April 14, 1916] 



SCIENCE 



515 



local excitation by an external factor may 

 become the starting point of a persistent or 

 permanent and primarily quantitative order 

 in the living protoplasm, and such an order 

 as this represents, I believe, a physiological 

 axis or the physiological individual in its 

 simplest form. The first order of this kind 

 to arise in a given mass of protoplasm be- 

 comes the chief, polar, or major axis, and 

 other similar orders established later deter- 

 mine minor axes, i. e., the symmetry. 



We now turn to the question of the na- 

 ture of physiological relation or correlation 

 in such an order as this. The fundamental 

 relation must be one of dominance and sub- 

 ordination. The region of highest irrita- 

 bility or rate of reaction must dominate all 

 regions of lower rate within the effective 

 range of the excitations transmitted from 

 it because to any stimulation of the system 

 it reacts more rapidly or more intensely 

 than other regions, and its greater irrita- 

 bility determines that it shall react to some 

 conditions which are not effective in other 

 regions. Consequently the excitations trans- 

 mitted from this region of highest rate are 

 more effective in determining the general 

 metabolic rate at other levels of the gradient 

 than the changes transmitted from any 

 other region. The region of highest irri- 

 tability or rate of reaction in such a gradi- 

 ent is then a physiologically dominant 

 region, because it is the chief factor in 

 maintaining the gradient after it is estab- 

 lished and so in determining the general 

 metabolic rate at each level. This dominant 

 region of the gradient is relatively inde- 

 pendent of other regions while they are 

 relatively subordinate to it. In general any 

 level of the gradient is dominated by higher 

 levels and in the absence of these higher 

 levels itself dominates lower levels. 



The region of highest rate of reaction in 

 the chief or major gradient becomes in de- 

 velopment the apical region or head of the 



individual and a definite localization and 

 course of development along the major axis 

 occurs, and the localization of organs with 

 respect to the minor gradients is also defi- 

 nite and characteristic. The orderly spe- 

 cialization and differentiation in such an 

 individual results from the differences, 

 primarily quantitative, which exist at differ- 

 ent levels of the gradient. 



These conclusions are based on many 

 different lines of evidence which can be re- 

 ferred to only very briefly: First, a gradi- 

 ent in metabolic rate in which the region 

 of highest rate becomes the apical region 

 of the individual has been demonstrated as 

 a characteristic feature of the major axis 

 in animals, at least during the earlier stages 

 of development. There is also much evi- 

 dence to show that the minor axes are rep- 

 resented by similar gradients. The physi- 

 ological individuals examined thus far in- 

 clude the amoeba pseudopodium and vari- 

 ous other protozoa, celenterates, flatworms, 

 echinoderms, annelids, fishes, amphibia and 

 birds, in all more than fifty species. Among 

 the plants various species of axiate algte 

 have also been examined and a similar 

 gradient with its region of highest rate at 

 the apical end of the axis has been found in 

 all. In many cases these dynamic gradients 

 are readily distinguishable before any 

 visible morphological differences along the 

 axes exist. 



Moreover, the very general existence of 

 developmental gradients along the axes in 

 both animals and plants constitutes very 

 strong evidence for the existence of meta- 

 bolic gradients, even where these have not 

 been directly demonstrated. As regards the 

 major axis of the animal, the so-called law 

 of antero-posterior development is essen- 

 tially a statement of the fact that morpho- 

 genie development begins or proceeds most 

 rapidly in that region which becomes the 

 apical or anterior end of the animal, and in 



