You wouldn’t think that an “aha moment” in an oncologist’s career would come from a meeting with a computer scientist. But USC’s David Agus credits that long-ago conversation for revolutionizing his view of cancer and its treatment.
As Agus tells it, Al Gore—yes, the former vice president—was visiting his lab when Gore nudged him to talk with an entrepreneurial engineer he knew. It was Danny Hillis, the celebrated inventor behind the Connection Machine, the parallel supercomputer at the forefront of artificial intelligence in the 1980s, who later took a leadership role at Disney Imagineering. “Do I really want to meet a guy from Disney, who designed computers?” Agus asked himself. Hillis was just as skeptical, but they got together anyway.
Turns out that Hillis offered an engineer’s perspective to Agus’ frustrations with treating cancer: He was an expert in modeling complex systems with lots of variables.
Over the course of their back-and-forth, something clicked with Agus. To find answers to cancer, researchers need to view the disease differently, he thought. They have to consider cancer as a disease of the whole body, not just defects in a cell that cause cells to grow out of control. “Cancer is a systems problem, not a biology problem,” he explains.
Since then, the two have paired up to analyze the vast network of a million proteins in the body and untangle how they relate to cancers in individual patients. But to tackle these kinds of problems, it takes calling in reinforcements outside the norm of cancer research—people like computer scientists, mathematicians and physicists. It could even mean bringing in people who might initially seem far removed from the field.
More than a decade after that first meeting, that collaborative concept has culminated at the Lawrence J. Ellison Institute for Transformative Medicine of USC. Agus, faculty member at the Keck School of Medicine of USC and USC Viterbi School of Engineering, is founding director and CEO of the Ellison Institute, which launched this summer with a generous $200 million gift from Larry Ellison, entrepreneur and founder of Oracle Corporation.
To find answers to cancer, researchers need to view the disease differently. They have to consider cancer as a disease of the whole body, not just defects in a cell that cause cells to grow out of control.
The Ellison Institute embodies interdisciplinary research, linking science with the holistic prevention and treatment of cancer. It’s part think tank, part cancer clinic and part educational outreach and wellness center. Visiting scientists, fine artists, filmmakers and chefs will all contribute to its atmosphere of discovery and well-being in a center to be created in west Los Angeles.
Agus is also co-principal investigator of the USC Physical Sciences in Oncology Center with Hillis, one of only 12 such collaborative outposts established by the National Cancer Institute (NCI) nationwide. The broad, multi-institutional team studies cancer by bringing in physical science-based approaches grounded in chemistry, math and physics.
Says Agus: “I’m at USC not just to treat cancer,” he says, “but to change how we treat cancer.”
Kuhn—a physicist—remembers the day some 10 years ago when he and Nieva were watching a patient walk across a parking lot. Nieva, an oncologist, told Kuhn that he could assess how well a patient was feeling simply by watching his movement.
The scientist in Kuhn was intrigued. Even more, he took that moment as a challenge. What does a doctor see, he wondered, that reveals a patient’s health condition—and its relationship to how well the patient will respond to treatment? And could that be quantified to ultimately help patients?
Today both men are at USC. Kuhn’s and Nieva’s mutual search for answers drives a quest to create cancer treatments tailored to each patient, a movement known as personalized medicine.
Called ATOM-HP (short for Analytical Technologies to Objectively Measure Human Performance), their project brings together researchers beyond medicine and biology to embrace psychology, engineering, chemistry, mathematics, physics and computer science. In part, it aims to measure how cancer patients feel, so that doctors can prescribe treatments that patients will better endure.
One advantage in enlisting a broad community against cancer is that cancer research “newcomers” don’t always know or care what’s considered impossible. “It’s the new questions that will lead to the next breakthrough,” says Scott Fraser, director of science initiatives in the USC Office of the Provost.
And Kuhn is a big advocate for the value of different perspectives. He’s Dean’s Professor of biology and a professor of medicine, biomedical engineering and aerospace and mechanical engineering, and he heads up cancer efforts as a founding faculty member of the USC Michelson Center for Convergent Bioscience. Convergent bioscience brings the life sciences together with engineering to improve human health, and it’s a major initiative at USC.
We need new tools because we don’t want cancer medicine to advance at the same rate it has over the last 20 yearsJorge Nieva
Consider what the ATOM-HP team is tackling: They’ll get information from sensors on patients to continually monitor their well-being—and, over time, the data could potentially help doctors decide if they need to change treatment plans. The project draws on the “Internet of Things,” a worldwide network of interconnected people and objects. Tools could include video, wearable devices and patient-reported data, which are developed and integrated by experts like engineers, computer scientists, psychologists and videographers.
“We need new tools because we don’t want cancer medicine to advance at the same rate it has over the last 20 years,” says Nieva, a Keck Medicine of USC medical oncologist and project leader of ATOM-HP. Others see promise in the pilot project: It has attracted funding from the NCI and the Department of Defense and is part of the Cancer Moonshot, a nationwide initiative to accelerate cancer research and therapies.
Learning Other Languages
Sometimes cancer researchers have to become proficient in the language of a different field to get things done. That’s the case for USC Viterbi’s Nicholas Graham, assistant professor in the Mork Family Department of Chemical Engineering and Materials Science, a chemical engineer who worked in a molecular pharmacology lab after grad school.
Cancer is about more than cells or tumors alone. Graham studies how different systems work together to help cancer develop, from the nutrients that fuel cancer to how cancerous cells communicate with each other and the tissue around them. Because these systems can be tremendously complicated, he uses computer models to understand them. That demands knowledge of computer science, statistics, biology, chemistry and more—far beyond the bounds of a traditional chemical engineer.
Fellow USC chemical engineer Stacey Finley, Gabilan Assistant Professor of Biomedical Engineering, also has cancer in her sights. Among other things, she studies how tumors feed themselves by convincing the body to build new blood vessels that nourish them. Tumors do this by communicating with the rest of the body through a complex set of signals. Therapies that block certain signals can keep blood vessels from growing, starving tumors. Finley models these networks mathematically, so she can conduct experiments virtually—much faster than could ever happen in a clinical trial.
Her goal is to develop and optimize personalized cancer treatments. “It’s the golden ticket we’re working for,” says Finley, part of the USC Michelson Center.
Finally, the ultimate disruptive partners in cancer research are the patients themselves. They’re an essential part of CancerBase, a grassroots collaborative in the USC Dornsife College of Letters, Arts and Sciences to create a global disease map of cancer. The new crowd-sourced effort could help patients learn about their disease trajectory and treatment options. Created in part by Kuhn—and one of three Cancer Moonshot projects involving Kuhn and USC—it’s run with the help of Stanford University scientists and social media companies. Also contributing are students from the USC Jimmy Iovine and Andre Young Academy for Arts, Technology and the Business of Innovation, who are designing ways to engage patients through social media and video.
Fraser, a champion for scientific innovation at USC and a USC Michelson Center researcher, sees a benefit for USC students learning in this cross-disciplinary environment: This next generation of researchers will be fearless about applying whatever technique might help them solve a problem.
He models that attitude in his own research by eagerly borrowing tools from other disciplines. Within the Translational Imaging Center at USC, for example, he takes a cue from filmmaking to understand the natural history of cancer cells—imaging tumors over an entire lifespan. Fraser calls it the cancer version of Boyhood, a film that followed a boy from ages 6 to 18. Investigators using the approach discovered an intriguing storyline: A lot of precancerous cells don’t grow up to form tumors. As Fraser says, “That makes it a much more interesting movie.”
At USC Norris Comprehensive Cancer Center, director Stephen Gruber is hopeful that this sort of animated exchange of ideas across science, engineering, medicine and the arts and humanities will result not only in a better quality of life for cancer patients, but also a longer life free of cancer.
“We are at an extraordinary inflection point in cancer care, where diseases once considered untreatable are not only manageable but are being cured,” Gruber says. “At USC, we are extremely fortunate that we have talented physicians and scientists who love working together.”