C. C. An evaluation of the effect Of s~oking on coronary ~ea~t diseases. I. Epidem~ologieal evidence. Joumnal of the American Medical Association 203 (3): 193-200, January 15, 1968. 8. 1969 Supplement, at p. ~. . 9. HAMMOND, E. C., GARFiNKLE, L. Coronar9 Heart Disease, Stroke, and -" • Aortic Aneurysm Factors in the etiology. Archives of Environ- mental Health 19 (2): 167-182, August 1969. 10. 1969 Supplement, at p. 12. "' ii.' 1969 Supp~ement, at p. 12. . 12. 1959 Supplement, at p. 13. "13. THORNE, M. C., WING~ A. L', PAFFENBARGER~ R. S. Jr. Chronic disease in former college students. VII. Early precursors of nonfatal eo~onary heart disease. American Journal of Epidemiology 87 (~): 520-529, May 1968. I~. 1969 Supplement, at p. ~9. • " 15. "BASSETT, D.R., ABEL, M., MOELLERING, R.C. jr., ROSENBLATT, G., STOICES, J., III. Multivariate analysis of dietary intake, ....... --~ette smoking, energy ~alanee and "stress" in relation to 'racial status., a~e, and coronary heart disease risk status in Japanese and Hawaiian men in Hawaii. American Jo~mnal of Cllnieal Nutrition 22 : 150~-1519, November 1969. • _ Clas_,.e,.... ~G~OA~" :.. -.- . :. s~e-- ""~- "-- " TIMN 0151913 -- "°" . , et _ . . ....

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION 16.a. EPSTEIN, F., OSTRANDER, L., JOHNSON, B.C., PAYNE, M.W., HAYNER, N.S., KELLER, J.B., FR/hNCIS, T. Epidemiologieal studies of cardiovas- cu.].ar disease in a total community Tecumseh, ~,LT.chigan. Annals of Internal Medicine 62: 1170, 1965. b. ROSE, G.A., ANMETELI, M., CHECCACCI, L., FIDANZA, F., GLAZUNOV, I., DeHASS, J., De HORSTFL~NN, P., KORNITZER, M.D., MELONI, C., MENOTTI, A:, VAN DER SANDE, D., De SOTO-HARTGRINK, M.K., PISA, Z., THOMSEN, B. A study of ischemie heart disease in middle-aged men: Prevalence comparisons in Europe. Bulletin of the Wo~ld Health Organization 38 (6) : 885'-895, 1968. e.. SPAIN, D.M., BRADESS, V.A., MATERO, A., TAKTER, R. Sudden death due to coronary atheroselerotie hear~ disease: Age, smoking ~ habits, and recent thrombi. Journal of the American Medical '"• 7" Association 207(7): 1347-1349, February 17, 1969. .~ ~ ~, d. CHIANG, B,N PERLM~N, L.V. FILTON P.M. OSTRANDER, L.D EPSTEIN, ~ ~ ~ F.. Sudden cardiac death and individual characteristics in ~ ~ ~ u~ Teehumseh, Michigan -- A prospective study. Address presented ~ ~ ~ ~ . to American ColleKe of Physicians at Chicago, Illinois, on ~ ~ ~ ~ e. EPSTEIN, F.H. Some uses of p~ospeetive observations in the £9 _~ ~ Q~ " Teeumseh co--unity health study." Proceedings of the Royal Society ~ ~ ~ ~ of Medicine 60 (i): 56-60, 1967. ~ ~ • ~o LELLOUCH, ~. AN~UERA, ~. SCHmAltZ Corrsla~:±ons entre l~usa~e ~ ~--~ du tabac et quelques earacteristiques cliniques et biolo~igues. ~ ~ ~ ~ " Bulle%Xn de l'Institut National de la Sanse et de la Recherche • g. TONELLI, ~., TUMIOTTO, G., BISBINI, P., RXeherche sulla influenza ~ ~ ~ di aleuni fattori esogeni ed endogeni nei riguardi delle malattie m~ '" cardiovasculari di natura arteriosc!erotica. Igiene e Sanita h. KEYS, A. ~o~onary diseases in seven eotmt~ies. Circulation ~i, •~ • • ~2 (Supplement i), April 1970. 17.a. GOULET, C.., ALLARD, C.~ PoiRIER, R. Etude~Epidemiologigue d'une population, umbaine Canadienne - Franeaise: faeteurs assoeies au p~ofil corenarien. L'Union Medical Du Canada 97 (89 : I104-i109~ August 1968. study involvin~ the aerospace manufacturing industry. Aerospace Medicine 16 (5~ : 719-727, May 1968. e. BASSETT, D.R., MOELLERING, R.C., Jr., RoSENBLATT, G., GREENBERG, D., STOKES, J.', III. Coronary heart disease in Hawaii~ serum lipids, and _ cardiovascular, an~hropometrXc, and related findin~ in Japanese and Hawaiian men. Journal of Chronic Diseases 21(8): 565-583, January 1969. • ........................ : .~TIMN 0151914

CONFIDENTIAL: . M/NNESOTA TOBACCO LITIGATION d. PAFFENBARGEE, R.S., Jr., THORNE, M.C., W~G, A.L. Chmon-~c d~sease ~n fommer college students. VIII. Characteristics in youth preduposing to hypertension in later years. American Journal of Epidemiolo~y 88 (i) : 25-32, 1968. e. ROSE, og..p_: ,e$-t,. fn. 16.b., above. - f. FRIEDMAN, M., ROSENMAN, R.H., STRAUSS, R'. The melationship of behavior pattern A to the state of the eoronamy vasculature. A study of fifty-one autopsy subjects.. Amemlean Journal of Medicine 4~{~): 525-537, Apmil 1968, g. PAUL, 0., Mac MILLAN, A., MoKEAN, H., PARK, H. Sucrose intake and coronary heart disease. Lancet 2 (7577): 1049-1051, November 1968. h. CHIANG, op. ,c~t. fn. 16.d., above. i. EPSTEIN, F.H., FRANCIS, T., Jr., HAYNER, N.S., JOHNSON', B.C., KJELSBERG, M.O., NAPIER, J.A., OSTRANDER, L.D., Jr., PAYNE, M.W., DODGE, H.J. Prevalence of chronic diseases and distribution of selected physiological variables in a total community', Teeumseh, Michigan. American Journal of Epidemiolo~y 81: 307, 1965. J. CHIANG, B.N., PERL~N, L.V., OS~RANDER, L.D., Jr., EPSTEIN, F.H. Relationship of premature systoles to coronary heart disease and • . sudden death in the Tecumseh epidemiologic study. Annals of Internal 'Medicine 70 (6) : i159-i166, 1969. k. HASKELL, W., FOX, S. Exercise and heart disease. •Post Graduate Medicine ~[3): 177-182, 1958. 1. WARDWELL, W. Socio-environmental antecedent to coronary heart-diseas'e in eighty-seven white males. Social Science of Medicine 2 [2): 165-168, 1968. m. GERTLER, M., WELSH, J.J., WHITER, H.H. Early diagnosis of coronamy disease and stroke. New York State Journal of Medicine 6G (21): 2765-2771, November 1956. n. OSCBERWITZ, M., KRASNOFF, S., MORETTi, L., SYME, S. The relation- . ship of myorcardial infarction to parental mortality and longevity. Journal of Chronic Diseases 21: B~I-B~8, 1968. .... o; CHIANG, B.M., PERLMAN, L.V., EPSTEIN, F.H. Overweight and hyperten- sion: A review. Circulation ~9 (3): ~03-W22, March 1969. llW0-1155, Decen~em 1968. co - ~duced ~ requ~ed by the ~- -, ~ID~AL ~ S~ of ~esot~, ~,urt s M~rch 7, 1998 Order . et ~L.v.. Philip Mo~s,-et ~. Co~ f~e N~),: C1-94-8565 JENKINS, C.A., ROSEEqe~AN, R.H., ZYZANSKI, S.J. Cigarette smoking. Its relationship to coronary disease and related risk factors ~n ~he Western Collaborative Group Study. Cimeulation

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION' 19. 1959 Supplement, at pp. 18, 20-24. • 20. "JENKINS, oD. cir. fn. 18., above, at pp. ii%9-i151,'i153. ~RIEDMAN, oD. ~ci~t.. fn. 17.f., above. 25. JENKINS, oo. cir. fn. 18., above, at p. 1152: 1969 Supplement, at .: 27. MULCAHY, R,, HICEEY, N., MAURER, B. Coronary hesmt disease, a • . study of risk factors in ~00 patients under 60 yeams. Geriatrics "2~(1) : i06-11~, January 1969. . 28. Id. at p. 108. "" 29. 1969 Supplement, at p. 25: 30. CEDERLOF, R., FRIBERG, L., HRUBEC, Z. Car'diovascular and respira- ±o, ry symptoms in relation to tobacco smok£nE. A s~udy on American ~wlns. Amchives of Environmental Health 18 (6): 93~-9~0, June 1969. 31.a. LUNDMAN, T. Smokin~ in relation to coronary h~art d/sease and • lun~ function in twins. A cotwin control study. Acta Medlea Scandinavica 180 (Supplement ~55): 1-75, 1965. b. CEDERLOF, R. Urban factor and prevalence 6f respiratory symptoms and "anEina pectoris": A study of 9,168 twin pairs with the aid of mailed questionnaires. A~chives of Environmental Health 13(6) : 7t~3-7~8, December 1966. e. CEDERLOF, R., FRIBERG, L., JONSSON, E., KAIJ, L. Morbidity among monozygotic twins. Archives of Environmental Health 10:3WG-350, February 1965. " d. CEDERLOF, R., FRIBERG, L'., JONSSON, E., KAIJ, L. Respiratory .. symptoms and "angina pectoris" in twins with refemence to smoking habits. Archives of Environmental Health 13 (5) : 726-737, December 1966. • e. CEDERLOF, R., FRIBEKG, L., JONSSON, E., KAIJ, L. Morbidity in unio- ruler twins in relation to smokin~ habits and residence. A pre- lqmina~y report. No,dish Hygienisk Tids]~ift %5: 71-75, 196W. f. CEDERLO~, R., The value of twin studies ~n: epidemiology. World I~R.,,~__ Meflic~l Journal i~(6)-. 16fl-171. November - Dehember, 1967. Produced cO ' ' . " . / ................... required ~y ~.~ ',N.FmENTIAL ~ .............. State of • Cour~ s M,a. M~_ esota, e~a ,, ~,,~.. ch7,1998,- _ . ;TIMN 0151916 1. ,,. r nni "-'~uer ~ UOurtFile . PMo " No.. C1 9g. .. ms, et at . .- " .8565 '

CONFIDENTIAL: SOTA TOBACCO LITIGATION $2. 1969 Supplement, at p. i~' "SS. ARONOW, W.S., KAPLAN, M~A'L'; JACOB, D. Tobacco: A ~aeto~ ~ ~g~a pecto~is. ~n~s o~ ~t~al Medic~e 529-536, Sept~be~ 1968. 3~.a. DO~E, J.T. Import~ee of dose response ~n ~e~s of total cigarette smoke, "ta~", ~d nicot~e: Car~ovasculam system. E.L., HOF~N~ D., editors. Toward a Less Ha~l Cigarette. B~}~SDA~ U.S. ~lie H@~th Semite, Nation~ C~cem ~skitute Mono~maph No. 28, at pp. ~3-~5~ 1968. b. DO~E, J.T., DA~ER~ T.K~ ~N~, W.B., ~NCH~ S.H., ~, H.A. ~e ~elationship of Cigarette smo~g to coronaW hea~ disease. Jou~ of %he ~erie~ Me~c~ Association 190 (10): 180-i12, Deee~e~ 7, 196~. e. SELTZER~ C.C. ~ ev~uation of the effect of smok~ on coronary heart disease. Journ~ of the Ame~ie~ MeScal ~sociation 35. 1969 Suppl~ent, at p. 25. 36. ~ 1969 Supplement, at p 25 " 37.a. LIL~FORS, I. CoronaW hea~ disease ~ :~e ~ins: Here~tary ~d envimo~ent~ factors ~ concordat ~d ~sco~d~t pairs. • Acta Medica Sc~dinavica, (Supplemen~ 511), 1970. b. LUND~, ~. eit. ~. 31, ~ove 38. CEDE~OF, ~. eit. fn. 30~, ~ove, at p. 939. 39. 1969 Supplem~t, at pp. 25-27. STRONG, J.P., RIC~S, M.D., McGILL, H.CI, ~., EGGEN,D.A., Mo~Y, M.T. ~ the association of cigarette smok~ wi~ comona~ ~d a0rtie athe~selerosis. .. Jou~al of Atheroselemosis Research i0 (3) : 303-317, 1969. SAC~, D.L~, GIBSON, R.W., BROSS, I.D.J., PIC~N, J.W. Re- lation be~een aortic atherosclerosis ~d the use of ci~amettes ~d ~cohol. ~ autopsy s~dy. New ~gl~d Jou~al of Medic~e ........... 2~9(26): i~13-1~20, Dece~em 26, 1968 .......... 1969 Supplement, at p. 26. ~, A.M., ~OV, V.S., ~TOVA, E.E. Atherosclerosis of the aorta ~d coronary vessels of the heart ~ cases of various dis- ~ases. Jou~al of Athemoselemosis Research 9: 179-192, 1969. JOU~N~ OF T~ A~RIC~N ~DIC~ ASSOCIATION. New mesearch sparks debate on smok~ ~d heart disease deaths. 207 (W): 66~-666, J~u~ 27, 1959. '

cONFIDENTIAL: "AS. .Id. at p.. 665. ~SOTA TOBACCO lITIGATION ~6o .I,d,. at p. 666. g7.a. HASS, G., HENSON, D., LANDERHOLM~ W., HEMMENS, A. P~evention of nlootine induction of atherocalcific thro.mboarteriteS in rabbits. Circulation 38(4, Supplement 6): 8, August 1969. . b. LELLOUCH, J., JACATOT, B., ANGUERA, G., GROSGOGEAT, J., BEAUMONT, J. Action chronique de la nicotine sur l'intima ao~tique du lapin. Indoen d'un iuhibiteur de la monoamine oxydase (I.M.A.O.). Journal of Atherosclerosis Research 8 (1) : 137-142, January-~ebruary 1968. ~8. 1969 Supp!~ment, at ~9. R.F. Alcohol, nicotine and The Medical Journal of WHET, AN, man. Australia 1(3): 77-83, January 20, 1968. 50. . HAREAVY, J. Tobace0 aller~y in cardiovaseulam disease: a review. Annals of alle.r~y 26 (8): q~7-~59, August 1968. 52. 1969 ~upplement, at p. 27. 53.a. SOLOFF, L.A. Glucose blockage of'nonesterified fatty acids in- ' crease produced by smokin~ in healthy and in coronary subjects. American Journal of the Medical Sciences 2~7: 580, 1964. b.. SOT.OFF, L.A. Plasma and red blood cell free fatty acid responses to glucose loads~ with a note on the effect of tobacco. American Journal of the Medical Sciences 2~6: 200, 1963. 5~.a. SOLOFF, o_~. cir. fn. 5~a., above. b. SOLOF~, oo. cit. fn. 53.b., above. ' 55. 1969 Supplement, at pp. 27-28. ' 56. DINTENFAS, L. Blood~ theology in patho~enesis of the coronary heart diseases. American Heart Journal 77 (1): 139-1~7, Janusmy 1969. 57. SOLVATEEN, P., KRISTJANSEN, P.F. Carbon monoxide, blood viscosity and development of Buer~er's disease. Zeitsehrift fuP K~eislauffor- smhunE 57 (8) : 790-792, Au£ust 1968. 58.a. SPAIN, Op. cir. fn. 16.c., above. SPAIN, D.M., BRADESS, V.A. Sudden death from coronary heart disease: Survival time, frequency of thrombi, end c~garette smoking. Chest 58(2): i07-ii0, August. 1970. 1909 Supplemlnt, at p. -28. -" I"TIMN .

CONFIDENTIAL: ' " MINNESOTA TOBACCO LITIGATION 60. U.S. Public Health Service. The Health Consequences of Smoking. 1968 Supplement to the 1967 Public Health Se~vic4 Review, U.S. Depaz~cment of Health, Edueat,~on ~nd Welfame. Publ~c Health Se~viee Publication No. 1969 (Supplement), 1968. • 61. JENKINS, or. pit. fn. 8"~, above. 62". I._~d. at p. 1152. 63. 1969 Supplement, at p. 28. : • 6~. STABLES, D.P., RUBENSTEIN, A.H., METZ, J., LE$-/N, N.W. The possible ; role of hem.co oncentration in the etioloEy ofmyo~-ardial infarction. American Heart Journal 73 (2~ : 1.55-159, Februamy 1967. 65. . I__d. at p. 158. .66° 1969 .Supplement, at p. 28~" ' 67.a. GOLDSMITH, J.R., LANDAW, S.A. Carbon monoxide and human health. Science 162 (3860) : 1352-1359, Decembem 20_, 1968. b. BREYSSE, P.A., BOVEE, H.H. Use of expimed aim-eambon monoxide for carboxyhemoglobin determinations in evaluatLng carbon monoxide exposures result/ng fmom the operation of gasoline fomk lift t~ueks in holds of ships. American Industrial Hygiene .~ssoeiation Journal 30 [5) : W77-W83, September-October 196~. e. CURPHEy, T.J., Carboxyhemoglob~n in melatlon to smoking. In: WYNDER, E.L., HOFYM~hNN, D., editors. Toward a Less Ka~mful cigarette. BETHESDA, U.S. Public Health Service, National Cancer Institute Mono~Taph No. 28: 231-235, 1968. 68. SIEVERS, R.F., EDWARDS, T.I., MURRAY, A.L., SCHRENK~ H.A. Effect of exposure to known concentrations of carbon monoxide : Study of t~affic officers stationed at the Holland Tunnel for 13 years. Journal of the American Medical Association llS: 585-588,. 19~2. • 69.. CURPHEY, or. tit.. fn. 67.e., above. 70. !d. at p. 231. 71~a. BROWN, B.B. Some characteristic E.E.G. differences between heavy smoker and non-smoker subjects. Neuropsycholo~ia 6: 331-388, 1968. ........ b~ THOMAS~ C.B: Oh 6igarett~e smSke, Eoronar9 heart d/sease and the ~enetic hypothesis. Johns Hopkins Medical Journal 122: 69-76, 1968. e. CAFFREY~ B. Reliability and validity of personality and behaviomal measures in a study of coronary heart disease. Journal of Chronic Diseases 21: 191-20~, 1968. required - ~ 0151919 by ~ Coures M O£~esot ~ch Z ;. " ~, et ~. •. • 1998

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION, d. DAMON, A., DAMON, S.T.~ KARPENDING, H.C., KANEL, W.B. Predicting coronary heart disease from body measurements of Fram/ngham males. Journal of Chronic Diseases 21: 781-802, 1969. 72. BROWN,.oD...ei~. fn. 71.a., above. 7~. THOMAS, o_p_. c~.t., fn. 71.b., above. b. CAFFREY; o_/!. ei__~, fn. 71.e., above. " 76.. .DAMON, op. eit. fn. 71:d.', above. 78. . HUTCHISON~ G.B. Nature of epiden~ol0gie evldenee: smoking and health. Bulletin of the New York Academy of Medic/he G4(12~ : 79. U.S. Public Health Service. The Health Consequences of Smoking. A Public Health Service Review: 1967. U.S. Department of Health, Education and Welfare~ Public Health Service Publication No. 1696, 1967. 80° U.S. Public Health Semvie~. A Special ~epomt on E~physema. U.S. Depa~-biient of Health, Education and Welfare. Public Health Service .Publication No. 1699, 1968. 81. Id. at p. 5. 82. Id. at p. 19. Id. atop. 639.~ 85. Id. at p. 637. 86. • 1969 Supplement, at p. 37. 87. 0~. cir. fn. 79. ~. above. .89.:. 0~..tit: fn. 79.~ above~ at pp~ 89-g0. 90. 1969 Supplement, at pp. 37'39. r~od~¢ed as requ~ed by the Courts " - State of • . . March 7, 1998 • Minneso~ .. Ord ~-ourt Fi/e No., CL0~'5~'~.;"ms, et al•

• CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION • 92.a. DePOMPEIS~ C., MARCONE, G. Indagine stat~stioa sulla morbillta' bronchitica nolle fornaci di laterizi e suoi riflessi in medicina soeiale, Nora II. Medieina Sociale 18 ~): 290-293, July 1968. b. BIERSTEKER, K. Bronchitisklachten bij Rotterdams gemeente-personeel. Nederlands Tijdschrift voor Geneeskunde 112 (26): 1208-1211, June 29, 1968. e. FLETC~R, C-M., TINKER; C.M., HILL, I.b., SPEIYER, F.E. A 5-year prospective field study of early obstructive airway disease. In: Current Research in Chronic Respiratory Diseases. Proceedings . of the llTh Aspen Emphysema Conference, Aspen, Colorado. U.S. Department of Health, Education, and Welfare, Public Health Service Publication No. 1879, at'pp. 249-252, 1969. d,LOWE, C.R. Chronic bronchitis and occupation. Proceedings of the Royal Society of Medicine 61(i): 98-102, January 1968. e. BRINEMAN, G.L., BLOCK, D.L. The prognosisin chronic bronchitis. In: Current Research in Chronic Airways Obstruction, gth Aspen .. Emphysema Conference, Aspen, Colorado. U.S. Department of Health, Education, and Welfare, Public Health Service. Publication No. 1717, at pp. 317-326, May 1968. f. IRNELL, L., KIVILOOG, J. Bronchial asthma and chronic bronchitis in a Swedish urban and rural population with special reference to prevalence, respiratomy function and soeiomedical condition. Scandinavian Journal of Respiratory Diseases Supp.lementum No. 66, 1968. - g. GANDEVIA, B. A productive eou£h upon request ~s an index of chronic bronchitis: The effects of abe, sex, smokin~ habit, and environment upon prevalence in Australian general practice. Medical Journal of Australia i(i): 16-20, January ~, 1969. h. SLUIS-CREMER, G.K., SICHEL, H.S. Ventilatory function in males in a Witwaterscrand town. Comparison between smokers and non- smokers. American Review of Respiratory Diseases 98(2): 229-239, AuEast 1968. 93, BRINKMAN, o_~..c.i.t., fn. 92. e., above. 9W. 1969 Supplement, at p. 95.. BRINKMAN, op..cir, fn. 92.e., above .... 96. ,I,0. at p. ~25. :~ 97. I_~d. at p. 322. ~s. 0_~z. .eit. fn. ~., above, at pp. 1156-1158. . ...................... _. "" !TIMN 0151921 _ . • . . .. . ~re ~ ANDt~,- • ~Or',,a ~.~." etaI. v. p~,[,:~'ctl 7, 19oo ,-, ' - " ".: "ms,

CONFIDENTIAL: ~ MINNESOTA TOBACCO LITIGATION 99. I_~fl. at p. 1157. 100. I~d. at p. 1158. 101.a. DePOMPEIS~ op. e±t~ fn. 92~'a., above. % ft. LOWE, OD. cir. fn. 92.d., above. e. IRNELL, pp. eft__, fn. 92~f., above: f. GA~DEVIA, o_~. OiL. fn. 92~g.~ above. g. SLUIS-CREMER, oD. eit'. fn~ 92.h., above. .102. FLETCHER, op. eCt. 'fn. 92~'e., above. :' 10g. I_~fl. at p. 250. lOW. LOWE, oD. eit.. f-n. 92.d~, above. I05. I_~d. at p. 102. ' ~ O '106. DePOMPEIS~ o_~. eft'. fn: 92.a., above. : i07. BIERSTEKEK, op. eit. fn. 92.b. ~ above. "108. IRNELL~ pp. e-q~~ fnl 92.f., above. '. 109. GANDEgIA, op. ci%. fn. 88.g., above. ll0. 1969 Supplement~ at p. 37. SLUIS-CREMER~ ~ "" : . 9±~. fn. 92.h.~ above. 112. Id. at pp. 236-237. llB. I,d. at pp. ~]~ 2B6, 2~7. " llS. IRNELL~ ~oD.. 9.i~. fn. 92.f., above. ll6.a. LA~f]~R~ P.J.~ BROOKS~ A.G.F. ~ WALLER~ R.E. Respiratory function measurements in a eohomt of medical students. Thorax 25 172-177~ 1970. b. PETERS~ J.M., MU~PHY, R.L.H.~ PAGNOTO~ L.D., WHITTENBERGER, J.L. • Respiratory impairment in workers exposed to "sa£e" levels of toluene diisocyanate ~TDI). Archives of Env~wonmen~al Health 20(3): 36~-367, 1970.

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION e. BOUHUYS, A., SCHILLING, R.S.J., van de WOESTIJNE, K.P. Cigarette smoking, occupational dust exposure, and ventilatary capacity. Amchives of Environmental Health 19 (6): 793-797, December 1969. llT. 1969 Supplement, at p. 38. ll8. BURROWS, B. The course of patients with chronic obstructive lung disease. In: Current Research in Chronic Respiratory Diseases. P~oeeedings of the llth Aspen Emphysema Conference, Aspen, Colo. U.S. Department of Heslth~ Education, and Welfare, Public ~ealth • Service Publication No. 1879, at pp. 25B-258, 1969. i19. I~d. at p. 257. 120. 1969 Supplement, at p. 38. 121. MITCHELL, R.S., SILVERS, .G.W.., DART, G.A~, PRETTY, T.L., VINCENT, T.N., RYAN, S.F., .FILLEY, G.F. Clinical and morphologic correla- tions in chronic airway obstruction. American Review of Respiratory Diseases 97 ~) : 5~-61, January 1968. 122. MITCHELL, R.S., WALTER, S.H., SILVER, G.W., DART, G., MAISEL, J.C. The causes of death in chronic airway obstruction: I. The Unreliability of death certificates and routine autopsie's. Amemican Review of Respiratory Disease 98:601-610, 1968. 123. 1969 Supplement, at p. 38. 12W. O_~. eit.. fn. W., above, at p. 90. 125.a. EOROWITZ, L., TORRES~ M.M., LEDBETTER, M.K. Chronic obstructive bronehopulmonary disease (emphysema9) in children with asthma. Joumnal of Asthma Research 6 (~): 211-217, 1969. b. pp. 9~it.. fn. 80., above. c. FELNSTEIN~ A.R. The intellectual morbidity of vital statistics. Medical Cotmterpoint 1(89 : B~-~0, November 1969. 126. HOROWITZ, o_~. ei.t. fn. 125.a., above. 127. Id. at p. 21. 128. ADELMAN, J.V.A. review and reappraisal of emphysema. Diseases of the Chest 51(2): 151-161, February 1967. . 130. STRAWBRIDGE, H.T.G. Chronic pulmonary emphysema (an experimental study). II. Spontaneous pulmonary emphysema in rabbits. American Journal of Pathology 37 (3): 309-331, September 1960. l oduced : nllesota, et Philip Mox %.etrde / . -' '.-ou.rt s March 7, 998

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION 131. 1969 Supplement, at pp. 38-39. 132. ADELMAN, ODo 9.i.t. fn. 129., above. 133. 1969 Supplement, at p. 59. 134. , PSTERS, J.M., FERRIS, B.G., JR. Smoking, Pulmonary function, and respiratory symptoms in a college-age group. American Review of Respiratory Diseases 95 (5): 774-782, May 1967. 135. Id. at p. 777. The Anderson and Ferrls paper meferred to is The Chilliwack mespiratory survey - 1963. Canadian Medical Assoc-~ation Journal 92: 899, 954, 1007, 1055, 1965. 136.a. TURIN0, G.M., SENIOR, R.M., GARG, B.D., KELLER, S., LEVI, M~NDL, I. Serum elastase inhibitor deficiency and alpha 1-anti- trypsin deficiency in patients with obstructive emphysema. Science 165: 709-711, August 15, 1969. b. WELCH, M.H., "REINECKE, M.E., HAM/~2LRSTEN, J.F., GUENTER, C.A. AntitrypsLn deficiency in pulmonary disease: The significance of "intermediate levels. Annals of Internal Medicine 71(3): 533-542, 1969. e, LIEBF.~MAN, J. Hete~ozy~o~s and ~omozygo~s alpha-ant~trypsin deficiency in patients with pulmonary emphysema (3, 5). New England Journal of Medicine 281(6): 279-28~, lS69. d. LIEBE~AN, J. Frequency of heterozy~ous and homozygous alpha- antit~ypsin deficiencies in patients with pulmonary emphysema. Clinical Reseamch 17(3): 509, 533, lg6g. e. KUEPPERS~ F., FALLAT, R., LARS0N, R.K. Obstructive lung disease , and alpha-antitrypsin deficiency ~ene heterozy~osity. Science 165: 899-901, AuEust 29, 1969. 137o 1959 Supplement, at p. 40. 138.a. FRASCA, J.M., AUERBACH, 0., PARKS, V.R., JAMIESON, J.D. Elect~on • microscopic observations of the bronchial epithelium of do~s. II. Smoking do~s. Experimental and Moleeulam PatholoEy. 9 (3) : 380-399, December 1968. b. FRASCA, J.M.~ AUERBACH, 0., PARKS, V.R., jI~MIESON, J.D. Electron microscopic observations of the bronchial epithelium of dogs. I. Control dogs. Experimental and Molecular Pathology 9 (3): 363-379, December 1958. 13.9. McLAUGKLIN, R.F., TYLER, W.S., CANADA, R.0. A s~udy of the subgross pulmonary anatomy in various man~nals. American Journal of Anatomy 108 (2) : 149-155, March 1961. ~E~ED AND COMFiDENTiAL .... TIMN 0151924. ProducedstateaS required by the Court's March 7, 1998 Order itt. ~':: " °£Minnesota, et al. v. Philip Mo~xis.

CONFIDENTIAL: " MINNESOTA TOBACCO LITIGATION lqO. 1969 Supplement, at p. 40. 141. ~oLAUG}~IN, 9P- cir. fn. 139., above, at p. 157. 1~2. 1969 Supplement, at pp. 40-W1. McLAUGHL~N, R.F., Jr., TYLER, W.S., EDWARD~, D.W., CKENSHAW, G.L.,' CANADA, R.O., FOWLER, M.A., PARKER, E.A.; REIFENSTEIN, G.H. • Chlorpromazine-induced emphysema. Results of an initial study in the horse. American Review of Respiratory Diseases 92 (4):. 597-608, October 1965. TYLER, W.S. Investigation of chronic pulmSna~y emphysema. Report of Activities for Years -03, 04, and 05. U.S. Public Health Service Grant HE-06101, Depamtment of Anatomy, University of California, Davis, Calif., January 1966. 1%5. MeLAUGHLIN, Qp. ci__~t, fn. i39., above. l~G. BOATMEN, E.S., MARTIN, H.B. Electron microscopy in pulmonary emphysema of rabbits. American Review of Respiratory Diseases , 91 (29 : 197-205, February 1965. 147.. 1969 Supplement, at p. ~i. l~8.a. FREEMAN, G., CRANE, S.C., STE~HENS, R.J., FURIOSI, N.J. Environmental factors in emphysema and a model system with NO2. • • Yale Journal of Biology and Medicine ~0(5/6): 566-575, April/June 1968. .. b.. FREEMAN, G., CRANE, S.C., STEPHENS, R.J., FURIOSI, N.J. Patho~enesis of the nitrogen dioxide-induced lesion in the rat lung: A review and presentation of new observations. American Review of Respiratory Diseases 98~): 429-4W3, September 1968. e. FREEMAN, G., STEPHENS, R.J., CR~NE, S.C., FURIOSI, N.J. Lesion of the lun~ in mats continuously exposed to two parts per million of nitrogen dioxide. Archives of Envimonmental Health 17 (2) : 181-192, August 1968. lq~. I~d. at pp. 183-18~. " 150. 1969 Supplement: at pp. W2-~3. 151. 1969 Supplement, at p. ~2. 152. DALHAF~q, T., EDFORS, M.L., RYL~NDER, R. Retention of cigarette smoke components in human lungs. Archives of Environmental Health 17 (5) : 7W6-7~8, November 1968. 153. LAMB, D., 'REID, L. Goblet cell increase in r~t bronchial epithelium afte~ exposure to cigarette and cigar tobacco smoke. British Medical Journal 1(56~5): 33-35, 1969. - ................... i TIMN 0151925 PRIVILEGED AND CONFIDENTIAL Produced as req,u.ired by the Court's March 7, i998 ~~1 ........... State of Minnesota, et al. v. Philip Mon~, eta/. Court File No_..

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION 15~. KRAHL, V.E., BULMASH, M.H. Studies on living eiliated epithelium. American Review of Respiratory Disease 99(5~ : 711-718, 1969. 155.a. L~MB, .op..eit. fn. 153., above. b. KRAHL, ~oD. ,cir. fn. 15~., above. 156. 1968 Supplement, a.t p. 71:" 157.a. LAMB, oD. Fit. fn. 153., above. b. KRAHL, co. pit. fn. 15¢., above. 158. LUCHSINGER, P.C., LaGAR~E, B., KILFEATH~R, J.E., Pamtiele clearance from the human tracheobronchial tree. American Review of Respiratory . Disease 97 (69 : IOW6-I050, 1968. 159. HADDAD, R.G., LUCHSINGER, P.C. D~sappea~anee rate of '131I-tagged macroaggregated albumin from the lung. Journal of Nuclear Medicine 10(8) : 560-561, 1969. 160. LIPPMAN, M., ALBERT, R.E. The effect of particle size on zhe regional deposition of inhaled aerosols in the human respiratory. tract. American Industrial Hygiene Association Journal 30<3): 257-275, 1969. 161. QUINLAN, M.F., SALbL~N, S.D., SWIFT, K.L., WA~NER, H.N., PROCTOR, D.F. Measurements of mucociliary funcZion in man. American Review of Respiratory Disease 99(1): 1~-23, 1989. 182. 1989 Supplement, at p. 55. 163. 1969 Supplement, at p. 55 l~W.a. GELF~ND, M., GRAHAM, A.J.P., LIGHTMAN, S': Carcinoma of bronchus and the smokin=~ habit in Rhodesian Africans. British Medical Journal 3 (5616): ~68-~69, August 2q., 1968. ~. ORLOVSKIY~ L.V. Znaehenie sotsial'no-~i~ienieh-eskikh issledovaniy pri izyehenii paka. (Significance of the social hy=~enic investiga- tions in a study of cancer.) Gigiena I Sanitariia 33(8): 71-73, 1968. 185. GELF~ND, op. eit. fn. 16%.a., above. 166. 1969 Supplement, at p. 58. -.- . 167. ORLOVSEIY, OPo eit_~, fn. 16%.h., above. 188. !d. at p. 73. 189. HILL, K.R. Epidemiology of cancer in the West Indies including some comparisons with Nigeria (Ibadan). In: Racial and Geographic factors in Tumour Ineldenee. Shivas, A.A., ediZom. Medical Monograph 2, Edinburgh University Press, at pp. 153-160, 1967.

CONFmENTIAL: ~..MINNESOTA TOBACCO LITIGATION 170. BRUNEL, M., LEPROUX, P. Quel~es aspects ~*ctuels du cancer des bronehes en milieu africain a Dakar. Medeeine D'Afrique Noii~e . 15(12) : 595-598, Deeembem 1967. 171. DENK, R., HOLZMANN, H., LANGE~ H.J., GREVE, D. Uber arsenspatsehaden ~ei abduzierten Moselwinzern. Die Medizinische Welt 20(ll): 557-567, 1969. 172. SHIMIZU, K: Ep~demiolog&cal study on lung cancer among A-hom~ survivors in Hiroshlma. Hiroshima Journal of Medical Sciences 16 (3-4) : 241-253, December 1967. 173. PEDERSEN, E., MAGNUS, X., MORH, T., HOUGEN~ A., BJELKE, E., HAKAMA, M., SAXEN, E. LunE c~.nce~ in Finland and Nor~ay. An '" epidemiolo~ical study. Acta Pathologiea et Microbiolo~iea Scandinavica, Supplementum 199, 1969. WAGNER, G. Probleme und ergebnisse einer ieographisehen pathologic der k~ebes. Amyneimittelforsehun~ 18 (8) : 953-964, 1968. 175. SKINNF[K, E.F. Smokin~ and lun~ cancer. Medical Trial Technique Quarterly 15(3): 59-61, 1969. 178. 1969 Supplement, at pp. 55-58. 177.a. KREYBERG, L. Aetiolo~y of lun~ caneem. A morphological epidemiolo~ical and experimental analysis. Oslo, Universitets forlaget, 1969. b; KREYBERG, L. Nonsmokers and the geographic patholoEy of lung cancer. Chapter 18. In: Liebow, A.A., Smith, D.E., editors. The, Lung. International Academy of Pathology Monograph, at pp. 273-282, 1968: 178. U.S. PUBLIC KEALTH SERVICE. Smoking and Health Report of the Advisory Committee to the Surgeon General of the Public Health Service. U.S. Department of Health, Education,and Welfare, Public Health Service Publication No. ii03, 1964, at pp. 173-175. 179.a. EYSENCK, H.J. Smoking, He_a_ith and Personality, Basic Books, New York, 1955. b. EYSENCK, H.J. TARR~NT, M., ENGLAWD, L., KISSEN, D.M. Smoking, personality and psychosomatic disorders. Journal of Psychosomatic Eesearch 7 : 107-130, 1963. c. EYSENCK, H.J. Personality and cigarette ~mokin~. Life Sciences 3(7): 777-792, 196~. • - d. KISSEN, D.M. Psycho-social factors in cigarette smoking motivation: A meview. The Medical Officer i0~: 365-372, December 16, 1960. e. SELTZER, C.C. Morphologic constitution and smokins. Journal PR-- the American Medical Association 183(8): 639-'6W5, February 23, 1963. KIVILEi~ED AND CONFIDENTIAL ...... Produced as requiredfM;,, by the~taLCOurt, s March 7, ][998 Order& ...~. ~iTIMN 0151927 State o-...~,,esota,, v. Philip Morris; et ai ..... ~ .... -,-:~ .... ~o~xrt F~Io No.: C1-94-8565

......................... - ..... ~- _'~:._t______ . CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION • . • f. SELTZE~'~ C.C. Occupation and smoking in colle~e graduates. ' Journal of Applied Psychology 48 (i) : 1-6,: Zeb~uar~ 1964. E. SELTZER, C.C. Constitution and heredity in relation to tobacco .smokinE. Annals of the New York Academy of Sciences 142: 322-330, • March 15, 1967. • h. SELTZER, C..C. Morpholo~'cal constitution and smoking: A further validation. Amehives of Environmental Health 17: July 1968. • 180. 1969 Supplement, at p. 56. 181.a. ASHLEY, J.B. Environmental factor~ in the aet~olo~y of lun~ cancer and bronchitis. British Journal of Preventive and Social Medicine 23: 258-263, 1969. ~. HUEPER~ W.C. Occupational "and'Env'iron~en'tal Cancer of the Respiratory System, Sprin~er-Verlag, New York, 1966. 182.a. KAWAI, M., AMAMATO~ H., HARADA, D. Epid~ologZe study of occupational lung cancer. Archives of Environmental Health 14: 859-864, June 1967. b. CROFTON~ E.C. A study of lun~ cancer and Bronchitis momtality in relation to eoal-minin~ in Scotland. British Journal of l~reventive and Social Medicine 23 (39 : l%l-lWW~ 1969. e. HUEPER, op...cir, fn. 181.~., above. 188.a. BOUCOT, K.R., COOPER, D.A., WEISS, W. The Philadelphia pulmonary neoplasm research pr0~ect. Medical Clinics of North America 54[3): 549-55B, May 1970. (race) ~. KERMAN, B. ~ ENTERL~E~ P.E. Lun~ cancer among the Jews and non-Jews of Pittsburgh, Pennsylvania~ 1953-1967 : mortality rates and cigarette smokin~ behavior. American Journal of Epidemiolo~y 91 (4) : 355-367, 1970. (religion) e. ASHLEY, oD. Cir. fn. 181.a., above~ (sulphur dioxide) d. LANE, L.B., SESKIN, E.P. Air pollution and human health. Science 169(B947): 723-73~, August ~l, 1970. (air pollution) e. HUEI~.R~ op. ci___~, fn. 181.b., above. (social and economic class) 18~. 1969 Supplement, at p. 57, 185. BRETT, G.~Z., BENJAMIN, B. Smokin~ h~bits of men employed in industry, and mortality. British Medical Journal 3 (5610) : 82-85, July 13, 1968. Produced as required by the Court's March 7,1998 Order itt _. _ State of Minnesota, et al. v. Philip Morris, et aL . ., _.. Court File No.: C1-94-8565 ......

CONFIDENTIAL: ~ MINNESOTA TOBACCO LITIGATION 186. 1969 Supplement, at p. 57. " 187. 1969 Supplement, at p. 57. 188. BRETT, 0_2..cir. fn. 185., a~ove, at p. 84. 189. BROSS, I.D.J., GIBSON, R. Risks of lung cancer in smokers who switch to filter cigarettes. American Journal of Public Health • and the Nation's Health 58(8): 1396-1~03, Au£ust 1968. 190. 1969 Supplement, at p. 57. 191. 1969 Supplement, at p. 57. ~ 192. LOMBARD, H.L.~ HUYCK, E.P. An epidemiolo~ieal study of lung cancer amon~ females. Growth 32 (i) : W1-56, March •1968. 19B. 196~ Report, at pp. 17B-175. 19%. 0O..cir. fn. 4., a~ove, at p. 1078. 195, U.S. PUBLIC HEALTH SERVICE. End Results in Cancer: Report No. U.S. Department of Health, Education, and Welfare, National Institutes of Health Publication No. 30, 1968. 197, LOMBARD, oD. eit. fn. 192, above, at p. 55. 198. 1969 Supplement, at p. 57. 199. SALZER, G.M. ~ KUTSCHERA, H.~ DECRISTOFORO, A. zur Frage einer Syntropie von Ulcus pepticum und Bronehuskaz~yinom. Bruns' Beitrage zur Klinischen Chirurgie 216 (4): 316-321, June 19681 260. HAENSZEL, W., KURIHARA, M. Studies of Japanese migrants. I. Mortality from cancer and other diseases among Japanese in the United States. Journal of the National Cancer Institute 40(1): ~3-68, January 1968. 201. STAMLER~ J., BERKSON, D.M., LINDBERG,. H.A. SOYUGENC, R., TOKICH, T.~ WHIPPLE, T. Does hypereholesterolemis increase risk of lung cancer in cigarette smokers? Circulation 38 (42 .Supplement 6) : 188, October 1968. 202. 1969 Supplement, at p. 57. 203. 1969 Supplement, aT pp. 57-58.~ 20W. 1969 Supplement, at p. 58. P~JvK~. . - iTIMN 0151929 Pz~uced as rem,;~^~ _D AND State ~._ YheCo ~ . ~AL • °~Vmtnesota ~, _, U~_s/March 7. .

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION• 205. VALAITIS, J., MeGREW, E.A., CHOMET, B., CORRELL, N., HEAD, J. • Bronchogenic carcinoma in situ in asymptomatic high-risk' population of smo]<ers. Journal of Thoracic and Cardiovascular Surgery 57 (3) : 325-332, Mamah 1959. 206. 1969 Supplement, at p. 58. 207. VALAITIS, 9P~ .e~t. fn. 205., above, at p. 33i. 208. 1959 Supplement, at p. 58. 209. AUERBACH, O., HAMMOND, E.C., GAR2INKEL, L. Histologie eha'nges in the larynx in relation to smoking habits. Cancer 25 (i): 92-i0~, January 1970. 210. 1959 Supplement, at pp. 58-60. 211.. AUERBACH, op. eit. fn. 209., above, at p. 95. 212. ZECHNER, G. Zum Be~riff des Raucherkehlkopfes Eine Kl~nisehe und pathologiseh-anatomische Untersuchun~. Monatssehrift fur Ohrenheil- kunde und Laryn~o-Rhinologie 102 (%): 250-259, 1958. 21B. AUERBACH, oD. eit. fn. 209., above. 21~. MUIR, C.S. The incidence of laryngeal cancer in Singapore. Journal of Laryn~ology and Otology 79: 203-213, March 1@85. 218. EINHORN, J., WERSALL, J. Incidence of oral carcinoma in patients with leukoplakia of the oral mueosa. Cancer 20(12): 2189-2193, December 1967. • , 21"8. 1969 Supplement, at p. 58. 219. WAHI, P.N. The epidemiol0o~y of oral and oropharynEeal cancer. A report of the study in Mainpuri District, Uttar Pradesh, India. Bulletin of the World Health Organization 38(~): ~95-521, 1968. • 220. 1969 Supplement, "at p. 58. 222. JA~S~ A.F., BRITO, R., JACOBSON, M.E. Bladder carcinoma--Natural history and Behavior in males in Kansas. Journal of the Kansas Medical Society 68(8): BB6-BBP, August 1967. 223. 1969 Suppl~ment, at p. PRIVILEGED AND CONFIDENTIAL i~iuced as required by me Court's March 7, f998 Order in I TIMN 0151930 ~ate ot Minnesota, et al. v. Philip Morr/s, et aL:

CONFIDENTIAL: MINNESOTA TOBACCO LITIGATION 224. ~RAUMENI, J.F., Jr. Cigarette smoking and cancers of the urinary tract: Geographic variation in the United States. Journal of the National Caneem Institute 41(5): 1205-1211, November 1968, 225. References to Fraumeni"s study appears in i969 Supplement, at p. 60. 226. WYNDER, E.L., MABUCHI, K., WHITM0t~E, W~F., Jr. The epidemioloEy of cancer of the kidney ~npublished~. 227. 1969 Supplement, at p. 50. 228. WYNDER, E.L. Personal correspondence addressed to The Tobacco " Institute, Inc. June 19 1970. 229. VAN DUUR~N B.L. Tobacco-Carcinogenesis. Cancer Research 28 ~i)" 230. 1969 Supplement, at p. 62. 231.a. LEUCHTENBERGER, C., LEUCHTENBERGER, R. Cyt01o~ic and tyro-chemical effects on p~imary mouse kidney tissue and lung organ cultures after exposure to whole, fresh smoke and its gas phase from unfiltered, charcoal-filtered, and cigar tobacco cigarettes. 5. LEUCHTEN~ERGER, C., LEUCHTENBERGER, R. ~ BLANC.HARD, J., DICKERT, M. Abnormal proliferative effects of the gas phase of charcoal filtered fresh cio~arette smoke~ on 3T3 cells. Presented 53d Biology, Atlantic City, April 17, 1959. 232. LEUCHTENBERGER~ C., LEUCHTENBERGER~ R. The need of experimental inhalation studies in animals for the problem of the influence of cigarette smoke on the induction of lung cance~. Zeitsehrift fur l~aeventiv Medizin 13: 122-129, 1968. 2~. WYNDER, E.L. HOFF~V~h|~, D. Experimental toSacco carcinogenesis. Science 152 (3855): 862-871, November 22, 1958. I~d. at p. 852. 235. 1969 Supplement refers to various articles by Wynder and Hoffmar~, at p. 61. 2B5. 1969 sUpplement, at p. 63. 237. 1958 Supplement, at p. 93. 238. 1968 Supplement, at p. 93. 2~9. 1959 Supplement, at p. 77 ~ ' " " TIMN 0151931. 2q0. 1959 Supplement, at p. 77.

CONFIDENTIAL: .. MINNESOTA TOBACCO LITIGATION 241.a. UNDERWOOD, P.B., KESLER, I(.F., O'L;~NE, J.M., CALLAGAN, D.A. Parental smokin~ empirically related to pregnancy outcome. Obstetrics and Gynecology ~ew York) 29(I): 1-8, January 1967. b. YERUSI~MY, J. Mother's cigarette smokin~ and sumvival of infant. American Journal of Obstetrics and Gynecology (St. Louis) 88 (4): 505-518, February 15, 1964.. 242.a. DUFFUS~ G.M., MaeGILLIVRAY, I. The incid4nce of preeelamptic .~oxaemia in smokers and non-smokers. Lancet 1 (7550) : 994-995 b. FULOP, T. Uber Fruh~eburten alleinstehende~ be~ufstati~er Frauen. Publique 8 ~) : 381-394, 1967. Sante ~ ~ ~ e. KIZER, S. Influeneia del habito de fuma~ sobre el embarazo, patio -~ ~ .~ y reeien naeido. Revista de Obstetricia y GinecoloEia de ~ Venezuela 27 ~) : 595-643, 1967. ~ ~ ~ ~. LACUSKA, A., BOHUNICKY, F.., FILO, S. Fa~cen~e a gestae~a. (Smoking ~ ~ ~ ~ and preEnancy.) Ceskoslovenska Synekologie 33 [3) : 197-200, 1968'. ~2 = ~ ~ .e. MULCAHY, R., KNAGGS, J.F. Effect of age, parity, and cigarette ~ ~'.~ ~ smokin~ on outcome of pre~naney. American Journal of Obstetrics ~ ~ ~ ~ and Gynecology i01(6): 8~4-849, .July 15, 1968. "~ ~,~ "-~ f. RUSSELL, C.S., TAYLOR, R., LAW, C.E. Smolcin~ in pregnancy, _~ "~ ~.~ maternal blood pressure, pregnancy outcome, baby wei~h't ~ ~ ~ ~ growth, and o~hem related factors A prospectiv~ study. British ~ ~ ~ (2 . Journal of, P~eventive and Social Medicine 22 (3): 119-126, July g. TERRIS, M., GOLD, E.M. An epidem~olo~ic study of prematu~±ty. T. Re~a'l:ion to smoking, heart volume, employment, and phys±que. Amerlean Journal Of Obstetrics and gyneeolo~y i03 (3): 358-$70. i h. TOKUHATA, G.K. Smoking in relation to infertility and fetal loss. • ' A~ehives of Environmental Health 17 (3): 353-359, .September 1968. 243.a. FULOP, o_/!. p.i~. fn. 2~2'b., above. b. TERRIS, oD. ei_~t, fn. 2~2.~., above. ,, "" 24~.a. DUFFUS, op. 9it.. fn. 242.a., above. .... b. KIZEK, op..elt. fn. 242.e., above. 245.a. LACUSKA, o_/1. eit.. fn: 2W2.d., above. b~. MULCAHY, oil. cir.. fn. 242.e., above. d. TOKUHATA, oD..eit, fn. 2W2.h., above. TIMN 0151932

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