Which classic experiment first provided direct evidence that a heritable factor from dead bacteria could change the phenotype of live bacteria, thereby implying that DNA is the genetic material?

Introduction / Context:
Before DNA was universally accepted as the genetic material, several experiments probed how traits are inherited. Frederick Griffith's 1928 work with Streptococcus pneumoniae revealed a process where a trait could be transferred from dead cells to living cells.

Given Data / Assumptions:

• Smooth (S) strain with capsule is virulent; rough (R) strain without capsule is nonvirulent.
• Heat-killed S cells alone do not cause disease.
• Mixing heat-killed S with live R leads to virulent infections in mice.

Concept / Approach:
Griffith observed that some heritable substance from dead S cells transformed live R cells into S phenotype. Later, Avery, MacLeod, and McCarty showed the transforming principle is DNA, cementing DNA's role as genetic material.

Step-by-Step Solution:

Verification / Alternative check:
DNase treatment in Avery’s follow-up abolished transforming activity, while protease or RNase did not, identifying DNA as the transforming principle.

Why Other Options Are Wrong:

• Transduction: DNA transfer via bacteriophages, discovered later by Zinder and Lederberg.
• Replication: DNA copying within a cell, not phenotype transfer between cells.
• Translation: Protein synthesis from mRNA.
• Conjugation: Direct plasmid transfer via cell-to-cell contact, discovered by Lederberg and Tatum.

Common Pitfalls:
Attributing Griffith’s findings to phage-mediated transduction or conflating his discovery with Avery’s identification of DNA.

Final Answer:
Transformation.