504 PROCESSES INFERRED FROM INDIRECT OBSERVATION 



different types of tissue, leading, as we shall see, to the favoring of 

 tissues of high metabolic rate, other tissues being retarded in their 

 growth by the successful competition of the favored tissues, (c) By 

 the onset of senescence, which ultimately terminates and prevents the 

 full fruition of the growth-process. 



3. Growth may take place in the absence of catalyzers added to the 

 diet, since they are produced by the growing tissues themselves or by 

 organs to which this particular function has wholly or partially been 

 delegated. The growth-catalyzers are therefore not essential dietary 

 constituents in the sense in which the growth-substrates are essential. 



4. Growth-catalyzers may be expected to appreciably influence the 

 rate of growth even when superadded to an already varied and abun- 

 dant diet, whereas, in normal animals, -provided all of the growth- 

 substrates be present in the dietary in abundance the addition of a 

 particular substrate in excess merely leads to enhanced exogenous 

 metabolism of that foodstuff and not to enhanced utilization for tissue- 

 building. 



5. There is no reason to assume that the growth-catalyzer for any 

 one group of tissues, is necessarily identical with that for any other. 

 On the contrary we have evidence, as in the effect of the interstitial 

 cells of the testes or ovaries upon the growth of secondary sexual charac- 

 ters, and of the secretions of the corpora lutea upon the development 

 of the placenta, that growth-catalyzers may exist which are specific 

 for individual tissues. Growth-substrates, on the contrary, facilitate 

 growth as a whole, and although at a low nutrient-level the high 

 metabolic rate of certain tissues may enable them to appropriate the 

 lion's share of the foodstuffs, yet under normal conditions all tissues 

 are similarly affected in differing degrees by the various growth- 

 substrates. 



6. Growth-catalyzers will be unable to initiate new growths, just 

 as other catalyzers are unable to initiate the reactions which they 

 accelerate. 



Several substances have been discovered to influence the rate of 

 growth of animals and of individual tissues when administered in 

 dosages which are devoid of nutritive significance and which correspond 

 in all of the particulars enumerated above with the anticipated proper- 

 ties of growth-catalyzers. Thus if Cholesterol be administered either 

 by mouth or subcutaneously to animals which have been previously 

 inoculated with pieces of Carcinoma-tissue, the growth of the tumor 

 .s enormously accelerated and out of all proportion to the nutritive 

 value which the minute dosage of cholesterol which is requisite might 

 be supposed to have, if we did not know that as a matter of fact the 

 greater proportion of administered cholesterol is excreted unchanged. 

 Not only is the rate of growth, of the primary tumor, as estimated by 

 s increase of diameter, increased by one or two hundred per cent., 

 the growth of Metastases or offshoots of the tunior in distant 

 organs and the percentage of animals displaying metastases are very 



