MUTATION 63 



slightly more efficient growth of the non-synthesising mutant 

 will have the result that it will outgrow the synthesising cells. In 

 the course of evolution the primitive cell, capable of tryptophan 

 synthesis, has been lost and now only arises as a " back 

 mutant " from the tryptophan-requiring organism. Fildes 

 has shown that such back mutants can be demonstrated in 

 cultures of Eberthella typhosa, and growth in a tryptophan-free 

 medium will selectively grow the mutants and so give rise to 

 cultures of the organism which are capable of synthesising their 

 own tryptophan. 



The spontaneous production of mutants can become highly 

 important in considerations of drug resistance. A chemo- 

 therapeutic drug such as sulphanilamide acts by inhibiting an 

 essential enzyme process (see Chap. V). If a mutational 

 alteration occurs which renders that particular enzymic 

 process non-essential, then the resulting organism is no longer 

 sensitive to the drug. One method of selecting such insensitive 

 mutants is to culture the organism in the presence of an amount 

 of drug which limits the growth of all the sensitive cells. Such 

 a procedure may take place accidentally during the clinical 

 treatment of a patient infected with the organism and the 

 appearance of sulphonamide-resistant strains of organisms 

 such as Staph, aureus is well known to medical scientists. 

 Selection of the mutants may arise accidentally, as described, 

 or as a result of deliberate cultivation in the laboratory. 

 Eesistance may arise in small steps or cells may rapidly become 

 completely resistant to a drug. One of the main drawbacks 

 to the clinical use of streptomycin is that many organisms 

 acquire a complete resistance to it within a very short period 

 of cultivation in its presence. 



The actual enzymic constitution of a cell is that portion of 

 its potential enzymic constitution that is selected by the 

 conditions under which it has been grown. Amongst the 

 factors controlHng this selection we may list the following: 

 (a) the chemical constitution of the medium, (6) the physico- 

 chemical conditions holding during growth, and (c) the "age" 

 of the culture. 



