PRODUCTION OF ANTITOXINS FOR THERAPEUTIC PURPOSES 241 



unit of antitoxin. In order accurately to determine this dose many 

 pigs may be required, but this method of titration is the key-note to 

 successful standardization. 



Such a titration for instance, has shown a toxin to react as follows: 



TABLE 1. METHOD OF DETERMINING THE L+ DOSE OF DIPH- 

 THERIA TOXIN 



One antitoxin unit+0.2 c.c. toxin = No visible symptoms. 



+0.22 



+0.24 



+0.25 



+0.26 



+0.28 



+0.3 



+0.32 



+0.34 



+0.35 



No symptoms. 

 = Usually no symptoms or a very slight reaction. 

 = Very slight congestion and edema. 

 = Slight edema at site. 

 = Edema; sometimes late paralysis. 

 = Acute edema and sometimes death. 

 = Always acute death about the fourth day. 

 = Death from second to third day. 

 = Death about the second day. 



Here the L+ dose is 0.32 c.c. The dose of toxin that just neu- 

 tralizes the antitoxin without causing symptoms has been called by 

 Ehrlich the L6 (limes zero) dose, and in this instance it is about 0.24 c.c. 

 This determination, however, has not the same practical value as the 

 L+ dose. 



The side arm 



FIG. 74. A KITCHENS SYRINGE. 

 is olueeed bv dipping the tip in carbolized vaselin. 

 holds stersat >fif w& ^ nledle h been entered, the N 

 pressure on the bulb; the side arm is then turned upward, when ^e contents flow 

 into the main barrel! and injected in this manner insures accuracy in dosage < 

 uniform bulk of inoculum. 



Having determined the L+ dose of the toxin, a series of six to eight 

 guinea-pigs are injected with this constant dose of toxin and increasing 

 amounts of the corresponding antitoxin serum; for instance, No. 1 

 would receive 0.001 c.c. of serum; No. 2, 0.002 c.c.; No. 3, 0.003 c.c.; 

 No. 4, 0.004 c.c. ; No. 5, 0.005 c.c. ; No. 6, 0.006 c.c., etc. If at the end 

 16 



