— A Biography of Cancer
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Part One: “Of Blacke Cholor, Without Boyling”
Farber’S Gauntlet
Farber’s staff tracked the disease in patients with meticulous attention to detail: every blood count, every transfusion, every fever, was to be recorded. If leukemia was going to be beaten, Farber wanted every minute of that battle recorded for posterity—even if no one else was willing to watch it happen.
A Private Plague
This was not so much a medical history of an illness, but something more personal, more visceral: its biography.
civilization did not cause cancer, but by extending human life spans—civilization unveiled it.
A Radical Idea
The ultimate survival from breast cancer, in short, had little to do with how extensively a surgeon operated on the breast; it depended on how extensively the cancer had spread before surgery.
The Hard Tube And The Weak Light
since X-rays could only be directed locally, radiation was of limited use for cancers that had metastasized.*
The very effect of X-rays killing rapidly dividing cells—DNA damage—also created cancer-causing mutations in genes.
Dyeing And Dying
It is almost—not quite, but almost—as hard as finding some agent that will dissolve away the left ear, say, and leave the right ear unharmed. So slight is the difference between the cancer cell and its normal ancestor.
Specific affinity relied, paradoxically, not on “affinity,” but on its opposite—on difference. Ehrlich’s chemicals had successfully targeted bacteria because bacterial enzymes were so radically dissimilar to human enzymes. With cancer, it was the similarity of the cancer cell to the normal human cell that made it nearly impossible to target.
Poisoning The Atmosphere
Every drug, the sixteenth-century physician Paracelsus once opined, is a poison in disguise. Cancer chemotherapy, consumed by its fiery obsession to obliterate the cancer cell, found its roots in the obverse logic: every poison might be a drug in disguise.
The Goodness Of Show Business
Scientists often study the past as obsessively as historians because few other professions depend so acutely on it. Every experiment is a conversation with a prior experiment, every new theory a refutation of the old.
The campaign against cancer, Farber learned, was much like a political campaign: it needed icons, mascots, images, slogans—the strategies of advertising as much as the tools of science. For any illness to rise to political prominence, it needed to be marketed, just as a political campaign needed marketing. A disease needed to be transformed politically before it could be transformed scientifically.
It set off a seismic transformation in his career that would far outstrip his transformation from a pathologist to a leukemia doctor. This second transformation—from a clinician into an advocate for cancer research—reflected the transformation of cancer itself. The emergence of cancer from its basement into the glaring light of publicity would change the trajectory of this story. It is a metamorphosis that lies at the heart of this book.
The House That Jimmy Built
Upstairs, the clean, well-lit waiting room had whirring carousels and boxes full of toys. A toy electric train, set into a stone “mountain,” chugged on its tracks. A television set was embedded on the face of the model mountain. “If a little girl got attached to a doll,” Time reported in 1952, “she could keep it; there were more where it came from.” A library was filled with hundreds of books, three rocking horses, and two bicycles. Instead of the usual portraits of dead professors that haunted the corridors of the neighboring hospitals, Farber commissioned an artist to paint full-size pictures of fairy-book characters—Snow White, Pinocchio, and Jiminy Cricket. It was Disney World fused with Cancerland.
Part Two: An Impatient War
“They Form A Society”
In 1831, Alexis de Tocqueville, the French aristocrat, toured the United States and was astonished by the obsessive organizational energy of its citizens. “Americans of all ages, all conditions, and all dispositions constantly form associations … of a thousand other kinds—religious, moral, serious, futile, general or restricted, enormous or diminutive,” Tocqueville wrote. “Americans make associations to give entertainments, to found seminaries, to build inns, to construct churches, to diffuse books, to send missionaries to the antipodes… . If it is proposed to inculcate some truth or to foster some feeling by the encouragement of a great example, they form a society.”
Bottom up social forming
“I am opposed to heart attacks and cancer,” she would later tell a reporter, “the way one is opposed to sin.” Mary Lasker chose to eradicate diseases as some might eradicate sin—through evangelism. If people did not believe in the importance of a national strategy against diseases, she would convert them, using every means at her disposal.
So epic
“These New Friends Of Chemotherapy”
Even mathematicians, the archbishops of the arcane, had been packed off to crack secret codes for the military.
For Carla, the physical isolation of those days became a barely concealed metaphor for a much deeper, fiercer loneliness, a psychological quarantine even more achingly painful than her actual confinement.
An Early Victory
Li had stumbled on a deep and fundamental principle of oncology: cancer needed to be systemically treated long after every visible sign of it had vanished.
This strategy—which cost Min Chiu Li his job—resulted in the first chemotherapeutic cure of cancer in adults.
Mice And Men
By charting the life and death of leukemia cells as they responded to drugs in these mice, Skipper emerged with two pivotal findings. First, he found that chemotherapy typically killed a fixed percentage of cells at any given instance no matter what the total number of cancer cells was. This percentage was a unique, cardinal number particular to every drug. In other words, if you started off with 100,000 leukemia cells in a mouse and administered a drug that killed 99 percent of those cells in a single round, then every round would kill cells in a fractional manner, resulting in fewer and fewer cells after every round of chemotherapy: 100,000 … 1,000 … 10 … and so forth, until the number finally fell to zero after four rounds. Killing leukemia was an iterative process, like halving a monster’s body, then halving the half, and halving the remnant half. Second, Skipper found that by adding drugs in combination, he could often get synergistic effects on killing. Since different drugs elicited different resistance mechanisms, and produced different toxicities in cancer cells, using drugs in concert dramatically lowered the chance of resistance and increased cell killing. Two drugs were therefore typically better than one, and three drugs better than two. With several drugs and several iterative rounds of chemotherapy in rapid-fire succession, Skipper cured leukemias in his mouse model.
Vamp
If we didn’t kill the tumor, we killed the patient.
In the folklore of science, there is the often-told story of the moment of discovery: the quickening of the pulse, the spectral luminosity of ordinary facts, the overheated, standstill second when observations crystallize and fall together into patterns, like pieces of a kaleidoscope. The apple drops from the tree. The man jumps up from a bathtub; the slippery equation balances itself. But there is another moment of discovery—its antithesis—that is rarely recorded: the discovery of failure. It is a moment that a scientist often encounters alone.
Such beautiful language
But the story of leukemia—the story of cancer—isn’t the story of doctors who struggle and survive, moving from one institution to another. It is the story of patients who struggle and survive, moving from one embankment of illness to another. Resilience, inventiveness, and survivorship—qualities often ascribed to great physicians—are reflected qualities, emanating first from those who struggle with illness and only then mirrored by those who treat them. If the history of medicine is told through the stories of doctors, it is because their contributions stand in place of the more substantive heroism of their patients.
An Anatomist’S Tumor
Dana-Farber Cancer Institute.
“A Moon Shot For Cancer”
In the past, they had pleaded to the nation for funds for cancer. Now, as they pleaded for the nation for a more coordinated attack on cancer, they found themselves colossally empowered in the public imagination.
Part Three: “Will You Turn Me Out If I Can’T Get Better?”
Knowing The Enemy
“Cancer is not necessarily autonomous and intrinsically self-perpetuating,” Huggins wrote. “Its growth can be sustained and propagated by hormonal function in the host.”
Counting Cancer
Every minor footfall and every infinitesimal step had been so obsessively reported in the media that it had become nearly impossible to discern the trajectory of the field as a whole. In part, Cairns was reacting to the overgranularity of the view from the prior decade. He wanted to pull away from the details and offer a bird’s-eye view.
Same with all fields
As Cairns had already pointed out, the only intervention ever known to reduce the aggregate mortality for a disease—any disease—at a population level was prevention. Even if other measures were chosen to evaluate our progress against cancer, Bailar argued that it was indubitably true that prevention, as a strategy, had been neglected by the NCI in its ever-manic pursuit of cures.
Part Four: Prevention Is The Cure
“Coffins Of Black”
potentially preventable.
But the simplest means of removing the carcinogen was perhaps the most difficult to achieve.
In the turbulent century between 1850 and 1950, the world offered conflict, atomization, and disorientation. The cigarette offered its equal and opposite salve: camaraderie, a sense of belonging, and the familiarity of habits. If cancer is the quintessential product of modernity, then so, too, is its principal preventable cause: tobacco.
The Emperor’S Nylon Stockings
But many epidemiologists argued that such cause-effect relationships could only be established for infectious diseases, where there was a known pathogen and a known carrier (called a vector) for a disease—the mosquito for malaria or the tsetse fly for sleeping sickness. Chronic, noninfectious diseases such as cancer and diabetes were too complex and too variable to be associated with single vectors or causes, let alone “preventable” causes. The notion that a chronic disease such as lung cancer might have a “carrier” of its own sort, to be gilded and hung like an epidemiological trophy on one of those balconies, was dismissed as nonsense.
By charting those changes over nearly a decade, Ford had begun to watch evolution in action. He had documented gradual changes in the color of moth coats (and thus changes in genes), grand fluctuations in populations and signs of natural selection by moth predators—a macrocosm caught in a marsh.*
It was Ford’s student Henry B. D. Kettlewell who used this moth-labeling technique to show that dark-colored moths—better camouflaged on pollution-darkened trees—tended to be spared by predatory birds, thus demonstrating “natural selection” in action.
“A Thief In The Night”
Rather than fussing about the metaphysical idea about causality (what, in the purest sense, constitutes “cause”?), Hill changed its emphasis to a functional or operational idea.
“A Statement Of Warning”
if tobacco sellers had “doubt” to sow into public minds, then tobacco opponents had something just as visceral: fear—in particular, fear of the ultimate illness.
He acknowledged openly that Rose Cipollone was aware of the risks of smoking. Yes, she had read the warning labels on cigarettes and the numerous magazine articles cut out so painstakingly by Tony Cipollone. Yet, unable to harness her habit, she had remained addicted. Cipollone was far from innocent, Edell conceded. But what mattered was not how much Rose Cipollone knew about tobacco risks; what mattered was what cigarette makers knew, and how much of the cancer risk they had revealed to consumers such as Rose.
The influx of annual settlement payments from cigarette makers creates “client-states” that depend on this money to fund escalating medical costs. Indeed, the real cost of the agreement is borne by addicted smokers who now pay more for cigarettes, and then pay with their lives.
It remains an astonishing, disturbing fact that in America—a nation where nearly every new drug is subjected to rigorous scrutiny as a potential carcinogen, and even the bare hint of a substance’s link to cancer ignites a firestorm of public hysteria and media anxiety—one of the most potent and common carcinogens known to humans can be freely bought and sold at every corner store for a few dollars.
“Curiouser And Curiouser”
testing the theory on humans was ethically impossible:
a normal volunteer [has] swallowed a pure culture of the organism,” he wrote). The critics had at last been silenced. Helicobacter pylori was indisputably the cause of gastric inflammation.
“A Spider’S Web”
But since doctors detected Hope’s tumor earlier, it seems, falsely, that she lived longer and that the screening test was beneficial. So our test must now cross an additional hurdle: it must improve mortality, not survival. The only appropriate way to judge whether Hope’s test was truly beneficial is to ask whether Hope lived longer regardless of the time of her diagnosis.
Even relatively small tumors barely detectable by mammography can carry genetic programs that make them vastly more likely to metastasize early. Conversely, large tumors may inherently be genetically benign—unlikely to invade and metastasize. Size matters, in other words—but only to a point. The difference in the behavior of tumors is not just a consequence of quantitative growth, but of qualitative growth. A static picture cannot capture this qualitative growth. Seeing a “small” tumor and extracting it from the body does not guarantee our freedom from cancer—a fact that we still struggle to believe.
Stamp
Cancer therapy is like beating the dog with a stick to get rid of his fleas.—Anna Deavere Smith, Let Me Down Easy
The leukemias that arose from the ashes of chemotherapy-treated marrows carried such grotesque and aberrant mutations that they were virtually resistant to any drugs, as if their initial passage through that fire had tempered them into immortality.
Selection of cells for replicative success and resistence to drugs
The stigmas attached to cancer—guilt, secrecy, shame—were recycled and refitted for AIDS, acquiring tenfold force and potency: sexual guilt, sexual secrecy, sexual shame.
the slow, contemplative “academic” mechanism of drug testing, Kramer groused, was becoming life-threatening rather than lifesaving. Randomized, placebo-controlled trials were all well and good in the cool ivory towers of medicine, but patients afflicted by a deadly illness needed drugs now.
The Map And The Parachute
In an essay titled A View from the Front Line, Jencks described her experience with cancer as like being woken up midflight on a jumbo jet and then thrown out with a parachute into a foreign landscape without a map:
“The white coats are far, far away, strapping others into their parachutes. Occasionally they wave but, even if you ask them, they don’t know the answers. They are up there in the Jumbo, involved with parachutes, not map-making.” The image captured the desolation and desperation of the era. Obsessed with radical and aggressive therapies, oncologists were devising newer and newer parachutes, but with no systematic maps of the quagmire to guide patients and doctors. The War on Cancer was “lost”—in both senses of the word.
in men and women above fifty-five, cancer mortality had increased, while in men and women under fifty-five, cancer mortality had decreased by exactly the same proportion. (Part of the reason for this will become clear below.)
Alterations in the pattern of lung cancer mortality also partially explained the overall age skew of cancer mortality. The incidence of lung cancer was highest in those above fifty-five, and was lower in men and women below fifty-five, a consequence of changes in smoking behavior since the 1950s.
The national stalemate on cancer was hardly a stalemate, but rather the product of a frantic game of death in progress. Bailar had set out to prove that the War on Cancer had reached terminal stagnancy. Instead, he had chronicled a dynamic, moving battle in midpitch against a dynamic, moving target.
Part Five: “A Distorted Version Of Our Normal Selves”
Under The Lamps Of Viruses
if the data did not fit the dogma, then the dogma—not the data—needed to be changed.
“The Hunting Of The Sarc”
Viral src—the cancer-causing gene—was cellular src on overdrive.
Cancer biology’s decades-long hunt had started with a chicken and ended, metaphorically, in the egg—in a progenitor gene present in all human cells.
Science is often described as an iterative and cumulative process, a puzzle solved piece by piece, with each piece contributing a few hazy pixels of a much larger picture. But the arrival of a truly powerful new theory in science often feels far from iterative. Rather than explain one observation or phenomenon in a single, pixelated step, an entire field of observations suddenly seems to crystallize into a perfect whole. The effect is almost like watching a puzzle solve itself.
Curious about such discoveries - evolution, quantum phsysics, emergence etc.?
The Wind In The Trees
Cancer was not disorganized chromosomal chaos. It was organized chromosomal chaos: specific and identical mutations existed in particular forms of cancer.
The Hallmarks Of Cancer
Cancer cells did not activate or inactivate genes at random. Instead, the shift from a premalignant state to an invasive cancer could precisely be correlated with the activation and inactivation of genes in a strict and stereotypical sequence.
Part Six: The Fruits Of Long Endeavors
Drugs Bodies And Proof
“If you start making exceptions and deviating from your protocol,” Debu Tripathy, one of the leaders of the UCSF trial, said, “then you get a lot of patients whose results are not going to help you understand whether a drug works or not. All you’re doing is delaying … being able to get it out into the public.”
A Four Minute Mile
What Bannister proved was that such notions about intrinsic boundaries are mythical. What he broke permanently was not a limit, but the idea of limits. So it was with Gleevec.
The Red Queen’S Race
Entire networks stopped smoking concordantly, like whole circuits flickering off. A family that dined together was also a family that quit together.
Smoking, this model argues, is entwined into our social DNA just as densely and as inextricably as oncogenes are entwined into our genetic material.
Thirteen Mountains
“cancer genome sequencing validates a hundred years of clinical observations. Every patient’s cancer is unique because every cancer genome is unique. Physiological heterogeneity is genetic heterogeneity.” Normal cells are identically normal; malignant cells become unhappily malignant in unique ways.
But the same core pathways were characteristically dysregulated in any tumor type, even if the specific genes responsible for each broken pathway differed from one tumor to the next. Ras may be activated in one sample of bladder cancer; Mek in another; Erk in the third—but in each case, some vital piece of the Ras-Mek-Erk cascade was dysregulated. The bedlam of the cancer genome, in short, is deceptive. If one listens closely, there are organizational principles. The language of cancer is grammatical, methodical, and even—I hesitate to write—quite beautiful.
The cancer optimist, however, argues that thirteen is a finite number. It is a relief: until Vogelstein identified these core pathways, the mutational complexity of cancers seemed nearly infinite.
Atossa’S War
In the end, every biography must also confront the death of its subject.
Science embodies the human desire to understand nature; technology couples that desire with the ambition to control nature. These are related impulses—one might seek to understand nature in order to control it—but the drive to intervene is unique to technology.
The characteristics of Germaine’s personality that had once seemed spontaneous and impulsive were, in fact, calculated and almost reflexive responses to her illness. Her clothes were loose and vivid because they were decoys against the growing outline of the tumor in her abdomen. Her necklace was distractingly large so as to pull attention away from her cancer. Her room was topsy-turvy with baubles and pictures—the hospital pitcher filled with flowers, the cards tacked to the wall—because without them it would devolve into the cold anonymity of any other room in any other hospital. She had dangled her leg at that precise, posed angle because the tumor had invaded her spine and begun to paralyze her other leg, making it impossible to sit any other way. Her casualness was studied, the jokes rehearsed. Her illness had tried to humiliate her. It had made her anonymous and seemingly humorless; it had sentenced her to die an unsightly death in a freezing hospital room thousands of miles away from home. She had responded with vengeance, moving to be always one step ahead, trying to outwit it.