10 QUATERCENTENARY STUDIES IN PATHOLOGY 



peritoneal exudates obtained from guinea-pigs infected in the peritoneum 

 with B. pestis. By means of two prophylactic injections of this fluid 

 or "aggressin," they succeeded in conferring a high degree of immunity 

 on mice, guinea-pigs, and rabbits. The injection of the substance was 

 followed by a period of hypersensibility. The theory of the method and 

 its relation to those of other workers will be discussed at a later period. 



Klein (1905), while investigating the vitality of the B. pestis in 

 certain organs, spleen and lung, and in the buboes of animals dead of 

 plague, found that though all the bacilli had been destroyed by the 

 process of drying over sulphuric acid, an emulsion of the organs, when 

 injected into mice, was capable of causing the death of these animals 

 within 20 hours. 



All the phenomena of acute plague are exhibited, without, however, 

 the B. pestis being present in the tissues. When the amount of emulsion 

 injected was insufficient to cause death, the animals, after recovery from 

 the local swelling and constitutional disturbance which resulted from the 

 injection, were found, on being tested at a later period, to be refractory 

 to infection, even when a virulent plague bacillus was injected. 



Guinea-pigs, inoculated cutaneously with a bacillus of moderate 

 virulence, develop a sub-acute form of plague, death occurring from the 

 fourth to the ninth day. The lesions found are necrotic buboes, necrotic 

 nodules in the spleen and liver, and particularly necrotic nodules and 

 patches in the lungs. In sections of such organs the central parts of the 

 necrotic nodules and patches are found to be crowded with bacilli, 

 whereas the peripheral parts, consisting of debris, contain few, if any, 

 bacilli. From this it may be inferred that the necrotic changes are due, 

 not to bacilli themselves, but to their toxin. 



Klein proposes to prepare a prophylactic substance from such 

 material. The bubo, enlarged spleen, necrotic lung and liver of guinea- 

 pigs which have died from sub-acute plague, are cut out, minced 

 aseptically, and then spread out in thin layers on sterile glass dishes, and 

 dried over sulphuric acid at 46° - 47° C. There is thus obtained " a 

 material which not only can be very easily and rapidly prepared, but 

 which is of a uniform and reliable efficacy, and in every way indeed 

 superior to any of the other prophylactics." Klein calculates that a 

 single large guinea-pig would yield 800- 1000 human doses of the new 

 prophylactic. 



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