An NCI-designated Comprehensive Cancer Center
By Abe Rosenberg | July 3, 2018

Russell Rockne, Ph.D., says a novel idea began percolating in his mind a few years ago.
As director of City of Hope's Division of Mathematical Oncology, Rockne spends his days building mathematical models to help us better understand how cancer works. Just as math, the “language of the physical universe,” can describe and predict the physics and mechanics of the cosmos, Rockne believes it can do the same for biology, showing us patterns for things we thought were totally random and disordered ... like uncontrolled tumor growth.

Math and Cancer

The idea of applying math to biology is not a new concept, but the field of mathematical oncology is barely a decade old, and City of Hope is one of only a handful of institutions devoting significant resources to it.
“A mathematical oncologist,” Rockne said, “uses math as a principal means of scientific investigation. It's one of the tools of our trade. And it's quite possible that we do not yet have the right mathematical structures to understand biological data.”
But which mathematical structures?
Enter Albert Einstein.
The famed physicist whose very name is synonymous with “genius” gave us entirely new ways of thinking about the universe, demonstrating with his theory of special relativity that time and space are not independent but connected, acting upon each other. His later theory of general relativity added gravity to the mix, showing how it “curves” space and time.
Relativity informs and explains a wide array of phenomena, like why it's necessary for clocks on orbiting global positioning satellites to “tick” at a slightly different rate than clocks on Earth, because satellites are moving much faster and are subject to less gravity than clocks on the ground. Without accounting for relativity, GPS measurements would be off by several miles each day.

Einstein and Accelerated Aging

For Rockne, Einstein was the missing piece of the puzzle.
“A few years ago,” he recalled, “three things happened at once. First, we celebrated the 100th anniversary of Einstein's theories, and everyone in the scientific community was suddenly talking about him. We also experienced this extremely pervasive use of RNA sequencing data, mapping it out in new ways.
“And I started having conversations with Saro Armenian [D.O., M.P.H., director of City of Hope's Center for Survivorship and Outcomes] about understanding cancer as a process of accelerated aging.”
Pulling all this information together, and aided by theoretical physicist and City of Hope postdoctoral fellow Davide Maestrini, Ph.D., Rockne assembled an interdisciplinary team (experts ranging from Pediatrics to Population Sciences) and co-authored a challenging new paper that for the first time uses Einstein's relativity concepts to mathematically plot through space and time the biology of cancer and the aging process.

The Chaos of Cancer

As head-exploding as that may sound, Rockne and Maestrini insist it's not.
“If Einstein looked at our math,” said Maestrini, “he'd probably say, 'This is trivial! I did this a hundred years ago!' We're taking his basic model and repurposing it.”
The paper lays out the differences between “chronological” versus “biological” age (you can look older or younger than you actually are because of outside factors, like cancer). It then methodically takes you through the evolution of “biological space-time,” explaining the aging process as changes not only in our physical space but also as the “dilation and contraction of biological time.” Someone stricken by cancer at an early age, for example, experiences rapid aging and a “contraction” of their biological time. On the other hand, someone cured of cancer through a stem cell transplant experiences a “dilation” of time.
But can cancer really be plotted this way, with or without Einstein? Isn't cancer unpredictable? Chaotic?
Not really, said Maestrini. As a living thing with an occasionally evasive nature, biology can be difficult to measure directly. But it's possible.
“Cancer is not a sentient being,” he said. “It is a considerably less variable, less chaotic system, with fundamentals that we may be able to predict.”

An Unlikely Alliance

Russell Rockne Russell Rockne, Ph.D.
Few would have predicted either Maestrini or Rockne going into this line of work, given their early histories.
“I hated math,” recalled Maestrini. “I wasn't any good at it. It seemed so complicated and weird. But eventually I started seeing math as a language, and as long as you followed the rules, it made sense."
For Rockne, the son of a designer and a scientist, math was “the last thing on my mind,” a way to guarantee gainful employment while he pursued his original passion: the arts. Eventually math's inherent artistic beauty resonated with him, and now he even spends his relaxation hours perusing math and science texts.
Math informs and guides our intuition,” he said. “Think of a catapult. Through trial and error, you can figure out how it works by firing it over and over again. But without math you'll never truly understand the process, and you'll never advance to the point of getting satellites into orbit."
“Right now there's no single math theory to explain how people age. With this paper we aim to use math to guide our intuition on cancer and aging, not only to better understand, but to predict.”

From Theory to Clinic

But how will a “theory” help a cancer patient? It won't. At least not right now. But that's the goal, and Rockne and his colleagues never lose sight of it. It's why Rockne insisted on that broad interdisciplinary group to conduct his research in mathematical oncology. Math and biology may not have co-evolved the way math and physics did. But going forward, cancer care and mathematics will be inextricably linked.
“We're entering an era where you won't be able to practice oncology without math,” he said. “Our next steps must be to push the data forward to help patients. That's the whole purpose for my being here at City of Hope. To use math to advance our understanding of cancer.”
And Einstein's theory? It's a 100-year-old idea whose time may have come. Again.
“The theory of relativity is well known,” said Maestrini. “So is the aging process. But we don't fully understand either one. Maybe, by combining the two, we'll get a better understanding of both. No one's ever done that before.”

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