150 VENOMOUS SNAKES AND THE PHENOMENA OF THEIR VENOMS 



duced by the same principles. This conception continued to prevail for 

 some time even after the discovery of antitoxins. 



While Calmette once made the claim that his antivenin was effective against 

 all venoms, the progress of immunity study did not allow this idea to remain 

 unmodified. Thus C. J. Martin first maintained that Calmette's antivenin, 

 mainly prepared with the cobra venom, is without therapeutic value against 

 the venoms of the Australian snakes. After much controversy Martin agreed 

 with Calmette in that this antivenin has a certain neutralizing effect upon 

 the neurotoxic principles of the Australian snakes, but its ineffectiveness as a 

 therapeutic agent comes from the fact that these Australian venoms owe their 

 toxicity largely to the haematoxic (lytic and coagulating) principles against 

 which Calmette's antivenin is without action. 



Through the investigations of later workers, especially those of Lamb, 

 even Martin's results have been made an object of some suspicion as to the 

 identity of the neurotoxins contained in the venom of Pseudechis and those 

 contained in the cobra venom. 



According to the results obtained by Lamb, the neurotoxins of Pseudechis, 

 Nolechis, Bungarus, and Naja are not identical as far as their affinities toward 

 the antivenins are concerned. The antivenin prepared with cobra venom 

 neutrahzes only this particular venom, but fails to counteract the neurotoxic 

 effects caused by the other colubrine venoms. Or, the antivenin derived from 

 the animal immunized with the notechis venom has the neutralizing property 

 only for this venom, but not for the others. Similar cross-examinations 

 revealed that the neurotropic toxins of snake venoms are not identical. This 

 question is extremely important in view of the therapeutic application of 

 antivenins in the case of snake bite, and I shall treat this subject in full when 

 I come to deal with immunity in snake venom. 



HISTOLOGICAL CHANGES CAUSED BY NEUROTOXINS OF SNAKE VENOM. 



A. Venom Neurolysis in Vitro. 



The actual histological changes brought about in vivo by the neurotropic 

 toxins of snake venom upon the nervous system have thus far been very 

 carefully demonstrated by the usual section methods. The work of Ewing, 

 Bailey, Kelvington, Lamb, and Hunter sufficiently establishes the relation 

 between the physiological manifestations of the neurotoxins and the anatom- 

 ical lesions which result from the action of the latter upon the nervous system. 



In 1903 Flexner and Noguchi * opened a new path through which the 

 destruction of the nerve tissues by venom can be directly observed under the 

 microscope. Their mode of demonstration consisted of exposing the excised 

 ganglia or nerve fibers to the venom solutions of varying concentrations and 

 observing the progress of neurolysis under the microscope. The animals 

 employed were Sycotypus canaliculatus , the periwinkle; Modiola modiolus, a 

 small mussel; and Mactra solidissima, the giant sea-clam. The nerve cells 



1 Flexner and Noguchi. On the plurality of cytolysins in snake venom. Jour, of Path, and Bac- 

 teriol., 1905, X, III. 



