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The rediscovery of Gregor Mendel's work on inheritance patterns by Hugo de Vries, Carl Correns, and Erich von Tschermak laid the foundation for understanding heredity. This sparked interest in finding the physical basis of inheritance, eventually leading scientists to investigate the molecular structure of genetic material.

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Biochemist Phoebus Levene proposed that DNA contained equal amounts of four bases (A, T, G, C) in what he called the 'tetranucleotide hypothesis.' Although later proven incorrect, his work identified the components of DNA and suggested it was too simple to carry genetic information, leading many to believe proteins were the genetic material.

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Griffith's experiments with pneumonia bacteria demonstrated that a 'transforming principle' could transfer genetic information between bacterial strains. This groundbreaking work suggested that DNA, not protein, might be the carrier of genetic information, though the exact nature of this principle remained unknown.

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1944: Oswald Avery, Colin MacLeod, and Maclyn McCarty Identify DNA

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1944: Oswald Avery, Colin MacLeod, and Maclyn McCarty Identify DNA

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Building on Griffith's work, this trio definitively proved that DNA was the 'transforming principle' responsible for heredity. Their meticulous experiments showed that DNA, not protein or RNA, was the genetic material. This discovery redirected scientific focus toward understanding DNA's structure.

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1944-1950: Erwin Chargaff's Base Composition Rules

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1944-1950: Erwin Chargaff's Base Composition Rules

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Chargaff's analysis of DNA from various species revealed that the amount of adenine equals thymine, and guanine equals cytosine (Chargaff's rules). This disproved Levene's tetranucleotide hypothesis and provided crucial clues about base pairing that would be essential for understanding DNA's structure.

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Chargaff’s Rules: First and Second Rules, Applications

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Franklin's precise X-ray crystallography work, particularly 'Photo 51,' revealed that DNA had a helical structure with the phosphate groups on the outside. Her measurements provided critical data about DNA's dimensions, the spacing between bases, and the helical nature of the molecule.

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1952: Alfred Hershey and Martha Chase Confirm DNA as Genetic Material

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1952: Alfred Hershey and Martha Chase Confirm DNA as Genetic Material

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The Hershey-Chase experiment used bacteriophages with radioactive labels to definitively prove that DNA, not protein, was the genetic material. This elegant experiment removed any remaining doubt about DNA's role in heredity and intensified efforts to determine its structure.

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1952: Linus Pauling's Triple-Helix Model

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1952: Linus Pauling's Triple-Helix Model

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Nobel laureate Linus Pauling proposed a triple-helix model for DNA with phosphates in the center. Although incorrect, his model spurred Watson and Crick to work more urgently on their own DNA structure, knowing that the most prominent chemist of the time was also pursuing the same goal.

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James Watson and Francis Crick combined data from Franklin's X-ray crystallography, Chargaff's base-pairing rules, and their own model-building expertise. They constructed physical models using metal plates and wire, testing different arrangements until they found one that satisfied all known chemical and physical constraints.

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Francis Crick, Rosalind Franklin, James Watson, and Maurice ...

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April 25, 1953: Publication of the Double Helix Model

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April 25, 1953: Publication of the Double Helix Model

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Watson and Crick published their famous paper 'Molecular Structure of Nucleic Acids' in Nature magazine, proposing the double helix model with antiparallel strands and complementary base pairing. This elegant structure immediately suggested a mechanism for DNA replication, revolutionizing biology.

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In the same issue of Nature, Rosalind Franklin and Maurice Wilkins published X-ray crystallography data that supported Watson and Crick's model. Franklin's paper provided the experimental evidence that validated the proposed structure, while Wilkins' work offered additional crystallographic support.

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1958: Matthew Meselson and Franklin Stahl Confirm Replication

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1958: Matthew Meselson and Franklin Stahl Confirm Replication

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The Meselson-Stahl experiment provided definitive proof that DNA replication was semiconservative, exactly as predicted by Watson and Crick's double helix model. This experiment confirmed that each new DNA molecule contains one original strand and one newly synthesized strand.