CELLULAR DIFFERENTIATION AND EXTERNAL ENVIRONMENT 



69 



in physiological condition to external or 

 physiological factors which we call stimuli. 

 There is, however, no agreement as to what 

 constitutes a stimulus. For some it is any 

 condition external to the cell concerned, 

 acting temporarily or continuously, which 

 produces a definite change or response in 

 the cell. Many developmental physiologists 

 speak of formative stimuli; according to 

 this definition gravity is a formative stim- 

 ulus for certain plants and even an anes- 

 thetic might be regarded as a stimulus. At 

 the other extreme of definition, a stimulus 

 is a relatively sudden action of an external 

 energy on the living system or some part of 

 its surface, bringing about an activation 

 which we call excitation. According to 

 this concept, the stimulus is merely an initi- 

 ator, a sort of trigger-action, and the char- 

 acter and energy of reaction depend on 

 the specific constitution, the physiological 

 condition, and the structural differentiation 

 concerned, not on the energy of the 

 stimulus. 



We have learned something about the 

 nature of excitation, but much remains to 

 be learned. According to a theory widely 

 held at present, it involves a reversible in- 

 crease in permeability, a depolarization of 

 the cell membrane, and an accelerated 

 metabolism. Change in the colloid sub- 

 strate and release of calcium have also been 

 postulated as the essential factors. Excita- 

 tion appears to be primarily a matter of the 

 cell surface and to be dependent on the 

 character and condition of the superficial 

 cytoplasm. 



Irritability or excitability involves more 

 than direct reaction to an external stimu- 

 lus. Living protoplasms are able to trans- 

 mit or conduct excitation from the region 

 directly affected by the external stimulus 

 to other regions of the same cell, to other 

 cells or cell groups. Transmission or con- 

 duction apparently occurs because a region 

 excited by an external stimulus becomes a 

 stimulus to adjoining regions, whether in 

 consequence of electrical changes involved 

 or in other ways need not concern us here. 

 The secondarily excited regions stimulate 

 others, and because excitation is in general 



followed by a refractory period during 

 which the region concerned cannot be again 

 excited, excitation may be transmitted as a 

 wave, radially in absence of a definite path 

 or along a structural path, such as nerve, 

 in a definite direction. In protoplasms 

 without differentiated conducting paths, 

 excitation usually undergoes a decrement 

 in intensity or effectiveness with increase 

 in distance from the point of origin, and at 

 a greater or less distance dies out. In 

 other words, an excitation-transmission gra- 

 dient results from the primary excitation. 



Since such an excitation-transmission 

 gradient may extend over protoplasmic 

 regions or cells which were not in any way 

 different from each other before the pri- 

 mary excitation, it represents a new pattern 

 of intergration and control superimposed 

 upon the surface-interior pattern. In 

 other words, integration and control on an 

 organismic scale by an excitation-transmis- 

 sion gradient are possible without any pre- 

 existing organismic pattern except a sur- 

 face-interior pattern. For integration and 

 control on the organismic scale by produc- 

 tion and mass transport of specific chemical 

 substances to take place, some degree of 

 temporary or permanent differentiation of 

 producing and reacting regions must al- 

 ready be present. 



Excitation is commonly regarded as com- 

 pletely reversible after the exciting factor 

 ceases to act, and in the highly differenti- 

 ated organs of excitation, nerve and muscle, 

 from which our concept of excitation is 

 largely derived, it certainly approaches or 

 attains complete reversibility. However, 

 we often find that external factors, some 

 of which excite when acting suddenly in 

 sufficient intensity, may, with local or dif- 

 ferential action of a certain range of in- 

 tensity and continuing for a certain length 

 of time, determine in a cell or cell mass 

 regional changes and differences which per- 

 sist as a physiological developmental pat- 

 tern, a so-called polarity or symmetry, 

 which constitutes the foundation for a pat- 

 tern of differentiation. In their early 

 stages these patterns appear to be quantita- 

 tive gradients involving the basal metabo- 



