Growth and Differentiation in the Nervous System 291 



tumor and the effects of an additional limb were stressed (37). We 

 concluded that the tumor calls forth atypical responses which cannot 

 he considered as merely an intensification of normal developmental 

 processes. The question was then raised whether these exceptional 

 effects were not due to some unique property of neoplastic tissues. 

 This hypothesis, suggested in 1953 (37). was ruled out 3 years later 

 when it was discovered that snake venom harbors a nerve growth 

 factor remarkably similar to the NGF of mouse sarcomas. When, 2 

 years later, it was found that the mouse submaxillary salivary glands 

 also possess this factor, it was definitely established that even normal 

 structures can harbor the NGF. At the same time, the difference be- 

 tween the effects elicited by the implantation of a limb and the effects 

 elicited by implantation of mouse sarcomas or by injection of the 

 venom or of the salivary NGF seemed to come into an even sharper 

 relief than before. 



The results obtained with these last factors established beyond 

 doubt that the specific protein can avail itself of different routes to 

 gain access to the nerve cells. While in experiments of transplanta- 

 tion of additional limbs we had only evidence of the role played by 

 nerve fibers in conveying the message from the periphery to the nerve 

 cells, now we were able to show that the NGF can utilize the nerve 

 fibers (intraembryonic tumor transplantation); it can utilize the 

 circulatory channels (chorioallantoic tumor transplantation or injec- 

 tion of the NGF into the yolk ) ; or it can diffuse in the medium, as 

 proved by tissue culture experiments. 



A next step in the investigation was the discovery that the NGF is 

 present in the receptive ne.ve cells and can also be detected in other 

 structures and body fluids. Of particular interest is the finding that it 

 is present in the serum of mammals, man included, and that it is 

 produced by undifferentiated structures such as embryonic cells ( 45 ) 

 and granuloma tissue experimentally produced in adult mammals 

 (44). 



The above results raised the question whether the NGF is produced 

 in a special organ and from there spread in the organism, or whether 

 it is normally produced by different types of cells. This question is 

 still undecided, although we believe that the evidence is in favor of 

 the second alternative. Since we have evidence that it is produced in 

 anaplastic tumors and it is present in embryonic tissues, we are again 

 faced with the problem which we considered as definitely settled: 

 Are the growth effects elicited by a transplanted additional limb en- 

 tirely different from the effects elicited by the NGF discussed above? 

 In order to answer this question, one should have a more precise 



