Teratogenesis 



709 



Witschi ('22, '30, '34) described several types 

 of tumors which developed in embryos from 

 overripe eggs of Rana tcmporaria. Briggs 

 ('41), and Briggs and Berrill ('41), from a 

 study of similar embryos, reported the ap- 

 pearance of several epidennal growths, one 

 of which was a papilloma that was benign 

 in normal hosts. It grew progressively only 

 in hosts which happened to be retarded. 



ABNORMAL GROWTH OF STRUCTURES 

 AND INDIVIDUALS 



Into this category we place cases in which 

 there is an anomalous size increase of the 

 organism or its parts but in which cell size 

 and differentiation are not affected. There 

 are many cases in which normal growth pat- 

 terns are distorted, either owing to deficien- 

 cies in growth-promoting substances or be- 

 cause of an excess of such factors. This topic 

 is covei-ed in Sections X and XI, and at 

 this point we shall merely mention that such 

 growth-disturbing conditions may affect one 

 part of the body quite differently than others 

 and thus lead to marked disproportions (see 

 also Huxley, '32). 



DEGENERATIVE PROCESSES 



Many types of anomalous development are 

 characterized, in one phase or another, by 

 degeneration of tissues. It must be borne in 

 mind here again that the destructive changes 

 are merely visible expressions of aberration 

 in some physiological process. The investiga- 

 tions of Mitchell ('43) and of Bodenstein and 

 Kondritzer ('48) demonstrate that at least 

 one of the disturbances preceding cellular 

 degeneration, after both x-ray exposure and 

 mustard gas treatment, is the inability of 

 the cells to synthesize desoxyribonucleic acid. 

 Ribonvicleic acid formation is not interfered 

 with. Degeneration may be extensive and 

 result in the destruction of the entire indi- 

 vidual. Sometimes it may be sharply localized 

 and involve only a given region or structure. 

 In some instances it has been shown that an 

 initially restricted focus of degeneration may 

 spread and involve cells which have the 

 capacity to survive when removed from the 

 degenerative influence. Baltzer ('30) and 

 Hadorn ('32) have found this to be the case 

 in their merogonic hybrids of Triton. 



Abnormal Degenerations. The heading "ab- 

 normal degenerations" seems redundant. It is 

 used here to emphasize the fact that degen- 

 erative processes occur quite frequently as a 

 step in normal morphogenesis (see below). 



Terata may arise either as an extension or 

 exaggeration of a normal degeneration or as 

 the result of degeneration where none is nor- 

 mally involved. There are many instances 

 in which degenerative changes follow a gross 

 distortion of morphogenesis. In the examples 

 which we shall give for this section we 

 should like to disregard these and include 

 cases in which the degeneration is one of the 

 first evidences of abnormality. 



Many instances of genetic incompatibility 

 are characterized by degenerative alterations. 

 When the genie disturbance is considerable, 

 as in the case of the merogonic hybrids men- 

 tioned above, large areas may become pyk- 

 notic at relatively early stages and eventu- 

 ally lead to the death of the individual. In 

 some cases the degeneration is more sharply 

 restricted. Greene and Saxton ('39) have de- 

 scribed a recessive mutation in rabbits which 

 causes brachydactyly (and other abnormali- 

 ties of the extremities) in homozygous reces- 

 sives. The anomalous condition was preceded 

 by dilatation and swelling of distal blood ves- 

 sels of affected parts on the sixteenth to 

 seventeenth days of development. Inman 

 ('41), in a more detailed examination of 

 earlier stages, reported that the first evi- 

 dences of this gene's expression were de- 

 generative changes in the endothelial cells of 

 these vessels as early as the thirteenth day. 

 On the eighteenth day red patches were 

 grossly visible. Hemorrhage and necrosis be- 

 gan on this day and became progressively 

 more marked. There was usually a sharp line 

 of demarcation between normal and necrotic 

 regions which, finally, formed an annular 

 constriction. The necrotic tissue sloughed off 

 and the stubs of the limbs were "healed" 

 by the twenty-fifth day of gestation. 



Cells may degenerate very rapidly, with- 

 out any apparent preliminary events, follow- 

 ing certain treatments. Mustard gas caused 

 this sort of degeneration in certain non- 

 dividing cells of the eye in Amblystoma (Bo- 

 denstein, '48). In other cells, in the same 

 work, degeneration occurred after a delay 

 which was characterized by inhibition of 

 mitosis, cell enlargement, increased baso- 

 philia and inhibited desoxyribonucleic acid 

 synthesis. 



Excessive Normal Degeneration. As men- 

 tioned above, cellular destruction may be a 

 normal part of a morphogenetic process. Scat- 

 tered cells whose large chromophilic droplets 

 are evidence of degeneration are encoun- 

 tered in many places in embryos (Ernst, '26). 

 More concentrated foci of such cells are 

 found to occur quite regularly in certain 



