432 INFECTION AND RESISTANCE 



easily disposed of, would, on the basis of the preceding assumptions, 

 result in a very gradual antigen destruction with consequent antibody 

 formation, so that, at the end of eight to ten days, there would be 

 present side by side remnants of unchanged antigen and newly 

 formed specific antibody. The destroyed antigen fraction, in other 

 words, gradually sensitizes the body to the fraction which persists and 

 has not yet been assimilated or excreted at the end of this time. Such 

 a point of view would explain, not only the reaction after a first in- 

 jection, but would account for the incubation time in such cases, and 

 for the differences between these reactions and both the "immediate" 

 and the "accelerated" reactions of cases twice injected. The bearing 

 which this point of view would have on the problems of incubation 

 time in general is obvious. 



The recognition of the anaphylactic nature of serum sickness 

 has led to many attempts to develop methods of antitoxin adminis- 

 tration by which these reactions could be avoided. Since it was de- 

 termined that the degree of reaction was directly dependent upon 

 the amount of the foreign serum injected, it was an obviously logical 

 procedure to attempt in antitoxin production to concentrate as high 

 a potency of antitoxin into as small as possible an amount of serum. 

 Attempts have also been made to alter the serum itself in such a way 

 that it would lose its properties of acting as an anaphylactic antigen 

 without suffering materially in antitoxin value. Bujwid 11 found 

 that serum sickness was less frequent after the use of sera which 

 had been allowed to stand for prolonged periods, and we have seen 

 that Besredka and others have claimed a reduction of toxic property 

 in sera heated repeatedly to 60 C. It was hoped, moreover, that 

 the so-called concentration methods such as those of Gibson, Banz- 

 haf, and others would yield an antitoxin that would be devoid of 

 anaphylactic properties. None of these methods of altering the 

 serum can, however, be said to have been satisfactory in that the 

 antitoxic property seems to be closely associated with the globulins, 12 

 which we have seen are at the same time closely associated with the 

 production of anaphylaxis. 



The conclusions of Rosenau and Anderson 13 regarding this are 

 based on direct experimentation with concentrated antitoxin made 

 at the New York Department of Health by the Gibson method. 

 They found the refined antitoxin, volume for volume, quite as toxic as 

 the unrefined, but since the same amount of antitoxin is by this and 

 other methods concentrated in a considerably smaller amount of 



11 Bujwid. Quoted from Friedberger and Mita, Deutsche med. Woch., 

 No. 5, 1912. 



12 Among others previously mentioned see also Turro and Gonzales, C. R. 

 de la Soc. de Biol., Vol. 69, 1910. 



13 Rosenau and Anderson. U. S. Pub. Health and M. H. S. Hyg. Lab. 

 Bull. 36, April, 1907. 



