TOXIN AND ANTITOXIN. 515 



like poisons are characterized by a haptophore and a toxophore 

 group, of which only the former effects the anchoring of the toxin. 

 Practically therefore only this group is important for the produc- 

 tion of antitoxins. This view is only the logical consequence of 

 the fact that on long standing the poison bouillon undergoes modi- 

 fications, resulting in the production of what I term toxoids. These 

 substances are characterized by this, that the haptophore group 

 has remained intact, while the toxophore group, depending on cir- 

 cumstances, has suffered partial or complete modification. Not 

 infrequently it can be shown that the formation of toxoid is quan- 

 titative, the combining power of the toxic bouillon being unchanged 

 despite a considerable loss of toxicity. 



Gruber, by means of certain calculations, appears to question 

 this fact; he refers exclusively to my very earliest publications in 

 which, naturally, the evidence was still incomplete. It would have 

 been better if Gruber had studied instead my later publications, 

 for then he could easily have convinced himself that my statement 

 is entirely correct. I shall mention but one of my poisons l as an 

 example. In this the L dose was originally 0.25 cc., the lethal dose 

 0.0025 cc. At the end of the investigation Lf had increased to 

 0.26 cc., the lethal dose, however, to 0.004 cc. The number of lethal 

 doses, therefore, in approximately the same amount of L^ had been 

 reduced from 100 to 65. Madsen 2 describes a poison in which the 

 neutralizing power remained constant during the course of two 

 years, while the toxicity was reduced one-half, from 0.02 to 0.04. 

 Furthermore Arrhenius and Madsen in their most recent work 3 

 describe the toxoid modification of a tetanus toxin. These consist 

 in the fact that the combining power remains intact while the toxicity 

 is decreased to one-sixth. It is seen therefore that the doubt thrown 

 upon my quantitative statements is due entirely to a disregard of 

 readily accessible facts. This quantitative transformation consti- 

 tutes a somewhat annoying fact for Gruber, and he therefore seeks 

 to explain it as follows: 



" Imagine, if you will, that 9 /io of the toxin molecules present 

 are changed into toxoids, the minimal lethal dose will then be increased 



1 Described in Deutsche med. Wochensch. 1898, No. 38. 



2 Annales de 1'Institut Pasteur., T. 13, 1899. 



3 S. Arrhenius and Th. Madsen, Physical Chemistry applied to Toxins and 

 Antitoxins, Festskrift ved. indvielsen af Statens Serum Institut, Kopenhagen, 

 1902; German in Zeitsch. fur physiol. Chem. 1903. 



