JlLY 3, lild.i.J 



SCIENCE. 



11 



the blood, is capable of being brought iuto 

 action, whence the injury is indicted. The 

 action of the complement depends upon its 

 possession of properties designated zymo- 

 toxic and toxophorie, through the influence 

 of which hjemoglobin is set free from red 

 corpuscles, various organic cells are dis- 

 solved, bacteria are disintegrated, and ciliar 

 and flagellar motions are suppressed. 



The intermediary bodies and comple- 

 ments iipon which serum activity depends 

 are contained within the blood ; but there 

 are certain kinds of natural poisons, of 

 which venom is perhaps the best example, 

 in which only the interjnediar.y body oc- 

 curs in the poison, the complement— the 

 directly hiirtful constituent— being sup- 

 plied by the blood. I have already dwelt 

 upon some of the principles of this poison, 

 and I wish now to state briefly that venom 

 possesses intermediary bodies capable of 

 bringing into play complements which 

 cause solution of many kinds of cells — 

 those contained in nervous, renal, hepatic 

 tissues and still other organs. All these 

 solvents, as Dr. Noguchi and I have been 

 able to show, possess a striking indepen- 

 dence of action which can not fail to excite 

 great wonder at the complexity of venom, 

 and aid in the undei'standing of the elective 

 affinities which poisons exhibit for certain 

 organs, to which not only is disease of these 

 organs to be attributed, but the selective 

 action of remedies ascribed. 



My purpose in bringing again to your 

 attention the subject of venom intoxication 

 is to present a remarkable instance of inter- 

 action of two substances, both of which are 

 poisonous, but one of which is capable of 

 affording protection from the other; a 

 therapeutic paradox which is explicable 

 upon the basis of the mechanism of im- 

 munity as formulated by Ehrlich. 



I have referred to the cytolytic action 

 of snake serum, and I wish now to tell you 



that the blood scrum of the rattlesnake, 

 moccasin and some other snakes is highly 

 poisonous to warm-blooded animals. Dr. 

 Noguchi and I have been able to .show that 

 the manner of action of the toxic principles 

 of snake .serum is comparable to that of 

 venom, with, however, one very important 

 difl:'erence. Both owe their poisonous ac- 

 tion to intermediary bodies; but the one, 

 that of venom, is able to attach the com- 

 plement, necessary to complete the injuri- 

 ous .sj-stem, of the animal poi.soned; while 

 the other, that of serum, can combine only 

 with its own complement. While, there- 

 fore, venom is active even after heating to 

 a relatively high temperature, serum is in- 

 activated at the temperature (58° C.) at 

 w^hich its complement is destroyed. This 

 temperature does not, however, affect the 

 serum-intermediary body ; and hence, wliile 

 the heated serum is no longer toxic because 

 it can not utilize a foreign complement, it 

 is still able to unite, through its inter- 

 mediary body, with cells for which it has 

 affinity. This affinity is especially for 

 nerve cells; and since the serum combines 

 with the same lateral chains or receptors 

 of the nerve cells that venom attacks, it is 

 possible by using heated serum to prevent 

 a later venom union. If, therefore, heated 

 snake serum is injected into guinea-pigs 

 they can be protected, for a time, from 

 fatal cobra poisoning. The duration of 

 this immunity is not great and its degree 

 is not high; for, on the one hand, the nor- 

 mal metabolism of the cell modifies or de- 

 stroys, sooner or later, the combined serum- 

 intermediary body, and, on the other, an 

 excess of venom can by mass action drive 

 out the weaker serum constituents. This 

 fact is brought readily into conformity with 

 the belief that receptors are, after all, de- 

 signed primarily, not as organs to be used 

 under stress of pathological necessity, but 



