HISTORY 1327 



ated, perhaps, by environment and improved sanitation. He has 

 failed to produce the disease in monkeys. 



It is curious the way in which different epidemics have been 

 reported as being characterized by special features; thus the Serbian 

 epidemic of 1914-15 showed a great tendency to gangrene of the 

 feet, while those in Silesia and Ireland have been associated with 

 bronchial and pneumonic complications. 



Causal Agent. — ^The next point in the history is the search for the 

 causal agent. In 1908 Yersin and Vassal succeeded in communicat- 

 ing the disease from man to man by the inoculation of blood, but 

 failed to infect rats, guinea-pigs, or rabbits. 



In 1909 NicoUe first produced typhus in a monkey by injecting 

 the blood from a patient, thus showing that the virus was present 

 in the peripheral blood. Later it was discovered that guinea-pigs 

 also could be infected. 



In 1910 Ricketts and Wilder, in Mexico, showed that the virus 

 was contained in the blood serum, from which it could be removed 

 by filtration through a Berkefeld candle. 



In 191 1 Wilder repeated the filtration experiments with confirma- 

 tory results, but subsequent experiments showed that the control 

 monkey may have been immune, a point subsequently confirmed 

 by NicoUe, Conor, and Conseil. 



In 1911 Nicolle, Conor, and Conseil considered that the virus was 

 mainly associated with the leucocytes, and that the plasma was 

 merely virulent from the debris of these cells. Red blood-corpuscles 

 and cerebro-spinal fluid were proved not to contain the virus. 



In 1912 Anderson and Goldberger showed that the evidence was 

 in favour of a parasite living freely in blood plasma, and not of an 

 intraleuGOcytic localization; and, further, they confirmed the work 

 of Ricketts and Wilder. 



In 1917 Miss Robertson summarized these investigations by stat- 

 ing that there is no recorded experiment which demonstrates that 

 an injection of the filtered serum from a typhus patient can produce 

 an infection. The conclusion is that the virus is too large to pass 

 through the pores of a Berkefeld candle in good condition. Further, 

 this virus is capable of producing a reaction on the part of the 

 patient, because after an attack there is a solid immunity against 

 subsequent attacks, both in men and animals. 



The causation of typhus remains undiscovered, though many re- 

 searches have been made, first by Hallier, who in 1868 described a 

 fungus as the causal agent ; and then by Klebs, who found bacilli 

 in 1881; and by Mott and Blore, who in the same year described 

 minute, screw-like, motile organisms as present in the blood during 

 life, and micrococcal-like bodies found in cells between the muscular 

 fibres of the heart after death. 



In 1891 Hlava described ovoid bodies which he believed to be 

 part of a streptobacillus; in 1892 Thoinot and Calmette saw flagellate 

 bodies; and in 1892 Lewaschew found a motile organism, sometimes 

 like a thread, sometimes oval and flagellate; in 1893 Dubieff and 



