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SCIENCE 



[N. S. Vol. LII. No. 1357 



the combinations and permntations and reac- 

 tions between tbe more complex bacteria and 

 cells in course of tbeir immunological trans- 

 formations. And tbus there came to be elabo- 

 rated the side-chain hypothesis of Ehrlich, 

 which vied with the phagocytic theory of 

 Metchnikoff as well as with the adsorption 

 theory of Bordet and the physico-chemical 

 theory of Arrhenius. And if in our busy lives 

 of to-day we think less of receptors and ambo- 

 ceptors, of complements and complementoids, 

 haptophores, and toxophores, and limit our- 

 selves somewhat more closely, perhaps even a 

 little too exclusively, to the observed fact 

 itself, yet it is well that we do not forget how 

 great at the time was the stimulus to research 

 and how rich the booty which accrued from 

 those labors tinged with the radiance of the 

 real scientific imagination of an Ehrlich, a 

 MetchnikoS, and a Bordet. 



Not all the high expectations of practical 

 benefit to follow from these discoveries have 

 been realized, but sometimes the very failures 

 have been turned to account in opening up 

 new, or illuminating old, avenues of progress. 

 In this connection it is instructive to recall 

 the early pronouncement of Behring made two 

 years after the discovery of antitoxin, and 

 while he was under the influence doubtless of 

 that great contribution : 



" The present state of the immunity ques- 

 tion," he says, "may be defined as follows: 

 Thus far no generally applicable explanation 

 for natural immunity has been forthcoming. 

 But of the artificially produced immunity it 

 jnay be said that the precise study of a 

 number of examples has so far advanced our 

 knowledge that we may assert with confidence 

 that the immune state arises from a pecu- 

 liarity of the blood and, indeed, of its cell- 

 free portion; in no instance in which a suffi- 

 ciently high grade of immunity has been at- 

 tained in an animal species, easily susceptible 

 to the infection in question, has the blood 

 withdrawn from the body failed to show evi- 

 dences of the presence of the immunity-con- 

 ferring substances." 



In this statement will be perceived the ex- 

 treme humoral view of the origin of immunity. 



which subsequent investigators failed to up- 

 hold. But he continues in a prophetic vein, 

 imfortiuiately likewise destined not to be 

 wholly fulfilled. 



"With the achieving of this standpoint the 

 next step in the winning of specific curative 

 agents for the infectious diseases is clearly 

 outlined: all that is required is the induction 

 in a susceptible animal species of a high de- 

 gree of artificial immunity, and then to test 

 the blood for the presence of protective and 

 healing substances." 



Time has exposed the fallacy of this over- 

 confident attitude and taught the distinction 

 between the two varieties of infectious disease 

 and their corresponding immune states, accord- 

 ing as their main eifects and symptoms arise 

 from the toxalbumins or poisons we have been 

 considering, or the intimate presence within 

 the organs of the microbes themselves. The 

 former variety chances indeed to be in the 

 minority, and hence it has come about that 

 the diseases to be successfully combated by 

 antitoxins are few in number, while those in 

 which the microbes penetrate deeply into the 

 body and which poison its tissues by means of 

 so-called endotoxin, are far more numerous. 

 The latter class includes such important dis- 

 eases as tuberculosis, typhoid fever, menin- 

 gitis, plague, cholera, the septicemias, and still 

 others. And yet the failures have been only 

 partial, and success has been and is still being 

 won against odds which were once considered 

 insuperable. 



What is striking is the capriciousness with 

 which the microbes themselves or their endo- 

 toxins lend themselves to the making of thera- 

 peutically effective serimis, as contrasted with 

 the ease and certainty of action in this respect 

 of the toxalbumins. All the latter seem capa- 

 ble of yielding abundant antitoxins, and this 

 independently of their precise source, since it 

 happens that toxalbumins resembling those of 

 bacterial origin exist also in the higher plants 

 — as in the castor and jequirity beans' — and in 

 the venoms of reptiles and insects. On the 

 other hand, it has not thus far been found 

 practicable to fashion curative serums for 

 tuberculosis, typhoid fever, plague, cholera. 



