BiologyISC Class 12 · Molecular Basis of Inheritance

The Search for the Genetic Material: ISC Class 12 Biology

Updated 15 October 2026 · Fact-checked

Griffith (1928) showed that heat-killed virulent S pneumococci could transform live harmless R cells. Avery, MacLeod and McCarty found the transforming principle was DNA, since only DNase stopped transformation. Hershey and Chase (1952) proved it: radioactive phosphorus (DNA) of phages entered bacteria, radioactive sulphur (protein) did not.

Notice that neither heat-killed S nor live R kills alone, but together they do, so something passed from dead S cells into R cells.

Illustration drawn for QuestionBuddy.

Understand Search for the Genetic Material

The question. By the 1920s genes were known to lie on chromosomes, which contain both protein and DNA. Which molecule carries hereditary information? Proteins, with 20 amino acids, seemed the better candidate. Three sets of experiments settled it.

1. Griffith (1928): the transforming principle. Bacterium: *Streptococcus pneumoniae* (also called *Diplococcus pneumoniae*), which causes pneumonia.

S strain: smooth, shiny colonies; has a mucous polysaccharide coat; virulent.
R strain: rough colonies; no coat; non-virulent.

Injected into mice	Result
Live S	mice die
Live R	mice live
Heat-killed S	mice live
Heat-killed S + live R	mice die; live S recovered from them

Conclusion: some transforming principle passed from the heat-killed S cells into live R cells and enabled them to make the polysaccharide coat and become virulent: the R cells were transformed. This must be transfer of genetic material, but Griffith could not say what it was chemically. A bonus point: heat that killed the S cells did not destroy the transforming principle, showing the genetic material is stable.

2. Avery, MacLeod and McCarty (1933-44): biochemical nature. They purified biochemicals (proteins, DNA, RNA and others) from heat-killed S cells and tested which could transform live R cells.

DNA alone from S cells transformed R cells.
Proteases (protein-digesting) and RNases (RNA-digesting) did not stop transformation.
DNase (DNA-digesting) did stop it.
Conclusion: the transforming principle is DNA. Not all biologists were convinced.

3. Hershey and Chase (1952): unequivocal proof. They used bacteriophages (viruses that infect bacteria) and *E. coli*.

Phages grown on medium with radioactive phosphorus (³²P) had radioactive DNA (DNA contains phosphorus, protein does not).
Phages grown on radioactive sulphur (³⁵S) had radioactive protein (protein contains sulphur, DNA does not).
Each batch infected *E. coli*. Blending removed the phage coats from the bacteria; centrifugation separated light phage particles (supernatant) from heavier bacteria (pellet).
Bacteria infected with ³²P-phages were radioactive; bacteria infected with ³⁵S-phages were not (the label stayed in the coats outside).
Conclusion: DNA, not protein, enters the bacterium and directs production of new phages: DNA is the genetic material.

Flow chart (Hershey-Chase): label (³²P or ³⁵S) → infection → blending → centrifugation → check radioactivity in pellet (bacteria) or supernatant (coats).

Properties of an ideal genetic material.
1. Replication: it should make its own copy.
2. Stability: chemically and structurally stable.
3. Mutability: scope for slow changes (mutation) needed for evolution.
4. Expression: able to express itself as 'Mendelian characters'.

DNA versus RNA. Both can replicate (base pairing, complementarity); proteins cannot. RNA has a reactive 2'-OH group on every nucleotide, making it labile and easily degraded, and RNA is catalytic, hence reactive; DNA is less reactive and more stable, and thymine in place of uracil adds stability. Both mutate, but RNA mutates faster, so RNA viruses evolve faster. RNA can directly code for proteins (better for expression and transmission); DNA depends on RNA. So DNA is preferred for storage of genetic information and RNA for transmission. In some viruses (Tobacco Mosaic Virus, Qβ bacteriophage) RNA is the genetic material. RNA was probably the first genetic material (RNA world); DNA evolved from it with modifications for stability.

Draw: Griffith's experiment. Checklist: four mice in a row; arrows from four syringes labelled live S, live R, heat-killed S, heat-killed S + live R; outcomes 'dies', 'lives', 'lives', 'dies (live S recovered)'.

Search for the Genetic Material: key facts

Griffith's four injections: $S \to die; R \to live; heat-killed S \to live; heat-killed S + R \to die$; Live S bacteria recovered from the last group.
Avery-MacLeod-McCarty enzyme test: $protease: transformation; RNase: transformation; DNase: no transformation$; Only destroying DNA stops transformation.
Hershey-Chase labels: $^{32} P \to DNA (inside bacteria);^{35} S \to protein (outside, in supernatant)$; DNA has P but no S; protein has S but no P.
Criteria for genetic material: $replication + stability + mutation + expression$; DNA best for storage; RNA better for expression.

How to answer Search for the Genetic Material questions

ISC asks the full procedure of an experiment with results and conclusion, 'what would happen if' variations, and DNA-versus-RNA reasoning.

1Name the organism and strains first: Streptococcus (Diplococcus) pneumoniae; S virulent, smooth, capsulated; R non-virulent, rough.
2Present each step of the experiment with its result, in order, preferably in a table.
3End with the conclusion in the scientists' words: transforming principle (Griffith), DNA is the transforming principle (Avery), DNA is the genetic material (Hershey-Chase).
4For 'what if' questions, ask: is any living bacterium present that could be transformed or could kill the mouse?
5For Hershey-Chase, explain why each isotope labels only one molecule (P in DNA, S in protein) and where the label ends up.
6For DNA versus RNA, use the four criteria and the 2'-OH and thymine arguments.

Search for the Genetic Material in real life

The idea, met in an everyday situation. Answer the question in your own words, then compare with the model answer. The one-line hook is what to remember.

Transformation and the spread of drug resistance

Suppose a hospital laboratory notices that a harmless strain of bacteria in a culture became resistant to an antibiotic after being kept in a flask that contained broken, dead cells of a resistant strain.

Explain this using Griffith's and Avery's findings, and suggest an experiment to identify the molecule responsible.

Try it first, then show the solutionSolution

The dead resistant cells released their contents, including DNA, into the medium.
As in Griffith's experiment, living harmless cells took up a 'transforming principle' from the dead cells and gained a new heritable property: transformation.
Following Avery, MacLeod and McCarty, divide the extract into three portions and treat them with protease, RNase and DNase before adding the harmless cells.
If only the DNase-treated portion fails to transform the cells, the molecule carrying the resistance is DNA.

Answer: The harmless cells were transformed by DNA released from dead resistant cells; enzyme treatment with protease, RNase and DNase would show that only DNA carries the trait.

Memory hook: Dead cells can still pass on their DNA, and with it their traits.

Tricks to remember Search for the Genetic Material

Short memory aids. Say each one aloud once, then use it on a question the same day.

S for Smooth, Shiny, Shell, Slays
S strain: Smooth colonies, Shiny, polysaccharide Shell, Slays mice. R strain: Rough, no coat, Remains harmless.
Use it when: Never swap the strains.
P for Polynucleotide, S for Sulphur in proteins
³²P tags DNA (phosphate backbone); ³⁵S tags protein (sulphur in amino acids).
Use it when: Hershey-Chase labels.
1928, 1944, 1952: G-A-H
Griffith, Avery, Hershey: 'Good Answers Hold'.
Use it when: Order of the experiments.

Search for the Genetic Material: solved examples

Ordered from board level to HOTS. Try each one before you open the solution.

Example 1: Griffith in a table · 3 marks · Short answerBoard level

Describe Griffith's experiment with the two strains of pneumococcus and state his conclusion. (A 5-mark question on this experiment was asked in 2024.)

Try it first, then show the solutionSolution

S strain (smooth, polysaccharide coat) is virulent; R strain (rough, no coat) is not. Live S injected → mice die; live R → mice live (1 mark).
Heat-killed S → mice live; heat-killed S + live R → mice die and live S bacteria are recovered (1 mark).
Conclusion: a transforming principle from heat-killed S cells transformed R cells into virulent S cells; genetic material was transferred (1 mark).

Answer: S kills, R does not, heat-killed S does not, heat-killed S + live R kills: R cells were transformed by a transforming principle.

Example 2: Criteria for genetic material · 2 marks · Short answerBoard level

List four properties a molecule must have to act as genetic material.

Try it first, then show the solutionSolution

It must replicate itself and be chemically and structurally stable (1 mark).
It must allow slow changes (mutation) for evolution and express itself as Mendelian characters (1 mark).

Answer: Replication, stability, scope for mutation, expression as Mendelian characters.

Example 3: Both strains heat-killed · 2 marks · Short answerHarder board level

What would Griffith have observed if both the S and R strains had been heat-killed, mixed and injected into mice? Explain.

Try it first, then show the solutionSolution

The mice would live (1 mark).
No living bacterium is present: dead R cells cannot take up the transforming principle and multiply, and dead S cells cannot cause infection (1 mark).

Answer: Mice survive: there are no living cells to be transformed or to cause disease.

Example 4: Avery's enzymes · 3 marks · Short answerHarder board level

Explain how Avery, MacLeod and McCarty used enzymes to identify the transforming principle.

Try it first, then show the solutionSolution

They purified proteins, DNA, RNA and other biochemicals from heat-killed S cells and tested which transformed live R cells; DNA alone did (1 mark).
Extracts treated with proteases or RNases still transformed R cells, so the principle was neither protein nor RNA (1 mark).
Extracts treated with DNase did not transform, so the transforming principle is DNA (1 mark).

Answer: Only DNase blocked transformation, so DNA is the transforming principle.

Example 5: Hershey-Chase step by step · 4 marks · Long answerHarder board level

Describe the Hershey-Chase experiment. Why was a blender used, and why was radioactive sulphur chosen to label the protein coat?

Try it first, then show the solutionSolution

Phages were grown on radioactive phosphorus (labels DNA) or radioactive sulphur (labels protein), because DNA contains phosphorus but not sulphur and protein contains sulphur but not phosphorus (1 mark).
Each batch infected E. coli; the blender sheared the empty phage coats off the bacterial surface (1 mark).
Centrifugation separated the heavier bacteria (pellet) from the lighter phage particles (supernatant) (½ mark).
Bacteria infected with ³²P-phages were radioactive; those infected with ³⁵S-phages were not (1 mark).
Therefore DNA, not protein, enters the bacteria: DNA is the genetic material (½ mark).

Answer: ³²P (DNA) entered bacteria, ³⁵S (protein) stayed outside; the blender removed the coats; sulphur labels only protein.

Example 6: A changed Hershey-Chase · 3 marks · Short answerHOTS / competency

Suppose a student repeats the Hershey-Chase experiment but forgets the blending step and centrifuges at once. (a) Where would the ³⁵S label be found? (b) Could she still conclude that DNA is the genetic material? (c) Suppose instead she labelled the phages with radioactive carbon (¹⁴C). Would that work? Explain.

Try it first, then show the solutionSolution

(a) In the pellet: the coats remain stuck to the bacteria, so they sediment with them (1 mark).
(b) No: both labels would appear in the pellet, so she could not tell whether protein or DNA entered (1 mark).
(c) No: carbon is present in both DNA and protein, so it would label both and could not distinguish them (1 mark).

Answer: (a) Pellet. (b) No, both labels go with the bacteria. (c) No, carbon labels both molecules.

Where students lose marks in Search for the Genetic Material

The slips examiners see most often, and what to write instead.

Mistake: Swapping the strains or calling R the heat-killed one
In 2024 examiners reported candidates who did not name R and S, swapped their virulence, or called R heat-killed instead of S.
Do this: S = smooth, coated, virulent; R = rough, uncoated, harmless; the heat-killed strain is S.
Usually costs: 1 to 2 marks.
Mistake: Missing the word 'transforming'
Examiners (2024) noted the conclusion written without 'transforming principle', and some named protein as the genetic material.
Do this: Conclusion: a transforming principle from dead S cells transformed live R cells (later shown to be DNA).
Usually costs: 1 mark.
Mistake: Misreading the 'both heat-killed' variation
In 2024 many candidates said the mice would die when both strains were heat-killed.
Do this: No living cells means no transformation and no infection: mice live.
Usually costs: 1 mark.
Mistake: Wrong order of steps
Examiners (2024) found the steps out of sequence, giving wrong results.
Do this: Use the fixed order: live S, live R, heat-killed S, heat-killed S + live R.
Usually costs: 1 mark.

Exam tips

For a 5-mark experiment, give aim, organism, procedure (table), observation and conclusion.
Mention both names: Streptococcus pneumoniae (NCERT) and Diplococcus pneumoniae (used in ISC papers).
Write years: Griffith 1928, Avery and colleagues 1933-44, Hershey and Chase 1952.
In Hershey-Chase answers, explain both the labels and the blending and centrifugation steps.
Use the four criteria as headings when comparing DNA and RNA.

Practice questions on Search for the Genetic Material

Write each answer on paper first. Open the hint only if you are stuck, and the answer only when you have finished.

Q1 · 1 mark · MCQBoard level
Which enzyme prevented transformation in the experiments of Avery, MacLeod and McCarty?
(a) Protease (b) RNase (c) DNase (d) Lipase
Hint
It digests the transforming principle.
Answer
(c) DNase.
Q2 · 1 mark · Very short answerBoard level
Why is the S strain of pneumococcus virulent while the R strain is not?
Hint
Colony appearance and coat.
Answer
S cells have a mucous polysaccharide coat (smooth colonies) and cause pneumonia; R cells lack the coat (rough colonies) and do not.
Q3 · 1 mark · Assertion-reasonHarder board level
Assertion (A): Hershey and Chase used radioactive sulphur to label the DNA of bacteriophages.
Reason (R): DNA contains phosphorus but no sulphur.
(a) Both A and R are true and R is the correct explanation of A.
(b) Both A and R are true but R is not the correct explanation of A.
(c) A is true but R is false.
(d) A is false but R is true.
Hint
Which isotope labels which molecule?
Answer
(d). Sulphur labelled the protein; DNA was labelled with radioactive phosphorus.
Q4 · 3 marks · Short answerHarder board level
Give two reasons why DNA is a better genetic material than RNA, and one reason why RNA is better for expressing information.
Hint
2'-OH, thymine; direct coding.
Answer
DNA lacks the reactive 2'-OH group present on every RNA nucleotide, so it is less reactive and more stable; thymine in place of uracil gives extra stability (also: double-stranded, can be repaired). RNA can directly code for protein synthesis, so it expresses characters easily, while DNA depends on RNA.
Q5 · 2 marks · Short answerHarder board level
How did Griffith's experiment show that the genetic material is stable?
Hint
Heat killed the cells but not their transforming ability.
Answer
The heat that killed the S bacteria did not destroy their transforming principle, which could still transform R cells. Today this is explained by DNA's complementary strands, which separate on heating but come together again when conditions allow.
Q6 · 2 marks · Short answerHarder board level
Name two viruses in which RNA is the genetic material, and explain why RNA viruses mutate and evolve faster.
Hint
Stability.
Answer
Tobacco Mosaic Virus and Qβ bacteriophage. RNA is less stable and mutates at a faster rate; with short life spans, RNA viruses accumulate and select changes quickly.
Q7 · 3 marks · Short answerHOTS / competency
Suppose, in a Griffith-type experiment, an extract of heat-killed S cells is first treated with protease and then mixed with live R cells and injected into mice. A second extract is treated with DNase before mixing. Predict the fate of the mice in each case and the bacteria you would recover from any dead mice.
Hint
Which treatment destroys the transforming principle?
Answer
Protease-treated: DNA is intact, so R cells are transformed into virulent S cells; the mice die and live S bacteria can be recovered. DNase-treated: DNA is destroyed, so no transformation; the R cells are harmless and the mice live (nothing to recover from dead mice).
Q8 · 3 marks · Case-basedHOTS / competency
Read and answer.
Suppose a researcher grows one batch of bacteriophages with ³²P and another with ³⁵S, lets each infect E. coli, blends, and centrifuges.
(a) In which fraction (pellet or supernatant) is most radioactivity found for each batch? (1)
(b) When the bacteria from the ³²P batch burst, some new phages carry ³²P but none carry ³⁵S in the other batch. What does this show? (1)
(c) Why did this experiment convince biologists more than Avery's work? (1)
Hint
What enters, what is passed on.
Answer
(a) ³²P batch: pellet (bacteria); ³⁵S batch: supernatant (phage coats). (b) Parental DNA is passed into the progeny phages, while protein is not: DNA carries the hereditary information. (c) It used a clean labelling method that tracked DNA and protein separately inside a living infection, giving unequivocal proof rather than relying on purity of extracts.

Test your recall

Answer in your head or on paper first, then open the card. Pulling an answer out of memory makes it stick far better than re-reading.

1.Which bacterium did Griffith use?Show answer
Streptococcus (Diplococcus) pneumoniae.
2.What did Griffith recover from the mice that died after heat-killed S + live R?Show answer
Living S bacteria.
3.Which isotope labelled phage DNA?Show answer
Radioactive phosphorus (³²P).
4.What makes RNA labile?Show answer
The reactive 2'-OH group on every nucleotide.
5.Name a virus with RNA as genetic material.Show answer
Tobacco Mosaic Virus (or Qβ bacteriophage).
6.In which year did Hershey and Chase publish their experiment?Show answer
1952.

Search for the Genetic Material: frequently asked questions

What is the transforming principle?

The substance from heat-killed S bacteria that changed live R bacteria into virulent S bacteria in Griffith's experiment; it was later shown to be DNA.

How did Hershey and Chase prove DNA is the genetic material?

Phages labelled with ³²P (DNA) made infected bacteria radioactive, while phages labelled with ³⁵S (protein) did not, so only DNA entered the bacteria.

Why is DNA preferred over RNA as genetic material?

DNA is chemically less reactive and structurally more stable (no 2'-OH, thymine instead of uracil, double-stranded), so it stores information more safely.

What would happen if both S and R strains were heat-killed and injected?

The mice would live, because no living bacteria are present.

What are the properties of genetic material?

It must replicate, be stable, allow slow mutation and express itself as Mendelian characters.