1006.] Resistance, of Mice to the Growth of Cancer. 183 



at different times according as they are in the positive or negative phases of 

 growth. 



When small doses of tumour, O'Ol to 0'02 gramme, are unsuccessfully 

 inoculated into young and susceptible mice, a second inoculatiou is often 

 successful; similar doses will give negative results in a large proportion of 

 adult animals at the first inoculation, and also on subsequent inoculation. 

 The differences between young and old mice and between the employment of 

 small and large doses explain contradictory statements to the effect that 

 apparently refractory animals of a primary inoculation can or cannot be 

 subsequently inoculated. When large doses of growing tumour are success- 

 fully inoculated into young mice, giving nearly 100 per cent, of success, the 

 same proportion is not always obtained in adult animals, although their 

 relative refractoriness can often be overcome by such an increase in dose, 

 provided the tumour tissue is in the positive phase of growth. Young mice 

 which prove refractory to such large doses also prove refractory on subsequent 

 inoculation, as also do adult and old animals. 



The nature of the tumour tissue inoculated is of great importance. Where 

 small doses give a maximum success, large doses may also do so, producing 

 very much larger tumours in the same time ; on the other hand, the larger 

 doses may be less successful than the small ones, this being explained by the 

 extent to which the simultaneous absorption of tumour tissue hinders growth. 

 The absorption of tumour tissue is inversely proportionate to the number of 

 cells growing in the graft. Whereas a large dose of cells in the positive phase 

 leads to large tumours and no immunity, a large dose of cells in the negative 

 phase* yields very few tumours, permits of much absorption, and gives a 

 high proportion of resistant animals. There is much talk about the " virulent " 

 and " avirulent " nature of different tumours, but the recognition of the fact 

 that the " virulence " of the cells of a single tumour fluctuates between 

 negative and positive phases will explain the contradictory statements of 

 those who have succeeded and those who have failed to induce immunity by 

 the injection of living tissue. It also explains the unexpected positive results 

 obtained in some curative experiments with immune sera and the absence of 

 any effect in others. Great care is necessary in accepting such positive results 

 as " cures " artificially effected, unless spontaneous absorption has been 

 excluded. For example, two tumours out of 12 disappeared after one or 

 two injections of rabbit serum. Spontaneous absorption occurred in the same 

 proportion of the control animals. The injections had no effect on tumours 

 of other series in which no spontaneous absorption took place. 



The phenomena discussed in the preceding pages point clearly to the inter- 

 * Cf. protocol, p. 178, and footnote. 

 VOL. LXXIX— B. P 



