122 



SCIENCE 



[N. S. Vol. XLIV. No. 1126 



invading microorganism. Such diseases, for 

 example, as epidemic meningitis, can be 

 cured by inoculating serum from animals 

 immunized against its causative agent, the 

 meningococcus. Still other diseases, prin- 

 cipally local affections, as, for example, 

 carbuncles, may be treated with consider- 

 able success by injecting the causative agent 

 itself; in the example mentioned, staphylo- 

 coccus. This latter form of treatment, or 

 vaccine therapy, as it is called, builds up an 

 active immunity and leads the animal so to 

 muster his reactive, protecting, forces as to 

 expel the invader. 



It is this latter method of vaccine therapy 

 which alone has been used with any suc- 

 cess in the treatment of typhoid fever. I 

 have already referred to the hopelessness of 

 affecting the course of typhoid fever in any 

 but a palliative way by the other methods 

 of treatment that have been suggested ; the 

 fever may be favorably influenced by the 

 continued use of cold baths, but the dura- 

 tion of the disease is little, if at all, affected 

 by such means. In 1893 Fraenkel began 

 the use of small doses of killed typhoid 

 bacilli injected hypodermically in typhoid 

 fever. For twenty years this treatment has 

 been tried with varying success by many 

 physicians, some of whom have published 

 their results. These results, although at 

 times encouraging, have never convinced 

 the medical world that the method is stri- 

 kingly successful. The best that may be 

 said of it is that it does no harm, and in the 

 hands of some physicians apparently short- 

 ens the disease and prevents some of the 

 unpleasant sequels by which typhoid is so 

 apt to be followed. 



During the past two years two innova- 

 tions have been made which, from the re- 

 sults attained by several observers, and in 

 view of the theoretical studies on hyperleu- 

 cocytosis to which I made reference, have 

 thrown an entirely new light on the possi- 



bilities of vaccine therapy in typhoid fever. 

 These two innovations are, briefly, as fol- 

 lows : First, the administration of the vac- 

 cine directly into the circulation, and 

 secondly, the use of a sensitized or serum- 

 treated vaccine instead of the plain 

 bacterial growth hitherto used. These pro- 

 cedures, introduced into practise by Thiro- 

 loix and Bardon, and by Ichikawa, respec- 

 tively, carried out the precise method of 

 treatment that we had already suggested 

 from our experimental results, and fully 

 justified our expectations. 



During the past year it has been possible 

 for us to carry out the intended treatment 

 in a number of cases in this vicinity, 

 through the great courtesy of physicians 

 who have allowed us to see their patients 

 and have been willing to accept our sugges- 

 tions in relation to their treatment. This 

 confidence and cooperation has resulted not 

 only in rapid amelioration in the majority 

 of cases, but through comparative study of 

 the successful with the unsuccessful eases 

 has suggested improvements which may in- 

 crease the percentage of favorable results. 



Let us consider what happens when a 

 killed preparation of sensitized typhoid 

 bacilli is given intravenously in a case of 

 typhoid fever. The introduction of some- 

 thing like one twenty-fifth of a milligram 

 of the vaccine into the circulation is fol- 

 lowed in a few minutes by a distinct shaking 

 chill, which is accompanied by a rise of the 

 fever of from one to two degrees. This 

 shaking and fever, which is seldom extreme 

 enough to be very uncomfortable, is accom- 

 panied by a fall in the number of white 

 blood corpuscles. Following this reaction 

 the fever rapidly falls so that in from six 

 to twelve hours the temperature has reached 

 normal, or even subnormal. This fall in the 

 fever is accompanied by a rise in the leuco- 

 cytes, profuse sweating, and a feeling of 

 well-being. The severe headaches, begin- 



