706 



Teratogenesis 



related to the former. On the basis of results 

 from the more completely analyzed cases, 

 most embryologists have abandoned the idea 

 that retardation per se may be the cause of 

 anomalies. 



Finally, the analyses of micromelias in 

 chicks have implications for an interpreta- 

 tion of phenocopies. There are, at present, no 

 indications that the effects of the Creeper 

 mutation are altered by nicotinamide therapy 

 (Landauer, '54). The blood-sugar levels are 

 quite normal in this stock (Zwilling, unpub- 

 lished). Despite the similarity in appearance 

 of the induced and genetic micromelias, ap- 

 parently the metabolic derangements leading 

 to the morphological condition are quite dif- 

 ferent. This is not surprising. The abnormal 

 carbohydrate metabolism probably has its 

 ultimate expression in quantitative or quali- 

 tative alterations of protein synthesis. Similar 

 changes in proteins may be produced by the 

 genetic factors by considerably different 

 pathways. In this case, again, the phenocopies 

 have not copied the initial metabolic action 

 of the genes. 



A CLASSIFICATION OF TERATA BASED ON 

 EMBRYOLOGY 



Rather than repeat the usual teratological 

 classification the writer will present a new 

 type of classification of terata based on knowl- 

 edge of inductive and morphological relation- 

 ships. It will be shown how dislocations in 

 normal processes may give rise to various 

 kinds of familiar malformations and, at the 

 same time, by drawing on both for examples, 

 it will be shown that there are no basic dif- 

 ferences, at least on the morphological level, 

 between genetic and experimental anomalies. 

 This classification is not final; there are, 

 doubtless, instances of over-simplification or 

 omission. The intent here is to be provoca- 

 tive rather than definitive. Many of the cases 

 have been placed in a given category even 

 though their analyses are not complete from 

 the present point of view. Future studies may 

 very well indicate the proper position of 

 these examples. It must be borne in mind that 

 many cases of teratological development may 

 involve more than one of the categories which 

 we present. Whenever the information is at 

 hand we have inckided some of the data in 

 regard to the physiological disturbances 

 which precede the morphological ones. 



Teratological development may result 

 from: 



1. Abnormal initial stimulus. 

 a. Initial stimulus absent. 



b. Deficient initial stimulus. 



c. Excessive initial stimulus. 



2. Abnormal response of reacting tissues. 



a. Absence of response. 



b. Partial or incomplete response. 



c. Excessive response. 



d. Mechanical interference with re- 

 sponse. 



3. Abnormality of both initial stimulus 

 and responding tissue. 



4. Abnormal differentiation of component 

 tissues. 



5. Abnormal growth of structures. 



6. Degenerative processes. 



a. Abnormal degeneration. 



b. Excessive "normal" degeneration. 



c. Failure of degeneration to occur. 



7. Abnormality of functional activity or 

 regulatory mechanisms. 



ABNORMAL INITIAL STIMULUS 



Initial Stimulus Absent. In most cases of 

 agenesis it is very difficult to establish 

 whether the initial stimulus is lacking or 

 whether the reacting tissvies are unable to 

 respond to the stimvilus. Probably cases of 

 anidian development in amniotes (in which 

 cells of the blastoderm may divide and even 

 form blood islands, but in which embryonic 

 tissue never develops) represent instances in 

 which the primary organizing stimuli are 

 absent; but this has never been definitely 

 demonstrated. There are, however, well es- 

 tablished cases involving secondary inductors 

 which show that the stimulus for develop- 

 ment may be lacking. Boyden ('27) and 

 Gruenwald ('37, '42) have demonstrated by 

 experimental procedures that the elaboration 

 of a metanephric kidney (in chick embryos) 

 depends upon the prior formation of a 

 ureteric bud. Normally this bud grows up 

 from the cloaca to the metanephrogenous 

 blastema and stimulates the latter to elab- 

 orate tubules, etc. The blastema does not 

 differentiate if the ureteric bud fails to reach 

 it after a surgical block (see Section VII, 

 Chapter 6). Substantiating evidence for this 

 relationship has been found in the case of the 

 wingless mutation of chicks (Waters and By- 

 waters, '43; Zwilling, '49). In the homozy- 

 gous recessives the metanephrogenous tissue 

 does not develop beyond the blastema stage; 

 this is associated with absence of the ureteric 

 bud. 



Deficient Initial Stimulus. Probably the best 

 example of this category is microcephaly 

 (reduced head). 



Excessive Initial Stimuli. An increase in the 



