620 



NA TURE 



[October 24, 1895 



these laminae which, acting as " films," give rise to all the colour 

 of nacre, practically : and the phenomenon should be included 

 amongst those of colours from " films," and not from " striated 

 surfaces," the latter being merely incidental, and for all practical 

 purposes contributing nothing to the efiect. 



C. E. Ben HAM. 



A RATIONAL v l a/-. / c/V SNAKE-BITE. 



AA'HEN it was established beyond dispute or cavil 

 ' ' that the serum obtained from animals, immunised 

 against bacterial infections and mtoxications, possesses \ 

 in a marked degree antitoxic powers — as distinguished 

 from antibiotic powers — and that such serum when mixed 

 in a test-tube with the bacterial poison in question will, 

 so to speak, neutralise the toxic efTects of such poison, 

 however deadly, it was merely a question of time, 

 opportunity, and patience that attempts would be made 

 to extend the principle of scrum-immunisation to other, 

 i.e. non-bacterial, poisons. Ehrlich was the first to show 

 us the way. He gradually accustoined animals to with- 

 stand comparatively large doses of abrine, ricine, and 

 robine, three vegetable toxines, all belonging to the 

 group of proteines, reacting as albumoses or globulincs. 

 In that manner he produced in the animals a relative 

 immunity, or perhaps, more correctly, a tolerance. He 

 found that though subcutaneous inoculations lead to 

 better results, that this immunity can be brought about 

 also by feeding. In whatever way the animal is prepared, 

 its serum eventually acquires specific antitoxic, immunis- 

 ing, and curative properties. It was thus demonstrated 

 that the wonderful discovery of Hehring and Kitasato — for 

 which Bchring, however, claims the sole credit — has a 

 scope much wider than at first was dreamt of. Behring 

 himself, to begin with, explained the action of the serum 

 as antibiotic or germicidal : but it soon became evident 

 that, though when injected into the animal body it causes 

 the destruction and death of the infective pathogenic 

 organisms, nevertheless its chief action is "vitally" anti- 

 toxic. For working with the tetanus toxine alone, separated 

 from the bacilli which produced it, its deadly effects can 

 be readily neutralised by a few cubic centimetres of a 

 powerful serum. And if we remember that "23 milligram 

 of tetano-toxine would represent the fatal dose for a human 

 being weighing 70 kilogrammes, then we can get an 

 idea as to what extraordinary changes must have been 

 produced in the serum, or rather in the blood and tissues, 

 of the immunised animal, to enable its serum instan- 

 taneously to remove the lethal effect of the toxine. The 

 only poison comparable to tetano-toxine in virulence and 

 rapidity of action is cobra poison, and it also resembles 

 chemically the bacterial toxmes, reacting as an albumose, 

 though for the sake of accuracy it must be mentioned, 

 that the poison of tetanus has been clearly shown by 

 Briegcr, Cohn, and Sidney Martin not to be an album- 

 inous body, and that possibly most of the bacterial 

 toxines may turn out not to be albuminous substances. 

 Still, so far as our present knowledge reaches, cobra 

 poison and other snake venoms are chemically closely 

 allied and analogous to the " toxalbumins " of bacteria. 

 It had also been demonstrated by several observers,' 

 that by means of oft-repeated injections of small sub- 

 lethal doses of snake poison (rattlesnake, cobra, or viper 

 venom; the resistance of an animal against the poison 

 may gradually be increased considerably, it may be 

 rendered "giftfest," to borrow a (ierman exprcssiim. In 

 fact, all the methods used for inducing a tolerance 

 against tetanus poison can be shown to work in the case 

 of cobra poison (this is the poison generally employed). 

 Thii, r.ilimitc ului'.r- work in this line follows directly 



'-'O .' K.-inlhack. ibitl.. 189a, vol. xvi. No». 



' .'"///. unJ. ,/. T 1,.iJ. d. tc cxviii. 1894, 



1 1 : Cortt^t. rtnti. 



■\, it'll/., p. 113. 



. . ^, p. j8i. 



NO. 1356, VOL. 52J 



that of Sewall's and of the writer of this article, has shown 

 that a so-called immunity can also be produced by' 

 gradually increasing injections of poison attenuated by 

 heat, iodine, trichloride of iodine, hypochloride of calcium, 

 &c. ; in fact, the analogy is complete. From this stage, 

 at which others had already arrived, Calmette went ahead 

 with Phisalix and Bertrand. Having previously attempted 

 both to prevent and to cure the effects of inoculation with 

 cobra poison by means of chloride of gold— wherein, how- 

 ever, as shown by the writer,' he faifed — he directed his 

 attention at once to the serum of immunised animals, and in 

 February 1894 he showed, before the Societe dc Biologie, 

 that on mixing cobra or viper venom with small quantities 

 of scrum obtained from an immunised rabbit the deadly 

 effect of the venom disappears, a fact at once confirmed 

 by independent observations of Phisalix and Bertrand. 

 In May 1894 and in .\pril 1S95, Calmette published two 

 concise papers in Pasteur's Aitnahs, containing a full 

 account of his results. These, briefly summarised, are as 

 follows : ( I ) The serum of an animal immunised against 

 snake poison (he used poisons of the following snakes : 

 Nitja tripuiiians and liajc, Crotahis tiurissus, liothrops 

 laineola/its, Ci-ntsh-s, P-ii-i/iitxhis porphyriacus., Hoplo- 

 ccphaliis Curtis and van'ega/us, Acanlhopis a/itantica, 

 Trinurcsiiriis ''iridis) possesses properties similar to- 

 those which the serum of animals immunised .against 

 tetanus and diphtheria possesses. (2) The serum of a 

 rabbit immunised against cobra or viper venom .acts 

 equally well against any of the other poisons, /.(■. there is 

 no specificity of action, as judged by the species of sn.ake. 

 (3) The serum possesses not only neutralising properties 

 when mixed with the venom in a test-tube, but possesses 

 also marked immunising and curatixc properties, /.(■. 

 poison injected after pre\ ious serum administration be- 

 comes powerless, and serum injected after previous 

 poison administration neutralises the effects of the poison 

 in the animal body, even after the symptoms of intoxica- 

 tion have already set in. Naturally the effect depends 

 on the degree of immunity of the serum giver and on 

 the proportionate amount of serum used. (4) The im- 

 munising effect produced by serum injections is not so 

 lasting as that produced by direct injections of the 

 poison, i.e. serum injections are incapable of rendering 

 animals " giftfest." Calmette alludes to other ni.itters, but 

 since these are of secondary importance and still debatable, 

 and not directly related to the subject of this article, we 

 must pass them over. There is, however, one point which 

 must be mentioned, since it is one afl'ecting the whole 

 principle of serum immunisation. He states that he has 

 succeeded in producing a " (iiftfcstigkcit " by means of 

 repeated intravenous injections of hypochloride of calcium, 

 and that the serum of such " chlorinated " animals will 

 neutralise, in the test-tube at least, the effects of cobra 

 poison. Roux elsewhere mentions - that the serum of 

 animals immunised .tgainst tetanus or rabies is capable 

 of neutralising snake \enom and of protecting other 

 animalsagainst subsequent intoxication with cobra jwison, 

 and that r.ibbits vaccinated against rabies can withstand 

 four to five times the lethal close of cobra venom ; and 

 also that abrine serum will counteract the effects of cobra 

 poison, .and cobra serum those of abrine. Calmette goes 

 so far as to say that an animal vaccinated against aljrine 

 may acquire a relative immunity against dipluheria, 

 ricine, and anthrax. If this be so, we sh.ill have to 

 modify our \ icws as to the specific action of antitoxic 

 serum, /'.(•. the first prim iple of serum therapeutics. We 

 require a number of control observations before we can 

 accept these remarkable statements ; partial contradiction 

 they have already received from (icrmany, ' and the 



> l.itHctl. (line II, i8t)j. The iisclcssiicsf. of »lr>'cliniiic vim previounl)^ 

 dcmon^lr.ilcd Ity the writer iti tiiv paper ii» \\k Journal 0/ Physiol0gy< 



2 .-inHaUi tic t tnst. Past. 1894, No. 10, p. 722. 



^ Khrlich emphatically denies any *iich vicarious counteraction with rcgi 

 to abrine and ricine (cf. Drnlsche Med. Wmliriiicliii/I, \o\. xvii. N" 

 p. 1118). 



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4 



