1906.] Resistance of Mice to the Growth of Cancer. 173 



either alone or in conjunction with one another, they determine the 

 phenomena of growth under artificial propagation. Hence, extensive control 

 experiments are necessary at every step in attempts to modify growth 

 artificially, for a low percentage of success may be due to a refractory 

 condition in the mice used, or to a lower energy of growth of the tumour 

 cells. In addition, other factors of less importance can introduce variations 

 which are detailed below, and must be excluded. 



The following precautions have been taken to obtain results which may be 

 legitimately compared. The differences which have been elicited in these 

 experiments are in many cases slight, and dependent on very subtle altera- 

 tions in the animals. In order to measure them, it has been found advisable 

 to work on the margin of maximum success in transplantation. In order to 

 obtain comparable results under otherwise similar experimental conditions, 

 attention must be paid to (1) the dose of tumour material, (2) the age of the 

 animals, and (3) the site of inoculation. The inoculations must be carried 

 out in such a way that " tumour formation " or " no tumour formation " can 

 be determined by the conditions of the animals for the most part. "We have 

 worked mostly with a " minimal tumour-forming " dose, although multiples 

 of this dose have been employed for special purposes. Large doses frequently 

 lead to the development of tumours in animals which are completely pro- 

 tected against, or refractory to, smaller doses. Then the refractory condition, 

 or relative protection, may only be indicated by the smaller size and less 

 rapid growth of the resulting tumours, as compared with normal mice. A 

 cleaner result is obtained when the dose, while sufficient to produce tumours 

 in normal animals within 10 days, fails to lead to any proliferation whatso- 

 ever, thereby indicating the presence of abnormal refractoriness in the animals 

 whose resistance is being tested. Our animals not being very highly protected, 

 many of the differences we shall record are only clearly elicited by the use of 

 small doses. The use of large doses obscures them when results are recorded 

 as percentages of successful inoculations. The difference between different 

 sites is best brought out by small doses, and obscured by the use of large doses. 

 Young mice are more susceptible to inoculation than old animals. The 

 difference in percentage of success may be as great as 60 per cent, between 

 animals of seven weeks, on the one hand, and those of one year old, on the 

 other hand. In the following experiments the control animals have always 

 been chosen of the same size (and therefore of approximately the same age) 

 as the animals whose resistance is tested. This precaution is necessary in all 

 such experiments, because the duration of the preliminary treatment whose 

 effect is under discussion, of itself entails an alteration in the susceptibility 

 of mice whose total duration of life is short. 



