In Griffith’s 1928 experiment, harmless bacteria were transformed into deadly ones. Specifically, a non-virulent “rough” (R) strain of *Streptococcus pneumoniae* picked up genetic material from a heat-killed virulent “smooth” (S) strain and permanently became virulent itself. This was the first demonstration of what scientists now call bacterial transformation: the transfer of genetic information between bacteria.
The Two Strains of Bacteria
Griffith worked with two strains of *Streptococcus pneumoniae*, a bacterium that causes pneumonia. The S (smooth) strain was surrounded by a polysaccharide capsule, a sugar-based coating that shielded it from the immune system. This capsule made the S strain deadly. When injected into mice, it killed them. Under a microscope, colonies of this strain looked smooth and glossy, hence the name.
The R (rough) strain lacked that protective capsule. Without the coating, the mouse’s immune system could recognize and destroy these bacteria easily. The R strain was harmless. Its colonies appeared rough and irregular because of the missing capsule.
The Four-Part Experiment
Griffith set up his experiment in four groups of mice to isolate what was happening step by step:
- Group 1: Mice injected with living S (smooth) bacteria. The mice died, and living S bacteria were recovered from their blood.
- Group 2: Mice injected with living R (rough) bacteria. The mice survived, because the R strain was harmless.
- Group 3: Mice injected with heat-killed S bacteria. The mice survived, because the heat destroyed the bacteria’s ability to function and reproduce.
- Group 4: Mice injected with a mixture of heat-killed S bacteria and living R bacteria. The mice died.
Group 4 was the shocking result. Neither the dead S bacteria nor the living R bacteria could kill mice on their own. But combined, something lethal happened. When Griffith examined the blood of these dead mice, he found living S-type bacteria, complete with the smooth capsule. The harmless R bacteria had somehow acquired the ability to build the protective capsule, turning them into the deadly S form.
What “Transformation” Actually Means
The transformation that occurred was a permanent genetic change. When the S bacteria were killed by heat, their cells broke apart and released fragments of their genetic material into the surrounding environment. The living R bacteria took up some of those fragments and incorporated them into their own genome. Among the genes they absorbed were the instructions for building the polysaccharide capsule.
Once the R bacteria gained those capsule-building genes, they could produce the smooth coating that shields against the immune system. They were no longer R bacteria in any functional sense. They had become virulent S-type bacteria. Critically, this change was heritable. The newly transformed bacteria passed the capsule-producing trait to all their offspring. This wasn’t a temporary chemical reaction or a one-time coating borrowed from dead cells. It was a lasting change written into the bacteria’s genetic code.
Griffith Didn’t Know It Was DNA
Griffith recognized that some substance from the dead S bacteria was responsible for the transformation, but he didn’t know what that substance was. He called it the “transforming principle” and speculated that cellular materials released from the broken-down S bacteria furnished raw building blocks that the R bacteria could use to construct their own capsule. This was a reasonable guess in 1928, but it turned out the mechanism was far more fundamental than recycling cellular parts.
It took another 16 years before scientists identified the actual molecule responsible. In 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty isolated DNA as the transforming principle. They systematically destroyed different molecules in the S-strain extract, including proteins, fats, and carbohydrates, and showed that transformation only stopped when DNA was removed. This was landmark evidence that DNA, not protein (which most scientists favored at the time), carried hereditary information.
Why the Capsule Matters
The polysaccharide capsule is what made the difference between life and death for the mice. Encapsulated strains of *S. pneumoniae* are dramatically more dangerous than unencapsulated ones. In experimental models, encapsulated strains cause disease in 20 to 70% of hosts at a given dose, compared to roughly 12% for unencapsulated strains. The capsule works by preventing immune cells from latching onto and destroying the bacteria. Without it, the bacteria are essentially naked and vulnerable.
This is why the transformation was so consequential. The R bacteria didn’t just pick up a minor trait. They gained the single most important factor separating a harmless bacterium from a lethal one.
Why Griffith’s Experiment Still Matters
Griffith’s 1928 experiment was the first demonstration that genetic information could pass between bacteria, a process now called horizontal gene transfer. Unlike the vertical transfer of genes from parent to offspring during cell division, horizontal gene transfer allows bacteria to acquire entirely new traits from unrelated or even dead bacteria in their environment. This is one of the main ways antibiotic resistance spreads between bacterial species today.
The experiment also set the stage for one of the biggest discoveries in biology. By proving that a “transforming principle” existed, Griffith created the puzzle that Avery’s team eventually solved. Their identification of DNA as hereditary material was a direct stepping stone to Watson and Crick’s discovery of DNA’s double-helix structure in 1953. Without a British medical officer injecting mice with dead bacteria in the late 1920s, the path to modern genetics would have looked very different.