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Authors: Sherwin B Nuland

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BOOK: How We Die
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These days, the Surgeon General’s warning stares out at us from every cigarette ad, and there are not many people who don’t take it seriously. No literate American adult is unaware of the cancer-causing properties of tars and resins, and most understand that those properties arise from the chemical irritation produced in living tissue by constant contact with the noxious substances. But as self-evident as it seems today, the concept that chronic irritation may cause disease was not always appreciated by physicians. At the time when Percivall Pott chose to go beyond mere clinical description of scrotal cancer by stating his conviction that it was the result of a highly specific response to soot, the theory of irritation and inflammation was still on very shaky ground, and indeed most of it was later discarded. Although the sweeps themselves called their malady the “soot-wart,” they seem not to have grasped the idea that cleansing themselves of the grime with an occasional wash might prevent it. They simply accepted as inevitable that a certain number of them would develop the condition and suffer an agonizing death—the risk came with the job.
Pott’s thesis that soot was the instigating cause of the cancer received immediate recognition. It led directly to a parliamentary decree that no chimney sweep might start his apprenticeship before he was eight years old and that all of the boys must be given a bath at least once a week. By 1842, no boy under the age of twenty-one was permitted to climb chimneys. Unfortunately, the law was so often broken that there were still plenty of under-age sweeps when Charles Kingsley was writing
The Water Babies
twenty years later.
As early as the days of Hippocrates and even before, the ancient Greek physicians had a clear understanding of the ways in which a malignant growth so often pursues its inexorable determination to destroy life. They gave a very specific name to the hard swellings and ulcerations they so commonly saw in the breast or protruding from the rectum or vagina; they based that name on the evidence of their eyes and fingers. To distinguish them from ordinary swellings, which they called
oncos
, they used the term
karkinos
, or “crab,” derived, interestingly enough, from an Indo-European root meaning “hard.”
Oma
being a suffix referring to “tumor,”
karkinoma
was used to designate a tumorous growth that was malignant. Centuries later, the Latin word for “crab,”
cancer
, came into common usage.
Oncos
, meantime, came to be applied to tumors of any kind, which is why we call a cancer specialist an oncologist.
Karkinoma
was said to be due to the stagnation within the body of an excess of a hypothetical fluid called black bile, or
melan cholos
(from
melas
, “black” and
chole
, “bile”). Since the Greeks did not dissect the human body, the cancers they saw were ulcerated malignancies of the breast or skin, and those of the rectum and female genital tract which had grown so large that they protruded through body openings. Accordingly, the fanciful explanation was supported by the common observation that cancer patients were indeed melancholy, and for obvious good reason.
The origin of
karkinos
and
karkinoma
was based, as were so many Greek medical terms, on simple observation and touch. As Galen, the foremost interpreter and codifier of Greek medicine, put it in the second century
A.D
., the appearance of this creeping, infiltrating stony mass, ulcerated at its center, which he so often saw in the breasts of women, is “just like a crab’s legs extending outward from every part of its body.” And it is not only the legs that are digging farther and deeper into the flesh of its victim—the center, too, is eroding its way directly through her.
The likeness is to an insidious, groping parasite, attached by sharp-clawed tentacles to the decaying surface of its imperiled prey. The clawing extremities ceaselessly extend the periphery of their malign grip, while the loathsome core of the burrowing beast eats silently away at life, able to digest only what it has first decomposed. The process is noiseless; it has no recognizable instant of beginning and it ends only when the despoiler has consumed the final remnants of its host’s vital forces.
Until after the middle of the nineteenth century, cancer was thought to do its killing by stealth. Its lurking force lay under the cover of hushed darkness, its first sting felt only when murderous infiltration had strangled too much normal tissue to restore the overwhelmed defenses of its host. The perpetrator regurgitated as malignant gangrene the life it had noiselessly chewed up.
We know better now, because we have come to recognize a different personality when our old enemy is seen through the microscope of contemporary science. Cancer, far from being a clandestine foe, is in fact berserk with the malicious exuberance of killing. The disease pursues a continuous, uninhibited, circumferential, barn-burning expedition of destructiveness, in which it heeds no rules, follows no commands, and explodes all resistance in a homicidal riot of devastation. Its cells behave like the members of a barbarian horde run amok—leaderless and undirected, but with a single-minded purpose: to plunder everything within reach. This is what medical scientists mean when they use the word
autonomy
. The form and rate of multiplication of the murderous cells violate every rule of decorum within the living animal whose vital nutrients nourish it only to be destroyed by this enlarging atrocity that has sprung newborn from its own protoplasm. In this sense, cancer is not a parasite. Galen was wrong to call it
praeter naturam
, “outside of nature.” Its first cells are the bastard offspring of unsuspecting parents who ultimately reject them because they are ugly, deformed, and unruly. In the community of living tissues, the uncontrolled mob of misfits that is cancer behaves like a gang of perpetually wilding adolescents. They are the juvenile delinquents of cellular society.
Cancer is best viewed as a disease of altered maturation; it is the result of a multistage process of growth and development having gone awry. Under ordinary conditions, normal cells are constantly being replenished as they die, not only by the reproduction of their younger survivors but also by an actively reproducing group of progenitors called stem cells. Stem cells are very immature forms with enormous potential to create new tissue. In order for the progeny of the stem cells to progress to normal maturity, they must pass through a series of steps. As they get closer to full maturity, they lose their ability to proliferate rapidly in proportion to the increase in their ability to perform the functions for which they are intended as grown-ups. A fully mature cell of the intestinal lining, for example, absorbs nutriments from the cavity of the gut a lot more efficiently than it reproduces; a fully mature thyroid cell is at its best when it secretes hormone, but it is much less inclined to reproduce than it was while younger. The analogy with the social behavior of a whole organism, like us, is inescapable.
A tumor cell is one that has somewhere along the way been stopped in its capacity to
differentiate
, which is the term used by scientists for the process by which cells go through the steps that enable them to reach healthy adulthood. The clump of immature abnormal cells that results from the blocking of differentiation is called a neoplasm, derived from the Greek word for a new growth or formation. In modern times, the word neoplasm is used synonymously with
tumor
. Those tumors whose cells have been blocked closest to the attainment of the mature state are the least dangerous and are therefore called benign. A benign tumor has retained relatively little of its potential for uncontrolled reproduction—it is well differentiated; under the microscope, it looks a lot like the adult it was close to becoming. It grows slowly, does not invade surrounding tissues or travel to other parts of the body, is often surrounded by a distinct fibrous capsule, and almost never has the capacity to kill its host.
A malignant neoplasm—what we call cancer—is a different creature entirely. Some influence or combination of influences, whether genetic, environmental, or otherwise, has acted as the triggering mechanism to interfere so early in the pathway of maturation that the progress of the cells has been stopped at a stage when they still have an infinite capacity to reproduce. Normal stem cells keep trying to produce normal offspring, but their development continues to be arrested. They do not attain a sufficient level of adulthood to do the work they were meant for or to look more than just a little like the grown-up forms they were intended to be. Cancer cells are fixed at an age where they are still too young to have learned the rules of the society in which they live. As with so many immature individuals of all living kinds, everything they do is excessive and uncoordinated with the needs or constraints of their neighbors.
Being not completely grown-up, a cancer cell does not engage in some of the more complicated metabolic activities of mature nonmalignant tissue. A cancer cell of the intestine, for example, doesn’t help out in digestion as its adult counterpart does; a cancer cell of the lung is uninvolved in the process of respiration; the same is true of almost all other malignancies. Malignant cells concentrate their energies on reproduction rather than in partaking in the missions a tissue must carry out in order for the life of the organism to go on. The bastard offspring of their hyperactive (albeit asexual) “fornicating” are without the resources to do anything but cause trouble and burden the hardworking community around them. Like their progenitors, they are reproductive but not productive. As individuals, they victimize a sedate, conforming society.
Cancer cells do not even have the decency to die when they should. All nature recognizes that death is the final step in the process of normal maturation. Malignant cells don’t reach that point—their longevity is not finite. What is true of Dr. Hayflick’s fibroblasts does not apply to the cellular population of a malignant growth. Cancer cells cultivated in the laboratory exhibit an unlimited capacity to grow and generate new tumors. In the words of my research colleagues, they are “immortalized.” The combination of delayed death and uncontrolled birth are malignancy’s greatest violations of the natural order of things. These two factors in combination are the main reasons a cancer, unlike normal tissue, continues to enlarge throughout its lifetime.
Knowing no rules, cancer is amoral. Knowing no purpose other than to destroy life, cancer is immoral. A cluster of malignant cells is a disorganized autonomous mob of maladjusted adolescents, raging against the society from which it sprang. It is a street gang intent on mayhem. If we cannot help its members grow up, anything we can do to arrest them, remove them from our midst, or induce their demise—anything that accomplishes one of those aims—is praiseworthy.
There comes a point at which home turf is not enough—offshoots of the gang take wing, invade other communities, and, emboldened by their unresisted depredations, wreak havoc on the entire commonwealth of the body. But in the end, there is no victory for cancer. When it kills its victim, it kills itself. A cancer is born with a death wish.
Cancer is, in every possible sense, a nonconformist. But, unlike some nonconformist individuals about whom there is much to admire, the nonconforming malignant cell has not a single redeeming feature. It does everything it can not only to disassociate itself from but even to destroy the community of cells that has given it life. As though to make certain that it is not confused with the conformist adult members of its original family, the cancer cell retains an immature and different appearance and even shape. This characteristic of malignant growth is called anaplasia, from the Greek term meaning “without form.” The anaplastic cell gives birth to anaplastic offspring.
But try as it may, only an unusual cancer is composed of cells that have changed their appearance completely enough to become unrecognizable as members of their own original tribe. Except in extreme cases, a careful look down the barrel of a microscope at a bit of the diseased tissue will suffice to reveal its ancestral lineage. Thus, a bowel cancer can be identified as what it is because it still has some characteristic features that betray its intestinal origin. Even far away from home, as when the bloodstream has carried its cells to the liver, the cancer’s face, almost no matter the degree of anaplasia, will usually give it away. Even cancer, that remorseless renegade that ran away to join the biological equivalent of Murder, Inc., retains some dimly recognizable traits of its old family and its old obligations.
The twin characteristics of autonomy and anaplasia define the modern understanding of cancer. Whether they are to be thought of as “ugly, deformed, and unruly” or more academically as “anaplastic” and “autonomous,” the cells of a cancer are wicked in ways far beyond what is implied by the scientific connotation of the word
malignant. Malevolent
, in fact, says it better, because it bears the implication of an element of ill will.
The deformity and ugliness of the individual cancer cell are most manifest in the irregularities of its distorted shape. Whereas the appearance of a normal cell in normal tissue differs hardly at all from that of its normal neighbors, the forms and dimensions of the individuals in a cancer’s cellular population are usually neither uniform nor orderly. They may bulge, flatten, elongate, round themselves out, or in some other way demonstrate that each is created as though with a mind of its own—it is an independent agent. Cancer is a state in which a breakdown has occurred in the communication and mutual interdependence between cells. That sequence of events noted above has taken place, in which the genetic characteristics of the malignant cell become altered, and everything else about the disease follows from that fact. Some of the environmental, lifestyle, and other causes of the alterations are known, some are being studied, and some are no doubt still unsuspected.
BOOK: How We Die
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