294 PHYSIOLOGIC GENETICS 



and important position on the threshold of the future of all sciences, from the physical 

 to the psychologic. 



Turning to the psychologic, I would like to make a few points in relation to the 

 position that to a psychologist, a rat is a rat and a mouse is a mouse. This should 

 not be so. One can, biologically speaking, parse the creature, mouse, into genera, 

 species, races, sexes, phenotypes, strains, and genotypes. If one takes almost any 

 aspect of the psychologic literature, for example, the effect of early experience, one 

 finds that general principles are developed that purportedly apply to all rats or all 

 mice, if not to all infrahuman mammals, so that such effects as those of early manipula- 

 tion on adult emotionality can be described and predicted. 1162 If, however, one goes 

 to the inbred mouse and samples different strains, what one finds is something quite 

 different. A majority vote of a population of mixed strains or of random-bred mice 

 may follow the general rules if the minority votes are discarded. Even with genetically 

 controlled materials, one can find situations (genotypes) in which the rules are followed. 

 One can also find genotypes in which, with exactly the same experimental techniques, 

 the behavior, measured in the same way, is exactly the opposite to that predicted by the 

 general rules. In still other genotypes, the same experimental manipulations will 

 make not a particle of difference to the later behavior. 430 Environment or nurture 

 has been nicely classified, controlled, and manipulated by psychologists and sociologists; 

 but nature remains to them merely a rat, a mouse, or a mammal. 



Another example approaches more closely the kind of thing that Dr. Russell 

 mentions and which, as Dr. Heston pointed out, is still not as close to the gene as we 

 would like to get, but, nevertheless, much closer. If one considers various genotypes 

 within the house mouse, either on the background of an inbred strain as in Dr. Cole- 

 man's work or by comparisons between strains, one finds differences in the ability 

 of the nervous system to handle common substrates. One of the things that we dis- 

 covered in our group through collaboration with investigators at the Roscoe B. Jackson 

 Laboratory years ago was that the controversy over the role of glutamic acid in behavior 

 was a situation of precisely the kind that I have been describing. The ability of this 

 simple substance to affect the nervous system and thereby behavior depended on the 

 genotype within a behavioral phenotype. Within that phenotype some strains existed 

 in which glutamic acid would give all of the positive effects claimed in the literature, 

 but for other strains this was not true. The ability of this substrate to affect the nervous 

 system and through this, the behavior, was a function of the genotype. 432 Moreover, 

 the way in which it affected the nervous system was also a function of the genotype. 

 In mice of the DBA/1 strain, the threshold of audiogenic seizures can be depressed by 

 administered glutamic acid. In other high-seizure strains, one cannot necessarily do 

 this. Along with alleviation of the seizures, one can improve learning performance 

 on mazes which are located on the thresholds of its ability and, therefore, represent a 

 mild stress. If this effect is compared to the effect of the same agent on another high- 

 seizure strain, DBA/2, it is found that, whereas the effect increases with dose and then 

 remains elevated in DBA/1 mice, other ways of handling the glutamic acid metabolically 



