May 26, 2015

The Discovery of DNA: Unraveling the Contributions of Frederick Miescher, P.A. Levene, Erwin Chargaff, Maurice Wilkins, and Rosalind Franklin

Understanding the structure of DNA was a turning point in the field of biology and genetics. The discovery was not the result of a single moment or individual—it was a cumulative achievement built on the work of several brilliant scientists. This article takes you through the key milestones and contributors that led to the unveiling of DNA's iconic double helix.


Early Beginnings: Friedrich Miescher’s Discovery of Nuclein

In 1869, German biochemist Friedrich Miescher made the first major breakthrough. While studying white blood cells from fish sperm, he isolated a unique substance from the cell nuclei. Miescher named this substance nuclein, which we now recognize as nucleic acid. His work marked the first step toward understanding the molecular basis of heredity.


P.A. Levene and the Building Blocks of DNA

Fast forward to the 1920s, when biochemist Phoebus A. Levene uncovered the basic structure of nucleic acids. Levene discovered that DNA is made up of three essential components:

  • A phosphate group
  • A five-carbon sugar (deoxyribose in DNA, ribose in RNA)
  • A nitrogenous base—classified into:
    • Purines: Adenine (A) and Guanine (G)
    • Pyrimidines: Thymine (T) and Cytosine (C) in DNA; Uracil (U) replaces Thymine in RNA

Levene concluded that these components form repeating units known as nucleotides, which are the fundamental building blocks of both DNA and RNA.


Erwin Chargaff and the Principle of Base Pairing

In the 1950s, Austrian-American biochemist Erwin Chargaff made a crucial discovery that laid the foundation for understanding DNA’s pairing mechanism. His research revealed that:

  • The amount of Adenine (A) always equals Thymine (T)
  • The amount of Guanine (G) always equals Cytosine (C)

This observation, now known as Chargaff’s Rule, suggested a consistent one-to-one ratio of purines to pyrimidines in DNA, hinting at a structured pairing system.


Visualizing DNA: The X-ray Crystallography Work of Wilkins and Franklin

The next major development came through the pioneering use of X-ray crystallography, a technique that allows scientists to study molecular structures based on how X-rays scatter through crystals.

Maurice Wilkins’ Contribution

Physicist Maurice Wilkins was instrumental in preparing highly purified and aligned DNA fibers. His work enabled clearer X-ray images that could be analyzed to determine molecular structure.

Rosalind Franklin’s Critical Photograph

Rosalind Franklin, a brilliant X-ray crystallographer working alongside Wilkins, captured the now-famous Photo 51—an image that clearly showed DNA’s helical structure. This photograph was a turning point.


Watson and Crick: Piecing Together the Double Helix

When James Watson viewed Franklin’s X-ray image, it sparked a breakthrough. Alongside Francis Crick, he began modeling the structure of DNA. Based on the image, they concluded:

  • DNA had a uniform diameter of 2 nanometers (nm)
  • It was composed of two intertwined strands forming a double helix

Their model explained how base pairing worked, aligning perfectly with Chargaff’s rules and Franklin’s image, and it clarified how DNA could replicate itself—an essential feature for genetic inheritance.


Key Takeaways for Curious Minds

  • 🧬 DNA was first identified as a distinct substance (nuclein) by Friedrich Miescher in 1869.
  • 🧱 P.A. Levene revealed that DNA consists of repeating units called nucleotides.
  • 🔗 Erwin Chargaff discovered base pairing rules that are crucial to DNA structure.
  • 💡 Rosalind Franklin’s X-ray crystallography provided visual proof of DNA’s helical form.
  • 🧠 Watson and Crick built the first accurate model of the double helix, combining data from all previous discoveries.

X-Ray Diffraction of DNA

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