242 PROTEIN POISONS 



pre-anaphylactic state. It covers the time necessary for 

 the development of anaphylaxis. The first injection of 

 the foreign protein is without manifest effect upon the 

 animal, but in reality it has a most profound effect. It 

 induces changes which may continue throughout life, and 

 may be transmitted from mother to offspring. The limits 

 of the pre-anaphylactic state have been studied only in the 

 guinea-pig sensitized to horse serum. In these studies 

 it appears that the shortest time required for the develop- 

 ment of the anaphylactic state is from six to nine days, 

 and the usual time from ten to twelve days. Otto, Rosenau 

 and Anderson, and Gay and Southard uniformly found 

 that large doses of the anaphylactogen (5 c.c. or more of 

 horse serum) prolonged the pre-anaphylactic state or 

 delayed the full development of sensitization. Friedberger 

 and Burkhard 1 have apparently contradicted this finding, 

 but since the maximum dose employed by the latter was 

 only 1 c.c., we fail to see that there is any conflict. Evi- 

 dently there is a maximum amount of anaphylactogen 

 which the body cells can dispose of within six or eight days, 

 and that this for horse serum in the guinea-pig is something 

 more than 1 c.c., and something less than 5 c.c. As has 

 been stated, Doerr and Russ found that when the sensi- 

 tizing dose was less than 0.001 c.c. of ox serum the pre- 

 anaphylactic stage is also prolonged. It seems rational 

 to conclude from all the evidence at hand that with sensi- 

 tizing doses of 0.001 to 1 c.c. of serum the average duration 

 of the pre-anaphylactic state is from ten to twelve days, 

 with a minimum period of six days. With sensitizing doses 

 above or below these limits the period of incubation may be 

 prolonged. 



The Anaphylactic State. Rosenau and Anderson, also 

 Gay and Southard, found that guinea-pigs sensitized to 

 horse serum remain in this condition for at least two years. 

 It may possibly continue throughout life. Vaughan and 

 Wheeler found that guinea-pigs lose their anaphylactic 



1 Zeitsch. f. Immunitatsforschung, iv, 690. 



