1032 PHYSIOLOGY 



until the animal is able to withstand a dose one hundred thousand times 

 as large as that which would have been fatal to it in the first instance. 

 When a condition of immunity has been produced in this way it is found 

 that the blood-serum of the animal has the power of neutralising the toxin. 

 Thus if the blood- serum from a horse which has been treated with large 

 doses of diphtheria toxin be mixed with an equal quantity of the toxin itself, 

 the mixture may be injected into susceptible animals without the produc- 

 tion of any effect. It is possible in this way to get a serum 1 c.c. of which 

 will neutralise many fatal doses of the toxin, and the antitoxic serum may 

 be injected into a susceptible animal and used to confer an artificial immunity 

 on the latter, or may be injected into a diseased animal and used thus as a 

 curative agent. Antitoxin thus plays a great part in modern therapeutics, 

 especially of diphtheria. In the case of tetanus the toxin has a specific 

 affinity for the nervous system and apparently travels up the axis cylinders 

 of the nerves to the central nervous system. By the time that it has arrived 

 at the central nervous system, and the spasms typical of tetanus have broken 

 out, the toxin is already so firmly bound to the reacting tissue that the in- 

 jection of antitoxin into the blood-stream has little or no effect on the 

 course of the disorder. The use of the tetanus antitoxin is therefore chiefly 

 as a prophylactic agent. 



The question of the manner in which the antitoxin is able to combine 

 with and neutralise the toxin is one of considerable practical importance. 

 In this process we have relations presenting marked analogies with the 

 neutralisation of acids by bases. If we define a unit of toxin as that amount 

 which possesses a certain power, i.e. which will kill a guinea-pig in so many 

 days, or will cause the complete haemolysis of 1 c.c. of blood in two and a 

 half hours, we can find the amount of anti-body which is just sufficient to 

 neutralise this effect, and this amount of anti-body can be regarded also as 

 one unit. If instead of one unit of each we take 100 units, the neutralisation 

 is effected in the same way. The process is found, however, to be more 

 complex when we take 100 units of toxin or lysin and attempt to neu- 

 tralise them by the fractional addition of antitoxin. In the case of a strong 

 acid and strong alkali we know that if 100 c.c. of alkali are just sufficient to 

 neutralise 100 c.c. of acid, the addition of 50 c.c. of alkali will leave half the 

 acid unneutralised. If, however, we try the same experiment in the case of 

 mixtures of toxin and antitoxin, it will be found that the addition of 50 units 

 of antitoxin will neutralise much more than half of the toxin, and the same 

 applies to other bodies of this class. Ehrlich has attempted to explain this 

 result by assuming that in any toxin there is a mixture of substances, some 

 having a strong affinity for the antitoxin, and others, which he calls toxones, 

 possessing only a slight affinity. In the 50 units of toxin first added the 

 toxins would satisfy all their combining powers, whereas the toxones would 

 not begin to combine until they were present in large excess. Arrhenius 

 and Madsen have drawn an analogy between the neutralisation of toxin by 

 antitoxin and the neutralisation of a weak acid, such as boracic acid, by a 

 weak base, such as ammonia. They show that in this case the general 



