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
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