Teratogenesis 



707 



number of indviction centers or fields is one 

 category of excess of stimulation. No excess 

 of material may be involved, merely the iso- 

 lation (physiologically or otherwise) of inde- 

 pendent organization centers. The result may 

 be partial or complete duplication of a strvic- 

 ture or organism. Such dviplication may 

 occur spontaneously or as the result of many 

 experimental treatments (Stockard, '21; Hin- 

 richs and Genther, '31; Torrey and Brene- 

 man, '41; Pasteels, '47; Lutz, '49, are but a 

 few of the references). 



Another type of excessive development re- 

 sulting from excessive induction would be 

 the increase in size of strvictures. Few of these 

 instances have been sufficiently analyzed to 

 ascertain that the increase is definitely due 

 to the evocating rather than the responding 

 tissues. Ranzi, Tamini and Offer ('46) have 

 described what they call a hyperinduction of 

 this sort in Rana csculenta and the axolotl of 

 Amblrstoma tiprjnum. When blastulae of 

 these species were kept in a solution of so- 

 dium thiocyanate for periods ranging to 48 

 hours there was considerable enlargement of 

 the notochord. Associated with this were en- 

 largement of the rhombencephalon, duplica- 

 tion of the epiphysis and other hyperdevelop- 

 ments. (They point to the similarity of these 

 malformations to the "Arnold-Chiari" syn- 

 drome of human teratology.) 



ABNORMAL RESPONSIVENESS OF 

 REACTING TISSUE 



Absence of Response. See Section VI, Chap- 

 ter 1. 



Partial or Incomplete Response. In this cate- 

 gory we place those cases in which the initial 

 stimulus for development is present and ap- 

 parently normal. The responding tissues, 

 however, cannot react completely, with the 

 result that there is a deficiency, either of 

 size or of form, in the ensuing structure. In 

 some instances of this type of aberrant de- 

 velopment the incomplete response may be 

 due to failure of the svibsidiary inductors, in 

 others the abnormal response may be more 

 directly linked to the initial evocator. An ex- 

 ample for this group is the recessive "wing- 

 less" mutation in fowl (Waters and Bywaters, 

 '43). Initial wing induction is apparently 

 normal, since wing buds are present in all 

 cases. However, in homozygotes, the apical 

 ectodermal thickening usually present along 

 the ridge of limb buds is missing from the 

 wing buds (Zwilling, '49). Saunders ('48) 

 has demonstrated that the apical ectoderm 

 plays an important role in the elaboration 



of the wing. Surgical removal of this struc- 

 ture at 72 hours resulted in complete absence 

 of distal parts of the wing. 



Excessive Response. While there is ample 

 evidence from transplantation experiments 

 that some tissues of embryos have far greater 

 potencies than are ever expressed under nor- 

 mal conditions, it is relatively rare to find 

 expression of these excess potencies in intact 

 embryos which are subjected to abnormal 

 physical or chemical conditions. True, one 

 finds frequent duplications of entire regions 

 of the body. However, these must be ascribed, 

 for the most part, to excessive or accessory 

 inductions and not to excessive response of 

 the reacting tissues. Accessory invaginations 

 have been observed following many types of 

 experiments (Pasteels, '41; Atlas, '35). 



There are a number of anomalies which 

 probably represent the result of excessive re- 

 sponse to secondary inductors. Hyperpha- 

 langy (enlarged digits due to excess number 

 of phalanges), Polydactyly (excess number 

 of digits), macrodactyly, hypermasticism (su- 

 pernumerary mammae), cases of supernu- 

 merary ribs and other similar anomalies 

 probably fall within this grouping. Patten's 

 ('52) case of neural tube overgrowth in hu- 

 man embryos may be a case in point. 



Mechanical Interference with Response. Un- 

 der certain circumstances it is likely that 

 both the initial inductive stimulus and the 

 reactivity of the tissue may be normal, yet, 

 owing to a mechanical alteration of the 

 spatial relationships, a strvictvire may de- 

 velop abnormally. One must bear in mind 

 that the mechanical alterations themselves 

 represent the expression of earlier derange- 

 ments, so that if the entire causal sequence 

 is to be determined one must reconstruct a 

 complete chain of events leading to a par- 

 ticular anomalous development. There are 

 numerous instances in the literature on trans- 

 plantation and explantation in which such 

 effects of alteration of the mechanical con- 

 ditions have resulted in distortions of de- 

 velopment. When an inductor-reactor system 

 is separated the structure involved usually 

 fails to develop. The best example of this is 

 the exogastrulated amphibian embryo dis- 

 cussed in previous chapters. Here the mor- 

 phogenetic movements fail to establish the 

 proper relation between the roof of the arch- 

 enteron and presumptive neural tissue. The 

 consequence is a complete absence of any 

 complex differentiation of the ectoderm. In 

 addition, there may be considerable distor- 

 tion of an organ as the result of disturbed 

 mechanical relationships. In the case of the 



