THE "WHY" OF CANCER: Physicians and physicists are working together to try to map out why cancer cells behave the way they do--and what can be done about it.
Image: From "A Surprising New Path to Tumor Development," PLoS Biology, Vol. 3, No. 12; 2005. Courtesy Creative Commons license
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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."
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8 Comments
Add CommentCongratulations on a very good idea. However, if I may, I am of the opinion that you could improve the program.
Reply | Report Abuse | Link to thisFrom reading the article I get the impression that you are relying mainly on professors, whereas there are thousands of brilliant people in development labs in industry with bags of lateral thinking abilities and dozens of years of problem solving experience that could make real contributions to the cross fertilization process you are hoping for.
Best regards
Michael Berman.
As a fan of Scientific American, I was extremely disappointed to read this article. Because SA is a relatively credible magazine, I typically expect the articles that I read in SA to also be credible. Sadly, this article did not live up to that level of expectation.
Reply | Report Abuse | Link to thisThe author's claim that the concept of physicists and biologists working together is "new" reveals her obvious lack of knowledge about the history of science, most notably in the period leading up to WWII through the 1960s. In this period, a number of physicists played a huge role in the establishment of molecular biology as a field, a handful of them switching from physics to biology (such as Leo Szilard). A notable example of another physicist involved in the advancement of the field is George Gamow who corresponded with Watson and Crick during their research on the double helix structure of DNA and was the first to try to understand genetic code using a theoretical approach. I suggest reading Michel Morange's "A History of Molecular Biology" which dedicates an entire chapter to "The Role of the Physicists" for more information on the subject.
Furthermore, the author's idea that someone with backgrounds in engineering and biochemistry could possibly hold any credibility in the field of physics shows a lack of knowledge about the fields of engineering and physics as they are quite dissimilar. The implication that the two fields are similar enough for someone to be an expert on either the social or academic aspects of both while specializing in a completely different field (biochemistry) is almost insulting.
I also find it amusing that the author seems to feel that a computer scientist has enough credibility in physics to call it "easy" relative to biology (another field he is not an expert in) or to even comment on the state of affairs in experimental physics. Unless the computer scientist miraculously also has a solid background in physics and has spent a significant portion of time doing experiments in the field, he likely has no credibility on the subject, and his comments are likely completely unfounded. I'd be curious to know if the statement, "With physics, you perform the same experiment many times and get the same result," is the author's or if she simply forgot to include quotation marks. If it is the author's attempt to comment on the subject, I call her credibility on the subject into question as well.
I think you are sharing an illusion that many hold. It is that most of the great discoveries are made by corporations in private industry.
Reply | Report Abuse | Link to thisThat just isn't true, now or in the past, from Darwin to Pasteur and from Einstein and Plank to Feynman.
For example, one of the major weapons against cancer, cisplatin, was discovered by two university professors. All together the professors and the university received about a million dollars for their discovery and, I suppose, a gold watch.
The big corporation has held the patent for more than forty hears and has made billions of dollars.
As somebody has pointed out already, the successful collaboration between biologists and physicists is not new in history. Ideally cell biologists, biophysicists and theoretical physicists would be the best combination since metaphysical logicians have been left out out of sheer prejudice about their relevance in this complex study where you will inexorably meet the unavoidable 'irreducible complexity' when dealing with 'life' issues. Been there, done that. I spent the period 1960-63 tracking by the hour the transformation of chick embryo fibroblasts into Rous Sarcoma cells using all the resources (cell cultures, electron microscopy, etc.)of Sloan-Kettering Institute Biophysics Division in Rye, N.Y. I was flabergasted observing how a white inert polynucleotide powder from a test tube would 'diffuse' across the normal, elongated cell membrane and change it into a round malignant, invasive cancer cell! The inert polynucleotide behaved like a truncated life that took over the resources of the cell to become 'animated'! When I lost the labeled polynucleotide from the cytoplasm I realized it was in the nucleus associated with DNA. I wished I had reported the details that later on won a nobel prize for Howard Temin's RNA transcryptase. Dr.d
Reply | Report Abuse | Link to thisThis is such a good news (: I hope we can find an effective way to fight cancer soon,
Reply | Report Abuse | Link to thisDylluvzjc
I was replying to mickeyberman's comment (first comment) by the way and not to the article.
Reply | Report Abuse | Link to thisAs for the article, I agree with h.yamamoto and Dr.d. I would add that the real problem is not collaboration among various specialized fields but the relatively small amount of money that is spent on cancer research itself.
Big Pharma does a very bad job at cancer research, spending most of their "R&D" money on advertising, making me-too drugs and tweaking already existing drugs so that they qualify for an extended patent life. That is, drug companies do only one thing really well: They make a lot of money.
Americans spend almost as much on Viagra and its derivatives as we do on cancer research. When you throw in cigarettes, we spend immensely more on those.
Not to mention war related expenses. Bang!
Amen!
Reply | Report Abuse | Link to thisI am in the teaching business where I discovered that poor teachers are usually subject-specific. More versatile teachers usually find their job easier and more interesting.
Reply | Report Abuse | Link to thisBiology, Chemistry, Physics, and Mathematics are simply knowledge organizational tools in information management. When it comes research, in any field, these boundaries should fall away wherever and whenever they become a hindrance.