MULLER 



erally assumed, perhaps gratuitously, 

 in nearly all previous theories con- 

 cerning hereditar\' units; this postu- 

 lates that the chief feature of the auto- 

 catalytic mechanism resides in the 

 structure of the genes themselves, and 

 that the outer protoplasm does little 

 more than provide the building ma- 

 terial. In either case, the question as to 

 what the general principle of gene 

 construction is, that permits this phe- 

 nomenon of mutable autocatalvsis, is 

 the most fundamental question of gen- 

 etics. 



The subject of gene variation is an 

 important one, however, not only on 

 account of the apparent problem that 

 is thus inherent in it, but also because 

 this same peculiar phenomenon that it 

 involves lies at the root of organic 

 evolution, and hence of all the vital 

 phenomena which have resulted from 

 evolution. It is commonly said that 

 evolution rests upon two foundations 

 —inheritance and variation; but there 

 is a subtle and important error here. 

 Inheritance by itself leads to no 

 change, and variation leads to no per- 

 manent change, unless the variations 

 themselves are heritable. Thus it is not 

 inheritance and variation which bring 

 about evolution, but the inheritance 

 of variation, and this in turn is due 

 to the general principle of gene con- 

 struction which causes the persistence 

 of autocatalvsis despite the alteration 

 in structure of the gene itself. Given, 

 now, any material or collection of 

 materials having this one unusual char- 

 acteristic, and evolution would auto- 

 matically follow, for this material 

 would, after a time, through the accu- 

 mulation, competition and selective 

 spreading of the self-propagated varia- 

 tions, come to differ from ordinary 

 inorganic matter in innumerable re- 

 spects, in addition to the original dif- 

 ference in its mode of catalysis. There 

 would thus result a wide gap between 



107 



this matter and other matter, which 

 would keep growing wider, with the 

 increasing complexity, diversit\^ and 

 so-called "adaptation" of the selected 

 mutable material. 



III. A POSSIBLE ATTACK THROUGH 

 CHROMOSOME BF:HAVI0R 



In thus recognizing the nature and 

 the importance of the problem in- 

 volved in gene mutability have we 

 now entered into a cid de sac, or is 

 there some way of proceeding further 

 so as to get at the physical basis of 

 this peculiar property of the gene? 

 The problems of growth, variation 

 and related processes seemed difficult 

 enough to attack even when we 

 thought of them as inherent in the 

 organism as a whole or the cell as a 

 whole— how now can we get at them 

 when they have been driven back, to 

 some extent at least, within the limits 

 of an invisible particle? A gene can 

 not effectively be ground in a mortar, 

 or distilled in a retort, and although 

 the physico-chemical investigation of 

 other biological substances may con- 

 ceivably help us, by analogy, to un- 

 derstand its structure, there seems at 

 present no method of approach along 

 this line. 



There is, however, another possible 

 method of approach available: that is, 

 to study the behavior of the chromo- 

 somes, as influenced b\^ their contained 

 genes, in their various physical reac- 

 tions of segregation, crossing over, 

 division, synapsis, etc. This may at 

 first sight seem very remote from the 

 problem of getting at the structural 

 principle that allows mutability in the 

 gene, but I am inclined to think that 

 such studies of synaptic attraction be- 

 tween chromosomes may be especially 

 enlightening in this connection, be- 

 cause the most remarkable thing we 

 know about genes— besides their mu- 

 table autocatalytic power— is the 



