Tobacco Documents Online

. .~'. ' -` l e , NCu) ENGLAND JOUFLNAL OF IvtED1CINE C%tar. 17, 1960 ) . / - ularly Nancy , who helped !dical-record .._.,..,.., .rt tlw tvcw York area and c1srwhcre, whtne assistance provided a rrur ial contributi„u to thr prrs- tnt study. REFFRE..crs 1. Dtaetir, T. T. Rheumatie fever: analstieal studv of 393 eases of rheunasie fever and 89 cases of elrorea. Am. J. M. Se. 172:199•221, 1926. :. Findlav, L. TAt RArrmatic le/tctioa in CAildAood. 167 pp. Lon- don: Arnold, 1't11. >L Roth. l. R.. Lineq. C., and 35'hittemorr, A. Heart disease in children: r:arutnatic troup: eertain aspects of aee at on•et and of recurrences in 4?,8 ravs ef juvenile theumatism ushered in by enajor ciiniral nuni(cuan„ns. Am. Ilrart J. 13:3CriA, 1937. 4. wih.,n, M. G.. and Luhschez, R. Recurrence ratrs in rheumatic fever: evaluation of ennl,~eic concepts and consequent preven4ative therapy. J.A.d(..4 126: 4? i•4i3. 1944. S. Jaeubs.on, F•. kheurnarie lever with ehona minor: elinieal study with special reference to prognosis. Acta pardiat. 33 (Supp. 7): 1•222, 1946. C Bland, E. F., and Jones. T. D. Rheumatic fever and rheumatie tsrarl disea.e: 20 year report on 1000 patients (ollowed since childhood. Circutation 4:8368i3. 1951. 7. }litchens, K. A. N. Recurrent attacks of acute rheurnatism in achool<hildren. Ann. RArrmat. D'u. 17:293-302, 1958. •. Jones, T. D. Diagnosis of rheunutie (ever. J.A.M.A. 126:481J{84, 1944. S. American lteart Association. Report of Committee on Standards and Criteria for Programs ol Care of the Council on Rheumatie Fever: )ONF.S criteria (mrRlifred) for guidance in diagnosis of rheumatte fever. Mod. Coectptt Cardiovar. D'u. 24:291-293, 1955. 90. MeCarty, M. Inrmune response in rheumatic fever. In RArrmatie - E'ever: A tympoziam Arld at the Univtnity o/ Alinntaota an ' i~ ss~o - ~ >< S 12. Fisrhel, E. E.. Frank, C. W., and Bellows, bt. T. St,dv of mani• festatinn of rhrurnane lever following cessation ol therapy. Cir- crfario. St:367•370, 1958. 13. Feinstein, A. R., SpaRnanlo, M.. and Gill. F. lurirbnre and •ie- nificance of reLnund phrrwmenon in acute rhesmraric (ever. Am. J. A(rd. (in press). 14. Frinaein, A. R., and Di Maw, R. Prv)gnnsric socnificanrr .+( valvular involvement in acute rheumatic (evrr. Is'ew Enp J. Aftd. 260:10fi1-1007, 1939. 15. Idrm. Unheard diastolic murmur in acute theuuutic festr. New Eeg. J. •t(ed. 260:1331-1333, 1959. 16. wood, If. F., et a1. Controlled study of thrre methods of pro= phylaxis against streptoc..ceal infection in population of rheusnatie children. 1. Streptococcal infections and recurrences of acute rheumatic fever in 6rst two years of study. Ntw Ent. J. A(td. 257: 394-398. 1957, 17. Feinstein, A. R., et al. Controlled studY of three methods of pro- ph%laais aeainat streptncoceal infection in population nf rhrunratie children. lt. Resulu of first three years of study, inchulin; methnd• for ev.luating nraintenance of oral prophylaxis. Nea EnR. J. 41td. 260:697-702. 1959. 18. Tarann, A. Relation of isolated reeurrenees of Svdenham's chorea to preceding streptococeal infections. New Eng. J. dlyd. 260: 1[0i- 1210. 1959. 19. DcLiec, E. M.. Dodge, K. G.. and McEwen, C. Prognostic sig- nifieance of age at onset in initial attacks oI rheumatic (ever. Am. Htart J. 26:681-684, 1943. 20. Boone, J. A., and Levine, S. A. Prognosis in "potential rheumatic heart di.ease" and "rheumatie mitral insufficiency." Aet. J. a!. St. 19i:764-770, 1938. 21. Brown, M. G., and 11'o1R, L. Recovery from acute rheumatic (ever without permanent cardiac damage. New En:. J. dltd. 223:242. -1940. 22. American Heart Association, Committee on Prevention of Rheu- lVavtmbtr 29, 317 and December 1, 1951. u.dtr the spnnsonAip o/ the Afianttota Htart Atrorietioe. Edited by L. Thomas. 349 pp. 23. Minneapolis: University of Minnesota Pre», 1952. 11. Wtwd, It. F., and McCarty, M. Symposium on rheumatic fever and rhrutnatie heart disease: laboratory aids in diagnosis of aht:umatie tever and in evaluation of disease activity. Aae. J, Mtd. 4. r, 17:768•774, 1954. matic Fever and Bacterial Endocarditis. Prevention of rheumaiic fever and bacterial endocarditis throueh control of streptncoccal infections. Mod. Coactpq Cardiova. Dis. 25 (Supp. 12):365-369, 1956. De Gnff, A. C., and Lingg, C. Course of rheumatic heart disease in adults: factors pertaining to age at initial infeetiun, development of cardiac insufhcicney, duration of life and cause of death. Am. Heart J. 10:4i9-477, 1935. Wtsod, H. F. Prevention of rheumatic (ever. Ant. J, Cerdio(. 1:436 463, 1958. Aff'e z, SOME PRACTICAL ASPECTS OF THE SMOKING-CANCER PROBLEI`i* ERNEST L. WYNDER, M.D.,fi AND DIETRICH HOFFMANIJ, Plc,D.$ NEW YORK CITY t \ T IIE majority of those who have investigated the epidemiology of lung cancer are in agreement that smoking, particularly of cigarettes, represents one of the causes of cancer of the lung. Several health au- tltorities have publicly supported this view. These include the United States Surgeon General, Leroy Burney, the Director of the National Cancer Institute, John Heller, the American Cancer Society, the Health Commissioner of the State of New York. l icnnan Hilleboc, and the public-health services of Great Brit- ain and the Netherlands.'-6 It is no longer an argu- ment whether smoking affects the dcvelopment of lung cancer, but rather a question of how the risk of the smoker can be avoided or reduced. The present report is designed to provide some practical answers to this question. ]hlltvious DATA It is an accepted principle in carcinogenesis that the greater the exposure to a carcincr,en, the greater oFeom the SeetNSn of Epidemiology; Divisiua of Preventive medicine. Slpan-lattering Institute. 1Asaxiate professor ..t preventive medieine, Sh.an-KenerinR Division, Cornell Universitr Afedrral Culleer; head, Section of Epidenuull•tly, Di- sision of 15reventive Afe.h.•n,e, bl.,an-F:etlerinR Inatrtutr, jVritinst researeh asu utr, Sectwn o( EpWetuinl..qy, nivisiun al PK- tttntist 1,1e3irrne, Sloan-l:r(tenuR Inslitute. the risk of cancer. This has also been established for tobacco smoke. Retrospective as well as prospective studies have shown that the risk of lung cancer rises with the number of ciaarcttes smoked. The Hatn- mond and Horn= report in 1958 showed that the non- smokcr's incidence of lttng cancer is 3.4 per 100,000 per year, and that of a person smoking half to I pack- a;e a day is 59.3; those smoking between I and 2 pack- ages have a risk of 143.9, and thou: smoking more than 2 packages 217.3. Dorn's" prosl7ective study on United States veterans and that of 1)0ll and I-lill' on Ilritisll physicians show similar results. laboratory data also show that as one increases the amount of condensate given to an animal, the tumor yield increascs.30 The importance of smoke-condensate yield has recently been demonstrated again in butt-length studies. Doll and Hammond have shown that the a.eraoc butt length of the British smoker is 18 fttm. as compared to 30 mm. for the American smokcr.t'•'a It has been proposed that this difference may account for the higher rate of lung cancer in- England." The amount of smoke condensate that comes into contact with the lung also depends upon the degree to which the smoker inhales, a factor not cacy to study. llowc.'cr, a majority of the published sft~•I~s

T . Vol. 262 No. 11 SMOKING-CANCER PROIiLEM- WYNDER AND IiOFFMANN S!1 ' . indicate that patients with IunG cancer tend to inhale tnorc than the control population."'" If the amount of flu;~lescent tnaterial in tobacco nnoke exhaled after inhalation is c.aminrd in ultraviolet light, as eotnpatcd with total fluorescent tnaterial, it is found, as Schmiihl, and his co-workcrs'a have shown, that the majority 'of the fluorescent material in tobacco- smoke condensate is absorbed by the lung. The available studies indicate that a reduction in the yield of smoke condensate of a cigarette and a reduction in the amount that comes in contact with the lun; will be followed by a reduction of the risk of lun; cancer. The purpose of the present investiga- tion is to determine how these ends can best be achieved and what progress has already been made in this field. METltons Laboratory Studies We determined the amount of smoke condensate of the ten leading American cigarette brands." For the collection of the mainstream smoke condensate we used a fully automatic Ethel Mark VI smoking machine, designed by the Cigarette Components Cor- poration of England. The cigarettes wcre.all bought on the open market in New York City dunnS July and August, 1959. We selected the cigarettes used for each run by weighing 200 cigarettes, taking the average weight and selecting only those that were within 20 mg. of the average weight. The determina- ~ tions of smoke condensate were based upon four runs on 10 cigarettes each. The condensate was obtained by electrostatic precipitation at an average voltage of 15,000.•olts. Since this high electrostatic field might change tlte composition of some of the components of the condensate, as our studies have indicated for cer- tain types of aromatic polycyclic hydrocarbons, we used a collecting system of cold traps for chemical analysis 4if the condensate. Otherwise, the smoking machine remained the same. All cigarettes were ignited with an electt•ic lighter and smoked with a 35-m1. puff volume for a duration of two seconds every minute to a 23-mm. butt length. The condensate was meas- ht over calcium it was dried to constant wei it d g cr ure a chloride. The condensate was not dried by heating at 110°C. to constant weight because of the possibiility that the polycyclic hydrocarbons would be affected. ,Tbe nicotine determinations were carried out by standard procedure.'0 In a special study we changed the frequency of the puff to two and three times per minute to determine the influence of such a change on the yield of smoke condensate. In another experiment we compared the quantity of smoke condensate collected from the first 30 mm. of an 85-nnn. cigarette to quantity from the second 30 nun. of such a cigarette. We also studied the ultraviolet fluorescence of in- haled and noninhaled cigarette smoke to determine how much of the fluorescent material is. absorbed upon inhalation. For each experiment the first ten pufis were taken on an 85-mm. unfiltered eipre::e. The puffs were taken by the same subject or.c: a TABt.t 1. Amotutt of Smoke Condtntate Contained in tAr Leading Brands of American Cigarettes. BaAN° NatoHas. Trsi Posmoss BY S+tzs, Stzi Swosu Coxotx- a+n/Cio- t.soamn.' Cro+arrn: 1959• Sta,. Aucrnt nl(. aat. Chester6eld 6 Plain !S 39.8=2.0. 2.66:0.14 Pall Mall 2 Plain BS 75.1±1.E 2.42±0.12 Camel I t'lain 70 30.2±1.3 2.G4±0.13 Lucky Strike 4 Plain 70 28.6±1.4 1.67±C.10 Eakm 7 Ftlur !S 26.0±1.3 1.8b±0.10 Winston S Fater ss 23.0_1.2 1.70+_0.09 Viceroy 9 Fitter !S 21.4±1.1 1.29±0.07 L fc 161 $ Filter iS 2t.72:1.1 1.37±0.0: Marlboro 10 Filter iS 20.l+1.1 1.32=C.0'i Kent S Filter !S 17.7±0.9 1.04;0.06 'Accordins to Woetten.e lwhere brands available in several lengths onty, iontest hneluded. l:or- respondint shorter eiprettea lower in smoke-ocndensate content. jE.perimental deviation included. minute. In 1 study the cigarette was attachea directly to a gas wash br,ttle containing spectrograde benzene, and the puffs were taken through the flask; in anot'r.er the puffs were taken into the mouth and then exhaled into a similarly prepared flask, and in the third, the puffs were deeply inhaled and then exhaled into t:e flask. To compare the benzo(a)pyrene content of the smoke condensate of the two leading American non- filter and filter cigarettes, chemical determinations o` this, the most potent carcinogenic compound so far identified in tobacco-smoke condensate, were made with the use of a method reported in detail else- where?t Clinical Studies We interviewed 304~ males over the age of forn regarding whether certain symptoms considered to be associated with heavy smoking, particularly chror-c cough, disappeared or diminished when they chaneed from nonfilter to filter cigarettes. A further objective of this study was to investigate whether filter smokers smoked more, less or the same number of cigarettes than they had previously smoked when using un6!- tered cigarettes. The subjects interviewed were pa- ticnts at Memorial Center, excluding those w:ii cancer of the respiratory tract, as well as a random sampling of the general population. Restnn Table I presents the data on the antount of smoke condensate yielded by the 10 leading American eicz-

: : TIIE NEW E\Gt.AND JC)L'R\:1L OF MED1C1N1: Mar. 17, 1960 n•ttt•s. whit lt, tc~~cthi r, accounu`/I for 8:1 Ix•t• cent of total ci-jtc•ttc sales durin!z 1959:' From these data scnnc gcnr•ralii:uicm• nia%- l,c derived: 77tc lcadin- kin,-circ cigarcttcs (85 mm.) haVc a higher content of smoke conden-ate than the lcadin:; rct;ular-si•rc ci•_arcttcs (70 mm.). '1'hc ntajrn itr of prr•,c•nt-da.• filter ci;arcttcs havc a sigmificantly 1MV/•r content of smokc condensate than nonfiltr•r ci-arrut•:. Thcrc is still an inq>,at:tnt clifTt•rr•ncc in smokl•- condrnsatt• content tof clilfcrcnt filter ci;atcttcs. A significant ilnhro.•t•Incnt in amount of smoke con- dcnsatc has taken ltl:rcc• in the majority of the filter cigarettes in the United States during tile last two )•ears. In general, the nicotine content of-a ,i.•cn ei;a- n•tte has ix:cn similarly decn•ascd as the amount of strtoke cundrnsatc has been reduced. . Figrn-c I compares the smokr condensate content of the first 30 nun, and the second 30 mnn. of/a kin- 0 . . ' , 12. tra~C. ----•~:.~. - - . .. t-- 0 lst 30mm. :: ••-r { ,-i Ftat-ttt: 1. Amount of Smoke Condensate from the First and Secoad Ilafr'es of an 8S-Mm. A'onfilter Cixaretee. siie American ci;arctte. Thc second half of the ciga- rcttc contains 43 = 2.2 per cent more sntokc conden- satc than tile first halL 1)ata on tile arnount of smoke condensate in a king- size unnftltcr cigarcttc when the frequency of puffs is eltanged from the standard values show such an in- crease to raise decidedly the amount of smokc condensate. 'I'hc y icld of smoke condensate amounts to 35.1 ntg-. when a smoker takes one huff a ntinutc, 53.0 nta. when ltc takes two a minute and -65.1 ma. when hc takes three a minute. Figttrc 2 shows a photoaraph of gas waslr bottles containing spectrogradc bcnzcnc into which cigarette stttokc has Ix-cn exhaled. It demonstrates that when srnokc is deeply inhaled, the atnount of fluorescent ntatcrial present in tile exhaled snroke is tmrkcxlly n~duccd as compared to that of tile cit-art•ttc stuokc tak.L-n otrly into tile nMUth. It is c•tinwtrd that tile dcu+it.• of lluula:ccncc in thc flask into which the cl~att:ttc srlttikc has lx•cn cxhalct) after deep inhala- ticm is alxrut !HJ lnr cent lecs than that in thc tla..k witlt ci;;att•tne smoke that has bccn taken only into tile tnouth attd then cxhalcd. '1'hix cstintatc agices with acttctl weight clctcrntinations of ci_arcttc-.nlnkr ctt:xlcn•atc bcforc and aftcr deep inhalation :t• 4il1- taincd from actual tcsts on smokcrc. Thc,c stllclit•.. on the baais of actual u-60hts of inllalcd ancl non- inhaled smoke condcnaatc, show that lon,-tcrzn smok- crs absorb 80 to 93 per cent of the condcns.ltc upon dc•cp inhalation. - I A. B C n Ftoukr: 2. Pu/is Taken into the Mouth, Not lnhol'ed and then F.xhaled throu.t6 the Bensene (rt ). PuQs Taken into the Mouth and Inhaled and then Exhaled fntu tlie l:la•k (B), Cigarette Attached to the Ffark and !'ujjed Uirertlt through tlie Ben:ene (C) and Gas iYaih b.ttJi l:nntainin; Spectrarrade Ben:ene (D). Table 2 lists thc ixnzt>(a )p)•rcnc content of fotn• popular American cigarettes of widely var.•ing suwkc condensate and indicates tllat, on a0gr:utt-1•or-grant basis, there is no appreciable difference in titc lx:nm- pyrcnc content of the cigarette-smoke enndcn.atc. '1'hesly data, however, also show that the higher tile Tmsr.c 2. Benzo(a)pyrene Content o/ Four Arneriran Ciru. rettes. BraAru Stu TuTa tsc.rr.(.}sY- L'cna.o(A)er- ('u-4aex- rtci O..- ec.W11.1 .u atan rw. u Fs.•/Cw- +uKm.. aS. 33.1_1./ n„r4/(ac- Aazrrs 00.r.ro. tAt1«0.1 Cw.. .r.Ttrx .wirrogwt. l.S+ 0.3 t',7ame1 70 7U.2_t1.3 3.SitO.S wirot.,n iS 23.Ot1.2 t.1St0.1 2.7±0.3 Kent i5 17.7±0.! 1.01r•0.1 1.10.41.3 •Ueretauaat by u+eer mntwd.s' smoke-condcnsate content of a given cigarcttc, the greater the exposure of a smoker to polycyclic hycLr.- curlxm. Ix-r gitcn nrnnlKr of ci;ar/•ttt•.. Autun;; al}1 makr smokers ovcr thc a-ge of forty, •l3 ixr cent h:t.c changed to liltcr cig:urttt•., rclk•ctitt., tile accelrtance of filter cigatt:ucs by the gctie•ral lxsltu- lation. F:xct•ht fnr the oc•casional person who int:rt'ast'J

. 0 Vol. _'6? No. ll WOKI\G-C:AICER PROBLEM ;- %1Y\DER A\D IiOFf'.%tAX% 543 his smoking hahitsm the data demonstrate that in t;cn- eral•sntokrrs who have shifted to filter ci,-,arettcc have nnt si_niticantly ehanue•el thcir :omunil,tion of ci,-,a- rcttcs. Amons the cntukc•rs who ned to smoke •or are still anokim, ncmfilu•r ci_arettec. 41 per cent complainc•d of dcfiniu• sytnptotwz. usuallv a chronic cou0h. Thc incidence of these .yntptoms %.•as found to incrcaw with the nwnbcr of ciuarcttcs consutucd. Amon,z thoce• .inokinu Icss than 16 citarcttcs Ix•r day 15 pe•r cent rontplaine•d of cytttptotnc assex•iatcd with .rnokitr,. and atm,nu tltow sniolcim, in c.ccss of 20 ci;aiettcs a day 52 per cent had sueh symletrnns. Fifty Ixr cent of the• hcarc• cmnkcrc re•portcd re,ression of s.nuptomc afte•r chan-.;iniv, from a nontilter to a ftltrr eigarrtte•. With more eascs at hand one could dc•tcr- tninc a•hcthe•r tltis intlrrocetne•nt in symptoms is in part a result of the• duration of smoking. It appears likeh• that if the stnokc•r lras IxY•n stnokim, heavil.• for a t,•rcat marr• ycar% thc eham,e•s in his bronchial tne ttta}' Ix• irrcvercible•. Iinrncc•vrr, since the study incbtdcd onl.• men over thc of forty. nearly tire entire z<rottp had suiokccl for twenty years. Dtsctastox For scmte .•ears our ~,roup has lxrn concerned with tht- utarked incre•aK• in Inn~ ,cancer and'ihe related role of cigarette uncrkiug. In 19,10 the nuroher af dcaths front lumg cancer in thc United States wa-. j3i3 for urah•c and 1fi26 for fcutalcs. In 1930 114.922 de•atltx front hur, cancer cx•curred in ntalks. and 3391 suc•h cb•ath:wc•re rclxorteYl for frtualc.: the ftmwrs for 195; ate 2ti: 2%7 and -1-It.t tr.pc•ctivch•. We ha%c often stated that thr mcrt t•ITectit•e way to alleviate the problem aould !k tu .tolr smoking, or at least to kecp it to a tniniruunt. Ilotvcvrr. it scrtns diflicult to cdu- catc• the pulrlic r(Trc•tive•Iv in thi, n••Itcct. in 1>art lK•- eatrse of the extt•n•it•e adcertisiniz, cantpaiun of tire tobacco induxtu.• to c•un.-incc it othen.•i•e. We thor- au-1-hl.• c•rtccntt•a!,c•. however. lrrc•c•nt t•ITorts Ibv tire Antetican (:ann•r Scx-irty iti tnakimg availalrlc to the ptthlic. particul:u•l.• the couth, data on the potential healtlt har,trcl. of eignan•tte <ntoking'. Practical Measures Ia+:c-~rn~r~I~-rnrtdrrnnlr c•ioarc•Nr.c. Althouch rduca- tica>.•tl e/i'c+rts mu,t Ix• continnetl. tcr are at prt••c•nt mttct•rntYl .vith .tclh that tire puhlic wi>;1Lt 1x• morr w•illin!g tu ac•ce•pt than to --,ic-e up sntokin:;. '1'hest• step:c utchrcle thc• rt•duction of amoke condensate lxr ci;a- n•ttr, t.hich can Ix• and is Ix•in, achict•cd through one ur uturc• of thr folloa•itt,gb mrtltcxls: '1'lie uK• af c•ITertirt• /ilters, which absorb as much srf thc- yne+ke condensate as practical. The .c•kxtion of tobacco .•icklinR lecc smoke eon- tlrn•atr. Thr uu• of le••c tolraccu Ix•r ci~arette. 'lltr uv' of Itii--hl.• porous or Ixrforatcd ciRarc•tte Ir,tlx r. It is tlcar from*Table I that most filter cigarettes arc si-nificanth• lower in smoke condcncatc than non- filtcr citiarcttcF. There is still considerable %ariancc. hcn.•cvrr, in the amount of eonclcnvtc in different types of filter civarcttcs - a difference that may not be apparent to the average smoker. The difierence in the smoke-condensate content of various American filter cigarettes. however, is less today than it was a .•ear or two ago. It is estimated that during 1939, 462,'r00.C00,000 cigarettes were sold in the L: nitcd Statcs.=' The ten brands that we have tested and recorded in Table I account for 83 per cent of the total volume of ei_a- rcttes sold. '1'!te first two positions (28 per cent of total sales, are still held by nonftltcr cigarettes. but thc third and fifth positions. as .rcll as the seventh through tenth positions. arc held by filter ei;arettes. Sianiftcant advance in sales has tx•en made in the filter fic•ld• as is apparent front tire marked increase in tire ucc of filtt•r civarettcs in this cottntn•. account- ing, for lcc. than 10 per cent of total cigarette sales in 193-1 and for 50.5 per cent in 1939. 77tc present data show that amom, the leading filter ciearettes there are sth•eral with a content of .ntoke conden~ate that is at lea.t a third less than that of tlte standard, re,ttlar. nottfilter chaart•tte. Similar reductions are obtained bv sorne other filter ci;arettct at prccent not anton, tle lcadint., ten brandx. according to Miller and Manahan.== with who.e detenninations our results arc in general agrcti•utent. Still lower condt•n.ate .alucs have been achieved hV the tu:utufacttue•rs of a new t:roup of ei!,arettrs currcnth• lx•in, introduced on the American tnarkct. such as 1)ul:c, l.ife and Sprin. It is too early to tcli w)tether cigarettes with sutokr-conderr.-ate .•alttes at this level will be accepted by the sntnker. However. the introductiun of such chgarettty by major American tobacco ccmtpanic" is..•elcomc. A review of the preK•nt field indicates that Atneri- can cinarette tnanufacturrrs are s;radualh• lowering tire smokr-rc,nclcn:•tte contcnt of the:r products. lir- eatta• of confusing advertising c•laints the public, ho..•- t-%-t•r, is not alwa\•x aware of the facts. It is for this rra-,on that tire data as prc~ented in this report and other stuclics nutst Ix• ntacle known not onl.• to tire trnYlical prctft•ssion bttt also to tire l,•ty lxthlic. It is hoped that tire prc.rnt trend of reducing tire sntoke eonden<:tte and nicotine values of leading Atnrrican ri!~aretttx will 1x followed be all tnajc•r tnanufacturcrs of filter eit;arrttcs in tite L'nited States. 1\'r predict that snch a trend will Ix• followed by a significant rc- duction in di<cavs associated with the sntoking of ci:;arrttxa, thr extent of a•hich, hot.•e.•er, cannot at prc•srnt Ix determined. Btdt Irn-tb• It is clear from this studr that the kiu!-sin: ci!,:ut•tte virlds morr tar and nicotine than ttis;ular-sin cigarcttrs. t:laims that tobacco is its own IK-%t filter arr tniclt'atlini, since it has lx'.n shown that

, 1 ' • S11 TI(t; \EN' EX(;I.A\I) JOI,'RNAli, OI' MEl)1(;I\E tile smokers erf kin'_-%iic cittarcttcs cmoke to the same butt 1en;th a% a smt•kcr of rc'_ular-ci•rc ciaarcttcs. Thtrs. .illcc tllc lattcr part td the ci',arcttc contain, (uolc condcn,,ztc and nicotinc thau tltc first part of thc ci',arcttr. tlu• vnc+kt•r of kin,_-.iic c•i-arcttcc in fact ih r•xlxt•e•(I u+ tut+rt• cif thcu• stlba:mcc: than tile sm<rkcr of rr,ular-5irc ci;arcttcs." A practical sn„cstion for tile smoker. tht•rcforc. is that hc should not slnokc the eigarettc to tht• vcn' butt. Ilc should try to put out his ei;arettc after consutniniZ it to the halfwav mark. Pu fJ frrque•ney and irlhalalinn. Studies cvaluatin' tile effect of frcclucncy of pufl's indicate that thc srnokcr should not pu(I too frequently on his ci,,a- rcttr. 711c smoker should a4o try not to inhale, or if lie must, not -e) deeply, since most of tile sluokc con- (lcnsatc is abselrbcd tyxm inhalation. It is probably for tllcsc rcaumc that lung cancer is less frequent among cit;ar and pipe smokcrs, even though pipe and cigar s/nokc has been shown to be at least as carcino- genic as cigarette srtlokc.=' hnpror'rrncnt of smoking syrnptonls. All these steps primarily influence the amotlnt of smoke that gets into the smoker's lun<s. Somc of tile stl.-Gestions arc more practical than otbcra• but all should be seriously .d eonsidcrcd by the cigarette smokcr. The prcdiction that lowering the -atlloullt of sntokc condensate in a given eigarettc will be followed by a reduction, though not an elimination, of diseases associated with smok- iing seems already justified in the clinical evaluation of sltlokcrs..•ho uscd to nnokc nonfiltcr cigarettes and ..lro havc now shiftc(1 tn filter cigarcttcs. From the present study material it cannot be concluded with certainty that there has been no over-all increase in cigarette consumption when a smoker shifts from a plain to a filter cigarette. C:ertainlv, there are some inveterate smokers ..-ho do not seem to get much ~satisfaction" out of filter cigarettes and therefore Inay tend to increase the number of cigarettes they consume. The present study suc,ests that, in general, 1(oHC.'cr, the smoker ot' filtcr ci;arcttcs has not sig- nificantly increased his consumption of eigarettes. Particularly important is the ohse•rvation that tends to confirm our clinical experience that half thc filter- cigarcttc smokers who have had sylnptonts frotn their "noking stated that tllcsc conditions improved after changing to filter cigarettes. This improvement is, of course, chicfly a result of the fact that tile 61tcr- ci,arette stn(+ker gets less slnoke condensate 1>cr given 1>Hdf of eigarctte. '1'hic impro.•cntent of tile smoke•r s rraetiort txxomcs cslxcially apparent whcn the smctkcr of an cfl'ivetivc filter eitrtrcttc shift% hack to a non- filtcr eigarette'y which Itl! rnlw I/rKlt e/ftPn quite harsh and 1)Itlnt,r ' Itrdu.tir,n uJ rartinurwrtc arud u,-cartinurcnt. Ao- uthcr appluach to thc problrrn under (liseue+ion ic tet (tctc(luinc whether we can quantitatively louk-r the aromatic lolvcyclic hydrocarbons in tobacco smoke, sutr.t:11N't•1i lllat we c'IomidCr to be tile tllajor Irlitlatlll" .1 Mar. 17, 1960 ccarcinogens in tobacco-slnok(• contlcnsatc.=' In thi% conncction we have been concentrating on rcducinL or modifying the couthustion tcullx•raturc of tobacco. As far as reduction of tltc• temperature is conccrn(•d. we have so far not bt•(•n successful in discuc•c•rinq a uscful wa.• of accomplishing tlli.. We hold tnc» t• ho}x_ for thl• lxrsxibilit% ' of modifying the coutbuaion of t<rbaccirs in such a..•ay that fewer aromatic lxd}•cyclic hydrot'arbons will bc fortnt•d. Studics tnust also hc• carried out in thc field of co-carcinogwr.c.:.. It is pos- sible that promotin; substances suclt as thc phc•nnls can be reduced tnorc cfficicnth' than t}IC initiatim, carcinr,cns. It is still too early to tell whether asolu- tion is possible in the ge•ncral direction of rcducinl; carcinogens or co-carcinogens, but work must bc con- tinuc•d in this area. SUMMARY AND CONCLUSIONS Some practical suggestions that should lead toward reducing the risk of cancer of the respiratory tract among smokers arc given. The following measures are suggested: moderation of smokin; for those who cannot give up the habit; usc of filter cigarcttcs with the lowest yield of smoke condensate; avoidance of slnokin-, the cigarette to the butt since there is sig- nificantly more smoke cond4nratc in tile latt-:r part of the cigarette; and not inhaling dxply since such a practice leads to much greater absorption of smoke condensate by the lungs. The bcnzo(a)p}7cne content of various cigarcttc- smoke condcn-atcs is similar when judged on agram- for-gram basis. Per cigarette, however, it incrcases to(cther with an increase in the arnotrnt of smokt• condensate. Thus, the user of a cigarette with a high yield of smoke condensate will be exposed to more benzo(a)pyrcnc than one smoking a cigarette witit a lower yield. Filter cigarettes tend to diminish synlptotns, csl)c- cially that of cough, often found to be associated with .mokin;. Further research must be carried out in alt at- tcmpt to reduce carcinogens ant) co-carcittog gcns fl'ottt tobacco-smoke cottdencate. )(tEFERE.\CES 1. Burney, L. E. Lans cancer and etcerive eipretu wwlint: Dr. Littlr'. rrplv. CA: flrrl. (:a.rrr Prelr. t:ii, 1958. :2. lletler. J. R. It Ynu're .rorried about cancer - ad.ire Irutn authority. 11. S. Xran Cst 11'.rt1 Rrjar !i (.'l):60 atnl /.:. afay ':i, 1!d9. '/. Atnrriran (:anrer Snriely. Annua) Report 1958. P. $0. 1 4. 11AIrl.re. I1. E. Aow.liut and hroUh. 7Ae Yra• Ynrl Ti.wr• Aata.t :'z•. lv:rl. 3. (:reat Britain. Mrtheat RCYare11 Cuuneil. TuWero snh.linr and ratwer ot IunY: ullw•ial statemeat. Ibrt. .1/. /. 1• 1 iI1, P~G7. li. Pr.t, rYe"re 1233). Prepared by Nrthrrl..nds alinntrs ..t ti..-i+l Allain ata.l Ibhlir Ilralth. Ihr /Irrcur. \rd.rtl.unL. 7. IlammonJ, E. C., atal tlorn, 1). Jntolinc atnl 46.41s rnrs - letwrl on (or11•Iuur aw.ullu 4.1 h•lluw-ul. u/ Ia:.aUS nw•u. 1 Tut.l nnnuliq. J..1.Af.A. 1ti:11S9•11Y . 1758. 1nw.kint arwl dr:.th tatrs • rrp.n un Lniw•hwr nM.ntlN .d I..II..N•ul. ..1 1N7.- -1{:t mrn. 11. lkath aatrs by uu.r. rbtd. r't'.6. B. 1),.ru. 11. P. T.d.a.en cun.umplwn and uu.uahw In.ns tan.er and uthrr diuasea. NI.. Hr«rt6 hrf. i7::,ec1•5s3. C/5'1. 2 L),.11, R., and ,h11. .\. It. Lntst r.nerr anJ odtrr s+ur. ut death in rrlati..n r.. .nw.lmc: .rrond rrtrnl mt aa.rlatuq ad UritWt d.r. J. 2:1u:1•11k11. 1956.

a . . Vol. °fi° No. 11 Cl'STIIOSIS - - KORN $45 tl/- M-.atkr. E. I... A.,pl. 1'.. aud Zirnlrr. I1. ltuth- of dd.,rru rar. rin..trnr.i.. It. D.,w•rr.p.,n.r .tudirs. C.nr.r 1~ 11'ttl:~rl. 1'ti7. 11. lhdl. R.• 1111. .\. It.• (,r-. I'. G.. and I'arr. F.. A. Lunt c.ncrr rnnrtality and Irncth .d rinrelte rnds: intrrnational comparison. 1'! }tammond. F.. C. L,ine rancer death rates in F.neland and Wal•s comparrd s.ith tho.r tn U.S.A. ll•it. Af. /. 2fA~•fi]4. 19J8. I3. llarmmond, l.. C.. and K'.ndrr E. L. Ciearetle .mnlins and lung cancer in Cannd.i. l.ancd. •Sf. .4• /. fin presfi. 14. rbll• R.• and llill, A. It. Sm,,tint and carcin,•ma nf luue: pre- riminary report. Brit. if, 1. 2;39.748. Irol1. t-'s. Br.eslow. L.• Noaehn. (i.. Ra•ewt.en. G.. and Abrsm.. If. 1:. (keupatinns and cic.arritr annkint as larmrs in lunt rancer. An. J. PrA. llealth 44 171•181. 1't;4. 16. Schwarv. 1).• and D.•nnia. 1'. L'ruquetr Lanr:ai•e •ur 1'itioloRie du cancer Lrnnrhn•pulan.o.~irr: n;Jlr dw /aLnc. Cnrrninr 4. AnO. dr larir 33:3G:1 1•3t'.tl, Octol.rr 30. 19i7. 17. lianmtond. F. C. Inhal.trian in rrLrt'w,n tu ra•pr aml auw,unt of tm..liug. /. A.n. Staful. .4. 61:3:r•51. 1!':r9. producuon of rarcinnma with tnbacco producta. V. Carcinoma i't- ductinn in rnlre wirh riear. pipe. and all-tnbacco riearette tar. Caerrr XnemrA It l°G1•T_'~I• 19i8. \1'.•nd.•r. F.. L.. and IinRrnann. D. Stud, of Inhaeco earrinre•nni•. VIL Rnlr of hishrr polyr>tlic h.drocarbons. Catcrr 12:1ri:)-1f8ti. 19:r!/. DEMONSTRATION OF CYSTINE CRYSTALS IN PERIPHERAL WHITE BLOOD CELLS IN A PATIENT WITH CYSTINOSIS* nmt) ><a)R., af-D•; ttOSTON Cl :STI\ E-S''OR aGE t•a.c1 c.•stin(his or Li~nac- Nanconi discasc is an conunon but intriauina disordcr, the ctiolo`sy and pa lo',t•nesis of a•hich are unknots-n. '1'l)c cardinal 1)atllo 'ical finding is the dcpos:tion of lar',c yuantitic: of .•stallinc cystinc in tlte tissucs, especially in the retictl ocndoClielial str.uc- ttsrcc and in the cornea and conjun ti~-a of the eve. In the case reported beloa', a patic t~.•ith provrd e;-stine-storage disease presented cystine T-stals with- in the white blood cells of the pcriphera( blood. A rerie.v of the literature indicates that this o`bservation 18. Schmahl. D., Con.brurlr. ti., and Druckrrv, 11. Fluoresxntmes- atnten an 7..tarettcurauch. .Ir:n.imiuel-F'nr,rlr. 4:7I-1S. 194. 19. N•nnt/en. It. M. Cisarcnte salrs in 1959 rrach all•lime },sh - 4.S': ahn.e 19i8. Prinlrr.' lnk 261 - I1i:19•2i. D,remhrr :5. 19Y'. :'A. Asuxiarinn nf ORcial Aeriruhural Chemi.ts. O!iuial .tfr:•-dr of Ana/vnl al the Auormtine ol O!hnnl At,uuiturnl (.6rm..:. t.-c~•r, edition. U)08 pp. WathinStnn. D. C.: The A•vciar on. 15i5. i'. tai. :1. 1foRmann. D.. and 1Y.nder. r.. L. Shnrt term drtrrmina+;nn of rarcinntrnic ar-imatic hsdrncarbans. .4sal. CArn. 32::'93, 1:61. ;':. \Gllrr, L. \I•, and \tonahan. J. Searrh Inr "vder ' -eisarattes. Itradrr'c l)itnr 13:37-i i. \nvrmLrr. 1WO• 23. Cronineer• A. B.. Graham. F•. A.. and 11'.nder. F.. L. Eaperimental a. amino arid excretion in the urine. Roentgenologic study confirmed the diacnosis of severe rickets. Stcrnal-bonr-marroylaspiration revealed normal r.:ariow. with "rare storaer lis with mixed oblone or honc.•comnrd crystalline ahado outlined by dense refractile c.•top:aym" i Fie• I r• Thc 'rieht-stained marrow sntcar containea,oh- lonc and sqyare yellowish crystals, mostly frcc. and less rommonly yEithin the c.•toplasn) of mononuclear cells. The patholot:i sl diaanosis was "cr>-stals in the bone marrow ion- ststent tth c.Ytinosis:" Slit-lamp examination of the eyes ckmo trated crystalline material in the corneas. ~-----~-.-..a..._.. ...-,..........,~.-,.~,. ., Itas not previously been rcportcd• The potcniial valtp• of this findino, in the diatmosis and study of )hls 4 srndronie ts apparcnt. ~ CASE IZEPORT . CD., a:1-tnonth-old cirl- was admitted from another I Th ' i k t l i of 195i l f r c e or e.a uat on/ , r y I. hospital on Ju s. •family and neonatal histories were noncontributorn-. Thr rhild appeared to develop nonnally Yntil the aSe of : months, when continuing wcieht aain,rceased. She did not sit alone until Ilt months c.f ate and n admission could nta stand. Physical examination showed sntall, irritahle girl who was 74 cm. tall and w'ciehed 8.6•ktz. The pertinent findincs included uorrnal vital signs, an open anterior fontanellc, frontal bossine. marked rachitic rosan'. prominrnt Harrison Rroow, marked cnlarcrment of the wrist, knee and ankle joints and >,cneralized weakness. The alxlomen was pro- tulx•rant ahhouch the liver edee exu•ntlyd only 2 cot. bt•• furw the riRht costal marcin. F•ichtccn teeth were present. F.xantination of the blood rrvcalyd a hemoclobin of 13•S t[nt. per 100 sul. and a normal white-cell count. The urine rtavr a + test for prutein• a.ienificant test for suear and intcmtittentl.• pusiticrt tests fur arrtuur. '1•hr srdiue•ut cun- qinetl white bkK,cl rrlls and Mraonl•ar raas. tirntut ' analyses of nonprutcin nitruecn. sut:ar, sol11tI11L IKUasstutlt. .hloride. birarlxwnatr, calrium and alkaline phosphatase wrrr twnual. 'fhr srrkna phu.phurus raneed frutn '= tu :1 tuc. tK•r 11nU attl. Krual funrtiun• as Incasurtv) by crratiniur clrarausrs, was nornwl, Thrre ..•as a snatl.rd. erneraliird increasr in tF.ww ahr tlrµ•ruu.rnl .,1 14diaUN.. (talsatd \t..lirwl h,lur.l. arwl the tlrt.utntrnl -d Sla.liriua Childrrn'• Ilnyntal. 4lnlqts in tutM•4ts. \1:...Mlura'n. GrrNVal Iluy.ital. ~' .~ . .c...:....-. ~ tr O tV ~ t tV '> V - O~ Pua•as: 1. Seri1^n o/ Clurtcd Bvnc-ttarto:t• .cfirt:tt. Ub- taincd daring the"kir;t :Idrui,siun, 1''ixcd ond Enrbcddrd in tlu 1-otral 1lannrr irtrd 5rainrd :f:itl+ Tolrfidins Bhre Eo;:as f l i00). The phutonficrograyh tcai•taken thrirrrh halj-croistd jolari.- ing lrn.ti to deanvnrtrate b r•lratcr u/ :irullt birelrnsjent r .#.tine crlttalt that u: nlie a®t( ub•ctue a lar,• na,m.arrl.ar '•foraici \eU- 'lltc p•atirut was arul hwur on a rreimrrt of'ealn iuta lar- tate. I gut. a day. vitaruin I).. 1t/.t)Clu unit, a da••. and a sjrccial sodium citrate sohrtion routainintc 1.4 sni;:inols of wxlium per snillililrr. in a dosace of I teastMC+tiful 3 timcs daily. St)e itnprunrd markedly in the next few nN•nt}:s and wilh inrrcaard .qsla•litr Lrcan at t:tttw and tt• c.un weicitt. The dctaaec of %il,tntin 1) was incrc.tsed tu (S.t'00 units daily after 6 uKmths aud continued at that Icvt•I to the rrrscnt