Document g7j4QMJvKGK3mjmRGzMRKk73

FILE NAME: Raybestos-Manhattan (RBM) DATE: 1943 Mar 15 DOC#: RBM018 DOCUMENT DESCRIPTION: Letter to Dr. Ludwig Hektoen from Dr. Gardner RE Results of Inhalation Experiment on Asbestos 'V March 15, 1943 1 Dr. Ludwig Hektoen, Chairman Committee on Cancer Researoh National Cancer Institute Bethesda, Maryland k Dear Dr. Hektoen: In analysing the results of i recent Inhalation experiment on asbestosls, Z was startled to discover that a snail group of 11 white aloe that had been inhaling asbes tos duct fron 15 to 24 nonthe shoved an excessive incidence (81.8) of pulconary cancer. This experience was quite at variance with the results in all our previous long-tern duct exposures which were summarized and published by Vorwald and Karr In the American* Journal of Pathology, January 1938. I would have attached little aignlflcance to this recent finding because of the ecall number of animals involved, but for the fact that the literature now contains sons 10 reports of pulnonary oancer In casts of hunan asbestosls. Even these I have heretofore attributed to selection of oaterlal as ve have found no cases of pulnonary tumor in surveys of employed asbestos workers. However, Gloyne, Kerevether and other English observers oontend that asbestos has a specific carcinogenic action on the lungs. The question is of considerable importance in indus trial medicine because of the associated compensation aspects arid from a scientific view point, it interests me a great deal. 1 1 1 C In view of this recent finding I have reanalyzed the results of a large number of dust inhalation experiments that ve hr.ve carried on during the pa9t 25 years. The incidence of pul monary tumors is shown in the appended table. It would appear that, exce.rt in nice, tumors have been generally unoomnon In the strains of different species that we had used. Guinea pigs h*ve shown oc casional adenomas of the lung whose inoldence is not Influenced by dust exposure or by the type of dust Involved. However, in white nice that survived for 15 or more months in our dust roone, various forms of lung tumors were much more frecusnt. The overage inoldence of such tumor* in a group of 143 mice exposed to 4 different quartzcontaining dusts was 18.83 but this appears small in oontrast to this incidence of 61.83 in the asbestos mice. In 51 younger nice that died or were killed after exposures of 10 or 11 months there was only one instance of pulnonary tumor. Therefore, either age or duration of dust exposure oust be important. -61 Oase s' 02046 ( I Ludvig Hektoen -2- Karch 15, 1943 I Kona of these experiments was planned to study 'teoinogenlo effects. Mice vere only used as there was space in the A * t roooa and cany of these aninals that died after short exposures a r e discarded without autopsy as they oould not have developed a sufficient amount of duet re:-.otion to be of Interest. The strain of u c e kept in the laboratory has changed fron tine to tine by ln- ll'tatlen of new stock. At one tine we did procure fron Dr. Kaud Slye fob? cancer susceptible stock but as these anlanls failed to reset to '_ihaled quartz ve lost Interest in the subject. M Obviously under such conditions, the results with cbeatos cean nothing but in view of the considerations which I have ited, Z believe they should be checked. A decisive answer to this estlon would be of real practical value. Fron what we have learned ibout the action of asbestlforo nlr.erals in the living body, I would' * t be surprised to discover that their oarolnogenio effects are dif- J r r t fron those of other ninerals. Their orystallographlo structure aFLi.qut. They apparently act as nechanlcal irritants rather than 'heolcally as la the oase with quartz and other force of free silica. a| crushing or grinding, asbestos fibres loose parctlcally all their Jiritatlng capacity; quartz on the other hand, beocnes core irritating s the particle size decreases. Asbestos provokes fibrosis only in the ngs of certain speoles; quartz excites such reaction in any organ of 7 speoles of anlcal that ve have tested. Asbestos ssens to have no fspecific action upon pulconary eplthellun but in one speoles, it causes unusual type of diffuse flbroeis which conpresses and distorts-the lthcllal-llned reeplratory bronchioles but often falls to obliterate em. However, this mechanise would not appear to be the one responsible r the couse tuoors for this is one of the species which develops no brosis on exposure. PorBlbly, the lack of reaotlon is due to sup- Jior upper respiratory protection agalnet inhaled foreign bodies. The 1unga of oioe, exposed to asbestos du9t for two years reveal relatively v fibre and all of these ore short and ooated to fore that peculiar ructure known ae the asbestoe body. f Xn order to verify our accidental dlsoovery of pos- ble oarclncgenlo action of fibrous asbestos, Z would like to rep * e couse inhalation experloent under properly controlled conditio would breed a large nusber of cancer susceptible Bios, splitting oh litter into three groups and keep a record of the ages of eaoh. a third of the offspring would be kept in a normal atmosphere as a ' o r f 'ol; another third would be exposed to quartz duet as a seoond j j r v d and the other third would be exposed to asbestos dust. We 1 Is i Dr. Ludvig Kektoen 3- Ilarch 15, 1943 Vould attenpt to obtain 500 nice for each group. The exposures 'ould apparently have to be continued for 15 to 24 nonths; Our routine In auch experlnents provideo for dusting S hours & day, 6 days a veek. We have all the neoesaary eoulpoent for auch experlner.ta and a trained laboratory personnel.* Funds are lacking however. Our previous atudy of aabeatosla which continued for a period of 7 years vas finanoed by th- Asbestos Association. Since this group of nanufacturera has already invested $30,000, I cannot ask then for further contributions. 1 discussed the natter with Dr. Rhodes at the Manorial Ho spital who favored and vas of the opinion that It vas vorthy of consideration by your cocclttee. I an therefore applying for a grant of $5,0C0 to cover the cost of the first year's expense. 1 had told Dr. Rhodes that 1 vould be willing to do the entire experlcent for this anount and ordinarily I should. How ever, on ny return fron Hev York, I found two proposals for investiga tions of other industrial dusts each of vhlch yield the Laboratory $5,000 a year. As Z have only two dust roocs at the present tine free for new vork, Z cannot afford to tie up or.e of then for two years for half the anount. Should you be favorably lnpressed vith this proposal I vould appreciate any orltlolsns or suggestions. . Sinoerely yours, LUO:?.EH Leroy U. Gardner, X. D. Direotor S 02048