X-ray visionaries

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Researchers at ASU's Biodesign Institute are pioneering the use of super-fast, super-bright X-rays to map out the structure of proteins. Their work is helping to replicate photosynthesis, develop better pain medications and more.

By Kirk Davis

Dec. 21, 2016

Video transcript

[laboratory sounds]

Narrator:  November 8th, 1895. German physicist Wilhelm Roentgen is testing out an early kind of vacuum tube in his lab when he notices something strange. A ghostly light from the tube seems to pass right through opaque objects of differing densities, illuminating what lay inside.

[background music]

It was a new kind of electromagnetic radiation, never seen before. He tested his new device on his wife's hand, over a photography plate. When she saw the world's first X‑ray, she reportedly said, "I have seen my death." A whole new world was instantly illuminated.

Roentgen's discovery immediately transformed medicine, and these X‑ray visions quickly became a cultural phenomenon.

So miraculous and alien, X‑rays even became one of the world's first superpowers.

Announcer: This amazing stranger, Superman! Empowered with X‑ray vision...

Narrator: But in reality, X‑rays were the key to unlocking one of the greatest scientific mysteries of the age.

London, 1952. Scientists raced to solve the structure of a mysterious molecule, DNA. Rosalind Franklin, a master of a new technique called X‑ray crystallography, photographed DNA for the very first time.

But unbeknownst to her, the photograph was shared with James Watson and Francis Crick, her competitors. Careful study of Photo 51 enabled Watson and Crick to deduce the structure and function of DNA.

Soon they burst into a local pub and declared they had discovered the secret of life. That discovery spawned a revolution and promised tremendous breakthroughs.

But despite incredible progress, the promise remains unfulfilled. We need a new breed of X‑ray visionaries who can save lives, help treat chronic pain without addiction, and advance the future of energy.

Nicole Zeig: It was exactly like falling in love.

Narrator: When Nicole Zeig was 16, she injured her back. Her doctor prescribed opioid pain pills. It took care of the pain, but then a new problem developed.

Zeig: And that first time I took that pill, I was instantly addicted. It provided everything in my life that some people would say a higher power or true love or something would provide.

Narrator: Zeig became one of the over two million people dealing with substance abuse from prescription opioids.

Zeig: It took me over eight years to get off of the pills. I had four abortions and that was really hard on me, and I endangered my life multiple times. I stopped breathing many times, and I ruined my family/ I really, really hurt them.

Narrator: What happens when those prescriptions run out? Addicts turn to the only available opioid they can get their hands on; heroin.

Zeig: I was seeking pain relief, not getting high. If I had been able to manage the pain without the side effects I would have saved myself years of literal hell.

Narrator: People like Nicole are hoping for a new wonder drug to find relief without the threat of addiction, but we've reached the limits of current X‑ray technology.

Petra Fromme, professor and director, Center for Applied Structural Discovery, Biodesign Institute: Life is a dynamic, it's not a static picture. And what we want to get is actually a movie of biomolecules at work, but there's one fundamental problem. X‑rays damage biomolecules.

Narrator: Without a clear picture, scientists are effectively left in the dark, unable to address the problem. But researchers at ASU are racing to bring a powerful new tool to bear; the X‑ray free‑electron laser. It's illuminating secrets from deep inside the brain for the first time.

John Spence, Regents’ Professor, Department of Physics: The X‑ray laser gives you very fast time resolution and it avoids radiation damage. We get the information we want first, before we blow up the sample.

Narrator: The XFEL re‑purposes a particle accelerator to create the world's most powerful X‑ray beam. This allows scientists to see deeper than ever before. ASU researcher Petra Fromme is pioneering this innovative new field of study.

Fromme: We let little crystals, which only contain hundreds of molecules instead of trillions, fly at room temperature in their native environments through the beam, and then essentially get snapshots of the molecules in action.

Spence: It makes solving protein crystal structures, getting pictures of them, much more efficient.

Narrator: Using the XFEL, researchers have now seen for the first time how opioids bind to receptors in the brain. This could enable the development of a new class of drugs that could deal with pain without euphoric side effects.

Fromme: We want to see if we can inhibit this receptor so that the drugs cannot bind anymore, developing drugs which can block the receptor without making you dependent, overcoming this drug abuse and essentially then the patients could be more or less cured.

Narrator: The XFEL also brings us closer to glimpsing the heart of one nature's greatest mysteries; the mechanics of photosynthesis. Every day the sun produces enough energy to power the world many times over, but there's no way to store it. Artificial photosynthesis would create the possibility of near‑limitless energy generation and storage.

Spence: Photosynthesis makes possible life on earth. It splits water to make the oxygen that keeps living things all alive.

Fromme: If we would know how plants can do it, then we could build artificial systems which are as efficient as nature but as stable as a man‑made system.

Narrator: The XFEL may one day help us reach our goal of creating molecular movies. We will finally see nature in action on the atomic scale. This groundbreaking approach is the focus of ASU's John Spence.

Spence: Our aim is to make molecular movies of the machines in living things which have a job to do, and we want to see how they work. In the case of photosynthesis, the sunlight falling on a leaf, you extract the molecule from the leaf that actually does the photosynthesis.

Fromme: With any conventional method, you cannot get this movie of the molecule in action because you undo what you do with the light, with the X‑ray damage.

Spence:  To start the cycle of photosynthesis, we shine light on them briefly...

Fromme: And then we can get the picture of the molecule in action. And we have just two years ago published the very first snapshot of the so‑called double excited state, and now we want to get the complete movie of the process.

Spence: Richard Feynman once said that all life on earth can be reduced to the jiggling and wiggling of atoms, so we want to see those wiggles, the wigglings that correspond to life.

Narrator: But there are major obstacles associated with the XFEL.

William Graves, associate professor, Biodesign Institute: There's only a few in the world, they're enormous. They cost about $100 million a year to operate, so it takes between one and two years of waiting to get your one day actually on the facility. As we know from computing, where if you only had three computers in the world, you wouldn't get much computing done.

Narrator: Researchers at ASU, such as William Graves have a revolutionary solution. Using new technology they can shrink the XFEL and create a compact version that could fit into a lab.

Graves: By combining modern laser technology and modern accelerator technology, what we want to do is allow you at a cost a hundred times less, to be able to do the same science.

Even the first simplified machine that we'll build can have a tremendous impact on medical imaging. Currently, X‑rays are primarily used to image bone versus soft tissue. We can't use X‑rays to look at soft‑tissue injuries, or plaques in arteries, or cancerous cells versus healthy cells.

We think we can have a really revolutionary impact on medical imaging by using the so‑called phase‑contrast imaging that allows us to see differences in soft tissue. We think it's going to be, in many aspects, better than the bigger machine. We think it will have an enormous scientific impact.

[background music]

Narrator: ASU seeks to be the world's first institution with a compact X‑ray free‑electron laser. Once built, researchers will have the power of an XFEL at their fingertips.

The CXFEL, combined with the innovation of serial femtosecond crystallography, will exponentially accelerate drug and energy research. Major breakthroughs in fields like health and energy won't be far behind.

We are the X‑ray visionaries who want to see the world like it's never been seen before. We are the trailblazers. We have the technology to open up unlimited vistas. Are you ready to change the world?

The Biodesign Institute is partially supported by Arizona’s Technology and Research Initiative Fund. TRIF investment has enabled hands-on training for tens of thousands of students across Arizona’s universities, thousands of scientific discoveries and patented technologies, and hundreds of new start-up companies. Publicly supported through voter approval, TRIF is an essential resource for growing Arizona’s economy and providing opportunities for Arizona residents to work, learn and thrive.

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