Document nk1gy36BmD6MZeGadyB8be8X

JANUARY 1949 I SCIENTIFIC S> tf'S!;5G>OVj5 vn v< VOL. 180, NO. 1 CANCER AND ENVIRONMENT Scientific and technological progress have exposed man to new phvsical and chemical agents. Some are believed associated with the rise of cancer as a cause of death by Groff Conklin NO i ;;it friOtf r HE industrial era in its full expan- been considered comparatively harmless. T.mil is barely two generations, old, set during that short period literally It has been established that certain agents to which people are exposed in in tituusands of entirely new chemical anddustrial occupations cause cancer if the rb constituents have been added to Ik n environment. Few of these con- ait, have been exhaustively analyzed Inr their long-range toxic effects on man. They are now being studied, however, as pii*'iblc contributors to the rise of cancer. The growth in the relative importance ol cancer as a cause of death is one of Gomnui rays Ultravioiat cays * X-roys ,, , the outstanding medical facts of the past jt) years. The disease has moved from nfhlli to second place in the U. S. since 1900. and today only heart ailments sur pass it. The reasons customarily given for this rise--improved diagnosis and the aging of the population--do not entirely, explain iL They provide no satisfactory tatter to the fact that approximately nrn and a half per cent of the known rtneer deaths in 1944 occurred in age fru|i' under 40. There is evidence, moretcr. that the disease is not an inevitable n>nei|utnce of bodily degeneration due to ge. although the changes of senescence under certain conditions may be con tributing factors. It seems certain that there is a net increase in true cancer deaths, if only because fewer people die Ifiuii other diseases than in the past. An explanation of this increase and of ihe causes of the disease is therefore being sought in our environment, so much n^^^-nplex than it was in 1900. The ui^^ lion is focused on carcinogenic agents, as the 'ubstances that produce rjneer are called, and on the general " * N.'viot- v tvv-i C'>b<M-bk>df' ft /:: Wsk". ' Crosl*v . v " **ip*-obeli* ,,( " , ,v-. V- ' s , .. . Folycydse./dratejb*>sW ' - tIV shoieoO'"- - Soot F;: Tor and AmJ.'fti - ' /ngjti t. Ettrogvii .k* l%* *."ic l r SchltiMome fismntotstjnv^ Vttuws. -. '.TV-V*. k . Clonoi'Ml ^ J question of the extent to which the in- CARCINOGENS known to be pres rrrose m cancer may he caused by agents ent in human environment are classi in the environment that have hitherto fied. Less certain agents are in italics. exposure to them is sufficiently intense and prolonged. As an example, over 75 per cent of the miners in the Schneeberg cobalt-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 learned 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 gen eral population. It is known also that certain common substances in concen trated doses can produce cancer; for ex ample, mouth cancers are uncommonly frequent in a tribe in India which smokes cigars with the lighted end in the mouth. This causes them to suffer frequent burns and to receive a concentrated dosage of tobacco tars. Although these are special cases of intense exposure, they naturally suggest speculation as to whether the average human being's relatively mild but longcontinued exposure to new substances in a contaminated atmosphere, in processed foods, in cosmetics and in other elements of our environment may be a contributory cause of cancer. We have as yet no con clusive evidence for or against this possi bility. W'e have no accurate estimate of how many of the artificial substance* common to our industrial civilization may be carcinogenic under special circum stances, nor how many seemingly harmless substances, interacting with others that appear to be equally innocuous, may pro duce carcinogenic results. There are, of course, many theories about cancer's causes; chronic internal irritations in the bodv, changes in cell (ORIGINAL SITES of malignant growths due to carcinogens in tlie en- ) ronment are scattered among almost all the organs of the body. Some agents, such a6 the aromatic amine dye intermediates, regularly affect the same organs even though they may use any one of many routes for attack. metabolism, tissue degeneration, viruss and so on. Most of these theories, ho* ever, describe mechanisms rather thai first causes. Indeed, with two or three azo dye hydroc. volved ceptions all of them seem to require tl> presence of a triggering agent. Possibly the most fruitful current theon is the one that attributes cancer to muij tions in body cells. Cancer-causing muti tions, it has been demonstrated by expert ments, may be produced by ultraviolc radiation. X-rays, radioactive substance; and a number of chemicals. While mop than 99 per cent of all cancers are stif of unknown origin, nearly all of thus* for which a proved cause has been fount! arise as the result of external agent-j These seem to mutate the cells into a stath icity of pletely One howevc some r mines < cancer deficiei found for yea and so can re produi just th which is, or can become, cancerous. [ The methods by which these external! agents act upon the body vary consul, erably, depending on the substance in1 volved. Some carcinogens may came cancer directly. Examples of these are tai. the mineral oils and certain dye intermeili' ates known as aromatic amines. Tars gen erally affect the skin. Mineral oils ma\ cause cancer of the lungs through inhala tion_ The aromatic amines, strangely, con centrate on the bladder, no matter whai their route of attack. Whether they enti-rt the body through the respiratory system.! the mouth or the skin, they gravitate t' the genito-urinary system and there build1 up a concentration that eventually cau-e- cancer. 1 Other agents seem to cause cancer hd altering organs so that the organ itself pro! duces a carcinogen, resulting in a cancer, The mechanism of this transformation id little understood. It is known that sonic, radiations and certain metallic compound; including the chromates, the arsenical?,| nickel carbonyl and possibly asbe-to?.' cause cancer in this relatively roundabout! way, j IN vh cep the sn search most ' have b suffer ' centra counti Fully genic propo arises portai the ch The of ca The t that c range hopel ready tional in an, even have to be Th RADIOACTIVE materials are less spe-j cialized in their effects: they can! unco* canct tion i produce a wide variety of cancers. TheO been may cause skin cancer by direct attack; on the skin, and lung cancer in people most carci; who inhale radioactive dust. When expo have sure is intensive and prolonged, as in the case of the women who worked in the radi( urn watch and clock dial industry sonit[ have anim gerot 25 years ago. they produce bone cancer. part And a slight but very prolonged exposure, thfcse to penetrating radiation can result m! niurr leukemia, a cancer of the blood cells. Tilt P' latter kind of cancer is often found aimm; is pm radiologists whose whole profe~sion.il is | tl lives have been spent in theoretically safe spec and well-protected dealings with A-ra\- cahc or radioactive materials. far ] Most subtle of all carcinogens arc pie. those believed to cause general metabolic prod disturbances that produce cancers in a and roundabout way. Thus the liver may pro mic< duce carcinogens that can cause it or some but other tissue to turn malignant. Among the spec agents thought to have this effect are the this 12 __ _______ _________ ivV -=- - j_BB 005398~7 |^Qj` f FU4 v i. viruses, rie. howiver than three exquire the "fit f, to ing niuta iy experiiltraviolet ib'iancea. hile more - are still of those en found il agents ito a state OUS. extern*] > considtance in i\ cause arc tar, utermedi Tar- gen oil- may th i nli ala!irly. con tier what hey enter v system, J' itate to 'ere build causes aaciT_bv! It-e'i a call niation if j hat some] un pounds j r-enicals; J a-bt-tos,' unda bout I less tpj. hev can 1 rs. They t attack | i people j n expo- j ,i- in the I the radi- j try some ! ' cancer, exposure W result in ells. The t id among % fes-ional ? ally safe h X-ray* E azn dyes and certain chlorinated aliphatic metabolic differences were completely un men who are employed in these plants. hydrocarbons. But the mechanism in derstood, human beings might be endowed Obviously such investigations present volved is so obscure that the carcinogen with resistance to certain types of cancer difficult problems and demand a high or icity of these substances has not been com by modifying The individual's metabolic der of judgment. It has often been said pletely proved. processes. Such ideas are still beyond the that statistics can be used to prove both One aspect of such indirect causation, , realm of practical application in man. In sides of a question. Environmental car however, is susceptible of proof. Among experimental animals, however, cancer cinogenesis is no exception. some Negro tribes working in the gold susceptibility or resistance to certain ex An example in American experience is mines of Africa, an excessive incidence of ternal carcinogens, such as several of the a study which was made some time ago of cancer of the bladder has been traced to azo dyes, may be created at will by the the incidence of lung cancer among 40,000 deficiencies in the workers' diet. It was omission or addition of certain vitamins in workers in an industry suspected of pro found that most of the Negroes had lived the diet. ducing a carcinogenic agent. It was for years on a vitamin-deficient diet of pap Without animal experimentation, scien known from studies in other countries that and sour milk. Only recently South Afri tific proof of the carcinogenicity of various lung cancers were exceptionally frequent can research workers have succeeded in substances and radiations would be nearly in this industry, and there was no evidence producing cancer of the liver in rats' fed impossible. On the other hand, laboratory that the American manufacturing methods just this diet. experiments alone cannot prove definitely differed in any major respect from those that such agents are dangerous to man. abroad. Yet this study reported no lung IN view of the relative novelty of the con Other methods must be used, and the prin cept of environmental cancer, and of cipal instruments so far available have die small amount of well-organized re- been statistical studies and medical rec cancers at all! In any group of 40.000 adult males several cases of lung cancer are bound to occur, merely on the basis of -carcli in this field, it is not surprising that ords. the incidence of the malignancy in the most of the known carcinogenic agents In large, unselected population groups, population as a whole. The results of the have been found in industry. Here workers variations in the incidence of one kind of study surely suggest a lack of thorough suffer exposures many times more con cancer are usually not sufficiently marked ness in the collection and evaluation of centrated than the average citizen en to be significant. That is why environmen data. counters in a non-industrial environment. tal carcinogens are usually difficult to de Fully 90 per cent of the known carcino genic agents are industrial, and a similar proportion of cancers of known cause tect. Up to half a century ago, indeed, evi dence of specific extrinsic causations of cancer was discovered largely by clinical A CLEAR example of the intelligent use of statistics as a tool in uncovering environmental carcinogens is the way in arises from carcinogens of industrial im observation. Physicians practicing in ur which cancers of the bladder were identi portance. These known agents are listed in ban or manufacturing areas began to fied as an occupational hazard in plants die chart on page ] 1, notice a remarkably high incidence of cer using the aromatic amine dye interme The difficulties in the large-scale study tain types of cancer among workers in in diates mentioned earlier. The following of carcinogenic agents are formidable. dividual trades. Such was the case' in the composite description, based on a number The modern environment is so ramified diagnosis of cancer of the scrotum in of European and American investigations dial efforts to evaluate it in terms of long- chimney sweeps. Discoveries by direct ob of this problem, illustrates the method: range carcinogenicity may appear nearly servation continue to he made, as in the The people in a certain industrial re hopeless. Nevertheless, the techniques al case of radium and X-ray cancers that oc gion have a frequency of bladder cancer ready developed in the study of occupa curred with alarming frequency among that is a slight fraction higher than nor tional carcinogens may be of some value people working with these agents in the mal. The variation is well within the range m analyzing the environment as a whole, not so distant past. of random probability, but the fact that even though more refined methods may several cases of this not too common ma have to be developed if such a program is lo be successful. The two principal methods now used to BUT observation has its limitations. Un lignancy have been found in a single less very careful medical records are community leads to a further study of kept, or unless workers remain in a carthe region. It is found that the incidence uncover the more obvious occupational cinogenic job for many years, the fact that of bladder cancer jumps from .02 per eancer hazards are animal experimenta the job is carcinogenic may escape notice. cent in the province as a whole to .1 per tion and statistical analysis. Cancers have Characteristic of environmental cancers is cent in the particular community under been produced in experimental animals by the long period between the beginning of study, an increase of 400 per cent. On most of the known physical and chemical exposure to the carcinogen and the actual further investigation it is learned that i arcinogens. Hundreds of other substances appearance of a tumor. A worker who among the workers in a particular dvc li.ne been and are being tested. Some that leaves a dangerous job before the cancer plant in the town, 5 per cent are suffering lure been shown to be carcinogenic in appears may later develop a malignant from or have died from bladder cancer-- animals have not as yet been proved dan tumor without realizing its origin. nearly a 5.000 per cent increase. Follow gerous to man. or else they do not form a The process of tracing cancers to their ing this clue, every operation in tile plant part of his normal environment. Among source through medical records and health is studied, and one particular job is found ihe-e substances are urethan, ergot, sele statistics has become a work of skilled de in which over 90 per cent of the workers nium, and diethylene glycol. duction. When a given community is found, have bladder cancer or have died from it. One aspect of the work on animals that on careful examination of its illness and Obviously the focal point of the disease i- important in considering human cancer mortality statistics, to have an unusual has been established. I- die phenomenon known as "species number of cases of cancer in certain sites, It is from just such relatively slight 'prrificitv." Many carcinogens that cause the biometrician at once suspects the pres statistical anomalies that much of the cancer in some animal species have thus ence of an active environmental carcino original evidence of carcinogenesis in in far proved harmless to others. For exam gen. The chances today are very great that dustry arises. Of course, as more carcino ple. certain tars, when correctly applied, it will be traced to one or more factories in gens become known and are added to the produce skin cancer in mice, rats, rabbits the area, since so few non-industrial car list, the statistical techniques change. With and dogs, but not in monkeys. Rats and cinogens have been found. Conversely, if the cooperation of the industries involved, mice get skin cancer from ultraviolet rays, it is known that certain plants are pro medical and public health experts go di but rabbits do not. The probability is that ducing or using known carcinogens, the rectly into the plants and study the opera specialized metabolism is at the bottom of statistician searches for evidence of an tions and the workers. Often, however. - this species specificity for cancer. If such --abnormal incidence of cancer among public medical and death records offer the *1 IfV uuiVsu i'iiGiVi rrG FILES ii.luuiit ui iiiiurmtiium. .Many industries actually do not know of the ex istence of carcinogenic hazards in their factories. The study is so new that only plants in which the incidence of specific cancers is notoriously high are aware of the problem. A few industries do know of ^^existence of carcinogens in their ^^Bs. and probably some of them have oped their own methods of coping with them. The reluctance of industrial manage ments to publicize the existence of a car cinogenic hazard is understandable, for it could easily become difficult for plants so labeled to recruit workers, or even to sell 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 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 who actually are associated with factories. It is an unquestionable fact that an appre ciable number of occupational cancers lip through the hands of doctors uniden tified. This is due in a great degree to a pected. i he incidence of lung cancer did closed; that the community be protecui*^ the carcinogen not diminish; in fact soon afterward can by the prevention of the discharge of ca of dangerous cers began to appear among workers who cinogenic wastes; that factories be 1 constant good bad been exposed for less than six years, a much shorter period than had been pre viously observed. What had happened was censed and inspected; that workers 1 provided with protective clothing, equi] ment and medical supervision. incJudio on the level ot and mists. Protective r that at the time when the protective meas ures were adopted the factory had also begun to iise a more finely ground material to improve production. The finer dust, though present in a much lower concen -frequent and thorough physical examini tiona. The Environmental Cancer Section t the Institute, which is a part of the U. S Public Health Service, is preparing a themselves are inexpensive, a their use is son discomfort the regular wearir tration than the original material, pene-- immediate, comprehensive campaign n clothing when trated farther within the bronchi of the education and information, the purpose o genic hazard : lungs. Thus despite the installation of the which is to bring physicians to a realizi all persons wo latest in protective devices and pro tion of the existence of the problem. Plan nus operations cedures, the cancer hazard was actually are also under way to make exhaustivi street and wor increased. surveys of major industrial areas in th work techniqc nation. These studies are essential prt dangers of exp IT is obvious, therefore, that the control liminaries.to the institution of the control Other, and of occupational carcinogenesis--and that Dr. Hueper has suggested. measures are even to a great extent of cancers stem Many of the control recommendation penditures foT ming from more indefinite environmental admittedly are far-reaching in their impli stances, entire be rebuilt Ot waste-control Ironic dust pt remodeling to > lions and keep tact with dan: DALLAS 60--80 percent could afford th oil other plantrequired to me at the same tin general ignorance of the occupational as pects of cancer. Physicians have never been adequately informed of the basic symptomatic and sociological factors in volved in identifying occupational carcino- NEW ORLEi 62--64 percent IN some inst possibly be an industry-w legislative and might be essen Pll T> lit medical profession should he bet ter educated about the need for ex haustive case histories which carry the 50--57 percent individual's job record in detail back as far as 25 years, about the urgency of check ing medical suspicions of industrial cancer hazards against careful epidemiological studies of all the workers in a plant, and DETROJ 25--40 percent \ about the paramount importance of im pressing plant management with the seri CARCINOGEN IN NATURE is sunlight. Such natural carcinogens, however, ousness of the problem. are few. An abnormally high concentration of arsenic in drinking water The standard protective and hygienic lias been shown to cause cancer of the skin and internal organs. Infec measures currently used in industry to tions of certain parasites have also been found to lead to malignant growths. .ombat industrial poisons and other health tazards are not always adequate for the l ontrol of occupational cancer. The fol lowing case history is a compelling illus tration: Some 30 years ago workers in one >< the newer metal industries began to levelop lung cancers. At that time the agents, if and when they are discovered-- is a public health problem of considerable magnitude. This is made even more ap parent by the scope of a control program that has been proposed by Dr. Wilhelm C. Hueper, head of the new Environmental cations. Years of work will be required to put them into practice with maximal effec tiveness. This is particularly true of the recommendations for social controls. Onj the technical side, some of the elements can he instituted at once and without great; ancers were found to remain latent from Cancer Section of the National Cancer expense, if management and labor can be! 10 to 15 years. The incidence was unusu- Institute. Dr. Hueper, one of the world's persuaded to agree to them. illy high in certain operations where the arcinogenic substance was present in paricularly high concentration as an airmrne dust. An effort was made to safeuard these operations. Up-to-date equiplenr for removing dust and fumes was tsti^gd. and a standard industrial hy- leading experts on occupational cancer, has studied the problem in the U. S. and elsewhere for many years. Several of the elements of his program have already been put into effect in European countries. The program proposes that carcinogenic agents be eliminated from industrial, mili For example, effective medical and sani-j tary supervision of exposed workers caul be undertaken immediately. This supervi sion should include X-ray examinations at frequent intervals; careful clinical study of suspicious lesions; preparation of ex haustive and detailed job analyses and ram was inaugurated, including rot^^e clothing. But the outcome was vactly the opposite of what had been ex tary and civilian use as far as is possible and practical; that manufacturing process es which must use such materials be -en* case histories; regular quarterly or semiannual physical examinations of all work ers who might possibly suffer exposure to elude factory 1 government, in recognizing oc ccrs as compel health codes to notifiable just . These measure: and carefully i of management sion, state publ tnenta, and stat A precedent h ready been set of communicab health law$! ai cooperation in private and pul How effective diminishing tht ered environme tii.n that only while, the knocancers would and social rest he established new carcinoget environment. Groff ence u consul tional J p* r | i1 ' ^ r'v J 7~Bb"0005400 W. I ^ Vi' l the carcinogenic agents; a constant review of dangerous plant operations to enforce constant good housekeeping and to check on the level of carcinogenic dusta, fumes, and mists. Protective measures for the workmen themselves are also simple and 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 carcino genic hazard is likely, daily growers for all persons working in or near the hazardnus 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 measures are likely to involve heavy ex penditures for management. In some in stances, entire factories would have to Ik: rebuilt. Others would require costly waste-control equipment, such as elec tronic dust precipitators, and extensive remodeling to enclose carcinogenic opera tions and keep the workers from any con tact 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 t the same time. IN some instances, such changes might possibly be undertaken as a result of an industry-wide agreement. In others, legislative and administrative enforcement ought he essential. Such action would in clude factory licensing and inspection by government, improved compensation laws recognizing occupationally acquired can cers as compensable, and revision of the lirnlih codes to make occupational cancers mitiliahle just as are many other diseases. These measures would require coordinated ml 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. \ precedent for such a program has al ready been set by the successful control d eunimunicable diseases through public health laws and through the organized cooperation in their enforcement of both private and public agencies. I low effective these controls would be in dimmi-liing the hazards of still undiscovired environmental carcinogens is a ques tion that only time can answer. Mean while, the known causes of occupational ranrrrs would be placed under technical and social restraint, and patterns would lie established for the future control of new carcinogens as they are found in our environment. Groff Conklin is a sci ence writer and a former consultant with the Na tional Cancer Institute. EXTREME CASE of environmental cancer is represented by record of aro matic amine plant in Germany. 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. piir0005401_i 15