598 RADIATION BIOLOGY 



even in the locality of the gene, to effect the given transition. The 

 energy must be applied in the right form, i.e., through the intermediation 

 of a chemical and dynamic configuration of appropriate kind, if it is to 

 succeed in reaching the gene effectively, so as to get it into a given 

 neighboring stable state. Thus, the "spontaneous" process which 

 initiates a mutation may give rise to a particular type of mutation more 

 effectively than ultraviolet does, and the latter in turn may favor some 

 other sort of change even more than ionizing radiation does. Neverthe- 

 less the energy of ionizing radiation is so great and splashes out in so 

 many directions that, despite its being to some extent preferential, it may 

 be expected to have the potentiality of giving rise to the great majority of, 

 if not all, the mutational effects producible otherwise, provided a large 

 enough amount of biological material could be observed. 



Another point (Muller, 1941b) which deserves re-emphasis is that the 

 level and type of chemical change involved in a gene mutation is still 

 unknown. There is no definite evidence whether it involves a change in 

 composition or arrangement within or among amino acid constituents; 

 an alteration of the foldings and interattachments of parts of a peptide 

 chain; or some kind of rearrangement or substitution of larger bodies, 

 such as elementary protein blocks, with regard to each other. Alterna- 

 tively, and perhaps more probably, it may primarily consist in one or 

 another change within or among nucleotides or tetranucleotides, in an 

 alteration of their mode of association, or in their arrangement within 

 still larger units of which they, through their complicated polymerization, 

 form parts. It would be futile to speculate at this stage on which types 

 of bonds are more probably involved. Moreover, the same kind of 

 uncertainties exist concerning the question of the nature of the chemical 

 change whereby a chromosome is broken if, indeed, that process can 

 more properly be referred to as a chemical rather than a physical one. 

 Equally gratuitous, as yet, is the question as to whether the break is 

 essentially in only one thread, whose axis is constituted of atoms in single 

 file, or whether several or many such threads arranged in parallel must 

 be broken simultaneously. 



Yet despite this lack of knowledge, remarkable progress has been made 

 during the last five years in unraveling the initial steps involved in the 

 production of gene and chromosome changes by radiation, as well as in 

 bringing to light a number of other features of the chain of events. 

 Again the picture proves to be one in which not only the physical but 

 also the chemical peculiarities are important, contrary to some earlier 

 views. It can no longer be assumed that an ionization occurring within 

 a gene is necessary and sufficient to cause a point mutation of that gene 

 or that some given luimber of ionizations occurring within a chromosome 

 thread is necessary and sufficient to cause a break of that thread. The 

 results of Stone and Wyss and co-workers and those following them, on 



