July 28, 1916] 



SCIENCE 



119 



considering whether typhoid vaccination is 

 of value, that you must accept as proved 

 beyond peradventure, but just how valuable 

 it is and in what way it may be further 

 perfected. In other words I am leading 

 you into those intricacies of detail which 

 any scientific problem attentively consid- 

 ered must present, and from the unraveling 

 of which new and important issues may 

 arise. 



Our former beloved professor of hygiene, 

 George Reinhardt, came to me some three 

 years ago and asked if I did not agree with 

 him that the student body in this univer- 

 sity should be offered the opportunity of 

 being vaccinated against typhoid fever. 

 "With no hesitancy at all I answered "Yes." 

 When he pressed me further as to the best 

 method of preparing and administering the 

 vaccine I felt unwilling to decide so impor- 

 tant a matter on the basis of literary 

 knowledge alone. In association with the 

 late Dr. Edith J. Claypole we undertook to 

 arrive at some conclusions on the subject. 

 "We found that nearly twenty different 

 preparations of typhoid vaccine had been 

 suggested, and each regarded by its author 

 as the best. Data, however, on which to 

 compare one vaccine with another were al- 

 most entirely lacking, that is to say a vac- 

 cine was approved because it had worked 

 well under a given set of conditions with a 

 more or less considerable number of men 

 without any direct comparison with other 

 vaccines. 



Three distinct improvements in the vac- 

 cines in vogue seemed possible. 

 First: All vaccines were admitted to pro- 

 tect, at best, for only relatively short pe- 

 riods of time, say about two years. 

 Second: Many of the vaccines advocated 

 were admitted to give rise, on adminis- 

 tration, to rather uncomfortable transi- 

 tory symptoms. 

 Third: The current method of administra- 



tion, three injections over a period of 

 three weeks or more, seemed an unneces- 

 sarily long period to wait for protection. 

 It was with these questions particularly 

 in mind that we began our experiments. 

 Out of them have arisen innumerable fur- 

 ther questions, some of which have given 

 rise to investigations of theoretical and 

 practical interest. In the first place there 

 had been no convincing experimental 

 method of comparing the relative protec- 

 tive value of various vaccines. The only 

 results of value seemed to be statistics from 

 inoculated men obtainable only after years 

 and under most uneven conditions. Cer- 

 tain experiments of Metchnikoff and Bes- 

 redka with anthropoid apes were suggestive, 

 but impossible to carry further, owing to 

 the expense of these animals. "We finally 

 adopted an experimental procedure in rab- 

 bits that had been used for other purposes 

 and which, with our modification of it, led 

 us to conclusions that were rapidly ob- 

 tained and apparently valid. It was found 

 possible to compare several of the best 

 typhoid vaccines in respect to the length of 

 time they protected rabbits against infec- 

 tion with living typhoid bacilli. As a re- 

 sult of many experiments of this sort we 

 came to the conclusion that a new type 

 of "sensitized" vaccine, as it is called, gives 

 rise to the most durable immunity. The 

 word "sensitized" simply means that the 

 bacteria in the vaccine have been treated 

 with the serum of animals that have been 

 highly immunized against them. It was 

 furthermore found possible to remove cer- 

 tain toxic elements (endotoxins) from these 

 vaccines with a further increase in immu- 

 nizing property. The final product, then, 

 a "sensitized vaccine sediment," as we call 

 it, not only protects animals longer from 

 infection than other vaccines, but is found 

 when injected into human beings to produce 

 little or no reaction. 



