Teratogenesis 



701 



sory ribs, scoliosis, lordosis), frequently they 

 cannot be distingviished from the dominant 

 rumpless by appearance alone. 



The genetic situation is further compli- 

 cated in that both the "penetrance" (i.e., 

 incidence of effected individuals) and the 

 "expressivity" (degree of the effect) may be 

 altered by both genetic and environmental 

 factors. Both of the rumpless mutations 

 (Dunn and Landauer, '34, '36; Landauer, 

 '45a) may be, by proper selection experi- 

 ments, modified strongly so that there is a 

 high incidence of "normal" tails even though 

 the mutant genes are present. Embryological 

 studies (Zwilling, '45a) demonstrate that 

 minor anomalies, which have no permanent 

 morphological effect, occur early in develop- 

 ment of some genetic rumpless chicks. Such 

 altered expression of a mutation is a result 

 of the genetic background upon and with 

 which a given gene must operate. In some 

 instances (Landavier, '33) only a single modi- 

 fying gene may be responsible, in others it 

 is evident that a complex of modifying fac- 

 tors is involved. Occasionally, as in species 

 or strain crosses, the modifying backgroixnds 

 are so diverse that the entire pattern of 

 dominance may be reversed. Reed ('37) has 

 reported a dominant mutation in Mus mus- 

 culus which causes anomalies which vary 

 from fusion of vertebrae to absence of the 

 tail (ribs may be absent or fused). When the 

 Fused gene is introduced into another species, 

 Mus bactrianus, it behaves as a recessive. 

 Many other examples of such phenomena 

 could be cited. 



Extra-genetic factors may alter the expres- 

 sion of a given mutant. Some of the early 

 experiments with Drosophila (Goldschmidt, 

 '38) have shown that the expression of many 

 mutants may be altered by increased or low- 

 ered temperatures at critical stages. The an- 

 alyses of Wright ('34) indicate that such 

 factors as age of mother and season (which 

 seem to affect the condition of the mother) 

 may influence the expression of mutant genes 

 in mammals. In view of the variable situa- 

 tions produced by both genetic background 

 and extra-genetic factors it is not surprising 

 that there are many cases, especially in hu- 

 man heredity, in which the mode of trans- 

 mission of a suspected hereditary character 

 is not certain. 



Environmental Factors. Virtually every en- 

 vironmental factor has been instrumental in 

 producing anomalies in some organism or 

 other provided that the factor is modified in 

 the proper way and at the proper time. Tem- 



perature variations, mechanical disturbances 

 (vibration, pressure), a host of chemicals, 

 irradiations with hard rays (x-rays) and 

 ultraviolet and modification of the gaseous 

 environment have all been shown to produce 

 effects when properly applied. [Gruenwald 

 ('47) has compiled most of the important 

 references to that date.] 



During the early part of the present cen- 

 tury efforts were made to relate more di- 

 rectly with mammalian terata the results of 

 experiments on anamniotes. For a long time 

 these attempts were equivocal. In most in- 

 stances it was demonstrated that toxic sub- 

 stances (heavy metals, etc.) increased the 

 abortion rate, but not, at least to any great 

 extent, the rate of prodviction of monsters. 

 Essentially the same conclusions were reached 

 when surveys were made of human alco- 

 holics or of people engaged in occupations 

 involving exposure to toxic compounds. In 

 recent years the unequivocal relation to mam- 

 malian terata of at least four factors has been 

 demonstrated: 



1. Considerable evidence has accvimulated 

 which shows that dietary deficiencies of preg- 

 nant mothers may be responsible for anoma- 

 lous development in their young. Much of 

 these data are in the agricultural literature. 

 One of the most conclusive analyses has been 

 contributed by Warkany and Schraffenberger 

 ('43). These authors produced a syndrome, 

 including micromelia, in rats by means of 

 a riboflavin-deficient diet. All symptoms were 

 eradicated by replacement therapy if the 

 riboflavin-containing diet was fed prior to 

 the thirteenth day of gestation. 



2. A number of avithors have described the 

 effects of irradiations (mostly x-rays) on the 

 development of mammals. Russell ('50) has 

 published a thorough analysis of the effects 

 on mouse embryos of whole body x-irradia- 

 tion of the mother. Dose and time after 

 copulation were varied. The data were an- 

 alyzed in terms of the incidence of various 

 anomalies as related to the time of irradia- 

 tion. Pre-implantation stages were non-re- 

 active. In implanted embryos the incidence 

 of most abnormalities rose gradually, reached 

 a peak, then fell off abruptly. A somewhat 

 different situation was revealed (Wilson, 

 Brent and Jordan, '53) in a less extensive 

 study with rats. These authors irradiated 

 only the exteriorized embryos. There was an 

 abrupt transition: 8-day embryos were merely 

 retarded in growth while those exposed on 

 the ninth and tenth days showed a number 

 of anomalies (see also p. 715). 



