Guest writer Stephen Curry is a world-renowned expert on crystals. No, not the shiny things on jewellery, but minute gems made from proteins or viruses. With lab coat and X-ray machine at the ready, he devotes his life to understanding the molecules of life and death. It’s laborious, but for Professor Curry, it’s an exciting and awe-inspiring adventure…
The joy of repetition
Repetition has a poor reputation. Think of massed ranks of blank-faced soldiers on parade. Think of the mindless drudgery of the assembly line. Think of the interminable beep, beep, beep at the supermarket checkout. Think of the ten-green-bottle torment of children’s songs. Repetition has a poor reputation – for being dull.
But it’s not all bad. Some find relaxation and creativity in the click, click, click of knitting needles. Warhol added a twist of colour to make vibrant art from duplication of Marilyn Monroe. No, it’s not all bad.
In Nature, repetition can be full of saving grace. Our existence depends on the geared rotations of the Earth’s diurnal round and the annual turning of the seasons as we orbit the sun. The sun’s life-giving light streams to us in sinusoidal cycles; light sparkles on a diamond, which can only be cut to alluring brilliance because of the perfect symmetrical repeat of its carbon atoms.
Brits and Germans with crystal-clear vision
That atomic order within crystals was hidden from us until the turn of the 20th Century, when physicists Max von Laue in Germany and a father-son team both named William Bragg in England figured out how to peer into the heart of solid matter. It was a beguiling trick of the light, worthy of a magician, but Von Laue and the Braggs were scientists.
Normally we cannot see the arrangements of atoms in crystals because they are simply too small. Atoms are far tinier than the spacing between successive crests in a light wave, and that makes it impossible to form an image, even with the most powerful microscopes. Instead we must turn to X-rays, a much smaller form of light, with crests separated by just the width of an atom. X-rays are reduced in size because they are more energetic and this also makes them far more penetrating. Anyone who has broken an arm or a leg knows of their revelatory power: they pass easily through flesh but cast a shadow of the damaged bone.
But shine a beam of X-rays through a crystal and something entirely different and wonderful happens. The beam bounces off the serried ranks of atoms and is split into tens or hundreds of rays that carry off an imprint of the crystal’s interior structure. Recorded on a detector, the rays create patterns of spots that look nothing like the atomic structure within the crystal but are related to it with mathematical precision. Thanks to techniques developed by the 19th century French mathematician, Joseph Fourier (who, incidentally, knew nothing of X-rays or atomic order, since he died before either were discovered), the spots captured by the detector can be transformed into a three-dimensional image of the atomic array within.
Soon after Von Laue had first revealed the X-ray pattern scattered by crystals and the Braggs had shown (with Fourier’s help) that they could reveal atomic arrangements, scientists realised that these techniques were applicable to anything that could be coaxed into crystalline form. The two-atom structure of sodium chloride, (table salt to you and me) was the Braggs’ original triumph. This was followed by the structures of chemical compounds such as vitamin B, drugs like penicillin, protein molecules and even whole viruses. As the years of the twentieth century rolled by, larger and larger molecules were revealed in all their atomic glory.
Crystals – the window on life’s inner secrets
So the dull repetition of crystalline order, through the method of X-ray crystallography, has given us a vista into the unseen world of the atom and the molecule. I have spent a large part of my professional life trying to crystallise molecules of protein, the natural nanotechnology from which life – and sometimes sickness and death (my particular interests are in the proteins made by viruses in infected cells) – are engineered. The protein machinery of life is bewilderingly complex but only by navigating the atomic landscape of these molecules can we understand living processes at their most basic level.
Protein molecules typically contain thousands of atoms arranged as a stubby-branched chain and folded into a structure that is configured for a specific job in the living organism. That job could be transporting nutrients, copying DNA, passing chemical or electrical signals or any one of the hundreds of vital roles that proteins take on.
The first protein structure to be uncovered by crystallography was of sperm whale myoglobin, a molecule that stores oxygen in the muscles and so allows the creature to hold its breath. These early results were rather crude since the quality of the data was limited – so the irregular twists and turns of the myoglobin protein chain that emerged were a visceral disappointment to the early pioneers. “Hideous,” said Max Perutz. The crystallographers’ dismay was due to the evident lack of order within the protein molecule; it seemed a poor relation to the repetitive but elegant DNA double-helix that had been uncovered by Watson and Crick a few years before.
But with better data came the realisation that the irregularity of protein chains is the necessary secret of their extraordinary diversity of function. It makes them unpredictable too. While almost all DNA sequences will form the iconic twisted ladder, protein structure cannot be divined in advance. Though we know how the DNA code of our genes is translated into the long chains of amino acids that make up proteins, we cannot easily predict how those chains will wrap up to form the three dimensional protein molecule and so must turn to experiment. But since proteins do not submit readily to crystallisation, we have to spend day after day re-running our trials to find conditions that will induce the molecules to line up in the requisite ordered arrays. In this game, beautiful revelation comes only through repetition.