THERAPEUTIC IMMUNIZATION IN MAN 467 



bacterial toxins. It was with snake poisons that Calmette definitely 

 showed that the union of toxin and antitoxin is a true neutralization 

 and is not accompanied by the destruction of the toxin. These ex- 

 periments, as we have seen, were elaborated later by Morgenroth, 

 who succeeded in producing the snake poison HC1 combination. It 

 is these poisons also that have been the subject of extensive study by 

 Flexner and Noguchi, by Kyes, and later by von Dungern and Coca. 

 This work has been sufficiently discussed in other places and need 

 not occupy us here. The important poisonous snakes may be divided 

 into the colubridse, to which class the cobra belongs, and the viper- 

 .idse, which includes the ordinary European vipers, the rattlesnake, 

 and most of the poisonous snakes of North and South America. Ac- 

 cording to Calmette the poison of the cobra is much more heat-stable 

 than that of the rattlesnake. Pharmacologically the poisons of these 

 two main classes of snakes show considerable difference. In the case 

 of the cobra there is very little local disturbance and the systemic 

 symptoms dominate the clinical picture. Calmette describes the 

 cobra bite as being followed only by a feeling of stiffness at the site 

 of the bite, followed very soon by great general weakness, difficulty 

 in respiration, slow heart action, and finally death with unconscious- 

 ness. In the case of the vipers the local symptoms are very much 

 more marked, there being great pain and swelling and apparent clot- 

 ting of the blood about the point of the bite, with a rather slower 

 onset of systemic symptoms. In a description by Sparr 41 of a case 

 of bite by Russell's viper there was almost immediate swelling of the 

 limb with a faint bluish tint around the pin-point puncture, and 

 within 15 minutes great weakness, restlessness, and retching. In 

 spite of very active local treatment, within a short time after the 

 bite, the patient died within 24 hours of asphyxia and heart failure. 



According to Calmette 0.0002 gm. of cobra poison will kill a 

 guinea pig; Noguchi states that 0.0005 gm. of rattlesnake venom will 

 kill a guinea pig of 250 gr. within 24-30 hours when injected intra- 

 peritoneally. The snake poisons apparently contain substances which 

 are especially active upon nerve cells (neurotoxins), and hemolysins 

 which act particularly upon the red blood cells. Flexner and 

 Noguchi 42 also speak of another poison which acts particularly upon 

 the endothelium of the blood vessels producing hemorrhages. 



According to Calmette the antisera which are produced by im- 

 munization with cobra poison are most strongly potent against neuro- 

 toxic poisons of the colubridse and, to a certain extent, against some 

 of the poisons of the vipers. However, the action of the cobra anti- 

 toxin against viper poison seems at best to be weak. On the other 

 hand, antitoxins produced with rattlesnake poison are not potent 

 against the cobra venom since, as Calmette states, the rattlesnake 



41 Sparr. Biochem. Bull., Dec., 1911, No. 2. 



42 Flexner and Noguchi. Univ. of Pa. Bull., Vol. 15, 1902. 



