RADIATION IN PRENATAL DEVELOPMENT 879 



report of abnormalities was by von Hippel and Pagenstecher (1907) who 

 obtained cataracts, microphthalmia, and lid coloboma in newborn rabbits 

 following irradiation with a high dose (21 H = Holzknecht units) on 

 days 7, 9, and 11, or 8, 10, and 12 after fertilization. Bagg (1922) men- 

 tions one case of "dislocation" of the spinal column in a rat fetus which 

 had been treated between the tenth and fourteenth days of intra-uterine 

 life with radium emanation. Several other fetuses in this group suffered 

 from extravasations in subcutaneous vessels and along meningeal sinuses 

 (Gudernatsch and Bagg, 1920). But since the same type of lesion could 

 be produced by injecting the mother 22 days before conception and since 

 it is unlikely that the activity of the circulating radiation source would be 

 maintained long enough to affect the embryos directly, an indirect non- 

 specific effect through lasting injury of the mother must be postulated in 

 this case. Hanson (1923) found that rat females in "later stages of preg- 

 nancy when given the proper dosage" of X rays produced litters in which 

 one or more of the young had serious eye defects, changes in the shape of 

 the skull, and paralysis of the limbs. When raised, they showed consider- 

 able growth retardation and nearly all proved sterile. De Nobele and 

 Lams (1927), reporting on what appears to be the same material as that 

 in which they studied radiation-induced prenatal mortality (1925)— 

 although it is possible that some additional animals are included in the 

 later publication — state that a few of the treated rat embryos which were 

 permitted to come to term were afflicted with microphthalmia, while 

 some of the irradiated guinea pig embryos later developed hydrocephalus 

 and dilatation of the lateral ventricles. Murphy and de Renyi (1930) 

 report foot abnormalities in all of five litters irradiated prenatally with 400 

 or 800 r. Since, unfortunately, the method consisted of giving a mixed 

 population of virgin and pregnant females a series of exposures and then 

 considering only those whose litters were cast within twenty-two days of 

 the last exposure, it is not known at what stages embryos were irradiated, 

 or even whether they were irradiated once or twice. 



On turning to the more extensive and more carefully controlled work, 

 it appears that the field has been explored in two general ways : (a) com- 

 parison of the results of irradiating a number of different stages in order 

 to determine whether the changes produced are characteristic of the 

 treatment day (Kosaka, 1927, 1928a, b, c, d, e; Job, Leibold, and Fitz- 

 maurice, 1935; Kaven, 1938a; Warkany and Schraffenberger, 1947; 

 Russell, 1949, 1950; Russell and Russell, 1950b) ; and (6) concentration on 

 one or two stages (Raynaud and Frilley, 1943b, 1947a, b, c, 1949a, b; 

 Wilson and Karr, 1950, 1951; Russell et at., 1951), or a certain group of 

 abnormalities (Pagenstecher, 1916; Kaven, 1938b; Hicks, 1950) with the 

 ultimate aim of tracing the genesis of the malformations. All experi- 

 ments (groups a and b) will first be briefly outlined in turn. Following 

 this examination of each experiment, particularly with regard to the evi- 



