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For millennia, humans have wondered about how the building blocks of the universe fit together. In the 20th century the science of x-ray crystallography revealed our molecular world at a level previously unimaginable, far beyond the limits of the microscope.

How did X-ray crystallography transform science and our ability to ‘see’ atoms?

What is X-ray crystallography?

X-ray crystallography is a scientific field concerned with revealing the structure of matter at the atomic level.

The essential method involves exposing a crystallised sample of a molecule to x-rays, usually with an instrument called an x-ray camera. 

The resulting photograph shows the pattern of diffracted x-rays as they passed through the crystal, from which scientists can then visually map its molecular structure using mathematics (now done using a computer).

Crystal structure before x-rays

Hand-drawn diagram showing crystals in quartz Science Museum Group Collection
Hooke’s microscopic study of crystals in quartz, Plate VII from Micrographia.

Gleaming with light and tantalising philosophers with their regular structure, crystals have always been at the centre of conversations about how the particles of the universe fit together.  

Snowflakes, for example, fascinated some of the earliest scientific investigators of crystals, like Robert Hooke (famous for his pioneering microscopic studies) and the astronomer Johannes Kepler

It was an 18th century French priest, however, who would lay the foundations of the modern study of crystals. René Just Haüy studied the outward structure of crystalline mineral forms, producing models. 

The British chemist William Hyde Wollaston took the study of crystals to new levels of precision, developing specialist instruments to examine and measure structure.

Wollaston reputedly used the models on the below right in his lectures on crystallography, including one to the Royal Society in 1813 announcing his key ideas on the subject.

Set of 19 models of crystal forms, early 19th century
Science Museum Group More information
Wooden model of crystal structure, made 1812–1813 and reputedly used by William Hyde Wollaston.
Science Museum Group Collection More information

The molecular world beyond the microscope

A new method to visualise the microscopic world was pioneered in 1912. This was the birth of x-ray crystallography.

Max von Laue, a German physics professor, was performing experiments with the relatively recently discovered x-rays. By bombarding crystals with x-rays, he hoped to find out if the rays consisted of particles or waves—the pattern they displayed on a photographic plate indicated the latter. 

That same year a father-and-son duo, William and Lawrence Bragg, realised the vast potential of von Laue’s crystal patterns.

Lawrence and W H Bragg stand together smiling Smithsonian Institution Image source
Lawrence Bragg (left) and William Henry Bragg

Employing a clever instrument and mathematics, the Braggs developed x-ray photographs of crystals, revealing how their atoms were arranged. From there, they were able to construct three-dimensional models or diagrams of atomic structures.

In our collection we have the x-ray spectrometer used by William Bragg in pioneering this technique, work for which the Braggs were soon after awarded the Nobel Prize.

Original Bragg x-ray spectrometer, developed by William Bragg at Leeds University, 1910–1926
Science Museum Group Collection More information

X-ray crystallography quickly became a revolutionary new field of science, driven by the development of the x-ray camera. Scientists uncovered increasingly complex atomic structures, visualised in the pre-computer age by beautiful molecular models. 
 

Gallery of molecular models

EXPLORE MOLECULAR MODELS MADE USING X-RAY CRYSTALLOGRAPHIC DATA

Women in crystallography

Revolutionary in their field, the Braggs were also progressive in their views on women working as scientists. They encouraged many to take up x-ray crystallography at a time when science was almost completely male-dominated.

Cylindrical dark grey tin can on a white background Science Museum Group Collection Image source
Tin can made into a simple diffraction camera by Kathleen Lonsdale at the Royal Institution, 1934–39

Among William Bragg’s 18 research students, 11 were women. One of his leading protégés was Kathleen Lonsdale. Before the commercialisation of the x-ray camera, Lonsdale made these specialist cameras herself, often from household items like food or drink tins. 

Lonsdale—who along with biochemist Margaret Stephenson was the first female fellow of the Royal Society of London—used her status to campaign for women in science, highlighting unequal expectations and the challenging conditions of combining family life with research. 

One of her students, Dorothy Crowfoot Hodgkin, became one of the most important crystallographers of the 20th century, solving the structures of medically important molecules such as penicillin, vitamin B12 and insulin.

 

Molecular model of penicillin by Dorothy Hodgkin, 1945.
Science Museum Group Collection More information

In 1964 Crowfoot Hodgkin became the first British woman to win a science Nobel, but she was not keen on the label 'woman scientist'—and must have been especially irked by the Daily Mail headline announcing her award, which ran "Oxford housewife wins Nobel Prize".

Yet for all the increased opportunities for women in crystallography, the field was not isolated from sexism and misogyny.

Prevailing sexist attitudes in science were (inadvertently) exposed by James Watson’s 1968 autobiographical account of the discovery of the structure of DNA in 1953. 

Photo print with black central circle on white background King's College London Archives (CC-BY-NC) Image source
X-ray diffraction exposure of B-type DNA, commonly referred to as "Photo 51"

Watson revealed he had used Rosalind Franklin’s all-important x-ray photograph without her permission in his work solving DNA's famous double helical structure, which led to Nobel Prize glory in 1962 (not shared with Franklin, who died before the award).

Not only that, he also criticised her physical appearance in his book, citing her lack of lipstick as a reason he didn’t find her attractive. "The thought could not be avoided," Watson wrote, "that the best home for a feminist was in another person's lab".

Franklin could not respond, as she had tragically died of ovarian cancer 10 years earlier. 

X-ray crystallography began as a science seemingly especially open to women, but did this trend continue?

While many of its pioneers were women (Lonsdale, Crowfoot Hodgkin and Franklin being the most famous examples), the field is still predominantly male today. 

In 1990 a study of the World Directory of Crystallographers found that the proportion of women was just 14% internationally; today the International Union of Crystallography's online list of eminent crystallographers is more than 90% male.

Women in XRC gallery

PIONEERING WOMEN IN THE FIELD OF X-RAY CRYSTALLOGRAPHY

A revolution in science and medicine?

The impact of x-ray crystallography on science and medicine has been immense, ushering in the era of molecular biology and the study of biological molecules from DNA to antibiotics. 

X-ray crystallography provided a method to 'see' beyond the limitations of the microscope, delving into the atomic structures of molecules. But towards the end of the 20th century, the microscope began turning the tables again. 

Some molecular biologists predict a relatively new technique called cryogenic electron microscopy—co-developed by 2017 Nobel Prize in Chemistry winner Richard Henderson—could replace x-ray crystallography as the dominant method of visualising larger and complex molecules.

One of the newest chemistry objects to join our collection is Henderson’s film scanner, which he used in his pioneering cryogenic electron microscopy work. 

It may mark the beginning of the end of x-ray crystallography as a cutting-edge field for probing the molecular world in the 21st century.

 

Find out more

Books

  • Soraya de Chadarevian, Designs for Life: Molecular Biology After World War II, 2002
  • Anne Sayre, Rosalind Franklin and DNA, 1975
  • Georgina Ferry, Dorothy Hodgkin: A Life, 1998
  • Mike Glazer, Crystallography: A Very Short Introduction, 2016

Online