Document 82BXO3LbMz271oBvzJ0v4OXrm

FILE NAME: Metropolitan Life (ML) DATE: 1936-1951 DOC#: ML250 DOCUMENT DESCRIPTION: Suppression of Saranac Experimental Finding of Lung Cancer from Inhaled Asbestos idgupor t, Conn. November 10, 19CG Mr. F* TI. Echluter, President, Thcrnoid i\ubbe>r Co*> Trenton, N. J. }Sy cear Mr. Echluter: The v.rittr end Mr. Vandiver Brov.n, of Johris-llunville, had Dr. LhacnozanfearnedncDre.wMictChonLnre.llit,trooyf Uardner, of Saranac,* New Xori-:, and thu Metropolitan Life Insurance Co., with reference to the 'Asbostosis situation in the Asbestos industry* As you no doubt know, Johnn-U&nville and ourselvou have been coins considerable wont, in conjunction v.ith the Metropolitan Life .Insurance Co., in the way of eliminating Asbestos Dust in our factories, end we have made a very satisfactory job of it. \tu have now reached the point where v:e can eliminate a large part of the Dust, but as yet nave no definite information nu to vhat Asbestosia will lend into. losis, but v.e do not find this, to be They claim the case. Sittillle,ndsvasttcoaTnnuobtergcou into court end state definitely and specifically that it will not co so. lungs, We anu nuaoymsoetw utphata Asbestos Fibrosis Fibres can, and co, get into the condition, which, for v.ant of a bet tor name, so.tio doctors have called Asbnstosis. Dr. Gardner has a v/ell equipped Laboratory, and a number of separate Dust Chambers in his Laboratory it Saranac, hie associates have been studying various types of Dust end for nhenuamndber of years, in connection with Tuberculosis, bat practically nothing has been cone v.ith Asbestos. tlyakepsniufrofmorIntvb.yoorditeonrdutsthtorreyec,ayremraoyr.s*tol,nyu:wnodsnytstithneegmsaetasiicnvaeDsuuvns-ititg.ienlvieosnstigaartciona,n,:i:rtal t Dr. G?;rcrier*s Laboratory charge is $b,0-Jd.PJ par yer r, and .ny otucy should be based on a throe year period, in order to got re sults that will stand up and bo accepted by trie* i.iocicul fraternity, ana, I believe, by the courts. I thiruc tlie Campons alion Laws in the various rtries wi dccouc more rigia in tnu nc/t fei. yearn uk;, no doubt, Asbestos, on account of the advertising it has had lately, will become or.o of the Compensation cases, and we should.m.vu all tins information v.o can par sibly get to submit to the Compensation Comminsiorin of the? V; ricur> states when the question of A.';bet t.ujsis comos up. / Schlter . n 11/10/23 work;-on experimenting'with Asbestos at once, and has suggested to us / that the Asbestos Industry take over this lust Chamber and employ M m to'carry on the experiments with guinea pigs and rabbits. The idea of Mr* Brown and myself would be to have four or five (or even more if v,e could get them) Asbestos manufacturers take over this study by subscribing an equal amount per year, for three years, and then v.c could determine from time to time after the find ings are made, whether wo wish any publication or not. i/iy own idea is that it would be u good thing to distribute the information among the medical fraternity, providing it is of the right type and would not injure our companies. This would mean, if four of us went in to carry on this work, it would bo;$1,2130.00 a year for each one of us for a period of threo years. If you are interested in this subject, I should like to have a meeting in New York, on Tuesday, November 17, at lit30 o*clock, at The Biltmore, or ,if this is not satisfactory, can make it any place you caro to have it* i I am asking the following to attend the mooting, Hr, Vandiver Brown, Johns-Manville, Inc.'' Mr. F. H. Schluter, Thorraoid Itubber Co*/ . Mr, A. i>. Blugden, keasbey & Mattison.Coi Hr. H. D. Laitont, Asbestos Manufacturing Co;-' . Mr. 0. M. Williams, Russell Manufacturing Co' Mr. 8. Simpson, H&ybcstos-Mcinhatton, Inc. / \ Is there any one' el3e you would suggest? Very truly yours, SS-G. President t November 20, 1936 LeRoy U. Gardner, M. D., Director, The Saranac Laboratory, Saranac Lake, New York. Dear Dr. Gardner* At -a meeting yesterday attended by certain brake lining manufacturers, Mr. Simpson and I were able to present to a fairly large group of interested corporations the proposal that one of your dusting chambers be engaged for .further experi mentation with asbestos dust* The proposal was very well received and it appears that not less than eight, and perhaps ten or more, corporations will participate in financing these further experiments along the lines discussed when we met with Dr. LSnxa and Dr. McConnell a few days ago. Accordingly, you may consider this letter as an authorisation to you to commence the contemplated experiments with asbestos dust for the purpose of determining more definitely the causes and effects of asbestosis. It is my understanding that, among other questions which it is anticipated these experi ments will answer, are the following* (1) VVhat concentration of dust is necessary to prouuce the fibrosis of the lungs which is designated as asbestosis. (2) Whether exposure to asbestos dust will produce asbestosis without the existence of previous Infection and whether the X-ray changes found in advanced human asbestosis can be reproduced In animals without infection. (3) Whether the fibrosis produced by asbestos is of the progressive type, that is, will the ,, fibrosis increase (one it has started) after exposure to the dust has ceased. (4) Whether the flbrosi3 resulting from exposure to asbestos dust is occasioned by the silicon con tent of the asbestos or by its fibrous structure. (5) Whether the presence of "asbestos bodies* has any diagnostic significance. It is also our understanding that these experiments will require approximately three years, which will mean that they will not be concluded until about the end'of the year 1939; and that they will cost $5,000 annually, or a total of $15,000. It is our further understanding that the results obtained will be considered the property of those who are advanc ing the required funds, who will determine whether, to what extent and in what manner they shall be made public. In the event it is deemed desirable that the results be made public, the manuscript of your study will be submitted to us for approval prior to publica tion. I shall appreciate your advising me if the foreg accurately expresses the proposition you had in mind. Also, let me know the manner in which you would like to have the funds ad vanced to you. Would you, for example, desire to have $1^50 paid quarterly in advance, or Jhst what arrangement would suit you best? Any method you suggest will be satisfactory. Since the experiments are being underwritten by a rela tively large group, it has been suggested tliat, as a matter of con venience, any communications regarding the work be addressed to me and I will, where necessary, communicate the contents thereof to Mr. Simpson and the other parties. You will be provided with funds by either Johns-Manvilie Corporation or Raybestos-Manhattan, Incor porated and we or they will secure from the other parties their pro rata contribution. I tributing parties. will advise you later of the names of the othe I shall appreciate your informing me at the earliest possible moment whether the arrangement as outlined herein meets with your approval. VB:T Sincerely yours, ZLVandiver Brown General Attorney / T hb Saranac Laboratory for the Study of T uberculosis of - THE EDWARD L. TRUDEAU FOUNDATION 7 CHURCH JTR^)Y */il> 4J Saranac I^kb^JN/Y. i \ J ' November 23, 193; /fi Mr* Vandiver Brown Johns-Manville Corporation 22 East 40th Street New York City w wet 4 U'Xfci.ovvitv Dear Mr* Brown: Your .authorization to proceed with the proposed asbestosis experiments at the Saranac Laboratory is acknowledged with satisfaction. We believe that such experiments can be ex pected to furnish asnwers to the questions which you have outlined. The estimated cost of $5,OO0annually for a period of three years, making a total of $15,000, is correct. Your suggestion to make advanced quarterly payments of $1,250 will be entirely satisfactory to the Laboratory. If this is not convenient any other arrangement that you may care to make will be acceptable. The Saranac Laboratory agrees that the results of these studies shall become the property of the contritutors and that the manuscripts of any reports shall be submitted fcr approval of the contributors before publication. I would recommend that the experiments be performed with pure Canadian csbcotos fibre containing re latively little serpentine rock oust. The "Kings Floats'1 uaeo in our first experiment was unsatisfactory owing to the fact that it contained such a high concentration of nonfibrous rock dust. If this meets with your approval I would suggest that a sample be submitted to the Laboratory for chemical and petrographic analysis. Having mutually satisfied ourselv9o as to the material to be used I would request that the companies agree to s uddIv a sufficient quantity of asbestos, ground to the f i n e s t state o f subdivision possible. 1 am not awure whether any of the contnoutors:have apparatus capable of reducing fibres to inhalable dimensions. If this request should not w r .v.^rowa,i'ov.c;o,ioe,p.<; prove practical some arrangement for its final reduction will have to he made by the Laboratory. But at least the material received by us should be broken to powder. It is impossible to estimate the amount of material necessary for the experiments at the present time as its behavior in our dusting apparatus has never been determined* With the ''Kings Floats" tests approximately 1200 pounds a year were required. It is conceivable thut a pure fibrous oust might be dissipated into the atmosphere more rapidly and hence even a larger quantity would be necessary. *ie are reedy to start the work at any time and will be pleased to examine samples of oust as soon as they can be procured. Thanking you for your cooporation in arranging this program, I am With best regards, LUG:CC 4 Mr. Vandiver Brown -2- February 24. 1543 Naturally, I ahall weloone any orltloisn that you cr any of the other oontrlbutora would care to offer. Should any cf then want to dlaouaa details, I-would bo pleased to ceet with then. May I take this opportunity to thank all the oponsoro throurh you the support that v 'e have had. Slnoerely yours, *L L U O : :S K Leroy U. Gardner, M. D. Director t t / .. The Saranac Laboratory FOR THE STUDY OF TUBERCULOSIS O f THi IPW AIO L HUOtAU FOUNDATION Saaamac lAU, N.Y. t February 24, 1943 Hr. Vandiver Brown Johns-Konville Corporation 22 East 40th Street New 'tor's., New lorlt Dear Mr. Erowr.: (t^^sT) ' 1 f - I have at last eucceeded in analyzing cost of cur vqlwkinoue experinental data end assessing the results!] I realize tfcaf"this should have been oompleted before thle, but the ecerrer.oy hao left se short-handed in the Laboratory and also necessitated =y doing a good deal of extra traveling'. I hope that the sponsors cf our study of asbestos!* will be oharltable and realize that the vori has far exceeded its original scope. We have done over 40 different sxpericents, cany of then divided into several parto, vhlch involved exposure of ar.icp.ls for 1 to 3 years to various du6ta. The buoiness of preparing ricrccceplc sections and oheoically analyzing the tlseues on core than 600 enicals has been a Job ir. itself. Hy tice for studying sections and analyzing data has been so H a l t e d that we are behind our ecr.edule. T have still not had tioe to write a J ull report of this vori which will of necessity be conographic. However, for the benefit cf the contributors, 1 as subcitting a table of contents and an an notated outline to indicato conclusions and the line of argument t will be developed. The latter itself occupies 15 pages, tut I hope they will find it sufficiently intereoting to read. 1 shall veri or. the final canuscript as I have opportunity. There ere a few expericente still lr. preg p e o s vh * A U should be ccapleted by the tlce we ere ready for th e Ahe war cr. cst.hoi8.of duet deterclnation, I oonslder iepertant er.ough tc in elude in the study. The question of cancer suscept ibiii ty now acer3 | core significant than I had previously ir.agir.ed. I tell eve I c&r. obtain support for repeating it free the cancer res eerch grouo. Ae it will take two or three years to oocplete such a study , I be it would better be onitted iron the present report, If it shoo becoce possible to cake this study, I hope that I any cc ur.t cr. of your cecbers to supply ne with enough pure, long fibr e ashes for the purpose. ? P-L-i;:i  t OUTLINE OF PROPOSED MONOGRAPH ON AS3E3T03I3 Saranac Laboratory Study under Grant from Asbestos Associating PART I HITMAN AS3EST03I3 1 Human Pathology - a atudy of 23 autopay oases,Illuatratad 2 X-ray Patterna In Aabeatosia, Illuatratad 3 Aah and Mineral Valuea in Hunan Aabaetoaia 4 Complications of Aabeatoeia (a) Susceptibility to infection 1 Tuberouloua ii Non-Tuberculoua iii Cancer of the lung 5 Disability, causes and cooparison with silicosis 6 Diagnosis . (a) History o f adequate exposure (o) X-ray film pattern (c) Physical examination (d) Aabeatoeia bodies in aputun, their significance ^ C* - 'v- PART II Experimental 1 Methods (a) Inhalation oxpooure to plant dusts. (b) Injeotion Into lungs through trachea of pure olneral, (o) Injection of pure minerals Into other organa. 2 Species Susceptibility Man, guinea pigs, raboita, cats, white mire and rati dogs. 3 Peculiar Characteristics of Aabeatosla (a) Unusual localisalon of chryaotlle fibre in lungs. . (b) Rate of resultant tissue reaction more rapid than to quartt. (c) Reaction to chryaotlle not progreoslve after exposure ceases; again the reverse of the situation in alllcoel (d) Asbestosis Bodies 1 Composition and methods of formation. 11 Occurence In different species, ill Formation does not parallel development of fibro3 lv Oradual disappearance after exposure ceases. 4 Comparative Effects of Different Asbestlfora minerals. ' (a) Canadian Chryaotlle. (b) Arizona Chryeotile, low iron. (c) Crooldolite 1 Bolivian specimen, stiff and elastic. 11 South Afrioan, soft and flexible. (d) Anthophyllite (e) Amoalte. (f) Treoolite. 5 Effects of Control Minerals (a) Orannular Serpentine, eoce chemical composition as . chrysotlle. (b) Olaaa Wool, a synthetic silicate fibre. (o) Bruoite, a fibrous magr.eoiun hydroxide almost free of silica 6 Chemical Composition of Asbestlfora minerals in Relation to Irritation.t (a) Nothing In composition correlated with relative irritat capacity. (b) Preliminary acid treatment i Hydrochloric aoid 11 Carbonic sold (c) Effeots of Aluminum - 7 Phyaioal Properties in Relation to Irritation a) Length of fibre b) Effeot of Crushing o) Heat treatment 8 Nature and Significance of Aabeatosis Body (a) Formation (b) Protective effeot preventing further irritation (o) Ultiaate solubility in tlaaue 9 Theorioe of Action of Aebestlform Minerals (a) Chemical - reaaona for considering invalid (b) Meohanical - experiaental denonatratlon of. 10 Ccapllcationo (a) Infection, tuberculosis and other varieties (b) Cancer of lung - experiaental data suggestive but not proven 11 Disability 12 Essential Features of Hazardous Exposure (a) Nature of dust - fibrous conponent and size factors (b) Ataoopheric Concentrations - probably lower than for quartz i Inadequacy of standard lnpinger sampling aethed which does not collect the dangerous fibres f 11 Electrostatic precipitatafsaapllng preferable but aeihod oust be aodifled * (c) 'Duration of Exposure 13 Recommendations for a New Standard of Safe Ataoepheric Co . centratlons- of Asbestos Dust (a) The Quaal-official standard-of 4 to 5 nillion partial per cu. ft. (b) Work upon better method of sampling (c) Necessity for comparison of results with X-ray fir.dir in employees 14 Prevention (a) Chemical means not.practical ? K U -^ i Acidosis necessary to dissolve fibre in longs worse than Aebestosis 11 Aluninua Thorapy Inapplicable H i Chief reliance still upon dust prevention with special eaphaoie upon the fibrous oonponents ASBE5TCSIj - A?r;ct0 outline indicating results 11 i - HUMAN A3BE3T03I3 1 Human Pathology and X-ray Patterns - Description Based upon 23 human autopaioe 2 Ash Mineral Values In Huean Lungg. 3 Complication of Aabcstoelei (a) Susceptibility to Infection 1 Tuberculous- High Incidence in English experience r.ot duplicated in surveys of American Plants. Available autopsy statistics deceiving because of sel ection of material. li Non-Tuberoulousu The same reason probably applies should be cheoked. by analysis of ab senteeism among asbestos workers. ill Cancer of Lung - Ditto, but there are now on record 10 cases of. lung cancer in asbestos workers. Compared to the total number of autopsies on asbcstoolo, this lnoldenco is excesslv No such frequency has been discovered in sillcools ^r other ferns of pneumoconio sis exoept^the Schneeberg mine's of radio active ores. The evidence is `suggestive but not conclusive that asbestesis may precipitate the development of cancer in auaceptible individuals. 4 Disability Clinical experience suggests that truly disabling asbestesis is manifested*by less striking X-ray changes than a corresponding degree of silicosis. Such disability in aobestools is due to disease within the lungs and not to secondary heart dlaeaee. As 4n silicosis, associated pulmonary infection increases the amount severity of the dust fibrosis with resultant accentuation of disability. There is urgent need for a careful physiological study of pulmonary function in asbestosls of varying severity. Undoubtedly, there Are cany diagnoeable cases with no significant disability. 5 Diagnosis depends upon three faotora. ( *) History of adequate exposure, usually 6 to 8 years, semelonger. at work where both the concentration and character of the -asbestos" dust are hazardous. - \c W W a r.V> ScYV'T'*#..' *% * * *'*t * -c u '.t 'a v * . '.-"* ^ * * t-b) Evidence of diaeaBejin a characteristic X-ray pattern. V'*-- ( s (c) .A physical jxaninrnon which reveals certain characterlati signs and nay reveal evidences of disability if present.. * * (d) Aabestosle bodiea la the sputun are conflrnatory when the previous faotora are* all positive. However, the bodies nay be absentparticularly 1:. the a'oser.oe of bronchitis : infection. Asbestoaubodles unsupported by other evidence do not rtaka .a diagnosis. 'Occaolohal ones have been found in about 15 autopsy speclneno of poroono with no known exposure and no fibrosis, probably of^non-ocoupatlonal origin. 00 A*** A-AAAAA PART II Experimental Asbcstoalo I Methods *^ < #* : 1 V .\' / I"' (a) Inhalation Expo sure a to Plant DusjC - Specific fibrosis. lungs, but no ohanges elaewhere.? . . . oifv- .. ..... .. .. (b) Injections of- Suspensions pf Pure Minerale Into Traohea`ri^ Sloilar results. , > ` ; (c) In lection of Suspensions of Purs'Mineralalnto other organs* . Fibres dissolved; no asbestosis bodies; tissue reaction`co: fined to phygooytosia and encapsulation. Cocoore'the '-'-s-- asbestos C f i t w of husan,;subjects -. *> v , " ;.. ''."`us II 32!ll SuB^^ibliy^; \ Unlike free slllcai, asbaatosMoea not 'produoe its spoolflo effec r n ** " Sulnea Pig 2+ 9-r VU W '*..... TT " -1..v *"v ;1 i 1.',..n Vhlte'Mouse`'0 -* Rabbit 4)9 *** H ..*3 . . - _ ,.Vhlto Rat \v .'iv*-' ; , + b very an:nll .tyels&L,JLflbgfltaa.bodle.i),,fI;...,..'Dog r 0 '*' v* o'" o -A? - o'r':-- v^v- III Peculiar Charaoterlstioft s i Asboatoall ... . - - r '' V * !.{v ' mlnsralaVin 'iunra differs frora that 1 Fibres like ohrysotile having a oertaln degree of flexibility and elaatlclty accumulate within the finest air tubes; granular duet la oarried further on and la widely aoattered through the terminal air spades. (b) Rate of tlaaue reaotlon to aobeetos la ouch more rapid than to an active duot like., quartz. Evidences of formation apoear as soon aa aufflolent oonoentratIon of fibres haa localized 'In apeoiflo areas; with quartz, there Is a latent period of nontha. (c) Reaction to asbestos doea not progress on oeasatlon of expos ure. Xoung scar tissue that cany have formed, contracts and becomes core dense but the area of Involvement decroaoes Insite. In allloosla, the .young nodulea become larger after exposure ceases. (d) Asbestosia Bodies are a speolflc concomnltant of this form of pneumoconiosis. They are due to a deposit of protein and Iron upon the surface of Inhaled fibres. In guinea pigs they form after about 60 days of oontaot with the tlsoue. They ore abund ant In man and guinea pigs, (See paragraph 2 above) but much larger in the former probably because the larger sited air tube admit larger fibres. In cats, rabbits and nice, there is an atypical coating of a few of the flbreo after nuoh longer resi dence In the lungs; In rats and dogs no bodies could be dis covered. From paragraph 2 It la apparent that their occurence does not parallel development of fi'oroeis. In lur.g Injection experiment), the bodies have .:eveloped nnfft fibrosis le-ouall p.cWr.r.ced. The number of bodies seems to decrease several years after exposure ceases. ,dl.fitlV.fl Ejecta Q l Different Aabg.aT3.gU Hinereis (a) Canadian i'hrvaotlle - highly Irritating. (b) Arizona ^hrvsotlle (low In Iron) equally irritating and pro duces Just, as Oflny asbestosia bodies as the Canadian product with over 11 times as much iron. (c) Crocldollte - Tha South African blue asbestos is known to cause as'cestoeis. Only a limited supply of this material in pure form was available, most of It was used'earlier in the work in non-productive experimente. For the later critical Injection teats Into the lungs, a Bolivian variety was substituted be cause of Its high purity. Its flbreo were much otralghter, stiffer and more elastic than the cottony South African variety. Perhaps because of these peculiarities, It has not given reactions comparable to chryootile. It produced aobestosis bodies but did not localize In the terminal air tubes nor cause any fibrosis. Teats now being repeated with a typical South African crocldollte with physical characteristics simulating chrysotlle. -4 (d) 'Anthoohvlllte -'stiff, straight fibres - atypical aobestools bodies foras slowly but no localization or fibrosis in lungs. (e) Anoolte - Ditto. . (f) Anohlbole - Ditto. ... . if) Trenollte - Ditto but vory fow asbestosls bodies - Observation being continued. //.*... . . ; `*-w V Control Mineral . ' ,* >*t (a) Granular Serpentine of sane chenioal composition as ohrrcotil. la inert causing no flbrools in lungs or other organs. <it.Vr attraots iron from the lungs but of oourae, no "bodies" dovoiot (b) Olwee ttool(a synthetlo silicate) fibres are not inhalabl'o froa air-borne suspensions, apparently because of their etlffncoa (the diaaeter is not responsible as some used were loss than'V' 1 alcron thick) On lnjeotlon into the lungs, they do not 7 localize in the air .tubes but are widely scattered. They cause no flbrools. After 3 or 4 oontho in oontaot with lung fluid,a few glass fibres take up iron but remain ocooth. They nover show the swollen ends and lateral projections of the true > asbestosls bodies. (c) Bruclte of Interest because it la a fibrous mineral praotlcaily free of silica (o.9). Crystallographically the arrangement of i t s a n d OH groups in oaoh unit oell is similar to that in chryaotlle. The sample used also contained about ie iron, pro bably from contaminating magnetlto. The fibres are stiff and needle like.' Observfllona not yet oonpletcd but after 2 months In the lungs, typipal asbestosls bodies develop but there is as yet no fibrosis. The fibre are soattered through the lung inote. of being, localized inside the terminal air tubes and tissue reaction"occurs around, instead of within the tubes. VI Chemical Composition In Relation to Irritation (a) Nothing in the following chemical compositions can be cor related with variations in capacity to provoke tiseue reaction. (See Table Next-Page) " Is W C*0 I ' /fVt  c ; 0<a Chrys- Crooidotlle olite 37.43* ..54,99*.. ^4:.-iz/CZiit r; i-** Antho-^vfi'1.:Aciooito .Aaphiw:i.7reco3JLtQjV^ruodtOr u h v l l l t o - 'hfiXa ;* j'. .. .*,>* * rf .. '* '4.88* 5a;04* :''66.20* ' 0.901`":'^ F- o 0, .2*35*.. 16.27* e* o . 0 4.291 AlsCh ... 0.361 .... 1.021 C<L 0 . .0,05* 0.791 0 38.77%' 13.85* 0 0,20 0.511 iyy" a \o s < ' '3.03*. r 7 .2l1 6,721 *'*'" 0 7' 0.255 33.83* 1.091 *f Jeol ' 9.25l*:?-''*' 0.561' 0.461 -0.441. 2.011 89.5** -. (3.291 0.52 0.33 12.221 23.20,1 v 0.40 4.451 0.401 'r>' 20 .'52,1 -63.991 6,78 0.91 ''* KvO . 0.08 --Q.67 ...0,15 0.10 0.12 0.99 * 0.15 L<aji5 < 1050 4.30 0.02 0*02 0.0 6 0.32 0.34 0.53 '>105 14.92 (b) 2.56 2,42 1.51 3.59* . 4* *. t*, H * Aold treatnent of ohryeotile fibreo T, 2.78 26.66 ':y' ^ 1 One hour In dilute or oonocntrated HCL does not alter ap pearance of fibre but after euoh treatcont It rapidly die aolves and disappears on injeoting into living tlssueo; 11 Treatoent with COg bubbled through water or lung Juice suspensions of chrysotile fibres cauacs partial solution with liberation of silioa and cagnesia. (c) Colloidal allumina does not neutralit the'effects of asbestc as it does quarts. On injecting chrysotile suspended in alunlnun hydrate solution, flbrceis and asbestos belles develop at the usual rate. It renalns to demonstrate whetr.er tb fibres*beooce ooated with a layer of aluminum conohydrate as has been proved in the case of quarts. Af they have, the ccs does not affeot their capacity to irritate tissue. VII Physical Properties In Relation to Irritation of Lunr Tissue (a) Length of Fibre Short chrysotile flbretunder 3 nierons ore practically inert. 20 to 50 nioron fibres cause typical fibrosis. The effects of longer ones could not be tested for technical reasons. ' (b) Crushing oompletely destroys the fibrous structure of chrysotile. Vlth loss of structure, all oapaclty to irritate disappear. t-Xls- VIII The physical chance altera typioal localisation'vithln the . lungs, no fibres*a develops,* reaotloiv linitod tophyegooytooiaV No asbestosla bodies' forned. , r ' `V; .t >' ***:rs*- I . . I'** , \ *-w I. .**J.4 V*Urf****^* >. 9 7 N%j\# ' * . *m /* . * . `4 > < *'l*^^*'*' Nature flignyflcarm'af AabeetorU Bqdiflfl .'V, . f `V ' ..:.***.. . ' (a) Bodies, probably result from dqposition'rof lron*and organio * natter on a olowly dlocolvlngjflbro .oi iaobeatoa'.-./Xho oouroo . of the Iron lo core lltol7 tobe the lung tlaoue than'the nlnoral lteelf oa tho ooatlng "la "Just 'as* heavy ;'on-fibrous nlnerale of lew Iron oontont.aa'upon, thooe`hlsh.ln Iron. /' v :*- i >.* y'l^f (b) The effect of aabeotoela' body\fornatlon'iio asounod to be pro-'V toctlre although It haa not been.pooolblo ;to. leolato a large '.u,, enough quantity of. these otruotureo In .unaltered'fora, for purpooea of teat. The ocooth'rounded-ends'presented-by tho ``v * bodies would not be noohanloally i r r i t a t i n g ' V- . * . :/ (c) If they were oapablo of cauelng'lrrltatlon,\tho flbroolo in the lungs should progress aftor oxpqouro .ceases .^whlch It doee not. (d) Tha gradual disappearance of bodice (ond'flbrea) long after ,* : exposure'I/oints. to ultlcate solubility i.r tlasuo fluids. (e) ^he bodies are probably a fortuitous oonoocnitant rather than'" a cause of fibrosis. Theories of Irritant Action of Aebestlfom Minerals (a) Chemical These experiments do not eonflra tho theory that asbestosla Is nerely a fora of olllcoslo resulting froa free silica liberated In the solution of a silicate aolocule. If this were true asbestos,like ouarti^phculd cause flbroal a in any organ of any -specleo for the experlacnts have shown that injected asbestos dissolves in thes*e locations. However , it does not, c*uae such reaction in any location but the lung 8 Of species. . * (b) Mechanical Irritation Ve are proposing the theory of nechnnicsl irritation which is aanifested only in the lungs because this organ is the only cr.e whose normal physiological functions involved high degree of nobility. Zxperlaents designed to prove the necessity for notic; In this tissue have failed for technical reasons. For this theory to be applicable,It la necessary that the fibres be concentrated In the fi/je terminal air tubes. It has be^rv,shown that only ohryaotlle of the aabeatlforn olr.eralJ thus fer nas the proper physical characteristics.to insure such localization, it is also essential that the flora shall percist long enough before it dissolves In the lungs of spades like nice, rata*dogs, it apparently dloaoivee so rapidly that It exerts no Irritation. iJlallarly rapid, solution uoy explain In part, the lack of fibrosis in organa other than the lungs, x % -7- The fibres must be long enough so that they cannot be connl - surrounded by phagocytic oella which'would prevent contao* c round, broken'ertds with the delicate cells supporting the^i Observation has demonstrated that these conditions nro reali guinea plge treated with long fibre chryootlle and fibrooio With the other asbestiforn minerals that have been tested* e all of the prerequisite were lacking and no fibrosis develop* (c) If the irritation were chenical, fine serpentine which i sans'chemical composition as chryootlle should have also fibrooio. Tho crushed chryootlle ehoudl have boon more than intact fibres, beonuoo of the greator ourfaco areas posed to body fluids. On the aeouaption that ohrysotile ouartt, becomes coated with a very thin layer of alumina treatment with oolloidal aluminum hydroxide, capacity .to flbro8la should be destroyed if the eotion were chemical euch i$ not the case. (d) ^he heavy coating resulting from asoestosla body forcatio. parently does stop tissue reaction but here the effects au probably mechanloal for reasons cited. (e) Heat sufficient to alter chemloal strue fire d eatroye peve to irritate but it also alters eoaontlel physical characte. c that affect localisation of the fibres in the lungs. X Complications (a) aU8ceotlbllltv to Infection dji h i Tu^ercui0U8 - Asbestos behaves like most other mineral/,! this respect and not like cuarts which specifically Inc re native susceptibility to the tubercle bacillus. This l.nfeoticn may spread for a time but then heals. The result fibrosis accentuates that caused by the mineral fibre. 11 Hon-Tuberoulous - of no greater frequency than in animals inhaling dusts of other kinds. Occasional epidemics of pneumonia occur in our duet rooms, but these are due to methods of housing rather than to duat; they also occu in unsxposed Animals. ill'*'- Cancer of Lunge k**tU*t*'f) Ho experiments vere*dealgned to elucidate this point tut certain evidence suggests that asbestosls cay actually favor development of tumors in susceptible species. 1 In guinea pigs, rabbits,rata, oats and dogs lung tusora are rare. 2 When these epeoies were subjected to 2 to 3 years in halation of asbaatoa dust, the Incidence of lung tumor was not inoreaaed. ' - . i (l(i> - b b (.*]) 3 Soce strains of whits aloe do develop tucore without i. apparent oauae. j 4 duch a strain of white nice vao unintentional!/ uced in three lnhalatlbh experiments with asbeetoa. 5 Of 11 aloe Inhaling long fibre aebeotoa for 15 to 24 nor.th 8 developed oallgrlant tuoora In their lungo and 0 of then had tunoro In other organa. T]ifi Incidence rate .S la excessive. 6 Of 22 aloe Inhaling short f-lbre aebeatoa for not longor tt 12 oontha only 3 developed lung tunors. Rate 13.6 7 Aa oontrola, we have only the experience with aloe in othe duet experiments. *or short perioda. there were 51 alee exposed to 4 other Kinds of duet for 10 to 12 oontha. Incidenoe of lung tuno: 1.9*. For long periods. there were 143 nice exposed to 4 differs: Kinds of duet, lnoludlng pure quartz, 23 to 31 oontha. Foj all this group of aloe the average incldenco of lung tuaor was 13.8*: the highest rate (25*7 was In a subgroup expoaec to flint dust. Thus the lnoide'nce of lung canoer In the long fibre aebeatoe aloe woe over 16 tlaee the average for aloe Inhaling other duets for coaporable periods and over 3 tinea the naxloun for any other'group Mice expoaed to the practically Inert short fibre aebeatoe showed fewer lung tunore although 7 tlaee noro than those In short expoour to other dusts. *hese observations are suggestive but not conclusive evidence of a cancer stiaulating aotlon by aabeatoa dust. They sire open to several orltlclaas.' The strain of nice was not the sane in the asbeetoa expericent, a a lq aany of the others oited; apparently the foraer were unuoually auooeptlble. Not enough aninals survived in the duat for longer th^in the 15 oontha apparently neceaaary to produce aany-tucora. Ahere were no unexpoaed controls of the a&ne strain and age er.d no diailar controls expoaed to other dusts. It la hoped that thla experiment can bs repeated under properly controlled conditions to deteralne whether asbestos actually favors cancer.pf the lung. XI Disability Cannot be deterained in animals, ^'he accidental deaths were froa the same causes net with in all our dust inhalation experi- cents. ' \ A.J.L- -la to'CS)- XII Essential Tnctorn si -- -- 1 g*coiiu,-8 ' 'vdri , .. .'. .;.T-. ,-*,...* '.;'V* '' ** * () Hature of Due* - ,. ' '' *'-" ' 1 .--.V. ^-Jey; ' 1 '^he hatrda Increases with the proportion of"Intact fibresWv In the duet. Oranular material'and crushed fibre are Inert diluents. . .) 11 ,The long fibres oust be thin enough (1-3 Microns) and short enough (under 50 Microns?) to be Inhaled. Ill Very short fibres (under 3 Microns) ore practically inert. (b) Atmospheric Concentration Still-under study. Apparently this factor is lower than In the case of duets ooaposed of granular minerals but methods of estimation are misleading. i I The average standard Publio ^ealth Servioe lmpinger count In the long fibre asbestos dust roon'was 40 million particles per cu. ft. of air. "his'concentration-caused fibrosis visible to the naked eye In 20 to 24 ninths. For conparlson the average lmpinger oounto in an experiment with pure quarti was 120 million particles per cu. ft.*and fibrosis developed at about the same rate. : . . - . ... II However, lmpinger oounts are deceptive because by this method of sampling very few fibres, which are the significant elements In the duet sure collected.'.;''--.v: ill Sampling with an electrootatio preolpltator la a cuch mere efficient means of colleoting fibres from air-borne sus pensions. Samples from our long fibre aobeatoo room showed that the dust In the air oontair.ed 32.5,* of fibres few of which had been oolleoted or counted In the lmpinger sample, The latter sampled largely the Inert granular parti oles. * ' lv As ordinarily employed precipitator samples are weighed and the results expressed In mg. per cublo foot of air." There is no means of oonvertlng such values into numbers of ^particles particularly when these vary in site, shape and '`speciflo gravity. 'i , v Simultaneous sampling with precipitator and standard lm pinger yielded the respective values of 0.65 mg and 60 mil lion partioles per oublo foot of air. f : vl *heoretioally the best Index of harard would be either the number or weight of fibrous elements In the dust. i (p- (p(a(3) -10- . (c) Duration of Exposure . *c ;<' , i Fibrosis visible to the naked eye after 13 months exposure Increases In extent In subsequent 13,months. . v t *. ( * . V* .*. ,v:-. * . mh. --an of ilf9 of our noet susceptible^laboratory animal 11 t h l rulnea pip has prevented continuing `exposure longer tin the guinea P*E thf oerlod only-the comparatively early three y e a r s . ^ h$Je beenproduced.- With the know- ' stages of asbesto *_ ^ probable that more extene: ledge that we have gained^ It is P long flbpe dlseaee could Juve teen proau^c r ^ chrysotlle. The long lived, specie,-11 C'8* io'-8 * ^ fortunately not susceptible-.. ^u..'-v; W ./ p t >' !bi ,,. . ->* T , . . . _ ^ ; > gram. v ,,Kano-Art have been minimal and v-e * obj.om,. of t h U pro, - `#' Recommendation fo r 'a Hew Standard of SafeAtmoonherlo Concentrates ;-::: of .Asbestos wust " .A * * Cvvr;- " ` i ,*-_f>+*0-.*.-.(a) W4hiolretmhierlelioins pnoartoifcfliecsialperstcaunbdiacrd,foottheo'fteanitratiisveforneequeo:ntly ouoted. *. \ ** ".`v V , '' , .f (b) This is probably unreliable because it-is'based upon sampling fc? +' , ' 4 with a standard ioplnger vhioh we haver shown does not collect n m f of the fibres that are the source of, hpiard. * (c) We now think that a standard should be based upon sample9 \v < r.-*- . * l l collected with an electrcstatio precipitator if it is feasible to determine readily the relative proportion of.fibres in such arterial. 'J ;V .. (v!) Work is still in progress upon the latter*polpt. . -y. ' vv '* - ; (e) To he of -value the new standard would.;hoYe>to'.':be correlated with thev'X-rry findings-upon;>mplcyeea-exposed/.to .different concentrations of dust. ,*; -'r " ' V ; -T :- .' .Tv* -' -:r\ 0 . * XIV Prevention of Asbestcala ' ' '* ,, > -------- .--------- * -- a. i-v^-o- ` The experiments have failed .to*'develop .anyVprnctical chemical r.euna of neutrallring the actXou'of fibrous asbestos... 1.1 a -. ... ` - ' -s''v-i.. ', l - '4,1 (a) To niter the hucanTlung 'so that it would.'diaaolve-'acbestos fibres rp.pialy like a rat would necessitate; (y-rocabl^? creating an aciddala wj-.ioh would be-.worse .than the effects the fibrosis. -v V- "+ *: A - i i . **J / *. '/*%>\ . . *f * ' ! i `/ ?%/. % . ` *-^^f '>^.v44V%,i \ :'* ^ ^ ; ; * . ...*:(l>..*. .* . ' ,\ A.*A**## >.* V . --. . . * - ! * >J. . ; -`i v *V*. -.t ( s:*.*: * * * <y. V **? % . * tM . . \ s,. * 1 of-' Cc - Cs Is (j * V. 1. in * **; -K* (o) ;However, U wi?V\d;blrot 'sreftt.Hhcoretil'intcrestVtt few oapeo ^itn. ^boXj'diapnooa'lfroo aobotooio.-.by -aiutai ( X ~ (i (p 0 0 T", -i'}' \jr: *.rp;.V..4-' IV'-. ' , ^V>VC^*\** i / - .:V w jri *..:V . ... .* . - 4 n & m . d . _ , </ ;.<- A *,i**->v<!j V. wmr :"<i p s *i .* * .. 3 , ;.Ve' V* . .i* LeRoy 0. Gardner, M. D., Director, The Saxm a c Laboratory, Saranac Laute, M*w fork. Dear *Drr. "Gardner : It a meeting yesterday attended by certain braxe lining manufacturers, 3Cr- Simpson and I were able to present, to a fairly large group of intcreated corporationa the proposal that one of your duating chambers be engaged for further experi mentation with asbestos dust. The proposal sas very well received and it appears that not less than eight, and perhipe ten or sore, corporations sill participate in financing these further experiments along the lines discussed when ve net with Dr. Lanza and Dr. McConnell a few days ago. Accordingly, you easy consider this letter as an authorization to you to commence the contemplated experiments with asbestos dust for the purpose of determining more definitely the causes and effects of asbestosis. It is. my understanding that, among ocher questions which it is anticipated these experi ments will anjser, are the following* (1) hat concentration of dust is necessary to produce the fibrosis of the lungs which is designated as asbestosis. t (2) Whether exposure to asbestos dust will produce asbestosis without the existence or^rewious Infection and whether the X-ray changes found in advanced human asbestosis can be^reproduced la aalnals without infection. ` (3) Whether the fibroeis produced by asbes-tos is of the progressive type, that is, will the fibrosis increase (once it has started) after exposure to the dust has ceased. 04037063 -2- (l) Whether the fibrosis resulting from oixposurt to asbestos dust is occasioned by the silicon con tent of the asbestos or by its fibrous structure. . (5) Whether the presence of asbestos bodies' has any diagnostic significance. It is also our understanding that these experiments will require approximately three years, which will mean that they will not be concluded until about the end of the year 1939; and that they will cost $5,000 annually, or a total of $15,000.I* It is our further understanding that the results obtained will be considered the property of those who are advanc- ing the required funds, who will determine whether, to what extant and in what manner they shall be made public. In the eTent it is deemed ...desirable that the; results be made public, ..the manuscript .of -your- 3tudy .will .be, submitted-/.to .us/:for approral-'.prior ..to .publics tlon. _____ I shall appreciate your adTislng at if the foregoing accurately expresses the proposition you had in mind, llso, let me know the manner in which you would like to hare the funds ad vanced to you. Would you, for example, desire to hare $1150 paid quarterly in advance, or Just what arrangeaient would suit you bejt? Any method you suggest will be satisfactory. Since the experiments art being underwritten by a rela tively large group, it has .been suggested that, as a matter of con venience, any communications regarding the work be addressed to meand I will, where necessary, communicate the contents thereof to kr. Simpson and the other parties. You will be provided with fundi by either Johns-kanville Corporation or Raybestos-kachattan, Incor porated and we or tt.ey will secure from the other parties their pro rata contribution. I will advise you Later of the nsaaea of the other con tributing parties. . I shall appreciate your inforaing me at the earliest possible moment whether the arrangement as outlined herein meets with your approval. ' Sincerely yours, Y3:T Vandiver Brown General Attorney 04037064 V U >: ~ -> o*- Tiin Saranac L aecratcry T H E EDWARD L. tor t h e St u d y or T uberculosis Ol' TRUDEAU FOUNDATION MJorh. nVs-aMn dGivnevrilieBroCwonrp o ra tio n 2H2ewBYoaortk -ICCtiht7 S t r e e t D ear M r. B ro w n : row ornct OCy*PQ"*T uD. ' 7 CllUHCH Vit> 1 Saramac Lax.s.r;N .*Y .: \. ;-s > * H oyjr.ccr 2 3 , 1S3G-. V 'i v \;CL *r.*-*"-- ' .. C-C.t IKLi*-->>lwv Y o u r a u t h o r iz a t io n to p ro c e e d w it h the p ro p o s e d o s te a te s is er.p e rir.e r.ta at the S a ra n a c L a b o ra to ry .12 a c k n o w le d g e d , w i t h a n x l s f a c t i o n . p e c te d to fu r n is\7he basonlwieovres ttho a tth esu cqhu oeaxtpioenrsin ownhtisch caynoubohaveox oouf t ltihnreede - y eTahros ,`e ms taimkiangte da ct oo at at l o of f$5$,1O5C,f0b0.n0n,..uicsHyc ofrorre cat. p e r io d Y o u r s u g g e s t io n to mako a d va n c e d q u a r t e r ly p a y m e n t s o f $ 1,250 w i l l b o a n t i r o l y s a t i s f a c t o r y t o th e L a b o ra to ry . I f t h is is not c o n vo n ic n t any o th e r arrangem ent t h a t yo u c a y c a re to make w i l l b o a c c e p t a b le . o f thoso and th a t n p p ro v a l Tho S a ra n a c L a b o ra to ry a g re e s th u t tho r e s u lt s s t u d i e s s h u 11 b o c o t t e t h o p r o p e r t y o f t h o c o n t r i b u t o r s ` tl:a m a n u s c r i p t s o f a n y r o p o r t s 3h u l l b o s u b m i t t e d f o r of the c o n t r ib u t o r s b o fo ru p u b lic a tio n v ' * ' I w o u ld rcccm rr.nrd t h a t th o e x p o rim o n ts bo p e rfo rm o d w i t h o u r ; C a n a d ia n cr.ccs r.oa' f ib r e -- c o n t a i n i n g r e l a t i v e l y l i t t l o a e r w e r . t i r . e i ' u c k o u a t . " `i h o " K i n g s F l o u t s " u - i e u I n o u r f i r s t e x p e r t i s e h t w u s u n s i\ t i s f a c t c r y o w i n g t o t h o fa ct th a t it flb rc u s rock c o n ta in e d d u st. _ I f such th is n h i g h c o n c a n t r u t i o n o f n o n m o o t s v /-- l t--h 7* o u r a pr p r o v a l I w c u l d suggest th a t sarr.plo bo V u b ir .it t o d to th e L a b o r a t o r y f o r c h o n lc a l and p e tr o g r a p h ic a n u ly a ia . H a v in g m u t u a l l y ' s a t i s f i o d c u r a o lv o s as to tho m a t e r i a l to be u s e d I v/ould re q u e s t t h a t the com panies n g ro o t o s u o o l v n s u f f l r* l o n e , - u m i i i t i : ; / o f a a c e s t o u , g r o u n d t o c n o f i n e s t at*, t o : o f s u b d i v i s i o n p o s s i b l e . 1 am n o t u w u r t j i . a t h u r any o f- tha e o n ti-io u to ra h u v e p p u ru tu s ca p a b le o f re d u c in g f ib r e s to '-ln h a lu b le d im e n s io n s . I f t h is re q u e s t shou ld n o t \ .* Mr.V.ProTm,Nov.23,193,p.2 \ wpriolvle, hapvrea cttoic baol sroartri.oo abryratnhgoemLeanbto rfaotro ryi t.s Bf iunta al t reloduuscttiotnh o m a teria l ro ceiv o d by ua should bo broken to poriticr. m a to r ia l n o c o ia n r yi s foimr ptohsesibexlep ertoimeesnttism aa tte ththeo parmesoeunntt otifm o Sd3o toi tms inbeedh-a v ioWrithin thoour "dKuinsgtisn gF loapa tpsa"rattue ss t shasapnprevoerirmsb,otoonly a12Cp0urepoufinbdrso uas yue aurst trnoirgnh tr e qbou idr eisds.ip aItte di s inctoon ctohivou batime otshpahtere mn oorcoo arsao pr yid. ly and hor.ee even a la r g e r q u a n tity would bo w i l l bo p lu a e e di'io toareer.rr rorolrdy3 tsuomsptiaers o fthoa uws torkas astooanny astimthe e vand can bo pro cu ro d . - `t h i s -program ,..X.Thaunnkiri: ; yo n fo r you: .c o o p o ra ticn in arran gin g . With boat regards, LUG :C C r > Sinceroly yours, J ,s.J 'Leroy U(.fy-JGiraor^d/ntoerr, Mc.D. 1 i \ PLAINTIFFS rv. '.1? EXHIBIT  n i im i -V............ 19 A, * Imm 1 V* la A fia ta A. f t Batata* T , taata ! V* B ta fiktaHiM 1ii faakaa li iB9** ftaatlalaltliw aa atalraw af Ita a a iH tta a a a tia * a lia i la aaita ta a vtl B a r M * la U H a ta ' a ffla , la astato ta l tata y ra w a li Ita a a a lla i y rta w lly ta rla ta w aaUal fa r Ita y u y iN af ta a rla a ta * l f l h > # t a ia a f Ita f atat i al it a i U fa f i n ta ai faapwr Maaarlatac Ita pr aiata alaitaa aA Ita Btaflatalta v i l i iiataaaaaaaa aal a l Ita laiaaaa tatan U iy . tta ta ta n a il# a a a l U a ta ta a f ito tatovtatai to s ta i m u ta *!* to lta t a i taaa aaataa i la a p a rl a aaall a i ta i ta rlla l Ir U a ia la Ira a n p a ri af Ita tafa n at i B A ta ta l gal l i l i aa B a i t i t r i la ita t a r a i la ton ta a y. P r. laaaa raparla! tta l ta rla ia rara* t a li a l laraaaa ta ta i ta i aaaaaa la a ll ita tann ata aai aalaa la fl 1 ita la ta ta toria ta aai ta ta i la tta i v ita p n a tta a lly a ra rfta if H a ta via aa aaaaaraai v ita ta vaa t a t a H a lf i ta l> rtaar ta i ta i a vary apatia aaaralay, ta l a f i r l aaal aly ita la i a ita i fa ia aaly i p r i t i ! aaa ja a r ta fara ta ila i. ta lla ta va ta f* a i f ta u rla ta la i l i aai a tata ta r a i tta l r w . ata i l i taaa I ta flaga lla avavjrtala It a l ta i tapparti ta rla Ita yvar aai ata a alaa a lla la p rtrlia fata Ita flla a aatataallal ta fa n a li la aaaaaallaa v ita a rila aaparlaaala ita aataalaa S rliaaM y ta affaat aa aalaala* Ita .affato aa p u n t i l i patata Ila aaataai la ta i p v a to lilly fSaltata Ita Iva atalaia a iataalaat Ila aa v a i! aa ra la tta raaaara prallaaa la ilffa ta ta kla ia af la ta ta ria i piatot aia* v it i Ita affata af I t i tata a ta n a tataca a i ta i * ta* l u n a t a la ta . laaata Sfata ta Ito Vallata fatata la ftarlataa ., via Ita taaa atM aialai v i l i ita la ta ta iartaar aai laataf aa a Sai af Ita aariy vata aa aalaalaa aaaaa. ta fa n a i Ila a f aia m at it a a la m fn a i I I a l anaaa t a i aa fa r aa ta ta a lla la p ir it e "a sta ti aaplaa" aa tan a n a i, t a li Ila i l ta i tota a m a sti la lava ita lata ta . to rt i aaaralary atta Ita to ta a tiy aaplaa n i favva ri Uaa. (la a lia ta a lly, Ita taataaaa af Ita tw iaaa t o r n a r li aai ftaatollaa ta ta rita ta . laaaa ta a ffa r ta . Xyaal a f i af IS O la pta Ita aattatal la tr i ta. ) US J*}?. Ir 1-- k u ta fim i te . IfM k Iha* 1 t w la l 111 te f im iU t t o U iM n n m 11 te te t e n Ite l te 111 M i tev* te tey te t e t e * te U te Ir* t e t e r 'i tetew l t i f : te te te r M lv ii U r te ite t e t e Ite l t e Ir Ifaah te teA m te te Ite atea rte l te 111 te ta n te te lte t 11 te im it e I ja l I I la p lte r te p iM tiK M i I M . v ,. , m n te teuaplaaa 1 l r i lrft> te Ite Vrat te l W at ite flr a l af tete ate tea Avtete te* Ifa a t Ite l te 111 M u ftf H M lU a te te n ite teta vtel I W h l a t e <*a tete I t e i tete te n te 11 ate te M lr Ite . t i O I te l i -- ftia a n a a lte ln a tete te tei ate. r. l t e i t i te mate te te te M ate v ite M i ateal tete A ala a tea te* te . te te n a la i te a te v ite Ite aa*avial. I aUlaA Ite l Ite ra a ( i l t i t la l af aaAavlal ate a l teaal tea te a ! ya rt-- tte t Aaallac It e Ite a ffiH af aateataa M al a t e telaga-m am A I te f e ir if a p iala ate te te lU ra i i i aal atea a aallaTteterf raparl. m wmtll Mr. ? teaw la p ira i aa I t e t e ? 1r. lana Ih n fh l * r. tema* a ll altaapl la >rateaa Ite aatira ate v a ria r Baatealaaa te te te . Cartear teA teA la a la i, ar tetear te i m Mra la I r Ite f l Aaallac r it e tea affaal af aatealaa ta l a teaaa tela ra ; la atete te teaaa va p lla i te A U a rl tear a la te . i f t e aalA m I I m IA* te a l 11 a a lU a lia r te teA raaalrai Ite a rla -- te t te a teftac Ite* d i af I I taalA te cal tal* aaaa a rl af ateca. te . team aafawa la Ite Ita la v ite aatealaa te te R r. Vateal* a f Ite Malr apal l i n Illa laMraaaa *,. teA antea!al a* Ite teaaa ana lla a aaA aacpalai Ite l te . Ipate atete ate m a f Ite lafaraallaa teataaA f r n teaaa laala la aaaaaallaa li l i te ate te te te la atete la a la rla !, te . team afraaA Ite l tela alpte te Ana. Mr. W ater'm tete It e l tea aaacaar te a A a fia ila Ja l la Aa U CnaAa la affaal tea affaala a f a la l a f im |cm I 11| teal tea la n Aaaa te m a lla la Ite tem fal affaala a f a te te la te , a te te teraaaaA Ite p ia l tete a ra ya rl I f praparai V S r . ipaak alaac tea lteaa n illa a i. aalA te a f a ^ U tel# la Ite a i f . < - ... ; B afarria I I r . lp te l'a r la ln n l I D r. la a n it e l te r a li aaa i f tea a a ta rU l a n l *1 aaali ha ja l la l *jahlUtehla* fa n Mr. B rna a a llte a it n lln la a a ilp a ila a la aar am agaanl tete !* Imaaaa lahaiataiy tela* yraviAaA It e l Item aal te m p a h lln lin af Ite m a l! a f v a ra te la v ite n ! r ate , la aal, i f &t lata tira a l la te Ite aarl af rapar! a aalA te |1U la t e j*hUa*ai. te harte te . Iu k m il aat laaWA p ahjaallaaahla ateateal ftea a r pala af la , aa. fa r aaaapla p r* l- tia a hatean aatealaa Aaal te aaaaar aaah aa te rtearaaaa h ite Mr. Cateaar te aala la tela la hla aaaamp*. I M . It e l raa I tea p Ite rapar! aaatalaaA ana t e t r U l teal n a a 'l la favarahl. ftea n r paite f rlav* a l i l i vm l prahahte * U lia c la U va i i patate hataan f Ite haaaftl 1 te p la a i frva Ite hatea a f Ite rpn* S r. U a ta aaaaraA Mr. t e a Ite l Ite ta lta l af tte te a ln n l la p a a lln aa Ite l aap raparl praparai h| la . Ifaafc 1 4 flrte te n h a llla A la fahaa-Maavttl hafar halac -- yahlla* alaawhara. Mr* W ater aaam lte Ite l te va lia * ! vaal I aap raparl n u W iitt tk w n U paraaal pw faal*. 1 a n ll.a a A Ite 1<M Aaal aaaa tete* hai han f ila p U irt te im a r a l Aatealaa n r t Ite paal I n a Ite ra jaam . a ll f M iahteA han naaarU r hraaa n i , n i aaantai a pn Ite faal It e l hla p ia d a a tln ith raapaal a a ll tete f Ite aaaa teA teA n A ra r f f n l ateta a n u ltr p la to a i aaaraai. a Ite ra - aaiiaa hai han aaa t o |*A Mr. VaaiaK r n iih ! Ite ! Ite a ia lh a n , tevarar, hai laaaaA n i p ila ilffa ra a U r la ta l i AaralapaA te l Ite ia iin a u l la ra lrn a vaparm i tera a n i ( m p a u l palhalaciaal ahaapa, hiah ha aal han faaai la Iha alhar a lp * . U r l u aaia ite r t i w i i t t M f, t m t fav t a l l i im I m i im i t a f r a I i I n I n U m m . l i t a a n l ita t a u m t a i f n m t a ta hai f iU m i ttaMMfk |MM A A t a i l l i p a y taA tam m uta f Ita in t a t t a ta M ta ta t a l, ta l ta a ll f ta ta ta taA fta A Ita t a lM i ! ta l tata ta fu lta I r i l t a Im m , t a amia M t a 'i I m m , ta l m ilit a , i l , , A m m taA M A ftota AMaalaala M m & la ii ta h h U u a lu . H U g t a t a ta Ita fw rw m ta Ita l u tami I Ita to m a lito w la y , ta a t t Ita i t a 1 a ia l a i la a a i m a a r M i'i ym jaala. w Ita Ita ir a t o ta ta 1 aaaaaruL Ma taatoiatm ta taa t a l i ta Ita tu tta ta aataala la a* t r a i l i mal i a aaA y a to U r ita f u i ta aarttar t r ta fam i U ita M M (ta t . It a t i I tata aa I t o t tta t o it la ta Ita -* -- 1* a flm Ita a a r t a a li tara la ta ita Ita Ita m alr ta la a H ta Ita , Ita m laaia a M ila ! aaA tta iv r a r t n aaltua* fa r lu t a , a r r a , Ita aam laaa ta a i a t a H a la U t ara a m r a iy ta ta la m i Ma ftaAlaga, ata tta t Ita M H a t. * k , laaaa yalA a A ita trita la la I r , 1 I , fa tta v i, ta la a tt M U | tra tta r ta Ita m a la ttia , taa ta M a rita m n r y aaa, m IIA fatolrltaal ta aarm rata Ita taM*a. M ay ta l MA a m y aamtf rt t n a lt f lt t a l araam I r tta aau a fIa rta U , ta rla Ita a r ta hai aM lata Ita aarrla a aaA la i f ia t ili man t i m ta a i af maaara fa r ito I m i, I r , l aaaa mla ral i i l Ita l ta u a la la luaaa a ma tta i -- t ir af Ita la tla a a i la aaar ta a M tt. ta Im iU la i | M m ta k r a a l aa /aaaaiy l i t i , aaA aa m i tia ra ta f i M a ri ta ya i la u rta a ia Ila la raaam Ila t a iiu tia ra i l i a lilla a f tra tta r ta ta ti f Ita latoratai? Xf ta la ta , aa af Ma fata i l i ta la tatala Ita ta m ilaa t a li af a tla la fla a l m la rla i ato IM aafiM 11 %m A la tita r a i am la a rriva la a * la taa U taratam , a l Ila a a ita* H a i ta laaaa r ia lia i l im i , m A la , taa, la acmaA m Ita a a ia rla l. m a L m m m || t|||M ||flf g |M | ih m m A i A A lila m # iA Ita tata lf |b m I h a|a| ram af Ita Jah aarar l l al ma, taa tla r ara t t a # , IM tr fa ri f Ita iah la fia ta ta aaA ita f am a m flu ita r Ita m M ilit ila laaA la ta l la alaatag ta la ra a ll m utata la w a Ma vaAr, t i I l i ara a la i af ita a aaA In a ila Ila ! t a li ta la va lra i la rim ila a am m a, fris a rti? Ita yrahlm am la am f a ttlm a a # m aa Ha taa tatorla af m ali, aaA Ita l la a la la Ito a a u lla ra U a Ila * ta ta n a la ttim i af t* . la n a m attar taa maakla ataal ila tu tta af u lu la , ta ra farra ta m a lia i l i utaataa, ar IH U t u u u u t a r li, ta h a aaavarai H a i .la ataal ta tu a ta ti t a r li. la aaaaaailaa IH Ila amarkamia a l (araam I I I ilaimaaaaaa a rti, ta ta t a a ii la bai favai Ha u lta I ta Oaiiam 'a taalw M lla, a m m a li la la a ia i fa r a m pari la Jth a a -ttu v ill, B r, Imaa n y lto H I u t a riti aai taaajM l i a lta IH Ila la m ai Ha ta y, u fa lla m i 0 Ita lia H ra a # H a m ia m i raaarta af ta taa ia tr, 1 fta i H a i Ham vara 11 tifa rm i aarlm af T a rl atal a m tm tr it a i a l u lu la u la t h laaaaaau t a r ili Ham la a lla l m arl a u la IH m ia m m a rti, a la ta ti t a r li, aai fia ta i aalata. Ita lia la tta ta t u a rU ta 1T1A iaram V . fama fra ilU t IH la v a rti la fia ta ta li!. Sf u rta U m arni, Ham la Im am lm la ivyM a lia a i fia ta ta li!. * lia i la u ta IH ila a la ta ti t a r li a iu ta i a fa ta ta li T , IM I IH 100 l u >Im v &H 0 m m im J m M IH a v lu 1 t o lu t Ha la fu u i l a a rm a rti, A flm r la iila t im i , I r , k H a a r r u lla H a i Ha la va Ia ita M t a li a tti la ta mm a sla ulva Itaa rlfta a U i u tm u ta i.  a n v iv lH r ti tilg vaiata*! w t t vttk Ii M Im h I IM a l i p lw figa M iij ta fia ta tu > w r w ftitfa t ilf c il . km M l N y ita k U U A li aa t t i a rili a la ta ti vtth m Ai aafc Iita la llra m attam i rat* ir M m H tl g ito y i| i y m im ta ^ m w I l ikm l i ta fM lIm it a v v lt t ta m ii tatarataa. m A . ilt a m m .! ta m ii ta fta lm ta u t ratara* v ili m ita i ta ta U ta mm ram i aim latalatlm m ta ita i ita % fla ta ta h t ta ita It ft a t a i ta* tallaatlaaa a n m fa r tata % fl* atim latra M a ta i t a t a ia .' Uma fa it IM ta* aaaalmalaa m ita ta ta* mi* ta ta* a ffM t tta t ta* Ita lm U a u ara taat ta fia aUaalataa tatavai* tatarata* aa* tata* fia ta ta la ata aa* ta* fata f tto rapata that alata la* a* aia* am ava M . Im a* aa* ta ta fa* il* piai** aa a haw au k la* m il ta w fita*taf**a la tita ta aaaala alm v a ili ta vaataai ataat hla ata ta atatal tata I t fvata hiy m a li tata it a li ta* aal a f ta* parai ta ttoaata tta tavhaialaa ata taa l i t a at tta M ila at atavia a ll lama ta avar a hla acpavlaaata fav tta vaat *f tta yaav aal V tta tta* ta ata taaaata. tta pattalagUt v i li tara haaa M a ta aataha* v ita Ma la tavpratatlaaa at taa a illa * , ta a lla i tha Jtaa ta va a ll ta ra ta lit a ta mm ata tata fra* hla tv ip ta tta *a ta lk ta laarara a* ra ra t taaat paaaftt* M ataat taa flv a t t r tta* . ta f ia at i Va aa la fa ln r fraa ta atlaalalaa tahaval a la fa ttla a ' v ra lta t that i t raa aat ta l tl avallarvi a ravy a r r im a i WM aa* arUaaaa that a* ta tatara tta laltaatlaa* ara taa %flu i* tta la ta 1r*(tatara1* fla tta ta laas* *J II t aa ta ta ltta a 1* ta m a lra aal that a* la u ta aaataat i f i l w l fratta* la tta r tta* rhai raaatal aar mah aaaalvalaa hlaaalti aal ta laaaa aaaaaval ta tta vapatlr* > ifm i M n at H I U t * ta l praiaaai Mm N N lt i m i ta f la fli to M i r t i to t to Al fMf M SS to feto. ' to to n i ftirt tottoft kapatattlita. ft H m k i t M m a l ir t it o i f t o t M it o tota to t fa ra i rap a ra to I t I to* to . arato a rtiH * l M tto l to . r i m to t a r r i to r M ito n H a r t v ita to t a ra vi f t o lt o A 'M a t ' arapto feto f ir n Ma ito a la m I , ia fa lla rla to to t Ito . Sa to t m lp a a i m b la v a flo r a a la to a a la rla l a i fa ra i a a t* raaaltol ran rat a i k a p a fM llta ta ftt. la toav. ftra la fa n ! m trto l a lto tola paratal a f toapatoM Uto. M ia la i a f a i a la * . to. B araitto aaataalai. toarara, t a l ila fciftrt aaiarlal--la tolto a ara1 Arato la i tara aiirltRiai. arti tara la a prato* al i Iffarra! ra v a ta fina %fla. a ila iranaiara ai afeapaiaWUia li nafta a lp i lava W a mira tota la %fla* ai fra tftfta r a r a la lallavai li toparia f irp f aiatUto ila narra la fa aa T u a a a frto l ara a m aa i I r . B ra k a t tfta p t l i toa a li la atoakU a ta i to a lla v w aai ila ptfw lelelea l ffa a i la aran i lp ila paaitola in f ila toa i Ito a ira , i r t r t t a toralaal atoarap af ila a l a t i . ftr. Taira Ita m i ila i ila aa laaia a pratoai pr iM a a ila affato aaafcaalaailp. V it i aplarlala ila i ato la ra lly U v a , la w vra . la a a li ila fta ra ila p aia la rara a to lv ila p ara. Ila la ra n ila i a toa i ila laatalalra a l avara ir t a ila % fla pavra p ia i aa la a ra i I l Irta la v a (to lto 1 ila v a c a i a n a t r i v a i), aai D a i l i laa aaap p a rtia l alaaa la l i . la p m ta a i, lavav a, la ra lla V la m a aai U f U to to lra l i aa a a i lato aa l i aa m a lv a i. to a to ir ap ffa v i la i f r a aaia V aapania l i aai ma tifa m i p a rtia l a la la toa tato f a ra ? tarata. a l, toat la la lla v a i toa iaaftnalra a ra li vatolaaly Irta n ta a t o t tla ararapa partial* alaaa ava. aliaf vaa asaraaaai. Ir a n , ila i ila ito iw rta lito a f aval fatoa w a ll lava aa affato la *^`*1 * 1 ila tatotortal tp tt-- paa ilto a i laipaa ra toa apariaaala te la aaia a l la m a . B a ll flaa aai aaavaa atoarlala ara M a lv a i la ila r it t a a ffra lito T ra , aai i l aa fa ll la i aa I t o l i tlaa aaai 1 lato la a lto la a ira ia la a aa t* toa i rato la iaaa ia arai vai* Ila ia to a lita !laa a l Ila i p ia s i. Baiar farla II* arati. * laaaa affarti Ila aarvtaaa la a apaallp toll# a toa Vati aaai itola f a sat fata m i l a, la aa taratati f toa aaapaap iralra la aaato* atapairai TaalllaUM h t a w ai laapaa. la ali la aalikaap tota la alai aai Ito Ir. Ilaaataat k m li la a m araaaa appltaaat tota la ali raara*  li m * w m IH M ! m hwHH < tt Pala M t t a i M A I i t N l A l l H fe p il l i ft MTMTMlftM lllM Itt k . Iflftftft feftft Sft ftftftU t fi k C M P M V M N U M la. > h M H H Wilia ftM w Mr. M M t M M | n M l r i U T U t t la iva a ftM ft M H ac feft k M f l MT h f t w r # t*m . i i m ftiani>i-- ttrtanm>iwirt m i w i m iwr m Mm la la i I m atta M M aia k M m ' i flla a . a U aa tta w W > H a v m I h n ta ya tp a ift a laNaaa. I M U m v m m ! p a a f t U P M a y p m l* f t a f U l y a ll H l I I m U n ir t la i . M a a l I M . M H . a f p ria Ma aaa f i M a p la lM a f IM ha>MU. 1 "H " x a v m CJ JCZ33IK HLD JJUKLLET 21, 1547 17 0XXLLL E m q Q IS n Z j TO ZK SIT3 iXD DU078S ixpcki or Z9U ju J* m m h . B n m n r i or r u j o a a o o i m n doit n m n o r a , U DZTEBXim d H J Z3CZST DLL? TO TXS BUUJLLC LiXOiTCKT P n m i voroi 1 . / k m Y. Lm i-. I* Tiahar 1. I. Ilmkfl T, Srevm 0 . V, l i t * 7 X, Ira ttro x g H M Jaahacx J* i+ Earn11io n J 7 Yoodard - Hr. Yoodard aorrmd aa chairman o f tha m atting. P LA IN T IFF S EXHIBIT 'ML'VDiJf <>Pninr & * m ooting v u aalloA to o r ia r a h c r tly a f t e r 2 7 J U lx JLX* T iihar* o f f i c e . I t a gen ix b * i boon prepared, tha s o o tin g p r im a r ily haring %Mt c a lle d fo r tlx parpoae of hearing a r e p o r t by Dr.d* L k u a ( s i Ik* K r tr p U U i L if t Insurance Company, r u s a a r iiiig tha j x i m t l U t i i r f I k axparlmaxti v i t l i i i l n i i m i earth k th i S m u s k k r t l t r r . The chairmen diapoaaed -v ith a r r r ir v o f tha in d a o tr ia l hygiena problona at Lcnrpoo vhiah k i been eortrod lx a p rrrlo a a s o o tin g , and l x r i t e d Dr Laxxa to f i n a report o f tha ln f o r s n t io n v h ia h ha had gathnred ox h i rooont tr ip to tha Sc u m Laboratory. ftggrt yz, Dr. Lau, 0001199 Dr. Lanza rep o rted that during h i t recen t v i s i t a t Saraxao h* had h a i a c e o ti to a l l tha senoranda and not l o f t by tha la t a Dr Gardner, aad ha had talkod v lt h p r a c tic a lly everybody thoro vbo v u eoneem od v i t h tha vox*:. fo r tu n a te ly , fir Gardner had had a r o ry capablo oocrotary, h a t, n n fo r tu x a to ly , aha had verfcoi fo r h ix r a ly approxim ately eao yoar b efore ha d lo d . Y hlla har ova knovlodge o f tha experiments d id a a t go hack beyond th a t y oar, oha d id hart a t har fin g e r tlp o ev ery th in g th at had happened daring tha yoar and oha vaa a lt o ab la to p rorid a fra*' the f l i t s u b s ta n tia l lxform atlox la eoanoetloa v it h a r llo r exporinoests v ith a e b e stee . I r ld o n t ly , Dr Cardnar had p la s x a d to la ana a ooorprrhanalr* art to la ox X sbestost l t o o ff a c t o s a a l s a l e , l t o o ff o o t o x human b ein gs; a i tr o ll aa ralatod resea rch probisms, prod u ction problems, tha o o a tr o l o f daat la d iffo r o a t kinds o f lad&ttrliJL plant a, o to . So had p r a c tic a lly flx ith o d tho part o f h i report dealing v it h tha o ffo o t of asbsstoa d aat ox human b ein g , and had an n ota to d \th a root o f i t , making rough not and comaont*. . ' * r Lanza v ro t* to Dr, Kenneth Lynch a t tha Hodl e a l School lx Chariot to n , 3 , 0 . , vbo had oox a aaooiatod v i t h tha la t o Dr Cardxar and h im se lf ox a l o t of th o o a r ly voik ox asbootoo c a se s , lnformod Mm o f th a s lt u a t lo x aa ha had found i t a t Saranac, and, a t f a r aa b oin g abla. to prorida smooth oop iss* vaa cone m od, to ld him I t had boon arranged to hare tha la to Dr. Gardner's a rita rr **v * -------------- `J" Exhib Irr. L a k u U f a r a e i Pr. I jx a h tb a t the M t e r ia l tU I V fe r r m r ie i t i k ix u n u U s la ahape th at Xa r l l M t hara te trp te ie elp h a r th U t Pr, O ariA T 1 h u i n m ^ X* hae reo a l t a i & rr>7 i th e f f e e l th a t, a fte ? Pr. IgTusX k i h a i u eppertuait7 te z u l a t k t t l t r l d i he r l l l d etarm lA vhethear l t 1* p e a a lh le te jm.\ 1 tecather l ymVliahahle fe r a . . v p - P r. k m j k u t i l w n n a tr tp te t k Y iit tJ*A.t i V n t th e f n t f Tehrcarr a k i T i o e i Pr. Lraoh th at ho r l l l ajrrtxc l f p e 1X1 te k r 'the n U r l e l m t t i k i i W f* r th a t 11*, Vmt, i k i U i t M t Ve m i ; t h , I t v i l i V* t r u n i t i i i m n k k i . t e r l x c P r. L u u 1! aheeaae. J r . l o a ad he rvmli 1**7 la tcuah trith J-X aVerni thle, ami alee aVout v k t Pr. L/aU M ielolei k est i l vlth th material, la i t i t k tbat thare va *mlt# a let i f material t e i at laaet th k i l i pari--thai damila* vlth tki i f f u t ef u t i f t i i iati oa w.. Velac*-- eeeaei te Ve fa ir l/ eewplete tasi ki Val Irrei lt vomii aafce a eatlcfter? reper. Kr* T. Prova imbuirei ae te vhether Pr, Iman themcht Pr. L/mah vomii attempi te 7retasi tk e itlre veri errarla* ' V e tte ' vhl&h Pr. Gardaer hai hai La alai, er vhether he vomii ooao Ir a te e a lj em th part ie-alin* v li th affasi ef AVestea tut n >* VeLer*; te vhlah Pr, L u ta impilai he i l i noi Varo, ilare Pr, Ijnsah vomii u t Leelie aWmt lt A t i l after he hai reoairad th A tee -- Val he vae hopia* that a ll ef it cauli Ve pmt late eeae eert ef ehepe, Xr. l r m referrei te th terte vlth aeVeste* vhlah Xr. 7ehaal ef th XetrepelltA Lift laeuraaoe 0,, hai eeaiaatei at th Klaee su e tlee a*, aai m**e*ted that Pr* Ijaah al*ht u h i aee ef th lafarmatioa eViaiaei froe th teete, la eaaaaetlea vlth th rark vhlah he le ahout te maiartake. Pr. L u u a*reed that thle al*ht Ve ieae. Xr. Jlaher remarked that th ceapta^ hae a ieflalte J iV te ie la fidisi a te affari th affarla ef a let ef prepaca,ail ila* that hae Veea iea la reU tiea te th harafal affeeti ef A h e a te s-iA t, aai he arpraiaei th eplaloa that a reper, if_preparai >7 Pr. L/aoh aloac th lixea rm tllA i, vomii Ve of-aaterlal halp te th 0 *170 7. Xefarrlxc le Pr. 1 7 1 0 !'1 1talm tal to Pr. Laaxa that he v ia li tee l i th material m t hi* o rali Ve ymt late *putii ahaVIe* fare, Xr. T. 3r m ealled attestlen to a atipmUtiea la our arraaceaeat vlth th arammo LaVoratory vhlah prerliai that there vomii Va a paVlicatloa ef th romite ef axperiiieata vlthemt ear eeaeext. Se aaii, l f lt ieet tara out to Ve th airi ef repert ve vomii Ve * la i te. U t # putii ahed, he hepei Pr. Ljaeh vomii A t lA lu ie aaj eVjeotloaahle xaterial froa emr pelai ef riev, a , fer xaaple, 37 rela tion Vetvaea aiVeatoa i u t aai naaaer, rooh aa th rifareaoe vhioh Pr. Pariaer hai aaie to thia in hi BOAcrcph. le aidei, that rea thom^h th repert oeatalaei tose u t arimi that vaan't t u faTorable, froa our pyoiat ef Tlev, ve r t l l l vomii prohaVl/ Ve v illlac te haT lt putii ahai Veejaaa ef th Veaaflt te Ve calami from th Vaiamo ef th repert. Pr. Lama ai aurei Xr. 3reva that th iateat ef th tateaeat la qmeetloa v a that tx j report preparai >7 Pr. Lpaoh vomii flr r t Ve emVaitted to JohA-Haarllle Vefere Vela* pnxVllehed eleevhere Xr, Jleher oemaeatei that he vemldaM vaat to oee aajr report ea aaVestea ' * theuaeai parcaat perfeot*. Se aacntloAi th lcht duat caie vhieh hai Vom fU e i acalaet th oompmxj at ieVeatee uria* th paat tvo or three jeare,"-all ef vhlah hai V e umaarilx throva out, aai coaaeated upoa th faci that thle timide otloa vlth roepAt to a ll eicfct jf th c a o s hai hai a mirer# effeot vhere coaaroait/ oplaioa va eoAeraed, aa th re- aetiaa hai V e nane toe cooi. Q O O H -Q ^^ Mr. V o o i a r i r a a a r k a i that th- m i n t h eaat, hovrrar, h a i t u m e d out ^uite iiffirasllx, a l a c e lt i e T e l o p e i that t h l a i l r i d u a l l n r o l T e d v a r e p e r t e i to V-r 1-- v Exhibit *0m parslrtsxt t m U < Is earixwrtlsx rltk U daslim ri vltk oalelxsd i Lx*axeecru eacrtk m that it apparmsril/ esmxsd them ax xx- xru d jorptlhlliV y U yxco m ix tad Z4 ( i l i t t pii died lx tks first m t x o i ? ti 1* 4* , rr { l t t j i f i k l I l k tram tkis o u t . B ars v m r t l l l n r r lr lx f 1 1 vith 14 aaxlis axparxra, 14 vltk 7 o t^ w tn i t k n V kaji ax 1 exf u j r u i l a i t l i far s rts7 t u z lxam affeets. 'A fter 10 maxth* sxptrmrv tiu marlarm sifosis at ths oalelxsd u rtk m t ** dstflxlt* fihrasls lx tks lexs, tmt a m a m l Vady resetUx vltk chroalo ixflxmaxtloa sal ixliks thxt ebtxlxad from ths rev. The *kucs t k ix tks lTsjhtia *o [iitk t k t x f l trails at ths i l U M tU t/j m i l lxtcr appear. alx / n ary, 1 W , t k fast enom ttntlsu vers lxsnmx+d r i t l n t mgr set atla t h u {i, This m dsxa far it n i ttn kt that the ixxtar at yaxrsxaxix m rrar. Oma kxxdred axd l i f t aex mar mixta pli vara aided*, 'Ixjeetlex exyariaests ixis soiatals, that Is, Ixtrmrtxsas, Ixrsn>omijar, Ixtratrxchsxl, &xd ixt tka heart, vara a ll aamplrtai seaia eaxsldsnkla tira Ai, lx f m r a l , $1*7 ekav that t ha nar u l a a t m l aarth k i v k t 5r# urtur 1 1 k a ? l i i 4 1st 1st n Xli seal vhlek ( h i ta a tt I yalxta (trTtlxita), Ala oosplstad vira the ixkalxtiom. i z ^ r l m t i vltk ' rsar Otilia, axis cxlxaa yl^fi ixjastad alt* vltk a mili t7ps at taVaral*.' I markad ohms vara akrrx from this n ^ r lM x t ami sa t o l u 7 ta emaxs tprssd at Aiaeas*. *J*y o i s m r ara expsrlants mala cxlaixad aarik vltk Ixtratrackmal ixjeetlax lx riiaea pls a tlx H/fle. J f tks x-ra ? rafraetUx mrthad,. this shave 24} errrtahallts* O l vas tka artk o l s l u i vltk saa u k Ixkalxtlox expsrlaexts vrrs r r l k n vltk ( i l x u pi j r r r l j u ta o y m x i ta tmVarela IxfaetUx, ales vltk trabareis lxfaetlsx. UL after exprare ta tmbsrels ixfeetiex. Sheaa experlasst c r i l l esxtlxxs fax st lasst ans mare raer; als lxkalxtlex axperixexts vltk I f f ls vlthomt asjr added lxfaetiex* The ixdieatiex ara m far that H^fl# atlmmlxtas tmbsrels ixfastisx** It vas felt that the comelusioa ramcha* at tka ead,- ta tka offset that the iadieatiexs are thxt Eyflo stimulates tuberela iafeetlos, vas rxthsr Aisturbln u d vas tks part of the Teport thxt al&ht Its ms some ee&earm. Sr* Israia vas adcd far his epixisx as to hov much time vottld ha rajjairad hsfsrs a dsflxlts ssxslmsiem cornil ha imashad about this, as ha etatad that it probably vomld txks mat11 tka amd r f tks yaar; ha thought ths taohsiolaa vho hxs ehxre of ths dartim af aximala vomld har ta carry os hie axpsrixeate far the re at at ths ysar, o i , by ths time ks cats tkrrok. ths pathologist v i l l hxra beam able ts oat oh my vltk his lmtsrprrUtioxs at tka alldsa. Hs added, that vhss ha ata Vaek fra kls trip ts tks Vast Coast, mWmt ths f i r t t June, hs vould Ilka ta 0 bade ts Sarasas, as sees as psaalbla after that, ts f l s i out yuat vha.t prorass hxa baa* axis. . .r.../, . ,.*V - To ax isquir7 from Kr, Zlsasbxst as to vhsthsr ' ths ixdiostloxs art that `ly f ls rtlmulxtaa tubarola lafaotiox' vas ths 1st Dr* Oardsar1 splxioa, Dr. :Lsxi& rapliad that it vas met, bat that it vas Mr. Dalshax'a imprsssiox. and that "hs 1 ooaaiderad a rsry aiperlenoad max. Kr. Zlsaabxrt laqulrd furthsr vhsthsr thsr vao "y rridsaeo that Pr. Oardsar hxd rexehad as/ rush oeaelualem him1 aI f ( u d Dr. Lasix xsxvertd 1a ths na^atirs. , Xr. E m W i t i I h r i i n * 4 to a p rcricu a raejuait ha bal s a la , th a t Dr, L a x a ehach, f p aaaltla, at l i m u a tho ix c t l ; axptri**ata v llh a tu p i * <1 i < f n m n i a r ih vhloh h ai oaat ram tha Carh a n l a f r a d a r l a i , vhich n i c ro d t i M a la a h m V i'H -lita , a a i vhlah h a i prW x4 tho r a a u lta that h a i U l u t x r o i Lar. flardxar'i t h la h la f . Laarpae haj th lp p a i latarxJL p e v i i n t i C*rhart, W t haa arrar th lp p a i flu x a d a a ls ix a i m aterial to t h n , u b i l u n a < i t aa va hai u r i r i m iha p a n io u la x uarpla a f m aterial la vhlah Dr. Gurdmar f i r a t dataetod e h r n t o h illt a Xr. I l m U i t a l t i t m a f la ta r a r t ta io t a raimo t i l Muye* a a i a r ^ l a a f th a t arpia. **< p r o s /t a i h it la ^ a ir ? aa ta vhathar P r. X*aa h a i f e n i 27 r r m e a ta l t l a tha l a t &r Oardatr' mato*. Dr Laaua viatad that vhila ha hai &t V m tila ta aaka a ohade ra thia ta p ia , ha thaa^ht lt v a l mat Va fiam lt far iz^tM ta Hala tha iIrai iafanfiatiaa. hjr v r it la ; ti l e m a , ai th*7 praVahlj oauli proTlit lt i r tha raoari th7 tMp thar af x V tri ocrrrlx; tha i l f m t H ap lii u k lx axparimaxta. Xr. Jravm txprtaaad icmVt that Pr. Qariaar hai earrlai a 0 7 imatin; zparlaaat vlth tha arpia la {uatlam. fha 'Carhart* ampia hai ; l r a hla tha elua aai, la fa lla rla ; up that alma ha hai a t a l f t ^ n * r Lampo flaxai ealolaai aatarlal aai foxai & raVrtaatial paront*; f ohi7thilita la l t . Ka kaav, vhaa ha femad aatarlal vith thli prentar* af ehr/rtohlllta, that ha hai a 'hai tetar*. Xr. E m k i l eoxtamdad. h m r r r , that tha Carixart **taritl--ta vklch a a ta ' iaath hai Van attrlimtad, orali hara t a n a yreimot af i i f f c m t prapcrtlai fraa l^ fla , ar tha parent*^t # ehr7thlllta lt eaxtaimod il^ht hara han g ra ta r thaa la I / f l l , aai far thlc raatn ha iallrrad lt laportast ta try to artaillah tha ureo aai rlria af tha Carhart ampia. fto far aa Lnpoo aatarlal raa ensartad. Xr. H m l u l thomght lt aheuld ha i i i V llahad vhathar ar aat tha phrvialagieal affaot la emtaad V tha partila alta af tha aat lahalai, ar tgr tha ehaeieal aaha-np af tha aatarlal Pr. L n ta hiarrai that tha aaVaitaa prodawt praiaoaa tha ffaot aehaaleally. Tlth aatarlal that ar h n le a llj aotir, haverar, ha aai tha fiaar tha? ar, tha ara aotlr th*7 ara. Eli impraaaln raa that tha tchalo loa at Sam as tata* tha X7I perdar Jat aa ha racaiTaa lt f r a Lempoo (vhleh la tha racular OMaaretal grada), aai that lt haa aa27 p an lela a l a la i t . la prelaai, hom ar, ta vrlta te 8am as and isquira vhathar it raa mead uat aa. it vaa rocairad, ar vhathar 27 ffort had bata aada to aparata it uuL uta iiffaramt partila alta* la tha sa tis; oxparixanta. Ea adtd, that ha hollara! tha taohaloiaa v o l i m tim a lj iataruiaa vhat tha sTara; partila alxaa vara Balief v&a ajqpraaaad, havrrar,' that tha drtarmiaatln af uah fasta vould hara xa affaet is ch&sgia; tha ladnatrlal h7;laa prahla at Locpoo ar tha taparla ata Vais; sada at S&rasac. Soth fia aai otaria aatarlal ara IxtoIto la tha prohlaa a ffa o tis; Lorpoe, aai it vaa f a lt that ma forthar tima atad ha loat la coala; to a aelaloa ai to vhat auat ha dona to rostral* th* ix jt ltustloa at that plaxt. Sl.t.flac iafo rt loarla; tha tis ;, Pr Laxta offarad hit aarrieoa la ugr capaoity vhila n tha Yast Coaat darla; tha xazt fror roxtho. Ea vaa lxfaraad af tha cc2pax7, t daaira to os^ l; a eorpatnt Taatllatlou Xaglaaar at Loatpao. Ea aald ha vtmld htap thi tx mixd aad lat Xr. Xlaanhait hasv i appllcaat vh*n ha cernid race*- f PLAINTIFF'S I ' I \ EXH1B1T II II --------- I nnm9.nnn Yhax aaatina m aaia af tha tart Wok which r i l l Dr. l r . ^Isumu r f Lm ii jn m lly ksav /kxitm wall axi iauVtlaii wamli iia eu a ra^purt that v prrrila far tha kwk amy * * itr ia l t l W lOQi. iaal r i l l 'lilia a a ia ', ami a at Ink lx writixc, Jr . k u rtaiai tkd W with hix. at U i lazu li, hia m n i am ilat w t it t u M ali r i l t i ww t m Dr Xr. Jrvwa { triad 1 Laxca that, Wall ha haTt mb&i Ii i ta talk rith fir. tmart la ixftlaa, ha aLckt m l ta i U s u t vUk kia a m o t r t j n t ha hai sad af a m i ricri ha Vallrrwi iiataucaoui aarth Lai. hai tha affaat af rrtarilxci tr aaalixc fit tW p r H n n t f t i k m l n i i la a atrlaia la iirlia a l wha, i f ha hai W o aa rila& rr a m , wrali hart ilad at a amah amrliar iata thaa hi did. Xr. Xa* ta il La Lrpti Dr. L o n m l i rlait lotpae imriac hia rla it t* tha Yacl Caart. .fir. k i u aaamrad Lim that ha azpaelai it; ami Xr. filahar R U i i t i i that, a k t ha r l a i t i tha plait, La alt I r a axi talk rrrr i k u t r l a l h f ( i m mattar* p i m o l l f with Xr. Yaatmoat, rmtLar thaa vith a (m p af fir ar aiz parplt. Xr, Yaatacxt, La a ii , Lai a M n ixtlsata & k tharwash kaarlaiff ami u xian U xilx af tha whala prahla* which La amid Vatttr impart la a earraraatiaa aloaa with Dr. laaxa thaa ha raid If a larcar group wart called lx. fir. L a in aakai Xr. U r n U i t ta ix f n Xr. Yastaaat that ha pxtWhly m l i r l i it Lascpae aaaatlxa imrlxc tha la ttir part af TaYroary, Xr. Yoadari i r a r k l r , Lamia that a ll that pratamt fa it ftita raliarai arar tha mat*i ha hai Vaaa alia ta aVtalx from Dr. Oariatr'a fila a , u wall aa tha rapart ha hai u i a aa tha iz p ir ia o ti ix ;r < rtu at Saraxac, far It u v armed spparcxt that tha etajaxy would cat practically a ll that it would hara cat had fir. Gardxer mat ilad, axeapt, af eouxaa, hia r o axpart ixttrpratatiox of tha axpurixtata. X. Zaxlltm oomsnni T he Sar a n ac Laboratory OP THE EDWARD L TRUDEAU FOUNDATION Sa r a n a c La k e, N.Y. U o r u.Cakonkr,M.D. DiucTua February 27, 1947 Kenneth M. Lynch, M.D., Dean Medical College of State of South Carolina. Charleston, South Carolina Dear Dr. Lynch: Dr. Lanza has asked me to get together and send to you all pertinent material in connection with the report Dr. Gardner was preparing for Johns-Manville, and this I have attempted to do. In one folder you will find progress reports that have been made from May 5, 1937, through February, 1943, when Dr. Gardner submitted to Johns-Manville an outline of a proposed monograph on AS3EST0SI3. Attached to the monograph are various data identified with it. I have copied from Dr. Gardner's notes his comments on papers on the subject by Dr. Gloyne and Dr. Kerewether, also*two outlines which may be of interest to you. There is also enclosed a draft of a paper by Dr. Gardner and Mr. Donald 5. Cummings; apparently this was to follow the 1931 preliminary report referred to which was published in The Journal of Industrial Hygiene, Vol. XIII, No. 2, February, 1931 (reprint enclosed). I have included considerable data on the susceptibility of animals to lung tumor, since this has a bearing on the AS3EST0SI3 problem. Dr. Gardner intended to carry on further investigation in this connection, and undouotedly his successor 'will wish to do so. In a second folder are a number of reprints, and in a third folder, the illustrations Dr- Lanza used in his book. "Silicosis and Asbestosis." All of this material, of course, we would eventually like to have returned to us. There are many gaps, I know, and if you will call on me from time to time as the need arises, I will try to provide any additional data which you may require. Sincerely yours, oC: A. J. Lanza, ivl.D. (Mrs.) Lillian R. 31inn Secretary to the late Dr. Gardner ?.S. The above is being sent to you by Railway Express. Please acknowledge receipt. Progress Reports - iiay 5, 1937 April 13, 1938 December 9, 1938 De censor 14, 1939 Boveober 3 0 , 1940 Decamber 4, 1940 Proposed Monograph. - February, 1943 (accompanying data} Dr Gardner *a comments on papers by Dr Gloyne and Dr Serewe then Two outlines Draft of a paper by Dr Gardner and Ur Donald S. Cummings Experimental data February 2G, 1947 Enclosures to Dr Lynch; UN Public Health. Bulletin 2b. 241 - A. STOTT OP AS3EST0SIS 13 THE ASBESTOS TEXTILE INDUSTRY Special Bulletin So. 37, Conaorarealth of Pennsylvania Depart* aent of Labor and Industry Harrisburg Penna. October 1 1934 - ASBESTOSIS * Part I Special Bulletin So. 42,Cassaonealth of Pennsylvania Depart* aent of Labor end Industry Harrisburg Penna. September 20, 1935 - ASBE3T0SI3 * Part IX and Part III Reprint So. 1665 fron the Public Health Reports, Vol. SO, So. 1, January 4. 1935, pp. 1 to 12 * EFFECTS OP TUI IXHALATIOH OF ASBESTOS DOST OS THE LUSGS OF ASBESTOS 30RSER3 Reprint * THE FOHHATIOS OF THE ASBESTOSIS BOOT IS THE LOSO by S. Hoodhouse Oloyne, K.D. (reprinted from Tubercle. June, 1931) Reprint * THE MORBID ASATOMT AND HISTOLOGY OF ASBESTOS IS by 3. Raodhouse Gloyne, H.D. (reprinted fron Tubercle, JUly, August and September, 1033) Reprint 1 A MEMORANDUM OB ASBESTOS IS by E. R. A. Herewether, M.D. (reprinted fron Tubercle 3oversber*Deceaber, 1933, January, 1934)' ~ Booklet - TEE PS0D0CTI0S AND GRA3DIBG OF ASBISTOS by Johnson's Company Tbatford Hines, Quebec, Oonada Reprint - MARTES OPERATIONS EMPHASIZE INDUSTRIAL HYGIENE PR02HH3 OF ASBESTOS INDUSTRY (reprinted fron The Illinois. Labor Bulletin. February 23, 1943 lasufe) Paper * AIR 3AMPLIS0 OF ASBESTOS DUST, COMPARISON OF IHPINGEH AND ELECTROSTATIC PRECIPITATOR METHODS by J. Wau Fehnel (given before the Twenty*fourth Annual Meeting of the American Association of Industrial Physicians and Surgeons with American Conference on Occupational Diseases and Industrial Hygiene, Cleveland Ohio June 5*8 1939) Illustrations used in book "Silicosis and Asbestoais" by A. J. Lanxa, M.D. February 26 1947 Enclosures to Dr. lynch y]}r) \J March 10, 1947 Dr. A . J . Lanza, c/o Metropolitan Life Insurance Company, 600 Stockton Street, San Francisco 20, Calif. Dear Doctor Lanza: I have received the material from Saranac hut have not yet had time to even review It. I shall do- that as soon as possible, In relation to the present very pressing season, and shall then let you know my thoughts on the whole proposition. With best personal regards, I am Sincerely yours, Kenneth M. Lynch, K. D., Dean. KMLikbp. CC: Mrs. Lillian R. Blinn Saranac Laboratory, Saranac, N. X. f Leroy U. Garoner,M.D. The Sar anac Laboratory OP THE EDWARD L TRUDEAU FOUNDATION S a r a n a c La k e , N.Y. March 18, 19L7 Kenneth M. Lynch, M. D., Dean Medicai College of th State of South Carolina Charleston 16, South Carolina C Dear Dr. Lynch: Enclosed are copies of an exchange of letters with Mr. Vandiver Broun of the Johns-Manville Corporation, which I believe you will find entirely self-explanatory. lou have no idea how grateful we are to you for ac ceding to Dr. Lanza's request that you undertake to bring Dr. Gardner's notes on asbestosis into transmittible shape. Sincerely yours, C MB: AD en c.. Manfred Bowditch Held Director \L> T he Sa r a n a c Laboratory OP THE EDWARD L TRUDEAU FOUNDATION Sa r a n a c La k e , N,Y. Lxroy U. Cahonkr.M.D. omscroit torch 13, 2SU7 Sr. Tandirer Brows, Secretary Jofana-tianvllla Corporation 22 East Loth Street See Xork 16, S, I* Boer Ur. Brows: Thank you Tor yoar letter of ILrch 12^ I a a r ply with your suggestion and an doing so b y /dctyn,r.g to u of your letter and enclosure, and of this rtpiy. glad .to lynch copies The d is tin c tio n which Dr discuss w ith se m ainly th at between fib rou s and toe d ust, whereas Drafting and h is colleagues re fe r to long " Ju st m at they man by those designati rrua is not cle a r and X fin d that we do not hare the o rig in a l paper* King fo r aa extended sta y and I an sura th a t th is was one of on which he and E r. Gardner exchanged n otes, though the paper TaNj7r6bai)ly suboltted fo r publication be-- fo re Sing le f t England* X aa taking etra, to secure a copy o f the paper* D r. Gardner, in Dr* lyn ch , makes the fo transcribed and sent to 1* TheJEnglish eirneed to aabeetoe regard to tuberculosis aprtnfy -m -Verat^ duplicated T n o u r Aacrican plants* 2m cs a s A S s U s tru c tu re / TOoUy iaro^ --, In e rt, those between 2C and 93 u. . crushed to castroy uia Tibrous ylv canse danagi\ the fib re s aunt be lo a r enough so that they T^coup ia t a iy surroun ded, h r P t u ig o c y t ic c a lla * km ol^srfn ^in h a lln g long fib re asbestos darelop la n r cancer. a fig u re azxteen~--ib4os thTV o f the average fo r other csta* JL o l_ 3 f nxra iauLung stiorE fib re rabeatoslim reinp -mng cancer, a figu re seres tins* the average foiTotESinjSSt**"'TBeSe'reeults are"suggestiTe, ra th e r than cooclnaive* '" -- -- - ... ... -- .. -- The bora quotations fro* Dr* Gardner* notes re given n e re ly fo r the purposes o f th is cor re spondence and not be regarded as anything aare* To what extent they say be m odified, in the lig h t o f other fin d in g s, in the final repo rt renains to be seen* S in ce re ly you rs, YBiAD tonfred Boeditch F ie ld D ire cto r *L II M e tr o po l it a n Life In s u r a n c e C o m p a n y On e Ma dison Avenue, New York io.N.Y. A n t h o n y J.L a n z a .M.D. A s s o c i a Mx o i c a i . Dir e c t o r B3LALTH A 2TD V TS U A R S June 25, 194.7 Dr. Kenneth M. Lynch Dean, Medical College of the State of South Carolina Charleston 16, S. C. Dear Dr. Lynchs I hare finally returned from my stay on the West Coast. I am planning to go up to Saranac on July 8th for a couple of days as I am anxious to confer with Dr. Vorwald. Before I go up, I would appreciate it if you would let me know what the going is with respect to the Gardner material. Is it work able and if so, when do you think a report will, be available? With best regards. Sincerely yours, A. J. Lanza, U.D. .Associate Medical Director June 30, 1947 - Dr* A* J, Lanza, Associate Medical Director, Metropolitan Life Insurance 1 Madison Avenue, New York 10, New York* Co*, Dear Mr* Lanza: Follawingour previous correspondence X received Gardner* s material and as well as X could, during the extreme pressure of r working on a large legislative program here, X examined It In reV. latlon to the expressed desire that some publication should be made of It, possibly even a monograph* I came- to the tentative conclusion that the more ambitious type of publication as a real monograph Is questionable, but that the partially completed manuscript which Gardner left oould properly be published as a final report upon the experimental program which so far as the immediate problem was concerned, had been ooncfeted* 'Then I got involved, in finishing up the year* a effort and de cided to delay my deolslon until X could review the question* Your letter came Just as X was turning the matter over in mind again* It appears to me that to use Gardner*s material in a monograph in whloh the writer would have to set forth his own views and add material of his own would be neither fish nor flesh and might be foul, ( to use a bad paraphrase. Although Gardner* s material would be used, the view point would not be his and the writer might not be able to accurately represent him, try as he migfct* Also the additional material necessary would not be Gardner's. In other words, to collaborate with anyone, posthumously, without that one having even contemplated it, perhaps would not be proper* On the other hand to submit his manuscript for publication practically as he has it written, with an explanation, would be to properly represent him* He undoubtedly meant to add to the manuscript, but it is worthy as it stands* a* Dr. JL. J. Lanza June 30, W My present Idea is that it should he sent to the same publication as Gardner*a first report on this study and entitled as a final report Please discuss this with the people in Saranac and let ne know what you. think and it any decision is reached C KML:rJ Sincerely yours, Kenneth M. Lynch, M. D., Dean C A. J. Lanza.M. D. Ok i M a d is o n A v e n t t e N rw Y ork Dr. Kenneth M. Lynch Dean, Medical College State of South Carolina Charleston 16, South Carolina Dear Dr. Lynchs I am very much obliged to you for 7 our thoughtful letter of June 30th and quite in agreement with what you say. I am going up to Saranac on July 8th and will spend a couple of days there during which I will have the opportunity of discussing this subject with Dr. Packard and Dr. Vorwald who has taken over as Dr. Gardner* s successor. I then hope your suggestion that Dr* Gardner* s manuscript be published can be accomplished within the next few months. There i3 a situation here which has given me and others who are interested in the successful continuance of the Saranac Laboratory, considerable concern. It. is almost ten years since various industries began anrami appropriations to the Saranac Laboatory for research in the effects of asbestos upon human beings who inhaled it. In that time, those of us who have been follow ing what was done at Saranac and who have had the opportunity of first-hand clinical information, have learned quite a bit, but there has been no authoritative pro nouncement embodying the results of the Saranac research. This state of affairs is nobody's fault, but it is quite unfortunate. During the war period, as you know, Dr. Gardner lost, through death, three of his chief assistants and could find no replacements for them. His efforts to carry on with all the added responsibilities due to these deaths, I think, were largely responsible for his own death. In the meantime, there has been quite a stirring up of activity on the part of State Industrial Commissions and similar bodies in the United States and Canada, with the result that there has been threatened legislative actions or procedures based upon assumptions as to "the effects of asbestos which may or may not be correct. All, concerned are looking to Saranac for a reply to their questions and it would be an immense help to both industry and constituted authorities if they could believe that some of the fruits of Dr. Gardner's activities will soon be available. I will write you again as soon as I return from Saranac which will be about July 11th. With best regards, I am, Sincerely yours, & A. J. Lanza, M. D M e tr o po lita n Life In s u r a n c e Co m p a n y One Madison Avenue, New York 10.N.Y. A n t h o n y J.La n z a .M.D. A s s o c ia t e M e d ic a i. D ir e c t o r HEALTH AND YTEUAXE July 14.,1917 *r> \ V Dr. Kenneth M. Lynch Dean, Medicai College State of South Carolina Charleston, 16, South Carolina ' 7nr o Dear Dr. Lynch: With further reference to my letter of last reek, X have just returned from a trip to Saranac where I discussed your letter of June 30th with Dr. Vorwald. I think we are all agreed that it is desirable that as much of Dr. Gardner's material as is workable be presented at an early date. It would be best if you could give.us such excerpts .of material as can be presented in one article dealing with asbestos. Please let me know if this idea meets with your approval. With best regards, I am Sincerely yours, <=H4 - A. J. Lanza, M. D. Associate Medical Director i t \ V% July 23, 1947 Dp A J LfiRZfl, Associate Medical Director, Metropolitan Life Insurance Company, Hew York, 10, R. X. Dear Dootor Lanza: I am sending herewith Gardner' a manu scripts as I hare arranged Joined and titled them in a proposed single publication. The: experimental report is left as it was, exeept for the heading Please pass Judgment on the title and footnote. i His monograph outline of human asbestosis contains little if any significant material Ro one else oan write what he intended without it becoming the writer's instead o T Gardner's. On the other hand, the outline on experimental asbestosis is more than that. It is really a summary of Gardner's observations and is valuable and publishable as It stands. I have put a heading on that part, deleted section 1, on "Methods", and renumbered the other sections The whole makes somewhat of a balky publica tion, but X believe that you oan indues the Journal of Industrial Hygiene to take it in this form. If not, let's split it into two. X a m sending the detached Part X of the Out line aide, in order that you may s ee what I mean. Please consult with such others at Saranac as you should and with the Absestos people, if that is in order. Feel free to rejeot any idea of mine which does not seem best and criticize freely. With best personal regards, I am Sincerely yours, XXLlkbp. Kenneth M. Lynch, M. D. Dr* Lanza Page 2 - July 23, 1947. P. 3. I am retaining for the present the other mat erial sent me. Can someone at Saranao reddily sunoly the references in. the manuscript? I am a bit short on time Should Cummings be in this? KML. f f (Prom Dr. Leroy U. Gardner's OUTLINE SUMMARY OF ASBESTOSIS) 9. Comallcations A. Susceptibility to Infection. i. Tuberculous. Asbestos behaves like most other minerals in this respect not like quartz, which specifically increases native susceptibility to the tubercle bacillus. This infection may spread for a time, but then heals. The resultant fibrosis accentuates that caused by the mineral fiber. ii. Non-tuberculous. Of no greater frequency than animals inhaling dusts of other kinds. Occasional epidemics of pneu monia occur in our dust rooms, but these are due to methods of housing rather than to dust; they also oocur in unexposed animals. ill* Cancer of Lungs. No experiments were parti cularly designed to elucidate this point, but certain evidence suggests that asbestosls may actually favor development of tumors in susceptible species. a. In guinea pigs, rabbits, rats, cats and dogs, lung tumors are rare. ' b. When these species were subjected to 2 to 3 years inhalation of asbestos dust, the incidence of lung tumor was not increased. o. Some strains of white mice to develop tumors without apparent cause. d* Such a strain of white mice was unin tentionally used in three inhala tion experiments with asbestos. , e. Of 11 mice inhaling long fibre asbes tos for 15 to 24 months, 8 developed malignant tumors in their lungs, and 6 of them had tumors in other organs. The incidence rate. 81.8# is execessive. / (2) f . Of 22 mice inhaling short fiber asbestos for not longer than 12 months, only 3 developed lung tumors. Rate 13.6g. g. As controls, we have only the exper ience with mice in other dust experi ments. For short periods, there wert 51 mice exposed to 4 other kinds of dust for 10 to 12 months. Incidence of lung tumor 1.9#. For long periods, there were 143 mice exposed to 4 different kinds of.dust, including pure quartz, 23 to 31 month; ( Fagoer ainlclidtehnicse-torfouplunogf mtiucmeor twheasa1v8e,r8# the highest rate (25#) was in a sub group exposed to flint dust. Thus the incidence of lung oancer in the long fiber asbestos mice was over 16 times the average for mice inhaling other dusts for comparable periods, and over 3 times the maximum for any other group. Mice exposed to the pra otically_..^ert_qhor&jCl.er asbestos- showed fewer lung tumors, although. 7 times more than liKose in short exposures to other dusts. These observations are suggestive but not conclusive evid ence of a cancer stimulating action by asbestos dust. They are open to several criticisms. The strain of mice was not the 'same in the asbestos experiment as in many of the others cited; apparently the former were unusually susceptible. . Not enough animals survived in the dust for longer than the 15 months ap parently necessary to produce many tumors. There were no un exposed controls of the same strain and age and no similar con trols exposed to other dusts. It is hoped that this experiment can be repeated under properly controlled conditions to*deter mine whether asbestcita actually favors cancer of the lung. The Sar an ac Laboratory OP THE EDWARD L. TRUDEAU FOUNDATION Sa r a n a c La k e , N .Y . bKIW* Wi.8*Miini Mf8. August Kenneth K. Lynch, M.D., Dean Medical College of State of South Carolina Charleston, South Carolina "x / w- V VK . f* I, 1947 i 'r : :d Dear Doctor Lynchr As you perhaps know, I have been released to inactive duty after five years and six months with the Navy. During the past two years of that duty I served as Director of the Medical Sciences Division of the Office of Naval Research. In that capacity my office enjoyed some correspondence with you.- Now, I have returned to Saranac Lake as Director of Research of the Trudeau Foundation and Director of The Saranac Laboratory in an attempt to discharge many of Dr. Gardner's obligations and commitments and to accomplish much of what he planned and en visioned . That task is indeed a tremendous one, yet my prewar years of association with him afford at least some background for the solution of the problems and issues confronting the Laboratory at this time. One of the problems relates to the collation of clinical and experimental studies of asbestosis accomplished by The Saranac Laboratory* In reviewing these studies and related correspondence, I learn of your kind efforts In editing Dr. Gardner's manuscripts and recorded writings for purposes of a report and publication. This matter has been discussed with-our mutual friend Dr. Lanza, who has kept the Laboratory informed by copies of correspondence pertinent to such publication. In consequence, a copy of your letter of June 30 to Dr. Lanza and his reply thereto have been forwarded to m e . I recognize your concern and appreciate the difficulty in presenting adequately the interpretations and views which Dr. Gardner recorded before his death. The manuscript which he was preparing constitutes a significant contribution. Its publi cation alarms me, however, lest'other evidence accumulated in the past several months might have caused Dr. Gardner to revise some of the statements which he recorded at that time.- In his interests and also because of the Laboratory, which must continue as a lasting memory in his honor,.I know you will agree with my alarm. I am sure that Dr. Lanza would concur. Therefore, Dr. Lynch, I would appreciate your comments and views so that our action con cerning the host of studies, reports and publications which we contemplate might be prepared accordingly. fX W Page 2 Kenneth M. Lynch, M.D. August 1, 1947 We at the Laboratory would welcome you at any time should you find the opportunity to visit us. Sincerely yours, AJV:LB CCr Dr. Anthony J- Lanza Arthur J * VorwaJLd,. M.D. Director of Research lhe Edward L. Trudeau Foundation f M e t r o p o l i t a n L ife In s u r a n c e C o m p a n y Frederick H.EcKER*ChairmanofthrBoard LEROYALlNCOLN.Awiaf./ One Madison Avenue, New Tore 10; N.Yi * . A n t h o n y J . L a n z a ,M.D. A s s o c i a i * Mx o ic a i. Dir k c t o r KXAX.TS a k b w i u h i , , rr yjj j August A) 19A7 Or. Kenneth SI. Lynch Dean, Medical College of the State of South Carolina Charleston 16, South Carolina *61 9 9nv jnii Dear Dr. Lynchs I am in receipt today of a copy* of the letter Dr. Vorwald wrote 70U on August 1st. X am not too clear about the * concern that Dr. Vorwald expressed. However, I note that at the end of his letter, he hopes that you might be able to pay him a visit. I am going up to Saranac myself on August 16th. Would you consider making a trip to Saranac at any time soon, possibly we could meet there on the 15th. Iou can fly from Hew lork to Saranac in about an hour and a half, which certainly takes the curse off that part of the trip. If you could find it possible to come, we would be glad to take care Of all your expenses and make reservations for you. Please do not think that I am trying to urge you to do anything for which you have no inclination and if you feel that you do not have the time to make such a trip, or that it is unnecessary, do not hesitate to say so. I have to go to Washington on Thursday so will telephone your office Wednesday afternoon to get your reaction to this letter. With best regards, I am, Sincerely yours, A. I. Lanza, M. D. Associate Medical Director Charleston, S. C., Aug. 7, 1947. TTTT.Efrffa m - straight message. . Dr. A. J. Lanza, Metropolitan Life Ins. Co., New York 10, N. X. (1 Madison Avenue) ACCOUNT SCHEDULE IMPORTANT MATTERS HERE UNABLE TO LEAVE AT TIME REQUESTED. LETTER FOLLOWS. (signed) K. M. Lynch. KML:khp^ 10:55 A. M. C f August 7, IP47 Dr. A. J. Lanza, Associate Medical Director, Metropolitan Life Ins. Company* New York 10, N. Y. Dear Doctor Lanza: Following your telephone call Wednes day morning, I received your letter of August 1 and I assume that you also received a letter from me which was then mailed Because of very pressing business here during that time, I do not feel that I can make the trip to Saranac on o r about August 15. If there should remain a reason for a conference there, it is possible that I might make it sometime in September, or I might at least get to New York City for a confer ence there, ir that may be desirable. Like you, I am not clear as to the reasons for the concern expressed by Dr. Vorwald. However, from the copy of,my letter to him which I sent to you, you may see that I think that the course to be followed should be decided by those on the ground. Without any knowledge of what Is in Dr. Vorwald's mind, I still believe Gardner's material is publishable as it stands and that nerhnpa revision by anyone else might not truly . represent him. On the other hand, if Dr. Vorwald is to carry on the work, it should be decided whether Dr. Gardner's efforts may be merged, with full credit to him. Y offer these suggestions out of a coopera tive interest, and I feel that the decisions should be made by you and him and your colleagues without regard to any other consideration of my participation than that. Incidentally, I wish to offer my congratula tions and best wishes on your new connections which I have seen announced. Sincerely yours, Kenneth M. Lrnch. M. D.. llMIillI .M.B. T he Sar an ac Laboratory OP THE HOWARD L TRUDEAU FOUNDATION S a r a n a c La k e , N .Y . August 8, 1947 Kenneth M. Lynch, M.D., Dean Medical College of the State of South Carolina Charleston IS, S.C. Dear Doctor Lynch: I appreciate the expression of your opinion as recorded In your letter of August 4 apropos the work accomplished by Dr. Gardner during his many years of research in the interest of asbestosis. All of us recognize the high degree of relative urgency regarding the correlation of our experimental and clinical studies for the purpose of a. report for the sponsoring in dustries and for publication. Every effort will be made toward an early accomplishment in that regard. I will appreciate your continued counsel and advice concerning it, so that in final analysis the contribution will be a creditable and lasting record in the memory of Dr. Gardner.. Your letter of July 30 and the manuscript which you en closed have been forwarded to me by Dr. Lanza. He will be in Saranac Lake on Saturday, August 16, and I will discuss the matter with him at that time. Please know, Dr. Lynch, that the Laboratory would be honored should you collaborate in the final publication. This point will certainly be considered at the time of discussion with Dr. Lanza. With sincere good wishes,. Cordially yours, AJV:LB CC: Anthony J. Lanza, M.D. Arthur J. Vorwal d, M. D. Director of Research The Edward L. Trudeau Foundation FEB-13-95 MON 17:18 r ` -Y J F HUMPHREYS ATTY FAX NO. 3043434186 X. ABSTRACT Introduction Asbestos -.ii-ners.li' 5. -Ixperi-ner/oal Jethodf?. 0 se** 17. 3XFERBJENTAL BESTOSIS v-Wr-r^TT 6 . Species Suscerptibij!At 7 7. Pecu~l1fir Charac teristics of Asbestos 8 . Rate of Tissue P-eaction to Asbestos Fibers 9. Asbestosis Bodies .*** ' ,1. IK^lgll.TOEBIKEg? X A c ^ s n - U v s Asbfs.! Kang *s Floats Aabcoteo ^ osx~-- --.__ ^ -- ^ -- 12. 13- Dusting Llsterial Dust Composition Hi. Dust Concentration 15. 16. 17. 18. 19. 20. 21. 22. 23- 2U- Reaction in Animals Guinea Pigs Rate and Type of Reaction Progression Infection Coincident with Dust Inhalation Infection after Dust Inhalation Asbestosis Bodies Rabbits Rate Sur-mary and Interpretation P. 05 n 1. L0. S 5 6 7 7 8 8 8 8 9 9 9 10 10 11 12 12 12 13 FEB-13-95 HON 17:18 J F HUMPHREYS ATTY FAX NO. 3043434186 P.06 26 Dusting listeria! 2t- Dust Composition 23. Dust Concentration - u 29. Size-frequency of Dust 30. Reaction in Animals 31- Guinea Pigs 32. Rate and Type of Reaction 33. Progression 3h- Aabestosis Bodies 35. Rats 36. Rate and Type of Reaction 37. Cats 38. Rate and Type of Reaction 39- X-ray Changes Uo. Asbastoais Bodies 111. Rabbits 1x2. Rate and Type of Reaction 1x3. Asbestosis Bodies Uli. Summary and Interpretation -7,1 iu u r a r cent baaj.-cc.5j^a " o e s i o f u u s u U6- Dusting Material [ a au JM* li7. Dust Composition u8. Dust Concentration Ii9. Size-frequency of Dust *'-- r:---* Pa^e lii Ih 15 15 15 15 15 17 17 18 16 19 19 19 20 20 2C 20 21 21 21 22 22 23 FEB-13-95 HON 17:18 J F HUMPHREYS ATTY FAX NO. 3043434186 . u t. J 1 4. c 50- Reaction in Animals Jj'1. Gui nea. Figs 52- Rata and Type of Reaction 53. Progression 5U- lymph Node Involvement 55. Asbestosis Bodies 56. Rats and ISLce 57- Summary and Interpretation ^ 4iw . 355KT UoMG-fxvo.. *1* J?Bj.-Bene fibop -Aabeatoa Duct-- . - ---- """ 55 Dusting Material 60. Dust Composition 61. Dust Concentration 62. Size-frequency of Dust 63. Reaction in Animals 61x. Guinea Pigs 65 Rate and Type of Reaction 66. Progression 67- lymph Rode Involvement 68- Asbestosis Bodies 69. Cats 70. Rate anci Type of Reaction 71- X--ray Changes 72. Rats 73- Rate and Type of Reaction P.07 ;*aee -o '23 23 2li 2h 2L 2h 25 26 26 26 26 27 27 27 21 28 2 9 29 30 30 '*0 30 31 l-htf-u-db HUN l i i i a J I- HUflPHKfcYS ATTY FAX NO. 3043434186 . P.08 7h. iu.ce 757c- h'.rtt?-?/ a n c t v .? . ..voiu- 7 G t Intratracheal IicpariTnonts 70, Coi-ipi-risor; cf Plbrous oni 30. Ccirparison of rurious l..::-. j>5 31. Ccsnparison of Icz^,-fiber \C. rh^'i-rilw Ja:svs 32. Intravenous J&peririents ^;-.*>d * Iiitro.peritoneai UvTXZV. OT:3T. SffE'liSBlTS r f-- t-- 35. P r o t e c t i v e A c t i o n cf Aliucinuis Cc:;cr;ou-.r-i 36. P o r a a t i o n of A s b e s t o s i s P e d i a s - IT* UDOCT-J^J T H E O R Y 0 * ^ I RI I T A S T A C T I O S ''W f--- f -- I-- \ j ; ---- K-- t i-nJrEnoXinii'X/r-c-0-^-1-1fC A T IC17.V 89. Infection 90. Susceptibility, to Tuberculous I:u action 91 Susceptibility tc Son--tubercu Icus Infection - 3 .GjLj. *tiU iiO JLfU O A 'V-lr: xJ --- ^ yiCTpl, T A B L E ? . -t-*-** T` 32 32 33 3k 3u 35 35 35 35 36 37 3? 38 38 3? iiO u3 - 7 FEB-13-95 HON 17:19 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 09 *3 abstract (' Asbestosis is a pulmonary disease caused^y the inhalation of asbestos dust. In animals if is"Characterize1by ^peribronchiolar''fibrss rhich /\ Y~ } MT**** ' ^ i(seems to be) the result jjC rmochanical, ither than^chemical, irritation of ><--"1 ^ / V / / the tissue by asbestos fibers. the long fibers produce a typical reaction; short fibers (are relative; y inert^u The filamented structure of the fibers is an essen tia l ^factor/i/n th< ^mechan--ism o f irritation*. -,ibiu-schua.rv-ac^ter- is t ic tissu e response can be/produci rd^by non-eiliceotis ^ 3-wsell as siliceo u s\/ fibrous m iiierals. ion of asbestos dust (apparently doee not alter significantly the cr<*. wv *** of experimfntal^tuberculosis in^guinei pigs. The^ H' asbestosis body, rfoldh is a specific concomitant of asbestosis and forms | soon after the entrance of the asbes Los fiber into the lung, is byliVefl^GT I prevent^further carnage to the tissue by the fiber and thus tar limit pro- I {pression of they'reaction -when exposure ceases. Aluminum does not exert a protective action against the tissue irritation of asbestos fibers as it does against/ that of quarts particle^. FEB-13-95 HON 17:19 j p HUMPHREYS ATTY FAX NO. 3043434186 P. 10 2. -- introduction tion of asbestos vest. The name asbestos, literally "unbnrnable, is not minerals Tihose characteristic feature is a structure composed of long, par allel, flexible fibers- This structure is uniq'as because the fibers are capable of repeated longitudinal subdivision to units of molecular proportions- i In length the fibers vary from a few microns to sis or more inches. Sonts varieties are stiffor than, others but many are sufficient!-,.- flexible to be spun into y a m and woven on modified textile machinery. 3- Asbestos Minerals The asbestos minerals are silicates of variable composition and belong to the serpentine and the amphibole groups. Listed below are the more coamon varieties. Amphxbole Group unthophyllite (Kg, Fe) silicate Amo3ite Amphibole (Kg, Fe, Al) silicate (Ca, Kg, Fe, Al, Ma, X) silicate 'I'reiaolD.ts (Ca, Hg) silicate Actinolite (Ca, Kg, Fe) silicate Crociaolite (Na, Fe) silicate Fe silicate Serpentine Group Chrysotile Kg silicate (hydrous ; FEB-13-95 HON 17:20 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 11 Xri.s bulk of tns iziuc ^ o*. coismcjrco jls crury^ , 3 TThich is mined in i'ne xketford region c trie Province of Quebec. 0^ Crocido-- late ana aruonite are also used conrriarcialiy but Li much smaller amounts. ChrysotHe occurs as veiny in serpentine, a raineral similar,' in chemical com position to chrysotilo ,by.t which exists in e s s sirs form aiv\ is made-oap o .____ microscopic fibers -without the parallel orientation characteristic of chrysc-- tile. The massive blue black serpentine, -which is smooth and soapy to the touch, is traversed by veins of fibrous chrysotil varying in width from a barely perceptible .line to six or more inches, lbs fibers run aci'oss the vein and not lengthwise -with the formation. Attention is directed to the mineral brucite, which, is often found in the 3sm formations with serpentine and chrysotila and may be fibrous in structure. It has no commercial value at present because its fibers ere not sufficiently flexible to be used in textiles but they are capable of repeated longitudinal subdivision. Unlike other asbestiform minerals, brucite is not a silicate and for this reason it has been a valuable tool in an. experimental evaluation of the action of fibrous ninerals upon lung tissue. HI K . EXPERJHE2!TAL A3BEST03IS For many years studies have been carried on -by the Saranac laboratory in an investigation of the cause, nature and development of asbestosis. The present re port is devoted to Experimental Asbestos is. In it are described the animal ex periments with various kinds of asbestos dust. Another report, to be prepared and issued later, will bo concerned with dumai: acbestosia ana cove.- tuc u Sm %.. aspects of workers who nave been exposed to asbestos dust in an industrial environment. - 3- FEB-13-95 MON 17:20 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 12 Although esbost-osic .in asn is a chronic e which requires years ta develop, it is possible to reproduce in one or more- species cf anirnai character istic tissue changes viiich are similar to the logic ns of human sabestosi3. Since the life-opan of the experimental animal is relatively short, it is not possible to'develop the characteristic lesions in animals v.rdsr tb.r uyuai -Sntrturoriai-Gaa- ditions. Consequently, to obtain a complete evalv.c.tion ci th-?. t53ue response to inhaled particulate and fibrous material, it is necessary to accelerate the reaction by employing higher concentrations of dust, than voulu ordinarily be en countered in industry Y/hile conditions of exposure are thus different, the information yielded b y experiments T ilt h animals is invalidable in furnishing a better understanding of the reaction of the human organism to Inhaled asbestos dust. 5. Experimental Methods For investigating the biological reaction of the experimental animal to the various asbestos minerals, tiro types of technique have bson employed, namely, the inhalation method and the injection method. In inhalation exprimenta, groups of animals -- up to 1QO or more guinea pigs and sometimes smaller numbers of rabbits, cats, dogs, rats or mice -- are kept for eight hours a day in a cubical -dust room, eight feet in dimension, in -which a. cloud of asbestos dust is maintained. At intervals during the experiment, a few animals eure sacrificed and the tissue examined to determine the nature and extent of the dust reaction. Sows animals are exposed for periods up to three years. The injection experiments. in uhich the dust, either dry or suspended in fluid, is introduced into the animal by the intravenous, intraperitoneal or intratracheal procedure, are used to determine whether or not a particular dust has a potential capacity to produce tissue reaction. -ii- FEB-13-95 HON 17:21 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 13 Long-term inhalation ej^periirjsnts furnish infcrraaiion upon wliich grsat reli ance is placed "when estimating the degree to rhieh a dust might be hazardous to industrial workers. Whether cr not atmospheric dust., even though potentially dangerous, can be inhaled, pass the natural defense barriers and reach the pul monary* tissue in quantities sufficient to cause damage can be determined only by inhalation procedures. Injection experiments are useful because in them, contact between the dust particles and tissues is assured and the potential capacity of the dust to produce reaction can be estimated accurately. When dealing with fi brous minerals like asbestos, the intratracheal method is valuable since it per mits observing the effect of the fibers on pulmonary* tissue. 6 . Species Susceptibility Unlike free silica, asbestos does not exert its specific effect in all organs of all species of animal (Table l). Injection of file quartz into various organs of the guinea pig, rabbit, rai^"Vat^ dog, chicken and even tadpole will produce silicotic nodules. However, lar injections of long or short fiber asbestos have resulted in a fibrous reaction in the lung and, to a lesser extent, in the peritoneum but not in other organs <** JUOX."i. JUl fl intlfa luu. V 7. Peculiar Characteristics of Asbestos rtr -- S fr iifin T V Experience has demonstrated that most of the particulate matter inhaled into the lungs of man and animal is 10 microns or less in maximum diameter. Larger particles apparently are excluded by the protective mechanism of the upper respir atory tract. In the case of ,fibrous materials, however, this restriction does not apply and fibers 100 and even 200 microns in length have been found in the termin al air spaces of human lungs. In ""all laboratory animals exposed to asbestos dust the maximum length of fiber found in the ltmtj rarely exceeds 60 microns- Not every kind of fibrous material is inhaled with equal readiness; for example, FEB-13-95 HON 17:21 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 14 the synthetic .fibers of -.cool iryy.rent.'-y t:.v. toe inx'isrtlble to y-aas easily through the nose, pharyrre, tracrea a-id bronchi and s&ldo.vi reach the terminal bronchioles and alveoli. Inhaled particulate matter coir.es to rest throughout the terminal air spaces (alveolar duct, afcr-ia,-alveoli) in all parts of the lunt5fis inhaleaFfeabsetca-- fibers are first retained in the respiratory bronchioles. These very small tubes are immediately distal to bronchioles lined by ciliated epithelium. Their oun essen tial lining is a Iot? cuboids! type- of apithcliura but. as their name implies, they actually function in respiration through lateral alveoli given off as pouches along their trails- Either these pouches, or ths abri.pt change in the character of the lining epithelium, or the decrease in diameter nf the tubo, or perhaps the combination of all three factors is responsible for local retention of the inhaled fiber. Only after aabestosis is rell established are appreciable numbers of fi bers carried into the more peripheral sir spaces. 8. Rate of Tissue Reaction to .cbs3tos Fibers The rate of tissue reaction to asbestos Is much more rapid thin to an active dust like quart*. Evidences of tissue response appear as soon as fibers have localized in sufficient concentration in specific areas. In rata receiving asbes tos fibers by intratracheal injection this evidence is visible os early &3 two weeks after injection; for quartz dust the latent period might be tvo ircrtcm or more. The behavior of the tissue reaction to 5.nhalea oust after the termination of exposure is not the same in pilicoaie aa in asbestosis. Jn silicosis, the young nodules become larger; in aabestosis, young scar tissue,that may have formed,con tracts and becomes more dense but the area of involvement decreases in size- Xf exposure to asbestos dust is terminated after & brief period, the recently--inhaled FEB-13-95 HON 17:22 J F HUHPHREYS ATTY FAX NO. 3043434186 P. 15 fibers in the lung may cause the fibrous tissue response to continue for & short tiras, until the fibers have been coated. This progression is of only a slight degree and of little significance. 5?. Aaboetosis Bodies ^ ____ _ The peculiar structure known a3 the asbestosis body or curious body is a speed,fio concomitant of asbastosis. The typical body is a golden-yellow, beaded or haustrated rod which may be either straight or curved. Often one or both ends are bulbous like a dumb-bell. The bodies vary considerably in length, and di mensions up to 250 microns have been recorded. It is believed that aaboetosis bodies are due to a deposit of protein and iron pigment upon the surface of inhaled libers. In guinea pigs they form after about 60 days of contact with the tissue. They are abundant in man and the guinea pig (see Table l) but are much larger in the former, probably because the larger- sized sir tubes admit fibers of greater dimension. In cats, rabbits and mice there is an atypical coating of a few of the fibers after much longer residence in the lungs. In rats and dogs no bodies could be discovered. Although the evidence is incomplete, it appears that the formation of the asbestosls body prevents damage to the tissue by the fiber. Vxevc myj. /vetcvp-fj. I. .DKAIAIION EXPERIMENTS '-- jfri-- -- *-*-'* t Four comprehensive inhalation experiments have been conducted at the Saranac sS' Laboratory with various forms of asbestos dust. In each of these investigations more than l60 animals ware used and the experiments were carried on far periods ranging from 2 to more than 5 years. The four kinds of asbestos dust employed are Identified as Ring's floats, s h o r t , fiber, 100 per cent ball--milled, and long-fiber asbestos dust. KEB-13-9b MON 17:22 J' h' HUflHHKtYS ATTY FAX NO. 3043434186 P. 16 ' ^bc.tos The first inhalation experiment conducted at the Saranac laboratory with asbestos dust was begun in 1928 Animals inhaled the dust for periods up to nearly three years and some guinea pigs lived for about four years after their months of exposure appeared in the February, 1931 issue of THE JOURNAL OF INDU STRIAL HYGIENE . At that time observations covered a period of only 2-l/li years and the conclusione as to the ultimate effects of inhaled asbestos QUBt were provisional. Results of the completed study shop that most of the conclusions drawn in the preliminary report were substantiated. A complete review of this experiment follows. 12. The dusting material mas a commercial variety of asbestos dust known as King's floats and mas composed of short fibers and particles of variable size. ` .......... * Corporation of 13. The dust composition (Table 2) reveala that the amount of fibrous chrysotile -was only lit per cent, a rather low value- However, there was suf ficient fibrous material to produce a characteristic fihrosis. ill. The dust concentration at first teas quite low and for impinger samples taken soon after the experiment was started, the average light field count.- by the standard technique was only 6.0 million particles per cubic foot of air. An appreciable number of large particles (or fibers) also -were present, as STUDIES ON EXPERIMENTAL PNEUKDC0NI0SI5. VI. Inhalation of Asbestos Dust., Gardner, L.U., and Cummings, D.E. J. Ind. Hyg., 1 3 '-6$-8I, 97--llli, 1931. - 8- FEB-13-95 HON 17:23 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 17 shown by sr average count of O.o million. .for particles greater than 10 ltdcrons. After the inhalation experiment had been under way for about t-*o years, the speed, of the rotating paddle in the dusting machine was increased and for the remain ing 9 or 10 months of tha experiment considerably sioro duet -sras dispersed into the- atmosphere - Average- crust counts for impinger samples 'collect'<^'Xtef'ihfs~'" change were 53-7 million for tha usual light-field method, and l.c million for particles larger than 10 microns. 15, Reaction in An.ims.ls to Inhaled "King's Floats" Asbestos Dust. Results of the investigations briefly summarized in Table 3, ahow that inhala tion of King's float3 asbestos dust produced a typical peribronchiolar fibrosis in guinea pigs but not in rabbits or rats. 16. Guinea Pigs, Seven groups of guinea pigs -were used. In three groups . the effect of a continuous and of an interrupted dust exposure -was studied; in tiro other groups the relationship between infection and dust exposure -was investigated. The remaining two groups were infection controls. 17. Rate and Type of Reaction.. Guinea pigs inhaling this dust for periods up to 33 months developed a characteristic fibrosis occurring in conical patches about the respiratory bronchioles. During th3 exposure the peripheral alveoli were not involved. The particulate elementar-^ in the dust were transported to the lymphatic system where they caused no signi ficant reaction; the fibrous elements remained fixed at the site of original localization and were seldom detected in the lymphoid tissue. Pleurisy and fi brosis in the septa were observed only when infection complicated the process. After exposure of approximately a year, a small azsount of cellular reaction had been produced about many respiratory bronchioles. As more dust was inhaled, it continued to accumulate in the same location and later stages of the disease FEB-13-95 MON 17:23 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 18 consisted of extensions of ths original lesions. Kawr areas were rot involved. Apparently, the inhaled fibers "'ere caught in the pocket-like alveoli that are given off from the lateral nails of the respiratory bronchioles. There they wore phogocytised and many of them were carried into the toO .1 by migratory cells. ^johonuclear leucocytes" attracted to the area caused an ppr<^i^l.el:llicKan'inE- of the bronchial wall. After 16 months a delicate fibrosis made its appssrancs- The process evolved so gradually that mitotic division of fibroblasts could rarely be discovered\ nevertheless, the number of fine intercellular collagenous fibers (fibrosis) steadily increased. As this fibrosis contracted, it partially closed the alveoli, and with this atelectasis the lining epithelium assumed its embryonic euboidal form. The result was the adenoma-like appearance that Tiillis described in guinea pigs inhaling silicon carbide- The longer exposures resulted only in more thickening of the walls of the air spaces, largely due to an in crease in tho amount of fibrosis. The fibrous tissue always remained cellular and never showed the hyalinization characteristic of silicosis. 18. Progression. The reaction produced in exposed guinea pigs did not pro gress significantly during a subsequent period of 37 months when the animals lived in a normal atmosphere Between 8 and 11 months after exposure ceased, the cellular reaction had been completely replaced by thin strands of fibrous tissue. Observed still longer, the scar tissue decreased in amount but in the last animal sacrificed, 37 months after discontinuing dust exposure, some fibrosis was still visible*! ' 19. Infection coincident with post Inhalation. Of the group of 10 guinea pigs infected with alter.-- uatu strain.! 31 died or were sacrificed before two years of dust exposure and were reported in tho paper by Gardner and C-unmiings mentioned FEB-13-95 ON 17:24 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 19 above. Seventeen of these died from intercurrent pneumonia- Briefly, the re sults rere as follava: 10 revealed some evidence of sprs3d of the tuberculous process; in 6 of these it vas confined to tha lungs and in the other L the abdominal viscera also -were involved- Usually a slight local extension of the tuberculous infection-hod occurred but subsequent healing heb-resulted-'in~id> brosis of both the pulmonary lesions and the secondary lesions in other organsThe healed pulmonary lesions shoved more fibrosis than is characteristic of either tuberculosis or osbestosis alone. The 9 animals, which were still alive after two years of dust exposure were sacrificed at intervals during the following year- In U of them the primary foci of infection had healed with fibrosis and even calcification and there was no evidence of progression. In the other 9 the tuberculous foci showed evidence of having previously spread locally: in U of them it had healed, by tha time of autopsy, -with excessive fibrosis; in the other animal there was a generalized chronic tuberculous pneumonia in one lobe and isolated primary tubercles, which were still active but had not spread, in the other lobes. Evidence of extension of the infection was first seen after 7 months of dust inhalation; during the next 20 months more than half of the animals showed an actively spreading tuberculosis and in 3 of them small cavities had developed. During th last 8 months no animals exhibited any evidence of active infection although in half of them the healed fibrous scars of previous extensions wears ob vious. Sixty per cent of the guinea pigs with spreading pulmonary tuberculosis showed tuberculosis of the spleen and liver. 20. Infeotion Superlmposed -Upon an Established jLabqatosis. Twelve guinea pigs, after in- haling asbestos Oust for nearly 2 6 month3 , were infected -with t u b e r c l e bacilli and then removed to normal air. The subpleural tubercles in the dusted animals were -1 1 - \ FEB-13-95 HON 17:24 J F HUHPHREYS ATTY FAX NO. 3043434186 P. 20 no more nuir-erous than in ncn-dustsd controls, but a considerable nuT.bor were found in the depths' of the lung about foci of asbestosio. The reaction to infec tion showed only slight local extension about the original sites in the lungs and tracheobronchial lymph nodes. The abdominal viscera "-ore involved in only persisted in the last animal, -which was killed lb isonths alter-: infection* 21. Asbestosis Bodies. Moderate numbers cf asbestosis bodies occurred in the lungs of the guinea pigs, becoming more numerous and more distinctly segmented in later months - 22. Rabbits Rabbits exposed to the acbeato3 dust for periods up to 19 months developed a low-grade foreign-body type cf reaction but no fibrosis. Although their lungs contained particy.la.te elements of the dust, fibers were not present, indicating that the upper respiratory mechanism of the rabbit is adequate to exclude fibrous foreign bodies. Two rabbits, after inhaling dust for 6 and 18 months, lived in normal air for snore than too years. At autopsy neither animal showed any evidence of cellular reaction or fibrosis in the term inal bronchioles nor -were there ary asoestoois bodies. 23. Rats. All the white rats had acquired an infection, resulting in the formation of pulmonary abscesses, before they came to autopsy. Apparently, so much heavy mucus obstructed their bronchi that very few fibers could have entered their lungs. j.n a few of th rats, an occasional asbestosi9 body was discovered but there was no fibrosis. - 12- FEB-13-95 HON 17:25 J F HUMPHREYS ATTY FAX NO. 3043434186 P.21 2k- uavnary and Interpretation of Inhalation Experiment with King's Floats Dust. The findings in the experiment with King's floats dust pan be summar ized under three headings. A. Effect of the inhaled dust on normal animals. The King's floats dust caused a charac teristic peribronchiolar fibrosis in guinea pigs but not in rabbits or rats. The fibrosis did not progress after the dust exposure m s discontinued and the guinea pigs transferred to normal air. B. Effect of the inhaled dust on tuberculosis in guinea pigs- In guinea. pigs in fected with attenuated tubercle bacilli and then placed in the dust room, the results were more variable than is usual in an experiment of this type. A few animals showed no sign of ^progression; in most of them there m s evidence of tem porary progression with subsequent healing; in one animal there was continuous progression to death. In contrast, when guinea pigs, after being infected, are exposed to quarts instead of asbestos dust, the infectious process continues to progress and eventually causes the death of the animals. On the other hand, ex posure of infected animals to a harmless dust like calcite or gypsum does not lead to ary progression of the infection. Oulnea pigs infected with attenuated tubercle bacilli following the termination of about -two years' exposure to asbestos dust did not develop progressive disease. The only modification of the infection was in its localisation, a few bacilli, being retained in the fibrous terminal bronchioles and forming tubercles there in addition to the usual foci beneath the pleura. In view of this variability, the unusual nature of the response and the high proportion of deaths from intercurrent pneumonia it is felt that definite conclu-- sions as to the influence of thir dust on the course of tuberculous infection are not justified. -13-95 MON 17:25 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 22 / dust to produ< l S i 0 U -57213 contact whetherpar not Vae/ bacterial *XSL ^ -- Xnh^l^tion Experiment with ^ ^ r t ^ f ^ e ^ A s b o g t o a Since hazardous duets like quarts are most effective in producing fibrosis when the particles ere 3 microns and lass in size, an inhalation experiment -eras carried on to determine whether this condition is true also for asbestos dust. It was thought that by using a short-fiber asbestos dust consisting almost entirely of fibers and particles smaller than 3 micron3 an accelerated tissue response might be initiated and an advanced reaction obtained in a short time. The previous inhalation experiment with King's floats asbestos, which contained fibers front 1 b b u to 1 micron or less in length as well as a great deal of particulate matter and which produced a typical peribronchiolar fibrosis in exposed guinea pigs, served as a basis of comparison. 26. The dusting material for this experiment -was forwarded from the UaxxviHe plant of the Johns-UanvUle Corporation. It was the remains of fibers collected in dust bins after a carding operation and screened to pass 200 mesh. Since the material as received contained many long fibers, it was ground in a steel ball mil 1 to reduce practically all the particles to 3 microns, car less in size. "Whan used alone in a standard dusting machine, this finely-ground asbestos tended to pack n the hopper and it became necessary to mix one volume of the un ground material with three volumes of the ground to generate a. satisfactory dust cloud. The addition of the smell quantity of unground asbestos was unfortunate because it confused the interpretation of results. Probably the minor amount of reaction that developed was due to the long fibers in the mixture although the FEB-13-95 MON 17:26 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 23 data of this experiment do not prore the point. 27. The composition of the short-fiber asbestos as received is disclosed by the chemical and petrographic analyses given in Tabls h- Semples taken before and after grinding yielded about the same values analyaSst*. inci rafting that there van no contamination from the mill or los3 of rater content. 28, The dust concentration varied somewhat during the experiment and light field counts for atmospheric samples collected inside the animal cages with the intpinger apparatus ranged from S3 million to 182 million. The average of counts was 130 million for the first year of the experimsnfc, 13U million for the second year and liiO million for the third year- 29. Slae-freq uency measurements of air-floated dust from inside the cages at & magnification of 13C0X revealed a great preponderance of fine par ticles (Table 5)- Nearly 90 per cent of the particles seen were smaller than. 3 microns. 30. Reaction in Animals to Inhaled Short-Fiber Asbsstoe Dust. Four species of animals -- guinea pigs, white rats, cats and rabbits - were used in this experiment. The results of the dust exposure, which are summarized in Table 6, will bo considered more in detail below. 31. Guinea Pigs. Eighty guinea pigs were originally placed in the dust room \ but 2 1 of them were later eliminated from the experimentand killed because of enlarged lymph node3 . Of the other 59 animals, US remained in the dust room until they were sacrificed or died from natural causes and 13, after being exposed to dust for 20 months, .were transferred to a normal atmosphere. 32- Rate and Type of Reaction. he type of tissue reaction to the inhaled FEB-13-95 HON 17:26 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 24 shcri--fiber asbestos -.xls Qsss-r.tirO.br 'ha suae as that already observed in the experiment with King's floats asbestos. The rate of reaction also was approxi mately the aazss but the extent of involvement- with the short--fiber dust was very much less and after 16 to 'L months of exposure only a very few small foci of reaction, which generally required microscopic examination fdr^deio'ctibnj~wera produced in the guinea page. Until exposures had continued for approTddcaiely one year, there was little tendency for dust-- containing phagocytes to collect into clumps. By 16 months phagocytes had begun to collect about the walls of a few of the respiratory bron chioles with a little proliferation cr infiltration of mononuclear cells in these walls. There were also some multinucleatecl cells but they were always of the inert foreign-body type. At 20 to 2h months the cellular clumps were sometimes quite marked and sometimes changes in the epithelium resulted in the adenoma--like or "adenomatoid" appearance previously described in Section 17. In most of the subsequent members of the series, the reaction remained cellular in type. In a few, however, fibrous elements dominated the picture. In the latter case, the collagen was pale in color and tenuous with no heavy swollen hyaliniaatioa. As in the rats described below, the alveolar Trails might be made up of a band of collagen supporting a layer of epithelium, but with no contained capillaries. In the tracheobronchial lymph, nodes the reaction was more pronounced in this experi ment than in the previous one with King's floats asbestos, probably because of the transportation of an excess of fine particles to the node3 in animals inhaling short--fiber asbestos. The reaction was essentially an increase in reticulum, rather than a fibrosis, with preservation of the original cells between the thickened reticular fibers. Diffuse chronic pleurisy without evidence of pulmonary infection was present in a few animals. -1.6- FEB-13-95 HON 17:27 J F HUMPHREYS FAX NO. 3043434186 P.25 33* Progression* In the 13-3/U months following the cessation of 20 months1 exposure to dust, progression of disease t b s r.ot definitely demonstrated but neither could it be absolutely disproved, owing to the varia bility of the response in different animals At the end of the dust exposure of 20 months two pigs were' read as -* and one as 2-*. Among the" 13 removed 'from duet, the findings were variable: in 2 the reaction was sj in it it nay -<; in 3 it was 3<-j in 3 it was h*} and in one animal it was *. It is quite possible that those with the most marked changes had already developed more reaction than the remain der by the time exposure ceased- Since the store severe reactions occurred spora dically and bore no relationship to the length of time after cessation of expo sure the differences were attributed to variation in individual susceptibility. This view received support from the chemical analyses (Table 7), which often re vealed comparable amounts of ash and silica in lungs with widely different amounts of tissue change. For example, the ash and silica values were quite similar for three animals in dust 20 months and then in normal air 13-3A months, yet the tis sue reaction for one animal was iiv; for another, and for the third, only . 3U. Asbestoela Bodies. The formation of asbestosis bodies was at first ex tremely limited. After *> months * exposure only a very rare short body could be found, usually inside of cells. Around the finest intracellular particles there were yellow deposits having the same color as the asbestosis body. Exposure of one year had permitted an accumulation of many longer fibers about which the asbestosis-body coating developed. Most of these were still short enough to be partially or entirely within phagocytic cells. By the 20th month and thereafter, they were comparatively numerous although still rare in comparison with the findings in the King's floats experiment. FEB-13-95 HON 17:27 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 26 3 ?. Whits Ttabs- Scrrt'nty--v.hi'es -shii-e rcto were exposed to atmospheric shorfc- fiboi' asbestos dvsft l'or periods up to 32 months. Saeri-- flcings during the first 10 sontha t;s t g s^de birvontoly aud Tor the remainder of the^espei'inent at less frequent intervals .... -- , -- -- ^ 36. Rate and Type of Reaction. The dust cells until 5 months rare widely scattered and er-dsted in foci only sporadi cally- Reaction m s limited to occasional slight thickenings of the septa about. small accumulations of dust calls. In a fen rats at 10 months, there was a sug gestion of early fibrosis but t}io change was so slight that it -would probably be overlooked -without the clump of dust cells to attract attention to the area. Only 10 animals -were exposed from 12 to 32 months. In each of them the lungs shewed minute patches of -well-defined fibrosis distributed like that of asbestos! 8 but without aabestosis bodies. The lesions, visible only at a magnification of 1^0 diameters or more, consisted of patches along alveolar ducts in which the walls of the air spaces were very thick, due to swollen collagen framework. Connective tissue and Foot-fiLelschowski silver preparations revealed complete loss of capil lary bed locally. Outside the collagen was a thin layer of epithelial calls. This did not resemble the "adenomatoid " change characteristic of guinea pig as-- bestosis. Ma pleurisy was present. Hear the lesions the air spaces wera filled with phagocytes containing grey to yellow particulate dust and a rare long naked asbestos fiber- Careful search failed to reveal even a suggestion of an aabesto sis body. The tracheobronchial nodes showed compact focal collections of mono cytic cells at 12 months and, at 20 months, some diffuse thickening of the retlculxm. In a few rats there was definite fibrosis along the margins of the node and extending into the mediastinal areolar tissue. Compared with the response to active dusts like quartz and cheru the reaction to short--fiber asbestos was negligible - FEB-13-95 MON 17:28 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 27 ?.6suits of cber.ri.csu. arislyses: r;.zx.'i cr* t.la rate sra given in Table 3 and the average value3 have been tabulate.i: in Table f for ccupcriscn -with similar values fbr rats inhaling other dusts, The concentration of atmospheric particles to, which tfcc animal3 -wore exposed tvss approximately tlia came for asbestos and quart; for the gypsunr-quartz mixture, it was about trico ar. high' and"for'chert- rive times so high. It rill be noted that tbs percentages iar asbestos re lower than those Tor quartz or chert but are similar to those for the Kypsuin-quarts mature, in which atmospheric agglutination tended to reduce the amount of dust inhaled. It might be inferred that the total quantity of asbestos dust inhaled was low or that it had been eliminated from or dissolved nitfciti the lungs. In the present state of our knowledge evaluation of ihssa hypotheses is not possible. 37. Cats. Twenty cats -ssr3 used in this Inhalation experiment -with the short-fiber asbestos. Eighteen were kept in the dust room until death) the exposure period ranging fren cue month to nearly h-1/2 years, and two, after a dust exposure of 31-1/2 months, -were removed to normal air. One of these was sacrificed 5 months, and the other 2k months, later. 38. Hate and Type of Reaction. The reaction was essentially that to an inert dust, even after more than U years of expo sure. The tissue response in this species -was confined to microscopic foci of fibrosis in the -walls of groups of subpleural alveoli, rather than in the pari-- bronchiolor areas. In one animal ths change -was extensive enough to be visualized on gross inspection of the section. f 39. X-Ray Changes. Only in the animal -Kith the longest exposure did the X-ray rsvsal definitely abnormal shadows. After 29-3/k months the picture "ras negative; after kS month3 a faint mottling could be detected throughout both lungs. At autopsy, 3 months le.ter, there 77a.? only microscopic FEB-13-95 HON 17:28 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 28 bronchioles. kO. Acbostocis Bodic On prolonged ssarch a few yo^J-cr stTpicnl apbestoais in 'em aniEsals exposed tor more than a year. Itl. Rabbits. Sight rabbits "were exposed to dust for periods extending from one to mora than fiv3 years. Ths last- animal was removed frost the dust room and Xot in normal air 6 months before being sacrificed. It2 *. Rate and Type of Reaction. There vras never enough fibrosis to be de teefcod grossly and there was no chronic adhesive pleurisy- Microscopic evidence of alveolar wall thickening tra-3 first detected after about 3 years of exposure and was seen in all five animals examined thereafter. In one animal that died of paralysis after nearly four years of ex posure the reaction was extensive eaotigh to be visible on gross inspection of tissue sections- The possibility of pulmonary infection in this animal could not be excluded. However, in another animal dying two years later the focal fibrosis was not nearly as obvious or as advanced. Areas of involvement, -which were largely visualized because of phagocytic reaction within the air spaces, tarried microscopically to become more fibrous with the passage of time but there was never much encroachment upon the lumen of air spaces and the architecture of the lung was preset ved. , U3. Asbestoeis Bodies. Asbestos bodies were not detected in rabbits that died early in the experiment but were seen in all animals that hud been exposed to the dust for more than throe years. FEB-13-95 HON 17:29 J F HUHPHREYS ATTY FAX NO. 3043434186 ' P.29 a]:. c->nnrg-y arid Interpretation. Tba ox-i^iTioC. pm-poso of ths experiment -&53 to evaluate the cheinical theory of the pathogenesis of asoestosis. It "was felt that if the tissue reac tion to asbestos Trere chemical in origin an accelerated or accentuated response would result from exposure to finely-divided asbestos, as is the case with quarts. Tliis experiment, in which the reaction vas slower and less extensive than -idtii Xing's floats, indicates that iha reaction (j^rotJSG^ is not primarily cheaicai in I/ nature. Of the four species exposed in this experiment only the guinea pig and rat reacted with characteristic peribronchiolar fibrosis. The cat reacted with atypical sub-pljsaral fibrosis and in the rabbit the fibrosis which occurred could not be positively attributed to the dust because of a strong possibility i of pulmonary infection. XLtV^j^h\AUATtbM` Tribulation Bxperirrc^nt^wl^h 10 P^r Cent^ As^osioa^ Duso. 31i the inhalation experiment with short-fiber asbestos dust a small quantity of ungronnd asbestos was nixed with ground material in order to produce a suitable dust cloud, `ban evidence of a dust reaction appeared in the guinea pigs during the experiment, it was not clear whether this was a tissue response to th9 small number of ~l.f>ng fibers in the ungrotmd asbestos or was a delayed effect of the more abundant fine dust. Consequently, another inhalation experiment was started, in which no unground material was used. f ' U6. The dusting material -me the ground short--fiber asbestos used in the previous inhalation experiment but no unground material was mixed with it. To obtain a sufficient amount of atmospheric duet, the design of the dusting apparatus -was changed to an open type of hopper and fresh dust was added daily. FEB-13-95 HON 17:29 J F HUMPHREYS ATTY FAX NO. 3043434186 ................ i urn n n i P. 30 Owing to the uendsncy of the ratsiti ; ;.-c ibi-m snail spherules 'iici prevented m e n of tiie fibrous portion fro::; ilcav.ing out oi the. hopper, the-dispersal of the dust was not entiralir oauisfactox-y and cuter 7 mouths of operation, the dust ing machins was racoEvertsu to its criminal design. To prevent "pilling" or the formation of spherules of asbestos, steel wire bruchas rers attached to the in side surface of the hopper and to the rotating padols. This arrangsment gave satisfactory results and was used for the remaining fl months of the experiment- u7. The composition of the zmsxr notarial (short-fiber asbestos) and of atmos pheric dust liberated fro- the bali-rjllled product in the dusting ma chine is given in Table 10 . The3? values are based upon petrographic study and X-ray diffraction analysis. The atmospheric sample was collected with an elec trostatic precipitator after wire brushes had been installed in the dusting machine. Previous to this, the ehrysotile content of the air-suspended material, was undoubtedly less than the 15 per cent value given in Table 10. In an inter im report, it was stated that the air-borne dust contained about 5 per cent of chrysotile before the wire brushes were used end up to 6 per cent afterwards, but these values were probably low. Quantitative estimates on ball-milled asbestos dust may be somewhat inaccurate because it is difficult to determine how much of a dust sample is fibrous chrysotile and how much is non-fibrous serpentine. US. The dust concentration for the first 7 months of the experiment was about 100 million particles per cubic foot of air. After the wire brushes had been installed, the dust counts were a little higher and the overall average for the first year was 106 million. The average of counts for the second year was 163 million and for the third year lU5 million. FEB-13-95 MON 17:30 J F HUMPHREYS ATTY FAX NO. 3043434186 P.31 m in Table 11. Two samples were taken, one before the wire brashes were installed and one after. It "will be noted that after the wire brushes were in use a greater proportion of Vry fine particles and also o lohgar fibers'was reliased into the air. 50. Reaction in Animals to Inhaled 100 Per Cent 3all-4&ll6d Asbestos Dust. Guinea pigs? rate end nice were used in the Inhalation experiment with the ICO per cent ball-milled asbestos dust. The results are sujnmrized in Table 12. 51. Guinea Flga. The experiment was started with 100 guinea pigs. As the dust exposure proceeded, there were 39 accidental deaths, 32 of pneumonia in an epidemic- After 28 months of dusting the 16 surviving guinea pigs were transferred to normal air. 52. Rate and Type of Reaction. For the first year of exposure practically the only reaction to the dust was the pre-- Hence of scattered phagocytes and an occasional minute asbestosis body. At 16 and 20 months no gross response was risible on the tissue section but microscopically peribronchiolar foci of inflammatory cells could be seen. At 2k months there was still no change large enough to be seen with a hand lens although microscopic examination revealed cellular accumulations about terminal bronchioles and many i' more asbestosis bodies, chiefly within cells. Chemical analyses of the lungs (Table 13} reveal that in spite of the limited tissue reaction considerable dust had been retained in the lung. FEB-13-95 HON 17:30 J F HUHPHREYS ATTY FAX NO. 3043434186 P. 32 revealed the changes described above and also very slight peribronchiolar fibre-- sis- After 0 montlis in normal air the findings ware similar but at 12 months 3 of'li animals showed gros3ly-visible characteristic peribronchiolar fibrosis with adenomatoid change. 5U. Lymph Bode Involvement, The tracheobronchial nodes were essentially negative until exposure had been continued for more than a year and a half. Animala sacrificed at 12 months and 16 months revealed a few minute collections of phagocytes containing particles but prac tically no fibers large enough to be recognized as such. After 20 months of exposure many monocytes filled with yellow granules were present. At 30 months there had been a slight increase in reticulum but no fibrosis. No further changes occurred in the nodes. Asbestosis bodies were not seen in the nodes of any of the guinea pigs. Asbestosis Bodies. Minute asbestosis bodies were observed aa early as 3 months after exposure began, but they did not be- come numerous until 16 months had elapsed. The bodies were short and practically all were intracellular, although at 20 months some were long enough to project beyond the cell borders. It is important to note that in the later months of exposure there was a dis tinct increase in the number ,of long fibers (pep to 70 microns in length) in the lungs and that after exposure ceased characteristic long asbestosis bodies were seen. 56. W h ite R a ts a n d M ic e . In t h i s e x p e r im e n t hO r a t s w e e x p o se d f o r p e r io d s up to 20 months and 2k mice for periods up to 12 FEB-13-95 MON 17:31 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 33 months. Neither species developed even a suggestion of asbestosis and reaction, was limited to phagocytosis of inhaled particles by widely-scattered dust cells which, remained free in air spaces or were transported to the tracheobronchial lymph nodes. Mo asbestosis bodies were found in the rata but in the mice there were a very few small non-haustrated forms within phagocytes. * In 2 1 mouse lungs sectioned there were 3 instances of pulmonary adenoma (llii). 57. Sunapary and Interpretation. The tissue reactions observed in this experiment ware much les3 extensive and slower in development than in the previous investigation with short-fiber asbestos. Since presumably there were fewer fibers longer than 3 microns in the material used in this experiment, the results tend to confirm the interpretation made in Section liix of the short-fiber experiment that the reaction jwtfMKLy is not primarily chemical in nature. The finding of long asbestosis bodies in animals inhaling the ball-grilled material is an example of the difficulty of completely eliminating long fibers from an asbestos preparation. In regard to progression of reaction after removal from dust, liiich was ob served in this experiment but not in the others, the following interpretation is offered: Then the reaction is well-developed at the termination of exposure,the contraction of the fibrous tissue would obscure any possible progression. In this experiment, however, since only the earliest stage of reaction was present at the time of removal from dust, its subsequent progress was apparent. It should be noted that the degree of progression was so slight that it can have little, if any, practical significance. FEB-13-95 NON. 17:31 J F HUMPHREYS FAX NO. 3043434186 P.34 1 \ After animals inhaling short-fiber asbestos dust for more than a year had failed to develop significant reaction, the hypothesis that asbestosis is pro duced by the mechanical irritation of long fibers was given added support. Since the King's floats asbestos used in the first inhalation experiment had a rather low content of fibrous clirysotila and contained considerable serpentine and other impurities, it was decided to conduct a new inhalation experiment with a purer form of chrysotile which would be richer in long fibers. 59. The dusting material employed in this investigation was obtained from the Marxville plant of the -Johns-l&snville Corporation. Samples of se veral varieties of asbestos dust were first submitted to the Saranac laboratory for examination and one kind, identified as Lot D, which was low in magnetite and chromite and had a fibrous content estimated to bo about 75 per cent, was selected as most suitable. Steel wire brushes were fastened to the inside sur face of the hopper and to the rotating paddle in order to open up the bundles of asbestos and liberate more fibers into the atmosphere. 60. The composition, of the long-fiber asbestos used in this experiment is indicated by the chemical and petrographic analyses given in Table 1U. It appears that this material was a much purer form of asbestos than the shortfiber dust used in other experiments. This is borne out by comparing the approx imate analyses of the long--fiber and short--fiber idust in Table 15- i 61. The dust concentration as revealed by impinger samples taken inside the animal cages was much lower than the concentration for the experiments with short--liber or ball--sallied dust. For the first year of the experiment with long--fiber asbestos the average of the light field counts was 32 million} for r/ FEB-13-95 HON 17:32^ J F HUMPHREYS ATTY FAX NO. 3043434186 P. 35 the second year, ii8 xdllior-; I'cr iiie third year, 31' million* snc Tor the fourth year, U3 million. Sscamination of the impinger samples Td/c-r. dark field ill'aoin-- stion disclosed that many fine pcrticleo less than ons ndcrcrn in size accompanied the larger particles end dark field counts were, on the average, about $ or 6 times larger than the light field counts. " -- -- 62. The sine--frequency of atmospheric samples of tha leng-fibsr asbestos dust and of the ball-mi H a d dust is 3howfi in Xsble lo. Both samples were collected with the electrostatic precipitator, it nd.ll ba noted that there was far more fibrous material in the long-fiber oust. 63. Reaction in Animals to Inhaled long-Fiber Asbestos bust. Gtiinea pigs, cats, rats and mice were employed in the inhalation experiment with long--fiber asbestos. Results of the experiment, summarized in Table 17, are described in greater detail below. \ 6k. Guinea Rigs. The experiment was started with 100 guinea pigs- After exposure had been carried on for a year, a severe epidemic of pneunvmia arose In the dust room and about one--third of the animals died or were killed. To replace them, 38 more guinea pigs were added to the surviving group in the. dust rocra. 65- Rate and Type of Reaction. Histological examination revealed grossly visible lesions in the lungs after 8 months of exposure to dust, consisting of cellular infiltration about the termin al f * bronchioles. At 12 months, there were adenomatoid changes in the air spaces and by the 16th month a definite fibrosis was present in these areas in half the jmicala_ The fibrous lesion could be seen macroscopically at 20 months. From this time on the reaction increased in- extent and in the amount of collagen and j \ * FEB-13-95 MON 17:32 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 36 j-;r V. 7L;.tV. -iorrt-'.j it had leArr-b our, into the parenchyma. The lesions were rather sharpiy localised and the extensions from different bronchioles choired no tendency to fuse, even in animals exposed for the rfirinum period (3 years). Although the intra-pul-tnonary reaction soraatiraes reached the pleura^, there Tra3 no involvement of tliat membrane. No emphysema was visible at any point. Some thickening of the larger bronchi with a chronic inflammatory infiltration was re vealed, but it probably was no mors than would be produced by a similar exposure to any dust. For the first F months the phagocytes consisted of monocytes or very snail giant cellsj later, giant cell formation was more prominent. After 16 months the giant cells were large, filled with yeilowish-fcrcran. pigmant and sometimes vacuolated. An occasional animal showed an Admixture of polymorpho nuclear leukocytes and, in guinea pigs exposed for a considerable period, eosinophiles. The reaction ttbs at first entirely cellular but by 16 months fi brous tissue formation was definite. However, it never attained a stage of hyalinination suggestive of silicosis. A moderate individual variation occurred among the exposed aiioals, both in the rate of developing lesions and in the stage of development attained at the end of exposure. Analyses of the lungs (Table 18 ) disclosed that although the tissue response was much greater in these guinea pigs than in those exposed to either short--fiber or ball-milled asbestos, the amount of mineral matter in the lung ash was lee. 66. Progression. In guinea pigs exposed to the dust for 20 months and than removed to normal air, there was a marked tendency for cellular inflammatory reaction to clear. Tills effect, accompanied by contraction of the fibrous tissue, resulted in a diminishing size of the focal lesions. Hone FEB-13-95 ON 17:33 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 37 20-month exposure period or those in animals T.hich regained in the dust room for more than 20 months- Fourteen months after dust exposure cessed- the foci in four of the six remaining guinea pigs were so snail that they were visible only with a hand lens. Reaction in the grcup exposed for 27 rsonth3 and thon transferred to a normal atmosphere was quit similar to the response in the 20-month exposure animals mentioned above- However3 small foci were always visible on gross inspection of sections of all guinea pigs of the 27-month series but in no instance was there evidence of extension of the reaction. 67. lymph Rode Involvement. Reaction in the tracheobronchial lymph nodes was first visible at the third month of er-- posure. At the 6th month patches of cellular connective tissue began to appear in the medulla and by the liith month most of the node had been replaced by cellular connective tissue. This picture, which resembled that in early silicosis, persisted to the end of the experiment. Some animals, bs a variant, showed heavy sheets of diffuse monocytes and large active giant cells but there was never any necrosis or hyaline formation.' The spindle-shaped new cells were yellowish in color from fine pigment granules that stained for iron. No fibers or asbestosis bodies were seen. 68. Asbestosis Bodies^ -^r Although asbestosis bodies were seea^as early as one month after exposure began, they were rare and hard to find- At 5 months more were visible, chiefly coiled inside giant cells, and at 8 month3 many bodies ware free in c o n n e c t i v e t i s s u e . T h e y became fairly abundant only moderately numerous - FEB-13-95 HON 17:33 J F HUMPHREYS ATTY FAX NO. 3043434186 9, Cats. Four cats icfcaleo the long--fiber asbestos dust for periods of ill. 25, 33 and h2 months, respectively, and were immediately sacrificed. Tro other cate, after being exposed to dust for 16 months, lived in a normal atmosphere for an additional 2U months. 70. Rate and Type of Reaction. Exposure for lk months was sufficient to produce cellular accumulations of phagocytes around terminal bronchioles and peripheral arterioles together with compact col i lections of similar colls in the tracheobronchial lymph nodes. At that time there were no typical asbestosls bodies, but smooth pointed yellow fibers were seen very rarely. TCith continued exposure, up to h2 months, reaction in the locations noted progressed to the formation of cellular connective tissue which made well-defined sheaths about the respiratory bronchioles and arterioles, marked lymphoid hyper plasia and lymphoid infiltration of bronchiolar walls. The bronchiolar epith elium was low and flattened, giving the tubes a smooth contour. Typical asbesto-- sis bodies were not formed although there was an occasional yellow, smooth, pointed fiber. No pleurisy was present. The reaction was similar in location to that in the guinea pigs, but fibrosis was much slower in development and had not reached the same degree of maturity. - fjL. x-itay Changes. Roentgenograms of three cats were made after exposure periods of 25, 33 and li2 months, but tissue changes were not dense enough to be seen on an X--ray film. t ' 72. Rats. Although 20 rats were placed in the dust room, many died from pneu monia and were not suitable for study. Five animals, of which one was exposed for 19 months and four for 2$ months, wore free from pulmonary infec tion and offer a basis for conclusions. 13-95 NON 17:34 J F HUNPHREYS ATTY FAX NO. 3043434186 P. 39 7 3- tvata c-nd Tyos of React! or.- 1 1 four animals sacrificed at 2$ months hewed a well-marked peribronchiolar fibrosis In the 19-month animal, reaction was just beginning. Asbestosis bodies were practically absent at both 19 and 25 rtenths although tiro small smooth bodies were fotad in the 19-month animal after a. long search. Thus^ these .animals fibrosis -without asbestosis bodies. 7k* Kice. Out of 20 white mj.ee U3sd in this experiment, 11 lived a year or more in dust and died or "ware killed without showing an appreciable degree of pulmonary infection. 75 Rate and Type of Reaction. Reaction rras limited to phagocytosis by mononuclear cells. Usually these were widely scattered through the air spaces; a limited ntnrfcer were grouped about the ter- Numerous asbestosis bodies were observed in animals killed late in the experi ment. Thus, these animals exhibited asbestosis bodies without fibrosis. 76. Summary and Interpretation. The purpose of this experiment was to evaluate the importance of long fibers in the tissue response to inhaled asbestos The results indicate strongly that long fibers are chiefly responsible for the reaction- Thus, in guinea pigs reaction developed earlier and became more extensive than in previous experiments in spite of a smaller concentration of atmospheric dust and a lover mineral con tent in the lungs. Furthermore, a typical peribronchiolar fibrosis was produced 9- ] * M > b * FEB-13-95 HON 17:34 J F HUHPHREYS ATTY FAX NO. 3043434186 in cats although In a previous experiment Jwith short-fiber dust it did not develop in this specios- The cause of the cellular fibrosis, in the lymph nodes of the guinea pigs is not clear. It did not occur in other inhalation experiments with asbestos. In order to determine to what extent the various fibrous minerals possess the' capacity to produce tissue damage, numerous infection experiments were per formed. In these experiments guinea pigs and rabbits were used and the mineral dust was injected by the intratracheal, intraperitoneal and intravenous tech niques. Far the purpose of simplification the findings in each series of testa have been condensed end reported in tables, to which reference will be made later- 78. Experiments Using Intratracheal Technique. Since the asbestos minerals do not cause a typical advanced fibrosis in extra-pulmonary tissue, the intratracheal technique is the perferred way of in troducing fibrous dust into the experimental animal. In this method th dust suspension is injected by means of a special needle or catheter deep into the trachea, from which it flows into the lungs. 79. Comparison of Fibrous and ffon-Fibrous Dusts. To demonstrate that the t' ability of asbestos to produce fibrosis resides in its fibrous character, the series of injection experi ments reported in Table 19 were performed. The tests were made with unheated long--fiber chrysotile and with chrysotile that had been ignited w destroy its -32- FEB-13-95 HON 17:35 J F HUMPHREYS ATTY FAX NO. 3043434186 P.41 flex ib le structure or h ill- a llied to i-cduce the laijgth cf ;..'iber v-o Z le s s. At t-hs r,e,7Ts tiKfi -or.trcl testis ware mads with serpentine- which i:os vtj sans chemical coTirponition. as ch rysotils but. Is non-fibrous , A review o i the findings -evsals that only the unheated long-fiber chrysabile produced fib ro sis, fib ers subjected, to ign ition or shortened by b a ll-w illin g had`lo st th sir capacity to causa serious tissu e danage- Ignition produced important changes in th3 chry~ sobi3.e fib ers, among then being lose of water, an alteration fror. n f'iaxibie to a b r ittle structure and pocsibly other changes. 80. Comparison of Various Long-Fiber Dusts. Sons very interesting findings are disclosed by the results cf the experiments included in Table 20. First, all the long-fiber asbestos minerals tested, -with the exception of anthophyllite, produced a typical fibrosis. It is not entirely clear why anthaphyllite behaved differently from the other asbestos minerals. Unfortunately, ^ of 0 animals died of pneumonia within the first two weeks of the experiment and the remaining animals were sacrificed at 1 , 8 and 12 months $ thus observations Trsre not made at the optimum periods of 2 and li months. Second, w ith the mineral brucite, which is not a s ilic a te but is a fibrous form of magnesium hydroxide, a characteristic fib ro sis lik e that of the asbestos minerals was obtained. Since the brucite used contained only 0.90 per cent s ilic a (as an im purity), i t is obvious that a siliceo u s component is not an essen tial factor in the development of asb estosis. Third, no fibrosis resulted from the injection of gla33 wool fibers, even though glass wool resembles asbestos in sonse ways. There are fundamental differ ences, however. A glass wool fiber 3 microns in diameter is & solid rod and, in s h o r t lengths, is fairly rigid, w h i l e an asbestos fiber of the same diameter is a bundle of extremely fine filtraente which impart to the fiber a high degree of flex ibility- I t would sessn t h a t t h i s structure and the associated flexibility a r e FEB-13-95 MON 17:35 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 42 important factors governing the capacity of a mineral to produce peribronchiolar fib r o sis. _ 8l . Comparison of Long-Fiber and Short-Fiber Dusts. With quartz dust i t has been'desnbnstrated-that the smaller the p a rticles, the more intense is the tissu e reaction, and that there is lit t le reaction to p articles larger than 3 mi.crons in diameter. In the case o f asbestos, however, the reverse is true and apparently only long fibers have ary sp ecific e ffe c t. This is confirmed by the data o f Table 21, in which a series of te sts with fibrous minerals is reported. TVhen the injected dust consisted of fib ers 20 to 50 microns long, a ll the minerals tested (except anthophyllite, as noted in Section 80) produced a fib rosis 3 when the m aterial was prepared by f ir s t grinding the fibrous dust u n til the length of fib ers was reduced to 20 microns and le ss (car, in some cases, 3 microns and le s s ), none of the injected sdasral dusts caused fib r o sis. 82. Experiments Psing Intravenous Technique. The experiments, described in Table 22, in which the intravenous method of Injection was employed, show that the asbestos minerals are far differen t from quartz in th eir action on tissu e. It has been repeatedly demonstrated that in tra - such as the liv e r and spleen. Asbestos m inerals, however, on xntravanous Injection generally produce only an inert type of reaction, as is revealed by the resu lts given in the ta b le. The reason for the early deaths in the experiment with chryaot ile p articles is not clear; i t may have been caused by s ilic ic acid liberated by the finely-ground mineral. FEB-13-95 HON 17:36 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 43 * 83- Experiments Using Intraperitoneal Technique. The results of Injection experiments with the intraperitoneal technique ore given in Table 23. It will he noted that the long-fiber duets produced a fibrous reaction while duste composed of particles 3 microns and Isas in size censed only an inert type of response. These experiments indicate also'that the fibrosis initiated by the irritation of asbestos fibers is not restricted to the longs, as was formerly assumed, but can be produced in the peritoneum as well. A number of additional experiments mare conducted to throw more ligrt on specific {bases of the asbestosis problem* 85. Protective Action of Alnadnum Compounds. Intratracheal injection of a suspension of long-fiber chrysotile to which colloidal aluminum hydroxide had been added revealed that the addition of the flirmrimniicompound 4 ^ not prevent the tisane irritation, produced by cfarysotile. If anything, the acute inflaznatory response to the injected fibrous mineral was accelerated. One month' after the last injection of the dust suspension the bronchiolitis was becoming fibrous. 86. Formation of Asbestosis Bodies. Hie iron in the coating of the asbestosis body appears to be derived from blood or tissue elements and not, as has been suggested, from the mineral fiber. Following subcutaneous injection of two kinds of chrysotile into the groin of guinea pigs -- one kind containing 2 per- cent and the other 0.2 por cent Fb2^3~ the asbestosis bodies were equally numerous at both sites of injection* r ... -vM 1 <2^ I ^ ' ' FEB-13-95 HON 17:36 J F HUHPHREYS ATTY FAX NO. 3043434186 P. 44 An attempt to produce asbestosis bodies in guinea pigs by implantation of three eilk bags containing fibrous chrysotiie was unsuccessful- ^One bag planted subcutaneously in the abdominal trail disappeared}-the other tiro bags, placed in the peritoneal cavity, produced a little foreign body reaction but no asbestosis bodied in a year. Intratracheal injection into guinea pigs o f asbestosis bodies recovered from human lung tissu e fa iled to produce the typ ical tissu e reaction to asbestos fib ers. The injected m aterial -was obtained by digesting with sodium hypochlorite solution lung tissu e removed at autopsy from an asbestos worker. The asbestosis bodies could be seen in the guinea pigs far at lea st a year after in jection . This experiment shoes that the asbestosis body has a rather resistan t coating which is not destroyed by moderate hypochlorite treatment and may be maintained in vivo far a year or longer. .IpTaaSC- unra. 'stIeqt ryU ."or" V-thrVuaVn.tV-~a-cTitrTioTn--o--r^V..asbVe--stoV.s .iquerais V- 'v n Two hypotheses have been proposed to explain the tissue Irritation and reac tio n Minimi by asbestos fibers; the chemical and the mechanical. In the chemical theory, which is based upon experience with quarts, i t is assumed that the as bestos minerals d issolve in the body flu id s and that in th is process their bases are leached sn^y to leave silica in a form capable of ixtltating tissues. Accord ing to this hypothesis, asbestosis would be merely an indirect silicosis. Several facts make the chemical theory untenable * (l) intratracheal injections of bru- cite fibers, which had a silica content of only 0.90 per cent, caused a typical fibrosis like that produced by the-asbestos minerals} (2) free-eilica particles increase in potency as the particle siae becomes less, but asbestos fibers shorter than about 10 to 20 microns are relatively innocuous; (3) aluminum FEB-13-95 HON 17:37 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 45 hydroxide neutralizes the irrita tin e siT set of quartz but not of asbestos} (li) serpentino has the same chemical composition as long-fiber chrysotile but i t doe9 not produce the same kind o f tissu e reaction} (?) there is a -ride range in the chemical composition o f the minerals which do cause asbestos is (see Table 2b). 2h view of^this evidence it seems more lik e ly that esbestosis ifi caused by an unusual mechanical irrita tio n from long asbestos fibers i Piubdbiy / thig irrita tio n related to the peculiar filamented structure of the fiber and the associated fle x ib ility , which are possessed by no other foreign body. For example, ign ition o f chrysotile fibers changed their structure and made them inert while the sane fib ers, before being heated, would product fib rosis (see Table 1?)* Further support for the theory of mechanical irritation i3 that asbestosis occurs in an organ of high m obility - the lung - and that a fibrous reaction can be produced by injection o f asbestos fib ers into the peritoneum, where there is also a degree of m obility, but not in other extrapulmonary organs ^ u 'iv bravili, c^uc&yoffs The experimental in vestigation with asbestos minerals was concerned prim arily w ith the e ffe c t o f the dust on normal tissu e but some attention was given to other phases, such as su scep tib ility to infection and occurrence of malignancy. 0?. Infection. The only experiment in which the effect of inhaled asbestos dust on a pul monary infection was studied was the. first inhalation experiment, carried on with ''King's floats" dust. It is, perhaps, unfortunate that infection attslies were not made in the other inhalation experiments also. FEB-13-95 MON 17:37 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 46 90. S u scep tib ility to Tuberculous In fection . The development o f & tuber' culous process'initiated at the beginning of exposure to asbestos dust, and also or an infection superimposed upon an established asb estcsis, was described in Sections 1? and 20._o th is re port. It -will be noted that asbestos, -when cla ssified according to th9 effect of a dust on tuberculous infection, would be placed below an active dust lik e quartz but above in ert dusts, such as ca lcite and gypsum. In animals infected with attenuated tubercle b a c illi, quartz w ill cause the infectious process to progress u n til the animal dies o f tuberculosis. Inert dusts w ill have no effect on the infection and the lesions w ill usually heal and th e disease disappear. Asbestos dust is in a different category, then the fibrous dust was being in haled during the evolution of the in fection , there was a spreading of the tuber culous process for a time but usually the stimulus for continued proliferation of the tubercle b a c illi was not sustained, the progression was arrested and healing followed. In guinea pigs infected with attenuated tubercle b a c illi following the completion of nearly .three years of exposure to asbestos dust, progressive disease did not develop. The only m odification of the in fection was one of lo ca lisation , a few b a c illi being retained in the fibrous terminal bronchioles and forming tubercles there in addition to the usual fo c i beneath the pleura. Such tubercles healed in a few months and there was nothing to suggest any influence on the course of the disease. 91* S u scep tib ility .to Non-Tuberculous In fection. There was no pointed experiment concerning the effect of inhaled asbestos dust on non--tuberculous infection. Intercurrent pneu- Sonia among animals exposed to asbestos dust was rather common, the frequency in guinea pigs exposed in the four inhalation experiments ranging from lo to 39 per FEB-13-95 HON 17:38 J F HUMPHREYS ftTTY FAX NO. 3043434186 P.47 cent. This incidental e r idance Erur^cciB the p o ssib ility of an effect of asbestos dust on non-tuberculc'.is in fection . Nevertheless, since such epidemics are not uncommon in inhalation expariaants with other dust-s and even in the colony of normal animals, i t is fe lt that the inhalation of asbestos dust does not exert a sign ifican t effect on. the su scep tib ility to ..non-tuberculous pulnonary infection. i 92. lfeoplRam. ifo sp ecific experiDent uas conducted to determine wheNher the inhalation of C p i c- asbestos favors the development/o f neoplasticjiiB ejse but certain observations on this subject\tiere recorded in/he outlinsoC the proposed moxiivpraph on asbestosis submitted by the late Dr. L./U. Gardner iif February 19lf3.- In it he called atten tion to the higi^. incidence i> lu^ cfcsfof Sunong nttc^ inhaling leng-fiber asbestos, In his experimental notes/howerW, ha^reTerred to t&ese lesions as adenomas. There is an ikportayt distinction between adenoto^ and cancer which should be made clea r. A canc\er i d a tumor, or neoplasm, capable ''of lo ca l in'asion and de- / / \ struction of tissu e , waich can distribute c e lls through the lymphatics or blood stream to produce isolated fo c i, ty'em which new tumors derolop. This phenomenon of dissem ination is fcncrici as m etastasis and any tumor which 'exhibits i t is a malignant growth, o f which cancer i3 one type. An adenoma, ot^ the c.her hand, is a so-called benign/or non-^lignant tumor (neoplasm) which may \nr toer not be capable o f lo ca l invasion but^which does not m etastasize. / \ In order to c la r ify the e\^act nature o f these lesio n s the pathological mater ia l is being carefully examined.\ Since i t is f e lt desirable to hay.: 'the benefit of Doctor Vorwald's judgment, a re\view o f the data on th is subject is \b^i_ng post poned u n til after h is return from Euhppe. Rather than delay the ent re report, further discussion w ill ba reserved foA a supplement to bo issued la t v. \ 13-95 MON 17:38 J F HUMPHREYS ATTY FAX NO. 3043434186 P. Owing to the vast amount' o f datayfncludeisn th is report i t seers renst convenient to sta te the conclusions/derii#i from the investigation and. vhen necessarwy*. lo llo p each one n ith a br/i^f resuss of the evics.ni,.ce. ^ _ 'Z-f A. Various forms o f asbestos/fibers produce a peribronchiolar fibrosis o lung6 o f guinea p igs, ratts,, cats and rabbits but not o f mice and dogs. Both inhalation and injection experiments provide or.plc support for th is conclusion / figures $ and 6 show the reaction to two different kindf of asbestos mineral. B. The mode o f aotion^ap^ea^3Q-^beJprf?>&rily ttechaniooi rather than |uXP- chemical in nature. 5 I ^ pCL/*.v. The evidence is given in section LXXXVIT Figures 1, 2, 3, 1 and 7 illu str a te the important points. The fibrous fiTanentr.d structure of agbeatis(a p p e t e u pla/*an essen tial part in the irritating action, since the solid fibers of glass wool do not produce fihrosis ee Figure 8 ). C. Short asbestos fibers Ido not produce vfibrosis The cumifanrlun is implied ir. the evidence mentioned in para graph B above, irtruants which further eupport this finding are r^periea ir. T'<bles 21 and 23. D. Typical fibrosis can be produced by an atmospheric suspension of asbestos dust containing only sn extremely small proportion of long fibers. In the inhalaticT experiment -with 100 per cent fcall-oillea o' - t'"` asbestos dust a typical, though delayed, fibrosis r?as FEB-13-95 HON 17:39 J F HUMPHREYS ATTY FAX NO. 3043434186 P. 49 obtained .n-:.;;. Ibbis ;. although lesi 1 per cant of the 7>i:-jz*i.c dust consisted of fibers! longer than 10 rrd.crons. ~s is shor/n in Table 13- In contrast, the intra tracheal in.;>ction experiment xdth fina asbestos dust con- taining nt long fibers f.a..i.l..e.d...t.e...p.r..c.d.Pue fibrosis. (ses Tablr 51). I, Inhalation oi i-sbestos duot -ppareRtlj dees not alter significantly the , 4*^ .. * eonse ox experimental .tuberculosis in guinea pigs a Vv.n-' This eoae^ttsien 33 tentative since tWe evidence on vhich it i3 based -ioe3 not conform vrith cur upual experience- R.efer- ence to T-afcle 3 to.11 3horr that T.'hen infection was coincident rith onss-- of dust exposure there uis temporary progression of the disease with subsequent healinaj when infection was initiated after 2o 3/k months of dyist exposure the course of the tuberculous disease was not appreciably altered. In contrast, it has been observed in experiments with mixed du3 ts containing quartz that if there is a slight Progression of the tubercu losis when infection and dust exposure are coincident, this effect is more marked (instead oi less, as with asbestos) when infection is initiated after a p; r:iod of dust exposure. t' This conclusion concerning the e 'feet of inhaled asbestos dust- on tuberculosis see'.as justi. isd because in the more sensi- tive test (infection initiated alter a period of dust exposure) there "was no appreciable increase in susceptibility to the tuberculov.s infection, ;. ><. lioTiersr, since the findings in ths l-'-h pi c .j-oU;' tc-qjoricnco, smo FAX NO. 3043434186 P. 50 FEB-13-95 HON 17:39 J F HUMPHREYS ATTY FEB-13-95 'HON 17:17 J F HUMPHREYS ATTY FAX NO. 3043434186 P.02 2 i PLEAXINHTIBIFITF'S I 4170.1 9 --------- AFFIDAVIT WASHINGTON DISTRICT OF COLUMBIA ) ) ss. ) BEFORE ME, the undersigned Notary Public, personally came and appeared MICHAEL RHODE, a person of the full age of majority, being of sound m i n d an d body, who, after being first duly sworn by me, did depose and say: I, M I C H A E L RHODE, a m a n e m p l o y e e of the A r m e d F o r c e s I n s t i t u t e of Pathology, Washington, D.c. I am custodian of the original a r c h i v e s of Dr. A r t h u r J. Vorvald. Pages 1 through V 7L attached hereto are true, correct and authentic copies of documents from Dr. Arthur Vorwald's archives. T h e p a g e s a t t a c h e d are _______ R e v i s e d v e r s i o n of A S B E S T O S I S Experimental Studies bv The Saranac Laboratory. Report to the J o h n s - M a n v i l l e Corporation, d a t e d J a n u a r y 31. 1949__________________ Dr. Vorwald was the Director of the Saranac Laboratory of the T r u d e a u Institute. U p o n his death, Dr. Vorwald's a r c h i v e s were donated to the Armed Forces Institute of pathology by his widow. i' Dr. Vorwald's archives are in such condition as to raise no suspicion concerning their authenticity; they were received by the A r m e d Forces Institute of Pathology from Dr. Vorwa l d ' s w i d o w after RHODE AFFIDAVIT - Pe 1 of 2 FEB-13-95 NON 17:17 j F HUMPHREYS ATTY FAX NO. 3043434186 P. 03 Dr. Vorwald's death; they are presently on file as authorized by law in the National Museum of Health & Medicine, Armed Forces Institute of Pathology, Building 54, Walter Reed Army Medical Center, Washington, ..D.C. 20306.-6000; and the archives haves-heen-in existence for 20 (twenty) or more years. SWORN TO AND SUBSCRIBED before me, the undersigned Notary public, on this the c ~/ day of April, 1992. My Ctoommmimsisiio^nn_Jxpires: ' NOTARY PUBLIC Printed Name: RHODE AFFIDAVIT - Puce J of I Metropolita* Lots Lxsctlvnce Cokpajce O n X a w b o A r n 7 S .H n M M O .H .Y . 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V Varf traly VB17 f o d l r n Broa Boerotary and * Attoiaoy. e A. . flahor L. C. Hart J. P. Voodard T s