SERUM THERAPY 531 



of the anthrax bacillus is mixed with some rat serum and inoculated into 

 mice, the mice suffer no harm (p. 518). 



Roux and Metchnikoff have proved that the bactericidal action of the rat serum 

 is only exercised when the serum is mixed with the bacilli ; if the culture and serum 

 be separately inoculated, the mice die of anthrax. These observers also showed 

 that the high degree of immunity to anthrax usually possessed by the white rat 

 is not due to the bactericidal action of its serum for they found that a large number of 

 white rats whose serum was known to be bactericidal were susceptible to the disease. 



II. Marchoux has shown that the serum of rabbits and sheep immunized 

 against anthrax by means of attenuated cultures, while possessing both pro- 

 phylactic and therapeutic properties, has no bactericidal or antitoxic action. 



The rabbits should be immunized by the method described at p. 528. Sheep 

 after being vaccinated by Pasteur's method are inoculated with larger and larger 

 doses of virulent cultures at intervals of a week until an amount equal to 200-300 c.c. 

 is given in one inoculation. The sheep must be able to withstand these enormous 

 doses before their serums become prophylactic or curative. The animal is bled 

 15 or 20 days after the last protective inoculation as experience has shown that 

 the serum is most potent at this period. The serum retains its properties for a 

 long time. 



(a) Marchoux obtained a sheep serum which had a titre of ^ QQ Q (1 c.c. 

 inoculated 24 hours before 0'25 c.c. of a virulent culture protected a rabbit 

 weighing 2 kg.). The inoculations were made beneath the skin of the flank, 

 the serum on one side the culture on the other. 



Inoculation of culture beneath the skin of the ear has more severe results, 

 and to protect the animal twice the quantity of serum used in the preceding 

 case must be given. Inoculation of culture into the peritoneum requires a 

 still larger protective dose of serum, at least 15 c.c. of a 2 - 00 Q serum being 

 required to protect a rabbit weighing 2 kg. When the culture is administered 

 intra-venously 20 c.c. of a & semm OT ^J prolongs the life of the rabbit 

 for 3 days beyond that of the control. 



The serum is equally effective whether inoculated intra-peritoneally or 

 sub-cutaneously. Intra- venous injection however appears to be less effective 

 since 10 c.c. of a 2 "Q 00 serum does not protect a rabbit weighing 2 kg. against 

 the sub-cutaneous' inoculation of 0'25 c.c. of a virulent culture. 



Note. A 3,006 serum has no prophylactic properties for guinea-pigs. Even 

 by using very large doses of serum Marchoux was able only to prolong life and 

 that but for a variable length of time. 



(b) The serum of a vaccinated rabbit inoculated at the same time as a 

 virulent culture ensured the recovery of the animal (rabbit) in 7 out of 24 

 experiments : in the remaining 17 cases the animal always lived longer than 

 the controls. The amount of serum inoculated varied from 7-17 c.c. The 

 rabbits which survived showed no symptom of illness while all those in which 

 an oedema developed, died. 



(c) A rabbit which was given 6 c.c. of the serum of a vaccinated rabbit 

 4 hours after the inoculation of bacilli survived. And another in which 

 the serum was administered 7 hours after the inoculation of bacilli died 

 108 hours after the control. 



With a -g^-fj sheep serum Marchoux was able to cure a rabbit inoculated 

 7 hours previously (dose, 7 c.c. of serum). With a 2 -J 00 serum the inoculation 

 of 10 c.c. given 24 hours after the culture was followed by recovery. 



If at the moment of inoculation of the serum there is a well-marked oedema 

 recovery does not take place even though relatively enormous doses of serum 

 be used (e.g. 15-20 c.c. of a 2 ^ serum). 



