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Nineteenth Century Foundations of Cancer Research Origins of Experimental Research*

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Nineteenth Century Foundations of Cancer Research Origins of Experimental Research* Nineteenth Century Foundations of Cancer Research Origins of Experimental Research* VICTORA. TRIÓLO (McArdle Memorial Laboratory, University of Wisconsin, The Medical School, Madison, Wis.) CONTENTS Caroline Brewer Croft Cancer Commission 22 Huntington Cancer Research Fund 22 INTRODUCTION 4 REFERENCES 23 Unit Concept of Structural Organization 5 Unit Concept of Disease 5 INTRODUCTION THE CLASSICINFECTION THEORY OF CANCER 5 Bacterial Theory 5 This review will discuss the origins of experimental Protozoan and Yeast Theories 6 cancer research through three selected topics: (a) the Mycetozoan Theory 7 classic infection theory of cancer, (6) studies on tumor Virus Theory 7 STUDIES ON TUMOR TRANSMISSION 8 transmission, and (c) studies on tumor growth. No Precursal Implantation Research 8 attempt will be made to appraise these subjects from a Doutrelepont 8 scientific or formally historical viewpoint, since several Discovery of Transmissible Canine and Rodent Neoplasms 9 excellent surveys of this kind are available (79, 175, 259, Novinsky and Hanau 9 263).' Moreover, critical evaluations in terms of recent Morau 9 Velich 9 trends can be made only by experts in each field. A few Establishment of the First Rodent Tumor Lines 9 of the earlier conceptual attitudes which have been Loeb and Jensen 9 distinctly altered by modern research will be pointed out Borrel 10 in footnotes. This paper, and others which are projected, Michaelis and Ehrlich 11 Bashford, Murray, and Cramer 11 is designed principally as a guide to nineteenth century Gay lord, Clowes, and Baeslack 11 cancer research, surveyed along the broadest lines. Its Tyzzer 12 scope includes the presentation of a more comprehensive Cumulative Results 12 bibliography than is now available in the English literature Canine neoplasms 12 on the history of cancer. Rat neoplasms 12 Mouse neoplasms 12 When the specific scientific relations of a previous era The Infection Theory in Tumor Transplantation Research 13 are examined it is correct to avoid a technical vocabulary STUDIES ON TUMOR GROWTH 13 not appropriate to that era. For example, terms such The Experimental Production of Tumors 13 as 'homologous,' 'heterologous,' 'isologous,' and 'autol- Cell transfer theory 14 ogous,' and their precise import for modern transplan Cell irritation theory 14 Growth mechanisms 15 tation work, cannot be applied to a few roughly Resistance and Immunity in Experimental Cancer 15 analogous procedures of 60 years ago. To the investigator Transmissible rodent neoplasms 15 working at the turn of the century the term 'cancer' Transmissible canine neoplasms 16 implied 'a malignant growth of epidermal origin,' and Further studies on immunologie protection 17 Physical and Chemical Research on Tumor Cells 17 frequent distinctions among cancer, sarcoma, and the Temperature and chemicals 17 other major categories of neoplastic growths are found in Radiations 17 the scientific communications of these times.2 Archaic Biologic implications 17 terminology where it appears will be qualified for the Biochemical Characteristics of Tumor Cells 18 sake of clarity. Protein constituents 18 The 'infectious' nature of cancer was first suggested in Enzymes 19 Nucleic acid constituents 19 the seventeenth century (79, p. 34), but with the rise of Inorganic constituents 20 modern bacteriology in the 1870's and 1880's the exact Immunologie Relationships 20 means were provided whereby the infection theory of Cytolytic and cytotoxic agents 20 CONCLUSIONS 21 cancer could be empirically tested. The possibility of Parasite Theory 21 this etiological breakthrough was entirely dependent upon Theories of Biological Origins 21 1A new history of cancer, Geschichte der Krebskrankheit, by Cell Autonomy Concept 21 Juraj Körbler (Zagreb), issued by Verlag Palm & Enke, Erlangen, Tumor Growth Research 21 is scheduled to appear in the near future. Tumor Metabolism Research 22 2Before 1855, the histogenic period of cancer research, all Research Programs in the United States 22 malignant tumors were designated as 'cancer' or 'carcinoma'. New York State Cancer Laboratory 22 The etymological relationship between the term 'cancer' (Gr. karkinos, crab) and the term 'carcinoma' (Gr. karkioma, from * This work was supported by grant CRTY 5002 of the National karkinos, crab) appears to have carried over so that 'cancer' and Institutes of Health, U. S. Public Health Service. 'carcinoma' retained equivalent meanings. Downloaded from cancerres.aacrjournals.org on September 27, 2021. © 1964 American Association for Cancer Research. TRIÓLO—Foundationsof Cancer Research the results of prior, systemic, and descriptive research. imbalance' (239, p. 78), nor Cohnheim's theory of These prior developments may be classed under (a) the 'embryonic rests' (1875 [59]) presented entirely convincing unit concept of structural organization and (6) the unit answers to the question of etiology.3 Cohnheim's argu concept of disease. The events which resulted in the ment was acceptable as an explanation for the occurrence formation of each concept were in many instances inter of certain complex tumors such as teratomas, but it was related. unsatisfactory for explaining the formation of carcinomas. Unit concept of structural organization.—The unit Thiersch's theory was palpably contradicted by Waldeyer concept of structural organization is based on the cell (1867 [250], 1872 [251]). Notwithstanding their limita theory, and Johannes Müllerin 1838, the year in which tions, these theories, and others which appeared later, Schwärmproposed the Cell Doctrine, first reported the provided the incentive for highly productive research. cellular structure of certain tumors (164). Müller's The rapidity with which microbiological research was work suggested the possibility of identifying malignant taken up by European and American medical departments tissues through different proportions and groupings of shortly after 1880 (53) reflects the broad medical aware cells. Subsequent research on cellular differentiation ness of its implications for every area of pathology. In pursued in the 1840's and 1850's by Müller,Remak, and microbiology a clear opportunity was presented for a others (192) repudiated a popular hypothesis that new solution of the cancer problem. This outlook channeled cells were formed from the intercellular matrix and research into the first widespread experimental attack on replaced it with the theory that all animal cells originate cancer. from pre-existing cells (Omnia cellula e cellula). Virchow, using this principle as the cornerstone of his Cellular THE CLASSIC INFECTION THEORY Pathology, formulated by 1858 (248), established the OF CANCER cell as the focus of tumor growth, but he misinterpreted Bacterial theory.—The existence of a cancer microbe the nature of endogenous cell formation (80, 259, pp. 4-5). was postulated as early as 1872 by Nepveu, and this Thiersch (1865 [239]) advanced decisive evidence for the assumption was again advanced in 1881 by Nedopil and epithelial (glandular) cell origins of epithelioma, through Cripps, but these authors offered no empirical evidence to the use of improved histological technics, and Waldeyer support their contention (263, p. 549). From a report (250), in 1867, produced further proof that all carcinomas read in 1886 before the New York County Medical were derived from the epithelial strata. These con Association by Laurence McNamara (151) it appears that clusions (a) corrected Virchow's belief that connective the subject was being actively pursued through the early tissue elements were capable of transformation into 1880's. McNamara announced that clinical and experi cancer cells and (6) established through analogy that the mental efforts thus far had failed to link a bacterium dictum'Omnis cellula e cellula,' had to be amended to 'Omnis with the cause of tumors and that tumors had never been cellula e cellula ejusdem generis' (A tumor is analogous to successfully inoculated, nor had they ever infected the any other new formation and results from the prolifera surgeon. He suggested that rapidly growing sarcomas tion of cells, of the same general character as the tumor). showed 'reactive' changes analogous to vegetable cells This conception provided a sound taxonomic and morpho infected with actinomycetes—namely, the production logical basis for cancer research in the 1870's. of small round cells in the earlier stages and giant cells in Unit concept of disease.—Between 1820 and 1860, the later stages resembling the inflammatory actions of largely through the initiative of the Paris Clinical School, the fungus in vegetable growths. Nevertheless, McNa a long established system of clinical diagnosis based upon mara conceded that if sarcomas were caused by a generalized symptoms gave way to concepts of disease, microorganism, it would be necessary to suppose that the each related to a localized, structural pathology (230). process required very favorable conditions. For example, the recognition of 'specific disease entities,' Concerning the microbic source of carcinoma McNamara such as 'pneumonia,' 'pleurisy,' and 'bronchitis' sup stated that the misplaced epithelial elements could account planted the vague nosonomic 'inflammation of the chest' for all the reactive changes in the cells of the matrix. If of earlier times. With the identification of local sites of a microorganism were to be considered the cause of this disease, research programs were able to pass to a con class of tumors, it was not clear why it
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