IB Biology HLDNA, RNA & the Genetic CodePaper 1 & 2Nature of Science~8 min read
The Hershey–Chase Experiment
For decades most scientists backed the wrong molecule. Protein looked like the obvious carrier of heredity — until two researchers found a way to label DNA and protein separately and simply watch which one went inside the cell.
📘 What you need to know
DNA was identified in 1869, but most scientists assumed protein was the heritable material, because there are 20 amino acids and only 4 bases.
In the 1950s, Alfred Hershey and Martha Chase showed that DNA, not protein, carries genetic information between generations.
They used viruses that infect bacteria, because these consist only of DNA inside a protein coat.
The experiment relies on a chemical difference: DNA contains phosphorus but no sulfur; amino acids contain sulfur but no phosphorus.
Radioactive sulfur (35S) labelled the protein coats; radioactive phosphorus (32P) labelled the DNA.
A blender removed viruses stuck to the outside of the bacteria, and centrifugation separated them.
Only bacteria infected by 32P labelled viruses were radioactive — so DNA had entered the cells.
NOS: the experiment was only possible because radioisotopes became available as research tools after the Second World War.
Which biomolecule is the heritable material?
DNA had been identified back in 1869, but for a long time most scientists assumed that protein was the heritable material. Their reasoning was not unreasonable: there are 20 amino acids and only 4 nucleotide bases, so protein simply looked like it had more room to store complex information.
In the 1950s, Alfred Hershey and Martha Chase settled the question. They showed that DNA, not protein, is a factor of heredity responsible for carrying genetic information from one generation to the next.
Why viruses were the perfect tool
They used viruses that infect bacteria. These viruses are ideal because they consist of only two things: DNA encapsulated by a protein coat. Nothing else is present to confuse the results.
So if you can work out which of those two parts enters the bacterium and makes it produce new viruses, you have found the molecule of heredity.
The method, step by step
Hershey and Chase took advantage of a chemical difference between the two molecules:
The key chemical difference
DNA contains phosphorus but no sulfur
Amino acids contain sulfur but no phosphorus
That difference is what makes the whole experiment possible — it means each molecule can be labelled separately.
Step
What was done
Why
1. Labelling
Bacteria were grown in separate media containing either radioactive sulfur (35S) or radioactive phosphorus (32P), then infected with viruses
The progeny viruses ended up with either 35S labelled protein coats or 32P labelled DNA
2. Infection
Unlabelled bacteria were infected separately with each type of virus
The bacteria should take in whichever molecule is the heritable material
3. Blending
A blender removed viruses still attached to the outside of the bacterial cells
Anything left outside the cell cannot be the heritable material
4. Centrifugation
The mixture was spun to separate the two components
Viruses are small, so stayed in the supernatant. Bacteria are larger, so formed a pellet
5. Measuring
Each fraction was tested for radioactivity
Radioactivity in the pellet means that molecule went inside the bacteria
Small viruses stay suspended in the supernatant; larger bacteria are forced to the bottom as a pellet. Where the radioactivity ends up tells you which molecule entered the cell.
The result and what it proved
Only the bacteria infected by the 32P labelled viruses (DNA) were shown to be radioactive.
This suggested that DNA, and not protein, was transferred into the bacteria — and therefore that DNA is the hereditary (genetic) material.
Why this design is so elegant. The experiment does not need to measure anything complicated. It only asks one question — which molecule got inside? — and answers it with a label you can detect from outside the cell.
Nature of Science: technology opens new possibilities
The IB uses this experiment to make a point about how science actually progresses: technological developments can open up new possibilities for experiments.
Radioisotopes became available to scientists as research tools at the end of the Second World War.
This enabled scientists in fields such as biochemistry and virology to run experiments that were not previously possible.
Isotopes are particularly useful for studying chemical changes during metabolic pathways or life cycles.
Without radioisotopes, Hershey and Chase could not have labelled the different parts of a virus separately, and could not have shown that DNA is the heritable material.
The idea being tested was not new — people had wondered for years whether DNA or protein carried heredity. What was new was the tool. Keep that distinction in mind for Nature of Science questions: sometimes progress comes from a better question, and sometimes from better equipment.
Worked examples
WE 1
Explain the use of two different radioactive labels
Explain why Hershey and Chase used radioactive sulfur and radioactive phosphorus in their experiment. (3 marks)
Point 1: state the chemical differenceDNA contains phosphorus but no sulfur, while the amino acids in proteins contain sulfur but no phosphorus.Point 2: what each label marks
So 35S labels only the protein coat and 32P labels only the DNA.
Point 3: why that is useful
This allowed the two molecules to be tracked separately, so they could see which one entered the bacterial cells.
Different elements → separate labels → each molecule can be followed on its ownstate both halves of the chemical difference — the “but no” part is what makes the labels specific
WE 2
Interpret the results of the experiment
Explain how the results of the Hershey–Chase experiment showed that DNA is the genetic material. (4 marks)
Point 1: the separation
Blending removed viruses attached to the outside of the bacteria, and centrifugation separated small viruses in the supernatant from larger bacteria in the pellet.
Point 2: the sulfur result
With 35S labelled viruses, the radioactivity was found in the supernatant, so the protein coat stayed outside the bacteria.
Point 3: the phosphorus resultWith 32P labelled viruses, the radioactivity was found in the pellet, so the DNA had entered the bacteria.
Point 4: the conclusion
Since only DNA was transferred into the cells that then produced new viruses, DNA must be the hereditary material.
Protein stayed outside, DNA went inside — so DNA carries the genetic informationdescribe both results, not just the DNA one. The control comparison is where the marks are.
💡 Exam tips
Learn which label goes with which molecule: 35S = protein, 32P = DNA.
Remember the separation logic — small viruses stay in the supernatant, large bacteria form the pellet.
Explain why the blender was used: to knock off viruses still attached to the outside.
Use the word suggested or provided evidence rather than “proved beyond doubt” if asked to evaluate.
For the NOS point, name the technology — radioisotopes — and say it became available after the Second World War.
Mention why viruses were chosen: they contain only DNA and protein.
⚠ Common mistakes
Swapping the two isotopes. Sulfur has no phosphorus in it — link P for Phosphate, which is in DNA.
Saying the bacteria were labelled. The viruses were labelled; the bacteria they later infected were unlabelled.
Forgetting the blending step, or not explaining its purpose.
Saying the pellet contained the viruses. The pellet is the heavier bacteria.
Claiming Hershey and Chase discovered DNA. DNA was identified in 1869; they showed what it does.
Describing viruses as living organisms in the answer.
Up next: Chargaff’s Data — the base-counting results that made complementary base pairing obvious in hindsight, and destroyed a rival theory in the process.
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