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 hematoxic (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, 
Notechis, Bungarus, and Naja are not identical as far as their affinities toward 
the antivenins are concerned. The antivenin prepared with cobra venom 
neutralizes 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 
IT 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,. 111. 
