10 



MEMOIRS OF THE NATIONAL ACADEMY OF SCIENCES. 



THE EFFECT OF VENOM UPON THE BLOOD CORPUSCLES OF A NORMAL RABBIT COM- 

 PARED WITH THE EFFECT UPON THE BLOOD OF A RABBIT IMMUNE TO FIFTY TIMES 

 THE MINIMUM FATAL DOSE. 



In the immunization of various animals to crotalus venom it was found that the rabbit could 

 withstand the effect of the venom better than the other animals ordinarily used for the purpose. 

 The immunization of the guinea pig is almost impassible. No matter how small may be the dose 

 given at the beginning of the process, before the minimum fatal dose has been reached, there is a 

 marked sloughing at the seat of inoculation, and the loss of tissue is so great that doses can be 

 given only at long intervals. Whenever the minimum lethal dose has been reached the animals 

 die. Kabbits, on the other hand, are not nearly so susceptible to the poison. Beginning with 

 one-tenth to one one-thousandth of the minimum fatal dose ami gradually increasing the dose, 

 injecting subcutaneously every four days (the interval depending, of course, upon the health of the 

 animal), most rabbits may be immunized to five or ten times the fatal dose with but very little 

 difficulty. When death occurs in these immunized animals it is usually through bacterial infec- 

 tion, but it may be due to the direct effect of the venom itself. In the attempt to immunize 

 rabbits to as high a degree as fifty times the minimum fatal dose much difficulty was experienced, 

 on account of the widespread local lesions produced. We succeeded in immunizing many rabbits 

 to twenty times the fatal dose, but with only one were we able to reach fifty times the minimum 

 lethal dose, and the blood of these animals was used in experiments with the following result, 

 which results we compare with those obtained in the use of normal rabbit's blood. 



In the blood of a normal rabbit there are about 5,000,000 erythrocytes and about 10,(101) 

 leucocytes to the cubic millimeter. In the immunized rabbit's blood we found 4,500,000 erythro- 

 cytes and 75,000 leucocytes to the cubic millimeter. When the blood of a normal rabbit was 

 mixed with equal parts of venom the erythrocytes became small, dark, globular, and adherent 

 in clumps, and they showed increased ductility; in a few seconds many of the corpuscles become 

 entirely globular and separate. When the blood of the immunized animal was mixed with equal 

 parts of venom the erythrocytes remained normal in size and appearance (except that they present 

 a slight reddish hue), and retain their biconcavity for about thirty minutes; they then become 

 but slightly smaller and globular. We see here in the immunized blood that the effect of the 

 venom is withstood for a considerable length of time, thus showing that the blood corpuscles 

 themselves have gained a certain amount of power of resistance to the poison in this period of 

 immunization. 



