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Compares domestic military sales to total U.S. sales data for each Winston style in order to determine "which Winston style might be best promoted in military bases." First half of years: 1974, 1975, 1976. "Recommendation: Pursue development of promotional items geared towards men (using Winston Box), or towards men and women (using Winston Longs)."


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Page 1: 500498340
November 23, 1976 Mr. S. C. Wooten, Jr. Re: OPPORTUNITY ANALYSIS FOR WINSTON IN MILITRAY BASES The question was raised as to which Winston style might be best promoted in military bases. To answer this question, comparative sales data was analyzed, comparing domestic military SOM data to the Total U.S. for each Winston style and respective category. Total Winston performs somewhat better in military bases than in Total U.S. Total Winston First Half. Of-Year 1974 1975 1976 Military 16.1% 16.3% 16.2% Total U.S. 15.4 15.7 15.3 Index To U.S. 105 104 106 The reason for this somewhat stronger performance tends to be due to Winston Box and Winston Longs. Winston Box First Half Of Year 1974 1975 1976 Winston Longs First Half Of Year 1974 1975 1976 Military 1.2% 1.1% 1.0% 4.0% 4.1% 4.4% Total U.S. .6 .... 6 .......... 6 3.0 3.1 3.!~ Index To U.S. ~_~ 2~_ 18 Additionally, the 100mm NFF Category is over-developed in military bases, whereas the Box Category is not. Box Category First Half Of Year 100mm NFF Category First Half Of Year 1974 1975 1976 1974 1975 1976 NA 9.2% 9.4% 13.8% 14.4% 15.1%~ Military Total U.S. 8.9 9.4 10.3 10.3 10.6 10.7 Index To U.S. - 98 91 134 136 141 (See Attached For Further Detail) RECOMMENDATION Pursue development of promotional items geared towards men (using W.inston_i~o_~_)_, or towards men and women (using Winston Longs)I- ...... Tim Key TJK/bs cc: Mr. J. H. Sherrill, Jr. Mr. T. L. Ogburn, Jr. Ms. E. N. Monahan Mr. D. G. Fought H~--K~---V. ~cCaffrey Ms. D. M. Clauss Mr. Jerry Darringer
Page 2: 500498341
Winston Winston Winston Winston Winston (K) (B) (S) (M) Lights Military SOM First Half Of Year • 1974 1975 1976 10.7% I0. 1.2 1. 4.0 4. .2 . .0 1% 1 1 3 7 9.8% 1.0 4.4 .i 85mmNFF 100mmNFF Hi-Fi Menthol Box 31. 7 29.7 29.2 13. 8 14.4 15.1 7.2 9.4 11.6 • 25.2 26.1 25.3 NA 9.2 9.4 Winston Winston Winston Winston Winston (K) (B) (S) (M) Lights _ Total.U,S., .SOM First Half Of Year 1974 1975 1976 ii.4% Ii.1% i0.4% .6 .6 .6 3.0 3.1 3.1 .3 .3 .3 .i .6 .9 85mm NFF 100mm NFF Hi-Fi Menthol Box 31.2 30.9 29.5 i0.3 i0.6 i0.7 9.0 i0.3 14.3 26.7 27.7 28.5 8.9 9.4 10.3
Page 3: 500498346
June i0, 1976 INDIVIDUAL COPIES TO: Mr. G. B. Whitaker Mr. R. F. Arfmann Mr. Y. W. Ford Mr. W. P. Hanes Mr. ~. Heist Mr. D. G. Samuel, Jr. Mr. R. V. Hall Mr. P. R. Watson Mr. H. E. Christopher Mr. J. T. Weller Ms. B. Kirby Mr. K. B. Hedrick Ms. E. Monahan Re: WINSTON LIGHTS DALLAS-FT. WORTH COUPON PROGRAM This is to inform you that WINSTON LIGHTSwill be circulating a total of 1,578M coupons through the use of a free-standing insert in the Dallas Times Herald and the Ft. Worth Star. This free-standing insert is basically a page.with a per- forated $1.00 off-a-carton coupon on the bottom of an ad which is inserted into Sunday newspapers. The inserts will be circulated in three waves in both the Dallas and Ft. Worth papers as follows: Date 8/8/76 News.. paper Dallas Times Herald Ft. Worth Star # Of Coupo~ 301,000 225,000 8/22/76 Dallas Times Herald 301,000. Ft. Worth Star 225,000 9/5/76 Dallas Times Herald 301,000 Ft. Worth Star 225,000 As these coupons will be distributed close to the Labor Day floor base, WINSTON LIGHTS will be placed in each display -- no less than 20 cartons/display. Fifteen cartons of WINSTON LIGHTS will also be placed in the VANTAGE 30-carton floor base scheduled for September 6-30.
Page 4: 500498347
June i0, 1976 Page Two The following will be required of each Department: SALES To notify Field Sales Force in Dallas-Ft. Worth of coupon program by DM letter. 2.. To arrange for loading of WINSTON LIGHTS and to arrange WINSTON LIGHTS be placed on the Corporate Labor Day floor bases and in the VANTAGE 30-darton floor bases. To receive copies of the WINSTON LIGHTS free- standing insert. MARKETING To provide tear sheets of WINSTON LIGHTS free- standing insert. 2. To contact Tax Department (R. V. Hall). 3. To arrange for production of free-staq~ing insert (R. V. Hall). o To provide a market list, mailing dates, and quantities to Sales and Traffic. MARKETING RESEARCH To determine redemption and conversion of free-standing insert and the value of waving. MANUFACTURING To provide 1 million additional units of WINSTON LIGHTS to be delivered to the Dallas warehouse and 1 million additional units to the Ft. Worth warehouse by August 8. TRAFFIC To insure additional product (IMM in Dallas and IMM in Ft. Worth) by August 8. If you have any questions or problems, please call. KM:pa cc: Mr. S. C. Wooten, Jr. Mr. D. G. Fought Kay McCaffrey
Page 5: 500498421
DANCER FITZGERALD SAMPLf, Inc./.¢ 7 M,~, .'i.~on A'.,e,~ue, qew Y~ ~k, N.Y. "1001 /Area Co~;/e 212 679-f~,00 :1.977 Ms. Rebecca S. Sidden Coupon Redemption Center R. J. Re~.~olds Tobacco Company Ninston-Salem, North Carolina Dear Ms. Sidden: Re: W~i.nston Le.6al .Coupons Nhen I talked with you on March 16, it was my understanding that you would furnish to me as soon as information obtained from Nielsen a report on any additional coupons which ,.~ere redeemed from the coupon.~ which disappeared en route .~rom Lura~, Virginia to t~e Now York Daily News. As you know, this Lnformatlon is needed so as to flnslize any claim to be m~de against the involved parties. Ac~ordlngly~. yo~ c¢,operatlon In getting back to me as soon as possible will be appreciated. ~nc ~ely yours, ~ ~ewls Ames I ~ssoclate Director ~/Buslness & Leg~ Aff~rs bcc: • t¸ M. Crohn, C. Standen, S. Nooten, J. Taylor, S. Adams, D. Boyd, N. James, J. Oxee, E. Stevens, R. Taverna
Page 6: 500498424
Newsoaoer Atlanta Journal Constitution Columbus Dispatch Des Moines Reg~&te~ indianapolis Star Memphis Commercial Appeal Milwaukee Journal New York News Phoenix Arizona Republic Toledo Blade Total Credit DFS Media 11/8/76 Circulation . 522,915 325,124 433,865 "354,965 285,457 529,089 2,460,000 339,874 207,503 Good Copies WINSTON 1976 AD-A-CARD CREDIT COMPUTATION Good Perce~t Credit Revuested 479,709 91.7 3.3 :-272,172 83.7 11.3 310,341 71.5 23.5 292,240 79.5 15.5 253,885 8819 6.1 466,734 88.2 6.8 2,275,000 92.5 2.5 279,106 82.1 12.9 166,400 80.2 14.8 Cost • Space S 5,156.32 3,313.72" 4,417.80 3,574.20 2,998.48 4,928.40 21,446.68 3,216.04 2,160.80 Add-A-Card S 2,805.88 3,305.73 2,735,40 3,683.58 2,550.79 4,743.53 17,058.82 2,5A3.36 1,352.94 Total $ 7,962.20 6,619.45 7,153.20 7,257.78 5,549.27 9,671.93 38,505.50 5,759.40 3,513.74 Credit Requested 262.75 748.00 1,681.00 338.51 6-57. ~9 962.64 7&2.96 520.03 $7,038.54 ~g~8 6bOOS
Page 7: 500498425
$. Adams D. Boyd W. James J. Oxee E. Stephens R. Taverna DFS
Page 8: 500498450
CONFIDENTIAL Decel~ger 3, 1976 DJ.stribution : R. F. Arfmann C. S. Baldwin, III R. H. Barker O. D. Barnhill F. J. Brannan C. W. Calary G. W. Chandler M. H. Crohn, Jr. R. H. Cundiff J. B. Dempster Arvel Dyer W. G. Enloe, .Jr. D. B. Fishel P. E. Galyan " R. N. Garner, Jr. J. B. Glenn G. E. Glover, Jr. R. V. ]{all W. P. Hanes August Heist E. L. Hicks '- R. C. Hill D. P. Johnson J. R. Martin S. G. Mason, Jr. J. W. McGrath R. B. Merrill T. E. Miller J. J. Murphy R. E. Neal ---T.-L. Ogburn, Jm. D. F. Pearson D. G. Samuel, Jr. J. H. Sherrill, Jr. \_wH: L. Speas, Jr. 11. Upchurch G. B. Whitaker L. A. Willson
Page 9: 500498451
Subject: CAMEL FILTER Box to be Discontinued in Selected Markets This is to advise you that we plan to discontinue CAMEL FILTER Box in the following markets: Des Moines Duluth Minneapol~s/St. Paul Houston Metro Corpus Christi We will continue our test markets in Sacramento and A~b~ny, New York, however. Per direction from Sales we will work current RJR inventory (3.7 week supply) through the pipeline in those markets where we are discontinuing the Brand, and we will not be picking product up. No additional CAMEL F/LTER Box product will be produced for discon- tinued markets. The elimination of all markets except Sacramento and Albany will reduce our average weekly sale from 124 cases/week to 73 cases/week. Manufacturing should reduce production accordingly. We appreciate everyone's help in coordinating this change and if there are any questions/problems, please advise. D. F. Edelschick DFE/pms
Page 10: 500498452
C. A. Tucker D. W. Grout A. H. Laurene Murray Senkus T. E. Sandefur, Jr. Ron Sustana Larry Wassong John Neal Keith Corlett Dan Murphy Margaret Daniel Betty Garner A1 Barnett Ron Beasley Larry Schreiber Ray Blevins T. J. Sullivan R. D. Sherrad R. E. Evans A. F. Cuccia H. E. Bass
Page 11: 500498672
Page 12: 500498673
Page 13: 500498674
Page 14: 500498675
Page 15: 500498676
Q3033N H3~V3S3~/Sd31S NOI~OV - WV3~ ~3WV~ 3HI 9NI3V~ SNOISI~BO ~orvk! - o Ol Xq3NIq $I $$3NI~ 3Hi NOIID3~IO BHi - IN3WNO~IAN3 3AIIII3dWO3.!SII ONV SS3NISQB - ]3WV3 3HI IQOBV MON~ ~AIlN3~Q3 3M IVHM -
Page 16: 500498677
Page 17: 500498678
CAMEL APRIL 1975 - APRI~ ~.977 NoN-FILTER DISTRIBUTION OF SMOKERS tu IL.IGHT " .. >" IHEAVY : MALE,~TOTAL) UNDER 35 35&'0VER X m FEMALE,(TOTAL) UNDER 35 35 & OVER ~ APRIL '76 ~PRIL '77 ~7,.3 28:~' 30,3 32,6 30,9 28~'3 40,2 40,6 41.4 87",'7 88~'4 85,5 21,8 19,6 18,5 65,9 68",'7 '67",'0 12,3 i],6 14,5 1,1 ,8 1,]. 11,3 ].0,8 13,3 ~ IIVHITE COLLAR 30.1 29','6 27.6 ~IBLUE COLLAR 48",'5 " 48.0 41.9 ~IOTHER 21",'4 22:,'4 30,4 UNDER $10,000 45,5 .44,1 32.8 $10,000 - $24,999 47.8 48,3 56,7 $25,000 & OVER 6.8 7,5 I0,4 SOURCE: NF0 3A WILLIAM ESTY COMPANY, INC. MARKETING INFORMATION CENTER
Page 18: 500498679
NoN-FILTER .APR I L 1975 CATEGORY - APRIL 1977 DISTRI~BUTION OF SMOKERS 0 ..-I ~ 0 x LIGHT AVERAGE HEAVY MALE~,(TOTAL) UNDER 35 35 AND OVER FEMALE~ (TOTAL) UNDER 35 35 AND OVER I*!H I TE COLLAR BLUE COLLAR OTHER AI~RIL 28;2 32,5 39,3 77,9 18,0 59,8 22,1 2,9 19,2 APRIL APRIL '77 29,3 3D,6 3.l ,9 3,q, 4 38,8 39,0 76,7 76:,'6 14,5 ]3,9 62~'2 62/7 2~;~'2 23,4 2,7 2,4 20",'7 2].,fl. 31,8 3.1.,'5 27,9 45~'7 45,4 41,0 22,'5 23,1 31,1 UNDER $10,000 44,6 $10,000 - $24,999 48",'1 $25,000 AND OVER T,'4 44~'6 36,4 ~8,~.~ 53",'4 7,1 .10,2 WILLIAM ESTY COMPANY, INC. ldARWETING INFORMATION CENTER
Page 19: 500498680
BASE C/~MEL. PEGULAR R, I~IoN-FILTER CATEGORY ~ OF UNIT VOLUME CHANGE APRIL 1975 - APRIL 1977 CAMEL REGULAR IIdN-FILTER CATEGORY % (37) (36) MEN (38) ~. (37) I~OMEN (35) " (33) VOL, (TOTAL) LIGHT (/41) (39) AVERAGE (/-I!I) (39) |IEAVY (3/4) (3/-I) AGE MEN 18-20 (69) (68) 21-24 (45) (51) 25-34 (41) (/47) 18-34 (TOTAL) (43) (48) 35-49 (/41) (36) 50 OVER (32) (31) 35 + 0VER(TOTAL) (36) (31) SOURCE: NFO 3C WILLIAM ESTY COMPANY, INC. CONSUMER RESEARCH
Page 20: 500498681
NU.N~EILTER CATEGORY %_ O_F..UN I T CHANGE APR ~ILIg/.Z BASE MEN WOMEN .VOLUME (TOTAl) LIGHT AVERAGE " HEAVY UNITS -3729q -30205 - 7090 - 4578 -11572 21145 (37) (33) (39) (39) (34) AC~ 18-20. .. - 425 (68) 21-24 - 685 (51) 25-34 -7837 (47) 18-34(TOTAL) -8947 (48) 35-49 -10823 (36) 50 & OVER -10502 (31) 35+ OVER(TOTAL)" u19522 (31) SOURCE: NFO 3D ~t WILLIAM ESTY COMPANY, INC.
Page 21: 500498682
CATEGORY_BY VOLUME MEN WOMEN VOLUME (TOTAL) LIGHT AVERAGE HEAVY 4175 79,2 20.8 11.2 28;7 60.1 4/76 85639 77,8 22,2 10.5 28,3 61.2 18-20 .6 .4 21-24 1,3 .5 25-34 16,0 13.3 18-34 (TOTAL) 17.9 14,2 35-49 29.2 28,4 50 & OVER 32.1 35.3 35 & OVER(TOTAL) 61.3 63.7 66795 78",'2 21,8 10,6 • 27.4 62,0 .3 1.0 13,2 14,5 29.3 34,3 66.3 SOURCE: NFO 3E WILLIAM ESTY COMPANY, INC.
Page 22: 500498683
CAIEEO_I].Y_BY vlJ L~LT.S. BASE MEN WOMEN VOLUME(TOTAL) LIGHT AVERAGE HEAVY :JZZ.5. ~176 104089 85639 82459 -- 66627 21651 19012 11658 29874 62558 8992 24236 52411 56795 ~223~i 14561 7080 18302 41413 18-20 21-24 25-34 18-34(TOTA~ 35-49 50 & OVER 35 & OVER(TOTAD 625 1353 16654 18632 30394 33413 65807 SOURCE: NFO WILLIAM ESTY COMPANY, IHC. 343 428 11390 12161 24321 3O231 54552 200 668 8817 9685 19571 22911 44285 3F " t
Page 23: 500498684
BASE MEN WOMEN VOL, (TOTAL) LIGHT " AVERAGE HEAVY AGE MEN" 18-20 21-24 25-34 18-34( TOTAL)'" 35-49 50 & OVER 35 & 0VER(TOTA_'~) CAMEL RIZGULAR ~ OF AP t77 -9.1.29 -.I.166 -1185 -3453 -5641,- (38) (35) (41) (44) (34) - ].52 (69) 288 (45) -2064 (41) "~50~" -~43)'" -3417 (41) -3209 (32) "-'6626 "(36) 'SOURCE! NF0 ~ 3G WILLIAM ESTY COMPANY, INC. CONSUMER RESEARCH I
Page 24: 500498685
BASE . MEN WOMEN VOLUME (TOTAL) LIGHT AVERAGE HEAVY AGE MEN 18-20 21-24 25-34 18-34 (TOTAL) 35-q9 ' 50 & OVER 35 & OVER (TOTAL) DISTRIBUTION OF CAMEL REGULAR VOLUME % 27571;-..~.. ~ 22115 88,0 89,4 ].2,0 10,6 17175 87,6 12','4 10','5 9',6 9,9 28,5 27,2 25,5 61,0 63,2 64,7. ,8 ,9 ,4 2,3 ,8 2,0 18,2 ].7,3 17,1 30,0 30,9 28,1 36",'7 39",'5 ~0,0 SOURCE: NFO 3H WILLIAM ESTY COMPANY, INC. CONSUMER RESEARCH
Page 25: 500498686
DISTRIBUTION OF CAMEL REG, VOLUME UNITS BASE MEN I~OMEN - VOLUME(TOTAL) LIGHT AVERAGE HEAVY _4175_ _4776 27571 22115 17275 24262 19771 15133 3308 2344 2142 2895 7858 ]6818 2123 1710 6015 4405 13977 11177 AGE MEN 18-20 21-24 25-34 "18-34 (TOTAL) 35-49 50 & OVER • 35 & OVER (TOTAL) 221 199 69 634 177 346 5018 ~826 .2954 5873 4202 3369 8271 6834 4854 10119 8735 6910. 18390 15569 11764 SOURCE: NFO ~ 3-I WlI.I.IA/~ ESI"Y COH.PANY, IN(:. CONSUMER ~ESEARCH
Page 26: 500498687
"~)NI "XN~'dWO~) Xl$~l S31VN ~39N~OA 01 - . '~ S~3~ONS 3N~IOA ~3[AV3B OL - -.9I.~IOI~3~1 SI S~317I~ 73WV3
Page 27: 500498688
# ,. A~RIJ.~7. 5_ __AI~.RI.k_.Z7. D.EEIfi RAi~ItLCS.L.1II.S.tRU~UII.QILD£jEI0KERSJ__CAI~E LAI LIER SMOK I NG LIGHT AVERAGE ! HF_AVY- VOLUME AP_J~._].9~ AP_RIL_]976 27.8 34.2 34.5 30.3 37,7 ~ 35,5 APRLL_197Z 29.7 27.2 43.1 }]ALE, (TOTAL) I_UNDER 35 3F & OVER FEMALE, (TOIALI._ UNDER 35 35 & OVER OCCUPATION WHITE COLLAR BLUE COLLAR OTHER 85.7 84.9 .. 86.9 • 38,'9 39','1 45",8 46.8 45.7 41.i '!4,3 15;1" 13,1 5.5' 5.3 4.9 8.8 9.8 8.2 30.6 31.3 48.3 47.7 21.1 21.0 26.2 46.2 27,6 !NCO~E UNDER $10,000 39.5 42.7 41.0 $10,000 - $24,999 53.2 49.4 51.1 $25,000 -& OVER 7.3 7,9 7.9 SOURCE: NFO APRIL '77, BOOK 10, TABLE 39 WILLIAA~, ESTY COMgANY, INC.
Page 28: 500498689
APRIL '75 - APRIL '77 PENETRATION OF 85t,'~M FFNM CATEGORY (INDEX) CAMEL FILTER NM L I GHT AVERAGE HEAVY X MALE(TOTAL,), UNDER 35 3S s OVER FEMALE (TOTAL), UNDER 35 35 & OVER iWHITE COLLAR IBLuE COLLAR IOTHER UNDER $i0,O00 $10,000-$24,999 $25,000 & OVER APRIL '75 A~RIL '7G APRIL '77 86 105 86 109 96 9! 105 99 121 126. 102 ]I]. ].]4 160 142 142 30 33 26 59 ~2 64 80 84 81 104 in2 ]01 136 133 127 104 108 117 98 93 94 95 107 73 SOURCE: NF0 4B WILLIAM ESTY COMPANY, INC. CONSUMER RESEARCH T
Page 29: 500498690
Page 30: 500498691
SMOKI NG VOILUME LIGHT 35.2 AVERAGE . 31,6 HEAVY " 33.2 34.9 36,4 30,5 29,3 . 34.3" SEX MALE, (TOTAL) 68.5 UNDER 35 51.4 35 & OVER 17.1 FEI'IALE; (TOTAL) 31.5 UNDER 35 22,7 35 & OVER 8~8 69,4 69.3 49,3 52.0 20.1 17.3 30.6 30.7 21,1 23,8 9.5 6.9 VIHITE COLLAR 43.1 I~LUE COLLAR 44,9 41.6 .33,7 46.5 48.4] OTHER 12,0 11.9 17,9 UNDER $10,000 35.6 36.3 34.3 $10,000- $24,999 .55.2 55.8 54.3 $25,000 & OVER 9,2 7.9 11,4 SOURCE: APRIL '77 NFO, BOOK 10, TABLE 65 WILLIAM ESTY COMPANY, INC. 5A
Page 31: 500498692
/~PRIL '75- APRIL '77 PENETRATION OF FULL FLAVOR ,~ION-MENTHOL CATEGORY (INDEX) MARLBORO NI'!FF (85MM) z ~: v ._l 0 0 ~-~. LIGHT AVERAGE HEAVY APR I L ' 75 APR I L ' 76 /~PRI L ?7 109 ]07 I06 100 97 99 92 97 96 X MALE, (TOTAL) UNDER 35 35 & OVER FEMALE, (To'EAL) UNDER 35 35 & OVER I'IH I TE COLLAR BLUE COLLAR UNDER $i0,000 $10,000-$24,999 $25,000 & OVER 1.02 135 59 96 125 103 3.53 130 62 60 94 99 !26 ]31 61 54 113 112 97 99 77 76 104 1.06 82 94 91 98 ]02 ]O5 10~ 119 I07 I06 SOURCE: NFO 5B WILLIAM ESTY COMPANY, INC. CONSUkiER RESEARCH
Page 32: 500498693
Page 33: 500498694
8P_IILAg . SBOKING VOLUME 1 LIGHT 32,4 32.7 34 :"4'l AVERAGE 31.7 31.5 HEAVY ~ 35.9 35.8 MALE,~(TOTAL) 67.3 67.4 29.8 .35.8 69 .0 ]_UNI}ER 35 38.1 35,2 40. I I 35 & OVER: 29.2 32.2 : 28.9 FEMALE; (TOTAL) 32.7 32.6 31.0 UNDER 35 18.1 16.8 18.2 35 & OVER 14,6 ..- 15.8 12.8 OCCUPATION WHIlE. COLLAR 38.1 37.3 32.4 BLUE COLI.~R 46.4 46.9 45.8 OTHER 15.5 15.8 21.8 UNt]ER $I0,000 38.0 39.7 34,9 ~;10,000 - 24,999 54.3 52.9 54.3. $25,000 & OVER 7.7 7.4 10.8 SOURCE: NFO APRIL '77, Book i0, TABLE 14 WILLIAM ESTY COMPANY, INC. 6A
Page 34: 500498695
Page 35: 500498696
AP_~ IL.19ZZ III~]T~.[B_ULLLON O_F__SM~E~ StrOKING VOLUME CAMEL MARLBORO NM FFF EJT.LIF.I~KIHG ~CAT, LIGHT 29,Z 56,4 34 4 • , ~:.~,\'. . m AVERAGE 27,2 29,3" 29,8 HEAVY ~ 34,13 135.8 SEX MALE, (TOTAL) 86.9 69,13 69.0 UNDER 55 45,8 52.0 q0.1 35 + OVER ~ 17,3 28,9 FEMALE,(TOTAL) 15,_ 1 ' 50,7 51.0 UNDER 55 4.9 25,8 18.2 35-+ OVER 8.2 6.9 12,8 WHITE COLLAR 26.2 33.7 BLUE COLLAR 46.2 48,4 OTHER 27,6 17.9 32.4 45,8 2!,8 UNDER $i0,000 ql. 0 34.3 $10,000- $24,999 51.i 54.3 $25,000 8 OVER 7.9 11,4 34,9 54,3 10.8 SOURCE: NFO WILLIAM ESTY COMPANY, INC. 7A
Page 36: 500498697
Page 37: 500498698
Page 38: 500498699
Page 39: 500498700
CALIEL_.EIL.'[EB,.2, AIXLB.QIIO_IU B O.I.N:I']E!~] HOL EF_B}}ILL.CAIEG_OJIY_ _ ~_O.F_.._UN I T VO.LIJIIE_CJ:IAB.GE APRIL_lgZS.--APJlILI£ZZ TOTAL CAMEL FFNM EI.LIEII MABLB.QIIO. 85MM CAT, (15) (18) (30) MEN WOMEN VOLU/~ LIGHT AVERAGE HEAVY (13) (17) (28) (20) (9) (24) (33) (24) (6~ (14) 18-20 (4O) (34) 21-24 +62 (6) • 25-34 18-34 (TOTAL) (4) (14) (1) (16) 35-49 (31) (9) 50 & OVER (13) (39) 35 & OVER(TOTAL) (22) (21) SOURCE: NFO WILLIAM ESTY COMPANY, IN(::. (21) ,,, (23) (23) (29) (27) (25) ..... (27) ii " (38) (32) 9A
Page 40: 500498701
UNJI. CHA_I~E A ~R IL_Igz~ '.L~_RtL_I92Z BASE MEN WOMEN VOLUME(TOTAL) LIGHT AVERAGE HEAVY 18-20 21-24 25-34 18-34 TOTAL.° 35-49 50 & OVER 35 & OVER(TOTAL) UNITS -1128 - 842 - 285 - 66 - 770 - 292 - 217 + 253 - 77 - 3i - 543 - Z69 - 812 SQURCE: NFO (15) (13) (28) (9) (33) (6) (4O) 62 (4) (1) (31) (13) "(22) 9B WILLIAM ESTY COA',PANY, INC.
Page 41: 500498702
DISTRIBUTION OF • CF VnLUME ~ BASE MEN WOMEN TOTAL VOLUME L I GHT AVERAGE HEAVY AGE MEN 18-20 21'24 25-34 ]8-34 (TOTAL) 35-49 50 & OVER 35 & OVER "(TOTAL) ;4/75 :~7646 86,8 13',2 9,9 30",'7 59,4 7,1 5,6 24",'7 22,7 26,7 i:6495. ~86~,'4 .13;'6 28,2 57,'8 6,9 25,3 19,5 29,5 ~5!8 88 ,9 11",'1 10,6 24,2 65,-2 5,0 10,6 27,8 43,4 18,3 27,2 45,5 SOURCE: NFO 9C WILLIAM ESTY COMPANY, INC. CONSUMER RESEARCH
Page 42: 500498703
DISTRIBUTION OF CF VOLUME UNITS BASE MEN WOMEN VOLUME (TOTAL) "4/75 _ 4i16 _ 4177 7646 :;6495 6518 6637 5612 5795 1009 883 724 LIGHT 757 916 691 AVERAGE 2347 1832 1577 HEAVY 4542 3754 4250 AGE MEN 18-20 543 338 21'2~ 428 448 25L34 1889 1643 ~8-3 (TOTAL) 2~GO 2429 35-49 1736 1267 50 & OVER 2042 ].916 35 & OVER (TOTAL) 3778 3183 326 691 1812 2829 1193 1773 2966. SOURCE:NFO 9D WILLIAM ESTY COMPANY, IN(;. CONSUMER RES£ARCH
Page 43: 500498704
~AIILBuRO_ FFNM 85.1]I~ ]~ OF UNI]'__C, BABBE APRIL 1975; APRIL 1977 BASE MEN WOMEN VOLUME (TOTAL) UN I TS -13013 - 8744 --.4269 LIGHT - 2597 AVERAGE - 5213 HEAVY - 5262 18-20 - 2278 21-24 - 546 25-34 - 3109 18-34 (TOTAL) - 5933 35-49 - 631 50 & OVER - 2311 35 & (~VER (TO'iAL) - 2942 SOURCEI NFO % (18) (17) (20) (24) "(24) (14) (34) (6) (14) '(16) (9) (39) (21) WILLIAM ESTY COMPANY, INC. 9E
Page 44: 500498705
MARLBORO FFNM 85FIM DISTI~IBUTIt)N BY VOLUME BASE MEN WOMEN VOLUME (TOTAL) L ] GHT AVERAGE HEAVY ' MEN 18-20 21-24 25-34 18-34 (TOTAL) 35-49 50..& OVER 35 & OVER SOURCE: NFO (TOTAL) 71626 70,8 29,1 56159 71.8 28,1 15','0 30,6 54,4 14,2 29.4 56",'3 8,5 12,'3 30,2 5ITO 11,6 • 8,3 191"9 7,8 10,8 30.0 48:'6 13,9 9,4 "'23 WILLIAM ESTY CO~A, PANY, INC. CONSUMER RESEARCH 58613 71,6 28,4 13,9 28,5 57,5 6,5 14 ,].. 31,6 "52,2 13,1 6,2 19,3 9F
Page 45: 500498706
MARLBORO FFNM 85 MM DISTRIBUTION BY VOLUME UNITS "'4175 4176 BASE 71626 56]59 MEN 50711 40322 WOMEN 209]5 15837 VOLUME(TOTAL) LIGHT AVERAGE HEAVY MEN .18-20 21-24 25-34 18-34(TOTAL)' 35-49 50 & OVER 35 & OVER (TOTAL) 10744 7975 21918 16511 38965 31618 6088 438n 8810 6065 2163L 16848 36529 27293 8309 7806 5945 5279 14254 13085 SOURCE: NFO ~ 9G WILLIAM ESTY COMPANY, INC. CONSUklER RESEARCH "'4/77 586]3 41967 ].6646 8147 16705 33703 38]0 8264 1.8522 3O596 7678 3634 113].2
Page 46: 500498707
~BB_8..519M_ CAIEG..OI~ % OF UNIT CHANGE APRIL 1975 - APRIL 1977 BASE MEN WOMEN VOLUME (T~.TA[) LIGHT AVERAGE HEAVY 18-20 21-24" 25-34 18-34 (TOTAl.) 35-49 50 & OVER 35 & OVER (TOTAL) SOURCE: NFO UNITS 62635 31209 14575 6280 20096 343~6 330U 1441 19076 9827 12273 22100 WILLIAM ESTY COMPANY, INC. (30) (21) (23) (23) (33) (29) (34) (10) (27) (25) (27) (38) (32---Z) ~ 9H
Page 47: 500498708
FFNB_.8.5~F1 I~.F._G.OJ~ D.ISTRIBUI ION OF V~.LUJ~ ~ ~/.76 BASE " 20981~ 164030 4/77 147179 MEN 69,6 70,0 71,0 WOMEN 30.4 3U, 0 29.0 _V_OLUME"(TOTAL) LIGHT 13,0 12,8 AVERAGE 29,5 29,6 HEAVY 5/,5 57,6 AEE_~ 18-20 4,7 4,0 21-24 7.0 6,1 25-34 25,1 24,4 18-34(TOTAL) 36~18 3~. 35-49 17.1 18,4 50 & OVER 15,6 17,1 35 & UVER (TDTAL) 32;7 35~5 SOURCE:. NFO .13,0 28.,4 58,6 4,2 9,0 26,3 3g,5_ 17.7 13,9 31,6 91 WILLIAM ESTY COMPANY, INC.
Page 48: 500498709
FFNB 8 5~ O_P~Y. I)_I_,S.T_~UTIQN OF BASE 4/75 ;~76! 4177 209814 164030 147179 MEN WOMEN .VOLOME'[TI~T~L) LIGHT AVERAGE HEAVY 146030 114821 10497 63784 49209 42682 27276 20996 61895 q8553 120643 . . 94481 19133 41799 86247 18-20 9861 6561 6182 21-24 14687. 10006 13246 25-34 52663 40023 38708 18-34 (TOTAL) .'77212 $6590 --$8136 35-49 35878 30182 50 & OVER 32731 28049 35 & OVER (TOTAL) 68609 582~I 26051 2O458 .46509 SOURCE: NFO 9J WILLIAM ESTY COMPANY, INC.
Page 49: 500498710
Page 50: 500498711
_FULL FLAVOR, NON'I']EIITHO.L..CATE.G_OR~ TREND_S OF. CIGARETTE_S~ITCHING CATEGORY NET CHANGE. CAMELFILTER 195. 19_Z.6 19ZZ _ IVIARLB.OEO FFNM " 19Z5. 1976 19ZZ 0 3,2 0 2.0 1,9 (0.3) WINSTON MARLBORO 1,0 (1.4) 3.5 i,i 0.4 1,4 FFNB -- (2,7) (1,2) BENSO~ & HEDGES TOT.-- 0,5 (1.2) (0.2) 0 0,3 CAMEL TOTAL ....... (0.2) (0,3) 0;i SOURCE: NFO IOA WILLIAM ESTY COMPANY, INC.
Page 51: 500498712
CA[.iEL F I LTERS SOURCEOF GAINS & LOSSES: CIGAI~ETTE SWITCHING FFNM £85~) DEMOGRAPHICS NET STOPPED NEW BASE ~ SMOKII.IG ~ ~ ~5 (.14.1) (28,2) - 9.4 (16.4) UNDER ~- ~5-YRS. OVER (6.5) (18.5) SOURCE: 791 (12.8) (17.3)- ~,i (12.~) NFO (13.6) (13,1) " (12.2) 10B WILLIAM ESTY COMPANY, INC.
Page 52: 500498713
Page 53: 500498714
EALL_'74 - '76 HID_-FLAVOR CATEGORY; _IREB])$ OF CJ_GAIIEIIE_EkU_ZCHING CATEGORY CAMEL.EILIEIL.__ .MARLBORO FFNrl_. 1975 !976 19.ZZ. °I.9Z5- 19Z6. 1977 1,0 (0,9) 2:4 0,1 0,6 0,3 1,0 .... 0 0,2 0 0,5 2,4 0,2 0,1 0,3 O,l, SOURCE: NFO V~ILLIADA ESTY COMPANY, II'~IC. 11A
Page 54: 500498715
Page 55: 500498716
EA~LL-'7G B I-F ] ~ I;,A.II'~_OP, Y.' 1REL~D_,S_Q.F C~III~ SI~I TCH I N~ CATEGORY V~RLDORO LIGHTS _ CAI~.L_E.ILT_ER 19./_6. 19/Z (4,2) (3,6) 1,2 (i,0) 0,5 . I']ARLBOR.~]~I___- 1975 L~76 19ZZ (1,3) (4,8) (3,0) (0,4) (1,1) (0,9)' WINSTON LIGHTS ~VA' 0 0 (O,Y) (1,4) (0,1) (0.3) (0,1) (1.8) (1,0) 1,2 (0,3) "(0.9) 0,1. KENT GOLDEN LIGHTS _ -- SOURCE: NFO (0.3) WILLIAM ESTY COMPANY, INC. 12A
Page 56: 500498717
Page 57: 500498718
Page 58: 500498719
Page 59: 500498720
Page 60: 500498721
'3111 "ANVdW03 A£$| WVIllltA, lii7vn~ ~BiiB~ - ~o^v-~. ~ow - INBWLOPN~ 9NI~OWS B~O~ - ''"gNIQIAO~d dO SW~3l NI "-qAIIISOd
Page 61: 500498722
CAMEL FILTER CCS SUMMARY PRODUCT IMA(~ES SMOKING ENJOYMENT ~ORE AME LESS TOTAL MALES MALES UNDER 35 6174 i177 6/.74 1/77 25~J 19 25 6~ 10 MALES 35 6/74 1/77 18 28 AMOUNT OF FLAVOR MORE SAME LESS 1 3.3 41 • 37 '41 33 16 16: 17 22 28 35 42 42 15 10 ,TAR AND NICOTINE "LEVELS MORE SAME LESS 25 29 29 35 20 24 49 42 46 41 53 43 12 12 13 15 i]. i0 QUALITY OF CIGARETTE BETTEB 28 37 SAME 55 46 POORER 9 5 25 29 ii 22 2] 58 54 61 63 12 8 !4 ].]. WILLIAM ESTY.CO/~APANY, INC. CONSUMER R~SEARCH
Page 62: 500498723
Page 63: 500498724
Page 64: 500498725
10/75 11/75 2/6 3/76 3/76 5/76 5/76 6/77 AD pLAYBACK "CAFE" "TREASURE HU:~T" "GO" "APPLE FARM "BEACIi HOUSE" "GOLD PA~ING" ~OCEANOGRAPHER" RECALL " TOT, 35~ . 35+ 37 36 38 30 31 29 24 75 22 27 75 29 25 22 29 31 35 27 23 ~ 21 ONE OR "VAIl" (i~w FORMAT) 25 31 18 33 24 17 2O 23 27 19 22 ONE OR MORE VI SOAL ELE{',EI-ITS 37 " 30 24 27 25 31 23 6/77 "BEACH" (NE~v FORMAT)~~! 24 2a 19 24 CAMEL AVERAGE 27 28 Pc4 NORM 21 20 26 23 27 i 22 16 2O I 17A
Page 65: 500498726
Page 66: 500498727
Page 67: 500498728
Page 68: 500498729
Page 69: 500498730
Page 70: 500498731
":)HI "~H~'clW03 /,,I,$~! W'g'l't'tI,A& 0~, 6L, ~L, LL, OT O~ • . .-.SNOI771W) • .In n~q'>4nq " -'tn T'I q~lrt~wA 09 $9
Page 71: 500498732
(HUNDRED THOUSANDS) TOTAL ALL AGES TOTAL MALE TOTAL FEMALE TOTAL WHITE TOTAL BLACK/0THER TOTAL 18-20 21-24 25-34 35-49 50 - OVER POP ATIn~! . U~.. .... ,, PROJECTIO~IS: BUREAU ~F.CE~ISUS . (JULY .'77 SERIES I I) 77"' 7g ..... c; . 7.. 80 .~ 82 83 84 -~5,, ~ 87__ 2167 2184 2202 2221 2242 2263 2285 2306 2329 2351 2372 1056 1064 1073 lq82 1.092 11.n2 1112 1123 1134 11~i4 1155 1110 1119 1129 1139 1150.1161 1172 1184 1195 ].206 1218 3.877 1889 1902 1916 1930 1946 1962 :1978 1995 2911 2027 290 295 300 306 311 317 " 322 328 334 340 346 129 129 .129 129 128 126 123 119 114 110 108 157 16,l. 16a 1~6 167 168 167 167 165 161 156 331. 339 35fl 356 375 379 385 392 399 405 350 357 3~3 ~368 373 389 402 416 429 443 ~58 557 564 571 578 583~ .... 589 592 596. 600 604 608 21B
Page 72: 500498733
POPULATION PROJECTIONS: BUREAU OF CENSUS (JULY '77 SERIES II) C77, .C.Z.9. LB.I.. "83_ '85 '87 [HUNDRED THOUSANDS) TOTAL ALL AGES 2167 2202 18-24 144 147 25-34 165 174 35-49 171 177 50 & OVER 249 265 2242 2285 2329 237"2 149 146 140 133 186 192 198 203 182 197 210 224 260 264 267' 270 18-24- 142 145 147 144 138 131 25-34 167 176 188 194 200 205 35-49 . 179 1B6 191 206 219 234 50 & OVER 308 316 323 .128 333 338 21C EEL@ 6~00S WILLIAM ESTY COMPANY, INC.
Page 73: 500498734
LA ~ c~ ~ 0 I I I oO o
Page 74: 500498735
'3N! "~,NVdW03 ,/L.I.S~I WVIlllM ']ZIS 1~!3H~3 Sll 3^0~V"%~ 'L86I 18 SNOI771@I 8'Oh 3HI MOHS IlIM dflOH9 39V ClO ~V3L b~-5~ 3HI
Page 75: 500498736
Page 76: 500498737
Page 77: 500498738
Page 78: 500498739
Page 79: 500498740
Page 80: 500498741
POPULATIUN PROJECTIONS: BUREAU OF THE CENSUS (JULY '77 SERIES II) % OF GAINOR (LOSS) 1977-1987 (HUNDRED THOUSANDS) TOTAL ALL AGES MALE 18-24 25-34 35-49 50 & OVER. 2167 2372. 9,5 18-24 25-34 35-49 50 & OVER 144 133 (7,6) 165 203 23,0 171 224 31,0 249. 270 8,4 142 131 (7,8) 167 205 22.8 179 234 30,7 308 338 9,7 WILLIAM ESTY COMPANY, iNC. 24B
Page 81: 500498742
POPULATION PROJECTIONS: BUREAU OF TOTAL P.nPULA ,,,,. .... OF CENSUS (JULY '77 SERIES II) TOTAL ALL AGES (HUNDRED THOUSANDS) TOTAL MALE TOTAL FEMALE TOTAL WHITE TOTAL BLACK/0THER TOTAL 18-20 21-24 25-34 35-49 50 ~ OVER 77"_ 1 78~ "'79' .i~0/_ 8i -:~?,_. 83 84 85 8.6 2167 49 51 87 13 O6 07 15 16 26 2184 2202 222122.42 .2263' 2285 49,8 48,'748",'7 48,7 48,7 48,7 51,2 51,3 51,351,3 51,3 51,3 86,5 86,3 .R6','3 86,1 86 85,9 13,5 13,6 13",'8 13,9~14 14.1 5,9 5:9 ..5','8" 5:7 5:'~ 5:'~ 7,3 7,5 7','5 7,5 7,4 7,3 15,5 15,9 ]6 16,7 ]6,8 16,9 16.3 16,5 1.6,6 16,6 ],7,2 17,6 25,8 25,9 26 26 26 25..°.. 230~ 2329 2351 48,7 48,.7 48,7 51,3 51,2 51,3 85.8 85,7 85,5 14.2-14.3 14.5 5,2 4.9 4,7 7,2 7,1 6,9 17 ]7,1 17,2 18 18.4 18,8 25.8 25,8 25.7 _87 2372 48,7 51.3 85.5 14,6 4,6 6,6 17.2 19.3 25.6 ~L@ 6bO0~ 24C
Page 82: 500498743
Page 83: 500498744
33,0 32,0 31,0 30.0 29.0 .28.0 27.0 26.0 SMOKING INCIDENCE PROJECTIONS (R JR PROJECTIONS) TOTAL SI:IOKERS- " 25.0 '77 '79 YEAR '81 '83 '85 '87 WILLIAM ES.TY COMPANY, INC. 25h
Page 84: 500498745
Page 85: 500498746
MALES 18-20. 21-24 ' .I 25-3.4 UNDER 35 .~_I~1~ B_P_0.EU.LATI~I I 0NS -1~ (MILLIONS) 2,35 1.88 • 3,24 2.82 .7,25 6,91 12,84 11.61. 35-49 8,04 50+ 7,57 35+ 15.61 7,35 6.68 14,03 -20 -13 -10 -9 -12 -10 18-20 2.10 21-24 2.66 25-34 5.92 2.17 + 3 2.87 + 8 6.03 + 2 UNDER 35 10,68 11.07 + 4 35-49 6.54 ~,62 + 1 50+ 6,06 5.70 - 6 35+ 12,60 12.32 - 2 WILLIAM ESTY COMPANY, INC. 26A
Page 86: 500498747
L~L~ , 6t~O05 . i i "1 i
Page 87: 500498748
18-20 -20 -22 -38 21-24 -13 ~18 -29 25-34 - 5 - 4 - 9 18-~4 (TOTAL) ~i0 ':11 :19 .35-49 - 9 + 6 - 3 50+ -12 - 9 -20 35 & OVER(TOTAL~ -10 "'1 -11 FEMAL~ 18-20 ÷ 3 -14 21-24 " + 8 - 1 25-34 + 2 - 5 18=34 (TOTAL) + 4 -'"7 -11 -11 -3 -4 35-49 + 1 + 4 + 5 50+ -6 -13 -18 35+ B OVER -" 2 '-4 - 6 26C WILLIAM ESTY COMPANY, INC.
Page 88: 500498749
BBDKIN~ (HILLIONS) 18-20 2,35 1,88 1,46 21-24 3,24 2,82 2,31 ~5-34 7,25 6,91 6,62 18-34 (TOTAL) 12,84 11,61 10,39 35-49 8,04 7,35 7.80 50+ 7,57 6,68 6.09 .35+ & 0VER(TOTAL)15.61 14.03 13.89 18-20 2,10 2.17 1.86 21-24 2.66 2,87 2,68 • 25-34 5.92 6,03 5.75 18-34 (TOTAL) 10.68 11.07 10.29 35-49 6.54 6,62 6.85 50+ 6,06 5.70 4,99 35+& OVER (TOTAL)12.60 12.32 11,84 "1975 SMOKING INCIDENCE AGAINST 1977 POPULATION PROJECTIONS, SOURCE: RJR MRD & BUREAU OF CENSUS JULY '77 WILLIAM ESTY COMPANY, INC. (SERIES II) 26D
Page 89: 500498750
Page 90: 500498751
18'20 21-24 25-34 UNDF.R 35 POP_U.LAT I ON_ PROJEC] 1D.I~.S (MILLIONS) 1,88 1.46 2.82 2.31 6.91 6,62 11;61 10.39 35-49 7.35 7.80 • 50+ 6.68 6,09 35+ 14.03 : 13.89 -22 -18 -4 -11 18-20 " 2,17 1,86 -14 21-24 2,87 2,68 - 7 25-34 6,03 5,75 - 5 UNDER 35 11,07 10,29 - 7 I ~ 35-49 6,62 6.85 50+ 5.70 4,99 35+ 12.32 11.84 WILLIAM ESTY COMPANY, INC. +41 -13 ~ ".,, -4 27A
Page 91: 500498752
Page 92: 500498753
SHARE OF MARKET (PERCE[~AGES)_ ' 77 ' 79 ' 81 ' 83 ' 85 ' 86 28A WILLIAM ESTY COMPANY, INC.
Page 93: 500498754
SHARE OF MARKET (PERCENTAGES) '17 '?___.B.8 "~9 ;8t] "81 '82 '8~ '84 '85 '86 '_8 FULL FLAVOR FILTER, ~ON-MENTHOL (85MM) 26,9 25",'i 23",'6 22.1 21,'i 19~7 18,6 17,5 16,6 15,6 HI-FI NON-MENTHOL (85MM) 12.8 15.7 18",'0 20,0 21.7". 23,4 24,5 25.8 26,8 27,9 28 (SOURCE: RJRSOM PROJECTIONS) 28B
Page 94: 500498755
SHARE OF MARKET (PERCENTAGES '77 '78 '79 FULL FC~VOR FILTER 57,3. 53,3 ~50,9 '80 LBI '82 '83 48,5 46,8 . 44.2 42,4 '4 '84 '85 '86 'SZ 40,8 39,3 37,5 36,2 ~ID-FLAVOR FILTER 10.2 9,1 HIGH FILTRATIOii 22.1 28,3. 7,9 7,3 6,6 5,6 5,4 33,1 3Z,O 40,2 44,4 47,2 5,0 4,6 4,5 4,5 49,6 52,1 54,4 56,1 MENTBOL FILTER 28,6 29,5 NON-FILTER I0,4 9,3 30,6 31,4 31,5 32,1 32,8 8.1 7.2 6.4 5?8 5.0 SOURCE: RJR SOM PROJECTIONS 33,2 3~,7 34,4 34.5 4.6 4.0 3.6 3.2 W~LLIAM ESTY COMPANY, INC. 28D
Page 95: 500498756
SHARE OF MARKET (PERCENTAGES '77. '78 '79 '80 '81 '82 '83 FULL FLc~VOR FILTER 57,3. 53,350,9 48,5 46,8 44,2 42,4 40,8 '85 '86 LB7_ 39,3 37.5 36.2 i.IID-FLAVOR FILTER 10,2 9,1 7,9 7,3 6,6 5,6 5,4 5,0 4,6 4,5 4,5 HIG~.I FILTRATIO[i 22,1 28,3. 33,1 37,0 40,2 44,4 47,2 49,6 52,1 5q,4 56,1 MENTHOL FILTER 28,6 29,5 30,6 31,4 NON-FILTER 10,4 9,3 8,1 7,2 31,5 32,1 6.4 5?8 32,8 33,2 3.~,7 34,4 34.5 5.0 4,6 4,0 3.6 3.2 SOURCE: RJR S0M PROJECTIONS WILLIAM ESTY COMPANY, INC. 9~LI~ 6U005 28D
Page 96: 500498757
Page 97: 500498758
Page 98: 500498759
Page 99: 500498760
CAMF.L F] LTER CCS SUMMARY SMOKER IMAGES TOTAL _M~LES °:MALES"35- BASE - MALES HEARD OF CAMEL FILTER ~177 1/_7~ 1/77 257 r~ 401 138 200 119 200 ~GE YOUNG 23,7 19,7 23,9 18",'323','5 2],3 IDDLE AGED 51,0 50,4 52,9 48,4 48,7 52,2 OLD 19,8 22,7 20,3 25,3 19,3 20,2 SEXMALE FEMALE BOTH 90,7 56,3 76,0 4,1 3,4 13,] 5,2 34,5 10,9 64.683,671,7 2.3 8,5 1,4 32",'3 7,9 26.1 IDEAS- MODERN 56,4 52,1 55,1 47,3 OLD FASHIONED 35,0 39,2 37,0 42,0 BOTH 5,8 8,8 5,1 10,6 0CCUPATION-FACTORY 54,1 54,7 60.,.1 64,2 0FF~CE WO~KER 28,8 28,6 29.,.0 20,9 BOTH 13,6 16,8 7,2 15,0 CITY SIzE-LARGE 5].,4 48,! 48,6 48,1 SMALL 33,1 37,0 39','1 39,2 BOTH 10,1 14,9 8,0 12,7 31A WILLIAM ESTY COMPANY, INC. CONSUMER R£$EARCH 58,0 56,8 32,8 36,4 6,7 6,8 47,1 44,3 28,6 36,9 21~O ].8,8 54,6 47,7 26,1 34,9 12',6 1.7,4
Page 100: 500498761
Page 101: 500498762
ilE~:IO_GRAPH I CS, D ISJ_~.IBU_tLO_[~_.O.F_.S,"IOKERS, L I'~M H I-F I__.(I15~ A. RI.L_lgZ6 AP- SMOKI NG VOLUME LIGHT 34.5 33.4 34.1 AVERAGE 29.0 28.7 27.9 HEAVY 36.5 31.9 38.0 46.9 46.8 MALE, (TOTAL) UNDER 35 35 & OVER FEMALE, (TOTAL) 16.9 16.2 30.0 30,6 53.1 53.2 20.5 : 18.9 32.6 3,4.3 48.4 19.1 29.3 51.6 UNDER 35 20,3 35 & OVER 31.3 O_CCUPAT I ON WHITE. COLLAR 53.4 51.3 47L3 BLUE .COLLAR 31.4 32.8 32.1 OTHER 15.0 15.9 20.6 UNDER $10,000 29.2 30.1 23,0 $10,000 -- $24,999 58.0 56.2 58:'5 $25,000 & OVER 12.8 12.7 18.5 TOIAL (000) 3,143 3,G63 4,107 SOURCE: APRIL '77 NFO, BOOK 10, fABLE 32 32A WILLIAM ESTY COMPANY, INC.
Page 102: 500498763
Page 103: 500498764
~].S.IJll]~.U.IJ.OB_@_.$~IOJ~EB.S_~,i.)_III-_J!] _~J]A ID$..I..~IT.I].[L..19ZZ SMOKING VOLUME LIGHT AVERAGE. HEAVY MARLBORO WINSTON KENT GOLDEN _LI(~.H_I_,S_ ._LIGHTS ~J~LI ~BJA.G_F. __LI.6HTS _ 37.8 34.3 35,4 32.7 35,7 27,6 32.4 25,2 26,1 29,8 34.6 33,3 34.4 41.2 34,5 MALE, (TOTAL) UNDER 35 35 & OVER FEMALE, (TOTAL) UNDER 35 35 & OVER 54.4 53.3 57 4O.3 25.3 27 14:1 28,~ 29 45.6 46.7 42 32.1 24,0... 21 13,5 22,7 21 ,3 50.7 .4 20,2 ,9 30.5 ,7 49,3 " .6 20,6 .1 28.7 41,9 9.9 32,0 58.1 16,0 42,1 OCCUPATION WHITE COLLAR BLUE COLLAR OTHER UNDER $i0,000 $i0,000 - 24,999 $25,000 & OVER 49,8 36.4 58,1 43,9 53.7 36.9 46,3 27,7 31.6 26.7 13.3 17.3 14,2 24.5 19,6 25.1 28,0 19,1 " 61,8 59,5 56.4 13,1 12.5 24.4 25.7 I ,9 58,2 64.4 16.1 17,6 SOURCE: NFO WILLIA/~', ESYY CO/~PANY, IHC. 33A
Page 104: 500498765
MARLBORO WINSTON KF_NT GOLDEN _I.I_GIIIB_ _L]_GIII~ ~]F.~J[I ~ LIGHTS .... SMOKING VOLUME LIGHT 111 101 104 96 105 AVERAGE 99 116• 90 94 107 HEAVY 91 8.8 104 108 91 MALE, ~OTAD 112 110 UNDER 35 211. 132 35 & OVER 48 96 FEMALE , (TOTAL) 88 91 • UNDER 35 158 118 35 & OVER 43 7~ 118 105 87 143 106 52 102 104 110 83 96" 113 106 101 79 68 92 135 OCCUPATION WHITE COLLAR 105 77 123 93 BLUE COLLAR 115 144 85 98 OTHER 65 84 69 119 UNDER $10,000 109 122 83 $10,000 -. $24,999 131 80 76 $25,000 & OVER 71 68 132 114 83 95 112 -78 69 87 81 95 SOURCE:NFO 33B WILLIAA~ ESTY COMPANY, INC.
Page 105: 500498766
Page 106: 500498767
~ASE TOTAL GAIN (Loss) NEH SMOKERS .STOPPED SMOKING SOURCE OF GAINS & (LossES) MARLBORO LIGHTS & WINSTON LIGHTS APRIL 1975 - APRIL 1975 MARLBORO LIGQTS I'IINSTON LIGHTS 85 224 100 &1 250 141 4,7 3,1 (5,0) 37,7 6,8 22,7 FULL FLAVOR FILTER 5,9 12~'] ]2,1 34,h 21,2 31,9 WINSTON FILTER _I,2 1.8 2,0 31,1 18.0 24,8 MARL.BORO FILTER I 8,2~ 8,9 7,0 ] !, 6. 2",'8 2, ] MID-FLAVOR. FILTER 2,2 i,0 (6,6) i,'2 2,8 HI-FI 2','4 (8,5) (8",'0) 11,5 (8,4) (12,1) MENTHOL TOTAL (4,7) I, 3. -- 4,9 (1,2) 4,3 FULL FLAVOR (1,2) 2,2 2','0 41,19 (2,0) 4,3 MID-FLAVOR (I,2) .... (] ,6) .... HI-FI (2,4) (,9) (2",'0 1,6 ,8 -- 34A WILLIAM ESTY COMPANY', INC. CONSUMER RE$1~ARC~H
Page 107: 500498768
Page 108: 500498769
Page 109: 500498770
Page 110: 500498771
FFNM CATEGORY. NET CH~NGE~ WINSTON KING MARLBORO KING, B&H CAMEL FILTER ,~V~ITCHING SOURCE OF GAINS & (LosSES) MARLBORO LIGHTS ~, FFNM CATEGORY APR I L APR I L APR I L 1975- 1976 1977 5,9 12,1"" "-12,0 1,2 2,'2 2,0 4','7 .. 10,3 7,0 (3,5) (,4) !,'0 1,2 (,4) -- ~ OF CATEGORY GAIN Art,to ..MARLBORO FILTER 139% 74% 58% BASE TOTAL TOTAL GAIN (Loss) MALE FEMALE UNDER 35 OVER 35 85 224 Source: NFO WILLIAM ESTY COMPANY, INC. CONSUMER RESEARCH I00 (5,0) (!2,8) 4,0 (].4,0) .34E
Page 111: 500498772
Page 112: 500498773
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TRF.I~D - NE~ ,~!,IOKERS GAINED % CATEGORV % OF TOTAL~MOKERS TOTAL SMOKERS MALES % GAIN ~ OF TOTAL SMOKERS FEMALES % GAIN ~ OF TOTAL SMOKERS FFNM 85MM CAT, % GAIN OF. TOTAL SMOKERS APRIL""75 AF~IL '76 AFRIL '77 ]0",871 24,7,3 9;938 7.,2 6,'3 7,1. 3,83 3,33 3,68 6.5 '5.7 5.5 3,04 2,69 2,65 6,'4 6,2 6,6 1,7 1,57 ] ,46 H~-F~ N,M: 85MM Cat, % GAIN % OF TOTAL SMOKERS 7 ,5 8,7 6','6 ,07 ",'81 ,88 18-24 % GAIN % OF TOTAL SMOKERS 25-34 % GAIN % OF TOTAL SMOKERS 35-49 % GAIN ~ OF TOTAL SMOKERS 50% + % GAIN %.OF TOTAL SMOKERS 12,8 11,6 12,6 1,'3 1,o+q 1.1 "" 7.3 6,6 6,4 1,2 1,8 1,36 51,LO 41,17 5","5 1,45 1,38 1.79 6','3 5",'i 5".'6 2,12 1,73 2,!0 35A WILLIAM ESTY COMPANY, INC. CONSUMER RESEARCH
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SMOKERS GAINED APRIL 1975 - APRIL 1977 MALES BASE % New % SWITCHED FEMALES BASE % SWITCHED 5782 13082 5148 7~'2 6,3 7,'i 14,8 17~'8 22,5 5089 1166] 4790 6.5 5~'7 5",'5 14,'i19,6 25,6 AGI8E _ 24 BASE 1].02 2323 868 • ~ NEW 12,8 11,6 12, 6 ~ SWITCHED "-' 20,2 23,4 33,9 25-34 BASE 2968 6733 2].11 % NEW 7,3 6,6 6,4 % SWITCHED 12,8 17,6 23,0 35-50 BASE 3'1457259" 3326 % SWITCHED 13, 1 ,0 21,9 51 + BASE 3656 8372 3733 % NEW 6",3 5,1 5','6 % SWITCHED 14,'919',6 24,0 *SWITCHING FIGURES INCLUDE WITHIN..CA~EGORY SWITCHES AND ARE . NOT COMPARABLE TO PREVIOUS YEARS, SOURCE: NF0 35B WILLIAM ESTY COMPANY, INC, COt~SUMER RESEARCH
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February 16, 1978 INDIVIDOAL COPIES TO: R. F. Arfmann C. C. Banks R. H. Barker R. V. Hall W. P. Hanes. K. B. Hedrick A. Heist Brenda Smelcer D. L. Westrick J. McKennau~ Re : S. G. Mason G. A. Mason B. Swaine P. R. Watson J. T. Weller G. B. Whitaker J. Dempster C. S.,Baldwin D. G. Samuels, Jr. CAMEL Filter Pop-Up Coupon Promotion This is to advise you that 30.1 million $i.00 Off Carton Pop-up Coupons will be inserted in a total of 2~' magazines scheduled for insertions per attachment. Also attached you will find a list of the publications and circulation of each. To insure the success of the program, the following is requested of your department: Sales To notify the Sales Force of the coupon program by DM letter. (Publication, circulation and issue date are attached.) To distribute sample copies of the CAMEL Filter Pop-up Coupon to the Sales Force (25 per division) for presentation purposes to load the trade and prevent out of stocks from occurring• (To be provided by April, .1978.) To request Field Sales Force insure adequate stock levels and maintain maximum distribution of CAMEL Filters during the pop-up coupon drop. To distribute "pre-booking form" to advise retail cigarette accounts of coupon program in their local markets. Objective is to make coupon program more effective at retail level.
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CA~EL Filter Pop-Up Coupon Promotion February 16, 1978 Page T~o Manufacturinq To in~~ure that p~-oduction and inventory of CAMI~L Filter is maintained in order to meet anticipated sales increases fol.lowing coupon redemptions. (July-August) To ":-~.uovide 200 million additional cigarettes, according to Traffic Department's timetables. Traffic i. To insure that additional product is available in public warehouses nationally during the weeks of April 17 - June 30. To insure inventory levels of CAMEL Filter are adequate to meet both normal movement and additional product requirements nationally estimated at 30 million units, spread heavily in May and tapering off in June. If you have any questions concerning this promotion, please advise. S. H. Klein SHK:pm Attachments
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Car Craft Car and Driver Crawdaddy Custom Bike Cycle Cycle World Esquire Field & Stream Guns & Ammo Hot Rod Mechanix Illustrated Motor Trend National Lampoon Oui Outdoor Life Penthouse Playboy Popular Mechanics Popular Science Road and Track Sport Sports Afield Sports Illustrated CA~,~L FJ iter Pop-Up Coupon Circulation (000) 300 725 150 135 450 300 900 2,000 425 800 1,650 750 600 1~001 1,700 6,300 4,500 1,006 1,800 550 1,300 54O 2,250 Issue Date May June May May May May May 9 May May May May May ~ May May May May May May May May May • May May 15 30,132
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Subject: PLACEMENT RECALL TESTING SCHEDULE FIRST QUARTER, 1978 Date: December 15, 1977 To: BRAND RESEARCH MANAGERS BRAND MANAGERS From: Connie L. Sharpe Attached is our tentative schedule for placement recall testing for. the first quarter of 1978. The purpose of this scheduling procedure is to minimize cost, accommodate the increase in recall tests planned for 1978, and to provide an opportunity to obtain readings on new executions, as well as track specific executions over time. information obtained quarterly via the advertising wear-out/magazine insertion forms provided by our agencies is utilized in the develop- ment of placement recall testing schedules. In the selection of test issues we choose those magazines which provide us with the best opportunities to: (i) accommodate all brands planning tests during the quarter, (2) test two or more brands in each issue (3) obtain readings on new ads and/or allow us to track specific ads over time. ~Please have your Agency notify us of an~ ad insertion substitutions, additions, deletions, etc. made in Time, Newsweek, U. S. News, People, and Sports Illustrated for this quarter as these revisions affect our testing schedule. Thank you for your cooperation in this planning process. any questions or if I can be of assistance, please call. Connie L. Sharpe Marketing Research Department If you have CLS/me Attachments CC: Mr. J. H. Sherrill, Jr. • Mr. D. W. Tredennick Mr. T. L. Ogburn, Jr. Mr. G. E. Harlow Mr. A. H. Johnston Mr. M. G. McAllister Ms. S. A. MacKinnon Mr. D. F. Pearson Mr. D. A. Cummins Mr. N. Glover Ms. E. N. Monahan Mr. G. Novak Ms. M. C. Falconetti Ms. S. H. McReynolds O R JR[ FOflrvf Z4ZZ--f~'. 7('?'0
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TENTATIVE PLACEMENT RECALL TESTING SCHEDULE JANUARY - MARCH, 1978 TEST ADS TO MAPES & ROSS TEST ISSUE TEST ADS SCHEDULED January: Newsweek 1/16 Salem "Collis"-100's(1P4C) Time 1/23 February: Newsweek 2/6 Newsweek 2/20 March: Newsweek 3/6 Salem "Herring"-King (1P4C) Now "Okay" (1P4C) Now "Special Satisfaction" (1P4C) Now "Significantly lower" (IP4C) 1/4 (Noon) 1/4 (Noon) 1/3 (Noon) 1/3 (Noon) 1/3 (Noon) i/ii (Noon) 1/25 (Noon) 2/8 (Noon) 2/22 (Noon) Time 3/20 3/8 (Noon) O O The following RJR ad wili be picked up ROP during first quarter .if we test according to the above indicated schedule: - Salem Lights "Ashtray" (1P4C)
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Inter-office Memorandum Subject: PLACEMENT RECALL TESTING SCHEDULE FOURTH QUARTER, 1977 Date:September 22, 1977 To: BRAND RESEARCH MANAGERS From:Connie L. Sharpe ' BRAND MANAGERS Attached is our tentative schedule for placement recall t.esting for~ the fourth quarter of 1977. The purpose of this scheduling procedure is to minimize cost, accommodate the increase in recall tests planned for the year, ~nd to provide an opportunity to obtain readings 'on new executions, as well as track specific executions over time. Information obtained quarterly via the advertising wear-out/magazine insertion forms provided by our agencies is utilized in the develop- ment of placement recall testing schedules. In the selection of test issues we choose those magazines which provide us with the best opportunities to: (I) accommodate all brands planning tests during the quarter, (2) t6st two or more brands in each issue (3) obtain run-of-press readings on new ads and/or allow us to track s.pecific ads over. time ~ . Please note that bec'ause of the holiday season the last test issue scheduled for the year is December 5t :1977; Mapes and v Ross must be in receipt of test ads by November 23 (Noon) in order to be in- cluded in this issue. Thank you for your cooperation in this Planning process. any questions or if I can be:of assistance, please call. Connie L. Sharpe Marketing Research Department CLS/me Attachments cc: Mr. J. H. Sherrill, Jr. 'Mr. D. W. Tredennick Mr. T. L. Ogburn, Jr. Mr. G. E. Harlow Mr. A. H. Johnston Mr. M. G. McAllister Ms. S. A. MacKinnon Mr. D. A. Cummins MS. E. N. Monahan Mr. G. Novak • Ms. M. C. Falconetti Ms. S. H. McReynolds If you have RJRI FORM 2&22-Rev. 7170
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TENTATIVE PLACEMENT RECALL TESTING SCHEDULE OCTOBER - DECEMBER, 1977 TEST ISSUE October: November : Time 10/3 Newsweek 10/24 People 11/7 11/14 Time 11/21 December: Time 12/5 TEST ADS SCHEDULED (i) Winston "Doug" (IP4C) TEST ADS TO I uV. .s oss 9/21 (Noon) .. 10/12 (Noon) 10/26 (Noon)' 1.1/2 (Noon)~ 11/9 (Noon). 11/23 (Noon) The following RJR ads will be picked up ROP d~ring fourth .quarter.if we test according to the above indicated schedule: ~ - More "More What" (IP4C) - Now "Extrusion" - Real (1P4C) "National Taste Test - Leaves in Basket" (IPB&W) "l~al Voted Best Low Tar - Leaves In Basket". (iPB&W) "Of All Major Brands - Cutter" (IP4C) ; - Salem "Boyd" (IP4C) - Sale_m Lights . "Burnfng Cigarette" (IP4C) "Ashtray" (IP4C) "Confrontation V - Dave Ness" (2PB&W) "Conf@ontation VII" (2PB&W) - Winston "Steve Reynolds - revised" (IP4C)°
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Date: June 27, 1977 Subject: PLACEMENT RECALL TESTING SCHEDULE THIRD QUARTER, 1977 70: BRAND MANAGERS/ASST. BRAND MANAGERS From: Connie L. Sharpe The attached is our tentative schedule for placement recall testing for the third quarter of 1977. The purpose of this scheduling procedure is to minimize cost, accommodate the sharp increase in recall tests planned for this year, and to provide an opportunity to obtain readings on new executions, as well as track specific execu- tions over time. If you have any questions, please call. Connie L. Sharpe Marketing Research Department CLS/me Attachment cc- Mr. J. H. Sherrill, Jr. Mr. T. L. Ogburn, Jr. Mr. G. E. Harlow Mr. D. W. Tredennick Mr. D. A. Cummins Mr. C. C..Standen Mr. M. G. McAllister Mr. A. H. Johnston Ms. E. N. Monahan Mr. T. J. Key Mr. J. G. Palmer Mr. S. Snyder Mr. D.H. Murphy Ms. M. A. Daniel Mr. G. Novak Mr. A. R. Cox Mr. R. C. Brown Mr. J. M. Wallace Ms. M. C. Falconetti Ms. S. H. McReynolds flJt"ll I OFIM :2422 -Hey. #/TO
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TENTATIVE PLACEMENT RECALL TESTING SCHEDULE JULY - SEPTEMBER, 1977 TEST ISSUE Ju~: Time 7/18 ~u@ust: People 8/1 People 8/15 Newsweek 8/22 People 8/29 September: Time 9/12 TEST ADS SCHEDULED Time 9/26 (i) Doral "Serious Smoker" (IP4C) (i) Vantage "Confrontation I" (IPB&W) (2) Salem "Kyle", "York"(iP4C) TEST ADS TO MAPES & ROSS 6/6 (Noon 7/20 (Noon) 8/3 (Noon) 8110 (Noon) 8/17 (Noon) 8/31 (Noon) 9/14 (Noon) RJR Ads to be picked up ROP during third quarter. (New ads not previously tested or tracking of specific ads over time to provide insight re: potential wear-out) : VANTAGE : • "Confrontation I" (2PB&W) - REAL "Hogshead & Scoop" - (2P4C and/or IP4C .Versions) "Leaves in Basket" (1P4C) "Feel the Real Taste Difference" "Taste Your First Natural Cigarette" - SALEM "Enjoy Real Satisfaction Light/Lights 100's" (Poster format) - WINSTON "Open Shirt" (85's & 100's - 2P4C) "Sweater" (Lights/Lights 100's} "2nd Male Execution for Light/Lights 100's" - MORE (To be determined) - NOW (Proposed New Ad)
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PLACEMENT RECALL TESTING SCHEDULE SECOND QUARTER, 1977 Date: March 28, 1977 Mr. S. C. Wooten, Jr. Mr. J. T. Winebrenner Mr. Do F. Edelschick Mr. N. J. Stevens Mr. C. W. Perry, Jr. Mr. E. M. Blackmer Ms. S. A. MacKinnon Mr. A. P. Ritchy Mr. D. G. Fought Ms. C. M. Burke Mr. D. N. Iauco Mr. M. L. Gann, Jr. ~ Mr. C. L. Sharp Mr. G. W. McKenna Mr. J. S. Carpenter Mr. M. A. Cannon From: Connie L. Sharpe The attached is our tentative schedule for placement recall testing for the second quarter of 1977. The purpose of this scheduling procedure is to minimiz~ .cost, accommodate the sharp increase in recall tests planned for this year, and to provide an opportunity to obtain readings on new executions, as well as track specific executions over time. If you have any questions, please call. Connie L. Sharpe Marketing Research Department CLS/me Attachment CC: Mr. J. H. Sherrill, Jr. Mr. T. L. Ogburn, Jr. Mr. G. E. Harlow Mr. D~ W. Tredennick Ms. E. N. Monahan Mr. T. J. Key Mr. J. G. Palmer Mr. S. Snyder Mr. D. H. Murphy Ms. M. A. Daniel Mr. G. Novak .Mr. A. R. Cox Mr. R. C. Brown Mr. J. M. Wallace Ms. M. C. Falconetti Ms. S. H. McReynolds
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TENTATIVE PLACEMENT RECALL TESTING SCHEDULE APRIL - JUNE, 1977 Test Issue April Tim___~e4/4/77 May, June Newsweek 4/25/77 U.S. News 5/9/77 ,People 5/16/77 People 5/23/77 Newsweek 6/6/77 People 6/13/77 U.S. News 6/20/77 _. Test Ads Scheduled More (More When?) (i) Winston (Norb) -ROP* (i) New Brand (I) • Salem (2) TEst Ads To Mapes & Ross 3/23/77 (Noon) 4/13/77 (Noon) 4/27/77 (Noon) 5/4/77 (Noon) 5/11/77 (Noon) 5/25/77 (Noon) 6/1/77 (Noon) 6/8/77 (Noon) RJR Ads to be picked up ROP durin~ second quarter: (New Ads not previously tested or tracking of specific ads over time to provide insight re: potential wear-out) - Vantage "Perfects"/"Smoker's Guide" - Winston "Norb"/"Open Shirt" dual pack spread/ "Silver Chain - Blue Shirt" - Salem "Boyd" - More "More What?" - Now "Extrusion"
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" [ 3~1.7 _~0 IVI,~ 73WV3I ., £NI)INIHI 3ISV~[ '[
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CAMEL FASHION LINE GUIDELINES l) Arr@ngement Licensing of the CAMEL Trademark would be the most sat- isfactory and viable arrangement (as in Germany).. 2) RJR Involvement Licensing arrangement would also minimize RJR's involve- ment, since the prime business is selling cigarettes rather than fashion. 3) Type of Manufacturer It is felt that our best opportunity for successfully selling such a program would be to the 4th or 5th largest manufacturer rather than the big three -- Levi, Wrangler, and Lee. 4) Appea~ Pre-testing is necessary to both assess appeal to the consumer and, importantly, to sell the selected manufac- turer on the value in terms of extra sales volume potential. 5) Material Denim is the most acceptable and the most widely used material and the least faddish. This is, of course, compatible with our image. 6) 7) Items and Style Cashal wear (i.e. jeans, shirts, blouses, jackets, etc.) in standard (not fads) styles to ensure longevity. Unisex " ~tems should be applicable to both male and female in line with current unisex usage of denim and'jeans, etc. (i.e. 40% of mens' jeans bought by women). O October 20, 1977 WILLIAM ESTY COMPANY, INC.
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CAMEL FASHION LINE ACTION STEPS/TESTING DETAIL The following is compiled only as an INITIAL OUTLINE for guidance. Detail costs, procedure and timing can change and will.be finalized after initial agreement. l) 2) 3) 4) 5) 6) Lega~ Gain RJR Legal approval to test the concept on campus under Playboy's CMR Program. Should a negative response result, an optional method of testing in singles complexes can be considered. Questionnaire Joint Agency/Playboy development of questionnaire. This would reflect the needs of the testing method, Brand imagery and objectives, and informational requirements most likely to induce manufacturer participation. Testing Proposal CMR To be developed by Playboy and conducted under their CMR Program. Number of respondents can range from 300-500, split 50/50 male and female'-over an age range of 17-23 years. Respondents can be spread over five campuses geo- graphically dispersed to reflect national appeal. Costs can range from $5 to $i0 per respondent; financing can be either from earned Playboy merchandising funds or, if not available, from Brand Budget. Material Requirements Two to three garments (M/F), photographs, three types of logo treatment, per campus. Timing (Test) Anticipated start date approximately'4-6 weeks after com- pletion of the above. In field 2-3 weeks. Final results 6-8 weeks after start. Manufacturer Proposal Formalize proposal and selling pitch and present to manu- facturer. To include test findings, European details of success, degree of exposure of CAMEL Logo from conven- tional advertising, licensing agreement, etc. WILLIAM ESTY COMPANY, INC. october 20, 1977
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October 5, 1977 Mr. Donald M. Roux Spotts International 1300 Highway 8 St. Paul, MN 55112 Subject: CAMEL FILTER Free Pack .Offer Dear Mr. Roux: Please note the attached letter from the office of the Attorney General of the state of Idaho. I believe that it is self- explanatory. The instance related in the attached letter is similar to previous occurrances. However, in those previous instances we have always pulled the card of the respondent where the person signed stating that he/she was 21 years or older. I have been informed that the case in question has occurred because of a mix-up on the part of your company. I am told that Mr, Humphries had ordered pens from a Kellogg Pen Offer, but received a pack of CAMEL FILTERS and a CAMEL FILTER coupon. This matter is of particular concern to the CAMEL Brand Group and the RJR Legal Department. In absolutely no instance do we want it to appear that R. J. Reynolds distributes unsolicited cigarettes to minors. " Attempting to resolve this problem, this is to request that you forward a letter to me explaining in detail how/why this situation occured. Be advised that I will then forward your letter of explanation with a cover letter to the Idaho Attorney General. Donald, please advise if you have any questions. receiving your res~0nse as soon as possible. I would appreciate CLS/pms Sinc~erely, Charles L. Sharp Assistant Brand Manager Attachment • cc: D. G. Fought, R'. V. Hall, H. N. Willis, T. J. Rucker O
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Mr ,W/Noah Subject : March 22, ]977 CAMEL FILTER Free Pack Offer Bill, your cooperation appreciated. { h/,-2 l~llq,Ni,'J~, This is to confirm our telephone conversation of yeste-r~ay af-ternoon. It Js understood that you will request that an RJRT Sales Representative deliver eight (8) 12M cases of CAMEL FILTERs to Spotts Internat~0nal. It is also understood that Spotts should receive this product no later than Wednesday, March 23, 1977. in th~s matter is very much C. L. Sharp CLS/pms co: D. F. Edelschick R. V. }{all J. A. Leinster
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CAMEL FILTERS SUMMARY INDIVIDUAL RACE SUPPORT Newspapers Magazines Programs Total Media Production IMSA Newspapers Magazines Programs Total Media Production $130,389 11,900 22,0'00 28,800 TOTAL: $173,065 17,248 16,000 20,800 TOTAL: 164,289 28,800 $193,089 206,313 20,800 $227,113 GRAND TOTAL: Budget: Overage: $420,202 $350,000 $ 70,202 (1977 Budget $445M) October 20, 1977 WILLIAM ESTY COMPANY, INC.
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SPECIAL FAtE~r]~ 1978 AMA EXPENDITURES Local Race support s .~nary. Date Location Oklahoma City Reading, Pa.' (New) Northfield, Ohio (New) Louisville, Ky. Harrington, Del. Columbus, Ohio San Jose, Calif.+ . Des Moines, Iowa (New) Middletown, N.Y. Toledo, Ohio Gardenia, Calif.+ Hous ton, Tx. + Chicago, Ill. Castle Rock, Wash. Peoria, Ill. (New) Springfield, Ill. (New) "Du Quoin, Ill. Indianapolis, Ind. + Syracuse, N.Y. Sacramento, Calif. (New) Charlotte, N.C. Daytona Beach, Fla. Louden, N.H. Sears Point (Soncma) Pooono, Pa. Riverside, Calif. Plus 4 more races+ 2,380 1,530 3,690 690 6,490 5,610 4,810 1,785 2,220 9,100 7,500 1,880 3,360 4,000 6,634 1,000 • 5,315 5,850 5,435 2,305 4,145 ~,265 4,620 5,465 6,585 2,685 20,040 130,389 Cycle News** 476 (W) 336 (E) 336 (E). 336 (E) 336 (E) 336 (E) 476 (W) 336 (E) 336 (E) 336 (E) 476~ (W) 476 (W) 336 (E) 476 (W) 336 (E) 336 (E) 336 (E) 476 (W) 336 (E) 476 (W) 336 (E) 336 (E) 336 (E) 476 (W) 336 (E) 476 (W) 1,904 (W) ii,900 22,000 Total Grand Media Prod. Total 2,856 960 1,866 960 4,026 960 1,026 960 6,826 960 5,946 960 5,286 960 2,121 960 2,556 960 9,436 960 7,976 960 2,356 960 3,696 960 4,476 960 6,970 960 1,336 960 5,651 960 6,326 960 5,771 960 2,781 960 4,481 960 5,601 960 4,956 960 5,941 960 6,921 960 3,161 960 21,944 3,840 22,000 164,289 28,800 3,816 2,826 4,986 1,986 7,786 6,906 6,246 3,081 3,516 10,396 8~936 3,316 4,656 5,436 7,930 2,296 6,611 7,286 6,731 3,741 5,441 6,561 5,916 6,901 7,881 4,121 25,784 22,000 193,089 *One Insertion per. Race **One ½ Page Insertion per Race WILLIAM ESTY COMPANY, INC. C~tober 20, 1977
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CAMEL FILTER SPECIAL EVENTS/IMSA 1978 IMSA EXPENDITURES LOCAL RACE SUPPORT SUI~ARY Date Location Daytona Be~ch, Fla. Sebring, Fla. Taladega, Fla. (New) Atlanta, Laguna Seca (Monterey) Tulsa, Ok. (New) Lime Rock, Ct. Mid-Ohio (Mansfield, Oh.) Brainerd, Mn. DaYtona, Fla. Sonoma, Ca. Hid-Ohio (Mansfield, Ohm) Atlanta, Ca. Daytona, Fla. + Two More Races Speed Motor Sport Sports Newspapers* News** ~ 11,270 453 12~785 453 5,200 453 9,940 453 13,970 453 1,570 453 16,600 453 13,885 453 8,950 ~53 11,270 453 10,930 453 13,885 453 9,940 453 11,270 453 21.600 906 $173,065 $7,248 Pro- Total Grand grams Media Prod. Total '625 -- '12,348 625 -- .13,863 625 -- 6,278 625 -- ii,018 625 -- 15,048 625 -- 2,648 625 -- 17,678 625 -- 14,963 625 -~ 10,028 625 -- 12,348 625 -- 12,008 625 -~ 14,963 625 -- II,018 625 -~ 12,348 1,250 -- 23,756 16~000' $I0,000 $16,000 $206,313 1,300 13,648 1,300 15,163 1,300 7,578 1,300 12,318 1,300 16,348 1,300 3,948 1,300 18,978 1,300 16,263 1,300 11,328 1,300 13,648 1,300 13,308 1,300 16)263 1,300 12,318 1,300 13,648 2,600 26,356 16~000 $20,800 $227,1]': * Twoinsertions per race ** One 546-iine insertion per race # One 3/5-page insertion per race WILLIAM ESTY COMPANY, INC. October 20, 1977
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August 29, 1977 Mr.. D. ~. Fought RE: RDF CONCEPT TEST RESULTS The attached report from John Wallace summarize~ the results of the RDF Concept Test. REcOS~ENDATIONS: MRD recommends the discontinuance of the RDF project for the following reasons: I) Even though the concept scores in the qualified potential range this is based primarily on a high difference rating. However, the concept's importance, the variable that seems to best relate to ongoinq market potential, is low. 2) RDF concept skews toward older and non-filter smokers in overall appeal, importance, and purchase. 3) Non-filter category is rapidly declining - 10.7% in 1977 to 7.9% in 1980. Non-filter smokers are brand loya~. 48% of non-filter smokers are over 50 years of age. RDF concept has failed to attract previous non-filter smokers. Apparently previous non-filter smokers are content with their current filtered products." The failure of RDF to attraqt previous NF smokers is critical since the. flavor of RDF at 14 mg. would probably be more appropriate for FF smoker needs than NF. Presently RDF at 25 mg. has the highest tar level of all major regular non-filter brands. MRD recommends testing a repositioning reformulation concept for CAMEL Regular as a lower tar cigarette. A reformulation which results in a tar l~vel less than 20 mg. would place CAMEL Regular at-the lowest in its category.
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Mr. D. G. F6ught Page Two August 29, 1977 CAMEL Regular repositioned as a same flavor, lower tar cigarette may a) ,b) attract smokers from competitive non-filter brands; possibly retard the rate of decline 0f the category in general and of CAMEL Regular specifically by offering another Option to non-filter smokers whose concern about the alleged hazards of smoking causes them to look to the filter category for a solution. Em~i l~Carr o~~~ " Marketing Research Department ERC:dmb Attachment Mr. C. L. Sharp Mr. D. H. Murphy Mr. M. G. McAllister Mr. T. L. Ogburn, Jr. Mr. D. W. Tredennick Mr. G. E. Harlow Mr. J. M. Wallace
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CONFIDENIiAL August 29, 1977 Mr. D. G. Fought RE: CAMEL FILTER NEW CAMPAIGN QUALITATIVE EVALUATION Background: Inan effort to develop a back-up campaign for CAMEL Filter, the agency has devised a copy approach linking CAMEL Filter's strong development in the West to the Brand's basic product promise of pleasurable smoking. The link is that the West typifies pleasur- able easy living and that CAMEL Filter fits in with this Western lifestyle. By combining two visual with two copy approaches, the following four executions were developed: Visual/Description Headline i) Casual-Beach scene with couple California Feeling 2) Casual-Beach scene with couple New West 3) Hedonistic-Man with two girls in bikinis 4) Hedonistic-Man with two girls in bikinis California Feeling New West Prior to evaluating any of these ads quantitatively a qualitative exploration was conducted to diagnostically aid in developing firm executions for testing. Findings : CAUTION: The projectibility of findings of this study is limited due to small sample sizes and the group dynamic effect operative in focus groups. However, the following findings, based on their prevalence among the respon- dents and our judgment, are sufficiently reasonable to act on in the manner indicated in the "Next Steps" section.
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Mr. D. G. Fought Page Two August 29, 1977 • Back-Up Campaign The casual beach scene visual appears to work much better than the hedonistic man with two girls visual among all age and sex groups for the following reasons: Casual Hedonistic • A relationship between the two individuals clearly exists. While this relationship is unde- fined it is a close one which all respondents could positively identify with/aspire to. If a relationship exists between the man and girls, it is of a short term, totally sexual nature. While some men could aspire to this on a fantasy level, a closer less superficial relationship was clearly preferred. • The couple depicted are not seen as coming from any parti- cular socio-economic class such that no barrier to identifica~ tion with the scene is presented. The people are seen as too upscale preventing most consumers from identifying with them. • The beach setting was seen as not only desireable but also attainable. This setting was seen to be too exotic to reasonably aspire to. In summary, the casual beach visual works better among all segments because in total it is not only more desireable on a fantasy level but also because it is seen to be more attainable on a practical level. "California Feeling" generally works better than "New West" because the latter phrase was devoid of real meaning or imagery. "California Feeling" did not get the same total positive reception in Seattle as in Indianapolis due to either local civic pride or to first hand knowledge that California meant not only easy living, bl6ndes, beaches and eternal sunshine but also urban congestion, crowded freeways and smog. While "California Feeling" and the casual couple on beach visual meshed nicely it should be noted that this approach does not appear to be consonant with the current campaign imagery. Whereas the couple depicted in the beach scene were perceived as warm, real people easily relating to each other whom one could easily identify with, George was perceived to be arrogant, cold and too perfect to be real. He does not really relate to others and is thus difficult to identify with. Thus, while a possible switch to a California Feeling campaign with the casual visual should take the brands smoker imagery in a different direction from the current campaign, it may be a more positive smoker imagery.
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Mr. D. G. Fought Page Three August 29, 1977 Current Campaig~ As suggested above reactions to the current campaiqn (stimulated by "Gold Panning,) -weregenerally negative. It shouldbe emphasized that these reactions were drawn from four groups on non-CArreL Filter smokers and only one group of CAMEL Filter smokers. George's chief failing seemed .to stem from the fatt that he was perceived to be a model who was supposed to represent a certain macho imagery. This overall perception of George as an advertising ploy was fed by perceptions of the Gold Panning situation as too contrived and posed, George's hair to be too freshly combed, his clothes to be too expensive looking and clean, etc. This perception of George as less than real becomes more important when contrasted to perceptions of WINSTON models as "normal" people and of the Marlboro cowboy as a real cowboy with real machismo. In a compe- titive frame George did not seem to be a credible spokesman. Next Steps: Back-Up Campaign We recommend that California Feeling headline with casual visual be further explored quantitatively to assess: - Universality of appeal. Do Teal problems exist for this campaign in the Brand's western stronghold? - Impact/memorability. Does the ordinariness of the people depicted hinder memorability? How much copy? There was some sentiment that California Feeling with the visual said it all and that without further explanation consumers can attach a broader meaning to the phrase. Relative appeal of OOAK imagery vs. California Feeling imagery within current CAMEL Filter franchise. In that the two appeals do seem to be diametrically opposed, it is critical to determine the risk to our current franchise of running the California Feeling Campaign.
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Mr. D. G. Fought Page Four August 29, 1977 Current Campaigq Since these groups suggested possible problems with the current OOAK campaign we will be Closely monitoring the campaign's market performance to see if there is evidence that the problems suggested by the groups occur on a widescale basis. Attached is the moderator's report providing a broader more detailed synopsis of the hypotheses gained from this study. ~aa~~~ePhaYrch Department DHM: dmb CC : Mr. J. H. Sherrill, Jr. Mr. T. L. Ogburn, Jr. Mr. G. E. Harlow Mr. D. W. Tredennick Ms. E. N. Monahan Mr. T. J. Key Ms. E. R. Carron Ms. Maria Falconetti Mr. M. G. McAllister Mr. C. L. Sharp Mr. Larry Wassong Mr. J. Neal Mr. M. Kram Mr. E. DiSpenza Mr. L. Gelsten Attachment
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Quantification Phase - A total of ten weeks from completion of initial phase to final report. Cost can only be approximated at the present time as $50,000 + 10%.
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Purpose The purpose of this study is to determine consumer acceptance of 2% Turkish Replacement in CAMEL Regular when compared to the current product. If successful, this would result in a cost-reduction through the increased use of cut-puffed stems. The measurement criteria of this study is nQ difference between the product with 2% Turkish Replacement and the current product." If the test results~ show no difference, or a significant win for the test product, the 2% Turkish Replacement should be considered for inclusion in the current product. Method CAMEL Regular smokers were mailed, through NFO/ two blind packs each of the current and test products for paired comparison purposes A mailback questionnaire was used to collect overall preferences, reasons for preference, thermometer ratings, direct questions on selected attributes, and demograp~hic data. ~ ~ . Conclusions The test product was significantly preferred over the current product and received a signfficantly higher rating. Perceptions of the test productare generally positive. It is felt there is no risk in adopting the test product. HRR/gsf 7/5/77 attachments cc: Messrs. G. B. Whitaker J. D. Barnhill Dr. A. H. Laurene F. H. Christopher, Jr. C. A. Tucker J. II. ~r. T. L. Ogburn, Jr. G. E. Harlow T. H. Eskew R. H. Cundiff D. P. Johnson ~. H. Murphy
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July 21, 1977 }It. Do Pc Johnson Subjeot~ Attached Hol~o Regarding WINSTON A Blend f0r:~red 'Tar' ~L FILTER I have no probl~m with the testing of the WINSTON A blend as you suggest. However, At does concern me ~at our 'tar' luvel would.{or could) be as low a~ 15 ~g. That ~.,~uld ~e very clos~ to ~e ~tar' level of our provo,ed D~~ oa~didate (14 mg) o ~e ~rand's goal for 1978 is to introduce a 17 ~g C2~L FIL'~R produo~ nationally, preparing a 15 mg oandldate for future 'tar' reductlo~s If necessary. Hence, it still appear~ viable from the Drand's standpoint to consider a 17 mg product meeting the ~rlteria below$ -. Maximizes appeal among 18-34¥~ar old males - At parity with current CAMEL FILTER product among current smokers - Performs ~8 well as currunt product p~rforms vls or vis ~arl~oro 85 amo||g Marlboro s~okers/ other ~5 ~ ~mokers {current product oonp~titiv~ te~t~ng no~¢ beillg ~chedul~d to dcterzain~ In-~nrh~t per£ormanoe of current product} Del, let me know if you want to disousso DGF/pms Attachment oo: C. L. Sharp~/ R. H. Cundiff J. Lo ~Kenzie D. Go Fought
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AZtozney At Law 41 U~Jion Square ~w l'o=k, N.Y. 10003 ~up~laor or ~'~s ~s~anoe oar~ wzll cqntaot ~ou soon, ~.~zaotox~ly in duo course, .
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RESEARCH l .J. I EYNOIJ)S TOi ACCO CO WINSTON-SALEM, NOP.TH CAROLINA August 13, 1968 rMr. Edwin J. Jacob Forsyth, Decker and Murray 51 West 51st Street New York, New York 10019 Dear Mr. Jacob: DEPARTMEN~ MPANY Copies of defendant witness articles listed in the a~tachment are being sent to you today in two separate shipments. Other articles are on order and will be forwarded to you as soon as we receive them. $inderely yours, da II. Bolin rmat ion Division R~B/fhv Attachment CC: Dr. Gisella L. Cahnman Mr. Don Hoel Mr. H. H. Ramm u/ Dr. Frank G. Colby o
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FF~ANKLIN 9 - (~,565 President R. J. Reynolds Tobacco Co. Winston-Salem, ]Corth Carolina Re: Coon v. Reynolds et al Registered Mail Retu~n" Receipt" Requested December 22, 1958 Dear Sir: This letter will give you notice that on December 12, !958, service of process was made upon you under Section 47.16 of thc Florida Statutes. We enclose herewith copy of the summons and amendment to complaint issue~ in the case. Process has been served on the Secretary of State of Florida as agent for you under the above Statute, whloh provides for service upon non-residents of the State of Florida doing business as individuals, partnerships or corporations in Florida. This service upon the Secretary of State of Florida constitutes valid service of the summons and amendment to complaint upon you. This notice is to fo~ally notify you of the institution of this amendment and of the service of process. Your answer in the case is required to be served within twenty days from the time you receive this letter. You should i~ediately notify your insurance company carrying liability insurance so that your interest will be pro- tected. This letter is urgent and should receive your i~ediate attention. Yours very trul~ F,urray .~aF./,, d r. l.IS/cb Enclosures
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HAROLD M. COON, ~lalntlff, V . R. J. RYY:~OLI~ TODACCO a Ne~ Jersey corporatlo~ business in Plorida a Florida I>e fendant ~. : Zh'~ERROGATORI£5 TO DZFEND~ 2. State the names and current addreeses of all defendant's executives ~ho have been and are currently r~sponslble for such research department, statin~ the dates each executxvc :~as so responsible. C~:. i ~. ,~.ts: . ~,:~ulll'~7 the iooatlO'~ fr:~ ':~Icn each t~bac~o is pu:'~']a~,cd b7 the def.:,nd~.t. 5. Give e brief de&crlpt~on of th: ~..anufacture of C$.y,el cigarettes.
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6. ~ro~ ~'bo~ does the defunct pu~cl~e the paper 7. State the content of ouch ~per u~e~ In ¢~el olg~r- ettes and glve a brief d~ecrlpt~on o~ it~ ~otu~. 8. State the defen~t*m 0o~ect~on elth the ~et~ Re~earch C~ttee, ~ E. 4~d Street~ New York, York. 9. ~tete ~f the ~efen~t eontri~te~ ~ey tO Committee de~a~li~ the ~.~te of toner ~r~v~ou~F In ~arate 10. ~tate ~ the ~eZen~t ~ cor~pon~c~ In lt~ ~oeeeeslon r~tlnc to the fo~tl~ o~ the ~eoo In~tr~ ~.e~rch C~ttee ~ ~t~Le ~h~ i~eh oo~r~n~enoe I~ ]oo~te~. 1~. State i~ the defen~nt ~e cor~nd~,ce ~ poese~eton r¢]atlr~ tO the dcf~ut's co~eetl~ ~lth the ~et~ Ree~h Co~tee ~d ~tate ~he~ ~uch aay be e~mined. 1~. State if t~e defender has in the paet ~5 collected medlcal ~rte co,ceding the er, oklng of clgarettes az~d ~tate where ~uch medlca~ ~e~o~s ~y be e~m~n~d. 1~. Btate th~ n~me~ ~d eu~e~t add~es~e~ of all of the defen~:~t's executlvea In the pa~t ~5 yea~'~ to whom ~uch r~ed~cal reports were x~ted. 14. State If the defendant sell~ or ~s eold Caael c!ga~ttez to ~,y of the co.orate ente~ri~e~ ~dch the ret~l out~ets ~o~ as ~ood F~Ir ~tores of i5. State ~ th~ defender m~Intaln~ ra~r~ of Its co,orate and ~ar~ ~eetlngs. If ~o, p~ea~e :tate ~he~ :uch reco:~s are located. 0 0 o
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tobaoco. f~ th~ leav~ of tobacco b~to~ they are u~zd In the of Camel ~Igarette~. 22. State the n&~es ~n~ curr~ut add~c~ of tis~r~ a~encles w~oh have :~ndled ~he defen~nt's when each ~,~ed %he vertl~!r~ ~I,d =~rketir~ of Ca~,e~ ¢i~a~,et~:-~ ~nd were ir~ cow,tact 0
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25. State the na~es a~d cur~nt addresse~ of Ill personnel ~n ~a~ ~,~'~n~ &~nc~ee who ~ this p~od w~re ~s~onsl~le for ~he a.~e;~c~c~s' ~na~ ' ~ of the adve~isiz~ for Camel cigarettes ~d. State the total e~en~Itu~s In ~ach of the ~ast 3~ year~ for ~dvertisln~ for C~el 27. ~tete If the deren~ut ~Intelns files of all adver- tleln~ for C~ei ci~arettee~ L~cludln~ ac~pt copy of ~o ~d of the pR~t 35 ye~rs. ~. State the tota~ c~en~tures of the ~ef~t for research 1~ e~ch of the pS~t 35 ~:~. ~S the ~fen~t ever eau~ed ~ualy~i~ of a~ke p~duced by C~mel elg~tte~? If ~o, please co~¢Sltloa Of the smoke of C~el cigarettes. 31. State if the defends ~kes yearly ~ports to its stoc~cholde~s. If so, state where such ,cpo,~, art l~cated. If the ~%~mes ~nd current aldresees of ~uoh Dersone. A~fred I. dmPont Bull~,
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! , ~erenci~to. the ~f~t R, O. ~old# ?ob~eeo Co,, I =et~o~~el ~%~etu~ of ~uch ~ee~h d~~t, detaJli~ ~he who have been ax, d are currently r~sponslble for such re.p~Jble. clEare~teI, 0
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./ ~se~ Ln Ca~e~ ei~e~ettes. c~*: to ~n~' oF t~ co.rate ~nte~rises t~sh n~nt~n
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March 4, 1959 Attached is the ad Mr. Gray referred to in his February 26 memorandum to you.
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CARL THOMPSON March 3, 1959 Mr. Bowman Gray, President R. J. Reynolds Tobacco Company Winston-Salem, North Carolina Dear Mr. Gray: Reaction varied to the draft advertisement transmitted February 17 which was drawn primarily fro~ the 1958 Report of the Scientific Director. Genera/ opinion was that the material was too heavy for mass circulation publications. Most suggestions were that the advertisement that was approved in principle last fall should be revised to: (1) Eliminate the two points that were in question and which resulted in postponing consideration of the advertisement, and (2) Incorporate the best points of the February 17 proof. The attached proof is a suEgested advertisement carrying out these suggestions. It is intended for publication in such magazines as were listed in our transmittal letter of February l7. Your adddtional suggestions will be welcomed as soon as possible. Sincerely yours, CT:tsm p Encl. Carl Thompson cc: Executive Committee The Tobacco Institute, Mr. James P. Richards o
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Statement by the Chairman of the Tobacco Industry Research Committee issued July 5, 1958, on the press release ot the U. S. Public Health Service There is a key word in the Public Health Service release. That word is "sta- tistical." As the Tobacco Industry Research Committee predicted several weeks ago, the Public Health Service study of veterans' statistics has come out with findings paralleling those developed by Hammond-Horn for the American Cancer Society, certainof whose paid staff are leading the anti-tobacco movement. This similarity of results is not surprising; it was inevitable. The government's statisticians used virtually the same questiormair.e as Hammond-Horn. They dealt with the same one factor -- tobacco smoking. They ignored all other factors. They admittedly included no clinical or laboratory research in their study. So they delivered the same results -- no newinformation. No answer to the statistical relationship exists. No reliable basis for deciding anything about the actual causes of lung cancer or any other human disease. In merely repeating the statistical procedures and covering the same limited scope as Hammond-Horn, the government's study is vulnerable to the same potential errors that have been pointed out by Dr. Joseph Berkson, chief biometrlclan of the Mayo Clinic, and other scientists, in reviewing the work of Hammond-Horn. Scientists agree that statistical studies cannot explain or answer anything. They only raise questions without answering them, revealing the need for further research of a clinical and laboratory nature. This study, like Hammond-Horn, attempts to fix on tobacco a relationship with not only lung cancer but a host of other diseases. Dr. Berksonhas pointed out in the case of Hammond-Horn that he finds it "quite incredible that smoking should cause all these diseases. It appears to me that some other explanation must be formulated for the multiple statistical associations found with so wide a variety of categories of disease." There is something less than fair as well as misleading to the public in the Public Health Service's repetition of the Cancer Society's device of dealing primarily with percentages rather than actual numbers in its press release. Talking of greater death rates in terms of percentages makes good scare head- line material. But it also serves to divert publicattention from the fact that lung cancer deaths during the two-and-a-half-year period numbered only 197 out of the scores of thousands of cigarette smokers in the 200,000 veterans surveyed. This play on percentages also serves to divert attention from the fact that, as Dr. C. C. Little, scientific director of the Tobacco Industry Research Committee, has pointed out, "The vast majority of cigarette smokers never get lung cancer and, therefore, there is no simple cause and effect mechanism resulting from cigarette smoking. " This study, like the earlier ones, neatly avoids the logical complications which would come from giving equal attention to other factors such as the veterans' previous medical histories--illnesses and infections, war injuries, other environmental exposures, dietary habits and physiological, psychological and hormonal differences, any or all of which may play a role in causation of cancer and other diseases.
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BRIEFS OF SELECTED March 1963 Scientific Research Reports (Note: Requests are.frequently received from science writers for.references on subjects related to research on tobacco and health. The follow|ng references are selected from published scientific literature screened regularly by the Research Library of the Tobacco Industry Research Committee. For more details, please consult complete paper.) 3-63 ERRORS IN CANCER DEATH RECORDS -- Result in "skepticism." After taking a close look at over 13,000 cancer death records, three Boston investigators conclude that there's ground for "skepticism" of the value of such records in studies comparing individual environmental factors with subsequent cause of death. "Sufficiently large" errors in recording cancer deaths by specific sites were found by Drs. Herbert L..Lombard, Evelyn Potter Huyck and Leonid S. Snegireff. Working with 1946-1958 death records of the Massachusetts Cancer Registry, comprising the accumulated life-time records of nearly all the patients of the state's 30 cancer clinics, the investigators found that the records overstated the actual number of deaths from cancer of the lung by more than 20.percent. Errors attributing primary lung cancer deaths to other causes amounted to 8.h percent. If one is interested only in the number of lung cancer cases, the recorded figure does not vary greatly from the correct figure, they reported. However, "if one wishes to correlate some variable such as cigarette smoking with lung cancer, the individual death records must be considered. Here, the error is far greater." Out of 13,307 death records and histories, primary lung cancer was recorded as the cause of 269 deaths, though it was found that h9 of these patients never had lung cancer, and one more was thought to be cured of the disease by the time of death. Cancer of the lung, unspecified as to whether primary or secondary, was listed as the cause of an additional 695 deaths, though 126 in this group never had primary lung cancer. The combined error for the two groups "constitutes a 20.~ percent overstatement of primary cancer" of the lung, they said. Similar errors in the death records were found for cancers of sites other than the lung. "It is rather surprising," the investigators said, "that so many physicians report a cancer death according to the site of the metastasis rather than by the primary site...errors of diagnosis have always occurred...and there has been speculation whether trend~ such as are found in lung cancer are as pronounced as they appear to be. Changes in the accuracy of diagnosis could well alter the statistics." "An appraisal of the cancer death record." Proceedings of the National Academy of Sciences; December 1962. Coples of the full published reports may be obta;ned, if not otherwise ava;lable to you, from: Executive Secretary, Tobcrcco Industry Research Cornm~ee, 150 East 42nd St., New York 17, N. Y. OXford 7-9790. 0 O.
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Page 2 !t-63 CHRONIC DISEASE STATISTICS -- Standard methods sometimes inapplicable. Statistical methods which work well in identifying the causes of acute infectious diseases• "have been disappointing" in the search for the causes of .chronic diseases such as lung cancer according to a study by Drs. Theodore D. Sterling, John J. Phair and Jagdish Rustagi of the University of Cincinnati College of Medicine. The investigators said that "depending solely upon methods of manipulation of numbers, smoking appeared to increase the risk of death from quite different causes -- at times cancer, at other t~mes circulatory disease." They showed that a similar bias could be introduced in a~study of industrial workers in which selection of age groups and mortality ratios produces an apparent Job health risk which actually may not exist. They pointed out "that this hazard could be claimed to affect death from lung cancer or from circulatory causes depending on one's reliance On mortality ratios or on differences in death probabilities. The congruence between the projected findings of this imaginary study to those of the lung cancer and smoking studies is noteworthy; especially if one keeps in mind that most populations of smokers so investigated were concentrated in the older age groups." They called for a re-evaluation of present statistical methods in chronic disease epidemlologybefore conclusions about the causes of such diseases are reached. Comparisons between smokers and nonsmokers "are always controversial," the investigators said, but they pointed out that populations may differ in many other ways besides smoking or not, and they therefore may vary widely in mortality and morbidity patterns during their life spans. • "The extent of these differences and theirforce on mortality in middle and older ages have not been truly explored," they said. "New developments in chronic disease epidemiology: Competing risks and eligibility." American Industrial H~iene Association Journal, November-December 1962. - XXX -
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BRIEFS OF SELECTED January 1963. Scientific Research Reports (Note: Requests are frequently received from science writers for references on subjects related to research on tobacco and health. The following references are selected from published scientific literature screened regularly by the Research Library of the Tobacco Industry Research Committee. For more details, please consult complete paper.) 1-63 ARTerIOSCLEROSIS AND SMOKING -- Study questions connection. A study of findings in nearly I000 autopsies indicates "that if an association exists between smoking practices and the development of arteriosclerosis or lesions resulting therefrom, it is at best tenuous and inconclusive," two New York pathologists report. The published statistical linkage of heavy cigarette smoking to coronary artery disease probably reflects more distinct clinical symptoms of the disease in heavy smokers rather than a cause and effect relationship, said Drs. Sig~und L. Wilens and Cassius M. Plair, who studied 989 consecutive autopsies on men performed at the New York Veterans Administration Hospital between 1958-1961. "The relation between cigarette smoking and heart attacks could be an indirect or even a fortuitous one," they said. The pathologists found evidence of distinct myocardial infarcts in approximately 20% of non-smokers, 25% of heavy smokers, 23% of moderate smokers, 25% of light smokers, 27% of pipe and cigar smokers and in 20% of those whose smoking habits were unknown or unclassified. The number of men in each category ranged from 70 (pipe and cigar smokers) up to 288 (moderate smokers). The researchers said that incidence figures in the categories did not "vary significantly," adding that "This finding is in direct contradiction to clinical findings and suggests that myocardial infarcts may be more productive of severe symptoms, and thus more easily recognized, in heavy smokers than in non-smokers." The doctors also graded aortic specimens, making allowance for the subjects' chronological ages. They found that the degree of aortic sclerosis was directly proportional to age in 60% of their subjects, regardless of smoking habits. In the other hO%, however, they found that premature sclerotic changes were more than twice as common among heavy and moderate smokers than in non-smokers and users of pipes and cigars. ~ne researchers concluded, "Tne incidence of myocardial infarction is only very slightly higher in heavy smokers of cigarettes than in non-smokers, and there is no consistent rise in the incidence of such lesions with degree of cigarette smoking. The incidence of other types of lesions related to arteriosclerosis is not affected by smoking habits." "Cigarette smoking and,arteriosclerosis." ~..cience, NOV. 30, 19~2. Coples of the full publi~ed reporf$ may be obtained, if not otherwise available fo you, from~ £xecuf~ve .~.r~,~oJ,,/, Tz~mz~.o I~uJ~O, Res~orck Cemm~'~, ~0 Eosf ~l~nd SI., New YorA 17, N. Y. OXford 7-9790.
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Page 2 2-63 LUNG CANCER IN AUSTRALIA-- British bring .it with them. Men and women who emigrate to Australia from Great Britain show higher lung cancer mortality rates than Australlan-born men and women, but lower lung cancer mortality rates than are found in England and Wales. The differences do not appear to be due to differences in smoking habits, according to Dr. Geoffrey Dean of Eastern Cape Provincial Hospital, Port Elizabeth, South Africa. Dr. Dean said his findings, similar to those he prevlouslyhad reported for his home country, are "consistent with the hypothesis that the contribution of air pollution to lung cancer has been seriously underestimated." Also, he wrote, the Australian data was basically in llne with that from previous studies of British immigrants to New Zealand and the United States. He first compared smoking habits of British ~migrants and native~born Australians and found Australians had smoked somewhat fewer cigarettes .per~:capitauntil World War II, but had caught up with and passed the British in the 1950's. As to smoking habits, Dr. Dean said, "Insofar as British immigrants have adopted the smoking habits of the country to which they have mlg~ated -- and the evidence from SouthAfrica suggests this is the usual practice -- British immigrants will have become heavier smokers than the men and women they have left behind them." Yet, during the years 1950 to 1958, British-born men migrating to Australia had a lung cancer mortality rate about 40% lower than the rate for men of the same age in England and Wales, and the corresponding figure for women was about 35% lower. In his SouthAfrican study, Dr. Dean found that only m~le immigrants from Great Britain in the 45-to-6~-year age .group had higher lung cancer rates than South African-born white men. The difference in rates of lung cancer mortalltyfor ~le Brltish-born Australians as compared with native-born Aussies was 67% higher for immigrants. Comparable figures for women showed rates for immigrants 33% higher than native-bornAustrallans, yet 3~%lower than for women who remained in England and Wales. "Lung cancer in Australia." The ~dical Journal ofAustralla, June 30, 1962 C) o 0
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BRIEFS OF SELECTED November 1962 Scientific Research Reports (Note: Requests are frequently received from science wr|ters for references on subjects related to research on tobacco and health. The following references are selected from published sc|entlfic literature screened regu|ady by the Research Library of the Tobacco Industry Research Committee. For more deta|ls, please consult complete paper.) 5-62 6-62 LOW LUNG CANCER AREA -- incidence in rural county is half that seen elsewhere. The incidence ~f~ung cancer in a rural Midwestern area is lower by almost half than the rate generally reporte~ according to Dr. John T. Tidd of Sacred Heart Hospital, Yankton, S.D. F~rthermore, almost half the lung cancer cases found there occur in non-smokers. The tumor clinic at Sacred Heart analyzed 1,089 cases of proved cancer seen since 1949, Dr. Tidd reports.. Most of these~patients resided in Yankton County in southeastern South Dakota, while the rest came from northeastern Nebraska. This is predominantly an agricultural area, Dr. Tidd said. Of this group 33 patients proved to have primary cancer of the lung, an incidence of 3 percent. Rates in hospitals elsewhere, Dr. Tidd pointed out, have ranged from 5.2 to 20 percent in recent years, and lung cancer has been ranked third or fourth in order of frequency among other cancers. InDr. Tidd's series, however, it ra~ked tenth. "In recent years a high correlation between the occurrence.of lung cancer and cigarette smoking has been developed statistically," Dr. Tidd added. "There is no reason to believe that cigarette smoking is any less prevalent in this area than elsewhere in the nation." In his study, 16 of the 33 patients did not use tobacco, the pathologist said. All nine of the women were non-smokers. Of the 17 who smoked, the majority (12) smoked one pack of cigarettes or less per day, he said. "A clinicopathologic study of lung cancer in southeastern South Dakota." South Dakota Journal of Medicine and Pharmacy, September 1962. PERSONALITY AND CANCER -- lung cancer patients, smokers show differing traits. Two British psychologists have found that the personality traits of lung cancer patients differ significantly from those of people without cancer. The traits of lung cancer patients also differ from the personality patterns of smokers. In general, the lung cancer patients "have a significantly diminished outlet for emotional discharge" compared with non-cancer patients. ~Smokers, on the other hand, tend to be more outgoing -- more extraverted -- than cancer victims and non-smokers, the investigators said. Coples of the full published reports may be obtalned, if not otherwise available to you, from: Executive Secretary, Tobacco Industry Research Comm~ee, 150 East 42ncl St., New Yore 17, N. Y. OXford 7-9790.
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Page 2 In a preliminary study, Dr. David M. Kissen of the University of Glasgow, and Dr. H. J. Eysenck of ~ondon's Institute of Psychiatry interviewed and tested 239 male patients admitted to chest clinics. Of these, 116 were found to have primary lung cancer, and 123 were found not to have cancer of any kind. The patients were rated by degree of "neuroticism" and "extraversion." The lung cancer patients were Judged somewhat extraverted and markedly low in neuroticism compared with the non-cancer controls, suggesting that "there is a true relationship between personality and cancer. Comparison of the test results with the smoking histories of the groups showed that contrary to expectations, the smokers did not score as low in neuroticism as the cancer patients. Their scores also differed from those of the non-smokers, but in the opposite direction. Thus, the psychologists conclude, "Lung cancer patients do not appear to be a random selection of cigarette smokers." "Personality in male lung cancer patients." Journal of Psychosomatic Researc~ Apr~l-~une, i9~2. C~ 0 c~ 0 -
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BRIEFS OF SELECTED ,Tuly 196~ Scientific Research Reports (Note.. Requests are frequently received from science writers for references on sub]eds related to research on tobacco and health. The following references are selected from published scientific literature screened regularly by the Research Library of the Tobacco Industry Research Committee. For more details, please consult complete paper.) LUNG CANCER INCREASE -- not related to external factors. The increase in lung cancer incidence in England and Wales between 1911 and 1955 "is strictly comparable to that of tumors of other regions (digestive tract, urinary tract, epidermis, etc.), a fact which does not in any way fit the hypothesis that this increase in lung cancer is related to exogenous etiologic factors, such as tobacco or at~nospheric pollution," reports a French scientist of the Pasteur Institute. Discussing his examination of"demographlc statistics," Dr. Roland de Ruyck says there is "evidence of a viral etiology, a congenital pathogenesis and genetically predetermined epidemiology" for all human cancer. Using statistics on the incidences in England and Wales of malignant tumors from different sites, Dr. de Ruyck also found the following: ..."For the last 50 years the endemic development of tumors (except for the leukemias and Hodgkin's disease) when expressed as the rate per i00,000 shows a progression which is an exponential function of the age of the patients." ..."The curve of endemic increase of cancer of the lung always has shown an exponential phase followed at about the age of 50 by a downward inflection and a decreased incidence which coincides with the beginning of a progressive increase in the incidence of cancer of the prostate. The previously reported inverse relationship between the incidence of cancer of the lung and that of the prostate is revealed in the English statistics, which show in addition that the higher incidence of lung tumors observed in England is offset by a proportionally lower incidence of cancer of the prostate." Dr. de Ruyck said his research gave rise to "the hypothesis that in man oncogenesis is a phenomenon which is concomitant with organogenesis and tissue differentiation." Further, he continued, "at the moment when the embryo has completed its metamorphosis into a Stage I fetus (in the 8th week) tumors which already exist in one or another of the primordial tissue anlagen already at6 following an autonomous course of development, which after a more or less brief clinical phase will cause death only 20 to 80 years later, at which time there may or may not be present various metaplasias. "It was our successfUl.isolation of the choriotropic virus from such metaplaslas, from the very start of our work, which .made the.above hypothesis an admissible one," he wrote. "From the multiplicity of t~unors to the unicity of cancer." C.om~tes.-Rendus des Seances de l'Academie des Sciences, April 9, 1962. o Co.o|es of the full published reports may be obta|ned,/f not ot/)erwbe ovo|lable to you, from: Execut;ve Secrefary, Tobcrcco Indusfry Research Comm~fee, 150 East 42nd St., New York 17, N. Y. OXford 7-9790. co .
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Page WILD MICE -- they develop lots of primarylung cancers. Primary lungcancers.may be the most frequent.~neoplasm in wild house mice and the reason is believed to be hereditary, says a report by two National Cancer Institute scientists. Drs. Howard B. Andervont and Thelma B. l~,nn found a total of 121 tumors in ,98 mice of a colony of 225 necropsied -- 21~ of the tumors were pulmonary, i0% reticulum-cell tumors, 5% each granulosa-cell t~unors of the ovary and hepatomas, and ~ hemangio- endothellomas. The pulmonary tumors, they said, were similar both microscopically and grossly to those occurring in laboratory mice. However, they reported, B/most all the wild mice developed single tumors as contrasted to multiple tumors often found in highly imbred mice such as strain A. "The consensus is that hereditary factors are important, if not predominant, in their occurrence," they wrote. "The most common tumor encountered in genetically heterozygous wild mice may also be controlled largely by hereditary influences." Howard B. Andervont and Thelma B. l~inn Laboratory of Biology and Laboratory of Pathology, National Cancer Institute. "Occurrence of tumors in wild house mice." Journal of the National Cancer Institute, ~y 1962. 3-62 A PHYSICIAN'S ADVICE -- to eliminate cigarettes, white shoes, beer,wives, etc. Writing in a Danish medical Journal, Dr. Stefan Jorgensen has some words of advice for his colleagues. He referred to an editorial in the Journal that said "The physician who is a heavy smoker of cigarettes will inevitably weak@n all official campaigning and information against cigarette smoking. "This implies that the physician should serve as an exemplary model for the people," Dr. Jorgensenwrote. He continued: "Colleagues! Can we not do even more? "Those white cotton shoes with rubber soles, which are so popular in the s1~mmer, cause a hot, marshy climate around and between the toes, favorable for the growth of the fungus epidermophyton. That physician, who wears white cotton shoes, will Inevltablyweaken all official campaigning and information against white cotton shoes and thus against this fungus disease of the foot. "The consumption of beer can produce undesirable conditions. The beer drinking -physician will inevitably weaken all official campaigning and information against beer and thus against headache, delirium and podagra (gout). "The bearing of many children is supposed to increase the risk of cancer of the uterine cervix. The physician who has many children will inevitably weaken all official campaigning and information against that sort of thing and thus against cancer of the uterine cervix. 0 U1 0 ~0
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~-62 Page "If one stands on a chair, one may fall down and break a leg. The physician, who stands on a chair, will inevitably weaken all official campaigning and information against this, and, consequently, against the suffering of a broken leg. -- "When one writes, some very foolish things may appear on paper. The physician who, etc. "Colleagues! Let us by our example contribute to elimination of the misuse, not only of cigarettes, but also of white shoes, beer, wives, chairs and paper." "Thoughts regarding the tobacco report." Letter to the ~ditor, Ugeskrift for lae~er, April 13, 1962. FJLMONARY TB AND LUNG CANCER -- combination being found more frequently. The rising incidence of the combined diseases of lung cancer and pulmonary tuberculosis results from longevity of TB v~ctims, increased diagnostic knowledge, and the occurrence of TB in older persons, says a New York chest specialist. The increased incidence of lung cancer "may also be a reflection of aging Of the total population and better diagnoses," writes Dr. Milton B. Rosenblatt. "The assumption that the increase was due to a carcinogen (tobacco) is not consistent with early studies which show a progressive rise since World War I." At one time it was widely believed that cancer did not occur in lungs infected with tuberculosis. Now, Dr. Rosenblatt said, pathologic studies have revealed a "high degree of correlation between significant calcified tuberculous loci and the site of origin of bronchogenic carcinoma." In previous years, he said, tuberculous patients did not live long enough to reach the cancer age. But with the advent of chemotherapy, more TB patients are living longer. Also, the previous predilection of TB for young adults has been replaced by an increasing rate of infection among older persons. The rise in incidence of lung cancer "still requires clarification," Dr. Rosenblatt said. "The attempts to simplify the problem by attributing the increase to the alleged carcinogenic effects of cigarette smoking leave many questions unanswered. "The rate of increase of bronchogenic carcinoma has changed little since the days of World War I, when cigarette smoking became greatly popularized and the alleged carcinogen could scarcely have had time to exert an effect. Insurance reports between 1917 and 1926 showed that the death rate per i00,000 had increased i00 percent. "Although the number of cases is increasing, the rate of increase Is declining, despite~ the increased consumption of cigarettes," he wrote. "Furthermore, there has been no substantial biologic confirmation of the statistical studies on smoking and cancer; bronchogenic carcinoma has not been produced experimentally by tobacco or its products. "The disease continues to be essentially one of men despite the increased smoking habits of women. Factors such as increased diagnostic acumen and longevity appear to offer a more rational explanation than statistical studies with-questionable conclusions." "Co-existence of lung cancer and pulmonary tuberculosis." Clinic.al Medl.c.ine, June 1962. 0 0 0
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BRIEFS OF SELECTED 1961 Scientific Research Reports ,~et~: R~u~t~ ~m ff~qu~nl~ ~;v~ from ~ience ~e~ for referenc~ on ~b~ ~ ~ ~rch on ~ and h~l~. ~e ~ilo~ng referen~ ore ~le~ from ~ubli~ed ~u~a~ ~ ~e Re~ L~ of the To~ Indufl~ Re~crch Comm~tee. F~ c~h ~plem ~W-) NAJOR LUNG C~J~CER FINDING -- a steady decline in the rate_ of increase. Three National Cancer Institute scientists report there has been a steeAy decl~ne im Che rate of i~crease in lung caacer deaths in Ohm U.S. simce 19~0. If this 1~rem~ coat'_mass, the (l!sease "~II reach a ~eak amomg t~e white male l~lAtloa im the foreseeable f~ture mad then start to decline," Obey sa~. "It is co~mo~ praatice to rock-_ dire predictions of the fu~,re position of camcer of the l, mg as a cause of death 'if present trezds continue'," the scientists say. "An ~--q~ortamt aspect cf present trends in this country, which is genera~ly Ignored, is t.he declining rate of ~ norP.R~e ." AmomK white men, they fo~ "a distinct tcndeacy in tb~ last 3 years (1956~-1958) for rates for those less than 55 years of e_~e tn level off." Among ~hlte ~omem, the yearly rate of ~ncrease has abc~at reached its peak a~1 slx~tld hegira to shov a decllve. Most studies of this type deal with the actual ~mber ~f deaths. The NCI selent!_-ts st~miled the rate of increase for successive periods to see what the__ treads w~re. ~en ~onslderlng trends in death rates: they say, ~thm rate. at which the. disease is rising or fslllng is of equal, im~orzamce to the increase or decrease iu actual rates." Their amal}~Is sbJ)~s that the average raCe of increP.se in lun~ cancer deaths amo=g white ~- has dropped by one-h~ f, from i0 _n~rc~mt to 5 percent, Slmce ~930. ~-br white womsu: the drop ~as f~om 5.6 percent to 2 percent for the as.me ~erlod. Projection of the l~resemt downward trend is speculative, the ~cientists caution, beca~se there ~e "stl I 1 ~ ~y u n~o~s ~~ the ~e ~ ~~ of t~ f~ces re~nslble for t~ re~ ~ncr~ase ~ I,~ c~cer ~i~...Not ~ le~t of t~se ~n~o~ is t~ ~estlon of ~w ~ of %he record~ ~cre~e is genu~e ~d ~ ~ch is ~f~." ~ ~1~rs ~ve no~d t~t "c~n~s ~ ~di~ practice ~ dea~ c~t~i~tlon pro~bly accost for a ~bs~ti~ ~ion of ~ re~ ~-e~e." A/exander G. Gill!am, M.D.*, Benno Milmore, M.D.. and J. W .... am Llo:.~.~ M So, "Trends of m~rtallty attributed to o carclno~u~ of the lung." Cancer, !~6_. ~*~o~" at Jonns Hopkin~ Unl-~er~ity School of ~,-giene and ~ablic ~a!t~ Cop;e: ~f the fM~ .~uSt;s~.¢ ~e~o,'~s m~y b~ obto;eed, ff ,.o~ e~her~;s~ o,oilable ~o y~u, f~: Ex~ Soc~¢tor.~, Tc~c~ l~u~ ~e~'~h C~, ~50 ~a# 42~ SL, ~%'ew York ~7, N. Y. OXford 7-97~.
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Page 2 5o61 b~USE ~ -- Flu virus helps produce ~man-type !uug cancer. A University of S~thern California research team has produced b~n-type lung cancers in mice by exposing them to im_eluenza v~rus smog. It is reported ~o be the first t~e ~m~n epldermoid-type lung csncers have been _~roduced in mice by usin~ a~ents thst are co~on in man' s ~nvirom~.nt. lYr. Dean V. Wiseley made s preliminary report on the continuing study at a recent me~ting of th~ Americ~u ~socittlon for Cancer Reseaxch. ~ scientlste are experimentJng ~tb f~ur groups of b~ mice each. At the time of ~ report, in 38 mice epidermoid changes in the lungs, Inclu4ing caace~s, ha~ occur~s a result of being expose~ to flu virus ~ manufaci~tre~ ~. A second group, expose~ to flu virus alm~ develope~ s~m~ms changes wi~ no aasoclate4 cancers. Mice expose~ to smog alone Tim ~rk ~e~n more than tn~ yea~s s~o to test the theo~ ~hat viral infections might be a factor in h~man lung cancer. I)ea~ V. Wiseley, Paul Ko~in, Pa~sy R. Fowler an~ Jagdish Trivedi. "T~e cc~abiue~ effec~ of zIpeate~ viral infection an~ exposure to carcinogenic aerosols on lmAlmonarytr~r Luducticn in C57 Bls~kMice." Proceedings of th~ American Association for Cancer Fesearch, ~arch 1961. ~ D~EASE I~ ~ -- they alsc get it. Even ~og~ g~t cardiovascui~r disee~e. This is disclosed in a study of 3,00C dogs of a3~ ages and both sexes by four veterinarians at the Unlvmrslty of Penmsylvanla's School of Veterinary Me~Ic~-~. Cliuical an~ autopsy studies sho~ signs of disease in 290 dog~ an a~tiomal 322 animals had signs ~gestlr~ heart ~st c~maon tvpe~ of heart disease found ~re chronic fibrosis, my~cardlal disease, ~ congenlt~i heart disease. q~ study, which is contSm~ng, did not come up wlthany breed, dietary or emvironm=n~a! f-_=tor~ upon ~ich ~ base an epi~,~ological su~-c~. T~e researc~rs did f~nd that chronic congestive heart failure ~ae 2~ times more ~requent inmate dogs than in females. D.K. Det~eiler, V.MoD., D.F. P~tterson, D.V.M., K. Eubber-, V.M.D., and R.P. Botts, D.V.M., M.P.H. "Tho prev~ience of spontaneously occurring cardio~-scular disease ~ do~s." American Jo.~rnal o.f Pu[olic Health, !9~i (Support credited: ~ation~l Institute_ )
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BRIEFS OF SELECTED June ~961 Scientific Research Reports (Note: Reque~ am frequently recelve~ from ~c~en~ wrffer~ for refe~encet on lub~'~ red.ted to ~e:~orch on t~bocco and heohb. The fo|low|ng referenc,~ ar~ ~elected from published scientific Ifferoture :creened regularly by t'~ Re,~,~rc~ iJbrory of the Tobacco ~ndu~'lry Re~crch Comm~. For ,,~re det~;|s, please co,~vlt coral,let, pop.r.) MAJOR LUNG CANCER FINDING -- a sternly decline in the rate of increase. Three ~atioual Cancer Instiimte scientists report th~ere has been a stem~y dee/Cue is the rate of increase im lung c~ncer deaths Is the U.S. since 1930. If this trend continues, the disease "w~11 reach a pea~ among the white male I~Im/atiom im the foreseeable future ~ud then start to ~ecl/ue,~ they ssT. "It is ~a I~actice to make (Li.re predictions of the :h'p,u'e positioz of caacer of the lung as a cause of death ' if present trends continue'," she scientists say. "An important aspect of present trends in this country, ~hich is generally ignored, is the declining rate of Increase." ?~h~ vb.ite m~a, they found "a distinct tendency in the last 3 years (19~6-19~8) for rates for those less than 55 years of e~ to level off-." Among white -~ome.-, th= z~ar!y rate of ~nerease has a~nout reazhed its peak and should begi~ to s~-." a decline. !~st studies of this tlnpe deal ~Ith the aa1~al number of d~atbs. ~e NCI sclent!s~ s~di~ t~ r~ of ~cre~e for ~cce~sive lmrlc~ ~ ~e ~t ~ ~n~ %~. W~n con,ider~n~ tre~s ~n dea~ rates, ~y ~, "t~ ra~ a~ which t~ disease is rls~ or ~a~i~ is of e~.~ ~~e ~ t~ Incra~ or decre~e ~ zc~A~ ra~s." Their ---]ysls shows that ~ av~ra~ rate of increase tu lung cancer deaths s~ whi~e men h~ drol~ by one-half, frcm iO nerceat to 5 p~rceat, si~c~ 19~0. For wh4te women, the drop -~-s .fknmm 5.6 percent to ~ percent for the same period. ProJectioa of the present downward trend is speculative, the scientists ca~tiom, because there are "st~11 too maayu~-L~no~ms .~arroundln~ the nature ~ =aga/.~ade of the forces responsible for the recorded in<rease in lung cancer mortality...Not the least of these ~knowas is the question of hov ~ca of the recorded increase is genuine and how much i~ artefact." ~ imvesti~tors have no%~l that "changes in medical practice and death certification probably account for a substantial portion of the recorded increase." Alexander G. G~lliam, M.D.*, Benno K. M~Imore, M.D.: sm.d J. William Lloyd, M.Sc. "'fr~ds of mortality attributed to o _" ....!n_ma of the lung." Canc~c~ i.~=v-j~hn=_ ~61 (*No~ &t Johns Hopkins U_l,~_slty School of Hygiene and .~blic Kealth~ Baltim~e) 5~r,~luq,', Tob,.c~co I.dv:hg" ~,sec, rch C,>mm;/'tea, )~) Ear/ 42-d S:t., ~ew "ore 17, .N. Y. OXi~.'-d 7-9790.
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Page 2 MOUSE ~ -- Flu virus helps produce human-type lung cancer. A University of Southern California research team ha~ produced hum~-~pe lung cancers i~ mice by exposing t~m to influenza yr.--us and smog. It is re~ort-_d to b~ the first time ~uman epidermoid-type lung cancers have bee~ produced in mice by using agents that s~-e common in ~s Dr. Dean V. ~iseley made a prel~mln~ry report ou the continuing at a recent ~eti~ of v~ Am~rlcan Association for Cancer Research. ~h~ scientists are experimenting with four ~roups of ~00 mice each. At the time of ~ re~or~, la 38 mice epldermold chaz~s in inclu~i~ cancers, ha~ occ~as a renault of being exposed to flu virus sz~ =~ s~og. A seco~ group, exposed t~ flu virus aloe, ~evelolm~ s~ eba~$ ~I~ ~o associated cancers. Mice exposer ~ smog alo~ ~evelo~ a~ cancers. The ~ork be~a~ more tha~ t~ ~ars a~ t~ test th~ theory that viral i~fectioms mi~ ~e a factor in h~man lu~ cancer. Dean V. Wiseley, Paul Kotin, Patsy R. Fowler ~ Jagd!sh Triredi. "TI cc~bine~ e~ct of re~a~ vir~ i~ectio~ ~ ~e ~ c~c~o~nic ~roso~ on ~nary ~ l~uction ~ C~7 ~ack Mi~." o~ ~ ~rlc~ ~sociation ~cr ~c~r ~se~ch, ~ch 1961. ~ART DISEASE IN DO~ -- they also ~et it. Even dogs gmt c~iovascular disease. This is ~Isclose~ la a study of 3,000 ~ogs of all ages and bo~h sexes by fo~,r veterinarians at the University ~Pennsylvss~ia's School of V=+~rinmry Medicine. Clinical and autopsy s~dies sho,.~l si~s of hear~ disease i~ 2~O ~ en a~d~tional ~2~ am~m~ s b~ signs suggesting heart disease. Most ~ types of heart i!sease found were chr~ic valvular fibrosis, myocardial disease, and congsnital heart disease. Th~ sty, ~i~ich is continui~_~%, did not come up with ~y breed, di~ts~y or e~vironmental factors upon which to base s~ epid~m~ological survey. ~S~ resear-b~rs did find that chronic congestive heart failure -was 2~ times more frequent in ~e dogs than in fem~l es. D.K. De,.miler, V.M.D., D.F. Patterson, D.V.M., K. Eubbern, V.M.D., and R.P. Bo~s, D.¥.M., M.P.H, "The prevalence of spontaneously occu~ng cardiovascular disease in do.~s." American Journal of Public Health, Februaa-# ~6~ [~uLrport credited: National Heart Institute )
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BRIEFS OF SELECTED Scientific Research Reports (Norm i~quests are frequently received from ~ence wrlten for referenc~ on suk~ re~m~ t~ r~arch on ~ and ~ ~ f~ refere~es are s~le~ f~om publi~ ~n~i~ i~ ~r~ ~y ~ ~e ~ ~ of the To.co ~ndu~ Re~rch Comm~e. F~ more det~i:s, pl~ ~ ~pl~ ~.) 1-61 SMCKIMG AND KF2uSTII -- tobacco called zest auctent tranquilizer. "O~e of %be present day problP~s is to determine whether the possible deleterious effect of smo~In~ oa ~he hear% and blood vessels uutw=i~)~ its s%abillz~ng effects ~psychic a~d emotional processes," says Dr. Carl J. Wl~er~ of Clewela~'s Frsak E. Bu~ts Educational Institute. Dr. Wlggezs' views are contained in the introduction to a 3bb-page r.cno~b. ~ ~ "~_-~i~..s_m~!.~ ~!~ect.~ nf Nic~Ine ~6 ~i~" ~bl!shed by ~e N~ Y~ ~~ of Sci~ce~. ~e said "tobacco is probably the most ancient tranqui!izin~ a~ent fn co~oause...~ a~Ino~ed ~bat "sll tranquilizing dru~s have certain side effects, q'oese m~y be beneficial, Indifferent, or undesirable." "It ~ay be ne-~ssary to re~-~se our current attired=" on ~he~her or not nicotine has a tberapeut!c vaiue~ said Dr. W!~ers, a~er =otir~ tha~ ~harmacolo~ %extbo~s say nlcotine is of no therapeutic value has only toxicological interest. (~ co~py Of ~e mon~raph is enclosed.) Annals of the N~w York Acadea4 of Selences, Sept. 27, !~60'. "~ardlo~asc,-la~ effects of nlco~ine and smoking." TBAND LL~G CANCER -- they oec%u- in the same patient. After s~Im~more tha~oO0 autopsies for evidence of t~erculosis, a Chi~a~o doctor says: ~Ome of the strlkin~ observations in this 5tudy v~s the large ~ of i)atientz Imvhcmmaligrm~t tamors were discovered in addltlomtotbe t~berculous infections." Dr. J. Robert Tbc~son of Chicago's Municipal q~aberculosls 3anitar~',m reposed hhat 89 of ~he patients over 70 years old showed evidence of ~u3mo~ary tuberc~alosis. Many of the 89 TBpatients also showed evidence of other diseases, IneludlnK hardenin~ of the kidney arteries and hepatitis. "Of greatesz significance was -hhe fact that some 33 patients also had cancer" -- !5 of them iung cancer. .~.~'.J~c,')', Io~o~:¢o tP~..xxt-,I R~reorcF~ Ccmmk'te~, i50 Ea~ 42rid St., N~,~ Y~>rj: !2: ,'4. Y. OX;or~
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Page 2 Dr. Thompson also said "there is definite evidence that the cancer ~c~aally In%~de -~lled-off or qniescent tuberculous foe! and re~cti'~~te 3-,.6~ MANAG~4ENT OF DISEASE -- what is tobacco's role? Thz role of tobacco as a possible cause of disease "is o~st as obscure to~ as, ~ay, a cen~Ar~ ago," acco~ ~ t~ee scientls~ at ~e MeScal ~lle~e of ~Ir~ni~, ~n ~c~. There are a "few" exceptloms, the scientists say, "of which the most u~equlvoc~l is ~obacco aL!erEy." Hot'ever, "a survey of a considerable ~mple of the clinical tobacco literature of +-h~c p~zt 50 yc°~--~ ~ revealed a significant ch~---~~- in Ol:>~nl~ reg~rdlng the place of to.hacco in ~he m~n~gement of ce-~J~n diseases. ~s latter is inde.nende~t of spe~_ulation or opinion re~srdi~ tobacco etiology..." ~%e scientists also said "There h~ long existed the r-~'[~z~[on %~h~t, so far as the smoldn4~ p atlent or person is ~ce~, ~e ~st all~ for a ~e bet~ ~e 'psy~z' b~neflt derived ~ s~ki~, ~d its '~slcal' ~..." The b~ik of +.he a_~tic!e I.~ 4evoted to a d/scussion of ~cb~-c"o's role i~ the ~~ of -.~ious ~ sea~es, i~ ~nich the ~est~ ~n of u~i~ ~r not ~i~ ~cc ~ ~ stu~ed. L~rsen, ~ul S., Ph.D., ~aa~, ~ar~'eyB., M.D., and Sl!vette, Herbert, ~h.D., ",C~-~aging con- cepts of the role of to~-cco im the =mna&ement of disease." American Journal of +~e Medical Sciences, ~ovemoer 1960'.' "(Support credited: Tobacco Industry Eeseareh O0~mzittee)
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BRIEFS OF SELECTED Scientific Research Re or#s Janm~.ry 1961 I ~NotI: ~'X~um (~rl .:~.~enfly r~eived from ~nce ~n~,~ for ref~.rence, on ~ub~c~ rel~--~@ t-~ re,earth on k:~c¢~ on~ heeJt~. Th~ ~cllowing re~erence~ ore ~elected ~'o.'~1 publlshe~ ~]¢,-1f~,c I~'atu~ ~cree:ted re~uJon~ by t,~e Re~ear~h L~rQry of 1he Tob~co Induslry Re~egrch Commi~lee. For .r~re de 1-6i 2 -61 SMOKING AND KEALTH -- tobacco cslled most ~ncient tra~nqui!izer. "One of the present day problems is to determine whether the possible deleterloDs effect of smoki~ o~ the heart and blood vessels outweighs its stabilizing effects ompsychic and emotional processes," says Dr. Carl J. W~ers Of Cleveland's Fran~ E. Bunt= Educational Institute. D~. W~ers' v~ews are contained in the introduction %o a 3~-~e ~no~e~h ~ ~e "~~s~ E~ts of Nicotine ~ ~6" by ~e ~ ~o~ ~ of Sci~ces. He said "tobacco is probably the most ancient tranquilizing agent in c~ use..." and noted ~t "all tr~nquilizin~ dr~gs ha~ certain side effects. T~ese m~y be benefic£al, indifferent, or undesirable." "It may be necessary to revise ~ar current attitude" on whether or not nicotine has a therapeutic Yalue, said Dr. Wigger~, after n~ing ~h~t pharmacology textbock~ say micotlme is of no therapeutic value and _h~s o~uly toxicological interest. (A capy of the monograph is Ann~ir of the New York Acade_~v cf Sciences, Sept. 27, i960. ':Cazct!ov~_sc-.,iar effects of nicotine ~nd smokia~." TB fJ~DLL~G C2u~'CE~ -- they occur in tb~ s~me patient. Aftez studying more than 800 autopsies for evidence of tuberculosis, a C>--~cago doctor says: "One oft he striking obser'~tions in this study ~as the large number of patlents imwhomm~liEnsn% tumors vere discovered in addition to the tuberculous Infectio~s." Dr. J. Robert. Tncmpson of Chicago's Municipal Tuberculosis -Sanitarium reported that 89 of the patients over 70 years old showed evidence of pulmonary tuber_~a!osis. M;~uy of the 89 TB patients also sho~red evidence of other diseases, includlngharden~ of the kidney arteries and hepatitis. "Of ~reates% significance w~s the fact that some 33 p~tients also had cancer" -- 15 of them ~n~=. cancer. ..~,o'e~:a.9,-, Tob~-~co h-d~....s_~ Rc~,.~rch C@,'am~e.c, LSO Ec'e. 42rid 5t.~ New Y~ 17, t4. f. O..Y.fo.~ 7-979'0. 0
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P~_.~e 2 Dr. Thompson also said 'there is ~elinl~e evidence ~n~% Lne cancer csz~ ~ctua!]y Is~de ~ed-off cr quiescent, tuberculous fezi ::nd ~ eaetlw~.te the ~sed." ~meri c~n Diseases, November 3-61 M&NAC, L~UE~f OF DISEASE -- w.~mt ts t.obacc9's role? The role of %obs~co as a possible cause of d~sease "'~,.s just as obscure %od~y as, ~y, ~ :~ a~,~' accordi~ to t~ee scientists at ~e Me~c~l ~llege of Vir~a, ~ Riced, There are a "few" exceqD~icns, the scientists say, "of vhlch the most uneq,,ivocal is tobacco aller~D'." However, "a ~urvey of a considerable sample of the c !n_'_ca~ tobacco literature of the lm~st ~ years has r~vealed a si~ificsn% chicle in oninlon re~ ~e piece of ~-b~--~- :n the ~na~ement ~ ce~,ain ai~=~'ses ~is latter Is inde~ndent of soezulat~un_ or opi.,ion r-ms"" ..... "~''-5 t~bst:o etlo]~..." The sol.fists elso said "'.--.uere P~s long cxiste~ for ~ br, lante b~t~e~ ~e 'psychic' benefit derived ~ne bulk of the az-t]cle is ..-=,.o,ed to a discuss!. , _-.f t~baezc's role in ~he ~n~g~mte~it Of v~r~o"~ &$.~eases, iu ",~ioh thu c"~t~:',' of usln~ or nc~ u&~nS ~eo h~ been studied. Laz-son, Paul S., ~h.D., Haag, 5~_~..ey 3., M.D., a~d Silve~:e, Herbert, Ph.D., "C-~ng~n~ coa- ce?ts of the role of tobacco in .~£ze rar~ement of dlsease." American Jotur.~i of the Medical Sciences, November ~-PJoO. (Suppo,~t credited: Tobacco Ind.~try Research Co~___ittee)
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BRIEF.S OF SELECTED September 1960 ' Scientific Research Reports (Note: Requests are frequently rece|ved from sc|ence wr|ters for references on subjects related to research on tobacco and health. The following references are selected from published scientific literature screened regularly by the Research Library of the Tobacco Industry Research Committee. For more details, please consult complete paper.) AIR POLLUTION (It seems major factor in lung cancer, says researcher) Lung cancer appears to be due to environmental factors like "the air we breathe," a researcher told a world meeting of chest experts in Vienna. In doing his study on air pollution and lung cancer in South Africa, Dr. Geoffrey Dean told the meeting, he investigated many factors, including the cigarette consumption of lung cancer patients and a control population. Of the lung cancer patients, 89 percent smoked an average of 31.7 ciga- rettes a day, he said, and of the controls, ~79 percent smoked 25.2 a day. "Not a very big difference," Dr. Dean said in reporting to the 6th International Congress on Diseases of the Chest of the American College of Chest Physicians. He said a higher percentage of the lung cancer patients in his study "had a past history of bronchitis" and that on the average they "tended to ~rinkmore heavily" than those who died from other causes. For the last 40 years the white South African has smoked much more heavily than the British and yet the lung cancer rate amongst the South Afrlcan-born is less than half the rate in Britain," he said. "British ~mml- grants to South Africa, however, who smoked less than the South Afrlcanbefore they arrived in the country and smoked about the same amount when they reached the South African cities, hs~ a much higher rate than the South African-born. "In South Africa the lung cancer rate even for the South Africau-born was very high in one~city~ l~rban, where air pollution was a particularly serious problem. Among the South African-born who died from lung cancer a- higher percentage h~l visited Brltain thau those who died from other cs~ses. Those immigrants who emigrated to South Africa at a later age died on average at an early age than those who emigrated younger. "In my opinion lung cancer would appear to be due to e~vironmental factors -- the air we breathe," Dr. Dean said. "This is affected by our social environment, whether it is urban or rural, the humidity~ etc., and by a personal factor, whether or not we smoke. There maywell be a s1~mmation effect. "This research suggests that too much emphasis has been placed on clga- rette smoking as a possible bronchial irritant and that pollutedurban air such as occurs in Britain and Durbanmakes a major contribution to the rapidly ris- ing incidence of lung cancer." Dean, Geoffrey, M.D. "Air pollution and lung cancer -- a South Afrlcan study." Paper given at 6th International Congress on Diseases of the Chest of the American College of Chest Physicians, Vienna, Austria, August 31, 1960. Copies of the full published reporls may be obfained, if nor oth~rwlse available to you, from~ Execufive Secrefary, Tobacco Indusfry Research Cornrn/ffee, 150 Easf 42nd St., New York 17, N. Y. OXford 7-9790. ul
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• (COPY of paper given August 31, 1960 at 6th International Congress on Diseases of the Chest of the American College of Chest Physicians, Vienna, Austria) GEOFFREY DEAN, M.D., M.R.C.P. (Lond.) Physician 601, Oasin Internist 69, Pearson Street Telephone 27854 Port Elizabeth Residence 31937 AIR POLLUTION AND LUNG CANCER - A SOUTH AFRICAN S~JDY. In 1947 1 emigrated from Liverpool where bronchial carcinoma was co, on and settled in Port Elizabeth in the Eastern Cape. South Africa has a white population of ~just over three million and they receive a high level of medical attention from South Africa's 8,000 doctors. I was surprised in my practice • in Port Elizabeth to find that lung cancer was very unco~non although cigarettes ~.~re cheap and most men appeared to be heavy smokers. Indeed statistics of cigarette consumption show that the white South African has been by far the heaviest cigarette smoker in the world for many years. In view of the reports stating that cigarette and lung cancer were associated I felt that the lung cancer mortality among South Africans was particularly worthy of close investigation. I therefore, studied the death certificates at the Buresn of Census for lung cancer deaths for the ten year period 1947 to 1956. I found that during this period the incidence of lung cancer in men had doubled but there had been very little increase in lung cancer incidence in women. I also found to my surprise that the incidence of lung cancer was very common among immigrants from Britain, although it did not appear to be in- creased amongst immigrants from other countries. I will now show a series of slides which depict the results of my analysis of the lung cancer deaths. The first slide sho~m the lung cancer rates for white South Africans from 1947 to 1956 : as it can be seen the ......
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-2- the lung cancer rate doubles during the ten year perio~ in men but there is very little increase in the lung cancer rate in women. This suggests that the lung cancer increase is a genuine increase and is not due to improved diagnostic facilities. (2) This slide compares the lung cancer rates for the Union-born British immigrants and other immigrants with the rate in England and Wales. It can be seen that the rate for British ~igrants is much hi~her than the rate for Unlon-born and for other immigrants. Most of the British ~migrants settle in the cities and the next slide shows the comparison between the different cities. (3) In each of the five cities, in the other urban areas and in the rural areas the lung cancer rate amongst British immigrants, aged ~5 to 6~ years, is very much higher than the rate for the South African-born. For other ~-~Igrants, however, it is much the same as the South African-born. You w~1 ] notice that Durban has a very high lung cancer rate even for the South African-born and that for the British ~-~Igrants in Durban the lung cancer rate is actually higher than the rate in Britain. (~) The actual lung cancer death rate for British immigrants is much greater than the expected death rate and the probability of this being caused by chance is less one in a m~ ] "~ ion.
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-3- (5) For other immigrants the actual lung cancer incidence is much the same as the expected incidence, quite unlike the British immigrants. (6) This is a comparison of cigarette consumption for adult white South Africans with the United States, Ireland and the United Kingdom from 1920 to 1955. Throughout this time the cigarette consumption for white South Africans was much hi~her than in any other country. • (7) Air pollution in South Africa has increased very rapidly in the last 20 years and in Durban it now compares with Kensington and St. Pancras in London. The results of the first part of this study were reported in the British Medical Journal last year and they can be summarized in this way. Although white South African men smoke much more than the men in Britain the incidence of lung cancer in South Africa is less than half the British rate. However, the British immigrants in South Africa have a lung cancer rate which is ~% higher than the South African-born rate. A much higher rate in British.immigrants occurs, in each of the five large cities, the other urban areas and rural areas. In South Africa there is a much higher lung cancer rate in Durban, which has the most serious air pollution problem .than in the other cities. In this city the lung cancer rate reaches a level of more than one in six of all deaths, aged ~5 to 6~ years, in British ......
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British Immigrants by 1956. Having completed the first part of this research I then proceeded to trace the widows of the lung cancer patients in order to discover the habits of their late husband~. I also studied a grou~ of~ controls, men who died in the same age and urbanization groups but not from lung cancer, and chose for the purpose the next man in the right group in the death certificate books. (8) ~ of the widows of the lung cancer patients were found and this slide sh~ws the report of cigarette consumption of their late husbands which corresponds very well with their own estimates of their cigarette con- sumption on their case recor~!s. It can be seen that 89~ smoked an average of 31.7 cigarettes a day. (9) This can be compared with the controls where 79~ smoked an average of 25.2 cigarettes a day: that is to say that i0~ more of the lung cancer patients smoked than the controls and the lung cancer patients who smoked smoked~ on average~ six cigarettes more a day than the controls;- not a very big difference. (i0) This slide shows that the men who died from lung canc~ h~1 ~high~r percentage of heavy smokers than the controls but that there was no significant difference in the smoking habits of the South Afrlcan-born and the United Kingdom- born although the U.K.-born ha~ a much higher lung cancer rate. The widows of m~ny of the Unlted-born said that their husband's ha~ ...... 0
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had s~oked less before they ca~e to South Africa and that they had then increased their cigarette consumption to South African levels. (ii) This slide shows that a higher percentage of the lung cancer patients had a past history of bronchitis th~ those who died from other causes. (12) The lung cancer patients on average tended to drink ~ore heavily than those who died from other causes. (13) I~ of the South African-born who died of lung cancer had spent an average of ~.3 years in the United Kingdom and only 8~ of the South African-born who did not die of lung cancer but died from other causes had visited the United Kingdom. (i~) The British ~,,~igrants who died at an early age, between ~5 and 5~ years, emigrated to South Africa at a late average a~e of 30; whereas the ~rltish l,~igrants who died at the later age~ ~ to 64 years, e~igrated at an earlier age of 2~ years. A~on£ the British ~-~igrants who did not die of lung cancer this difference was not seen. To summarize: For the last forty years the white South African has smoke& much ~ore heavily than the British and yet the lung caner rate a~ongst the South African-born is less than half the rate in Britain. British ~,~igrants to South Africa~ however, who smoked less than the South African before they arrived in the country and s~oked about the sa~e a~ount when they ..... .
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-6- they reached the South African clties~ had a ~uch. higher rate tb~n the South Afrlcan-born. In South Africa the lung cancer rate even for the South African-born was ver~ high in one clty~ Durban~ where air pollution was a particularly serious problem. A~ong the South African-born who died from lung cancer a higher percentage had vlsited Br~tain than those who died from other causes. Those In~igrants who e~igrated to South Africa at a later age died on average at an early age than those who emigrated ~unger. In my opinion lung cancer would appear to be due to environmental factors - the air we breathe. This is affected by our social envlron~ent~ whether it is urban or rural~ the humidity etc., and by a personal factor~ whether or not we s~oke. There may well be a sum~atlon effect. This • research suggests that too much e~phasls has been placed on cigarette s~oklng as a possible bronchial irritant and that polluted urban air such as occurs in Britain and in Durban • ma~e a major contribution to the rapidly..rising incidence of lung cancer. Geoffrey Dean~ M.D., M.R.C.P., Senior Honorary Physiclan~ Eastern Cape Provincial Hospital~ Port Ellzabeth~ SOUTH AFRICA.
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HII, I~ a~D KNO'~L'I'ON, INc. ; Confidential for Members No. 33-60 INFORMATIONAL MEMORANDUM August 30, 1960 Re: "Briefs of Selected Scientific Research Reports" Attached is a copy of a new service being sent primarily to science writers and editors throughout the country. It is intended to bring to their attention, and thereby stimulate press treatment, often-overlooked articles in the medical and scientific literature deallngwith re- search on tobacco and health and related subjects. No regular schedule is planned for distribution of these "Briefs." They wlll be sent out whenever appropriate material is available. Hill and Knowlton, Inc. Public Relations Counsel 150 East Forty-second Street New York 17, N.Y. cc: Tobacco Institute and TIRC Members Public Relations Representatives
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BRIEFS OF SELECTED Scientific Research Reports (Note: Requests are frequently received ~from science writers for references on subjects related to research on tobacco and health. The following references are selected from published scientific literature screened regularly by the Research Library of the Tobacco Industry Research Committee. For more cletails, ple,ase consult complete paper.) 1-60 "SMOKING" MICE (No lung cancers developed) Four scientists report that mice exposed to cigarette smoke daily for periods of one month to almost two years show "extreme variability" of response, indicating the possibility of a virus influence that is being further studied. No lung cancers developed in the animals, they reported. The researchers said "the wide spectrum of findings and the independence of dose and duration of exposure to cigarette smoke would seem to detract from the importance of cigarette smoke as an injurious a~ent invariably affect.lng the major bronchi and would, rather, point to contributing factors characteristic for the individual animals." There may be elements in the host that render the tissue suscep- tible to alteration from exposure to the smoke, they said, noting that "viruses deserve special consideration, the more so since they occur with a certain frequency in mice and are capable of producing respiratory lesions." " They said they now are doing research in two areas : the detection of latent viruses in mice prior to exposure of cigarette smoke, and the effect of exposure to virus in addition to exposure to cigarette smoke. They conclude their report with these observations: "i. Regard/ess of dose or time-of exposure to .cigarette smoke, there was extreme variability of response from mouse to mouse, ranging from 'no. alterations' to bronchitis associated with atypical epithelial proliferation. "2. No relationship between severity or frequency of bronchial lesions and dose or time of exposure to cigarette smoke was found. "3. There was an absence of invasive bronchogenlc carcinoma in mice exposed to cigarette smoke, even in those that had nearly life span exposure. "~. There was a decrease in the frequency of bronchial lesions, suggesting reversibility, after cessation of exposure. Cop;es of the full published reporfs may be obta;ned, if not otherwise available fo you, from: Executive Secrelary, Tobocco Industry Research Comm~ee, 150 East 42nd St., New York 17, N. Y. OXford 7-9790. o u~ o
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Page "5. An early increase of intranuclearprotein (before microscopic alterations) was followed by a gradual increase of deoxyribonucleic acid (DNA) content. "6. There was a retn~rn-to normal intranuclear protein and DNA content, suggesting reversibility of cytochemical ,! changes after cessation of exposure. Leuchtenberger, Cecilie, Ph.D., Leuchtenberger, Rudolph, Ph.D., Zebrun, William, Ph.D., and Shaffer, Patricia. "A correlated histological, cytological, and cytochemical study of the tracheobronchial tree and lungs of mice exposed to cigarette smoke." Cancer, Vol. iS, No. ~, J~ly-August 1960, Pp. 721-732. (~uppo~ credited: Tobacco Industry Research Committee) ~-.~ ARSENIC (No experimental evidence of a role in lung cancer) No experimental evidence has shown an association, between arsenic in cigarette tobacco and the increased frequency of lung cancer, say three scientists of Harvard Medical School. Speculation concerning an association has received "wide and deplor- able publicity," wrote Drs. B. L. Vallee, D. D. Ulmer, and W. E. C. Wacker in a review of literature on arsenic and health. "It is particularly important, therefore, to point out that at present these conjectures lack any experimental basis whatsoever~" they said. "Attempts to induce cancer by painting the Bkinof experimental animals with arsenical solutions have been largely negative and an increase .of the arsenic content of cigarettes has failed to influence the development of lung tumors in albino mice," they reported. "In su~ry, the production of arsenical cancer in mice has never been satisfactorily demonstrated." They said that arsenic is found everywhere in nature, and in various forms it has numerous industrial and medicinal uses. Soils may vary in content from fractions of a part per million (ppm) to as much as ~0ppm. Low concentrations are present in volcanic gas, in spring and seawater, and in all animal tissues and fluids. Vallee, Ulmer, Wacker. "Arsenic toxicology and bio- chemistry." AMA Archives of Industrial Health, Vol. 21, Pp. 132-151, Feb., 1960. (~pport credited: None) 0 t~
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CHOLESTEROL (Cleveland specialists measure it in smokers) Cigarette smoking had no effect on the serum cholesterol aud lipoproteln concentrations of 20persons tested by Dr. Irvine H. Page, Cleveland, 0., heart specialist, and two associates. They reported a te~twith 15 smokers and 5 non-smokers. The rapid smoking of two non-filter-tlp cigarettes had no effect in modifying serum cholesterol or lipoprotein levels, they said. The experiment was undertaken, they said, because it had been sug- gested that cigarette smoking is in some way causally related tomyocardlal infarction and coronary atherosclerosis. "This is diffi~alt toprove," theywrote. "Many investigators believe that the evidence is good forthe association of hypercholesterem~a and accelerated atherogenesis. If it could be shown that cigarette smoking is followed by a rise inserumcholesterol level, this could be interpreted as evidence in favor of a relationship of smokingand atherogenesis." Page, Irvine H., M.D., Lewis, Lena A., Ph.D., Moinuddin, Mohammed, Ph.D. "Effect of cigarette smoking on serum cholesterol and lipoprotein concentrations." Journal of the American Medical Association, Pp. 1500-1502, Nov. 1959. (S~pportcredited: None) ~MOKING BY TWINS (Like and unlike, depending on kind of twin) A significantly greater concordance was found within pairs ~f iden- tical (like) twins than within fraternal (unlike) twins with respectto amount of tobacco smoked, type of tobacco used andform of smoking, reports a Danish researcher!nastudy of 894 pairs_oftwins bornin Denmark between 1870 and 1910. Age, sex and residence are factors affecting these concordances, ~says Elisabeth Raaschou-Nielsen of the Instigate of Human Genetics, University of Copenhagen. "Thus both genetic aud environmental factors play a part in forming the smoking habits of the individual .... ," she says. "Attempts have been made to investigate a possible constitutional association between regular smoking and certain diseases. The number of affected twins is too small to permit any conclusion." She said findings similar to hers also have been reported by ~ir Ronald A. Fisher and L. Friberg et al. Raaschou-Nielsen, Elisabeth. :'Smoking habits in twins." Danish Medical Bulletin, Vol. 7, PP. 82-88, June 1960. ~pport credited: U. S. Public Health Service) t~ 0 0 Oo t@
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¥OR: that" ~e general~ not based on complete ~8 acetate ~o£entifie ~ovZ- e~e~ ~. Robe~ C. ~ckett~ as~cia~ s0ientifie ~ree~r of the ~ust~ Rese~ch ~ttee said ~. "~t ~s been ~o~ for ~eneratto~ t~t ~kln~ sll~ht~ the p~se ra~ to ~ve a ll~ that ~ ~rsons fAn~ help~ in ~ett~ the de~s of in~nse ~e~ livi~" he ~ld the ~ ~ett~ o~ the ~erlo~ ~llege of ~gtolo~. "~t beyond t~s, little ls es~blls~ scientiftcal~ about to~oeo effects on the he~." '~oba~co use has been ~th a~pla~e~ ~d oon~e~ for ~thout much ~et~ ~o~ a~ut its" ~. ~ockett s~Id. "It has ~en a solos of rel~ation ~ enJo~ent to ~i~ ~ even has been as kt~i~ v~tous h~ bacteria. "Xt ~so h~ ~en ch~ged ~th le~ ~ Ins~lty~ ~gesti~ • terillty, ~tenee~ ~ess, ~ a ~st o~ other slants. It ie that e~e~ scientific investigation shoed replace £o~lore ~ tion In such ~tters. '~he Tobac~ ~dustry Rese~ch ~t~e Is sup~rti~ solentlfi¢ ~nve~ti~ation into ~ phases of ~acco ~se ~ h~ heath ~ O~er.. .' ~ get t~ fa~ts~" ~. Hocket~ ~t~. "~e ~e not atte~tt~ ~ ~ or . ~s~rove ~y ~ttc~ ch~e~ bu~ ~sh on~ ~ g~n ~ seignti~e W
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~e said cOns/derable research is currently, belnS sponsored in~ such su~ects ~ ~ the e~ects o~ to.co ~kl~ on ~ ~t ~d vessels o~ llv/n~ vol~er~ the tnfl~nce o~ :~nE on the bl~ flov of the skin ~d Cf the musele~ o~ the ~ extre~tiesj ~ the ~nt o~ corona~ bled ~v ~n h~s ~fo~ ~ ~r ~he intravenous injection o~ nicottne~ ~ ~r s~ki~ ~e said the C~tee ~s so ~ ap~ved ~ s doll.s In rese~ch ~ts rec~e~ b~ its 8alentitle ~vls~ ~ ~e to iude~ndent scientists a~ le~i~ ~spit~s ~d t~o~out the co~tr~. ~, H~kett said a pr~ objective o~ the Sc~ti~io A~vAso~ ~d: ~£eh develops ~ ~ots the ~se~ch pro~'~ for the Is to ~ther the se~h ~or the cs~e or c~ses o£ o~cer~ 1~ e~ce~, ~ of e~ov~ ~es~ ~d f~ the control of these diseases. Attention ~so ~e given~ he ea~d~ to rese~ch ~ro~eo~s t~t ~d ~ the ~erst~n~ ~ tob~c~ s~ke ~ tie ~stltuents: '~d ~co use by ~op~e. ~. ~ckett said the ScientiSt ~dv£so~ ~& ~ra~s ~hout h£u~oe or i~uence £n dec£din~ ~d d~ot~ t~ ~ avenues of se~oh. ~so, he ~1~ the seleDtlsts ~o ~eive re~ch ~ts do the~ ~rk in c~le~ .~eedom. "~o~ess ~11 ~e slow ~ ~ie~," he sald~ ~ut there t8 eve~ rea~n to exact ~ke4 a~v~¢e8 eventually t~ the ~reventton, trea~ent ~d c~e o~ the v~Aou8 cOnstitu~ion~ diseases ~leh ~e ~eatest present ~ ~t~e health -oo
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o o o
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co~uzer by ~!yiug ~.t ~uch lit~in~ ~:.~ ~ ~ig~fic~c¢ to him -- ~.n~ ~rhc~,~ ~Y mi~-l¢~-!im£ him, c~ ~-oul~ ~v¢ l~.cn ~one ~y ~.~ J~t c~te~ con~cra~£ r.lcotimic ~ci~. A ~.imil~r di~cr~-Ice ~ild ~e r~ndcre~ by ~..ng labe!~ that imply the use of c~garct~e[ may induce c~-nc~r or ~ea~ di~.ca~e. n~ti~ ~, t~ ~--~: "~ ~~ of t~m I~" You ~reat~. It ~" In- ~ ~er," ~, ~In~ ~lic~ ~c~cncc ~oes not F~o~" vary ~ch about better ~t~e~ prirary c~a~ and l~irect influer..cea t~t aid ..~e,.~:~ ~bly s~" ~t ~t ~hing FAY ~lp ~uce It, dirtily or-l~ctly. Obvlouzly, It ~,Md t~ ~ogsly ~air ~ ~o~e ~due ~t ~ t~t ~o~!e eo~z~e in cu~tity, If t~ Is ~o s~b~t~ti~ ~ ~ls. f~ ~ ~. -.,
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on ~,ob~oco pro,~uot~. t~Ith ea~oer do mot =u~st tJ~t ~lootlme is ~volve~.
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or cuz:~ati~ effects. T~r¢~ aro ~dhcr re~oz~ Wh.v any ~ugset.te~ labeli~ of aicoti~e content of ci~tte~ t~al~ be misl~adin4; z.ul meaaiz~leae. - o 0
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re~ult~ will n~t give a~v i~M.dc&t~u of t/~v ~mount ~f emoM~ that will Neither ~o the -,~.rlou~ e~-T.¢nt l~.~ar~tory :xe~v.~er:.'cr.,t~ ¢~Ie,.,,e illusion that such kn~le~e exi~ta h,~s been cre~te~ by execrated i~utlleity ~Iren to cert~i~ ~-rovc~ worki~
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A Scientific Perspective the Cigarette Controversy II
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Note- Certain of the quotations in this booHet are from Government docu- ments and are in the public domain. All other quotations herein are included by special permission of the authors and publications. No part of t~ document may be reproduced for any advertising or trade purpose. TOBACCO INDUSTRY RESEARCH COMMITTEE 5400 Empire State Building New York 1, N. Y.
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Introduction No activity in all the vast field of medical research is being carried on so intensively, in so many areas and at such cost as the effort to track down the causes and cure of cancer. With the whole world anxiously waiting for some word of success, any reported identification of a cause of cancer arouses im- mediate and wide public interest. This has happened in the past year with the promotion of a theory by a number of research doctors that cigarette smoking may be in some way linked with lung cancer. In papers read before scientific groups and published by medical journals, Doctors Ernest L. Wynder, Evarts A. Graham, and Alton Ochsner and others maintained that the sharp rise in lung cancer reported in this country was "compatible" with the greatly increased use of tobacco. A similar statistical association was suggested in England by Doctors Richard Doll and Bradford Hill. In addition to this alleged statistical association, considerable atten- tion was paid to reports of experiments in which Doctors Wynder and Graham had been able to induce skin cancer on mice by application of cigarette tars. Some doctors have gone on record as accepting these views. But other distinguished medical authorities and research scientists have questioned the validity of the statistical methods and the conclusions drawn from laboratory experiments with mice. Among basic questions raised is how much of the apparent rise in lung cancer is real and how much is due to other reasons such as better diagnosis and the aging population. These other authorities find no proof establishing that cigarette smok- ing is a cause of lung cancer. Especially significant is the stand taken by the National Cancer Institute of the United States Government. In a report pub- lished in April, 1953, the NCI says: "Aside from the statistical significance and apparent realness of these associations there remains the question of whether smoking is etio- logically related to lung cancer. Considerations are presented which
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lead to the conclusion that the etiological (etiology: the science of causes of diseases) significance of these associations remains un- established." Because of the wide publicity given statements made about tobacco by Doctors Wynder, Graham and Ochsner, many laymen and even physicians are unaware of the extent to which these statements have been questioned by other authorities. It is in the interest of science and of the public that these other views be brought to public attention, and it is for that purpose that this compendium is being published. The following pages contain the statements of many qualified cancer experts and organizations in the United States and overseas. The Tobacco Industry Research Committee does not suggest that these views represent the entire body of scientific opinion on the subject. searchers the world over are studying dozens of theories in attempts to solve the mystery of cancer. At latest count there were more than 850 cancer research grants active in the United States alone, any one of which might pro- duce evidence to unlock the secrets of lung cancer. As set forth in its public statement on January 4, 1954, the position of the group comprising the Tobacco Industry Research Committee is that they "accept an interest in people's health as a basic responsibitity and paramount to every other consideration in their business." In that spirit, it is believed that no serious medical research, even though its results are inconclusive, should be disregarded or lightly dismissed. The important thing is to recognize the urgent need to explore every scientific avenue which could lead to discovery of the cause of lung cancer. .The Tobacco Industry Research Committee has pledged its aid and assistance to the research effort into all phases of tobacco use and health. The joint effort, of course, will be in addition to that already being contributed by individual companies. TOBACCO INDUSTRY RESEARCH COMMITTEE 5400 Empire State Building New York 1, New York ~J~
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Comment on Current Theories Questions Role Cigarette If excessive smoking plays a role in production of lung cancer, "it seems to be a minor one," according to Dr. W. C. Hueper, Crnief of the Cancerigenic Studies Section, National Cancer Institute. Writing in a 1953 issue of the Rhode Island Medical ,~ournal, he says: "It may be concluded that the existing evidence neither proves nor strongly indicates that tobacco smoking and especially cigarette smoking represent a major or even predominating causal factor in the production of cancers of the respiratory tract and are the main reason for the phenomenal increase of pulmonary tumors during recent decades. If excessive smoking actually plays a role in the production of lung cancer, it seems to be a minor one, i/judged from the evidence on hand."1 Many Comparable Correlations Prof. R. D. Passey, Director of Cancer Research at England's University of Leeds, cautions "let us be sure of our evidence." In a February, 1953, letter to the British Medical lourtml, he says: "In view of the present interest in the relationship of smoking to lung cancer there is undoubtedly a large body of opinion, both professional and lay, which accepts, as though it had been proved, that smoking is the main cause of the recorded increase in lung cancer; and no doubt there is considerable distress in the community on this account. In the present state of our knowledge, is this anxiety really justified?... "It is easy to call to mind other close statistical correlations. What catches the popular fancy is the way the rise in the habit of cigarette-smoking goes hand in hand with the rise in lung cancer mortality. But in the long history of our profession's attempt~ to elucidate the causes of cancer, it has found many correlations of a comparable nature which have in the end proved false .... "It may be that a proportion of lung cancers in man are induced by tobacco smoke; at the moment we do not know, but let us be sure of our evidence before we scare the public.''2 "None o[ Evidence Conclusive" A public statement November 27, 1953, by the Damon Runyon Fund says that the evidence is not conclusive. "It is recognized that lung cancer is now more common than it was one or two decades ago. Many suggestions as to the cause of this increase have been made; the possible relationship of air pollution, vehicle exhaust fumes, smok- ing and other factors have been widely mentioned. Some of these surmises are purely speculative, some are dras~ from statistics, others derive from the experimental induction of cancer in animals of these materials. However, none of these factors has as yet induced in experimental animals lung cancer of the kind seen in man. None of this evidence is conclusive but does urge the need for carefully controlled research to secure the answer. Three questions arise which require solution: first, is there a causal relationship; second, if so, what factors are responsible; third, how can they be eliminated?"3 3
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Unwarranted Conclusion Dr. Max Cutler, internationally noted cancer surg~n of Chicago, says, "I feel strongly that the blanket statements and conclusions which appeared in the press that there is a direct and causative relation between smoking of cigarettes, and the number of cigarettes smoked, to cancer of the lung arc absolutely unwarranted." During the last 30 years Dr. Cutler has published two books and dozens of medical papers on cancer. His unsolicited statement follows: "I feel strongly that the blanket statements and conclusions which have ap- peared in the press that there is a direct and causative relation between smoking of cigarettes, and the number of cigarettes smoked, to cancer of the lung are absolutely unwarranted. "Medical literature has numerous examples of such fallacious conclusions which have been proved to be wrong in the light of subsequent experience. This whole question of cause and effect deducted on a statistical basis is subject to the greatest fallacies. One way I like to emphasize it is to say that simply be- cause one finds bullfrogs after a rain does not mean that it rained bullfrogs." "'To accept the conclusion that has been drawn of a direct causal relationship between smoking and cancer of the lung simply because there has been an increase in both, appears to me unscientific and hazardous. "From all the available evidence, I think it is conceivable that in a very small, probably infinitesimal percentage of sensitive individuals smoking may ultimately prove to be one of numerous contributing factors in lung cancer. "Under these circumstances, is it wise to scare the public and create wide- spread anxiety among millions of people on the flimsy evidence that has been presented?"* Facts and Fancies Need to be Sorted Need for a calm, objective appraisal of evidence is emphasized by Professor D. W. Snfithers, Director of Radiotherapy at England's Royal Cancer Hospital. In his report, entitled "Facts and Fancies About Cancer of the Lung," appear- ing in the June 6, 1953 British Medical Journal, he says, "the moment the word cancer is mentioned to the public (of which doctors are but a part)* emotion is aroused and any calm objective view of the value of evidence presented becomes most difficult." Following is complete text of his conclusions: "The startling rise in the recorded death rate from lung cancer is in large part due to change in numbers and age of the population and to improved diagnosis. It is due in part to a real increase, but we are not yet in a position to say how great that real increase is. "The size and the difficulty of this problem are clear to us all. Although the five-year survival rate for the fortunate few who are operable when they first .reach hospital has risen from nothing to between 20 and 30% in 20 years, and while much can be done with x-ray treatment to relieve suffering and some- times prolong life for the less fortunate ones who are, nevertheless, still in fairly good general condition, there are still thousands of these patients each year for whom no real attempt at treatment is being made. "Since we all have to die, since some 90,000 people are doing so each year with lung symptoms, and since this number is failing well, we should ask our- selves how far we are performing a useful service by helping to make a public issue of a comparatively smatl change within that group, which may be in large *Pro]essor Smither~' parenthetical statement. 4
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part due to our own method of recording. We should not be too readily swayed by those who demand that the public be told 'the truth' while we are still attempting to sort the facts from the fancies for ourselves, especially since 'the truth' when told may not appear to them in at all the same light as it does to us. Anthony Hope once wrote that 'telling the truth to people who misunderstand you is generally promoting a falsehood.' "The moment the word cancer is mentioned to the public (of which doctor~ are but a part) emotion is aroused and any calm obiective view of the value of evidence presented becomes most difficult. It is important that the medical profession take note of this die, cult problem of lung cancer and help to deal with it more e~ciently, but it is also important that they do not make matter~ worse by merely joining in a cry and increasing the alarm. "A sensible view of the relationship of smoking to this problem, for instance, should be and. after some wild comments in the lay and medical press, is now being presented to the general public; but no comparable effort seems to be going into an endeavour to persuade the authorities to cleanse the air of our industrial towns. As a profession which speaks so much and so rightly of the need to allay the cancer fear we should beware of putting extravagant accounts of rising cancer death rates and their causes before the public, especially when neither the magnitude of the one nor the degree or responsibility of the other has yet been fully established."6 More Accurate Tests Needed Internationally known in the field of cancer investigation, Dr. Clarence Cook Little, Director of the Roscoe B. Jackson Memorial Laboratory at Bar Harbor, Maine, believes "If smoke in the lungs were a sure-fire cause of cancer, we'd atl have had it long ago. The cause is much more complicated than that." Dr. Little's laboratory is credited with breeding a million laboratory mice per year. In connection with a recent New York Town Hall program, Dr. Little stated: "In proving a cause-and-effect relationship between any substance and any specific type of cancer in man, it is essential that a logical and rational approach to the problem and to the interpretation of data be employed. "From a laboratory point of view, I do not feel that a definite cause-and- effect relationship between cigarette smoking and human lung cancer has been established on a basis that meets the requirements of definiteness, extent and specificity of data which the seriousness and implications of the problem de- serve. Further and more accurate experimental tests and methods of analysis of the many factors involved should be devised and utilized. "For these reasons I would regret any undue alarm on the part of the public at this time."~ Statistical Associations "Etiological Signilleance . . . Unestablished" Three National Cancer Institute specialists, Dr. A. G. Gilliam, Chief of Epidemi- ology, and research associates J. Cornfield and D. A. Sadowsky, in a 1953 report of the Institute's .~ournal, have questioned the relationship of smoking to lnng cancer. Their report contains the following observations: "... In this study an association of about the same degree as that observed with cancer of the lung has been shown between cancer of the larynx and cigarette smoking. A phenomenal increase in cancer of the larynx, such as that recorded for cancer of the lung, has not been observed in this country. If the association between cigarette smoking and lung cancer is of etiological sigaifi-
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cance, some explanation is needed as to why a corresponding increase in laryngeal cancer has not followed an increase in cigarette consumption, with which this disease is also associated. "These data also provide no evidence that age at onset of disease is influenced by the quantities of cigarettes smoked .... "In the same fashion these data provide no firm evidence that risk increases with increase in duration of smoking. When age was kept constant no clear-cut trend in this direction was apparent.... "It would therefore appear that though the association between cigarette smok- ing and lung cancer seems real, the significance of this association remains unestahlished.... "Aside from the statistical significance and apparent realness of these associa- tions there remains the question of whether smoking is etiologically related to lung cancer. Considerations are presented which lead to the conclusion that the etiological significance of these associations remains unestablished."7 Clinical Data Questioned Experts at the University of Texas School o[ Medicine have studied the statistical associations employed in relating cancer to cigarette smoking. Dr. Paul Brindley, Chairman of the Department of Pathology, Dr. R. H. Rigdon, Director of the Laboratory of Experimental Pathology, and Mrs. Helen Kirchott, Research Asso- ciate in Pathology, have reported on these studies. Drs. Brindley and Rigdon, in a 1950 report in the Texas State lournal o] Medicine have questioned whether there is an etiologic factor in lung cancer. They also ques- tion the basic data on frequency of lung cancer, citing "variation in the clinical data and the difterence in these data and those obtained from autopsies." Their observations: 'The distribution of the cases of cancer of the lung in the districts of Texas as reported to the State Health Department does not suggest to us any etiologic factor as playing a significant role in the production of pulmonary neoplasms. Furthermore, nothing significant as to the etiology is noted in our cases studied at autopsy." "From this study of primary carcinoma of the lung at autopsy there is in- sufficient evidence to prove that the frequency of this neoplasm in all malig- nancies has increased during the past twenty years. There is no evidence to indicate that cancer of the lung is increasing in the female within this period. One of the factors contributing to the confusion relative to the frequency of cancer of the lung is the variation in the clinical data and the di/terence in these data and those obtained from autopsies. A second factor contributing to this problem is the failure to separate data referable to these tumors in the white and Negro patient. In autopsy series the frequency of cancer of the lungs may be established more readily by determining the percentage of these tumors in all neoplasms rather than only their incidence in routine autopsies."s Diagnostic Factor In a 1952 paper, published in the Spring Texas Reports on Biology. and Medicine, Dr. Rigdon and Mrs. Kirchoff question the theories advanced on the increase in lung cancer, and find that control of infectious diseases, increased aging of the population and other factors are significant. Quoting from this paper: "There is such a wide variation in the significance of the theories advanced to account for the increase in the frequency of cancer of the lung that the data, in our opinion, do not justify the conclusion that cancer of the lung has actually increased as a result of any one so far advanced~. The statistical data presented 6
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by some investigators relative to cigarette smoking are impressive; however, there is such a wide variation in control samples that, in our opinion, additional sampling is needed to warrant their conclusibns. There is no significant correla- tion between the amount of tobacco consumed and the death rate for cancer of the lung in the United States. There is, however, a significant correlation in the United States between the population to physician ratio and the population to bed ratio and the number of reported deaths from cancer of the lung. Better diagnoses, decrease in the number of deaths from infectious diseases by both prevention and therapy, and the increased aging of the population ~eem to be more significant factors than any one or group of carcinogens to account for the apparent increase in the frequency of carcinoma of the lung.''~ the Facts" Dr. Rigdon and Mrs. Kirchoff made a broad analysis of the statistical data that have been aimed at cigarette smoking. Their paper, entitled "Smoking and Cancer og the Lung- Let's Review the Facts," contains the following observations: "Regardless of the fact that some of the groups have very few cases, we would like to emphasize that in each of these three studies the percentage of individ- uals who smoked less than 15 cigarettes a day and did not have cancer of the lung is much higher than that of the corresponding group who had bronchio- genie carcinoma. Furthermore, as far as we know the cases of cancer of the lung studied by Doll and Hill (1950) and Breslow (1951) were not proven by pathologic examination, while the study by McConnell and associates (1952) was based on proven cases of cancer of the lung. The latter investigators con- cluded that 'no significant difference was found in the incidence of smoking, or of the proportion of cigarette-smokers, in the two groups'." "As you know, Dr. Ochsner has been interested in smoking and cancer of the lung for several years. However, from a review of his publications it would seem that his opinion has varied relative to this relationship. In 1941 he pre- sented a graph showing the comparison of the death rate per 100,000 popula- tion from cancer of the lung with the production of tobacco and automobiles in the United States during the period 1920 to 1936. Of automobiles and cancer of the lung, Ochsner and associates concluded that there was no significant relationship, but they did find an obvious parallelism between the increased production of tobacco and cancer of the lung. In 1948 Ochsner and his group stated that 'although we previously were of the opinion that the chronic irrita- tion resulting from excessive cigarette smoking was a factor, this cannot be proved. However, the fact that there is a parallelism between the number of cigarettes sold in the United States and the increased incidence of bronchio- genie carcinoma is interesting .... In our series we have not been able to show that there has been a higher incidence of smokers than in the average popula- tion of a whole.' Then in 1952 Ochsner said, 'For some time two of us have been convinced that there is a causal relationship between the increased inci- dence of bronchiogenic carcinoma and the increased use of cigarettes.' Ochsner (1951) said that Dr. Evarts Graham has said to him, 'Yes, there is a parallelism between the increased incidence of bronchiogenic carcinoma and the sale of cigarettes; but also there is a parallelism between the increased incidence of bronchiogeulc carcinoma and the sale of nylon stockings'." "In summary it may be said that in our opinion the data available today do not justify the conclusions that the increase in the frequency of cancer of the lung is the result of cigarette smoking. The statement that carcinoma of the bronchus has actually increased in frequency is in our opinion open to question. Further- more, adequate studies are not now available on the frequency of cigarette smoking in the population. These factors would be necessary in establishing a causal relationship between smoking and cancer of the lung."10 7
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"Evidence Gave Equivocal Results" "How Much o[ the Rise Is Real"? A Hospital Survey Dr. W. C. Hueper, Cancerigenic R+search Studies Section Chief at the Federal Government's Cancer Control Branch, National Institutes of Health, says the statis- tical relation is "in urgent need of supporting biolo~c e¢idence." In 1953 he re- ported in the Rhode lsland Medical Journal: "The apparent lack of uniformity in the human material analyzed by the different authorities is further demonstrated by the appreciable differences in the sex distribution of lung cancers reported at different times, from different regions and by different investigators. The male to female sex ratio fluctuates between 2:1 to 20:1 (Hueper). It is noteworthy, however, that the uniforndy observed prevalence of lung cancer among males has in general become in recent years even more pronounced than in former decades. This observation strongly militates against a predominant causal role of cigarette smoking in the production of lung cancer, because all previous experience in the field of occupational cancer indicates that given the same type of carcinogenic exposure for both sexes and at the same time an increasing equalization of the intensity of exposure, there occurs a narrog~ng of the gap in incidence rates of the two sexes and not a widening, which actually exists. This interpretation of the diverging sex related frequency trends is not fundamentaUy affected by the statement that the interval between the start of tobacco smoking and the appearance of a lung cancer is between 20 to 40 years (Wynder and Graham; Ochsner, DeCamp and DeBakey; Schrek, Baker and Ballard). Even if women may not have indulged on a large scale in tobacco smoking some thirty years ago, there can be little doubt that the cigarette smoking habit has made during this period much greater strides among women than among men. "The purely statistical approach leading to the assumption of the existence of causal relations between two coincidental events and trends is, thus, in urgent need of supporting biologic evidence in man, since the available experi- mental evidence gave equivocal results."l~ The Metropolitan Life Insurance Company during 1953 issued a statement saying the data were far from conclusive. "In the present state of knowledge it is difficult to account for the recorded increase in the mortality and morbidity from respiratory cancer, or even to determine how much of the rise is real. Improved techniques for diagnosis and the greatly increased frequency of theh" .use have resulted in many cases being detected and reported which, in the past, would have been overlooked. This applies especially to diagnostic x-rays in medical and hospital practice. Men- tion, too, should be made of the increase in the number of physicians with training and experience in this field. Contributing in a lesser way. to the more frequent discovery of cancer of the respiratory tract is the increasing use of the bronchoscope and of cytological examination of lung secretions .... The role of other factors, such as coal tat products, excessive tobacco smoking, and specific contaminants, is still far from conclusive."1* A survey of lung cancer patients by Dr. E. D. Gagnon of the Chest Clinic at Montreal's Notre Dame Hospital revealed (as translated from the French) : "Since February, 1949, bronchopulmonary cancer was observed in 120 men and 5 women admitted to the thoracic clinic of the Notre-Dame Hospital in Mon- treal. Of the 125 patients, 97 were over 50 years; the oldest was 79 and the youngest 21. Fifty patients smoked more than 20 cigarettes daily and 10 did not smoke. Etiological factors discussed in (medical) literature are so numerous and so contradictory that it is impossible for us to be sure of one etiological factor. Many statistical analyses have tended to incriminate tobacco (esp. as cigarettes) but there are iust as many analyses that negate such an etiology.''~3 8 u~
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Much More Research Necessary Dr. Milton B. Rosenblatt, Associate Clinical Professor of Medicine, New York Medical CoLlege and visiting physician to the New York City Hospital, in a paper read at the New York Medical College, March 16, 1954, stated: "The tremendous increase in the incidence of lung cancer for the past two decades has furnished a therapeutic challenge to the medical profession. Many explanations have been offered/or the unusual increase in incidence but smok- ing at the moment occupies the prime position in the lay press. However, the public which is already so concerned about cancer should not be unduly alarmed without proper justiflcatioa. A great deal of thought and experimental investigation is necessary before any definite conclusions can be reached. "The increase in the incidence of lung cancer can be attributed to two main causes. The disease was clinically unrecognizable 25 years ago - bronchoscopy, the perfection of x-ray technique, cytological studies, etc., have been developed in recent years. At the Brompton Hospital in London (which specializes in chest diseases) there were only 29 bronchoscopies between 1926-29; at the present there are more than 800 done each year. The second factor for the tremendous increase has been the general awareness of the disease and the intensification of pathological studies. It has been commented philosophically that a sharp rise in incidence in certain institutions was coincident with the establishment of pathology departments. Much has been made of the increase in autopsy statistics in lung cancer on the assumption that autopsy statistics reflect the general trend in population. "Necropsy records are subject to the same errors of distortion, lack of control and misinterpretation as clinical data. The widespread use of antibiotics has resulted in fewer hospital admissions and fewer deaths from infectious diseases, and proportionately, more from malignancy. "Probably the most important consideration in the explanation for increase in incidence is the age distribution of patients with lung cancer which is a disease of older age groups. The span of life has steadily increased and with it has come a proportionate increase in the number of potential candidates for lung cancer. There are now four times as many people, age 65 or over in the U. S., as there were in 1900. "The evidence pointing to smoking has been chiefly on a statistical basis. A statistical correlation does not signify that there is a cause and effect relation- ship. Analysis of numerous statistical studies shows that there is actually very little difference in the incidence of smoking between cancer patients and control patients, particularly if the statistics are evaluated with respect to age groups. In the report of Mills and Porter, the percentage of heavy smokers in the control group equalled or exceeded that of the cancer patients in the respective age groups. Ochsner stated that the carcinogenic effect of cigarette smoking does not become evident until approximately 20 years. Also that the death rate will increase steadily so that by 1970 it wRl be 29.4% per 100,000 of popula- tion. This is merely a form of extrapolation, or educated guessing, and is not to be interpreted as establishing a cause and effect relationship between lung cancer and smoking. "Pathologically lung cancer in mice resembles only remotely bronchogenic carcinoma in the human. The occurrence of lung tumors in mice in the course of experimental studies may be incidental inasmuch as lung cancer often occurs spontaneously in mature mice. "A great deal more research must be done before one can establish the etiology of lung cancer or, as a matter of fact, all cancer. The recent ability to diagnose lung cancer plus the fact that it occurs only in older age groups, which have increased tremendously during the past two decades, seems sufficient to explain the increased incidence of the disease. Although the percentage of heavy smokers (20)'ears or longer) between 40 and 45 years of age is very large, the incidence of lung cancer in this group.is negligible."~4 9
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Calls Mice Conclusions 'Dangerous" '~Tissues Respond Differently" British Experimental Studies Tobacco "Relatlvely Unimportant" Dr. Jonathan L. Hartwell of the National Cancer Institute says it would be "danger- ous to conclude that man is resistant or susceptible to a given carcinogen" merely on the basis of experiments with a single species of laboratory animal. In the "Survey of Compounds Which Have Been Tested for Carcinogenic Activ- ity," Second Edition, published by the Federal Security Agency, Public Health Service, Public Health Survey # 149, page 2, Dr. Hartwell says: "Another pit/all is the attempt to carry over, without reservation, to man, con- clusions based on animal experiments. We do not know whether man is more or less susceptible than mice to particular carcinogens. Some animal species, such ~s the rat, rabbit and dog, are much more resistant to certain chemical carcinogens than is the mouse, and vice versa, while in the monkey none o[ the powerful carcinogens has been shown to produce tumors. It would, therefore, be dangerous to conclude that man is resistant or susceptible to a given carcinogen merely on the basis of experiments with a single species of laboratory animal... Two other National Cancer Institute scientists, Dr. Murray J. Shear and Joseph Leiter, are quoted from the lournal ot the National Cancer Institute, Vol. 2, 1941-42, page 254, as saying: "... there are pronounced differences in the response of different species to the action of compounds carcinogenic in the case of the mouse... Furthermore, in the mouse itself, it is now abundantly evident that different tissues respond differ- ently to the same compound... The mode of administration may also influence the results markedly. The dose may be too high as well as too low... The solvent or vehicle may affect the results profoundly... Moreover, the sex of the animal is not without influence on the results... Diet, too, may be an important factor ... "...the term 'carcinogenic potency' as used in these studies is not to be con- sidered as an invariable property inherent in a compound but is merely a summary of the results of particular experiments and is valid only for animals of the species, strain, sex, age, diet, etc., of the particular animal employed, as well as for the dose, menstruum, mode and site of application, etc., of the compound in question."16 In a 1923 edition of the British Medical Journal, the late Dr. Archibald Leitch, then Director of the Cancer Hospital Research Institute, London, had this to say about an attempt to induce skin cancer in mice with smoking tobacco fractions: "... We applied these fractions to two series of mice for many months. They produced epilation of the areas to which they were applied, and they induced chronic ulcerations, but in no single case did any neoplastic reaction result. We have thus no evidence in support of the contention that tobacco smoke contains a cancer-producing property, though we may not therefore conclusively reject the idea that there is something connected with tobacco smoking which may be operative on the oral mucous membrane of human beings. But what is of more theoretical and practical interest is the fact that here we had a substance with a very marked irritative effect on the skin in that it lJroduced chronic lesions and yet no turnout formation supervened. We might say that it is not a specific irritant of the tumour-producing elass."z7 Reporting on studies of tobacco smoking and cancer in 1932, four British research- ers at the University of Birmingham, Drs. F. W. Mason Lamb, E. Ashley Cooper, and Prof. E. L. Hirst, and associate Edgar Sanders, had this to say: "The fact that only one tumour has been obtained in the course of subjecting a large number of mice to the action of tobacco tar, compared with the very high incidence of cancer in mice treated with coal tar. indicates that tobacco is relatively unimportant in the causation of cancer.''*s 10
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A 1932 American Experiment "It Remains to be Two American investigators, Dr. Emil Bogen, Director of Laboratories and Re- search at Olive View Sanitorium, Olive View, California, and his associate, Russell N. Loomis, reported in 1932 in the American !ournal o! Cancer on attempts to induce skin cancer in mice. Following quotes are from their report: "in the mice treated with the tobacco tar, no marked changes in the skin were observed."... "From these experiments we may conclude that the cutaneous application of a tar derived from the destructive distillation of tobacco did not possess the irritat- ing and ephithelial-stimulating properties that lead to the production of neoplastic growths, as tested upon the skin of mice and rabbits."*9 In a 1952 contribution to the British Empire Cancer Campaign's 30th Annual Report, the Campaign's Yorkshire Council observed that "it remains to be shown that smoking can give rise to lung cancer." An extract from the Yorkshire Council's contribution to the report reads as follows: "With the evidence available at the moment, it is not possible for anyone to say with certainty that lung cancer can be caused by smoking, or that it cannot. "Nationally we are faced with a large rise in the numbers of reported cases of lung cancer: in the Registrar-General's Statistical Review, 1946 to 1947 (Text) there is the statement: -'Comparing the rates in 1947. with the mean annual rates 1921 to 1930, men between 45 to 75 show a 10-fold increase.' "At the same time there has been an increase in the habit of smoking c!garettes which is due, in some part, to a change-over in the national habit of ptpe smoking to that of cigarette smoking. What is not so well known is that the increase in the total consumption of tobacco has, in that period, been less than is supposed. "In 1900 the total consumption per annum of ali tobacco goods in the United Kingdom was 7.2 lbs. per adult male, in 1920 9.1 lbs. and in 1951 9.6 lbs. Yet in 1871 the consumption of tobacco, mainly in the pipe, was some 5.7 lbs. .per .adult male. Thus, from these figures of the consumption of tobacco, smok- ing ~s nothing new, nor is the increase per male in recent years outstanding. "If in theh" recent paper (1952) Doll and Bradford Hill are correct when they infer that the pipe is suspect as well as the cigarette, it must be admitted that the increase in tobacco consumption from 5.7 lbs. in 1871 to 9.6 lbs. in 1951 has little correlation with the great increase recorded by the Registrar- General. If tobacco smoke can induce lung cancer, it has caused this condi- tion since Sir Walter Raleigh introduced tobacco into England, but the condi- tion has not been widely recognized until the recent diagnostic means were available. However, it remains to be shown that smoking can give rise to lung cancer. "If, at some future date, it should be shown that some lung cancers are the result of smoking it would still remain to be established what proportion of the total cases are dependent on the habit. We are surely on firm ground when we state that a large proportion, how large we do not know, have nothing to do with smoking. For instance, Doll and Bradford Hill found 40 non-smokers out of their 108 women with lung cancer."z0 "Evidence Not Convincing Enough" Reports from Lay Media Dr. Walter B. Martin, president-elect of the American Medical Association, in an ABC network television interview, December 16, 1953, said, "I do not think the evidence is convincing enough to establish as a positive fact that cigarette smoking is necessarily the cause of cancer of the lung." 11
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Following is a verbatim excerpt of his remarks: "We have knog~ a long time about the tremendous increase in lung cancer. My first observation on that was in a scientific article that came out in 1922. It pointed out that cancer of the lung was on an increase at that time. "It is true that we have been interested in the parallelism between the increase in cigarette smoking and the increase in cancer of the lung. But there are some other parallels such as the increased use of internal combustion engines, although there is no positive proof that a connection exists. "We are very much interested in the recent work that has been reported in connection with the relationship between cigarette smoking and lung cancer, but I would like to point out that this is an animal experimentation which does not indicate the definite part tobacco plays on humans. We think that the proper attitude is one of caution and we hope that further investigation will be made to establish positively whether it is a factor .... "... On an individual basis we doctors advise a great many people not to smoke. At the present time I still think it is a matter between the individual physician and his patient as to what advice should be given. "'I do not think the evidence is convincing enough to establish as a positive fact that cigarette smoking is necessarily the cause of cancer of the lung." When Dr. Martin was asked ff he smoked, he replied: "I've smoked long enough to have incurred all the possible dangers and don't think I will stop now." Additional Factors Need Study "Too Much Talk" The New York Times for April 30, 1953, reported that Dr. John R. Heller, Director of the National Cancer Institute, questioned the connection between smoking and cancer. Following are pertinent paragraphs from the Times' Washington dispatch: "Dr. John R. Heller, director of the National Cancer Institute, says any con- nection between heavy smoking and lung cancer has not been definitely estab- lished 'to our satisfaction.' "Dr. Hetler said lung cancer has increased 'severalfold' among men in the past twenty-five to thirty years. But there has been no similar increase among women, he added, even among heavy smokers. "He conceded that 'there is a very high correlation between heavy cigarette smoking and the occurrence of lung cancer.' But, he added 'our *** scientists seem to feel that there are some additional factors which we have not yet dis- covered or studied sufficiently, which may have a bearing on this particular problem.'" Dr. Anthony J. Lanza, Chairman, Institute of Industrial Medicine, Post Graduate Medical School, of New York University, says "more knowledge is needed before any conclusion can be reached." Following are pertinent paragraphs of a January 15, 1954, report from San Juan, Puerto Rico, as carried by the New York World Telegram and Sun: "Dr. A. I. Lanza, Chairman of the Institute of Industrial Medicine, Post Graduate Medical School of New York University, says more knowledge is needed before any conclusion can be reached regarding a possible connection between cigaret smoking and lung cancer. "'There is too much talk and too little action in relation to tobacco as a cancer cause,' Dr. Lanza said. 'Scientific investigation is in less than embryonic stage, and lung cancer statistics show little. "'Sixty million Americans smoke, and the few hundred cases studied do not show much about tobacco as a cancer cause.'" 12
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IVith Other Nations says that, percentage-wise, lung cancers are more prevalent in Austria, England and the Netherlands than in the United States. As quoted in the Chicago Daily Tribune, November 4, 1953: "Dr. Harold Stewart, National Cancer Institute, Bethesda, Md. cited reports that lung cancer accounts for about 17 per cent of all cancers among men in Austria, England, and the Netherlands, 9~ per cent in the United States, 2 per cent in Japan, and half of 1 per cent in Thailand (Siam). "'Yet I understand that the smoking habits in Thailand are about the same as in the United States,' he said. He added that mice exposed to heavy cigarette smoke 40 hours every week for eight month~ or more did not show any in- crease in lung cancer." Baltimore Specialists Question Proo/ On the basis of experience with hundreds of cases of lung cancer, Dr. William F. Rienhoff, Jr., pioneer lung surgeon and assistant professor in surgery at Johns- Hopkins University, Baltimore, has been quoted as saying "there is no proof whatsoever that cigarette smoking causes pulmonary disease." Drs. Rienhoff and Lawrence M. Serra, both chest specialists, are quoted in a story which appeared in the Baltimore Sun, July 13, 1950. Following is the perti- nent text of the newspaper report: "Several Baltimore doctors, questioned yesterday, largely expressed disagree- ment with the recently published view of five investigators that 'excessive and prolonged' use of cigarettes 'seems to be an important factor' in cancer of the lung. "In studies reported in the Journal of the American Medical Association, it was stated that of 605 male cancer patients interviewed in three St. Louis hospitals, only 1.3 per cent were nonsmokers, while 51.2 per cent had smoked the equivalent of more than twenty cigarettes a day over a period of many years. "Dr. William F. Rienhoff, Jr., Baltimore surgeon, said that 'I have reviewed more than 500 cases of lung cancer that were operated on and a large number that were inoperable, and I have found no relation whatsoever to smoking.' Feels There Is No Proo! "He declared that 'there is no proof whatsoever that cigarette smoking causes pulmonary disease. I feel very definite about this.' "Dr. Rienhoff and Dr. Lawrence M. Serra, chest diagnostician, cited the vastly greater number of lung cancers that occur in men in comparison with women. "The ratio of persons developing this disease is about eight men to one woman, according to Dr. Rienhoff, "yet,' he added, 'women are almost as heavy smokers as men.' Idea IVas Advanced Before "Saying that 'I don't believe smoking plays much of a part at all' in lung cancer, Dr. Serra recalled that clinics in New Orleans a few years ago expressed the conclusionthat smo "1ring did play a big part in this disease, then he added, 'but most clinics have not borne this out at all." "A surgeon who asked to remain unnamed declared that 'what strikes one forcibly is that smoking is so prevalent there would be a lot more lung cancer if this were the cause.' "Dr. Rienhoff expressed the same view. 'The other doctor said that lung cancer 'is not as prevalent as you might think in comparison with many other diseases. Three doctors do practically all the operating for this disease in Baltimore.'" 13
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Dr. RienhoI~'s March, 1954, Position: On March 8, 1954, Dr. Rienhoff, who is credited with being one of the first to remove suecessfuUy an entire lung, made the following statement: 'q'he highest concentration of tobacco smoke, whether it be from cigarettes, pipe, or cigars, is naturally in the mouth, the naso pharynx, the trachea or windpipe, and probably very slight penetration of smoke into the right and left primary or stem bronchi. Now, it would seem if tobacco smoke were the cause of a cancer of the primary bronchus, which has exactly the same mucosal lining or epithelial lining found in the main windpipe in the neck or trachea, that there would be an equal increase in carcinoma of the lining of the mouth, pharynx and main windpipe or trachea; and there certainly has not been a comparable increase in cancer of these regions of the upper respiratory tract. "Most of the patients with cancer of the lung which we see do not have can- eer of the primary bronchus or near the trachea but in the peripheral alveolar regions, that is, the small air sacs or cells far from the main bronchi. "At the present time women are smoking almost as much as men and there has not been a proportionate increase in cancer of the lung in women. Just as in cancer of other organs, there must be a sex tendency; for instance, cancer of the breast is very infrequent in men and more frequent, as everyone knows, in women. "If one were to chart the increase of cancer of the lung with the increase in the number of automobiles in the urban districts, from which most of our patients with cancer of the lung come, it seems to me a definite parallel between the automobiles and cancer of the lung would be evident. Incomplete combus- tion of gasoline and additives/or supposed more power, together with tar from the roads, the smoke from diesel engines and pollution of the atmosphere in my opinion probably play a greater role in the production of lung cancer than tobacco. "Other facts that vitiate a conclusion that tobacco causes cancer are that doctors are now aware and looking for cases of lung cancer and diagnosing it more frequently; and even patients are more aware of the symptoms and signs; more thorough postmorten examinations and operations revealing cancer of the lung all help to improve the statistics collected by the various health departments. Anti-biotics preserve more patients for the cancer age. "Unproven correlations are dangerous. It is quite true that alcohol to excess will produce, in some sensitive individuals, cirrhosis of the liver, but because cirrhosis of the liver exists and can be connected with many diseases and nutritional disturbances other than the use of alcohol, it would certainly not be a very strong argument against the use of alcoholic beverages. "Excesses in eating, drinking or smokin, g may have a harmful effect on the general body metabolism, but to say that cigarette smoking causes lung cancer would indeed be premature. There has to my knowledge, up to this time, March, 1954, been no factual proof whatever produced to support the loose, unscientific and irresponsible statements that are continuously appearing in newspapers and magazines.''2t Yale Test Proves Negative Results of an experiment conducted by Dr. Harry S. N. Greene, Yale University, are reported in the November 8, 1953, New York Herald Tribune: "Dr. Wynder set up a smoking machine, collected the smoke from cigarettes and distilled from this smoke a tar. The tar he painted on the backs of eighty-one mice, 44 per cent of whom developed cancers on the painted spots. "But at the same meeting, conversely, Dr. Harry S. N. Greene, of Yale University, described an even more sensitive test for tobacco carcinogenicity. He took tobacco products and implanted them in the armpits of mice together with a bit of tissue from an unborn mouse. No cancers developed, even though most other known carcinogens produce cancer under these circumstances."
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Vital Statistics Results of Case-Findlng Survey The findings of a committee of Boston specialists who searched for cancers in the chest x-rays of 536,012 persons are quoted below for the light they throw on statis- tical conclusions about the increase in lung cancer. These are quoted from a report by Dr. James M. McNulty in the January 1954 New England lournal o! Medicine: "This paper presents the findings of a detailed follow-up study of the clinical records of 398 patients suspected of having lung tumor by a roentgenologic review board that interpreted the films of a total of 536,012 persons. It was pre- pared under the auspices of the medical subcommittee on nontuberculous diseases of the Boston Chest Survey and conducted with funds provided by the Massao chusetts Division of the American Cancer Society. This survey extended from September 15, 1949, to February 1, 1950. 'Table I summarizes the results of the present follow-up study of all cases. It is noteworthy that there were 39 cases (9.8 per cent) of proved bronchogeni¢ carcinomas among a total of 398 cases in which tumor was suspected. Thirty° three of the 39 patients were men, and 6 were women. There was 1 case in the fourth decade, 6 in the f~th, 14 in the sixth, 13 in the seventh, 4 in the eighth and 1 in the ninth. *'Follow-up Results in Cases Classified as Presumptive Tumor Result 0f Study No. of Cases Primary bronchogenic carclnoma-proved .................................... 39 Primary bronchogenic carcinoma-presumptive ............................ 13 Metastatic pulmonary tumors ........................................................ 19 Other types of cancer .................................................................... 1 Miscellaneous group ...................................................................... 275 No follow-up report ...................................................................... 51 398,,2~ Five Tables on Death Causes In any health study it is important to consider the incidence of a fatal disease in relation to the death rate from other causes. An examination of the latest issue of Vital Statistics o] the United States, Volume III, 1950, brings into focus the relative standing of lung cancer as a cause of death. Note that in more than hal~ the cases of deaths attributed to lung cancer the lungs are not specified as the starting point of the cancer. Data in the following tables are taken h'om the official figures recently published by Secretary Oveta Culp Hobby of the Department of Health, Education and Welfare: I-Deaths ]rom All Causes-1950 ........................................................1,542,4543.~ II-Cancer vs. Major Death Causes--one in seven. No. Deatl~ Diseases of circulatory system ...................................................... 588,323 Neoplasm (cancer) ...................................................................... 216,107 Diseases of nervous system .......................................................... 170,256 Accidents, poisoning, violence .................................................... 116,376 Diseases of early infancy .............................................................. 60,989 Diseases of respiratory system ...................................................... 60,539 Diseases of digestive system ........................................................ 54,699 15
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Five Tables on Death Causes (Cont.) III-Lung Cancer vs. Non-Cancer Death Causes-one in eighty.2~ No. Deaths Arteriosclerotic heart disease, coronary ...................................... 321,003 Accidents .................................................................................... 91,249 Hypertension with heart disease .................................................... 85,193 Pneumonia ................................................................................. 40,523 Tuberculosis, all forms ................. ~ .............................................. 33,959 Nephritis & nephrosis .................................................................. 28,147 Diabetes mellitus .......................................................................... 24,419 Lung cancer, unspecified .............................................................. * 10,695 Lung cancer ................................................................................ ** 7,618 Larynx ........................................................................................ 1,852 • not specified as primary source of neoplasm • *specified as primary source of neoplasm IV-Lung Cancer vs. Other Cancer Causes-one in twelve..6 No. Deaths Genital Organs ................................................................................ 34,742 Stomach ........................................................................................ 24,258 Intestine ........................................................................................ 23,000 Breast ............................................................................................ 18,973 Prostate .......................................................................................... 11,339 Rectum .......................................................................................... 10,383 Urinary Organs .............................................................................. 10,044 Pancreas ...~ .................................................................................... 8,952 Leukemia & aleukemia .................................................................... 8,845 Lymphosarcoma ............................................................................ 7,911 Lung Cancer, unspecified ................................................................ "10,695 Lung Cancer .................................................................................. ** 7,618 Larynx .......................................................................................... 1,852 *not specified as primary source of neoplasm **specified as primary source of neoplasm (Following are the basic figures on respiratory cancer as they appear in Vol. IH, Vital Statistics of the United States.t7 V-Malignant Neoplasm oI Respiratory System. No. Deaths Of larynx ...................................................................................... 1,852 Of trachea, and of bronchus and lung specified as primary ............ 7,618 Of lung an.d bronchus, unspecified as primary or secondar~ .......... 10,695 Of other parts of respiratory system .............................................. 1,054 Total ........................ 21,219 16
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Reference Index Hueper, W. C., M.D., "Air Pollution and Cancer of the Lung", Rhode Island Medical Journal, pp. 34-36, January, 1953. Passey, R. D., Prof., "Smoking and Lung Cancer", British Medical lournal, p. 399, February 14, 1953. Damon Runyoo Fund, Statement issued November 27, 1953, from the Fund's head- quarters, Astor Hotel, New York, New York. Cutler, Max, M.D., Personal Communication dated March 3, 1954. Smithers, D. W., Prof., M.D., F.R.C.P., D.M.R., "Facts and Fancies About Cancer of the Lung", British Medical lournal, pp. 1235-1239, June 6, 1953. Little, Clarence Cook, M.D., Personal Communication, March 18, 1954. Sadowsky, D. A., Gilliam, A. G., M.D., and Cornfield, J., "The Statistical Association Between Smoking and Carcinoma of the Lung", Journal o/the National Cancer Insti- tute 13 (5), pp. 1237-1258, 1953. Rigdon, R. H., M.D., and Brindley, Paul, M.D., "Primary Carcinoma of the Lung", Texas State lournal o/Medicine 46, pp. 885-889, 1950. Rigdon, R. H., M.D., and Kirchoff, Helen, "A Consideration of Some of the Theories Relative to the Etiology and Incidence of Lung Cancer'~, Texas Reports on Biology and Medicine 10 (1), pp. 76-91, Spring 1952. Rigdon~ R. H., M.D., and Kircboff, Helen, "Smoking and Cancer of the Lung - Let's Review the Facts", Texas Reports on Biology and Medicine 11 (4), pp. 715-727, Winter 1953. Hueper, W. C., M.D., "Air Pollution and Cancer of the Lung", Rhode Island Medical Journal 36, (1), pp. 24-30, 34, 36, 52, 1953. Metropolitan Life Insurance Company, 1 Madison Avenue, New York, New York. Statistical Bul., Vol. 34 No. 2, p. 3, February, 1953. ~s Gagnon, E. D., M.D., "Bronchopulmonary Cancer: Statistical Analysis of 125 Cases", Union Medicale du Canada, Montreal 82, p. 767 July, 1953. Abstract in Journal o! the American Medical Association 153 (10), p. 986, 1953. 14 Rosenblatt, Milton B., M.D., "Relationship of Smoking to Cancer of the Lung", a paper presented before The Society of the New York Medical College, March 16, 1954. ~s Hartwell, Jonathan L., M.D., "Survey of Compounds Which Have Been Tested for Carcinogenic Activity", Second Edition, Federal Securi .ty Agency, Public Health Serv- ice, Public Health Survey Publication #149, p. 2, 1951. ~s Shear, Murray J., M.D., and Leiter, Joseph, lournal o/the National Cancer Institute, Vol. 2, p. 254, 1941-1942. ~ Leitch, Archibald, M.D., "The Experimental Inquh'y into the Cause of Cancer", British Medical Journal, Vol. 2, p. 3262, July 7, 1923. ~a Cooper, E. Ashley, M.D., D.F.C., F.I.C.; Lamb, F. W. Mason, M.D.; Sanders, Edgar, M.Sc.; and Hirst, E. L., D.F.C., F.R.C.; "The Role of Tobacco-Smoking in the Pro- duction of Cancer", Journal o! Hygiene, Vol. XXXII, No. 2. (From the University of Birmingham.) Undertaken at the request of the Birmingham Commission of the British Empire Cancer Campaign, April 1932 (British). lg Bogen, Emil, M.D., and Loomis, Russell N., M.S., "Tobacco Tar: An Experimental Investigation of its Alleged Carcinogenic Action", American Journal o! Cancer 16, pp. 1515-21, 1932. ~0 An extract from a contribution to the 30th Annual Report for 1952 of the British Empire Cancer Campaign by its Yorkshire Council British Empire Cancer Campaign, 11 Grosvenor Crescent, London SWI, Captain F. B. Tours, OBE, RM (Ret.), Secre- tary General. 17
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Rienhoff, William F., M.D., Statement dictated March 8, 1954. McNulty, James M., M.D., "Clinical Follow-up Study of 398 Patients Suspected of Having Lung Cancer Discovered in the Boston Chest X-ray Survey", New England lournal o/Medicine, Vol. 250 (1), pp. 14-17, .Tanuary, 1954. Vital Statistics o! the United States, Volume Ill, U. S. Department of Health, Educa- tion and Welfare, p. 76, 1950. Ibid., pp. 76-118. Ibid.,pp. 76-118. Ibid., pp. 84-90. Ibid., p. 86. PAGE Bogen, Emil, M.D ................................................. 11 Brindley, Paul, M.D ........................................... 6 Cooper, E. Ashley, D.F.C., F.I.C ............. 10 Cornfield, J ................................................................ 5 Cutler, Max, M.D ................................................. 4 Damon Runyon Fund ....................................... 3 Gagnon, E. D., M.D ........................................... 8 Gilliam, A. G., M.D., Dr. P.H., F.A.P.H.A .......................................................... 5 Graham, Evans A., M.D., D.Sc ................ 7 Greene, Harry S. N., M.D ............................... 14 Hartwell, Jonathan L ........................................ 10 Heller, John R., M.D ........................................ 12 Hirst, E. L., Prof., D.F.C., F.R.S ............. I0 Hueper, Wilhelm C., M.D ......................... 3, 8 Kirchoff, Helen ................................................... 6, 7 Lamb, F. W. Mason, M.D ............................... 10 Lanza, Anthony J., M.D .................................. 12 Leitch, Archibald, M.D .................................. 10 Leiter, Joseph ............................................................ 10 PAGE Little, Clarence Cook, M.D ......................... 5 Loomis, Russell N., M.S .................................. 11 Martin, Walter B., M.D .................................. 11 McNulty, James M., M.D ............................... 15 Metropolitan Life Insurance Company ............................................................ 8 National Office of Vital Statistics ... 15, 16 Ochsner, Alton, M.D ........................................ 7 Passey, R. D., Prof ............................................. 3 Rienhoff, William F., M.D ................... 13, 14 Rigdon, R. H., M.D ........................................ 6, 7 Rosenblatt, Milton B., M.D ......................... 9 Sadowsky, D. A .................................................... 5 Sanders, Edgar, M.S.C ..................................... 10 Serra, Lawrence M., M.D ............................... 13 Shear, Murray J., Ph.D ..................................... 10 Smithers, D. iV., Prof ........................................ 4 Stewart, Harold L., M.D .................................. 13 Yorkshire Council, British Empire Cancer Campaign ...................................... 11 18 o o o~
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Oonduct of the Pro~ra~ The Tobecco Industry Research Committee is an agency vhich sponsors research into questions rel~tln~ to tobacco use an~ health. It ~as or~anize~ earl~ in 19~ by representative~ of tobacco m~nufactur~rs, ~rowers an~ w~re- horsemen. The Committee itself neither ol~rates an~ research facility nor exercises a~ role in determining the nature or conduct of the program other th~n that of provtdin~ the necessary l~mds. The Scientific A~v~so _ry Board to the Tobacco Industry Research Cc~n~ttee is invested v~th fU~ resl~)nsibility for research ~o~cy an~ prog~un. .This Boe~d is con~osed of ~n ~de~n~nt scientists~ p~sici~s~ ~d edu~tors vho ~~ their o~r ~sti~tio~l ~fil~tions. It is essenti~ auto- n~s ~d se~-~~t~g. At p~sent th= ~ers ~ se~g t~e-~ ~ ~ ~elr ~ e~Ire. No ~r ~s ~ti~d from the B~ for ~use s~ce its or~i~ati~ ~ut %he~ ~ve been seve~ ~e ~se~h p~ ~s ~ the fo~ of ~ts-~-ald ~o es~bllshed ~vesti~rs ~ ~co~ized ~dlcal schools~ hospi~s~ ~iversltles ~ ~search 4-~i~s ~r a sys~m ~lose~ ~se~l~g t~t ~ use by such agencies as the Nati~ ~ti~s of H~Ith~ ~rlc~ Hea~ Assoclati~ ~n other heal~ a~ncles. Appli~tlons for ~ts f~ such ~vesti~tors ~ ~v~" ~ c~i~tlon by the B~ on the ~s~s of scientific ~rlt ~ ~ such p~s~ ~se~ch pro~ects ~ve received app~ ~d f~clal sup~ from the ~e B~ ~so s~ors ~o~ ~d~ble ~scusslon ~et~s to which Re~s) ~e~e ~scusslo~ so~t~s le~ to ~c0~Itlon of ~ps ~ ~ov~d~ t~t sh~ ~ fi~d, of hey ~c~i~es that ~ ~e applicable of ~sti~ti~. Hence they ~ le~ ~ ~It~tlve on the ~ of the p~ rese~h pro~ects ~d ~ di~ct effo~s ~ ~terest q~llfled e~s RecIpi~ts of ~ts-~-a~ ~e assu~d co~le~ scientific freedom the c~ct of ~e~ ~vesti~tlons ~d ~ ~~8 the ~sults of their researches ~ the ~cep~d sclent~Ic ~er t~u~ ~dlc~ ~d scientific ~ou~Id ~ on t~ p~tfo~ of ~cal ~ sclen~Iflc z~letles ~d confesses. ~e ~vesti~tors ~cei~ ~ts fr~ the Co~ittee a~ alone res~nslble for publication or fe~- ing of their ~se~ch f~dings. Such publlcatlon¢ ~ ~dentifled as ~sult~g from ~ts-~Id of the To~cco Indust~ Research Co~4ttee o~ by the c~t l~e ac~ovle~g assls~ce from the Co~t~e~ o~n ~th assls~ce al~o from other ~t~ asencles. 0 0 0 O~
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-2- The fina~n3s of the Tobacco Industry Research Con~tttee research program thus enter the ~eners/ stockpile of scientific and mefical Information relevant to the subject of tobacco use and human health. In this way the infor~ation becomes available for evaluation by the entire fraternity of =edical and scientific men and contributes to the ~ulual~ progressiv~ develol~ent of better understanding and perspective. An Annual Repor~ is published by the Scientific Director of the Tobacco Industry Eesearch Committee~ Dr. Clarence Cook Little~ in which all grants that have been made are reported~ together with a statement of the purpose of each stud~ the investisator who is to direct it and the institution in which the work is to be done. A~I scientific papers that have ~e~n published during the course of the year are listed with full reference to the orl~l ,,- literature and with an abstract of the fina~ngs~ approved by the principal /. author. In addition~ the Scientific Director gives his own analysis of status ~.,; .. of the problem as a whole and of the be.arin~s of individual studle~ on the .,\~: i,i~: general state of knowledge of the .subject. q,~..~ ~"-'- ~. ~ ~ Since "~ucePt~on of the ~ro~n~ a total of $3~ 200~000.00 has ~een made :~;,~: ~-"~vatlabl~ tothe Scientific A.~visory Bo~__rd for its investi~ations. A~out ..... $2~1~0.6~ of this has been allocated to scientists for specific studies." -.~- ." Of .this totals. $1~506~Y32.07 has been appropriated for stu#tes bearin~ more " ;: ~" "" or less directly, on cance'r. Thirty-nine distinct stud/es ~n various aspects :.. of cancer have be~n approved in thirty-five different instituti~ns. Of these -'- ~: " t~wnty-three have'~ direct or indirect ~earing upon cancer of the lung. ...~ .., • ~ . . . . ~ " . • -"" -" Results of Research "r~i'~ ~ ~ " In~a~tton S~udies. ~,.~ .~. .~.~:~./;~ "--.~ ~ . o : .... ~- " Five studies ha~e Luvolved the exposure of experimental an~Is to ~. ~ ~.. inhaled cigarette s~oke. Drs. George. E, Moore and Fred Bock of ~he Roswell "~:'~ Park Memorial Institute h~'ve exposed mice of tw~ strains to 'cigarette smoke ..:~ . . ~atlon in a machine ~hich controls the puffin~ conditio~ to .~.~ ..... ' "close~v the manner of ~n,~-u-. smokln~ for periods approachin~ the entire "-"~ .... normal llfespan of the anlm~is after weanlng, No lung cancers of the type :-..~ prevalent in humans w~re Froduced. L~ng adenom~s of ~he type that occur • ":~ " n~tur~y in these mice occurred no mo_~ frequently than in unerposed mice. smoke ~ion ~y CF~ ~ce which were e~-o Painted on the skin with the potent ca~cino~en~ metl~y~cho]~threne. No s~ne~lstic effect was observed.- Dr. Herbert R. Hawthorne and Dr. Alfr~d S. Frobese of the University of Pennsylvania set up the necessary machinery for introducing fresh cigarette smoke directly into the lunss of dogs through artificial openings in their windpipes. The smoke was produced under carefully controlled conditions of puffin~ volume~ duration and frequency in order to assure that the co~positlon of the smoke would resemble closely that of smoke normally inhaled by The stud~ ~as continued for more than three years and individual dogs received the smoke of 10-20 cigarettes daily for n~y months. No lung cancers developed. T-ae animals were eventually sacrificed for p~thological ex~mir~tlon of their lungs, hut no report has been received concerning this e~dnation.
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-3- Dr~ B. L. Freedlander an& Mr. Frederick French of ~t. Zion Hospital in " tion for ~ so~t ~ffer~t ~se. ~ fo~ t~t ~e suscepti~i~ty of ~ce ~ I~ ~n~s of the t~ t~t c~ ~ ~uced ~y feed~ u~th~e de~n~ u~n ~ supp~ of a ~.~ nlac~ they ~sh ~ ~~e whether ~ ~en~ of to~cco ~ ~ ~uence the effective ~pp~ of this vl~ ei~er ~rect~ or ~~. ~o ~sults ~ve ~t ~en ~~. ~s "hyperpl~sia or me~aplasla" at a~y age above 25 years. Less than 30 percent of all cases studied~ Including both sexes and all ages, had ,~ll sections examined showing =ucosae classed as Males show~d changes departing from "no~l" more often t~u females, but both metaplasia and hyperplasi~ did occur frequently in fe~es. Ci~_rette smokers in this stud~ showe~ fewer "normal" sections than non-smo.~ers.
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"~'~ " " ~'..., ~, ~y a rough division of occupations int~ "hazardous" (those . - ~ose ~ f~ ~d o~ers~ ~o cons~s~nt excess of ~- -'- -'" p~z~ or ~~s£a ap~a~d ~ the stu~ ~ ~ of ~hese .- . ~. -. - ~e ~ups, ' ' 5- Stu~ of ~he ~cur~nce of ~p~sla or ~~sia by the size of the ~gest city ~ ~ch the cases ever ~slde~ ~vealed no differences. 6, Metaplasia was present in more cases dying from lung cancer --_-- - ~ in those who died from other c~ncers or from aLt other ~. causeso " ~':~--"~;T-~'~~-'~'" "I~, Rus.-ell Weller of the West Chester Cow-,unity Hospital is continuing "~-~'~:.~-~ -h partl.of th~s. study by ~mS a more minute ex~m~atlon of h~s collected lungs ~.:" - • of t~ ~ffer~g centers as to how c~cer arises ~ tissue, Options ~ffer ~ ~* ~: ": " - "':'- 3J ~e n~er of cases of bronchitis ~ ~ ~oup or the • ~.. ~ - ..~..~ .- ~ ~verity of the ~-~l-~tion see~ to bear no re~tion ~u "," .... . either ~ the intensity of the ~ke do~se or to the
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pre~tion of skin tests impossible for the purpose of forecasting effects on the lung. - ".: -.- " "" Dr. Fred G. Bock of the Ros'~ell Psrk Memorial-Institute has painted Swiss mice with ci~rette .~,moke condensate, with au& without mechanical irrt't~.tton ~md with or wt_.thout irr~.diation with X-~ys.
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o ~
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• ~i' "-°~ :'." ",:." "''': "." '*'" . ' '"" "" ." " ~ ." "~.""~..'.~ "*"% ~. ~ *" o'O " - "-" .'. " " .-- " "- • * " " .*" i. "-- "' ~,'o.'.': ~..., - . -.": ", " -" ; ,.-'.- ,, 7 .~ " . , • " "~ " "" .," -.-~,~ .,~" ,, :-. " Dr, A, C.~rk ~riffinj formerly of Stanfor~ University and now at • ~.-'-.9. 2.acetylamlnofluoren_~ to inauce precancerous chanses in the liver. One ~ % group was exposed to ~nha~tion of cisarette smoke and another injected with a laboratory prel~rztion of smoke condensate (probably abnormal in composition) prepared by burning ci~rette tobacco in a glass funnel. Both tcbacco smoke exposures secmed to delay somewhat the appearance of pre- caacerous liver chanEes.
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ph~o~non t~t ap~s pro~s~g as a ~sts for a ~st ~th~. He obse~e~ t~t ce~ t=rs ~ch ca~-ot ord~ri~ ~ t~sp~ted st~ of ~ce ~ v~ch ~ey ~ alien~ ~ "~e" ~d ~ow if the a~ f~st ~d (or ted) ~th ~c~oge~c ~ocarbons for a ~rl~ of t~ prior ~ ~e t~sp~t. ~e t~ dur~g which the t~sp~t ~ ~w is ~d ~ t~ do~ of ~~bon ~lven. ~ith sufficient do~e~ e~n noel s~ ~ the a~ st~ c~ be t~sp~d success~ for q~ti~ti~ ~ its e~l~tion ~y c~rison of a ~ co~ection of nuclear ~ocar~ns is ~der ~y. To~cco ~s not yet ~en ~s~d s~ce results could no~ ~ ~~ ~til ~re ~asic "~rk ~s been ~ne for ~ ~ " " ~. T. M.' So~e~ of the University of ln~ ~s ~de~en ~. ~ide ~her stu~ of ~ carc~os~icity ashy ~th~ ~se~ on t~ res~nse n~er of such ~ar~ is to ~ ~de in ~11~1 ~th tests by Dr. ~b~'s . ~,. ~ ~'~ -~.., - . ~ ~ ~ ~- ",,.~ ,~. ,. - G~ts ~ve ~en m~ ~ four ~bo~rics for (1) tm~ ~rso~el ~" / ~" . ~ t~ k~d of vork~ (2) atOnE to es~bllsh s~s of ~rlous h~ t~e~es es~-ial~ 1~ tis~e, (3) obse~ the ~ture of c~es fr~ no~l ~/"" to ~i~t cells ~ (4) obse~g ~d descrlb~g the res~nses of such tissue ~~-" " ~ ~cco ~e ~lents ~d other aEents. ~ ~or~ O~ ~ of Jo~s Hopk~s University~ Dr. C~rles M. Po~~ - of ~e ~Iverslty of Te~s ~dic~ B~ch~ Dr. ~id M. Pace of the University of Neb~s~ ~d.Dr. P~li~ C~r of the ~be~ Eius~ ~cal Colle6e , " . e~ged ~. thes~ ~es. "~ ~ork is of a long-~ge ~ture ~d no ~sults ~~ appl~cable to the p~blem of h'" ~ 1~ c~cer ~d ~cco use - " Miscellaneous " " Se~e~l other s~dies ~ve o~ ~direct bear~g on the effects of ~k~g on the h,~n subject. , ~ ~ Dr. E. M. Butt of the University of Southc~ ~lifo~ia ~s been ~ " "~vesti~t~ the s~ge of ~rlous t~ce ~Is In hu~ l~gs ~d livers " ~ ~ se~ch of Nsslble clues ~ the pre~!ence of ~,ieu~r ~ise~ses " ce~in localities.. .... . ~"
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Vo...',~.. "" .~. ' .... • .- ,.-, ...... : t . :,'- '~ . ... ".., . • .., , - •.. ' ... . ~ . , *,".o • ~.,,.,,~,,, ~'~ " °, ,~.. - ~" ~--~, ".'.-'*" • ".-s '.." -' , ", - ,,,- * "'. • . ,"~ .,." .'"..:','~ .... ''~'. - .,-"+= --': +~"+' ~. ~el S+~f of the Insti~ for C~cer Rese~ch ~ the ~e~u" ~." .~'~- • + / 2~, Hospi~ Rese~h I~ti~ ~s investi~ ~er hov e~c~o~nt~, azo ~s .[~. ~ ~~... ~ -. ... ~ ~co~m~ ~ ~e~ pro~ co~stituents ~f the liver. : .~ ~.-- .. "~ ~ s~ of ~he ~c~ b~ ~~sia N ~sts~ce, He ~s sho~ boy lrrl~- ~ " tion ~ f~st ~uce p~ depletion of a tissue a~ ~flec~ ~ ctrculatIo~ ' . of ce~ prote~s as ~o~ul~ ~ the se~ ~en ~c~ased ~si~ce to ~her damaEe. As resistance increases, the initial hyperplastic r~sl~nse falls off sharp~y and the resistant sk~u loses ibs hyl~r~lasia. Skin responds to tobacco smoke inch as it does to other agents. Dr. Isaac Schour of the University of Illinois College of Dentistry directed a basic stud~ of the pathology of human oral tissues, especially as Dr. Charles E. Sher~v, Jr. of the University of Rochester School of ~e-diclne and~ l~en-tistry directed a "stGdy of old chest X-ray plates of persons who ~ere eventual~y dlagno~e~ as having lung cancer. The main ~ur~ose was to improve the interpretation of the earliest cban~es diagnostic of lung cancer as revealed .by radiology. As a by-product of this stud~, an enal~sis was made of the occupa- tions of the l~rsons whose histories vere collected. This shoved that persons whose occupations eubJected them to In~lation of dusts and ~ ~es were more like~7 %o be heavy smokers than persons not so exposed. Dr. Hans Falk of the University of Southern California has made an~l~tical studi~s to coml~re the traces of pol~nuclear hydrocarbons in mainstream and side- strea~ smoke ~roduced under various conditions. He has also observed effects of smokes on the ciliary activity and ~ucous flow in isolated bronchi of several s~imal Sl~cieso
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Octc~e~ 22, 1970 F I:~OH: SUB3ECT: Industry Technical Committee W. T. Hoyt, Executive Director Meeting of the Industry Technical Commlttee, Tuesday, November 3, 1970. A meeting of the Industry Technical Committee will be held in The Council's offices (II0 East 59th Street, 10th floor) on Tuesday, November 3, 1970 at 2:00 P.M. The ~rimary purpose el the .meeting will be to discuss smoxing machlnesand the work done at ~ason Research Institute. In the event that you cannot attend this meeting you may want to send an alternate. Will you please return the duplicate copy of this memorandum, noting your plans regarding attendance. W.T.H. • • WTH:ek att. I (will not) I' attend the meeting on November 3, 1970. S~gnature
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2422 REV. 5'67 INTER-OFFICE MEMORANDUM Subject: To: Evaluation of Smoking Machines by Council for Tobacco Research Date: De~ember 3, 1969 [- The Scientific Advisory Board for the Council for Tobacco Research is setting up a program to evaluate four smoking machines for inhalation research on laboratory animals. Machines are being furnished by R. J. Reynolds, Philip Morris, Mason Research Institute, and the German tobacco industry (Dontenwill machine). I am Chairman of a subco~unittee from the Industry Technical Committee to assist the Scientific Advisory Board in the evaluation of the machines. A meeting has been called of the subcommittee to discuss the protocol for the evaluation of the machines. Other members of the subcommittee are: Drs. Osdene and Carpenter of Philip Morris and Dr. Nielson of R. J. Reynolds. The meeting is to be held in the Council for Tobacco Research office at 9:30 a.m., Friday, December 5. MS:has Cc: Mr. E. A. Vassallo ~'-
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/ Mr. E. H. Ramm~ Mr. E. A. Vas~llo June 3, 1970 MEETING OF RESEARCH DIRECTORS OF THE TOBACCO INDUSTRY THE TOBACCO INSTITUTE - WASHINGTON, D. C. J~NE 2~ 1970 Present: Amerlcan Tobacco Company Preston H. Leake, Assistant Director of Research E. C. Cogbi11~ ~arlager of A~alyc~cal ~esearch Brovn b Wlllt~_mon Tobacco Company I. W. liughes~ Director of Research Liggett & Hyers Tobacco Company Wllllam W. Ba~es, Vice President & Director of Research .John F. t/illl-m-~ (present at Pesticide session only) ".orillard Corporation A. W. Spears~ Dirt.trot of Research & Development Claude 1. Lewls (present at Pesticide session ~nly) Philip Horris, Inc. Hel~u~ Wakeham~ Vice President, Recta: ~ & I, evelopme[,t Thomas S. O~dene~ Director o~ Research H. A. Nanzelll (present at Pesticide session only) R. J. Reynolds Tobacco Company Hurray Senkus, Dlrectbr of Research F. G. Colby (present at Pesticide session only) 1TEHS ON AGENDA I. Report of the Agrlcultural Residues Comwlttee Claude I. Lewis, Chairman (Lorillard) A. M. Hanzelll (Philip Horrls) John F. T/illlams (Liggett & Hyers) James E. York, Jr. (American) John E. Kennedy (Brown & ~qilliam~o~) F. C. Colby (R. J. Reynolds)
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• • 2 Heeting at Tobacco Institute June 2, 1970 Two years ago, the Research Directors of the tobacco industry appointed the Agricultural Residues Committee to survey the literature in the public domain ~, twelve selected insecticides on a shared labor basis. This gooling of resources would then afford each company a report on the teelve insecticides and an appreciable savings in labor. The subdivision of labor was as fol|o~s: ' Company Assigned Insecticides American DDVP Carbon tetrachlorlde Bro~n & Nilllmason Parathion Liggett ~Ryers Lorlllard Guthi..t (Azlnphosm~gnyl) Sevln (Carbaryl) Philip Eorrls • )~-30 Penar g. J. Reynolds DD (ridden-D) EDB-85 I~ the last six months the Agricu~tural Residues Committee has expanded the survey on these insecticides to include in-company Information of a non- proprietary naturc. The complete reports have been reviewed and accepted by the Research Directors at the present meeting. As further action at the pre~ent meeting on residues, the Committee recognized that additional analytical cork needs to be done on some of the insecticides, particularly the study of the fate of some of these pesticides residues cm tobacco. 8oreover, it was pointed out that the general nature of their propo..-~d work is s~llar to the program being undertaken at North Carolina ~;tate University. Thus, it ~at decided to delegate Dr. N. 8ares of • Liggett &~yers to see if all or part og ~he proF ~sed wo~k might be carried out by N. C. State University. A.planning meeting for N. C. State University work will be held in .Raleigh on June 5. R. J. Reynolds will be represented at that meeting by Fir. Ivan t;eas and Dr. C. E. Teague, Jr.
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1~eet~ng at ~obacco ~nstitute June 2, 1970 Dr. Bates will make available the survey of the ^grlcultural Residues Committee to the workers at N. C. State University to expedite the work that might be undertaken there. Dr. Bates will report to the Research Directors st a meeting in Nashlngtoa on July 7. 2. ~eport on Chemosol Hurray Senkus reported that the manufacture by R. J. Reynolds of Cbemosol test cigarettes ~nd appropriate controls was completed last month. The cigarettes were shipped on AprI1 29 to Bazleton Laboratories) Inc. In Falls Church, Virginia, On Nay 6, Jo__,~s L. Gargus wrote to Hr. R. H. Cundlff acknowledging receipt of the Che~osol cicurettes and the control cigarettes In goo~ condition on Hay 4, 1970. Hazleton viii co~pare one lot of the cigarettes with the second lot. Hazleton does not kno~which is te~t an~ ~hlch is ccatr~l. Tests will be made for benzpyrene in s~ke and for effect of s~6ke on the skin of. mice. Che~)sol o~ners maintain that. their additi-ve-reduces-ber, zpyrene in smoke; and that it also reduces effect on ~kin of mice. I)ete:~nlnatlon of benzpyrene by Hazletoa vll~ requir~ a month or skin painting ~x~erlments at Hazleton will require t~o years. Contact with Hazleton during these tests on behalf of the tobacco Industry will be maintained by the law firm of C~vington & Burllng, legal representatives for the tobacco industry. They will see to it that the tests wil]: -dhere to the protocol agreed upon by Chemosol and by the Research Directors cL the tobacco industry. 3. Smokir, g Hac,.~nes for the Scientific Advisory Board (SAB) of the Council for Tobacco Research. Hurray Senkus repo~t~d as follows: In December 1967, the SAB requested the Research Directors of the tobacco industry to develop smoking machines for inhalation st~dles concerning smoking nnd health.
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~leet.ln~. at Tobacco Instltute June 2, 1970 In response to this request~ the Research Director. appointed a con~aittee to assist the SAB in their program. Co~ittee members appointed were: Hurray Senkus~ Chairman Thomas S. Osdene (Philip Horris E. b. Nielson (R. J. Reynolds) R. D. Carpenter (Philip H~rrls) By 5~nuary 1, 19~0 the Committee had arranged for the following: 1. Design and construction of the PJR machine 2. Redesign and construction of the Phl|lp Horris machine 3. Redesign of the ~alton machine (Boston) Redesign of the Donten~111 machine (Han~ur8~ Germany) February 26~ 1970, all machines (2 R. ~. R~ynolds, 2 Ph~Hp Hor~ls, 1 ~alton~ and 1 Dootenw111) were delivered to Hason Research Institute~ ~orcester~ Hassachusetts where they are to be evaluated for the SAg. Esaluation of the RJR and Philip Horris machines is nearing co~p|e~ion. The ~alton and Donten~ill machines require further ~odiflcation before evaluation can be started. Hason Research comments dd'th~ R~k ~ndPh~'~Y~1~-:m~chlnesdre as follows: ................................................... R. J. R~ynolds The machine is mechanlcally difficult to operate and does not permit smoke-alr dilution. It is the feeling of A3R ~hat this can be corrected by further improvement. It has s~me distinct assets from standpoint of inhalation studle3, such as visibility of animals, easy cleanlng, purge system~ mobility and others. It is m: opinion thBt it ~s the best machine of th~ four being tested. Phili_I[Horris The machine requires further modification if it is to be subjected to prolonged use; in particular, certain moving parts must ,e protected fro~ falling ashes wblch render the machine inoper~#~. Animals are not vlslble~ which is a serious h~ndicap. Also, the machine emits large volumes of smoke into the room, which necessitates provision of ~ special hood• On the other hand, the machine is quiet, permits dilution of smoke with at one time.
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Heetln£ a!: T~bacco Institute ~]une 2~ 1970 ~altcn and Dontem-~il~_. Hachi~es Further modifications are necessary before evaluation can be started. Hason peraonnel viii attend to these modifications by dealing directly vith ~lomburger O/alton) and Dontenwill. : .* 4o Smoking-lIealth Research of the l~.~ac,~tion Research Foundatior, of the An~rican ~dical Association and ~f th~ Council for Tobacco Research. C~s~derable discussion ensued regarding the above progr~s. the t~cco i~dus~ h~s spent ~16 milli~ on the ~R program ~ the ~ program. i~atu~all~, ~he Research Dlrc~tor~ have ideas ~s ~o f~e c~e~ of research in these areas~ based on results to date. It is possible that the oFinions of the Research Directors may be helpful to the tobacco industry in the further conduct of s~oklng-health research in these two areas. Accordingly~ two committees have been appointed to prepare ...... a critique- ~nd recon~endations on the two programs. Drs. ~akeha~ (Philip Horris) Hughes (Brown & gilli~son) and Leake (/u~e_rican) rill prepare a critique and reco~endstlons on the ~rR prosram. D~s. Spea:rs (Lorillard) Bates (Liggett & Hyers) and Senkus (~eynolds) rill preIare a critique and recomr.endations on the AhA program. A ~eeting will be held on July 7 to prepare final critique and recom- mendations. 5. CORESTA Dr. W&keh~m reported on plans for the forkhComing CORES~A meeting in Hamburg~ Germany. September 13-19~ 1970. At present, Brown & ~illiamson, Philip Horris, Lorillard, Reynolds and, most recently~ Liggett & Hyers~ are me~bers. Dr..Colby and I are slated to ettend the Hamburg meeting. The primary aims of CORESTA (Cooperation Centre for Scientific Research Relative to Tobacco) are to develop analytical procedure~ and technological practices that could be adopted on a world-wide basis. R. J. Reynolds' interests to date are confined to analytical pro,~dures. Haus Neuerburg is participating in this area through Herr Jodl~ Chief Chemist for Haus Neuerburg.
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Meec~g at Tobacco !n~t~tute June 2, l~?O 6. Symposium on the Benefits of $:aoking Philip. Harris' Research and Development personnel~ upon consultation ~ith their Chairman of the Board, Hr. Cullman, had conceived the idea of organizing a symposlum on the benefits of smoking. This would consist of presentation of papers on the subjeCt.by eminent scientists. The ~hought was to hold it in Janua~" 1971 bet~ winter and spring semesters of most L~Itcd State universities. .~ In thinking about it further, Philip Horris' people decided it would "be desirable to hold the symposium ~nder the sponsorship of the CTR rather than under the sponsorship of an indivldual company, or some other group. Thus, ~ith that in mind, Philip Horrls will discuss thei~ plan ~ith certain key people at the CTR ~ June 17. Dr. Wakeham will inform the R~search Directors of the tobacco industry about the d,~cislon of sponsorship of the symposium by ~he crR. KS:has Dr. C. E. Tengue Dr. E. D. Nielson H~arra)¢lsenkus - ~
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CONFIDENTIAL - FOR USE OF COUNSEL Mr. H. H. Ramm/ September 11, 1969 MINlYrES OF I'tEETING OF INDUSTRY TECHNICAL CO>~MITTEE - C,T.R. NEW YORK, N. Y. - SEPTEMBER 10D 1969 Present: Eo S. Harl~w Arthur Buxke J _~et Br~ Robert Sanford J. C~mpbel I A. W. Spears H. Wakeb am T, S. Osdene M. Senk~ E. D. Nielson W. Bennett R, C. ~ockett W. T, Hoyt J. Kzelsher J. H. Brady - American Tobacco - American Tobacco - ~merican Tobacco -,,.Brown & Ni11Iamson - Imperlal Tobacco - Lorillard - Philip Morris - Philip Morris - I~. J., Reynolds - R. J. Reynolds - U. S. Tobacco - C.T.R. - C.T.R. - C.T.R. - C.T.R. - C.T.R. - C.T.R. The agenda for the mee'ting was: Election of officers for I.T.C. Reports on status of smoking machiaes tc be furnished ~o the S.A.B. •nd co be furnished by: R. J. Reynolds Tobacco Company Phillp Morris, Inc. Brown & Willlamson Tobacce Company Discussion of the evaluation of the performance of swoklng machines in ~i~al exposu~'e. o
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2 I. Election of Officers Preliminary to the election, it was agreed that, barring unforeseen developments, (l) officers would be rotated alphabetically by tobacco companies, and (2) the Vice Chairman elected would succeed the outgoing Chairman. The term of office would be two years for the sake of continuity. To establish good rapport between the S.A.B. and the I.T.C., the Chairman of the I.T.C. is expected to attend the quarterly meetings of the S.A.B. Inasmuch as the preceding Chairman was from Brown & Williamson (Griffith), the incoming Chairman will be from Lorillard and he would be succeeded by the Chairman from Philip Morris. On this basis, Dr. A. W. Spears, Director of Research and Development at Lorillard was elected Chairman, and Dr. Helmut Wakeham, Vice President and Director of Corporate Research at Philip Morris was elected Vice Chairman. Dr. Spears' ter~n will expire in May, 1971. New officers would be elected in April, 1971, preceding the May Quarterly Meeting of the S.A.B. Both the incoming Chairman and the outgoing Chairman of I.T.C. will attend the May, 1971 Quarterly Meeting of the S.A.B. to establish continuity. 2. Status of Smoking Machines R_e_port from R. J. Reynolds Tobacco. Comp_any Dr. Senkus reported that R. J. Reynolds will have two machines ready for delivery to the SoA.B. on October 15. He agreed to deliver one of these machines for testing, presumably some place in the northeast, perhaps at the Mason Research Institute as now being contemplated by Dr. Hockett. A special truck will be provided by R. J. Reynolds for delivery of the machines. Report from Philip Morris~ Inc. Dr. Wakeham reported that both of the Philip Morris machines are ready for delivery. It was agreed that the R. J. Reynolds truck will pick up one of the Philip Morris machines on its way through Richmond, for delivery along with the R. J. Reynolds machine to the place w~ich is yet to be determined. Dr. Lisanti will inform R. J. Reynolds and Philip Morris where the machines are to be delivered. Report from Brown & Williamson Tobacco Company Dr. Sanford represented Bro~ & Williamson at this meeting and made the following report: Bro~ & Williamson will not provide any smoking machines to the S.A.B. as was originally contemplated. The machine which was being developed under Dr. Griffith's supervision for Brown & Williamson at Battelle Memorial Institute, is not yet operable. Further development of. the machine is now being done under the auspices of the Tobacco and Health Research Institute at the University of Kentucky. O - tJ
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3. Evaluation of Smokin~ Machines A subcon~nittee, to be known as the Planning Committee of the S.A.B., has been appointed to take charge of the evaluation of the performance of smoking machines in animal exposure. Members of the Planning Committee are: Dr. Richard Bing Dr. Leon O. Jacobson Dr. Clayton G. Loosli Dr. Sheldon C. Sommers According to Dr. Furst of the C.T.R. staff, the Planning Committee will likely evaluate four machines, namely, the Reynolds machine, the Phi]ip Morris machine, the Dontenwill machine developed in Europe, and the Walton modification of the Walton machine. All machines are to be tested side by side to obtain valid comparisons on extents of exposures. In making the evaluation of the four machines, it was recognized that assistance will be necessary from the I.T.C. Committee, especially insofar as some chemical and analytical determinations are concerned. Accordingly, Dr. Spears appointed an I.T.C. Subcommittee to work with the Planning Con~ittee of the S.A.B. Members of the I.T.C. Subcommittee ~re: Dr. Murray Senkus, Chairman Dr. E. D. Nielson Dr. T. S. Osdene Dr. R. Carpenter - R. J. Reynolds - R. J. Reynolds - Philip Morris - Philip Morris A discussion followed as to possible means of determining whether" any smoke entered the respiratory tract of any animals during exposure in the machines. Dr. Nielson reported that measurement of CO in the blood stream can be made. He showed data which established that these measurements will be useful in the evaluation of the machines. Dr. Osdene of Philip Morris reported that they have had very promising results of determining extent of inhalation by animals of smoke, using radioisotopic procedures. This will likely require further development but it is a very promising approach. Dr. Spears of Lorillard showed data on use of silver nitrate and a very stable organic compound (4,4'-dichlorobenzophenone) as additives to tobacco which can be used as nonradioactive tracers.
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In view of the leads opened up by Reynolds, Philip Morris and Lorillard, it appears likely that the Planning Committee of the S.A.B., In cooperation with the Subcon~ittee of the I.T.C., will have available a means for the dete.rmination of extent of exposure of animals in the various smoking machines. Dr. Senkus will arrange for a meeting of the two committees early in October at which time plans will be made for evaluation of the smoking machines. The meeting adjourned at 12:15 P.M. ~:has Cc: Mr. E. A. Vassallo Murra.~ S~n~us-
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December 9, 1968 MINUTES OF THE MEETING OF THE SMOKING ~CHINE SUBCOMMITTEE OF THE INDUSTRY TECHNICAL COMMITTEE~ COUNCIL FOR TOBACCO RESEARCH - NEW YORK~ NEW YORK DECEMBER 6, 1968 PRESENT: C.T.R. - Hoyt, Hockett, Kreisher, Lisanti, Brady, Little S.A.B. - Loosli, Andervont, Cattell Brown & Williamson - Griffith, Esterle, Spivey Lorillard - Spears Philip Morris - Osdene R. J. Reynolds - Senkus, Nielson, Fluck, Trivette The purpose of the meeting was to discuss the smoking machines for inhalation research which are being developed by Brown & Williamson, Philip Morris and R, J. Reynolds. R. J. Reynolds Machine The prototype of the R. J. Reynolds machinewas delivered to the C.T.R. offices and was exhibited at the meeting. Dr. Fluck discussed in detail the mode of operation and answered questions which were put forth by members of the S.A.B. and C.T.R. Brown & Williamson Machine A prototype of the Brown & Williamson machine is now being contructed by Battelle Memorial Institute. Construction will be complete by the middle of January, 1969. Representatives of Brown & Williamson showed slides which depicted various parts of the prototype. The unique feature of the machine is that it will deliver fresh smoke to the animals continuously. This is achieved by means of a carousel arrangement equipped for smoking 30 cigarettes. The cigarettes are smoked in rotation, with a two-second puff for each cigarette. O
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Philip Morris Machine The Philip Morris machine was built some time ago and is now being used in experimental studies by the Swedish subsidiary of Philip Morris. Like the Brown & Williamson machine, it delivers smoke continuously to the animals, using 30 cigarettes on a carousel arrangement. FUTURE ACTION Mr. Hoyt informed me at the end of the meeting on December 6 that a decision on a smoking machine for inhalation research was to be made at the S.A.B. meeting on December 7-8. On checking with Dr. Griffith, who attended the December 7-8 meeting of the S.A.B., I was told that there was hardly any discussion of the machine, nor was any decision made as anticipated by Mr. Hoyt. It was my impression from the remarks made by Dr. Loosli that all three machines will be recommended for use in future studies that are to be sup- ported by the CoT.R. and the choice of any one machine will depend on the objectives of the C.T.R. grantee. MS :has ~ enkus
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CONFIDENTIAL - FOR USE OF COUNSEL ONLY October 28, 1968 Mr. H. H. Ramm MINUTES OF MEETING OF INDUSTRY TECHNICAL COMMITTEE - C.T.R. NEW YORK, N. Y. - OCTOBER 25, 1968 Members Present : E. S. Harlow Arthur Burke R. W. Griffith, Chairman J. Campbell G. Shelton A. W. Spears H. Wakeham M. Senkus W. Bennett W. T. Hoyt R. C. Hockett V. Lisanti - ~ American Tobacco - American Tobacco - Brown & Williamson - Imperial Tobacco - Larus & Brother - Lorillard - Philip Morris - R. J. Reynolds - U. S. Tobacco - C.T.R. - C.T.R. - C.T.R. The following items were on the agenda: I. Reference Cigarette Dr. Griffith reminded those in attendance that development of a reference cigarette was initiated by the C.T.R. staff at the I.T.C. Meeting in December, 1967. Dr. G. W. Stokes, Director of the Tobacco and Health Research Program at the University of Kentucky, was approached on this matter early in 1968 and had agreed to sponsor the reference cigarette. Dr. Stokes, working with members of the I.T.C., has now formulated plans whereby the University of Kentucky will arrange for manufacture of the reference cigarette and be the distributor. Attached is a letter from Dr. Stokes which is being mailed to cigarette manufacturers as an invitation to produce the reference cigarette for the University of Kentucky. ~n o
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UNIVERSITY OF KENTUCKY ~October 23, 1968 Industry Research Representative: Enclosed is a letter of intent that describes the intent" of the ~niversity in the development of the reference cigarette and the specifications for the reference cigarette. An'attempt is made to establish an. ~nvironment that will ~ermit us to.proceed with logic towards the completion of the d&tai!s involved in selecting a manufacturer for the reference cigarette. Notethe item on which ! will expect you to respond as follows: An i~mediate indication (yes or no) of your company for the ~anufacture of reference cigarettes, and by November !, 196~ (or as soon as possible thereafter), a firm quotation on the item as presented. Sincerely, , G. W. Stok4s, Director GWS:jf
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• LETTER OF INTEk~ The reference cigarette is being developed to satisfy a specific research need of scientists working to clarify the tobacco-health interrelationship. The need for a reference cigarette, recognized by the total scientific community as a stable reference that will, as nearly as possible, be maintained over time. The reference may be used by all those that desire to do so. Supply of the reference will be determined by intent-to-purchase and other requests without limitation. The intent is to satisfy the research requirement. It was recognized at the outset tha~ to make available such a reference cigarette, the separate talents of scientists at the Universities, Industry, and Department of Agriculture would be needed. The mutual respect and trust of all those cooperating has been rewarding. The objective to develop specifications for the best reference cigarette that the combined thinking of such a group could yield was defined. This objective has been satisfied. Supplying the reference cigarette to the scientific community will be a major accomplishment. The attached specifications have been determined using factual info_~mation with adjustments based upon experiences of several major cigarette manufacturer~. We recognize that the grade selection of tobacco usea for the first reference ruin as extremely important. To put tege'dqer a blended reference cigarette that.is both acceptable and is "easily" reproduced requires extremely sound judgment. Thi~ responsibility must be fully recognized in establishing the first- run grade.blend. The ultimate care given to the selection of grades that are uniform, that are available, and that will pe_~mit reproducibility from run to run, year to year, and company to company is most important. The smoothness of this ~ndeavor will • be enhanced by our (The University of ~entucky and the ~elected manufacturer) ability to co~m~nicate with one another. • Certainly we recognize the importance of reproducibility on which the life of the reference cigarette depends. Any decision that .involves reproducibility must be made with care and logic. We recognize that once a manufactured is selected and has produced a few runs, it would be to the adva~atage of "reproducibility" to stay with one manufacturer indefinitely. This should be possible if mutually acceptable. We recognize that frequent runs (within reason) will permit a slight drift over time rather than more In~reqaen~ runs that would tend to favor greater differences between runs.
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4 Me recognize that in supplying the reference to the scientific ' con~.unity we are accepting a responsibility to supply each researcher with the best reference available and one that will add meaning to his research effort. We recognize that if this job is done properly, advances in tobac6o and health research will be accelerated. This statement is' prepared to transmit the intent of the University of Kentucky in the development of the reference cigarette. The future will include other research samples and variations and no attemot will be ~de to enumerate at this time. In order that a selection of a manufacturer can be made for the development and negotiation of a contract that will lead to the production of the reference, we ~ust identify as precisely as possible an item to wlnich each interested company may respond. The item: I0 ~illion reference cigarettes made and packaged as to e~closed specifications. (no storage - no shipping costs - no costs other than making and packaging). Costs to include those related to tobaccos, manufacture and packaging costs~only. It is understood that a formal contract will be negotiated between the manufacturer and the university of Kentucky. 10-23-68 j=
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5 SPECIFICATION FOR BLENDING The Reference Cigarette will be blended from the following ingredients, using the indicated amounts of each. LBS. PER lO0 LBS. OF BLEND F1 ue-cured Tobacco Primings 6.0 Lugs 7.7 Cutters 2.9 Smoking 4.6 Leaf 18.9 Total 40.I Burl ey_Tobacco Flyings 5.3 Lugs 4.7 Leaf 12.9 Tips 2.0 Total 24.9 Flue-Cured Stems Oriental Tobacco (will include grade distributions) Maryland Tobacco Sugar Glycerine Total 14.2 II .6 l.l 5.3 2.8 I00.0
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II. SPECIFICATIONS FOR THE REFERENCE CIGARETTE DESIRED BY TOBACCO AND HEALTH RESEARCH PROGRAM I. NonLFilter Type 2. Length: 85 n=n. + 0.5 mm. 3. Circumference: 25 mm. + O.l mm. 4. Weight: Limit of Variation + 3% of Mean Weight 5. Moisture Content: 12.3% + 0.2% 6. Firmness: Within Commercial Limits 7. Width of Cut: 32-per-inch , 8. Pressure Drop: 7.6 cm. (H20) ~0.2 cm. 9. Paper: Ecusta Reference A; or, Schweitzer P lO. Nicotine Level: 1.7-I.8% in tobacco blend Note: If certain specification factors are not attainable, alternate specifications shall be suggested by the Manufacturer for the consideration of Tobacco and Health Program, University of Kentucky. I0-23-68 jf
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2. Smoking Machine for Inhalation Research Dr. Griffith, Chairman, asked for a report from M. Senkus, Chairman of the Subcommittee of Smoking Machine for Inhalation Research. Chairman Senkus read the following report: "The Scientific Advisory Board, at the Quarterly Meeting on May 25-26, 1968, requested the Industry Technical Committee to assist as rapidly as possible: A/ in the development of a satisfactory smoking machine for inhalation research; and B/ in the development of procedures for determining the extent of smoke exposure. "The S.A.B. request was considere~ by the I.T.C. at the June 6, 1968 meeting. In discussing Items ~ and B above, it was decided that action on Item B should be delayed until a satisfactory smoking machine has been developed. "In order to expedite the development of a smoking machine, Chairman Griffith appointed a Subcommittee comprised of Murray Senkus, Chairman, Alexander Spears and Helmut Wakeham to coordinate development of the machine; he also agreed to be on the Subcommittee, ex-officio. "Upon consultation with members of the C.T.R., the decision was reached to rely on the capabilities of research organizations of the industry. "A survey was made of members of the C.T.R. and, as a result, three companies, namely, Bro~n & Williamson, Philip Morris and R. J. Reynolds volunteered to develop independently a smoking machine for inhalation research. In the meantime, the Subcommittee had several discussions to set • forth the desired characteristics for the smoking machine. "The characteristics which the Subcommittee believes to be desirable are as follows: I. Cigarettes in the smoking machine should be smoked in a horizontal position. 2. The smoking parameters should include, the chief specifications of the F.T.C. method to determine nicotine and tar; namely, puff frequency, puff volume, puff duration, butt length, etc. 3. The machine should be provided with the capability to remove the particulate phase from the mainstream by filtration from 0% to 100%. 4. Means should be provided for purging of smoke between puffs. 5. Deposition of solids inside the machine should be minimized as much as possible; this would be done by adoption of suitable design and materials of construction. 6. Age of smoke to the animal should he no more than four seconds. 7. The butt end of the cigarette should be re-exposed to air between puffs (free smoking); restricted smoking conditions may also be desirable, as in the FoT.C. procedure in which the butt of the cigarette is not exposed to the atmosphere (restricted smoking).
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8. Smoking can be In the forward manner (air being forced into the forepart of the cigarette) or in the reverse manner (smoke drawn through the butt end of the cigarette). 9. Means should be provided for variation of puff duration, puff volume and puff frequency. Means should be provided for dilution of mainstream smoke with air and other gases. Means should be provided to expose simultaneously more than one type of animal to smoke in the smoking machine; for example, mice and rats. The machine should be capable of smoking numerous cigarettes simultaneously. Smoke should be monitored at point of exposure to the test animal. Exposure should be limited to anterior position of the animal. "The Subcommittee has reviewed the development program on the smoking machine within the industry. There are now three machines at various stages of development. Each of these meets at least ten of the smoking characteristics set forth by the Subcommittee. ,! "Further development of the smoking machine is in progress. I0. II. 12. 13. 14. In a discussion of the report presented by Chairman Senkus, it was agreed that the I.T.C. Subcommittee on Smoking Machine for Inhalation Research should expedite whatever development work remains to be done. It is believed that at least one of the machines will be ready for presentation to the S.A.B. in about a month. In any event, the I.T.C. Subcommittee for the Smoking Machine will meet with the S.A.B. Smoking Machine Committee (Dr. Loosli, Chairman, Drs. Sommers and Jacobson) on December 6, 1968 to present a progress report. It is hoped that at that time a prototype will be available for adoption by the S.A.B. There was also some discussion on development of procedures for deter- mination of extent of smoke exposure in animals. A procedure was proposed by Philip Morris. The I.T.C. Subcommittee will discuss this procedure and perhaps others with Dr. Loos!i's Committee on December 6. 3. S.A.B. Problems Dr. Griffith called attention to the recent increase in applications for smoking-health research being submitted to the C.T.R. In response to the increase, and the unavailability of funds to support the greater number of applications, a special committee has been appointed in the S.A.B. to re-orient the C.T.R. smoking-health program. Members of the Committee are Drs. Loosli, Sommers, Jacobson, Huebner and Bing.. Election of Officers of C.T.R. Dr. Griffith was re-elected as Chairman to serve until October, 1969. Dr. Alexander Spears was elected Vice-Chalrman. O O- ~O O~
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SCIENTIFIC ADVISORY BOARD Howard B. Andervont, Sc.D. 8201 Rayburn Road Bethesda, Maryland 20034 Richard J. Bing, M.D. Professor and Chairman Department of Medicine School of Medicine Wayne State University 1400 Chrysler Freeway Detroit, Michigan 48207 313 961-7302 Kenneth M. Lynch, M.D. Chancellor Medical College of South Carolina 80 Barre Street Charleston, South Carolina 29401 803 723-5911 Home: 803 873-3267 (study) 873-7142 William F. Rienhoff, Jr., M.D. 1201 North Calvert Street Baltimore, Maryland 21202 301 685-8574 McKeen Cattell, M.D. Department of Pharmacology Cornell University Medical College 1300 York Avenue New York, New York 10021 212 734-1832 Sheldon C. Sommers, M.D. Director of Laboratories Lenox Hill Hospital I00 East 77th Street New York, New York 10021 212 879-8000, Ext. 551,2,3,4,5,6,7 Robert J. Huebner, M.D. Chief, Laboratory of Viral Diseases National Institute of Allergy & Infectious Diseases Bethesda, Maryland 20014 '" 301 496-3301 301 656-4000 Leon O. Jacobson, M.D. Dean, Division of Biological Sciences University of Chicago 950 East 59th Street Cnicago, Illinois 60637 312 684-6100 Dr. C. C. Little R.F.D. #I Ellsworth, Maine 207' 667-8934 0460~ Clayton G. Loosli, Ph.D., M.D. Hastings Professor of Medicine & Pathology School of Medicine University of Southern California • 2025 Zonal Avenue Los Angeles, California 90033 213 225-1511 or 225-3131 "4
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I0 6. Dr. Chopra, Dr. Bockett informed the I.T.C. that a recent grantee, Dr. Chopra at A.T.& T. at Greensboro, N. C., will need some assistance in his work on the C.T.R. Grant. Dr. Griffith appointed Drs. Senkus and Spears to a committee to assist Dr. Chopra. Future Meetln~s of I.T.C. The Smoking Machine Subcommittee will meet with Dr. Loosll on December 6. Other meetings will be called as needed. The meeting adjourned at 12:00 nodn. I~ :has Murray ~nkus o o o c~
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CONFIDENTIAL - FOR USE OF COUNSEL Oh~Ly "August 19, 1968 MINUTES OF MEETING OF COMMITTEE OF INDUSTRY SCIENTISTS, THE TOBACCO INSTITUTE, WASHINGTON, D. C., AUGUST 16, -1968 Members Present: R. W. Griffith, Chairman - Brown & Williamson E. S. Harlow Arthur Burke H. W~keham ~A. W. Spears M. Senkus "E. D. Nielson E. R. Fluck - American - Ameri ~can - Philip Morris - P. Lorillard - R. J. Reynolds - R. J. Reynolds - R. J. Reynolds Absent: W. W. Bates - Liggett & Myers I. Report on Visit to Bio-Research Institut~ Inc..., Cambrld~e.~ Massachusetts As Chairman of the Industry Technical Committee of C.T.R., Dr. Griffith visited Bio-Research Institute recently at the suggestion of Dr. C. G. Loosli of the Scientific Advisory Board. The purpose of the visit was to discuss the development of a smoking machine for inhalation research. Development of the machine is being conducted by Dr. Freddy Homburger. Workers at Bio-Research Institute have demonstrated that mice can be forced to breathe through the mouth by constriction of the nose~with a rubber band. Substantial progress on development of the machine is being made. Dr. Charles Keith of Celanese has examined the machine and believes that the smoke therein is representative of normal cigarette smoke. II. Reference Cigarette Dr. Griffith reported that specifications for the reference cigarette being made available by the University of Kentucky are about complete. There was some discussion on the purchase of tobacco to be used in the blend of the reference cigarette. It was agreed to recommend to Dr. G. W. Stokes, Director, Tobacco Health Research Program, University of Kentucky, that tobaccos for the reference cigarette should be purchased from Universal Leaf Company. Bids for the manufacture of the first lot of cigarettes will be mailed to the tobacco companies in the near future. O O
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2 III. AKrlcultural Residues A literature survey is being conducted on agricultural residues by a subcommittee of the tobacco industry. The search is being confined to the literature in the public domain~ Mr. W. W. Menz of the Science Information Division of this Company represents R. J. Reynolds on the subcommittee. The tentative plan is to prepare a manuscript which will contain information on various pesticides which are now being used. An effort is being made to estimate the cost of preparing the manuscript. The Committee will also attempt to obtain a bid on the preparation of such a manuscript by an outside organization. IV. Exchange of Literature with A. D. Little It was tentatively agreed earlier this year that various tobacco companies would submit reports to A. D. Little for compilation of an industry-wlde health-smoking survey. So far, only one company (R. Jo Reynolds) has submitted reports. Another company (Philip Morris) submitted data sheets on compounds occurring in tobacco and in smoke. In view of the limited response~ Dr. Kensler recommended that preparation of the planned survey be abandoned. V. Smoking Machine The Smoking Machine Subcommittee (M. Senkus, Chairman, A. W. ~Spears, an~ R. W. Griffith) circulated a proposal on a smoking machine to members of the Committee of Industry Scientists on July I, 1968 (copy attached). The report contained suggestions for characteristics of the smoking machine for inhalation research. Invitations were also made in the report for members of the industry to submit proposals for the smoking machine at the meeting on August 16.~ In my telephone conversations with various Research Directors of the tobacco industry, some two weeks before August 16, it was my understanding that Brown & Willlamson, Philip Morris and R. J. Reynolds would present proposals on smoking machines on August 16. R. J. Reynolds came fully prepared to make proposals on three machines. Contrary to my expectations, neither Brown & Willi~m~on nor Philip Morris came prepared to make a proposal. Under these circumstances, I declined to present a proposal on design and construction of a smoking machine for inhalation research. There was considerable discussion at the meeting as to characteristics of a smoking machine for inhalation research. The discussions centered mainly on characteristics which are considered essential. For example, Dr. Griffith insists on holding the cigarette in a "free" position between puffs as in human smoking. By "free" position he means where the end of the cigarette is exposed to the atmosphere, in contrast to the "restricted" position as in any analytical smoking machine.
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3 Dr. Wakeham and Dr. Grlffith indicated that they would be ready to submit proposals in October. It was decided that a meeting of the 'Committee of Industry Scientists will be held in New York on October 24-25 for a further consideration of the smoking machine. Dr. Grifflth reported that Dr. Loosli of the Scientific Advisory Board expressed anxiety over the status of the smoking machine. He feels there is an urgent need for the machine. Moreover, he feels that work should be started on determination of extent of exposure of an experimental animal to cigarette smoke, Dr. Grlffith reminded him that the Comm~ttee of Industry Scientists had delayed this study until the development of the smoking machine had been completed. Contrary to the recommendations of Industry Scientists, Dr. Loosli feels that this study should not be delayed. VI. Next Meetin~ of the Committee of, Industry Scientists The next meeting will be held in New York on October 24 and 25. MS:has Cc: Dr. W. M. Bright Murra.~ Senkus
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June 26, 1968 PROPOSAL ON THE SMOKING ~CHINE This memorandum contains some background information and a proposal from the Smoking Machine Subconunittee to the Conm~ittee of Industry Scientists (C.I.S.) of the cigarette industry. Members of the Subconm~ittee: Murray Senkus, Chairman A]exander Spears Robert Criffith (Ex Officio) The proposal contained herein is being presented to members of the Committee of Industry Scientists in response to the May 25-26, 1968 request of the Scientific Advisory Board of the Council for Tobacco Research. The Scientific Advisory Board, at the regular Quarterly Meeting on May 25-26, adopted a resolution to request the industry scientists to assist as soon as possible (1) in the development of a satisfactory smoking machine for inhalation research, and- (2) in the development of procedures for determining the extent of smoke exposure. The S.A.B. request was considered by the Con~ittee of Industry Scientists at the June 6, 1968 meeting at the Tobacco Institute in Washington. Members in attendance were: Robert Griffith, Chairman Wi 11iam Bates E. S. llarlow Murray Senkus Alexander Spears lle Imut Wakeh am
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In discussing items 1 and 2 above, it was decided that action on item 2 should be delayed until a satisfactory smoking machine has been developed. During discussion of item i of the above S.A.B. request, two dependent sub-iteu~ were identified which required early resolution, namely~ (a) how will the development of the smoking machine be financed? (b) should the design and construction of the prototype be carried out within or outside the industry. In order to expedite the fulfillment of item 1 of the request by the S.A.B., including the determination of sub-items (a) and (b) above~ it was decided at the Conm~ittee of Industry Scientists meeting on June 6 to appoint a Smoking ~iachine Subcommittee and to refer item 1 of the S.A.B. request to the Subcommittee. Appointed to the Subcon~nfittee were: Murray Senkus~ Chairman Alexander Spears Robert Griffith (Ex Officio) The Smoking Machine Subcommittee was charged with the formulation of a proposal for the development of a smoking machine for inhalation research. As the preliminary step in the formulation of the proposal, legal representatives of the cigarette industry, together with representatives of the Tobacco Institute and The Council for Tobacco Research, met in San F~ancisco on June ]8 with scientific representatives of the cigarette industry to consider sub-items (a) and (b) of item I ~f the S.A.B. request. It was decided at that ~,eeting that (a) Cost of development of a smoking machine and construction of prototype will be shared by me~ers of the cigarette industry. (b) The machine will be developed and the prototype will be constructed within the cigarette industry, i.e., no outside contractor. The above decisions on sub-itches (a) and (b) of item I enabled the Smoking l.lachine Subcon~dttee to proceed further with the preparation of the proposal to the Conu~ittee of Industry Scientists. Forthwith the Subcommittee
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met twice in San Francisco, first on June 19 following proposal was formulated. .P~roposal on the Smokln~ Machine for Inhalati¢ Sub commi t tee I. Financing Cost of development of smoking machine is to be shared by members of the cigar II. Developer of Smoking Machine Development of smoking machine and cons done by a member of the cigarette indus III. Selection of Developer Selection of the developer is to be mad~ Committee of Industry Scientists. Selection of developer will be based on from the various cigarette companies that are of the machine. To assist members of the Committee of In selection of the developer, the Smoking Machl inclusion in the proposal - estimated cost of development and - estimated time for above - estimated unit cost of commercial and then on June 20. The n Research - from Smoking Machine nd construction of prototype tte industry. ruction of prototype will be ry. at a forthcoming meeting of the the consideration of proposals interested in the development dustry Scientists in making the ~e Subcommittee recommends construction of prototype production, using several arbitrary annual production rates, i.e., I0 per year, I00 per year, and I000 per year. IV. Preferred Features of the Smoking Ma Members of the Smoking Machine Subcommit the following features into the machine: i. It is preferred that the cigarette b, ii. It is preferred that the cigarette b~ F.T.C. method for "tar" and nicotine zhlne ~ee recommend incorporation of smoked in a horizontal position. smoked with the precision of the
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ill. vii. Filtration capability, ranging in removal of "tar" from 0% to 100%, (i.e., Cambridge Filter) is desirable. Purging capability between puffs is recommended. Deposition of solid on walls inside machine is to be avoided. It is recommended that age of smoke to be delivered to animal be no more than two seconds. Machine should have adequate self-monltoring devices. V. Other Features In making the proposal, it will be advisable to specify the following: li. iii. vii. i. Will cigarette remain in a restricted condition (as in the F.T.C. procedure) or in a free condition (as in human smoking)? Will puffing be in the reverse or in the forward manner? Will machine have capability for variation of puff duration, puff frequency, puff profile and puff volume? iv. Will machine have capability for dilution of smoke with air and/or any other gas? v. Will machine have capability for splitting of puff? vi. Will machine be designed for numerous animals or for a single animal? Please specify. Will machine smoke one cigarette at a time or numerous cigarettes simultaneously? Re commend at ions The members of the Subcommittee recommend the following course of action at the forthcoming meeting of the Committee of Industry Scientists: i. Please be prepared to either accept in principle this proposal of your Subcon~nittee or r~ject it. 2. With the anticipation that the proposal will be accepted, please come prepared to consider proposals from members of the cigarette industry for the design and construction of the prototype of a smoking machine for inhalation research.
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From the desk of W. T. HOYT Henry: For J~ne 3, 1968 / yo~r The Council l~or Tobacco Research - U.S.A. ~33 Third Avenue, New York, N.Y. 10017 o
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COUNCIL ]~O1¢ TOBACCO ];~I'~SI~AI~CII -U.S.A. ~33 THIRD AVENUE NE~" YORK. N. Y. 10017 ~y 29, 1968 Dr. R. B. Griffith Director of Research Brovm and Williamson Tobacco Cbrp. 1600 West }Hll Street Louisville, Kentucky Dear Bob : This ~ll serve to remind you that at the Scientific Advisory Board meeting the Board requested the Industry Technical Committee to assist as rapidly as possible: A/ in the development of a satisfactory smoking machine for inhalaidon research; and B/ in the development of procedures for determining the extent of smoke exposure. Sincerely yours, W. T. Hoyt Executive Director WTH : abh o o o
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CONFIDENTIAL - FOR USE OF COUNSEL ONLY May 3, 1968 Mr. H. H. Ra,~: MINUTES OF MEETING INDUSTRY TECHNICAL COMMITTEE The Tobacco Institute May 3, 1968 Members Present Dr. R. Griffith, Presiding Dr. Murray Senkus Dr. H. Wakeham Mr. E. S. Harlow Dr. Alexander Spears As agreed at the April 26 meeting of the Committee, this meeting was held to review the Mason proposal and to prepare recommendations for members of the Scientific Advisory Board for the forthcoming meeting of the S.A.B. on May 25-26, 1968. The report and recommendations to the S.A.B. will essentially be as follows: The Industry Technical Committee, with the information now at hand, is unable to evaluate the smoking machine contemplated for use in the proposed program of mouse inhalation experiments. Members of the I.T.C. feel that the smoke delivered to the animal should be substantially the same as the smoke which is produced for chemical analyses in the commonly accepted analytical procedure for total particulate matter and nicotine. Mason should obtain such information as a necessary part of evaluating their smoking machine. For this purpose they will need advise which could be obtained from the industry or from an appropriate outside consultant. The Industry Technical Committee has restricted its consideration to the delivery of smoke to the animal by the machine and does not feel competent to evaluate the machine from any other standpoint. There are certain inadequacies in the machine under consideration. Among them are: Placement of the cigarette in a vertical position is considered undesirable since it leads to alterations in the burning characteristics. A horizontal position would be preferred. o - o
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2 t In the current model, smoke is expelled from the chamber in response to animal movement which undoubtedly leads to alterations in smoke concentration. Smoke entrained in the Cambridge filter chamber of the Mason machine ages for 58 seconds (between puffs) and then becomes a part of the next puff. This is considered undesirable. The material of which the vessel is composed could inflvence composition of smoke. Selection of an appropriate material should be made. The criteria suggested for comparison of smoke with that collected for chemical analysis are given below. I. "Tar" in milligrams per cigarette and milligrams per puff. 2. Nicotine in milligrams per cigarette and milligrams per puff. The ratio of nicotine to "tar" is one index of smoke character. 3. Phenols in milligrams per cigarette and milligrams per puff. 4. Isoprene in milligrams per cigarette and milligrams per puff. 5. Acrolein in micrograms per cigarette and micrograms per puff. 6. Carbon dioxide in milligrams per cigarette and milligrams per puff. o Carbon monoxide in milligrams per cigarette and milligrams per puff. Ratios of carbon dioxide to carbon monoxide is sometimes used as an index of smoke character. 8. Nitric oxide and nitrogen dioxide each in micrograms per cigarette and micrograms per puff. Procedures for the determination of the aforementioned constituents are available and are used routinely in analyses of cigarette smoke. Information concerning them may be obtained from the literature or can be provided to the Mason Research Institute if necessary. The above evaluations and possibly further modifications of the machine should be completed before any inhalation studies are started. MS:has Cc: Dr. W. M. Bright Murray Senkus
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CONFIDENTIAL - FOR USE OF COUNSEL ONLY April 29, 1968 Mr. II. H. Ramm: MINUTES OF MEETING OF THE INDUSTRY TECHNICAL COMMITTEE WITH REPRESENTATIVES FROM THE COUNCIL FOR TOBACCO RESEARCH, 633 Third Avenue, New York, N. Y. April 26, 1968. R. B. Griffith- Presiding Present: C.T.R. - Ame ri can Brown & Williamson - Griffith Hockett, Hoyt, Brady, Lisanti and Kreisher - Burke and Harlow Larus & Brother - Shelton Philip Morris - Osdene P. Lorillard - Spears R. J. Reynolds - Senkus U. So Tobacco - Bennett The purposes of the joint meeting of I.T.C. and C.T.R. Staff, as stated by Dr. Griffith, were to: Discuss the latest modification of the mouse smoking machine at the Mason Research Institute, 2. Discuss the proposal from the Mason Research Institute. In preliminary remarks, Dr. Griffith reported that the Mason Research Institute proposal was discussed at the Scientific Advisory Board (S.A.B.) meeting in LaJolla, California on March 2. S.A.B. members con- jectured at that meeting that if the Mason proposal is undertaken, it would lead to a greatly expanded program; therefore~ the industry should approach the Mason proposal with caution in view of the foreseeable magnitude of the total program. As Chairman of the Industry Technical Committee (I.T.C.), and sole representative of the I.T.C. at the S.A.B. meeting, Dr. Griffith was asked to prepare a report for the S.A.B. to assist the S.A.B. in the consideration of the Mason proposal. In anticipation of the above request, members of the I.T.C. visited the Mason Research Institute in December 1967. More recent visits by members of the I.T.C. were made on April 24 and 25. A subconm~ittee of the S.A.B. visited the Mason Research Institute during the early part of April 1968. o o -
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2 Discussion of the Smoking Machine The writer and Dr. Ridlon visited the Mason Research Institute on December 8, 1967 with Dr. Nielson, and with Dr. Nystrom on April 24, 1968. The best machine exhibited on December 8 left much to be desired, In my report to the I.T.C, on April 26 I stated that considerable improvement has now been made on it. Nonetheless, I reported that further improvement is necessary. My specific recommendations for changes were: The cigarette is smoked in a vertical position; it should be smoked horizontally. The nechanics of achieving the purge in the exposure chamber require modification. In view of the large opening in the exposure chamber, the pressure inside and outside are essentially the same. A slight positive pressure on the inside would be desirable and could be achieved by means of a constriction of the vent. In view of the excellent progress which had been made on the modification, I expressed the thought that the personnel at Mason are capable of developing a satisfactory smoking machine for mice. According to Drs. Harlow and Spears, an important consideration in further modification is that there should be some means of monitoring the amount of smoke which is inhaled by the mouse. They also emphasized that the smoke produced by the machine should be the same as that produced by the machine now being used by the F.T.C. The redesign should be done with this fact in mind. Members of the I.T.C, agreed that although substantial improvements in the design of the machine have been achieved, it is by no means ready for use. The Mason Research Institute Proposal Dr. Hockett was asked to discuss the Mason Research Institute p ropos al. In introductory remarks he mentioned that in many of the experiments on animals the objective has been to determine the tumorigenicity of smoke. The production of tumors as an end point may be an inadequate program. A more useful approach might be to determine the various effects which are produced prior to the appearance of a tumor. Therefore, experts at Mason were asked to consider these antecedents. They have done considerable work on cancer antecedents in other investigations and would therefore be qualified to design these experiments. The program now being considered by Mason would be confined to mice. Several menders of the I.T.C. pointed out the deficiencies of the mouse as an experimental animal for the study of the relationship between smoking.and health. These deficiencies had already been discussed by members of the C.T,R. staff with Mason personnel. The people at Mason feel that meaningful data could be obtained on mice. Moreover, in view of the foreseeable magnitude of the total program, the use of other animals may be prohibitive on the basis of cost alone. Other reasons for use of the mouse are:
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3 I. It would be desirable to determine if previous results with mice are erroneous, 2. Strains of mice with very well known characteristics are readily availab]e. The program would entail about 24,000 mice and would last about two years. A rough estimation of the cost is $2 million. Suitability of the Mason Research Institute to Undertake the Program I. ANIMAL FACILITIES The capabilities of the Institute were discussed. Dr. Lisanti emphasized that the Institute meets all of the standards of animal handling. It is contemplated that the work on smoke would be carried out in an isolated building. 2. STAFF Dr. Griffith pointed out that the staff is relatively small, "would be a serious matter if any of their personnel were to leave. 3. OTHER TESTING FACILITIES It Dr. Lisanti has investigated other possibilities. Industrial Bio-Test Laboratories, Inc. at Northbrook, Illinois is another excellent testing laboratory. At present, Bio-Test is deficient in some disciplines, such as immunology~ histology and virology; further, they do not have any smoking machine experience. However~ in view of their excellent physical facilities, financial resources and reputation, they could "gear up" in a" relatively short time. Action to be Taken by the Industry Technical Committee The Industry Technical Committee will make a recommendation regarding the Mason proposal for the S.A.B. meeting (likely dates - May 25-26). The I.T.C. will meet in Washington on May 3 to review the Mason proposal, the Mason smoking machine and to prepare the recommendation for the S .A.B. MS:has Co: Dr. W. M. Bright enkus
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April 4, 1968 Mr. H. H. Ramm Minutes of Meetings - Washington, D. C., April 2, 1968 Industry Technical Committee Board of Directors of T.I.T.L. Industry Technical Committee Meeting Present: Robert B. Griffith, Chairman - Brown & Williamson Murray Senkus, Vice Cha&rman - R. J. Reynolds William W. Bates Edward S. Harlow Alexander Spears Helmut Wakeham - Liggett & Myers - American - P. Lorillard - Philip Morris The following items were discussed: Io Reference cigarette for the University of Kentucky for the tobacco and health research program 2. Smoking machine for the inhalation studies to be conducted for the CoT.R. at the Mason Research Institute 3. Tobacco residues • i. Reference Cigarette Dr. G. W. Stokes of the University of Kentucky has had discussions with Drs. Griffith and Bates concerning a reference cigarette to be used in the tobacco and health research program at the University of Kentucky. From time to time, Drs. Griffith and Bates have kept the other Research Directors informed regarding these discussions and have asked for certain recommenda- tions. Dr. Stokes expects to decide on the reference cigarette by May i. It is anticipated that the blend composition of the cigarette, using whole leaf percentages, will be approximately as follows: flue-cured - 54% burley - 34% Turkish - 10% Maryland - 2% However, since after stemming of the whole leaves, the flue-cured stems will be incorporated in the strip blend, whereas the burley and Maryland stems will be excluded, the composition of the strip blend will differ from the above.
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2 The grades of tobaccos to be used in the cigarettes will be based on Government removal figures for domestic cigarettes. The cigarettes will be nonfilter, 85 mm. in length. Bids for the purchase of these cigarettes will be submitted by Dr. Stokes to the major cigarette companies. Complete specifications will be provided with the bid. Dr. Stokes expects that the company which accepts the bid will provide a description of the manufacturing process to enable any subsequent manu- facturer to duplicate orders for cigarettes. 2. Smoking Machine It was agreed that members of the~I.ToC, will meet with the staff of the C.T.R. on April 26 to review the proposal(s) of the Mason Research Institute. Dr. Griffith reported on the meeting of the Scientific Advisory Board which he attended as Chairman of the I.T.C.; the meeting was held in LaJolla, California on March 2 and 3. The merits of the various animal smoking machines which are being con- sidered by the Mason Research Institute were discussed at the S.A.B. meeting. It was agreed that a subcommittee of the S.AoBo will make an "on-sight" visit to the Mason Research Institute to enable further consideration of this matter at the forthcoming meeting of the S.A.B. on May 4 and 5. In addition, members of the I.T.C. will visit the Mason Research Institute during April to revaluate the machines and then meet in Washington on May 3 to prepare an advisory report for the S.A.B. meeting. 3. Tobacco Residues Dr. Griffith and Dr. Spears recommended that the I.T.C. should undertake a review of residues in tobacco because of: i. increasing interest in this area by various government agencies 2. increasing interest in these problems on the part of European governments, particularly West Germany 3. increasing awareness of residues in various agricultural products, i.e., i. aflatoxin in peanuts ii. insecticides in foods - and others. There was general agreement that in anticipation of the above, it would be of interest for members of the tobacco industry to undertake a cooperative program.
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The objectives of the program would be: i. To determine the nature and the amounts of residues in tobacco 2. To determine the fates of these residues during smoking 3. To study the implications of these residues, particularly their pyrolytic products in smoke. The program would consist of four phases. These are: i. Review of the literature 2. Pooling of unpublished data on this subject from the various Research Departments of the tobacco companies 3. Additional new laborator# work, if needed, to determine fate of some of the residues in tobacco 4. ~ Some biological studies, if needed, to determine tolerances. The new laboratory work under Item 3 above would be shared among members of the I.T.C. The biological work under Item 4 above could be farmed out to established biological research laboratories outside the tobacco industry. The literature review could be started immediately. It would be useful to do this regardless of whether the other phases will be undertaken. However, the review of the literature (Phase i) will be delayed pending agreement on the part of managements of the companies to proceed with the program. Meetin~ of the Board of Directors of the T.I.T.L. Present: Helmut Wakeham, Chairman William W. Bates Robert B. Griffith Edward S. Harlow Murray Senkus - Philip Morris - Liggett & Myers - Brown & Williamson - American - R. J. Reynolds Dr. Wakeham called the meeting to discuss the status of employment of a scientist to assist the Director of the T.I.T.L. in the operation of the laboratory. The Executive Manning Corporation of Washington, D. C. has been recruiting candidates for the opening. A number have been interviewed and, in fact, an offer had been made to one of them; the offer had been rejected. Members of the Board of Directors of the T.I.T.L. believe that prospects of employing an individual for this opening are not promising. Accordingly, it was agreed that each member of the T.I.T.Lo would furnish a scientist for a one-year period on a rotation basis to assist Dr. Steele, Director of the T.I.T.L.
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I volunteered the services of Mr. B. Allen Harbin of the Analytical Division of this Department for the first one-year assignment. He will begin the assignment at the T.I.T.L. on May I. It is anticipated that Mr.,Harbin will remain on R. J. Reynolds' payroll. The T.I.T.L. will reimburse Reynolds for the salary and will reimburse Mr. Harbin the difference in" cost of living. MS:has L~ 0
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ThE COUNCH, FOR TO]~ACCO l~x]CS]~A]¢Cn-U. ~.A. " April I, 1968 The Council for Tobacco R~search - U.S.A. SUBJECT: W. T. Hoyt, Executive Director Meeting of the Industry Technical Committee, Friday, Apr~l ~6, 1968. A meeting of the Industry Technical Committee w~ll be held dn The Council's offices (633 Third Avenue) at 9:30 A.M.~ Apr~l P6, 1968. Will you please return the duplicate copy of this memorandum, noting your p]ans re~ardin~ attendance at both the meeting and lunch? W.T.N. WTH: ek encl. k will w~ll attend the meeting. be presgnt for lunch.
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CONFIDENTIAL - FOR LEGAL USE ONLY February 21, 1968 Mr. H. H. Ramm: MINUTES OF MEETING OF DIRECTORS OF RESEARCH, WILLIAM HILTON INN, HILTON HEAD ISLAND, SOUTH CAROLINA, FEBRUARY 14-15-16, 1968. R. B. Griffith - Presiding Present: William W. Bates - Liggett & Myers Robert B. Griffith - Brown & Williamson Edward S. Harlow - American Murray Senkus - R. J. Reynolds Alexander Spears - P. Lorillard Helmut Wakeham - Philip Morris Allan J. Topol - Covington & Burling In a preliminary consideration of the items to be discussed, it was decided to depart from the agenda which had been planned in Washington on February 5. Instead, only those items were pursued which were of interest to every member present. Epidimiology and the medical aspects of smoking were excluded from consideration since these items were not of interest to some members of the group. A. DISCUSSION OF ITEMS OF MUTUAL INTEREST I. Smoking Machines for Determination of Nicotine and Solids At least three smoking machines have been developed to determine nicotine and solids in smoke. These are (I) the Eastman Chemical machine, (2) the Falling Column of Water machine (American Tobacco Company), and (3) the Phipps and Bird machine designed by Philip Morris. The Phipps and Bird machine is now being used by the Tobacco Institute Testing Laboratory and the Federal Trade Conm~ission laboratory.
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2 Although any one of these machines will give reproducible data, nicotine and solids determined by these means do not really represent the an~ount of smoke and nicotine which are inhaled by a smoker. Further work is needed to study the characteristics of human smoking. These data may be useful in the design of a smoking machine for analytical purposes which would throw more light on human smoking. In this con- nection there was considerable discussion on behavior of smoke in the various steps during the inhalation of a cigarette. A study of this behavior might show, for example, that an appreciable amount of smoke is retained in the mouth. In any event, the information which would be generated in this kind of study could show that the data currently being published by the F.T.C. are meaningless. II. Development of New Analytical Procedures for Components Other than Solids and Nicotine It is anticipated that the F.T.C. will publish data on other smoke components such as acetone, acrolein, acetaldehyde, carbon monoxide, hydrogen cyanide, nitrogen oxides, polycyclic hydrocarbons, and others. At this time the procedures for these components differ from one industrial laboratory to another. It would be desirable to agree on procedures which would be acceptable to all parties. It will require considerable joint effort to decide on the various procedures. A cooperative effort of the various research departments of the industry appears desirable. III. Current Awareness Considerable work on chemistry of tobacco, tobacco smoke and its properties is in progress outside of the tobacco industry in the various laboratories in the United States and abroad. In many cases the problems being studied in the various laboratories are known to the public. It may be possible to anticipate the results of some of the experiments and to have in readiness scientifically sound interpretations of these results. IV. A~ricultural Residues Certain materials, such as polonium, insecticides, and mycotoxins, are alleged to be present in tobacco. The amounts and determination of these materials are of interest to the industry. V. Control of Composition of Smoke Various "would be" inventors are attempting to control composition of smoke, either by use of additives or filters. In most cases, the con,pm~ies are approached by these inventors on an individual basis. Although the individual approach has its merits, an industry-wide con- sideration of some of the additives and filtering devices may also be necessary, as in the case of Chemosol.
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VI. Research Organizations Outside the Tobacco Industry The volume of work on ~tobacco outside the industry and industry supported organizations is expanding rapidly. Some examples are: the University of Kentucky, U.S.D.A., state experiment stations, Sloan Kettering Institute, and others. It would be desirable to establish efficient communication between some of these research organizations and the technical organizations of the tobacco industry. For example, the program at the University of Kentucky would have taken a different folm~ had the desired information been made available to the University of Kentucky. VII. Review of Articles and Textbooks on Tobacco Sore of the publications on tobacco and tobacco smoke are quite misleading. A means is needed whereby these various publicatlons can be reviewed promptly and objectively for the press. The Science editorial by .Abelson (copy attached) is a case in point. The argument presented there is misleading. VIII. Beneficial Effects of Smoke The Advisory Committee in its 1964 Report on Smoking and Health to the Surgeon General allowed that smoking may be beneficial (last para- graph, page 32, of the Report). How do we go about identifying some of these beneficial effects? B. MECHANISM FOR MUTUAL COOPEP~ETION It was agreed that the items listed above and others of interest to members of the industry could be dealt with on an industry-wide basis. Each of these problems is basically a scientific problem and can be solved only by obtaining scientific facts which would put tobacco and its consumption in a proper perspective. Owing to the complexities of the problems, their solution would require a very large effort involving many disciplines. The effort required is beyond the capabil~ties of any single company and therefore united action is indicated. United action on the part of the industry could be obtained if a cigarette research institute were established. The problems and the objectives of the institute would be to assemble, generate, and evaluate scientific information about cigarettes, cigarette components, smoking behavior, etc. of common interest to the members, apart from the medical aspects of smoking and health, and to make such information available to the member companies and such further use as the members may deem appropriate.
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4 Examples of projects to be undertaken by the institute are cited in Section A above. Such an organization would be likely to increase the efficiency of research of each individual company and the industry as a whole. It was recognized that there would be many problems, such as choice of projects, distribution of information, and others. It was emphasized that the establishment of the institute would be justified only if all cigarette manufacturers joined the organization. No all-inclusive organization is in existence at present. Care would be taken to avoid duplication of efforts of existing organizations, such as T.I.T.L., C.T.R., and the Research and Education Foundation of the A.M.A. C. RECOS~ENDATIONS TO BE ~LEDE TO COMPANIES BY INDIVIDUAL DIRECTORS Directors of Research of Brown & Williamson, Liggett & Myers, P. Lorillard, Philip Morris and R. J. Reynolds stated that they would recommend to their respective Managements the establishment of the institute. Director of Research of American Tobacco Company stated he was undecided whether he would recommend it to his Management but would give the matter further consideration. MS:has Att. Article from Science Vol. 158, No. 3808 Dec. 22, 1967 o o o
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22 December 1967, AMERICAN ASSOCIATION FOIl TIlE ADVANCEMENT OF SCIENCE Science serves its readers as a forum lor the presentation and discussion of impor- tant issues rclaled 1o the advancement ol selence, inclt, ding the presentation of mi- nority or conflicting points of view, rather than by pnblisl,ing only material on which ~11 arlicles published in Scicncc~including edilorlals, news and comment, and book revlews~nre signed and reflect fl~e indi- vidnal views o~ lhe authors and not o~clal points of view adopted by the AAAS or Ihe instilutlons with which lhe aulhors are a~lialed. JOH~ T. E~S~LL JoH~ Wic~ep F. ~erV D~W~ ~Og~ON J. F. ~IAC~ONALO CI.ARENCE - Editorial Editor ~ubli~het ~t~slne~s ~Ianagel DAEL ~'OLFLE ~h~S ~USSBAU~I Managing Editor: l~,ol;~t':T V. ~l$$islarl! Editors: EL~N E. ~IURPIIY, JOllS R,~GLE ~'ews Ottd Comment: JOIIN CA~I[~ ~RYCE ~ELSO~, ~OBER~ J. S&%~UELSO~, ~A~ILLO. Contributing correspondents: ~NGE~ ~IGEL CALDer, ~'I~OR K. ~ICEtltENY Book Reticles: ~YLX'IA Editorial ~sslstaats: JO~NNE ~ELR. ~OULPl~, ELEANO~E ~, ~EN CARLI~. ~RXYCE ~INGER, ~CY HXMIL~O~, EL~NOE JOIINSO~ ~U[~ LECKY~ ~IIERI~E I.lV- ~YA~. ~RBA~ S}IEF~E~ *£,tropenn O~ce: ~i~e Tlce Farm, ~3st [lag- ~urne. Berkshire, England. Telephone Didcot 3317 Direclo~ P¢oduction ~ARL J. ~CHE~AGO ~OSE ~IARIE ~O~I~GNOLO Adrettislng Sales ~la~agc¢: R~clIx~D L. CII~LtS Sales: New York, N.Y., 11 W. 42 St. (212-PE- ~185S): RO~tRI S. Scotch Plains, N.J., 12 Unami L~ne (201-8S9- 4S731: C. RVCelA~D C~ttls Medfield, ~lzss. 02052. ~ Rolling ~ane (617-359- Ch;cago, IlL ~9611, 919 N. ~licM~an Ave., Room 42~ (H2-DE-7-4973): llt~e~eT 1.. RL'e~L~X~ InS An~':I¢S 45, C~li[.. ~255 ll:vCrly Blvd. (213- EDI]O~IAL CORRESPONDENCE: 1515 Mzss~- ~huse~ Ave., NW. ~V~s]:ingto~. I).C. ~005. Pl~one: 2~2-3S7-717 I. CaMe: AdvzncescL ~Vz~hin~ton. ~opies o~ ~qr, s~ructi~n$ for Contributor~" CORRESPONDF.NCEr Rm. 1740, 11 W. 42 St., ~ew York, N.Y. 1~36. Pho~;e: ~I2-PE 6-1S5S. Volume 158, Number 3808 A Damaging Source of Air Pollution Public concern about air pollution has grown rapidly during lhe past few )'ears. In. a recent poll, 80 percent of respondents felt that additional measures should be taken to mi,aimize Ibis problem. Most people, when lhey consider air pollution, lhink of the automobile, the smokestack, or lhe tr~*<h h~,rnor Fol~' n~;n~ tfl a mo~t damaoine source of air pollulion~the cigarette. One of lhe loxic products of the automobile is carbon monoxide. Exposure for 1 hour to a concentration of this gas of 120 paris p~ million causes inactivation of about 5 percent of lhe body's hemo- globin and commonly leads 1o dizziness, headache, and lassitude. Con- ccntrations of carbon monoxide as high as 100 ppm often ~cur in garages, in tunnels, and behind automobiles. Such concentrations are tiny in comparison with lhose (42,000 ppm) found in cigarette smoke. The smoker su~ives because most of the time he breathes air not so heavily polluted. However, in a poorly ventilated, smoke-filled, room, concentrations of carbon monoxide can easily reach several hundred parts per million, lhus exposing smokers and nonsmokers present to a toxic hazard. Another air ppllutant issuing from automobiles is nitrogen .dioxide. Nitrogen dioxide is an acutely irritating gas; also, it gives rise to nitrite, a potential mutagenic agent. Concentrations of NOe as high as 3 ppm have been noted in Los Angeles, and levels of 5 ppm are con- sidered dangerous. Cigarette smoke contains 250 parts of NO.e per million. Many of the toxic agenlk in cigarette smoke do not have counter- parts in ordinary air pollution. One of these, hydrogen cyanide, is particularly noteworthy. It is highly active against respiralory enzymes. Long-term exposure to levels above 10 ppm is dangerous. The con- centration in cigarette smoke is 1600 ppm. These inorganic pollutants are three of many noxious substances that have been found in tobacco smoke. Among others are acrolein, aldehydes, phenols, and carcinogens, an important one of which is benzo(a)pyrene. Evidence points to synergistic effects among the toxic agents. The phenols, though not themselves notably carcinogenic, in- crease markedly the carcinogenic potency of benzo(a)pyrene. The toxic effects of cigarette smoke are also enhanced by other environmental factors. A recent study of asbestos workers showed a very high incidence of lung cancer among smokers, in contrast to a low incidence among nonsmokers. In a group of 283 asbestos workers who had a history of cigaretie smoking, 24 of 78 deaths were due to bron- chogenic carcinoma. Of 87 asbestos workers who were nonsmokers, none died o[ lung cancer during a comparable period. A study of the uranium miners stricken with lung cancer has also revealed an effect related Io smoking. The role of fatalities was much higher among smokers than anaong nonsmokers. Another example of a synergistic effect is seen in the smoker who breathes polluted urban air. The incidence of lung cancer among smokers is higher in the city than in rural areas. The principal effects of smoking are borne by the smokers themselves. They pay for their habit with chronic disease and shortened life. In- volved are the individual's decision and his life. However, when the individual smokes in a poorly ventilated space in the presence of others, he infringes the rights of others and becomes a serious cor, tributor to air pollution.~PmuP H. ABELSON
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CONFIDENTIAL - FOR USE OF COUNSEL ONLY MINUTES OF MEETING OF INDUSTRY TECHNICAL COF[MITTEE WITH REPRESENTATIVES FROM THE COUNCIL FOR TOBACCO RESEARCH, 633 Third Avenue, New Yorkj N. Y. December 8, 1967 Present : American - E. S. Harlow, Miss Janet Brown Brown & Williamson - R. B. Griffith Imperial - D. A. Coulson Liggett & Myers P. Lorillard - Philip Morris - R. J. Reynolds - U. S. Tobacco - C.T.R. - W. W. Bates C. O. Jensen T. S. Osdene M. Senkus W. B. Bennett~ Jr. - C. Co Little, W. T. Hoyt, R. C. Hockett, V. Lisanti The meeting was opened by Mr. Hoyt at 2:15 P.M. with the announcement of the following agenda. I. Election of Chairman and Vice Chairman for Industry Technical Committee (I.T.C.) of C.T.R. 2. Future activities of I.T.C. 3. Manufacture of nonfilter cigarettes. Discussion of 5-year chronic studies. 4. Visit to Mason Institute in Worcester, Mass. to view smoking machines. Election of Officers Mr. Hoyt announced that the membership of I.T.C. is as follows: Griffith - Coulson - Harlow - Shelton - Bates - Jensen - Wakeham - Senkus - Bennett - Brown & Williamson Imperial American Larus Bros. (not present at meeting) Liggett & Myers Lorillard Philip Morris (not present, represented by Osdene) R. J. Reynolds U. S. Tobacco
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Minutes of Meeting of 1.T.C. with C.T.R. December 8, 1967 Members present elected: R. B. Griffith - Chairman M. Senkus - Vice Chairman It was agreed the Vice Chairman will, in effect, be Chairman-Elect. Tentatively~ the term of office will be 18 months. Mr. Hoyt~ at this point, relinquished the Chair to Dr. Griffith. 2. Functions of I.T.C. Mr. Hoyt, Dr. Little and Dr. Hockett informed the group that within the present framework of C.T.R. the chief function of the I.T.C. is to act as an advisory group to the staff at C.T.R.. and to the S.A.B. They expressed the hope that the election of officers will enable a smooth flow of information from I.T.C. to S.A.B. and C.T.R. staffs. Dr. Griffith assured the C.T.R. staff that every effort will be made henceforth to maintain good con~unications between the groups. It was agreed that Dr. Griffith would represent the I.T.C. at S.A.B. meetings. Dr. Senkus will be the alten~ate. It was agreed that copies of applications for research grants and descriptions of proposed work would be made available to Dr. Griffith as early as possible prior to S.A.B. meetings. He plans to discuss these informally with members of the I.T.C. and will be able to talk on behalf of the entire I.T,C. Committee at the S.A.B. meetings. It was tentatively planned to have regular meetings of the I.T.C., preferably on the Friday before the S.A.B. meetings. For the time being, formal minutes of the I.T.C. meetings will not be kept. It was stressed that meetings of the I.T.C. and communications (preferably by telephone) between members of I.T.C. and between I.T.C., S.A.B., and C.T.R. staffs should be informal. 3. Test Cigarettes Dr. Lisanti proposed that nonfilter cigarettes be made available to the S.A.B. to arrange for 5-year chronic studies. He estimated that approximately 30 million cigarettes would be required. After a short discussion, it was decided that the design of the cigarette for these studies be referred to a sub-committee. Dr. Griffith appointed Dr. W. Bates, Chairman, Liggett & Myers, Dr. C. O. Jensen, P. Lorillard, and Mr. E. S. Harlow, American as members of the sub-committee.
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Minutes of Meeting of I.T.C. with C.T.R. December 8, 1967 They will come up with a reconm~endation as to type of cigarette~ i.e., length, circumference, type of tobacco, and percentage of casing, etc. It was agreed the cigarette would be a nonfilter. 4. Demonstration of Machines by Mason Institute Dr. Kreisher announced that he made arrangements with Mason Institute for a demonstration of four animal smoking machines. Demonstration of the smoking machines has been scheduled for December 13 and 15. Representatives from R. J. Reynolds will attend on December 15. They are: Drs. M. Senkus, E. D. Nielson and S. Ao Ridlon. MS:has Cc: Dr. W. M. Bright Murray~enkus
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CONFIDENTIAL - FOR USE OF COUNSEL ONLY September 27, 1967 Mr. B. H. Ramm MINUTES OF MEETING OF INDUSTRY TECHNICAL COMMITTEE WITH REPRESENTATIVES FROM THE COUNCIL FOR TOBACCO RESEARCH - September 25, 1967 Present : American - E. S. Harlow, A. W. Burke, Miss Janet Brown Brown & Williamson - R. B. Grlffith, R. Manford Larus Bros. - G. Shelton Liggett & Myers - W. W. Bates P. Lorillard - A. Spears Philip Morris - T. S. Osdene R. J. Reynolds - M. Senkus, E. D. Nielson C.T.R. - C. C. Little, W. T. Hoyt, R. C. Hockett, J. M. Brady V. Lisanti Dr. Hockett opened the meeting by stating that meetings of the Industry Technical Committee with personnel of C.T.R. have been infrequent. It is plm~ned to hold meetings more frequently. Dr. Little conjectured that it might be advisable to hold these meetings either immediately before or after ineetings of the Scientific Advisory Board; in any event, relation- ship between the Industry Technical Committee and C.T.R. is to be worked out. Dr. Hockett then reviewed what he considered some of the more urgent projects currently being sponsored by the C.T.R. These are the investiga~ions which are now being conducted by Leuchtenberger, Homburger, and Furst.. In the early stages of work by these investigators considerable time was spent in developing smoking machines for the animals used in the studies. After considerable effort, machines were designed whereby ciga- rette smoke was introduced into the respiratory tracts of the animals. These smoking conditions however do not simulate human smoking. The Leuchtenbergers, in their experiments, got indications of changes in lungs which appeared undesirable; nonetheless, cancerous condi- tions were not developed. On re-examlning the experiments it was discovered that the mice were infected with viruses and it was thought that these infections may have contributed to the changes in the lungs which had been observed. The personnel at C.T.R. have recently reviewed the work and have concluded that it would be desirable to develop a smoking machine for the rodents which would more closely simulate the human smoking conditions.
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- 2 Dr. Lisa~ti has been in touch with Mason of Worcester, Massachusetts who has obtained the three smoking machines which have been in use to date. He has m~de arrangements with Mason for a demonstration of the three machines during the first week in December. It was agreed at the meeting that each Company member of the C.T.R. would send representatives to view the demonstration. The performance of the machines would be studied and a recommendation by the Committee would then be made to determine which machine and/or modification would be most suitable for studies on rodents. It was emphasized that in these future studies careful con- sideration will be given to the possible role of viruses. The amount of smoke to be inhaled, and other important factors will also be taken into consideration. Dr. Hockett pointed out that in studies to date most of the work has been done by using rodents as the experimental animal. Selection of rodents as experimental animals was based mainly on convenience. It is now becoming increasingly evident that rodents are highly sensitive to cigarette smoke and have shown no incl~natlon to habituation. Other animals have been considered for smoke studies and some recent results indicate that the dog offers a good posslbility as an experimental animal for the correlation with effects on humans. In particular, the data recently obtained at Battelle Northwest have attracted considerable interest. In view of the promising preliminary data, Dr. Nielson had visited Dr. Bair at Battelle Northwest. Dr. Hockett called on him to make a report on his visit. .Repo_r_t__b/f Dr. Nielson Dr. Nielson reported that he was very favorably ~mpressed with the competency of the personnel at Battelle Northwest. The study was started under the sponsorship of A.E.C. to ~nvestigate the effects of radioactive agents. A strain of beagle dogs was selected for these studies. The dog colony is derived from a long breeding program. The animals are now free of the many canine diseases and other complicating factors which are usually associated with the nondescript dog. After the study of effects of radioactive dusts was started, it appeared desirable to personnel at Battelle Northwest to also investigate the simultaneous effect of smoking. Accordingly, it was necessary to develop smoking machines for the dogs. Much to their surprise some of the dogs became habituated smokers. The early data indicate that habltuat~on is ascribable to nicotine. In this one respect, dogs appear to be slmilar to man. There has been no such indication in rodents. In fact, rodents appear to be highly sensitive to nicotine. The smoking studies on dogs at Battelle Northwest are very recent. It was recognized that it would be of interest to determine some of the important parameters of the smoking character~stlcs of dogs, such as optimum puff volume, preferred daily intake of cigarette smoke, and various other factors. In any event beagles appear to be very promising experimental 0
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animals i~n the study of effect of smoking on the biological system. One of the animal smoking problems has been to get a measurement of smoke actually inha|ed. The Battelle Northwest people are using their radio- isotope studies as one of the first good measurements of volume of smoke inhaled a~d retained. In the studies at Battelle Northwest to date the fate of smoke components after inhalation by the beagle is determined by a radioactive tracer technique. The process is as follows: Prior to s~oking, the tobacco is subjected to neutrons whereby certain radioactive elements are formed. For example, stable bromine captures ~ neutron and beco~es radioactive. During smoking the radioactive bromine travels wlth the smoke and is easily traced by suitable Instruments in the body of the dog. In spite of the very preliminary nature of these experiments, Mr. E. S. Harlow, Associate Scientific Director of American Tobacco Company, was critical of these studies by pointing out ~hat appeared to hlm inade- quacies in these tracer techniques. In surarnation, Dr. Nielson stated that the beagle shows promise as an experimental animal. One of its chief virtues is the similarity of so~e of the human and canine smoking characteristics. On the other hand, the roden~ differs markedly from the human In this respect. It would appear that because of this marked difference, much, If not all, of the data on rodents obtained to date may be meaningless. Future Relations 0f Industry Technical Commlttee~ Personnel of C.T.R., and the Sc~entiflc Advisory Board Drs. Griffith of Brown & Williamson and Bates of Liggett & Myers inqu~red as to the role of the I.T.C. In addition, Dr. Bates mentioned that certain information which has been passed on from the industry people to the Sc:[entiflc Advisory Board has been ignored and expressed a feeling of frustration In this respect. Dr. Little replied that "your feeling of frustration is shared by us". He felt that contacts by the I.T.C. personnel at C.T.R. and S.A.B. should be more frequent than they have been In the past. Dr. Bates pursued further the role of the I.T.C. and stated that the I.T.C. ought to be a major factor in a decision on grants. Dr. L~ttle and Dr. Hockett countered by saying that the I.T.C. ought to be only advisory. Miss Janet Brown of American Tobacco Company stated firmly that I.T.C. could only act in an advisory capaclty~ if at all. She thought that certai~ proprietary considerations might preclude any ~ind of dialogue between ~he I.T.C. and C.T.R. Dr. Bates then inquired if it would be possible to distinguish proprietary from nonproprietary considerations. Miss Brown replied that it would ~ot be easy to distinguish one from the other. Mr. Harlow of American then proposed the idea of appointing a permanent representative from the I.T.C. who would attend all of the S.A.B. meetings where various applications for grants would be considered. He would then report on the S.A.B. meeting at a special meeting of the I.T.C. Accordingly, there would be no direct dialogue between the entire I.T.C. Coacaittee and the S.A.B.
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Future Meetings of the I.~.C. I. As mentioned above, the I.T.C. and perhaps other members of the industry will visit Mason in Worcester, Massachusetts for a demon- stration of smoking machines for studies on rodents. II. The I.T.C. will meet with personnel of C.T.R. on Friday, Decen~er 8. This meeting will take place just prior to the forthcoming S.A.B. meeting on December 9 and 10. The meeting of the I.T.C. which Is being reported here was held just after the S.A.B. meeting of September 23 and 24. Dr. Wakeham of Philip Morris attended the meeting of the S.A.B. on September 23 and 24. Ne did not attend the present meeting of the I.T.C. nor was there any discussion of the deliberations on September 23 and 24 of the S.A.B. Murr~y~Senkus :has Cc: Dr. W. M. Bright
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FROM: Robert C. Hockett, Associate Scientific D~rector SUBJECT: Meeting of the Committee on September 25, I~67. C) A meeting of the Industry Technical Committee will be held in the conference room of ~he Council (633 Third Avenue, New York, N.Y. 10017) on Monday, .September 25th at 9:30 A.M. It is ~l~m~ed tO conclude before lunch. Each member of the Committee is invited to bring also the chief of his organization's biological research if there be such. Topics for discussion will include: I. The role of the I.T.C. in the conduct of tobacco smoke inhalation research. 2. Recommended standards for the develo.nment and evaluation of mechanical devices for smoke inhalation by animals and other test obJectiv6s. "3. ~he monitoring of smoke dosage by the inhalation route. 4. Tobaccoproducts for use in such studies. Please let us know whether you w~ll be present and who will accompany you from the technical department of your compare. R.C .H. RCH:ek
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~eptemLer ]~, 19(:,7 Dr. Robert C. Eockett Associate Scicntlflc Director T,~e Council for ~obacco r, csearc~ - 0.~.~-. 633 Third Avenue Ne~" York, t~ York ltOl7 L~ar Bob: He have your recent z~.orvnd~.~ nunou~clr~ the ,,eetlug the Industry Techvical Co=,;tttee r,n 9~pte.r;t.ar 25, 1767. Dr. Eldon 13. l:tel~on and I are planz~iug to ettend. £1ncerely yours, Y!urr~y ~euku.~ Dr. W. 14. r, rtght Nr. i1. H. P~u~n ~ Dr. E. D. Nlelson
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Septembe~ 25, 1967 TO: ~ndustry Technical Comzaittcc FHO:d: Robert C. Hockett, Associate Scientific D~rector S,~.I~'oq'.~_. -.~-.-o~'*~'~*~'~ of the Cor~mittee on September 25, 1967. A me~t~ng of the ~ndustry Technical Co~:~ittee w~11 be held ~n the conference room of The Council (633 Third Avenue, New York, N.Y. 10017) on Monday, September PSth at ~.~.M. It ~s planned to conc]odc before linch. Each member of the Co~ittee is ~nv~ted to bring ~so the chief of his orgen~zation's b~o]ogica! rcsc~ch if there be such. Topics for d~scussion ~ii include: ]_. The role of the ].T.C. ~n the conduct of tobacco smoke ~halat~on research. P. Recommended stsndards for the development and cva].uat~on of mechPni6al devices for smoke ~nh~]at~on by animals ~nd other test objectives. 3. The monitoring of smoke dosage by the ~nhalat~on ~ route ~ ~ 4- Tobacco products for use ~n such studies. P]cese let us know whether you w~ll be present e~d who w~l]. accompany you from the techn~ca~ department of your comps~y. RCH: ek
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1961 e cco Z sTx t SE .C.-CU iTTE , The follo~l~8 psreon~ ~re present st the recent ~estt~8 of t~ Tec~l,l ~lttee of ~ TobJceo Z~t~ Res~rch blt~l (C~tm.n of ;~ o~ T~C), ~. C. C. Lttttl (~Jl~ttflo Directors ~nsocla~ Dlrec~re ;lie)0 ~. W. T. ~ (~e~tlve Dlrectoro J. ~1~ T~s~ ~.). ~ ~ett~ m ~ld tn Dr. ~oc~ett described th~ present status of the tobacco-h~81th situstlo~ under the follovin8 headless, cArdtovssculs~ diseases0 peptt© ulcer0 1~ Ca~t..oVS_ s~ulsr bt s.ess.e. Statistical studies have slu~m an association betvee~ ahd ~ t~t~n~e o~ ~rdiovls~18r dtmse. ~ st~ies ~ ~t teke into oc~t t~ her t~t ~s a~r ~n ~y ~actors other ~n ~kl~, 0.8.~ dte~o stressj physics1 activl~. ~e o~ ~ ~in dl~fere~os ~y the bl~ ~sssls in ~ers and ~kers. To or ~te~ fat ab~tton the Frmin~ha~ stody (conducted by the National l~rt Assoclstion)~ it was found that the tncida~c~of~vas ~ot related to aaokl~8 habits. Ho~mver this study does suffer ~rom the deficiency that no r~utt~e autopsy is c~n~ucted on the people dyi~8 durin8 this study. With respect to t~troabosts, smokln~ appeared to be related to acute stt~sc~s of throubosis, but moat of the persons dyin8 from such an attack had vary little blockase of the arteries. The TL~C~-~s sponsored • study on the desres of blo~ of ~ s~eri81 eyst~of seet~t victim. ~ls desks of blaise viii be ¢~vi~ ot~ ~J o~ lax0 rJ~ diet, ~nt of physic1 activate ~ ~kt~ to ~e~t~~r s~ ~elstto~ist. A defiet~ of this study to ~t th ~te o~ t~ ~bits of ~ acctd~t vlctt~ are ~¢es~rily ob~tned fr~ s~iv~ fri~S or relatives. Animal studies conducted by Dr. Wenzel (TIRC grantee) shoved that nicotine had an effect on the c~rdtovascular syste~ of tsbblta but. !1
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t~t t~ ~ant ~ ~. W~el ~4 ~t ~h ~n~. ~soquent e~ert- ea'.rdlovas~r lyst~ o~ w~bttg. effect of nicotine tn cardiovascular dtse~ce le dependent on the pro~etn leve| of the host's diet. An inadequate pz~tetn diet ~.lus nicotine produced a such Steerer effect than an s~equate protein diet plus nicotine. Pectic Ulcer_ Zn the paste most physicians considered that the hTperacidity observed in ul~r pstJ~ ~s priced by ~kt~. ~¢~t studies ~ s~ t~at ~kt~ ~s ~ eff~t on the ~trett~ of 8~ acid otter tn ul~ ~tt~ts or tn ~ml person. ~ a ~lt ~ny physt~tm ~v ~eel ~t t~ ulc~ ~tt~t tea ~ectft~ ;~ o£ ~rgon t~ere- ~gt~ly. Zf ~ls ~ t~ for ulc~ patinae, It ~y 01~ ~ t~ tn ~ ~ of o~ dts~res. Dr. gtssen~ • physician and psycholostst frcxn Scotland, plan8 to stud~ ulcer victius. He hes been invited by t.~e TT~c to ueet v|th its nevly forued PrjcholoLy Committee. shay that clSsrette stoke ts £ c~ueal factor or that ttts t_~_~ mJor causal factor of this disease. St~ce an|toni studies usir~s Inhaled cigarette masks have not yielded eptderuoid ¢orctn~m~ of the lun8, many persons have caked vh~ther the muse is immune to this tuner t~. Eptdermoid carctr~e~s of the lun~ have been produced in mice exposed to radioactive materfsls but not in mice exposed to uethylcholenthrene vapor, The TIRC teals that more animal studies sre required on this particular phage of the lung ~cer probleu. sy~rgl~ ~n ~r~in rinses and :obac~ ~ke. ~ree groups of ant~Is ~ tr~ lJ follovss C~ A ~s e~s~ ~ ~bn~ in an t~latlon ~rl~tl Cro~ B ~s ~sed to a ~n~nce~ vl:~sl ~ C ~s ~d to b~th the ~c~ ~ke a~ t~ vies. ~,e degrce of Inflmtlon obse~d In t~ lu~ of ~ C ~s ~ too're pro~c.d t~n ~t obse~ed In t~ ]u~s of ~roup A or ~ ~. ~ t~rs ~re obse~ed.
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Dr. l~rttn (Scion P~II) has re~orted the follovingt On~ StOUp of tr~d vl~ 8 ~t~s~ld 1~el of ~hylc~lsnth~e cr 3~ b~Jrdj i~ • ~e~d ~ ~l ~ted vlth ~t~ the vies a~d th5 ~ly~cll¢ h~r~n, ~o letter ~oup d~eloped lu~ t~ro~ ~e~ss ~lth~ of ~ first ~ 8~s developed ~rs. In s fourtk j~ t~d vtth vies 8~ tobac~ ~e, ~ t~r8 ve~ noted. Dr. l~otin (California) in his study dmnased th~ lunss of to s~tlc ~S~ t~ oth~ @x~s~ ~ s~tic ~8 onty. ~ of t~ ~ni~18 e~os~ to ~th the s~tlc ~8 and ct~sj ~ of ~ 8n~ls e~sed 4ev~lo~d I~4 t~rJ. At tl~8 annual mee~tn8 of ".he A~ertcan Asso-.Istion for. cancer ~=oarch In April. 1~. ~. ~S~ re~lt8 of his s~dio8 In vhlch to~c~ ~ke co~sste ~8 applied to ~1 s~sin mice. J~ut~Jj ~l~e fr~ so ct~ttes. ~ frm pipe to~ ~kod as ctSaret~s. ~ three ~~tes ~ ~n c~d vhl~ ~ttl t~ ~ert~nt lost~l ft~i~o rill c~11e~e t~ e~ttet:~l ft~l~ vht~ ssaoctati~ vl~ ct~re~ ~ke but a 1~ ~ of association vlth tier a~ pt~ ~ke. indt~ t~t a ~p of lives 1o~ ~n t~ controls. connie, ~ ~8 s hlah¢~ t~r incidence t~n t~ ~oups tr~ted Vi~h t~ Ot~ ~ sister E. Cahtll (Haas,) is checkin~ the enalytieal procedures employed by Sat~erloe in hie e~udy on tt~ areeni_.._...c content of tobacco. Studies conducted by TI~. KrsnteLs hays shown ~hst tobac~ and tobac~ s~ke ~n~in nl~l. ~e con~ntration of t~ nickel in the s~)~ is ~ 1~. If t~ nt~el in the ~bacco ~ke ~ present a0 ni~l ~r~nyl, t~ ~unt ~uld ~ t~fficien~ ~ ~use in test ~l~ls. To ~to. nickel ca~nyl ~s ~t ~ found ~obl¢~ ~os ~t its de~e~i~tion pre~nts dtffl~lt~es. I~-e. ~ez~ach end ~n~ ~ere to speak in Cincinnati .on lun~ cancer a~d 8mokin8. Th~ at~ched clJppin8 describes their H~-, Thomson (Hill and ~ovlton) e~ke fez a fev mir~tes on public relations. The press at present Is ~t as exile on the lu~ cm~ce~- s~ki~ issue 8s it ~8 ~ or ~ee y~rs ago. ~e appears to ~ little
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4 ~r. ~. R. Gallova¥ Dr. Hurray ltes~rch l~psr truant
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The ~ollo~tnS persons were present 6t the quarterly ~eettn~ of the Industry Tecl~n~cal Co~alttee of the Tobacco Industry Research Co~lttee~ Hr, Par~:le (Chair, s of IT:), Hr. I~oyt (~xecuttve Secretary of TIKC), Dr. I~c~tt (~C), Hr. Shelton (L~rus a~d Bros.)t [~. Stephsno (Stephsno Bros.), Dr. i~rro~ (Philip Horris)t Hr. 3ennett (United and Dr. Kod~;n~sn (~. J. Reynolds Tobacco Co.). The ~eetin8 va~ held in the offices o~ the ~1J~.. ~r. 14ockett s~-~_~rized • proposal suh~itted by ~Iph ~r (~Iversity ~T. ~ ~s ~llected 8ppro~'~tely I~ p~e poly~cli= hydr~Jr~ trosraphi~ dst8 ~ ~e relatto~hip of t~ ~ l~els tn~e~s~i~ approach ~ the s~u~ o~ ~rcl~S~sin ~d he ~ ~eated ~t ~ of ~ 1~ ~d~ ~llected by ~r ~ c~cl~g~sln ~tu~. ~. ~u~ell t~kes ~lce of a partt~l~ ~ pein~ ~e~ mice vi~ a ~ ~t~ ~rcl~sen. mice to ~ ~rci~gen s~s a ~a~ation, ~ mice tn hilly s~ltive ~ile oth~ ~lce ~e o~y sItSh~ly se~ttive to this c~und. ~. ~u~ell takes s~r61 of ~c htshly rests~n~ mice i~r~ ~; he a1~ ~es ~ of t~ hilly se~i~iv~ nice ~d i~reeds ~. Et~t ~zstlo~ ~ve ~ b~ed in e~ch of t~se is p~pos~ ~t e8~ series ~ ~sted vith the ~ou~s ~ll~ted by ~. In ~d":tion. these ~oun~s ~re ~ be tested by t~ ~e~t of D~. S~ep~ 8s ~ell ~s t~ trJ~plan~ttoh ten.qua of Ru~In. In ~is way t~ s~les of ac~ivl~y for t~se set ~. It will ~ of In~t ~o dcte~l~ w~ ~se scal~ are ~ab].e ~ o~ ~r. I~ Is ~I~ p1~d t~t t~ ~sition of ~ on ea~ of ~se Jc~les vlll ~ de~i~d. ~ts still le~ves the prob1~ of equa~l~ t~ results ~ ~ ~rlence. The seccnd subject of discussion at this meetin~ wa.~ the symposium h~Id in California on "The Air lee Breathe." This s~sl~ v~ 8~ored by ~C ~ was quite veil atten~d. Ap~roxi~tely 3~ per~ were pres~ d~i~ t~ 8~sl~. ~ pa?~ pre~ented by ~tin on ~Ilutio~, ~d ci~rette ~ on cille~ activity yes ~Ite ~II recelv~ e~ 8~t,d t~ us~ul p~ose of putti~ ~e r~Inder of the papers ~Ir proper p~ectiv8. ~ dls~sslo~ ~een ~nd ~ ~rk~n on ~ validity or ~alldity of t~ statistical ~'.udtes with respect to cIsjre~e, s~ and I~ c~e~ v~s the ~t controversial subJ~t pre- sented duri~ ~ s~osi~. C~ of the que~tlo~ co~ernin~ t~ sta~istlcal r~ul~8 ~-as ~'hy ~he tnci~e of lu~ cancer 0
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~ eiSs~t~ ~kl~, £vt~ntly ~ ~d ~ 8~d s~r to this Th~ third point dts~sad st ~t~, ~ts ~t~ pa~rs ere sc~led on oll relstto~hip of ~se ~tertsls ~ ~rdl~s~lar dis~ses, A brief ~tll~ The absorption and fete of ntcottnel b, Phereacolostcal action of nicotine end smokt~! e, 1he influence of ntcottn~ and smokies on the peripheral ©lr~uletton! d, 11~ action of nicotine end 8ruskin8 on the coronary e, Significance of eleetroeardiosrsphl¢ end b~lltsto~ardtosrsphi~ chan~es induced by sm0~taS! f. O~her aspects of phare~colo~ of nicotine and smoking| 8, F-fleets of nicotine end emokln,j in c~rdiovss~ulsr disorders| and h, 1he effects of ~moktn8 and diseases of the peripheral ~v~scu'. 'r Approx2mstely nix papers ere to be 81v~n m~ier e~ch of the he~din~s listed. The I~perlmental studies of Leu=htenberger ~re aRain ~uch~r8~ ~8ed mt~ ~ ciga~e ~e for prolo~ p~rt~s of e~ert~tal 8~Io. ~r. bro~httts ~s ~ obsemd ~orsdtcsliy in ~ ant~18 ~8~ ~ elSa~ ~ke. ~ere in ~ ~p~rent ~letion- ship ~~ t~ t~t~ of this b~httis and dmtto~ of t~ ~su~ of t~ e~erf~ntsl shills ~ ciKaretto ~. ~ch~rger ~J al~ obse~d lu~ similar ~ ~se ~d by ~ch a~ls these 1~ c~ses disappear t~ ~rl~ntsl ut~ ~ an l~cti~ vies. t~se vt~s-kr~d ~ni~ls ~ cigarette s~k~. ~, E~ is providi~ a~ c~st.~ t~ v~rious vl~ses to ~ used by ~uchte~e~er. Several other stu41es were di~cussed~ namely, the anthropometrlc study conducted at Harvard. In thls study, already partly reported by Seltzer, l~cArthur ar~i ~th in several pu~li~tlo~, the r~Intlonship bet~en 0 W 0
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3 ~okin~ and p~r~nsltty factors ~ ~kt~ prattles, ~ ~b)~ts I~1~ In ~is s~ v~O ~8rd s~ud~s, ~ f~ ~e r~ul~ ~e ~ ~ ~cltl~, ~ of the i~r~ l~c~rs ~d In ~is s~dy v~ t~t a htsh d~ee of f~l~ty In ~y ~ild ~ per~llty v~ relat~ ~ 8 hi~ ~ of ~kl~ or ~ ~ssl~ ~kSq. It Is plmd ~ ~elate ~ ft~i~ on ~c~ s~ dtf~er~ ~e ~tlc~ ~n ~kers ~ ~kers ~i~ r~pect JiC~rl V~ I~lstion ~ ~lsti~ VO~ ~i~red tn ~ ~se of t~ ~rs. ~i~ ~iU ~ ~ s~u~ ~e m of ~ fso~r8 ~ tm~tt~tto~ Dr. Itse~ reported se~r~l years ~o ths~ smoke~ ~ s fester blood clotLtu8 ttm~ ~ c~pared vt~h nonsmokers, • In a Tr~oSpOnscred study recently completed, no consistent findSnSJ coapsrable to those reported by EIsen vere noted. Zn s~other T/3CoSpOnsored study, it v~ ~t~ ~t ~8 ~ 1~ bl~ pressures t~ ~~8. ~ int~re~tton of ~i~t~ ~d ~ ~ ~ In~es~ ~ ~ ~ I~ cessa~t~ of ~ki~ by a ~ ~ ~uld i~r~ his bl~ a~ ~ ~ him ~re p~o~ ~ ~rdl~l~ ~ltcstl~. It has ~ reported by s4~ezal lnsestts~toro that saokln~ increases the cholexterol level o~ the blood. Dr. Zrvln& Pose found in his study that the cholesterol level in smokers vse no~, vex7 m~eh different from that obc~d in nm~maokers. In s study on the c~rcinogenic activity of ". ,4,9,10-dibens~yrene constituent of ¢lEarecte szn~ke), Dr. 14omburger fount this ~lycyclic hydro~r~,n ~ ~ ve~ active ~ muse ski~. In a skin paintl~ ~erl- ~. I~ petit of hl~ mice ~loped skin ~.
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ceupound wu 8pplled to the uterus of fmtle mice, s~o per~t o~ ~ ~ ~o~ o~ ~ ~ s~rsi~o~ etee, tt u~ fou~ ~t t~ ~us Dr. ]3oe.kett then concluded the meotin8 vith • brSef outll~ of tt~ of lnt~est t~t w111 ~ appesri~ t~ ~ ~ ~ut~e. ~t t~ ~xt ~ett~ In Ju~j 8 J~ 18 ~ ~ ~ltt~ to the ~C by ~he ~ci~ttfic ~l~ ~-d o~ ill liX y~rl of ~eratton, Copies of ~8 s~ rill ~ supplt~ ~ ell psrtict~ti~ ~s of T~C. ~ ~ Yo~ or111~11~ outll~j thts s~81~ ~ld ~ ve~ bad for Z~. ~e s~st~ Is ~t~ ft~ed Jointly ~ ~ ~ Yo~k C~r ~¢18tyj ~ ~J~ Ci~c~ ~lety, ~ ~ ~ York ~ld~ of ~diei~. Tho next meet|n8 o£ the XTC of TLRC is resistively scheduled for aid.June. 1960, H~. ~ Gray lql". ~. 13. Rim= Fir. r~u~eth H, Hoover Dr. Hurr,y Senku8 R£SF.JJ~(:Ii ~PART~.J4~
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October 8~ 1959 S~E:]~ 2,4,~ 19~9 The follo~inapersons vere present st the quarterly me, tin8 oE the Znd~str~Technic~l Committee of the Tobscco |ndustry ~esearch Commttteel Hr. Parma1, (Ch~truan of ITC). Kr. I~ (TI~C), Dr. Little (TLqC), Dr. Hockett (TL~¢)o I~. Shelton (L~rus& Bros.)e Dr. Stephan, (Stephan, Brae.), Dr. ~ (~mar|¢m~Tobscso Co.), Hr. Tucker, I~. Wade (arovnk Wlll|mesonTobs~¢o Carp.), ~r. Betlnett (Onlte~ States Tobacco Coo), Hr. Ttmmson 01111 & [novlto~), ~r. Coulaon (?m. er|al Tobsc©o Co.), end Dr. Jtodsmtn (R. J. ~)~oldsTobacco Co.). The meetihS~-:s hal~ l~ the,[flees of the TI~C. Dr, Hock, it s~rlzed t~o symposia held in con~unction~lth various mee~4rs of ~ S¢l~tifi¢ Advl~ ~d of T~¢ on cer~in s~Je~t8 of i~te~st ~ t~ ~ceo J~t~. ~of t~ln~ints~t~ln~tlo~ ,tt~. ~t8~o Interbred bye. ~kett e~ ~. Little ms ~ t~lcetton of t~ rlst~ s~t~ of t~ ~ of T~¢, ~e pa~tclpants ap~ ~ enjoy sct~ttfic ~ first s~sim ~scri~ v~ t~t i~olvi~8 s ~ssJ~ ~ the bi~s~y of carc~t~. Zt vss ~ld ~rly in t~, of ~, s ~le~ topic sl~e t~ ~~nts of ~c~ ~keo air pollutants, f~ additives, etc. are The main disc~sion of the btoasaay of carcl~£ens yes cancelled pr|- s~rlly vith tl~ I, lo~saay of the activity of the polycyclic aromatic hydro- carbons. The~ork of Dr. l~n~mtin ~ubin (Bayl~, University) ~snoted sad the re~ultsobtt~in~by him may have lona r~nse |uplicatiohs. Dr. very keen to present his results. He had observed that certain strains of mice ~hlch~.t~ rtsist~t to tmr transplantation on pslntln~tth • known carcinogen, e.8., 3,~ohenspyteneor 2~-zethylcholsnthrene, for • perlodnot sufficient to elicit t~s~rs in these animals, shoved positive takes in trans- plantation ex~rlments. The dosa£e aruSpotency of the polT~yCliC aromatic hydroca~oon employed vss very Ju~ortant in this study. The •uthor then conductc~5 an extensive study to investigate the behavior of a nunberof hydrocarbons to check their relative potency in this transplantation experi- ment. The general activity in the s~rles studied vss that reporte~ previously for carcinogenic activity in skl~ paintin$. Th- author has since collected a £reat ntnber of polycyclic hydrocsrbons (in the neiEhborhoodof 125) viii attempt in the future to arrange these hydrocarbons in • graded series. ~any of these cow~ounds hsve never been tested for carcinogenic activity. Dr. ~ub~n has ~ot considered tobacco 8~oke as such up to the present time. A co-yorker of ~r. ~ubin, Dr. ~ecker, collected these hydrocarbons fro= v~rious laboratories in E~Isr~, the United Steles ~ France.
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In conjunction vith the study of D~, i~ubln, Dr, Beckez la conductln~ a ab~tJon sp~ra of t~se ~~s a~ t~ ~l~tio~hIp of t~ ~ t~ c~rct~nic ~ctivtty, ~ fo~ t~t ~ could S~ these c~~s had to ~ qut~ p~e, ~e deco~sltion of the~ hyd~z~s vhich sects on ~s~ ~ li~t, oxygen, etc. vas ~pt at a mint~. Dr, Bout~ell (~ho la vorkln8 vith Heidelberger) suF~eated to st this s~slm t~t he ~uld like ~ ~loy his e~erl~tel (~t 8~cJfl~) ~ check the results obtal~d by R~tn ~d ~tlo~ yes t~ stay of ~, St~p~ ~loyl~ ~ r~la, s~st~d t~t St~'s ~t~d mi~t sere as an addition1 crder of ~t~ of ~ese c~s, Step~ ~pres~d his ~llll~ss to ~ ~ el~ take over his stay, sl~e he yes ot~r thins, Att~ts ~re ~l~ ~de to acquire a "psrmcia ~rt" c~k the ~s~ts of t~ ~ln a~ ~cker st~ ~d t~ Sou~lt sty, S~no of the i~rticipanta vho ~ere not identified by ~sl~ did ~t ~lder ~t the ~sults shrined in ~he~ 8t~ie8 outlined or su~s~ ~ld be ~ I~lc~ttve. For o~ thins, t~ stay co~t~ by R~in Is ally ~t o~ of t~ dereliction of ccr=i~tc activity, AI~ ~ntt~ ~ t~ fact ~t ~y test of this vith ~J~ct ~ ~e ~lml ~lo~d~ the s~raln~ a~ the pr~odms, Dr, Little ccmue~t..~d on this ay~;>ositu as follovs! He said that if 3.~-b~nzpyra~ ~t,k~d thi~ In potency tn t~ nf the ~ove testa a~ zanked l?th I~ ~te~y t~ s~ther, this -~uld s~ t~t ~li8~e on one test t8 hiahly ~lse. ~t8, ~ cons~de~d. ~utd ~ ~ ~tde~e to co,terser W~er, ~ zeltes prl~rlly on t~s r~sults of skin pa;nti~S experl~nts. Ir.,t~e). 8 varie~y of c~tl~es (different ~lycycllc hyd~c~o~) ~ ~lo~d In o~ ~ries. ~ ~sults viii th~ ~It ~ c~t~lo~I~ of t~ chatt~s, ~e~ also viii deels~te individ~t re8~ l~ th[8 Ih'. Hoclmtt also ~entioned agsln the studies being conducted by ~b~er In ~Ich ci~r. pipe. and ¢I8~rette ~baccol are ~inS ~ked tn the fo~ of ctg~ttes, ~e tara obt~i~d the~fr~ are ~l~ ~plied to t~ ~ ~r~In of mice ~ed by ~er. It Is ~p~ t~t the results. ~ obitS, v111 tb~v readable ~t on th~ ei~lifled 1nte~retatlo~ offend by ~er e~ a~. to t~ ~sul~s of their expatiate. Rockett also r~ted that theze~ere no reporL8 in the~Icsl or scientific literature to incriminate 3.~-benzpyrene or ~o~e~hylcholsnthrene sl~ciftcslly as a I~8 carci~gen
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3 Dr. Hockett discussed s second s~mposiu~ al~o held In ~pt~er ~teh chronic or acute I~ conditto~ as rele~ed to !~K pat~lo~ later st~ of c~t~ ~ di~ussed. ~e pa~ictpants In this e~rt~ttl/stJ ~o ~re inherited prl~rily in J~t~l ~rk. ~ u~er k~ c~lttons. (~hester) at ~i8 s~si~. Flnke is s physician specializtnJ dl~s ~ ~ obae~ed ~ny parlors ~lth ~hy~, 8s~. 1~ ~er. tnfl~, etc. rt~e ~s ht~ty t~remd ~ith the fact t~t 1~ ca~er ca~s vi~d by him had fre~nt histo~ of di~s~s other t~ 1~ carci~. F~ a series of ~1~ patients obtal~ fr~ the Soches~er jNae ~ obtst~ ti~8 ~ ~i~l c~rt8 of the~ patients often s~d ~ p~l~ hls~ o~ 1~ dl~a~, ~er~ ~n the~ pati~ts ~ c~c~, el~r b~ tnqul~ of ~lr ~c~r or t~ir relatives0 it v#s fo~ case t~t a 1~ htsto~ of I~ disuse 8~ ~lt~tt~ ~d ~ ~eri- e~d by ~ psti~ts. Finks then collected • Kreat n, _,~er of Xorsy plates frms the ~o~bester area. ~ ~ t~t ~y pati~ts suffert~ on their Xoray pls~s p~fo~ 1~ eh~e8 prior ~ t~ ~l~t of 1~ ca~r. FJ~ ~uld like to disease ~t~ ~ a ~h 18r~r n~F of 1~ ~er patt~ts ~ t~t t~ ~letio~htp ~t~en these varlo~ diseases 8~ 1~ cJ~er d~elo~ lnte~a~ in t~ fl~l~e of Fin~ and said t~t ~ ~uld a~t to ~r- t8~ 8~h a 8t~y vith ~e date available at J~ ~pkins. Rl~ff said t~t he ~uld ~ able to ~loy 8 ~h lar~er s~le t~ t~t ~ by Ylnke in ~heJter. Dr. Sprunt (University of Tennessee) conducted s study em~loyl~ rabbits. The~ ~tmals ~ere injected vith certain bacterial toxins (~hich the result of various lnfectton~) into the luns8. A htsh co~cm~tration of t~ ~xi~ ~ ~ a~ it ~s ~ted in c~Ses ~c~. To ~te, ~ 1~ cancer easels ~ tr~. Xn a~ther stay ~loyt~ hyd~chlortc effects ~ ob~. ~ver, iu this latter of antibiotics ~d to ~ ~ to ~ep t~ ani~ls alive. Vo~ald al~ ~nd~ted an 8~1~1 ~orl~ in ~tch varto~ d~ts. berlitz, etc., ~re in~ec~ed into the p~holo81col ~nditio~ obeal~ are bein8 Dr. Le~chtenberser is continulns her exp~.lmenta in which mice are exposed by Inh~latlon to tobacco sa~oke. Xt vau noted v~ ~ of the mic~ de, loped b~hi~ls. ~%en these ani~ls ~ sacrlficed~ the pat~l~gicaX conditions ch~ed in ~ l~s ~re the s~ ms t~e ~ich ~ investigators called precancerous. Alt~u~ ~ of the animls had ~n t~
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4 ~8 ~ted in ~y of t~e. ~ ~~ ~ ob~d e~t~r. I~ 8~ral, ~ the the ~ o~ t~ ~t~ls t~re did ~t appear ~ ~ ~y rela~to~htp t~t In the ~t~. Zt ~as s~s~ that t~ i~l~lon ~ies ~y ~ve ~en trt~ered fi~i~ r~Jlls t~ ~rk of ~'e~11 S~ley ~d his 8~ ~ t~ vlr~ t~ of J~cti~ ~I~ ~ ~ in t~ ~sr lutes. Dr. 1~ockett them mentioned 8 study c~nduc~ed by Dr. Shetton rxmaers plans ~ ~ this stay. Dr. Little described • study on healthy, sssd people, )~ny of these t~d smoked for ~ ~ 73 ~rs. ~rs ~ dest~ds k~e to s~ct81 n~ut this ~pulatl~ other A~ o~d a~ c~r tn ~s~ ~s co~tdo~ sutt~le Lot s~h a stay. ~ ~x's o~ 8~. ~e~ ~pls 8~ vllZl~ ~ c~rate in s~h 8 stay. ~y vJri~ states 8~ pls~ vith this ~pulJti~. To et~r in ~to~r or ~r. ~959. ~r ~ ~r~ ~ J~l~d in ~his lar~-s~le stay. s~. ~ ~ar. ~ ~s~ ~o ~ Inte~J~ ~ q~stlon- D~. Little sS~in ~entlor~ the fact that they ~ould like ~ set ~ a etvln" s~y. pro~bty vi~ ~~ ~lp ~ tt~y t~ factors I~olved tn identical ~i~. ~ls ~utd ~ ~ ~te~lon of ~ st~ies ~or~ed by Sir ~m~ld Fleer in ~land ~ b7 ~1~r8, e~ a~. Some o~ the miscellaneous points mentioned obse~,~d t~t t~ ~s ~ ~strJct~on of the bl~ ~s~Is of c~n ~ sttrlbut~ ~ t~ •ction of nicotJ~. It vas •leo suKKested that it mlKht be • Sood idea to orSanise • public syn~ozl~n to pre~t all ~ ds~ ~ the public on th= rels~lo~hip between tobacco ~ h~lth ~ t~ p~ltsh this s~sl~ as a-~aph. Attire ere beins ~de to ~t ~ s~h a s~osi~ ~lch viii probabl~ t~ place tn t~ s~ri~ of I9~. It Is ~d that s~h a s~sl~ viii ~ held at the New York Acad~ of Stile and the n~le~ of the pa~lctpan~s ~111 ~ the tha~ varlo~ ~orelsn ~s ~111 ~ccep~ invitation~ ~ ~r.end or to psrtl- o
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Another eyuposltm plannad Se o~ to bo held at the University of Csltfor,~la. The ~ntvars|ty of Cslifor~ta i8 ora~ntstn8 • prosrsn in ~hich various doctors and rese-__r~.~ ~ ~tll ~t¢ipa~. ~lly ~hto ~o s~ fluvial ~sts~ ~ ~ obtain. ~ts 8~sl~. 1~ the Iqr. C~rl Tonp~on of R|ll end Enovlton uotod ~ t~ ~8 ~t 80 ~h ~1~1 p~llct~y vtth ~s~c~ ~ ~ ~kt~-~al~h probl~ as ~fo~ ~ , p~. ~ ~'s Di8~ a~tcle orl~l~lly,Jc~d~ed for ~s late s~ ~llp~bly~t ~~til ~or ~~ 1959..AI~ I~ t~ ~ -. • ~1~ ~ ~kt~ ~11 ~r ett~ ~ly in 19~ tr Isle 1952. ~ts ~lt~ttce. tt les~t~, is a ~lW a~tele.
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K~It~C OF T~ INDUSI~Y TECHNICAL The follovlng p~rsons veto present at th~ quarterly ~eti~ o~ I~ Te~l~l ~tt~ of ~ To.coo ln~Jt~ ~se~rch ~tt~l ~r. P~l~ (~l~n of l~), ~. ~ (T~C), ~, Little (T~C), ~kett (TIRC), ~. O'~efe (Philip ~ls To, coo ~y), ~. ~uis S~p~ (S~p~ Bro~rs), ~. ~r (~lcan Tobacco ~y)~ ~. Little ~d ~t If t~ ~ ~y t~s of ~se~ch ~ ~ ~o~tl~ ~ t~ ,c~anles In q~sticn .s~18 ~esl .f~e, ~ ~esti~ ~ ~ ~lentlfie ~dvlso~ ~a~ of T~C. If ~ am a~r~rla~ t~ Scl~tific ~vlsory ~erd ~uld ~n solicit ~se~h t~stl~ ~ ¢a~ ~t t~ su~o~d res~ p~Jec~. ~0 Little ~s~rl~d briefly ~ of ~ p~ec~ al~ady In p~g~ss ~~lo~d ~ ~t. ~era is n ~at md for ~ ~~ i~lstl~. p~t~ ~. Cat~ll is ~tiri~ on ~ly 1~ 1959 f~ ~ ~p~t ~m~ ~t ~ll ~ity ~d ~ viii ~ able ~ ~ ~ ~ ~ a~~tl~ t~ of ~e~h pro~set. ~. Little ~ntl~d ~ l~lation s~dies~ ~k~ re~ntl~ s~dles~ eto, ~ld ~ ~ ~ val~l@ e~dy In ~t ~ ~s~l~ could ~ m~lly co~a~d ~ t~ m~l~ tl~ o~ ~is clll~ ~¢tion ~r~ vith I~ ¢~e~ Little In ~l~ t~ sidle-celled ~l~l: psr~¢lst va~ used ~or ~ of ~ ~ntlal c~i~g~Ic activity of ~cco ~. ~Is t~ of s~dy ~ ~ ~Jor a~ta~ss c~ap~ss a~ rapidity. P~ll~l~ m~ k~ en~i~eni¢ and ~n-carci~g~l¢ ~ents ~ ~en ~/ t~t ~. ~or~ F ~i~t of ~ ~lst~ ~par~n~ o[ t~ ~i~sity of Tor~ ~d ~cently ~sl~d hl~ In ~ila~lphia ~ obtain i~omtl~ a~ut this p~cla ~lquo. ~. ~ight Is ~en~y co~tl~ re~h a ~r~t fr~ ~ ~atio~l C~er I~tl~ o~ ~. ~ ~ £or this ~sea~h project ~e originally provi~ by t~ ~erial To~¢¢o ~y Ca~ ~ t~ ~atio~l Ca~er I~tit~te of Ca~ s~lfl~lly for ~ ~stlsetion of cig~t~ ~ks. App~ntly~ ~. ~l~t ~ ¢~ed ~evl~ly. his ~sent~h ~d ~ cond~ted In ~tlon vl~ ~.
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at $1oanoKetterlr~ Institute, ~ York, 14o~, his resesrch Is m0r• or less bets8 conducted indirectly for the Imperial Tobacco Company of Csru~d~. Dr, ~lSht te also a consultant for the Tennessee Eastman Coc~an¥.) Dr. Little then noted that more I~or~tion v~s required on statistical dst• with respect to lun8 cancer m~d smokir~. A difficulty •rises ~ t~t first class biosta~ts~tci~ a~ difficult to acquire. ~e feelt~ t~ Sclenttftc ~i~ ~srd ts that s~ ~y ~ve to be 8ssl~ either to ~rk ~i~ ~rk~n a~ t~ ~yo Clinic or to ~ vl~ ~ other ~II-~ blost~tisticsl ~. ~e sts~tstt~l s~y o~ particular tn~eresL l~Ivi~ t~ 8~e ~ ~ ~Xch death rates c~n~. The L~Ited States Vital $~tistlcs indicts that the rate at ~ich 1~ ca~er death rates su~ests ~ in~l a~t is ~rki~. ~e rate at ~hlch I~K cancer death rates c~ differs f~ t~ ~e of o~er c~cers ~ to ~ ca~ed ~te~1 ~gents, e.~.. skin ~cer, etc. ~. Little su~st~ that be frultful ~ ~ttack the pros~cttve statlsti~l st~les o[ ~~ ~II ~ Hill, a~ ~ by {s) crttlci~ of the ~t~dolo~ i~Ived~ d~trett~s that t~ ~ta are inte~retsble in ~t~r Little then mentioned that much ~ork ~as needed in the field of psychosomatic factors., F~rquis •t the University of I~.lchl$~n in presently conductin8 a study to ahoy that clssrette ~noke behaves as a mild tran- quillizer. He has recently developed • satisfactory essay procedure 1~celved a l~nt from TIF.C to continue his studies. Dr. Little also noted that u~ch lnfor~ation ~as desired on the psychoscc~tic factor respensible for • personas •tattle@ to-~noke. This factor is~lso bale8 studied by the ~ricm~ Cancer ~oclety but for a different reason. The ~rlcan Cancer. ~oclety hopes that the information obtelne~ will pro~e a point! the Title ~ould like to. ace the research carried out in order to obtain the information. Also, the Scientific Advisory Board feels that • tudies are required to determine the effect of cessation of ~nokinS on the incidence of various diseases. ~ Xn cor~ectlon vlth psychoso~tlc factors, a confe~rence is planned vlth investigator• ~ ~ve b~ ~tl~ statistical st~les Involvl~ h~n tvi~ 8~ ~ effe¢~ o~ ~kJ~ on identical data ~l~dy collected by ce~stn i~tl~tor8 are ~. as yet, ~lete. ~ ~clentiftc ~i~ ~rd ~a ~t o~ of t~ ~ve~ a~ncles viii ~c~ 8uffici~ly interest~ in this pro~ect to obtain ~leto i~omtion on tvlns t~o~u~ the ~Ited Another project of note is s study of the health of •~ed s~okerl, t.e.. persons over 70 years of age ~ho have s~oked continu~lly for • lon~ period of time and appear to be still in ~ health. $~ch subjects as steroid ~etabolism. etc. in the aged person ~ould be l~ortant in this study. Een- tlon ~as l~ade of the results of • study already reported by $1o~n-Eetterln~ Institute on the effect of ad~lnJstration of certain steroids on certain heart conditions. ~n addit(on, the .Scientific Advisory Bo~rd ~ould like to see a study conducted, lnvolvir~ aged persons, in ~hich ell pertinent lnfora~tlon on their lives yes collected, Such l:e~8 as the diseases they have suffered throughout their live-'. ~here they lived, what they ate. ~',tere they ~orked. e~.c. ~ould be tabulated for their ~ole life span.
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The Selentiflo ~sor7 3oard also feels that • ~ role o~ p~vl~ i~ecti~, i.e.. Infl~a. i~l~ of 1~ ~ ~d ~ o~ val~. A ~e~ clt~l ~ viii ~ s~tl~ble ~ ~t it viii ~ ~sslble ~ ~la~ ~ i~tl~ti~ o~ ~ ~ti~ effect ~t~en ~. Little ~ mtio~ • ~8ph ~1~ viii ~ ¢~le~{ by Vallee of ~e~O in ~ ~ ~ ~ ~11 ~ ~ ~8i~d. Also. ~lle~ ~ ~t~d. ~ o~ t~ s~dies Little •lie ~d t~t ~al ~s~ipto on arsenic in to~ccos ~ tobacco ~ audited ~ ~ ~ ~ Jo~ ~sul~ pre~d in ~ p~r dis~s~d ~crtp~. To ~. ~8e ~scrIp~ ~ ~t ~en published ~ any ]ou~l.. Dr. Little ~m~lu~ed his presentation vith • fev brief cogent• on some of tho studies in progress to sho~ the effect of vitamin or dietary deficiency oR tim inoidenCe of fun8 C~ncer or other types of cancer. TI~ ~ork of ths Hi. Zion Hospital group on the effect of niacin on the cf lnter~gt ~ tl~ of • group in V~ksachusotts (l~arvard Dental School and o o 0
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of ~ lt~. ~e lat~ ~nditlon Is ~e p~l~tly ~ die~ ~ftci~ies. ~t~te~le8 ~ ~in t~8 of ~. Another stu4y ~entioned vas that lnvolvtn~ the relationship beb~en t~_e s~oktn~ h~blt ~nd vlt~cin C content of ~hs s~o~rls ~lood. Evidently, beery s~ckers shov 1or vitc~tn C content. #.t present, tho ~nnin~ of tl~ cbservatio~ |s highly conjectural. D~. l~ockett then co.nested on sou~ of the conferences either ~Id recently or pla~d for cardiov~l~ studies. A~ ~tr ~l~i~ ~d dis~se~ the ~ants ~ ~en ~ for appr~i~ly f~ ~ars. ~ ~Jor ~int of rate.st ~d fr~ ~sa v~lablllty of ~ l~lvi~ls ~ed ~ clr~Istlo~ These lstter observations ~re noted by four other independent vork~rs| na~ly. Bln~. ]~llett, H~f~enschtel and Sc~ltthermer. At th8 cardiovascular conference, I~. Thoeu~ summarized her ft~ ~ s~,l~ ~t~ cardio~e~l~ pict--s. It v~ f~d t~t ~se ~ ~n ~re di~ctly ~la~d ~ ~ or ~re ~rso~ ~ ~d died of ~ ~se~e. ~. ~ c~l~d ~t ~ ~ c~dlov~cul~ plc~s ob~i~d vl~ these ~ ~ ~re p~b~ly ~ ~ ~redlty. ~o evide~a~e h~s been obtained to ~o ~e causes ~y ~Jor ~ ~ t~ h~l~y c~diov~1~ s~t~. ~ t~ o~r h~, ~ ~le~e ~ ~en obtai~d os ~ ~r or ~ ~b~cco ~ is ~I~Io~ to ~rso~ vi~ exlsti~ c~rdlov~scu1~r disease.
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In m~oth~r sy~ost~u that vss held by the Tuberculosis Society, ~ ~tly ~ed i~ fisld of s~dy ~ 1~1~ i.e., 1~ ~r, ~~, etc., ~. ~t~ yes ~ ~ sit ~ ~ p~l. ~ p~l ~tsted of t~ fo11~1~ ~rs~t ~ In ~latt~ ~ di~e8 of ~ I~.~ Certain nlnor topics ~re dizcussed at t~ e~ of t~ ~tt~ of ~ IT¢. ~ of ~se v~ t~ a~e ~n~ ob~t~d for t~ ~bli~ti~ ~o~ ~ ~sl~." ~li~ by ~ ~cco l~tltu~. ~ m~or Cr~tlcim ~ ~ or le~ ~lt~n~ ¢~ ~ ~ ~t this ~bltcsti~ is ~l~ ~ta p~p~ s~t. (~ ct~lstio~ of ~is publi~ti~ ~t it ~ ~t p~nt ~rk or t~ ~ul~ of ~t~Je~ ~S~ ~ ~tl~l ~~0 ~so~ ~ ~o~ p~em ~t uTob~ ~ ~slth~ ~blS~tlon ~ f~ ~ of ~e ~ of ~ ~t ~tl~ of ~ ~~ ~lea~ ~tt~e ~ s~led for ~p~ 1~. 1939. l~~ly foll~l~ ~ q~rly mtl~ of ~ o o t~ 0 t~ o~
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The follo~ln8 persoas vere present at the ~arch 15 Industry techntrAl Comtttme of the Tobscco Industry lesesr¢h Dr. Hockett revimmd sc~ of the resesrch conducted ~Ser &tent4 fro~ the Tobacco I~u~tr~ l~sesrch Cc~tttee. Some of ths cellulsr cl~n/Ss observed in the b~onchtttc mice ~ stutl~ r~d f~ ~ I~lstton ~ea~tj ~ ~llul~ ~s rspl~y dt~sr~d. mice ~t ~ lef~ ~ ~ i~lation meant did ~t s~ ~1~ of 1~ cs~er in ~y t~. s~c~d ~ of mice are nov under trestmnt and ~ ~sl~ 8tt~tt~ ~l~ m ~ sm s~aln ~ed In b ft~t ~~nt. effect of Vl~n A ~ ~ cellular c~s o~d In ~ 1~ 2. Dr. Hockett then discussed tlst ~rk of the Pathology Oroup. is a ~ at p~losts~ ~lch ~l~d s cer~t~ ~r of sll~ of prm of ~ ~ S~s. ~ ~12ular c~ ob~d ~re hi~ tu s~ of t~ sli~s e~t~d. ~ case o~ v~ ~c~d ~t ~d ~t ~en ~d pre~ly In ~ patt~t~s hts~, by ~ dtffe~t pst~lo~sts ~ ~ resul~ c~sred. Z~tts11~ e~rl~n~ ~d tn~l~d ~ slt~+ vhl~ ~ read by ~1~ dlffe~nt pJ~lo~ts~. 5cie~¢ J~t in t~ ~ar furze. The /~ir Pollution /5oard ~s quite interested In the results of this stud7 plan t~ t~ke over this a~dy ~nd to extend it to ~e~er~1ne r~m 8~e~t o~
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air pollutant~ l~ v~rious ers~ o~ ~ ~tted S~tes in relatl~ ~ ~. ~tt t~ ~rl~d a 8~ ~~d at ~ N~. Zion ~8~ltll ~ of niacin in t~ dict. ~ ca~i~ni~ ~nt 8t~Jed I~ this ~n~ o~ ~ ~t~18 t~ated ~ith t~s ~rlsl. ~ t~ ~t of ta t~ diet ~ i~sssde t~ ~ of 8~ct~ ~c~mdJ ~. ~kett ~scrt~d ~e ~rk of ~ at to~ll ~a~ in ~f~aIo0 Yo~s in ~iCh ~k 8~died t~ eff~t bf 8kin pst~ti~ of ~ba~ ~e ~a~ ~ mice. ~ ob~l~d a few p~tll~ end •fev caret~ ~ 1o~ ti~ ~d afar prol~ t~a~nt. ~ also of ~tltto ~ ~ actl~ in t~r pro~ti~n ~ ~o ~ c~s~. ~ ~ ~l~d fr~ his ~rlmnto ~t ~ba~ ~ or It ~ sus~ptJble to ot~r carct~nic ~nts. ~ts ts ~~ vl~ t~ ~ults of t~ s~dies of P~ssey end ~otln. pt~ ~ ~ ~ faintly stared by ~rger (Bl~ese~ch ~rstortes, C~brl~Se, ~s,). ~s s~dy is ~ ~ a c~ ~ the ft~i~ of k~r. ~stt-~ ~dJcal ~lle~ of S~th Cs~ttn~) f~d ~st ~ (8) t~ u~ O~ ~ ~ of mice ~a8 t~s~d~lth ~¢¢o ~ ~wrs ~ o~d In t~ tobacco ~ke c~ste ~ ~ i~ t~ ~ ~S. ~Jtt-~ co~l~d ~t ~ nt~ ~tre os~rly se~ttt~ 7. ~'lth respect to tl~ phat~n~colog~ of nicotine, the ectl~ of nlcotl~ In t~ ~1 "wet is ~i~ s~dted by ~reon (~dt~t ~lle~ of ~ J~l ~Xo~d Is t~ ~S. La~n~ ee in~s~d in ~te~t~ ~ts~ll~s of t~ nitric. Also of inte~st are t~ centers of t~ 8~t~ ~l~ a~ affec~d by nicoti~ and/or i~ ~lttes. in~ti~a~d h~n sub,acts and t~tr ~h~or on t~a~nt ~th ni~ti~e ~ fo~ ~stentJally t~ s~ ~~ds in t~ h~an urene r3 in ~ uric. ~s suj~s~ that t~ nicoti~ is ~1lzed almilarly in t~ found irt ~ ~s t~d with nicoti~ and in h~ tree~d ~ith nicott~ ~ra al~o found In th~ ~t~ o~ t~ h~bltuat s~ker.
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Subject ~ l~y 9~ 1958 Stennary of a meetin$ of Industry Technical Con~nittee of the Tobacco Industry Research Committee held in Richmond, Virgl...nia .on l~_y Sj 19~ The following persons ~ere present at the meeting of the Industry Technical Cow~lttee of the Tobacco Industry Research Committee held at 10~00 a.m. on Hay S, 1958s }4essrs. Hoyt (TIRC), O'Keels (Philip Horrl$), Coulson (Imperial Tobacco Company), t~ennett (t~ited States Tobacco Company), Shelton (Lsrus and Brother), Stephano (nephew of Dr. Stephano, Stephano Brothers), Reid (Carreras)~ and Felton (British American Tobacco Company) and Drs. I~ntley (Im~erlal Tobacco Compsny)j Hanmer (American Tobacco Company). Hockett (TIRC). Dupuis (Philip Horris)~/ end ~od~n (R. J. P, eynolds Tobacco Company). F~. Coulson discussed the situation in Crest ]~ritain with regard to the attitude of ~oth the Dritish ~overr~ut end t~ ~cel ~esearch Co~ll ~n re~rd to t~ c~rette s~k~-health contr~ersy. Cool.retie pro~s~n~ ~ ~een ~r~ided by t~ ~lnister of Education to the effect t~t yo~ ~erso~ atten~l~ sch~l should ~t ~ke. So~ research ~s ~en conducted by t~ ~dlcal Research Co~il on the s~ki~-~lth controversy. ~st of the doctors a~ physicia~ in ~e~t ~ritain are ver~ ~luct8nt to oppose t~ Hedi~l Res~rch Co~ll. ~ t~ tobacco lud~tr~ ~ud/or the ~C ~ve ~eat difficulty In o~inl~ ~dical a~lsors In Crest ~it~lu. ~ls ~'as o~ of the ~ln differences ~et~eu t~ ~C in ~eat ~l~iu ~nd t~ TI~C In the ~it~d States. Dr. ~entley described a v~sit to the laboratory of Dr. H. S. N. Creese at Ne~ Haven, Connecticut. At presentj Dr. Creese is not Involved in any tobacco smoke e~erimentation. Ito~ever, Dr. Creese did describe his york in ~hich tobacco smoke ~ud/or tar vas applied to e~bryonic lur~ tissue. Under these conditions the tobacco tar vas not found to be carcinol;enic. Using similar techniques~ Dr. Creese h~d fourul that the kno~ cercinogens~ e.8., 20-methylcholanthrerm, ~ave positive results. In a series involving thousands of mice, tobacco s~ke condensate or tar vss al~mys neF~stive under these conditions. Dr. Bentley received the impression from Dr. Creerm that Dr. Creeue vas firmly convinced that tobacco smoke condensate vas nor~ercinogenic to lung tissue. Dr. Bentley had ~uestioued Dr. Greene as to ~hether or not his experiments had been done on ~ Quantitative basis and Dr. Creerm had said tilt'they ~ere not. Dr. l~entleySs criticism of the ~ork of Dr. Greene consisted of the £ollowlngs 20- lqethylcholsnthreue is a very strong carcinogen. Tobacco smoke condensate may be carcinogenic but very s~eakly so and the amounts used by Dr. Greene in his experlo ments~re very small compared to the ~n~unts used by other ~orl<~ra. Dr. /~cntley made the &rgu~nt that Dr. Grccn~ may have £ailed to detect the rankly carcinogenic actlo~k o~ tobacco smoke condensate because the ~mounts Dr. Creene used ~ere below the threshold limits for this ~terial. Greene .evidently had expressed the opinion that sl:in painting experiments using tob.~cco smoke condensate vere unxealistic and vere not ~alld as a screening technique.
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Dr. l~entley and several other persons at the meetlr~S (namely, Drs. Bockett and ~s) ~li~d t~t t~ ~ork o~ ~ee~ ~ould ~v~ ~antng~ul. ~, ~eld and ~. ~puls asked ~y dup1~ca~d. ~, ~cke~t ~ t~ co~n~ t~ nlcian In this s~cisl ~c~iq~ involving e~r~nic tiss~ and althou~ ot~r ~ople ~d tried this te¢~lque t~y ~d ~ lnlo n~ro~ difficulties In th0 tec~l~l a~les i~olved. Dr. Bentley then continued with ,the description of a visit to the establish- ment at ~r liarbor, I~alne. lie left liar l~rbor vlth the impression that the investl- l~atora there flrmly believed that clg~rette smoke condensate was a ~eak carcinogen. Host of the persons to ~hom Dr. Bentley spoke believed that NynderWs experimental results in various snip1 species and strains ~ere consistent with the statistical results obtained from human subjects. They also believed that the skin painting technique was valid for screening. However, they were disturbed by the fact that the skin painting experiments required such a long period of time. Dr. ~entley spoke with Dr. OJynne (a former colleague of Salaman in England) ~o ~aa studying the sebaceous Eland suppression technique. Also. Dr. b%Vnne was studying the aterol content of the skin and the chan~a in the sterol content on paint- ing with various carclnogen~. The amounts of certain skin sterols seemed to vary with the activity of the carcinogenic material used in the experiment. Another t~>e of experiment being conducted by Dr. b'h~/nne was a study of the enzyme systems and the change in these enzyme systems during skin painting. Actually, Dr, Cvynne had done very little to date with cIF~rette smoke condensate. Host of the ~ork involved the use of l~ovn carcinogens or noncarclnogens, Dr. Bentley did state that he received the impression from CuTnne that b%~mehad done considerable work on cigarette smoke condensste uhlchhe did not care to discuss at the present time. Another sertes of experiments described at t~ar Harbor was lung c~lwer tissue transplantation. The advantages of this type of experiment was that lung tissuewas being used; the disadvantages ~ere that no phagocytes ~ere present and the mucus secretion was absent ~hen compared with lung tissue in the host. In these experiments pure c~rcinogenic or noncsrcino~enic agents ~ere usod. Tobacco smoke has not yet been investigated but evidently this material will be investigated in the near future. Dr. Cvynne. in a conversation with Dr. Bentley. had stated that he firmly believed that tobacco smoke was a ~eak carcinogen and quite possibly ~as a cocarcinogeu. Dr. ~ had previously worked with Salaman, a specialist in cocarcinogenesis studies. Dr, B~ntley described some of the work done by the T~SC In Crest Britain. InvestlF~stors in Great Britain have found that r~lther the printl~ t~ ~ed on ci~- rette paper nor t~ ci~rette paper itself provided enough 3.~-~p~e~ to accost for t~ total a~unt in ci~rette s~. Arsenic In tobacco s~ke could ~ ~led ~t as a carcinogen In t~ lung cancer sit~tion.
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Vrs. Day, Lssnltskl and Blacklock, members of the Hedlcal Research Council in Great ]~ritain. are so~e of the persons vho are uneasy about the lung cancer- clgerette smoking controversy in England and these investigators are particularly concerned about the attitude of the l~dlcal Research Council in regard to this con- troversy. Th~se person~ have asked the TI~C for certain cigarette smoke condensat@ fractions and certain quantities of vhole cigarette condensate for experim~nt~1 purposes. The THSC is uneasy about this sltu~tion because they have no control vhatsoever over atatermnts issued by Day. Lasnitski or Blacklock on the results of their experiments and these persons viii be using ~terial provided by the THSC. Dr. ]~entley also visited F. G. Bock at the Rosvell Park Hemorial Institute in ~ffalo. Dr. Bock outlined his ~ork in considerable detail. Evidently the data presented to Dr. Itentley ~as substantlally the same as Dr. l~ock presented at the AACR meeting in Philadelphla in April. 1958. Evidently Dr. I~ock expressed the opinion that he cor~tdered 1~mder to be a ~slncere evangelist~ in the cigarette s~oke-lung Cancer Controversy. Some of the research projects tmder~ay under Dr. Bock0a supervision are as follovs! extension of tl~e sebaceous gland suppression test to the hamster| the investigation of the c~rclnogenic activity 0£ tobacco itself| the action of snuff capsules on the cheek pouch of the hamster| the In~luerwe of filter tips on the car- cinogenlc activity of cigarette smoke condensate. ~ith respect to the latter experiment. Dr. /~ock found that cigarettes vlth or ~lthout filters gave tar possessir~g unifor~ ~c~ivity ~en cool.red on a ~ss ~sls. ~t Is. o~ ~a~ of ~r ob~i~d from a no~iltered ci~rette ~ssessed t~ sa~ or al~st t~ sa~ carclno~nlC aCtiVity as o~ ~am of ~r obtai~d fr~ a filtered ci~rette even t~ugh t~ filtered ci~rette my 81ve ~lightly less ~r t~n a ~nfiltered ci~rette. Dr. ]~entley h~d also visited the A. D. Little Corporation in Boston but the persons to vhom he spoke vould n~t discuss in de,all any of their w~rk on ciga- rette smoke. This ~as probably due to the Liggett and Hyers contract with A. D. Little. Dr. Bentley also visited ~lth Dr. Homburger ~ho is convinced that cigarette smoke condeRsate Is carclno~enlc and ~o also ~lleved t~t ~e ~ni~l ~ta collected to ~ are In accord vi~ t~ ~ta provided by h~n statistic1 studies. ~ly t~se of ~11 a~ Hill a~ l~nd and Ho~. The THSC in its o~n experimental york had investigated the use of additives in ci~rettes for t~ reduction of t~ 3.4-be~p~e~ content of ci~rette s~. It fo~d t~t sever~l c~~, e.g., cupric nitrate, would decrease t~ ~unt of ~p~ In ci~reete s~ by approxi~tely ~ ~rcen~. ~e co,pond In particular, potassi~ brute, increased the 3.~-~p~e~ content o~ cigarette s~ke by a f~c~r of t~ee ~ fo~. Hr. Reid had visited ~lth Cusin in France and du~ing the visit had discussed the palladlu~*Impregnated cigarette paper experiments. Evidently the French vorkers are claiming a 99 percent reduction in the 3.4-b~nzpyrene content o£ cigarette smoke condensate by using this technique.
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On Friday. N#y 9. Dr. Bentley plaru~d s visit vith Hueper in ~ashir~ton and then ~as proceeding to Hontreal. Canada. ~here he p1ann~d a visit vlth Dr. GeorF~ Nright. ~ith re~ard to the di£giculty encountered by the THSC in its att~n.~t to obtain competent n~dical advisors~ Dr. llockett of£ered the su~estion that suiteble medical a~visors might ~e recruited either in the United States or Canada. The THSC are a little hesitent a~out takin~ such a step.
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Alan Eod~uua 8ub~eet~ 5~mar~ of a Report ~o the lndust~ Technical ~ttee Of the Tobacco- Robez~, C Rocke~ on Janus Ii -1 Studies on different aetho~ of appl£catAo~ of e~arette moke tar and c~sarette smoke ta~ fractions to different mouse strains aze in pro~rese, These may be alluded ~nto rye ma~n headtn~s~ ek~n pa~ntin~ t~es and • The affect of paintin~ eisarette emoke eondensate on ~le; that yore 8hayed or plucked ~s studied, It v~ obeerved that the mouse has a def~n~_te hal~ cycle which t8 not ~rest~y lnf/uenoed by shaving, Hovever~ the pluckin~ technique ~ntea~upt| the hair cycle and the cycle restarts, Zt 18 possible that differe~t hiolo~ical re~ult~ ma~ be obtained by paintin~ obeys4 and ?nsitl~ tumor ~roduetton wan obtained by patntins & solution of smoke ecmd~usato on the 8hayed adee~ although the ~r~entaK, of tumor-bearin~ anJsuLtS ~as not u g~eat as ~n the study re~orted by V~m~ler~ The skin paintin~ technique offers an aid to the sta~7 of ~rlous fraotions of the smoke condensate Vher~by the most active fraetio~ are sub- ~e~te4 t~ close scrat~, T~ ~t~tln~ tect~tq~e s~tfer from t~o dle.sd~nts4e of r~qulring le-.| pez~ode of time (the lifo open of the anin~ ]~l~ted) for ~ssessaent of the results, 8.. In~_ .lati.on Stu~dies Kite confLned in a specLal chasber ver~ re/~atedly exposed to freshly pr~psred cigarette smoke. These ~bsla~ton etud*es ha~e bern ~n progress for incidence in the experimental and ~.be control animals e~m thouSh the e~ner~ent~ ~ yer~ noticeably eta~ed b7 th~ tobacco smoke and tar. Apparently~ a
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These studies are enployS~ bunan ~ tiseuo. Prior to the ~te~ pm¢~o ~wl~ of t~ a~ Of ~ ~ ~ ~ ~O~o is ~ t~ ~to ob~4-~ ~ ~ a st~ Is ~t h~ ~ ~o~o ~ ~ eye tochnl~o are und~ 8tud~. Here a~ln~ tho oFfoete of bersdity and onviroo- nent~ ~nte~ In~ any ~t~In~tati~ of ths r~ults obtaln~d. £t this ~oint~ Dr. Hockott mentioned briefly, without indicst5~ tho sourco of his 5nforzatlon~ thst Lts~ett and P~yersj ~bo retain a. D. Llttlo and C~tpa~y as eonm~.tm~t,~ h~ instituted • ro~etitio~ of the ~xporiaeot,s desezd.bod by 1~,ynder, Orahs8 end Cr~n£e~. A. Do Little and ~ repeated the ex~ri- aente of ~ynde~, Ombm end Cr~nin~e~ as near~y u pos~lblo. T~ ~esulte of the expor~nto woFo a~ follow~! the ~ d~v~lo~ t~u~l~ (both ~~ end ear~nc~aa) such as z~orted by Vynde~ et alt the ~r ~j~eSdenco was qulto llI. Cardio~_St, ud.te~ The L~flue~oe of n~otino and total clear.to 8~oke ou tho eard~o- vascular oysteu ~ under otUdyo Ther~ ~ro 13 or 1~ pro~ecte devoted to thee and after roce~vinK 8n ~n~octS~ of • roll qumtity of ~o. It ~ ~e~ st~ ~e t~m~ ~p ~ the ~tie8, ~ the op~site~ i. o., ~ ~mtion of ~ t~mtum of ~o ~~es on Wood to studytn~ the effect of 8ueb eoe~ dru~ a~ ~~ b~ ~% ~st~es~ ~ the t~t~ ~ on ~ tm~mtm d~ the ~ties. The ~n for ~ t~o ~ ~ d~tmte vhethor.or ese of c~ar.ett~e whereby a catheter i~ Introduced ~nto ths h~art ~ tn~ blood
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~t~oy£~ this teehn~.que, the blood flow ten he neaeured, At ~t~ ~te p~ ~ s~ o~er ~, vh~e ~~ of the ~e8 ~e ~s~t, The ~ ~t~ ~ ~o ~ ~ h~ ~ons ~e~to t~t ~o Another study ~8 ~oncerned with the effect of s~okin~ on cerebral • elrculatibn, llo significant changes in ©orebr~l circulation wore found with nicotine or tobacco 8noko. ' A J:~nel of 1~ consultinK pathologists has ~ ob~. Thee ~n ~e~, ~t~ C~os~ ~~ 8~ of e~oo~ ~ ~ t~o ~ o~o~ ~ ~t~ ~~ t~r t~.ob~n~. ~t~ ~s~ a so~ of ~c~s~ o~d~ f~ ~~ ~ ~~t. the s~~ ~ ~ ~ ~ s ~me~tm for fL~ . ~s ~t~~ cf v. The poyr~olo~Lc~l s~udto8 are not suFFiciently advanced fo~ ~nterpr~- " tatio~ of t~ mulls obtained. In ~oune~tion with heart di8~% it has born noted that heart d~- .VI. Oast.~inte~t.in~..1 St.~Lto~ In 8tu~N on patimta sufferS~ fn~n peptic ulcer8~ no slsnl£~csnt cliff etcH b~ro obtained bet~em ~o~r~ a~d r.j~-s~oker8, or betvem 8~okers before and ~f~ex" ~okin~ cigarettes. i~ockott ~n~ioned that it is l~eslble that there will be ette~ts the ~te~tu~ (~b~ t~oo of ~e~ ~d Se£~) ~ which ~t~o c.e. gr. I/,, FT. ~
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tlII. L A~D I~NOWLTON, I~c. Confidential for Member~ I h~'OP~,~TI OF~L F~IORANDT@~ PR Memo NO. 41-60 November 17, 1960 To: Officers and Executive Committee The Tobacco Institute, Inc. Re : Sclentific Perspective" The enclosed is a working draft of the "Scientific Perspective," as it is referred to as a supplementary item in the approved Institute budget. This is now going through final clearances. As you consider this collec- tion of excerpts from scientific papers, you will want to keep several points in mind. Purpose. Its primary purpose is to impress upon scientists and doctors the extraordinary variety of research done and continuing on factors that may influence lung caucer. It will also offer a chance for lay press publlcty and will be used in continuing contacts with writers in the field. In its present draft form, the co21ection has already been helpful, particularly in discussions with ~ORTUNE editors about the now "postponed" article on smoking and cancer. Format. In general, the present format is proposed. This avoiSs a note of finality of a regularly printed booklet. It is consistent %5th the idea that this is a working and e~-panding doc~nent. It may avoid certain problems involved in formal publication. And it is easy to read or thumb through. Distribution. Primary distrlbutlonwill be to a selected but fairly large group of scientists, physicians and professional publications. Copies will be offered upon request through various media, ~ncluding news stories and/or small advertisements in professional journals and in TOBACCO AND HEALTH. Issuance. The issuing group prefexgt.ly would be the Tobacco Industry Research Committee because of the scientific char- acter of the item (although printing and distribution would continue to be an Institste project). Clearances. Me~oers of the Executive Committee and their public relations staff are requested to make their comments and suggestions on examination of this draft. Because of the nu~ber and diversity of the materials from which the excerpts are taken, it would be desirable to avoid getting individual permission from each author and p~blication for use of the excerpts in this form. The Instit~te's legal counsel is now examining the document with the question of such clearances under consideration.
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-2- In these excerpts care has been t~ken not to distort or quote out of context any of the excerpts and to be sure the authors' basic positions are not misrepresented by the selection. Sometimes material was retained, even though somewhat irrelevant, to make sure that this was SO. Bibliography. In the present draft, the reference numbers ~-eg. 40-b, 3-d, 2-e, etc) are working codes only. In the final version, these references ~.~ll be conse-~iveiy num- bered to refer to a complete bibliography listing the sources of sll excerpts and a~so the additional references listed at the end of various sections. Note also that the $85,00Obodgeted for this item was in- tended solely for out-of-pocket costs of duplication and distribution. The costs of preparing this draft come from the regular staff time and out-of-pocket budget. We would appreciate suggestions, arid presmme that it may be desired to discuss this at the December 15 Executive Committee meeting. Hill and Knowlton, Inc. PJollc Relations Counsel !50 E~t ~nd Street Ne~-" Tork 17, N.Y. At%.entioo: Carl Thompson M~. Be'~ms.n Gr-a~ ~ Mr. ~arles B. Wa~e
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RESPIRATORY CANCER Collected Excerpts from Scientific Literature This .reference work is comprised of excerpts from published literature concerning medical and scientific research on problems of respiratory cancer. It has been prepared from the-scientific library of the Tobacco Industry Research Committee and is made. available in this form as an information paper. 1961 Compiled by: Tobacco Industry Research Committee, 150 East ~2nd Street, New York 17, N.Y.
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CONT~S Introduction I. What causes lung cancer? A. Lung cancer is related to numerous and varied factors B. Lung cancer is related to previous respiratory diseases C. Lung cancer is related to occupational and environmental causes D. Lung cancer is related to stressl vlrusesl hormonal disturbances~ and genetic factors II. Who gets lung cancer? III. How much lung cancer is there? A. Under-reporting of lung cancer in the past B. Errors in mortality data of various types C. Analyses of the cigarette-lung cancer statistical studies IV. Where does cancer start in the respiratory tract? A. 0ral and laryngeal disease incidence B. Studies of the tracheobronchial tree C. Classification of lung tumors D. Site of origin of lung cancer V. What are the results of experiments? A. Smoke inhalation tests B. Injection and implant tests C. Species differences D. Applicability to humans E. Chemistry of smoke 0 0 0
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INTRODUCTION This collection of excerpts presents the results ofresearchbymny scientists into the causes~ nature~ and incidence of human respiratory cancer. Most of the authorities quoted have ms~e cancer research their life work. In assembling these representative selections froma vast sci- entific literature~ it is expected that the d~tafromvarious disciplines and areas of investigation will prove of interest and value to workers in these scientific fields. Among the scientific disciplines represented here are surgeons~ pathologists, internists; cytologists~ roentgenologists and other medical specialists; biochemists and other laboratory researchers, and biostatisticians. Few practicing physicians and scientists find tLme to personally re- search the literature, or to assemble and read the 5rowing volume ofdoc- umentatlon on respiratory cancer. Accordingly, these excerpts have been kept as brief as possible and yet remain faithful to the authors' views on the points presented. They can serve as a guide to the context of the full papers. It will be clear to the reader that thesescientists do not consider that there is any simple answer or any sintle answer to the problem of respiratory cancer. The fact that conscientious workers do not agree in their conclusions shows that research has not been limited to an arrow, one-way track. Perhaps the more important differences are on such ques- tions as these: • Is respiratory cancer really increasing by leaps and bounds, or is it only recognized oftener than in the past? • Can respiratory cancer be caused by inhaled solid~ liquid~ an~ gaseous substances or by viruses, hormonal disturbances, and previous respiratory diseases? • Do inherited characteristics or ~he many stressful aspects of mod- ern civilization play dominant or contributory roles in the onset of can- cer? • Do combinations of such varied.possible factors determine the on- set of cancer and its specific localization in the body? One of the hopeful signs for the future is the fact that present and proJected research is not limited to any one of the "possible causes of resplratorycancer. Many authors have noted that their results have ralsedmore questions than they have &nswered. The recent results of research have emphasized the great complexities of respiratory cancer• Hence, it is imperative that encouragement and support be given to con- tinuedand expanded research alongeverypath that maylea~ to a solu- tion of the problem• Perhaps scientists will find away to cure cancer before they have determined its cause or causes. 0
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-2- This survey recogn.izes the claims by those who believe that respiratory cancer is due primarily to the action of inhaled substances, particularly cigarette smoke, on the lungs. Such claims have been reiterated with empha-. sis during the past six years. Numerous scientists in many countries have investigated this theory. However, no qualitatively new data regardin~ the question of tobacco's effect have been produced since the original re- ports. On the other hand, a good deal more evidence has appeared that points in quite other directions. Further, scientists are not all preoccupied with this single "tobacco" approach to respiratory cancer: -of 295 papers presented at the American Association of Cancer Research proceedings in April 1960, only three were concerned with tobacco. There were eight papers on tobacco and nicotine among 2526 papers presented before the Federation of American Societies for Experimental Biology, also in April 1960. Similar relationships of tobacco research to general research in cancer and other human diseases are shown in the proceedin@s of both these organizations in 1957 and prior years. It seems likely that an emotional response has been awakened by the disproportionate attention given to the tobacco-lung cancer theory in lay publications and on occasion in medical Journals. Much of the research on tobacco has been most valuable and is an important contribution to our knowledge. It should be continued. Until research has discovered the cause or causes of respiratory cancer every possible lead must be fol- lowed diligently, with appropriate scientific detachment, so that the truth may be known.
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I. WHAT CAUSES LUNG CANCER~ Few biological problems have proved more difficult--and more funda- mental--than the question of cancer's cause or causes. More than half a century of medical research has yielded knowledge of a relative handful of specific carcinogens, but not any widely applicable principles of can- cer causation or any real understandin~ of the mechanisms involved. The continuing search spans all the disciplines of medicine and bio- logy. Hundreds of scientific papers on carcinogenesis are published in medical Journals in every country every month--thousands every year. The confllctin~ evidence and opinions in this massive outpourin~ of work test both to the uncertainty of our knowledge and the need for further studies, for each new fact raises at least as many questions as it answers. What is true of cancer in general is~ of course, true of the question of respiratory cancer and-the various other forms of intrathoracic tumors in h,,-~ns. No" one yet has adequate answers; no single theory fits all the facts. The highly publicized studies of tobacco use and lung cancer will be discussed further along in this survey. It is the purpose of this sec- tion to report the reasonings and conclusions of leading authorities, who, with many others, have firm opinions on what may cause lun~ cancer. These opinions fall into four general groupings. They hold that: A. Lung cancer is related to numerous and varied factors. B. Lung cancer is related to previous respiratory ~isease~ C. Lung cancer is related to Occupational and environmental cause s • D. Lun~ cancer is related to stress, viruses, hormonal dis- turbances and gene.$ic, factors. -000-
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I-A i A. LUNG CANCER IS REIATED TO NUMEROUS AND VART~n FACTORS Many authors have reviewed the extensive literature on lun~ cancer and have listed the various external and internal factors suspected of causing the disease. The followin~ sel~ctlons are typical of the opinions expressed. -o0o- CLEARLY A~ENTS LISTED G. Burroughs MIDER, M.D., Associate Director of the Na- tlonal Cancer Institute in Charge of Research, reported his findings in September 1956 (2~-m) as follows: "The total effort of all interested parties has produced, Over the years, only six clearly identifi- able agents that are known to cause cancer in man: (I) x-rays and some of their constituent parts (wheth- er generated by machines or by artificially induced or naturally occurring radioactive substances makes little difference if experimental data are correct)~ (2) ultraviolet irradiations, (3) arsenic, (as potas- sium arsenite, usually after prolonged medication), (4) beta-naphthylamlne, (5) benzidine, (6) ~-amino- diphenyl..... "A much larger number of substances,essentially mixtures, has been incriminated in the production of cancer in man. Soots, shale oils, paraffins, unde- fined materials associated with the production of nickel, chromates, an~ isopropanol have increased the hazard of developing one or more types of can- cer among persons exposed. "The list is not complete, but interest in the others is far overshadowed by a suspected etiologic relationship ~etween certain environmental factors and the increasing frequency of p,lmonary cancer."
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I-A 2 ~ THINGS BI,~MED FOR LUI~ CANCER R. H. RIGDON~ M.D.~ Professor of Pathology at the University of Texas Medical Branch~ Galveston, listed some "of the various factors which have been blamed for lun~ cancer (lO-r) as follows: "Time does not permit a discussion of the many a~ents which have been su~ested as the etiology of fun8 cancer. Among those con- sidered have been tuberculosis (ll-e), syphilis l lS-p), ~n~luenza (ll-b), diphtheria and measles 25-m)~ chronic p,11monary ~n~lammation (19-&)~ pulmonary scarriz~ (23-w), roa~ dust (Z-w), dust from groomin~ horses (31-h), motor exhaust (39-m)~ war gas (36-b)~ cigar makers an~ sorters (3~-b), arsenic (~-n), chromium (l-u), asbesto- sis (z6-1), silicosis metap sia (l-k), tar (2~-p)~ heredity (12-s)~ trauma (10-w)~ air pollution (32-m)~ cigarette smokin~ (27.-w), and inhalation of printers 4n~ while readin~ the mornin~ newspaper (9-a)." 0 0 0
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Chester M. SOUTHAM~ M.D.~ Head of the Oncogenic Virology Section of the Sloan-Ketterin~ Institute, discussed viruses in the field of cancer in a re- cent sy~posoum on cancer (~l-s): "Cancer is very frequently discussed as if it must be the result of a single type of causative agent. Such an exclusive con- ce~t seems entirely unjustified. To espouse the hypothesis of viral oncogenesis does not necessitate the abandonment of unquestionable evidence that ~hemicals, radioactivity~ hor- mones~ and genetics are causative factors in these diseases. "On the contrary~ the experimental data lend credence to the idea that neoplastic dis- eases are often~ perhaps usually~ a result of coincidence of multiple forces rather than of a single etiologic factor .... "Thus~ the apparent barriers to accept- ance of viruses as possible oncogenic agents in man have disappeared under the ~radual ac- cumulation of experimental evidence. There still remains unanswered~ however~ the ultimate objection that~ as yet~ there has been no di- rect evidence that any h,,~.~ cancer is in fact of viral etiology." 0 0 t~
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NO ONE AGENT EXPIAINS LUNG CANCER Paul E. STEINER, M.D., Professor of Pathology at the University of Chicago~ in 195~ analyzed "Eti- ologic factors in cancer revealed by ethnic and geotraphic studies" (37-s) as follows: "The cause of human lung cancer cannot be explained by a single agent any more than is pneumonia which has numerous bacterlal, viral~ parisitlc~ and chemical causes among which a few agents predominate and account for most of the cases. In pneumonia, the pre- • dominating agent may vary with geography, race~ time~ and other factors. So it ap- pears to be in lung cancer, No one agent ac- counts for all cases. The tumors that are found in Himalayan tigers and other animals, in infants and children~ and in non-smokin~ adults cannot be attributed to cigarette smoking .... "The sex difference in frequency of those tumors which are not sex-limited prob- ably~ at least in part, indicate unequal ex- posure to some environmental agent .... In the Mexicans of Los Angeles~ the virtual sex equalization of lung cancer at the hith level usually shown by men is in contrast with the situation shown until recently in Norway where the sex difference was slight because of low levels in the males." 0
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I-A For further reading on the conjectured origins of respiratory cancer see 3-a~ 56-b, 57-b~ ~O-b~ 5~-h, 13-m, l~-m, 6-0, 52-p, 53-P, 5~-P, 21-s, 35-s, 36-s, 38-s, ~O-s
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B. LUNG CANCER IS RELATED TO PREVIOUS RESPIRATORY DISEASE In the epidemiological detective work that must be done to understand lung cancer~ researchers have found some of their best clues in the pattern of other respiratory diseases. As the toll of these afflictions--particular- ly tuberculosis and influenza-~has ~ropped over the past several decades~ the apparent incidence of more specific diagnoses such as lung cancer has increased. Evidence that this may be more than a chance association comes first from studies of leading pathologists on both sides of the Atlantic at the time of the great influenza pandemic of 1917-19. At that time~ many researchers who examined the lungs of influenza victims found multiple lesions which they considered to be pre-cancerous. On the basis of these findings~ they pre- dicted t~t many of those who survived might develop lun~ cancer ~, the years ahead. Other pathologists found scars left on the lungs by he&led or dormant tuberculosis~ by chronic bronchitis and other lun~ diseases. Still others found lung cancers growing in the scar tissue. They~ too~ came to the con- clusion that lung cancer might be an aftermath of earlier pathology of the respiratory tract. Similar lesions have now been found in the lungs of vict~w~ of the Asiatic ~n~luenza p~ndemic of 1957. Both clinical and statistical studies have confirmed this association between previous lun~ disease and lun~ cancer. Its significancen-like that of all other statistical associations in the lung cancer picture--is still to be determined; but the following excerpts from the extensive literature on this aspect of the problem suggest its importance as a factor. -o0o- -@
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I-B 2 Part i - The Older Literature The toll of deaths in the United States during the influenza epidemic of 1918 awakened wide- spread i~terest among numerous pathologists who had studied the lungs of many of the victims and believed that many of the survivors had sustained lung damage that might lie dormant for years. The followin~ selections are typical of such findings. METAPL~SIA FROM INFLUENZA CAN BE CAblE OF LUNG CANCER -O00 - Professor M. ASKANAZY~ M.D., of the Institute of Pathology at Geneva, Switzerland, conducted autop- sies on 320 victims of the influenza epidemic be- tween July ii and Dec. 31, 1918, and selected 90 tracheobronchial trees at random for microscopic study. He reported the formation of squamous epi- thelium in 38 cases (8-a), and said: "The transformation of the entire epi- thelium into sq1~amous epithelium can be re- garded as an act of regeneration or as the result of a direct formative irritation, as is the case with any inflammatory tissue pro- liferation .... The development of squamous epithelium in the air passages is not a specific factor in influenza, even in acute infections of the respiratory tract, for I recently noted it twice in genuinely typical pneumonia too ..... "In connection with the development of tumors and metaplasia of the epithelium in the air p~ssages, there has been.., a concurrence of opinion to the effect that the squamous epithelium whlch forms the tumors is not em- bryonically aberrant but is produced meta- plastically .... The fact that metaplasia can be a precancerous phenomenon remains undisputed." O
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II~FL~A, LUNG CA~ FACTORS Moses BARRON, M.D., of the Department of Patho- logyandMedicine, University of Minnesota Med- ical School, discussed the incidence, pathology and relative importance of carcinoma of the lun~ in 1922 (9-b), as follows: "A careful review of the literature demonstrates the increasin~ importance of this disease. Some of the reports are not reliable because cases are reported as pri- mary carcinoma without necropsy or histolog- ic studies. Statistical study, therefore, loses in value on account of the unverified cases,,,, '~erhaps the.chief etio~o~ic f~ctors are inflammatory conditions, and of these, tuberculosis is the most important .... M~y series of cases in the literature ~ve proved that carcinoma is not infrequently found as- sociated with ~tuberculosis~ developing espe- cially in the scars and walls of tuberculous cavities.... "I believe that it is not at all un- likely that another chronic ~-~lammatory process maybe responsible for'a m~mher of p1,~monary cancers encountered during the past few~ears. It is possible that this might ex- plain the rather strik~ increase inincidence recently. I have In mind the ~n~luenza epi- demic of 1918-1919... In discussing this sub- Ject with pathologists from other hospitals I foun~that the same impression of an in- crease inincidence since 1918 seems to obtain."
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LUI~ CANCER PREDICTED IN SURVIVORS OF IHFLUEN~ Milton Charles WIh~ERNITZ, M.D., late Hea~ of the Department of Pathology at Yale University, con- sidered the lesions caused in lungs by the influ- enza epidemic of 1918, in a book written by him and his medical colles@ues (21-w). They said: "It has seemed desirable to contribute to the ~athology of v~rious phases of influ- enzal pne,~onia an~ to attempt to correlate this with other types of acute respiratory in- ~tion~ in the hope that the prognostica- tlons which suggest themselves may be of aid in the prophylaxis and possibly in the treat- ment of the more insiduous and progressive p,.Imonary chan~es that may follow this disease... "It is rare to see such activity on the part of the epithelium as that frequently en- countere~ in influenza. The alveoli may be lined by newly formed cubical cells, and mi- totic figures in the injured bronchiolar lin- in~ occur in abundance .... In a number of cases, epithelial proliferation has been so extensive that it could not be differentiated histologi- cally from an invasive~ ~allgn~nt neoplasm. "There is no reaso~ to believe that ma- lignancy might not result from the continuous st~tlon of the epithelium to proliferate, in the chronic inflan~atory process of the lung in influenza, Just as chronic infection in the lung of a mouse results in a much higher percentage of spontaneous neoplasms of the re- spiratory tract in this species than in those anin~is where chronic p,.1~onary processes are unc~n. It will be interesting, indeed, to see whether, as a late manifestation, there is an increase in the number of now relatively rare epithelial new growths in the respiratory tract of ms~l. "A basis for the interpretation of the respiratory lesions of influenza is offered by the analogous changes in the respiratory tract initiated by the inhalation of poison gase S." 0 0
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ROLE OF CHRONIC INFLAMMATION IN LUNG CANCER Michael G. WOHL, M.D.~ Pathologist at the Methodist Hospital of "Omaha in 1920 when he wrote on lun~ cancer (22-w)~ is now at Phila- delphia. In his l~per he called attention to the relative neglect of lung cancer in those "The interest in primary ~umors of the lungs has been renewed for two reasons -- first, due to the re'cent development of intrathoracic surgery and modern deep X radiatlon~ the scientific diagnosis and therapy of the latter is becoming a matter of more than academic interest; secondly~ the recent wave of pulmonary infections~ such as streptococcic bronchopneumonia and influenza~ constitutes, an important factor in the formation of pulmonary neoplasia.... "It must be stated that in the ad- vanced form it is pretty nigh impossible to trace definitely the origin of these tumors, since the ~n~iltratin6 tumor mass involves both bronchi and alveolar tissue. Histologically one may also find structures within a single tumor resembling the gen- erally accepted cases of all three varieties .... "That chronic inflammatory changes often precede or predispose to the forma- tion of carcinoma is too well known to re- quire, detailed discussion .... Bayle, Wolf and others (quoted by Moise~ 1921~ p. 745) (iO-b, 35-m~ 23-w) have called attention to the frequent coexistence of carcinoma and tuberculosis of the lun6s. In chronic bronchitis and in reparative lesions follow- ing bronchopne~monia there is often a marked epithelial overgrowth with frequent meta- plasia of alveolar epithelium .... "Thus there is considerable evidence in favor of chronic irritation preceding carcinoma. The possibility of carcinoma bein~ induced by acute inflammatory changes has recently been brought to the medical at- tention by the work of Winternitz and his ssociates (19 ) 0
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I-B For other papers relatln~ to observation of an association of respiratory lesions with bronchial carcinoma see.5~-b~ 10-b~ ll-b~ ll-e~ 15-f~ 26-g, 21-g, 30-h, ~2-h, 51-m, 25-m, ~8-m, 15-p, 3~-p, 13-s, 22-~, 51-s, ~8-s, ~9-s, 23-w
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LUf~ CANCER ARISES IN HEMORRHAGIC SCARS IN LUNGS Part 2 -- The Recent Literature There is a steadily increasing amount of modern research that shows lung cancer associated with prior or concurrent tuberculosisI pneumonia1 in- fluenza and lung lesions of diverse characters. A few t~pical quotations £ollows and a supple- mental bibliography is provided at the end of this section. -oOo - / . / Josef BALO~ M.D.~ Eugen JINASZ~ M.D., and Judith TEMES, M.D. of the Department of Pathological Anatomy andExperimental Cancer Researchs Medical University~ Budapest~ Hun6~ry, have found the scars from internal bleedin~ associated with lung cancer development in fifty cases (3-b), and re- port similar findings by others in a 1956 paper. They said: "In the human lung~ proliferation of alveolar epithelium frequently occurs in the border of hemorrhagic ~n~arcts. -Such epithe- lial proliferation may arise in several foci in the same infarct and can occur around sev- eral ~-~arcts..o. '~un~ cancer can develop from the epi- thelial proliferation at the site of ~-~arcts. This can be alveolar-cell carcinoma~ but through metaplasia squamous-cell carcinoma Can also occttr. "Epithelial proliferation occurrin~on the border of hemorrhagic infarcts of the lung cannot be the result of exogenous noxious agents but is the result of the action of endogenous factors. Anoxemia~ regeneration~ and the ef- fect of irritative substances liberated at the site of necrosis -- necrohormones -- are re- sponsible for this epithelial proliferation."
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LUNG CANCER IN WAR GAS SURVIVORS R. A. M." CASE, of the Institute of Cancer Research, Royal Cancer Hospital, and A. J. LEA, of the Brit- ish Minlst .ry of Pensions and Nat~on~l Insurance, in 1955 wrote on "Mustard gas poisoning, chronic bronchi%is and lun~ cancer (~-c)." They said: 'We have ma~e an examination of the mor- tality experience Cf 1,267 war pensioners who suffered from mustard gas poisoning in the 191~-18 war, and who were still alive on Jan- uary i, 1930. It was found that almost all (over 80~) had chronic bronchitis at that date. In subsequent years a statistically significant excess of deaths attributed to cancer of the lung and pleura has been observed amongst them (29 deaths found compared with fourteen expected) .... "The evidence indicates that chronic bron- chitis may be associated with the subsequent de- velopment of cancer of the lun~ and pleura, un- less it is assumed.that .the excess of deaths attributed to this disease is entirely due to diagnostic bias." 0 0
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I~ LUI~3S FROM 1957 INFLUENZA Dr. P. DeBAAN of the Pathology Laboratory of Leiden State University, the Netherlands, reported in 1959 (~-d) that the metaplastlc changes in the trachea and bronchi which were described in 1918 (see 8-a, 21-w) have been-found in proven cases of influenza-virus infection in the 1957 epidemic too. He says: "Dutch investigators have shown that these epithelial changes arise after degeneration and sloughing off of the epithelium have already taken place, very early in the course of the illness .... The late epithelial changes therefore can be looked on as the result of regenerative ~rowth.... They introduce the pathologic process and are still en- countered long after the acute infection is over .... "It is therefore possible that the 'tumorlets,' to the extent that they are of bronchiolar epithe- lial orlgin~ originate in proliferation produced by a virus infection of the lung." U~
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~-B 8 PREVIOt~ LUN~ DISEASES FOUND ASSOCIATED WITH LUNG CANCER A recent writer on this subject is Walter FINKE~ M.D., of the Department of Medicine .Of the Genesee Hospital~-at Rochester~ N.Y., (8-f) who said: "The case histories of86patients with lung cancer were reinvestigated thoroushly in ~egard to previous chronic pulmonary.dis- eases and severe respiratory illnesses. In addition~ a roentgenologic historywas ob- tained on 63 of these patients. "Sixty-five per cent of this group proved to have had a long-standin~ chronic bronchltis~ often associated with chronic asthma or sus- pected to be tuberculosis. In six patlents chronic pulmonary tuberculosis had been known to exist ten or more years before the discovery of the cancer. 0nehad silicosis~ and two a chronic chest ailment caused by gas poisoning in World War l. "The most frequent acute pulmonary ill- nesses in the patients' distant past were epi- demic influenza in 1918-1920 and noninfluenzal pneumonia. Seventy-sevenper cent had suf- fered at least one and 43~both of these ill- nesses or multiple attacks of pneumonia." 0 0 ¢~
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LD~D CANCER PRECEDED BY TUBERCULOSIS E. C. MEYER~ M.D., J. H. SCATLIFF, M.D., and G. E. LIHDSKOG, M.D., of the Departments of Surgery and Radiology, Yale University School of Medicine, in 1959 reported on their study of a po'ssible connection between respiratory tuber- culosls and hronchogenic carcinoma (28-m).. They said: "One hundred consecutive case histories of bronchogenic carcinoma were reviewed in which the tuberculin skin tests had been re- Ported on the clinical record. Included in the data collected for each patient were the age, sex~ smokin~ habits, past history of tuberculous contact or infection, and the histologic type of carcinoma and its opera- bility .... Tuberculin skin tests... (also) were given to one hundred males in the same general age groups as those with bronchogenic carcinoma.... "Ninety-five per~cent of the carcinoma ~roup had positive tuberculin reactions as opposed to 80 per cent of the control. There was a greater correlation between bronchogenic carcinoma and the ix~i~ve tuberculin reaction than with cigarette smoEin~. Eighty-six per cent of the carcinoma group and 77 per cent of the control group were smoEers .... 'Trimary tuberculous loci were seen radio- logically in ~7 per cent of the (test) series .... In 15 of the i00 cases there was definite radio- logic evidence of re-lnfectlon tuberculosis ..... • In only i0 of the I00 cases could an anatomic- radiologlc association of tumor and tuberculous lesion be established.... "Thlr~y-eight cases in the i00 comprising the carcinoma-tuberculin test group were sub- ~ected to the removal of a lobe or lung. Of these, 33 specimens were still available for study. •... The pathologic reexamination of these 33 specimens...(added) four cases of pathologically associated tuberculosis and carcinoma to the i0 diagnosed radlologically .... 0
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I-B i0 "One ~ay conclude from these results that the tuberculin skin test~ ~n cases of broncho~enic carcinc~a~ is more constantly positive than is the history of cigarette smok~.. • • "It seems reasonable to consider bron- cho~enic carcinoma as an abnor~l process of epithel~al regeneration ~n the lug. As with simple inflammation~ it may have a va- riety of etiologic agents. Recent studies of 'lung-scar cancers' seem to support the theory that it is the scar~ and only remote- ly the agent causin~ the scar, that is im- portant in the pathogenesls of the disease. "Tuberculosis is a common cause of pul- monary scars.... The shortcomings of a purely statistical approach to tumor ~athogenesis is well demonstrated."
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I-B II - ORIGIN OF LUNG CANCER IN SCARS FROM TUBERCULOSIS Dr. Philip SCHWARTZ, Director of the Warren (Pa.) State Hospital, has been an authority on respiratorypathologyfor more than 40 years. In 1919 he was on the Medical Faculty oft he University of Budapest, Hungary; later he was Professor of Pathology at the University of Frankfort, Germany, and for many years he was Chief of the Department bf Pathologyat the University of Istanbul, Turkey. Following are excerpts from a series of papers, publlshed in 1960 (65-s) on the origin of lung cancer in tuberculosis lesions: ."Patho-anatomical and statistical investigations disclosed i) that benign and malignant tumors often arise in bronchial scars of tubercular origin, and 2) that the spectacular increase in the frequency of malignant pulmonary tumors during the last decades in the United States was primarily caused by the transformation of the age-class composition of the population and the decrease in the tuberculosis mortality, which accompany growingprosperity .... "In the morphologicalpart of our programwe evaluated not only observa- tions in which benignandmalignant tumors were associated with bronchial lesions of tubercular Origin, but also numerous cases of commonPerforative scars.**. "Fresh lymphonodogenic lesions of the bronchialwall -- penetration and perforation focl--.occurboth in primary infections and during the development o~ chronic pulmonary tuberculosis. We deal in these cases with the ingression of tuberculosis inflammation into the bronchi starting in recently diseased lymph nodes; the process displays all stages of an infiltration from the period in which the basic structure of the bronchial wall still is preserved, up to the complete destructlonlof, cartilageand mucosa. 0 0 0
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I-B "There are acute lesions which completely sever the continuity of the affected bronchus: we are speaking of mutilation defects. However, much more frequent are involvements which only cause circumscribed disruptions, erosions and ulcers, mostly of the anterior bronchial wall, and which eventually cicatrize without detach- ing the bronchial tube. Perforatlve loci of this group may sometimes appear very extensive -o we observed defects up to ~ cm. lon~ and 3 cm. wide -- producing correspondingly large scars, funnel-shaped, flat, star-llke, and sometimes resembling a surgical suture or a centipede. "Nevertheless, in respect to the develop- ment of tumors, perforatlve lesions of a lesser si~e, producing small~ flat or nodular, some- times trough-shaped scars, are also important and~ because of their frequency~ perhaps even more so. • • • "Every person living in countries in which pulmonary cancer frequently occurs may be considered contaminated by tuberculosis up to the age of 30 at the latest. Thus, we may assume that lymphonodogenlc bronchial le- sions occur in practically every patient af- fected by bronchial cancer .... "According;to observations made by the present author in Turkey, the United States and in Germany, clearly visibleperforative scars occur-in approximately 254 of the cases examined by routine autopsy in a general hos- pital .... No doubt, the actual number of perforative bronchial scars and their macroscop- ically invisible sequelae is much higher than can be discovered by bronchoscopy and autopsy." o
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I-B 13 Similar views were expressed by Dr. C. Eugene WOODRUFF and associates, of the Detroit Department of Public Health, in 1952 (25-w): "The decrease in the death rate from pulmo- nary tuberculosis has been accompanied by a present-day increase in the number of persons in the 50- to 60-year group with healed primary tu- berculosis foci .... It would seem from the pres- ent studyj as well as from the work of others (6-s, 2~-w)~ that in many cases the various pul- monary abnormalities left by the healing of a primary tuberculosis focus are factors of impor- tance in the localization of bronchogenic carci- noma .... It seems evident that the young men who.., were able to survive their primary tuber- culosis infection are now~ S0 to ~0 years later, the persons particularly susc~ptibleto th~ de- velopment of carcinomas of the lung."
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For other papers on the association of previous lung diseases and injuries with cancer see 67-b, 3-b~ 9-~ iI-~ 12-b~ ZS-~, 60-b, ~3-~, ~9-~, 33-0, 36-0, 5-c, 6-0, 7-c, 8-c, 31-c, 21-c, l-d, 2~-d, 16-f, l-g, ~-g, 32-g, 22-g, !7"-h, 9"~, 5-i, 6-i, 25-1, 18-m, 61-m, 20-m, 27-m, 28-~, 31-m, ~-o, 6-o, 3-P, ~6-p, 35-P 7-~, 8-p, 9"P, ~8-p, 36-p, l-r, 2-r, 3-r, ~-r, 5-r, 16-r, 70-s, l-s, 6-s, 7-s, 9-s, ll-s, lO-s, 12-S, 15-s, 66-s, 27-s, 39-s, 2-t, 3-t, 9-t~ 12-w, l~-w, 2~-w
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I-C 1 C. LUg} CANCER IS REIATED TO OCCUPATIONAL AND ENVIRONMENTAL CA~ES There is evidence .that a variety of factors in environments and occupations may play a role in specific cases of lung cancer, but there are differences of opinion on the extent and" nature of their contribution to the total lun~ cancer incidence. The findlu~ of high lun~ cancer mortality in thickly- settled and industrial areas and the low death rates in. rural areas is one illustration of this. Further comments on such factors are in Section II following. Followin~ are typical references on occupational an~ environmental factors believed related to lun~ cancer mortality. 0 0 o -4
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OCCUPATIONAL LUN@ CANCER Dr. P. Lesley BIDSTRUP, formerly of the Depart- ment of Research in Industrial Medicine at the London Hospit~l~ En~land~ discussed occupational causes of lun~ cancer in 1959 (18-b) as follows: "The occurrence of fun6 cancer as an oc- cupational disease in certain industries has resulted in a ,tendency to cl~Im that inorganic substances such as nickel~ chromium and, asbes- tos are carcinogenic. Such a tendency repre- sents a misuse of the statistical and epidemlo- logical data upon which the ev.idence is based. "It should be remembered that... (with few exceptions), the evidence supportin~ a causal relationship between a particular substance and the incidence of lung cancer is limited usually to the occurrence or use of that substance in only one of the n~ny industries in which it may be present .... "The possibility must be considered that there is a factor or factors cow,non to all the industries concerned. The observations of Faulds and Stewart (~-f) in their studies on hematite miners have focusse,d attention again on the pos- sible association between chronic irritation -- either mechanical or infective -- scarrin~ and neoplastic chan~e."
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I-C 3 ADVENT OF AUTOMOBILE PARAT.T.km'R LUllS CANCER INCREASE C. O. S. BLYTH BROOKE, of the Public Health Depart- merit, Finsbury Health Center, London, England, re- ported on "The incidence of cancer of the lung 1932- 1956" for England ana Wales in 1958 (24-b). ~uotes from his paper follow: "It is clear that other factors are con- cerned in the phenomenal rise of the death rate from cancer of the lung in recent years apart from that of smoking, however firmly its rela- tionship with the latter be regarded as estab- lished .... "The investigation reported here has been pursued in a search for evidence Of the time when the first ehan~es occurred which led even- tually to the manifestation of lung cancer an~ death from this cause.... "The findings here reported indicate that the development of cancer of the lung now seen may have been at least partly determined durin~ the 'teen ages.... "The suggestion is made that one explana- tion of available data is that early in the cen- tury there was an almost explosive increase in the bronchocarcinogenetic forces. It is not the purpose of this report to discuss the nature of these forces which might have operated or their origin, but thoughts turn involuntarily towards the rapid development at that time of motor-car traffic."
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~ LU~ CANCER DEATHS ACCOUNTED FOR A study was made of the mortality of men a~ed ~5 to from various respiratory diseases, includin~ lun~ cancer~ ~y economic class and also in contrast to levels of air pollution from domestic chimneys and industry in 8S country boroughs of England and Wales where the~ lived. Charles DALY of the Social Medi~ cine Research Unit of the British Medical Research Council, rel~rted in 1959 (l-d) that only 35~ of vat- iations in lung cancer incidence between the towns could be attributed to the combined effect of both pollution and social conditions. He said it was in- possible to track down most of the remaining 6~% dis- crepancy. He reported: "As far as the proportions of non-smokers and cigarette smokers only are concerned, there is little indication that the average amount smoked varied very much from one ~roup of towns to another. At the most~ if we consider the num- ber of cigarettes smoked per ~ale in these groups of towns~ we get an increase of about 18~ related to a 6~ increase in the lun~ cancer death rate. It my be, of course, that an index of present smo~4~ habits is inadequate and that a measure of smokln~ habits 30 years ago is more relevant here. That may be so: but to explain away the differential in lun~ cancer death rates between towns in terms of smokin~ habits would imply that substantial changes had taken place in the smoking habits of the popul~tions in whole ~roups of towns .... "It seems likely, therefore~ that neither dif- ferences in domestic or industrial air pollution, in smokin~ habits~ or in social factors can ac- count for more than a relatively small proportion of the variation observed in the death rates for lung cancer in the various county boroughs. In seeking for some other factor which could be re- sponsible for the variation~ a number of analyses were carried out. One interesting result which emerged was the fact that lun~ cancer seemed to be highly related to respiratory tuberculosis, in so far as those towns with a high death rate from one disease tended also to have a high death rate from the other." 0 0
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I-C 5 OCCUPATIONAL CA~C~R~ LISTED T. M. FRASER, M.B., Ch.B., Resident in Aviation Medicine, B. D. DINMAN, M.D., Associate Professor, and W. F. ASHE, M.D., Professor and Chairman of the Department of Preventive Medicine, Ohio State University School of Medicine, reviewed the liter- ature on occupational cancer (12-f) from the findlu~ of scrotal cancer in chimney sweeps. (20-p), through the successive incrimln~tions of paraffin from coal, arsenic, excessive sunlisht, dyes, x-rays, chromates, nickel, asbestos up to isopropyl alcohol in 1952. They continue: "These are by no means all of the cancers whose origin has been attributed to occupation. Legal 'files are filled with allegations of can- cer produced by a single trm:v~a .... It is evi- dent that occuPational~cancer exists~ and be- fore we can prevent it or protect against it~ it behooves us to learn how many varieties there are, to observe where they occur~ and to define the etiology as precisely as possible. '~/nen considering o~cupational cancer of the respiratory system, which in this context includes the tract from the nose and paranasal sinuses to the alveoli, it is pertinent to ob- serve that there has been a considerable over- all increase in the incidence of lung cancer durin~ the past 25 years. How much of this is due to improved disgnosis and greater frequency of autopsy and how ~ch to atmospheric pollution, increased exposure to occupational carcinogens~ and other as yet unknown factors can only be a matter of opinion."
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6 ENVIRONMENT AMD OCCUPATION IN L~G CANCER "W• C. RIPPER, M.D., Head of the Environmental Can- cer Section of the National Cancer Institute, with a backgroun~ of 35 years of clinical, teaching, and research experience~ analyzed many factors in environmental and Occupational lung cancer in a Monograph-published in 1956 (35-h). He said: "Epidemiologlcal studies on the frequency of lun~ cancer among members of large industrial ~roups and trades have brought to light the ex- istence of marked variations in the liability of persons engaged in different occupations to cancer of the lung .... (A listin~ of) lung can- cer death rates for seven industrial @roups in Ohio shows a striking difference between the rates for a6ricultural laborers and for employees in the non-ferrous metal industry~ with rates for transportation workers occupying a position di- rectly behind the rates for nonferrous metal workers • "It seems to be characteristic of inhabit- ants of a~ricultural areas to rank first in death rates from cutaneous cancer and last in rates for pulmonary cancer. This is in accordance with the relationship between solar radiation and skin can- cer and the relationship between low concentra- tions of carcinogenic air pollutants and lun~ cancer. "Nonferrous metal workers, on the other hand, often have contact with dust, fumes, and vapors of some carcinogenic metals, such as chromium and nickel~ or with arsenicals which are impurities in many nonferrous metals (copper, zinc, silver). Transportation workers are exposed to the ex- haust from gasoline and diesel engines, petrole- um lubricants, and dust from asphalted roads .... "The comprehensive panoramic view and analy- sis of the total epidemiological, medical and ex- perimental evidence available on exogenous respir- atory carcinomas and carcinogens leave no doubt of the fact that not only large occupational popula- tion groups but also the general population .have definite and prolonged contacts with one or sev- eral of these agents. '~or most of these a~ents, adequate conclu- sive proof of their carcinogenicity is provided . by epidemlological, medical and experimental data ....
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"It is therefore reasonable to assume that inhalation of the same agents~ in a mitigated form as air pollutants~ by the gen- eral population is responsible for a consid- erable portion of the lur~ cancers attribut- able to such contacts. "If' this coherent and logical picture presented by the evidence supportin8 the var- ious occupational respiratory cancers and~ espe6ially, the coal tar fume cancer of the lung, is compared with that available for the cigarette smoke lun~ cancer, even upon super- ficial examination, several additional seri- ous defects and inconsistencies not previ.ously pointed out become apparent. "It is surprisin~ to note the absence of positive statistical associations between lun~ cancer and cigarette cough~ although this lat- ter symptom is clinically characteristic of chronic chain smokers. Despite the fact that the lips and oral mucosa are constantly bathed in the tarry liquor oozin~ from the lip of the cigarettes and despite the contact of these parts with the smoke comln~ from the clgarettes~ there is no consisten~ statistical association with cancer of these parts. The assertion that no tarry material exudes from the cigarette tip is belied by the evident fact that chronic ciga- rette smokers are observed to have brown-stained fin~ers. There is~ on the other hand~ not a s~n~le record available of cancer of the fingers attributable to cigarette tar. Such cancers of the fingers would be equivalent to the numerous cases of coal tar cancers of the hands for which records are available...."
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"The best tl~t can be said about the ex- perimental evidence on hand regardin~ carcino- genic properties of to~cco ,~r is that it in- dic~tes the c~rcinogenic agents in some rette tars through the use of hy~e~'~ac-t~ive~~-~ ~als. There is no evidence that these ovser- v~tions of the sk~, of a strain of selectively inbred mice have any equivalent in man.... '~or these reasons, it voul~ be most in- Judiolous m~n~y to base the future preventive control of lun~ cancer hazards on a theory of such doubtful scientific merits and to concen- trate the ~-~ediate epldemiologlcal and experi- mental efforts on this al~arently overprops@an- dized concept. The apparent wisdom of such an attitude is readily apparent from the fact that not only a great deal of the circumstantial epi- demiological evidence but also practically the entire factual and conclusive evidence available on specific exogeneous causes of respiratory can- cers indicates that "these cancers are either of occupational origin or points to industry-rel~ted factors. Not only large occupational groups but also the members of the general population have contact with these agents in v~rious forms and intensity."
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I~.DI~IOI~ LUN~ CANCER? Egon LORF/~, Senior Biophysicist of the National Cancer Institute at Be~hesda, Md., discussed the biologic effects of lon~ continued irradiation in 1950 (22-i). He had previously (21-1) concluded from a review of the experimental data that "it is doubtful wheth.er ra~on can induce lun6 tumors in experimental animals~" and that "the opinion that radon is the sole cause of the lung cancer of the (Schnesberg-Jcacb~-thal) miners therefore can- not be m~intained." His 1950 repor~ was based on nine years of experimental study of "permissible" doses of x-ray exposure in animals. He said in par~: "Lung tumors occur spontaneously in a nu~.- her of stra~-~ of mice. They are of alv~ol~r origin, develop slowly~ and rarely cause death. Hence incidence data in experiments coverin~ the whole llfe span are merely suggestive. To obtain quantitative data~ an experiment was per- formed in which mice of strain A~ which is the most susceptible strain known, were exposed chronically to an accumulated dose of approxi'- mately 2,500 r given at the rate of 8.8 r in eight hours daily .... 75~ of the irradiated ani- mals showed lun~ tumors as compared with ~5~ of the non-irradiated group.... Data obtained thus far indicate that lun~ tumors are induced by a direct effect of the irradiation on the lung and that no systemic effect is involved.... "The carcinogenic action of chronic irradia- tion has been observed in three species, one of which, the ~,~nea pig, is considered one of the least susceptible animals to" spontaneous tumor formation. It seems that we are Justified in as- sumin~ that this carcinogenic action of chronic irradiation will hold for other species as as for man. We are ~ust beg~nnlng to acquire some ~n~orm~tion as to the mechanism of tumor induction, or more specifically regardin~ the role which the endocrine system plays in radia- tion carcinogenesis of certain organs, but we are still a lon~ way from understandin@ the fundamen- tal process by which irradiation changes a normsl cell into a cancer cell." " -o0o -
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I-C 10 For other pal~ers on occupational and environmental fact6rs in lun~ cancer etiolo~ see 6-b~ l~-b~ 2-c, 35-c, l~-c, 3-d, ~-d, 5~, 8-d, i~, 2-e, 3-f, 4-f, 7-8, 8-g, 9-8, 31-g, lO-g, ll-g, 21-h, 26-h, 32-h, 33-h, ~-h, 36-h, 37-h, 4~-h, 2-1, 3-1, ~-1, 6-1, 3-m, 13-m, 14-m, 15-m, 16-m, 17-m, 31-m, 3~-m, 41-m, ~2-m, l~-p, 2~-p, 2~-p, 26-p, ~-p, l-s, 2-s, 3-s, 5-s, 16-s, ~-t, 5-t, 5-v, 15-w 0 o 0
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D. LUNG CANCER IS RELATED TO STRESS~ VIRUSES~ ~ORMONAL DISTURBANCE ARD GENETIC FACTORS The masnltude of what is still ,,-~nown--In lun~ cancer as in other basic biological problems--becomes apparent when we survey even a fraction of the recent studies on possible causes. I~o possible mechanism--internal or external~ genetic or environmental~ infectious or physiologic--goes un-~ represented; there is evidence for them all. Thus the number, of identified viruses known to cause cancer in exper- imental animals has increased astronomically with recent improvements in laboratory and experimental methods. Demonstrations of associations tween lung cancer and prior viral diseases are spurrin~ research in this 8/ea o On another front~ evidence~ of the potent role of hormones, and other mediators of the internal environment~ in the e~rly stages of carcinogene- sis is accumulating stea~£1y. An increasing body of study" I~-~, hormonal changes with human stress~ and stress with the behaviors peculiar to the complex structure of modern civilization. Thus~ smoking~ dr~k~n~ and other pursuits are considered to be as much a reflection of the special environment of the individual as are the states of his health~ and "cause-and-effect" arguments may i~-~ what is merely concurrent: the man who is likely "to develop cancer of the lung as a result of severe stress and functional disturbances may be the ~ of man who will smoke heavily. By the same token~ functional and ~-~ectious diseases may be more likely to affect the "stressed" than the "unstressed" individual. The following few selections are representative samplings of the ex- tensive literature dealing with the varied factors suspected of cancer causation. 0 0 0
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~-D 2 VIRAL AND NON-VIRAL THEORIES RECONC~.~? Don~to G. ALARCON, M.D., Fellow of the American College of Chest Physicians and Medical Director of the Sanatorio San An~el of Mexico City~ re- v~=~dMexican lung cancer data in 1959 (7-a), and found a n~rked coincidence with the higher cancer-proneness of immigrants to a country than of'natives reported by several authors (~0-~, 3-d, 2-e, 13-m, l~-m, 6-r, 35-s, 36-s, 37-s) in South Africa~ New Zealand~ Israel an~ the United States. He visualized the possibility that a la-. tent infection or exposure to a "foreign" virus to which no immunity existed in the ~mmigrant might explain the susceptibility of the newcomer to cancer. He said: "Search for causes of cancer of the lun~ has been focused on two groups of admittedly. responsible factors: intra- and extra-cellular ones. The first group includes: a) hereditary and b) enzymatic~ and other factors. The sec- ond group includes: a) physical~ b) biological and c) chemical agents. "The hereditary factor is well-known from the study of neoplasms in animals. Some strains of laboratory animals are more prone to cancer than others. These strains have been bred for research purposes. "In order to explain the mechanism of trans- mission of certain biological agents (i.e., viruses) it has been postulated that they act on the chromosomes~ bringing about chan~es in the genes which virtually convert the gene into a gene-virus ~apab!e of transmittin~mutation through generations. This theory has sought to reconcile the viral and non-viral theories of the origin of cancer .... "Less known and less extensively studied ~ factors than those included in the intra- and ~ extra-cellular groups are of much interest,o They are those which may cause the great var- o iation in geographical incidence of cancer.~ Moreover~ certain miKratorymovements reveal~ differences in the incidence of cancer amon~ natives and immigrants in various countries....
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"A viral infection~ incurred prior to en~t~ation, latent, like many viral infec- tions~ for lon~. periods of time until a sud- den provocation arouses the neoplasm to ac- tivity -- such an hypothesis may explain the difference; or else~ exposure to foreign viruses to which no previous ~unity exists.... "To this attractive hypothesis the new _kn~led~e of the experimental concepts of tency~ inhibition and maskin~ of viruses as expounde& by Huebner ~O-h ~ Andervont Goodpasture 2~-g in 1957 give support to the possibility of a dormant viral infection as factor for the develol~nent of cancer of the lung."
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I-D 3a HEREDITY, AGE AND HOP~ONE INFLUENCES ON VIRAL CANCER Howard B. ANDERVONT, Sc.D., of the National Can- cer Institute, Bethesda, ~., in 1957 (12-a) re- viewed the marked desree of association of netic, hormonal and age factors with virus in- duced cancers in various species and strains of laboratory animals, and the bearin~ this re- search may have on solving h~,~-~n cancer problems. He said: "Many factors are involved in the main- tenance or alteration of the host-virus re- lationships which influence the occurrence of virus-induced tumors: The purpose of this paper is to discuss briefly three fac- tors~ namely genetic, hormonal, and age, which are Enown to exert a pronounced in- fluence upon the susceptibility of exper- imental animals to the development and transplanta- tion of these tumors .... "The ~portance of genetic factors in virus-induced tumors are best understood in the laboratory mouse, for the simple reason that hishly inbred strains of these animals are available which permit the in- vestigator to ~valuate the influence of a virus upon animals of known genetic con- • stitutions .... "The age of the host is often crucial in heterologous transmission of viruses and most successful efforts to overcome species resistance to tumor viruses are de- pendent upon the use of youn~ experimental animals .... Age factor~ in susceptibility to viruses probably reflect the inability of newborn and young animals to produce antibodies, or, with the viruses of chick- en lymphom~tosis and mouse mammary tumor~ the young are highly susceptible to a virus which remains quiescent for months before tumors occur .... "Hormonal stimulation is important in many forms of cancer including some virus-induced tumors .... Extensive studies have been made of hormonal factors " influencin~ leuP~emias and mammary tumors in the mouse, and there are several good reasons for such studies. -O O~
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"(i) The tumors arise spontaneously in a common laboratory animal. (2) They usually occur spontaneously in middle or late life or~ when induced with viruses, the incubation periods extend over months. (3) They do not appear at the site of inoculation; a characteristic which could make them more responsive to hormonal activity than those tumors occurrin~ promptly at the site of administration. (4) Of most importance~ they are studied in inbred strains of animals showin8 a high or low incidence of tumors in which the relationship between virus~ genetic factors, and hormonal factors can be accurately determined.... "Genetic, hormonal age factors are important in the occurrence and ~rowth of _~-~ny tumors in experimental animals. ~e fact that the influence of these factors is not limited to virus-induced tumors indicates that tumors of known viral etiology should not be considered as belonging to a 6istinct or peculiar group of neoplasms. Indeed, the diversity amon~ virus-induced tumors is sufficient to include all types of experimental tumors .... "~le specificity of tumor viruses has been one of the major obstacles facin~ those who attempte~ to detect a virus in human tumors .... In brief, the growing ability of investigators to surmount genetic factors by the use of newborn animals and by hormonal stimulation may enable them to transmit tumor viruses of one species to another species."
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CHROMOSOMAL ABNORMALITY A. G. BAKIE, M.B., W. M. COURT BROWN, M.B., Patricia A. JACOBS, B.Sc., of the British Med- ical Research Council Stoup for research into the general effects of radiation~ at Western General Hospital, Edlnbur~h, and J. S. MILNE~ M.B., general practitioner in East Lothian, Scotland~ collaborated in chromosome studies in human leukemia reported in 1959 (2-b). They said: "The occurrence in neoplastic cells of chromosome abnormalities~ both of number and form~ is now well established~ althouth their frequency and sitnificance in relation to carcinogenesis rema~n~ uncertain .... "Three possibilities may ~e considered. Firstly the chromosome changes may arise as epiphenomena in a ~rossly disordered bone- marrow; secondly the visible chromosome chan~es may include the fUn_aa_mental chan~e which has conferred neoplastic qualities on the marrow cells; and thirdly it is possible that the chromosome chan~es are the conse- quences --perhaps the remote consequences -- of a more subtle alteration in the genetic constitution of the leukemic cell. This last interpretation seems the most likely." 0 0
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ON VIRAL 0RIOII{S .W. Ray BRYAN, of ~he Laboratory of Biolo~D', Nat~cnal Cancer Instltu~e~ ~e~hecda, MA., ~n 19~ (57-b) presented a reconside~tlon Of ~he r~ture of neoplasia In the li~t of ~cent ad-4ances in cancer research: cer Is not a sln~le disease, bu~ a ~up of diversified diseases loEical ~nlfes~tlons ~d d~Xc blolo~cal properties In c~on .... "By far the g~-eatest majority of spon- taneously occum'in~ human neoplasmm ~re associated with etiological agents tha~ are still ~own (Bo)~, 1953) (56-b). ~e pos- sibility %hat vi~ses ~y be Involvea In the h~an diseases ~o a considerable degree is suggested by the discovery of ~ny new tu- mor rinses of-laboratory an~al8 durln~ the last few years." u~
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ROLE OF VIRUS IN TUI©RS AND INFECTION Leon DMOCH0~SKI, M.D., Ph.D., of the University of Texas M.D. Anderson Hospital and Tumor Institute an~ Baylor University College of Medicine, Houston, • reviewed ~5~ papers treating of viruses and tumors in 1960 (27-d). He said: "Electron microscopy has.., undoubtedly contributed to present-day knowledge of all cell structure by revealing an essential sim- ilarity of the structure of cells of plants, animals, and man. It has further shown that cellular components have certain physiologi- cal and chemical functions .... Present-day electron microscopy has shown that viruses are not molecules, as at first considered when tobacco mosaic virus was crystallized, but have a complicated structure like that of cells. It has helped to show the basic constituents of specific activity of viruses and their localization within a virus particle. '~hen one has learned that nucleic acids are the basis of viral activity, the question arises whether or not the nucleic acids, es- pecially deoxyribonucleic acid, are respon- sible for the malignant chan~e.... The part played by a virus in infection or t~,~or in- duction may at first sight appear to diminish in favor of its component -- the nucleic acid; in other words, the part played by the virus may be merely that of a postman delivering a message. However, it still ren~ins to be shown that infection or tumor induction by nucleic acids can occur under natur~l condi- tions • "The nucleic acids~ at least under ex- perimental conditions, have been shown to ~ form the basis of a new approach to the study of disease in general and of tumors '~ in particular. Only a combination of morpho- o logical, biochemical, biophysical, and per- o= haps some new~ as yet unknown, methods will show ~ whether we have, indeed, landed or have been stranded at the molecular level. The constant reallzatlon~ however, that no matter what happens at the molecular level, it is the cell and the host which eventually becomes afflicted with cancer, may lead to a true understanding of neoplastic disease."
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I-D 5 ACCEPTED BY BIOLOGISTS Jacob IrCRTH, M.D., of Harvard Medical School, in his Presidential Address before the American Association for Cancer Research in 1959 (20-f), said that "one- sided theories" arise as scholars in diverse disci- plines pursue various leads with their o~n techniques, hence there is an "eternal need for a meetin~ of the ways" among- scientists. "So arise one-sided theories: cancer is a virus disease, or an abnormal differentiation, or a somatic, mutation, or an immunologic dis- order, or a self-perpetuatin~ defect in oxida- tive metabolism, or an adaptive deletion of a cell component. "Any of these theories may be overwhelminsly true within the horizon of one discipline. But they appear faulty on many scores when considered by scholars of other disciplines as the universal basis of the many diseases named cancer. On the other hand, such theories do elucidate some fea- tures of some cancers and thus need not~ be dis- coura~ed.... "The follo~in~ appear to us cancer biologists to be established facts about cancer: "i. Neoplasia is a state in which cells, nor- really lim~ted~ proliferate with no restraint. "2. This state can be brought about by changes either in host or in the cell. The former type of neoplasm is termed dependent, the latter auton~nous. "3. The basic derangement in the host can be due to sustained excessive stimulation or to a de- ficiency of natural restrainin~ forces. "~. The basic derangement in the cell can be cytogenic, or it can reside outside the self- replicatin~ apparatus of the cell, as in parasitism by virus. The former is an autonomous, the latter a virus-dependent, neoplasm. "5. S~ne autonomous tumors respond in varying degrees to their physiologic regulators; others do not. "6. The trend is for progression 'from bad to worse;' from good to poor responsiveness; from near- ly normal function to no function." o o o 4~
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VIRAL AGENTS I~ N~ TUMORS CAUSE MICE CANCERS James T, GRACE Jr., M.D., and his colleagues Drs. Edwin A. MIRAHD and Joseph A. DiPAOLO at the Roswell Pare Memorial Institute, Buffalo, N.Y., have found viral agents, seemingly cap- able of producing cancer in mice, in h~_~m~n tu- mors (13-g). As recounted by the New York State Department of Health Bulletin, they said: "There appears to be a definite rela- tionship between injection of human tumor extracts an~ appearance of tumors in mice.... (We are investigating) the possibility that oncogenic viruses are implicated." Of 606 mice receiving direct inocula- tion of unfiltered hv~-~n tumor extracts, 26 developed cancer, as did ~7 of the 791 mice receiving filtered extracts. Some mice developed four to six cancers. No tumors appeared in mice injected with healthy hu- man tissue culture preparations. From this, the researchers concluded that "normal h~-a~n tissue is not related to the appearance of animal tumors, at least not under the time limits of these studies..... (Results of the study showed) no correlation between the type of h~-~n tumors employed an~ the types of. tumors appearing in mice." The greatest number of cancers in mice, mostly breast tumors of pregnant mice, resulted from injections of extracts from persons with acute leukemia. 0
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I-D 7 AND CANCER P. C. KOT.TRR, Ph.D., D.Sc., Professor of Cyto- genetics~ Institute of Cancer Research~ Royal Cancer Hospital of London, England, discussed heredity and cancer in 1959 (8-k). He says: "A s,,,m~ry has been made of our know- ledge of the inheritance of susceptibility to cancer in mice and men. It has been pointed out that in both organisms the mode of ~-~eritance is usually complex, involv- in~ a large n,~m~er of genes. In man it has been shown that there is pro~ably a stron~ inherited predisposition to cancer in cer- tain sites, particularly the stomach and breast and to a less extent the cervix and uterus. Incidence of tumors at other sites has been insufficiently investi~ted from .the hereditary point of view. It remains to be seen~ for instance, whether it will be possible to demonstrate a hereditary com- ponent to cancer of other parts of the body such as the lung and the bladder. "The evidence from studies of twins lays more stress on the i~portance of the environ- ment in the etiology of cancer and shows how in most cases identical susceptible genotypes do not meet with exactly the same environments. Racial differences in the frequency of inci- dence of cancer are not well documented and it is not easy to partition the hereditary and environmental components of susceptibil- ity. But again the stress must be laid on environmental factors, particularly in con- siderin~ such a genetically heterogeneous population as the h:,~-~n race." u~ 0 o U~ 0 o
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i-D 7a DDTIONS Charles T. BINGHAM, Blue Hills Hospital, Hartford, Conn., in 1960 (55-b) told the Anniversary Consress of the Pan American Medical Association in ~exlco City that there is much evidence that emotion plays a large part in the etiology of cancer: "Since hormones and virus infections ~nd oxygen supply are all known to play some part in cancer ~rowth, emotion~l stress must be considered too. The e~idence.., must be sousht for in the case histories of people who have died from cancer, and it should be looked for in the environment, the personality and the bacP~round of the patient .... '%~hen stress factors have sensitized a certain tissue unit, symbolically-determined ~y the subconsciou~ operation of the brain~ it becomes vulnerable to tissue chan~e .... Good emotions such as hope and faith and love certainly lead to health -- obviously bsAi emo- tions such as fear, anger, resentment, guilt, shs~ne, etc., are very unhealthy. This paper deals with the influence of these bad emotions on the development of cancer in specific areas of the human body in specific individuals."
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~PSYCHOLOG ICAL FACTORS IN CANCER Lawrence LeSHAN, Ph.D., of the Institute of Applied Biology, New York City, reported on extensiv~ research into psychological states as factors in the development of malignant diseases in1959 (8-e). ~uotations from his paper follow: "ghena f~eld is in its infancy as this one is, with many lines of investigation proceeding simu~taneously~ and before any over-all body of theory has been formulated, it is extremely dif- ficult to sum it upbriefly. In tryin~to eval- uate the present situation in this area~ certain factors appear to emerge: "I) There seems to be a correlation between neoplastic ~isease and certain types of psycho- logical situations. This has been widely reported as a result of cllnlcal,observations~ experimental studies, and statistical investigations. "2) The most consistently reported psycholog- ical factor has been the loss of a major emotional relationship prior to the first-noted symptoms of the neoplasm. It seems to be established that this has occurred more often in cancer patients than in the various groups w~o were used as controls. "3) There appears to be some relationship be- tween personality organization and the time from the first-noted symptoms of a neoplasm until the patient dies. "4) There maybe some relatlonshipbetween per- sonality organization and the type or location of a neoplasm. The evidence that different types of peo- ple tend to develop different types of cancer is ex- tremelysus~estive. "The data an~ leads so far produced in this field seem worthy of further investigation. This is an exciting and stimulating field which is bound to lead into many provocative problems~ and may point the way to new means of approaching the neoplastic process."
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I-D 9 ORIGIICS OF HU~J~ CANCER Sir Henease 0GILVIE~ MoCh.~ KBE~ LL.D.~ FRCS~ Consult- In~ Surgeon at Guy's Hospital~ London~ England, drew upon a lifetime of medicine and surgery for views on psychological factors in carcinogenesiss published in z957 (2-o). id: • "~'.Ike most gener~l surgeonss I have treated an~ watched many cases of cancer. S~ne were rel- atives; many were friends; others~ comin~ as pa- tients~ died my friends. I have slowly come to frame in my m~-d an aphorism that never can ~e statedas such~ ~ecause no statistics can be ad- vanced to support it: 'The happy man never gets cancer. '.... "The instances where the first recognizable onset of cancer has followed almost immediately on so~-~_- disaster~ a ~ereavement~ the break-up of a relationship~ a financial crisis~ or an accidents are so numerous that they suggest that some con- trolling force that has hitherto kept this out- ' break of cell communism in check has been removed. "The lat~ appearance-of second~ries~ sug6est- ing that over the years s~ne undetected cancer cells have been lyin~ latent and kept in check by some un- known restraining force~ is a co~onplace after op- erations for c~ncer of the breast. Very often -- indeed~ so often as to suggest that if the true cause .could be discovered the problem of cancer treatment might be solved -- the signal for renewed ~rowth seems to have been some unhappy event." 0 0 0 o~
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I-D i0 ~q~ VIRUS ~q~EOR~ OF Wendell M. ST~ Ph.D.~ Professor of Biochemistry and Director of the Virus Laboratory at the University of California at Berkeley~ Nobel Prize winner in chem- Istry in i~6~ discussed the virus etiology of cancer in 1957 (33-s). He said: "Evidence for the virus etiology of cancer has cc~e frc~ so many different laboratories and has been of such good quality and quantity that I find it very difficult to understand why so many investigators have continued to have such a firm blind spot with respect to the virus causa- tion of cancer. Many investigators accept viruses as etiological agents for animal cancers but are unwillin~ to consider them of etiological impor.- tance in cancers in man.... 'Recent advances in the cultivation of human cells in vitro and especially in the newer know- ledge of certain properties of viruses warrant today a marked chan~e in our thinking on the prob- lem-of human cancer. The time has come when we should assume that viruses are responsible for most~ if not all~ k~nds of cancer~ includin~ can- cer in man~ and design and execute our experiments accordingly ~ ~ • "The recent flndings in the virus field indi- cate more and more that the virus problem and tl~e cancer problem are one and the same. The experi- mental evidence now available is consistent with the idea that viruses are the etiological agents of most~ if not all~ cancer~ including cancer in man. Acceptance of this idea as a working hypo- thesis is urged because it will result in the do- in~ of experiments that might otherwise be left undone~ experiments that .could result in the solv- ing of this great problem. The past few years have seen the development of important new tools~ and if we take full advantage of "these we could easily tip the scale towards the solution of the cancer problem."
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GENETIC CONCEPT OF CANCER The genetic concept for the origin of cancer has been the lifework of Leonell C. STRONG, Sc.D., Ph.D., in recent years workln~at the Biological Station, Roswell Park Memorial Institute, Buffalo~ N.Y. In recent papers on this subject (~3-s & ~4-s) he. said: "The'various types of cancers which arise in the mammalian body have~ at least~ one char~ acteristic in common. Cancer arises because the organism b~s lost control of a definitive part. Perhaps durin~ the agin~process the mechanism that keeps the individual in equilibrium is dis- rupted, and as a result of this loss of control of all the parts cancer of one or more elements is able to originate and to ~row at the expense of the rest of the body." (~3-s) "I... should like to reaffirm my faith in the genetic concept of the origin of cancer ori- ginally formulated in 1926 -- that a chan~e com- parable to a somatic mutation was involved. This change was defined as applYin~to any formed constituent of the cell, either nuclear or cyto- plasmlc, that could duplicate itself, affect the physlolo~yof the cell specifically, and be transmitted by cell division." (~-s) O
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I-D For further documentation on viruses as possible causes of human cancer and recent discoveries extendin~ the range of known viral" cancer see l-a~ l~-s~ ll-a~ 12-a~ 6-a, ~-b~ 82-b~ 78-b, 79-b, 69-b, 55"b, 57-b, 80-b, 81-b, ~2-c, 35-c, 26-d, P~-d, 9-a, 27-d, 20-d, 35-f, 19-f, 26-f, 13-g, 3~-g, ~O-g, 6-k, 22-k, 6h-m, 1-o, h6-p, 35-P, 12-p, h8-p, 19-p, P_t-p, 35-r, For o~her co~en~s on s~ress and psychological ~ac%ors In carc~ogenesls s~e i0~# l-b, 16-b, 13-f, 6-g, ~3-h, 2-E, 7-1, 15-1, 9-m, ~-m, Fo~ ~ai%io~l ~ on gene~Ic# ho~o~! o%her endogenous ~ac~rs ~ cancer see 21-b, 29-b~ ~-b, ~l-b, ~6-b, ~7-b, ~-b, ~8-b, 9"c, ~-c, 2~, 3"f, ~-f, lO-f, 17-g, I-i, 16-1, 17-1, 5-m, ~-m, 8-n, ~-p, 33-r, ~-r, Z3-s, 78-s, 2~-s, S5-s, ~-s, 30-s, ~-s, 55-s For studies on psychological ~ physiologi~l dlffe~nces between smokers and , non-smo~rs see 12-e, lO-f, ~-h# 15-1, 16~i, 18-1, ~-m, 23-m, lh-s
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Experiment 1 Cigarettes were smoked on an Ecusta-type smoking mach~ parameters) and the smoke was passed through a Cambridge 100 ml. of 2,4-DNPH in 2 ~ hydrochloric acid 2,4-DNP hydrazone was collected by filtration, dried, and Cigarette smoke was drawn (35 ml. puff) into the moutt a Cambridge filter, .retained in the mouth for 3 seconds, ar into 2,4-DNPH solution. 2,4-DNP hydrazone weight determine Reductions of aldehyde ketone content of 40-67Z were obtair different cigarettes. Experiment 2 In a similar type of experiment, an acetaldehyde-nltr( solution (3 mg/ml) was reta£ned in the mouth for various tJ and then exhaled into plastic balloons. The acetaldehyde the inhaled and exhaled gas was measured by VPC. Table I results obtained. SubJect Table I " Acetaldehyde Adsorption by BuccalCavlty Mouth Retention Decrease in Time~ Seconds Acetnldehyde, % A 3 8 10 ~0 65 I00 ~ 5 .67 L" 2 25 14 3 42 5 56 6 66 Experiment 3 Experiment i was repeated in greater detail with the results: I. Mouth retention (3 seconds) of vapor phase reduced aldehydes and ketones by 47-60% (2,~-DNP 2. Mouth retantlon (3 seconds) of vapor phase reduced isoprene by about 10% (VPC). ne (standard Iter into . The eighed. through d exhaled .d as above. .ed for 5 ,gen me periods :ontent of bows ollowing O. 0 o 0
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Lung tuhalation of vapor phase reduced aldehy , and ketones by 80-90% Mouth retention (3 seconds) of whole smoke reduc~ partlculate phase by 10-15% (Cambridge fllterpaq Lung inhalation of whole smoke reduced partlcula~ phase by 80-90%.(Cambridge filter pad). Other workers have shown that mouth retentlon of an~m solutlons.reduce ammonia by 76-88Z (Biedenbeck) or 83-90% The ammonia in cigarette smoke is reduced on mouth retent and by lung inhalation by 98Z (Laskowskl). .Experlment 4 If cigarette smoke is passed through filter tip cont~ varying amounts of water and then through a Cambridge fill aldehydes and ketones are reduced as follows (one Camb, pail for 8 cigarettes): 50 ~g. water, 20%; 100 mg. water, 27%; 150 mg. water, 33Z; 200 mg. water, 38%." Repeating thls experiment with a new Cambridge fllte, each cigarette, we obtained the followlng reductions: 50mg., 12%; 100 mg., 17%; 150 mg., 27%; 200 mg., 28~ Comparison of the two sets of data indicate some ald~ ...... ~kdtones-areretalnedby mdlst-TPH-on-Cambridge filter pad _Experiment 5 -. % • If vapor phase of cigarette smoke is passed over a m~ " of filter paper, the following reductions in aldehyde and ~. (2,~-DNPH method) were obtained: Filter Water Reduction, paper added, g strip mg. w x 1 0 0 0 2.0 x 5.0 200 23 2.0 x 10.0 ~00 ~1 This work was conducted in 1963-4. These experiments are, of course, all very prellminar ~o another project resulted in suspension (termination) of described studies. Alan Rodgman mla-alr - (Wilke). .on by 56% er pad, the 'idge filter pad for .hydes and Ist strip ketones r. Asslgr~ent the above
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in er o ice Mamorandum Subject: Scientific Advisory Board Meeting December 10-12, 1971 New York, N. Y. Date: December 14, 1971 To: Mr. E. A. Vassallo From: Murray Senkus Attached are the minutes of the Scientific Advisory Board (SAB) of the Council for Tobacco Research (CTR) meeting which was held in New York on December 10-12, 1971. I attended as a representative and Chairman of the Industry Technical Committee (ITC) of the member tobacco companies. Please distribute in the Main Office as you see fit. I am certain that Jack Roemer would like to see a copy. Att. /has
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D~cember 13, 1971 Hinutes of Heetlng of Scientific Advisory Board (SAB) cf Council for Tobacco Research (CTR) December 10-12, 1971 - New York, N. ¥. (Please see attachment for attendees) A. PlanninK Con~lttee. I.. R~port.byDr. Sheldon C. Sorn~ers of the Eeetlng of the Plsnnln~ Co..-mtttee ~n C~lca~o, November 2~,,1971 Nessrs. ~ and Hoyt and Dr. Hockett also attended. a. Nitrosa~nes in S~o~e In 'view of recent reports in the literature of the presence of nltrosamlnes in c/8arette smoke, a testing program6n the carclnogeniclty of nltrosamines is .belleved to be deslzable. Dr. Furst ~as requested to visit Dr. P. Shu~Ik at the Epley Institute in Lincoln, ~ebraska to dlscus~ the testing program. b. Differences Betsaeen Ci~aL,._Pl_~ and Cigarette S~okes :ad ~heir Gas Phases At thelrmeetlng lu Chicago, the Planning Coumlttee raised the question ~hether the above differences ~hould be iuve~tigated in chronic experiments. A~ter discussion of this proposal it vas decided not to pursue this ~atter. c. Sm~kJ.n~Nachtne Status The follo~Ing expenditures ~ere approved: 1. Cost of modiflcatlons - $I0,000. ?. Preperation of operational manual - $5,000. 3-&, Hachlne balance study and Ivng deposition study - not to exceed $60,000 - this may have to be extended. 5. Services of C. W. ~ystro~ o~ ~eynolds - eu amount not to exceed $7,000. .d. Coasulci__n~.S,e:r_.vic_es_ _of__D_r.__~a_y__Le_v~ Approval ~ $&,000 gas given for studies on nucleic acids in "C" particles. e. Use of Old Hic~ ~mb.ers of the SAB agreed that the idea of usln~ old animals in the study of cardlore~piratory ~nd other changes in mice at an advanced age is a good one. The CTR s~aff ~I11 continue to contact people for opinions on this subject. f. i:~C~n~ation Ses~ic.n for Ir~duscry The l~ovember 16-17 Information ~ession was reported ~o be a success.
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Hinutes o[ gAB HeeLing ~ecember 10-12, 1971 Hew York, ~. Y. Page two ~._ Asbestosis Prolec_t ]'~mbers of the CTR staff are trying conscientiously to get this most important, project going. h. Fractionation of Condensate ~eloy Laboratories was funded $16,200. Eleanor Hacdonald Computer Services An 4motmt of $6,257 was appropriated to allot completlon of runs computer data cards. J... Chodosh-Eichel Grant "~ This study~sa discussed at length at the November 16-17 meeting. Support of the study uill continue at the current level through January 1972 and then ~ilI be s~vlewed, • : Ex£stin~ l'ro~ects I. ~Io-~search Institute Contract Two projects are tmdexway' at the Institute. One i~ Jet smoke Impingement ou the skins of mice using whole smoke ~nly; in the other study, Hamburger is exposing hamsters, long term, using the so-called vertical Walton smoklngmachlne. II. The Furst Contract Furst is studying lung retention characteristics of Fe203, SI02, A1203 and benzpyrene. Inorganlcs appear to be permanently retained; ~hereas, benzpyrene is removed completely in three days, and 50Z in 3--~ hours, whether given Independently or along with any of the Inorganlcs. It is not knmm ho~ benzpyrene is removed but it could be by way of hydroxylase. C. Toba=co Working ~roup (TWO) ~e Chalr.~n of the Industry Technical CommltCee (ITC) reviewed the TWG" progr~ since its inception and also discussed the forthcoming experiments whi-h m:e to be started (1) in January 1972 [skin painting only; synthetic tobaccos, puffed tobaccos, aatl-~ucker~n8 agents, etc.] (2) February 15, 197~ - the Auerba~h dog experiments to determine effects of nicotine and homogenization; (3) July ]972 studies on filtratlon. Members of the gAB seriously question the advlsability of doing the Auerbach experiment. It was agreed that the writer and Dr. Wakeham will attempt to maet with Dr. Cori ~t NCI to set forth scientific data before hi~t in the hope that the ~ NCI ~;ill decide to abandon this experiment o O
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l~nutes o[ SKB Heeting December 1012, 1971 Hew York, N. Y.. Page three D. Consideration of Appllcations John ~_Cralghead. ~!.D~ - University of Vermont - Burlington, Epithellal Cell Transformation and Csrcino~a Indu=tion by 'tO" ~vpe ~A Viruses. Appllcat.lon vas approved; th~s is considered to be an important project. BaruJ Bcnacerraf~ H.D~ - Harvard Hedlcal $chool - ~oston~ Haas. Control of $~eclfic Cell~la~ and Humors1 Immune Responses to Neoplastlc and Non-neoplastlc ~iss~es, Consideration vas deferred for one year to enable Benacerraf to modernize his program and to prepare a feasibility report. Nayne L. ~yan, Ph.D. - University of t~ebraska College'of Hedlclne - Omaha~ Neb. The 3',5' Cyclic ~n0phosphate System in Carcinogenesis. Deferred for a site visit by a member of the CTR staff, John P, Delaney~ N.D.~ Ph.D. - Ni11Iam Kubie~k. Ph.D.- Unlverslt~y of Hinnesota Hinneapolls. Hinn. Smoki~ and l'[cotlne on Circulation in the Loeer Limb. Approvad for a second terminal year. Carleton H. Saker~ Ph.~.- University of South Florlda - Tampa, ~la. Hicrovascular Blood Flo~ Distribution and Small Vessel Reactivity. D£sapproved, [xederick D. Baker, Ph.D. -~New York State Department of Health - Albany, N. Y. Biochemlcal Alteratlons Follovlng Carbon Honox,ide (CO) and CO-Cadmium Exposure. Disapprcved. Rober[C. Rosan, H.D. - Cardinal Glennon Hemorial Hospital for Children - St. Louls~ Hissouri Ribosomal Patterers of Lobular Differentiation. Approved, Northy Investigator; excellent and relevant project. Allen B. Cohen, H.D. - Sa~ Francisco General Hospital - San Francisco, Calif. Role 6f the Human Alveolar Hacropbage in the Production of Emphysema. Approved. Considered to be a capable Investigator. Irene P. Goldring, Ph.D. - Albert Einstein College of Hedlclne - Bronx, New York. Development of an Animal Hodel of Emphysema vith Chronic Obstructive Pulmonary Disease. Disappro'~ed. ~udh Eha;~at, Ph.D._ Central Action of Nicotine (Chronic Adminlstr~tlon)." Approved with the understanding ~hat the work is to be completed in what will no~ be a second-y~ar s~udy. - St. Louis University School of Hediclne - St. Louis, Hissourl Walte~ B. Essman, Ph.D. - Q~eens College - Flushing. Ne~ York. Nicotine Ac~ioz~ Upon Hemory Consolidatlon, Approved.
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• PLivur.es of SAt l.,'cetin~ December 10-12, 1971 New" York, N. Y.. Page four ~Leppld~..Cpl.d~t~n, D.Sc~.- Nay Jersey Heuropsychlatrlc Institute - Princeton, N. J. knAnalysls ¢,~ Behavlorlal and EEG Chan~es Produced by Chronic Nicotine Administration in Rats. Approved. Duane G. Wenzel~ Ph.D. - The University of Kansas - Laurence, Kansas. Effects of Nicotine and Carbon Nonoxtde on Vascular Ltpi4 Disposi.elon. Approved ~£th the understaudlug that the study is to be completed in tvo yea~s. Gary D. Friedman~N.D.,_N,S. - Kaiser Foundation Research Institution - Oakland~ Call[. Characteristics of Smokers and Non-smokers. Approved. Believed to be a vorth~hile epldemiological study~ Eleanor J,.Hac4onald, A.B. - N. D. Anderson Hosplt~l & Tumor Institute - Houston, Te~ Regional Patterns of Cancer of Each Site in Five Large Rc~!ons InTe~a~., l~eferred for further Information and for reconsideration at the forthcoming SAB m~eting, • Arnold R. Kap~n. Ph.D. - Psychiatric Research Foundation of Cleveland - Cleveland, O ~Taster' Cenotypas, - Antitryp_si~ Deflci.ency Cenotypes, S~¢klnRo Personality Variables, and Constitational Disease Predispositions. Disapproved. Anthouy_A._ Alb~nese, Ph.D.- Burk~ Rehabilitation Center - ~hite Plains, Effec~ oC Nicotine on Protein and ~luo Acid Hetaboli~m in Humans. Disapproved. Norris Pollard. Ph.D~ - Lobuad Laboratory - Uaiverslty o£ Notre Dame - Notre Dame. Indiana Effect of Clg~rette Smoke on l~nologlca~ system. Deferred for further information; action at the forthcoming SAB ~eeting. ~eorge Blauchard Lucas~ Ph.D. - North Carollna State L~iverslty - Ralelgn, N. C, The Role of Fu.~l in the Producti~t of Toxins iu Ci~arette Smoke. Disapproved. There is no basis for the existence of fungi in tobacco and .certainly no l~kelihood of survival during smoking and trausfe~riug into smoke. Bernard Hanese Ph.D~ - Sen Fernando Valley State College - Northrldge, Calif. and Charles A. CriCks, H.D. - The Prudential Insurance Co. of ~eerfca - ~estern Home Office - Los Angeles, Calif. ~piromeLrlc Evaluation of 1200 Normal Adults. Approve~. Hot to exceed ten months. Charles L. ~ose,._~.D. and Benjamin Bell~ M.D~.- Veterans' Adm[nlstrat~on Deferred to next meeting for fuller evaluation by s£sff. 0 0 -4
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~linutes of SAB Heeting He~ ~ork, N. ¥.. Pag~ five Brian E. Henderson. N.D. - Univ. of SouthernCallfornia and Paul Te~asakl, Ph,D. U.C.L.A, Hedlcal Center; Hurray Gardner, H.D. - Univ. of Southern California. Tire Relationship of l~ukocyteAnti~e~i¢i.ty and Genetic Susceptibility to Cancer. De£erred for site visit and better targeted protocol. CarroZl E. Cross~ H.D. - Univ. of California School of Hediclne - Davis, Calif. Effects of Tobacco Smoke on the PulmonaryAlveolar HacrophaRe ~Cy~o~i~etics,' Phagocytic Abilities and Biochemistry. (Last year*s title was Effects of Cigarette Smoke on the Pulmo. nary L¥cphoretlcular System). Pro rata January-¥ebruary-Harch, then to be considered again in Hatch 1972 at the SAB meting. W~.~- Hicrobiological Associates, Inc. - Bethesda, Haryland. Renewal of Contract for ~roject A: to develop in vitro transformation systems to assay quantitatively the carcinogenic potential of various chemical and environmental coatamlnants and to stud~ possible activation of virel oncogenes; • Pro~ect B: to apply the ~n vitro assay systems developed in Project A and to ~the i__~yltr_.o.ce11 tranrformation effect and vlral expression resultlng fr~] exposure of cell systems to known chemical carcinogens #nd knotm carclnog~n analogs an~ envlronmental contaminants; Project C: to continue development of in vlvo assay systems to complement thos~ in Project A and to study relationshlp (In vlvo) of tobacco smoke and smoke components to vlral expression; Project D: to malntai~ a Leuchtenberger-Sne11 ~ouse colony to support p~oJects a~d contracts as directed by the Project Officer. Durlng the proposed contract period, this colony wlll be converted £rom a conventlonal to an SPF colony. Approved for $150,000 (down from $256,000 requested). Projects to be adjusted by ~Icrc~iologlcal Associates accordingly. E. Carbon Honoxide Studies The Chairman of the ITC inquired ~hether any grants are being solicited for ~ork on carbon mon~ide. None of the present projects are CO-targeted exclusively although.CO is "plggy-backed" on nicotine studies. ~t was agreed tha~ the C~R staff should attempt to establish CO-targeted projects. Dr. Summers appointed an ad hoc committee to revte~ this subject and make proposals. Next Heetln~ The next mcetlng of the Scientific Advisory Board ~111 be held in Pasadena, Callfornla - Hatch 2&-26, 19~2.
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}Lt~utes o[ SAD }~eetlng December 10-12, 1971 Pase six Follo~ing is a list of attendees. Shcldon C. Summers, Chairman - N. U. Gardner Howard B. Andervont Richard H. Blng HcKeen Cattell Robert J. Huebner Leon O. J~cobson Clayton G. Loosli Kenneth Herrill Lynch Hans Heler Henry H. ~m, President Nilliam ~. Hoyt, Executive Director J. Uorris¢,n Brady A. Furst Robert C. Hockett John Kreisher ~Incen~ Ltsanti Leonard S. ~ahu Hurray Se~us. Chair_ms_n Scientific Advisory Board tl ~t tt tl tt tl |t ~t tl It it t| |t Council for Tobacco Research t! tt It II tt tt tl it It II tt I! tt tW tl tt t! . Industry Technical Co~nittee
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COUNCIl, ])'OR TOBACCO |{I.:sEAI{cH-U.S.A., INC. 110 EAIBT 59TI~ NEW YORK. N. Y. ]0022 I1ovember 15, 1971 Mr. A. H. Galloway Chairman R. J. Reynolds ~ndustries, Inc. ~inston-Salem, ~orth Carolina 27102 Dear Alex: ~ am dellghted to advise you that Dr. William U. Gardner, Professor of Anetomy and fon,~rly Chairman of the Department of Anatomy at Yale Unlvers~ty, has become a member of The Council's Scientific Advisory Board. Dr. Gardner is an authority with respect to cancer and its causation and has an international reputation. Mem~ers of the Board and the staff are of the opinion that Dr. Gardner's knowledge and experience will be of great assistance to us. Sincerely, HHR:ek H. 1!. Pemm Pres i :ent cc: Mr. H. C. R~emer t~ o c)
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PUBLIC RELMI(~J$ COUN$[L ~1~ COUNCIL FOR ~B~CCO ~SEARCII-U.S,A.s TOBACCO-HEALTH GP~NTS ANNOUNCED I IlELPS REVIVE FRAMINGH~q ilEART STUDY New York -- Grants £or 18 new studies trite tobacco and health and for renewals of a nv~nber o~ on-goSng projects have been made since January ~ by ~e Council £or To~a¢~o Resea~¢h-U.S.Ao, In¢o~ it was a~1ounced today. The total ~as • he awards~ made to ~ndepondent scientists who conduct the studies in their o~ medical schools, hospitals and research in- stttutions, ~nclude one that ~s helping keep a~£ve the famed Framingham Heart Study. ~4ajor parts o£ this proJect~ which was to have been ended for lack o£ £ederal £unding~ are being con- tinued with support ~rom The Council and other agencies. The Council f~nctJons as a sponsoring agency £or studies into tobacco and health. G~ants and contracts are awarded by The Coun- c~l on the roco~endatlon o~ the Sclen~c Advisory Board~ group or 10 physicians and scientists responsible ~or ~o Council's i~lg cigarette con~anies and,organizations o~ tobacco growers and warehousemon~ i~ has ~do ~26 original awards and many more newals to 26) scientists for a total of mo~e than $20~000,000. The new studies cover work in the ~ields o~ c~ncor, heart d~sease and c~ron~c pulmonary ailments. ~tong them areI ...Smoking classes~ risk factors and cardiovascular soase. (Th~s ~s part o~ the Framingham Heart Study.) ,..Characteristics o~ smokers and nonsmokers, ...Stud~os o~ tumor-causing ...Changes ~n cytology o~ the tracheo~ronchial tree. ...Role o£ the human alveolar ~crophages in ~he pro- duction o~ emphysema. ,,.Behavioral hypo~tension and arteriosclerosis: Of nlcotino. IIII I I II Ill
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CLIFFORD BARGER~ M.D.. Robert Henry P£eif£@r P~ofessor of Physiology, Ha~vard Medical School, Boston. "Behavior- JACK CHALON, M.D.t Asslst~nt Professor of Anesthesiologyt Albert Einstein College o~ Medicine, Bronx, in ~raohoobronohial cytology,u ALLEN B. COHEN, M.D., Assistant P~ofessor o~ Hed£c£ne, Unl- versify o£ Cali~ornia at San Francisco. "Role o£ the human alveolar macrophago In the production of emphysema." THONAS R. DA~BER, M.D.s Associate Pro£essor o~ Nedic£ne, Boston Unl~ors£~y School of Nedloi~e. "Smokln~ o~sssea, ~Isk ~aot- o~e and cardiovascular disease." h'ALTER B. ESS~N, Ph.D., Professor of PsycholosY and Bio- ~.Y. "Metabolic response to stress -- tobacco smoke JOHN R. ESTERLY, M.D.~ Associate P~o£essor of Pathology, Uni- versify o£ Chicago School o~ Medicine. "The resolution Of pulmonary ~njury." ED~ R. FISHER~ M.D., D~rector of Laboratories, Shadys~de on structure and /~nct~on o~ co~onary arteries and plasma GARY D. FR~ED}~Ns N.D. Senio~ Ep£demiolog£sts Department 0£ Hodlcal Hotbeds Research, Ka~se~ Foundation ~esearch Xn- stitute, Oakland, Cal. "Charaoterist£©s o£ smokers and ~onsmoko~e • u HUC~I FUDENBERG, M,D.s Section o£ Hematolo&y and Y.nununology~ Francisco. "Collagen antibodies in relation to the etiology Of emphysema." J. A. HAYES, M.D., Associate Patholo&is~, ~allory ~ns~ttute o£ Pathology: Boston C~ty Hospital• "A detailed morpholo~ical study o£ the sputum and bronchial %roe ~n patients w~th chronic 5ronchltls £ollowlng detailed ollnioal study du~ng ATTALAtlKAPPAS, H.D.~ Head~ Laboratory of Metabolism and Pharm- acology, Rockefeller Universtty~ New York City. "Poly- cyclic hydrocarbons: o££ec% on detoxi~ioatlon mecbanlsms."
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CHAP, LES McARTI~R~ PhoD.~ Psyoholog£s¢ to the University Health ing o£ the di££erences between smokinE and nonemokinS pop- ulations by recent quit%in8 o~ mauy smokers and the pl~oatim~s £or d~mmic explanation of smoking behavior," LUCIO SEVERX, ~oDo, Diroetor~ ~net£tute of Morbid Anatomy and PerugSat Pcruglat Z%a~y, "Blood-borne ca~olno~ens ~n mouse lung ~umorlgenosls~~ UNA SMXTHI Ph,D,~ Assls%an~ P~o~esso~ of Biology~ University o~ Miami School of Modlclne~ Coral Gables~ Fla, "The role o£ endothelial cells In non-ven%£1a¢ory ~unetlon o~ che lunE," ELLIOT S. ~SELL~ M.D,~ P~o[ossor and Chai~mant Department of Pharmacology, Pennsylvania S~a%e Unlversi%y Colle~e of Medic~ne~ Hershey, .R~dlo-lmmunoaesay for nlco¢~e,|! YASUSHI ~ATANABE~ Ph,D.~ Associate Hember! Wiscar Ins¢~¢ute o£ ~a%omy and DioloEY~ PhiladoIph~ao "S%udles on on¢ogenlo A. STANLEY ~LTMAN~ Ph.D,~ Associate Professor in PharmaooloEy and Research~ Research Institute Of %he Brooklyn College of Phsrma¢oloEyt Lone ~sland Unlvers£ty: Brooklyn: "Aou%e and ¢h~onlc o£~ects of nicotine on spontaneously hypertensive and normotenslve THO~S Co WESTFALL: Ph,Do~ Associate Pro[eesor of Pharm~¢oloEy~ Unlvers~%y o£ VirE~nla School of Medlo~ne~ Charlottesville, "Mechanism o£ action of nicotine on peripheral and central -0-
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Tn~.: COUNCH, ]~'Ol~ TO]~ACCO I~J.:sEA]¢cH-U.S.A., INC. 110 EAST 59TJl STREET NE%~" ,'OI{K. ~'. ,'. 10022 October 26, 1971 Dr. William U. Gardner Professor of Anatomy Yale University School of Medicine 333 Cedar Street New Haven, Connecticut 06510 Dear Doctor Gardner: Your letter of October 12th was discussed today with representatives of the major participating member companies and I am delighted to advise you that this has removed the concern over your inability to make yourself available on a full-time basis for the twelve months commencing July i, 1972. In your letter of September 22, 1971, you outl~ned the basic terms of your employment as you and I had discussed them except that I indicated to you that you would become Scientific Director beginning July i, 1972 rather than Scientific Consultant. During the firs{ twelve months you would be employed on a half-time basis and beginning July i, 1973 on a full-time basis. As indicated ~n your letter, your compensation for the twelve months beginning July 1,.1972 would be at the rate of $45,000.00 per annum and for the period beginning July i, 1973 at the rate of $75,000.00 per annum. The compensation would be payable in equal monthly installments. At the present time I am not certain how this proposed arrangement squares with the rules of wage stabilization, but this ~s a matter that will have to be clarified by legal'opinion or otherwise. At the meeting of the Scientific Advisory Board held on September 25, ]971, the members were unanimous in extending to you an invitation.to become a member of that body. I assume that your letter of September 22, 1971 indicates that-you are willing to serve on that Board, effective immediately. The next meeting of the Board is scheduled for December 10-11-12, 1971 in New York City and the Board members, Mr. Hoyt, Dr. Hockett and I all look fo~;ard to having you attend your first meeting at that time. As indicated to you, prior to your becoming Scientific Director you will receive a per diem fee of $150.00 in connection with attending meetings of the Board and other time devoted to the work of the Board. In addition you will be reir~ursed for your traveling and other expenses connected with such activity. Prior to July i, 1972, we may also have occasion to consult with you on matters relating to the work of The Council. This would be apart from your activity as a member of the Scientific Advisory Board. For such consulting services you would receive a per diem fee of $]50.00 and be reimbursed for your traveling and other expenses. c)
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'l'm~ Cot~,~-CtL J~o~t '1'o]~Acco l~t~s~,',A]~cn-U.S.A., I~'c. Dr. William U. Gardner -2- October 26, 1971 When {he time approaches for you to become Scientific Director it may be to the mutual advantage of both of us to enter into a written contract setting forth the arrangements in detail, including matters that we have not yet fully discussed such as a possible desire on your part to defer part of your compensation and the term of your employment. I would appreciate your advising me in writing as to your assent to this letter. When I have received that I will be in position to advise the members of The Council and of the Scientific Advisory Board that you have become a member of that Board and that we anticipate you will become Scientific Director as of July ], ]972. If you have any questions please telephone me. In case you are unable to reach me at the office you can reach me in Winston-Salem, North Carolina at (919) 723-2553. Your knowledge and experience, I am confident, will be of great assistance to The Council and its Scientific Advisory Board in the most important work it has undertaken. Personally I am looking forward to our association with you. S~ncerely yours, H. H. Ramm President HHR:ek
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Please note and return. H. C. R. 10-21-71 o o o
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"]'HI.: COUNCIL ]7'0/{ TO}~ACCO ]{ESEAI~CII--U.~.A., INC. l].0 F.~kST ~gTH STRElh~T NE%~" YORK. N. Y. 10022 October 19, 1971 Mr. A. H. Galloway Chairman R. J. Reynolds Industries, Inc. Winston-Salem, North Carolina 27102 Dear Alex : ~ am pleased to advise you that Dr. Hans Meier, Senior Staff Scientist, The Ja~.son Laboratory, Bar }{arbor, Maine 04609, has become a member of The Council's Scientific Advisory Board. Dr. Meier is a recognized authority in the field of genetics, especially as applied to mice and other animals that are extensively used in cancer research. Members of the Board and of ~]e staff are of the opinion that Dr. Meier's knowledge, experience and judgment should be of considerable aid to us. Sincerely, H. H. Ramm President HHR:ek cc: Mr. H. C. Roemer
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Mr. E. S. Harlow Dr. I. W. Hughes Dr. A. W. Spears Dr. llelmut Wakeham September 29, 1971 Re: Walton-Morrlssey Smoking Machine ¢ On my recommendation as Industry Technical Committee representative to the Scientific Advisory Board of CTR, the Board authorized, at its meeting on September 24-26, assignment of an Industry man full-tlme for a reasonable period to assist Mason Research Institute in the completion of development of the Walton-Morrlssey Smoking Machine. This will consist of the following: (I) Determination of smoke delivery to appropriate animals using dichlorobenzophenone as a tracer~ (2) determination of smoke delivery to appropriate animals using Cl~-lebelled dotriacontane as a tracer, (3) preparation of an Operation Manual for the smoking machine, and (4) attend to other details which would facilitate the adoption of the smoking machine for inhalation research. As will be seen from the accompanying letter of agreement, R.J.R. .Industries, Inc. can assign Dr. C. W. Nystrom to this task, if this is agreeable with each of you. Please feel free to suggest other approaches. I am agreeable to assignment of an employee from any other CTR member company. The Smoking Machine' Committee of SAB has concluded that Mason Research Institute requires the assistance of an Industry employee in what is now the final stage of development of a smoking machine for inhalation research. I am told by the staff at CTR and by Dr. Loosli, Chairman of the Smoking Machine Committee, that time is of the essence. Please give me your comments on this memorandum today if possible. Should selection of Dr. Nystrom meet with your ~pprov~l, he will begin his assignment early in October, 1971. /has Attachment ; ~ Murra~ Senkus
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I~urray Senkus Director of Research The Council for Tobacco Research - U.S.A., Inc, 110 East 59th Street New York, New York 10022 Attention: Mr. W. T. Hoyt, Executive Director R.J.Reynolds Industries, Inc. Winston-Salem, N. C. 27102 September 30, 1971 Dear Sirs: ~ '. You have requested the services of Dr. Charles W. Nystrom in connection with work being performed on your behalf by Mason Research Institute. We are willing to make the services of Dr. Nystrom available to you on the terms set forth herein. It is understood that you will reimburse Dr. Nystrom directly for (a) costs involved in travel from his home, which is in Winston-Salem, to the Institute and return, and (b) lodging and subsistence while he is visiting the Institute. You agree to pay us promptly after the end of each calendar month the sum of $2,242 representing salary and fringe benefit costs; in the event Dr. Nystrom's services are required for any period less than a month a pro rata payment will be due. It is understood that either you or we may terminate the arrange- ments made hereby at will• If the foregoing is acceptable, please sign and return to us the enclosed copy of this letter Very truly yours,• R. J. REYNOLDS INDUSTRIES, INC. Director ~f Research ACCEPTED: DATE: TIIE COUNCIL FOR TOBACCO RESEARCH - U.S.A., INC.
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9-29-71 The Couuctl for Tobacco Research - U.S.A., Xuc. 110 East $gth Street Ne~ York, Ne~ Yo~ 1~22 At~eu~ Hr. W. T. Hoy~ ~ecu~£ve Director Dear S~rs: ~ ~ve r~ues~ed ~he se~ces of Dr. ~artes ~. ~sCr~ tn c~o~t/ou ~ith wo~ be~g perfo~ ~ y~ be~lf by ~s~ Research I~ti~ce. We are ~11~S the se~ices of ~. ~scr~ ~ailable Co y~ ~ the sac for~ It ~ ~ent~ ~t y~ ~11 re~urse ~. ~str~ dlrectly ~or (a) c~ts i~olv~ ~ Cruel ~r~ h~ h~, ~Ich ~ in Wl~t~-Sal~, to the ~tl~te a~ re~, a~ l~g~g a~ s~tence ~lle he ts vleit~ the X~tl~te. Y~ agr~ to ~ ~ pr~tly after the ~d of ~ m~th the 8~ of 8_ r~res~t~g ss18~ ~ ~r~ge benefit costs; ~ ~e ~t ~. ~str~'s se~icu are r~lr~ ~ ~ ~ri~ less ~n s ~th 8 pro rs~ ps~t ~11 due, Zt ~ ~e~t~ tha~ et~ y~ ~ we ~y te~te the a~a~ts ~de ~reby at ~11. I£ the £~;egot~ ~ acceptable, ptease s~ ~ ~J
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to us the enclosed copy of this letter. Very truly yours, Director of Research .... THE COL~CIL FOR TOBACCO RESEARCH - U.S.A., INC.
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YalcUnivcrsity 22 September 1971 SCHOOL OF MEDICINE 333 Cedar Street Deparlment of ,4natomy }~. H. If. Ramm, President Council for Tobacco Research, Inc. 110 East 59th Street New York, New York 10022 Dear Br. Ramm: I hope that you will excuse the delay in my reply, but I have had my regular activltges complicated by a very complete physical examina- tion before committing myself to this letter. All seems excellent except for a small hernia au~aented by Doria's clean up activitites. I agree to: serving as a member of the Scientific Advisory Board to the Council of Tobacco Research beginning immediately, ~and in antici- pation of assuming half time responsibilities as "Scientific Advisor" beginning July 1, 1972 (probably classified asa Scientific Consultant) and in anticipation of becoming Scientific Director beginning July i, 1973. The period October i, 1971 to June 30, 1972 will be considered a pro- bationary period during which the Council for Tobacco Research and I will determine whether the anticipated future will be mutually effec- tive but, thereafter, will be firm. It is understood that stipend prior to June 30, 1972 will be on the usual per diem basis and, after July i, will be $45,000 per annum until fall time responsibility will be assumed and, thereafter, beginning at $75,000 per annum. The sincere interest of the Scientific Advisory Board of the full time staff whom I have met and the representatives of the tobacco industry in .problems of health and ways and means of assessing contributing factors and of improving them has been noted. The enthusiasm of the members of the Scientific Advisory Board for the general policy of the Council for Tobacco Research has been appreciated and is primarily responsible for my decision t6 assist in the endeavor of determining the relevance or
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22 September 1971 Mr. B. H. Ramm, President Council for Tobacco Research, Inc. page Two. irrelevance of different aspects of environment upon disease processes, particularly pulmonary and cardiac. I am confident that the tobacco industry is interested in quantitative methods for determining contributory factors to age-associated disease, with consideration of intrinsic.(genetic or familial) and prevalent ancillary environmental changes. This is a most challenging problem, and I recognize my limited experience in all except the cancer area and appreciate your confidence that I may broaden to encompass the other aspects of cardio-respiratory diseases. Sincerely yours, William U. Gardner, Ph.D. Professor of Anatomy WUG :Lee ',J't u1
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THe.: COUNCIL :I,'O~t To~CCO R~.:s~:~¢c~-U.S.A., ]No. llO ~;AST figTH STREET NE~" YORK, N. Y. 10022 September 2, 1971 Mr. A. H. Galloway Chairman R. J. Reynolds Industries, Inc. Wlnston-Salem, North Carolina 27102 Dear Alex: You will, I think, be interested in reading the enclosed copy of an address that Dr. Robert C. Hockett gave last Hay at the Conference on Social and Economic Issues Confronting the Tobacco Industry in the Seventies, which conference was sponsored by The College of Agriculture and Center for Developmental Change of the University of Kentucky. In his address Dr. Hockett outlined the philosophy of the plannlng and execution of the research program of CTR. Footnote references made in the address have not been included but will be sent to you upon request. Sincere ly, H. H. Ramm President HHRzek encl. cc: Hr. H, C. R~e~er
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AN OVERVIEW OF THE TOBACCO AND HEALTH ISSUE (Conference on Social and Economic Issues Confrmnting'the Tobacco Industry in the Seventies) Sponsore~ by The College o£ Agriculture and Center for Developmental Change, University of Kentucky, Lexington, Ky. May 17-19, 1971 RobertC. Hockett, "Ph.D., Associate Scientific Director The Council for Tobacco Research -.U.S.A., Inc.(1) A few"years ago I had the privilege of attending a previous symposiumhere at the University of Kentucky when appropriations for tobacco and health research had been received from the United States Department of Agriculture. Among the presentations made a~ that ~ime were several given by members of the University and Experiment Station staff and faculty, who provided a very considerable parade, of talent. I remember especially being, impressed by the potentials for mDdifying the.chemical and physical properties of tobacco by means of genetic manipulations, variations in cultural conditions and by alterations in processing methods. The repetitive ~lea of these scientists was,-"If the investigators of health problems can tell us how they wan£ tobacco altered to make it 'safer' for smoking in the form of cigarettes, we are quite confident of being able to accomplish the changes desired." There was, ~owever, n6 answer given to this question. The geneticists, biochemists, agronomists and processing, experts were compelled to retire without having been given any clear goals toward which to target their investigations. The inability of health research@rs at ~hat time, to provide such goals, did not, of course, stop all progress. It did however, compel the il g~n~ticists and agronomists to conduc~ their studies largely at a descri~tiv~ level, that is to record and catalo~ the changes in tNe ultimate~ composition.
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processed tobacco or its. smoke tha~" can be br6ugh£ about by the kinds of systematic alterations they can achieve. For example, it has been possible to determine how the kinds, amounts and application schedules, of nitrogenous fertilizers affect the levels of certain nitrogenous constituents in theproduct tobacco and the corresponding levels of several nitrogen compounds in the smoke.(2) Thus a stockpile of information.is being built up which can be drawn upon if and when' criteria can be defined fpr assessing any health consequence of higher or lowe~ levels of such compounds in smoke• ' Obviously, if there were some simple, reliable system for testing tobacco or its smoke for relative "safety," for human use, a much more highly organized and systematic program could be plalned for achieving the goal of maximum s~fety, and carried out more efficiently than the present" descriptive work which cannot truly be targeted toward a health goal. This is the kind of plan'ned program that Experiment Station personnel and health agencies would like to undertake. Unfortunately there is no simple ihdividual test or even battery of tests adequate to guide such a program. Such" tests as exist are no better than the hypotheses or conjectures on which they are based. T~e complexity of this problem has not everywhere been recognized ind eagerness, for a systematic "safety program" has apparently seduced some investigators into placing an unjustified reliance upon certain test syst@ms such as mo~se skin painting with cigarette smoke condensates. H~wever, before commenting upon this test method and others regarded as better by their proponents, we should pause to comment, upon the origins of the view that cigarette smoking is a "major hazard to human health." There is not time today for any detailed examination of the evidence. You are all aware, however,, that the conjecture has arisen largely out of epidemiological studies that reported statistical associations between cigarette smoking and the rates of incidence or death rates from several diseases. These
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included cancer in several sites,-v~rious cardiovascular diseases and chronic ailments of the lung as well as numerous other diseases in such variety and dSversity, in fact, as to.strain credulity.(3) " It is universally conceded that the causes of diseases cannot ever be d:~ermined by such epidemiological studies alone.(4) These may point to areas in which laboratory experiments with animals integrated with human clinical "observations are needed to explain and i~terpret t~e real meaning of statistical relationships gleaned from human population s~u~ies. Experts in the field have pointed out many unsolved'problems relating to the epidemiological approach. Perhaps the most disturbing criticism of existing studies i~ that in human populations, the smokers and no~smokers are self-selected instead of being assigned at random ~o these groups as would be ? the case in any competent animal experiment. (5) At present we do not know enough about the conscious or unconscious motivations involved in the adoption or maintenance of cigarette smoking to judge fully the niture and extent of the differences between the smoking and non-smokihg populations or to determine whether these differences are themselves associated with disease predispositions apart from smoking. Nevertheless, wherever such differences have been explored" at the levels of-personality, body build, electroencephalography, style of life, vocational interests, or psychological makeup, they have been found to be real, It is important to look for still other differences and ~specially to find out in each case, whether or not the differences themselves or any health differences associated with them antedated adoption of the practice of smoking. In lung cancer studies, especially, many authorities have pointed out the inadequacy of death certificates as evidence with respect to cause of death,(6) and the great probability of under-diagnosis in earlier times on account of general unawareness of the disease(7) and the lack of clinical diagnosti? methods, particullrly of methods which could readily differentiate between this L~
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disease and others such as "galloping consumption" or pneumonia. Post-mortem pathology was actually capable of providing a rel~able diagnosis for a century before the disease reached any very general medical consclousness.(8) In those few centers where autopsies were conducted frequently, the disease was not only recognized but found to occur at a rate c~mparable to that which is reported today.(9) . The @ecent development of a virtually universal consciousness of the disease together with dissemination of such techniques as improved diagnostic " radiology, bronchoscopy, exfollative cytology, and exploratory thoracotomy, have greatly increased the yeporting of the d~sease, These developments are certainly to be applauded insofar as they bring about more effective treatment.. Their widening ~pplication, nevertheless, has probably produced a qui~4 fictitious picture of the exteni of actual increase in incidence of the disease over a period Qf time. Something has certainly been added to the picture by over-diagnosis due to the recent spotlightof attention on this disease.(10) While this situation may not greatly affect the responsibilities of the medical profession in the realm of management, it presents a problem to the students of etiology who depend upon an accurate picture 0f changing incidence over time if they are to make reliable correlations with environmental factor~ that have similarly changed over the same period. Other problems remain unresolved. The ordinary death certificate does not always by any means reflect or include all the information gained post- mortem or even clinically, and continues to be primarily a document required for (II) legal purposes rather than a sophisticated medical report. For example, the distinction between primary lung cancer and secondary metasta£ic cancer in the lung is not by any means easy to make in many cases, and since it is of relatively little importance tothe physician responsible for treatment, is not generally attempted with @ny assiduity. To the student of O o o t~
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o o etiology, however, this distinction is of pri~e i~portance. I'am advised that the death certificate data tabulated by the government statisticians do not provide • . : .... any firm basis for apprehending time trends in the incidence .of-~rue primary ~" ~ ~-~~ carcinoma of the lung. (12) Many other confusing problems could be mentioned but because of time limitations I will mention only three more. One is the matter of substantial differences in the incidence of lung cancer in various geographical areas, which do not correlate with the reported levels of c~ar~tte smoking in those areas.(13) There are areas where lung cancer is reported to be very high while cigarette smoking is minimal and others with the reverse situatiQn.(14) Adequate .analysis of all the factors that may be involved would require resources on a scale that can probably be provided only by a major international health agency. A second problem is the persisting substantial differences between lung cancer incidence in females as compared to males, including overall incidence, relative incidence of the various cell types and a different pattern of association with cigarette smoking.(15) Still a third enigma is the gradual rise in the age of " peak incidence of cancer in the lung during the era when cigarette smoking was steadily increasing.(16) One would expect the age of Peak incidence to declineif an increasingly prevalent environmental agent were the major causative factor. In view of such limitations and uncertainties in the interpretation of these epidemiological studies, the Scientific Advisory {o~rd to The Council for Tobacco Research, has adopted a rather agnostic attitude toward the existing epidemiological evidence. They have not abandoned epidemiological studies,, but are sponsoring several investigations by statisticians who are further analyzing great col~ections of data already accumulated in .m.ajor clinics, in the hope of gaining new insights. Meanwhile they are concentrating particular attention upon . experimental and. clinical studies. 0 • 0 W
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Their policy is to emphasize study .6f the ~iology of "those diseases reputed to be linked statistically with tobacco use. The three diseases or classes of diseases particularly involved.are cancer, diseases o{ the cardiovascular" system and the chronic pulmonary diseases such as emphysema, bronchitis, asthma and other~. These happen to be the diseases that have become the greatest current medical problems since substantial conquest of the great infectious diseases of the past. They are all largely unsolved as to etiology~ They are all "constitutional diseases," which means that they develop slowly over a long period of time and come about through r~latively gradual failure or distortion of normal bodily mechanisms. Xn their-certainly multifacEorial origin, it can hardly be doubted that congenital differences in the efficiency and reserve capacity of enzyme systems, hormonal capacities and balances, and in the operation of homeostatic control systems are involved. Of course environmental influences place constant demands on these internal mechanisms, but their capacity to meet these demands and to continue to adjust to them effectively must depend to a large degree upon genetic endowments. The medicine of the future must certainly be increasingly preventive It would seem destined to undertake discovery of potential as well as palliative. - weaknesses in the b~dy's internal mechanisms in time to protect them against. challenges-beyond their capacity, or, better, to fortify those adaptive "'~ capacities against premature breakdown. This goal does not diminish emphasis upon the need for placing reasonable controls upon the cH&llenges of the environment but it does impose the additional task of describing the role of many bodily functions in dealing with the vast number of inescapable environmental agents. No one supposes that the vast research implied by this statement • will be accomplished quickly or easily. Meanwhile, to the extent that functional deficiencies can be detected in individuals, they can be taken into account, not only for bolstering his inadequate internal mechanisms but also for giving him selective protection against the challenges he cannot handle adequately. A familiar illustration is provided by the diabetic, whose deficiencies in th~ O o
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metabolic handling of carbohydrates are~sometimes managed by reducing the load his metabolic machinery is called upon to handle,.'and sometimes by bolstering his available insulin supply, or by both. Another illustration is the congenital glucose-6-phosphate dehydrogenese deficiency responsible for t~e condition known as "favism," that develops when persons deficient in this enzyme consume lava beans. The same beans are eaten with impunity by persons with a "normal" enzyme component. Obviously if fa~a beans were i.nvestigated by the health authorities of a kingdom where the enzyme deficiency was universal, the~ would be rated as poisonous whereas in a kingdom of normal persons they would be rated as wholesome and nourishing. Thus Lucretius' dictum of two thousand years ago has been verified: "What is quite literally food to 6he maymay be fierce poison to others." The significance of this enzyme deficien~ extends bez~nd the matter of lava beans since it also infiuences the effects of certain drugs used in areas where lava beans are unknown. I am not aware of any method for offsetting deficiencies in this enzyme and have the impression t~at in this case the only recourse is avoidance of agents that the deficient patient cannot handle. All the foregoing has been mention6d here to explain the philosophical atmosphere in which the program of The Council is being pianned and carried out. It 9mphasizes etiology of the diseases that have been mentioned, now little " .understood, and it places great attention upon congenital and constitutional factors as essential .to the understanding of etiology. Investigation of the responses to tobacco smoke is very definitely included in the program, but th4 design of biological test systems for such investigations is tremendously influenced by the.concepts of constitutional disease that have been outlined. I use the plural "systems" advisedly since I feel sure that quite a considerable number of systems will have to be used, hopefully interlocking systems, before the ~igsaw puzzle can be filled out toshow whether, how, to what extent and in ~ whom the smoking of cigarettes can contribute to etioiogy of any constitutional disease. ~
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This now brings me back-5o the mous~-skin painting te~t" for further comment. Some of you will recall that following the epidemiological reports that aroused-the 'original' concerns about tobacco, .a number of.che.mists undertook. analytical work aimed at finding out whethe~ any of the so-called "carcinogenic s~bs~ces" already known to chemistry ~ere present in tobacco smoke~ • This search required .fractionation of smoke. New and powerful separation techniques, particularly chromatography, and physical-chemical techniques for identifying substances in very m~nute quantities were brou.ght .to bear. Many of the well-known "chemical carcinogens" belong to the class 6f polynuclear hydrocarbons. It turned out that the most abundant me~ber of this class detectable in cigarette smoke by modern methods was benzpyrene. Several ]~ighly skillful chemists failed to detect any benzpyrene at all in smoke because of the very minute amounts. In earlier times it would probably have been reported as undetectable. But finally it was agreed .that it is actually present. You may recall newspaper headlines reporting that a "carcinogenic substance had. been i~entified in cigarette smoke." But this is a ~quantitativ. e age. It is no longer sufficient to ask, "Is there enough to be of any consequence?'.' "Is it there?" We must also ask, Meanwhile, biological investigators recalled the history of coal • tar investigations that led to discovery of several carcinogenic polynuclear hydrocarbons in this complex mixture. Coal bar painted o~ the skins of mice produced cancers and this test was therefore used to guide chemical fraction~tions until several of the active ingredients such as benz~yrene were finally isolated. The same technique was applied less logically to cigarette smoke condensates perhaps because these condensates, bein~ black and viscous, look-something like coal tar and also because .biologists were familiar with the mouse-skin painting techniques. Although several investi.gat.ors had negative results, others reported
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a marginal activity if sufficient q~antit/es .df c~ndensate were 'a~plied to sensitive mouse strains for a long enough time. The tumors so produced were ~mostly non-malignant, and thosejudgedto be malignant-h~ littl~ Invasivepdwer. and did not metastasize or "seed" to other parts of the body as do mouse skin tumor~ induced with benzpyrene. Especially notable is. the fact that even this faint activity cannot be attributed to benzpyrene since the latter can be'added to smoke conden~ates to increase the content thirty-five fold withou£ altering the mouse-skin activity. This finding largely removed the spotlight of suspicion from benzpyrene as a potential cancer agent in cigarette-smoke. Nevertheless, no other substance has emerged out of analytical studies to replace benzpyrene as an object of suspicion. These findings have not generated any newspaper headlines. Primates (monkeys and apes) are very much more resistant to skin painting with the "carcinogenic" polynuclear hydrocarbons than mice or rabbits.•. Though it is not feasible to conduct such experiments with men,the relative great resistance of human cells to "malignant transformation" by such substances has been confirmed in tissue cultures. It has also been pointed out that c~tain- medicinal salves containing coal tar have been used harmlessly by humans for generations in the treatment of skin disorders, whereas these same salves readily induce skin cancers in mice. Of ~rse, human smokers e~ose.their skins to cigarette smoke for years on e~d and often have yellow fingers, but no skin tumors have ever been reported from such exposure. .. The mouse-skin painting test has persisted nevertheless, being used on the assumption that it might measure overall "carcinogenic" effects of a whole battery of substances, including perhaps unidentified carcinogens, inhibitors, ~nd promoters, acting in concert. The test has been used, in fact, as a guide to modifying tobacco ~roducts on the assumption that a diminution of mouse skin o o o ~o
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o • activity by the corresponding smoke condensates will be an indication of greater "safety" in its use by man. As I have said, I regard this as a very naive assumption. While skin testsof this kindmayprovide some certain kinds of information that will ultimately be useful in building the total mosaic of knoew~edge, they certainly do not provide any simple or direct measure of any human hazard in cigarette Smoking~ For one thing the tegt includes'the tacit assumption that the only effect of consequence in relation to lung cancer pathogenesis is the potential activity of tobacco smoke as a direct contact carcinogen. There is no reason to'assume that this is so-and-toneglect a dozen other hypothetical possibilities. If delay in clearanbe ~f air-borne carcinogens from the lung shoul~ be.a factor in lung c~rcinogenesis, then the effects of tobacco smoke on lung'clearance mechanisms might be r&levant. If chronic irritation, of the lung increases its susceptibility to carcinogenic influences from any source, then potential irritants in tobacco smoke might be relevant. If inadequacies of the immune system permit repetitive bacterial or viral i~fections of the lung that pave the way to eventual malignancy, or lower the ~efences against "transformed" cells, we may be interested in the.effects of chronic smok~ inhalation on the immune system. .And so on. .- : I oncesummarized some of the inadequacies of the mouse-skin p~inting system in relation to the human lung cancer problem by pointing out that it involves the "wrong material, in the wrong form and in the wrong dose, : applied to the wrong tissue of the wrong animal.''(17) Smoke condensates are the-"wrong material" in that they do not contain all the ingredients of whole smoke that impinge upon the lung surfaces of smoker~. They are Stale, relatively speaking, and may not contain all the short, lived substances present in fresh smoke.- They may contain other u~ o o
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artifactual substances formed during storage but not present in "f~esh smoke. (18) Condensates differ from fresh smoke in physical form, being "blobs of glob" instead of.an aerosol of tiny liq~d droplets bearing electric ~arges. Skin painting as ordinarily practiced, uses dosages Mat con6entrate a far greater amount of mate~al on a unit area of skin than is'experienced by ~y ~quivalent area of Me enormo~ internal lung surface during normal human sm~ing.(19) The skin is Me wrong tissue in Mat it differs radically from Me l~g, being protected by fat- soluble sebaceous material while Me lung surfaces are bathed by a hydrop~ilic mucus. And it differs in a good many o~er ways as well.
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o; A complication in such s£udies is the fact that handlingand confinement in the machine is stressful for animals so that "machine controls" ~must be employedwithout actual smoke exposure, as well as unhandled cage controls if the effects of smoke inhalation are to be separated from stress effects. Unfortunately this device does not allow us to s£udy smoke effects separately from those of stress, but it has .opened the way to some most interesting studies of the biochemical effects of stress. We hope we are now ready to begin studying the effects of smoke exposure on a considerable number of bioiogical and biochemical systems such as those hinted at in the ~iscussionof constitutional disease eti61ogy above. At this stage we are far from ready to compare different varieties of tobacco. Oh the contrary it is necessary to use a uniform, fully described ~'reference cigarette"to minimize variations in the smoke being used in these investigations. We are indebted to the University of Kentucky for undertaking to provide such cigarettes. Still further we have found it necessary to improve the • standardization of animals. For most studies," cesarean-derlved animals substantially free from pathogens are employed and their virus profiles are determined as fully as possible. The availability of many inbred strains of.mice ." with known congenital tumor susceptibilities still recommend6 the useof mice for much cancer research. As inbred strains of hamsters and information On their virus status have developed, studies with this species have been started in 6as~s where the larger lung and greater blood volume are an advantage. Recently, still another dimension has been added to the cancer studies through application of the viral genome conceptof cancer.(21) This concept postulates that leukemia, sarcoma, and carcinoma are all expressions of a ver£ically-transmitted "vir~l genome" present in all mammalian cells, which
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probably performs some normal and ~e'cessary function in the embryonic stage and then is normally repressed or "turned off." This repression may ultimately fail under influences such as aging,-exposure to radiation, viral infection, chemical agents or others still undescribed. Under certain circumstances the genome may give "$ise to transferable (but rarely spontaneously transmissible) "C-type virus particles" that can produce cancer in a suitable host. The ramifications of the concept are enormously complex. But it appears to be providing a rational interpretati6n of many empirically described differences in the "susceptibility" of various mouse strains to cancer, and techniques for manipulating these susceptibilities exp~rimentally. ~n The Council program, we hope that the use of models based on these concepts will help elucidate the interplay between;internal mechanisms of cancer susceptibility and resistance o~ the one hand, and the role of external agencies on the other. In this instance, it is possible that pursuit of the ramifications of the viral genome concept could discover some general method for identifying cancer-susceptible persons and bolstering their defenses to prevent the disease. In The Council program of exposing animals to the inhalation of whole, fresh, normal cigarette smoke, it is possible to distinguish several categories. First, there are the purely descriptive studies~ Following exposure of various strains and species to defined •levels of smok~ for various p~ri~ds, they are sampled for description of the histopathological state of the lungs and assayed for selected bloch~mical and immunochem~cal changes. If any disease ultimately develops, antecedent changes can hopefully be assessed as early warning signs. o o o
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In other cases, the effe~t~ of smok~ inhalation on a "specific biological system that, by good evidence, is thought to be related to disease • ~> fsusceptibility are being observed. For example, there can-be little doubt of" ~ the importance of the pulmonary alveolar macrophages in the defense of the lung : .... against extraneous material. Hence the influence of smoke inhalation upon the mobilization, metabolism and pbagocytic capacities of these scavenger cells is being studied. In such cases, the exposure of the ~hole animal to smoke inhalation followed by collection of macrophag~ is considered preferable to test-tube exposure of the latter, since all the homeostatic and feedback mechanisms are operational in the whole animal. In a test tube, the effect of smoke on mobilization of macrophages cannot be seen and the important role of ~this factor in the total effects is neglected. in the present stage it may be said that we are searching for ~systems that might show significant biological effects of smoke inhalation under conditions reasonably comparable to those of normal human exposure. after such systems have been developed and evaluated will it be reasonable to Only use fixed biological systems for comparing different tobaccos or different smokes, or of attempting fractionation to identify the active ingredients, or of delving" into the biological mechanisms of the effect with a view to offsetting them. I feel that there are important criteria to be applied in selecting systems for study. We are attempting tQ §~}~ct systems Eat have a high probability of bearing upon th~ diseases in which we are interested. If such criteria are not used in selection, a program can d~enerate into the colle~ion. of interesting but presently useless information rather than providing answers • to clearquestions. For example, our Scientific ~dvisory Board is presently disinclined to sponsor further studies on ~he possible effects of nicotine or o o smoking on blood clotting mechanisms ~ecause of substantial doubt whether ab~$rmal clotting mechanisms are really involved causatively in "c~ronary occlusion or myocardial infarction."
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The Council has still ~nother objective'in attempting to provide positive models for the production of sguamous carcinoma in the lungs of animals. o~L~/If'some simple method can be devised that does not depart .too radically from the. kinds of experiences met by men in daily life, it could be most useful. If lung cancer of the type that is prevalent in man could be produced repetitively at a sharply reproducible level, say 20%, in mice or some other animal, the way would be opened for a'great many organized systematic studies to see how age, sex, hormones, irritants, stress, diet, infection a~ many other factors might influence the level and rate of incidence of the tumors. I fear that I may now be close to exhausting the time and my listeners without ~xhausting my subject. May I nevertheless refe~ briefly to three more. aspects of The Council program. First is the matter of cardiovascular diseases of which several, especially coronary artery disease, are reputed to be more frequent in cigarette smokers. In the earlier stages of our program, a great deal of nicotine pharmacology study was sponsored in the hope of finding some clues as to why such an association should exist• In fact no substantial clues were found. Meanwhile twin studies in Sweden have shown the predominant importance of hereditary factors in'this disease.by, comparing identical twins one'of whom has been a cigarette smoker while the other has not. No significant differences in cardiovascular functions or symptoms or in age at death were observed• A less comprehensive study of American twins pointed in the same direction. At present there are two outstanding needs in our coronary disease. study program. First. is a good method for the controlled production of ~coronary atherosclerosis in some experimental animal. The lesions should be comparab{e to those found in man, anatomically and histologically, and should be produced by methods not too "contrived" or~"unphysiological." If the condition
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could be produced at will and with predictable severity, then the influence of many environmental factors, including smoke exposure and nicotine, could be ~i~1-sthdied systematically. Of course attempts have been made to measure the condition of human coronary arteries post mortem and relate severity of the lesions to environ,- mental factors• It is very difficult to get accurate data on life habits, such as smoking, diet, exercise, etc., retrospectively after the death of a patient. Yet the most random post mortem samplings.of the healthy human population are probably ~hose provided by accidents, especiallyautomobile accidents. Several studies of accident victims have reported no relation b~tween the degree of atherosclerosis and amount of smoking.(22) But the difficulties of such human" studies recommend the concurrent use of an animal model for expeaiting systematic attack on the problem. Another key problem, still unsolved, is that of measuring with ~ccuracy the relative rates and amounts, of nicotine absorption into the body by smokers of cigarettes, pipes and cigarsrespectively, under real-life conditions, as well as the rates of disposal and metabolic change of this alkaloid under these conditions. A knowledge of the kinetic pattern should solve the question whether there are significant differences in.the nicotine dosage of smokers in these three categories when smoking in the normal fash$on. This is most important to know because pipe and cigar smokers are reported to" develop coronary artery disease even less often than nonsmokers.(23) If it should turn out that they absorb as much nicotine as cigarette smokers, an~ attain similar peak levels in the blood, of comparable duration, it would seem ~o follow that nicotine could not be implicgted in'coronary artery disease. this proved to be the case there could be a redirection of effort into more If. promising channels~
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In the study of chronicrespiratory diseases, partichlarly in determining their causes, a basic problem is the lack of g.enerally accepted ." ./.clinical distinctions among the various .respiratory diffi.cultie.s.. These ~ .... include emphysema, bronchitis, asthma, and even certain heart ailments. -~ Inadequate definitions and the lack of uniform clinical distinction of these conditions" have confused attempts at epidemiological studies of causation or aggravation. It appears also that diagnostic uncertainties and doubts, as well as changes lh ~he popularity of such terms as "emphysema," may have resulted in a fictitious increase in reported incidence rates.(24) Hence, The Council is supporting.a long-term study in a pulmonary disease clinic where comprehensive and repetitive observations can be carried out on many chronic patients over a lon~ period of time. The hope is that numerous biochemical, pathological and radiological observations can eventually be correlated with the clinical course to produce better definition as well as improved diagnosis and trea~nent of chronic lung disease entities. At the same time, new etiological insights may develop. A relatively new aspect has been added to emphysema studies by the -discovery that a lack of the enzyme inhibitors which normally protect the lung-" from "digestion" by. proteolytic enzymes.from bacterialor from bodily origins is a factor in this disease. This enzyme deficiency, being clearly congenital, is another example of the kind of deficiency that may predispose to many other constitutional diseases. At the present time, most of the pharmacological studies being supported by The Council are concerned with the effects of nicotine and/or "" smoking 0nthe central nervous system, with the object of learning more about why people like, need or want to smoke. It has been shown, that nicotine reaches the brain of mammalian species, presumably including man. In certain ways ~t. facilitates the learning processes.in rats and there is evidence that it can produce a true tranquilizing effect in man.
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- 18- In summary, I have attempted to present an "Ov&rvlew of the Tobacco and Health Issue" by describing where The Council is placing the emphasis in its program and why, since this involves implicit jud~,ents as to the validity.and significance of the various observations that have given rise to present widespread attitudes on the subject. If youwished me to lookInto the crystal ball and forecast future developments in th~ general climate of opinion, I would have to say that my particular crystal ball.may not be infallible. But the present prevalent attitudes toward the tobacco-health issue have such momentum apparently, and the progress of sound and methodical research is unfortunately so slow, that I would expect the situatioh.for tobacco producers and processors to becom~ somewhat worse before it improves. But at the s~me time, "I believe that as we gain a better understanding o~ the origins of.the constitutional diseases, there will be a progressive attenuation of the claims that oigarettes are a "major health hazard. C) . 0 U1 0 O%
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ADDENDUM Requirements for any Mechanical Arrangement for Expgsure of An~.mals to the Inhalation Cigarette Smoke under Conditions Comp~rable~t~ "those of Human Smoke Exposure ~ For the past 15 years The Council for Tobacco Research - U.S.A., Inc. has been concerned with the'proper bioassay methods for tobacco smoke inhalation research. The scientific staff recommends that the following factors be considered when using an animal model. First and foremost, meaningful data can only be obtained if the whole smoke delivered to the lungs of the animal is i~ the same physical and chemical state as that which reaches the respiratory tract of the human during normal ' cigarette smoking. Since most animals cannot be made to conform spontaneously to such conditions, the smoke for inhalation by animals must generally be produced by mechanical means and delivered to the animal under the right conditions. In order to accomplish this, it is necessary to use a mechanical device - smoke inhalation exposure machine - that will produce conditions simulating hLtman s~oking as closely as possible. It~hould meet the following requirements: i." It must produce s~oke'by intermittent puffing of individual cigarettes(1) with accurate, and reproducible puff volumes, puff durations and puff intervals, all regulated to fall within the range of human smoking mechanics as determined by observation of human smokers, smoking normally. The conventions most generally adopted at present are a 35 ml. puff of two seconds duration, taken at one-minute intervals, to a 23 ml. butt length. The machine should, however, ~ave the capability for accurate modification of these puffing c6nditions in order to extend the range of possible observations. 2. It should have a port to permit sampling of the smoke stream for • chemical or gas chromatographic analysis, when desired. '~ 3. In order to permit biological compar~isons of gas-phase effects with those of whole smoke, the machine should permit insertion of a Cambridg~ " filter to remove particulate material from the smoke and allow only the gas-vapor phase to reach the animals. ~ :~ ..... 4. Since human smokers draw a puff of smoke into the mouth and then inhale it into the lung along with fresh air, the smoke must be diluted by air in a ratio determined by human experience. The ratio of dilution by human smokers is determined by the~individual's puff volume (15 ml. to 45 ml.) and his tidal volume. These vary so that the ratio of dilution may range from i:4 to 1:40 at the extremes. Mechanical devices need to be adjustable over such a range as this so that the ratio will be known in any individual experiment and can be varied. "(1)Under special, carefully controlled conditions, two or three cigarettes may ~ be puffed simultaneously. . o~
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5. The time of smoke transit" from the burning zone of the cigarette to the lung surface must be close to that which occurs in human smoking (or within the range) so that the smoke will be of comparable age in terms of fractions of a second. This age control is to insure that chemical and physical changes such as are known to occur rapidly in smoke after its instant of formation will be comparable for the animal and man. Such age control is usually achieved by regulating the distance from the burning zone of the cigarette to the lung surface of the animal, but can also be modified by ~egulating the rate of flow. If this cannot be made the same as for man, the distance must at least be constant'andbe known. These requirements also make.it necessary to expose animals in individual .containers where t~.ey occupy fixed positions rather than in groups. 6. Since humans inhale smoke-plus-air from the oral cavity without its passage through the nasal turbinates where particulates might be trapped and thus fail to reach the lung, it would be'an advantage to induce experimental animals to inhale through the mouth. This is being attempted through nose sealing with rodents with the disadvantage that the procedure is made much more traumatic. Mouth inhalation is easier to attain with dogs but at the cost of othe~ complica- tions. 7.. Since smoke inhalation by humans is intermittent, and air is inhaled between puffs, there is a minimal buildup of carboxyhemoglobin in the blood in normal smoking. Animals must be given similar intermittent conditions by purging smoke and gases from any chamber .in which they may be housed, or by giving adequa£e access to air between smoke inhalations. If this is not done, blood carboxyhemoglobin builds up to a point where significant physiological effects reshlt. 8. Animals must be @xposed with only.the breathing apparatus in the mainstream of smoke. If there is smoke contact with the fur, they will preen themselves or lick one another and receive dosages of nicotine and other smoke constituents that are not taken into account. 9. Since some of the conditions described as necessary are traumatic to animals, stress effects may complicate the results. IIence "machine controls" subjected to all the same conditions as experimental animals except for actual smoke "inhalation must be used to apprehend such effects. (Very substantial stress effects have been observed in recent studies.) Gradual training and habituation may be. of some value in reducihg s~ress. .. i0. Some metho'd of measuring t~e' actual exposure of lung surfaces to smoke, both to gas-phase and to particulate material, is necessary if dose- response relationships are to be determined in other than very qualitative terms. Gas phase contact with lung surfaces is best indicated at present by blood carboxyhemoglobin determinations since carbon monoxide is not appreciably absorbed in the oral or nasal cavities but is rapidly taken up by ~he blood through the pulmonary membranes~ Blood analysis for carboxyhemoglobin is suitable 'for routin@.monitoring of gas-vapor phase exposure of the lung.
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Measurement of lung contact s~ecificall~ wi~% particulates" is more difficult since a tag is needed that is present in the particulates but absent from the gas-phase. Nicotine fulfills this requircmeht but its ~sorption, transport and metabolism are so rapid that quantitation of lung contact with particulate matter by analysis of lungs removed and fixed i~nediately after exposure is "not satisfactory. .~indications of minimum ~osage have been obtained by this method. Tobaccos to which dichlorobenzophenone or 14C-dotriacontane-16,17 have bee~ incorporated produce smoke containing d~e tag specifically in ~]e particulate ~ase. Experiments are unde~ay to determine lung dosage of smoke particulates by use of these tags Such methods may serve to calibrate the function of particular machines, under defined conditions with particular animal species, but do not appear ~uitable for routine monitoring use. • COMMENTS Most of the conditions listed above have beenattained satisfactorily with new equipment designed to expose small animals including mice, rats, guinea pigs and hamsters. Other conditions such as low stress and direct inhalation of smoke from the burning cigarette (instead of mechanical puffin~) have been .attained with dogs at ~]e sacrifice of various advantages of the smaller animals. N~ system for e~posing primates.tha~ meets all the specifications • listed has, as yet, come to our attention. Animals used in inhalation studies should be fully described as to age,. sex, weight, nut[itional state, physical condition, virus components, extent of surgical trauma, and the degree of stress to which they are subjected. Appropriate numbers of both sham-smoke~, ~nd cage-held animals should serve as controls. The end points to be sought include more than morphological alterations and the presence or absence of tumors. They als~ should include appropriate ~ ~io~emical measurements and their analysis. ~ultivariant analysis should then b~ applied to the data obtained from the systematic observations of the controlled parameters relative to the smoking machine, the animal model, and the biological and bio~]emical measurements. By these means, it may be Rossible to interpret some of the biological effects resulting from exposure of animals to cigarette smoke. Hope~ully these data can eventually be applied to the human. Past experiments, where the sole objective was the attempt to induce t~u~ors, must be carefully and cautiously interpreted in light of today's knowledge.
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Dr. Frank G. Colby If you want copies of these original papers, please let me know. o o
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September 2, 1971 Mr. H0 11. P.amm The Councl] for Tobacco P.esearch 714 Oaklakm Avenue ~qinston-Salem, l~orth Carolina Literature on Nitrosamines in Cigarette Smoke Dear Hr. Ramm: In response to your request which Dr. Senkus transmitted to me yesterday afternoon, I ~m sending you attached the most recent pertinent literature on the above topic. If'additional information is needed, please ca]l me at 761-2481. Att. Cc : ttCR / Bibliography • : ' 1. Pailero M.; Klus, H., DETEKMINATION 6F NITRO~AMTNES IN C~GARETTE SMOKE CONDENSATE, Fachl. Mitteilung Osterr. Tabak 1971 (12) 203-11 (~ay 1971). 2. N-NITROSI~MINES, U. S. Atomic Energy Comm., Rept. Jan. 1-Sept, 1, 1970, ~2-43 (3an. 1971) P, JR Class No. Textbook TS 2240 Gu. 3. :Lijinsky, W.; Epstein, S. S., NITROSAMINES AS ENVIROh~AENTAL CARCINOGENS, Nature 2~5 (5227) 21-23 (Jan. 3, 1970). Johnson, D. E.; Milaar, J. D.; Rhoades, J. W., NITROSAMINES IN TOBACCO SMOKE, U. S. Dept. HEW, Public Health Serv., National Cancer Institute, Toward a Less Harmful C~arette, National Cancer Institute Monograph 28, 181-89 (June 1968). 5. Bar~emsyer, ti., DETECTION AND DETF&MINATION OF DIMETtWLNITROS.~IINE in CIGARETTE SMOKE, Paper, Tobacco Ch~.,ists Research Conf.. 23rd, Oct. 22-2~, 1969. 6. Kroeller, E., DETECTION OF NITROS~IINES IN TOBACCO SMOKE AND FOOD, Dettt. Leb~:nsm.-Rundsch. 63 (10) 303-5 (196V). 7. Neurath, G. • CONCERNING TNE OCC~RP.ENCE O~ N-NITROSO COMPOUNDS IN TOBACCO Facperientia 2__3 (5) l~00-4 (May ~15, 1967).
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Memo to Messrs. A. H. Galloway ~/ William S. Smith Colin Stokes Chas. B. Wade, Jr. August 27, 1971 Annexed is a curriculum vitae on Dr. William Gardner, who has been proposed as a candidate for the post of Scientific Director of CTR. I have been told that he is a specialist in cancer research and that he has a very fine reputation as a scientist. He is presently a Professor of Anatomy at Yale University. He is also President of the International Union Against Cancer. I expect to meet Dr. Gardner on or shortly after September 7. I plan to ask Dr. Senkus to accompany me. Mr. Ramm has advised me that Dr. Gardner is so heavily committed to Yale and other duties that should we desire to appoint him Scientific Director he could not give us any time until July I, 1972. Thereafter he could only give us 5~% of his time for another year, because he would need to stay on at Yale for that length of time to preserve certain pension rights. Should he appear to be suitable for the post, and should he
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-2- be interested in taking it, I am hopeful that we can make some arrangements to obtain his services sooner. I am most reluctant to wait until July I, 1973 for a full time Scientific D~rector. If you have any comments or suggestions, I should appreciate your advising me. Dr. Murray Senkus H. C. R.
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April 13, 1971 Hr. E. A. Vassallo ANNUAL MEETING OF INDUSTRY TECHNICAL COMMITTEE C.T.R. - NEW YORK, N. Y. - APRIL 7, 1971 Present: E. S. Harlow A. Burke I. W. Hughes D. E. Edmond W. W. Bates A. W. Spears H. Wakeham T. S. Osdene Murray Senkus W. Bennett. R. C. Hockett W. T. Hoyt . V. Lisantl - American Tobacco - American Tobacco - Brown & Williamson - Imperial Tobacco - Liggett & Myers - Lorillard - Philip Morris - Phi llp Morris - RJR Industries, Inc.' - U. S. Tobacco - C.T.R. - C.T.R. - C.T.R. Election of Officers The primary purpose of the meeting was to elect new officers of the Industry Technical Conr~ittee. I was elected Chairman to succeed Alexander Spears who has just completed a two-year term. Ward Bennett of U. S. Tobacco was elected Vice Chairman. I will serve as Chairman of I.T.C. until May, 1973. As Chairman of the I.T.C. I am expected to attend all quarterly meetings of the Scientific Advisory Board of C.T.R. and respond to scientific questions as they are raised during the Board's review of applicatlons for grants sent in to the C.T.R. Staff. The Industry Technical Committee (I.T.C.) assists the Scientific Advisory Board of the Council for Tobacco Research on non-medical scientific aspects of smoke technology. o o O
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Annual Meeting of Aprll 7, 1971 Page two Smoking Machlne for Inhalatlon Studies The newly developed smoking machine wlll be known as the Walton-Morrlssey Smoking Machine. Dr. L1santl of the C.T.R. staff reported on its status. Evaluatlon of the new Walton-Morrissey smoking ~achine has just been completed at the Mason Research Instltute in Worcester, Massachusetts. The machine Is now ready for use In smoking-health research on the various projects supported by C.T.R. at various Instltutlons. The machines w111 be built on order bY an approved manufacturer. .l~:has Mr. Colln Stokes Mr. W. S. Smith Mr. C. B. Wade Mr. H. C. Roemer Dr. S. O. Jones Murray~nkus
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o . o UNIVF, ItSITY Oi: CAI,IFOI/NIA, I~OS ANCEI,I~S Mr. H. Henry Ranm~ Chairman and President The Council for Tobacco Research- U.S.A. ii0 East 59th Street New York, New York 10022 Dear Mr. Ran~: The ~nvitation to be Director of Research for the Council on Tobacco Research is indeed exciting. The diversity and quality of your research programs on cancer and diseases of the cardiovascular and respiratory systems were most ~mpressive and the opportunity to contribute decisively to the national and international medical research effort by funding the most highly competent research groups in selected areas who may be passed by because of the trend toward categorical research support is more challenging than I had realized. My decision to decline your generous invitation is then based largely on the fact that my heart is really in Medical Education. Even so, I enjoyed meeting you and your associates very much and am confident that were it not for my deep in- terest in the UC~A School of Medicine at a critical time in its history, we might have had a profitable and gratifying association. With warm appreciation, AFR:pm Sincerely, A. Frederick Rasmussen, Jr. Associate Dean C
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FOR: THE C_0UN~IL FOR TOBACCO P,O,R,_.REL~ASE AM'S OF ~EpNESDAY, MARCH ,2~_, t97~ New York, March 23 -- Significant £indings related to smoking and health, turned up in studies by independent scientists, are described in the 1969-?0 Annual ~eport o£ the $cient~£o tar of The Council tar Tobacco Research-U.S'.A., issued today. Slow but steady progress continued to be ~de and results continued to be published by investigators whose research was supported by grants ~romThe Councllt said Dr, Clarence Cook Ltttle,,£amed cancer researcher and geneticist. He noted that in the per~od covered by his Repo~t, ~he Council augmented its regular grant-In-aid program with search contracte~ thus "re-emphasizing Its desire to speed up the search tar ~he answers to lunK cancer~ heart disease~, chron- ic respiratory ailmentst and other diseases. "T~e process is naturally slow and painstaking because these diseases are ~nenensely complex and have been a££1tcting mankind £or hundreds~ even thousands~ o£ years'||' D~, Little w~ote, "~hile bits and p~eces of ~n~ormat~on about them are reported by entist8 almost every day~ the t~me when the humerus parts the ~11 ~uzzle ~111 be assembled into a cohesive p~cture can- not be pre~icted. "Claims that the puzzle has been solved are totally un~eal- istic by s©lent££Sc standard's and mislead~n~ to the ~bll~ There are ~ar too many' ~estions that re~in ~answered at thai tame." still upon the causation of the disease8 mentioned "slnoo any possible effects o~ to~a¢oo use can be ~nterpreted onl~ in this cent ext." "~he Council for Tobacco ~eaearch w£1~ oontlnue ~te p~ogram in the belie£ that valid sc~ent£~ic conclusions can come only ~om unbiased and complete research," the Report {~ore ) I~ II II I I I
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Since The Council was established in |9~, its :esearch pro- gram has been directed by a Scientific Advisory Board cur~ently consisting of 10 distinguished physicians and scientists, Through June 1970, the Report notes, the Board has awarded stints to 2~9 independent scientists in ~89 hospitals, universities and research institutions for a total of $17~262,O00. These investigators entt~ic Journals reportin~ on this Council-supported work. -O- ~RIEF. HIGHLIGHTS FROM DR. LI~TLE'S Viruses and Cancer The Council is supporting several studies directly related to the theory that cancer may develop from a latent C-type viral ;enema, or genetic potential, found in all mammalian cells, The genome, according to the theory, is normally repressed and inactive, and there is a complex interplay o~ internal and terns1 factors thai'determines ~hethe~, when and how the re- pression control mechanism is somehow broken and cancer An ultimate hope is to contribute toward discovery of methods for Inhibiting or delaying derepreaelon o£ the latent cancer home as a means of preventing or deferrtn8 cancer in humans. • obacco Smoke Studies In a long-term smoke inhalation experiment with mice, no equamoue cell tumors~ the type claimed by some to be associated with smokin8 iu humans, have been found in any o£ the hundreds animals that hays so far been exposed and then subjected to patho- logical exam~nation. ~he m$ce have developed adenomas and idaho- carcinomas, the types o~ lung tumors they get without any exposure to smoke. Progress has been made in developing a smoktn$ machine exposing experimental animals to the ~nhalat~on o£ whole, freah~ normal cigarette smoke under conditions simulatin~ human exposure as closely as possible. Some of the machines are now being used in preliminary studies by various Council grantees. (more) O~
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Heart Research The Council has helped supportresearch £rom which has come a method for measuring blood flow An the arteries that feed the heart muscle without inserting tubes or resorting to surgery. This method1 repeated and confirmed in 1969-70 with tests on'animals and humans, has important implications in the entire field o£ heart di- sease. It has been shown by this method that nicotine does not re- duce blood flow in normal arteries that supply the heart m~scle but generally increases it a£ter the manner of mild exercise. In addition to an ±ncrease in "mecl~anical" coronary blood £1ow~ there is an increase in "nutritional" blood flow as well. Another study reported during the year suggested a negative effect of nicotine on blood clot £ormatton. This research was done with animals. Being continued is a long-term study o£ medical students to learn what characteristics, measured at an early age, wlll turn out to be predictors of early cardiovascular disease. There have been ~1 premature deaths among the subjects, $~ ~rom suicide. The other l? deaths were due to accidents~ coronary heart disease~ can- car, and other ailments. Statistical evidence ~aa r~ported by the researcher do~n~ the study that certain precursors of suicide, cident~ fatal heart attack, and fatal stroke are already present and can be identSfied in youth. Chronic ~es~iratory ~ise~se A Council grantee examined the lung tissues o£ ~00 apparently "healthy" adults who d~ed suddenly and unexpectedly, citer living and working in an urban area noted for its air pollution~ but who had no known disease history. Certain changes (called metaplasia) were £ound in the lung cells o£ both smokers and nonsmokers. How- avert of great importance was the £inding that various degrees these changes were present in a surprisingly h~gh proportion -- percent -- of "healthy~ adults who had never smoked cigarettes, cigars or pipes. There were no cases o£ so-called carcino~ in sttu £n either the smokers or nonsmokers. (more)
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~ra~_~ve P~tterns An ongoing study supported.by The Council deals with the ef- fects of n£©otine or Jmoking on the brain waves of human Jects. One significant observation from the study so far is the implication that heavy smokers may have a different basic prevailing brain wave pattern from that of nonsmokers. The vestlgator believes this pattern may be congenital and that it antedates and influences the adoption of tobacco use. ~orld Literature on Tobacco The Council is continuing sponsorship of a project that has been of great benefit to researchers and others .interested ~n smoking and health. This is the collectlon, abatractlng, and an~lysls of the ~orld literature on tobacco, £ncludlng mental and cllnic~1 studies. A second supplement to the graph on this subject, titled "Tobacco -- Experimental and Cl~nlcal Studles," first published in ~96t, is expected to be published soon. o I II II I I I I I
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T~E COUnCiL FOR TOB.¢CCO RESE~C~ . U.S.A. II0 EAI!~T fiO~H S~ ~W ~OZK. N. Y. ]O02U February 9, 1971 Mr. A. H. Galloway Chairman R. J. Reynolds ~ndustrles, Inc. Wlnston-Salem, North Carolina 27102 Dear Alex : Attached is a copy of the minutes of the Annual Meeting of members of The Council for Tobacco Research - U.S.A., Inc., held on January 29, 1971, and a copy of the ~dnutes of the second meeting of the Board of Directors of The Council for Tobacoo Research - U.S.A., Inc. Sincerely, W. T. Hoyt Executive Vice President WTH: ek atts. cc: Mr. H. C. Roemer
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ndAss~ciates, bz~ P. O BOX 523 • 13 lINCOLN ROAD • GREAI NECK. NY. 11021 • (212)895 7445 FOR: THE COUNCIL FOR TOBACCO RESEARCH-U.S.A., INC. FOR RELEASE IN AM'S OF TUESDAY~ JAN. 26t 1971 RAMM ASSUMES LEADERSHIP OF COUNCIL FOR TOBACCO RESEARCII New York -- H.tl. Ramm, a long-time tobacco industry executives has been elected chairman and president of The Council for Tobacco Research-U.S.A.~ InCa He had been act- ing chairman for the last two years. Recently lie retired from R.J. Re3~lo]ds Industr~es~ Inc., l¢inston-Salem~ N.C. Ramm~ a native of Chicago~ received his undergraduate education at the University of ~linnesota and was graduated from Harvard Law School 5n a929. tie practiced law in New York City until 19~6 and then joined the R.J. Reynolds Tobacco Company in ~'inston-Sa]em as solicitor and assist- ant to the chairman of the board. He was e]ected a direc- tor of the company in 19~6, ~became general counsel in 1955, and a vice president in 19~ ". 1970~ when R.J. Reynolds Industries was formed~ he became chairman of the executive committee~ senior vice president~ genera] counse]~ and a director, lie held these positions until his retirement on December ~, ~970. The Council for Tobacco Research had its origin in when representatives of tobacco manufacturers~ growers and warehousemen organized the Tobacco Industry Research Com- mittee to support research by independent scient2sts into all aspects of tobacco use and health. The research pro- gram is the responsibi]ity of a Scientific Advisory Board~ currently consisting of ~0 noted physicians and scientists~ which has so far awarded grants to 2~ scientists for a total of more than $~7~000~ 000. -0-
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Memo to Nessrs. A. H. Galloway William S. Smith Re: CTR Meeting' January 13, 1971 January 12, 1971 I telephoned Mr- Hoyt this morning and ascertained from him that the agenda for tomorrow's meeting encompasses the £ollowing items: Adoption of By-Laws. Conflnna~tion of me~bers. (cigarette manufacturers) Ther~ are eight Class A and seven Class B members (warehousemen, growers, etc.). 3. Election of officers. follows:. The proposed officers are as Chairman and President . Hr. Rsn~ Executive Vice President and Secretary - Mr. Hoyt Vice President - Robert C. Hockett Treasurer - Chandler H. Kibbee (He has been Treasurer, and is ~n Executive Vice President of Phillp Horrls.). Assistant secretary and Assistant Treasurer - Elizabeth C. Kelly (She is now an Administrative AsSistant to Mr; Hoyt.) ~ " 4, Resolutlon concerning a fldellty bond. 5. Resolutlon appointing an Executive Cou~Ittee. ~hlch is intended to consist of Messrs. Cullman, Finch, Galloway, Tlsch and Walker.
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-2- 6. Itesolutlou fixing regular meeting dates for the Board of Directors. ~. .. . . 7. Resolution adopting a seal. 8. Bank resolutlon or resolutlons, 9. Adoption of 1971 budget, revised lu accordance with increases discussed at the last meeting of the Executive Committee of the unincorporated association. I0.. Adoption by the eorpor'ation of the Retirement Plan of the unincorporated association, s Igued yes terday by Mr. Smith. 11. as amended by the document Kesolutlon authorizing a general assignment and agreement, pursuant to which the corporation will receive the assets and assume the llabilitles of the association. unincorporated 12. Resolution covering the adoption by the corporation of~the various special projects heretofore authorized to be carried out by the unincorporated association. The information retrieval system is one of these special projects, 13.. Approval of contract with Hr. Ranch. 14. Adoption of a resolution authorizing officers of the o o
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-3- corporation to sign contracts and do other acts, presumably in the general foi~n of the resolutlon we have authorizing o£flcers to act in the luter/~n~ be~e~en Board meetlugs. There will-also be discussion o£ the tithe and "place o£ the annual ~eetiug,. and discussion of budget procedures. H. C. R.
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THs CounCiL ~oa Tobacco I~r-ss~cH-U..S.A., I~c. Dec_~er ~0, 1971 ~F ~he Proposed Stud~ Cannot Produce ~eaningi~l Results _T~e prl~e considerations e use of a tracheost~y is ~uch too artificial - trau~atic in itself a~d utterly unlike real b~an ~'he s=oke ~ received into the ~o~u-y systea h~- ~ ~e ~l~l~ ~ ~ Is ~t ~n~lled ~ the re,oval of ingredients by contact t~e ~o~th area in h~nan r~oking is not d~plicated the temperature at ~hic~ the ~ake is ~n~aled is ~o~ controll~ d. the degree of ln~idiftcation ~s ~_~_~n~m l~ere is ~o ~easure~ent of the actual lun~ dosage of particulate ~aterlal (tar) for cc~parison vith hu~n experlenc.. ~he technical requirements for properly handling the fixation, 8ectio~l~, ststn~__ng a~d e~4u~n~ 1,~n~s for (1) en~hy~e~atou~ char~es a~1 (2) for neo~.lastlc changes (cspecla~ly ti~, ~uclp~ent ones) are so dlffcrent that these studies cannot realistically he co~i~ed into one. (The ~c lung can, t ~e used for both purposes). ~ne art of ]~atbology is such that there vi].l alv~ys be s~ious d~ities ~ng ~logists ~ ~e ~te~re~tion o~ lesions t~at ~ be relat~ ~ nellie, especl~1~ ~en these ~e ~ or ~ciulen~. Hence, i~ su~ lesions ~e ~ be ~ ~ ~~ ~ a s~u~, th~ ~;st be ex~t.e~ ~epe~en~ ~ bl~d ~ a l~e n~ber (a ~el) of ~tholo~sts ~ ~e in prac~c~, hilly e~erl~ced, relatlvely yo~g. Bec~e this ~Int Is so ~rt~t, the t~k c~t be le~ ~ ~ one ~ ~ a ~ ~ ~f-~s int~tes. Big n~es of s~escent or
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THE COUNCIL ~OR TOBACCO I~ES~ARCH--U.N.A., INC. December 30, 1971 out-of-practice pathologists ~ean nothLug here. Consensus is es~entiel. I refer particularly to the traditional ~ethods of pathology using visual ex~natton of slides under the light ~Icroscope. However, it is i~perative now to use other techniques as well - behavior of suspect cells in tissue culture, electron ~Icroscope exe~!nations, bchavior on trans- plantation. Search for ~etastases is al~y$ ~ost important. Other types of observations, beyond ligbt-nL~croscope pathology are necessary in these days - for exa~le, blo~cal ~I i==r,~o]Jogic~ changes. Such experiments ~ust be continued throughout the ~ornal life-span of the antffial~ used if all the changes that might be significant are to be apprehended. No arbitrary time-sche~le or cut-off date can be set since it night completely defeat the objectives. @ Because of the i~ortance of ~ole life-span observations, do~ ~tY not be very suitable for th~s kind of study. Certainly, if dogs are u~ed, short-lived breeds should be ¢~ploy~. P~reover, "~he demonstrated importance of using patt~gen-free aninal~ in long-ter~ inhalation experL~ent$ is a stron~ argument against the use of' dogs since in-bred, ]~at~c~e~-free anln~ls are ~ot generally available. The use of ~m-~tandardized ~s requires that far larger n~bers be ~ployed for obtaining statistically valid res-ol~. ~oreover, the ln~mocbe~ical reagents necessary for deter- mining the stattm of the C-type RNA viral genoa, are not yet available for dogs. The plan ~oes not show whether the necessary criteria are met for the production of "fresh, whole, normal a~oke'. ($e~ attached memoranda). ~econd .ar~ con~ l~er~tious ~o origln~lly stated purpose of the proposed expert, hi was to ~zwer the question: "Does the result of a £kin pa~.nting ex~rl~ent provide a valid prediction of the degree of ~ effects When ctgexett-, smoke is inhaled dally by n~le beagle dogs," Since the plan to include cigarettes ~a~e'or reconstituted sheet has now been abandoned, this purpose has been lost since there is no infor~ation (that I know of) about the relative effects of condensate from high nitrogen and low nitrogen tobaccos on mouse skins. 0 O~
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• ~ Cou.~c~. ~o~ TobAcco RESEAItCtI-U.S.A.. INC. December ~0~ 197.1, Separate o~servetlon of ~hole smoke inhalation versus inhala- tlon of gas phase on~y, should be included in any such stud3r. there eoou~h high available at the University of Eentucky for an adequate I~ ~hese investigators have enough space to handle the m=~er of ~ogs needed! Logistic l~t~tio~s shou1~ ~ot ~e alloyed to ~_n_~luence t~e experi=ental design for a sJ~n_!elcant experiment. Better ~ot do it if it can,or be done well, Robert C. Hockett
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Subject: Meeting at Council for Tobacco Research December 21, 1971 Date: December 22, 1971 "[o: Mr. E. A, Vassallo From:. Murray Senkus .P.urpose of Meeting The meeting was held at the Council for Tobacco Research (CTR) to discuss Eur£her Auerbach smoking experiments on dogs, under sponsorship of the National Cancer Institute (NCI)~ Present at Meetin~ Vincent Lisanti William T. Hoyt Robert C.. Hockett Alex Eoltzman Roger Saleeby Helmut Wakeham H. C. Roemer Murray Senkus Council for Tobacco'Research Philip Morris ' R. J. Reynolds |! Background • The National Cancer Institute, under the direction of Gio B. Gori, is negotiating with Auerbach to conduct f~rther smoking experiments on dogs.. As defined by NCI, the objective is to determine the effect of nicotine on smoking dogs. Thus, one set of cigarettes will be smoked on a group of dogs which will produce'2 mg. of nicotine per cigarette; the other set of dogs will 5e smoked, using low nicotine tobacco, something on the order of .2 mg. of nicotine per cigarette. The Scientific Advisory Board (SAB) of the CTR, at its meeting on December 10-12, 1971, concluded that the experiment would be, meaningless from a medical standpoint, and we should make every effort to convince NCI to abandon the experiment, The basis for this reasoning is as follows: Smoke w$11 be delivered to the dogs through an incision in the throat, thus whole smoke will be presented to the lungs.~-DEi~,g human smoking, smoke is first presented to the mouth where the aldehydes~re removed from the smoke; therefore, as a human inhales, the sm:oke w0_u_%d--be quite different from the smoke which would be presented to the dogs. FORM ~.422--Rev. 7no
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Meeting at CTR 12/21/71 Page two ~ Conclusions Reached at the Meetin$ It was concluded that discussio= of the pertinent scientific .data with Dr. Gori will convince him that the Auerbach experiments should be abandoned. The staff at CTR will assemble the information that is to be submitted to Dr. Gori. The Research Directors of the tobacdo companies will meet with the CTR staff on January 17 to prepare the final report at • that time. In a telephone conversation, Dr. Gori has agreed to meet wi~h the Research Directors on.January 18 to discuss these dater - ~ /has
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Dr. l~obnor V~ce.~er 22, 1971 of-Docamber 6, 1971, from Dr. Little The extent of tobacco usage makes it one of the ~.~re profound and po~orf, l influences on hu~ physlolo~. I believe the planning beard ~ay be quite adeq~mto in the cat, oracular and pu1~ona~ fields. I don'~ believe, h~evor, tha~ It quite rca~es this do~reo o~ coherence and excellence In ~he c~cer field or with respect to ~enetic or ~oloculsr ~pocts of rcsear~ on c~cor. Rosoar~ ~ cancer h~ become inc~asingly co~lex ~t the sa~o ti~o that It 6~ ~achod ~nt promlso# I thi~ ~e cancer p~blem could best be h~dlod b~ a special s~-co~tteo including~ amongst othe~, D~. Car~er ~d ~ler, or by tholr ~ddltlon to the plying board. Beyond this. I bollevo, Dr. Littlo's reco~cndations of consultatlvo grot~s should be piven sorlous considoratlon. Currently, the possibilitlos for supporting research in the $ very large and complex tattered areas defined by the SAl~ and its planning .~roup are broad indeed and it stands to reason that carefully picked advisory .~roups could ~ako reco~endatlon$ of Interest and Importanc~ to the SAB snd to Staff as well. Robert J. ITuobnor, Dr. ltockett tlt. lle),t
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CTR-IJSA MONITORING LIST DECF~ER 21, 1971 Select articles you wish to receive by marking your initials adjacent to them. Return to Eileen Finnan. MEDICAL NEWS-TRIBUE~ 3/h5: November 8, 1971 "Smoking still by appointment" (News: the call from ASH to the Queen to withdra~ the Royal Warrant i~ unlikely to meet with any regal response) 5 MEDICAL WORLD NEWS 12/~6: December i0, 1971 "Clinical promises" (Review of cyclic AMP) LANCET 2; December 4, 1971 57-8 "Lungcancer among populations having lung irradiation" Archer, V.E. (Letter) i~61-2 "Smoking and neuroticism" (Letter: in kindness, one can only describe the case for °a connection between smoking and psychological distrubance as not proven) 1260-1 Freeman, J. "Cannabis encephalopathy?" (Editorial) "Cerebral atrophy in young cannabis smokers" (Evidence of cerebral atrophy was demonstrated by air encephalography in lO patients with histories of consistent cannabis smoking over a period of 3-11 y~ars) - 1219-2~ Campbell, A. M.G. et al COMMUNITY MEDICINE 126/20: November 12, 1971 "Cigarettes(warning)" (News) "Scottish anti-smoking display card" (News) A~.RICAN JOURNAL OF PJBLIC HTALTH 61/12: December 1971 "Survey of-adolescent drug use. I. Sex and grade distribution" (Found increase in the reported ~ of daily smokers after a lO-yr interval, but also an increase in the % of boys who report they have never smoked) 2~io-~ Johnson, K. G. et al NATION'S HEALTH December 1971 "Smoking: major British killer" (News: Sir Godber noted that tobacco-associated di- seases help keep the British male~.s life expectancy at 69.1 years, one of lowest in the Western world) 7 BRITISH JOURNAL OF I~USTRIAL MKDICINE 28/4: October 1971 "Effect of extremes of temperature and humidity on the goblet cell count in the rat airway epithelium" (No increase in n~mber or area of goblet cells was found in any group, although with irritants previously tested, such as tobacco smoke, a markedincrease has been found in this time) 369-7~ Jones, R. et al "Bronchitis in men employed in the coke industry" (The combination of cigarette szokinc E and previous employment in a dusty industry also had a Sis~i~icant effect o~,~.~?,.;..! o ventilatory capacity) 3~ - B Walker, D.D. et al ~
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CTR-USA ~K)NITORING LIST DECEMBER 22, 1971 BRITISH JOURNAL OF INDUSTRIAL ~.~DICINE (Continued) "A comparative study of respiratory function in female non-smoking cotton and Jute workers" (Cotton workers had a significantly higher prevalence of bys- sinosis, persistent cough, and of dyspnea than jute workers) Vallc, F. & Zuskin, E. 364-8 NEW ENGLAND JOURNAL OF M~DICINE 285/25: December 16, 1971 "Cannabis, nicotine and alcohol compared" (Letter: Did not seem reasonable to the author to compare the toxicity of alcohol and nicotine with that of cannabis ingredients, as J.C. Garriot did[N.E.J. Med. 285: Sept 30]). Heyndrickx, A. 1437 MODEm~ MEDICINE 39/25: December 13, 1971 "High lung cancer risk in coke oven workers" (News) Lloyd, J.W. 93 MEDICAL NEW~S-TRIBU~ 3/47: November ~2, 1971 "Carry, on smoking even in hospital" (News: most experts have concluded that it is impossible to ban smoking completely in hospitals) 5 CHEST 60/6: December 1971 "Effects of cigarette smoking on hemodynamics at rest and during exercise~ l.,Normal subjects" (By decreaseing the stroke volume response to exercise, smoking a single cigarette significantly alters the hemodynamic response to exercise in a direction opposite to physical training) 531-6 Goldbarg, A. N. et al AMERICAN JOURNAL OF CARDIOLOGY 28/6: December 1971 "Prevention of coronary disease--let's begin with the children" (Editorial: Ch~idren should be encouraged not to start smiting cigarettes) 745 Adams, F. H. ~DICAL JOU~L OF AUSTRALIA 2/26: December 25, 1971 "Oh, Mr. Snedden!" (Editorial: About the hazards of smoking) NEW SCIENTIST 52/773: December 9, 1971 1315 "Tiny virus may begin new cancer search" (News) ~DICAL JOUR~AL OF AUSTRALIA 2/25: December 18, 1971 "~rihuana studies" (A review) 1261-5 BRITISH MEDICAL JOUIL~AL 4: December 18, 1971 "Lung cancer and sun-dried tobacco" (Q & A: Evidence of an association between cigarette smoking and lung cancer findings in France are similar to those ih Great Britain, the U.S., etc) 743
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CTR-USA~ ~Dk~'TORING LIST 3. DECEMBER 2~, 1971 CIRCULATION 4~4/6: December 1971 "Use of exercise testing for diagnostic and functional evaluation of patients with arteriosclerotic heart disease" (Blackburn et al have been able to show that a positive exercise test has a prognostic significance that is independent of age, blood pressare, serum cholesterol, obesity, smoking, and physical activity) Blomqvist,.C.G. 1120-36 LANCET 2: December 11, 1971 "Cerebral atrophy .in young cannabis smokers" (Letters to editor: referring to paper byDr. Campbell [Bec 4, p. 1219] ). R~ssell, W. R. & Nattrass, F.J. 1314
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INTER-OFFICE MEMORANDUM Subject: Demonstration of Lorillard Smoking Machine Dote: December 17, 1970 .To: Mr. E. A. Vassallo A smoklngmachlne developed by Lorillard Research Department was demonstrated at Lorillard Research Center on December Present: John E. Kennedy - Brown & Wllllamson E. S. Harlow - American E. C. Cogbill - " T. Carpenter - Philip Morris Ward Bennett - U. S. Tobacco A. W. Spears - Lorillard F. Schultz - " J. R. Wagner - ". W. P. K~rschsteln - " J. Kreisher - C.T.R. Staff V. Lisanti - " " A. Rodgman - R. J. Reynolds C. W. Nystrom - " M. Senkus - " Background In June 1968, the Scientific Advisory Board (SAB) of the Council for Tobacco Research (CTR) requested that the Research Directors of the tobacco companies assist the SAB in (i) development of smoking machines for animal inhalatlon research, and (2) to evaluate these machines. The Industry Technical Cormuittee (ITC) of the CTR appointed a subcommittee to arrange for design and manufacture of prototypes. To date, several prototypes have been built and furnished to the SAB.for evaluation. These are: the Dontenwi11 (German) machine, the Walton-Morrlssey machine, the Phillp Morris machine and the Reynolds machine. The Idason Research Institute has evaluated these machines for the SAB and, based on these evaluatlons, is now designing a prototype which incorporates the best features of the Walton-Morrlssey machine and Reynolds machine. . o
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2 Demonstration of Lorillard Smoking Machine December 14, 1970 In the course of the above events, Lorillard also worked on the design of a prototype. This prototype was built about a month ago and was shown to industry representatives over the past three weeks. The machine incorporates many of the deslrable features of the machines which have already been evaluated by the SAB. One shortcoming of all of the machines tested to date is the llmlted number of animals that could be tested by a given machine at one time. For instance, the Reynolds machine accommodates only five animals at one time. The Lorillard machine can test as many as i00 mice at one time, and possibly more. This one feature appreciably reduces the cost of research on inhalatlon of tobacco smoke by animals. My personal opinion is that Lorillard has done an outstanding Job in designing and building the prototype. Future Action Representatives from all company members of the CTR have now observed the operation of the Lorillard machine and have reported orally to Dr. Spears, the Chairman of the Industry Technical Committee. Dr. Spears will report to the SAB at a forthcomlng meeting of the SAB. 0 The meeting will likely be ~eld in January 1971. On the basis of Dr. Spears' report, the SAB may decide to have the Lorillard machine evaluated at the Mason Research Institute. 1¢S :Jhb Cc: Hr. Colin Stokes Hr. W. S. Smith Hr. H. H. Ramm Mr. H. C. Roemer H~~urr Senkus \ Jr. '\, o o o~
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THE TOBACCO INSTITUTE, INC. 1776 K STREET, NORTHWEST WASHINGTON, D.C. 20006 296- ~434 WILLIAM KLOEPFER, JR. December ii, 1970 H. H. Ramm, Esq. .J R. J. Reynolds ~o~acco Co. Winston-SaWN. C. 27102 Dear Henr~: My hearty congratulations to you (and to our associates for their wisdom in their selection) on your designation to the post of leadership at the Council for Tobacco Research. ~ know that all of us on the staff are looking forward to even closer communication between our two organizations than we have had in the past. I know that you share our concern that all of us must do everything possible to emphasize our industry's great concern for proper scientific exploration of the smoking-health controversy. On a minor point, appreciating possible sensitivities here and the~e with respect to understanding the nature and pur- pose of "contract" research, the enclosed news release struck me as a good illustration and an indication of the receptivity to this approach. If we are not in touch soon, let me extend our sincere best holiday wishes to you and to Mrs. Ramm. Cordially, William Kloepfer, Jr. njp enc
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R,J.Re~,nolds Industries, Inc, Winston-Salem, N. C. 27102 k~,urray Senk'us . Director o! Research December 7, 1970 Dr. A. W. Spears Director of Research and Development Lorillard Corporation p. O. Box 20968 Greensboro, North Carollna 27,420 Dear Alex: Re: Demonstration of Smoking Machine R. J. Reynolds Industries, Inc. will be represented at the demonstration by Drs.• Alan .R°dgman and C. W. Nystrom. • In all likelihood I will also attend but may be a little late owing to a meeting which had been scheduled for early that morning'. " Sincerely, ~S:has Bc'- Mr. N. ~. Hoyt / / Mr. E. A. Vassa~lo Mr. I~. C. ~erJ Dr. P. C. Markunas Dr, A. I~. Laurene Dr. C. E. Teague Murray Senkus \. ¶
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NEW YORK. N. T. Dcocmbcr ], 1979 Dr. Murray Senkus Director of Research R. J. Re3molds Industries, Inc. Winston-Salem, North Carolina 27101 Dear Doctor Senkus : Members of the Scien-t!fie Advlsory Board, Industrial Technical Co:::uittcc an8 staff of The Council for Tobacco Re~carch-U.S.A. are ~nvited %.o attend, or to send theh" rcprcscntt..tivcs to, a dcnonstrat~on of the thirty-port smoking mscbinc for en~ra:~] exposure. This demonsh'ation ~i!l be hel~ at the I.orilla~d Research Ceutcr, ~20 English Street, Greensboro, North Carolina on Dece~.~er 14, 1970 at ll:OO A.M. Ti~ere will bca slide pre~ent~.tion an~ an ol,portu~£y to observe th~ smoking ~a?chine in operation. Hilton Inn },.~.~,,e ~, Street 830 W. '""~" " Oreensboro~ N. C. " : 9i9- 75/0811 _elepnone }'~ther ~nfoz~:aii~on (trausports.tion, special needs etc.) eau be arranged through the office of Dr. Alex Spears, DirecCor of" Research a,,~ ])ew~.!oynent, LoriSlard Research Center, telephone mu~be~ "919-?75/9R54, who ~¢ill be the host for this presentation. Sincerely yours, A~.~oc~te Scientific Director Jl~::is o
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.November 19, 1970 Mr. E. A. Vassallo Listed below are memberships for The Tobacco Institute, Tobacco Institute Testing Laboratory, The Council for Tobacco Research, CORESTA, and the various technical committees in these organizations. Also listed are company sponsors for the Education & Research Foundation of the American Medical Association and members of the ComMittee for Research on Tobacco and Health of the Education & Research Foundation, A.M.A. I. _The Tqb_a£co _~_.ns_t_itu_t_e__-- C~omj~n_z Memberships The Block Brothers Tobacco Co. Brown & Williamsnn Conwood Corporation G. A. Georgopulo & Co., Inc. Helme Products, Inc. Larus & Brother Liggett & Myers Philip Morris R. J. Reynolds Scotten, Dillon Co. United States Tobacco Co. Tobacco Institute Testing Laboratory - Board of Directors Murray Senkus, Chairman William W. Bates I. W. Hughes He]rout Wakeham E. S. Harlow R. J. Reynolds Liggett & ~ers Brown & Williamson Philip Morris American It ~ii be noted that American Tobacco Company participates in the TITL although the company is not a member of The Tobacco Institute. II. The Council for Tobacco Research - U.S.A. - Sponsors American Tobacco Bright Belt Warehouse Association, Inc. Brown & Williamson .Burley Auction Warehouse Association Burley Stabilization Corp. Burley Tobacco Growers Coop. Assoc. Imperial Larus & Brother P. Lorillard Maryland Tobacco Growers Association Philip Morris R. J. Reynolds Peter J. Schweitzer Div. Stephano Brothers Tobacco Associates, Inc. United States Tobacco Co. The Council for Tobacco Research - Industry Technical Con~nittee Membership (ITC) A. W. Spears I. W. Hughes H. Wakeham M. Senkus J. Campbell G. Shelton W. Bennett E. S. Har]ow P. Lorillard Brown & Williamson Philip ~orris R. J. Reynolds Imperial Larus ~nited States Tobacco Co. American
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Although Liggett & ~ers is not a formal member of the C.T.R., the company participates in the sponsorship of programs which are initiated by the legal representatives of the various tobacco companies, some of whom may not be formal members of the C.T.R. The Council for Tobacco Research (CTR) - Scientific Advisory Board (SAB) Sheldon C. Sommers, M.D., Chairman Research Director, The Council for Tobacco Research.- U.S.A. Director of Laboratories, Lenox Hill Hospital Professor of Pathology Columbia University College of Physicians and Surgeons New York, New York Kenneth Merrill Lynch, M.D., Sc.D., LL.D. Chance]for and Professor Emeritus of Pathology Medical College of South Carolina, Charleston, South Carolina *Howard B. Andervont, Sc.D. Scientific Editor, The Journal of the National Cancer Institute Bethesda, Maryland R~chard M. Bing, M.D. Director of Cardiology and ]ntramura] Medicine Huntington Memorial Hospital, Pasadena, California Professor of Medicine University of Southern California School of Medicine Los Angeles, California McKeen Cattell, Ph.D., M.D. Professor Emeritus of Pharmacology Cornell University Medical College, New York, New York Robert J. Huebner, M.D. Chief, Viral Carcinogenesis Branch National Cancer Institute - Bethesda, Fmryland Leon O. Jacobson, M.D. Dean of the Division of Biological Sciences Regenstein Professor of Biological Sciences University of Chicago, Illinois Clayton G. Loosli, Ph.D., M.D. Hastings Professor of Medicine and Pathology University of Southern California School of Medicine Los Angeles, California William F. Rienhoff, Jr., M.D. Professor Emeritus of Surgery Johns Hopkins University School of Medicine, Baltimore, Maryland (*) Retired
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3 Ill. The American Eed~ca] Association - Education & Research Foundation - Company Sponso~ Brown & Williamson Liggett & Myers P. Loril]ard R. J. Reynolds Philip Morris A~-ERF Committee for Research on Tobacco and Health Maurice II. Seevers, M.D., Chairman Professor and Chairman, Department of Pharmacology University of Michigan Richard J. Bing, M.D. Professor and Chairman, Department of Medicine Wayne State University College of Medicine, Detroit, Michigan Robert J. Hasterlik, M.D. Professor, Department of Medicine University of Chicago Earl A. Evans, Jr., Ph.D. Chicago, Illinois Paul Kotin, M.D. Research Triangle Park, North Carolina Marvin Kuschner, M.D. New York, New York Paul S. Larson, Ph.D. Haag Professor, Chairman, Department of Pharmacology ~ed~ca] College of Virginia - Richmond, Virginia Richard D. Remington, Ph.D. Bouston, Texas Ira Singer, Ph.D., SecretarX Assistant Director, Eedical Research American Medical Association Chicago, Illinois IV. CORESTA United States Members American Machine & Foundry Celanese Genera] Cigar Liggett & >~ers P. Lorillard Philip Morris Procter & Gamble R. J. Reynolds P. Schweitzer Tennessee Eastman
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TOBACCO INDUSTRY ORGANIZATIONS Organization Council for Tobacco Research Tobacco Working Group How Research is Represented M. Senkus, Mcmbcr of Industry Technical Committee, an Advisory Committee, advisors to Scientific Advisory Board M. Senkus, member of TWG, Advisory Group, Advisors to NCI Meetings Attended by Research Representative Three to four per year, no set schedule Four to five per year, called as needed Number of Cigarette Companies in Organization 5 a Approximate Annual Budget $2,000,060 None RJR Share Based on share of industry sales None Tobacco Institute Testing Laboratory M. Senkus, Chairman of Board of Directors of Laboratory c Once per year 5 AMA-ERF No formal representation; Once every two years M. Senkus attends some special AMA Seminars, also reviews and comments on research proposals $200,000 $2,000,000 $40,000 Based on share of industry sales CORESTA M. Senkus, RJR Once every year Representative $500 a. Liggett & Myers not a member; b. Brown & Williamson, Liggett & Myers, and American not represented; c. Lorillard not a member; d. American not a member; e. American not a member. November 20, 1970
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Dr. Robert C. Hockett, Associate Scientific Director, The Council for Tobacco Research - U.S.A. 110 East 59th Street. New York, New York 10022. Dear Bob: : Enclosed are copies of artlcles that appeared in J.A.N.A. and RODALE'S HEALTH BULLETIN concerning the views of Dr. Russell Sherwln of the University of Southern Callfornia School of Medicine as to damage to the lungs caused by polluted air. In RODALE'S HEALTH BULLETIN it is ~stated Dr. Shard, in believes that such damage may be a critical factor in lung cancer. I gather from the J.A.M.A. artlcle that he belleves it could be a crltical factor in emphysema. I know nothing about Dr. Sherwin and bring these articles to your attention with the thought the CTR might cause inquiry to be made and possibly support an appropriate research proJec~ with Dr. Sherwin. 9incerely. H. H.
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~ovem~er ~0, 1970. Mr. N. T. Roytp Executive Directorp The Councll for Tobacco Research -U.S.Ao~ 110 East 59th Street~ New York, New York 10022° Dear Tom: I enclose a copy of a letter dated October 28 received from Arthur J. Stevens and a copy of my answer. Sincerely, HHR:W Enclosure H. H. Ramm.
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FORM 2422 RE V. 5/67 INTER-OFFICE MEMORANDUM Subject: Date: November 9, 1970 To: Mr. H. H. Ramm The German paper described in the attached summary is of obvious interest. Colby FGC/pgg Art. (Staemmler, M. et al, INFLUENZA-VIRUS UND LUNGENKREBS IM TIERVERSUCH, Z. Krebsforsch. 7_~6 (No. 3) 283 (1970)) Cc: E. J. Jacob ~ ~,I''l~ O
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From the desk of W. T. HOYT ///~/~o The Council For Tobacco Research - U.S.A. 110 East 59th Street, New York, N.Y. 10022
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October 13. 1970. Mr. Executive Director, The Council for Tobacco Research U. S. 110 East 59th Street, New York~ New York 10022. Dear Tom: A few days ago Dr. Senkus visited the T.R.C. in ~ngland. Enclosed is a copy of portions of his report which Z thlnkmay be of interest to us in the C.T,R.~ particularly the reference to smoking machines that are in use in England for inhalation research. Sincerely, H. H. Rammo 4
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Meeting With Sir Phil~p Rpgers. Chal...rman .of the Tobacco Research Council Prior to my departure for England, Sir Philip Rogers invited me for lu~eh on September i0.'~ During lunch~ he outlined the arrangements he had made for me .; ,; ~ '" to visit the Harrogate Laboratory of the T.R.C. the following day. • ,',. . .....~ ...--..: He discussed in general terms the attitude toward smoking whicl '" " " :" gl ...... prevails in En and. . i.' " He felt that, in general, the public is not greatly concerned • ~ .-: .-. ~., - about smoklng/health problems; however, the Health Ministry is making an'; .' .. [.....i..i... effort to deter smoking by (I) controlling advertising, (2) by warning • ..~":-,~... notices on cigarette packages, (3) establishment of antl-smoklng clinics ':.. " .','~ ;" and (4) asking doctors to set examples by stopping smoking, ;~ i.''~' He felt that the adamant attitude of the Ministry is somewhat .. i}'. premature since all of the facts regarding smoking and health have not ~..~,..!i'. been ascertained. Considerable basic research remains to be done in the'I : ""~' smoking/health area and this is to be ~he function of the Harrogate ...' Laboratory of the T,R.C. being supported by the individual tobacco companies, il.i . . '.~.- There is a definite dellneation.between types of research at Harrogate a~d : .:.,'-:."i. research in the tobacco companies. The Harrogate research is long-range, i ~'..i~ ,,~ ~i ....fundamental in nature; whereas, the individual laboratories conduct research ,.".. :.".!. i!.~:~:' . • $~r Philip was a most gracious host and was very pleased .with
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August 14, 1970 1~ E ['I ORAN DU TO : FI(OM : SUBJECT: Scientific Advisory Board W. T. I{oyt, Executive Director SAB Meeting, September ]8-20, 1970. "-'he ~ext meeting of the Scientific Advisory BoE.r8 will be held at the New York Athletic Club (59th Street a~d Seventh Avenue) at 9:30 A.M. on Friday and Saturday, Septend)er ]8-]9, and ]0:00 A.M. on Sunday, Septemloer 20. Will you please return the duplicate copy of this memorandum, advising of your attendance? W. %'. Hoyt WPH:ek enc]. ] w~l ] ," ] wJ}l (wi II not) (wi] ] not) (will not) (will not) (will not) (wJ ] ] not) attend the SAB meeting on Friday, Segtecuber lSth. attend the SAB meeting on Saturday, September 19th. attend the S2h~ meeting on Sunday, September 20th. be present for lunch on September ]8th. be present for lunch on Septen£oer ]9th. be present for lunch on Septem!,er 20th. Signature
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August 12, 1970 TO : FROM : Scientific Advisory Board W. T. Hoyt, Executive Director In order to arrange for the joint meeting with the Coramittee o:~ Tobacco and Health of the AMA-ERF, it has been decided to hold a joint dinner meeting in Chicago on the night of January 14, 1971. This, of course, will eliminate a December meeting of the SAB in New York; therefore that meeting can be held in Chicago on January 15-16-17, 1971. Dr. Singer of the ~-ERF advises me that there is a serious room shortage in Chicago at that time, hence he has arranged to hold a block of rooms at the Drake Hotel for the nights of January 14-15-16, 1971. In order to make these reservations secure and to receive confirmation from the Hotel, it will be necessary for us to have information as to your requirements. Will you p~ease therefore fill out the necessary information below and return one copy of this memorandum to me as quickly as possible? PLEASE REPLY PR0}:PTLY. W.T.H. ~H:ek encl. Please make the following reservations for me: Single Thursday, January 14, 1971 Friday, January 15, 1971 Saturday, January 16, 1971 Double Signature
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August 12, 1970 ~;MORAN DUM TO : FROM : Scientific Advisory Board W. T. Hoyt, Executive Director In order to arrange for the joint meeting with the Colm~dttee on Tobacco and Health of the ;2,tA-ERF, it has been decided to hold a joint dinner meeting in Chicago on the night of 0anuary 14, ]97]. This, of course, ~ill eliminate a Decenfoer n~eetJng of %he SAB in .Ne~.: York; therefore that meeting can be held Jn Chicago on January 15-]6-17, 1971. Dr. Singer of the AMA-ERF advises ~:le that there is a serious room shortage in Chicago at that tir~.e, hence be has arranged to hold a block of rooms at the Drake Hotel for the nights of January 14-15-16, 1971. In order to ,qake these reservations secure and to receive confirmation from the Hotel, it will be necessary for us to have information as to your requirements. Wi~! you please therefore f~!l out the necessary info,~ation below and return one copy of th~s memorandum to me as quickly as possible? PLEASE IL~,PLY P_~:OMPTLY. W.T.H. WTH : ek encl. Please make the following reservations for me: Single. Thursday, January 14, 1971 Friday, January 15, 1971 Saturday, January ]6, 1971 Double Signature
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Jury 22, 1970, Dr. Robert J. Huebner, Chief, Viral Carcinogenesis Branch, National Cancer Institute, Bethesda, Maryland. 20014. Dear Bob: I appreciate your letter of July 9 concerning Dr. ILsns Meler. Undoubtedly Eenetics is an i~nportant area for consideration by the CTR and its Scientific Advisory ]5oard. Until the CTR has obtained a new Scientific Director I think It probably v~uld be inadvisable to suggest additions or changes in the SAB. In the meantime I ~ould think that Dr. Meier could be used as a consultant. Sincerely, 14. R. Ran~, CC: -Mr. W. T. Hoyt o 0 o
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~EPART~.4ENT OF" HEALT~-I. EDUCATION..a, ND ',VELFARE I~LJ~tLI.~ 1.4EALTH ~ILRVICE Hr. Henry H. Ra~wm Vice President and General Counsel N.J. Reynold; Tobacco Company Winston Salem, North Carolina 27101 Dear Henry : The ~ne bie!ogical ares not covered by B~a;d and one that is involved in all the chronic disease problems with whtch th~ Board is concerned, including lung caner, is genetics. lhe 139 cf liO smokers who do not get cancer of tha lun~ are obviously ge~ericall) different, prob~ly refle¢~1~g a general resistance to cancer. I have just suS~itted ~ papers to the Proceedings o~ the National Academy of Sciences which report the genetic cat a~J chicken cnb~'o--ai! the ccl!s in ~he early have it. It nc~ ~ppears that soce of the genes (~hich ~e now can study in the laboratory) which are responsible for the devel~pncnt of the c;&r~.'o from egg to birth are aJso resg~ns~le for cancer. J~cks~,n L~bc, ratc~ (Bar Harbor, Maine) as ~ useful member of the 5oar~. i.~ans Js probably also recognzzed ~ one of the world's outstanding animal pathologists. Sincerely, cc: Mr. .T. lloy*. Robert J. Huebner, H.D., Chief Viral Carcinogenesis Branch National Cancer Institute
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AVENUE, NEW YORK, NEW YO~K 1OO1"7 July 20, 1970 Mr. W. T. Hoyt Exe ~ltive Director The Council for Tobacco Research - U.S.A. II0 East 59th Street New York, Ne%, Yo~k 10022 Dear Mr. Hoyt: Increasing demands on all corporations, including ours, for a wide range of contributions have forced our Board of Directors to review our commitments, including our commitment to The Council for TobD.cco Research - U.S.A. This con'~mitment is one of the largest in our contributio~budget and we continue to ])elieve, after seventeen years of unrestricted grants for research in the field of smoking and health, that this activity is worthwhJ.le from the standpoint of the smohing public and from that of. our stockholders. As you know, our Company has always held the positS.on that the activities of CTR should be directed to- ward matters of scientific substance and should not ~e tainted by propagandistic considerations. ~;e believe that only in this .%.'ay can the industry's effort be accepted and respected by the scient.ific commun i ty. I allude to this because passage of the latest Act affecting cigarette .labeling and advertising may well give rise to pressures to make a "grandstand play" involving CTR by dr~-natically increasing its budget. This letter is to info~'m you that our Company is oppose.d to this type of thinking %;here the CTR is concerned. The scientific community i~.~ well aware
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;.~. W. T. Hoyt - 2 - July 20, 1970 that the quality of a rmsearch effort cannot be judged by the dollars expended on it and the dis- pensing of large sums as a public relations gambit may well produce a result which is exactly the op- ' posite from that which CTR was organized to achieve. The pressures and considerations I have described above, plus our obligation to our own stockholders to exercise prudence in evaluating our commitment in any particular direction, leads me to bring this in~tter t~ your attention even though we have acceded to past substantial CTR budget increases as a major contributor on the basis that added funds were desir- able to broaden the scope of CTR's research program. I am addressing this letter to you well in advance of ~]e October 9 scheduled meeting of CTR members so that you will be aware of our position in pre- paring your plans for the future. So that other major contributors of CTR may also be aware of our views in this matter, I~ informing them with copies of this letter. I~eI~ely' " R~ert B. ~;~ker Chairman of the Board and Chief Executive Officer cc: Mr. Joseph P. Cullman, 3rd Chairman of the Board Philip Morris Incorporated Mr. E~in P. Finch, President Brown & Williamson Tobacco Corp. ~. Alexander H. Galloway Chairman of the Board R. J. Reynolds Industries, Inc. ~. Robert P. Tisch, President Loew's Theatres Inc.
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FORM 2422 RE~V. 5/67 INTER-OFFICE MEMORANDUM Subject: Critiques on .Smoking and Health Dote: July 2, 1970 To: Mr. H. H. R~mm The Research Directors of the tobacco companfes are preparing critiques on smoking-health research which is supported bY the tobacco industry under the auspices of (1)/the American Medical Association - Education & Research Foundation (AMA-E~), and (2) the CounCil ~f6r Tobacco Research (CTR). On June 30, ~/ met with Dr. Willlam-~ates, Vice President & Director of Research for LigSett & Myers, and Dr.. Alex Spears, Director of Research and Development for ~orillard, to prepar4' a critique on the AMA program. Drs. Wakeham (Philip/~Morris), Leake (American), and Hughes (Brown & Willis~.~on) will prepare a/~ritique on the C~TR program. All of th Research Direct~ors will meet in Washington on July 7 to prepare a revised crlt~que on both programs. The fol ing are am.o~g recommendations which will be made by the AMA-ERF Subcommittee' at the Julyo7 meeting. Scie t. fie representatives of the tobacco companies supporting the AMA-ERF prSgram atteHded the presentations by grantees at Scottsdale, Arizona, May 6-8, 1970. Thee" general opinion of the scientific representatives was that only about!50% of/the program was directly related to alleged smoking-health problems. ~Addi~{onally, a large number of the presentations dealt with acute - f pharmacologi_ca'l effects o nicotine. It is believed that undue emphasis is being given to nicotine. In view of the results which have been obtained to date, the following areas deserve special attention. Heretofore, qualified investigators were not readily obtainable because of availability of funds from the U. S. Government. Now that Government support has been reduced, less difficulty will be experienced in finding qualified investigators. o The AMA-ERF Committee has n0't sought assistance to date on smoking techniques and other matters involving tobacco technology. A reminder that help is available from the tobacco industry would be in order. On the basis of titles of papers, some duplication is evident in on-going projects of AMA and CTR. Closer liaison between AMA and CTR would avoid these duplications. Murray S enkus MS :has Cc: Mr. Colin Stokes Mr. E. A. Vassallo
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Medical tlniversity of south carolina 80 BARRE STREET/CHARLESTON, SOUTH CAROLINA 29401 June 23, 1970 Dr. C. C. Little Litt]e Haven R. F. D. 1 Ellsworth, Maine 04605 My dear C. C.: I have just read your 1968469 Report of the Scientific Director of the C.T.R.-U.S.A. from "kiver to kiver," and I want to congratulate and compliment you on its comprehensive and clear coverage of the real status of the questions about the effects of tobacco use by humans. Although I have had the privilege of "proof reading" most of your previous .reports -- and have studied all of them -- this one particularly expresses my own position in better terms than I could formulate, even to myself. I do not know how wide the circulation of this Report may be, but I do know that a great number of people in the medical and scientific worlds, as well as publicity agents and politicians should somehow be induced to read it. The trouble is, I don't know how that could be done; the great mass of all classes has simply accepted as gospel what the "exhorters" (Stanley Reimann) say. It used to be just sinful to smoke cigarettes; now it is mortal. Trusting that the "long hot summer" will not be hard on Bea and you, and with best wishes from us. Sincerely, KML: j ch / Ho/t CC: Mr. W. T. Mr. Henry Kenneth M. Lynch, M. D.
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June 1B~ 1970. Addison Yeamani Esq. i Brown & Nilliamson Tobacco Corporatlon~ 1600 Nest Hill Street~ Loutsville~ Kentucky. 40201. Dear Add: Undoubtedly since sending a copy o£ your letter to me of June I concerning the CTR to certain individuals you have received my snswer to youof June 16. So that the record may be co~ple~e I am sending a copy of my letter of June 16 to the sanie individuals. Sincerely~ B. It. Ramm~ Vice President and Ceneral Counsel. CC: - Eessrs..Haas • Hetsko Smith Stevens C1ementB Kornegay Kloepfer
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June 16, 19700 Addison Yeaman, Esq., Brown & Nilllamson Tobacco Corporation, 1600 Nest Hill Street~ Louisville,. Kentucky. 40201. Dear Add: I am sorry for the delay in answering your letter of June 1 but as I told you on the telephone yesterday I have been so busy that I dldn'.t even have a chance to read your letter until I had to take a trip to Chicago last Thursday. The purpose of that trip was to interview a possible candidate for Scientific Director of the CTR, He is a very impressive, able person with a Ph.D. and M.D. and is in charge of a large research operation for one of the outstanding drug companies. ~ether we can get this individual or not I do not know at this tlme6 You will recall that at the meeting on May 15 in New York I stated that I thought it was important for the CTR to formulate a research program more directly targeted on the problems that we in our industry need to have solved. -I stated that I did not think this could be done without a very top flight, highly respected Scientific Director supported by an able staff. I also indicated that I thought the role of the SAB should probably be advisory rather than that of a declslonmaker. I indicated that we had some people both on the SAB and in the CTR staff who are good and it would be necessary to try to effect the changes in a way that would not alienate them. I would hesitate at this time to try to formulate a definitive operational organization. This I believe must largely be left to the Judgraent of the Scientific Director. Hopefully we can obtain one who has had experience as an administrator of research. The man I talked to in Chicago last week definltely o o .
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Addison Yea~ap Esq,.. June 16~ 1970, Page2, .' recognizes the need for advisers including some on a fulltime basis. He frankly stated that research in medical problems requires so much knowledge that no one individual is capable of.formulatlng or executing a meaningful program without experienced and highly qualified advice and assistance from others. For the time being I feel that it is important that I devote such time as I have in trying to locate the proper Scientific Director, This is not going to be an easy task, The efforts made so far have not been fruitful except the man that I spoke with in Chicago last week has not definitely said "No~o At a meeting last Friday at the Institute with Earle~ Horace~ Bill Kloepfer and Fred Panzer they stressed the importance ofproceeding with the reorganization of the CTR promptly, They recognize that getting a new Scientific Director has first priority, In view of the success that the Institute has had in obtaining qual~fied personnel through Spencer Stuart and Associates they reca~m~ended that I try this group, I had hoped that on the basis of leads furnished me or to be furnished to me I could obtain a better qualified person than through an organization like Spencer Stuart, However I do not want to leave any stone unturned and hope to be able to find out tomorrow when I go to New York whether the Spencer Stuart organization thinks it can be of assistance. Of course obtaining Spencer Stuart will involve some expense but I asstm~e we are all ~illing to bear our respective parts, Incidentally when I was in Chicago last week I called on our old friend Dr. Blasingame to sea if he could furnish any leads. He now is in the medical consulting business and if he turns up anyone for us this ~111 Involve some expense. Bing called me today and said that he had a ~an in m~nd and that he would shortly send me papers about him to see whether I am interested,
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Addison Yeaman~ Esq. June Page 3. The Scienti£1c Director I belleve will be the chief key to our problem wlth CTR and I would llke to feel certain that we are obtaining the rlght man and will have no regrets for the future, Si~cerely~ H. H, Ravin. Vice President and General Counsel,
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1~00 West Hill ~treet .,Louisville, Kentttck~l ,~0201 Messrs. Haas Hetsko Smith Stevens Clements Kornegay Kloepfer Under date of June 1, I addressed a letter to Henry Ramm as Chairman of the Council for Tobacco Research, in which I set out the views of Brown & Williamson with respect to the future of that organization. I did not at that time send a copy of the letter referred to to any other person, as I felt it only proper that Henry have the opportunity to express his own reactions to our suggestions prior to my communicating B~W's views generally. In a telephone conversation with me Monday, Henry said that there was no major area covered by my letter to which he had any substantial disagreement; it, therefore, seems timely to put our views to you. It is the opinion of Brown & ~lliamson that a close examination of the role CTR has played .in the past and might play in the future should have the highest priority and we would hope that some very early date could be set for discussion of this matter. I would hope that we could meet for such discussion at sometime earlier than July 8 or, if not, that we devote some time on that date to this problem. Sincerely,, cc: Mr. Ran~S
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AI)])I SON "Y l~ A]~f -~ N June I, 1970 H. Henry Ramm, Esq. Vice President & General Counsel R.J. Reynolds Tobacco Company Winston-Salem, North Carolina 27101 Dear Henry: At the outset, let me tell you that Ed Finch found your report on the status of affairs at the CTR highly informa- tive and helpful, which of course was no surprise to me in view of the conversations you and I have had over consider- able time. Earle~s comments in that area also contributed, I think, to bringing the whole matter of CTR's possible future into proper focus. We in Louisville recognize that over the years the CTR's grants have produced some "good science," but science which has not provided us with either much material useful on the offensive, nor much that was very meaningful on the defensive, in terms of effect on the public and ultimately Congress. We have long felt that we are less well served by the existing system of making grants upon unsolicited application over a very wide field than we would be were we to determine the specific areas relating to tobacco and health toward which meaningful research projects might be directed, with such planned research directly commissioned or contracted for, coordinated and supervised on a continuing 'basis by qualified staff at CTR. The accomplishment of that sort of planning, direction and coordination requires a very substantial re-organization and re-orientation of CTR as it now exists. First of a11, there is the need for a highly qualified scientific director, supported by "section directors" and a "manager" for project administration, adequate permanent staff at the scientific level and, finally, a new definition of the function of SAB. I attach a schematic representation which I hope will indicate the kind of organization we would like to put forward as a basis for discussion.
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H. Henry Ramm, Esq. -2- June l, 1970 I fully agree with you that the association with the CTR of such men as Sommers, Furst, Jacobson, Blng and Loosli, and certainly Huebner, has been and can in the future be of inestimable value. In a newly oriented organization, it seems to me that an advisory board constituted of people of that caliber would be of tremendous utility in consulting with the director on the general direction of the programs (the objectives having already been agreed at a higher level) and on those institutions and scientists most capable of carrying out the contracted work. There is no intention on our part to press for total abandonment of the making of grants, fully recognizing that CTR should remain free to receive applications for projects and make grants thereon where the proposed work is significant or fits in with the Council's own program. It seems to us that the industry has not used our respective research directors to the extent which their skills and expertise would justify in relation to CTR. We would suggest considerable thought be given to whether they could not, as a functioning committee, serve a very useful purpose in CTR as appears in the chart. I realize that this is a somewhat sensitive area but I suggest that it is one which might usefully be explored and discussed The function of the SAB and the Industry Scientific Committee could be defined as follows: SAB - advisory to the scientific director in ter~s of research programming and selection of grantees. Industry Scientific Committee - advisory to the scientific director in terms of industry expertise. The greatest value of the latter committee will be during the formative period of the re-activated and re-organized research program. Its continuance as a committee is doubtful after the program is under way. Primarily, each research director will then have the responsibility of briefing his own executive. This, of course, will necessitate some form of continuing contact with the director and grantee staff. Finally, in the structure we envisage CTR should have at the top level of responsibility a permanent chairman responsible to the Board. The representation of each company on that Board is of course strictly and exclusively a matter for decision by each company. It is Ed Finchts view that he would prefer to delegate the representation of Brown & Wllliamson to one of our Executive Vice Presidents, advised by our Director of Research, but, to repeat, that is a question for each company to decide for itself. o o o~
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H. Henry Ramm, Esq. -3- June 1, 1970 In summary, it is the view in Brown & Willlamson that CTRts past performance, in terms of its contribution to the industryts posture in the face of attack on the health issue, does not justify the current rate of cost but that properly re-organlzed and re-orlented it could serve the industry's needs. What I have said in this letter is not at all to be taken as fixed or frozen and is put forward as an expression of our views with the sincere hope that it can lead to useful discussions. We do feel rather strongly that such discussions should go forward at a very early date. While I recognize that it is imperative the search for the scientific director go forward as expeditiously as possible, we consider (as I indicated to you on Friday) that it would be highly desirable and helpful to you in that search were the new directions for CTR to be clearly laid down so that the new director may be fully aware of the industry's intentions and hopes. Before I go any further with our colleagues in discussing Brown & Williamson*s views in this matter, I would much appreciate your comments and suggestions. S£ncerely,. ms
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From th~ desk of / , W.'T. HOYT " The Council For Tobacco Research -U.S.A. 110 East 59th Street, New York, N.Y. 10022
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CO~:I P.ANY 10017 June 12, 1970 Mr. ~q. T. Hoyt Executive D~_rector The Council for Tobacco Research - U.S.A. 110 East 59th Street Now York, New York 1002.2 Dear Tom: Even in scientific or academic raatters, I am sure we all want the timin9 and quality of our public state- ments to reflect a businesslike and efficient industry. This morning I was given an "advance copy" of your 1969 annual report. Fran%;ly, I find it difficult to understand why it has %a~;en you so much longer this year to publ~sh the report than in previous years, especially in view of the very considerable addition to the operating budget %~hlch we went along wJ.th, a decision I now regret and question. Certainly, the companies which support CTR should have your annual report available prior to the time they report to their own stockholders. Apart from timing, I find the section on "Status of Current Research," pages 6 thru 17, less cogent, less specific, and less informative than i:x any annual re- port you have ever pub!i~hed. In other words, the quality is poor. On pages 6 and 7 you come to grips with the difficulty of ~nterpreting single variable statistical studies under "/.:ultivariate. Analysis.'~ You talk about testing many factors which tend to cluster with cigarette stroking statistically. However, the only one you single out and identify is "secularity." For my own information, I would llke you to send me a memorandum listing the factors -v:hich appear to cluster_" with cigarette smoking stati~tically, different,_'ating, if you can, bet~¢een those already demonstrated to so cluster and those still under investigation as pes.--;ible other factors implicated in the cigarette association studies. Sincerely, Robert N. t!eimann President
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6/24/70 Dear Bob: Report. Let me acknowledge your letter of June 12, 1970. I regret the delay in the issuance of %he Annual While I am not sure that the time ~chedul~ of the various companies in producing their reports to stockholders are such that prior publication of our Annual Report would be possible, obviously we want to get out our report as promptly as possible. This year an extraordinary accumulation of matters beyond our control, including Dr. Little's illness, culminated in a delayed Report, for which I apologize. The addition to the operating budget was attributable to increases in budgeted items which bear no relation to preparation and production of the Annual Report, for which (except for mechanical production) Drs. Little and Hockett are chiefly responsible. I'm sorry you feel the quality of the Report is poor. Yours is the only adverse comment we have received. Others, in- cluding members of our Scientific Advisory Board, have commented favorably and have told us they feel the Report is good. An Associated Press treatment of the Report, which seems to me un- usually favorable and which was published the week after your letter, is attached, if you have not already seen it. Radio carried a similar story. The pilot study of longevity was designed, as stated on page 7 o~ the Anl,ual Report, ~or the develo'pment o~ new com- puter methods. As approved by the Scientific Advisory Board,
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the study was not intended to make any independent investiga- tion of factors implicated in the cigarette association studies, as such. In the Boston study the older than 70 group had: been less worried; been older than their spouses; conserved their energy; had mothers who died at a ripe old age; looked younger, under 40, than their age; been not easily aggravated; been fussy about food; not expressed themselves well; been physically more active than the average on %he job in the 20 to 29 decade. In addition, they probably had: not caught cold as easily; had more intelligence; had poorer school performance; been less impulsive; had fewer illness4s in the 40-49 decade; been less active than others; had better health in the 40-49 decade; had a poorer sense of humor; had less occupational hazard; been married; been more active off the job in the 40-49 decade; been less active off the job below age 20 to age 29; been less adapt- able; been less active on the job in the 30-39 decade; not~nded to look on the dark side of things. The demonstrated secularity effect, however, raised the question to what extent, if at all, the apparent association of pipe or cigar smoking and inverse association of cigarette smoking with these factors is real or significant. Sincerely,
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"I'HE EVENING STAR N~W YORK (~) -- Thel "We are not dealing with sim- Council for Tobacco Research-[pie diseases and we cannot ex- U.S.A. says that findings from[~ct simple ~nswers," said the . .research it s~nsored durhg the[council's report, ~nd "it is " last 15 years do not confirm st~-'parent from the great ~mount of .. t~tical evidence hcriminating research reported ~smoking as a cause of lung cam]variety of genetic and environ- *,cer, heart disease and a chronic]m~ntal,, factors may be . 'lung ~seases. ] vo,ved. The counc~'s 19~-69 annual ] It said "mem~vs of the board !re~rt issued yesterday by its] and of other scLatific organiza- ~. ~ "~" "r~-~ ~ ~ tlo~s are oph~lStlC that answers heart ~tsease ano o ne~ mscas ~cepted fact that a sta~stical ~s.I .. . " - ~" ~ " ril n~ es, and investigators ~re con- ___lat.on. ~s not necessa y o. ~] . . . .by t o b a c e o manufactarers,] P--" • growers and warehousemen, has,I ~~ - ma~e granLs total~g $I~.5 mil-~ ~t~O ~/EIS~ . fion since 19M.- " - I BEAUT (AP)--Soviet ~ch~ ~ The funds went to 239 had~]olog~ts ha'¢e uneart~d a mud " pendent scientists workhg in 1M[w~stle ~at may ~ " hospi~!s, ~ersitie~.and re-]old, h an excavation projec~ ~earcn institutions, xnese re-!a~ut 2~ miles nort~ of Ba~- searchers publ~h~2~scient~-Idad,t pr~ ream from th-e ic papers. - Iraq~ capital
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Frqm the desk of The Council l:or Tobacco Research - U.S.A. 110 East 59th Street, New York. N.Y. 10022
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R{_ITGERS UNIVERSITY The State University o[ New Jersey CENTER OF ALCOHOL STUDIES " " Smithers Hall 1Very Brunswlc&, Netv Jersey o89o3 June 5, 1970 Dr. Robert C. Hockett Associate Scientific Director The Council for Tobacco Research - Uo S. A. llO East 59th Street New York, New York I0022 Dear Dr. Hockett: In accordance with your request, I am submitt|ng some comments about the presentations'on June I. The proposition by Dr. Barbar~B. Brown that the reason why some people smoke is that smokers and nonsmokers have different electrocerebral acti- Vity is intriguing. A basic difficulty, as you indicated during-the meeting, is the "chicken and egg" problem. Except by means of a longi- tudlnal, prospective study which might well be impracticable, any causal relationship would seem to be untestable. However, with her present approach, including former smokers, Dr. Brown could possibly demonstrate important differences without implying predisposition or causality. If she plans to pursue this, the work needs a great deal more discipline in several respects-: I. Selection of subjects. How can one try to make sure that the subjects are comparable other than in smoking habits and directly related variables? At least the following kind of basic d~ta should be presented: ages, numbers of each sex, length of time es smokers, ages et which smoking begen, general health, and so on. As well, it would be helpful to try to determine not only how much each subject smokes but also how deeply he inhales. " 2. Procedures. Exact. d~tails of electrode placement and recording p~ocedures and times should be given. For example, time since last smoke is important° For another example, reference was made to recording the EEG of one smoker for six hours. If this was continuous, the subject would almost certainly be demonstrating EEG effects of withdrawal.
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RUTGt RS UNIV] RSITY Robert Co Hockett -2- CENTER OF ALCOHOL STUDIES Smlthers Hall New Brunswick, New Jersey 08903 ,June 5, 1970 3. Analysis of results. The findings would seem not to be open to bias so long as the automatic analysis technique is used. However, Dr. Brown was supplementing this with clinical interpretation of the r~cords. To insure against bias, this should be done "blind." Confidence would be increased by a demonstration of high "test-retest" reliability in these interpretations. Also, if more than one person examines the records, some indication of interrater reliability would be worthwhile. Some of the differences inthe various measures are quite small, and the amount of variability between and within subjects in each group are not given. The latter of course have direct bearing on whether the observed differences between groups are different from those which could have occurred by chance alone. Appropriate statistical evaluation is badly needed. The work of Dr. Walter B. Essman was most interesting, insofar as the presentation went. I regret that time did not allow us to hear E~re from him, The other speakers all discussed their work fairly, and I think their presentations spoke for themselves. If you wish any clarification or have any questions, please do not hesitate to call on me. The day was interesting and instructive. attend. My expenses are listed on the attached sheet. With best regards, Thank you for having me Sincerely yours, Henry B. ~/lu rph Associate Professor of Psychiatry HBMIIcb Enclosures
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I~MOKa.NDUM FROM: SUBJECT: The Scientific Advisory Bo~-d Robert C. Hockett The June 1 Conference on Effects of Nicotine and/or Smoking on the Central Nervous System. (See our letter of May 95, 1970) The conference ~:as held as planned and seems to have been regarded by the participants as very interesting an4 stimulating. My ovm criticism is that too much time was spent in the description of experiments and not enough on the discussion of findings, their interpretive integration and suggestions for future confirmations e~d extensions. Since I presided, this situation ~¢as my o~.m fault aud might have been avoided by different advance planning. However several persons y~ho ~.~ere exposed to all the presentations should now be in a position to give good private counsel along such lines. We asked Dr. Leonide Go!dstein to act as a reporter and he has submitted the resu~n6 that is attached. We think it is a good job. We also asked Dr. Murpl~ree to eo~ent partieldarly on Barbara Bro%m's work, its validation and extension. His letter is also attached. We had hoped to have several more selected guest scientists but two or three, including Dr. Pfeiffer, ~.;ere unable to attend at the l~st minute. It would ~lso have been advsmtageous to have more members of the Board present, but dt seemed best, on balance, to hold the ~eeting, even on short notice, before Dr. Domino left for a long absence. All the particip~nts a~'eed that another such session should be held soon e~d several reco:v~.ended that thought be given ot plannino~ another public sy]&oosi~ such as the Cotuucil has held ~,~ith the New York Ac~de~,y of Scieuces. If this should be done, participation by A.M.A.E.R.F. grantees and investigators sponsored by the T.R.C. end the German Verbsnd should certainly be ~'ransed. Perhaps a cooperative undert~kino~ should be considered ~,:hen the ti~e is ripe. RCH: vr att aeh_~ents R. C. H.
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BUREAU OF RESEARCH IN NEUROLOGY AND PSYCHIATRY NEW JERSEY NEURO.PSYCHIATRIC INSTITUTE BOX 1000 PRINCETON. NE~ JERSEY 0S540 HUMPHR¥ OSMORD, ~,:RCP~ I:)PM June 3, 1970 TEL. 609 EXT. 432, .Dr. Robert C. Hockett Associate Scientific Director The Council for Tobacco Research-USA 110 East, 59th. Street, New York, N.Y. 10022 Dear Dr. Hockett: Please find enclosed a Resume of the papers presented at the June first Heeting. I drafted this report from the notes I took during the presentations and discussions. I may have made quite a few mistakes, for which I apologize. It is not always easy to g!ve an abstract of rather complex and elaborate research projects. I found the Heeting interesting and informative. I think more such should be organized with perhaps more time for both presentations and discussions. I know that this is not easy with the present day busy schedule of everybody. • If anything, all I heard reinforced me in the belief that what is needed is a careful analysis of the changes, bioelectrical, behavioral, and biochemical, which occur during chronic nicotine administration. This should be done on as many different species as possible, so as to avoid possible errors due to species specificity, different from that of man. I agree entirely with you that man is the ultimate object of our experimental work. In case you need me, please let me know~ in any way I can. I will be glad to help Sincerely yours, Leonide Goldstein, D.Sc. LG:mtr Enclosures: Report Expense account
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Resume of the papers and discussions presented during the Conference on the effects of Nicotine and/or Smokin9 on the Central Nervous system, organized by the Council on Tobacco Research-U.S.A. New York City, June 1, 1970. The Conference was opened by Dr. Robert C. Hockett, Associate Scientific Director of the Council. Dr. Hockett pointed out that the basic questions facing present day research in the field of CNS effects of nicotine were the following: -Why do people become smokers; -What advantages (if any) they derive from smoking; -What harmful effects (if any) are resulting from smoking; -Why is it so difficult, at least to certain individuals, to stop smoking. It ~.zas Dr. Hockett'S hope that the papers to be presented and the discussions to take place would if not solve, at least throw some light on these important questions. • The first paper, entitled "Nicotine induced behavioral changes and turnover rate of biogenic amines in the brain" was presented by Dr. Budhev ~hagat, St. Louis University Medical School, St. Louis Mo. Dr. Bhagat described experiments performed on mice, involving chronic nicotine administration at the dos.e of 0.5 mg/kg, SC, 5 days a week (no injections on Saturdays and Sundays) for 12 weeks and more. First, Dr. Bhagat showed that systolic b!ood pressure is significantly elev~i~ed following 4 weeks of nicotine treatment. However, it returns to control levels after 12 weeks, in spite of the continuation of nicotine
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-2- administration. The growth curve and food consumption of nicotine- treated animals were not different from saline controls. When steady.state levels of norepinephrine (NE) were determined at various intervals along the 12 weeks period, no changes were found between nicotine-treated animals and sa]ine controls. However, when the uptake of NE and the rate of synthesis were determined, itappeared that these were significantly higher in nicotine-treated an|mals. The change was quite prominent after 6 weeks of chronic administration. Experiments were performed in which ethanol was administered ~hronica]]y (oral route.) There were no changes in NE uptakei the rate of NE synthesis was decreased. I/hen nicotine and alcohol were administered chronically, at the same time, the rate of synthesis of NE was found to be increased. Thus nicotine compensated for the decrease due to ethanol. Some observations were made with amphetamine. It was found that in chronically nicotine treated animals, amphetamine toxicity was decreased for low doses and, on the contrary, enhanced for high doses. Turning to human subjects, Dr. Bhagat pointed out that 78~ of chronic alcoholics are heavy smokers (3 packs a day or more) while on]y a small percentage of heavy smokers are chronic alcoholics. One interpretation of these findings is that in smokers there occurs an adaptation to higher than normal levels of NE production and utilization. Alcoholics compensate for the reduced rate of NE production by smoking. The question as to why some people (smokers) feel better when their catecholamine metabolism is elevated remains open.
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-3- The second paper was presented by Dr. Thomas C. ilestfa11,Oniversity of Virginia School of Hedicine, Charlottesville, Va. It was entlt]ed: "Influence of nicotine and related drugs on the uptake, storage, release and turnover of catecholamines in central and peripheral tissue": Dr. Westfall pointed out that in many respects his data, chiefly obtained on measurements of catecholamine metabolism in the heart of rats, confirmed Dr. Bhagat~s findings on the brain of mice. Dr. Westfa]l called attention to 3 successive changes occurring in the urinary excretion of epinephrine of Rats treated chronically with nicotine (I mg/kg, S~, twice a day.) By comparison with saline-treated controls one finds: o -After 3 days, an increase -After 7 days, a decrease -After 14 days a return to normal levels. Three mechanisms could be involved: -Nicotine could induce the formation an enzymes responsible for its own metabolization; -Nicotine could produce a decrease in the release of catecholamines -Nicotine could increase the inactivation of catecholamines. With the concept that the particular mechanism at play would depend on the levels of nicotine in the tissues. However, attempts to demonstrate the existence of such mechanisms have not been successful thus far. Sleeping time (induced byNexobarbital or Zoxazolamine) was not found to be affected by chronic nicotine treatment. The activity of nicotine-oxidase in the liver was not found to be changed after 3, 8 and 14 days of chronic nicotine administration.
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-4- The possibility that enzyme induction is produced by benzpyrenes rather than by nicotine was raised. Dr. Westfall examined the possibility, that the rate of catecholamine depletion is dependent-upon nervous activity. If this be the case, one should find changes in the activity of the 2 enzymatic systems involved in the metabolism of catecholamines, MAO and COMT. Following chronic nicotine: -For ~0 significant increases weFe found at days 2 and 4 in the heart and at days 4 and 8 in the liver. -For COMT, increases were found in the liver; however, there were no changes in the heart. -The relative amounts of both enzymes were found to be increased during chronic nicotine administration. The possibility exists that enzyme induction is due to the increased synthesis of catecholamines rather than to nicotine itself. Dr. Westfall confirmed Dr. Bhagat's findings of an increase in turnover rates of catecholamines (47 days of chronic treatment). The increase in systolic blood pressure was also found. It occurred after the increase in turnover rate. Discussing the papers presented by Dr. Westfall and Dr. Bhagat, Dr. Barbara Brown raised the question of the possible stressful effects of chronic nicotine administration. Could it be that during chronic nicotine administration there occurs and habituation to stress? The main point was that of relevant controls. Is saline, which had no effect according to Dr. Brown, a valid control for nicotine which exerts such strong effects?
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-5- A paper entitled "Effects of tobacco smoking and nicotine on the central nervous system" was presented next by Dr. E.F. Domino. The University of Nicl.igan, Ann Arbor. Dr. Domino reviewed briefly his own data, as well as those of other research workers, on the effects of single administrations of nicotine on the electrical activity of' the brain, chiefly the cortex, the reticular formation, and the limbic syst~n. Although nicotine effects cannot be abolished when the cardiovascular changes it induces are blocked, these effects can be suppressed by discrete lesions in the mesencepha]ic reticular formation and/or high rostra] transections. This indicates the involvement of the reticular formation in the cortical effects of single doses of nicotine. It should be emphasized that Dr. Domino referred here only to the first phase of the action of nicotine, namely the arousal phase. As found out by Dr. Norton, Goldstein and many other, there is a second phase in single nicotine injections, a phase of sedation. However, this was not discussed by Dr. Domino. The cho]inergic system appears to be in the forefront of the effect of acute nicotine. Dr. Domino descri'bed recent experiments in which stimulations and recordings are performed at different levels of the optic tract of animals. The evoked potentia!s produced by stimulation of the tract are recorded from the visual cortex and/or the lateral geniculate bodies.- These potentials are abolished by 5-HT and by LSD. When thus suppressed, they can be restored by stimulation of the reticular formation or by treatment v~ith nicotine.' This constitutes another indication of the involvement of nicotine with the reticular formation. The lateral geniculate bodies are extremely rich in cholinesterase. Hence it is important to characterize and measure nicotine effects on that structure. From the ~ata at hand, it would appear that acetylcholine acts
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-6- as an excitatory modulator, and 5-HT as an inhibitory modulator. Dr. Domino emphasized his view that future work will have to be. performed on discrete systems, with the use of recently developed methods, such as microelectrode injection and recording procedures. Next, Dr. Domino examined the stimulant effect of nicotine on discharge of Renshaw's cells. This can be blocked by mecamylanine. An interesting observation is that in subjects lying immobile on a reclin|ng chair, the patel]ar reflex is markedly depressed by tobacco smoking, with an indication of dose-effect relationship, whi.le no change occurs when a lettuce cigarette is used. Experiments were designed in which nicotine was to be administered thFough inhalers of the type used to administer epinephrine and isoprotereno] to asthmatic subjects. Unfortunately up till now these experiments could not be properly performed, because the "inert" propellant of inhalers (freon) turned out to be quite irritant. ~ev~er types of inhalers are to become available shortly. The reduction of knee-jerk reflex produced by nicotine prompted Dr. Domino to remark that this could be indeed an indication of a positive effect of smoking. A decrease of such an activity could be beneficial to individuals in hyper-stimulated states. Dr. Domino insisted that the Council should emphasize such positive effects, and not only fight against the claims of cancerigenous action. During the discussion, Dr. Pradhan ~rought up the question of the initial state of the system when nicotine is administered. Dr. Goldstein pointed out that the most interesting and important work of Dr. Domino was only related to single administration. Furthermore he raised the question
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-7- of the significance of the depression of the patellar reflex. Such an effect does not seem to exist in subjects who are actively engaged in physical activity. Thus we should study the effects of nicotine as closely as possible to the conditions under which it is administered- in everyday life. Dr. Ulrich Schaepp.i,Mason Research Institute, Worcester, Mass., was the next speaker, presenting a paper entitled "Nicotine administration to the rostra1 areas of the cat brain; effects upon EEG and autonomic system= Changes in EEG and behavior induced with the protracted intravenous administrations of small doses of nicotine in unrestrained cats". In the cat nicotine administration is followed by 2 distinct cortlcal EEG changes= First, a brief stimulation phase (desynchronization) and, next, a prolonged sedation phase (hypersynchronization). Whennicotine is administered through the vertebral arteries, thus reaching ~irst the lower brain stem, the effect is more pronounced for both phases than when nicotine reaches more rostra1 parts of the brain, as obtained by carotid artery administration. Next, Dr. Schaeppi described the changes in the cortical and subcortical EEG, posture~ motility, and state of the autonomic nervous system, when nicotine is infused intravenously in freely moving cats. One of the surprising findings was that in a number of animals, such an injection brought about a state of immobility. This was evident with 10 ug/kg and affected all the animals used with 30 ug/kg. This state of immobility appeared to be different fro~ chlorpromazine-induced so called catatonia, since the nicotine-treated animals could be "aroused" into locomotion with a variety of sensory stimulations. Another observation was the appearance in the lateral amygdala of bursts of high voltag'e activity in 2 frequency bands, 40 Hz and 14-16 Hz.
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"8- Dr. Schaeppi summarized his data as follows= Dose of nicotine (ug/kg iv) I IO 30. 100 Autonomic stimul. Immobility EEG synchrony Hippocampal theta Amygdala bursts 0 (tremors and convulsions) 0 II II ( O = no change; + = definite effect ) Dr. Schaeppi mentioned his intention to pursue the study of the bursts in the amygdala. In the discussion, Dr. Brown mentioned having seen these bursts and pointed out that they were more prominent in the nuclear, part of the amygdala. The next paper entitled "Effects of nicotine on behavior and its interaction with drugs" was presented by Dr. Sachindra N. Pradhan, from Howard University in Washington, D.C. Dr. Pradhan described a variety of behavioral situations in which nicotine was tested in rats. A constant comparison with the effects of amphetamine was made. In a general way, without going into rather complex systems of conditioned responses, it can be said that both nicotine and amphetamine increased the rate of responsiveness of the animals. However, Dr. Pradhan insisted on the fact that in induly excited animals nicotine decreased the activity, while in sedated ~ animals it increased the rate of responsiveness. In his view the effects of ~ nicotine are both state and rate dependent o The main part of Dr. Pradhan's presentation was on the effects of nicotine m (and amphetamine) on the rate of self-stimulation in animals equipped with electrodes in the reward center of the hypothalamus. Although a large individual variability exists, it appears that at a dose of
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50 ug/kg IP nicotine produces initially a decrease in responsiveness; this is followed by a significant increase above pre-drug levels. Amphetamine produces only an increase. When the rate is decreased by fatigue or low doses of phenobar~ bital, nicotine brings back the very high level of bar pressing. This effect can be blocked by mecamylamine and by reserpinization. ADH does not produce nicotine-like effects. Scopolamine was found to potentiate the effects of nicotine in 50% of the animals. Dr. Pradhan offered a working hypothesis according to which nicotine acts on both adrenergic and cholinergic neurons. According to the state of the stores of neurotransmitters at the time of administration, one or the other will be affected thus producing a stimulation or a decrease of the activity. This model is rate-dependent ~ith, as a final result, the maintenance of homeostasis. Dr. Walter B. Essman from Queen's College, Flushing, N.Y. presented next a paper entitled "Nicotine action on memory consolidation". When mice are placed in a small chamber, from which they can jump into a large chamber, they most often do so. If a shock is applied to their feet when they land in the large chamber they learn immediately to avoid such a motion. The memory can persist up to 3 months or more. If retrograde amnesia is induced in such animals with electroconvulsive shock (ES) they loose the memory. However, when nicotine is administered prior to ES, one finds retention of memory in a number of animals. ES produces increases in 5-HT and 5-HIAA. The.sequence nicotine + ES prevents the increase in 5-HT. Similar effects were obtained with a number of metabolites of nicotine. The maximal action on memory retention is obtained 15 min. post-drug administration; O O
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-10- it disappears 45 min. post-drug. Dr. Essman described a variety of procedures in which nicotine and acetylcholine activity, and certain features of protein synthesis, werestudied in vitro in isolated synaptic vesicles. Following ES there occurs a decrease in bound acetylcholine. This effect is not present when nicotine is administered. The data can be summarized as follows: Acetylcholine Ac~tylcholinesterase ES alone decrease increase Nicotine alone decrease increase ES ÷ Nicotine increas.e no change Sixty minutes post-nicotine administration there occurs a 500% increase in vesicular protein synthesis. ES produces a decrease in protein synthesis. With the combination of ES and nicotine, one finds a 16 fold increase in protein synthesis. Dr. Essman's conclusion was that nicotine appears to play an important role in memory acquisition and retention. Dr. Barbara B. Brown from the Veteran's Administration Hospital, Sepulveda, California, was next on the program with a paper entitled "Exploration of the differences in EEG patterns - subjective state correlates in smokers and non- smoker subjects" The data she presented is contained in one Table. and 3 Graphs which were distributed, so they will be only briefly described. The method used was to analyze "EEG abundance" for 3 frequential domains, aIRha (8-12 Hz), "rhythmic" beta (16-24 Hz) and theta (3-6 Hz). Instead of the usual short intervals of recording, Dr. Brown analyzed 5 minute samples 0 C~
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-11- of EEG obtained at the beginning, middle part, and last part of a continuous 2 hours recording. There were altogether 88 subjects of which 26 were non- smokers, 11 former average smokers, 12 former heavy smokers, 13 average smokers (I pack a day), 13 heavy smokers (2 packs a day) and 13 very heavy smokers (3 or more packs a day). Although overlaps exist interesting differentiation can be seen, chiefly for the fast rhythmlc activity in smokers. "A11 other differences seen can be found in the graphs. Dr. Brown believes that heavy smokers use nicotine to synchronize their. EEG. She believes that there is a genetica] predisposition for the defects seen in heavy smokers, which nicotine helps to live with. A number of other differences can be seen between smokers and non-smokers. Thus in the control of one's ov/n physiological functioning (brain waves, heart rate, blood pressure, body temperature, etc~) heavy smokers are very slow to learn, while non-smokers are very fast to learn. Seventy per cent of heavy smokers cannot obtain visual imagery; they have trouble conceptualizing their own bodily functions. The last paper was presented by Dr. L. Go]dstein,from the N.J. Neuropsychiatric Institut~ in Princeton. It was entitled "Study of bioelectric differences between nicotine-habituated and non-habituated organisms by use of high energy phosphate compounds and psychoactive drugs". Dr. Go]dstein described first the niCotine-induced changes in the base-line quantitated e]ectrical activity of rabbits. Chronic nicotine administrations were perforated for 3 weeks on male albino rabbits equipped with electrodes in the cortex, the reticular formation, the hippocampus and the an~ygdala. 200 ug/kg of nicotine were. injected subcutaneously 5 times daily. Controls were run with chronic saline administration. Statistical analysis of the distribution of amplitude levels per successive epochs of 2 seconds revealed a change. The characterist|c uni-
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modal distributions were replaced at cortical and hippocampal levels by bimodal distributions. The extent of mutual involvement between structures was estimated by the ratio of the variances between struc- tures. Chronic nicotine administration produced a gradual increase for the pairs cortex/hippocampus and cortex/amygdala. Next, Dr. Goldstein reviewed the data obtained with single dose administrations of nucleosides and nucleotides, and also with 4 psychoactive agents. While in absence of chronic nicotine treatment, Adenosine, AMP and ATP produced a weak sedative effect. Following 2 weeks of chronic nicotine these same drugs, at the same dose levels brought about pronounced stimulant effects. The sedative effects of ch]ordiazepoxide were markedly reduced in nicotine-treated animals; desmethylimipramine, on the contrary, had more marked sedative effects in treated animals than in saline controls. No changes were seen in the effects of deanol and 5-HT. Dr. Goldstein presented, next, a very brief discussion of these results, insofar as their possible bearing on tobacco smoking in man. He mentioned a recently introduced hypothesis by Routtemberg according to which there are two alternate systems in the brain.contributing to global homeostasis. One involves the reticular formation and leads to "drive" oriented arousal, while the other depends on the limbic systom and produces "incentive" oriented arousal. If this concept is applied to the findings of the study just described one might conclude that prolonged chronic nicotine administration produced a shift from drive- oriented type stimulation (i.e. essentially.over-stimulation) to incent- tire stimulation (i.e. goal-directed, meaningful, stimulation).
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It could be that people become chronic smokers when they find a relief to a s.tate of overarousa] of which they might not be conscious. There are as many papers in the literature describing nicotine as being a stimulant as papers describing it as being a tranqui|]izer. The advantage of the concept just outlined is that it leads to accept both apparently contradictory positions as being both true. In fact it describes nicotine effects as being of anti-depressant nature. Some doubt was expressed as to the action of nuc|eosides and nucleotides since some data indicates that in some species these do not cross the blood-brain barrier. However, Dr. Go]dstein indicated that even if the effects are indirect, the reversal produced by nicotine wo~]d suggest a primary effect of the alkaloid on the brain, as evidenced by differentia] reactivity to drugs. A direct, e.g. with labelled compounds, appraisa| of the action of nuc]eosides and nuc]eotides on the brain remains to be performed. In his closing remarks, Dr. Hockett pointed out that among the most promising new developments of research on the effect of nicotine and tobacco smoking on the brain, experimentation performed under conditions of chronic administration occupies a centra| position. What is needed no~ is not more pharmacology of nicotine, since ~his is we]] known, but n~ore research in the situation existing with smoking in man. This calls, of course, for studies under prolonged chronic administration of nicotine and perhaps other tobacco products. Dr. Hockett mentioned the possibi]i~ty of a third Symposium of the Ne~ York Academy of Sciences, to be organized soon. Leonide Goldstein, D.Sc.
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Mo THE UNIVERBITY D. ANDERSON HO,GPITAL AND OF TUMOR Texas Medical Center May 8, 1970 TEXAS II~J STI TU'IE Houston, Texas 77025 W. T. Hoyt, F~xecutive Director The Council for Tobacco Research 1 I0 ]Bast 59th Street New York, New York I0022 Dear Tom: The day after you called I went to see Bill Alban. I shoxved him my immense computer output on the data and had him send his three head statistical workers over here to my office to sfart a series of reports of deaths from each cause by the three ethnic groups. I have age-specific, age-adjusted, m~d crude rates for each of thesefor each sex, for Latins, Negroes, and Anglos, and for totals in each ethnic group and grand totals. Carl ]Brhardt, formerly Head of Statistics and Records of the New York City Health Department, prepared reports like these in Connecticut before as- suming the New York Department directorship, when he was Assistant Director of Vital Statistics in Connecticut. After he left, Bill Haenszel published them under his own name, and probably .got his Washington job as a result. This will be good basic data and. wonderful use of the material. I have all the respiratory causes of death computed separately and together by year. ]Bnclosed is some of the output to give you an idea. I wrote to The American Statistician allerting them to this project and they arc going to- publish my comments in the near future. ]Bnclosed is a copy of a paper from the data on my tape which was read in San Francisco and has been acepted for publication in the Texas Journal Of B~01ogy ancl Med~in~ :: I worked on the suggestions of Dr. Little that 2% or 5% off the lung cancer rates would alter the picture. It didn't work out very dramatically because the earlier data is some ~vhat unreliable. It does show that there may be some improvement in diagnosis as time goes by. I ~vill send it with the work- sheets, giving the original numbers in case some one there wishes to make further use of the material. I am sending a graph U.sing Houston data, related to the )'ears famous antibiotics were introduced. It makes a dramatic graph which you might find useful and one which accouuts for n~ st of the switch in causes of death. One graph is of the U~ited States as a whole, the other of Houston. On the Houston graph you will note inclusions of current interest,
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W. T. Hoyt Page i.e., heart, cancer, and stroke. Then I give total respiratory disease. Under this I give the major inclusions in the total respiratory category; i.e., (1) influenza and pneumonia, (2) tuberculosis, (3) the respiratory cancer category, and (4) asthma. Influenza and pneumonia started up again from their low in 1950. It's interesting that the first supposed breakthrough in production of lung cancer in animals from cigarettes is by the ubiquitous Auerbach, the only pathologist who claims to identify "in situ" cancer in assorted lungs, who claims never to have known of~a case of lung cancer in a non- smoker (notwithstanding David Karnofsky or Godias Drolet - famous Head Statistician of the American Tuberculosis Association for 40 years, who never smoked anything in his life - both of whom had primary lung cancer). The method of springing their results is reminiscent of Ivy and Krebiozcn; to a specially invited group of reporters and science writers, with special stage effects. In 1956, She first week in June, the Third National Cancer Conference was held in Detroit. It foilowed by a few days, the Ewing Meeting at the Memo- rial. Auerbach presented his findings on serial sections of lungs at the .Ewing Meeting. He was asked by Dr. Fred Stewart, Pathologist of the Memorial, if he ever had seen any multiple loci of lung cancer in the 'same person. Auerbach said he had not. Then Fred Stewart drew a diagramatic sketch of the bronchi and lungs, showing th..e area that would be reached by cigarette smoke, and said quite obviously there would be multiple loci of cancer in smokers or else cigarette smoke had nothing to do with can- cer induction. Dr, Stewart said he never had seen mul.tiple primaries in lung either. Well, at the Third National Cancer Conference, at a cocktail party given by Pat McGrady, attended by 40 or 50 people including Dr. Little, Auerbach called for a press conference, so Pat invited him up. In great excitement he said he had the final proof. That examination of his specimens showed multiple loci of cancer. Then he held up the sketch of Stewart and demon- strated. One visiting pathologist from Turkey ~mmediately challenged him, reminded him that a few days before he had never seen one insta.nce of multiple cancer loci in one lung and had so publicly reported before many of those present at the cocktail part~ who had also been at the Ewing Lecture. How then had he reversed himself on the same source data? Auerbach said he had resectioned and restudied the material. The other pathologist asked him if hehadused soft orfixed tissue. Auerbach said t~oft~. The other pathologist then said that Auerbach undoubtedly was seeing different parts
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" W.T. Hoyt Page 3 of the same tumor. Auerbach had no answer for that and left. At the time none of the science writers carried the storyi nor did Pat McGrady. Dr. Little will probabl~ remember the incident. It certainly caused some excitemen.', at the gathering .... I just this morning saw the full page account of the letter exchange on Auerbach's claims and think it is very thought provoking. The brain ~vashing has been going on so long without challenge it will only be ~'the quiet silent majority" who will really face the facts. At the Anderson, Walter Burdette of the Surgeon General's Committee, now Associate Director of Research here' and high committee man of the Cancer Society, and Clark Griffin, American Cancer Society Life Fellow in Biochemistry and also a Mormon, are both pressuring to get the Insti- tution on record favoring the "theory". At the time of the International Cancer Congress, the Anderson is giving an award for the best suggestion for a TV commercial on smoking and lung cancer. It.was to b~ presented by Tony Curtis, head of the "I quit smoking" group. Now that he has been arrested in London and fined for smoking marihuana, they },ave to find someone else. Dr. Jack Healey, a smoker himself is the one who has to make the. decision. Dr. Howe, Head of Medicine, Dr. White, Head of Surgery, Dr. Healey, Head of Rehabilitation and Planning, Joe Boyd, Vice President in Charge of Administration, and Dr. Haas, Head of Biology are all cigarette smokers. It is certainly a long and unscientific story. The end will be when the true cause of Cancer is really found, probably. Have you ever thought of having a study done on the major statis~ical papers such as was done on the Kinsey Report. Sincerely, Eleanor J. Macdonald Epidemiologist E JM :kr Enclosure s
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W. T. Hoyt Page 4 Has anyone in your group given any thought to asking the American Statistical Association to appoint a.committee to evaluate the methodology in the Hammond and other studies since the economy and welfare of several states and of a major industry are at stake because of these reports? Brownlee did a fine brief review in the Journal of the American Statistical Association. The American Statistical Association appointed a committee to advise the National Research Council Committee for Research, in problems of sex, and came up with a detailed 330"page critique. The Kinsey Reports used the same methods Of non-random sampling, that these others have used. You could obtain a copy of the report from the American Statistical Association. -The analogies are exact. It was pretty clever of the group responsible for the ap- pointment of the Surgeon General's Report Committee to have Cochran on their Committee since he headed the highly critical committee on the Kins.ey Report. Carl Hopkins now of U. C. L. A. wrote the critique of the Kinsey Report among females (enclosed). His line (marked) on Page 188 tells the story. Incidentally, Dr. Hopkins is Chairman of the Fa.culty of the School of Public Health, and is also directing the California Center for Health Services Research, Los Angeles 900Z4, California. 0 o
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Hayl8, 1970. Hr. W. T. H~y,t~ Councll for Tobacco Research- 110 East 59th Street~ New ¥ork~ New York 10020. Dear Tom-'., ~" The "other day you gave me three sheets of an artlcle entitled "Emphysema Produced in Smoking Dogs" containing the questions to Dr. Auerbach and his answers. None of these sheets indicated the publication from which the pages were taken. T would appreciate your giving me the re ferenc e • Also I ~ould appreciate your sending me another copy Of the job descriptions of the staff of the CTR; SincereZy, HHR:W Vice President and General-Counsel. o o 0 o c~
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~I~HE C()UNCII~ I~OR TO]~ACCO R]~;SEARCII-U. S.A. NE~" "~'ORK, N. Y. 10022 May 21, 1970 Mr. Henry H. Ramm / Vice President and General Coup{el R. J. Reynolds Tobacco Compan/ Winston-Salem, North Carol~t~27101 Dear Henry: / / The three pag/s I handed you at Scottsdale entitled "Emphysema Produced in Smoking Do~s" were the questions and answers at the conclusion of a paper,delivered ~y Au~rbach. This symposium has been published under the title 'Inhalatio~ C~cinogenesis," and covers the Proceedings of a Biology Division, ~Rid~r~ational I,aboratory, conference held in Gatlinburg, Tennessee, October 8-11, 1969, sponsored by National Cancer Institute and the U.S. Atomic Energy Commission, with the publishing date Apr~l 1970. Should you wish to obtain this document it is available as CONF-691001 for $3.00 from: Clearinghouse for Federal Scientific & Technical Information National Bureau of Standards U.S. Department of Commerce Springfield, Virginia 22151 You will find attached the copy of the job descriptions of The CTR staff you requested. With all best w~shes, Sincerely, W. T. Hoyt Executive Director WTH:ek att.
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W. T. HOYT, Executive Director i. Supervises and administers all lay activities of The Council. Calls meetings, presides where necessary, signs checks covering payrolls, the General account and the Special Projects fund. Is responsible for the organization and conduct of Council activities, and provides executive guidanc~ in those matters where coordination is needed between different disciplines such as science, public relations, law and other. Serves as focal point for liaison between the Scientific Advisory Board, the scientific staff and the tobacco industry, including its legal representatives. Administers office routine and procedure. space, letting of contracts, etc. Handles renting of office Acts as executive secretary to the Scientific Advisory Board, prepares minutes of such meetings, and is responsible for all actions taken therewith. 6. Handles all personnel matters. A~ninisters all Council financial matters and is responsible for: Budgets, assessments and collections for the General and Special Projects accounts. ~ Grant and contract payments and refunds. Audits. Federal, state and city tax returns. Pensions. Insurance. Payrolls. , o o
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ROBERT C. HOCKETT, Ph.D., Associate Scientific Director ~. ~upervises all scientific staff services relating to the Scientific Advisory Board. This encompasses arranging agendas, preparing material for meetings, handling negotiations with applicants for grants-in-aid, visits to grantees and prospective grantees, assembling of scientific data, evaluation of new techniques and new developments bearing on tobacco and health, executing plans and programs defined by the Board including arrangements for informal cohferences of scientists. Administers grants and contracts, solicits and reads progress reports and provides for their distribution. Scientific liaison. Arranges for attendance at meetings of various scientific and medical societies, as well as contacts with government and private research agencies. Scientific analysis and .industry cooperation. Q Works with tobacco industry personnel and its legal representatives on a broad variety of matters including testifying at hearings, in law suits, and preparation of material in connection therewith. Scientific literature. Supervises the systematic collection and analysis of scientific and medical literature pertinent to the interests of The Council, and the preparation and distribution of digests and abstracts of the most important new research reports to members of The Council and the Scientific Advisory Board. Public statements. Participates in the preparation of the Annual Report and, from time to time, addresses industrial, scientific and lay groups on the program and activities of The Council for Tobacco Research. Represents The Council in contacts with writers, authors and others seeking information concerning The Council. -4
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J. MORR]SON BRAt)Y, M.D., Associate Scientific Director Maintains and develops appropriate contacts with both clinical and basic science segments of the medical and related allied sciences. (Over 300 anhouncements of medical programs and scheduled scientific meetings are received annually.) Assists Jn and helps develop prospective plans for research investi- gation appropriate to The Council's program. Assists in ]~aison with the A~aerican Medical Association, foi]ows activities of the Association's House of Delegates and maintains contacts with its Board of Trustees. Reviews and consults on grant-in-aid projects of The Council having clinical or administrative problems. Supervises arrangements for showing and manning The Council's exhibit at appropriate medical meetir~gs. Informs prospective grant applicants of The Council's program and the mechanics of applying for grants. Maintains wherever possible contacts wJth specialty professional 0rgan~zat]o;~s such as the ;~merican College of Chest Physicians, American College of Cardiology, An'~erican Thoracic Society, etc. follows the activities of the American Public Health Association, American Heart Association, American Cancer society, etc. Also
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JO}~ H. KREISHICR, Ph.D., Associate Scientific Director Assists in scientific services required by the Scientific Advisory Board. Consults and provides scientifi~ liaison with specific g~antees, govermnent agencies, researchers and institutions primarily in fields related to cancer, virus, respiratory diseases and biochemi stry. ~akes site ~'~sits to grantees and reports on the conduct of the project. }.~.onitors specific contracts an~. grants as assigned. Supervises the accounting and reporting of f~ds spent ~nder the grant-in-aid program. Endeavors to locate centers of excellence in hie sciences suitable for initiated projects.
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¥iCEtgf F. LISAh~i'I, D.M.D., Scientific Associate Assists the scientific program on a part-time basis. (3 days a week) Assists in scientific services required by the Scientific Advisory Board. Consults and serves as sc~_entific liaison with specific grantees, goverr~nent azencies, researchers and d nstitutions. Makes site visits to grantees' and reports on the conduct of the projects. Monitors specific contracts and gu~,.nts as assigned. Endeavors to locate centers of excellence in bio sciences suitable for initiated projects.
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KENNETH L. AUSTIN, Director of Literature Research Directs literature search, reporting and retrieval in the areas of tobacco and health, related areas of health research, and new directions in scientific and medical endeavor. Surveys the literature for papers presented by Council g1antees and other similar organizations and for papers and comments by scientific figures who have been or may be called upon for testimony in the area of tobacco and health. This work comprises four correlated operations: _S_e_a_r__c_h_: direct monitoring of 162 scientific journals and 14 abstracting services, v:hich together publish abstracts or titles of papers in 4,600 U.S. and foreign journa]s. ~t_~_n~g_: by means of a month].y Current Digest with occasional attachments and supplements. Filing: maintaining a comprehensive library of more than 60,000 scientific papers, with translations of important foreign papers, and more than 14,000 abstracts prepared~before and during the ]5-year Current Digest publication period. _R!'~_tJ-_J__e_va__] : maintaining a catalogue by subjects, principal authors, and university or location, with brief description of the paper listed and a coded rating by its relation to the tobacco and health question. The catalogue at present comprises more than 3,200 pages under 460~ rubrics in the areas of cancer and the lungs (300+), head and nec)[ (27) , heart and circulation (85) , psychology (I0), other systemic conditions (30) , and miscellaneous items. Papers, references and bib1~ographies are provided on request to the supporting organizations and their legal, scientific and public relations staffs, as we]] as to The Tobacco Institute, Inc., the Central Library, representatives of Canadian and British tobacco organizations and other parties at interest.
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• Tesunoo ~e~eue9 pue :lUepTSeaci ~OTA I ~nq ~uasozd aq o~ alq~ oq ~ou ~IT~ I • &~puo~ ~xau pIaq aq o~ o~uoao~uoa olq~-punoa ~o ~m ~UTSTAp~ ~Z ~ ~o aa~oI ano~ ao~ no~ ~u~q~
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r]~I ! E (~OUNCI L FOR ~]~OBACC0 R E~EARCtI - U. S. A. ll0 F.AST fiOTH STREET NE~" ,'ORK. N. Y. 10022 May 25, 1970 Mr. Henry H. Vice President_r .and General Counsel R. J. Reynolds Tobacco Company Winston-Sal~, North Carolina Dear Henry/: The enclosed copies of letters and of a list of participants will inform you concerning plans for a round-table conference on Monday, June 1. You are very welcome to attend. Sincerely, Robert C. Hockett, Ph.D. Associate Scientific Director RCH:vr encls.
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Ma,y 2~, 1970 Dear Doctor At the Scientific Advisory Boe~d :~eeting on May 17, ?~e mLno~m.ccd that a rotund-table conference is to be held on Jm~e I. The main p~'pose of the conference is actually to consider the ~nplic~tions of Dr_. Barbara B. Bro'~m's h~m~n~ electroencephalographic studies on smokers mqd non-smokers and the effects of nicotine. Planning of follow-up programs will certain].y require confin~ation .by independent investi- gators, exp~rt assists_nee in interpretation ~z,d advice on v~lids, tion, extension or ~q3plication of findinzs. For this r~ason, ~.:e are inviting several other C.T.R. ~rantees in the fields of netu'oph-.~'~acolo~y an[~ several guests. Time has been short for plarming because of the desirability of boldinz the conference before certain of those involved were du~ to leave for lono~ absences. Nevertheless, we have been able to line up enough grantees ~n8 outside consultm]ts~ we thi~, to make ~ conference ~el! worth;.:hilc at this t.~xne. A copy of our letter to the pa~'ticip~mts is enclosed, 8,1ouE with ~ list of those ~.fnose presence we e~ect. Of we hope that several ,,:,,:,,~.~h~-..~ of the S .... n~_.f,.c ,na~ be able to attend. Please telephone if you esn be present. Sincerely yo~s, RCn. vr encls. Robert C. ]Iockett, Ph.D. Associate Scientific Director
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THE COUNCIL I~OR TOBACCO RESEARCH-U. 110 EAST ~)TH STRE]:~I' NEW" YORK, N. Y. ]0022 May .21, 1970 Edward F. Domino, M.D. Department of Pharmacology University of Michigan 6~0 Medical Science Building Ann Arbor, Michigan 48104 Dear Doctor Domino: In carrying out its commission to sponsor a broad program of research into tobacco use and human health, The Scientific Advisory Board to The Council for Tobacco Research has found it very useful to hold informal, ~npublicized, roundtable conferences. More than thirty such conferences have been held on a ~de variety of topics to consider the state of knowledge, appraise developmenhs, select new objectives, develop perspective and especially to assess newer available techniques. Participants include recipients of grants-in-aid from this Counci!whose studies are related to the topic t~der discussion, members of the Scientific Advisory Board and Scientific Staff of the CoUncil, and selected guests whose research has distinguished them in ~he field concerned. Attendance is generally limited so that participants will all have opportunity tocontribute in a relaxed and informal atm~osphere. Another such conference has been arrsnged for Monday, June i, 1970. The topic is Effects of Nicotine and/or Smoking on the Central Nervous S~stem. Within this broad topic, there will be special focus on evidence suggesting that genetically based "prevailing encephalo- graphic patterns," which are modified by nicotine, may antedate the • adoption of human smoking practices ~nd play a role in their deter- ruination. Such ~ topic as the latter can hardly be discussed productively in isolation from relevant material in the field of neuropharmacology and in the study of behavioral effects of nicotine in animals. Hence several investigations in these latter areas are to be included in the program. Present recipients of Council grants are invited to m~_ke twenty ninute presentations of their findings and of studies in progress, as they relate to the conference subject. A blackboard and projectors will be available.
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TI~E COUNCIL FOR TOBACCO RESEARCH- U.S.A. May 21, 1970 The meeting ~Ii be held in the conference room of the Council on the tenth floQr of the building at ll0 E~st 59th St., New York 10022, beginning at 9:30 A.M. A ~-oup luncheon will be served about noon in a nearby hotel and discussions continued into the afternoon as long as seems worthwhile. Out-of-pocket expenses ~.611 be met by The Council. Since you have already ifidicated that you expect to be present, this letter is intended to confirm the arrangements and give you further details about the plans. Wew~ll appreciate receiving a confirmation of your pl~u to attend emd ps2-ticipate. Sincerely yours, Robert C. Hockett, Ph.D. Associate Scientific Director RCH:vr
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Effects o~" Nicotine and/9.r Smoking on the Central Eervous System Conference of June l, 1970 Grantees of C.T.R. 1. Barbara B. Bro~n, Ph.D. Veterans' Administration Hospital, Sepulveda, California Subject: Exploration of the differences in E.E.G. patterns - subjective state correlates in smoker and non-smoker subjects. Ed~'ard F. Domino, M.D. The University of Michigan, Ann A~-bor Subject: Effects of tobacco smoki.ng and nicotine on the centrsl nervous system. Ulrich H. Schaeppi, M.D. Mason Research Institute: ~'[orcester, Mass. Subject: Nicotine a~inistration to rostral areas of the cat brain: • effects upon E.E.G. and autonomic system. Changes in E.E.G. and ~ehavior induced ~.~ith the protracted intravenous a~ministration cf small doses of nicotine in tun- restrained cats. ~. Leonide Goldstein; Sc.D. Ne}~ Jersey Ne~u-opsychiatric Institute, Princeton, N. J. Subject: Study of bioelectric differences between nicotine-habituated ~nd non-habitusf~ed orgenisms by use of hi~n-ener~jphosphate compo~mds and psych,tropic drugs. Thomas C. Westfall, Ph.D. University of Virginia School of Medicine, C~_a~-lottesville, Subject: Influence of nicotine and related drugs on the upt~/~e, storsge, release and turnover of catechol~mines in central 8_ud peripheral tissue. Budhev Bhag&t, M.D. Saint Louis University Medical School,~. louis~ Mo. Subject: Nicotine induced behavioral chsnges emd t-~rnover rs~e of biogenic ez~nes in the brain. Walter B. Essman, Ph.D. Queens College, City University of Ne~¢ York, Flushing, N. Y. • Subject: Nicotin~ action On memory consolidation. Sachindra N. Praggn~_u, Ph.D. Howard University, l,[ashingtcn'~ D. C. Subject: Effects of nicotine on behavior an~. its interaction ~th drugs. Guests NaimKhaz~m, M.D. Associate Professor of Psychiatr2 Mr. Sinai School of Medicine Fifth Ave. at lO0 St., New York, N. Y. 10029
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-2- 2. Henry B. Murp~_u'ee, M.D. Department of Psychiatry Rutgers Medical School Ne~ Bruns~ozick, N. J. C~rl Seltzer, Ph.D. Senior Research Associate in Biological ~hnthropology Dep~tment of Nutrition, School of Public Health Harvsmd University, Boston, Mass.,
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H. H. RA[,~,~ 19th FLOOR As noted on page one of the enclosed newsletter: "There is divers|ty of op|nion regarding tobacco use and health. Charges against tobacco are w~dely public|zeal, but less attention is given to materials which indicate that differing op~nlons exist. Th~s publ~catlon reports some of these materials." The Company feels it is important for its management personnel to be aware that the smoklng/health controversy ~s a continuing one w~th more than one v~ew constantly being expressed. Therefore, beg~nnlng with the enclosed issue, you will be receiving regularly Reports On Tobocco and Health Research, which is published quarterly by the Tobacco Institute Inc., primarily for members of the medical and scientific professions. Internal Communications Department
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Reports on Tobacco and Health Research IN THIS ISSUE Lung Cancer, p. I Rate of Increase, p. 2 Research Needs, p. 3 Vol. 9 No. 2 Winter 1967.8 There is diverdty of opinion regarding tobacco use and health. Ckorge~ ogolnst tobacco ore wido|y publidzed, but attent~ is glvon Io materials whlch indicate that differing opinions exist. This publication reports some of these Independent Swedish Studies of Twins Reveal... Genetic Factors Affect Heart, Lung Syndromes 'Smoking Is Probably Not Associated With Coronary Disease' A detailed study of 196 pairs of twins indicates that cigarette smoking is probably not associated with cor- onary heart disease, high blood pres: sure, or high blood cholesterol levels, according to two Swedish investi- gators." The study also indicated that both the tendency to smoke, and susceptibil- ity to heart disease, may be due to constitutional differences between peo- ple, the authors said. Twins are widely used in studies of the possible effects of heredity upon disease, since the inheritance factors operating in each pair can be known *Lundman, Torbjorn, and Blomftrand, Roll: "Smoking in relation to coronary heart dis- ease and lung function in twins." Acts Medics Scandinavica, Supplement 955:1-75, 1966 with some precision. In the Swedish study there were 92 pairs of identical (monozygous) twins, whose inherit. ance is identical, and 104 similar (dizygous) twin pairs, who differ from each other genetically. The Swedish investigation con- firmed earlier findings that identical twins are more likely to have the same smoking habits than are similar twins. In fact, the authors say, "it proved ex- tremely difficult to find enough mono- zygotes that were discordant with re- spect to smoking" to satisfy the condi- tions of the study. Tests of blood-fat levels and other measurements with the twins "would seem to support the theory that smokers and non-smokers have constitutional differences." The authors conclude that "Cigar- ette smoking is probably not associ. ated with coronary heart disease, whether of the overt or the silent form... "Cigarette smoking most probably (Continued on page 2) Constitution Is Found To Be Important Element In Cough and Angina Studies of 7,801 pairs of twins have revealed a marked influence of consti- tutional or genetic factors on both respiratory symptoms and angina pec- toffs, a series of Swedish-papers reports." The studie~ also revealed an asso- ciation of some other symptoms with smoking in which a causal relationship "is difficult to imagine," the investi- gators say. (Continued on page 4) *"Morbidity among monozygotic twins," ,4rclt. Envir. Health, 10/2:346, February 1965. "Respiratory symptoms and 'angina pec- toris' in twins with reference to smoking habits," .4rch. Envlr. Ilealth, 13/6:726, 1966. "Hereditary factors, "spontaneous ~oe~/l~I and 'smoker's cough.'" ArcA. Envir. )4:401, March )967. Survey Suggests Lung Cancer Susceptibles Relationships between lung cancer mortality, age, and smoking among men in eight major metropolitan areas are "incomprehensible according to current ideas as to how smoking affects lung cancer incidence," according to Dr. Percy Stocks of England." Some of these relationships, he says, may suggest the hypothesis that only a limited part of the population is in- berently susceptible to the disease. The areas studied were Belfast, Dub- lin, Helsinki, Oslo, Copenhagen, Liver- pool, North Wales and Wrexham. In most of these cities, it was found (Continued on page 3) Study of Two Israeli Populations Finds... Smoking, Cancer Statistics Don't Match Lung cancer of all types occurs three to four times more often in the ocidental (European-American) im- migrant population of Israel than in the oriental (Asian-African) immi- grants, even though smoking is about the same in both groups. ~ This "discrepancy" in the smoking theory of lung cancer is reported in a study by two Israeli doctors published by the World Health Organization." *"Can the deviating lung-cancer-smoking relationship in Israel be explained by dif- ferent distribution patterns of histological types?" Cancer Mortality and Morbidigy in Israd: 1950-1961. World Health Organiza- tion. Geneva, 1967. The differences in lung cancer prev- alence between these two majorpopu. lation groups cannot be explained by. (Continued on page 4) CORRECTION The report on "Assessing the Cor- onary Profile" (from Geriatrics, Feb- ruary 1967) in our Fall 1967 issue incorrectly identified a company as being the large New York corporation from which the population studied was selected. The study group was not from the corporation named in our story. We regret this inadvertent error and apologize to the company and authors.
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British, U. S., Canadian Figures Show... Lung Cancer Increase Rate Slowing; May Stabilize in 1975, Then Decline The rate of increase in lung cancer should reach a plateau "before rather mortality appears to be slowing pro- than after 1975," Of the U.S. trend, gressivdy in England and Wales, the the Gilliam team said "the disease will United States, and Canada, and may reach a peak among the white male stop or even reverse by about the mid- population in the foreseeable future 1970's, vital statistics indicate, and "then start to decline," possibly The British and U.S. figures also in- about 1983. dicate that almost all of the recent in- The Canadian statistics were pre- crease in incidence is accounted for by ,anted by Dr. E. W. R. Best, chief, epi- persons born before 1901. demiology division, Canadian Depart- The most recent analysis is that o! ment of National Health Welfare)"" the British. Registrar General, dated He said Canadian trends are "consist- May 1965 but not available in the ant with the hypothesis that the male United States until last year." lung cancer mortality rates are near a [No explanation or speculation as peak," but does not project a date. to the reasons for the detected trends The British report noted that the is offered in any of the analyses. How- rates had already stabilized in 1957. every some scientists have noted that 62 for all age-groups up to 60 years, a decline in the rate of increase of while for males aged 60-64 years the lung cancer is consistent with th~ as- increase in this period was only about sumption that much of the apparent 25 percent (compared with 50 percent rise in incidence is due to improved in the period 1951-57). For males be- diagnosis and awareness of the tween 65 and 80, the percentage in- disease.] crease was also cut in half. The report also noted that the in- Decline Is Steady cidence of lung cancer in males born after 1901 has increased very little, if The U.S. figures, analyzed by the at all. It says: "It is the increasing late Dr. Alexander Gilliam and associ- death rate due to this disease in the ares of the National Cancer Institute, elderly survivors of previous cohorts showed a steady decline in the rate of that accounts at present for the rising increase of all respiratoD, cancers from trend in lung cancer mortality in re- 1930 to 1958, particularly among cent years in England and Wales." white men and women." The same- However, these rates are converging trend appeared for cancer of the lung toward the predicted overall plateau in only, in the period 19-t6-1958. the mid-1970',. According to the British figures, the • decline in the rate of increase up- Men Chiefly Affected peared in males for the period 1956- 1962. The Gilliam findings for the U.S. Canadian figures are less complete, showed that in the period 1930-1958, but in the decade 1952-1961, the rate the average rate of increase in lung o| increase of reported lung cancer cancer deaths among U.S. white men mortality in Canada averaged 6.9 per- dropped by one-half, from 10 percent cent per year for the first five years, to five percent; and that for the period for all ages, both sexes. In the last five 1956-1958, this decline was confined years of this decade, however, the almost solely to white men under 55 comparable rate of increase was 3.3 years of age (that is, those born after percent per annum, the turn of the century). The overall Britain's Registrar General esti- figures for the total period 1930-1958 mated that the British death rate indicated declines in all age groups ex- cept for those above 65 years of age. *Registrar General's Statistical Review o! (The Canadian figures are not age. England and ~Fales Ior the Year 1962, Part specific.) llI, May1965 The U.S. figures showed declines **"Trends of lung cancer mortality attri- for both sexes, although smaller for bhted to carcinoma of the lung." Cancer, May-June 1961 women than men. The British staffs. ***"Lung cancer mortality trends in Can. tics showed no decline for women. The ada."Canadian Medical .4ssociation Journal, Canadian figures do not provide this Januar~ 19, 1963 information. 2 Tobacco and Health Research Published by THe- TOBACCO II~STJrUTr-, INC. Address correspondence to: Tobacco and Health Research c/o The Tobacco Institute, Inc. 1735 K Street NW Washington, D.C. 20006 The Institute does not necessarily agree with theories advanced or con- clusions expressed in the studies re- ported in this publication. CHD in Swedish Twins does not result in persistent hyper- ~,el~ Suir~ nn g [ah~ sgthi nbe ln°c°edt hPer ~ SoUo ~e ]p'~e sSis ~Cr ee . is lower for smokers than non-smokers. "Cigarette smoking .seems not to produce any elevation of the serum cholesterol or triglyceride lards. On the contrary, there is some evidence . that the levels are lower for smokers than for non-smokers. "There is reliable evidence of a sig- nificant genetic component in coron- ary heart disease and related para- meters." The authors also found that "Cigar- ette smoking gives rise to a significant increase in the respiratory symptoms -- of chronic bronchttis, an ~ncrease ~n ~- the unevenness of ventilation.., and "~'. an increase of airway resistance." "The results of the present study concerning heredity and coronary heart disease provide a basis for the theory that constitutional differences between smokers and non-smokers can give rise to excess morbidity and ex- cess mortality from coronary heart disease in smokers," the authors con- clude. The British report also showed a greater increase in lung cancer incid- ence in rural areas than in urban dur- ing 1956-1962. However, the report noted, rural incidence is expected to remain substantially lower than urban incidence for some time to come; and the rural mortality figures show the same trend toward stabilization as the overall figures do.
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Stocks: Cancer Theory (Continued ]rom page 1) that the relationship between lung san- ccr death rates and amount smoked declined after age 55. In contrast, the relationship seemed much "higher than expected at about age 40. In a subsequent paper, Dr. Stocks estimates that in 17 of 20 countries, cigarette smoking appears "the most important factor in determining na- tional death rates of men from lung cancer before age 45," hut "air pollu- tion by coal smoke is as important as cigarette smoking in determining rates at ages over 55."# The mean rate of incidence of lung cancer in the 55-64 age group, in the 20 countries analyzed by Dr. Stocks, was 19.4 times higher than that for the 35-44 age group in 1962-63. The investigator points out that some facts "seem incompatible with current ideas about the role of smok- ing and air pollution on lung cancer causation." Among these are: 1. Among even long.term, heavy smokers, "only one-tenth of such men die eventually from lung cancer." 2. Among all lung cancer victims, the proportion of heavy smokers de- creases with age, even though duration of smoking increases. 3. The risk of lung cancer falls off within a few years after cessation of smoking, which is incompatible with the theory that the disease process re- quires about 20 years of exposure to the smoke. 4. Men are universally far more susceptible to lung cancer than women, regardless of smoking habits. These and other findings, Dr. Stocks proposes, may possibly be susceptible to explanation by "a hypothesis that smoking and air pollution affect only those persons who have first developed a susceptibility to lung cancer." "In ~placcs therefore where there are more heavy smokers," he explains, "this would lead to more deaths at an early age, depleting the numbers of susceptibles surviving to later ages and leaving fewer to die in those age groups. This would lower the ratio of death rate at 55-64 to that at 35-44 as actually observed" in the surveys. *"Recent epidemiological studies of lung cancer mortality, cigarette smoking and air pollution, with discussion of a new hypo- thesis of causation." British ]. Cancer 20/4:- $95, December 1966. ~"Lung cancer and bronchitis in relation to cigarette smoking and fuel consumption in twenty countries." British ]. Prey. $oc. Mad. 21/4:181, October 1967. Research Official Declares: Unity Needed To Solve Disease Puzzle Dr. Robert C. Hockett, associate scientific director, The Council for Tobacco Research - U.S.A., has called for cooperation between government and industry, aimed toward "piecing together the jig-saw puzzle picture of factors and influences that cause or aggravate such diseases as cancer, cardiovascular ailments, and chronic lung diseases." In a paper recently delivered (see box below), Dr. Hockett. proposed that research be directed toward the following questions: 1. To determine whether or not there are in fact health hazards in cigarette smoking; 2. If there are, to define and meas- ure them; and, 3. To elucidate their mechanisms by laboratory and clinical studies. 4. To develop new mathematical methods of handling large, multlfactor studies in the field of epidemiology. 5. To place particular emphasis upon studies of "predictor" factors in longevity, especially among twins. 6. To duplicate more closely the conditions of human smoke inhalation in animal experiments. Existing epidemiological studies, Dr. Hockett notes, fail to establish that any single factor is causally con- nected with higher or "excess" death rates among the total population. "The fallacy in concluding that these 'excess deaths' are caused by smoking is obvious to any thoughtful person," he comments. "If we knew that the sub- jects of study were alike in all other respects and that the only difference was in their smoking or non-smoking, we might be able to conclude that the difference in mortality was caused by the smoking. But we know just the opposite from such studies as have been made so far." Dr. Hockett adds: "This does not deny the possibility that cigarette smoking - or excess sleep or tranquil- lizers - may help bring on some excess deaths. I am only saying that Copies of "Where Do We Go From Here in Tobacco and Health Research?" by Robert C. Hockett, Ph.D., are available on request from The Council for Tobacco Research - U.S.A., 633 Third Avenue, New York, New York 10017. the present studies do not establish this as a fact and they give us no idea of how many so-called 'excess deaths,' if any, are attributable to smoking. "This is why The Council is giving assistance to a very ambitious study of the many human factors associated with relatively longer life and with relatively earlier death. A tremendous number and variety of observations are being made upon the people being studied. Smoking habits are only one. We are trying to find out how other life habits and characteristics tend to cluster with smoking or with non. smoking and how these may serve, singly or in groups, as mathematical 'predictors' of longevity .... "The methodology developed will be available for use by various govern- ment agencies and other groups con- cerned with similar problems .... " Dr. Hockett notes that Surgeon Gen- eral William H. Stewart told a con- ference in September 1967, "The door to cooperation has always been open. It remains open." "The tobacco industry initiated not only cooperation but leadership in seeking reliable answers long ago," Dr. Hockett points out. "It set up and financed The Council for Tobacco Research as an independent commis- " slon of scientific and medical men to investigate tobacco use and human health. "There has certainly been no lack of very realistic and constructive coop- eration. However, if the present call for cooperation from the Surgeon Gen- eral requires acceptance of ari the cur- rent doctrines, viewpoints, and dogmas of the Public Health Service, there must be reservations. We conceive the ultimate objective to be so piecing together the jig.saw puzzle picture of factors and influences that cause or aggravate such diseases as cancer,. cardiovascular ailments, and chronic lung diseases that these can be better prevented, delayed or Controlled. "We feel that our cooperation to- ward this end will be most effective if we can maintain and exercise our in- dependent judgment." Dr. Hockett concludes: "It is fortunate that in scientific work a variety of different working hypotheses andcontrasting viewpoints can stimulate good research. We hope to continue and intensify our work along the lines outlined here." 0
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Call Constitution More Important Than Smoking (Continued]tom page 1) They also note that their survey In the analysis of respiratory symp- toms, it was found that although smokers show more such symptoms than non-smokers, they do not show as many more as do persons with a genetic predisposition to cough. Angina pectoris, on the other hand, occurred with equal frequency in smokers and non-smokers. The studies investigated the inci- dence of cough in identical-twin pairs in which one twin was a smoker and the other a non.smoker. The existence or non-existence of cough in the non- smoking twin of the pair was assumed to define whether his smoking co-twin belonged to a "high-risk" or "low- risk" group. Calculation of the relative risks for the two groups, the authors found, showed that smoking increases the in- cidence of cough by a factor of three, but that the effect of constitution increases it by about six. "In light of these figures, the role of smoking in the development of cough, though well established, is markedly less than the role of the con- stitution in the individual case," they comment. "The individual belonging to a'nonsusceptible' constitution group might well smoke without running more than half the risk of developing cough run by a non-smoking individ. ual belonging to the 'susceptible' con- stitution group. If he belongs to the 'susceptible' group, the smoking indi- vidual runs an added risk of develop- ing cough which is only half the increase that smoking provokes in nonsusceptible individuals." These results, they say, demonstrate "that for the individual the genetic influence is relatively more important in the development of cough than is smoking." Angina Findings When only the first-born members of each twin pair were considered as a group, smokers showed an increased frequency of angina pectoris as com- pared with non-smokers. This differ- ence disappeared, however, in a com- parlson of 1,924 twin.pairs consisting of one twin who smoked and one who did not. "The findings of a similar frequency of angina pectoris among smokers and non-smokers is in agreement with certain data recently available from the Framingham and Albany studies," the authors comment. showed an increased incidence of "back trouble" among smokers. "It is difficult to imagine a causal connec- tion with smoking in this ease," they say, "and the finding seems to suggest that in an investigation with such similar groups as these, factors with- out any direct connection with smok- ing may be of decisive importance." The studies were conducted by a group of five scientists headed by Dr. Buns Cederl~f of the Institute of Hygiene, Karolinska Institute, Stock- holm, and published in a series of three papers from 1965 through 1967. Dr. Cederliif and one associate in the studies, Dr. Lars Friberg, are cur- rently directing a stud)" of 8,000 male twin pairs sponsored by the U. S. Pub-. lic Health Service and the American Medical Association, at the University of Cincinnati. The research, based upon the Swedish studies, "seeks in- formation on the relationship of such environmental factors as tobacco smoking and air pollution to certain cardiovascular and respiratory com- plaints," according to the National Research Council, which compiled the twin registry being used. Eye III Is Called Nutritional Disease "The available clinical and pathological data suggest that tobacco-alcohol amblyopia is the same as other types of proven nutritional amblyopia. Clinical experiments have been carried out on patients who were al- lowed to continue their usual consumption of alcohol and to- bacco, but who were given ade- quate diet supplemented by B vitamins. All of the patients showed some degree of recovery of their visual acuity and a re- duction in the size of the scoto- mata despite the fact that they continued to drink and smoke. Therefore, the term 'tobacco- alcohol amblyopia' and its clas- sification under the toxic ambly. opias seems unjustified and the term 'nutritional or deficiency amblyopia' seems preferable." -Pie'rre M. Dreyfus, M.D.: "Nutritional disorders of obscure etiology." Medical Science, April 1966 4 Lung Cancer in Israel (Continued trom page 1) assuming a "smoker's" and a "non- smoker's" type of cancer, the authors found. The study was undertaken, the doctors say, because of "certain pecu- liaritles of the smoking situation in Israel" that did not conform with findings in some other Countries. Lung cancer (as with most other types of cancer) occurs in oriental immigrants to Israel at a "considerably lower rate" than among immigrants from Western countries. However, a smok- ing survey indicated that the orientals did not smoke less; "they might pos- sibly smoke more." Drs. J. Rakover and Gertrude Kall- ner studied case records of lung cancer patients from three major depart- ments of chest diseases in Israel, cov- ering most of the lung cancer cases in the country. The material analyzed spanned the period 1950-1961. Smok- ing histories were obtained for 426 histologically confirmed cases of lung cancer. Of these 426, it was found, 85 occured in persons born in Asia or Africa, while 341 were in those born in Europe or America. In terms of rates per I00,000, the lung cancer prevalence wa¢ 16.9 for Western-born, and 5.9 for the orientals. It was then postulated that this dif- ference might be explained by assum- ing a different ethnic distribution of two types of lung cancer, one (adeno- carcinoma) being characteristic of non-smokers, and the other (squam- ous cell carcinoma) of smokers. When the Israeli material was examined from this point of view, however, the incidence of adenocarcinoma as well as other histo]ogieal types of lung can- cer was found to be between three to four times as great among the occi- dental population as in the oriental group. The rate per I00,000 of adeno- carcinoma among the occidentals was 5.9, and for the orientals, 1.7. This preponderance held true for non-smokers as well as smokers, the authors point out. "... it might be assumed that in this case, the smokers" cancer would be equally distributed while the non- smokers' type would prevail in the oc- cidental part of the population," the physicians say. "From the "material presented above, however, just the op- posite conclusion must be drawn." 0 0 0
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Reports on Tobacco and Health Research YoL 9 Ko. I Fall 1967 IN THIS IlitiUE Animal Tests, p. 2 Diet & Heart, p.$ Cancer Links, . p.4 C~ Large Navy Study Shows,., Lower Birth ~ights Do~'~ Affec~ Survival Although infants born Io mother* ~ho smoke weigh k~ on the average ~ ~ i~ide~e of ~estational pro. n~turity ~ ~reater, th~ findin~ ~r to ~vc no clinical siEnifiea~e, according to a two-Tear =tud~ 48,5~ pre~nanclea by four Navy ph?sici~." In addition, ~. Cads• Paul B. Un- derw~ and a~iat~ ~ound a ~sur- pt~in~ and slgnificant~ d~a~ in I~ i~i~e o~ pre~lam~ia amon~ ~ ~ing mother. T~ ~ndings ¢onGrn~ an earlier ~ud)' a~ led D~. Un~rw~. (Am. [~ mumps of p~in~ studi~ ~¢ ~n published on the ~ible e~ ~ ~ternal smoking on ~irl~ ~¢i~ mn~ premalurlty, ~ ith vsrylog ~ul~ T~ Underw~ stud) ap~rs Io ~ ~ ~r~t yet ~ pr~tive study ana])'z~ data ='P~ ~okin~ empirically ~lat~ to I~l~;~. Ma~ 16. 1~ Two Studies Assess 'Risk Factors' As Coronary Disease Predictors Hard-Driving Personality, ],ii~tl~rotci,t, llype,'iension Arc Found Proguostic A specific b,:havlor pattern--the hard-driving personality -- signifi- cantly increases the risk of coronary bears all•case, = follow-up study of 3,1~2 1non has confirmed." The stud)• was conducted by Dr. Ray H. Rosenman of Mount Zion Hos. pitM, San Francisco, and five col- leagues in San Francisco, Burbank, Calif., and Chapel Hill, 1~. C. begin. nlog in 1960. They found that the pres- ence of abnormalities in lipoprotein pattern and of hypertenslon were also prognostic of heart disease. The behaviour pattern implicated "is characterized particularly by ex- cessive drive, al~gressi~eness sad am- bition, frequently in association with = relatively greater preoccupation with (Continued on page 4) ="Coronsrr heart disease in the Western ¢olltboratit¢ group =tud~.~ Journal ~1 tAe Ame,icaa Medical As~ciatlon. 195:~, Jan- ua~ tO. 1~ Almost All Cancer Deaths Highest in Urban Areas, PIIS Figures Reveal; Patterl~ Called Unique Death rates front slmmt all forms mortality with increased urban den- of cancer for the 20-year period Iqb'~ were hlphett in the m,~t highly ~pu~t~ urban =~as, reachin ffak in Washin~on, D.C., a~otding to U. S. Public Health ~rvic¢ figure." "Si~ ~ deaths were r~otded t~i&~, not by place of death, the ~ttem b a te~'lion not o[ cot~enlra- li~ of h~pitM ~r~ic~ but of s~ual ~rtality in the r~ident ~po- ~tio~~ the authors ~i& ~is ~ttern of i~ea~ ~er ~'Ret~l ~ttetns in ~tt~itI kom c~ ~ t~ U=itcd 5~" C~acct. Mal I%7 tit) showed up fur respiratory cancer. for cam'or of lhe intestines (except rc~itun, t= cunccr u[ the breast. ea~er of the genilourinaff iexcept ~r~ix). The only general category of cancer that ~ailed to lob low the ~tlern. according Io the v~tigalurs, ~us cul~er of the skin, and they i~int uut that lira figur~ for this category lump together two quite different kinds of caners. The reglonal ~ttern for cancer starts with m~cra/ely high death rat~ (Conllnued on ~ge 3) Of Eight Factors Weighed, Sinoking Is Discounted As 'Unimportant Variable' Smoking is "an unimportant vari- able in the early recognition of cur- unary heart disease," according to long.term study published in the medi- cal journal 6"eriatrics.° The study, begun in 19~, site•pied to /,ssess the usefulness of eight fac- tors- of which smoking was one- in the detection of coronary-prone in- dividuah in s group of 490 men aged 23-79, who were examined routinely in the medical department of l~e~ York's Union Carbide Corporation. The other seven factors measured were hlood cholesterol levels, blood phot- ]~h,,liplds, body build and weight, eight, blood uric acid, blood pro- sure, and family history. • Prediction Score lti~h In the group, 32 men were con- sidcred to be coronary-prone on the basis of relatively high ~eores in the seven factors. Of these 32, 22 subec- ~uently had s heart attack |m)'ocar- ial infarction) and eight more have a)'mpt,,ma of heart disease (angina peclurls). Two have ken judged free of the disease, giving a positive pro- diction of 9-1 percent. Of the 458 individuals judged not purl. only four have developed syrup toms of the disease. 2"he investigators did find that the coronary-prone group smoked more cigarettes daily than did the control group. They comment: "'There is no doubt that Ihls other published data indicate an sociation between cigarette smoking (Con:inued on page 2) • "A~e.~|ng the coronsrlt prufde.." Cethstrics. }'¢brua=7 1~67 .2"
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In Intact.Anlmal Experiments... Cigarette Smoke Fails to Interfere With Pulmonary Clearance Processes Exposure of animals to cigarette ~clenllsts note, lung edema is held Io smoke did not interfere with polmnn- indicate ahnormallti~ in the ckar. ary clearance, according to the late mace pr~s. ~o fluid retention was Dr. Charl~ ~. ~lle and h~ a~qn- found, the~ ~y. cial~ of Jefferson Medical College, ~e authors note that some ~ien- l'l~ilndelpbia." ti~ts hove reported that cigarette "~e~ ~ults," the ~entlsts ~ay, smoke is cabbie of inhlbhln$ the "are at variance with the current llt- partlcle-trans~rllng action of the tilt- erasure on the sublet." They ~int ated cells llnin$ the re~plratory tract. out that previous ex~rlments were They add: "The inhibit,ry eff~t on confined Io I~ting the effect of clga- lung clearance, however, has not ~n ~ette smoke on ciliary activity [o[ ex- convlncln~ly demonstrated by dir~t cised ~tio~ of bronchial epi~e- inv~tigatlon of ~is Fr~... ilum].~elrex~riments, on the other must ~ kept in mind that the ten- hand, were d~igned In measure lung dency has ~n to demonstrate u ~e- clearance us a whole' in the intact ducllon in ciliary lu~ion and onl~ animal. Io infer from this thbt a ¢orres~nd- (Since ~elr pa~r was accepted for ins reduction in pulmonary clearance publication, the ~ientlsts repo~ in lak~ place." their ~, their ~ul~ have ~en con~rmed by a study by W. J. Bair and J. V. Dilley, anduup~rted by a Role Of study by ~ E. Alert and a~iate,, both re~rted at ~e ~ond lnterna- ,~o,,~ sm~,x~ 0, ~,~.~,a v,,.In Condensate Cance~ ,~=,,av,~,~c.~s,mg,.~.~ 'Seriously Questioned' Particle Uptake Unaff~ted Four French investigators, publish- ing in ~e Iour~ o[ the ~'~ In the t~, rabbits and mi~ were Co~r I~t~u~ (U.S.A.), have ex~d intermittently to connotes- ou~ly que~tloned" the theory that ~e tion~ of clgarette smoke on a ~hedule ~ntpyrene content ol cigarette smoke simulating human smoking ~tterns. conden~te "plays a leading ~rt~ in Two different ty~ o[ radio-actlve ~ncer." t~t ~rlicl~ were u~d to a~ay both ~e Fresh authors ~y: rapid and &layed clearance, t~ au- "One etplanation [or the ca~ino. th~ rearS, genlclty of such a comple~ mixt,.e as In one ~ri. of tests, 26 ~ts of cigarette smoke conden~le would lm •ree or rome o~ations were made to delhi I +ul)slan~ lunda~nlMly on Eve or more pairs of eabblu. In a res~nslble lot it... M~t ~cond ~ri~, there were 179 ob~a- along ~e~ lln~ incriminate alone on si~ ex~ed rabbits, and 174 pyrene (Be} found in cigarette stones ob~atlons on six control cabbie, condensal~, but in amounts lar from Both filter and non.Eher cigarettes su$clent In induce, by them~h'~, were I~led. In a third ~ri~ of ex~ri- experlmentM lumor~ either carclno- meats h was found that removal of in- mas o~ ~rcomas.. ~e complete car. haled carbon particles [rom the lungs cino~enlc activity of lee condensate by the white bl~d cells was not inhib- ~nnot ~ explained In this manner, since conden~te [eactlons containing ited by cigarette smoke, and was tually increa~d by ex~sure to the no BP show carclnogrnlc activity. Neverlhe~, some authors ~lieve smoke of non-Eher cigarette. ~e ~'hite bl~d ~11 ex~rlmen~ that the BP content mi[ht at ~st ~ involved 1~ ex~rimental rats and 20 considered as an 'indicator' of the controls. In ~e~ studio, fluid reran- llon was also measured, sin~. ~e ""~nm[s]p~rcne~ntenl I1~ ol ~garelle ~ke ~nd,n~ate--¢~ul~ • "~'e Influen~ o[ cigarette ,~ke on ~n~ e[short-te~ and ~n~.lc~ leith" Philip~ clearance." AtcAives ~1 En~ir~nmemt~I ~r ¢t ~ Fnnce, l. A'~d. C~,c~ I~ Hedt~. 1~:~. May 1~M:573. ~ovem~r 1~ Tobacco and IfeMIh Research Published by TIlE ToR.~C¢O I~$TtTffTF., 1~¢. "Addr~ corr~ndence Io: Toba~o and Health R~arch ¢/o ~e Tobacco Inrthute, I~. 17~ K SI~I ~.W. Wa~hlnglnn, D. C. 2~ peeled lumorogenic acllvhy of con- densetes." To tr~t this hypothesis, the four ~ci- enlists of the French Cam'er tie,catch Institute and ~ational Institute for Heal~ and M~icM R~h ttudi~ ~ smoke condensat~ in 21 ex~ri. meaL*. ~ey ~asured the blolo~icM activity on mou~ skln-a standard test ~ of cigarette smoke enriched with ~ntpytene. In their ex~rlments they applied conden~let ¢ontalnln~ added amoun~ of ~pyrene up to 30 tlm~ the amount print in ~elr ~natural" (unenric~d) conden~t~ Reaullt Seem 'Conclusives They found no correlation ~twe~n biological activity (including appear- ance of cancers) and the benzpyrene content of the condensates. The~ re~ulL% they ~a)., ~'+m "con- clu,ive enough an thai the part BP is oflen suppo~d to play in experimental anlmsl carclnogene~|s by ¢iga~etle smoke is now Io be ~eriously que~. lioned," Smoking Discounted As Coronary Variable (Continued ]tom ~ge 1) and coronary heart di~a~, but this do¢~ not prove a causal relationship. It it, Ihetefore, not surprising that the i~lu~ion o[ ¢i$areUe tmoklng as additional variable in the linear dis- ¢rlminali~n anal)'tit increamd finn bF a mgli~ble 0.~. smoking did not add at MI In the ,ificalion value ol ~e profile ~ote, was dimounted as an unlm~rlant variable in the early r~o~ilion coronary heart di*~." T~ aulho~ are Dr. Menard Gert~r end H. !1. Whher of York Unlve~ity ~hool of Medlci~, and Dr. J. J. ~el~h, medicM dir~tor of Union
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bs'YC'a Anli-Coronary Club Finds,,, Diet Lowers Heart Disease Incidence Among a group of 814 men be- tween 40 and 59 tears of age, a diet relatively rich in polyunsaturated fatty acids has significantly reduced obesity, serum cholesterol levels and hypertension, according to Dr. George Chdstakls and a~iat~ of t~ New York City ~rtment of Heahh.s Smokin8 did not a~t the r~uhs, he ~id. In addition, the incidence of "cor- onary even~" was significantly re- du~d. as compared with a control ~group of 4~ men of the ~me age, ~e ~uthors ~y. Smoking llabils Unchanged "~he d~rce~ in morbidity ex~rl. enc~ by the ¢xperinwutal group coulJ not ~ a~ri~d to any change in cifarelte-smoklng habits," they add, "since inv~tlpation of this ~rameter indicated similar smokln8 ~tterns in the ex~rimental and control 8rou~ ~th on eotry to the study sod st the ti~ of o~rvation." *"E~t of the Anti-~rons~ ~ub program iourn~ o~ tAe ~merican Mediful ~ssn~ Among men aged 40 to 49 who used the special diet for five )'ears, there was a heart.disease incidence rate of 339 per 100,000, compared to among the non-dieters, the investi- gator* found. In the 50 to 59 age group, the rates were 379 per 100,000 among the dieters sod 1,331 per 100,000 in the control group. More Sludy Needed The men in the study volunteered after learning of the "Anti-Coronary Club" through newspaper and radio atmouncements. None had experi- enced coronar)' ]war| disease before the study began. Although much more study is needed, sernln choh'sterol reduction seems worthy of consideration as preventive ntedical program for the community, the authors say. " "The practicing physician can use the serum cholesterol determination to screen his hlgh.rlsk patients. Armed with knowledge, skill, and time, he can practice preventive medicine in his own office in an effort to reverse the risk factors affectlog his patients," the investigators suggest. PHS's 20.Year Survey Finds... Urban Density Cancer Correlated (Continued./tom ~age 1) on the Pacific coast, lower rates in the B~'k) Mountain states, and then grad. ualiy increasing rates from west to east. ]'he highest rates occur in Penn- sylvania, New Jersey, New York and the District of Columbia. Bates are low in rural New England and the S~uth Central states, and lowest in the Deep South. Mortality from cancer of the res- piratory ,)stem "followed the cancer regional pattern very strongly," the imestigators noted, in the latter half of the' study. Male death rates from re~plratory cancer were four times the females' rates, with the rates for Cau- casian females actually showing a de- cline in the later period. Death rates front diseases of the cir- culatory system showed the same se- lationship with urban density. Both these relationships were called "firm, consistent and highly significant" by the authors of the study, Eleanor J. Macdonald and associates of the Uni- vershy of Texas, Ilouston. They said the correlation was the most striking to enterge from the study. CV Pattern Similar The authors point out that *'no other categories of disease have patterns re- motely resembliog" the cancer death rate pattern, except diseases of the cir- culatory system. "The pattern of urban density ex- plained the very high death rates con- aistently experienced by the District of Columbia since the whole of the district is urban by definition," they added. "This gave the clue to the fact that it was dcnsily of population rather than tndustrializatioo' that par-,, alleled the cancer mortality pattern. The study did not include Alaska or llawaii, sioce it was conducted before these two territories hecame states. Emotional Repression Called Characteristic Of Lung Cancer Victim Individuals capable of discharging their emotional conflicts appear to be less likely to develop long cancer than are emotionally repressed people, ac- cording to Dr. David M. Kissen of Southern General Hospital, Glasgow." The study, which confirms previous work by Dr. Kissen and that of other investigators, involved 866 men aged 55-64, of whom 218 had lung cancer, 76 had psychosomatic illnesses, and 72 had non.paychosomatic diseases. These were part of a larger group (over 930) which had not yet been reported on at the Ihue of Ituhlicullou. Diaereses Unknown At the three interviews with paticttls were conducted, Dr. Kisseu notes, noue o| the diagnoses were known to h|m, nor had a dia~gno~is of cancer been given to any pattenS. The patients were all recent admissions (during 1958-63) to one of three hospitals and were not under his clinical care dur- ing the experiment. The lung cancer patients showed a higher incidence of both childhood and adult "adverse life situations" than did the non-cancer patients. Dr. Kissen also reports that differences be- tWeelt the cancer patients and the non- psychosomatic patients were consider. ably larger than those between the cancer victims and the psychosomatic patients. The main adverse childhood sltua. tion reported was disturbed parental unity, while Ihe major adult situations were disturbed Interpersonal relation. ships (mainly with spouse) and work upsets. Prevention Suggested Valid measurements of such per- sonality factors, Dr. Kissen suggests, may prove to be an important aid in the early diagnosis of cancer. He adds iu conclusion: "Even more attractive however is the possibility of helping to ~revent the onset of cancer . . . Intensive pre- ventive measures directed at the vul- nerable minority should be more re- warding titan indiscriminately di- rected general propaganda." *"Psychmoclal factors personality and pro. vention n luna cancer." TAt Mtdieal O~¢er, Sept. 2, 19~
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In Three Different Countries.., Cancer Rates Show Odd Associations Death rates for cancer of the bind- After tabulating the figures for the der for males in 20 countries over the 14 sites involved, Dr. Hewltt noted: ~riod 1956-1959 •re aesochted with death rates from cancer of the intes- tine, rectum, pancreas, prostate and skin, •s well •s cancer of the lung, an Oxford researcher has pointed out.s Several previous papers had noted the •~soc;atlon between bladder can- cer and lung cancer, and suggested shared rehtlon whh smoking" •s an explanation. Dr. David tlewln at Ox- ford's Department of Social Medicine, • nabzlng cancer mortality data for 14 sites previously offered by British, American and Japanese workers, com- mooted: "It is, of course, the shared relation with amoklng which makes the car. relation between these two particular sites •n intere~tlng one. Before con- cluding that the obvious mcanlng is the correct one, however, it will be necessary to place this finding in the general context of inter.carrel•Clans among cancer tiles." '"C~eer a! lung sod of bladder." Leltsr, TAe L~scet, April 2, t966 Heart Personality Pattern (Continued Jrpm page 1) competitive activity, vocational dead- lines, and similar pressures," the entlsts say. "An enhanced ~ense of time urgency is usually abo exhibited by subjects possessing this interplay of endogenous behsvior hctors and exogenous pressures, with v•rloos re. 1,1., ~.d ~It I1,1h Sul,Jr~'l~ I. s m'.,td, en.ha,ll.g group also occaslon•lly exhibit tame of these ch•r•cterlstlcs, the authors ~y, but to • lesser de£rce, "Although st•tlstic~lly significant differences in weight, cigarette smok- ing. prevalence of dystollc hyperten- tlon, and ~erum lipid values were found in the 39.to 49-year-old seg- ments of the two behavior pattern groul~," they add, "it is questionable whether these •mall differences are of true clinical relevance." '~hey conclude that "piesent result~ clearly indicate that the presence or absence of s particular overt behavior pattern carries a profoundly important prognostic relevance. To our knowl. edge, this factor has not been studied previously in any systematized "Of the 91 possible pairs formed by these sites nn less than 11 show s cor- relation significant at the I~ level and • further eight at the 5~ level .., It will ~ ~'en that the bladder and lung both belong to a group of per. haps seven sites for which mortalil~ rates tend to be positively associated, while there is a negative association for the mortality attributed to cancer of the liver and of the stomach." 22 Others Found Among other alatistlcslly signifi. cant •ssoclations, Dr. Hewitt found that cancer of the lung was also posi- th'ely associated with cancer of the in. testine, of the xectum and of the pan. cress. There were also 19 other associations involving neither the lung nor the bladder, such as one between cancer of the prostate and cancer of the skin, and one between cancer of the thyroid and leukemia. ion in any large.sash epidemlologlc study. The resuhs oi the present study strongly suggest that if its presence or absence is not included in the assess- ment of olher probably prognostic in- dices, grave errors in interpretation may be made." Muhiple Theories In Emphysema *'There mast be 15 theories in the etiology in emphysema and you are quite entitled to take your pick among these, It is prol~bl)" as good as anyone she's pick. But that is not really the questinn we can yel •*k. We have to be tare we are looking • t one condition... And when the pracllcing physician is faced with a man of 45 with • chronic cough and • good deal of dysp nea, he is challenged to predict what the lung is like. Until he seriously tries to do this, it's ex- traordinarily hard to re•lice how bad the methods are at his disposal to make any differenti- ation between bronchitis with airway o~truction, aqhms with spasmodic airwa) ohstruelioo, often chronic Ibolh of those having •n intact lung parenchy. real, and the differing kinds of emphysema . . . The first thing you learn when you try In pre- dial accurately the morphology of ~e lung in people, and follo~ them over a long period of time, is that in this main endeavor, we have hardly )'el begun." -D. V. Bates: "The ~hallen~ of PuT•nosey Emphysema." ,,,,. c.,,,,a ,',,,~.~ o-,,. 'Low Birth Weight Does It:,',,|,.,,,,l i,,.., ~.t÷ I I t, ubmltled h,,m .11 ~vod,l.~dde Naval in~tsllatlon~, gathered b)' attending phvslcia~ upon admission of ~e m~e~ in the lair r~m. ~e sub- j~ were classified into [our ~te- gori~: non.smokers, and amoke~ o[ 1-10. ! l~0, and 30 or more cigarett~ ~r day. Approalmalely hall of the mothers were smokers, with the major- icy falling into the 11~0 cigarett~ a day categor)'. • ~ ~lampsla Deceased ~e study showed "a definite'de- cr~ in biflh weight and i~rcagd prematurit7" in ~e infants of sank. ins ••then, the authors ~y. How. ever, 'fibs clinical im~rta~e of the~ fin0in~ was mlnlmlz~ sl~e t~re Not Affect Survival' tt~ It,t h.,wSle |. i,ethttld Idily," 5bc'th'The incldence o| pre.ecl•mps|a, mild and severg decreased di- ~octly with the amount the mother~ tmoked," the authors reporL "For. thee•ore, if pre.oclampala w,,s pres- ent, a slgnlfieantly higher percentap~ of the non.smokers developed the severe form lending credence to a po~ sible protective effect of smoking on Io•emi•.~ The maximum effect, they found. was reached with moderate smoking. The authors conclude: "~hen using perlnatal survival an end point, no adverse effect of Carnal or paternal smoking cluing pregnancy was demonstrated in this group of 48,505 prefnancle*." :t
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AMERICAN CANCER SOCIETY, INC. 521 WEST 57th STREET, NEW YORK 19, N. Y. • PLAZA 7-2700 ~anuary 16~ 1959 MEFFORD l~ RUNYON F.XECLrrWE VIC~ Pi~E~IDFN'[ Hr. Ja~es P. Richerds President end ~ecutive Director The Tobacco Institute, Inc. Nash~ton 6, D. O. Dear ~r. Riohards: Your letter of ~eptember 17, 19.58, to Governor Kohler, Chairman E~ of D~eotor~ ~s b~n ~re~ ~nsider~. The B~ ~t~ot~ its ~ttee ~ ~ok~ a~ Health to fo~ate the ~iety~e Acco~~, this o~i~ti~ constitutes its official Yo~ seem to be not o~mpletely ~n~or~ed on the Sooletyts position cm the relation of smoking and lung cancer whloh kills some 35~000 Amerloans every year and which is the leading cause of cancer deaths in men. Your letter states "the Tobacco Institutels feeling that a few dividuala in the Society seem to be concentrating more on the fight against tobaeoo than on the avowed basle p~rposes of the Soelety.a O~r announced ~rposes are to find cures for all forms of ~ancer a~d to dis- cover the cause or causes of the disease and thna ultimately make it possible to prevent its onset. Me are fighting for these objectives in every possible On November I~ 1957, at its Annual F~et~, the Board considered the report of the Study Group on Smoking a~d Health with which ~ are familiar. This report included the following oonolualon: ~The sum total of scientific evidence establishes beyond reasonable doubt that cigarette smoking is a causative factor in the rapidly increasing incidence of human epidermoid carcinoma of the lung. The evidence of • cause-effect reletlonahip is ~dequate for considering the initiation of p~blic health ~ea sill's a es The Board at that time offlcia~ly oons~rred in this opinion .a~d took the following action:
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.Directed that the Public Health Services of th.,~, ~'~deral Goverr~nent and of the several states and their sppropr~:~,~ agencies be urged to proceed with such ~easures as present knowledge indicates are needed for the protection of the hea~th of the people in th~s respect. @ Directed that evidence in this fte].d be br~nght direct he attention of the physician as ~t develops. It ~ctf:l- .~ ded that sn ~ssue of ~ ~ dovot~ to this ~ubJcct ~.~ ~;~'~:;t the letter to Dr. L~tt]e ~i~ a~e~re~ ~n the AT~h'f~C ~.~. _~ .'~ for October, 1957 and his rep~ be v~blished, ~nd the rc,~~<,~'~ of the S tudy Grou~ be reorlnted, ~ fu~her tb~t ~e H~on~ end Horn be m~de a~i]~Bb].e" ~ ~l] upon request. Th~ ~r~ - Apr~l Isle of CA ~s devoted to this A.~proved the testir~ of ez]>~rlment~] mater~sl o~ how to acquaint the high ~chool student w~th the possible ~,a~Pu] effects of c~garette am eking. Reco~ne:,ded thet further research in the f~eld of ~okin~ and air I~Llutlon sn~ their effects on health~ and pe.rtlcu_!arly lung cancer, be supported. These directives reflecte~ the mature ~nd ~eer]y unan,~o~s Judgment ef ~he Seclety~ ~ Boa,~d. Subsequent action has been Lu ~ccor~noe w~th these decisions. Since the Board took its po,~.tion o~ th~ subject In the Fsl] of .]9~7 the re~lts of the ~m~slve ~,tudy by Dr. Do~ of the United States ~blle ~e~Ith ~rvice have been ~shed and ~t agr~.es ~n ~ll essential res~cts w~th the ~mr~v previous stmdle~ wh~ ~ve been re~rte~ ~n the ~c~entiflc press and t~s ~-ther ~p~orts the B~,~s decision. The Society is convinced that it wJ].l only confuse the publ~c and therefore serve no useful purpose to engage in debate with the tobacco in.~ustry~s s~kesn~en ~uch as the Tobacco Instltute and the Tobacco Industry Research Cc~ittee on the slgnificanoe of increments of evidence as they appear. To the easua] reader ode statement is about a,~ good as ~notber ez~d it is only a r~u~te fraction of the reading public that h~s the t~me o~ the exp~rSence to evaluate the evidence. However, we repes.t and em~,hssi~e ~hst no evidence of any kind has ever been produced that is Incense_steer w~th the ~ew that ~xcess~ve cigarette smokJ.,,~:" is one of the principal ~uses of lung cancer; that the gre~t preponder~r~ce of scientJflc evaiu~tlon soeepts this concl~sion; and that it also accepts the mounting body of evidepcc indicting tl~e cigarette as a shortener of llfe.
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Mr. Jails P. R~oh~s --3-- aan'.-'~,*7 16, 1959 Yeur long c~a~un~cation and the enclosures thereto oontsi~ the die8enting v~ews of various ~ientiets who do not accept these conclusion. ~ of ~se ~otet~ons are s~t~nts ~t of ~nte~ ~h~oh ~ ~l~ev~ do not fa~ re~esemt the scientist's t~s ~i~. Other quotations are fr~ m~ora~a pre~ ~ staff ~bers of the Society for t~ ~ sldersti~ of its ~tte~s a~ ~ess ~ ~t~ t~y are e~roved ~ the B~ t~y s~ not ~c~ty ~li~. Nothing new ~ms presented to cha~ge the conclusions of our Board as to the validity of its conclusions reached we]~ over e y~ar ago| of the vledc~ end neoeeslty of the actions slnoe then~ s~d of the consistency of t~ese ectlcms with ~he objectives of the Soolety in the fight om earnest. The A~eriozn C~ncsr Society ,ocepts the weight of evidence di~ting t~t c~tte ~ok~ is oD~ of the ~Jor ~u~s of ~g ~D~r ~ ~n ~s. S~geon Genii ~y Bu~y ~ J~ ~, 1957 ~ ~bllo Health ~i~ feels ~e ~igh~ of t~ ~vldea~ is ~n%~ ~ o~ ~re~i~, ~t ex~ssive ~~ is ~e of t~ ~usative factors ~ I~,~ It is not necessary for e_~ scientist to accept this con~lusio~ mot for ~v a~i~ ~ ~~ ~ to be cx~uded ~fo~ def~i~ ~ie ~alth iv ~n. I~ ~d ~u~o ~s~a~ s~fer~ ~ ~.th to ~it for absolute p~of of a relatio~hip bet.,on o~a~tte ~ a~ part of their production to fi~ter cigarettes they too recognize the fast t~ ~ars and nicotines constitute health hazards. This is furor borne o~t by ~he~r advert, is~ng clai~-s which vi~ with ~eoh other o~ polr~,~ ~.~t the effiolensy with which the filter in The future course of action of the Society will be ~arefully ~- sidereal and will be deoide~ by the Board of Directors. It its responsibility to the public es ~t sees it, ~ased o~ the praises stated above end suboequent fecbs ss they d~velop. Thi~ letter in effect restates a~d re~ffir~s the Society's poslt~on as explained last Ju~e in a c~z~ioztion to Mr. T. V. Har~.nett, Chairm~n of the Tobacco Industry Hesearch C~tt~e, a copy of which is attach~ for your ~formmtlcm. Yours very truly, Attsohment
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THE TOBACCO INSTITUTE, INC. .~l;tTIt 1017, BAKIt BU~Lm:¢~. 91~ 17T~ S~r N.~. WASHINGTON, D. C. /~ovembeF 17, Ig58 ~k'. Box~a~ Or~,, President R. J. Reynolds Tobacco Coupany IBnsto~-. ~ale~, North Carollna Cancer Society, l~onal ~ts of ~e Ko~ letter, ~lth ~ po~g f~ts ~la~ve to ~b~co O~er. Very slncere]~r, J~mes P. Richards. 0
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1 From th~ de~k of J. P. RICHARDS For your info~natlon. JPR
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THE TOBACCO INSTITUTE, INC. SuH~ 1017, B~ BUlLYINg, 910 171"H S'r~l" N.W. WASHINGTON 6, D. C. PHONt~ METIOPOLIT.4~ 8-2144 COPY September 17, 1958 Governor Walter J. Kohler Chairman of the Board of Directors American Cancer Society Kohler, Wisconsin Dear Governor Kohler: Mr. Ragland and I enjoyed very much meeting and talking with you and Mr. Runyon last Wednesday in New York. We appreciate your taking so much time from a busy life to discuss with us the ob- Jectives of the American Cancer Society as well as some problems of the tobacco industry. With this letter, I am.taklng~advantage of yourexpressed willingness to consider in more detail The Tobacco Instltute's feeling that a few individuals in the Society seem to be con- centrating more on the fight against tobacco than on the avowed basic purposes of the Society. During the past several years, the American Cancer Society and this country's tobacco industry have had a mutual interest in seeking to unlock the secret of lung cancer. You evinced-a ready-understanding of why. all parts of the tobacco industry, from grower to final consumer, are anxious to have the question of tobacco's involvement settled scientifically. With this letter, I would llke to enlarge somewhat on the industry's position and the reasons for it. The three attach- ments go into greater detail on certain points. We are all aware, of course, of the wide differences of opinion among scientists as to the interpretation of statistical data concerning the alleged relationship of tobacco use and can- cer. These statistical reports are at times contradictory, often inconsistent, and, as the Public Health Service pointed out in July, are not supported by laboratory and clinical re- search.
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Governor Walter J. Kohler September 17, 1958 Page Two Exploitation of charges against tobacco based ~on much-debated evidence may work a genuine disservice both to orderly scientific progress in the conquest of cancer and to the millions of people who find in tobacco a simple and inexpensive source of pleasure. The tobacco industry places the people's health above every other consideration in its business. We support the idea that the public should be given the facts about smoking and health, but believe that all the facts should be presented. Quite naturally we are concerned when the highly respected and widely supported American Cancer Society seems to take the attitude that the case against tobacco use as a major cancer cause is proved, even though the reported statistical association of tobacco, as weli as other factors such as animal fats, with the incidence of heart disease is not accepted by heart disease authorities as showing a causal relationship. As I discussed with you, it seems to us that recent publica- tions and statements from Cancer Society officlals show that there are sc~e in the Socletywho are insisting on full acceptance of the tobacco-guilt theoryand on a Cancer Society pollcythat would campaign to abolish the use of tobacco. I give later in this letter our reasons for believing this. As the Society's Chairman, you know that there are divergent scientific opinions and research findings as to the validity and ultimate soundness of the tobacco-guilt theory. Ther@ is increas- ing scientific recognition that many other factors, Includlngalr ~ollutants, may not have been given sufficient attention, because of the preoccupationwith the publicized tobacco theory. In viewof your expressed interestbecause of your position in the Cancer Society, I am discussing at greater length in three attachments the following points which we touched on in our con- versation last week: i. The Tobacco Industry Research Committee's i~terest in supportln~ scientific investigations into all phases of tobacco use and human health. Grants from the Tobacco Industry Research Committee are awarded by a ten-man Scientific Advisory Boar~ to independent in- vestigators in established educational and research institutions. Complete scientific freedom is accorded~all grantees in carrying out their work and publishing results. So far, about ~5 papers resulting fro~ T.I.R.C.-supported research have been published in medical~udscientific journals, thus contributing to the body of knowledge concerning tobacco and health.
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Governor Walter J. September 17, 1958 Page Three Kohler - The Scientific Director has reported that none of the work reported to date confirms the tobacco-guilt charges, while demon- strafing that there is no quick or simple way to determine whether any one factor has a role in inducing h~nan lung cancer. The Scientific Advisory Board agreed on the following statement of position: "The problem of causation of lung cancer by its very nature presents many variables including age, sex, and other biological factors. The evaluation of these is further complicated by techni- cal and statistical factors... --"The Scientific ~Advisory.Board believes that definitive conclusions or predictions of IndividuaS risks are unwarranted by the present state of knowledge in this camplex field of lung can- cer causation. "In advising and educating the public, we believe that scientists should be as cautious today in accepting a claim that a cause has been found for cancer as they have found it wise to be in the past in accepting a claim of a cure for cancer." 2. The American Cancer Society's public position on the ques- tion of tobacco use as well as certain proposals that have been suggested by the Society's staff as part of its polic~ on smokin~.. Some Cancer Society officials four years ago -- in 195~ -- were actively pressing for a crystallized position implicating smoking as a major cause of lung cancer. The 1957 Annual Report of th~ American Cancer Society, while proposing that individuals be given all the facts (emphasis mine - J.P.R.) so that they.can make individual decisions, actually outlines a concrete and organized campaign against smoking. In light of our conversation about statements impugning the integrity of scientists working with the Tobacco Industry Research Committee, I wonder if you would look again at the articles on the inside front cover and on Page 71 of the March-April 1958 issue of CA - BU~.T2TIN OF CANCER .PROGRESS. So~e quotations are given on Pages 2 and 3 of Attachment No.2. Your attention is also directed to the short paragraphs at the end of pages. These appear to be direct attacks on the tobacco industry's motives and on the integrity of scientists who have voluntarily undertaken the responsibility for developing the research program for the Tobacco Industry Research Committee.
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Governor Walter J. Kohler September 17, 1958 Page Four Regarding our concern over the Cancer Society's future position relating to restrictive measures against the tobacco industry, I refer to the Cancer Society document developed by the ACS Administrator for Lung Cancer Research, which we recognize may not yet be offi. cial policy. Sections from this document are cited on Pages 4 and 5 of Attachment No. 2. There is reference here to the ACS's possible position on policies and activities that would oppose Federal programs for tobacco price supports, would urge increased insurance rates for smokers, assist in legal actions against tobacco companies, and encourage restrictive legislation and regulation of the tobacco industry. Some of these we discussed in our conversation the other day. The document concludes that the "most obvious solution to the problem is to have people quit smoking." 3. Excerpts from recent (1958) scientific and science news reports showing a great variance in opinion of the possible in- nocence or guilt, or of the degree of innocence or guilt~ of tobacco as a cause of cancer. Some citations reveal varying degrees of acceptance of a statistical association between cigarette smoking and lung cancer but emphasize the paucity of evidence, if any, to show why this association exists, if it does. Other citations, being selective, do not purport to set forth the full view of the sources. They do, however, indicate the n~merous areas of uncertainty about the tobacco-cancer theory. Together, such expressions and reports pose a strong argument against an extreme and positive position in regard to the guilt or innocence of tobacco in the present state of knowledge. We hope you will review these items. We also hope that those in the Society who, like yourself, represent the dedicated thou- sands of medical and lay volunteers in the cancer movement, will see the need for and will insist upon application of the normal cautions of scientific prudence and of the historic American sense of fair play before Joining in or supporting an all-out attack on smoking as a human custom. Very sincerely, ~nclosures (3) (signed) James P. Richards, President & Executive Director
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Attachment No. i -- Page i TOBACCO INDUSTRY RESEARCH COmmITTEE 0r~anlzation The Tobacco Industry Research Committee was organized early in 195~ by the chief officers of nine of the cigarette and tobacco products manufacturing companies in America and five organizations of @rowers of leaf tobacco and tobacco warehouse associations. Its formation was prompted by the assertion of claims that there was a relationship between cigarette smoking and lung cancer. At that time the tobacco industry~stated through the Co~nittee that it had a responsibility to help in the investigation of such claims. The Com- mittee also stated that: 'He accept an interest in people's health as a basic responsibility paramount to every other consideration in ottrbusiness." Objective The purpose of the Tobacco Industry Research Committee is to sponsor independent research into every phase of tobacco use and health, and particularly into the alleged relationship between the use of tobacco and lung cancer, and to make available factual information on this subject. Research Polic~ and Pro~ra~, A Scientific Advisory Board of ten independent doctors and research scientists has responsibility for research policy and program. Members of this Board have unqualified scientific freedom in all phases of their work. The Board invites research scientists and organizations to submit proposals for specific research projects. In addition, it originates such projects as will contribute to its program, and asks appropriate scientists to undertake such projects. It obtains additional advice from experts who attend informal topical conferences conducted by the Scientific Advisory Board. The Scientific Advisory Board is made up of the following: Clarence Cook Little, Sc.D., LL.D., Litt.D., Scientific Director, Tobacco Industry Research Committee and D~rector Emeritus, Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine. Richard J. Bing, M.D.,Professor ofMedlcine,-Washington Univer- Sity Medical Service, VA Hospital, St. Louis, Missouri (as of July i, 19 8). McKeen Cattell, Ph.D., M.D., Professor of Clinical Pharmacology, Cornell University Medical College, New York, N.Y. t@
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Attachment No. I -- Page 2 Julius H. Comroe Jr., M.D., Director, Cardiovascular Research Institute, University of California Medical Center, San Francisco. Leon O. Jacobson, M.D., Professor of Medicine, University of Chicago; Director, Argonne Cancer Research Hospital, Chicago, llllnois. Paul Kotin, M.D., Associate Professor of Pathology, University of Southern California School of ~dicine, Los Angeles. Kenneth Merrill Lynch, M.D., Sc.D., LL.D., President, j)ean of Faculty and Professor of Pathology, Medical College of South Carolina, Charleston. Stanley P. Reim~ann, M.D., Sc.D., Director Emeritus, The Institute for Cancer Research and The Lankenau Hospital Research Institute, Phil- adelphia, Pennsylvania. William F. Rienhoff Jr., M.D., Associate Professor of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. Edwin B, Wilson, Ph.D., LL.D., Professor Emeritus of Vital Statistics, Harvard University, Cambridge, Massachusetts. Grant Awards Since the Committee's formation, $2,700,000 has been appropriated for use through 1958; $2,161,000 has actually been awarded in the form of grants through mid-19~8. There have been 9S original awards and 102 renewals to investigators in recognized institutions. To date, ~9 grants have been concluded and others are now in their fourth year of operation. Results The stated-poli~y of the Tobacco Industry Research Committee to all grantees provides complete scientific freedom in conduct of research and in publication of results by each grantee in acc~epted medical and scientific Journals or before accepted medicaland scientific societies. Thus far, about ~5 papers have been published in scientific Journals by scientists acknowledging support of their work by the T.I.R.C. These research results cover a number of areas. However, special note is made here of those dealing directly with experiments involving the tobacco smoke and cancer problem. As with similar experiments spon- sored elsewhere, none of the TIRC-supported scientists have found the presence of any substance in tobacco smoke to be a factor in cancer causation nor have inhalation experiments with animals and tobacco smoke resulted in inducing lung cancer. 0 0
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Attachment No. 2 -- Page i DISCUSSION OF AMERICAN CANCER SOCIETY POSITIONS ON SMOKING It is recognized that a difference exists between the American Cancer Society's officially adopted policies and positions and certain opinions and attitudes expressed by individual officers or staff mem- bers of the Society, as well as policies proposed for the ACS that are not yet officially adopted. Frequently, however, the public is not aware of such differences. A Review of the Record In 1954, a preliminary report of the Hammond and Horn statistical study, "Smoking and Death Rates" was given before the American Medical Association. This preliminary report emphasized a statistical associ- ation between cigarette smoking and deaths from cancer, especially lung cancer, and heart disease, and expressed the opinion of the authors that there was probably a causal relationship. A few months later, at the Society's annual meeting, the Vice Chairm~ of the Board proposed a conference of federal and voluntary Imblic health agencies to discuss the smoking-health situation. He said, "The American Cancer Society should not be the only one in the smoking controversy." He suggested that smoking in connection with heart disease was a more pressing problem than the smoking-lung cancer theory. Neither at this time nor subsequently did the .American Heart Assoclationaccept the~Hammond-Horn findings ~onsmoking and heart disease