SUMMATION BY CHAIRMAN* 



Samuel P. Hicks 



Harvard Medical School and New England Deaconess Hospital, Boston, Massachusetts 

 The investigators have given summaries, and the discussants have added to this 

 invaluably by emphasizing important points and questioning others. I will comment 

 on matters that were not discussed and add information about the mechanisms of 

 retinal, cortical, and cerebellar malformations produced in fetal and neonatal 

 rats by 150-300 r of 250 kv conventional x-rays, a dose range widely used because 

 of its selective effect and tolerability. The malformations are of prime importance 

 to many of the experimental and behavioral studies to be reported later. 



In presenting his experiments Dr. Rugh has raised the important question of 

 whether low doses (a few r) may impair the development of the embryo long 

 before it begins to differentiate a nervous system. It is well-known that such early 

 embryos have extraordinary powers of regulation and restitution, and a substantial 

 number of cells may be lost; yet apparently normal individuals result. Dividing 

 early embryos into two parts may result in two apparently norma! individuals. 

 What we don't know is whether such embr)'os are really normal, although they 

 have been reported to be so. The work Dr. Rugh and others are doing aims at 

 exploring one aspect of this. At the morphologic level, the problem remains one 

 of establishing a statistically sound relationship between the presence of necrotic 

 cells in early embr^^os and an effect of low doses of radiation. There is no problem 

 with higher doses — cells are killed. "Spontaneous" cell death has a way of turning 

 up in a variety of circumstances during development, sometimes as a necessary 

 normal process. As the dose of conventional x-rays is increased above 20 r at 

 almost any stage of embryonic life, the number of dead cells increase, yet it is 

 difficult to show that development has been impaired. In some later stages, for 

 example when the neural folds are forming, the rat embr>'o can recover to a 

 remarkable degree from excessive cell loss after 100 r or even 200 r, and it does 

 so in a manner such as that described long ago in amphibians by Harrison and by 

 Detweiler. Cpnira.ry to \:t:hatjp.r^ Rugh said, injuredpartsdo catch up successfully. 

 In the face of this remarkable capacity for ernbryos toregulalestnicture after 

 cell loss, we may have to look at other parameters when the resulting animal 

 looks normal, but does not measure up in some aspects of function or behavior. 

 Mutations and chromosome aberrations in the early embryonic somatic cells, 

 alterations in other organ systems that indirectly affect the brain, and the indirect 

 effects that irradiation of the mother has on her fetuses are some things to be taken 

 into account. 



Dr. Brizzee's approach to the study of the effects of radiation on cortical growth 

 is a new and promising one because some of the divided doses he gives probably 

 kill few cells. Sixty r will kill some of the primitive cells. The single doses around 



* This research was supported by the A. E.G., the U.S. Public Health Ser\'ice, and 

 the United Cerebral Palsy Association. 



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