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 data presented in this paper establish the finding that multiple specific protective antibodies exist in rabbits in response to immunization with Group B streptococci. The summary in Table I indicates the serological types into which Group B streptococci have been divided on the basis of their antigenic composition. This classification is dependent upon passive protection of mice with antibodies directed against the specific antigens, and types are defined in these terms. Heretofore, it was thought that type-specific polysaccharides accounted for all such protection in Group B streptococci. Certain exceptions of cross-protection between types due to minor polysaccharide determinants soon appeared; cross-protection reactions based on protein determinants in at least two types were also discovered. The present experiments show that specific antibodies directed to either polysaccharide or protein antigens of a single strain can be protective against infection with streptococci containing these antigens.

In spite of 50 years of extensive use of penicillin, group A streptococci remain exquisitely susceptible to this antibiotic. This observation that continuing susceptibility has occurred despite the development of resistance to other antimicrobial agents prompted a day-long meeting at Rockefeller University (New York) in October 1996. Among the most likely explanations for this remarkable state of continued susceptibility to penicillin are that beta-lactamase may not be expressed or may be toxic to the organism and/or that low-affinity penicillin-binding proteins either are not expressed or render organisms nonviable. Other potential explanations are that circumstances favorable for the development of resistance have not yet occurred and/or that there are inefficient mechanisms for or barriers to genetic transfer. Recommended future actions include (1) additional laboratory investigations of gene transfer, penicillin-binding proteins, virulence factors, and homeologous recombination and mismatch repair; (2) increased surveillance for the development of penicillin resistance; (3) application of bioinformatics to analyze streptococcal genome sequences; and (4) development of vaccines and novel antimicrobial agents. Thus far the susceptibility of group A streptococci to penicillin has not been a major clinical or epidemiological problem. A similar observation, however, could have been made decades ago about Streptococcus pneumoniae. It is therefore vital for the scientific community to closely examine why penicillin has remained uniformly highly active against group A streptococci in order to maintain this desirable state.