40 



NATURE 



[May 



897 



Eroperty, it killed those animals into which it was injected, and 

 y no amount of artificial training could their serum become 

 endowed with any immunising effect. Exactly similar results 

 were obtained with frogs, and whilst the normal blood of these 

 animals was repeatedly proved to be quite devoid of all toxic 

 action on mice, yet after the frogs had been inoculated with 

 abrine, and trained to acquire an immunity beyond their brother 

 frogs towards this substance, their blood invariably killed the 

 mice into which it was injected. Dr. Calmette concludes from 

 these observations that natural immunity to a particular toxin 

 does not imply the existence of a specific anti-toxic substance in 

 the blood of such refractory animals, and that whilst apparently 

 warm-blooded abrine-refractory animals can be trained to elabo- 

 rate anti-toxins, cold-blooded abrine-refractory animals cannot 

 produce such anti-toxins in the normal conditions of their 

 existence. The latter portion of this generalisation receives 

 some support from Metchnikoft's observations of the same 

 phenomenon in the case of tortoises and tetanic-toxin. 



Prof. Calmette next proceeds to discuss the properties of 

 serum derived from those animals in which the immunity to a 

 particular toxin is not natural, but has been artificially induced. 

 We are again for this purpose taken back to anti-venomous 

 serum, and some additional information is given incidentally of 

 the wonderful efficacy which characterises this remarkable 

 remedy for snake bites. Perhaps one of the most astonishing 

 properties of this serum is the rapidity with which it operates. 

 Thus if two cubic centimetres of anti-venomous serum be 

 inoculated into the marginal vein of a rabbit's ear, it at once 

 confers upon the latter immunity towards snake poison. Imme- 

 diately after the injection of the serum, venom sufficient to 

 destroy an ordinary rabbit in a quarter of an hour may be 

 injected with impunity into the vein of the other ear. Its 

 degree of therapeutic efficiency is also extraordinarily intense, 

 as is well illustrated by the following experiment : four rabbits 

 are inoculated with a quantity of venom sufficient to destroy 

 them in two hours ; one of these is left, whilst the other three 

 receive, one hour and three-quarters later, an intravenous injec- 

 tion of serum equal in quantity to one four-hundredth part of 

 their weight. Whilst the unprotected rabbit dies in two hours, 

 the other three remain in perfect health. " Voila done un serum 

 qui," writes Calmette, " d'emblee, sans reaction prealable de 

 I'organisme, produit I'insensibilisation absolue des cellules a 

 regard du venin." 



Of great importance in their practical bearing are the experi- 

 ments which are recorded on the local action of anti-abrine and 

 anti-venomous serum respectively. As is well known, abrine 

 was at one time used for the treatment of trachoma, but unfor- 

 tunately the subsequent suppuration which attended its use was 

 in many cases so intense and so dangerous that it had to be 

 abandoned for therapeutic purposes. 



Now Calmette has found that by applying anti-abrine serum 

 to the local parts affected, the inflammatory action of abrine is 

 modified in a very remarkable manner, and the hope is held out 

 that by using this serum, and so controlling the inflammation 

 induced by the application of abrine, this valuable substance 

 may once more be reinstated in the therapeutics of ophthalmology. 

 Anti-venomous serum has apparently the same local immunising 

 action as the anti-abrine serum. 



Another practical point of great importance concerning these 

 serums is also dealt with in detail ; this is the diagnostic value 

 attaching to their use. Aheady Pfeiffer and other investigators 

 have shown how, by means of serum, it is possible to differ- 

 entiate between cholera and other non-pathogenic vibrios, and 

 to distinguish the typhoid from the closely-allied B. colicoviDiitnis. 

 A most interesting opportunity occurred for testing the dia- 

 gnostic power of anti-venomous and anti-abrine serums respec- 

 tively. In India the natives frequently wreak their vengeance 

 on their enemies by poisoning their domestic animals, and the 

 substances selected for this purpose are those which they know 

 will be with difficulty detected by expert analysis. Two 

 materials are specially favoured by them for this purpose, i.e. 

 abrine and serpent venom. One method of administering the 

 poison consists in taking short pieces of wood shaped in the 

 form of a club, in the thick end [of which small-pointed rods are 

 carefully fitted. These rods are composed of a hard greyish- 

 looking substance. Armed with these tiny clubs, which they 

 can easily conceal in their hands, they inflict small scratches, 

 scarcely visible, upon the cattle, but in the production of which 

 the pointed end of the little rod is broken off, and in this 

 manner the cattle become inoculated with the poison. Some of 

 these small broken-off points were sent by Mr Hankin, of 

 NO. 143;, VOL. 56] 



Agra, to Dr. Calmette for examination. On dissolving these 

 fragments in water and inoculating the liquid into rabbits, the 

 latter died, exhibiting the symptoms typical of abrine poisoning. 

 The same quantity of this liquid mixed with some anti-abrine 

 serum produced no toxic result whatever. Thus Dr. Calmette 

 considers his diagnosis of the poison employed as being abrine 

 fully justified. In a somewhat similar manner the use of 

 serpent venom was also detected. 



These results open up a new avenue to the physiological 

 detection of toxins, whether of animal, vegetable, or bacterial 

 origin by means of serums. 



Some extremely interesting experiments were also made to 

 ascertain whether toxins and antitoxins were capable of modi- 

 fying one another outside the body itt vitro. The follow- 

 ing examples give some idea of the results obtained. 5 cubic 

 centimetres of anti-venomous serum were mixed in vitro with 

 4 milligrammes of cobra venom, and this mixture was injected 

 intravenously into a rabVjit. The animal remained unaffected ; 

 at the end of an hour, this same rabbit was again intravenously 

 inoculated with i milligramme of venom. It died thirty-five 

 minutes afterwards. Thus although its death was slightly de- 

 ferred beyond that which was noted for the control animal, yet 

 it succumbed almost as readily as if it had received no protective 

 serum whatever. Again, 5 cubic centimetres of anti-venomous 

 serum were mixed with 4 milligrammes of venom and i cubic 

 centimetre of a 10 per cent, solution of hypochlorite of lime, 

 and the whole was inoculated into a rabbit. This same animal, 

 on subsequently, receiving a dose of venom usually fatal, suffered 

 no ill-effects at all. In this case. Dr. Calmette points out, that 

 whilst the serum had remained unaffected by the addition of 

 a chemical substance, the toxic nature of the venom had, on the 

 contrary, been entirely destroyed. Hence it is claimed that 

 when toxins and their anti-toxins are mixed in vitro, the former 

 do not appear to undergo any change or modification through 

 the presence of the latter. Therefore, either these substances 

 can remain side by side outside the body intact, or, if any 

 combination between them does occur under these circumstances, 

 it is a combination which is so unstable that the application of 

 heat or various chemical substances is able to easily bring 

 about their disunion, restoring to either the properties they 

 possessed before being brought into contact. Dr. Calmette, 

 in concluding his most valuable memoir, records a large 

 number of experiments made to ascertain what is the 

 degree of protective power exercised by anti-toxic serums 

 of different origin and certain liquids on animals inoculated 

 with abrine. It has been found that broth freshly prepared, 

 normal ox-serum, anti-tetanic serum, anti-diphtheritic serum, 

 anti-anthrax serum, and, above all, anti-cholera serum, exert 

 individually a decided immunising action with regard to abrine. 

 Although the protective action of these so-called foreign serums 

 is not so pronounced as in the case with anti-abrine serum, yet 

 they do most undoubtedly confer a certain degree of protection. 

 Dr. Calmette considers that this artificially induced immunity 

 must be regarded as a condition in which the cells of the body 

 are specially stimulated, and are thus enabled to either temporarily 

 or permanently resist the action of particular poisons. 



The mechanism of immunity will not permit itself to be 

 lightly mastered, and it is only by the conduct of painstaking 

 and patient inquiries, of which those just described are such a 

 splendid example, that a comprehension of this most important 

 as v.-ell as fascinating phenomenon can ever be hoped for. 



ON THE VARIATION OF LATITUDE.^ 

 A T the autumn meeting of the National Academy in 1894, 

 "^ which was the last occasion upon which the author asked 

 for its attention to this subject, he presented the numerical theory 

 of the motion of the pole, synthetically derived from the observa- 

 tions from the beginning of the history of the astronomy of 

 precision up to that time, in its complete development, exactly 

 as it stands to-day. Since then he has been interested to com- 

 pare it with the various series of observations, as they have 

 been published from time to time, not only for the purpose of 

 verification or improvement of the numerical values of the 

 various constants, but also to detect any additional characteristics 

 which these later data might make apparent. These additional 

 investigations have individually been neither extensive nor im- 

 portant enough to call for separate publication ; since their 

 general result has been merely a satisfactory confirmation of the 

 1 Abstract of a paper read before the National Academy of Sciences at 

 Washington, April 21, by Prof. S. C. Chandler. 



