Studies on the origin of bacterial viruses. I-IV.

I. The Incidence of Phage-Producing Cells in Various B. megatherium Cultures Analyses of small samples containing a few cells each show that lysogenic B. megatherium produces phage particles in groups of from 10 to 1000 depending on the megatherium strain and the culture medium. These groups probably correspond to the number of particles produced by a single cell. The proportion of such phage-producing cells varies from <1 x 10(-10) to about 1 x 10(-2) depending on the megatherium strain and the culture medium. If a culture produces two types of phage, the different types usually appear in separate samples. If mixed samples occur, the number of such samples is about what would be expected for the probability that two separate groups would appear in one sample. This result indicates that the appearance of a distinct phage type is the result of a change in the bacterial cell rather than a change in a phage particle, since in the latter case a mixture of the two types would result. II. The Effect of Ultraviolet Light on the Incidence of Phage-Producing and of Terramycin-Resistant Cells in Various B. megatherium Cultures Low intensity of ultraviolet light increases the proportion of both phage-producing cells and of terramycin-resistant mutants. The increase in phage-producing cells is greater than the increase in terramycin-resistant cells. High intensities of ultraviolet light cause practically all the cells of some B. megatherium strains to produce phage. The number of terramycin-resistant mutants cannot be determined under these conditions. The effect of ultraviolet light varies, depending on the megatherium strain and the culture medium. III. The Effect of Hydrogen Peroxide on the Incidence of Phage-Producing and of Terramycin-Resistant Cells in Various B. megatherium Cultures Low concentrations of hydrogen peroxide increase the number of phage-producing cells and of terramycin-resistant cells, concomitantly, from two to five times. High concentrations of hydrogen peroxide cause almost all the cells of some strains of megatherium to produce phage. IV. Calculation of the Incidence of Phage-Producing Cells The time rate of the appearance of phage particles in normal cultures, or in cultures treated with ultraviolet light or hydrogen peroxide, may be calculated by the same equations which predict the occurrence of terramycin-resistant mutants in B. megatherium cultures. These equations predict that the number of mutants will increase more or less in proportion to the concentration of mutagenic agent, so long as the mutation rate remains very small compared to the growth rate. As the mutation rate approaches the growth rate, there will be a very rapid increase in the proportion of mutants. This explains the striking effect of higher concentrations of mutagenic agents. In order to calculate the results after exposure to strong ultraviolet light or hydrogen peroxide, it is necessary to assume that the change from normal to phage-producing cell occurs without cell division.