April 23, 1896J 



NATURE 



593 



powerful as an antidote, in the conditions of these experiments, 

 I hat even the 1/2500 part of a cubic centimetre, equivalent to 

 ;il)out the one-hundred-and-fiftielh part of a minim, acted as an 

 etticient antidote, while even with the one-two-thousandth part 

 of a cubic centimetre not only was death prevented, but there 

 w as almost no symptom of poisoning produced. In the experi- 

 ments of this series with one-and-a-half the minimum-lethal 

 dose, recovery occurred when the doses of antivenene were '32 cc. , 

 ■3 cc. , '28 cc. , *25 cc. , and "24 cc. per kilogramme ; but "23 cc. 

 and "2 cc. failed to prevent death. In the experiments with 

 twice the minimum-lethal dose, recovery occurred when the 

 doses of antivenene were "5 cc. , '4 cc. , and "35 cc. ; but "3 cc. 

 and "2 cc. failed to prevent death. In the experiments with 

 thrice the minimum-lethal dose, a dose capable of producing 

 death in less than two hours, recovery occurred when the doses 

 of antivenene were 7 cc. and "65 cc. ; but death occurred with 

 6 cc. , '55 cc. , and 5 cc. With four times the minimum-lethal 

 dose, recovery occurred with 1*5 cc. , 13 cc, and 12 cc. , and 

 death with I cc. With five times the minimum-lethal dose, 

 recovery occurred with 25 cc, 22 cc, 2 cc , 18 cc, and 

 I 5 cc. ; but death with i '3 cc. With eight times the minimum- 

 lethal dose, recovery occurred with 26 cc. and 25 cc. ; but 

 death with 2*4 cc, 2-3 cc, and 2 cc. And even the enormous 

 <lose of ten times the minimum-lethal failed to produce death, 

 01 any important .symptoms, when it had previously been mixed 

 with 3 "5 cc. and 3*4 cc. of antivenene for 

 each kilogramme of animal ; and it only 

 succeeded in producing death, although 

 not until the lapse of several hours, when 

 the dcses of antivenene were 3*3 cc, 

 32 cc, 3 cc, and 2*5 cc. per kilo- 

 gramme. 



These results show a remarkable, an 

 almost directly proportional, accordance in 

 the increment required in the dose of 

 antivenene for each increment in the dose 

 of venom. In the diagram the compara- 

 tively straight direction of the oblique line 

 separating the fatal from the non-fatal ex- 

 periments is noteworthy, considering that 

 the conditions of the experiments, in regard 

 both to the animals and the substances 

 used, could never be absolutely the same. 

 Indeed, from twice the minimum-lethal 

 dose of venom upwards, the addition of 

 little more than "3 cc. per kilogramme 

 represents the addition in the quantity of 

 antivenene required for each addition of 

 a minimum-lethal dose of venom. Appar- 

 ently the antivenene is able in this pro- 

 portion to prevent death from almost any 

 lethal dose of venom, however large it 

 may be. 



These results are in marked contrast with those that occur I 

 when an antidote acts because of its physiological properties, 

 and they alone suggest that the antidotism is rather the 

 effect of a chemical than of a physiological reaction. The in- 

 dications obtained with doses of twice the minimum-lethal and 

 upwards cannot, however, be carried down to the minimum- 

 lethal dose. The quantity of antivenene required to prevent 

 death from this dose is much less than might have been antici- 

 pated when the results of experiments with larger doses are 

 considered. Thus, it appears that while "35 cc. of antivenene 

 per kilogramme is required to prevent death from twice the 

 minimum lethal of venom, the minute quantity of the i/2500fh 

 of a cc, or nearly 1000 times less (-0004 as compared with 

 S cc ), is sufficient to prevent death from a little more than 

 minimum-lethal dose of venom. It is apparent that this 

 M.inute quantity of antivenene does not render inert the whole 

 ot the minimum-lethal dose. All that is required in order that 

 tlie minimum-lethal dose should not produce death being that 

 (mly a minute portion of it should be rendered inert ; for, if 

 this dose be the actual mininum-lethal, the rendering inert of 

 any portion of it, however minute, will prevent the remainder 

 from causing death. 



In the second series, experiments with the antivenene of the 

 liorse have been completed only with one-and-a-half the mini- 

 mum-lethal dose of venom. When this dose was injected into 

 the subcutaneous tissues of one side of the body, and, immediately 

 thereafter, a dose of antivenene into the subcutaneous tis.sues of 



NO. 1382. VOL. 53] 



the opposite side, it was found that antivenene in doses of 3 cc. 

 and 33 cc. per kilogramme failed to prevent death, but that 

 3 "5 cc. and 3 '6 cc. per kilogramme were able to do so. 



In the third series, experiments have been made with the 

 minimum-lethal, one-and-a-half the minimum-lethal and twice 

 the minimum-lethal dose of cobra venom. With the first of 

 these doses, recovery occurred with '5 cc. , "45 cc. , and "42 cc. ; 

 but death with "4 cc, '3 cc. , and '25 cc. of antivenene, 

 administered thirty minute? before the venom. With one-and-a- 

 half the minimum-lethal of venom, 2*9 cc. and 27 cc. of anti- 

 venene were able to prevent death ; while 2 dec, 2*5 cc, 2*3 cc, 

 and 2 cc. each failed in doing so. With twice the minimum- 

 lethal dose of venom, recovery occurred when the doses of anti- 

 venene were 5cc., 4*5 cc, and 4 cc. ; but 39 cc, 3 8 cc, 

 3 '5 cc, 25 cc. , and 2 cc. were insufficient to prevent death. 



In the fourth series, where the results give the truest indica- 

 tions of the antidotal value of antivenene in the actual treatment 

 of snake-poisoning, it was found that recovery occurred in the 

 experiments in which "8 cc, 7 cc, and "65 cc per kilogramme 

 of antivenene was injected thirty minutes after an assuredly 

 minimum-lethal dose ('00025 P^"" kilo.) of venom ; but that the 

 antivenene was insufficient in quantity to prevent death when 

 '6 cc. or any smaller quantity was administered. In this series, 

 further, it was found that 3^4 cc. and 3*2 cc. per kilogramme of 

 antivenene were sufficient doses to prevent death after one-and- 



a-half the minimum-lethal dose of venom, but that 3 cc, 2'8 cc, 

 and 2*5 cc. per kilogramme were insufficient. In a correspond- 

 ing series of experiments made with the antivenene derived from 

 rabbits which had last received thirty and fifty times the 

 minimum-lethal dose of cobra venom, it was found that 5 cc. 

 per kilogramme of this antivenene was the smallest dose by 

 which death could be prevented in an animal which had received 

 twice the minimum-lethal dose of venom thirty minutes pre- 

 viously. 



Attention is conspicuously drawn by these facts to the remark- 

 able difference in the dose of antivenene which is required to 

 prevent death when it is mixed with the venom before adminis- 

 tration, as contrasted with the doses required when the two 

 substances have not previously been mixed together. Restrict- 

 ing attention to the experiments in each series in which the dose 

 of venom was the same — to the experiments with one-and-a-half 

 the minimum-lethal dose, for instance — it appears that in order 

 to prevent death, when this dose was mixed with antivenene 

 before administration, only '24 cc. of antivenene is required ; 

 whereas when both substances were injected simultaneously, but 

 under the skin at different parts of the body, the required dose 

 of antivenene is 3*5 cc. ; when the antivenene was injected 

 thirty minutes before the venom, it was 27 cc. ; and when the 

 venom was injected thirty minutes before the antivenene, it was 

 3 "2 cc. per kilogramme. 



It is impossible to consider the great difference between the 

 dose of antivenene required when the two substances, though in 



