In 1928, British bacteriologist Frederick Griffith conducted experiments focused on Streptococcus pneumoniae, the bacterium responsible for pneumonia. His research centered on understanding how virulence, the ability to cause disease, was passed down through generations of bacteria. This investigation unexpectedly led to the first demonstration that bacteria could transfer hereditary information between strains, establishing a new concept in biological inheritance.
Identifying the Bacterial Strains
Griffith’s study relied on two distinct variations of Streptococcus pneumoniae, differentiated by their appearance in culture. The Smooth (S) strain produced shiny colonies due to a protective polysaccharide capsule. The capsule prevented the host’s immune system from destroying the bacteria, making the S strain virulent, or lethal, to mice.
The Rough (R) strain formed irregular colonies and lacked the polysaccharide capsule. These bacteria were readily recognized and eliminated by the host’s immune defenses. Without the protective capsule, the R strain was non-virulent and could not cause disease in a laboratory animal.
The Four Key Experiments
Griffith systematically tested the effects of injecting these two strains, alone and in combination, into laboratory mice. The first two tests served as controls. Mice injected with the live, non-virulent R strain remained healthy, as their immune systems successfully cleared the infection. Conversely, mice injected with the live, virulent S strain quickly died from the resulting pneumonia.
The third experiment involved heating the virulent S strain to kill the bacteria before injection. Mice injected with these heat-killed S cells survived, demonstrating that the ability to cause death was destroyed by the heat treatment. This result suggested that the living structure of the S bacteria was necessary for virulence.
The critical and most surprising test involved mixing the heat-killed S strain with the live, non-virulent R strain before injection. Although the S strain was dead and the R strain was harmless, the mice injected with this mixture developed pneumonia and died. Griffith isolated live bacteria from the deceased mice, which were identified as the virulent S strain, complete with the smooth, protective capsule.
Defining the Transforming Principle
The unexpected recovery of live, virulent S bacteria from the dead mice meant that the harmless R strain had acquired the ability to form a capsule and cause disease. This change was stable and heritable, as the newly formed S bacteria passed the trait on to their offspring. Griffith concluded that some material from the dead S bacteria survived the heat treatment and entered the live R bacteria.
This substance was dubbed the “Transforming Principle.” Griffith proposed that this principle carried the genetic instruction for making the protective capsule and transferred this information to the living R cells, transforming them into the deadly S form. The experiments provided the first clear evidence that a chemical substance could carry hereditary information and cause a permanent alteration of an organism’s traits. Griffith’s work established the phenomenon of bacterial transformation.