TOXINS AND ANTITOXINS 73 



influence of light, radium, and oxiding agents. There is an incuba- 

 tion period and the venoms are definitely and specifically antigenic. 



Venoms act in extremely small amounts. The fatal dose of 

 cobra venom for man is probably o.oi to 0.03 gm., rattlesnake venom 

 0.15 to 0.3 gm., and poisonous sea snakes o.ooi to 0.003 S-' or ten 

 times as toxic as cobra venom. The bite of the cobras produces 

 little pain and local reaction, probably due to its small content (2 

 per cent.) of globulin, which contains the local irritant property of 

 the venom. A feeling of stiffness spreads from the region of the 

 wound, followed by vertigo and weakness of muscles of locomotion, 

 tongue, jaw, esophagus, and preservation of senses, resembling a 

 very acute bulbar palsy with death in a few hours. Gushing, how- 

 ever, finds that the action of the poison is particularly upon motor 

 nerve termini. The venom of the vipers produces a marked local reac- 

 tion, probably due to its large (25 per cent.) globulin content, with 

 pain, swelling, local bleeding, blood in the serous membranes and 

 hematuria. Nausea and vomiting, excited reflexes, and even con- 

 vulsions are followed by prostration, paraplegia of lower extremities 

 which extends upward and resembles an acute ascending spinal 

 paralysis with death in one to three days. Langmann states that, 

 " if the patient recovers from the paralysis, a septic fever may de- 

 velop; not rarely there remain suppurating gangrenous wounds 

 which heal poorly." The suppuration of snake bites (viperidse) 

 has been the subject of considerable study; Welch and Ewing 

 ascribed this to loss of bactericidal property of the blood after venom 

 poisoning. Flexner and Noguchi demonstrated a loss of the com- 

 plement of the blood, an element necessary to its full bactericidal 

 power. They believed that the complement was used up by the 

 venom whose amboceptors require complement for their action, 

 therefore leaving little or none free for the bactericidal amboceptors. 

 Morgenroth and Kaya claim that the complement is actually de- 

 stroyed by the venom. Of considerable importance in favoring infec- 

 tions must be the local necrosis of tissue caused by the venom and the 

 associated hemorrhage, aided by the customary radical surgery of 

 the wound. 



The production of antisera was placed on a practical basis by 

 Calmette in 1894 and Frazer in 1895. Calmette attenuated cobra 

 venom for the first four injections by the addition of equal volumes 

 of i per cent, gold chloride solution, and then gave small doses of 

 the native toxin, gradually increasing until a powerful antivenin 

 was developed. Phisalix and Bertrand attenuate viper venom by 

 heating the first dose to 75 C. and then after two days giving one- 

 half the minimum lethal dose of toxin. It was at first thought that 

 the antivenin produced by cobra venom would protect against all 

 venoms, but it was soon shown that the sera were specific for the 

 venom employed. Antivenin also neutralizes that element of venom 

 which induces loss of bactericidal power of the blood. Noguchi has 

 shown that the antivenin of rattlesnake venom neutralizes the 



