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Bliley Lorillard

[CTR Research Proposals]

Date: 01 Jan 1965
Length: 46 pages
01124376-01124421
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bliley_lor 01124376-01124421

Abstract

Summarizes tobacco industry research projects designed to mitigate the relationship between smoking and disease. Offers projects intended to refute "misleading statements regarding cigarette smoking, commonly apprearing in anti-smoking propaganda." Includes several population-based data collection projects. Presents geographic studies designed to establish differences in lung cancer distribution that fail to correspond to differences in smoking habits. Outlines project description, purpose, term, cross reference, and "recommended auspices."

Fields

Type
REPORT
Summary
Author (Organization)
CTR
Named Person
Berkheiser
Saiger
Hammond
Kreyberg
Ochsner
Gillliam, Dr.
Rosenblatt
Diehl, Dr.
Wynder
Auerbach
Langston
Passey
Wolfe, Dr.
Russek
Herman, D.
Perrone
Poche
Leuchtenberger
Saffioti
Radford
Hockett
Yerushalmy
Hester
Kinsey
McNiven
Harris
Dmochowski
Trentin
Huebner
Toolin
Stewart, S.
Named Organization
CTR
Surgeon General's Advisory Committee
Senate
SAB
Region
Hawaii
Japan
Yugoslavia
Poland
Ireland
Sweden
Puerto Rico
USA
Mexico
Africa
Keyword
Ten City Survey
Classification 132-163
Amish Menonites
Mormans
nuns
Seventh Day Adventist
Framingham
Kasparian
Polonium
Nitrosamines
Sprunt
Harris inhalation index
I-2
II-25
A (II-1,3,4)
A (II-2)
A (II-5,44)
II-10
A (II-8,9,10,22,23,32,33)
A (II-14,15,16)
Thesaurus Term
Industry sponsored research
Cancer
Disease
Tobacco use
Tobacco industry structure
Lung cancer
Cigarette ingredient
Cardiovascular disease
Smoke
Data analysis
Animal research
Respiratory disease
Pollution

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Page 1: 01124376
Project: I - 2 Demonstrate that there has been a change in the population com~osition in about the last 50 years due to the survlval to the ~hronlc disease are of persons we~tk lungs, w~k h~rts, a. Document the decline In deaths from respirntory d~se~se, hy ~e. b; Autopsy study shOW,DE otherwise da~ged lungs In ~ople With lung ~ancer (Berkhe~er type work). c. Demonstration of the fac~ ani~is with ~evlously da~ged d~elop lun~ cancer. d. Plot thera~u¢Ic advances the c~nges in death rates foF ~esp~atory disease. e. Doc~en~ %he face that ~h~ ~' ~otal re~p~a¢ory mo~b~ity declining. C_ross Reference: Purpose: To: II (i) Illustrate that the population composition has changed, and thus support the constitutional hypothesis. (2) Sho~ that ag0-adjusted death rate ~ompar isons cannot demonstrate that
Page 2: 01124377
I reported increases in various diseases associated wi~h smoking are a~trtbut- able to smoktng. Term: Long, with possible short-term results. R~econnnended Auspices: C.T.R. and OUtside. II Purpose: A study %o documen~ the decrease in mortality from respiratory diseases other ~han lung cancer. (~ollowin~ this study consider a similar study with regard to all chronic disease deaths.) To support the hypothesis that death from respiratory dlse~ses has been reasonably constant and.th~ ~ho only real ehan~ehas 'been in the type of respirator~'disease causing death. Term: Shor~. ~ecommended AusP,i~es: Outside.
Page 3: 01124378
II, - i II - 3 Pro,j ecZ: A (I7-I,,.3,4) Arr&n~e for a cri¢ique by ~ panel of experCs of sta.tistics relied upon by the Surgeon- General's Advisory CommitZee. l~/r~ose: To demonstrate that the conclusions based upon apparent statls~i.cal associations are no~ justified. Term: Short~ Recommended Auspices: Ad Hoc. l:,ro~ect: purpose: Sailer study involvln~ inclusi~on of m~ny - more v~riahles in statistical analyse~. To seek to. reduce the correl,ation of smoklnE and disease by ~n~roductlon of additional variables. Term: LonE, with possible short-term results. Recommended Auspices: Ad! Hoc .... II Pr o.~ ect: Cri.~ical re-ex=mina~ion of Hammond m~tched pair analyses. Dependinz on results, further check could be done by comparin~ the twin studies to Hammond's m~tched pairs. purpose: To follow up suggestions that Hammond's matched pair s~udy will fall apart under critical evaluation. Term: Lon3, with possible short-term, results. Recommended Auspices: Ad "
Page 4: 01124379
Project: A Specific reZut~on, possibly by the panel of experts, o~ misle---ding s1=~emen~s re- gardin~ ci~are~:e smoking, com~monly appearing: In. ~nt~-s~okin~ propaganda: ~. 250,000-300,000 excess deaths per year from smoking. b~ One million school children of ¢oday wil~ die f~om l~un~ c~ncer b~ore ~h~y 70 yea~s of a~e. c. 14.4 minutes of li~e are los~ wi~h each ci.~e~ s,~o.~ed. purpose: 'd. One in every %en smokers will ge~ lung c~cer. e. Twenty-seven mi:llion people liv'ing ~eday will die prematurely due ~o smoking. To refu~e untrue s~a~emen~s commonly made in endeavorln~ ~o =farm ~he public ~bou~ cigarette smoking. Term: Shor~. Recommended Auspices: Ad Hoc.
Page 5: 01124380
II - 5 II - 44. Project: A A collec¢ion ¢o be made of'gredictions that have nee com~ true", including: a. "AfCer women have been smokln~ for a longer period of time, the incidence of female ~ung cancer will equal: tha~ of men.." b. "The ma:le population will be decimated by lung cancer in ten years." • c. "The curve of iun~ cancer will be like tha~ ofother cancers." d. "Benzpyrene and other ingredients of ~obacco smoke or condensate act as direct carcinogens." e. "The age of pea.k incidence will become lower." Purpose: To demonstrate that the predictions made years ago by the proponents of the cigarette causation theory have not come ~o pass and many have been~bandoned. Term: Short. Recommended Ausp.ice.s : Ad Ho~. : Pros ect : ~ur~qse: Document that, regardless of what latent period is assumed, %here has been no parallel increase of lung cancer with ¢iEarette smoking, To illustrate that, even usin~ any latent period; suggested; by ICreyborg, Ochsner or others, theincrease reported in lung cancer has not ~aralleled the increase in cigarette consumption, Term: Short. Recommended Ausgi.ces: Outside.
Page 6: 01124381
II - 8 A' ~II-8,9,10,22,23,32,33) II Project: Collect d~ta for selected areas or countries concerning incidence and mortality.~ith re- spec~ to the pertinent diseases: (a) by years; (b), by sex; (c) by a~e; (d) by area; including urban rural; (e) by. race; (f) by country of origin. Purpose: To establish zeogr~phiiea:l differences in, distribution of lung cancer a,nd~other per- tinen~ diseases not corresponding to dif- ferences in smokin~ habits. Term: Long, with possible short-term results. Recommended Auspices: Outside. II - 9 Project: ,Study o~ geographic differences in the dis- ~rlbu~ion of lung cancer and the other per- ¢ilnen¢diseases among world populations. Purpose: To demonstrate geographic differences in the incidence oZ the.pertinent diseases. Term: Shor~. Recommended Auspices: Outside.
Page 7: 01124382
II- i'0 Project: puTpose: Cell, oct data £or selectcd areas or countries regardin~ szokinc habits, usin~ available indicia includinz per capita, male-~emale, a~e, etc. To secure data to correlate with cancer in- cidence and incidenceof the other pertinent diseases for use in. further studies. Term: Shor~. Reco~ended~Auspices: Outside. II- 22. Project: Purpose: Determine whether to¢al cancer incidence in ethercountries is increasing and whether lung cancer is increasing or decreasing in proportion to o~h~r cancers. ~or this purpose use age-adjusted ~i~ures. To investigate whether ~here is simply a change in si'~e of cancers and not an increase in total cancers. Term: Short. Recommended Auspices: Outside.
Page 8: 01124383
A (iIv~-P/,9,10~22,23~32,33) ~7 _ 23. Pro~ ~ec ~: Purpose: S~udy, in other countries, alon~ the l,ines done by Dr. GilliRm in ~he U,S.A., respecting chan~es in the rate of increase of lung cancer. To investigate whether the rate of increase of lung c~ncer is leveling o~f, as previously- indicated in Oilli~m"s wor~ Term: Short. Recommended Auspiees: Outside. II- 32. Project : Purpose: Further documen~ znd! analyze the Ten, City Survey and Prindle's comparative survey on ai~ pollution to show th~tv~despread dif- ferences in. the incidence of !un~ c~ncer and the other pertinent diseases ~re not explainable by d~fferences in s~ing habits. To demonsZ~ate that s~oking habits do no~ account for widespread~differences in incidence of the pertinen~ diseases. Term: Short. Recommended Auspices: Outside.
Page 9: 01124384
A (~I-8,9,~!0,22,23,32,33) II: ( II - 33. ~ke geogruphical comparisons of disease rates o.f i.mmigratin~ groups v~th those of n~i.ve popui~.%ions, usin~ Dean type anslyses (consider J~p~nese, I[a~nilans~ YuEoslavs, Po~es~ Irish, 'S%vedes,Pue~o ~ic~ns). Purpose: To demonstrate a dlfferen~ incidence of lun~ ¢~nce~ and the other pertinent disezses in ethnic ~roups not ¢o~respondin~: ~o their smoking hnbits:. Term: Long, %~Zh possible short-~orm results~ Reco..-unended Auspi, ces: Outslde. "
Page 10: 01124385
A II 14. Project: Purpose: ~urther study nnd documentation, of ~he frequency o~~ metastasis to the lung of cancers a,risi, n~ in other prilm~ry sites. • To demonstrate that a subsZantial per- centage of l:un~ cancer m~y be primary in o~her si~es. Term: Short. Recoimended Auspices:: Outside. II - 15 15. Projec¢: Purpose: Term: Recommended Auspices: Studi~s of ~he Zype done:by Rosenbl~E~ rela~inZ, to "~he difficulty in iden~ifylng lung eance~ :~ primary or secondnry. To demons~rL~e th=~ much of ~he claimed incidence" of lung cancer may be me,asPic. ShorE. Outside.
Page 11: 01124386
A (II-14, 15~ 16) Pro~ect: A'nalyze the accuracy o,~ vital stati~stics reportin~ primary and secondary lun~ cancers. Purpose: To demonstrate ~hat many cancers of the lun~ reported uudor Cl~assific~ion IS2-I~3 of vital statistics arose in other sizes and were~seconda~y in the lung. Further @urpose ' to refute Dr. DiehI's letter to the Sen=re which in substance stated tha~ practically all of the cancers so reported were primary. Term: Short. Reconuzended Auspi,ces : Outside, Ad Hoc.
Page 12: 01124387
A (II.2S, 30, 31) II - 28. Pro~ect: Purpose: A study of areas that constitute pockets of high lung cnncor incidence without rel.stion to smokin~ habits (compnrinz New Orleans, Ten Cit[ Sux-vcy, E1 Paso, New Yo~k City, Pittsburgh and perhaps ~exlcan vlomen and Dr. Palmer's pro~ect in. the southern part of Africa). To illustrate that there are areas which have a hIch incidence of lunz cancer not cor{espondinz to smokin~ hsbits. Term: Long, with possible short-term results. Recommended Auspices: (h:tsilde. 30. P~o~ect: A study of areas which, constitute pockets of low lunE cancer incidence not correspondin~ to smokins habits. (Consider survey of desert and mountain state areas, most of which were omitted by H~mmond in his s~udy.) Purpose: To demonstrate th=t cancer incidence is no¢ related to ~okin~ hzblts. Term: Lon~, %vith possible sho~t-term results. Recommended Auspices: Outside.
Page 13: 01124388
II II -Sl. Pro~ec~: A study o~ the incidence of lunG: cancer and: other pertinent diseases in non-smoklng popu- lations (compare ~mish, ~enonltes, nuns and! Mormons; consider a re-do of the Seventh Day Adventist studies done by Wynder~ as to which question has been raised.) Purpose: To establish the incidence of lung cancer in ~on-smoking populRtions, Term: Lon~. Recommended Auspices: Outside.
Page 14: 01124389
A (II-47; IV-l,9; %'-2) II Pro~ect: Collect emphysema cases among non-smokers and amonc yovnc people. Cross-Reference: IV Purpose:, To demon~tTate that both non-smokers nnd- yo~n~ people who have smoked briefly have emphys~ma~ thus dilutln@ any asso~lation between smelting and emphysema. Term: Long~ with possible shore-term results. Recommended Auspices: Outside. z. project: Collect cases of epidermoid lung cancer in non- smokers.: Prepare a slide demons~ration. Cross-Reference: and ~ Purpose: To demonstrate that epidermold lung cancers do occur in non-smokers and thus refute assertions that these cancers only occur in smokers. Term: Short. Recommended Auspices: Ad HOC.
Page 15: 01124390
A IV- 9. project: Collect autopsy data showing so-called "pre- cancerous" changes in non-smokers occurring as aresult of systemic causes, e.g., substances such. as cortico-sterolds or some vlta~in deficiency, etc, Cross-Reference: III and V Purpose: To demonstrate that so-called "pro-cancerous" changes occur from systemic conditions brought about by medicines in co,men use, as well as other systemic factors, and not necessarily through direct contact with inhalants. Term: Recommended AuSpices: Long-term, with possible short-term results, Outside. V-- 2. Project_: Collect and prepare visual demonstrations of sl, ides showing Auerbach-type:changes in the lungs of a large number of non-smokers. Cross Reference: IV Purpose: To demonstrate the so-call:ed pre-cancerous changes are found in the lungs of non-smokers. V Ter~: Short.. Reconnnended Auspices: Ou ts id o.
Page 16: 01124391
Pro~ ect: Purpose:. Arrange for a vew of the literature with regard to emohysema, particularly to document that the cau.~3 or causes of emphysema are To document how little is known about the cause or causes of emphysema., Term,: Short o "~ecommendedAusp~ccs: Outside.
Page 17: 01124392
A (III-2) [( III llll - 2, CollectS11 o~ th~unpub,lished negative animal experiments ~,th tobacco (including skinpain,ting nnd ir~hal,ation) o Cross-Referenc~:i VI Purpose: To bring togo~her the negative results with respect to efforts to produce the pertinent diseases in animals with, tobacco. Term: Short. Recommended, Auspices:: .~d Koc.
Page 18: 01124393
A (III-14) Ill - 14. Project: Studies to determine whether there are cancers "without so-called "pre-cancerous" changes and to demonstrate that there are so-called "pre- cancerous" ch-~nges which do not progress to cancer. Collection of slides showing these. A slide and history demon.stra~ion of "pre-cancer" in ~eas ot~r than (e.g. uterine cervix, oral cavity, skin, e~c.), which ~ve recessed ~ re~in~ the s~e £~oughout a ~r£od of ye~s She~ diagnosis~ ~oss-Re~erence: V ~ose: To demons£ra~e tha~ the so-called "pre- cancerous" changes referred $o by Auerbach and o~rs ~e no~ in fact prec~sors C~cer. Te~: ~ng, with possible shor$-tem results. Reco~ended A~pices: Outs£de.
Page 19: 01124394
I'II -- IT, A (III-17; IV-5) Pro;~ect.: Clinical studies to be conducted by Lan~ston and others to show that duration and amount smoking have no relation to the age of peak incidence of lung cancer, Cross-Reference: Purpose: To fortify Passey's observations that the amount and duration of smoking do not affect the time when lung cancer appears and thus tO Cast doubt on any causal hypothesis. Term: Long, wlth. possible short-term results. Recommended Auspices: Outside and Ad Hoo (Langston study now inproEress), Project: Conduct a study to compare the age of peak incidence of lung cancer in d~fferent geo- graphical areas. Endeavor to tie this in- formation to the peak age of starting smoking, if posslble, and also to the average age at death in the particul'ar, area. Cross-Reference: II • " Purpose: To determine whether the peak age of lung ~ancer incidence is affected by variables and, £~,so,, to demonstrate wha~ variables affec~ it. Also to refute Kreyberg"s theory of a 40-year l'atent period. Terg: Short. Recommended Auspi.ce~: Outside.
Page 20: 01124395
III ~II - 26, Pro~ect:i Purpose: Documentation of the discrepant data in the Alb~ny and ~T~mingham studies concerning Ca~d~ovascul~r disease (expansion of ob- servations o~ Dr. ~o~ffe.) Correlate Albany and Framln~h=a findln~s with Russek findings that there is mo~,~ hear~ disease inno~-smokers th~n in ex-smokerso To demonstrate the inadequacy of exlstlnE ep,ldemiological data indicating smoking as a cause.of hen~ disease. Term: Short. Recommended Auspices: Ou~slde.
Page 21: 01124396
A (III-31) Expand the Kasparian type experiments which measure the effect on an artery size, of cigarettes, alcohol, etc., and determine whether an investigator can measure the effect of Stress and other factors besides smoke and alcohol on the coronary arteries. Cross-Reference: IV purpose: To develop a means for measuring the effect of stress on the coronary arteries as a sus- pect in the causation of cardiovascular disease and to show no effect on the coronary arteries of the inhalation of cigarette smoke. Term: Short. Recommended Auspices: Ad Hoc.
Page 22: 01124397
IV- 10. Pro~ect: Collect colored! pho~o~raphs of gross lun~ tissue o3 smokers and non-smokers from a variety of ~eo~raphical areasp including cities of varyin~ population density. Cross-Reference: V Purpose: To refutethe popular misconception that smoking cigarettes changes the gross al)- pearance of human lungs. Term: Short. Recommended Auspices: Ad Hoc.
Page 23: 01124398
VI.- 5. Pro.Jec~,: • Consider skin-p~intinK tests with believed harmless subst-~nces in every-day use such as tom~to juice, eg~ yolk, skin salv~s, coffee, etc. ~rpose: To inyes~i~e whether skin cancers can be ~uced by p~intin~ wiCh a v~r~ety of so- called ~rmless substances as was done with ~ob~cco smoke condensate Lon~. Reco~ended A~plces: Outside. (C.T.R. would llke w~k in this field, bu~ Ad Ho~questions adv~ab~llty of C.T.R.
Page 24: 01124399
II - 6 Further studies (a) to point out the chain of association .which producvs a statistical but non-causal association between cigarette smoking and certain dise~essuch, as pepticulcerj cirrhosis o~ ~he liver~ etc. Cross-Re~erence: III ~nd IV' II l~u~pose,: To demonstrate that many associations are obviously non-causal and that~ accordingly, there is no adequate basis for claiming that causation is established by any particular association. Term: .Long. Recommended Auspices: Outside and Ad Hoc, with C.T.R. assistance.
Page 25: 01124400
B (II-19) II -- lg. Pro~ect: Expand Doris'Herman*s study to show that the lncrease in lung cancer incidence £s primarily adenocarcinoma and not epidermoid at least in certain geographic areas. Cross-Re~erence; Purpose: Term: Recommended Auspices: III To refute the theory that the increase in lung cancer is primarily epidermo£d. Long~ with possible short term results. Outside. •
Page 26: 01124401
B (II-36) , ,I, iI -36. P~o~ect: Purpose: Investigate possibility of additional statistical studies, such as those made by Perrone and Poohs, which sho~ed no association between smol, in~ and lun~ cancer. To refute the many st~tlstlcal studies in which an association is shown. Tel"m: Long, Recommended A~spices: Outside.
Page 27: 01124402
B (III-3) lll--S. Pro~ ect: Purpose: Examine the or~=ns of Louchtenberger's nice for any pathological changes, and compare smol¢in~ and, non-smoking nice. Todetermine~ether sn~ing resulted in any patholo~icalchancos in ~ouse organs and to give a basis ~or a lonE-term study of diseases other than lun~ cancer by inhalation experinenta- tiQn. Te~m: .Short, but possibly resulting, ln long-term pro~ecto R~commended Auspices: Ad Iloc°
Page 28: 01124403
llIl- 5. Pro~ect: Conduct Saffio~£ type oxperlment involving the use of hemn~ite dust in putting benzpyrene ~n the~lun~s which produce I00~ cnncer in experimen~nl anlnals bus ~nstead of benzpyrene use whole smoke, Cross-Reference: IV, V and Vl - \ Purpose: To'e~lore ~hc ~ossibilit~ of showing no p~oduction of lung cancc~ bY the use of cigarette smoke in a ~o~ most closely res~mbllng the who~e smoke, while cancer is produced I00~ by the use of known carcino@cns such, as benm- pyren~. Term: Short-term pilot. Reco-,~ended Auspices: C.T.R. (Saffloti not to be used).
Page 29: 01124404
III- 19, l~o~ec~: Conduct experlmen~s to check ~he accuracy of Radford~s identifica~ion and measuremen~ of polonium. Ex~mlne human lungs in ~nokers and non-smokers dupllcatlng R~dford's.experi- mento Measure polonium in pipe and cigar smoke. Check oral cavity tissues for polonium, posslble polonium dose response studies In mice. Secure relevant da~a of h~'mnn dose response to polonium" from the A~omi¢ Energy Commission (from mlnes in the Western United States of America), Investigate the source of polonlum in huma~ existence and where tobacco gets polonium. .Compare sources In the atmosphere and otherwise and check geographical differences in polonium content of tobacco; compare wi~h lung cancer incidence. Explore posslbilicy of ch;cklng .polonium count in gr~zlng .Term: T6 do basic fete.arch onthe presence and importance o.f polonium'in the envLronment, including tobacco. Long, with possible shor~-termresul~s. Rec~nmended Auspices: C.T.R. (SABwill conside~ paz~ Of '~hls next week).
Page 30: 01124405
Pro~ ect: l~trpos~: Inves$iEaCe ni~ros~mlnes. Basic research to investigate whether nltrosamlnes in ciEarette smoke play any Important role in the caus~tlon of dlse~Seo Term: LonE. Recommended Auspices: C.ToR.
Page 31: 01124406
Project: Purpose: Investt~te free ~ad£cals, Baskc research to tes~ theory that z'ree r&d£ca~s £n smoke cause d£se~se. Term: Long. Reconmended Ausp£ces: C.T.R.
Page 32: 01124407
purpose: Xnves~igatQ ~l~nddQr cancer enzyme block. To test ~he ~heory ~ha~ ciEare~te, emok£nE causes &n enzyme block whlch £n ~urn ~use8 bladder cancer. .Term: LonE, RecOmmended AusPices : C.T,R, (Proposed by Dr. Hockett).
Page 33: 01124408
I~I - 32. Pro~ec~: purpose: Experimental studies of smoking and prematuritT, Confirm Yerushalmy's and Hester's work on the non-.effect of mothers' smoking on the,well- being and health of their babies. T erm: Lon~. Recommended Auspices: C,T.R.
Page 34: 01124409
s Project : Combine~. review by. pathologists and a statistician of al, l Auerbach-type data, Includin~ a rearran~gement of the data for a mu~ti-variable analysls~ Also a revicw of ~roblems in classifying cancer and "'pro-cancer". Cross-Reference : IV Purpos..____~e: To, question Auerbach's conclusions by showing the existence of relevant variables and that his total cases were too, few to permit analysis of these variables. To document the extent of disagreemen~ among pathologists about histological classlf!catiO~So Term: Long. Recommended Auspices : Outs
Page 35: 01124410
VI - 3. Pr o~ ect : pose Determine and document the occurrence of human types of lung cance.r in animals. To establish that -nimals can develop human types of lung cancer, and that, therefore, mouse adenomas are not an appropriate index of carcinogenic activity. This will fortify ottr position ~ha~ only the production of human type lu.ng cancer in animals is relevant. Term: Long. Recommended Auspices- C.T,R. and Outside. VI VI - 4. ,,Project_: Comprehensive studies O~ lung aden,om~s in various s~rains of mice, including both susceptible and resistant strains. Purpose:. TO show that lung adenonms are not an appropriate index of carcinogeniciiy. Term.: .Long, with possible short-term pilots. Recommended Auspicos : C.T.R., Outside and Ad Hoc.
Page 36: 01124411
Project: Purposez A study of differences between smokers and non-smokers and between the pertinent disease victims and contrbls In the following known o~ suspected genetically tnfluencedcharac- (a) b~ochemtcal: (e.g. blood type, endocr~ne~ (b) 'neurologlca~ • (c) sensory (e.~. taste, sm~ll, etc.) (d) use of alcohol (In this connection check Klnsey data and similar behavior studies.) Term: Recommended'Auspices: To support the constt~u't~onal hypothesis regarding the pertinent diseases. Lon g. ~ C. T.
Page 37: 01124412
C (llI-l~ IV-13,14,15) ,Pro~ ect,: Extensive progrnm of experiments in, animals involving production of the pertincnt diseases by inhalation techniques and oCherwiSeo This ~11 be a major undertaking involving use of numbsr of investigators and laboratorles~ The first objective is the establishment of usable experimental models for production of the pertinent diseases. In each series of experi- ments, many variations will be systema¢ically imposed upon the modelo The program w~ll take man~ years, ~u¢ m~ny useful results should be available within'two years or so from initiation of the pro~,'~no Some of this work is underway and much of i~ can ~o. for~rard concurrently° • Takin~ o~erlment~ production of lung eancer by ~l~tl.on techniques as an e~ample: Io Dc~'olop n b~sic model by which c~nco~ can be ~eprodueed .in a ~Iven torya~±m~l with a particul~r aEent with pre~ictabiefrequencyo , 2°. Vary the agent--i,eo see Wha~agenCs, including, tobacco ~noke, will produce III-1
Page 38: 01124413
C (III-i; IY-13,14,15) III
Page 39: 01124414
C (III-1; IV-13~14~15) Expand the Sprunt~type experiment tnvolvtn~ the damaging of animal lungs -with various a~ents~ including vlruses~ to produce tun@ cancer. .Purpose: To determine the el.feet of previous . lung damage and virus in the production of lung cancer. Term: 'Long. Reco~uaended.Auspicgs~: C,T.R. Project: Continue experiments to, induce bung 'cancer by the in~ection of common viruses, by common viruses plus smoking, or viruses plus pol'lutlon, or viruses plus bacteria. Cross-Reference: Purpose.: To i;nves¢igate the role of viruses in lun~ canoes causaEion. Term: Lon~. " Recommended Auspices: project) C.T.R. (Presently proposed
Page 40: 01124415
C (III-1; IV-13,14, 15) Pro~'ec~: Purpose: Term: ~tudy possfble carcinogenfcity of X-ray (~n both diagnost£c and therapeut£c doses)'and drugs, by adding these factors In experiments ~volvlng damaged lungs, viruses and other suspected carcinogenic factors. To inves$igate X-rays and. drugs as possible • factors in lung cancer causation. Lon~. Recommended Auspices: C.T.R. IV
Page 41: 01124416
Pro~ect: Studies C (I11-6,7; VI-I,2) a. To determine more accurate measurement of actual irahalation by humans of pipe, clear and. cigarette smoke. (E.~. blood '~nd urine tests by ~cNiven et al.) b. To ascertain the difference between the effects of c~arette, pipe and cigar smoke on animals. Co 'To find chemical and physlcal differences in cigarette, pipe and ci~arsmolte. Cross-Reference: .II III -- 7. Term,: To test the reliability of inhalation data in smokinghistories obtained by present methods and to explore the various forms of smoke for differences which may contribute to the epi- demlologlcal data, Recommended Auspices: C.T,R. ~ro~ect: Study to demons~ra:te by carbon 12 ta~ged tobacco that the Leuchtenber~er index of carbon, mono:~de intake is more reliable than the Harris ind,:: in the measurement of inhalatiO~o Cross-Reference: VI Purpose: To develop rei~ab!o methods for measurement in future inhala~ion research and to expose the inadequacy of the~arris inhalation index. Term: Long. Recommendod Auspi,ccs: C.T.R.
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C (III-6,,7; VI-I,~'-) P~oO ect: put pose Devise methods" to measure inh~lation and exhalation of smoke in people and in ani~ls. Establish the dt~ferenee's between ani~ls and ~n and between dOg,event men with regard to both ~la~ion and ex~latlon, Includtn~ and c~ar smoktng £n ¢h~s study. Also com~re in an~16 the amount of s~ke brough~ tn¢o the lungs in. smoke with t~¢ which ~y be ~orced tn¢o the~ lungs through other means. To investigate a method or methods by which human smoking hab~-,1;s can best, be approximated for expertmen¢al purposes, • Term: Long. Recommended Auspices : C.T.R. ~
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C (III-6,7| VI-I,2) vi- 2, PTo/iect': Compare the whole smoke used by C.oT.R. .. with the who.lo smoke used by others, includin~ Harris, to see if chemical or physic-~-i differences in the smoke can be .shown. Compare the various methods with hunmn smoking. Cross-Reference: III To determine which experimental smoking • techniques best approxlm~to the smoke inhaled by the hunmn smoker nnd: to investl- gate the de,-Tee Of d Lfference between the smoke H~rris used and that Inhaled by the human ~moker. Term: Recommended Auspices : Lon~ Ivith possible shoat-term results. CoToR.
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c Conduct experiments involving the introduction into animals by means other than inhalation of a variety ofharmless and harmful substances to show tha~ lung cancer nnd changes in lung tissue ¢'an be produced systenically and are not specific ~o the inhalation of cigarette smoke. Cross-Reference: IV and V Purpose: To demonstraCethat lung cancer can be caused bysysCemic infl:uenco and no¢ n.ecessar~ly by inhalation. Term: Long, with possible shore-term results. Recommended Auspices: C.T.R.
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~ojec~: Experiments to investigate possible carcinogenic e~fects of polio vaccines (Dmochowski)., ~lu vaccines, etc. (See also work o~ Trentin, Huebner, Toolin, Sarah Stewart, etc.) To explore the possibility tl~t various vaccines may be factors in the causation of • cancer. Term: Long. Recommended Auspices: C.T.R.
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• VII - 2. P~ o,~ ect : Put posle.: Recommended Various experiments show~n~ effects of stress (including p~rt~cularly those already done) superimposing smoking. T~ investi~ate~he possible ~llev~ting effec%s of smokin~ onl stress. ~n~, with p~siblo shorE~te~m results. C.T.R.,: Ou%side an~ ~d H~,

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