THE OUTLOOK FOR THE FUTURE 267 



of these bacteria, by inoculating the soil with grubs heavily infected 

 with them. 



Comparatively little is yet known of the ability to control, by means 

 of antibiotic agents, diseases caused by protozoa, such as malaria and 

 trypanosomes, virus infections, and certain bacterial diseases such as 

 tuberculosis. 



These instances suffice to arouse hope that even greater progress can 

 be expected in the control of disease by utilization of the activities of 

 antagonistic microorganisms. So far, most energies have been directed 

 to the treatment of acute infections caused by bacteria. Less is known 

 of chronic infections. Whether or not man will ever be able to control 

 all diseases caused by the numerous microscopic and ultramicroscopic 

 forms of life through the utilization of the activities of antagonistic 

 microorganisms, he will have gained sufficient knowledge from the 

 mode of action of these organisms, and of the substances produced by 

 them, to justify further hope in the possibilities thus opened. 



MODE OF ACTION OF ANTIBIOTIC SUBSTANCES: 

 A FIELD FOR THE PHYSIOLOGIST 



Finally, there remains the fourth important group of problems in- 

 volved in the study of antibiotic substances, namely, the mode of action 

 of these substances upon bacteria. The fact that different agents vary 

 greatly in their bacteriostatic and bactericidal action upon different, bac- 

 teria is well established. A number of mechanisms have been pro- 

 pounded, some of which hold true for one substance and some for more 

 than one. Each of these mechanisms involves some extremely puzzling 

 physiological problems. To take only two illustrations: 



(a) If a given substance interferes with the utilization by the bacteria 

 of a certain metabolite in the medium, as in the relation of sulfa-drugs to 

 ^-amino-benzoic acid, one must assume that the sensitive bacteria re- 

 quire the metabolite in question and the resistant forms do not, or that 

 the resistant bacteria synthesize larger concentrations of the particular 

 metabolite than the sensitive forms. Since the sensitivity of the bacteria 

 to an antibiotic substance is often more of degree than of kind, as in the 

 case of actinomycin, the assumption would be that the metabolite is 



