Cancer mortality rates have, on average, not budged for the past 40 years, despite billions of dollars in annual research expenditures. Looking for fresh insights into cancer research, the National Institutes of Health launched 12 physical science oncology centers at universities around the U.S. in 2009. The program has been funded for a five-year trial run, with each center receiving $15 million. The funders hope cancer research, which has benefited from tools made by physicists, can also benefit from the unique perspectives held by physicists about cancer as a physical system.
Among the directors of these centers, Princeton University’s Robert Austin holds perhaps the most controversial perspectives on cancer. Austin, a member of the National Academy of Sciences, believes we might have cancer for a reason. It’s a tradeoff, he says, for the rapid evolution our species has leveraged to become the dominant force on the planet. He also suggests that cancer might have another purpose: to act as a form of programmed death, much as we age to preserve the long-term fitness of our species.
One of the main challenges facing cancer researchers, according to Austin, is a tumor’s ability to evolve resistance to chemotherapy. He thinks this trait shares many characteristics with antibiotic resistance among bacteria. To that end, his lab builds specially designed microenvironments to study how antibiotic resistance evolves. The team’s inspiration is the late geneticist Sewall Wright, who claimed evolution speeds up when small groups of microbes are forced to live in partial isolation from other groups.
Following Austin’s talk at the February 2013 meeting of the American Association for the Advancement of Science in Boston, SciCom’s Chris Palmer hustled through Beantown’s snowy streets with Austin — on his way to catch a train — to discuss the war on cancer and his unsettling views.
What is cancer?
I have two answers. One is it may be due to a fundamental, general instability in any system that has mutations going on where you’re reproducing yourself. There’s a fundamental danger there. It’s the risk that the system is willing to accept in order to evolve.
It may also be plan B in the sense that we’re supposed to age and die. It’s very important that we die. If you take good care of yourself so the normal ways of death don’t happen, the system will go ahead and turn something else on to make sure that individual ceases.
So, cancer is like programmed cell death?
Yeah, it’s apoptosis on a large scale. That’s why the immune system gives it a pass. In fact, the body might even fight your attempts to reverse the process, because it actually wants it to happen.
"We should stop using the word 'cure.' It’s the wrong word to use. We don’t want to cure cancer. We have to have cancer."
Are you saying that cancer is ultimately good for us?
Yeah, on a species level. We all know that to evolve, we must have mutations.
We became rapidly evolving because we have cancer. Cancer is more prevalent in humans, because that is the mechanism driving our rapid evolution.
Does everyone have cancer?
We all have cancers going on in us. We all have tumors.
Is it a modern phenomenon?
It’s always been there, I’m sure. But I think it’s getting more common in recent times because we are evolving so quickly. We may be selecting for cancer.
What does that say for whether we will ever find a cure for cancer?
We should stop using the word "cure." It’s the wrong word to use. We don’t want to cure cancer. We have to have cancer. The hope is that you can keep cancer under control for a long enough time to die from something else without a huge loss of quality of life.
Should we just give up on chemotherapy?
No, no. I don’t think we should give up on chemo, per se. We just do it in a simple-minded way right now. We give patients as much as they can tolerate.
This guy, [pediatric oncologist] Bart Kamen, who died of cancer recently, argued for metronomics. In other words you need to dose a person, look at the response, then adjust the response to what the dose did. We need to be more intelligent about the way we’re delivering these things.
Instead of trying to kill the cancer, we [should] try to maintain it. In other words, maybe we should feed the tumor instead of starving it. Avastin was this anti-angiogenesis drug, meant to starve a tumor by cutting off its blood supply. That drug has failed miserably. These cells simply evolved the ability to survive on less blood. They actually ended up more dangerous than if they hadn’t given any drug at all. So, by starving them, we actually created an absolute monster.
So, we should try to keep the tumor happy?
Yeah. Keep it happy and quiet. Can we learn to do that? I think that’s not impossible.
What else works?
What does work is surgery. The earlier you detect it, the better off you are.
What triggers the transition from tumor to metastasis?
I figure it’s a stress-related thing. In other words, I think the tumor slowly becomes a more stressful environment. The idea is that these tumors' cells decide to break out and move somewhere else.
Ninety percent of all cancer deaths are due to metastatic transitions. You can usually live with most tumors. They won’t kill you necessarily, but when they metastasize, they definitely kill you.
Let’s get back to chemotherapy. How do tumors evolve resistance against it?
Cancer is characterized by cell reproduction, so [chemotherapy drugs] try to stop cells from reproducing. One of the most common ways to do that is to screw up the DNA — cut it, block it, things like that. That’s a very common stress that cells are used to seeing, and like bacteria, they have ways of getting around it.
Another thing is that chemotherapy usually kills cells and reduces the population down to the scattered population around the periphery of the former tumor. That’s a recipe for disaster, too. As Sewell Wright was trying to say, when you break a population down into many small populations under stress, that’s actually a very robust way for evolution to proceed.
How is a tumor’s resistance to chemotherapy similar to antibiotic resistance in bacteria?
Oh, it’s the same basic thing. With an antibiotic, you stress the bacteria. There’s a network in the bacteria called the SOS response, which senses the antibiotic and proceeds to try to evolve a way to solve the problem the antibiotic is posing. I think there are similar networks going on in eukaryotic cells that sense stress and they turn on the oncogenes [genes with the potential to cause cancer], for instance. They try to evolve proteins that get around that problem.
What role does stress play in cancer?
Huge. Enormous. I think one of the primary drivers of cancer is stress. Most of what you call stress are environmental insults. Almost no Japanese women get breast cancer. [Then] they move to the U.S. and eat the U.S. diet and their breast cancer rates shoot up. Prostate cancer is almost unknown in rural China, and here it’s one of the primary killers. Psychic stress, physical stress, chemicals, carcinogens, hormones — all this other stuff that we put in our food and our water system definitely has a role to play.
I think in adults, the beginnings of cancer are probably related to stress. And then once the cancer starts to develop, I think that stress accelerates the evolution of resistance.
Do we have a good animal model for cancer?
No, no. That’s the problem. Mice have been useful models, but a human tumor in a mouse behaves very differently than a tumor in a person. That’s why all these drugs only have five percent success rates.
Do other primates straddle the knife’s edge between rapid evolution and high cancer rates?
Yeah, I think so. But it’s politically incorrect to work with higher primates — particularly the great apes. No one is going to let you give an ape cancer.
How does your lab research cancer?
We’ve learned how to evolve antibiotic-resistant E. coli very quickly using fundamental principles, and now we’re building devices to do the same thing with cancer cells. We’re learning the rules by which cancer cells evolve resistance.
Then the next thing I’m going to do is go after the origins of cancer. How does it actually begin? A deep question is to take regular cells and start them on the road to cancer. We absolutely don’t understand that. It’s sort of a cheat to work with cells that are already cancerous. Once it happens, I think it’s irreversible. But if you can prevent it from happening, then you really might be getting somewhere.
Why is the National Cancer Institute teaming up with physicists?
NCI is acutely aware of the fact that they’re not winning the war on cancer, and it’s going to get incredibly expensive as time goes on. So, they organize these workshops to try to bring physicists in to see if there could be some synergy.
What can a physicist offer the field of cancer research?
We look differently at the problem. We haven’t been doing this forever. It’s not our profession. And so we’re more willing to take a 40,000-foot view of the thing. The other thing is we have a more quantitative approach, which uses numbers and tries to be more brutal about it.
Is NCI’s partnership with physicists paying off?
It’s too early to tell. We’re only in the fourth year. We may not get renewed because I think that cancer is an enormously complicated thing that will take us more than five years to sort out in some big-picture way. They ask, "What are the clinical implications?", but it may take us time to figure out that important question.
What is the main problem with traditional cancer research today?
We don’t have a deep understanding of cancer. What we try to do is kill cells, fundamentally. That may not be the right approach. We would have much greater leverage if we tried to prevent the cancer. There’s not nearly enough work on prevention and way too much work on a cure, which I think is doomed to fail.
What are the most effective prevention strategies?
Right now, half the cancers are due to smoking. If we were rational, which we’re not, we would just make smoking so incredibly expensive that people would simply stop doing it. That would halve the cancer rate tomorrow. The other thing is our lifestyle is quite bad in the United States, and it’s getting worse. Sedentary behavior, junk food, putting all sorts of growth hormones in meat in order to make it cheap — all these things lead to cancer, actually. We understand that. But the profit margins overwhelm common sense.
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An edited version of this conversation was published online at The Scientist on April 3, 2013.
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Chris Palmer, a graduate student in the Science Communication Program at UC Santa Cruz, earned his bachelor's degree in psychology and biology from Northern Arizona University and his PhD. in neuroscience from the University of Texas at Austin. This year, he has worked as a reporting intern at the Monterey County Herald, the San Jose Mercury News, and Nature News. He will report this summer for The Scientist as a remote science writing intern.
© 2013 Chris Palmer
