STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE 

 INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES 



Induction of Transformation by a Desoxyribonucleic Acid Fraction 

 Isolated from Pneumococcus Type III 



By OSWALD T. AVERY, M.D., COLIN M. MacLEOD, M.D., and 



maclyn Mccarty,* m.d. 



{From the Hospital of The Rockefeller Institute for Medical Research) 



Plate 1 



(Received for publication, November 1, 1943) 



Biologists have long attempted by chemical means to induce in higher 

 organisms predictable and specific changes which thereafter could be trans- 

 mitted 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 trans- 

 formations 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 or- 

 ganisms brought convincing evidence that the R forms growing under these condi- 

 tions had newly acquired the capsular structure and biological specificity of Type III 

 pneumococci. 



The original observations of Griffith were later confirmed by Neufeld and Levin- 

 thai (2), and by Baurhenn (3) abroad, and by Dawson (4) in this laboratory. Subse- 

 quently 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 



* Work done in part as Fellow in the Medical Sciences of the National Research 

 Council. 



137 



[Reprinted by permission of The Rockefeller Institute for Medical Research from 

 The Journal of Experimental Medicine 79: (2) 137-158, February 1, 1944] 



:°7 



