The question: what carries the instructions?
Children look like their parents because genes pass from parents to children. By 1900 scientists knew that genes sit on chromosomes. Chromosomes are made of two main substances: protein and DNA.
Protein looked like the better choice because it is made of 20 different building blocks, while DNA seemed to have only 4 bases. So which one is the genetic material? Three experiments answered it.
Griffith's experiment (1928): something changes bacteria
Frederick Griffith worked with a bacterium that causes pneumonia. It has two kinds:
- S type: has a smooth, slimy coat and causes disease (kills mice).
- R type: no coat, rough colonies, harmless.
| Injected into a mouse | Result |
|---|---|
| Live R | Mouse lives |
| Live S | Mouse dies |
| Heat-killed S | Mouse lives |
| Heat-killed S + live R | Mouse dies |
In the last group Griffith found live S bacteria in the dead mouse. Some substance from the dead S bacteria had entered the harmless R bacteria and turned them into the deadly S type. This change is called transformation, and the substance was named the transforming principle. Griffith did not know what the substance was.
Avery, MacLeod and McCarty (1944): the substance is DNA
These scientists took an extract from heat-killed S bacteria and tried to find out which chemical did the transforming. They broke down one chemical at a time with enzymes and mixed the extract with live R bacteria:
- Enzyme that destroys protein: transformation still happened.
- Enzyme that destroys RNA: transformation still happened.
- Enzyme that destroys DNA (DNase): transformation did not happen.
So the transforming principle is DNA. Many scientists were still not fully sure, so one more experiment was needed.
Hershey and Chase (1952): the phage labelling experiment
A bacteriophage (phage) is a virus that infects bacteria. It has a protein coat and DNA inside. Alfred Hershey and Martha Chase used a smart trick. They used two special kinds of radioactive atoms to give different parts a glow:
- Radioactive sulphur (³⁵S) goes into protein, because protein has sulphur but DNA does not.
- Radioactive phosphorus (³²P) goes into DNA, because DNA has phosphorus but protein has almost none.
- Two batches of phages were made: one with labelled protein, one with labelled DNA.
- Each batch infected bacteria.
- After a short time they ran the mixture in a blender to shake the empty coats off the bacteria.
- A centrifuge spun the mixture: the heavy bacteria sank to the bottom (pellet) and the light coats stayed in the liquid.
| Label | Where the glow was found |
|---|---|
| ³⁵S (protein) | In the liquid (outside) |
| ³²P (DNA) | In the bacteria pellet (inside) |
Conclusion: only the DNA entered the bacteria and made new viruses. So DNA is the genetic material of the phage.
What the experiments tell us
- Griffith: some substance can carry a feature from one cell to another.
- Avery: that substance is DNA.
- Hershey-Chase: in viruses only the DNA enters the cell and directs everything, so DNA is the genetic material.
Why we say 'main'. In most living things (bacteria, plants, animals, humans) DNA is the genetic material. But some viruses, such as the tobacco mosaic virus and many flu and COVID viruses, have RNA as their genetic material. So DNA is the main genetic material, not the only one.
A genetic material must be able to (1) store information, (2) copy itself exactly, (3) pass to the next generation, and (4) change rarely (mutation). DNA does all four. See how in DNA structure and DNA replication.
Try it: be the scientist
In the 3D: on the last step press Label the protein, then Run experiment. Write where the glow ended up. Repeat with Label the DNA. Predict first: where do you think the glow will go?
At home: make a paper model. Draw a phage on card. Colour the coat yellow and the inner DNA blue. Cut out the coat and the DNA separately. Put them in two small boxes marked 'liquid' and 'bacteria'. After the 'infection', which colour goes in the bacteria box?
Key formulas and definitions
- Griffith: dead S + live R → mice die (transformation)
- Avery: protein-destroying enzyme → still transforms; DNase → no transformation
- Hershey-Chase: ³⁵S labels protein; ³²P labels DNA
- Result: ³²P is found inside the bacteria; ³⁵S stays outside
- Genetic material: stores, copies, passes on, can mutate
Worked examples
1. In Griffith's experiment, 4 groups of mice are injected: live R, live S, heat-killed S, and heat-killed S with live R. How many groups die?
Live S kills, and heat-killed S + live R kills (the R bacteria are transformed into S). Live R and heat-killed S alone do not kill. So 2 groups die.
2. A student adds an enzyme that destroys DNA to dead-S extract, then mixes it with live R bacteria. Predict the result and explain it.
No transformation happens, so all the bacteria stay R and the mouse lives. The enzyme destroys the DNA, which is the transforming substance. Without it, R cannot change into S.
3. In the Hershey-Chase experiment, phages with ³⁵S-labelled protein infect bacteria and are blended. Where is the radioactivity found, and what does it show?
It is found in the liquid, outside the bacteria, because the protein coats stay outside and are shaken off. This shows that protein did not enter the cell, so protein is not the genetic material.
Common mistakes
- Saying DNA contains sulphur. Sulphur is in protein, phosphorus is in DNA.
- Thinking heat-killed S bacteria alone kill the mouse. They do not; they need live R bacteria to transform.
- Mixing up who showed what: Griffith saw transformation, Avery found it is DNA, Hershey-Chase confirmed it in viruses.
- Believing DNA is the genetic material of every organism. Some viruses use RNA.