THE BACILLUS AND THE BACTERIOLOGY OF DIPHTHERIA 211 



From the facts set forth in the table, Ehrlich believed that the diph- 

 theria bacilli in their growth produce a toxin which, so long as it remains 

 chemically unaltered, has a definite poisonous strength with a definite 

 value in neutralizing antitoxin. This neutralization he believed to be 

 a chemical union, in which two hundred fatal doses of toxin for a 250 

 grams' weight guinea-pig combine with one unit of antitoxin. The 

 toxin is, however, an unstable compound, and begins to change almost 

 immediately into substances which are not, at least acutely, poisonous, 

 but which retain their full power to neutralize antitoxin. These sub- 

 stances, according to Ehrlich, fell into three groups. The first has 

 more affinity for combining with the antitoxin than the toxin itself 

 (protoxoids). The second has the same affinity (syntoxoids). The 

 third has less affinity (epitoxoids). The development of Ehrlich's 

 theories of the chemical nature of this union of pure and modified 

 toxin with antitoxin is described on page 165. The toxin with 

 its haptophore group intact but with its toxophore altered is the 

 toxoid. 



According to him, if a mixture of toxoids and toxin is added to anti- 

 toxin, the protoxoids first combine with the antitoxin; then the syn- 

 toxoids and the toxin combine in equal proportions, so long as the 

 supply lasts, with the amount of antitoxin remaining, or, if there is a 

 surplus, with enough to satisfy them; finally, if any antitoxin remains, 

 the epitoxoids unite with it. 



The results of these experiments of Atkinson and myself 1 were fully 

 in accord with those published by Ehrlich as to the varying neutral- 

 izing value of a minimal fatal dose of "toxin;" they, however, also 

 indicate roughly a general law in accordance with which these changes 

 occur. 



The neutralizing value of a fatal dose of toxin is at its lowest in the 

 culture fluid when the first considerable amounts of toxin have been 

 produced. After a short period, during which the quantity of toxin 

 in the fluid is increasing, the neutralizing value of the fatal dose begins 

 to increase, at first rapidly, then more slowly. 



While the culture is still in vigorous growth and new toxin is being 

 produced, the neutralizing value of the fatal dose fluctuates somewhat, 

 but with a generally upward tendency. After the cessation of toxin 

 production the neutralizing value of the fatal dose increases steadily 

 until it becomes five to ten times its original amount. 



In our experiments the greatest value for L + was 126, the least 27. 

 As at six hours L + was only 72 and at twenty-eight hours only 91, we 

 doubt whether L + ever reaches above 150. 2 When we seek to analyze 

 the above-described process we find certain facts which seem partly 

 to explain it. 



In the fluid holding the living bacilli we have, after the first few 



1 Journal of Experimental Medicine, vol. iii., No. 4. 



* L+ = fatal doses of toxin required to kill a guinea-pig in four days after having been mixed 

 >vith one unit of antitoxin. 

 LO = fatal doses of toxin required to fully neutralize one unit of antitoxin. 



