Avery, MacLeod and McCarty: DNA is the Transforming Principle

Biology · Molecular Basis of Inheritance · NEET

Oswald Avery, Colin MacLeod and Maclyn McCarty (1933-44) found the biochemical nature of Griffith's "transforming principle". They purified proteins, RNA and DNA from heat-killed S cells and found that only DNA turned live R cells into S cells. When they used DNase (which digests DNA), transformation stopped; but proteases and RNases did not stop it. Memory hook: "Only DNase kills the transformation, so DNA is the transforming principle."
Avery, MacLeod & McCarty: which molecule transforms R into S?Purified fromheat-killed S cells+ Protease (digest protein)+ RNase (digest RNA)+ DNase (digest DNA)Transformation STILL happensTransformation STILL happensTransformation STOPSOnly DNase stops transformationDNA is the transforming principle
Avery, MacLeod and McCarty digested each biochemical in turn. Protease and RNase did not block transformation, but DNase did. Since only destroying DNA stopped R-to-S transformation, DNA is the transforming principle.

Your doubts, answered

What exactly did Avery, MacLeod and McCarty prove?

They proved the chemical (biochemical) nature of Griffith's transforming principle. Griffith only showed that some 'principle' moved from dead S bacteria to live R bacteria, but he did not know what it was made of. Avery and his team purified proteins, RNA and DNA from heat-killed S cells and tested each one. They found that DNA alone from S bacteria caused R bacteria to change into S bacteria. So the transforming principle is DNA.

How is Avery's experiment different from Griffith's experiment?

Griffith (1928) used live mice and showed that heat-killed S bacteria could transform live R bacteria into virulent S bacteria, but he did NOT know the chemical nature of the transforming material. Avery, MacLeod and McCarty (1933-44) worked in a test tube (in vitro) with purified biochemicals and enzymes to identify that the material is DNA. In short: Griffith discovered transformation; Avery identified the molecule (DNA).

Which enzyme stopped transformation and why is that the key point?

DNase (an enzyme that digests DNA) stopped transformation. This is the most important result for NEET. Proteases (digest protein) and RNases (digest RNA) did NOT stop transformation, so protein and RNA were ruled out. Since only DNase blocked it, DNA must be the transforming principle. Do not confuse DNA with DNase, they are different: DNA is the material, DNase is the enzyme that destroys it.

Why is Avery's experiment not called the 'final' or 'unequivocal' proof?

Because not all biologists were convinced by it. Some still thought a small amount of protein contamination might be responsible. The unequivocal (final) proof that DNA is the genetic material came later from the Hershey-Chase experiment (1952) using bacteriophages and radioactive labels. NEET often traps students here: Avery gave strong evidence, but Hershey and Chase gave the final proof.

What organism did Avery, MacLeod and McCarty use?

They used the same bacterium as Griffith, Streptococcus pneumoniae (the pneumococcus). They took the heat-killed virulent S (smooth) cells, purified different biochemicals from them, and tested each on live R (rough) cells to see which one caused transformation.

⚠️ The NEET trap
Avery, MacLeod and McCarty gave the final (unequivocal) proof that DNA is the genetic material.
Avery, MacLeod and McCarty identified DNA as the transforming principle, but the final/unequivocal proof came from Hershey and Chase (1952).
🧠 Avery = biochemical characterisation (which molecule). Hershey-Chase = final proof. NEET 2017 and NEET 2023 both put Avery as a wrong option and Hershey-Chase as the correct answer.

Real NEET questions

NEET 2017

The final proof for DNA as the genetic material came from the experiments of

A · Griffith
B · Hershey and Chase
C · Avery, Mcleod and McCarty
D · Hargobind Khorana
Solution: Griffith showed transformation and Avery, MacLeod and McCarty identified DNA as the transforming principle, but the unequivocal (final) proof that DNA is the genetic material came from Hershey and Chase's bacteriophage experiment (1952). Avery is the classic distractor here.
NEET 2023 Phase 1

Unequivocal proof that DNA is the genetic material was first proposed by

A · Frederick Griffith
B · Alfred Hershey and Martha Chase
C · Avery, Macleoid and McCarthy
D · Wilkins and Franklin
Solution: The unequivocal (conclusive) proof came from Hershey and Chase (1952). Griffith showed transformation and Avery, MacLeod and McCarty biochemically characterised the transforming principle as DNA, but the definitive proof is credited to Hershey and Chase.
NEET 2024

Match List I with List II. A. Frederick Griffith; B. Francois Jacob & Jacque Monod; C. Har Gobind Khorana; D. Meselson & Stahl :: I. Genetic code; II. Semi-conservative mode of DNA replication; III. Transformation; IV. Lac operon

A · A-III, B-IV, C-I, D-II
B · A-II, B-III, C-IV, D-I
C · A-IV, B-I, C-II, D-III
D · A-III, B-II, C-I, D-IV
Solution: Griffith is matched with Transformation (III). This is the same theme: Griffith discovered transformation, and Avery's team then proved the transforming principle is DNA. Learn the scientist-to-discovery pairs in this chapter as a set.

Solved Molecular Basis of Inheritance NEET PYQs

Try the real previous-year questions from this chapter — each with the answer and a full solution.

See all 88 Molecular Basis of Inheritance NEET PYQs ›
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Frequently asked

In which years did Avery, MacLeod and McCarty do their work?

They worked from 1933 to 1944 (often written 1933-44). This is after Griffith's 1928 experiment and before the Hershey-Chase experiment of 1952.

Why did they use proteases, RNases and DNase?

To test which biochemical is the transforming principle. Proteases destroy protein, RNases destroy RNA and DNase destroys DNA. Only when DNA was destroyed (by DNase) did transformation stop, so DNA is the transforming principle. Protein and RNA were ruled out.

Is DNA the same as DNase?

No. DNA is the genetic material (the transforming principle). DNase is an enzyme that cuts and digests DNA. NCERT even asks you to note the difference between DNA and DNase, so read the spelling carefully in exam options.

Before Avery's work, what was thought to be the genetic material?

Protein. Before Avery, MacLeod and McCarty, most scientists believed the genetic material was a protein. Their experiment shifted the evidence toward DNA.

Which scientist is matched with 'transforming principle' in NEET matching questions?

Griffith is matched with 'transformation' (discovery of the transforming principle). Avery, MacLeod and McCarty are the ones who found this principle is chemically DNA. Keep the two separate.