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>ilcr- fatinn work ;|ucs 22. ers in iorted H'StOX etion. ouary thort. chant it Dis in the T I J ^ 1 J .1 ' J c!.. I 1 -1 _ t yi American Jrrarnal of Industrial Medicine 20:685-700 (1991) HISTORICAL PERSPECTIVES IN OCCUPATIONAL MEDICINE s Changing Attitudes and Opinions Regarding Asbestos and Cancer 1934-1965 Philip E. Enterline, PhD literature published in the years 1934-1965 was reviewed to determine attitudes and opinions of scientists as to whether asbestos is a cause of cancer In Germany, the issue was decided in 1943 when the government decreed that lung cancer, when associated with asbestosis (of any degree), was an occupational disease. In the United States, however, there was no consensus on the issue until 1964. Opinions of scientists over a 72 year period are shown and the contributions of various cultural, social, economic and political factors to these opinions are discussed. A lack of experimental and epidemio logical evidence played a major role in delaying a consensus. Other important factors included a rejection of science conducted outside of the U.S. during this period, par ticularly a rejection of German scientific thought during and after WWII, and a rejection of clinical evidence in favor of epidemiological investigations. Individual writers rarely changed their minds on the subject of asbestos as a cause of cancer. Key words: epidemiology, mesothelioma, lung cancer, asbestosis, literature review, history of medicine INTRODUCTION Observations on disease in human populations have made important contribu tions to our knowledge about causal factors in disease It is tempting to ask, however, why it took so Jong to discover things that are today so obviously true. How could we have long missed the association between cigarette smoking and lung cancer, for example. The answer must lie, in part, in what data were available, how data were interpreted by medical observers, and what factors influenced these interpretations. Clearly, some of these interpretations must have been wrong, and if the reasons for Department of Biostatisties. Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA Address reprint requests to Philip lr. Bnterlinc, Ph. D , lirneritus Professor of Biosiatisrics, Department o f Piostatlstics. Graduate School of Public Health, University of Pittsburgh, 130 DeScto Street, Pittsburgh, PA 152bI. Accepter for publication February 15, 1991. ff) 1991 Wiley-Uss, Inc. tr these wrong interpretations were known perhaps this would ever so slightly accelerate scientific progress in the future, An excellent example of a costly delay in arriving at a consensus is the situation with regard to asbestos. Why did it take so long to recognize the association between asbestos and lung cancer7 How was it discovered':' Who contributed to the discovery, and who detracted? What role did the various health disciplines play in arriving at a final consensus? What was the evidence ai various points in time and how was it interpreted' Clearly, scientific thought does not take place in a cultural, social, economic, or political vacuum. What role did these factors play in arriving at a consensus? METHODS In order to sec how medical observers viewed the possibility of an association between asbestos and cancer, all of the open literature on asbestos and cancer was examined, from the first article written in 19?4 through 1965, when the issue appears to have been settled. First, ail of the literature on asbestos and cancer referenced in the index Medtcus and elsewhere for the years 1934-1965 was examined. This included building on references in each article found. In addition, every issue of Ixmcet, the British Medical journal, and the Journal of the American Medical As sociation (dr these years was searched for any editorials or communications which mentioned asbestos and cancer. Also, all available textbooks on occupational meriicine, toxicology, and pulmonary cancer were examined. For all foreign-language articles a complete translation was obtained. As a method of summarizing how, at different points in time, the writers were interpreting the literature and observations then available on the subject of asbestos (or asbestosis) and lung cancer, each article was classified as to bow the writer or writers felt about the relationship between asbestos and lung cancer as: 1) asbestos definitely causes lung cancer; 2) asbestos possibly causes lung cancer; or 3) the relationship is unproven. For the First two categories, a subdivision was made as to whether it appeared that the writer thought asbestosis must or must not be present for cancer to occur. This classification was made independently by this authoT anti Dr. ITT, Higgins, then professor of epide miology at the University of Michigan. A similar classification was made on articles dealing with mesothelial tumors by only this author. For articles on asbestos and lung cancer there were surprisingly few disagreements. These were worked out by dismission. The results of this review are presented to demonstrate how opinions differed on the subject of asbestos and cancer, to show how opinions changed or drifted over a 32 year period, and to identify the kind of scientific publications and the kind of writers that contributed most directly to a final consensus. In addition, a narrative is presented on what appear to be the highlights in the progression of scientific thought toward a consensus and on factors that appear to be associated with this progression. Some of the material presented is from the monograph Asbestos and Cancer-- The first Thirty Years, privately published by this author in 1980. An early draft of this monograph was Ihi: basis for an editorial published by this author in 1978. CONTEMPORARY OPINIONS A total of 104 papers or writings were located which dealt with the subject of asbestos and lung cancer and which were published through 1965, the date by which | i ' i j j I | 1 > j* , ! J I j j ' ! : I J I r | J j ' j | the assoc iai lished. Tab sifted. This observation and whethe cases invol unproven c ciation beh presented, t name of the the author t name of the sant is refci theses. Uns The a rapidly frort during the p Between 19 that suggesi cancer. Dur in 1956, th relationship change in tl cause of !u position on appear true inconsistent whereas wri there are ik language ot articles in th made up th< 1943. A tota malignant rr this cancer mesothelioir causes mesc which the ca it was indee Few a: rnesotheliorr resolved. At identify wit! common dis Moreover, tl ological evil existed and 1 .aT derate nation tween very, '} at a was jt social, ; at a la'ion a was 'pears =ed in This >Le of '// A.vwhich rnedguage >w, at aliens article tween xistos t two ought ii was ipidelicles l lung w dis- d on ver a ul of ;ve is >ught Siotl- cer-- aft of jet of vhich Attitudes, Opinions: Asbestos and Cancer 1934-1965 687 the association between asbestos and lung cancer seems to have been firmly estab lished. Table I shows how articles dealing with asbestos and lung cancer were clas sified- This table also indicates the type of article, whether based on animal or human observations, whether the original article was in some language other than English, and whether the author conditioned this opinion on type of asbestos fiber, in a few cases involving negative animal experiments, the writing has been put under the unproven column even though the writer may have personally believed in art asso ciation between asbestos and cancer Usually, however, where original data were presented, the writer's opinion coincided with what the data seem to show. Only the name of the first author is given. Where textbooks had chapters written by other than the author or editor, the name of the textbook author appears in parentheses after the name of the chapter author. Where discussants of articles are referenced, the discus sant is referenced and the name of the first author of the article is shown in paren theses Unsigned editorials are referenced only as "editorial." l he general impression gained from Table J is that opinions shifted fairly rapidly from "unproven" or "possibly causes cancer" to "definitely causes cancer" during the period linotn the first published observation on lung cancer in 1934 to 1942. Between 1942 and 1956, not much change occurred except perhaps for a few writings that suggested that asbestosis was not necessarily a precursor to asbestos-caused cancer. During this period, many writers remained unconvinced of a relationship and in 1956, there seemed, in fact, to be a retreat from a consensus as to a causal relationship The period 1957-1963 also seemed to be one of uncertainty with little change in the position of individual writers on the question of whether asbestos is a cause of lung cancer In fact, most individual writers held firm to their original position on whether asbestos is a cause of cancer. Perhaps this is unfortunate. It does appear true in all of science, however, that it is better to be wrong than to be inconsistent. Textbook writers were among the last to acknowledge a relationship, whereas writers of editorials were among the first. Note, for example, that after 1951, there arc no editorials in the unproven column but five textbooks. Articles in a language other than English are indicated by an asterisk. Nearly all of the early articles in the proven column were in German and it is clear that German writers had made up their minds about the relationship between asbestos and lung cancer by 1943. A total of 61 papers or writings were found that dealt with the subject of malignant mesothelioma and asbestos. Whether asbestosis needed to be present for this cancer to occur was never an issue. Table II classifies articles that deal with mesothelioma as: 1) asbestos definitely causes mesothelioma; 2) asbestos possibly causes mesothelioma; and 3) the relationship is unproven. Included are articles in which the cancer was not recognized as a mesothelioma but in retrospect appears that it was indeed a mesothelioma. Information is coded as in Table I. Few authors ever expressed doubt about the relationship between malignant mesothelioma and asbestos exposure, and by [953, the issue seemed to be fairly well resolved. Actually, rare diseases like malignant mesothelioma are relatively easy to identify with occupational exposure, so that many of the problems in Linking more common diseases, such as lung cancer, with asbestos exposure did not apply here. Moreover, those who observed mesothelial tumors did not usually demand epidemi ological evidence. The main problem was in agreeing that such tumors actually existed and how they should be defined. Until the report by Wagner et al. in L960, - $.n) : i r : i:> B-s r o r. HUidci I ' w bi!t 11-31 It 1 1 t bH8 Enterline T ABLE I, Opinions of Auction, Publishing 1*03-1965 Regarding the Causal Relationship Between Asbestos anti Lung Cancer* Y'sar iST>4 1935 1936 193* Definitely causes lung cancer Without {tsFiestoxis Only after asbestos i> JNonJmnnn {Of fHt.MTIIJE (Of 1939 :Baader (R) v*u\ TOI l `442 194-1 1946 1947 1948 'Nuidrrunn (O.a) l-mzbach {OJ Wegrfui {R| 1 Wela fO} 1 Wedfcr (!){} Waller (2) (R) Hoemkc |D} Hneper (R{ Hroper U) {R} Hueper (2) (R] Saila | R! 1949 1911 145.! Metewether {OJ LW -Smith {R} Wyets |0} Editorial Hueper tR} Owen fO.qf Stoll {O} Tabershaw fK] Hucper {ftf * Werber jof 1953 Clcrramescn {E} WE Smith (Rj tssdbacher ,Or * Weiss {OJ Tioemke jO> 1955 Doll |0} Hditonal (1) Editonal (2) ftunter {qf Knox {Cf yRambola {C,ff tPonigliati, Barlios f<J} tHucper (2) fO} Bunser 'Of Merewether {()} Huepet (3) {R} Possibly causes lung cancel Without asbestoses r>-ily after asbestos is Lynch (0| Egbert {O} 'Teleky (R} 'Koetsch {R} KIoit {0} LSaape |0} 1'Desmeu!es {O} Holleb {Of Heuper {T} Hornbctger {Of Kcrnaway (OJI .yiicb {Oj (Jurckw {Of Ding IR} ftloync \0\ 'lictircus {Rf Lynch (Of ftrpsJow {O} Lynch (0} KW Smith {R,f} Jacob {O} Unproven Wood {Of Oloyne {Of Gloytw {Of Vcrwaid {O.a} Editorial {1} Editorial (2) Gfoyne {T} Lynch {0( ILO (R} Larua {T} Gartner {R} Wampler {T} King (O.af Wegel ius {O} Warren {RJ Tcteky (T) Vorwald fO,,ajf Rchrens {O.af Sax {T} WE Smith (1] |R,a} WE Smith (2) 10} Cartier [R} 1 -anz-a {R} Vorwjlti (Cj Cartiei {Of Hueper (1) {0,3} (contiiwei) f j j , I TABLE I. Opinion Between Asbestos t Di Year ]9S6 Without nsbestosis 1057 1958 'Schmahl {O.a.i 1959 'Bolilig {O} 1960 1961 .Schepcrs (Tf Gilson [T.f] Ki tuc {Of 1962 1963 Mane use iO| 1964 1965 poll {O} Elwoud {O} Oetlle {O} Selikoff 1.0} Editorial (I) Working Group, i'iac {e; *0. original article (ohse lion (letters, etc ); T, text quote from other sourceFor example author's last expressed the opinion thai one author only the first a year articles are identified ] 11 >! i;>-} It) (2) n d \ HI III , n 1 It uHK.ai h ryj /QV i A1 >! !} |0,a[ ' cotitmuedi h* l' r vr W 1 Actinides, Opinions; Asoestos and Cancer 1934-1965 689 TABLE L Opinions of Author'. Publishing 1933-1965 Regarding the Causal Relationship Between Asbestos and Long Cancer* (Continued! Definitely causes JU l camrcr Possibly causes fung cancer Without V>;if uchecroG* Only after tsbestatre M>S/h Welle; U'l Huepcr (R) 'Boldi# {Rf Wnthout /ibht.StcK!1 Only alter i.lci-.-i. GoMhlait {T|'francia jO.f) McGee fcj) Umprovcji Ki,enbiiil! fT) Todd jOl Ifammotid {T} Bohltg (K) f juries-Wiiiiams jut O Donnell jO) Sax {Tt f-'swrhal! (T.tj) Lyocii -.(S al bdiforiai 193* Schnvihl {O.u-Vjl Ooldblatt {Ri ' Bohiig {OJ ( Tiauvri {Oj- Niindtr 4T1 Bran]) {Oj 'Bohlig {O} I 959 inm ir, t'Oj- 1 JttHots j 1} Mueper /T* 'Bohniu (LJ {0} 'Bohme (2) {O} Kckardt (T? "Korttvrk |R.fJ ocLrtrpcis fT}Gilsnn }T\fi 'Knnig {Oj Real {(J) Anderson {O- Johnstone {Tj Duim{0} t%i Heard ;0 lchschi {Of Y'raink**! {O}- Trimble {C} 'K/rymicn [R| \Sc/yfTK:zykie'*icz Johnstone {('.!} l I*#-/ 'C^jjpeU {O} 'Del-aguirhniitiie IO} Hunter H i Cordova |Oj 'Fiiificrland (O) Quiirigurt jOf j "h'nj Mdriuu!*} 'I'OJr Leathcan {0} Knowles {Ol Walters [(.)} Yanrut {Oj KW Stmlh jT) 1964 Doll {O} Elwood (O) Settle {>{ SelikoTf {0} 'Noetunckx [Ot Buchanan {O.i) 'biavratil (0} "Kogan {Oj Gafaicr {T} Atri. College of Chest Physician i'R.fl 1963 l-jditnnal i If Wording Group, UiAc jfc} UnlTH ifB BJmeK {OS' Hmscn {R} Irwies-Wiliianis {Oj Editorial (2) Anspach (Oj Pfliiirji (0) Andrew*, {T.qj *G, original article (observations, studies, experiments): R, review article; E, editorial; C, communica tion (letters, etc.); T, textbook or monograph; 1, foreign language article (not English); a, animal data; p, guote From other source--no opinion expressed; f, association depends on type of fiber, e*. sarcoma only, for example author's last name {0,it,f} indicates an original article on an animal study where the author expressed the opinion that the association is dependent on tire type of fiber Where there was more than one author only the first author's name is given. If that author published, more than one article in a single year articles are identified by (I), (2), etc. 6W Rnterline TABLE U. Opinions of Aalhurs Publishing 1933--1965 Regarding the Causal Relationship Between Asbestos and Mesotbeiiai Tumors* Year IP 13 1934 1943 Definitely causes mesothelioma 'WcdJtr (1) IR> fWalter (21 (Of Possibly causes mesothelioma Unproven Liloyne {O} Wood {Of these cancel articles folk single writei tons on the t asbestos moi literatuf 1951 1953 1953 Weis-s {O} Doig WE Smith (1) {R} Tlrhrcns {0,af Carlier JR} The ea Crloyne ;n E autopsy in 5 these two cat i 1954 Idler (01 1955 i 1956 Bonscr {Of 'Baftlig (R) asbestosis ca case from the I in two cases 19.5K im Gilson {T.ff 'Konig {O/ +Van tier School K)} Keal {Of Wagner |0} Schepcih {T,fl correlation m facing an uc writers quick animal study 1961 Sieges (O) 'trankel {0} Heard {Q| Knox {0! white mice as this the expe 19f>2 McNulty {0,1} J> withers {Cf discovering tl 1963 Thompson {O} Wagner {O .a} MeCaughey jr} F.ntieknap (Cl S timbers fit ,f} Mancuso (0) Walters {R( llontci (TJ Knowles 10} Thompson government i asbestosis (of January 25, i 1950. In 1943 most recent m writing in tie l'*>4 1965 Thompson (Q Lawson (!) {C* I -awsim <2', jC} Buchanan (0,t} Flnticluiap fO} Hourihane (Of Noemnckx (OfOctlle {{)} Owen fO| WU Smith `O.a} Dutra [Q,qj Etraes (Of Hinson {R} Sclikoff fO] Wfc Smith -jO.a.fj Gafafer (F1 Murray {R.fi Elwoixl lo.ti Fbwlei [()} Sclikolt {O} Editorial (ff Am. College of Chest Physicians {R,t} t mesothelioma From th< very popular attention The discovery shoi his 1935 repot fulfilled in ord rate in the occ a significant er association of genic propertic Gkrync's lifeti cancer. Nearly Steel {Of seen at autops ' Anspach jO| Editorial (1) Editorial (2) (f) See Table I for explanations of symbols and style concern for the that necropsy t cancer, wherea l 15 and over w< Lynch, ti asbestos and li Attitudes, Opinions: Asbestos and Cancer 1934-1965 691 these cancers were not a major focus of research. Table II shows that a flood of articles followed the appearance of the paper by Wagner et al., and in 1965 not a single writer expressed doubts about the relationship. Many did condition their opin ions on the type of fiber, however, believing that crocidnlite asbestos was the type of asbestos most likely to be related to mesothelioma literature highlights The earliest recorded observation on lung cancer was a report by Wood and Gloyrie m England in 1934. They reported two cases of lung carcinoma seen at autopsy in 53 cases of asbestosis. In 1935, Gloyrie gave a complete description of these two cases. Also in 1935, Lynch and Smith reported a case of lung cancer in an asbestosis case from the U.S., and in 1936, Egbert and Geiger also reported such a case from the U.S. In 1938, in Germany. Nordmann added two cases of lung cancer in two cases of ashestosis, making a total of six, and concluded, "A cause-effect correlation must be present here, even if I had been the only observer. We are indeed facing an occupational cancer which affects asbestos workers. " Several German writers quickly accepted Nordmann's views. In 1941 they were reinforced by an animal study in which Nordmann and Sorge reported pulmonary carcinomas in two white mice as the result of asbestos dust inhalation. Other German writers considered this the experimental evidence needed for proof, and gave Nordmann credit for discovering the relationship between asbestos and lung cancer. In 1943, the German government issued a decree declaring cancer of the lung, when associated with asbestosis (of any degree), to be an occupational disease (Rcichsqcsetzblatt I, P. 85, January 25, 1943). A similar decree was issued by the West German government in 1950. In 1943 in the U.S., Heuper declared that "Asbestosis cancer of the lung is the most recent newcomer among the occupational cancers of this organ." Also Wedler, writing in German 11943a], concluded that asbestos was also a cause of malignant mesothelioma. From the American point of view, German literature and German laws were not very popular in 1943, and the work of Nordmann and his followers received little attention. The situation was not helped by the fact chat Gloyne, to whom credit for the discovery should have gone, was extremely cautious in interpreting his findings. In his 1935 report, Gloyne quoted Bridge and Henry [I928J on conditions that must be fulfilled in order that cancer be classified as industrial in origin: 1) that the incidence rate in the occupation under review should exceed that in the general population, to a significant extent; and 2) that in the occupation concerned, there should be sufficient association of the workers with a substance proved experimentally to have carcino genic properties. 'These conditions are accepted by most scientists today; however, in Gloyne's lifetime, these conditions were not fulfilled with regard to asbestos and cancer. Nearly all the evidence dealt with the association of ashestosis and cancer as seen at autopsy. In a paper published posthumously in 1951, Gloyne expressed concern for the selection obviously at work in picking cases for autopsy, pointing out that necropsy records at the London Chest Hospital showed 21.3% primary lung cancer, whereas in the general population, only 2.4% of deaths from all causes at ages 15 and over were due to malignant disease of the lung. Lynch, to whom most give credit for discovering the relationship between asbestos and lung cancer, was no less skeptical [Lynch and Cannon, 1948]. He 692 Enterline expressed concern not only with the problem of selection but also with the lack of experimental evidence. Only Nordmann and .Surge [19411 claimed to have produced cancer experimentally with asbestos, while experiments by Vorwald and Karr [ 1938], King et al. [1946], Vorwald et al. [1951J, Behrens [19511, and Hueper [I955aj appeared to be negative. Moreover, Smith [1952aJ, in a review of animal work with asbestos, concluded that the study by Nuniinann and Sorge [19411 appeared to dem onstrate that asbestos did not provoke lung tumors, since of the two tumors reported in asbestos-exposed animals, one was, based on photographs presented, merely a squamous cell metaplasia, while the other, asserted to be an adenocarcinoma, "is a type of tumor that can arise spontaneously from the mouse adenoma/' Even Hcuper [19521 seemed to agree with this and, outside of Germany, Smith's views on Nordmann's work, gained some acceptance. Another problem in the U S. was the attitude of leaders in the field of pneu moconiosis -particularly Vorwald [1953] and Lanza [1952] Their expressed concem was the tack of experimental data. In addition, the possibility of a different relationship between asbestosis and lung canart as compared with silicosis and lung cancer must have been disturbing. Lanza [1952] was also concerned about the same selectivity that worried Gloyne and Lynch, and he wondered, in regard, to English claims of an association in autupsied cases of asbestosis, how many cases of lung cancer would be found if lungs from any sort of population were subject to the same minute scrutiny. The situation could have been resolved, from the American point of view, in a report by Merewether in 1949. He compared lung or pleural cancer in cases of asbestosis reported for compensation with lung or pleural cancer in cases of silicosis, and found that 13.2% of the asbestosis cases had cancer at autopsy whereas only 1.3% of the silicosis cases bad cancer. This was clearly an important study in bringing about a consensus in Great Britain. In the U.S., however, this seems to have given birth to a new idea: there is a relationship between asbestosis and cancer in England and in Germany but not in the U S. This idea apparently originated with W.E. Smith in 1952 [1952a|; however, another Smith (K.W.) enlarged on this in 1955, stating that there was a difference due to the type of fiber used in England and Germany as compared with the U S. In 1955, the Italian writer Rambola also felt that this was an argument for a difference between Italy and England. The argument was also repeated by Eckhardt [1959], Gilson [1960], and Johnstone and Miller [I960], There was no answer to the question of fiber type, and it no doubt delayed acceptance by those who were uncertain as to whether a problem truly existed in the U S. There was, however, an answer to the question concerning selection that both ered Gloyne in his 1951 article fn 1955, Doll reported on an epidemiological study of the type envisioned by Bridge and Henry [1928] in which it was shown that the incidence of lung cancer in a group of asbestos-exposed workers in England greatly exceeded that in a comparable group in the general population. This marked an end to a period when conclusions were based largely on pathological and clinical obser vations and opened the door for contributions by biostatisticians and epidemiologists. It probably also set back acceptance of a relationship between asbestos and cancer in the United States by another decade The epidemiologists demanded epidemiological evidence. In 1956, for exam ple, Hammond and Machle stated that with regard to a relationship between asbestos and lung cancer, "there are at present too few cases and too little epidemiologic data I I i f \ I > 1 to establish a s Cancer ot the reports contribu increases in age the same age, s an iKcupational The first t in North Amerii negative. Thus, Answers" secti no epidemiolog among Amcrict epidemiologic : evidence now s The turnii of a positive epi in 1964 by Seli 1964 cortfercnc Effects of Ash* session was de1 demiological st mors. Of a tota cancer (these p; asbestos caused a relationship, opinion was ex| was a consider cssary for pathi between asbest On eurrer cases wit informal exposure; J.C. Gils human exposui solved problcrr carcinoma, anc idemiological) There car of the lung and 1964 confcrenr cnce and of the a Working Gn Against Cance chairmanship c the lack of re produced Carr [1938], vr j 1955a] i work with red to dem urs reported !, merely a oma, "is a vvii ni^uper s on Nord ic! of pneuessed cona different is and lung jt the same to English iCK of lung .0 the same view, in a n cases of if silicosis, ereas oniy in bringing lave given n England /.E. Smith 55. stating onnuny as his was an 0 repeated (it delayed sted in the that bothpcal study >n that the nd greatly ,ed an end ical obserliologists. 1 cancer in for examn asbestos loCm7~e data Attitudes, Opinions: Asfcestca and Cancer 1934-4965 693 j to establish a significant relationship.'" In t95H, the Committee on Occupational \ Cancer of the AMA Council on Industrial Health concluded that individual case reports contribute little to an understanding of occupational cancers anil that "specific increases to age., sex, and sitc-specilic cancer incidence above normal incidences for the same age, sex, and site represent the only reliable evidence for the existence of an omipational cancer hazaid." The first two epidemiological studies ot this kind on asbestos and lung cancer in North America [Braun and Truttn, 1958; Dunn el al., I960] were considered to be negative. Thus, as late as 1961 [Johnstone] it could be stated in the "Questions and . Answers" section of the Journal of the American Medical Association that "there is no epidemiological evidence [of an association between asbestos and lung cancer| among American workers." Despite a!! of the case reports, and despite the positive epidemiologic studies by Merewether [1949] and Doll [I955|, the epidemiologic evidence now seemed to be negative . The turning point came in 1963 with the publication by Mancuso and Coulter of a positive epidemiologic study of workers front an asbestos textile plant and a study in 1964 by Selikoft et al. of asbestos insulation workers. These were followed by a 1964 conference held by the New York Academy of Sciences on the Biological Effects of Asbestos [Annais of the New York Academy of Sciences, 1965|. One session was devoted to experimental studies of asbestos and neoplasia, one to epi demiological studies of asbestos and neoplasia, and one to diffuse mesottieliai tu mors Of a total of 65 papers presented, 23 dealt in varying ways with asbestos and cancer (these papers are not separately referenced here). On the question of whether asbestos caused cancer, no opinion was expressed in three papers, while 20 supported a relationship On the question, of whether asbestos caused iitcsothelial tumors, no opinion was expressed in four, while the remaining 19 supported a relationship. There was a considerable difference of opinion on the question as to whether it was nec essary for pathologically detectable asbestosis to be present for a causal relationship between asbestos and lung cancer. As J.C. Wagner [1965] put it: On current evidence, the earlier view that carcinoma of the lung occurs in cases with a significant degree of asbestosis is strongly supported, but information is still required to confirm that there is no correlation between exposures per se and these tumors (i.e. in the absence of asbestosis) J.C. Gilson 11965], in a discussion of unresolved problems associated with human exposures to asbestos, also reflected this view. In addition, he saw as unre solved problems: 1) the relationship of the type of asbestos to asbestosis, bronchial carcinoma, and mesotheliai tumors; and 2) the need for systematic prospective (ep idemiological) studies of workers exposed to asbestos. There can be no doubt that the question of whether asbestos causes carcinoma of the lung and diffuse mesothelioma of the pleura and peritoneum was settled at the 1964 conference. Probably the best indication of the views expressed at the confer encc and of the questions that remained to he answered is contained in the report of a Working Group on Asbestos and Cancer sponsored by the International Union Against Cancer. This working group met at the time of the conference, under the chairmanship of Thomas Mancuso, and their report was published in 1965. IC c 694 Fjiterliae I In 1964, the Johns-Manville Corporation placed the following warning label on I than research com packages containing its asbestos products: j education is base health effects like This product contains asbestos fiber. Inhalation of asbestos in excessive in the future. quantities over long periods of time may be harmful. If dust is created i when this product is handled, avoid breathing the dust. If adequate ven l tilation control is not possible, wear respirators approved by the U.S. REFERENCES Bureau of Mines for pneumoconiosis-producing dusts. American College of knee. Comma CONCLUSIONS Anderson J. Campagn | literature A,ref The answer to the question as to why it took so long to accept the causal Andrews C'h (1965): Boston: Little, relationship between asbestos and cancer is not a simple one. Clearly, the matter Annals of the New Yi I involved a decision as to what is acceptable and conclusive evidence. Perhaps a special set of rules is needed for relationships like asbestos and lung cancer where Anspach M, Roitzsch Mesotheltoms some other biologic response, such as asbestosis, can be used as evidence of signif Baader IrW (1939): A Behrens W ( 1 IS It: tJ icant exposure, and the rules proposed by Bridge and Henry 11928] were not appro Behrens W (1952). U priate alter all. Many writers were convinced of a relationship long before epidemi Boendte F 11943): As ological and experimental evidence was available. Aside from the high incidence of lung cancer in asbestotics, they were impressed by the predominance of cancer in the lower lobes, the time lapse between exposure and disease, the high incidence in females, and the young age of many of the cases seen. Moreover, there were rea Boemke F (1953): D;i Hut dig II. Jacob G (I Wrxheitsclir 8 Bnhlig It. Jacob G 1 Gesundheic \ 3' sonable theories regarding mechanisms by which asbestos could cause cancer. These Botilig H, Jacob G. arguments were seldom acknowledged by contemporary epidemiologists and bioslat isticians. On the other hand, there wen* scientific reasons for delay in accepting a rela tionship. There were no good experimental data showing that asbestos was a carcin Unfalimed Bet Bohme A (Hi 959a 395. Bohme A (2) < 1959b -tel. ogen and very few positive epidemiologic data. There were political reasons, mostly Bonscr GM, Faulds reflecting the war with Germany and a rejection or lack of knowledge of much of the German scientific literature and thought during and immediately following World War Ii There were economic reasons, since the asbestos industry probably exercised some control over research, and findings unfavorable to the use of asbestos were operatives and 25:126 133. Braun 1X3, Truan TL Health 1 7:f>34 Hreslow L (1955): In, clearly not in their interest. There were cultural reasons, in that, somehow being an . Bridge JO. Henry SA American during the 1940s and 1950s was being different, and ideas which originated I.undon, July, outside of America were not readily accepted. Finally, there was a failure by the scientists themselves. Some were too modest, did not read the literature, were mar ried to outdated ideas, or were unable to evaluate the data available to them. Some of the problems that confronted health scientists in the past, and which Buchanan WD (1964) Occupational f Cartier P (1952): In di Tumor Prnbleri Cartier 1' (1955): Son delayed acceptance of a relationship between asbestos and cancer, have greatly di- l 11-204-207. minished. Techniques needed for the conduct of experimental and epidemiologic f Cauna D, Totten ItS, studies have greatly improved; research information is much more widely available; where occupational hazards are concerned, industry is much more open with infor mation than in the past; international political tensions have changed; more Binding sources are available to conduct research; and there is better recognition that many Champeis J, De Lagu aux po&sieres i Chauvet M (1958): A Clemmesen J 11953): of Medical Set types of cancer can be prevented and, thus, that more research is needed. On the other * Cordova IF, Testuk I hand, the nature of science has probably not changed very much. Case reports, which signaled a problem with asbestos, arc still given little weight; being consistent is still more important than being right; research conducted in the West is more important t 1 187. 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FI COMMEN1 Cadmiui George Kaz Key words: cai ini With re I199l| refer t no clear dose Doll [ 1985J r a result of c< collected to t< have been ob: United States prostatic care provided no e SMR for pro* 5-year update to 75, thus si Howeve exists for lull) Frauenhofer I to inhaled cat most appropri rise to lung ca Gagliardi et a Septemlxr 19 ionic cadmiur potency of ca The autl They correct!; their text, to 1 Armstrong an Centre for Knviro England. Address reprint n lege of Science,1 2BP, England. Accepted for pub < 1991 Wiky-l