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On the Physical Chemistry of the Toxin-Antitoxin Reaction: with 
Special Reference to the Neutralisation of Lysin by Antilysin. 
By J. A. Craw, Research Student, Lister Institute of Preventive Medicine. 
(Communicated by Dr. C. J. Martin, F.R.S. Received March 22,—Read 
April 6, 1905.) 
Ehrlich (1898) (1903) came to the conclusion that the toxin secreted by 
B. diphtherie is neutralised by diphtheria antitoxin much as an acid is by a 
base. The course of the neutralisation seems to him to indicate the presence 
of several toxic substances and atoxic forms of the same substances in the 
toxic fluid which are successively neutralised by the gradual addition of anti- 
toxin. After complete neutralisation of the various toxins, a substance— 
toxone—remains which has the property of causing diphtheritic paralysis, and 
also of neutralising antitoxin. Similar constitutions have been ascribed by 
Ehrlich and his pupils to other toxic fluids, and to the hemolytic filtrates or 
lysins obtained from certain bacterial cultures. 
On the other hand, Arrhenius and Madsen (1902) (1904) concluded that 
the toxin-antitoxin reaction is quite analogous to the action of an acid on an 
alcohol, and that the chemical laws of mass action, which hold for the latter, 
apply equally well to the former. The chief reaction is considered to be a 
reversible one between two substances only, toxin and antitoxin, and when the 
system has reached equilibrium, a fraction of the toxin and also of the anti- 
toxin remain free. The toxone effect they ascribe to a trace of free toxin. 
The numerical relations deduced are approximately in agreement with the 
experimental observations they have made on equilibria obtaining between 
toxins and antitoxins, and likewise between lysins and antilysins. Nernst 
(1904) has, however, pointed out that the laws of mass action are not appli- 
cable to these reactions. 
Bordet (1903) expressed the view that the fixation of toxin by antitoxin is 
similar to the fixation of a dye by a tissue, and the author has shown that 
this conception is consonant with the chemical and physical properties of 
antibodies in general (1905). 
The two substances most thoroughly investigated by Arrhenius and 
Madsen, viz., diphtheria toxin and tetanus lysin, do not admit of exact deter- 
mination. The estimation of the free diphtheria toxin is rendered uncertain 
by reliance on animal experiments, and tetano-lysin is itself a most unstable 
body. Todd (1902), however, discovered a relatively stable lysin in the filtrate 
