Muller: Production of Mutations 



the way in which natural evolution has 

 occurred, under the guidance of natural 

 selection. Thus the Darwinian theory 

 becomes implemented, and freed from 

 the accretions of directed variation and 

 of Lamarckism that once encumbered it. 



It is probable that, in a state of nature, 

 most species have a not very much 

 (though somewhat) lower frequency of 

 gene mutation than would be most ad- 

 vantageous for them, in consideration of 

 the degree of rigor of the natural selec- 

 tion that occurs in the given species. A 

 much higher frequency would probably 

 lead to faster genetic degenerative pro- 

 cesses than the existing selection could 

 well cope with. But, under conditions 

 of artificial breeding, where selection 

 can be made more effective, a higher 

 mutation frequency can for a time at 

 least be tolerated in some cases, and 

 larger mutations also can be nursed 

 through to the point where they become 

 suitably buffered. Here it may become 

 of practical use to apply X-rays, ultra- 

 violet, or other means of inducing mu- 

 tations, as Gustafsson especially has 

 demonstrated for X-rays. This will be 

 especially true in species which natural- 

 ly undergo much inbreeding, or in which 

 there is a well expressed haploid phase, 

 or a considerable haploid portion of the 

 genotype, for under these circumstances 

 many of the spontaneous mutations that 

 might otherwise have accumulated in the 

 population and that could be brought to 

 light by inbreeding, will have become 

 eliminated before they could be found, 

 and the natural mutation rate itself will 

 be lower. 



We have above largely confined our- 

 selves to considering the relation of the 

 production of gene mutations to the 

 problems of the general method of evo- 

 lution, including that of the nature of 

 hereditary variation, because this has 

 been, historically, the main line of ap- 

 proach to the subject of artificial muta- 

 tions. It was from the first evident, how- 

 ever, that the production of mutations 

 would, as we once stated, provide us 

 with tools of the greatest nicety, where- 

 with to dissect piece by piece the physio- 

 logical, embryological, and biochemical 



structure of the organism and to analyze 

 its workings. Already with natural mu- 

 tations, such works as those of Bon- 

 nevie, Grueneberg, Scott-Moncrief, Eph- 

 russi and Beadle, etc., have shown how 

 the intensive tracing of the effects, and 

 interrelations of effects, of just one or a 

 few mutations, can lead to a deeper un- 

 derstanding of the complex processes 

 whereby the genes operate to produce 

 the organism. But there are thousands 

 of genes, and it is desirable to be able to 

 choose them for study in an orderly fash- 

 ion as we proceed with our dissection 

 process. For this purpose we have 

 thought that it would often be advan- 

 tageous to produce mutations artificially 

 in abundance, so as then to take our 

 pick of those more suited for successive 

 steps in our analysis. The work of Bea- 

 dle and his co-workers on Ncurospora in 

 recent years, followed by similar work 

 of Malin and Fries and of others, has 

 brilliantly shown the applicability of this 

 method for studies of the paths of bio- 

 chemical synthesis of amino-acids, vita- 

 mins, purines and pyrimidines. And yet, 

 in a sense, the surface of the subject as a 

 whole has barely been scratched, and 

 we may look forward with confidence to 

 the combination of this technique with 

 that of tracer substances and with all the 

 other techniques of biochemistry, physi- 

 ology and experimental embryology, for 

 the increasing tmravelling of that sur- 

 passingly intricate tangle of processes of 

 which the living organism is constituted. 

 There is no time, however, to go further 

 into this subject here. 



Chromosome Analysis 



For we cannot neglect here a brief 

 outline of another phase of the artificial 

 mutation work, more specifically of in- 

 terest to geneticists : that is, the further 

 analysis of the properties of the chromo- 

 somes and their parts, gained chiefly 

 from studies in which parts have been 

 removed, added, or rearranged. We have 

 already spoken, in passing, of the studies 

 of the mechanism of such structural 

 change, in which a relatively simple gen- 

 eral scheme lying at the basis of all such 

 alterations has emerged: namely, break- 



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