August 5, 1921] 



SCIENCE 



101 



methods, were inclined to regard the discovery 

 of the pathogenic agent of some well-known 

 disease as the beginning of the end of its 

 prevalence. To have isolated, recognized, and 

 cultivated a bacterium and produced some sort 

 of pathological changes in an inoculated ani- 

 mal was considered equivalent to half or more 

 of the battle won over the depredations of such 

 organism. For many years these living 

 agents, but more particularly the unicellular 

 organisms among them, overshadowed all else 

 and they became synonymous with the causes 

 of disease. To-day we know that to have iden- 

 tified the microbic agent of any pathological 

 process is but the beginning of the solution of 

 the immediate problem and that it answers but 

 one of a long series of questions. In spite 

 of this somewhat discouraging fact, a very re- 

 markable series of discoveries in the biology 

 of disease have originated in this study of 

 microorganisms. I need mention only the 

 bringing to light of bacterial toxins, the dis- 

 covery of their anti-toxins, hypersensitiveness 

 or anaphylaxis, the phenomenon of acquired 

 immunity and the collateral phenomena asso- 

 ciated with it, such as the production of ag- 

 glutinins, precipitins, complement-fixing bod- 

 ies, and above all the specificity associated with 

 the action of disease agents and the reaction 

 of the host. Every one of these fundamental 

 discoveries has had a far-reaching influence 

 on the immediate development of the medical 

 sciences. Every one in its way has dominated 

 the thoughts and activities of large groups of 

 investigators and there has resulted a very 

 unequal, even chaotic, development of our 

 knowledge of the conditions governing dis- 

 ease processes. Throughout this period domi- 

 nated in turn by disinfectants, toxins, anti- 

 toxins, agglutinins, opsonins, complement fix- 

 ation, and hypersensitiveness, there is evident 

 some system, some purpose, and that is to 

 find the exact place of living agents in the 

 phenomenon of disease. From the more or 

 less exaggerated point of view held at the 

 start of their dynamic energy in the process 

 there has been a more accurate, more scientific 

 conception of their place as necessary condi- 

 tions of disease making headway. 



It is now evident that the relation of living 

 agents, from the ultramicroscopic forms up 

 to the higher parasites, is different for every 

 agent or at least for every group of biologi- 

 cally related agents. "We know now that the 

 depth and extent of their etiological signifi- 

 cance varies from an almost exclusive causa- 

 tion to one of relatively insignificant propor- 

 tions. For the latter group the environmental 

 and hereditary conditions completely dominate 

 the situation and the particular germ found 

 in one place may be replaced by others in an- 

 other place. In most disease processes, there- 

 fore, the living agents are more or less gov- 

 erned by other factors. This is indicated by 

 the great variation in the intensity of specific 

 infectious diseases, by their seasonal appear- 

 ance, by the sudden appearance and disap- 

 pearance of outbreaks, and the difficulty of 

 maintaining an epizootic among animals ex- 

 perimentally. Again, it is indicated by the 

 difficulty of inducing disease with pure cul- 

 tures in species of animals in which the dis- 

 ease occurs spontaneously and in the decline 

 of virulence in artificial cultures. 



Now it may be answered that when we fail 

 to induce disease we do not know how to in- 

 troduce the agent and where to deposit it. But 

 the how and where are in themselves limita- 

 tions of the activities of the specific agent. It 

 may also be answered that the microbe with 

 which we try to induce the disease has been 

 attenuated by culture. True, the microbe 

 needs the host to maintain its virulence. This 

 is a significant limitation. Any one who has 

 been confronted with a disease of unknown 

 etiology and has in due time found the living 

 agent knows how little or how much this means 

 when he tries to construct the mechanism of 

 the disease with its aid. In many cases the 

 mystery remains as deep as ever until other 

 necessary conditions have been isolated from 

 the complex of causation. 



Perhaps one of the most promising move- 

 ments to bring into correlation with parasitism 

 the other necessary conditions of disease is 

 the study of epidemiology not from a sta- 

 tistical but from a biological viewpoint. To 

 observe that of a given number of exposed 



