So far, progress has been slow. The difficulties which have 

 to be overcome are naturally very great, because so little is 

 known about the biological principles which determine the 

 processes of infection and immunity. More laboratory data are 

 needed. 



In this review I have put together what appear to me to be 

 the main items of interest. I have not attempted to make a 

 complete historical record of all the work which has been done 

 in the period under survey, because the work is not all of equal 

 value, and an undiscriminating digest of the whole of it would 

 be more confusing than helpful. 



The Starting Point. 



For the purpose of considering the present position of the 

 pneumococcus problem, it is convenient to begin with the work 

 of Neufeld and his associates.* 



Confining their attention to virulent pneumococci obtained 

 from cases of pneumonia, Neufeld and Handel found that the 

 greater number of these were identical, both serologically and 

 in all other respects. These formed their " typical " group or 

 " Pneum. I." A good serum, prepared by immunising a rabbit, 

 ass or horse with any one of these strains, would protect an 

 experimental animal against infection with a large dose of any 

 strain belonging to this group. But other virulent strains were 

 found which differed from the preceding serologically, though 

 resembling them in other respects. These they termed "atypical." 

 A " typical " immune serum would not protect against an 

 " atypical " strain, nor would a serum produced by an " atypical " 

 strain protect against a " typical " strain. The " atypical " 

 strains, again, were subdivided into serological groups ; a serum 

 prepared with a member of one group would protect against 

 each of the members of that group but not against any members 

 of another group. They had already, in 1912, found three such 

 groups and expected that extended investigation would reveal 

 more. 



In protection tests on animals they found that the serum 

 did not act in accordance with the law of multiple proportions. 

 For example, 0«2 c.c. of a serum protected mice with certainty 

 against 0-1 c.c. of culture, which was at least 100,000 times the 

 lethal dose ; but one-tenth of this dose of serum gave no protection 

 against 0-01 c.c. of culture and failed to give regular protection 

 against much smaller doses of culture ; and, when the quantity 

 of serum was reduced from 0*2 to 0-002 c.c, its protective power 

 had entirely disappeared. From many observations, made by them 

 and other investigators, they came to the general conclusion 

 that the quantity of serum injected must attain a certain 



* The article on pneumococci by Neufeld and Handel in Kolle and 

 Wassermann's Handbuch der pathogenen Mikroorganismen (2nd Edition, 

 Vol. IV., 1912) gives a good summary of their own work and its relations 

 to that of other investigators. 



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