210 ERNST FREESE 



De Vries discovered tlir (ir.<t spontaneous "mutation," wliirli \va!< later 

 shown to be a rcciproeai translocation. These higher organisms were 

 useful for discovering new genetic phenomena and for investigating, 

 both eytologieally and genetically, gross changes of the genetic material. 

 With the desire to examine in detail the smaller chromosomal variations 

 it became necessary to employ simpler genetic systems of organisms 

 possessing a shorter generation time, thus enabling the experimenter to 

 grow large populations and to statistically analyze genetic traits over 

 many generations. The utilization of these systems acc{)mj)anied the 

 advancement of specific knowledge about recombination and mutation. 



An important step in this direction was made by developing the 

 genetics of the fruit fly, Drosophila. This genetic test system has been so 

 refined that the frecpiency of x-ray-induced lethal mutations could be 

 measured (]\Iuller, 1927), i.e., changes in the X-chromosomc that are 

 lethal to the progeny receiving this chromosome. Radiation-induced 

 nuitations have also been observed in barley by Stadler (1928). Since 

 then all kinds of radiations have been examined. 



The first chemical mutagens were found only much later; for exam- 

 ple, urethan + KCl which induces chromosomal breaks in Oenothera 

 (Oehlkers, 1943), nitrogen and sulfur mustards CAuerbach and Robson, 

 1946), formaldehyde (Rapoport, 1946), and diethylsulfate (Rapoport, 

 1947a,b) which induce mutations in Drosophila. Since then many weak 

 and a few strong chemical mutagens have been found. 



The next step toward simpler genetic systems was the use of micro- 

 organisms, e.g., Neurospora, Aspergillus, yeast, and bacteria, which 

 could be grown on a defined medium and for which biochemical mutants 

 could be isolated, i.e., organisms that need the addition of a certain 

 nutrient to the minimal medium. For each of these systems the induction 

 of mutations both by radiations and chemicals has been examined. If 

 the functional difference between the mutated and the unmutated organ- 

 ism is known one can distinguish forward mutations, which result in the 

 loss of a biochemical function, and reverse mutations, which restore this 

 function. Reverse mutations usually occur much less frequently than 

 forward mutations but their frequency can be measured more easily, 

 because omission from the medium of the extra nutrient, necessary for 

 the growth of the mutant, selects for the revcrtant type. This selective 

 procedure enables one to determine the frequency of revertants even in 

 diploid cells for which the measurement of forward mutations is difficult. 

 [For a review of recent methods and results for bacteria see Ryan 

 (1961).] 



A most important step toward an understanding of mutagenic mech- 

 anisms was the development of bacteriophage genetics. Since Hershey 



