540 Spontaneous Cancer in Mice. 
importance of local than to general or constitutional changes. When an 
attempt is made to induce increased resistance in spontaneously attacked 
mice, by the same means as are successful in normal mice against implanta- 
tion of cancer, they seem to be totally ineffective against the implantation of 
the spontaneous tumour in the mouse in which it has arisen. There seems to 
be an insensibility of the cell in its own animal to reactions which are 
effective against strange cells in the same surroundings. 
The outstanding result of this inquiry is the production of evidence of 
possible Jocal causes of origin, on the one hand, and the absence of general 
constitutional changes favourable for growth on the other. The importance 
of local factors for other forms of cancer has long been recognised, and has 
been drawn attention to repeatedly in previous publications of the Imperial 
Cancer Research Fund. As knowledge of them increases, their many-sided 
nature appears more and more clearly. Whether they be animate or 
inanimate, bilharzia, nematodes, growth of other cancer cells as in the 
development of sarcoma as in Mouse 469, or mechanical, chemical, and actinic 
influences, the ultimate result of their action may be the same—the creation 
of new cell strains with powers of continuous growth. On the one hand, 
this process of cancerous transformation shows a close association with 
chronic irritative changes; on the other it has many points in common 
with what is known as spontaneous variation, giving rise to sports in animals 
or plants. The part played by the chronic irritant is obviously a mediate 
one, either so that it produces the altered conditions under which the first 
departure of the cell from the normal may take place, or by giving 
spontaneously occurring sports of cells opportunity of multiplying and by 
degrees adapting themselves to a new mode of life, similar to what is 
observed in propagated tumours. This hypothesis rests on the assumption 
that the malignant transformation of the tissues may take place by stages, 
for which there now seems to be ample evidence both from the facts 
obtained from observation of spontaneous cancers and from those obtained 
in propagated tumours. The nature of this process is still unknown, but 
it is possible that it is being elucidated indirectly by the study of the 
variations which, as recorded in another paper, have been demonstrated to 
occur in cancer cells during their continued propagation. The hope of 
being able to investigate the nature of the process by more direct methods 
lies in the possibility of being able to reproduce experimentally the conditions 
under which it may take place. 
