From the time of Rous and Yersin, who first reported the toxicity of sterile filtrates from cultures of the diphtheria bacillus some 70 years ago, the means by which diphtheria toxin exerts its lethal effect has not been discovered. Following the injection of large doses of diphtheria toxin into susceptible animals there is a prolonged latent period of many hours during which no ill effect of any kind, either morphological or biochemical, can be detected. It is now generally agreed (1, 2) that all of the familiar signs of diphtheria intoxication including gross and microscopic morphological damage to tissues, increased resistance of the animal to insulin (Corkill (3)), reduced capacity to synthesize carbohydrates (Cross and Holmes (4)), or to metabolize lactic acid (Dawson and Holmes (5)) and decreased stores of muscle phosphocreatine (Pinchot and Bloom, (6)) are all secondary effects which follow by many hours a primary injury the nature of which is unknown. Peters and Cunningham (7) examined various oxidative enzyme systems which had been treated with toxin in vitro, but could find no untoward effects. Pappenheimer and Williams (8), using the metamorphosing silkworm Platysamia cecropia as the susceptible animal, found that only those tissues characterized by an active succinoxidase system, or undergoing rapid growth and development dependent on the succinoxidase system, were sensitive to the action of toxin; whereas tissues which were deficient in the succinoxidase system were insensitive.With the advent of improved tissue culture methods and consequent stabilization of certain mammalian cell lines in vitro, more homogeneous cell populations became available for use in studying the effects of toxin. Lennox and Kaplan (9) and Placido Sousa and Evans (10) found various cell lines to be susceptible to diphtheria toxin.

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LEVINE, JAMES S. (Yale University, New Haven, Conn.), AND NORMAN STRAUSS. Lag period characterizing the entry of transforming deoxyribonucleic acid into Bacillus subtilis. J. Bacteriol. 89:281-287. 1965.-The kinetics of appearance of transformants as a function of time of exposure to deoxyribonucleic acid (DNA) has been studied in Bacillus subtilis. A short lag period of approximately 1 min at 37 C is evident when the transformation is terminated with deoxyribonuclease. The length of this lag is independent of the genetic trait transferred. Moreover, the lag is unaffected by transforming DNA concentration, by the presence of homologous unmarked DNA, and by shearing and cross-linking of the transforming DNA. The lag shows a strong inverse temperature dependence. The energy of activation is 13.9 kcal. The lag is abolished when the transformation is terminated by washing instead of by addition of deoxyribonuclease. These results are taken to indicate an immediate adsorption of DNA to cells, followed by a deoxyribonuclease-sensitive period of 1 min, during which time the genetic trait is entering the cell. These results make feasible an investigation of the configuration assumed by the DNA molecule during entry into the cell.

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