958 CONTROL OF BIOLOGICAL PRODUCTS 



Techni(jue. — The tests were made on the sides and abdomen. At first the hair was dipped 

 and then shaved off but later a barium sulphide and starch depilatory (i volume of barium 

 sulphide to 15 volumes of starch) was found more satisfactory than shaving and less irritating 

 to the skin. The toxin dilutions were injected intracutaneously about 3 to 4 cm. apart, the 

 dose being contained in o.i cc. The reactions were read in a bright light after from eighteen 

 to twenty -four hours when they had reached their maximum. At this stage they were usually 

 quite similar to those observed in human subjects. They varied in degree according to the 

 potency of the dilution injected and the susceptibility of the goat, from slightly reddish areas 

 from 1.5 to 2 cm. in diameter, with little or no swelling, to larger reddish areas from 4 to 5 

 cm. in diameter, with considerable swelling. All reactions faded within from forty-eight to 

 seventy-two hours and there was seldom any pigmentation. 



Controls of diluted toxin heated at 100° C. for one hour, of uninoculated broth containing 

 0.5 per cent phenol and of mixtures of toxin with scarlet fever antitoxic horse serum, induced 

 no reaction. Normal horse serum, however, did not neutralize the toxin. 



A number of other workers have attempted to duplicate this work on goats but 

 generally with results that failed to warrant a continuance of the use of these animals. 



ANTI-BACTERIAL SERA 



But three of these — anti-meningococcic, anti-pneumococcic, and anti-dysenteric 

 — are subjected to official tests. In each case the results secured with any given serum 

 are compared with the results secured simultaneously with a control serum distributed 

 by the Hygienic Laboratory. The standardization of these sera is complicated by the 

 existence of several types of the organism which differ immunologically from one an- 

 other. 



ANTI-MENINGOCOCCIC SERUM 



It is to be regretted that there is no satisfactory laboratory test for the thera- 

 peutic activity of this valuable preparation. Agglutinins, complement fixing bodies, 

 bacteriotropins, and even protective antibodies have been titrated; but it is generally 

 recognized that none of these tests separately, nor any combination of them, does 

 much more than show that the animals from which the serum has been derived have 

 been immunized more or less intensively against certain strains of the meningococcus. 

 In the United States agglutination tests are very generally used, but occasionally 

 complement fixation is employed. The serum under test, to be reported as satisfac- 

 tory, must equal the titre of the control serum or at least fall below it by not more 

 than one dilution. 



The sera are polyvalent and must contain antibodies for the types of the four 

 principal groups of meningococci. A sample protocol showing two commercial sera 

 slightly superior to the control is shown in Table VI. 



ANTI-PNEUMOCOCCIC SERUM 



Official tests in the case of this serum apply only to protection against type I 

 pneumococcus, since this is the only type of infection possibly benefited by the serum, 

 and the clinical evidence of the usefulness of even this type of serum is by no means 

 strong. Mice of about 20-gm. weight are the test animals. The test dose of a culture 

 maintained at nearly uniform virulence for mice is not mixed with the serum, but is 

 injected intraperitoneally a few seconds after the serum. The period of observation for 

 the mice after inoculation is ninety-six hours. Two tests of at least four mice apiece 



