8 ROBERTS RUGH 



3. The embryo can be killed by irradiations which for any species are less 

 than the lethal dose for the adult, and consjenital effects may be produced by 

 exposures of about 2^,r that of the LD/50/30 level (Figs. 1-27). 



4. If the embryo survives the irradiation, it has powers of topographic 

 repair which are not known to the adult. But it cannot step up cell produc- 

 tion to replace cells lost trom radiation necrosis, so that the net result is a 

 deficient embryo or fetus — deficient in those cells or those tissues which are 

 most damaged at the time of irradiation (Figs. 28-35). 



Every one of its systems may be affected by exposure of the embryo or 

 fetus to ionizing radiations, but the most obvious effects appear to be on the 

 central nervous and the skeletal systems. Probably the most common and 

 graphic effect, one most frequently reported from Hiroshima and Nagasaki, 

 as well as in experimental radiobiology, is microcephaly. This is not an 

 isolated condition, and all those so affected undoubtedly exhibit other 

 anomalies. There is often stunting, microphthalmia, and loss or reduction of 

 other parts indicating deficits (Figs. 21-35). 



But anomalies designated as congenital may be caused by irradiation at 

 times other than during differentiation. First, exposure of the sperm cell or 

 its precursor may produce the anomaly in all succeeding generations due to 

 chromosomal effects. Second, irradiation of the ovary may cause the anomaly 

 to appear in successive generations. Third, the embryo is most likely to de- 

 velop specific anomalies if the differentiating organ concerned is irradiated 

 directly. Fourth, the embryo at any time from the moment of fertilization of 

 the egg through the completion of organogenesis may be caused to develop 

 the same type of anomaly. Once organogenesis is completed, congenital 

 anomalies can no longer be caused by irradiation (Figs. 1-12 and 17-20). 



Thus, congenital anomalies involving the central nervous system may be 

 caused by irradiation of either germ cell, of the actively differentiating 

 organism, or of any stage prior to this. 



In our studies we have concentrated on the cerebral hernia or exen- 

 cephalous condition where the midbrain protrudes through the cranial roof. 

 This is a graphic and readily observable maldevelopment, and any fetus 

 exhibiting this condition is presumed also to have other, possibly less graphic, 

 but even more serious effects. Since this anomaly is readily observable, it has 

 been a convenient marker of severe irradiation damage to the developing 

 embryo (Fig. 21 and Table I). 



Exencephalia has been produced by the irradiation of the mouse testis or 

 ovaiy and has appeared in successive generations following a single exposure. 

 True, its frequency is very low, but it is a severe and lethal anomaly which 

 can be genetically produced. It has also been produced by exposing the 

 mouse embryo at any time from fertilization through gestation day 8.5, and 

 in the earlier stages with doses of as little as 15 r. Exposures of 5 r at certain 



