370 



NATURE 



[August 1 8, 1898 



•centimetres of anti-venomous serum, after twenty-four 

 hours it was killed, and instead of "2 c.c. of serum 

 ■sufficing to kill as usual a guinea-pig, "4 c.c, of this par- 

 ticular eel's serum was required. 



In this connection we may quote an observation of 

 Calmette's,! made in the course of his classical experi- 

 ments on the toxic character of the blood of venomous 

 serpents, that the toxicity of the blood of such reptiles 

 may be entirely removed by inoculating them with anti- 

 venomous serum. Thus a large specimen of the naja 

 tripudtufis received a series of anti-venomous serum 

 inoculations, and two weeks after the last inoculation it 

 was killed, and its blood was found to have lost all its 

 ■toxic character,^ whilst that of another untreated naja 

 iripudians exhibited its customary complement of lethal 

 -qualities. 



It would be interesting to determine in the case of 

 -eels and vipers the relative quantity of anti-venomous 

 rserum which is required to remove the toxicity of their 

 'blood respectively, for, curiously, the blood of eels is 

 three times more toxic than that of vipers ; and whilst 

 the blood of eels acts as a preventive, protecting an 

 animal from the lethal action of vipers' blood, the latter 

 has no corresponding power to protect an animal from 

 the fatal effect of eels' blood. 



Of great interest are the numerous investigations 

 which have been carried out by Wehrmann to ascertain 

 the action of various other serums as well as biles of 

 •different origin upon this eel- serum. Anti-venomous 

 serum, it appears, acts as an antitoxin towards eel- 

 serum, for it not only protects animals from a subsequent 

 otherwise fatal dose of eel-serum, but if administered 

 •even after the eel-serum has been introduced into the 

 animal, it nullifies its effect, and the animal lives, 

 whilst it also neutralises the action of eel-serum outside 

 the animal's body in vitro. Different varieties of serum 

 •did not, however, all operate as successfully as anti- 

 •venomous serum. For example, anti-tetanic serum pro- 

 duced no effect upon the toxicity of eel-serum ; neither 

 •did the normal serums of horses and rabbits. Anti- 

 diphtheritic serum, on the other hand, acted as a pre- 

 ventive, and also neutralised the toxicity of eel-serum 

 in vitro., but was not endowed with any curative power 

 :in respect to its toxic action. 



Wehrmann has next studied the effect produced by 

 bile derived from eels, from oxen, and from vipers, not 

 only on the toxicity of eel-serum, but also on that of 

 viper-serum and viper-venom. Now Fraser {British 

 Medical Journal., July 1897) has recently asserted that 

 the bile of serpents and other animals is antitoxic as 

 regards serpent-venom, that it not only has a neutralising 

 .action i7t vitro., but that it has also a distinct, although 

 ■feebly marked, curative power in respect to this venom. 

 Fraser mentions the interesting fact, in support of his 

 ■observations, that in some countries the natives have a 

 practice of administering the bile of a serpent to people 

 who have been very badly bitten by poisonous snakes. 



According to Wehrmann, viper-bile has a preventive 

 .as well as neutralising action with respect to viper- 

 venom ; but he does not say that he has found it to possess, 

 as Fraser has done, a curative power. This viper-bile 

 has also a preventive and neutralising action as regards 

 ithe toxic properties of viper-serum and eel-serum. 



Ox-bile, on the other hand, was found to possess no 

 •antitoxic action in the doses employed by Wehrmann 

 on viper-venom, neither was it endowed with any pre- 

 ventive or curative powers in respect to eel-serum. 



Eel-bile, again, was devoid of all preventive or cura- 

 tive powers in regard to eel-serum and to viper-venom. 



1" Contributions a I'itude des venins des toxines et des serums anti- 

 toxiques." (^Annates de t Institut Pasteur, vol. ix., 1895.) 



2 The toxic properties of the venom of this naja tripudians were not in 

 Any way affected, indicating, as Calmette points out, that the lethal prin- 

 •ciple of which the venom consists is not elaborated in the blood, but in the 

 ■cells of the venom glands of poisonous reptiles. 



NO. 1503, VOL. 58] 



It was able to neutralise the toxicity of both these toxins 

 in vitro., and had a greater degree of neutralising power 

 in respect to the venom than to the eel-serum. Thus, 

 according to Wehrmann, the biles he has employed are 

 not endowed with strictly antitoxic powers, as was claimed 

 for serpent-bile by Fraser, but act apparently as a diges- 

 tive more than anything else upon the serums and venoms 

 with which they are mixed. 



We now come to the experiments which have been 

 carried out on the artificial production of immunity in 

 animals from the toxic action of eel-serum. 



Although heated eel-serum can afford protection to 

 animals, yet immunity thus acquired, as we have already 

 seen, is of so temporary a character that this method is 

 not, as a rule, employed. The plan usually adopted by 

 investigators consists in inoculating increasingly large 

 doses, either intraperitoneally or intravenously, of 

 ordinary eel-serum into the animal it is desired to render 

 immune. By this means Maglieri and Wehrmann have 

 both succeeded iii immunising rabbits against the effects 

 of ten, twelve, up to twenty (Maglieri) otherwise fatal 

 doses of toxic eel-serum. The period over which the 

 treatment has to be extended is somewhat lengthy before 

 the requisite stage of immunity is reached. Thus, about 

 three months must elapse before a rabbit's serum has 

 acquired the degree of protective power to render it of 

 use for experimental purposes. Hericourt and Richet 

 have succeeded also in immunising a dog against eel- 

 serum, and have obtained a protective serum from this 

 animal. 



According to Wehrmann, the serum of a rabbit im- 

 munised against eel-serum acts both as a preventive and 

 curative with regard to the serum of vipers, and to the 

 serum of eels, as well as to the venom of vipers. This 

 observation supports the opinion frequently expressed by 

 Calmette in his memoirs, that the idea of the specific 

 character of toxins and their antitoxins is not justified 

 by experiment ; that, on the contrary, the serums of 

 animals immunised against one poison may be, and 

 frequently are, curative as regards other poisons. 



It will be remembered, however, that Calmette's asser- 

 tion, that the serum of an animal which had attained a 

 high degree of immunity against cobra venom was 

 equally valuable as a remedy against the poison of all 

 snakes, has not been supported by other observers ; for 

 as regards the venom of the Indian daboia, for example, 

 Cunningham,! of Calcutta, has found that Calmette's 

 serum is inoperative, and therefore useless. 



C. J. Martin, of Melbourne,^ has still more recently 

 tested Calmette's serum for antidotal action in the case 

 of the venom of the tiger snake {Hoplocephalus curtus) 

 and the venom of the black snake {Pseudechis por- 

 phyriacus), and in the matter of both these venoms he 

 obtained no antidotal action with Calmette's serum. 



Some interesting experiments were also made by 

 Martin to ascertain if Calmette's serum possessed anti- 

 dotal action in respect to one of the two proteid con- 

 stituents to which, according to Mitchell and Reichert,^ 

 the venoms of snakes are supposed to owe their poisonous 

 properties. Apparently, if the serum is introduced under 

 the most advantageous circumstances, i.e. injected in 

 considerable quantities directly into the circulation before 

 the poison (in this case one of the proteids separated out 

 from the venom of the Australian tiger snake is inocu- 

 lated), the serum exhibits decided protective properties ; 

 but the immunity thus produced is so slight, that 

 Martin is of opinion that it is practically valueless as a 

 remedial agent, even against one only of the poisonous 



1 "Scientific Memoirs, by Medical Officers of the Army of India," vol. ix., 



^ " The Curative Value of Calmette's Anti- Venomous Serum in the Treat- 

 ment of Inoculations with the Poisons of Australian Snakes " {Intercolonial 

 Medical Journal of Australasia, Xxxgxiit \?,()i). „ ,,, c- ■ ,. 



3 " Researches upon the Venoms of Poisonous Serpents ( bmithsoman 

 Contribution to Knowledge," vol. xxvi., 18S6). 



