The Gene: An Intimate History
Quotes from the Book
The art of medicine is long, Hippocrates tells us, "and life is short; opportunity fleeting; the experiment perilous; judgment flawed.
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.
But the story of leukemia--the story of cancer--isn't the story of doctors who struggle and survive, moving from institution to another. It is the story of patients who struggle and survive, moving from on 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.
Cancer was not disorganized chromosomal chaos. It was organized chromosomal chaos
In God we trust. All others [must] have data. - Bernard Fisher
Down to their innate molecular core, cancer cells are hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves.
Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing. —Voltaire
In 2005, a man diagnosed with multiple myeloma asked me if he would be alive to watch his daughter graduate from high school in a few months. In 2009, bound to a wheelchair, he watched his daughter graduate from college. The wheelchair had nothing to do with his cancer. The man had fallen down while coaching his youngest son's baseball team.
This was yet another colonial fascination: to create the conditions of misery in a population, then subject it to social or medical experimentation.
One swallow is a coincidence, but two swallows make summer.
The daughter of Lithuanian immigrants, born with a precocious scientific intellect and a thirst for chemical knowledge, Elion had completed a master's degree in chemistry from New York University in 1941 while teaching high school science during the day and preforming her research for her thesis at night and on the weekends. Although highly qualified, talented, and driven, she had been unable to find a job in an academic laboratory. Frustrated by repeated rejections, she had found a position as a supermarket product supervisor. When Hitchings found Trudy Elion, who would soon become on of the most innovative synthetic chemists of her generation (and a future Nobel laureate), she was working for a food lab in New York, testing the acidity of pickles and the color of egg yolk going into mayonnaise. Rescued from a life of pickles and mayonnaise…
Cancer's life is a recapitulation of the body's life, its existence a pathological mirror of our own.
In the laboratory, we call this the six-degrees-of-separation-from-cancer rule: you can ask any biological question, no matter how seemingly distant—what makes the heart fail, or why worms age, or even how birds learn songs—and you will end up, in fewer than six genetic steps, connecting with a proto-oncogene or tumor suppressor.
It was Disney World fused with Cancerland.
All cancers are alike but they are alike in a unique way.
How can one capture genes that behave like ghosts," Weinberg wrote, "influencing cells from behind some dark curtain?
This was the tenth month of my "fellowship" in oncology - a two-year immersive medical program to train cancer specialists - and I felt as if I had gravitated to my lowest point. In those ten indescribably poignant and difficult months, dozens of patients in my care had died. I felt as if I was slowly becoming inured to the deaths and the desolation - vaccinated against the constant emotional brunt.
Cancer is an expansionist disease; it invades through tissues, sets up colonies in hostile landscapes, seeking “sanctuary” in one organ and then immigrating to another. It lives desperately, inventively, fiercely, territorially, cannily, and defensively—at times, as if teaching us how to survive. To confront cancer is to encounter a parallel species, one perhaps more adapted to survival than even we are.
Specificity refers to the ability of any medicine to discriminate between its intended target and its host. Killing a cancer cell in a test tube is not a particularly difficult task: the chemical world is packed with malevolent poisons that, even in infinitesimal quantities, can dispatch a cancer cell within minutes. The trouble lies in finding a selective poison—a drug that will kill cancer without annihilating the patient. Systemic therapy without specificity is an indiscriminate bomb. For an anticancer poison to become a useful drug, Meyer knew, it needed to be a fantastically nimble knife: sharp enough to kill cancer yet selective enough to spare the patient.
I had a novice's hunger for history, but also a novice's inability to envision it.
That this seemingly simple mechanism—cell growth without barriers—can lie at the heart of this grotesque and multifaceted illness is a testament to the unfathomable power of cell growth. Cell division allows us as organisms to grow, to adapt, to recover, to repair—to live. And distorted and unleashed, it allows cancer cells to grow, to flourish, to adapt, to recover, and to repair—to live at the cost of our living. Cancer cells can grow faster, adapt better. They are more perfect versions of ourselves.
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: "There you are, the future patient, quietly progressing with other passengers toward a distant destination when, astonishingly (Why me?) a large hole opens in the floor next to you. People in white coats appear, help you into a parachute and — no time to think — out you go. "You descend. You hit the ground....But where is the enemy? What is the enemy? What is it up to?...No road. No compass. No map. No training. Is there something you should know and don't? "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.
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.
Indeed, cancer’s emergence in the world is the product of a double negative: it becomes common only when all other killers themselves have been killed.
In Lewis Carroll’s Through the Looking-Glass, the Red Queen tells Alice that the world keeps shifting so quickly under her feet that she has to keep running just to keep her position. This is our predicament with cancer: we are forced to keep running merely to keep still.
Emblematic of this era was the prolific Viennese surgeon Theodor Billroth. Born in 1821, Billroth studied music and surgery with almost equal verve. (The professions still often go hand in hand. Both push manual skill to its limit; both mature with practice and age; both depend on immediacy, precision, and opposable thumbs.)
Cancer thus exploits the fundamental logic of evolution unlike any other illness. If we, as a species, are the ultimate product of Darwinian selection, then so, too, is this incredible disease that lurks inside us.
In 2010, about six hundred thousand Americans, and more than 7 million humans around the world, will die of cancer. In the United States, one in three women and one in two men will develop cancer during their lifetime. A quarter of all American deaths, and about 15 percent of all deaths worldwide, will be attributed to cancer. In some nations, cancer will surpass heart disease to become the most common cause of death.
Every era casts illness in its own image. Society, like the ultimate psychosomatic patient, matches its medical afflictions to its psychological crises; when a disease touches such a visceral chord, it is often because that chord is already resonating.
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About Siddhartha Mukherjee
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The Gene: An Intimate History
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