July 28, 1916] 



SCIENCE 



117 



simpler and almost as reliable method of 

 laboratory diagnosis has been devised by 

 Widal and by Gruber, depending on a 

 principle that had been previously dis- 

 covered in laboratory experiment. Bordet 

 in particular is responsible for having 

 shown that the blood serum of animals that 

 have been given injections of a micro- 

 organism may be distinguished from the 

 serum of normal animals by the fact that it 

 clumps the microorganism in question. 

 This fact was applied by "Widal in his now 

 famous test for typhoid fever, which de- 

 pends on the presence of this agglutinating 

 substance in the serum of those that are 

 suffering from typhoid fever. This sign 

 occurs in nearly all cases of the disease, al- 

 though more frequently in its later stages. 

 Our present methods of protective vacci- 

 nation against typhoid fever depend on 

 principles that have been dimly appreciated 

 but at times suecessfuly used by very primi- 

 tive peoples throughout the centuries. It 

 had been observed that those who recover 

 from certain of the infectious diseases are 

 thereafter protected from them. With this 

 fact in mind the Orientals practised arm to 

 arm inoculation with smallpox virus which 

 usually produced only local evidence of the 

 dread disease and was followed by protec- 

 tion from it. Jenner made this haphazard 

 and dangerous method of prophylaxis a safe 

 one by utilizing virus from a modified 

 form of smallpox, namely cowpox, which is 

 not only harmless, but gives equally good 

 protection. Full understanding of the prin- 

 ciple involved and its application to other 

 infections, however, was dependent on the 

 advent of bacteriology a century later. 

 Pasteur not only separated out the causa- 

 tive agents of a number of diseases, but 

 found that he could so modify their viru- 

 lence that they no longer produced fatal or 

 serious effects when reinoculated into ani- 

 mals. Those that had been treated with 



these modified germ cultures were found, 

 however, to be protected against fully viru- 

 lent original growths of the microorganism. 



Facts such as these were early discovered 

 in respect to the infections produced by the 

 typhoid bacillus in small animals. Beumer 

 and Peiper in 1887 found that mice that 

 had recovered from a non-fatal dose of this 

 organism would subsequently withstand 

 doses that were fatal to their untreated 

 brothers. Shortly after, following a very 

 important discovery by two American scien- 

 tists, Salmon and Smith, it was found that 

 this same protection could be effected in 

 animals by the previous injection of cul- 

 tures of the typhoid bacillus that had actu- 

 ally been killed by heat. 



In 1894 two German scientists, Pfeiffer 

 and Kolle, on the basis of further theoret- 

 ical studies, were led to try the effect of 

 giving human beings small hypodermic in- 

 jections of dead typhoid bacilli. They 

 found that the doses they used produced 

 certain uncomfortable but transitory symp- 

 toms, but that the blood of such treated 

 individuals when subsequently examined 

 contained antibodies which indicated that 

 they were protected against typhoid fever. 

 At the same time, and independently, A. E. 

 Wright began similar inoculations in Brit- 

 ish soldiers who volunteered for the pur- 

 pose. The inoculations did them no harm, 

 and as larger and larger groups of these 

 vaccinated men came into being and were 

 subjected in war to the same dangers of 

 typhoid infection as were untreated men in 

 the same regiment, it became evident that 

 they were much less likely to contract the 

 disease than the uninoculated, and when 

 such vaccinated men did at times come down 

 with typhoid fever, the disease almost in- 

 variably ran a milder course than in the 

 unvaccinated and the mortality among 

 them was distinctly lower. 



It took something over ten years to con- 



