APS News

May 2011 (Volume 20, Number 5)

Physics Sheds Light on Cancer and Bacteria Evolution

By Gabriel Popkin

Cancer and bacteria have a lot more in common, it turns out, than the fact they can kill us. Both types of cell live in highly regulated communities, communicate with their neighbors using signaling molecules, and undergo rapid evolution when exposed to environmental stresses. Physicists who presented their research at this year’s APS March Meeting hope to use experimental techniques and models from physics to unlock the secrets of such deadly phenomena as tumor metastasis and drug resistance.

In a session on the physics of evolution, Robert Austin, professor of physics at Princeton, laid out the challenges for physicists taking on cancer: mortality rates for the disease have mostly been flat in the past three decades, and in some cases are rising; moreover, what treatments we currently have tend to moderately extend life, but rarely save it. Austin heads the Princeton Physical Sciences Oncology Center, one of twelve centers around the country that are applying techniques and insights from the physical sciences to the battle against cancer. He says, “We welcome crazy ideas.”

One of those “crazy ideas” is the possibility that cancer represents a sort of atavism—a regression to the evolutionary past, in which ancestral, normally noncoding regions of human DNA start being expressed again. Despite the fact that tumor cells are mutated versions of our own cells, they are very poorly differentiated, resembling embryonic stem cells rather than the more specialized cells that make up our tissues. “Cancer is evolution running backwards,” said Austin. To understand this, “We need to build biological time machines. Can we invent a time machine that runs cells backwards?”

Robert Riehn, a professor at North Carolina State University, described research aimed at better understanding this backward evolution of cancer. Riehn studies changes that occur in cancer cells at the epigenetic level, where DNA transcription and gene expression are controlled. He and his colleagues use microfluidics devices called nanochannels to stretch out small sections of tumor cell DNA, and fluorescent markers to observe important signatures of epigenetic changes that occur in cancerous cells. These changes can lead to the expression of normally silent genetic programs which Riehn and others believe lead to the evolution of the dangerous metastatic behavior that makes cancer such a big killer.

Others presented studies of drug resistance and metastatic behavior related to changes in cells’ environments. Guillaume Lambert, a graduate student at Princeton, described research using microfluidics techniques to expose tumor cells to chemical gradients of drugs, nutrients, or other chemicals, and measure their evolutionary response. Along similar lines, Qiucen Zhang, also a Princeton graduate student, described a method of rapidly “fixing” drug resistance in a population of bacteria in as little as ten hours, by growing the bacteria in a micro-environment containing a gradient of the antibiotic ciprofloxacin (Cipro). Meanwhile, Liyu Liu, a postdoc at Princeton, presented research on the metastatic behavior of cancer cells he grew on microchips, in environments called “tepuis,” whose name was inspired by a form of isolated mesa found in the Guiana Highlands of South America. By placing different types of cancer cells in the “lowlands” and allowing them to invade the tepuis, Liu is hoping to determine some of variables that influence metastatic behavior. Lambert, Zhang, and Liu all work in Austin’s group.

Theorists also got in on the game, presenting several models for understanding cancer development. Simone Bianco, a postdoc in bioengineering and therapeutic science at the University of California, San Francisco, studies the changes that occur in internal architecture when a cell becomes cancerous. Bianco presented a way to model these changes in a “multidimensional morphology state space,” which he hopes will lead to insights into the mechanism of tumorigenesis. Ping Ao, a professor of physics and engineering at Shanghai Jiaotong University in China, described an approach using network theory to map cancer onto a fitness landscape, similar to an energy landscape that might be used to model protein folding. Ao said, “As physicists, we want to know if there is a simple perspective behind all the complexity” of cancer.

Another theme that emerged from talks on both cancer and bacteria is the use of game theory, a concept borrowed from math and economics. Austin argued that current cell-death treatments tend to leave behind only the most aggressive cancer cells, which are the ones that have evolved the most radically. “We need a game theory approach to dealing with cancer,” he said. “How can we design a selection pressure that rewards slow growth, decreased mutations, and belonging to a community?”

A number of researchers in Jeff Gore’s lab at MIT applied game theory to the evolution of drug resistance in bacteria. Tatiana Artemova, a graduate student in Gore’s lab, investigated how cooperation between different strains of bacteria helped them develop resistance to a new antibiotic. In a related talk, Hui Chao, an undergraduate in the lab, explored how “cheating” non-resistant bacteria may take advantage of drug-resistant bacteria to survive in an environment that contains an antibiotic. Both speakers used quantitative models of cooperation and cheating to describe the evolution and behavior they observed.

While too early to tell if any of this work will lead to the long-sought cures for cancer and drug-resistant bacteria, it is clear that physicists are bringing new tools to the table. “Through our naivete, physicists are not bound to the paradigms of biology,”  Riehn said. “We ask other questions.”

Or as Liu put it, “We go in with our intuition. I am not afraid of failure.”

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Editor: Alan Chodos

May 2011 (Volume 20, Number 5)

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Articles in this Issue
Promise Lies Ahead for Superconductivity After 100 Years
Fukushima Disaster Alters Dialogue at Nuclear Session
March Meeting Teems with Graphene Talks
New Awards Issue a Call for Nominations
APS Website Hosts Ethics Training Materials
Materials Physicists Attracted to Spider Webs
Spice Ingredient Touted as Explosive Detector
Physics Sheds Light on Cancer and Bacteria Evolution
Letters to the Editor
The Back Page
Members in the Media
This Month in Physics History
The Education Corner
Inside the Beltway
Zero Gravity: The Lighter Side of Science
Profiles in Versatility