Biologists have long attempted by chemical means to induce in higher organisms predictable and specific changes which thereafter could be transmitted in series as hereditary characters. Among microorganisms the most striking example of inheritable and specific alterations in cell structure and function that can be experimentally induced and are reproducible under well defined and adequately controlled conditions is the transformation of specific types of Pneumococcus. This phenomenon was first described by Griffith (1) who succeeded in transforming an attenuated and non-encapsulated (R) variant derived from one specific type into fully encapsulated and virulent (S) cells of a heterologous specific type. A typical instance will suffice to illustrate the techniques originally used and serve to indicate the wide variety of transformations that are possible within the limits of this bacterial species.Griffith found that mice injected subcutaneously with a small amount of a living R culture derived from Pneumococcus Type II together with a large inoculum of heat-killed Type III (S) cells frequently succumbed to infection, and that the heart's blood of these animals yielded Type III pneumococci in pure culture. The fact that the R strain was avirulent and incapable by itself of causing fatal bacteremia and the additional fact that the heated suspension of Type III cells contained no viable organisms brought convincing evidence that the R forms growing under these conditions had newly acquired the capsular structure and biological specificity of Type III pneumococci.The original observations of Griffith were later confirmed by Neufeld and Levinthal (2), and by Baurhenn (3) abroad, and by Dawson (4) in this laboratory. Subsequently Dawson and Sia (5) succeeded in inducing transformation in vitro. This they accomplished by growing R cells in a fluid medium containing anti-R serum and heat-killed encapsulated S cells. They showed that in the test tube as in the animal body transformation can be selectively induced, depending on the type specificity of the S cells used in the reaction system. Later, Alloway (6) was able to cause

Biologists have long attempted by chemical means to induce in higher organisms predictable and specific changes which thereafter could be transmitted in series as hereditary characters. Among microSrganisms the most striking example of inheritable and specific alterations in cell structure and function that can be experimentally induced and are reproducible under well defined and adequately controlled conditions is the transformation of specific types of Pneumococcus. This phenomenon was first described by Gri~th (1) who succeeded in transforming an attenuated and non-encapsulated (R) variant derived from one specific type into fully encapsulated and virulent (S) cells of a heterologous specific type. A typical instance will suffice to illustrate the techniques originally used and serve to indicate the wide variety of transformations that are possible within the limits of this bacterial species.Gri~th found that mice injected subcutaneously with a small amount of a living 1~ culture deri, ed from Pneumococcus Type H together with a large inoculum of heat-killed Type III (S) cells frequently succumbed to infection, and that the heart's blood of these animals yielded Type HI pneumococci in pure culture. The fact that the P~ strain was avirulent and incapable by itself of causing fatal bacteremia and the additional fact that the heated suspension of Type HI cells eoataincd no viable organisms brought convincing evidence that the 1~ forms growing under these conditions had newly acquired the capsular structure and biological specificity of Type III pneumococci.The original observations of Griffith were later confirmed by Neufeld and Levinthal (2), and by Banrherm (3) abroad, and by Dawson (4) in this laboratory. Subsequently Dawson and Sia (5) succeeded in inducing transformation in ~tro. This they accomplished by growing R cells in a fluid medium containing anti-R serum and heat-killed encapsulated S cells. They showed that in the test tube as in the animal body transformation can be selectively induced, depending on the type specificity of the S cells used in the reaction system. Later, Alloway (6) was able to cause

The cultural characteristics of a bacillus capable of decomposing the capsular polysaccharide of Type III Pneumococcus were described in the preceding paper (1). The decomposition of the specific carbohydrate was shown to be due to the action of an intracellular enzyme which may be extracted in active form from the bacilli. It was pointed out that the enzyme acts only on the capsular polysaccharide of Type III pneumococci and does not affect the specific carbohydrates of certain other encapsulated bacteria. In this respect, the enzyme exhibits a selective action which is as unique in its specificity as is the serological reaction between the capsular polysaccharide and homologous antibody. Furthermore, it was shown that the breaking down of the complex sugar by the enzyme is accompanied by a loss of the serological spedficity of the carbohydrate. This form of decomposition by a biological agent represents a splitting which is less drastic than that accomplished by chemical hydrolysis with acid and heat. The fact that the breaking down of the sugar molecule is, in each instance, accompanied by the loss of its immunological specificity furnishes convincing evidence that the capsular polysaccharide itself is the substance responsible for the type specificity of pneumococci.The observations recorded in the preceding paper concerned the action of the enzyme on the chemically purified polysaccharide removed and separate from the bacterial cells. In its native state the capsular substance forms a morphological structure which conditions the antigenic and serological reactilons of the cell as a whole, as well as its power to invade and multiply in the animal body. It was of special interest, therefore, to ascertain what effect this specific enzyme 73 on

1. A specifically reacting substance of bacterial origin is present in the cell-free fluids of young cultures of pneumococcus. This substance is present when the organisms are growing at their maximum rate and undergoing little or no cell death, and consequently its. presence is not dependent upon cell disintegration but represents the extrusion of bacterial substance by the living organism. 2. The blood and urine of rabbits experimentally infected with pneumococcus contain a similar specific soluble substance during the early hours of the infectious process. 3. Human beings suffering from lobar pneumonia have in their blood and more frequently in their urine a specific soluble substance of pneumococcus origin. The amount of this substance present in the urine varies in different individuals and the presence of a large amount is of unfavorable prognostic import. This specific precipitin reaction in the urine is of diagnostic value. 4. Rabbits injected with soluble pneumococcus material continue to excrete this substance for a considerable period of time. 5. The specifically soluble substance obtained from bacterial cultures and from the urine during infection is not destroyed by boiling, by precipitation with alcohol, acetone, or ether, or by trypsin digestion. 6. Studies are in progress at this time on the degree of toxicity and on the antigenic properties of the substance.

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