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FILE NAME Kent KNT DATE 1949 Jan DOC KNT114 DOCUMENT DESCRIPTION Journal Article - Cancer and Environment Scientific American _,~ fy rn Sree a ne eo. ot ae seone te , Sr JANUARY 1949 57 . 57 57 SCIENTIFIC AMERICAN VOL 180. NO 1 _ CANCER AND ENVIRONMENT Scientific and technological progress have exposed man to new physical and chemical agents Some are believed associated with the rise of cancer as a cause of death - by Groff Conklin i : THE industrial era in its full expan- sion is barely two generations old yet during that short period literally thousands of entirely new chemical and physical constituents have been added to g > uman environment Few of these con- .Vituents have been exhaustively analyzed for their range toxic effects on man They are now being studied however as possible contributors to the rise of cancer The growth in the relative importance of cancer as a cause of death is one of the outstanding medical facts of the past 30 years The disease has moved from eighth to second place in the U. since 1900 and triay only heart ailinents sur- --- it The reasons customarily given for this improved diagnosis and the azing of the population not entirely explain it They provide no - satisfactory answer to the fact that approximately seven and a half per cent of the known cancer deatles in 1941 securred in age groups undir 40. There is evidence more 1. that the disease is not an inevitable consequence of bodily degeneration due to age although the changes of senescence under certain conditions may be con tributing factors It seems certain that He is a net increase in true cancer dieuths if only because fewer people die from other diseases than in the past An explanation of this increase and of the causes of the disease is therefore being sought our environment so much rere complex than it was in 1900. The investigation is focused on carcinogenic jagents as the substaners that produce tative are called and on the general question question of the extent to which the in- 1 se in cancer may be caused caused by agents de environnvent the have hitherto been considered comparatively harmless It has been established that certain agents to which people are exposed in industrial veenpations cause cancer if the , es o . er ae * Tre - Alpha rays me. Beta rays Gamma rays Ultraviolet rays we = | + Chromates 1 . Nickel carbonyl - : . Beryllium ; my : e omai ese yDey,g Ah, . Anthrocene oil Aromatic amines Benzol . * Carbon black ' . Creosate Mineral oils Paraffin oil . Polycyclic hydrocarbons : Shale oil Tar and Pitch Aniline . Azo dyes - Estrogent -_ Cr et 1S ae ee PX feces Schistosome hematobium Virves . Clonorchis sinensis eres ae + wees CARCINOGENS known to be press ent in human ens ironment are classie fied Less certain agents are in italies exposure to them is sufficiently intense and prolonged As an example over 15 per cent of the miners in the Sehneeberg uranium mines of Germany die of lung cancer more than 50 per cent of those in the Joachimsthal uranium mines across the border in Czechoslovakia die of the same cause In the 18th century it was fearned that among chimney sweeps exposed to intense concentrations of soot deaths from cancer were between three and four times as high as those in the general population It is known also that certain common substances in concen trated doses can province canerr for ex- ample mouth cancers are uncommonly eve frequent in tribe in India which smokes eigars with the lighted end in the mouth FS This causes them to suffer frequent burns and to receive a concentrated dosage of tobacco tars Although these are special cases ni intense exposure they naturally suggest speculation as to whether the average human being's relatively mild but longs continued exposure to new substances in a contaminated atmosphere ^fin processed foods in cosmeties and in other elements our environment may be a contributory catise of cancer We have as yet no comis clusive evidence for or against this possi- bility We have no accurate estimate of how many of the artificial substances cont ionto our trial civilization may be carcinogenic under special ciremus stances nor how many seemingly harmle -substances interacting with others that appear to be equally innocuous may pri duce carcinogenic results There are al ventese. many theories alion cancer's causes chronie internsi irritations in the lusty changes in ceil metabolism tissue degeneration viruses and on Most of these theories how ever describe mechanisms rather than first causes laulced with two or three ex- - q SINUSNickelcarbonyl wt weeds,2 A a 7 4 MOUTH rete Betel re nut and tobacco chewing | THYROID Jodinedeficiency - Neg? ae q BRONCHI Nickel carbonyl a : q LUNGS Radioactive substances Asbestos Ns ~~ Chromates - Nickel carbonyl Tar fumes 4 LIVER Dietary deficiency reptions all of them seem to require the presence of a triggering agent Possibly the most fruitful current theory is the one that attributes cancer to muta- tions in body cells causing muta tions it has been demonstrated byexperi- experi- ments may be produced by ultraviolet radiation Xrays radioactive substances and a number of chemicals While more than 99 per cent of all cancers are still of unknown origin nearly all of those for which a proved cause has been found arise as the result of external agents These seem to mutate the cells into a state which is or can become cancerous The methods by which these external agents act upon the body vary consid erably depending on the substance involved Some carcinogens may cause cancer directly Examples of these are tar the mineral oils and certain dye intermedi- ates known as aromatic amines Turs gen erally affect the skin Mineral oils may cause cancer of the lungs through inhala Aro3matic me q BLADDER Aromatic amines wo ; Schistosoma hematobium tion The aromatic amines strangely con- centrate on the bladder no matter what their route of attack Whether they enter the body through the respiratory system the mouth or the skin they gravitate to the genitourinary system and there build | up a concentration that eventually causes 7} cancer Other agents seem to cause cancer by altering organs so that the organ itself pros resulting duces a carcinogen in in a cancer The mechanism of this transformation is little understood It is known that some radiations and certain metallic compounds including the chromates the arsenicals nickel carbonyl and possibly asbestos cause cancer in this relatively roundabout way tad BO< NE BONE MARROW - ioe % PERS:ee tiees e ORIGINAL SITES of malignant growths due to carcinogens in the en vironment are scattered among almost all the organs of the body Some agents such as the aromatic amine dye intermediates regularly affect the same organs even though they may use any one of many routes for attack 12 RADIOACTIVE materials are less spes RADIOACTIVE in their effects they spes produce a wide variety of cancers They may cause skin cancer by direct attack on the skin and lung cancer in people who inhale radinactive dust When expos expos sure is intensive and prolonged as in the ease of the women who worked in the radi- nun watch and click dial industry some 25 years ago they produce bone cancer And a slight but very prolonged exposure exposure to penetrating radiation can result in leukemia a cancer of the blund cells The latter kind of cancer is often found among radiologists whose whole professional lives have been spent in theoretically safe and protected dealings with rays or radioactive materials Must subtle of all carcinogens are Those believed to cause general metabolic disturbances that prosince cancers in a roundalmut way Thus the liver may pros duce carcinogens that can cause it or some other tissue to turn malignant Among the agents thought to have this effect are the N . f . a fa ee we and > Or ders and certain chlorinated aliphatic hydrocarbons But the mechanism in- usdund is so ulsure that the carcinogen- carcinogenjeity of these substaners has not been com- Vetely prised One aspect of such indirect causation however however is susceptible of proof Among soome Negro tribes working in the gold mings of Africa un excessive incidence nf cancer of the bladder has been traced to deficiencies in the workers diet It was found that most of the Negroes had lived for years on a deficient diet of pap and sour milk Only recently South Afri- can research workers have succeeded in producing cancer of the liver in rats fed just this diet f a IN view of the relative novelty of the con- -cept of environmental cancer and of the small amount of organized res search in this field it is not surprising that most of the known carcinogenic agents have been found in industry Here workers suffer exposures many times more coh- centrated than the average citizen en- counters in a industrial environment Fully 90 per cent of the known carcino genic agents are industrial and a similar proportion of cancers of known cause arises front carcinogens of industrial im- portance These known agents are listed in the chart in page 11 The difficulties in the scale study of carcinogenic agents are formidable The modern environment is so ramified that efforts to evaluate it in terms of long range carcinogenicity may appear nearly hopeless Nevertheless the techniques already developed in the study of necuputional carcinogens may be of some value in analyzing the environment as a whole even though more refined methods may have to be developed if such a program is to be successful , The two principal methods now used to uncover the more obvious necupational vancer hazards are animal experimentation and statistical analysis Cancers have bern produced in experimental animals by most of the known physical and chemical carcinogens Hundreds of other substances have been and are being tested Some that have been shown to be carcinogenie in animals have not as yet been proved dan- gerous to man or else they do not form a part of his normal environment Aming these substances are urethan ergot sele- nium and diethylene glycol One aspect of the work in animals that is important ^finconsidering human cancer is the phenomenon known as species specificity Many carcinogens that cause cancer in some animal species have thus far proved harmless to others For exam ple certain tars when correctly applied produce skin cancer in mice rats rabbits and dogs but not in monkeys Rats and mice get skin cancer from ultraviolet rays but rabbits do not The probability is that specialized metabolism is at the bottom of this species specificity fur cancer If such metabolic differences were completely understood fuman beings might be endowed with resistance to certain types of cancer by modifying the individual's metabolic processes Such ideas are still beyond the realm of practical application in man In experimental animals however cancer susceptibility or resistance to certain external carcinogens such as several of the . azo dyes may be created at will be the omission or addition of certain vitamins in the diet Without animal experimentation seien- of tific proof the carcinogenicity of various substances and radiations would be nearly impossible On the other hand laboratory experiments alin^'cannot prove definitely that such agents are dangerous to man Other methods must he usesi and the principal instruments so far available have been statistical studies and medical records In large unselected population groups variations in the incidence of one kind of cancer are usually not sufficiently marked to be significant That is why environmental carcinogens are usually difficult to deteet Up to half a century ago indeed evis dence of specific extrinsic causations of cancer was discovered largely by clinical observation Physicians practicing in ure ban or manufacturing areas began to notice a remarkably high incidener of cer- tain types of cancer among workers in individual trades Sich was the case in the diagnosis of cancer of the scrotum ^fin chimney sweeps Discoveries by direct ob- servation continue to be made as in the case of radium and ray cancer that nee eurred with alarming frequency among people working with these agents in the not so distant past UT observation has its limitations Un- less very careful medical records are kept or unless workers remain in a car- cinogenic jub for many years the fact that the job is carcinogenic may escape untice Characteristic of environmental cancers is the long period between the beginning of exposure to the carcinogen and the actual appearance of a tumor A worker who leaves a dangerous juh before the caneer appeurs may later develop a malignant tumor without realizing its origin The process of tracing cancers to their source through medical records and health statisties has become a work of skillei de- duction When a given community is found on careful examination of its illness and mortality statistics to have an inusual number of cases of cancer in certain sites the biometrician at once suspects the press ence of an active environmental carcino gen The chances today are very great that it will be traced to one or more factories in the area since so few industrial car einogens have been lound Conversely if it is known that certain plants are piem ducing or using known carcinogens the statistician searches for evidence of an abnormal incidence of cancer among men who are employer in these plants Obviously such investigations present dillicult problems and demand a high ore der af judgment It has often been said that statisties can be used to prove both sides of a question Environmental ear cinogenesis is no exception An example in American experience is study which was made some time ago of the incidence of lung cancer among 10.000 workers in an industry suspected of producing a carcinogenic agent It was known from studies in other countries that lung cancers were exceptionally frequent in this industry and there was no evidence that the American manufacturing methods differed in any major respect from those abroad Yet this study reported no lung caneers at all In any group of 40,000 adult males several cases of lung cancer are bound to secur merely on the basis of the incidence of the malignancy in the population as a whole The results of the study surely suggest a lack of thorough- ness in the collection and evaluation of data CLEAR example of the intelligent use of statisties as a tool in umeovering environmental carcinogens is the way in which cancers of the bladder were identi- fied as an occupational hazard in plants using the aromatie amine dye interme diates mentioned varlier The following composite description based on numbwe of European and American investigations of this problem illustrates the methumi The people in a certain industrial region have a frequency of bladder cancer that is a slight fraction higher than nor- mal The variation is well within the range of random probability but the fact that several cases of this not too common ma- lignancy have been found in a single community leads to a further study of the region It is found that the incidener of bladder cancer jumps from .02 per cent in the province as a whole to por cent in the particular community under study an increase of 400 per cent On further investigation it is learned that among the workers in a particular dye suffering plant in the town ^per cent are from or have dies from bladder cancer- nearly a 5.000 per cent increase Follows ing this elue every operation in the plant is studied and one particular jul is fonund in which over 90 per cent of the workers have bladder cancer or have died from it Obviously the focal point of the disease has been established It is from just such relatively slight statistical anomalies that much of the original evidence of carcinogenesis in industry arises Of course as more carcino gens become known and are added to the list the statistical techniques change With the emperation of the industries involvest medical and pubdie health experts ge dis rectly into the plants and study the opera- tions and the workers Often however publie medical and death records offer the 13 C . @ . o only reliable source of information Many jadustries jadustries actually do not know the ex- of istence carcinogenic hazards in their actories The study is so new that only ants in which the incidence of specific cancers is notoriously high are aware of the problem few industries do know of the existence of carcinogens in their plants and probably some of them have developed their own methods of coping with them The reluctance of industrial manage- ments to publicize the existence of a carcinogenic hazard is understandable for it could easily become difficult for plants so labeled to recruit workers or even to sell perted The incidence of lung cancer did not diminish in fuct soon afterward rane cers begun to appear among workers who had been exposed for less than six years a much shorter period than had been previously observed What had happened was that at the time when the protective meas ures were adopted the factory had also begun to use a more finely ground material to improve production The finer dust though present in a much lower concen-tration than the original material pene- trated farther within the bronchi of the lungs Thus despite the installation of the latest in protective devices and pros cedures the cancer hazard was actually closed that the community be protected by the prevention of the discharge of ear- cinogenic wastes that factories be censed and inspected that workers be provided with protective clothing equips iment and medical supervision including frequent and thorough physical examina tions . The Environmental Cancer Section of the Institute which is a part of the U. Public Health Service is preparing an immediate comprehensive campaign of education and information the purpose of which is to bring physicians to a realization of the existence of the problem Plans are also under way to make exhaustive their commodities To make factories em- ploying carcinogenic materials safe to work in furthermore sometimes requires extensive and costly alterations If one firm makes such alterations and others do not the competitive position of its product increased IT is obvious therefore that the control of occupational carcinogenesis even to a great extent of cancers stemming from more indefinite environmental surveys of major industrial areas in the nation These studies are essential preliminaries to the institution of the controls that Dr. Hueper has suggested Many of the control recommendations admittedly are reaching in their imupli- is endangered . Generally speaking however employ ers are no more responsible for the lack of information about industrial cancer than are the many thousands of physicians who have cancer patients in industrial areas or liis actually are associated with factories It is an unquestionable fact that an appreriable number of occupational cancers -lip through the hands of doctors unidentified This is due in a great degree to a general ignorance of the occupational as pects of cancer Physicians have never been adequately informed of the basic symptomatic and sociological factors insolved in identifying occupational carcino- City DALLAS NEW ORLEANS r . : Percent of total possible sunlight 60-80 percent 62-64 percent Skin cancers per 100,000 population 140 129 genesis THE medical profession shoull be bet ter educated about the need for cx- f 3 a : PITTSBURGH * | 50-57 percent 37 . haustive case histories which carry the individual's jub record in detail back as far as 25 years about the urgency of cheek- ing medical suspiciuns uf industrial cancer hazards against careful epidemiological studies of all the workers in a plant and about the paramount importance of impressing plant management with the seri unsness of the problem The standard protective and hygienic measures currently used in industry to combat industrial poisons and other health | hazards are not always adequate for the control of occupational cancer The following case history is a compelling illus tration Some 30 years ago workers in one at the newer metal industries began to develop lung cancers At that time the cancers were found to remain latent from 10 to 15 years The incidence was unusu- afly high in certain operations where the carrinogenie sulistance was present in par- ticularly high concentration as an air- burne dust An effort was made to sale- guard these operations date ripuirpipu-ip- ment for remusing dust anul fumes was installed and a standard industrial hy giene program was inaugurated including protective clothing But the outcome was exactly the opposite if what had been ex- - DETROIT * 25-40 percent 24 : \e CARCINOGEN IN NATURE is sunlight Such natural carcinogens however are few An abnormally high concentration of arsenic in drinking water has been shown to cause cancer of the skin and internal organs Infe tions of certain parasites have also been found to lead to malignant growths agents and when they are discovered discovered is a public health problem of considerable magnitude is made even more apparent by the scope of a control program that has been proposed by Dr. Wilhelm C. Hueper head of the new Environmental Cancer Section of the National Cancer Institute Dr. Hueper one of the world's leading experts in nccupational cancer has studied the problem in the U. and elsewhere for many years Several of the elements of his program have already heen put into effect in European countries The program proposes that carcinogrisic agents be eliminated from industrial mili tary and civilian use as far as is possible and practical that manufacturing processe es which must use such materials be en- cations Years of work will be requires to put them into practier with maximal effectiveness This is particularly true of the recommendations for social controls On the technical side some of the elements can be instituted at once and without great expense if management and labor can be persuaded to agree to them For example effective medical and sani- tary supervision of expused workers can be undertaken immediately This supervis sion should include ray examinations at frequent intervals careful clinical study ost suspicious lesions preparation of ex haustive amb stetajoi bs banialdyso es and ruse histories regular quarterloyr semis animal physical at examinations allworks allworks ers who might possibly suffer exposure to ^' foe ot fe , ee + + r dl He ^arcinogenicagents a constant review of dangerous plant operations to enforce . constant good housekeeping and tocheck the level of carcinogenic dusts fumes ~-l mists and ~ Protective measures for the workmen themselves are alsosimple relatively inexpensive although the enforcement of their use is sometimes made difficult by the discomfort they cause They include the regular wearing of respirators and sealed clothing whenever exposure to a carcin~-s genic hazard is likely daily showers for all persons working in or near the hazard- ous operations use of separate lockers for street and work clothes and adoption of work techniques that will minimize the dangers of exposure Other and more important technical of. eeeeN measures are likely to involve heavy ex- penditures for management In some instances entire factories would have to ree be rebuilt Others would require costly TET control equipment such as elec LES N tronic dust precipitators and extensive remodeling to enclose carcinogenic opera tions and keep the workers from any contact with dangerous agents Few plants could afford the necessary changes unless all other plants in the same industry were required to make the same improvements the same tinte t N some instances such changes might possibly be undertaken as a result of industry agreement In others Megislative and administrative enforcement f might essential Such action would in- clude factory licensing and inspection by government improved compensation laws recognizing occupationally acquired cancers as compensable and revision of the health codes to make occupational cancers ee TT notifiable just as are many other diseases These measures would require coordinated and carefully planned action on the part ' of management labor the medical profes sion state public health and labor depart . ments and state and Federal legislatures A precedent for such a progrum has al ready been set by the successful control of communicable diseases through public ; health laws and through the organized comperation in their enforcement of both private and public agencies How effective these controls would be in diminishing the hazards of still undiscov ered environmental carcinogens is a question that only time can answer Meanwhile the known causes of occupational cancers would be placed under technical and social restraint and patterns would be established for the future contrul of new carcinogens as they are found in our environment asewe%y? wey *. nn 2 i eee Se POPULATION OF COUNT=Yx! WHICH PLANT IS LOCATED ~ 0.1 percent affected vad : = WORKERS IN DEPARTMENT WHERE CARCINOGENIC ACTIVITY TAKES PLACE < 20-50 percent affected - cae vse. =~ WORKERS DIRECTLY INVOLVED ! IN THE CARCINOGENIC ACTIVITY -_! SEs 90-100 percent affected , Grof Conklin is a sci- ence writer and a former consultant with the Nu tional Canere Institute : cn sees EXTREME CASE of environmental cancer is represented by record of matic amine plant in Germany aro- Of workers directly in contact with chemical 90 to 100 per cent developed cancer of the bladder Running from top to bottom is illustration of statistical analysis used to locate such hazards