Document 50R45Jaz7L1VQa1238o3k9YL5

PLAINTIFFS (g EXHIBIT March 15, 1243 Dr. Ludvig Hehtoen, Chairman Committee da. Cancer Research. Rational Cancer Institute Bethesda, Maryland Dear Dr. Eehtoen: . Xu analyzing the results of a recently'completed inhalation experiment on asbestosls, I vaa startled to discover that a snail group of 11 white nice that had been inhaling asbes tos dust from 15 .'to 2-1 months showed an excessive incidence (31.2,^) of pulmonary cancer. This experience was quite at variance with the results in.all our previous long-tern dust exposures which were summarised and published by Vorvald and Karr in the American Journal of Pathology, January 1933. I would have attached little significance to this reaent finding because of the 9mall number of animals involved, but for the fact that the literature now contains some 10 reports of pulmonary "tar.eer in cases of human asbestosls. Even these I have heretofore attributed to selection of material as v/e have found no cases of pulmonary tumor in surveys of employed asbestos v/orhers. However, Gloyne, Merevether and other English observers contend 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 and from a scientific view point, it interests me a great deal. In view of this recent finding I have reanalyzed the results of a large number of dust inhalation experiments that we have carried on during the past 25 years- Ths incidence of pul monary tumors is shown in the appended table. It would appear that, ence;t in nice, tunors have been generally uncommon In the strains of different species that we had used. Guinea pigs have shown oc casional adenomas of the lung whose incidence is not influenced bydust exposure or by the type, of dust involved. However, in white mice that survived for 15 or more months In our dust rooms, various forms of lung tumors were much more frequent. The average Incidence, of such tumors in a group of 143 mice exposed to 4 different quartzcontaining dusts was 13.8$ but this appears small In coatrast to this incidence of 81.S% In the asbestos mice. In 51 younger mice ,S that died or were hilled after exposures of 10 or 11 months there \ was only one Instance of pulmonary tumor. Therefore, either age or a duration of dust exposure must be important. 00012350 010253 Dr. ' Hekt ;sn n "\ ' . w _ 'J 1343 - ?Ione of these experiments was planned to study J caecinogenlc effec:a. Mice were only used as there was apace in the durrt rooms and many of these animals that died after short exposures vere discarded without autopsy as they could not have developed a sufficient amount of dust reaction to be of interest. The strain of nice kept in the laboratory has changed from tine to tine by Im portation of new stock. At one tine we did procure fron Dr. Maud. Slye sore cancer susceptible stock but as these aniarls failed to react to inhaled quarto we lost Interest in the subject. Obviously under such conditions, the results with aabe3tcs mean nothing but in view of the considerations which I hs.7e cited, I believe they should be checked. A decisive answer to this question would be of real practical value. Fron what we have learned about the action of asbestiform cineral3 in the living body, I weald not be surprised to discover that their carcinogenic effects-are dif ferent frea those of other ainerals. Their crystallographic structure Is unique. They apparently act as nschanica! irritants rather than chemically as is the case with, quarts and other farts of free silica. Cn crushing cr grinding, asbestos fibres lco39 carcticail7 all their Irritating capacity- quartz on the other hand, beccres tors irritating as the particle sice decreases. Asbestos provokes fibrosis only in the lungs of certain species; quartz excites such reaction In any organ of any species of animal that we have tested. Asbestos seems to have no specific action upon pulmonary epithelium but in some species, it cause an unusual type of diffuse fibrosi3 which compresses and distorts the epithelial-lined respiratory bronchioles but often fails to obliterate then. However, this mochanlsm would not appear to be the one respcnslb for the reuse tumors for this 13 one of the species which develops no fibresis cn exposure. Possibly, the lack of reaction is due to sup erior upper respiratory protection against inhaled foreign todies. The lungs of mice, exposed to asbestos dust for two years reveal relatively few fibre and all of these are short and coated to fora that peculiar. structure known as the asbestos body. In order to verify our accidental discovery of pos-- v aible carcinogenic action of fibrous asbestoa, I -would like to repeater the mouse inhalation experiment under properly controlled conditions I would breed a large number of cancer susceptible mice, splitting !v each litter into three groups and keep a record of the ages of each. Cne third of the offspring would be kept in a normal atmosphere as--a--', control; another third, -would be exposed to quartz dust as a second control and the other third, would be exposed to asbestos dust. We , 00012351 OIA'2 o i ^r. -- ^v-v^- ..c -- .u2. -. . 15, 1343 i-* ;< if uo .llerot to obtain 500 nice for each grout. 1 n o ~r "'*' o file a:pnrently have to be continued for 15 to 14 months. Cur routine in ouch experiments provides for dusting Q hours a day. -mys vee.-c- q have all the necessary ecuitment for such ex UJ nj c periments and a trained Laboratory personnel. Tunes are lachir. however. Cur previous study of asbestosl3 which continued for period of 7 years was financed by the Asbestos Association. 3i....& this group manufacturers has already invested 3C,CC0, I cannot ash then for further contributions. 1 discussed the ratter with Dr. r.hcdcs at the Memorial Hospital who favored and v;as of the ir.ion that it ..as v/orthy of consideration by your cosrslttee. I an ereforo applying1 for a grant of 5,000 to cover the cost of the rst year'3 expense. I had told Dr. Hhodes that I would be willing to do the sr.tlra experiment for this amount and ordinarily I should. How ever, on cy return from Hew Lorh, I found two proposals for investiga tions of other industrial dusts each of which yield the Laboratory 15,000 a year. .13 I have only two dust rooms at the present time free for new v/orx, I cannot afford to tia up one of them for two years for half the amount. Should you he favorably impressed with this proposal I would appreciate any criticisms or suggestions. Sincerely yours, LUG: ?.3H Leroy U. Gardner, X. D. Director 00012352 N 010255