Document da8objrJqbzJ9wVD54rJY4NDG

A Landmark Case in Asbestosis Irving J. Selikoft, MD, Morris Greenberg, MB The first published account of disease attributed to occupational asbestos exposure was that of Nellie Kershaw, who died in 1924, The circumstances relating to that case are described and explanations are given for its not having a greater impact on policy at that time. This case, starting in 1898, is set in the context of missed opportunities for preventing a major public health hazard. The effects of this hazard are still being witnessed today. (JAMA. 1991;265:898-901) THE FIRST death due to pulmonapr asbestosis described in the medical lit erature was reported by Cooke.' A more detailed record ofthe findings was subsequently published on December 3, 1927.! It was this latter study that gave the disease its name, "pulmonary asbes tosis"; the previous short note was titled "Fibrosis of the Lungs due to the Inha lation of Asbestos Dust." The unfortu nate patient's name was Nellie Ker shaw. There had been other cases of illness and death attributed to asbestos inhalation before hers, but the observa tions had either been sequestered in a British departmental committee's min utes1 or governmental papers4,1 or pa tients had been seen by practicing phy sicians in areas near asbestos plants and the cases clinically noted but not made the subject of scientific reports.4 Nellie Kershaw's case was somewhat different. Her illness had been diag nosed during life by her physician, Dr Walter Scott Joss, and he had certified it as "asbestos poisoning" to an official medical benefits agency that referred the case to the asbestos company for which she worked. Second, the medical diagnosis was influential in having a postmortem examination done and the From the Department ot Community Medicine, Mount Sinai School of Medicine of the City University of New York Reprint requests to Research Office. Mount Sinai Medical Center, 19 E 98th St, Box 7059. New York, NY 10029-6574 (Dr Selikoff). findings reported. The case is reviewed herein after a passage of some 70 years and is set in the context of the long-playing tragedy of asbestos, a story of missed opportuni ties for avoiding a worldwide disaster. THE LIFE AND DEATH OF NELLIE KERSHAW The story, pieced together from a patchwork of surviving published and unpublished records, is that of Mrs Nel lie Kershaw of Rochdale (near Leeds, England). Bom to Elizabeth and Ar thur Kershaw in 1891, she lived her short life in Rochdale, marrying Frank Kershaw, a tiler's laborer. In the man ner of the time, she had left school in 1913 at the age of 12 and had gone to work in a cotton mill. After about 5 months, she moved to a local asbestos factory (Garsides). There she stayed for 14 years, transferring to Turner Broth ers Asbestos Company on December 31, 1917, at the age of 26 years, where she worked in the textile factory at a roving machine. Such facilities were rather new; commercial exploitation of asbestos in Britain started around 1880, with three or four kinds of goods being made. By 1892, over 100 varieties were in production.6 Environmental control was poor and health complaints were common. From the accounts given by her fam ily and her physician, Mrs Kershaw's health had been "quite good" while working at the cotton mill and at Garsides. While working at Turners, after her daughter was bom (around 1920 at the age of29), she started being treated by her panel physician for a lung condi tion. For 2 or 3 years her pulmonary symptoms waxed and waned but she continued to work until the week ending July 22, 1922, when she was issued a National Health Insurance sickness cer tificate of unfitness for work that gave entitlement to payment of benefit under specified circumstances. (The textile works' manager later stated that during her 4 lk years of employment she was absent for 24 months or so, but this may have been due to maternity absence.) Being too ill to work, Mrs Kershaw applied for National Health Insurance benefits to the Newbold Approved Soci ety (a Rochdale Friendly Society ap proved under the National Health In surance Act, to which she had contributed). Unfortunately, as the sickness certificate given to her by her physician, Dr Joss, bore the diagnosis "asbestos poisoning" rather than a nonoccupational cause that would have en titled her to sickness pay, she was not qualified for benefits from that source. The president of the society wrote re peatedly on her behalf to persuade Turners that they should compensate her as her condition should have quali fied under the Workmen's Compensa tion Act (J. Blomley, letter to Turner Brothers Asbestos Company, Septem ber 13, 1922). Under the Workmen's Compensation Act, employees who con tracted certain diseases, as determined by the government, were entitled to payment by their employers. It was general practice for employers to take out insurance, although it was not, strictly speaking, compulsory. At that 898 JAMA. February 20,1991--Vo! 26S, No 7 LandmarkCase in Asbestosis--Selikoff&Greenberg LAM 019060 dfmc- 683 turer provides to any source (exempt ing the Department of Veterans Af fairs); manufacturers will not be able to raise prices to Medicaid faster than the rise in the Consumer Price Index (New York Times. November 6,1990:D-2). While public costs have gained in creasing attention, aggregate public benefits have not been analyzed. They include, at the least, the reduced risk of contracting an untreatable rare disease or condition, potential health care cost savings, and the fuller societal partici pation of people with orphan diseases. As just one example, patients with Par kinson's disease who can slow their dis ease progression with the orphan drug selegiline may save the public $10 mil- lion per wesk by delaying the initiation of disability payments and by providing tax revenues while they continue to work. lb the extent that Medicaid, Medi care, and private carriers cover the cost of orphan product prescriptions, the larger issue of costs and benefits to the public may become more prominent and should be considered. CONCLUSION The Orphan Drug Act has resulted in new products developed for patients with rare diseases and conditions. This has been achieved at a cost to some com panies, and to some patients, that was not intended and that has added issues of affordability to the debate. These is sues will need to continue to be exam ined as changes evolve in technology, third-party payer coverage, and possi bly in product protection. If msgor changes in the Act are proposed in the future, they should be viewed within this larger context to assess their rela tive costs and benefits for companies, patients, and the public. Thanks are due to many who have provided infor mation and assistance including Marlene Haffher, MD, director ofthe FDA Office of Orphan Products Development, and her staff; Catherine Taylor of the FDA Document Management and Reporting Branch; Thomas Copmann, PhD, director of the PMA Commission on Drugs for Rare Diseases; Ab bey Meyers, director, National Organization for Rare Disorders; and Arthur K. Asbury, MD, for his editorial suggestions. References 1. Gibbons A. Billion dollar orphans: prescription for trouble. Science. 1990;248:678-679. 2. Drugs for rare diseases. Lancet. 1976;2:835-836. J. Rawlins M. No utopia yet. BMJ. 1977^:1076. 4. Russo J. Profitable and non-profitable drugs. N Engl J Med. 1978^99:156. 5. Van Woert M. Profitable and non-profitable drugs. NEnglJ Med. 1978;298:903-906. 6. Lasagna L. Who will adopt the orphan drugs? Regulation. 1979;3:27-32. 7. Devita, V, Oliverio VT, Muggia FM, et al. The drug development and clinical trials programs of the Division of Cancer treatment, National Cancer Institute. Cancer Clin Triala 1979;2:195-216 8. Althius T. Orphan drugs: debunking a myth. N Engl J Med. 1980;303:1004-1005. 9. Finkel M. Drugs of limited commercial value. NEnglJ Med. 1980;302:643-644. 10. Asbury C, Stolley P. Orphan drugs: creating a policy. Ann Intern Med. 1981;95:221-224. 11. Karch F, ed. Orphan Drugs. New York, NY: Marcel Dekker Inc; 1982. 12. Bloom B. Socially optimal results from drug research. In: Martin S, Link E, eds. Impact of Public Policy on Drug Pricing and Innovation. Washington, DC: American University Press; 1976:344-370. 13. Interagency Task Force. Report to the Secre tary of DHEW on Significant Drugs of Limited Commercial Value 1979. Rockville, Md: Food and Drug Administration; 1979. 14. Federal Drug Development Program, July 17, 1981. Washington, DC: US General Accounting Of fice; 1981. 15. Preliminary Report on the Survey ofDrugsfor Rare Diseases, March 9, 198S. Washington, DC: US House Subcommittee on Health and the Envi ronment; 1982. 16. Asbury CH. Orphan Drugs: Medical vs Mar ket Value. Lexington, Mass: DC Heath; 1985. 17. Asbury CH. Systems Approach to Orphan Drugs Ann Arbor, Mich: University Microfilms International; 1982232. 18. Waxman HA. The history and development of the Orphan Drug Act. In: Scheinberg IH. Walshe JM, eds. Orphan Diseases and Orphan Drugs Manchester, England: University Press; 1986:135145. 19. Hanson RW. The pharmaceutical development process: estimates of development costs and times and effects of proposed regulatory changes. In: Chien R, ed. Issues in Pharmaceutical Economics. Lexington, Mass: Lexington Books; 1980:151-181. 20. Patent Term Extension and the Pharmaceuti cal Industry. Washington, DC: The Office of Tech nology Assessment; 1981. 21. Schwartxman D. Innovation in the Pharma ceutical Industry. Baltimore, Md: The Johns Hop kins University Press; 1976:106-107. 22. Harris R. The Real Voice. New York, NY: Macmillan Publishing Co Inc; 1964:21-25. 23. Scharf SF. Orphan products: the question of products liability. Am J LawMed. 1986;10:491-513. 24. Asbury CH. Medical drugs of limited commer cial interest: profit alone is a bitterpill. Int J Health Sen. 1981;11:451-462. 25. Orphan Drug Act. Washington, DC: US House of Representatives; September 17,1982. US House ofRepresentatives report 97-840. 26. Health Promotion and Disease Prevention Amendments of 1984, PL 98-551. 27. Finkel MJ. The US orphan drug development programme: incentives and results. In: Scheinberg IH, Walshe JM, eds. Orphan Diseases and Orphan Drugs. Manchester, England: University Press; 1986:159-168. 28. Orphan Drug Amendments of 1985, PL 99-91. 29. Hearings Before the House Subcommittee on Health and the Environment, 101st Cong, 2nd Sess (February 7, 1990) (testimony of Gerald J. Mossinghoff). 30. Hearings Before the House Subcommittee on Health and the Environment, 101st Cong, 2nd Sess (February 7,1990) (testimony of Abbey Meyers). 31. Approved Designated Orphan Drug and Bio logical Products, June 1982-December Si, 1989. Rockville, Md: Food and Drug Administration; 1990. 32. Hearings Before the House Subcommittee on Health and the Environment, 101st Cong, 2nd Sess (February 7,1990) (testimony ofJames S. Benson). 33. Mossinghoff GJ, Copmann TL. Orphan Drugs in Development. Washington, DC: Pharmaceutical Manufacturers Association; 1989. 34. Orphan Designations Pursuant to Section 526 of The Federal Food, Drug, and Cosmetic Act as Amended by The Orphan Drug Act (PL 97-iH) Through December 81, 1989. Rockville, Md: Food and Drug Administration; 1990. 35. NMEs Approved 1988-89.- Rockville, Md: Food and Drug Administration. Compiled annually. 36. Shaffer M. Drugs and Biologicals Approved: FDA Talk Papers. Rockville, Md: Food and Drug Administration; 1984-1989. 37. Miller D. FDA timely approval of break through drugs averages 4.1 years. PMA Newslett. 1989;31(40):2. 38. McLeod DC. Biotechnology: product develop ment and evolving patent law. Ann Pharmocother. 1989:23:605-606. 39. Crawford M. Patent claim buildup haunts bio technology. Science. 1988;239:723. 40. Report of the Pharmaceutical Manufacturers Association: Analysis of U.S. Biotechnology Pat ents, 1989. Washington, DC: Pharmaceutical Man ufacturers Association; 1990:3. 41. Meeting of the Pharmaceutical Manufacturers Association Commission on Drugs for Rare Dis- eases, Washington, DC (1987) (testimony of George Goldstein, MD). 42. Hearings Before the House Subcommittee on Health and the Environment, 101st Cong, 2nd Sess (February 7, 1990) (testimony of George Rathmann, PhD). 43. Fraier SD. Human growth hormone is not an orphan. N Engl J Med. 1989;321:1124. 44. Amgen, Inc vChugat Pharmaceutical Compa ny and Genetics Institute, 1989, WL 169006 (D Mass) and 13USPQ2,1737. 45. Recombinant Erythropoietin: Payment Op tionsfor Medicare. Washington, DC: US Congress Office of Technology Assessment; 1990:72-74. OTA-H-451. 46. Hearings Before the House Subcommittee on Health and the Environment, 101st Cong, 2nd Sess (February 7, 1990) (testimony of Gabriel SchmergeU 47. Hearings Before the House Subcommittee on Healthand the Environment, 101st Cong, 2nd Sess (February 7, 1990) (testimony of Thomas Wiggans). 48. Rudman D, Feller AG, Huskote SN, et al. Effects of human growth hormone in men over 60 years old. NEnglJ Med. 1990;323:1-6. 49. Vance ML. Growth hormone for the elderly? N Engl J Med. 1990;323:52-54. 50. Hearings Before the House Subcommittee on Healthand the Environment, 101st Cong, 2nd Sess (February 7,1990) (testimony ofJean McGuire). 51. Hearings Before the House Subcommittee on Healthandthe Environment, 101st Cong, 2nd Sess (February 7,1990) (testimony ofBrian Tambi). 52. HR 4638,101st Cong, 2nd Sess, April 26,1990. 53. Miller D. PMA executive committee adopts resolutions on . . . orphan scheme. PMA Newslett. 1990;32(17):2. 54. Miller D. Biotechnology receives special atten tion in budget. PMA Newslett. 1990;32(5}:3. 55. Miller D. Orphan drug bilife effect on incentives led to pocket veto, Bush Bays. PMA Newslett. 1990;32(44):6. 56. DiMasiJ, Hanson R, GrabowskiH, Lasagna L. The cost of innovation in the pharmaceutical indus try. J Health Econ. In press. 57. Tfemin P. Technology, regulation and market structure in the modern pharmaceutical industry. Bell J Econ. 2979;10:427-446. 58. Schondelmeyer S. Drug pricing in the pharma ceutical marketplace. Presentation at the Health Policy Forum; December 14, 1990; Washington, DC. 59. Health Care Financing Program Statistics Medicare and Medicaid Data Book, 1986. Wash ington, DC: Health Care Financing Administra tion; 1988:68. 60. Lewin R. Big first scored with nerve diseases. Science. 1989;245:467. JAMA. February 20. 1991 -- Vt>l 265. No 7 LAM 019061 DPMC-12684 Orphan Drug Act--Asbury 897 Death certificate Issued April 2,1924, tot Nellie Kershaw. LAM 019062 time, asbestos-associated disease was not specifically scheduled and, conse quently, Mrs Kershawb employers were not compelled to compensate her. Her condition might have been accepted under the loose classification of "silico sis." Turners rejected this application and alerted its insurance company, ex pressing the opinion that it would be "exceedingly dangerous" to accept "any liability whatever in such a case." They felt that they ought to do all in their power to "repudiate the claim" (Turner Brothers Asbestos Company, letter to the London and Lancashire Insurance Company, September 21,1922). Mrs Kershaw wrote to the company: What are you going to do about my case? I have been home 9 weeks now and have not received a penny--I think itb time that there was something from you as the National Health refuses to pay me anything. I am needing nourishment and the money, I should (have had 9] weeks wages now through no fault of my own. (Mrs N. Ker shaw, letter to Turner Brothers Asbestos Company, 1922) No record has been discovered of how the Kershaws managed during the last 20 months of Nellie Kershaw'S life. There is a record that Turners told Mrs Kershaw of the insurance company's negative response in September 1922. In her last 5 weeks, her husband stated that she gave up going to a physician since she saw no improvement (Roch- dale Times. March 15,1924). She died at 6:30 AM on March 14,1924, at the age of 33. THE CORONER INVESTIGATES The very diagnosis of asbestos poi soning made by her panel physician, Dr Joss, attracted the attention of the coro ner of Rochdale, one of whose duties was to inquire into unnatural deaths. The coroner, E. N. Molesworth, started an inquiry promptly on the day of death but adjourned it for a postmortem to be carried out by the local police surgeon. An obscure 24-line account of the first inquest under the heading "Married Womanh Death: Tired of Going to See Doctors," was spotted by Turners, who suggested to their insurance company that it would be in their interests for them both to be represented at the in quest (letter, March 17,1924). After the postmortem, although death was stated by the pathologist, Dr F. W. Machichan, to be due to pulmonary tuberculo sis and heart failure, a further adjourn ment was made to allow for microscopic examination of the lungs for a definitive diagnosis. Following this, the inquest was resumed on April 1, 1924. It was reported on the next day at length in the local newspaper (Rochdale Times. April 2,1924:8). Far from making a sim ple inquiry into the death, the coroner held a full inquest with a jury and was advised by Dr Machichan as coroner's pathologist, Mr Barrett as HM Inspec tor of Factories, Dr S. A. Henry as Med ical Inspector of Factories, and Dr W. E. Cooke, pathologist at Wigan & Leigh Infirmaries, also attending. The hus band was represented by a solicitor, and the company was represented by a bar rister advised by Dr W. H. Bateman, a local practitioner. Extensive informa tion was provided by Dr W. E. Cooke, who had carried out microscopic exami nation of the lungs. He had found healed tuberculosis (old scar tissue in the left lung and a calcified tuberculous gland). Such findings were "extremely common in town dwellers and dwellers in urban districts." There was fibrosis in the lungs, and in some sections, particles of mineral matter were seen. The patho logic findings, with old scar tissue in the apex of the left lung, suggested com pletely healed tuberculosis. Second, there was "fibrosis of the lungs due to inhalation of mineral particles." Dr Cooke had received samples from Dr Henry of settled dusts that were "simi lar in size and shape to those found in the lungs of Nellie Kershaw." The patholog ic findings and microscopic examination ofthe asbestos dust led to the conclusion that the mineral particles in the lung originated from asbestos and were, be yond a reasonable doubt, the primary cause of the fibrosis of the lungs and therefore ofdeath. Dr Joss also testified, and stated that JAMA. February 20.199' -VOI26S. No. 7 Landmark Case in Asbestosis -- Selikoff & Greenberg 899 D PM C -12685 the reason he certified that the deceased was suffering from asbestos poisoning was that she had worked with asbestos "and he had previous experience of such a lung condition for many ofhis patients, who were asbestos workers." He stated that he saw 10 to 12 cases a year, occur ring in persons working with asbestos (Dr W. J. Joss, written statement to HM coroner, 1924). Following the in quest, a death certificate was issued on April 2, 1924, stating that Nellie Ker shaw, female, 33 years of age, died of "fibrosis of the lungs due to the inhala tion of mineral particles" (Figure). Dr Cooke introduced his note of 1924 with the statement that his case was of importance because it was the first in jBritish medical literature to be definite ly proved. In addition, he noted that medical men in areas where asbestos was manufactured had long suspected the dust to be the cause of chest disease, a point noted by others.w In support of his hypothesis he quoted Prof J. M. Beattie's animal experiment, details of which were to be given by Merewether and Price.' COMPENSATION 10 YEARS AFTER NELLIE KERSHAW There are no records of Nellie Ker shaw or her estate's receiving compen sation. Tten years later, asbestosis was scheduled as an occupational disease eli gible for benefit. By April 1934,2 years into the new scheme, of 29 claims sub mitted to Turners, seven were settled at an average cost of what then would have been approximately $370 (F. G. Brook, internal company report to Sam uel Turner, April 20,1934). MISSED OPPORTUNITIES BEFORE NELLIE KERSHAW In 1898, a quarter of a century before Nellie Kershaw's death and not long af ter the early expansion of the asbestos industry, the Chief Inspector of Fac tories for Britain had included asbestos among the four most hazardous dusts.* The report maintained that danger to the health of workers could easily be ascertained and that cases of injury to the bronchial tubes and lungs were med ically attributed to employment. Rec ommendations were made for the ap plication of ventilation to asbestos processes. Two years later the need for ventilation in textile and nontextile as bestos works was still being stated.* In 1899, an asbestos worker was re ferred to Dr Montague Murray, a physi cian at the Charing Cross Hospital, with severe nontuberculous pulmonary fi brosis that was shortly to kill him at the age of 33. The patient informed Dr Mur ray that he had worked with asbestos for some 14 years. The first 10 years were spent in the carding room of an asbestos textile factory, where process es are similar to cotton textile manufac ture; of the 10 people working in that room when he started, he claimed to be the last survivor. Unfortunately, this case was not commented on until 1906, during an inquiry of a departmental committee of the British government into the compensation for industrial dis eases.* The committee had been charged with investigating which conditions might be added to the list of compensa ble diseases. Its members had heard of Dr Murray's case and asked him at the inquiry whether he thought that asbes tos should be included in the list. He advised against this, judging that now that it was known that asbestos expo sure could cause serious, even fatal, dis ease, appropriate precautions would be taken, and there would be no need for compensation. The report of the com mittee reads: Dr Murry: One hears, generally speaking, that considerable trouble is now taken to prevent the inhalation ofthe dust, so that the disease is not bo likely to occur as heretofore. Committee Member. Do you think it still may occur? Dr Murray: Ifthere is dust, certainly. Dr Murray's advice was taken and asbestos-induced illness was not added to the list of compensable diseases, A report from the French Factory Inspectorate in 1906* mentioned some 50 deaths attributed to asbestos expo sure in an asbestos textile factory that had operated for 15 years. Dr Thomas Legge had discussed the problem with the Inspector of Factories in 1898, and his colleague Dr E. L. Mid dleton was aware of the circumstances ofthe Murray case. The Chief Inspector of Factories report for 1910 gave an ac count of how, after following up infor mation from the Registrar General, five deaths due to phthisis were identified in 5 years among staff at an asbestos fac tory employing fewer than 40 workers and how exhaust ventilation was recom mended and annual medical examina tions were instituted." At about this time the Factory Department of the Home Office sponsored a study by Prof J. M. Beattie on the effects of asbestos dust inhalation on guinea pigs. N o publi cation has yet been identified. The Factory Department's observa tions and misgivings led it to make in quiry of Canada's Department of Labor as to their experience with asbestos in Quebec, the source of much of Britain's asbestos. They were reassured. An offi cer of the department had investigated the matter in January 1912 and found no difficulty (.Labor Gazette. February 12, 1912:761) He visited a large asbestos mine and mill and stated that "all the women found here looked strong and healthy." While "one of the oldest medical prac titioners in Thetford expressed the view that the asbestos dust . . . had a weakening effect on the lungs of those employed," another medical practitio ner stated that the employees of the asbestos company affected with lung troubles had been so affected previous to their employment in the mill. It was stated generally that "the record of deaths from lung diseases is not higher in the centers of the asbestos industry than elsewhere." No physical examinations were done or mortality data provided, and the Fac tory Department, with this reassuring reply to their inquiry, did not pursue the matter further, despite the appearance in the US medical literature of a report in 1918, that radiological abnormalities were found in roentgenograms of asbes tos workers11 and another that noted that insurance companies refused to give policies to such employees." Fol lowing the 1906 inquiry, Legge visited the factory concerned twice and alerted the Medical Officer of Health.a No clini cal examinations were made during in vestigations over the next 20 years, "which alone would have revealed its serious and insidious nature. . .looking back in the light of present knowledge, it is impossible not to feel that opportu nities for discovery and prevention were badly missed. " THE LEGACY OF NELLIE KERSHAW One can only speculate on what might have happened if Turners, which was a prominent company in the industry, had acknowledged Mrs Kershaw's claim and had recognized the hazard presented by asbestos. Employees, factory floor su pervisors, and management would have been alerted to the hazard and would have begun to seek effective controls. Turners, through the Trade Associa tion, would have ensured that other members would follow suit; insurance companies might also have insisted on such measures to decrease their liabil ities; public awareness would gradually have come into being; public health au thorities would have responded with ap propriate regulations and rules; engi neers would have developed means of avoiding exposures; and men and wom en could have worked with much less risk and have suffered much less dis ease. All these eventually came to pass, but it took years, decades. 900 JAMA, February 20.1991 -Vol 265. No. 7 Landmark Case in Asbestosis--Selikoff & Greenberg LAM 019063 DPMC-12686 Instead, the factory went on as be fore. When additional deaths began to be reported in medical journals, the Factory Department returned to Roch dale. A survey found many instances of asbestosis among the workers. It was observed that, after 20 years, 80% would have evidence of fibrosis.' The Factory Department met with Turners and other asbestos manufac turers, and prepared a set ofregulations (1931)." For reasons not yet known, however, the regulations were not to apply to most users of the asbestos products, such as construction workers, insulators, and shipyard employees. The general requirement was that man ufacturing processes should not release any asbestos dust into the working envi ronment, though there was the proviso that this might occur if unavoidable. There is evidence of schemes of dust control proposed for asbestos from ear lier publications in 1898* and 1906,* but the extent of their implementation has not been ascertained. In the first periodic examinations of scheduled workers, of the 326 workers employed for 10 or more years, 26 (8%) were suspended and 64 (20%) found to have "distinct fibrosis," roentgenographic and clinical signs of asbestosis (DrC. L. Sutherland, Chief Medical Of ficer of the Silicosis and Asbestosis Medical Board, report to under Secre tary of State, Home Office, 1933). Com menting on the second report, Merewetner noted: Ifthey [the Medical Board] had accepted this fact [that there is always present a greater degree of asbestosis than there appears to be, judged by accepted standards in silicosis] ... it would have been forced to suspend a very large number of workers . . . which would have raised a panic in the industry [Dr E. R. A. Merewether, letter to Dr J. C. Bridge, HM Senior Medical Inspector ofFac tories, 1934]. Little was reported about the use of the regulations within the plants. Lan cet, 40 years later, wryly summarized their application as having been "a pious aspiration. Perhaps that explains Turner's workers continuing to have much disease, and having later been the source of a wealth of clinical and epide miologic data, helping to define the di mensions of asbestos-associated dis ease. This included a study in 1955 that demonstrated that lung cancer was 10 times as frequent among its long-term employees as among British citizens in general" and another that reported that, 50 years after Mrs Kershaw's death, asbestosis was widely prevalent among workers in the factory." Would a different approach have made an appreciable difference? There is evidence that this could have been so. First, we know that with improvements in exposure control within the plant, death rates significantly decreased.18 Second, the scientific contributions de rived from the unhappy experiences of Turner's workers were an important part of the preeminent contributions of British scientists to our understanding of asbestos-associated disease and its control. These were, at least in part, the outcome of efforts of Dr John F. Knox, a capable and conscientious physician who after the Second World War moni tored the work force as medical officer to Turner Brothers Asbestos Company and collaborated in the analyses of causes of death. ""He did as much as he could to speed the application of expo sure control measures. COMMENT The story of Nellie Kershaw is one of unmitigated tragedy. At the personal level, the death in poverty of a young mother struggling for 20 months against progressive asphyxia from res piratory failure is painful enough. That the circumstances ofher death did not at least provide stimulus and guidance to help protect others adds to the tragedy. This lost opportunity tells us again that "science is necessary but not sufficient. " Reference* 1. Cooke WE. Fibrosis of the lungs due to the inhalation ofasbestos dust. BMJ. 1924;2:147. 2. Cooke WE. Pulmonary asbestosis. BMJ 1927;2:1024-1026. 2. Report of Departmental Committee on Com pensation for Iruluetrial Diseases. London, En gland: HM Stationery Office; 1907. Command 3946. 4. Haddow AC. Clinical aspects of pulmonary as bestosis. BMJ. 1929*,2:580-681. 5. Hie Chief Inspector of Factories and Work shops. Annual Report far the Year 1898. London, England: HM Stationery Office; 1899. 6. Lee DHK, Selikoff U. Historical background to the asbestos problem. Environ Ret. 1979;18:800314. 7. Merewether ERA, Price CW. Report on the Effects of Asbestos Duet on the Lunge and Duet Suppression in the Aebeetos Industry: I. Occurrence of Pulmonary Fibroeit and Other Pulmo nary Affections in Asbestos Workers. London, En- gland: HM Stationery Office; 1930. 8. Hie Chief Inspector of Factories and Work shops. Annual Reportfor 1901. London, England: HM Stationery Office; 1902. t. Auribault M. Sur hygiene et la securite des ouvriers dans les filatures et tissages d'amiante. Bull Inspection Travail. 1906;14:120-132. 10. Hie Chief Inspector of factories. Annual Re portfor the Year 1910. London, England: HM Sta tionery Office; 1911. 11. Pancoast HK, Miller TG, Landis HRM. A roentgenologic study of the effects of dust inhala tion upon the lungs. AJR. 1918;5:129-138. 12. Hoffman FL. Mortality from respiratory dis eases in dusty trades. Bull US Bur Labor Stat. 1918*431:176-180. 13. Legge T. Asbestosis. In: Henry SA, ed. Indus trial Maladies. New York, NY: Oxford University Press; 1934:190-191. 14. Asbestos Industry Regulations London, En- gland: HM Stationery Office; 1931. SR EO 1931, Command 1140. 15. Asbestos in the air. Lancet. 1976;1:944-945. Annotation. 16. Doll RS. Mortality from lung cancer in asbestos workers. BrJlnd Med. 1955;12:81-85. 17. Lewinsohn HC. The medical surveillance of asbestos workers. JRSoc Health. 1972;12:69-77. 18. Peto J, Doll R, Howard SV, Kinlen U, Lewinsohn HC. A mortality study among workers in an English asbestos factory, fir J Ind Med. 1977;34:169-173. 19. Knox JFf Doll RS, Hill ID. Cohort analysis of changes in incidence of bronchial carcinoma in a textile asbestos factory. Ann N Y Acad Sci. 1965;132:526-535. 20. Knox JF, Holmes S, Doll R, Hill ID. Mortality from lung cancer and other causes among workers in an asbestos textile factory, fir J Ind Med. 1968;25:293-303. JAMA, February 20,1991 --Vol 265. No. 7 LAM 019064 Landmark Case in Asbestosis--Selikoff & Greenberg 901 DPMC-12687 Brief Report The Prevalence of Gallstone Disease in Very Old Institutionalized Persons Jack Ratner, MD; Andre Lisbona, MD; Marvin Rosenbloom, MD; Max Palayew, MD; Sharon Szabolcsi, RN; TessieTupaz, RN We present the results of a study that was undertaken at a large geriatric nursing home to assess the prevalence of gallstone disease in very old institutionalized persons. One hundred seventeen residents underwent ultrasound examination of the gallbladder. Two thirds of 82 women and half of 35 men had gallstone disease. When stratified for age, 80% of women and men over the age of 90 years were positive for the disease. In summary, the prevalence of gallstone disease in our very old nursing home population was found to be unexpectedly high. (JAMA 1991;265:902-903) PERSONS 85 years of age and over (very old) currently constitute the most rapidly growing portion of the Ameri can population; this is also true for most other industrialized nations.w Chole cystitis with cholelithiasis is the most common acute abdominal surgical emer gency in patients over the age of 50 years1 and in the elderly.4 Because ofthe above and our frequent finding ofunsus pected gallstones at necropsy, the diffi culty in diagnosing abdominal disease in the elderly,u and the ease of ultrasound examination, we decided to study the prevalence of gallstone disease in our nursing home. The sensitivity and specificity ofultrasound is 95%, which is higher than any other investigative method for gallstone disease.w Methods The study protocol was approved by the hospital ethics committee. The cate gory of gallstone disease was used for residents in whom gallstones were found or who had undergone a previous From the Maimonides Hospital Geriatric Centre, Mon treal, Quebec (Dr Ratner and Mss Szabolcsi and Tupaz); and Sir Mortimer Davis Jewish General Hospital. Montreal. Quebec (Drs Lisbona, Rosenbloom. and Palayew) Reprint requests to Director ot Professional Services. Maimoniaes Hospital Geriatric Centre. 5795 Caidwe'i Ave. Montreal, Quebec. Canada H4W1W3 (Dr Ratner) cholecystectomy. One hundred seven teen residents of Maimonides Nursing Home (Montreal, Quebec) were studied with abdominal ultrasound. Most were admitted because of inability to care for themselves, due mainly to neuropsychi atric and/or physical disorders. Another 19 residents were not entered into the study because of refusal (five), poor compliance (three), or an inconclusive examination (11). The mean age was 83.8 years (SD, 9.0) and 12 residents were over 95 years of age. The residents were Jewish, middle class, 50% were bom in Russia or Poland, and 20% were bom in Canada. Ultrasonography ofthe gallbladder was performed by two ex perienced radiologists (A.L. and M.R.), using a 5x real-time ultrasound unit (Siemen's Sonoline) with a 3.5-MHz ro tary mechanical sector scanning trans ducer. A diagnosis of gallstones was made by well-accepted criteria; echogenic opacity in the gallbladder with acoustic shadowing. For gallstones less than 3 mm where acoustic shadowing was not seen, the movement ofthe opac ity with change in position was the main criterion for diagnosis. Patients who had undergone a cholecystectomy docu mented by history, who had a right up per quadrant scar with no demonstrable gallbladder on ultrasonography, and Table 1.--Prevalence of Gallstone Disease in Study Population Gallstone Disease Women Men Total No Yes Total 28 17 45 54 18 72 82 35 117 Table 2 -- Prevalence of Gallstone Disease by Age and Sex in Study Population Age, y 50-70 71-79 80-89 >90 Women (%) 3/5 (60) 9/16 (56) 22/36 (61) 20/25 (80) Men (%) 0/3 (0) 5/9 (56) 9/18 (50) 4/5 (80) those who had stones were classified as having gallstone disease. Results Fifty-four (66%) of 82 women and 18 (51.4%) of 35 men had gallstone disease (Table 1). Of the 82 women, 28 had a normal gallbladder, 29 had undergone cholecystectomy, and 25 had gallstones. Of the 35 men, 17 had a normal gallblad der, eight had undergone cholecystecto my, and 10 had gallstones. Although the gender difference with gallstone dis ease was not significant, the 95% confi dence interval for the difference in pro portions ranged from -0.05 to 0.34. The power to detect gender differences in gallstone disease was low (0.32) due to a relatively small sample. A two-wayanalysis of variance revealed a signifi cant difference in mean age between those with gallstone disease, 85.6 years (SD, 8.0), compared with those who were disease-free, 80.8 years (SD, 9.8) CF[1,113] = 7.20; P<.01). No signifi- 902 JAMA, February 20. T991 --Vo! 265, Nc 7 Gallstone Disease--Ratner et al LAM 019065 DPMC-12688