The Emperor of All Maladies: A Biography of Cancer (84 page)

In a broader sense, the Red Queen syndrome—moving incessantly just to keep in place—applies equally to every aspect of the battle against cancer, including cancer screening and cancer prevention. In the early winter of 2007, I traveled to Framingham in Massachusetts to visit a study site that will likely alter the way we imagine cancer prevention. A small, nondescript Northeastern town bound by a chain of frozen lakes in midwinter, Framingham is nonetheless an iconic place writ large in the history of medicine.
In 1948, epidemiologists identified a cohort
of about five thousand men and women living in Framingham. The behavior of this cohort, its habits, its interrelationships, and its illnesses, has been documented year after year in exquisite detail, creating an invaluable longitudinal corpus of data for hundreds of epidemiological studies. The English mystery writer Agatha Christie often used a fictional village, St. Mary Mead, as a microcosm of all mankind. Framingham is the American epidemiologist’s English village. Under sharp statistical lenses, its captive cohort has lived, reproduced, aged, and died, affording a rare glimpse of the natural history of life, disease, and death.

The Framingham data set has spawned a host of studies on risk and illness. The link between cholesterol and heart attacks was formally established here, as was the association of stroke and high blood pressure. But
recently, a conceptual transformation in epidemiological thinking has also been spearheaded here. Epidemiologists typically measure the risk factors for chronic, noninfectious illnesses by studying the behavior of individuals. But recently, they have asked a very different question: what if the real locus of risk lies not in the behaviors of individual actors, but in social
networks
?

In May 2008, two Harvard epidemiologists
, Nicholas Christakis and James Fowler, used this notion to examine the dynamics of cigarette smoking. First, Fowler and Christakis plotted a diagram of all known relationships in Framingham—friends, neighbors, and relatives, siblings, ex-wives, uncles, aunts—as a densely interconnected web. Viewed abstractly, the network began to assume familiar and intuitive patterns. A few men and women (call them “socializers”) stood at the epicenter of these networks, densely connected to each other through multiple ties. In contrast, others lingered on the outskirts of the social web—“loners”—with few and fleeting contacts.

When the epidemiologists juxtaposed smoking behavior onto this network and followed the pattern of smoking over decades, a notable phenomenon emerged: circles of relationships were found to be more powerful predictors of the dynamics of smoking than nearly any other factor. Entire networks stopped smoking concordantly, like whole circuits flickering off. A family that dined together was also a family that quit together. When highly connected “socializers” stopped smoking, the dense social circle circumscribed around them also slowly stopped as a group. As a result, smoking gradually became locked into the far peripheries of all networks, confined to the “loners” with few social contacts, puffing away quietly in the distant and isolated corners of the town.

The smoking-network study offers, to my mind, a formidable challenge to simplistic models of cancer prevention. Smoking, this model argues, is entwined into our social DNA just as densely and as inextricably as oncogenes are entwined into our genetic material. The cigarette epidemic, we might recall, originated as a form of metastatic behavior—one site seeding another site seeding another. Soldiers brought smoking back to postwar Europe; women persuaded women to smoke; the tobacco industry, sensing opportunity, advertised cigarettes as a form of social glue that would “stick” individuals into cohesive groups. The capacity of metastasis is thus built into smoking. If entire networks of smokers can flicker off with catalytic speed, then they can also flicker on with catalytic speed. Sever the ties that bind the nonsmokers of Framingham (or worse, nucleate a large
social network with a proselytizing smoker), and then, cataclysmically, the network might alter as a whole.

This is why even the most successful cancer-prevention strategies can lapse so swiftly. When the Red Queen’s feet stop spinning even temporarily, she does not maintain her position; the world around her, counter-spinning, pushes her off-balance. So it is with cancer prevention. When antitobacco campaigns lose their effectiveness or penetrance—as has recently happened among teens in America or in Asia—smoking often returns like an old plague. Social behavior metastasizes, eddying out from its center toward the peripheries of social networks. Mini-epidemics of smoking-related cancers are sure to follow.

The landscape of carcinogens is not static either. We are chemical apes: having discovered the capacity to extract, purify, and react molecules to produce new and wondrous molecules, we have begun to spin a new chemical universe around ourselves. Our bodies, our cells, our genes are thus being immersed and reimmersed in a changing flux of molecules—pesticides, pharmaceutical drugs, plastics, cosmetics, estrogens, food products, hormones, even novel forms of physical impulses, such as radiation and magnetism. Some of these, inevitably, will be carcinogenic. We cannot wish this world away; our task, then, is to sift through it vigilantly to discriminate bona fide carcinogens from innocent and useful bystanders.

This is easier said than done. In 2004, a rash of early scientific reports suggested that cell phones, which produce radio frequency energy, might cause a fatal form of brain cancer called a glioma. Gliomas appeared on the same side of the brain that the phone was predominantly held, further tightening the link. An avalanche of panic ensued in the media. But was this a falsely perceived confluence of a common phenomenon and a rare disease—phone usage and glioma? Or had epidemiologists missed the “nylon stockings” of the digital age?

In 2004, an enormous British study was launched to confirm these ominous early reports. “Cases”—patients with gliomas—were compared to “controls”—men and women with no gliomas—in terms of cell phone usage. The study, reported in 2006, appeared initially to confirm an increased risk of right-sided brain cancers in men and women who held their phone on their right ear. But when researchers evaluated the data meticulously, a puzzling pattern emerged: right-sided cell phone use
reduced
the risk of
left-sided
brain cancer. The simplest logical explanation for this phenomenon was “recall bias”: patients diagnosed with tumors
unconsciously exaggerated the use of cell phones on the same side of their head, and selectively forgot the use on the other side. When the authors corrected for this bias, there was no detectable association between gliomas and cell phone use overall. Prevention experts, and phone-addicted teenagers, may have rejoiced—but only briefly. By the time the study was completed, new phones had entered the market and swapped out old phones—making even the negative results questionable.

The cell phone case is a sobering reminder of the methodological rigor needed to evaluate new carcinogens. It is easy to fan anxiety about cancer. Identifying a true preventable carcinogen, estimating the magnitude of risk at reasonable doses and at reasonable exposures, and reducing exposure through scientific and legislative intervention—keeping the legacy of Percivall Pott alive—is far more complex.

“
Cancer at the
fin de siècle,
” as the oncologist Harold Burstein described it, “resides at the interface between society and science.” It poses not one but two challenges. The first, the “biological challenge” of cancer, involves “harnessing the fantastic rise in scientific knowledge . . . to conquer this ancient and terrible illness.” But the second, the “social challenge,” is just as acute: it involves forcing ourselves to confront our customs, rituals, and behaviors. These, unfortunately, are not customs or behaviors that lie at the peripheries of our society or selves, but ones that lie at their definitional cores: what we eat and drink, what we produce and exude into our environments, when we choose to reproduce, and how we age.

“Every sickness

is a musical problem
,”

so said Novalis,

“and every cure

a musical solution.”

—W. H. Auden

The revolution in cancer research
can be summed up in a single sentence: cancer is, in essence, a genetic disease.

—Bert Vogelstein

When I began writing this book, in the early summer of 2004, I was often asked how I intended to end it. Typically, I would dodge the question or brush it away. I did not know, I would cautiously say. Or I was not sure. In truth, I was sure, although I did not have the courage to admit it to myself. I was sure that it would end with Carla’s relapse and death.

I was wrong. In July 2009, exactly five years after I had looked down the microscope into Carla’s bone marrow and confirmed her first remission, I drove to her house in Ipswich, Massachusetts, with a bouquet of flowers. It was an overcast morning, excruciatingly muggy, with a dun-colored sky that threatened rain but would not deliver any. Just before I left the hospital, I glanced quickly at the first note that I had written on Carla’s admission to the hospital in 2004. As I had written that note, I recalled with embarrassment, I had guessed that Carla would not even survive the induction phase of chemotherapy.

But she had made it; a charring, private war had just ended. In acute leukemia, the passage of five years without a relapse is nearly synonymous with a cure. I handed her the azaleas and she stood looking at them speechlessly, almost numb to the enormity of her victory. Once, earlier this year, preoccupied with clinical work, I had waited two days before calling her about a negative bone marrow biopsy. She had heard from a nurse that the results were in, and my delay had sent her into a terrifying spiral of depression: in twenty-four hours she had convinced herself that the leukemia had crept back and my hesitation was a signal of impending doom.

Oncologists and their patients are bound, it seems, by an intense subatomic force. So, albeit in a much smaller sense, this was a victory for me as well. I sat at Carla’s table and watched her pour a glass of water for herself, unpurified and straight from the sink. She glowed radiantly, her eyes half-closed, as if the compressed autobiography of the last five years were flashing through a private and internal cinema screen. Her children played with their Scottish terrier in the next room, blissfully oblivious of the landmark date that had just passed for their mother. All of this was for the best. “
The purpose of my book
,” Susan Sontag concluded in
Illness as Metaphor
, “was to calm the imagination, not to incite it.” So it was with my visit. Its purpose was to declare her illness over, to normalize her life—to sever the force that had locked us together for five years.

I asked Carla how she thought she had survived her nightmare. The drive to her house from the hospital that morning had taken me an hour and a half through a boil of heavy traffic. How had she managed, through the long days of that dismal summer, to drive to the hospital, wait in the room for hours as her blood tests were run, and then, told that her blood counts were too low for her to be given chemotherapy safely, turn back and return the next day for the same pattern to be repeated?

“There was no choice,” she said, motioning almost unconsciously to the room where her children were playing. “My friends often asked me whether I felt as if my life was somehow made abnormal by my disease. I would tell them the same thing: for someone who is sick, this
is
their new normal.”

Until 2003, scientists knew that the principal distinction between the “normalcy” of a cell and the “abnormalcy” of a cancer cell lay in the accu
mulation of genetic mutations—
ras, myc, Rb, neu
, and so forth—that unleashed the hallmark behaviors of cancer cells. But this description of cancer was incomplete. It provoked an inevitable question: how many such mutations does a real cancer possess in total? Individual oncogenes and tumor suppressors had been isolated, but what was the comprehensive set of such mutated genes that exists in any true human cancer?

The Human Genome Project
, the full sequence of the normal human genome, was completed in 2003. In its wake comes a far less publicized but vastly more complex project: fully sequencing the genomes of several human cancer cells. Once completed, this effort, called
the Cancer Genome Atlas
, will dwarf the Human Genome Project in its scope. The sequencing effort involves dozens of teams of researchers across the world. The initial list of cancers to be sequenced includes brain, lung, pancreatic, and ovarian cancer. The Human Genome Project will provide the normal genome, against which cancer’s abnormal genome can be juxtaposed and contrasted.

The result, as Francis Collins, the leader of the Human Genome Project describes it, will be a “colossal atlas” of cancer—a compendium of every gene mutated in the most common forms of cancer: “
When applied to the 50 most common
types of cancer, this effort could ultimately prove to be the equivalent of more than 10,000 Human Genome Projects in terms of the sheer volume of DNA to be sequenced. The dream must therefore be matched with an ambitious but realistic assessment of the emerging scientific opportunities for waging a smarter war.” The only metaphor that can appropriately describe this project is geological. Rather than understand cancer gene by gene, the Cancer Genome Atlas will chart the entire territory of cancer: by sequencing the entire genome of several tumor types,
every
single mutated gene will be identified. It will represent the beginnings of the comprehensive “map” so hauntingly presaged by Maggie Jencks in her last essay.