Griffith’s Experiment

In the early 20th century, scientists knew that Mendel's "factors" (genes) were located on chromosomes, but the chemical identity of genetic material remained unknown. The debate was between proteins (complex, varied) and DNA (simpler structure) as the hereditary molecule.

Frederick Griffith, a British bacteriologist, was not searching for genetic material - he was trying to develop a vaccine against pneumonia. His 1928 experiment with Streptococcus pneumoniae accidentally opened one of the most important doors in the history of genetics.

To investigate why certain strains of Streptococcus pneumoniae caused pneumonia in mice while other strains did not, and whether virulence could be transmitted between strains.

Organism: Streptococcus pneumoniae (also called Pneumococcus) - a gram-positive bacterium that causes pneumonia.

S Strain vs. R Strain

Griffith conducted four separate experiments using mice as the test organism:

Griffith’s experiment

Experiment 1: Live R Strain Injection

• What was injected: Live, non-virulent R strain bacteria
• Result: Mice survived
• Inference: R strain bacteria are harmless; they are destroyed by the mouse immune system

Experiment 2: Live S Strain Injection

• What was injected: Live, virulent S strain bacteria
• Result: Mice died of pneumonia
• Inference: S strain is virulent due to its polysaccharide capsule; live S strain bacteria were recovered from the dead mice

Experiment 3: Heat-Killed S Strain Injection

• What was injected: S strain bacteria killed by heat treatment
• Result: Mice survived
• Inference: Heat kills the bacteria and destroys virulence; dead bacteria alone cannot cause disease

Experiment 4: Heat-Killed S Strain + Live R Strain (Critical Experiment)

• What was injected: A mixture of heat-killed S strain + live R strain bacteria
• Result: Mice died of pneumonia ← Unexpected and critical!
• Inference: Live S strain bacteria were recovered from dead mice — the R strain had been transformed into the virulent S strain

Observations Summary:

Griffith concluded that the R strain bacteria had been transformed by some substance from the heat-killed S strain bacteria.

This substance - which he called the "Transforming Principle" - carried genetic information that:

1. Enabled the R strain to produce a polysaccharide capsule
2. Converted it into the virulent S strain phenotype
3. Was heritable (the transformed bacteria retained S strain characteristics across generations)

Griffith did not identify the chemical nature of the Transforming Principle - he only demonstrated its existence.

Griffith's experiment, while landmark, had the following limitations:

• Did not identify the chemical nature of the Transforming Principle
• Did not prove that DNA was the genetic material
• Could not explain the mechanism of transformation at the molecular level
• No biochemical isolation of the responsible molecule was attempted
• In vivo only - the experiment was conducted in mice, not in isolated cell cultures

1. Frederick Griffith's 1928 experiments on Streptococcus pneumoniae shifted from developing a pneumonia vaccine to investigating the transmission of bacterial virulence.
2. The study compared two distinct bacterial variants: the virulent, encapsulated S (Smooth) strain and the harmless, non-encapsulated R (Rough) strain.
3. Baseline experimental controls established that mice survived injections of either the live R strain or the heat-killed S strain independently, but perished when injected with the live S strain.
4. The pivotal final experiment revealed that injecting a mixture of live R strain and heat-killed S strain unexpectedly caused fatal pneumonia, resulting in the recovery of live S strain bacteria.
5. Griffith concluded that a heritable "Transforming Principle" transferred from the dead S strain and assimilated by the live R strain, converting it into a virulent phenotype.
6. While the experiment successfully demonstrated genetic transformation, it was limited by its inability to biochemically identify the transforming substance or confirm it as DNA.