The war on cancer has been a long, slow slog, but a new breed of soldier, with a new set of skills, is entering the fray.



Historically, biologists have studied cancer through trial and error, testing molecular pathways and treatments one by one in hopes of finding a cure. That approach has not led to one. In October 2009 leaders at the National Institutes of Health (NIH) National Cancer Institute launched a campaign to draw more scientists, engineers and thinkers outside of the field into the cancer research sphere. The hope is that collaboration between traditionally disparate fields will produce new tools for cancer treatment—and perhaps get biologists and doctors thinking more like physicists.



"They threw up their hands and said, 'We're not winning this battle; we have to invite people in with different points of view,'" says Daniel Hillis, a computer scientist, roboticist and inventor who previously served as vice president of Walt Disney's Imagineering division.



Now Hillis is applying his engineering expertise to the search for a cancer cure as the principal investigator of one of several major new organizations that channel the talents of doctors, biologists, physicists and engineers into figuring out how and why cancer develops.



"The death rate from cancer hasn't changed much since the 1950s," explains David Agus, the head of the University of Southern California (U.S.C.) Westside Prostate Cancer Center and co-investigator, along with Hillis, of what the NIH calls a Physical Sciences–Oncology Center (PSOC). "We need new innovations and new ways of thinking," Agus says.



For instance, to this day cancer researchers cannot properly predict or control how and when chemotherapy works. "There is no real data that shows that chemotherapy hits only the cancer cells," Agus says. Whatever its mechanism, the delicate biomolecular dance between a chemical treatment, cancerous cells, and the healthy living tissue around them works well for some patients, but completely fails to help others. Agus and his colleagues want to know why.



His U.S.C.-based team, comprising 20 investigators from nine different institutions, is only one of 12 separate PSOCs in the country. One center based in Princeton University, headed by biophysicist Robert Austin, is using microfabrication techniques to understand what kind of micro-environments contribute to chemotherapy resistance for some patients. Another, led by astrobiologist Paul Davies of Arizona State University in Tempe, is investigating physical differences between tissue that becomes cancerous versus tissue that stays healthy by comparing three-dimensional images of single cells. The NIH has dished out more than $60 million to the various PSOCs since the project's inception.



At U.S.C. the researchers hope to finally find out the "why" of cancer by building the ultimate computer model of cancer—a model that captures everything from how a single molecule moves all the way up to the physics of how a tumor spreads in a host organism.



It is an ambitious task, and the PSOC has five years and $16 million to complete it. "Maybe it's so complicated that we can't do it, but eventually someone has to do this," Hillis says. Someday, with a model like the one Hillis dreams of, doctors could take patient medical data, run it through a computer simulation, and determine whether or not a specific treatment ought to work before trying it out in the real world.



But before you can build a physical model of cancer, you must first get biologists and physicists talking.



"They don't get each other's jokes," says Parag Mallick, a biochemistry professor at the University of California, Los Angeles. Mallick is uniquely capable of understanding both groups because his research has always been a mash-up of engineering and biochemistry. Part of the goal of the PSOC program is to develop more experts with that kind of interdisciplinary expertise, so he spends a lot of time on education and outreach—including getting physicists and biologists to laugh at each other's jokes, or at least to understand them. "It was rare for physicists, engineers, mathematicians and biologists to go to conferences together before the PSOCs were created," he says.



To build a model of cancer from molecule to mammal, Mallick is trying to figure out how to bridge all of the different scales on which biology operates—the atomic/molecular, the cellular and the whole organism. There are entire labs dedicated to each individual scale, from the nano to the macro. "Ultimately we want to know the tumor's state. Is it growing or dying? How is it moving?" Mallick says. There are hundreds of properties that affect a tumor's condition—from its size and growth rate to the temperature of its environment. All of these things affect how cancer develops and spreads.



"Once we know what all the moving parts are and how they interact, cancer research goes from a black art to an engineering technology," says Richard Bonneau, a professor of biology and computer science at New York University. Bonneau and his colleagues are building the part of the computer model that shows how cancer cells behave at the molecular level. They will then connect it to other models on different scales at different institutions. After all the pieces of the collaboration come together the team should know how a mutating protein affects a tumor's spread in a mouse.



As Hillis and his colleagues bring their skills to bear in the war on cancer, they also must adjust to a different research environment. "The first thing I did as principal investigator was become certified to euthanize mice. It's surprisingly difficult and complicated to humanely kill a mouse," Hillis says. He has a new respect for biology. "It makes physics look easy," he says. With physics, you perform the same experiment many times and get the same result. But give a mouse a shot, and it responds a little differently every time.



The most difficult adjustment for physicists who take up biology may be feeling the sense of urgency inherent in clinical oncology. "This week two patients died of cancer," Agus says. "It's a different way of looking at it if you're in the trenches facing cancer and cancer patients every day."