# The Real X-Men

If you want to answer the question ‘who are we?’ you might first need to ask the question ‘what are we?’ Answering that would almost certainly require X-ray crystallography.

Most people are familiar with an X-ray and its basic principles; X-rays pass through materials at different intensities to produce light and shadows on a film. X-ray crystallography is similar, except that the shadows it casts create a complex puzzle that, when it was first used, fundamentally changed the way we looked the physical world.

In 1914 Max von Laue, a German physicist, won a Nobel Prize for demonstrating the diffraction of X-rays by crystals. These diffraction patterns, resembling astrological charts drawn in Morse code, became a pre-war magic eye puzzle with scientists all over the world trying to link these speckled patterns to determine the atomic structure of the crystals in question.

It took the father-and-son team of Sir William Henry Bragg and William Lawrence Bragg to solve it. William Lawrence looked at the problem in a new way by thinking about the structure of the material itself rather than the behaviour of the X-rays. He proposed that crystals were arranged in highly organised repeating sheets, stacked one on top of the other, a set distance apart. With the assumption that each of these sheets would act as an imperfect mirror, and X-rays bouncing off lower mirrors would interfere with the X-rays bouncing off higher mirrors in a predicable way, they formulated Bragg’s law. It was deceptively simple but at last showed the existence of atomic particles.

What this law demonstrates is that if you want to find out how atoms are arranged in a particular material, it helps to have a lot of them in a very uniform arrangement. This is why crystallised structures are used. The high energy and small wavelength of X-rays make them ideal to fire at crystals. Exactly how X-rays deviate from a predicted path is directly linked to the size and position of the atoms they encounter. Bragg’s law helped scientists to calculate the number, size and relative position of atoms in a material, turning 2D patterns into 3D structural models.

The Braggs were awarded a Nobel Prize in 1915 and at 25 years old William Lawrence was the youngest ever recipient. He received the news while fighting in the trenches of World War I where things were far from sterile and organised. But the Nobel legacy does not end there.

After the war, William Lawrence set up a crystallography group at the Royal Institute. It was there that Kathleen Lonsdale used X-ray crystallography to answer the biggest question in analytical chemistry at the time: the configuration of the benzene ring, a type of molecule made up of carbon atoms arranged in a ring. Her approach continues to underpin the analysis of such structures, collectively termed aromatic molecules, to this day.

In 1945, Dorothy Hodgkin pioneered the field of protein crystallography, discovering the structure of penicillin, vitamin B12, and later insulin. John Kendrew and Max Perutz solved the structure of haemoglobin, the protein found in red blood cells and responsible for transporting oxygen around the body, in 1962. Three years later David Phillips was able to use crystallography to work out how lysozyme, an antibiotic found in tears, worked.

But perhaps the most controversial discovery came earlier, in 1953, when Rosalind Franklin gave the now iconic photo 51 to a PhD student she was supervising to discuss with Maurice Wilkins. However, the image was shown without permission to James Watson. Watson and Francis Crick used data from the photo to help define the size and structure of DNA. In 1962 the Nobel Prize was awarded to Watson, Crick and Wilkins. Franklin, who had died four years previously, was not credited. It is hotly debated if Franklin would have solved the structure of DNA independently.

All told, nearly 30 Nobel prizes have been awarded to research using X-ray crystallography. It has profoundly influenced many scientific disciplines. From the structure of humble table salt to the design of new pharmaceutical drugs, X-ray crystallography has allowed us to understand what we are made of and how we work, and right now the Curiosity Rover is using it to find out where we may have come from.

Bentley Crudgington is a second year PhD student studying Virology

Images: Stamp of Max von LaueLysozyme structure (Wikimedia Commons); drawing of Image 51 (Kate Whittington)