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In 1869, Swiss scientist Johann Friedrich Miescher isolated a mysterious substance he called nuclein — later known as DNA. For decades its importance remained unknown, but in the early 20th century, Russian-born American biochemist Phoebus Levene identified its building blocks, called nucleotides. His incorrect “tetranucleotide” hypothesis slowed progress, yet his chemistry was foundational.

During the 1940s, at Rockefeller University in New York, Oswald Avery, with Colin MacLeod and Maclyn McCarty, demonstrated that DNA — not protein — carried genetic information. At Columbia University, Austrian-American chemist Erwin Chargaff discovered that in DNA, adenine always matched thymine, and guanine matched cytosine. These base ratios provided a vital clue.

Meanwhile, early X-ray diffraction work by William Astbury in Britain hinted that DNA might be regular and helical, though his samples were too dry to reveal clear patterns. Swiss chemist Rudolf Signer prepared exceptionally pure DNA and supplied it to researchers in London, enabling better images in the decade to come.

By the early 1950s, DNA’s structure became an international race. At King’s College London, physicist Rosalind Franklin and her PhD student Raymond Gosling perfected X-ray diffraction of hydrated DNA fibers. Their most famous result, Photo 51, clearly displayed the signature cross of a helix. Fellow King’s researcher Maurice Wilkins worked on parallel diffraction work and helped interpret DNA’s overall organization.

At Cambridge University, James Watson and Francis Crick constructed theoretical models based on chemical reasoning, geometry, and existing data. Crucially — and controversially — they saw Franklin’s unpublished measurements and Photo 51 without her permission, which immediately confirmed the helical nature and dimensions. Franklin herself was skeptical of premature models, unwilling to declare a helix until mathematically certain.

Across the Atlantic, legendary chemist Linus Pauling at Caltech attempted to solve DNA as well, proposing an incorrect triple-helix. His near break-in spurred British urgency.

With Chargaff’s ratios, Franklin’s diffraction measurements, and their own model-building insight, Watson and Crick realized that the two strands run in opposite directions and pair via complementary bases. On February 28, 1953, they completed the double-helix model — elegant, self-replicating, and explanatory.

Three papers were published together in Nature (April 1953):

1. Watson & Crick: the model
2. Franklin & Gosling: data and images
3. Wilkins and colleagues: supporting diffraction evidence

Only Watson, Crick, and Wilkins received the 1962 Nobel Prize in Physiology or Medicine. Franklin’s crucial contributions were overlooked in her lifetime; she had died in 1958. Gosling, as a student, was never considered.

Subsequent research expanded the picture. Aaron Klug, later Franklin’s colleague, developed methods to understand DNA-protein complexes and received a Nobel in 1982. In Japan during the 1960s, Reiji and Tsuneko Okazaki discovered discontinuous DNA replication (Okazaki fragments), clarifying how the helix duplicates.

In summary

The double-helix discovery rested on:

1. Miescher — discovered DNA
2. Levene — identified nucleotides
3. Avery, MacLeod, McCarty — proved DNA is genetic material
4. Chargaff — base pairing ratios
5. Astbury — early diffraction attempts
6. Signer — provided pure DNA for diffraction
7. Franklin & Gosling — definitive X-ray evidence
8. Wilkins — supporting diffraction and access
9. Pauling — competitive pressure and structural insights
10. Watson & Crick — final model and theoretical synthesis
11. Klug, Okazakis — later structural and replication insights

The discovery was not the product of a single genius or laboratory, but a global, cumulative, and sometimes contentious scientific collaboration.