68 



(1) It might be thought that the result is due to the precipitins 

 and agglutinins contained in the immune serum or to bodies closely- 

 associated with these and simultaneously produced. (2) As the 

 serum is not bactericidal, it might be assumed that it merely 

 modifies the cocci in such a way as to make them susceptible 

 to the natural defensive mechanism of the animal. 



The difficulty with regard to (1) is that agglutinins, preci- 

 pitins, &c, do not always run parallel with protective power. 

 " For instance," to quote from the Rockefeller investigators, 

 " we have had sera with high protective power and little or no 

 " agglutinating power, and vice versa." So it seems necessary to 

 recognise that there is some obscurity about the nature of these 

 protective substances. Those who hold the " unitarian " view 

 that all antibodies for a given type of pneumococcus are funda- 

 mentally one and the same would probably appeal to " antag- 

 onistic forces " or " buffer action " (see p. 58), the explanation 

 being that the antibody which is present is both agglutinative 

 and protective, but adverse physical conditions inhibit either 

 the one action or the other. As for (2), it is only necessary to 

 add that, in addition to direct action of the serum upon the 

 cocci, there may be an indirect action, i.e., the serum may 

 stimulate the animal's resistance in some specific manner, as is 

 thought to be the case in the therapeutic action of anti-anthrax 

 serum. 



The question then arises as to how much importance ought 

 to be attached to these experiments on mice. There has been 

 a natural temptation to hope that they will provide the key 

 to the preparation of therapeutic sera, the idea being that the 

 value of a serum will depend on demonstrable protective sub- 

 stances, and that therefore the desideratum is to produce sera 

 of high titre in protection tests on mice. Unfortunately, the 

 problem has been found to be much more complicated, apart 

 from the obscurity, mentioned above, as to the real nature of 

 the substances protective for mice. 



First, there is a difficulty about active immunity. If the 

 production of this condition always ran parallel with the sero- 

 logical development of the antibodies which protect mice, it 

 might be thought that the mechanism of protection was the 

 same in the two cases. But this parallelism does not always 

 hold good. It may be found that the animal, though it has 

 become immune against the homologous strain and against no 

 other, has not developed any specific antibody which can be 

 demonstrated, as shown by failure of tests for precipitation, 

 agglutination, and protection of mice. Examples are also 

 recorded where the converse result has been obtained; the 

 animal undergoing immunisation has developed the usual specific 

 antibody but has failed to become immune. It therefore appears 

 that active immunity must be due to some factor other than 

 these substances, and that such substances, when demonstrable, 

 are concomitant effects rather than causes of active immunity, 



