W. L. HOLMAN 103 



demonstrable which indicate or suggest the combined work of two or more micro- 

 organisms. Zoeller' has used "cumulative cultures" to express the results obtained by 

 him in certain biological combinations. Synergism may be conveniently qualified, 

 when one or the other result dominates, into an "antagonistic synergism" and a "be- 

 neficent synergism." "Antagonism" alone should probably be retained for outstand- 

 ing examples of one-sided harmful effect. 



GENERAL CONSIDERATIONS 



There are numerous examples of bacterial associations in every field of bacte- 

 riology. In man and animals natural infection with more than one bacterium is rela- 

 tively frequent, and the particular combinations which may occur often determine the 

 course of the disease. There is an enormous literature on this phase of the subject but 

 no very definite conclusions have been drawn. It would be futile to go into the prob- 

 lems of tuberculosis and secondary infections, or those of typhoid fever, gonorrhea, 

 influenza, and many other diseases. Certain phases of these I shall briefly discuss, but 

 this article will deal largely with some of the outstanding phenomena studied experi- 

 mentally, and I shall not confine myself to the pathogenic bacteria although the 

 greater amount of work has been done on them. 



EARLY EXAMPLES OF ASSOCIATION 



Among the early observations we find the recognition by Pasteur'' of the harmful 

 effect of "wild" yeast on the normal fermentation processes in the beer and wine in- 

 dustries. He further noted the beneficial effect of aerobic forms which developing a 

 scum on the surface, and using up the oxygen, favored anaerobic growth. Winogradsky^' 

 isolated an aerobe which only fixed nitrogen from the air in the presence of other bac- 

 teria. Burri and Stutzer^ demonstrated that horse feces split nitrate with the produc- 

 tion of free nitrogen. He isolated from the feces B. coli communis and a strict aerobe, 

 and these two in combination gave the same result. The B. coli could be replaced by 

 B. typhosus, and therefore it was the strict aerobe which gave the actual gas produc- 

 tion. Previous to this, Marshall Ward^ described a yeast and a bacterium which to- 

 gether formed a ginger beer-like product in a saccharine fluid. 



ANAEROBES 



Nencki* reported, with a double culture of B. paralactici and B. chauvoei the for- 

 mation from glucose of normal butyl alcohol, a substance not produced by either cul- 

 ture alone. He believed his results might help to clarify certain difficulties in obtain- 

 ing infections in animals with single pure cultures. Novy^ quoted Roger (1889) as 

 the first to show that B. prodigiosus added to the bacillus of malignant edema ren- 



' Zoeller, C: Compt. rend. Soc. dc bio!., 92, 435, 497, 686. 1925. 



^ Pasteur, L.: Oeuvres de Pasteur (reunies par P. Vallery-Radot). Paris, 1922. 



3 Winogradsky, S.: Compt. rend. Acad, de sc., 118, 353. 1894. 



■* Burri, R. and Stutzer, A.: Centralbl. f. Bakteriol., I, Orig., i6, 814. 1894. 



sWard, Marshall: Phil. Tr. Roy. Soc, B, 187, 125. London, 1892. 



^Nencki, M.: Centralbl. f. Bakteriol., I, Orig., 11, 225. 1892. 



'Novy, F. G.: Ztschr.f. Hyg. u. Infektionskrankh., 17, 209. 1894. 



