Indirect Selection and Drug Resistance 31 



Heritable changes 



There would probably be full agreement so far but for the 

 question of the heritability of individual changes in drug 

 adaptation. In order to avoid irreconcilable disagreement at 

 a later stage, we must agree on operational definitions of what 

 is heritable and what is not; only the former type of change is 

 of direct interest to the geneticists. Considering the necessity 

 of distinguishing individual from populational adaptation, the 

 heritability of an observed change in a population must be 

 examined as much as possible at the level of single individuals, 

 and not limited to that of the population as a whole. As 

 this is often technically impossible, compromises should be 

 attempted and their results analysed with care. For most 

 ordinary work the following definition, which corresponds to 

 what is routinely done in many laboratories, was found to 

 be useful. A population is considered to contain resistant 

 individuals, if single cells isolated (usually by plating) from 

 it and allowed to grow into colonies in the absence of the 

 selection medium, are found to be resistant, the test being 

 carried out on samples from such colonies, or sub-cultures 

 from them. 



These "minimum" requirements for heritability have 

 obvious shortcomings, but unless we accept an unequivocal 

 definition, confusion is inevitable, as has indeed happened. 

 Further definitions may be elaborated: this one has the ad- 

 vantage of corresponding to the usual procedure, and of being 

 simple. It will fail on exceptional occasions, for highly mutable 

 and poorly growing mutants. But if any sluggishly reversible, 

 directly induced adaptation is taking place, it should be picked 

 up with this procedure. 



Pre- or postadaptation 



Since it has been ascertained that heritable changes in drug 

 resistance, or any other trait, do in fact occur after treatment 

 of the population, the question has repeatedly arisen: is the 

 change induced by the drug itself or does, this simply select 



