42 THE BIOLOGICAL PROBLEM 



difference of gravity, as well as the death-toll of the infections 

 which they determine and to understand better the mode of 

 dissemination of the disease, by finding the different types in 

 the mouths of healthy or convalescent individuals. Finally, 

 the notion of 'type-specificity' has provided us with the only 

 rational basis for the production of an immunized serum which 

 has proved its value in the treatment of infections of type I. 



In the course of their first experiments, Avery and his 

 collaborators naturally asked themselves : To what could be due 

 this extraordinary specificity, and in what part of the microbe 

 it resided? How could it be possible that organisms so com- 

 pletely identical from a morphological point of view were so 

 different from the point of view of their immunological 

 properties? Previous observations furnished the clues that 

 put the searchers on the road to success. 



The pneumococcus is a unicellular organism which is 

 surrounded, under certain well-defined conditions of growth, 

 by an envelope more transparent than the microbe itself, 

 visible under the microscope and known as the 'capsule'. 

 This capsule is particularly well developed in pneumococci 

 which grow and multiply in the body of animals. During 

 their growth, the capsulated cells secrete in the midst of the 

 culture a diffusible substance which, in solution, presents the 

 characteristics of type-specificity of the organisms from which 

 it derives. This substance is found not only in the filtrates of 

 young cultures but also in the humours of animals experi- 

 mentally contaminated, and in the blood and urine of the 

 patients during the evolution of pneumonia in man. The 

 faculty of elaborating this product increases with the virulence 

 of the pneumococcus, and there is every reason to believe 

 that the capsule of the micro-organism is constituted mainly 

 by this specific substance. Thus, around each microbe, there 

 exists an ectoplasmic layer or capsule capable of reacting 

 with the serum of an animal immunized against the same 

 microbe, the so-called anti-serum. This reaction is remarkably 

 specific and occurs only when the anti-serum and the capsular 

 substance are of the same type. The problem, then — and it 



