Cathal O’Connell
Cathal O'Connell is a science writer based in Melbourne.
It’s on. The world’s most powerful X-ray laser, the European X-ray Free Electron Laser, has blasted its first sample.
Firing pulses more than a trillion times more intense than sunlight, and often obliterating anything it touches, the XFEL may sound like a supervillain’s death ray. But the XFEL is actually a revolutionary scientific instrument that will open a new window on the structure of molecules, could accelerate medical research, and take high-speed snaps shots of ultrafast chemical processes, such as photosynthesis, for the first time.
The machine is huge: a vacuum tube cooled to –271 Celsius, lined with superconducting magnets, all buried underground and stretching 3.4 km from Hamburg to the neighbouring town of Schenefeld in the German state of Schleswig-Holstein.
While two other XFELs are already in operation – one in Japan and the other in the US – neither can currently match the European XFEL in terms of the intensity of light, or the rapidity of its X-ray pulses. Today marks the culmination of a decade of planning, 1.2 billion euros of investment, and more than a century of research into the nature and practical use of X-rays.
“I have seen my death,” said Anna Bertha Röntgen when her husband, Wilhelm, showed her a ghostly X-ray image of the bones in her hand. It was 1895, the year Röntgen performed the first systematic study of what he called ‘X-radiation’. The X-rayed hand image caused a global news sensation, and Röntgen’s scientific paper became landmark scientific work, eventually winning him the inaugural Nobel prize for physics in 1901.
X-rays are a kind of electromagnetic radiation, just like visible light, except with a much shorter wavelength. Their ability to penetrate many materials, such as your body or your luggage, make them useful for medical imaging and airport security screening. But they are useful in another, and arguably more important way: X-rays can reveal to us the structure of molecules, including proteins, often described as one of the ‘fundamental building blocks of life’.
The wavelengths of X-rays are comparable to the smallest spacings between atoms in a crystal or molecule. This means that when you fire an X-ray beam at a collection of chemically bonded atoms, the rays interfere with each other and are deflected in different directions, depending on the structure, in a process called X-ray diffraction. By recording and analysing the pattern of diffracted X-rays you can work out the spatial arrangement of the atoms, or the ‘structure’ which the atoms make. That’s exactly what Rosalind Franklin did for DNA in 1951, in work that enabled Watson and Crick to then piece together its double-helix structure, ultimately bagging the two men the Nobel prize.
“You have to be able to visualise molecules at the atomic level to have a window into how they work,” says Brian Abbey, a physicist at La Trobe University who is leading the contingent of Australian scientists in Hamburg for an early turn of the XFEL. He points out that in its 100-year history, X-ray crystallography has been crucial to at least 15 Nobel prizes across physics, physiology or medicine, and chemistry.
The problem is that, as its name suggests, X-ray crystallography needs crystals – and a lot of very important molecules don’t easily form crystals. Today, two-thirds of the proteins encoded by the human genome, literally thousands of them, don’t have known structures – largely because it hasn’t been possible to image their structure with X-ray crystallography.
But XFELs change all that. By generating incredibly intense X-ray beams, XFELs can generate X-ray diffraction images from tiny crystals, smaller than any that have been imaged before.
“The goal is bigger than any single application,” says Adrian Mancuso, a leading scientist and group leader at European XFEL in Hamburg. “The goal is to broaden the class of particles we can look at.” He gives the example of proteins in the membranes of our cells that are particularly finicky to image, but are also major targets for drugs in medicine. “If we can do even a part of what we think we can do, it will be a big deal.”
Most X-ray sources work on the same basic principle: if you accelerate electrons, they emit radiation. In Rontgen’s day, that meant applying a voltage to electrons in an evacuated glass jar – the same technology that old TV-tubes were based on. Since the 1950s, the world’s most intense X-rays have been generated at synchrotrons, huge rings where electrons do laps at almost the speed of light. As the electrons bend around the track, they can give off X-rays more than a million times brighter sunlight at the Earth’s surface.
XFELs can produce X-rays a billion times brighter still.
Like a synchrotron, an XFEL starts by revving electrons up to almost the speed of light. However, it sends them in a straight line, rather than a circle.
Zipping along with an energy of 17.5 GeV (a bit more than a thousandth the energy of particles whizzing around the LHC at CERN) any change of direction will cause the electrons to give out X-rays. So in the next step, the electrons are run through a gauntlet of magnetic fields, called undulators, which send them along a wiggling path. At each wiggle the electrons emit X-rays.
What makes XFELs special is the way the X-rays continue to interact with the electrons inside the beamline. Moving in a straight line, rather a circle, the electrons and X-rays travel along the same path. The slightly faster X-rays knock into the electrons, corralling them into a tighter bunch. Each kick stimulates the electrons to give out more X-rays – this amplifies the original light many times over, and produces a beam which is ‘in synch’ like a laser beam.
The result is an X-ray beam so bright that any molecules in its path will be obliterated. But because the pulses are incredibly short, the XFEL can extract information about the structure of the molecules before the sample explodes. “It’s ‘diffract before destroy,’” says Abbey.
The first sample the Australian team will study is a protein crucial to autoimmune disease and Alzheimer’s research ongoing at the University of Queensland. The protein only forms tiny crystals, and so nobody’s been able to figure out its structure. Yet.
But the most exciting thing, says Abbey, is the possibility of making real-time molecular movies. “That’s what’s got people really buzzing.”
The idea is to use European XFEL’s short pulses to take images of processes such as chemical bonds breaking and forming, a bit like how an ultrafast strobe light might be used to analyse the whirring flap of a hummingbird’s wing.
Each XFEL pulse lasts just 50 femtoseconds (50 millionths of a billionth of a second). Light in a vacuum can travel 7 times around the Earth in one second; but in 50 femtoseconds, it would creep only about a third of the way across one of your hairs.
At this timescale, chemistry is almost at a standstill.
In 2014, scientists used the XFEL based at the Stanford Linear Accelerator Center to make a molecular movie of photosynthesis in action. The team shone visible light on tiny crystals of the molecules involved in photosynthesis, and snapped images of changes in the arrangement of the molecules as they split water into hydrogen and oxygen. By combining snapshot images from many experiments, they could build up a molecular movie showing the reaction taking place.
But while the American machine can generate about 100 frames per second, the European XFEL can produce 27,000.
By repeating the same measurement many times to reconstruct the chain of events, it could be possible to generate molecular movies running at millions of frames per second. That will allow chemists to track the transient bends, twists and folds of molecules like never before.
But with all this new capability comes new headaches: “One of the issues with XFEL is the sheer size and scale of the data sets that are produced,” says Marjan Hadian-Jazi, a data scientist based jointly at La Trobe University and at European XFEL in Hamburg.
In the entire history of X-ray diffraction so far, crystallographers have figured out the structures of about one hundred thousand proteins, requiring about a billion X-ray diffraction images. European XFEL can record a billion diffraction patterns in a single working day.
The current software for processing X-ray diffraction data simply can’t handle the torrent. During a recent stay in Hamburg, Hadian-Jazi helped write new code to rapidly screen and interpret the data as it comes in. That will bring the system up to par with other ‘big physics’ experiments dealing with hundreds of terabytes of data per day – such as the CMS and ATLAS experiments at CERN’s Large Hadron Collider.
Just as the LHC was built with a grand goal in mind – to discover the Higgs Boson – the European XFEL is charged with its own grand quest.
“One of the most exciting possibilities is that someone will eventually be able to make these measurements on a single molecule,” says Abbey. “That would be a Nobel prize–winning breakthrough.”
That means X-ray crystallography without the crystals: an achievement that would remove the last remaining constraints on what can be studied with X-rays – allowing scientists to image individual molecules, for example, sprayed in a cloud across the X-ray beam.
“We hope this will be the one, but it will take a few years to see if we can do that experiment on this facility,” says Abbey. “We’re in the midst of the next revolution in X-ray science.”
