812 



SCIENCE. 



[N. S. Vol. XVI. No. 412. 



researches we became acquainted with a 

 class of poisons secreted by certain bacteria, 

 and present in solution in culture fluids. 

 The evidence is conclusive that these sol- 

 uble toxins enter, as assimilable substances, 

 into direct combination with constituents 

 of the body cells for which they have an 

 affinity, and only thereby are enabled to 

 bring about immunity or to exert toxic 

 effects. As shown by the modifications of 

 toxins called toxoids, the toxic property 

 may be destroyed without loss of the com- 

 bining power, and without removal of the 

 immunizing power. According to Ehr- 

 lich's helpful conception, based on a large 

 amount of experimental evidence, and now 

 very generally accepted, the combining 

 power of the toxin molecule resides in a 

 group of atoms, designated as the hapto- 

 phore group, with affinity for the corre- 

 sponding haptophore groups of the side 

 chains or receptors of cellular constituents, 

 and the toxic power pertains to another 

 and less stable atom complex in the mol- 

 ecule. 



By means of these facts, and legitimate 

 deductions from them, we are enabled to 

 explain in a satisfactory way susceptibility 

 to poisoning by these soluble toxins, their 

 selective action upon the cells of the body, 

 and their cpiick disappearance after injec- 

 tion into the circulating blood. In one 

 infectious disease and in one only, to wit 

 tetanus, are we able to explain the clinical 

 and pathological phenomena in minute de- 

 tail on the basis of our Icnowledge of the 

 causative microorganism and its poisonous 

 products. The nearest approach to this 

 instance is diphtheria, but here we have 

 not yet been able to follow the trail of the 

 toxins within the body so perfectly, and, 

 as Flexner and I have shown, in addition 

 to the soluble toxins there is an intracel- 

 lular poison concerned in the production of 

 the false membrane. Interesting investi- 

 gations, which have greatly helped to elu- 



cidate the nature of these toxins, have 

 been made on various similar vegetable and 

 animal poisons, such as ricin and abrin 

 from the former source and the venom 

 of snakes, spiders and other poisonous 

 animals. 



The high hopes which were raised by the 

 discovery of the soluble bacterial toxins 

 that at last the way was opened for us to 

 penetrate into the mysteries of the mode 

 of action of pathogenic bacteria were soon 

 doomed to disappointment, for similar 

 powerful toxins, though diligently sought, 

 could not be detected in the cultures of 

 most other bacteria, and these among the 

 most important ones, such as the tubercle 

 bacillus, the typhoid bacillus, the cholera 

 spirillum, the pneiunococcus, the pyogenic 

 micrococci. This disappointment was all 

 the more acute because there was and is 

 every ground for confidence that whenever 

 we have in our possession a powerful toxin 

 of this class, a strong protective antitoxic 

 serum can readily be obtained. 



Notwithstanding these negative results, 

 the belief was not abandoned that bacteria 

 harm the body mainly by poisoning, for it 

 rests upon strong clinical and pathological 

 evidence, as well as upon the stv;dy of the 

 distribution of bacteria in the infected 

 body. The search for poisons was turned 

 from the fluid part of cultures to the bac- 

 teria themselves, and thus Pfeiffer suc- 

 ceeded in demonstrating as an integral 

 constituent of the bodies of cholera spirilla 

 toxic substances, which are liberated only 

 when the bacteria degenerate or die. In- 

 tracellular poisons, which indeed pre- 

 viously, thoiigh of a different nature, had 

 been extracted from bacteria by Buchner 

 and by Koch, were subsequently found 

 within typhoid bacilli and a number of 

 other pathogenic bacteria. 



It is of more than purely bacteriological 

 interest to recognize the distinction be- 

 tween the small group of pathogenic bac- 



