The project began under the guidance of the U.S. Department of Energy’s SLAC laboratory, with the intent to come up with biological applications for X-ray lasers that were paired with the power of mile-long particle accelerators (BioXFEL). But first, they needed to overcome a formidable issue: the radiation power of large particle accelerators that was needed to see molecules at near-atomic scale often would quickly obliterate the delicate crystal samples before any data could be collected. Then, in 2000, Hajdu and Richard Neutze published a game-changing paper that theorized a way to not only record images of the mechanisms but also produce a movie showing them at work. 

Next, in 2006, experimental work led by Chapman proved for the first time that it was possible to “outrun” the radiation damage by using a very short pulse of the powerful X-ray beam. As the technique’s name implies, the light pulses occur over an astonishingly short time frame, measured in femtoseconds. A femtosecond is one quadrillionth of a second. To give a sense of just how brief this is, one femtosecond is to one second as one second is to about 32 million years.

In parallel in Arizona, Spence’s lab was building a device for sample delivery as well as crystallographic, data-deciphering algorithms. Despite the project being high risk at the time, the appeal was undeniable as Chapman’s experiments showed potential. The complexities of the project were also clear early on, such as the X-ray laser’s instability and scientific hurdles to overcome with the sample injection device. 

In 2010, Spence was part of a worldwide team to develop the first theory and methodology to dig deeper into the biological world using XFELs.

His team consisted of professors Petra Fromme, Uwe Weierstall, Rick Kirian, Alex Ros, Brenda Hogue and Bruce Doak. Fromme created the microcrystals that led to the first success of the project. Doak, Weierstall and Spence were then able to extend the recording time for the images. Weierstall built the first sample delivery device for the microcrystals, which was further refined by Doak. The synergy of the ASU BioXFEL team even extended outside the lab — with the formation of the "Who Knew," a bossa nova band that recorded an album and performed at the yearly BioXFEL conferences.

The X-ray laser structural biology work was ranked among the top 10 scientific breakthroughs of 2012 by Science magazine.

In 2013, they secured $50 million in funding from the National Science Foundation to form a seven-university BioXFEL Science and Technology Center (ASU, Stanford, University of Wisconsin-Milwaukee, Cornell, Rice, State University of New York at Buffalo and University of California-San Francisco). The XFEL consortium has been devoted to the development and application of hard X-ray lasers to biology for the last decade. This funding gave the team the opportunity to focus on diseases that have evolved to evade the effects of antibiotics, and to make movies of proteins in action.

In 2019, ASU received a $10 million gift to enable the completion of the first room-sized version of the technology, the Beus Compact X-ray Free Electron Laser (CXFEL) Lab, to make the technology more accessible to the worldwide research community and to speed up the pace of discovery. Donated by Leo and Annette Beus, the gift has funded this first-of-its-kind compact X-ray technology in the world. With nearly the same performance as the mile-long XFELs, the instrument has potential applications in medicine, the renewable energy economy, the computer industry and beyond.  

In 2020, the Royal Swedish Academy of Sciences awarded one of the physics research community’s highest honors, the prestigious Gregori Aminoff Crystallography Prize, to John Spence and his colleagues Janos Hajdu from Uppsala University, Sweden, and Henry Chapman from Hamburg University and DESY laboratory in Germany.

They received the award in honor of their innovative work in the structural imaging of molecular mechanisms with powerful X-ray free electron lasers. Their work provided the foundation to precisely see molecular machines like biomolecules, a major advancement for the field of structural biology and its potential applications to improve drug targeting, pharmaceuticals and renewable energy.

“Besides his scientific brilliance, John will be remembered for his personal kindness, including to me as the new chair, and his caring attitude as a teacher and mentor,” said Patricia Rankin, chair of the Department of Physics.  

“His books were bestsellers in the community — required reading for every microscopist. Among many achievements in crystallography, he will be remembered for the work he did with ASU’s Michael O’Keeffe in imaging chemical bonds.” 

Spence's zest as a science writer was on display in his recent book "Lightspeed" (Oxford University Press, 2019). During a sabbatical, Spence visited many of the places where the historical measurements of the speed of light were first made, and he told the tale of the improbable connections between the search for an absolute frame of reference in the universe (the Aether) and Einstein's theories leading to the equivalence of mass and energy.

“He was remarkable in so many ways, from his pioneering accomplishments in multiple fields of physics, to his renaissance scholarship, to his personal hobbies of sailing, soaring and music,” said former Department of Physics chair and longtime colleague Peter Bennett.

“Most remarkable however was his totally unassuming persona that radiated kindness, generosity, curiosity and youthful energy. He was a personal hero for me as a scientist, colleague and friend. My memories of John span from early days as a fellow Moon Dog (Spence’s band name) to a recent colloquium on 'Lightspeed,' delivered to a packed room of colleagues here at ASU. It was particularly rewarding to engage with him as department chair over the past seven years. He delivered consistently at the highest level, in the department and across the university, all while making it look easy. His passing is an immeasurable loss to us all.”

Spence leaves behind his wife, Margaret, sister Penny, and son Andrew.