FIG. 20.-Resistance to subsequent inoculation of tumour 32, may apparently develop after tumours have arisen, in consequence of a preliminary treatment with mouse-skin injected immediately before the primary inoculation. Mice 1- 5. Normal mice Mice 6-10. Mice treated with emulsion of skin of mouse-embryos 2 days Inoculated 24.1.08 with 0.025 c.c. of emulsion of tumour 32, in Mice 1-10 reinoculated 14.2.08 in left axilla with 0025 c.c. of emulsion of tumour 32; at the same time mice 11-19 were inoculated with the same dose of the same material, as control; Exp. 32/24 C. infective agent or virus. While in many respects we must regard resistance to inoculation as an active immunity, it is not yet definitely proved what is the exact mechanism of the process. The quantitative relations which subsist between degree of resistance and amount of tissue absorbed, render it probable that active substances in the body fluids play a rôle in producing the results. It has been mentioned in earlier papers that up to the present it has not been possible to demonstrate directly any anti-bodies in the serum of mice naturally or artificially resistant to cancer. Similarly in Russell's experiments by histological examination of grafts in immune mice, direct evidence of their existence cannot be obtained. Attempts. to demonstrate such substances in an indirect way have also given negative results. We have tried whether young, born of mice rendered highly resistant by repeated inoculations, were any more resistant than normal mice of similar age. Ehrlich's experiments on ricinimmunity showed that anti-bodies can be transferred from the mother to the young through the milk. It is also possible that such substances might be transferred by the placental circulation. The accompanying table shows the results of a corresponding experiment in the case of cancer. Twenty-one young mice, 2-6 weeks old, bred from mice which were injected repeatedly with large doses (0.25 cc.) of Jensen's tumour, were inoculated with 0.02 gr. each of Jensen's tumour (exp. J. 94 E, 26.6.07). At the same time twelve young normal mice of similar age were inoculated with the same dose as control. The result shows that the young of immune parents are not more resistant than normal animals. The negative result points conclusively to the absence of anti-bodies in the milk, since six young, 2 weeks old, developed rapidly growing tumours, while still sucking a highly immune mother that had been six times inoculated with 0·25 gr. of Jensen's tumour. The reactions responsible for the resistance which can be induced to the inoculation of malignant new growths, present many new features as compared with the well known reactions to infective organisms and their products. In particular they exhibit a higher degree of specificity, both as regards the species of animal and as regards the individual tissues of a species. At the same time they are of even greater delicacy. It has not been possible to reproduce them in new animals, by passively immunising them with the fluids of resistant mice; no evidence has been obtained of the natural conveyance of resistance from highly immune mothers to their offspring, and still less has it been possible to reproduce these reactions in vitro. The only change we have recognised is an active immunity in the resistant animals themselves, revealed by using living cells as indicators. Nevertheless the changes which can be induced experimentally are strikingly demonstrated; they can be elicited at will; quantitative relations have been shown to exist between the degree of resistance of the animal and the amount of tumour tissue or normal tissue inducing it, as well as between the dose of tumour tissue with which the resistance of an animal is tested. We are at present unable to determine whether the phenomena depend upon actual substances formed by the resistant animal and interacting with substances in the cancer cell, or are manifestations of vital activities less easily defined. As regards the hope of a practical outcome from these observations, we consider that it is not at present to be sought in the direction of a curative serum which can be employed after the manner of antitoxic sera, since the body fluids appear to be incapable of conveying anything to other animals, nor in the direction of a vaccine which will prevent the development of cancer. In fact we have found that mice which were highly protected to inoculation, subsequently developed spontaneous tumours of their own (cf. p. 322), an observation recently confirmed by Thorel. any An emphatic caveat must be entered against the premature application of of the results to man until such time as they can be extended to animals suffering from spontaneous, as distinct from inoculated, cancer; but the results obtained encourage us to continue the work, in the hope that ultimately it will be possible to control the growth of cancer in man. Before this goal can be reached, we shall require to learn much more of the actual mechanism by which mice can be rendered resistant artificially, and at the same time, of that which is responsible for natural healing. The hope of applying practically the results of the experimental study of cancer must lie in the direction of imitating or reinforcing the processes of natural cure. LITERATURE. BORREL, A.-Le problème du Cancer. (Bulletin de l'Institut Pasteur, T. V. no. 12–15, 1907.) BRIDRÉ, J.-Récherches sur le cancer expérimental des souris. (Annales de l'Institut Pasteur, T. 21, Octobre 1907.) HAALAND, M.-Beobachtungen über natürliche Geschwulstresistenz bei Mäusen. (Berliner klin. Wochenschrift, 1907, no. 23.) SCHÖNE, G.-Untersuchungen über Karzinom-immurität bei Mäusen. (Münchener med. Wochenschrift, 1906, no. 51.) Weitere Erfahrungen über Geschwulst-immunität bei Mäusen. (Verhand- Untersuchungen über Geschwulst-immunität bei Maüsen. Verh. d. Deutschen LEWIN, C.-Experimentelle Beiträge zur Morphologie und Biologie bösartiger Geschwülste bei Ratten und Mäusen. (Zeitschrift f. Krebsforschung, Band vi. Heft 2, 1908.) FLEXNER, S., & JOBLING, J. W.-Infiltrating and Metastasising Sarcoma of the Rat. (Journal of American Medical Association, vol. 48, 1907.) HERTWIG, O. & POLL, H.-Zur Biologie der Mäusetumoren. (Abhandlungen der Königlichen preussischen Akademie der Wissenschaften, 1907.) EHRLICH, P.-Experimentelle Karcinomstudien an Mäusen. (Arb. a. d. Kgl. Institut für experimentelle Therapie zu Frankfurt a M., Jena, 1906.) Experimental researches on specific therapeutics. (The Harben Lectures for 1907. London 1908.) THOREL.-Kasuistisches zum Kapitel des sog. Mäusecarcinoms. (Verhandlungen der Deutschen Patholog. Gesellschaft zu Kiel, 23-25 April 1908; Centralblatt für allgemeine Pathologie, 1908, no. 10.) [For papers from the laboratory see complete bibliography, Appendix I.] REPORT ON A STUDY OF THE VARIATIONS IN THE SECRETION OF HYDROCHLORIC ACID IN THE BY S. MONCKTON COPEMAN, M.D. CANTAB., F.R.S., AND H. WILSON HAKE, PH.D., F.I.C., F.C.S. (From the Chemical Laboratory of Westminster Hospital Medical School.) THE object we had in view in commencing this research was to determine especially, among other constituents, the physiologically active hydrochloric acid in the gastric contents of mice suffering from cancer, as compared with normal mice under identical conditions of feeding and periods of digestion *. The experiments, of which the following is a brief summary, were commenced in December 1905 and continued up to the present time (June 1908) and have recently been described in detail in a paper now published in the Proceedings of the Royal Society' †. The term physiologically active hydrochloric acid is intended to include both the free acid and that combined with proteids and nitrogenous organic bases, since, as originally pointed out by Lüttke and recently referred to by Willcox, much misconception has arisen in the use of the terms "free" and "combined" as applied to hydrochloric acid in the *We found that the only chemical work which had been done in connection with mice along these lines was by Dr. Cramer in the Laboratories of the Imperial Cancer Research Fund, and referred to by the author in the 'Biochemisches Centralblatt' (Bd. iv. p. 65, Juni 1905). Dr. Cramer estimated the total acidity in the gastric contents of mice inoculated with alveolar carcinoma (Jensen), and found no diminution in this respect on comparing the results with those he obtained with normal mice. The paper in the 'Proceedings of the Royal Society' gives full particulars of all the methods employed by us and a discussion of their precise value from the chemical point of view; only a brief résumé of results is possible in this Report, but tables are appended giving detailed data of each series of experiments. Deutsch. Med. Woch. 1891, p. 1325. |