Don't care how they do it, just kill it!

From his fourth-floor window at Tampa's Moffitt Cancer Center, Robert A. Gatenby can look down to where patients stand waiting for valets to retrieve their cars. They have gone through chemotherapy, biopsies, radiation. They are pale, anxious, resolute. Some will live and some will die: a young woman with short hair, clutching her partner's hand; an older man, alone. Students from the nearby University of South Florida pop out of patients' cars. Peppy and dressed in blue vests, these cheerful valets look as if they could be working at a luxury hotel in the tropics. But nobody here is on vacation.
Gatenby says he sometimes sees patients retching after chemotherapy, which reminds the 62-year-old radiologist that his Integrated Mathematical Oncology Department—the only full-scale outfit of its kind in the nation—does not have the luxury of time. Mathematics is not generally known for urgency. Few lives hinge on proof of the twin prime conjecture, but the mathematicians and oncologists Gatenby has assembled in Tampa are trying to tame the chaos of cancer in part through the same differential equations that have tortured so many generations of calculus students. By mathematically modeling cancer, they hope to solve it, to make its movements as predictable as those of a hurricane. The patients down there, fresh from treatment, need shelter from the storm.
Gatenby's small corner of Moffitt bears little resemblance to a medical center: There are no white-coated doctors frantically rushing to save patients or synthesizing miracle cures deep into the night. You might think you've found yourself in a sleepy academic department where abstract ideas are kicked around like a soccer ball on the college green. Which, come to think of it, is actually a pretty accurate description of what goes on in Gatenby's lab, though not at all a pejorative one. The mathematicians in his employ are convinced that we do not really understand cancer and that, until we do, our finest efforts will be tantamount to swinging swords in utter darkness. As far as these Tampa iconoclasts are concerned, your average cancer doctor is trying to build a jetliner without having grasped aerodynamics: Say, how many wings should we slap on this thing?
A Malicious Green Cloud
We have been fighting the War on Cancer since 1971, when President Richard M. Nixon declared that the "time has come in America when the same kind of concentrated effort that split the atom and took man to the moon should be turned toward conquering this dread disease." Four decades later, 1,665,540 Americans per year hear the dreaded diagnosis, and about 585,720 die annually from some variety of the disease, according to the American Cancer Society. Smallpox and polio have been cured or largely eradicated, but cancer remains the same scourge it was 4,500 years ago, when the Egyptian doctor Imhotep mused, in what may have been civilization's first stab at oncology, about how to treat "bulging masses on [the] breast." Modern oncology makes incremental advances, with a melanoma drug that extends survival by three months passing for a major breakthrough. This is nobody's fault, but everybody's problem.
Gatenby is tired of a fight we keep losing. After 30 years, he has come to the uneasy conclusion that cancer is smarter than we are, and will find ways to evade our finest medical weaponry. The weary warrior wants to make peace with cancer's insurgent cells—though on his own terms, terms that would spare the lives of many more patients. To some within the medical establishment, this might seem preposterous, but Gatenby relishes the role of the outsider.
Gatenby grew up in the Rust Belt town of Erie, Pa., where 12 years of Catholic school instilled in him "an incredible hatred of dogma." At Princeton University, he studied physics with some of the greatest scientific minds of the 20th century. Figuring he wasn't fated to join the physics pantheon, Gatenby turned to medicine. But medical school at the University of Pennsylvania was dismayingly similar "to the rote learning of catechism" he remembered from Saint Luke School. It felt like he was "going backwards."
Whether in the lab, the classroom or the clinic, Western medicine relies on cautious experimentation, its zeal for breakthroughs tempered by the Hippocratic injunction to do no harm. But that can foster a frustrating incrementalism that is itself injurious. David B. Agus, one of the nation's most prominent oncologists and a professor at the University of Southern California, explains that "you are not rewarded, in general, for taking risk. It's very scary to do something radically new."
Gatenby specialized in radiology and, after receiving his medical degree in 1977 and completing a residency, went to work in 1981 for the Fox Chase Cancer Center in Philadelphia. Fox Chase is to cancer research what the Boston Garden was to professional basketball. It was home to David A. Hungerford, one of two researchers responsible for discovering the Philadelphia Chromosome, a major clue to cancer's birth within the human genome. Among its current √©minences grises is Alfred G. Knudson Jr., whose "two-hit" hypothesis holds that cancer is triggered by an unfortunate accumulation of errant genes, harmful outside events (too much sun, too much red meat) or a combination of the two.
The study of genes did not interest Gatenby back then, nor does it interest him now, even though much of medicine is now in the thrall of genomics. Gatenby wanted to discover cancer's "first principles," the basic ideas behind the seemingly sudden explosion of cells that want to kill the very body that nourishes them. Sure, you could know the BRCA1 gene better than you know your own mother, but unless you had some insight into why it caused a furiously impervious breast cancer, you were trying to find your way out of a forest by studying the bark of a single tree. Gatenby sought to understand cancer with the same totality that Newton had understood gravity.
As with Newton's famous laws of motion, mathematics seemed to hold the key. Math had been used to model the weather and financial markets, which like the human body are fickle and incredibly sensitive to outside forces (a run on Greek banks; a low-pressure system moving down from Canada). Gatenby saw no reason the same could not hold true for cancer. He spent a year reading math, which puzzled his colleagues. Then, while visiting the Cloisters museum in upper Manhattan with his family, he took a sheet of stationery and started scratching down equations he thought could get him closer to cancer's fundamental truths.
"To say they hated it would not do justice," Gatenby says of the response of his Fox Chase colleagues. Other oncologists told him that "math modeling is for people too lazy to do the experiment" and that "cancer is too complicated to model." The latter is a refrain that, 30 years later, still dogs Gatenby and his staff at the Integrated Mathematical Oncology Department, which includes five mathematicians with no formal experience in medicine.
Among those five is Sandy Anderson, a young Scotsman who dresses as if he were on the way to a Beck concert. There is a bottle of single malt on his desk. "Of course cancer is complex," Anderson tells me, brogue rising. "But how can you say it's too complex? That complexity should be viewed as a challenge that we have to try and tackle. And just because there's complexity doesn't mean there aren't simple rules underlying it.
"What we'd love to do is have everybody's own little hurricane model for their cancer," he explains. This is less a metaphor than you may imagine. Anderson shows me computer models of a breast cancer's growth, the cells spreading like a malicious green cloud across the screen. Different versions of the model show what happens when different treatments are applied: Sometimes the cancer slows, but sometimes it explodes. This seems like an intuitively rational approach to the disease, predicting how it responds to a variety of treatments. But it isn't common. There are about a dozen drugs for breast cancer approved by the Food and Drug Administration. Depending on which form of the disease is diagnosed and at what stage it's discovered, there's a maddening number of viable drug combinations. Best practices exist, but these can be anecdotal, doctors simply doing what they think works. The War on Cancer is fought by competing bands with their own weapons, cancer's chaos exacerbated by our own dismaying disorder. Anderson would like to provide the onco-soldiers with battlefield maps.
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