i8g6. SERUM THERAPEUTICS. 109 



the treatment than chronic cases. It is probable that, in a disease 

 with an incubation period so long as that of tetanus (about ten days), 

 the appearance of severe symptoms indicates that the mischief is 

 done and that it is then too late to hope for much from serum thera- 

 peutics. It may be, however, that improved methods will overcome 

 this difficulty. 



Public attention has been chiefly directed to the application of 

 the method to the treatment of diphtheria. Here success has been 

 much more apparent, and a sufficient body of facts is forthcoming to 

 allow of definite conclusions on the subject. 



The original discoverer of the diphtheria bacillus was Klebs, but 

 the demonstration of its causal relation to the disease is due to Loftier, 

 while the work of Roux and Yersin has added important confirmation 

 to the proof. It has been shown that the bacillus, remaining localised 

 at the seat of infection, usually the throat, produces its constitutional 

 effects by the powerful toxins to which it gives rise. With filtered 

 cultures of the bacillus, containing these toxins in solution, it is 

 possible to reproduce experimentally in animals many of the 

 phenomena of the disease, including post-diphtheritic paralysis. 

 Actual membranous inflammation of mucous membranes, such as 

 characterises the disease in man, is with difficulty produced in 

 animals by living cultures of the bacillus, though this can be done, 

 notably in the trachea of kittens : nevertheless the organism is highly 

 pathogenic for many of the lower animals, producing typically an 

 intense local inflammation and swelling at the seat of inoculation, 

 frequently with rapidly fatal results. Animals vary, however, in their 

 susceptibility to the poison. The artificial immunisation of animals 

 against diphtheria was carried out by Frankel, Behring, and others, 

 and Behring showed that the toxins in a diphtheria culture were 

 neutralised by admixture with serum from an immunised animal, 

 though the bacilli were not killed. Dogs and goats were found to be 

 less susceptible to the disease, and hence to be more readily 

 immunised than rabbits and guinea-pigs, but Roux's choice of the 

 horse proved a happy one, since that animal is not only readily 

 immunised, but on account of its bulk is capable of furnishing anti- 

 toxic serum in large quantities. The horse, therefore, is the animal 

 now employed, and it can be immunised by successive inoculations, 

 either with the filtered toxins from diphtheria cultures or with living 

 bacilli. It would appear that the method advocated by Klein, in 

 which, after a preliminary injection with diphtheria cultures sterilised 

 by heat, increasingly virulent doses of living bacilli are successively 

 inoculated, yields a good result in a shorter time than does the method 

 of Roux, in which toxin only is injected, and, moreover, that the serum 

 so obtained has more antitoxic power, and can therefore be employed 

 in smaller doses than that of Roux. In any case, the effect of one 

 dose must, as Behring pointed out, have completely passed away 

 before the next is injected. After four or five inoculations, extending 



