auerbach: effects of chemicals 129 



sometimes heatedly. There are good reasons, theoretical as well as 

 observational, for answering it in the affirmative, but decisive 

 experimental evidence would be desirable. One possibility of obtain- 

 ing such evidence was to look for a chemical that would produce 

 o-ene mutations but no chromosome breakage. No clear case of 

 this kind has been encountered. Although mutagens differ widely 

 in their chromosome-breaking ability, most of them can be shown 

 to possess this ability to some extent and none can be shown not 

 to possess it. The opposite is not true. Several compounds that 

 break the chromosomes of plants have failed to produce mutations 

 in Drosophila. This, however, cannot be taken as evidence that 

 these substances act on intergenic bonds rather than on genes, unless 

 it can be shown that they can also break the chromosomes of Droso- 

 phila. A priori, it is probable that substances that can do this will 

 also produce small deficiencies that appear as recessive lethals, and 

 position effect rearrangements that appear as visible mutations. 

 There are good reasons for supposing that a substance that breaks 

 plant chromosomes may not have the same effect on Drosophila 

 chromosomes. Not only are the metabolic differences between these 

 organisms likely to affect the action of introduced chemicals. It 

 should also be kept in mind that plant chromosomes, in contrast 

 to the very stable chromosomes in the germ cells of Drosophila, 

 are easily broken, e.g., by low doses of X-rays, excessive oxygen 

 pressure (21) or, conversely, anoxia (60). Thus, only a substance 

 that fails to produce mutations in the same organism in which it 

 produces chromosome breaks can be used as evidence in favor 

 of distinct intergenic bonds. No clear case of such a substance has 

 so far been found. 



Again chemical mutation research has failed to provide a 

 decisive answer to a definite question. An answer, albeit still a 

 partial one, has come from a different field of genetics. Analysis of 

 the fine structure of the genetic material in bacteriophage has shown 

 that a mutation may affect only one or at most a few nucleotides 

 (12), surely a change that must be called intragenic. Since, however, 

 the chromosomes of higher organisms are much more highly struc- 

 tured than those of bacteriophage and, in particular, have various 

 types of protein intimately associated with their DNA, the rela- 

 tion between intergenic and intragenic changes remains an impor- 



