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the tumour cells. With Bashford and Cramer we drew attention to its importance in 1906-07. In fact this adaptability, in which may be included for convenience the resistance to such injury as necessarily occurs on transference to new hosts, is probably the most important determining factor in deciding whether a spontaneous tumour shall grow or not. This seems to be the explanation of the otherwise remarkable observation which we have frequently made and which is recorded by Gierke, and Hertwig and Poll, that spontaneous tumours inoculated into animals in which transplanted tumours are already growing, are only positive in them when the spontaneous tumour is also capable of growing in normal mice.

The other problem of the relative avidity of the cells for nourishment as compared with non-cancerous tissue-elements, is nevertheless one of great interest from the standpoint of the nature of the metabolic processes in play in the growth of cancer. In order to obtain more insight into these relations, experiments were devised in the following manner :-Mice spontaneously affected with mammary new growths had these removed by operation. The transplantability of the growths was tested on normal animals, and when a sufficient number of operated animals had been obtained their suitability for the growth of an easily transplantable tumour was tested and compared with a similar or larger number of adult and aged animals. Clean experiments of this kind are extremely difficult to carry out on a large scale. The interval between the operation and the subsequent transplantation necessarily varies between somewhat wide limits, and the number of cases in which the transplantability of the spontaneous tumours has been tested is too small to permit as yet of firm conclusions. The spontaneous carcinomata, as shown on preceding pages, frequently recur after apparently total extirpation, and in those in which local recurrence does not take place, metastases in the lungs are often found after death.

Therefore, even if we discard hypothetical constitutional differences for the present, the animals are not strictly comparable with noncancerous subjects of similar age. The results obtained in two such experiments are given in the accompanying graphic records (fig. 47). The first of these shows (32) that while in normal animals not one

16 A

tumour grew progressively, in two of the cancer mice, tumours developed and reached a large size. In four others, temporary proliferation was followed by absorption of the small tumours primarily arising.

(32) 15 G

In the second series three mice (112, 115, 118) developed tumours which grew rapidly and progressively to a large size; in a fourth (105) a tumour first appeared five weeks after inoculation at the point of entrance of the inoculating needle and also grew progressively. In two mice (97, 107) tumours developed, but grew very slowly, and after reaching a moderate size remained stationary till death. Finally in three animals no growths appeared, or only a temporary proliferation. The normal animals inoculated at the same time with the same material developed tumours showing a similar gradation; three (4) grew progressively, two remained stationary for a long period, and, in the remainder temporary proliferation was either followed by absorption or the result was negative from the first. It must be noted that the transplantable tumour used for these experiments is one of the most rapidly growing in existence. It is not exceptional to obtain tumours of 10 to 15 gr. in ten days, starting from a graft of not more than 003 gr., an increase in mass of thirty to forty times in this period. For experiments of the kind under consideration this strain (32) has the additional advantage that all animals are not equally suitable, so that it grows progressively in only 50 per cent. of the inoculated animals in most cases. It is therefore particularly suitable for experiments in which slight differences between animals have to be elicited, and shows these differences both by variation in percentage of success and rate of growth. Together the two series of experiments show, that the transplantable tumour adapts itself, on the whole, more readily to the conditions present in animals spontaneously affected than to the conditions in animals of approximately the same age in which cancer has not spontaneously arisen. The further question now arises: what influence does the transplanted tumour exert on the organism as a whole, of a mouse the subject of spontaneous cancer? Does the transplantable tumour grow at the expense of the animal's tissues, or, is sufficient additional nourishment elaborated to supply the materials for the rapidly forming tumour-tissue? Further, how does the transplantable tumour compare in rate of growth with the tumour which has arisen spontaneously in the animal itself, when recurrence-in reality its continued growth-takes place? To these questions the experiments furnish a partial answer. As to the first two, by weighing the animals throughout the course of the experiment at regular intervals and after death determining the weight of tumour arising from the transplantation, it can be shown easily that the tumour does not grow at the expense of

the tissues of its new host in the first instance. On the contrary the animal as a whole increases in weight pari passu with the growth of the tumour because food materials are elaborated in sufficient excess for the nourishment of the graft. It is only in the later stages, when the growth has reached a relatively enormous size, that the animal fails to supply food at a quick enough rate. This is seen in the case of mice 105 and 112 of fig. 45, in which the whole increase in weight (7.5 grams in mouse 105, 4.5 grams in mouse 112) is represented by the transplanted tumour. In mice 115 and 118 the transplanted tumour has in the end increased at the expense of the mouse, but the course of the weight-curve shows that this condition is not established at once. It supervenes when the total mass to be fed becomes excessive. Cancerous mice, on the whole, respond better to such calls than do young, still growing normal animals; arrest of growth soon takes place in young animals, and the whole increase in weight which the organism should have exhibited normally at a given age is represented by the weight of the new growth.

It

may be concluded that the transplantable tumour establishes itself in the spontaneously affected animal in consequence of its great adaptability to new hosts, that it shares the food supply in common with the normal tissues without starving them, and that its growth results from the capacity its cells have to adapt themselves to the conditions in which they are placed, and to utilise the nourishment presented to them for the formation of new elements, and not because they take up that nourishment with greater avidity. When the spontaneous tumour recurs, its growth progresses as a rule more rapidly than that of the transplanted tumour, even although its energy of growth as tested by transplantation into normal animals may be much inferior to that of the transplantable growth. This fact is illustrated in figs. 44 & 45, in the tumours numbered 97 and 107, in which the spontaneous tumours recurred and grew progressively, though slowly, while the transplanted tumours practically remained stationary. This phenomenon would be quite inexplicable on the assumption of a differential avidity for food. material as the principal determining factor in their relative rates of proliferation, but is at once intelligible when the importance of adaptability is considered. The spontaneous tumour requires to make no effort of adaptation; it is in its native environment. The food materials presented to it are those to which it has always been accustomed. It is probable that the factor mainly responsible for its ability to compete successfully with the cells of a growth which, on equal terms (e. g., in

normal animals), would easily outstrip it in energy of proliferation, is that the spontaneous tumour is at home with its surroundings and food supply.

The relation of a spontaneous tumour to the animal in which it is growing cannot be described in the simple manner imagined by Ehrlich by postulating a differential avidity for food-stuffs in accordance with the side-chain theory. The relative avidity with which tissue-elements and tumour-elements take up nourishment must remain vaguely speculative so long as we measure the avidity of the tumour cells by proliferation, i. e., formation of new material, while tissue-elements no longer actively growing, cannot be expected to manifest anything of the kind in adult animals. The experiments referred to above, where young growing animals remain of small size while the tumours grow rapidly, have an apparent bearing on this point. Slow growing tumours do not exert the same influence. In the latter case the animal grows at much the same rate, whether a tumour develops or not. The retardation observed when the transplanted tumour grows with great rapidity, while appearing to speak for a greater avidity of the tumour cells, does not necessarily imply this. The tissue cells, although adding to their numbers during growth, also diminish in their call for new formative material (water, oxygen, etc.) by passing into the differentiated condition. The tumour cells do this to an infinitesimal extent, so that every step forward in new formation of tissue adds to the mass capable of further growth. The extent to which degeneration (frequently extensive in rapidly growing tumours) eliminates their requirements does not seriously invalidate this consideration. With some tumours, notably a transplantable spindle-cell sarcoma of the rat which we have obtained from Professor C. O. Jensen, the weight of tumour produced in a given time is almost exactly proportional to the initial dose, and in this case the condition of equilibrium, in which, while the tumour grows progressively, the total weight of animal and tumour remains stationary, is much more rapidly attained with the large dose than with the small one It is difficult to see why this should be so if the tumour cells extracted food-stuffs in a way and with an energy which leaves an insufficient quantity for the tissues of the host, because as soon as the tumour arising from the small dose had attained the size of that which initiates the growth with a large dose, the weights of animals and tumours in the two groups should exhibit a parallel behaviour.

It is only in the case of different strains of transplantable tumours, or of different series of the same tumour, that a comparison of avidity