The search for the molecular basis of heredity was a significant scientific endeavor of the twentieth century. By the 1940s, evidence confirmed that deoxyribonucleic acid (DNA) housed the genetic blueprint for life, but its physical structure remained a mystery. Determining the complex architecture of DNA was necessary to understand how the molecule could store, transmit, and replicate genetic information. This structural solution paved the way for the entire field of modern molecular biology.
The Scientist Behind the Lens
Rosalind Franklin, a physical chemist and X-ray crystallographer, captured the definitive evidence needed to solve the DNA puzzle. Franklin arrived at King’s College London in 1951, bringing expertise in X-ray diffraction techniques developed in Paris. Her skill involved preparing highly ordered fibers of biological molecules and meticulously setting up the apparatus to capture their diffraction patterns.
Franklin controlled the humidity levels around the DNA samples, isolating two distinct molecular forms: the drier A-form and the highly hydrated B-form. X-ray crystallography involves directing a beam of X-rays at a fibrous molecule. The X-rays scatter as they strike the atoms, creating a pattern of spots on photographic film that is mathematically translated into the molecule’s three-dimensional structure.
The environment at King’s College was marked by professional tension, particularly with her colleague, Maurice Wilkins, who mistakenly believed Franklin was meant to be his technical assistant. Despite this difficult relationship, Franklin and her graduate student, Raymond Gosling, obtained increasingly clear diffraction images. On May 6, 1952, after a 62-hour exposure, they created the image famously known as Photo 51.
Decoding Photo 51
Photo 51 is an exceptionally clear X-ray diffraction image of the “wet” B-form of DNA, presenting a visual pattern suggestive of its molecular shape. The most prominent feature is a dark, characteristic “X” shape in the center, which is the signature of a helical structure. This cross pattern indicated that the DNA molecule was a helix, spiraling around a central axis.
The image provided precise quantitative data essential for building an accurate structural model. The angle of the X-pattern’s arms directly revealed the pitch of the helix’s spiral. The distance between the diffuse, dark spots on the top and bottom, known as the tenth layer line, allowed calculation of the helix’s major repeat. This measurement showed the helix completed one full turn every 34 Ångströms (Å).
Closer inspection revealed a stronger repeat unit corresponding to the distance between the stacked base pairs. This smaller distance was calculated to be 3.4 Å. The fact that the helix pitch (34 Å) was an exact multiple of the base pair spacing (3.4 Å) suggested there were ten repeating units (nucleotides) per complete turn of the spiral. The clarity and symmetry of Photo 51 indicated a highly regular, uniform structure.
Proving the Double Helix
The definitive measurements extracted from Photo 51 became the essential parameters for the final DNA structure model. James Watson and Francis Crick at Cambridge University were attempting to construct theoretical models, but they lacked the empirical proof provided by Franklin’s X-ray data. Watson was shown Photo 51 by Maurice Wilkins, without Franklin’s authorization, and immediately recognized the helical nature and its dimensions.
The photographic data, combined with Franklin’s internal report indicating the phosphate groups were on the outside of the molecule, allowed Watson and Crick to finalize their model. They proposed a double helix structure consisting of two antiparallel strands coiled around a common axis. The sugar-phosphate backbone formed the outside of the helix, while the nitrogenous bases paired horizontally on the interior, held together by hydrogen bonds.
This double helix structure, published in 1953, immediately explained how genetic information could be copied, with the two strands separating to serve as templates. Franklin’s paper, containing Photo 51 and its analysis, was published simultaneously, providing the necessary evidence to support the model. Although Franklin’s contribution was not fully acknowledged in her lifetime, Photo 51 provided the foundation for the structure that launched the age of molecular genetics.