Document 0LkoyvqwQrkBOkrYxJGaEkKRk

r ! Q.A.M.A. Conference on Proposed Reaearon Institute of Occupational Haalth. Montreal (Antiaua - Hovambar 21t-27th. 1965) \ - -----"Q, . The Agenda of the Antique meetings ms divided Into two min groups of discussions (a) review of objectives, opportunities and priorities and (b) the organisation and mans of achieving objectives. 7 Tha first group of discussions was divided into.-- 1 Epidemiolo<y 2 Experimental pathology 3 Environmental conditions. 4. Supervision of tha haalth of workers 5. Immediate oontrol measures PLAINTIFFS EXHIBIT ASA-202 This group occupied tha greater part of tha time of the oenfereooe. The opinions expressed and statements made revealed that the climate of opinion and the state of knowledge had not ohanged materially from tha position at the How Tork conference in Ootober, 1964* The review was valuable in disolosing the objeetlveo of the epidemiological study, proposed by Professor McDonald (MoSlll), of the population of the two areas in Quebec. There was general agreement with the objectives in that the survey should be prospective sal retrospective sad that it should taka into consideration the health of the population in the area not involved directly in mining and milling activities. Tull details of the survey were presented for discussion. The review dlaolosed the arrangements in different domtriee, (Plnland, Italy and Coneon Sarket group} for supervising the health of workers, for research, etc. at industry national and international levels. The olose agreement of these arrangemsnl with thoee in the OX and in Canada was interesting though there'were some differences in detail. Perhaps more significant in the discussion of topic were the views put fbrmrd in favour of pulmonary function test units at mlnas and factories for obtaining data on pulmonary function before employment and at intervals throughout the period of employment. It emerged that la naay countries compensation boards were putting more empbasJ on the results of PT tests in determining degrees of disability and rather lass emphasis on radiographlo evidence. However, all speakers expressed the belief that OT and radiographs were not substitutes for, hut valuable supplements to, a thorough appreciation of the patient's condition based on allnioal observation. Concerning oontrol measures for dust oonditiems, it appeared to be aoeepted thats-1 * 3 1. tha 6-3 method of dust sampling and the preoipltator techniques ptve results which differed aarkadly from aaoh other. i 2. any one technique was subject to a margin of error (i.e. la reproduoabllitjr by the asms observer or when different observers counted the same sample) of the order of - 20 per oent. 3. membranes filter methods sere less llabls to glvs 'eounting errors' than any other method and give more easily reprodnolble results. Monitoring methods far Instsgtaneoos control over dust concentrations at strategic paints ssrs advooeted and ALV 000AAAA The general opinion was against tatting up aa arbitrary ataadard for duat oonoentretions la ainfs and. Bills aa auoh duat oontained large aaounta (valuea of up to 85 per oent were quoted) of Bother rook partiolaa whose relation to the geneaia of aabeatotio oonditioaa aa at beat probleaatioal. Graviaetrio oethoda found only one adrooata (Gilson) and hit oaaa aa weakened by hia adaiasion that Bill and nine duat had variable ooepoaitloaa (i.e. aa between ohryaotile flbroa and rook partiolee) and ao without aubaequent analytea of aeeetaarily large saaples, the aabeatoa haaard oould not be aaaeaaed. Moreover, it waa pointed out that, aa duat oonoeatrntiona fell with adequate control, the value of a gravinetrio eethod wee reduoed (beoauae of saall aaaplea) unleaa the tlae of oolleotioa waa inoreaaed to long perioda of aany daya or even weeka in order to aeoure a large enough sample for analysis. Although the meeting waa untraaaeled by preaa repreaeatativea and the spectre of publioatioa, it waa not until the laet seaaion that them waa any atteapt aade to indulge in forward thinking on the probleaa of asbeatosis. It aeeaed to ao that I had to undertake thia oryatAl-gacing task. Although I waa deliberately provocative ia challenging present concepta (evaa those hypotheses put forward by ayself) and ia putting forward possible iaplioatioaa of the PVC-M oxide work in preventing the developaect of fibrosia induced by silica, ao response waa elicited ia publio, though private diaousaiona later Indicated a wide Interest ia ay address, the full text ia belag duplicated for liaited oiroulatioa. The seooad group of diaousaiona on organisation, initial programme aad priorities waa ooapmasel Into one aeasion. Although the very short dlaouaalc on the organisation of the projeot indicated that one on the liaea of the Aabeatoaia Researoh Couaoil beat fitted the intentions of the Q.A.M.A., a oop; of the AC constitution was given to Mr. Xarl Llndell (Canadian J-M) for ooasideratioa. Private diaousaiona la whloh I took part were favourable to ay view that the projeot should not be linked with a apeoifio university but should be independent ao that it would coatlane te be free to deoide upon lines of aotioa aad priorities. The first priority was given to tbs sponsorship of the survey suggested by Professor MoDoaald and it was agreed that thia should be got going ss aooa ss possible. The second priority appeared to be the setting up of s oeatml archives aad information unit whloh would atteapt to beooae a mfemaoe eenti for the following typea of inforaatiom- (a) card oataloguea of all published aaterlal on aabeatoaia, lung oaaosr, dust ooatrol asthods and asdioal oam of workers ia tha niaiag, billing and prooessiag of asbestos (of all types of mineral). (b) s repository for ooapany moords on pemosael laoludiag aedioal rnoorda and mdiogmpha froa eaoh ooapany. The moorda oa file would include only those whloh concerned aea not now eaployed by the ooapaaiea. These arohlves would be available for study. (s) reports of goveraaeatal ageaoies dealing with the aebeetoo haxard. (d) mports,etc. froa aoa-goveraaeatal organlastioaa (e.g. ARC, PRD Cardiff and Johannesburg) on research projects. * (e) any other source aaterlal. The organisation^ suoh aa iaforwatioa aervioe would mquim the serv of a special library*trained person engaged oaa consultant basis for s lia period. A report to be expeoted in about Boatha would provide a basis disouaaioa of this part of tha project aad its possible eoat. The 'arohlva i1 i ^ Into one wiving world oovemge whloh would ALV 0003^34 Thirl priority would bo given to an exploration of basic research projects but the nature aad scope of these would depend cb the appearance of suitable full-tire workers la university departments with adequate facilities. It was agreed that full-time workers (paid by the new organisation) in speoiflo projects was likely to lead to results more quickly than sponsorship of part-time research work. The problems of lung cancer and mesothelioma ware disouesed briefly. As the Deni nl on Government had already initiated a nation-wide surrey on mesotheliomata, it was agreed that this problem oould be left for future consideration. The incidence of lung cancer would be assessed is the McDonald survey and an analysis of the situation would be possible only after the lapse of sane years. The Xnax-Doll aethods were agreed to be the best approach. After the Antigua meeting visits to Asbestos, Thetford Mines and Montreal provided opportunities to discuss the problems confronting the mining industry in Quebeo in more detail than waa possible at Antigua. It soon emerged that whatever form the 'Institute* will take, its first duty oust be to give advice, based an ell available information, to the industry on problems of iminedlate relevance. To do eo the 'steering committee' (corresponding to the Research Ccondttee of the ARC) must build up its information and archives section to provide a basis an which to formulate its sdvlos and by world-wide contacts secure up-to-date knowledge. The Idea expressed at Antigua that the 'steering acornlttee' should Include among its members some scientists acquainted with tho asbestosis problsa in all its aspects received universal support. This support was gives, not only on the groumia of having around a table sene Independent informed opinions on problems but also beoause in oases of confliot of opinion on the value of proposed research work they would be -- `he 'steering committee' towards a decision. >- From discussions with Mr. MnrieU and Mr. Sabourin in Montreal it was elear that major decision*by the tA.M.A oould not be expeoted before the January meeting of the association. I have expressed the opinion that whatever form the 'Institute* nay take it should <) be financially Independent and not roly on outside support from aqy source unless such support is 'without strings*. 0>) be independent of any other Institution - university or governmental - so that its policy can be determined by the needs of the Industry. (o) Mot indulge la capital expenditure on buildings at least until the needs of the institute for offices, library and other (pace are known acre aoeurately. (d> sponsor research in established university departments rather than to create a separate research unit which would be expensive both to build aad equip. The principle of investing in the productivity of individual research workers Is likely to prove sore profitable both in the long aad the short torn than to attempt to set up a research institute. (*) provide la its 'steering oomedttae' a forum for discussion of immediate problems and a means to decide how such problenb are to bs attacked aad by whom. t (f) have the resources to flaaaoe a modest programme of sponsored research sad meet the ooat of an information aad archive* section likely to beeome a world oentrw of information on every aspect of asbestos as an industrial hasard. Outside support for this lstter programs* would be forthcoming provided it Is planned with imagination and foresight and administered with efficiency. At v JW/JHC :./6; TRANSCRIPT OP SPEECH 3Y DR. JOHN BEATTIE AT Q..A.M.A. CONFERENCE cn PROPOSED RESEARCH ^ INSTITUTE OP OCCUPATIONAL HEALTH IN MONTREAL 21st to 27th November 1965 During the past three days almost every aspect of the problem of asbestosis has been reviewed. I feel however that these reviews seem to indicate that the position has not changed materially since the meeting at the New York Academy of Sciences in October 1964. I cannot agree that this is so, for several significant new lines of work not considered here, have. In my opinion, presented a challenge to our thinking on the whole problem of fibrotic change associated with siliceous dusts and perhaps also to our attitude towards the cancerous changes associated with exposure to asbestos dust. In fact I consider that 1965 may well mark a turning point In the history of asbestosis, as for the first time the possibility that fibrotic change induced by siliceous dust may be controlled by chemical agents, is no Longer a pipe dream. I think we have all accepted the idea that a reduction of the concentration of a toxic dust leads to a fall in the incidence of the disease conditions induced by such dusts. The factual evidence presented by Bamblin (i960) showed that there was indeed a spectacular drop in the incidence of asbestosis after the introduction of efficient ventilation of the working areas in an asbestos textile factory. Coincident with this was a corresponding fall in the incidence of lung cancer in the same working population. I think we should express this in more precise terms by saying as we diminish the amount of du3t which is respired per unit time the chances of accumulating in the lungs a toxic dose of asbestos dust are diminished. Paul Orbss has emphasised that the capacity of the lungs to rid themselves of Inhaled particles is finite for any pair of lungs and if this clearance capacity is exceeded particulate matter will accumulate with progressive diminution of the ability of the lungs to effect clearance. The precise mechanisms whereby this clearance is effected need not concern us here. If the ideal working conditions were to be specified then the concentration of the toxic dust would have to be zero. Paul Gross's work suggests that something less ideal would produce an elimination of the dust hazard. The problem in asbestos mines is not quite as simple as in a factory using separated fibres for in the milling of the rock to separate the fibrous material it is Inevitable that the Inhaled du3t consists of mixtures of varying proportions of crysotlle fibre and mother rock. This complicates the picture of lung clearance of the dust. The capacity of the lungs to clear dust may depend solely on the particulate matter inhaled but there may be a differential clearance of the two constituents of the dust in the mills at the mines. A very small concentration of fibrous material in the inhaled air may be toxic because the clearance mechanism is choked by what may be of itself a non-toxic material (serpentine). The situation in the Quebec mining areas must be Cont'd... 2 regarded as unique and the approach to reduction of the dust hazard cannot be a -simply steady progress towards reduction of all dust. Some attempt must be made to assess the capacity of the lung to eliminate each of the tr/o major uuustitueiu,_ oi the dust and to determine whether or not one or other constituent accumulates at a greater rate than the other under precisely controlled conditions. If this is to be done, as it must be done, on experimental animals, it will require a well planned programme of investigation which must take into consideration the work of those who have already studied the production of controlled dust clouds and the effect of these on experimental animals. There is little doubt tnat such experimental work would influence and be influenced ty the programme and the findings of the epidemiological survey proposed by Professor McDonald. It is all the more important therefore that in any organisation set up by the Q.A.M.A. some forum for discussion of work in progress between those engaged in all types of investigative work should be provided. The idea of a prospective and retrospective epidemiological survey has received unanimous approval at this meeting and it is to be hoped that it can be started as soon as practicable. I have the feeling that the development of future investigative work will take place naturally as the survey throws up problems demanding a solution. The survey will, I am sure, throw up many gaps in the information available but as these' become apparent steps can be taken to remedy them. It is almost certain that the survey will demonstrate again the need for serial lung function tests on the mining and milling population so that incipient cases of asbestosi3 showing defects of lung function can be followed before these people show clinical signs and symptoms of the disease and before a characteristic radiological picture is obtained. The development of "on-the site" centres for the study of pulmonary function seems to be inevitable though che practical difficulties are considerable. The training of competent technicians who can be entrusted to carry out the tests will require time but the results will become more and more rewarding as time passes. The classical discipline of pathology using the optical microscope has presented us with a fairly complete picture of the typical changes which take place in the lungs as the asbestotic lesion is formed and developed. With the application of the electron microscope to this same problem a new dimension has been added - the ultra-structure and function of specific formed constituents of the cell Itself. It is now possible to follow the development of a macrophage containing minute particles of crysotile into a fibroblast and to determine v/ith accuracy where these particles are situated within the cell. The transformation of a motile cell-the macrophage-into a "fixed" cell which produces filaments of a collagenous material represents not only an alteration of cellular structure but the imposition of a complete new metabolic pattern resulting in the production of the complex protein-polysaccharide polymer known aa reticulln or collagen. What is the mechanism which calls into being the set of enzymes responsible for this lntra-cellular synthesis, and what part does the crysotile fibre play in inducing this change? Until these questions can be answered we shall not be Cont'd... dl '..s rr.r.oouv -3- in a position to state precisely how pulmonary fibrosis following asbestos exposure is brought about. Various speakers have referred to the clear distinction between the pattern of fibrosis produced by silica dust and that produced by crysotile. None however ventured to explain this difference. I think most of us might have ascribed the fibrogenic properties of crysotile to the release of silicon dioxide units from the crystal structure of crysotile and that these units were the ultimate fibrogenic agents. I think most of us would be sceptical of this explanation for we would be faced with another more difficult problem. How does the crystal structure of crysotile disintegrate within the cell? Davis has shown that it is possible to induce living macrophages in tissue culture to ingest sub-microscopic particles of crysotile and to see these particles lying free within vesicles of the cell sap (cytoplasm). These vesicles are called phagosomes and almost certainly contain fluid. It has been suggested that chemical substances can be secreted by the cell into the phagosomes and that these substances might disrupt the crysotile lattice. The possibility that small amounts of the disintegration products might diffuse back into the cell sap (cytoplasm) has been considered as the stimulus to the production of the fine fibrils of reticulin or collagen and thus effect the' transformation of the macrophage into the fibroblast. Schllpkotter has shown that macrophages can take up fine particles of crystalline silicon dioxide and transform themselves into fibroblasts. The macrophages can also be induced to take up (as fine particles) a polymer called poly-vinyl-pyridine N-odlxe. When the macrophage Ingests silica alone transformation into a fibroblast takes place rapidly but if silica and the polymer are ingested at the same time the transformation does not take place. If Instead of Ingesting silica the macrophage ingests fine crysotile particles along with the polymer there is no inhibition of the transformation into a fibroblast. Clearly the ultimate fibrogenic substance of crysotile is not free silica units released from the crystal lattice as these would be "mopped up" by the polymer. The intriguing possibilities opened up by these experiments of Schlippkotter and Holt are obvious. Holt has gone further and shown that when silica goes into solution as orthosilicic acid <t bonds with the polymer in such a way that the oxygen atom of the polymer links up with a molecule of ortho silicic acid and at the same time forces the polymer chain to expand and expose more oxygen atoms for linkage with the polymer. In this way a single molecule of the polymer can bind a very large number of orthosilicic acid units present in the reacting solution. If this is Indeed the mode of action of the polymer within the cell phagosome we may assume that the silica units are not released as such from the crystal of crysotile or, if they are, some ion present in the crystal Interferes with the oxygen bonding oy the polymer. It would appear that here La a tool which cannot fail to throw a floed of light on the nature of the fibrogenic action of crysotile. It may also open up the possibility of a therapeutic approach to asbestosis. ) Cont'd... A! V >q I do not wish to discuss the problems of carclnonatGus changes following exposure to asbestos dust for these are outside my province. The studies of Davis on biopsy material from a human case of mesothelionatosis have shown certain structural peculiarities of the malignant cell3 whose significance is as yet unknown but which may in the future be of Importance in attempting to eradicate such tumours. I mention this work only to draw attention to the need for securing fresh human material from persons exposed to asbestos dust and for examining this material by both the optical and electron microscopes. Only by using such material can the results of experimental work in animals be checked in man. The chances of obtaining human material either at operation or by biopsy in cases of exposure are not great but co-operation with thoracic surgeons can be secured and if only two or three specimens can be examined in a year the results are always rewarding to both the surgeon and the investigator. I have been much impressed by the statements on regional differences in the incidence of pleural plaques between the two mining areas in Quebec. We know little or nothing about the reasons why the pleural tissues should produce thick layers of collagenous material nor do we know the cells responsible for producing it. Heglonal differences in the incidence of plaque formation and in the Incidence of oesotheliomata are a challenge to a detailed study of the nature of the inhaled material and it3 fate within the body. There are many questions which could be asked but until details from the epidemiological survey are available to confirm that regional differences are significantly so, such questions would be Irrelevant. As 1 see it, the primary question which was posed by the Q.A.U.A. was to review the objectives of an organisation to be set up by the Association and then to advise on how best to achieve these objectives. I think the objectives are clear to all of us and may be summarised as "the reduction and elimination of any hazards to health presented by exposure to asbestos dust in the mining, milling and processing of asbestos". The hazards to health arising from exposure to asbestos dust can be divided into two main categories (a) impairment of pulmonary function due to changes in the ability of the diffusion membrane of the lungs to transmit oxygen and carbon dioxide and to structural changes within the lung which decrease its ability to expand and thus reduce the ventilating capacity of the lung, or which directly reduce the area of the diffusion membrane (to) cancerous changes in the lung and pleural (and possibly peritoneal) membranes associated with known exposures to asbestos dust. The reduction and elimination of the health hazards are in the first instance an engineering responsibility but this responsibility has to be shared with those who are able to give guidance on possible danger spots for operatives and with those who keep a check on dust levels. Although hazards to health are known to exist within the mining communities in Quebec, the extent of the hazards has not been determined. Within a very short time from its initiation the epidemiological survey will be able to provide an approximation of the extent of the hazards which will come closer and closer t.r> true 1 Cont'd... Al V OAAAAAA -5- picture as time goes on. Moreover the survey will be able to determine whether the hazards vary from mine to mine (and associated mills). Prom 3uch information it will be possible to take steps to reduce the hazards and possibly introduce a purely arbitrary standard to which the dust counts may be referred. It is almost certain that as time goes on attention will be paid a3 much to the nature of the materials contained in the dust samples and the relative magnitudes of each as to the absolute counts of dust particles. It would be irrelevant here to discuss techniques for dust counting though these will have to be as uniform as possible if the results obtained from the counts are to be of value to the industry as a whole. Dust counting and dust control by themselves are of little value unless they can be of use to those directly responsible for the health of the workers in the industry. Improvements in the health of the individual worker or at least a diminution of morbidity rates invariably follows when dust levels fall. Periodical health examinations are essential after acceptance into the industry but these should include pulmonary function tests designed to discover if impairment of function has occurred and the nature of the impairment. The organisation should ensure that such tests sire made in such a way that results from one site can be compared with those from another. This will demand the training of technicians by an agreed laboratory and the acceptance of the test results by the compensation authority. It is impossible to 3et out in any detail the scope of any programme of research designed to obtain an insight into the nature of and causation of asbestosls or the cancerous changes associated with asbestos dust exposure. There is little doubt that the key to any programme of research is the discovery of the right person to carry out a specific project. The projects selected should be linked with problems of a fundamental nature which require attacks by more than one discipline. This 13 the best way to build up a team of men with a common objective and is in the end the most economical of men and resources. I am satisfied that it is essential to have full time workers supported by grants to them personally. These grants should be made in the first instance for a minimum period of two years renewable annually provided the organisation is satisfied with the progress made. The grants should cover not only a specific stipend for the research worker (which can be reviewed at intervals) but also the costs of technical assistance and laboratory expenses. Capital grants for equipment may be required from time to time but these should be considered on the merits of the case at the time and not included in the annual grant. Such equipment could remain the property of the organisation until it determines otherwise. I have given already some of the lines of fundamental work which seem to me of Importance at present. If these or any of them are to be followed it may be necessary to supplement the grant to the individual concerned to enable him to travel Cont'd... 6\ v and work with those who are already working along these lines. Visits of this kind should be of sufficient length to ensure that the worker is able to master any new technique or better to work in collaboration cn a problem for a sufficient time for him to make a significant contribution which can be published. In emphasising the need to sponsor fundamental research I do so in the knowledge that the basic research of today is the applied science of tomorrow. ALV 0003941