Chronology of asbestos cancer discoveries: experimental studies of the Saranac Laboratory

Our plain-English summary of Chronology of asbestos cancer discoveries: experimental studies of the Saranac Laboratory, by G.W. Schepers (American Journal of Industrial Medicine, 1995).

The study

• Author: G.W. Schepers
• Journal: American Journal of Industrial Medicine
• Published: 1995;27(4):593-606
• Type of article: Historical article
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This commentary challenges a recently published perception that Dr. Le Roy Upson Gardner had not actually discovered in 1942 that inhaled chrysotile fibers could induce malignant neoplasia in mice. The handwritten laboratory notes and some of Dr. Gardner's slides have recently been found. They verify that the tumors he saw in the mice included truly malignant neoplasms. Gardner had by then also accumulated 11 cases of human lung cancer (two mesotheliomas) derived from Quebec asbestos miners and millers. An inhalation study designed by Dr. Gardner and conducted between 1951 and 1954, using cancer-insusceptible mice, yielded neoplasia risk ratio of 5.7 compared with control animals. The studies also showed that the primary effect of chrysotile is to cause epithelial proliferation in alveoli adjacent to bronchioles. Chrysotile type asbestos bodies were shown to remain only transiently ferruginous, but even though invisible in direct light they can be visualized at high magnification through use of phase contrast and polarized light micrography.

In plain English

This article was a commentary, not a new study. The author, a former director of the Saranac Laboratory, responded to a 1993 letter by Dr. Enterline. That letter questioned whether Dr. Le Roy Upson Gardner had found in 1942 that inhaled chrysotile caused malignant tumors in mice. The author drew on Gardner's handwritten notes, held by the author under court order, and on personal recollections. According to those notes, Gardner judged 9 of 11 mice exposed to chrysotile aerosol to have developed neoplasia, an incidence of 81.8%. The author reported a later mouse study designed by Gardner, with 179 mice inhaling chrysotile and 181 unexposed controls. After 14 months, lung tumors were found in 9.5% of the exposed mice and tumors in 5.5% of the controls, a risk ratio of 1.73. An unpublished statistician's report gave a cumulative risk ratio of 5.7 in the final months. Two guinea pigs that had inhaled chrysotile seemed to show early carcinoma. The author concluded that Gardner had already resolved whether chrysotile causes cancer in animals, while noting that the mouse slides had vanished and could not be checked.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Commentary: a historical account and rebuttal, based on the author's recollections, unpublished laboratory records, and Dr. Gardner's handwritten notes
• Who was studied: Experimental animals at the Saranac Laboratory: 11 mice described in Gardner's notes; a later mouse study of 179 chrysotile-exposed mice and 181 unexposed controls; guinea pigs from experiment 770 (1936 to 1942). The author also mentioned a laboratory file of Quebec asbestos workers' cancer cases.
• Exposure: Inhaled chrysotile dust. In the later mouse study, exposure was daily at about the then threshold limit value of 5 million particles per cubic foot of air. Guinea pigs inhaled long fiber chrysotile for up to 34 months. The author also discussed KAYLO, an asbestos-containing thermal insulation dust.
• Main results:
  • According to the author's account of Gardner's notes, Gardner judged 9 of 11 chrysotile-exposed mice to have developed neoplasia. That is an incidence of 81.8%, said to be six times the usual tumor rate in this mouse species at the laboratory.
  • In the later mouse study, after 14 months of exposure, 9.5% of the 179 chrysotile-exposed mice had developed lung tumors, compared with 5.5% of 181 unexposed control mice that had developed tumors: a risk ratio of 1.73.
  • The author reported that the laboratory statistician's report, which was never published, gave a cumulative risk ratio for neoplasm of 5.7 in the final months of the mice's lives.
  • Two guinea pigs from experiment 70 that had inhaled chrysotile seemed, in the author's view, to show early phases of carcinoma formation.
  • The author reported finding nine human lung cancer cases and two mesothelioma cases in a Saranac Laboratory file on Quebec asbestos workers.
  • A rat study launched by the author, using chrysotile and beryllium sulfate exposures, gave inconclusive results.
• The authors' conclusion: The author concluded that Dr. Gardner had already resolved whether chrysotile causes cancer in animals, and that Gardner's mouse tumors included truly malignant ones.
• Limitations the authors state:
  • The mouse slides vanished, so what Gardner saw cannot currently be verified.
  • The author could not check what kinds of tumors occurred in the later mouse study, because the protocols and slides had been removed.
  • The KAYLO animal study was not designed to test whether the dust causes cancer.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Saranac Laboratory, Chrysotile, Neoplasm, Lung Cancer, Mesothelioma, Alveoli, Asbestos Bodies.

Related studies

• Asbestos: a chronology of its origins and health effects — R. Murray (1990)
• Asbestos: a chronology of its origins and health effects — L. Arblaster, E. Renvoize, et al. (1990)
• Characteristics of tumors and tumor cells cultured from experimental asbestos-induced mesotheliomas in rats — J.E. Craighead, N.J. Akley, et al. (1987)
• Chrysotile asbestos fibers mediate homologous recombination in Rat2 lambda fibroblasts: implications for carcinogenesis — K. Lezon-Geyda, C.M. Jaime, et al. (1996)
• Chronic effects of dietary exposure to amosite and chrysotile asbestos in Syrian golden hamsters — E.E. McConnell, A.M. Shefner, et al. (1983)
• Malignant mesothelioma resistance to apoptosis: recent discoveries and their implication for effective therapeutic strategies — F. Villanova, A. Procopio, et al. (2008)

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