172 Perspectives in Microbiology 



influence of antibiotics, of strains that were resistant ini- 

 tially. Except for staphylococci, however, none of the or- 

 ganisms causing infections generally treated with penicillin, 

 chloramphenicol, or the tetracyclines has developed signifi- 

 cantly increased resistance; and on the basis of considera- 

 tions that we will not have time to discuss here, it is un- 

 likely that such resistance will develop sufficiently to inter- 

 fere seriously with the therapeutic use of these antibiotics. 

 The very real problem of increased resistance to streptomy- 

 cin during treatment of tuberculosis has been largely met 

 by modified treatment schedules and by the use of para- 

 aminosalicylic acid or isonicotinic acid hydrazide in con- 

 junction with the antibiotic. 



Even if the problem of the development of resistance 

 is not so urgent as the lay press would have us believe, 

 it is a problem of broad biologic significance and interest, 

 the mechanism of which has not yet been resolved. There 

 is now an overwhelming body of evidence, stemming from 

 a number of experimental approaches, that the highly 

 streptomycin-resistant organisms which can be demon- 

 strated in any bacterial culture represent spontaneous 

 mutations that occur approximately once in every 10^ 

 cell divisions. It is, however, not equally clear that the 

 slightly increased resistance which develops after expo- 

 sure to low concentrations of any antibiotic, and which 

 sometimes appears to involve a large proportion of the 

 population, is similarly the result of a spontaneous muta- 

 tion. The possibility has not been excluded that in the 

 latter case we may be dealing with the adaptation of the 

 organisms to the drug. The difficulty with this explana- 

 tion is that it implies the inheritance of acquired char- 

 acters, since this minor increase in resistance may persist 

 for many generations in the absence of the antibiotic. The 

 experimental evidence in favor of adaptation is at best 

 suggestive, but it does warrant further exploration. In the 

 case of penicillin, we have been able to show that the 



