with depression in the proliferation of the carcinomatous tumours. On the other hand, in tumours already well advanced in the mixed stage, the epithelial (carcinomatous) component may again outgrow the connective-tissue (sarcoma) and the picture of an ordinary carcinoma reappear. This secondary suppression of the sarcoma seems to synchronise with a higher energy of growth on the part of the carcinoma. Meantime, however, we consider it inadvisable to enter on a hypothetical discussion, all the more because the phenomena lend themselves to an objective investigation, and further data are required.

By further propagation the sarcomatous elements acquire, by degrees, increased powers of growth, which allow them at last to outgrow the carcinoma, and to continue as pure sarcomata. This latter part of the sarcoma development seems to be an evolution of a new and stronger strain of cells independent of the organism in which they are growing, and many facts speak for a similar process of evolution playing an important part in the earlier stages. Principles similar to those laid down by Darwin in explaining the origin of species of animals, may also to a certain extent be applied to explain this development of a new kind of connective tissue cells during continued transplantation.

While in our last, best followed cases, there is strong evidence of the importance of continued transplantation in the development of sarcoma, in other cases this factor does not come in at all. In tumour 129 the primary growth already shows stroma cells with sarcomatous properties. Also in our third case (37/2 C) in which changes, probably sarcomatous, have taken place between two operations, another factor must come into play. We have no means of deciding how the sarcomatous component of the spontaneous mixed tumour has arisen. In the 2 C case formative influences exercised by the carcinoma cells on the connective tissue of the host, seem to play the most important part. When we reflect upon what these two groups of conditions, viz. on the one hand the repeated transplantation, on the other the formative influences exerted by the carcinoma cells, may have in common, there appear to underlie each of them chronic irritative influences similar to those emphasized by Bashford as probable mediate etiological factors in numerous forms of human cancer, at the beginning of this Report. The observations we have recorded on the development of experimental sarcomata seem to help us to an understanding of how chronic irritation may lead to development of malignant new growths. Through the continuous, or intermittent but frequently repeated incitation of the regenerative powers of the cells in some cases a strain of cells may

be evolved, with enhanced power of regeneration and proliferation, no longer subject to the normal regulative forces of the organism. This conception is not formulated on abstract speculations, but on actual observations of all stages of the development of sarcoma under experimental conditions. The importance of the development of sarcomata as described in this paper, lies in the fact that it allows us to attack directly, and by experimental methods, the question of how cells with apparently normal biological properties turn into malignant elements.

LITERATURE.

ALBRECHT, H.: Ueber das Karzinosarkom des Uterus.
Pathologie, Band ii. Heft 1, 1908.)

APOLANT, H.: Die epithelialen Geschwülste der Maus.
lichen Institut für experimentelle Therapie zu
1906.

(Frankfurter Zeitschrift f.

(Arbeiten aus dem KönigFrankfurt an M. Heft 1,

: Ueber die Entstehung eines Spindelzellensarkoms im Verlauf lange Zeit fortgesetzter Carcinomimpfungen bei Mäusen. (Verhandlungen der deutschen patholog. Gesellschaft zu Meran, 1905.)

Die experimentelle Erforschung der Geschwülste. (Handbuch der pathogenen Mikroorganismen by Kolle and Wasserman. 1ster Ergänzungsband, Heft 2, Jena, 1906.)

—: Ueber künstliche Tumormischungen. (Zeitschrift f. Krebsforschung, B. 6, H. 2, 1908.)

BASHFORD, E. F.: Einige Bemerkungen zur Methodik der experimentellen Krebsforschung. (Berl. klin. Wochenschrift, 1906, no. 16.)

BASHFORD, E. F., MURRAY, J. A., & CRAMER, W.: Source of the Constituent Elements of New Growths obtained by Artificial Propagation. (2nd Scientific report of the Imperial Cancer Research Fund.-Part II. Taylor & Francis, London, 1905.)

: Stroma is a Specific Reaction on the part of the Host. (Ibidem.) Comparison between the Transmission of an Infective Granuloma of the Dog and Carcinoma of the Mouse. (Ibidem.)

: Action of Radium on Transplanted Mouse Tumours and its Relation to the Spontaneous Arrest of their Growth. (Ibidem.)

: Einige Ergebnisse der experimentellen Krebsforschung. (Berl. klin. Wochenschrift, 1905, no. 46.)

BASHFORD, E. F., MURRAY, J. A., & HAALAND, M.: Ergebnisse der experimentellen Krebsforschung. (Berl. klin. Wochenschrift, 1907, nos. 38 & 39.)

BORREL, A.: Epithélioses infectieuses et epithéliomas. (Annales de l'Institut Pasteur, T. xi. 1903.)

Le problème du cancer. (Bulletin de l'Institut Pasteur, T. iv. nos. 12- 15, 1907.)

BRAUN, W.: Klinisch-histologische Untersuchungen über die Anheilung ungestielter Hautlappen. (Beiträge zur klinischen Chirurgie, Bd. 25, 1899, p. 211.)

EHRLICH, P.: Experimentelle Studien an Mäusetumoren.

Lecture at the 1st

Internat. Congress for Cancer Research, Frankfurt-Heidelberg, 1906.
(Zeitschrift für Krebsforschung, Band 5, Heft 1-2, 1907.)

: Bemerkungen zu den Aufsätzen des Herrn Dr. Orthner.
Wochenschrift, no. 49, 1907.)

(Wiener klin.

EHRLICH, P. & APOLANT, H.: Beobachtungen über maligne Mäusetumoren. (Berliner klin. Wochenschrift, 1905, no. 28.)

: Zur Kenntniss der Sarcomentwicklung bei Carcinom-transplantationen.
(Centralblatt für allgem. Pathologie u. path. Anat. 1906, no. 13.)

Erwiederung auf den Artikel des Herrn Dr. Bashford. (Berliner klin.
Wochenschrift, 1906, no. 21.)

(Ibidem, 1907, no. 44.)

: Ueber spontane Mischtumoren der Maus. EHRLICH, P., APOLANT, H. & HAALAND, M.: Experimentelle Beiträge zur Geschwulstlehre. (Ibidem, 1906, no. 2.)

ENDERLEN: Histologische Untersuchungen über die Einheilung von Pfropfungen nach Thiersch und Krause. (Deutsche Zeitschrift für Chirurgie, Bd. 45, 1897, p. 453.)

GAYLORD, H. R., & CLOWES, G. H. A,: On spontaneous cure of Cancer. (Surgery, Gynecology, and Obstetrics, vol. ii. no. 6, June 1906.)

HAALAND, M.: Les Tumeurs de la souris. (Annales de l'Institut Pasteur, no. 3, 1905.)

: Ueber Metastasenbildung bei transplantierten Sarkomen der Maus. (Berliner klin. Wochenschrift, no. 34, 1906, and Zeitschrift für Krebsforschung, Band vi. Heft 1--2.)

- Musekräft og experimentel kräftforskning. (Norsk magazin for lägevidenskaben, 1907, no. 2.)

HANAU Erfolgreiche experimentelle Uebertragung von Carcinom.

der Medizin, vol. 7. 1889.)

(Fortschritte

V. HANSEMANN, D.: Verhandlungen der deutschen pathol. Gesellschaft zu Meran,

1905.

JENSEN, C. O.: Experimentelle Undersögelser over Kräft hos mus. Copenhagen,

1903.

: Experimentelle Untersuchungen über Krebs bei Mäusen.

Bakteriologie, Bd. xxxiv. 1903.)

: Biolog. Selskabs Forhandlinger, 1901-02, pp. 6 & 20.

(Centralblatt für

: Nogle Forsög med kräftsvulster. (Hospitalstidende, no. 19, 1902.)

KRAUSE, F.: Ueber die Transplantation grosser ungestielter Hautlappen. (Verhandl. d. Deutschen Gesellschaft für Chirurgie, Berlin, 1893, p. 46.)

LEWIN, C. Experimentelle Beiträge zur Morphologie und Biologie bösartiger Geschwülste bei Ratten und Mäusen. (Zeitschrift f. Krebsforschung, Band vi. Heft 2, 1908.)

LIEPMANN: Münchener med. Wochenschrift, 1907, no. 27.

LOEB, LEO: Further experimental investigations into the Growth of Tumours.
Development of Sarcoma and Carcinoma after the inoculation of a carcino-
matous tumour of the submaxillary gland in a Japanese mouse. (The
University of Pennsylvania Medical Bulletin, July 1906).

Ueber Sarkomentwicklung bei einem drüsenartigen Mäusetumor. (Berl. klin.
Wochenschrift, 1906, no. 24.)