THERAPEUTIC IMMUNIZATION IN MAN 487 



Frankel did this as early as 1893. He was followed by Petruschky 89 

 and Netter and in 1912 Ichikawa began the intravenous injection 

 of typhoid vaccine in patients with the rather astonishing results of 

 obtaining in many cases rapid falling of temperature and often ap- 

 parent shortening of the disease. Boinet in 1912 obtained similar 

 results and recently the same thing has been done by Gay. 89a 



Of these writers the only one who recognized immediately that 

 perhaps the intravenous injection of such vaccines was not due to 

 purely specific activity was Ichikawa, who thought the paratyphoid 

 bacilli injected into typhoid cases often produced similar results, 

 and soon after this Kraus obtained similar degrees of temperature 

 and favorable results by injecting colon bacilli into typhoid patients, 

 into a few cases of pyocyaneus infection, and into streptococcus septi- 

 cemias. 



With Jobling and others we have believed from the beginning 

 that at least an important factor in the activity of these vaccines 

 was non-specific, due perhaps to a rapid mobilization of leucocytes 

 and of ferments. This is discussed in another section on page 522. 



At any rate the therapeutic results obtained justify the cautious 

 continuance of such intensive treatment in various diseases. 



ACTIVE PROPHYLACTIC IMMUNIZATION IN CHOLERA 



Attempts to protect human beings against cholera by prophylactic 

 vaccination were made as early as 1885 by Ferran, 89b a pupil of 

 Pasteur. At the time at which Ferran's experiments were done little 

 was known regarding the production of immunity with killed cul- 

 tures or with bacterial extracts, and Ferran, under the influence of 

 the French school and its endeavors to immunize with living attenu- 

 ated organisms, applied similar methods to cholera. First experi- 

 menting with guinea pigs, he soon applied his method to human 

 beings, inoculating them with small quantities of living broth cul- 

 tures of cholera spirilla. In many of his experiments he gave, at the 

 first injection, 8 drops of a fresh broth culture, following this after 

 8 days with 0.5 c. c. of a similar culture. There is no reason why 

 Ferran's method should not have yielded excellent results. How- 

 ever, it is stated that he worked with impure cultures, and other 

 observers, notably Nikati and Rietsch, van Ermengen, da Lara, and 

 others, failed to obtain encouragement in their subsequent investiga- 

 tion of this method of vaccination. 



The method which Haffkine 90 worked out some years after Fer- 



89 Petrusehky, Cent. f. Bakt., 1, XIX, 1896. 

 89a Gay. Arch, of Int. Med., 1914. 



89b Ferran. C. E. de I'Acad. ties Sc., 1885. 



90 Haffkine. The Lancet, February, 1893; Brit. Med. Journ., December, 

 1895. 



