TOXINS AND ANTITOXINS 259 



They also noted marked variation in the degree of immunity which 

 develops in guinea pigs. Active immunity when once established 

 persists throughout the life of the guinea pig. Theobald Smith 

 recommended that the method be used to immunize children to 

 diphtheria. 



Behring, who Avas the first to produce active immunity in the 

 lower animals to diphtheria toxin and to immunize a child pas- 

 sively with antitoxin, was also the first to use toxin-antitoxin mix- 

 tures to immunize children against diphtheria. This was in 1913 

 shortly before Schick published his susceptibility test, Behring 's 

 work was interrupted by the war. 



Susceptibility Tests in New York. — In 1914 Park, Zingher and 

 Scrota determined the susceptibility of a large number of indi- 

 viduals and during the next year immunized about 10,000 infants, 

 children and adults. They were the first to recognize the value 

 of the Schick test in studying the immunizing effect of diphtheria 

 toxin-antitoxin injected into human beings. Park (1932) says 

 that by 1917 they had determined that 80 to 85 per cent of those 

 receiving their 31^^ preparation at weekly intervals were immune 

 and that in a majority of the cases the immunity lasted several 

 years. In 1918 they started an immunization program which con- 

 templated the immunization of all children in New York City. 



Park's Pioneer Work on Active Immunization.— In their 

 earlier work they noted a small percentage of severe reactions to 

 the 3L^ toxin-antitoxin mixtures. They also found that the best 

 immunizing mixture is one having such a toxicity that one human 

 dose will kill a 250 gram guinea pig in about four weeks. IMix- 

 tures containing less toxin are poor immunizing agents. They 

 according!}^ adopted a toxin-antitoxin mixture containing 0.1L+ 

 dose of toxin per dose (usually 1 c.c.) in place of those containing 

 3L^. to 6L^ doses of toxin. 



Preparation of T.A.T. — According to Banzhaf (1928) this is 

 usually prepared in 40 liter lots. Only toxin that has become 

 stable through ageing and with a residual toxin content of at 

 least 5L^ doses per cubic centimeter is employed. Concentrated 

 and purified antitoxin containing at least 2,000 units per cubic 

 centimeter is selected for the partial neutralization of the toxin. 

 To prepare a 0.1 L^ toxin-antitoxin mixture, they place 4,000 L^ 



