422 



NA TURE 



[September 3, 1891 



Cure of this Disease." He stated that his previous experiments 

 on swine fever had proved that in immune animals the bacilli of 

 swine fever were destroyed, not by the cells of the animal, but by 

 a bactericidal substance present in the blood. It had been 

 clearly proved by his experiments that the bacilli of swine fever 

 were destroyed almost immediately after their introduction 

 under an immune animal's skin. Applying these researches to 

 the disease produced in rabbits by the inoculation of the Diplo- 

 coccus pneiunonice of Fraenkel, he showed that non-immune 

 rabbits died within twenty-four to forty-eight hours after the 

 introduction of the virus. But if such animals had been pre- 

 viously treated with the blood or serum of animals rendered 

 artificially immune against the diplococcus of Fraenkel, such 

 animals did not die, but recovered after the introduction of ex- 

 tremely virulent diplococci. Moreover, when the Diplococcus 

 pnetwiotiia: was inoculated into an animal, it was possible to 

 cure it by injecting shortly afterwards some of the serum of an 

 animal rendered artificially immune. In the blood of animals 

 rendered artificially immune against pneumonia we possessed an 

 excellent cure for the disease. Not only would it be possible to 

 cure men afflicted with pneumonia by these injections, but we 

 could, by preventive inoculations applied in time, put a stop to 

 the spread of an epidemic in a school or a prison for instance. 

 His experiments, together with Dr. Doenissen's, had a great 

 practical as well as a theoretical value. 



Dr. Ehrlich, of Berlin, stated that he had lately made a 

 number of experiments with ricin which threw great light on 

 the question of immunity. According to Robert and Stillmark, 

 ricin was an extremely poisonous body, for it acted fatally when 

 such small doses as o 03 mg. were injected into an animal's 

 veins. When absorbed through the alimentary canal, a dose 

 100 times larger could be easily tolerated. Nevertheless, even 

 then, it was so toxic that, according to Robert's reckoning, a 

 dose of o'i8 gr. would prove fatal to a full-grown man. It had 

 a harmful influence on the blood, producing coagulation of the 

 red blood-corpuscles, and thromboses, more especially of the 

 vessels of the alimentary canal. 



In his opinion the toxicity of ricin greatly depended on the 

 species of animals used for experiments, the animals most sus- 

 ceptible to its action being guinea-pigs. Thus, a guinea-pig 

 weighing 385 grammes died eleven days after the inoculation of 

 07 cc. of a I in 150,000 solution of ricin, the post-mortem 

 examination showing characteristic haemorrhages in the ali- 

 mentary tract. One gramme of this substance might therefore 

 prove fatal to 1,500,000 guinea-pigs. White mice, on the other 

 hand, did not die after much larger doses, and this immunity of 

 mice against this poison might be increased by subcutaneous 

 injections of ricin. The same result might be obtained, how- 

 ever, far more easily and without any chances of failure, by 

 feeding mice with ricin. It was best to begin whh small, 

 harmless doses, gradually increasing the amount until the or- 

 ganism was accustomed to the poisonous substance. In ten 

 days a mouse might then be inoculated with a deadly or even 

 larger dose without suffering any evil effects. Thus, whilst 

 doses of 1/200C00 gramme was absolutely fatal in normal 

 animals, mice fed daily and in increasing quantities with ricin 

 suffered no harm after the injection of i/iooogr. or 1/500 gr., 

 or, occasionally, of 1/250 gr. 



Whilst a 0'5 or i per cent, solution of ricin applied to the 

 eye of a normal animal produced severe inflammation and 

 panophthalmitis, the application of a 10 per cent, solution of 

 ricin produced no effect on the eye of an animal previously fed 

 with ricin. In other words, this was distinct proof of the 

 existence of a local as well as of a general immunity against the 

 poison. Strangely enoughit was almost impossible to render the 

 subcutaneous tissue immune against ricin, and even in exceed- 

 ingly immune animals the subcutaneous injection of ricin pro- 

 duced distinct necrosis of the subcutaneous tissue. 



It was a remarkable fact that this immunity appeared quite 

 suddenly on the sixth day, and then increased slowly, so that on 

 the twenty-first day the animal could stand a dose which was 

 400 times higher than that fatal to a normal animal. 



This immunity against ricin appeared to be permanent, for it 

 was still present in immune mice which had not taken ricin for 

 a period of six months previously. 



He had been able to extract from the blood of animals 

 rendered immune against ricin a body which had the power of 

 counteracting the toxic action of ricin, so that a powerful solu- 

 tion of ricin was rendered harmless by admixture with the blood 



NO. II 40, VOL. 44] 



of immune mice. It was also possible to render animals 

 immune against ricin by injecting the blood of immune animals. 



He had obtained similar results with abrin, which would be 

 shortly published. 



Dr. Ritasato, of Tokio, shortly summarized the results which 

 he and Dr. Behring had obtained with the virus of tetanus. 

 According to these observers, the blood of a normal rabbit has 

 no influence on the toxines secreted by the bacillus of tetanus. 

 But when a rabbit had been rendered artificially immune against 

 that disease, its blood had the power of destroying the toxines 

 secreted by the specific bacillus. Nay, more, the blood of rab- 

 bits made artificially immune against tetanus with trichloride of 

 iodine, rendered mice not only refractory to tetanus but also 

 cured the disease when already in progress. The blood, how- 

 ever, did not appear to act on the tetanus bacillus itself, but on 

 the toxines secreted by the bacillus.. 



Dr. Adami, of Cambridge, thought that it was impossible to 

 doubt that in a large number of infectious diseases the process 

 of phagocytosis was extremely marked. He was of opinion that 

 it was quite possible to accept both views of the question. The 

 controversy had taken placechiefly as to the phenomena observed 

 in the rat ; in that animal phagocytosis was only to be observed 

 with difficulty, and the serum of rat's blood undoubtedly pos- 

 sessed bacteria-killing properties to a high degree. 



Dr. Rlein, of London, stated that frogs and rats were insus- 

 ceptible to anthrax, but that these animals could be made 

 susceptible to the disease by a variety of means, indicating that 

 their normal power of resistance was due to certain chemical 

 conditions of the blood. If the bacillus of anthrax was introduced 

 into the lymph-sac of a chloroformed frog, this animal always 

 died of anthrax. Rats inoculated with anthrax and kept under 

 the influence of an anaesthetic also died of anthrax. He had been 

 unable to find any evidence to show that in these cases the 

 leucocytes had lost their power of swallowing up bacteria, and 

 therefore the susceptibility of chloroformed animals to anthrax 

 could only be explained by some chemical changes taking place 

 in the serum of the chloroformed rat or frog. 



Dr. Metchnikoff, of Paris, who was greeted with loud and pro- 

 longed cheering, said that, of all the objections which have been 

 raised against the theory of phagocytes, doubtless by far the 

 most important was that formulated by Behring and Nissen : 

 namely, the fact that the serum of guinea-pigs vaccinated against 

 the vibrio of Metchnikoff had bactericidal powers on the same 

 vibrio. Whilst the serum of normal guinea-pigs allowed the free 

 development of a large number of these microbes, the serum of 

 vaccinated animals killed the micro organisms at the end of a 

 few hours. MM. Behring and Nissen were convinced that this 

 fact formed a complete explanation of the acquired immunity of 

 guinea-pigs against the Vibrio Metchnikofi, and that it might 

 serve as a model for a theory of immunity. His own researches, 

 however, proved the contrary. If one studied the phenomena as 

 they occurred in the living animal, one noticed at once that the 

 bacilli inoculated into immune guinea-pigs remained alive for a 

 very long time. Some vibrios were taken into the interior of 

 leucocytes at the point of inoculation, whilst others developed 

 perfectly in the liquid exudation. To show this, one had only 

 to take a drop of the latter, and place it in the warm chamber ; 

 the leucocytes perished when taken out of the organism, and 

 allowed the bacilli contained in their interior to develop freely. 

 The vibrions thus multiplied and filled the leucocytes, which 

 swelled and eventually burst, allowing the microbes to pass 

 freely into the liquid part of the exudation. Here the develop- 

 ment continued, and one obtained very abundant cultures from 

 the liquid exudation of the immune guinea-pig. If one ex- 

 tracted a small quantity of such a culture, and introduced it into 

 the dead serum of an immune guinea-pig, this serum not only 

 did not kill the bacilli, but also gave a more abundant develop- 

 ment than the serum of a non-immune animal could do. The 

 study of the phenomena in living animals made artificially im- 

 mune against the vibrio of Metchnikoff, instead of overthrowing 

 the theory of phagocytosis, furnished on the contrary an evident 

 proof in its favour. The theories of the attenuation of virus in 

 the bodies of immune animals, and of the neutralization of the 

 toxines, could not be applied to his case, as the vibrios re- 

 mained very virulent, and because the immune guinea-pigs are 

 as sensitive to the toxine of the bacillus as the non-immune 

 animal. 



This example showed yet once more that one must not be 

 content with studying the phenomena of immunity outside the 



