NATURE OF THE GENETIC EFFECTS 461 



mine the composition of all these substances and the nature of the complicated 

 interactions whereby they cooperate to make the organism what it is. . . . It is 

 evident that one chief method of attack in this new type of physiologic analysis, 

 a method which must be of high eventual im])ortance to pathology, as well as to 

 physiology and embryology, would be the alteration or the excision of individual 

 genes, one at a time, out of these thousands of genes, followed by intensive 

 embryologic, physiologic and physicochemical study of the effects thereby 

 produced on the organism. In other words, if we had the abihty to change indi- 

 vidual genes we should have, in effect, a scalpel or an injecting needle of ultra- 

 microscopic nicety, wherewith to conduct the most refined kind of vivisection or 

 biochemical experiments on our experimental animals, not experiments in which 

 gross parts are removed, injected, or otherwise changed, but experiments in 

 which the finest, most fundamental elements of the body fabric are separately 

 attacked. . . . Changes in the genes which have arisen spontaneously and are 

 already at hand can of course be used in such a study, but many of the most 

 instructive types of these have already been largely weeded out by a process of 

 . . . natural selection, before we can find the individuals containing them, while 

 many of those still existing lie scattered far apart and concealed. . . . Hence the 

 question of the production of changes in the hereditary material by means of 

 roentgen or radium rays becomes all the more urgent. 



Since the time v/hen this was written, the method of utilizing the 

 differences of reaction provided by mutant genes has had its greatest 

 success at the biochemical level of investigation, and it is here that genes 

 intentionally produced by irradiation have been employed most exten- 

 sively for gaining further insights into the nature of some of the basic 

 processes occurring in the protoplasm of organisms. Before the rise of 

 the radiation technique and to a lesser extent afterwards, spontaneous 

 mutations were employed in such studies. Examples are the work of 

 Scott-Moncrieff , Robinson, and others, on the biochemical steps involved 

 in the synthesis of flower pigments, that of Ephrussi and Beadle, of 

 Klihn, and of others on the synthesis of insect eye pigments, studies of 

 Onslow and of a number of other investigators on the biochemical 

 genetics of mammalian coat color, and observations of Penrose, Garrod, 

 and other medical geneticists on the group of oxidative processes in man 

 which are affected in hereditary cases of such conditions as phenyl- 

 pyruvic amentia and alkaptonuria. But since the employment of radia- 

 tion in genetics has become more widespread, the attack along these lines 

 has been greatly extended and facilitated by the aid of the mutations thus 

 produced. It is natural that, thus far, the work with the radiation muta- 

 tions has been carried on mainly with microorganisms, since, as noted 

 previously, this is the type of material which yields returns along such 

 lines most quickly and economically. 



This is not the place to review the important results obtained by the 

 application of this mode of investigation to the mold Neurospora by 

 Beadle, Tatum, Horowitz, Bonner, and their associates, the pioneers in 



