Click a mouse, a tube, the water bath, a plate or the microscope, or a key word in the panel.
The diagram you meet in a test: an S cell with its capsule, an R cell without one, the DNA that transforms R into S, and the two kinds of colony. Switch between the labeled diagram, a blank one to test your memory, and a quiz where you place each label yourself. You can also download both versions.
Tap a word, then tap the numbered box it belongs to (on the diagram or in the list below). Tap a filled box to take the word back. On a phone, swipe the diagram sideways to see every number.
Ten questions, chosen at random from twenty, about the experiment, the two strains and what it proved.
Tap an injection, then tap what happens to the mouse. Some of these Griffith never tried: use what you know about the capsule and transformation.
Sort the ten features.
Streptococcus pneumoniae (the pneumococcus) causes pneumonia. Under the microscope its cells come in pairs (diplococci). The S strain wraps each pair in a slimy polysaccharide capsule, so its colonies look smooth and shiny. The R strain is a mutant that cannot make the capsule; its colonies look rough. (The R strain in these experiments was derived from a type II S strain.) The capsule is what makes S dangerous: white blood cells called phagocytes cannot easily grip it, so S cells escape and multiply in the blood. R cells are engulfed and cleared.
Live S kills a mouse. Live R does not. S cells killed by heat do not, because dead cells cannot multiply. Those three results are the controls: each shows what one ingredient does on its own. Then Griffith injected live R together with heat-killed S. Neither should kill, yet many mice died, and live, encapsulated S-type bacteria grew from their blood. Heat-killed S alone never produced living bacteria, so the living cells must have come from the R strain: the R cells had been transformed.
Heating kills the cells but leaves much of their DNA intact. Pieces of chromosome from the dead S cells, carrying the working capsule genes, are taken up by a few R cells. One strand enters and lines up with the matching stretch of the R chromosome, swapping the R cell’s faulty capsule genes for the S strain’s set (homologous recombination). The cell can now make capsule, and because the change is in its chromosome, every daughter cell inherits it. The capsule type of the recovered cells matched the dead strain, not the R strain’s original parent, so this was not just a reverse mutation. Griffith did not know what the transferred material was; Avery’s group purified it and showed that only enzymes that destroy DNA stopped it.
(1) New to the topic? Open the 2D diagram view first: all four experiments side by side on one screen. (2) Turn on Predict first and run experiments 1 to 4; check your score. (3) Run experiment 4 in the Microscope view and watch phagocytes engulf the R cells while a few orange transformed cells multiply. (4) Open the Molecular view and step through how the DNA gets in. (5) In Design your own, try live R + heat-killed R: why does that mouse live? (6) Do Avery’s enzyme test and predict every plate before you incubate.
| Experiment | Injected | Mouse | Live bacteria recovered from the blood | What it shows |
|---|---|---|---|---|
| 1 | Live S | Dies | Live S | The S strain is virulent (control) |
| 2 | Live R | Survives | None | The R strain is not virulent (control) |
| 3 | Heat-killed S | Survives | None | Dead S cells cannot cause disease (control) |
| 4 | Live R + heat-killed S | Dies | Live, encapsulated S-type | Living R cells were transformed by material from the dead S cells |
In Griffith’s own work the bacteria were injected under the skin of mice; not every mouse given the mixture died, and transformation was a rare event in each mouse. The simulation shows a typical outcome. Its “bacteria in the blood” graph is an illustrative model (growth, clearance by phagocytes and a small transformation rate) chosen to reproduce the classic results, not measured data.
| Treatment of the purified extract from type III S cells | Transformation of R cells? | Conclusion |
|---|---|---|
| None | Yes | The extract contains the transforming principle |
| Protein-digesting enzymes (trypsin, chymotrypsin) | Yes | It is not a protein |
| Ribonuclease (destroys RNA) | Yes | It is not RNA |
| Enzymes that break down DNA | No | It is DNA |
The purified material also had the nitrogen-to-phosphorus ratio expected for DNA (about 1.67), and as little as about 0.003 µg was enough to transform R cells. Transformed cells were seen as large, glistening, smooth colonies among the small, rough R colonies, and their new capsule type was passed on to every later generation.
| Year | Who | Finding |
|---|---|---|
| 1928 | Frederick Griffith | Bacterial transformation: a “transforming principle” from dead S cells changes living R cells |
| 1944 | Oswald Avery, Colin MacLeod, Maclyn McCarty | The transforming principle is DNA |
| 1952 | Alfred Hershey & Martha Chase | When a bacteriophage infects a bacterium, its DNA (not its protein coat) enters the cell |
| 1953 | James Watson & Francis Crick (using data from Rosalind Franklin and Maurice Wilkins) | The double-helix structure of DNA, which explains how genes are copied |
In 1928 Frederick Griffith injected mice with two strains of Streptococcus pneumoniae. Live S (capsulated) bacteria killed the mice; live R (no capsule) bacteria and heat-killed S bacteria did not. But a mixture of live R and heat-killed S killed the mice, and live S-type bacteria were recovered from their blood. Something from the dead S cells had transformed the living R cells.
Key takeaway: a mixture of two harmless injections killed the mouse because R bacteria were transformed into S-type.The S (smooth) strain makes a polysaccharide capsule, forms smooth shiny colonies and is virulent. The R (rough) strain is a mutant that cannot make the capsule, forms rough colonies and is not virulent, because phagocytes can engulf it.
Key takeaway: S = capsule, smooth, deadly; R = no capsule, rough, harmless.The slippery polysaccharide capsule makes it hard for phagocytes (white blood cells such as neutrophils and macrophages) to grip and engulf the bacteria. The S cells therefore survive, multiply in the blood and cause septicaemia. Without the capsule, the immune system clears R cells quickly.
Key takeaway: the capsule protects S bacteria from being eaten by phagocytes.Some of the living R cells took up DNA released from the dead S cells, including working capsule genes. They began to make capsules, escaped the phagocytes, multiplied and killed the mouse. Their offspring were also encapsulated, so live S-type bacteria were found in the blood.
Key takeaway: living R cells were transformed into virulent S-type cells.No. Heat-killed S bacteria injected on their own never produced living bacteria or disease. The living bacteria in experiment 4 came from the R strain: they had gained the capsule of the dead strain’s type. The dead cells supplied only genetic material.
Key takeaway: dead S cells do not revive; living R cells are changed.No. Griffith showed that transformation happens, but he did not identify the substance responsible (later called the transforming principle). In 1944 Avery, MacLeod and McCarty purified it and showed that only enzymes that destroy DNA stopped transformation, so it is DNA. Hershey and Chase (1952) added further evidence with viruses.
Key takeaway: Griffith discovered transformation; Avery and colleagues showed it is caused by DNA.They are controls. They show that live S kills, live R does not and heat-killed S does not. Without them, a death in experiment 4 could have been blamed on either ingredient alone. With them, the only explanation left is that the ingredients interacted.
Key takeaway: controls show what each ingredient does alone.Some bacteria, including pneumococci, can become naturally competent: they make surface proteins that bind DNA fragments from the surroundings. One strand is pulled into the cell while the other is broken down. If the strand matches part of the chromosome, it can replace that stretch by homologous recombination, so a faulty gene can be swapped for a working one.
Key takeaway: competent cells take in one strand of DNA and recombine it into their chromosome.Transformation is one of the ways bacteria share genes, including genes for antibiotic resistance and new capsule types that let pneumococci escape vaccines. It is also a basic laboratory tool: scientists transform bacteria with DNA to make insulin and other medicines and to study genes.
Key takeaway: transformation spreads genes in nature and is used in genetic engineering.It is the name later given to the unknown substance from heat-killed S bacteria that changed living R bacteria into S-type in Griffith’s experiment. It survives heat, it changes inherited characteristics, and it was later identified as DNA.
Key takeaway: the transforming principle is DNA.