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SCIENCE 



[N. S. Vol. XLIII. No. Jill 



minor axes definite developmental gradi- 

 ents also exist. In the axiate plants essen- 

 tially similar relations are found. The de- 

 velopment of the individual proceeds from 

 the apical end, the growing tip of the axis. 

 In axiate organs and parts also metabolic 

 gradients and developmental gradients cor- 

 respond, so far as observation goes at pres- 

 ent. In processes of experimental repro- 

 duction or reconstitution in pieces of the 

 lower animals the same relations between 

 metabolic gradients, axes and the course of 

 development have been found to exist as in 

 embryonic development. 



Second, experimental teratogeny affords 

 evidence of great value concerning axial 

 metabolic gradients and even makes it pos- 

 sible to demonstrate their existence in cer- 

 tain cases where other means are technically 

 unavailable or unsatisfactory. The method 

 of experiment along this line depends upon 

 the fact that the degree of susceptibility of 

 living protoplasm to at least many, perhaps 

 to all, agents commonly characterized as 

 depressant or inhibitory, is very definitely 

 related to the rate of metabolism together 

 with the correlated protoplasmic conditions. 

 This relation is briefly as follows: to a 

 high intensity of action of agents and con- 

 ditions, which kills without permitting the 

 protoplasm to adapt or acclimate itself, the 

 susceptibility varies in general directly with 

 general metabolic rate. The higher the 

 rate the earlier death occurs, and vice versa. 

 To a low intensity of action which permits 

 the protoplasm to adapt or acclimate itself 

 to some extent, the susceptibility in the 

 long run varies in general inversely with 

 the metabolic rate, because, the higher the 

 rate, the greater the capacity for, and rate 

 of acclimation. We see these relations more 

 or less clearly in the susceptibility of young 

 and old organisms to various external con- 

 ditions. To extreme conditions the young 

 with their higher metabolic rate are more 



susceptible than the old. Medical practise 

 in the administration of drugs to children 

 and adults recognizes this difference in sus- 

 ceptibility, though so far as I know it has 

 never been formulated in general terms. 

 On the other hand, the young organism 

 adapts or acclimates itself more readily 

 and rapidly than the old to conditions 

 which are not too extreme to permit accli- 

 mation. There is a large body of evidence 

 in support of these conclusions concerning 

 susceptibility which can not be considered 

 here. 



The point to which I wish to caU atten- 

 tion is the relation between susceptibility 

 and metabolic rate on the one hand and 

 developmental control and experimental 

 teratogeny on the other. If the major axis 

 of the animal egg, or embryo, is primarily 

 a metabolic gradient with the highest rate 

 in the apical region, we should expect this 

 gradient to appear as a susceptibility gradi- 

 ent to various external factors. This I have 

 found to be the case. By subjecting, for ex- 

 ample, the unfertilized egg or the embryo 

 of the sea urchin in various early stages to 

 rather extreme action of various agents and 

 conditions it is possible to obtain a gradient 

 in inhibition of development in which the 

 apical region is most inhibited, the basal 

 least. On the other hand, with agents or 

 conditions whose action permits some degree 

 of adaptation or acclimation, the apical 

 region, though at first most inhibited, is in 

 the long run least inhibited, the basal most, 

 because the apical region possesses greater 

 capacity for acclimation than the basal. By 

 this means two opposite types of teratolog- 

 ical larvae are obtained, the one with apical 

 region most inhibited and therefore dispro- 

 portionately small and retarded in develop- 

 ment, the other with the apical region least 

 inhibited and therefore disproportionately 

 large and advanced in development. Be- 

 tween the two ends of the axis the degree of 



