A dramatic example of the harmful environmental insults to nineteenth-century workers is provided by Sir Percival Potts' description of carcinoma of the scrotum occurring in the chimney sweeps in London. These poor boys, under ten years of age, were forced in and out of chimney pots, rubbing carcinogenic materials from domestic soot into their filthy clothes. In 1863, in his Water Babies, Charles Kingsley wrote of his main character, Tom, a chimney sweep: "Once upon a time there was a little chimney-sweep, and his name was Tom. He cried half his life, and laughed the other half. He cried when he had to climb the dark flues, rubbing his poor knees and elbows raw; and when the soot got into his eyes, which it did every day of the week."

Literary men thus roused public conscience. And with public servants like Lord Shaftesbury who fought for relief for women and children (Fig. 3), great social reforms, backed by legislation, took place in Europe.

The United States lagged behind Europe in legislation to control harmful working conditions, and in attention paid by physicians to the effects of toxic materials. A few deeply interested individuals eventually stimulated the Government and labor organizations between 1907 and 1920 to take action; Dr. Alice stands among those few who made influential personal and professional contributions. In 1910 she attended the International Congress on Occupational Accidents and Diseases, which she describes as follows: "

8

"The Congress was a very interesting experience for me, meeting and hearing the famous authorities I knew so well from their writings. But for an American it was not an occasion for national pride. There were but two of us on the program, Major Bailey Ashford, with a paper on hookworm infestation in Puerto Rico, and myself with one on the white-lead industry in the United States which revealed only too clearly the lack of such precautions as were a commonplace in the older countries. It was still more mortifying to be unable to answer any of the questions put to us: What was the rate of lead poisoning in such and such an industry? What was the system of compensation? Finally Dr. Gilbert, of the Belgian Labor Department, dismissed the subject: 'It is well known that there is no industrial hygiene in the United States. Ça n'existe pas.'"

"Everyone with whom I talked in the United States assured me that foreign writings could not apply to American conditions, for our workmen were so much better paid, their standard of living was so much higher, and the factories they worked in so much finer in every way than the European, that they did not suffer from the evils to which the poor foreigner was subject. That sort of talk always left me skeptical. And presently I had factual confirmation in my disbelief in the unhappy lot of the American worker through the reading of Andrea's manuscript on 'phossy jaw' in *** the match industry in the United States * * * the abscess may form in the upper jaw and works up into the orbit, causing the loss of an eye. There are cases of men and women who had to live all the rest of their days on liquid food. The scars led some women to commit suicide. Here was an industrial disease which could be clearly demonstrated to the most skeptical."

In 1906 the European countries agreed to forbid the manufacture or import of white-phosphorus matches. But not until 1931 did the United States Government act to forbid import or export of such matches.

This record has been changing steadily since the 1920's. Many industries seek excellent medical and engineering advice and use it to control hazardous jobs. Aub's 10 work on lead poisoning and Martland's contribution to the study of radium-induced damage" are outstanding examples of studies whose influence is still in effect in prevention and handling of certain industrial diseases. While the press is justly criticized for dramatic and often false reporting, credit is due the newspapers for help given in bringing the plight of the luminous-dial painters in New Jersey (Fig. 4) to the attention of the medical profession and the courts in the years just after World War I. Legislation and the efforts of organized labor have forced reluctant industries to take steps to control hazardous work.

Thompson, W. G. The Occupational Diseases: Their causation, symptoms, treatment, and prevention. New York: Appleton-Century, 1914.

S Hamilton, footnote 40. P. 127.

Idem., footnote 1. P. 115.

10 Aub. J. C., Fairhall, L. T., Minot, A. S., and Reznikoff, P. Lead poisoning. 4: 1-250, 1925.

Madicine

Martland, H. S. Occupational poisoning in manufacture of luminous watch dials: general review of hazard caused by ingestion of luminous paint, with especial reference to New Jersey cases. J.A.M.A. 92: 466 and 552, 1929.

Workmen's compensation statutes and state health and safety laws have caused great improvements in working conditions.

My share in the story begins when Dr. Aub suggested I consider the study of occupational disease. In September, 1945, about three years after the death of a fluorescent lampworker, Manfred Bowditch, then head of the Division of Occupational Hygiene, handed me a large file with the findings of Tabershaw, my predecessor, and his own carefully collected notes, and bade me give the matter of illness in Massachusetts fluorescent lampworkers my whole attention. I have been at work on this problem ever since. Much credit is due Bowditch for his tenacity in pursuing the answer to the question of what in the industry caused what was then named "Salem sarcoid."

Combining reports from the medical literature and data from a registry of cases begun in 1952 with my clinical experience, I want to present facts that point out lessons for control of beryllium poisoning and other man-made diseases. There are lessons from this material for physicians, for industrial hygienists in and out of industry, for policy makers in governmental agencies and also for industrialists.

It must be admitted that several critical pieces of evidence needed for final judgment on the toxic effects of beryllium are still missing. For example, there is little knowledge of the chemical and physical properties of various beryllium compounds that, if known, might help explain differing biologic effects. In addition, results of experimental studies on animals have been confusing in part because beryllium compounds used have differed from one laboratory to another. Data in the Registry have several serious weaknesses. Figures on populations at risk are either inaccurate or not to be had. Quantitative information on exactly what the sick worker was exposed to, and at what level, is also lacking. Unfortunately, by no means all cases of beryllium disease are known to the Registry, not even all those so diagnosed. Some case records at hand are incomplete, and some lost to follow-up study. The help of over 300 physicians who have sent case records to the Registry is gratefully acknowledged* as making what I have to offer of real value. In contrast, with rare exception, industry and insurance companies withhold data on occupational disease-its character and incidence. This fact has great influence on the acquiring of knowledge of industrial illness in other as well as the beryllium-using industry in the United States. Before I present accumulated Registry data, a review of steps leading to its inception holds lessons of value. In the first place, the history of the recognition of beryllium poisoning by physicians tells a story. The ten years required seemed long to me, a novice, but compared with my earlier sketch of occupational-disease history, were relatively short. The acute disease, causing irritation of skin and mucous membranes after exposure to acid salts, was understandably considered due to the acid radical and not to beryllium; thus, identification was easily missed. Acute beryllium pneumonia could and did pass for one of viral origin, or, in serious cases, a chemical pneumonia with pulmonary edema, a pattern response produced by phosgene and other irritants.

The chronic illness, with its nonspecific symptoms and signs and x-ray films of the chest, might parade, as it did and still does, under various diagonses. Its x-ray appearance is confused with that of tuberculosis and Boeck's disease most often, as well as with silicosis and metastatic cancer. Its pathological picture has been confused with leprosy, tuberculosis and, most often, with sarcoidosis. Delay in the onset of some cases of chronic beryllium poisoning is a fact that helps explain industry's failure to realize its responsibility, since many affected workers left the industry years before the onset of their symptoms. A critical fact in the failure to recognize beryllium poisoning sooner is the ignorance of many physicians of the existence of industrial illness. This is undoubtedly changing, but even when a doctor considers his patient's job, rarely does he take the chronologic work history required to bring to light a past exposure to beryllium. Few American medical schools teach students how to take an occupational history in the same complete fashion in which a medical history is taken. Dr. Alice, studying lead poisoning," writes, "Hospital sheets noted

Thanks are especially due to Drs. Joseph C. Aub, Christopher H. Wood, Lloyd B. Tepper, John D. Stoeckle, David Freiman, H. S. Van Ordstrand, Joseph DeNardi, Charles Chesner, Edward M. Kline, George W. Chamberlin, John Bishing, G. P. Desjardins and Thomas Mancuso. I acknowledge with appreciation the courtesy of Little, Brown and Company in allowing free use of material iin Hunter. footnote 4. Mrs. Emily W. Rabe and Mrs. Dimity S. Berkner provided great skill and patience in preparing the diffuse Registry data for presentation.

12 Hamilton, footnote 1. P. 10.

carefully all the facts about tobacco, alcohol, and even coffee consumed by the leaded man, though obviously he was suffering from none of these poisons; but curiosity as to how he became poisoned with lead was not in the intern's mental makeup." Because of the ignorance of the medical profession of occupational illness and its mimicry of other diseases the patient with chronic beryllium disease was ill cared for originally. Delay in realizing that the sarcoid-like disease was caused by his occupation meant that the patient's exposure to beryllium might continue, his claim to compensation was not established, and appropriate treatment was postponed. Since industry and governmental agencies were not at first warned, their help was delayed.

A second lesson is to be found in the use made of published literature on the subject of illness in the beryllium industry. The errors in judgment that were made are, in retrospect, surprising. The story of beryllium poisoning illustrates well the fact that in this country we tend to believe that though a trade does cause disease elsewhere, it will not do so here. Of serious psychoses occuring in the viscose-rayon industry, Dr. Hamilton wrote in 1938 13 :

"Since we were using the same process, I was not surprised when stories began coming to me of acute insanity in churn room men and spinners in viscose rayon plants. The medical journals were full of reports from all over Europe and from Japan, not from the United States. In 1904 two cases were reported in this country, in 1905, one; in 1914 I published two . . . I doubt if any American medical student ever heard a word on the subject."

18, 19

Before 1942 the Russian, German and Italian literature contained reports of beryllium-related worker illness describing much of what we have experienced since.14 15 16 17 Why these reports were ignored in the United States is uncertain, but heavy responsibility rests with Public Health Service Bulletin 181, The Toxicology of Beryllium, published in 1943. Mention is made of some of the European reports. Then, after a description of a limited number of small-animal studies, the first line of the summary reads, "The foregoing investigation indicates that beryllium is of itself not toxic." It is ironic that the first patient of the Massachusetts series identified as suffering from chronic beryllium poisoning had died the year before this statement appeared. Reports of illness in United States beryllium workers appear in 1943." Nevertheless, industry and the Atomic Energy Commission adopted the conclusions of the Public Health Service bulletin, causing delay in recognition of the hazard and needless, dangerous overexposure in an unknown number of workers. This bulletin, with its tragically wrong conclusion, was widely and continually circulated until the late C. R. Williams, in 1960, called attention to the fact that it had not been withdrawn from sale. Another important error in the literature is persistently quoted. Shilen et al.," in 1943, found dermatoses and respiratory ailments in workers extracting beryllium and making alloys. They concluded that fluorine compounds and oxides of nitrogen, not beryllium, were responsible. In spite of evidence of disease caused by pure beryllium or beryllium oxide alone come current literature continues to insist that the presence of fluorine is required for the toxic effect.

21

Two erroneous points made at the Beryllium Workshop of 1961, now published, create confusion in the minds of those charged with prevention of beryllium disease. One was that the high-fired oxide is harmless, independent of dose. In fact, workers who have been exposed to a mixture of high-fired and low-fired beryllium oxide have become ill. been exposed to high-fired oxide alone.

13 Idem., footnote 1. P. 388.

There are no workers known to have The second point of confusion arises

14 Weber, H. H., and Englehardt, W. E. Investigation of dusts arising out of beryllium extraction. Zentralbl. f. Gewerbehyg. 10: 41, 1933.

15 Zamakhovakaia, E. M., Martsinkovskii, B. U., and Syrochkovskii, E. E. On question of effect of beryllium fluoride on organism. Gig. Tr. i. Tekh. Besopasnost' 2: 23, 1934. 16 Meyer, H. E. über Berylliumerkrankungen der Lunge. Beitr. z. Klin. d. Tuberk. 98: 388-395, 1942.

17 Gelman. I. Poisoning by vapors of beryllium oxyfluoride. 18:371-379, 1936.

J. Inaust. Hyg. & Toxicol. Chemical pneumonia in work

Is Van Ordstrand, H. S., Hughes, R., and Carmody, M. G. ers extracting beryllium oxide: report of 3 cases. Cleveland Clin. Quart. 10: 10-18,

1943.

19 Kress, J. E., and Crispell, K. R. Chemical pneumonitis in men working with fluorescent powders containing beryllium. Guthrie Clin. Bull. 13: 91-95, 1944.

Shilen. J., Galloway, A. E., and Mellor, J. F., Jr. Beryllium oxide from beryl health

hazards incident to extraction. Indust. Med. 13: 464-469, 1944.

21 Aub, J. C., and Grier, R. S. Acute pneumonitis in workers exposed to beryllium oxide and beryllium metal. J. Indust. Hyg. & Toxicol. 31: 123-133. 1949.

22 Workshop on beryllium. Kettering Laboratory, Cincinnati, Ohio, January 1961.

from repeated statements that only a few persons as a result of delayed sensitization will acquire chronic beryllium disease. This concept proposed by Sterner in 1951 must be investigated. It has been used prematurely and unwisely, however, and continues to be reported in the literature as a fact and not a hypothesis as Sterner used it.23 In the absence of data on exposed populations and numbers of sick workers, fundamental investigation is urgently needed to establish this point and make it useful in the study of toxic beryllium effect. A few articles, such as "Beryllium's Toxicity Is Largely Myth," " led not only to confusion when it appeared in 1949 in a technical journal but to cynicism about motive since the Saranac Symposium of 1947* had established the fact that most, if not all, United States beryllium-using industries were suffering worker illness.

In contrast, when Walter Winchell learned of the indolent wounds caused by beryllium-containing phosphors from broken flourescent tubing, he broadcast to "Mr. and Mrs. America." Winchell apparently helped stop the occurrence of these traumatic granulomas. Fewer than 100 of these indolent wounds were recognized and documented-remarkable in view of the wide use of fluorescent lighting.

The use made of animal study in the understanding of the biologic effect of beryllium contains a third lesson. Acute beryllium disease was reproduced by Stokinger et al.,, 27 and their studies were used to set permissible limits of beryllium exposure. In contrast, confusion of opinion regarding chronic disease was increased by conclusions drawn from experimental work on animals, a trend so unfortunately begun by the Public Health Service in 1943. By 1950 Davies and Harding, in England, and Policard, in France, among others, had produced granulomatous lesions with beryllium, as had Gardner before his death in 1947.28 Controversy over how closely these animal lesions were to the human form led to a curious reluctance to agree that beryllium was causing illness in the United States industry. Differences in compounds, methods, animal species and doses used, as well as length of experiments, must all have played a part in explaining the fact that the chronic disease (except the subcutaneous granuloma) was not reproduced in animals in a fashion to satisfy until after a large number of cases had occurred among beryllium-exposed workers. Surely, the lesson is that animal experiments must be used as only one, relatively modest, part of the study of a man-made disease.

29

What Registry facts are available from which to derive lessons? I have tried to use a method advocated by Sherlock Holmes : "The difficulty is to

30

23 Sterner, J. H., and Eisenbud, M. Epidemiology of beryllium intoxication. Arch. Indust. Hug, & Occup. Med. 4: 123-131, 1951. 24 Beryllium's toxicity is largely myth. Product Engineering, September, 1949. Pp. 155 and 156. Trudeau School of Tuberculosis, Saranac Lake, New York. Pneumoconiosis: Beryllium, bauxite fumes, compensation: Sixth Saranac symposium: Leroy U. Gardner memorial volume. Edited by A. J. Vorwald. 659 pp. New York: Harper, 1950.

20 Stokinger, H. E., et al. Acute inhalation toxicity of beryllium. IV. Beryllium fluoride at exposure concentrations of 1 and 10 milligrams per cubic meter. Arch. Indust. Hyg.

8: 493-506, 1953.

Stokinger, H. E., et al. Acute inhalation toxicity of beryllium. I. 4 definitive studies of beryllium sulfate at exposure concentrations of 100, 50, 10 and 1 mg. per cubic meter. Arch. Indust. Hyg. & Occup. Med. 1: 379-397, 1950.

Tepper, L. B., Hardy, H. L., and Chamberlin, R. I. Toxicity of Beryllium Compounds. 190 pp. Amsterdam: Elsevier Pub. Co., 1961. (No. 13, Elsevier Monographs on Toxic Agents.) P. 114. Vorwald, A. J. Pathologic aspects of acute pneumonitis and pulmonary granulomatosis in beryllium workers. Occup. Med. 5: 684-689, 1948. 30 Doyle. A. C. A Treasury of Sherlock Holmes: Selected and with an introduction by Adrian Conan Doyle. New York: Garden City bks, 1955. P. 381.

686 pp.

detach the framework of fact, of absolute undeniable fact it is our duty to see what inferences may be drawn."

once done..

We have on hand 725 records (Table 1) added to through the years because of increase in latent period and increasing awareness of beryllium disease (Table 2). Though incomplete, Registry data show this poisoning to be a serious industrial illness with a 26 per cent mortality.

TABLE 2.-Registry data-Number of cases added from 1956–65

The fact that the chronic disease, with its greater disability, develops in 6 per cent of acute cases is striking. Within this group a series of importance to report occurred in a research laboratory where 250 workers were similarly exposed. Of 22 patients with beryllium poisoning from this group, 7, or one-third, had both the acute and chronic forms of the disease. There are two practical lessons: prevention of the acute disease will control the occurrence of the chronic; and if the acute form should occur, further beryllium exposure must be forbidden. Interpretation of the data presented today will be of greater interest if one recalls Sterner's suggestion of 1951 that chronic beryllium poisoning is the result of an autoimmune response of a small percentage of workers exposed for short periods. That the chronic disease follows the acute favors this proposal except for the fact that most workers continued to inhale beryllium after recovering from the acute disease, so that dose may be the more important factor. Sterner speculated that beryllium might reside in the lung for long periods and eventually act as an antigen. These data (Table 3) from post-mortem studies of beryllium present in lung and other organs, in varying amounts years after exposure, suggest that without any regularity beryllium leaves the lung and may be found throughout the body. Much more investigation is needed to support or deny the concept that beryllium acts as an antigen.

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