220 C. P. RHOADS 



concern the variation which is characteristic of cancer. One example is 

 found in the fact that when tissues composed of undifferentiated cells 

 come into contact, they unite. This is seen in wound healing, during em- 

 bryological development, and with neoplastic tissue. The temporary 

 union of undifferentiated cells and their subsequent permanent junction 

 is an important architectural process in embryology (5). The terminal 

 part of the floor of the penile urethra, for example, is formed by the 

 union of the lateral walls of the urethral groove, and in the normal de- 

 velopment of the embryo is replaced by ordinary firm connective tissue. 

 Gonadal hormones can cause the two uniting epithelial edges to become 

 keratinized so that union is impossible and hypospadias results. The 

 squamous cancer of the uterus induced in mice by Allen and Gardner 

 (6) provides a notable example of wholly abnormal differentiation 

 caused by an extracellular agent. The whole vast field of cancer produc- 

 tion by hormones is relevant to this question and makes available ample 

 evidence of the susceptibility of cells to general controls. It would be 

 desirable to have additional data concerning the effects of the hormones 

 and the carcinogenic chemicals on embryological development. We lack 

 precise comparative observations of their effects in causing differentia- 

 tion and possibly dedifferentiation of similar material susceptible to pre- 

 cise study. Reference to Needham (7) is desirable on this point. 



The future may well see experiments designed to test more exactly the 

 flexibility of function of cells at various stages during differentiation. It 

 is not impossible that the assumption of adult differentiated form in- 

 volves a constant succession of losses of genes, or controlling elements, 

 with consequent loss of ability to carry out a variety of functions coinci- 

 dent with concentration on a comparatively small number. This em- 

 phasis on certain limited functions could well give the distinctive charac- 

 teristics and abilities possessed by highly specialized tissue. The constant 

 tendency toward decrease in the number of functions capable of being 

 executed would, of course, lead to a progressive handicap to the cell in 

 surviving in a standard environment and in time to the very impossibility 

 of doing so. This progressive change would eventually mean the death 

 of the cell, and indeed, this is precisely the fate of differentiated tissue. 

 Is it too fanciful to believe that the endocrine glands are accessory or- 

 gans created to m.aintain, in their terminal, highly differentiated phases, 

 the metabolic activity of cells which are necessary for only a part of 

 life's span? Certainly when these glands are extirpated, specific highly 

 differentiated cellular systems are put at a great disadvantage and die, 

 or at least become inactive. 



