13.2 DNA as the Hereditary Material

For many years, scientists debated whether DNA or protein was the hereditary material. Three landmark experiments settled this question.

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1. Griffith's Experiment (1928)

Frederick Griffith worked with two strains of Streptococcus pneumoniae:

Experimental Results

When Griffith examined the dead mice from the last group, he found live S-strain bacteria. The heat-killed S-strain had somehow converted the harmless R-strain into virulent S-strain.

Conclusion

Griffith proposed that a "transforming principle" — some chemical substance — passed from the dead S-strain to the live R-strain, permanently changing its hereditary properties. This heritable change is called transformation.

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2. Avery, MacLeod, and McCarty Experiment (1944)

Oswald Avery, Colin MacLeod, and Maclyn McCarty set out to identify the chemical nature of Griffith's transforming principle.

Method

They extracted material from heat-killed S-strain bacteria and treated separate samples with different enzymes:

Conclusion

Only DNase (which destroys DNA) prevented transformation. This conclusively proved that DNA is the transforming principle — i.e., DNA is the hereditary material.

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3. Hershey-Chase Experiment (1952)

Alfred Hershey and Martha Chase used T2 bacteriophages (viruses that infect E. coli) to provide further proof that DNA is the genetic material.

Rationale for Isotope Choice

• ${}^{32}P$ (Phosphorus-32) → labels DNA (DNA contains phosphorus in its sugar-phosphate backbone; proteins do not)
• ${}^{35}S$ (Sulfur-35) → labels Protein (amino acids methionine and cysteine contain sulfur; DNA does not)

Procedure

1. Two batches of T2 phages were prepared:
   • Batch 1: proteins labeled with ${}^{35}S$
   • Batch 2: DNA labeled with ${}^{32}P$
2. Each batch was used to infect E. coli bacteria.
3. After infection, the mixture was agitated in a blender to separate phage coats from bacteria.
4. The mixture was centrifuged: bacteria (heavier) formed a pellet; phage coats remained in the supernatant.

Results

Conclusion

Since only DNA entered the bacterial cell and directed the production of new phage particles, DNA is the genetic material, not protein.

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Summary Comparison of the Three Experiments