Authors: Dan Fagin
Mystery and dread have always been the close consorts of cancer. The disease’s causes and progression have never been well understood, and its prognosis (at least until recently) has typically been dire. Cancer is older than humanity: In a Kenyan lakebed in 1932, anthropologist Louis Leakey found a fossilized lower jaw of a hominid ancestor, possibly
Homo erectus
or
Australopithecus
, that included a malignant bone tumor. A tumor has even been discovered in a dinosaur bone at least a hundred and fifty million years old.
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The oldest surviving description of cancer is a papyrus from approximately 1700 B.C. but is probably a copy of a document at least a thousand years older. The fifteen-foot scroll, stolen from Thebes by tomb raiders in 1862 and sold to an American adventurer named Edwin Smith, includes a description of an attempt to treat tumors of the breast with a cauterizing “fire drill.” For “bulging tumors,” the scroll’s anonymous author notes, “there is no treatment.”
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The Greeks fared no better. While surgical removal of tumors was sometimes tried in ancient Egypt and India, Hippocrates preferred diets that were supposed to reduce “black bile” and restore the body’s “humoral balance.” But after watching his diets and more aggressive treatments fail, Hippocrates wrote in
Aphorisms
, “It is better to give no treatment to cases of hidden [internal] cancer; treatment causes speedy death, but to omit treatment is to prolong life.”
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Hippocrates did make one lasting contribution by observing that bulbous tumors, especially when encircled by veins, looked like crabs. He used the Greek words
carcinos
and
carcinoma
, derived from the word
karkinos
,
or crab, to describe the condition. Celsus, the venerated Roman physician whom Paracelsus boasted of surpassing, translated that to
cancer
, the Latin word for crab.
The description fit, not only because of the shape of the solid tumors but also because of seemingly inexorable nature of cancer’s progression. “Cancer the Crab lies so still that you might think he was asleep if you did not see the ceaseless play and winnowing motion of the feathery branches round his mouth,” Rudyard Kipling wrote in an 1891 story, “The Children of the Zodiac.” “That movement never ceases. It is like the eating of a smothered fire into rotten timber in that it is noiseless and without haste.”
The ancient healers were flummoxed by cancer for the same reasons that stymie present-day researchers. Tumors are as diverse as the sixty bodily organs in which they can arise. Some grow slowly, while others spread with stunning rapidity, often by hitching a ride in the bloodstream to other parts of the body, the process known as metastasis. Some are hardened masses that distend the skin, while others are buried deep in the body cavity. A few types of cancer, including leukemias, rarely form tumors at all unless they have metastasized to other organs. Most frustrating of all, various cancers respond very differently to treatments. Despite Hippocrates’ attempt at a unifying taxonomy, it turns out that cancer is not one disease but many—more than 150, by most definitions. Their only common characteristic is supercharged cell division, growth run amok.
The first person to grasp the essential nature of cancer was another irascible, opinionated man of science: Rudolf Ludwig Karl Virchow. A diminutive, humorless, and hyperkinetic German born in 1821, Virchow was a physician who also made important contributions in an astonishing number of other fields, including anthropology, paleontology, and the biology of parasitic worms. In his spare time, he designed the Berlin sewer system and helped to excavate ancient Troy.
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His chief fault was Paracelsian self-confidence, which made him reluctant to accept ideas he did not originate, including the two most important of his lifetime: Louis Pasteur’s germ theory and Charles Darwin’s theory of universal common descent via natural selection. A fiery liberal who manned the Berlin barricades during the
failed revolution of 1848 and was later a leading reformer in the German parliament, Virchow believed that social progress came through vigorous observation and testing, not abstract theory. “Medicine is a social science,” he declared in
Die Medizinische Reform
(The Medical Reformation), a radical newspaper he published during the tumult of 1848, “and politics is nothing else but medicine on a large scale.”
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A prodigy who could read Latin and Greek by age twelve, Virchow became fascinated with microscopes soon after choosing medicine for a career. While still in medical school, he began conducting microscopic examinations of diseased tissue, something almost no one else was doing at the time. His medical approach was as radical as his politics because, even as late as the mid-nineteenth century, the humoral theories of Hippocrates still held sway and illnesses were regarded as mere indicators of the same underlying problem: a bodily imbalance of blood, yellow bile, black bile, and phlegm. That is not what Virchow saw in his microscope. He saw groupings of diseased cells in bodies that were otherwise healthy. Diseases, he reasoned, were not signs of an organism out of balance. Instead, they were distinct, specific processes that could be monitored through close observation of aberrant cells under the microscope. Thus was born the science of microscopic pathology, the essential discipline of modern medicine, which Virchow championed for the rest of his long and extraordinarily productive life.
Others had previously suggested that the cell was the basic unit of life, but Virchow was the first to propose that it was also the basic unit of disease.
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An epigram he popularized but did not originate,
omnis cellula e cellula
(all cells arise from cells), therefore meant that cell division must be the means by which illnesses spread inside the body. Pathological processes begin, he reasoned, when a healthy cell malfunctions under the influence of some outside force. Virchow erred in rejecting Pasteur’s idea that the outside disruptor could be a living microorganism, a germ. Actually, both men were partly correct: Some diseases were microbial in origin and others were not, but almost all involved the disruption of cells in specific parts of an otherwise healthy body. With their separate insights, Virchow and his rival Pasteur drove a stake through the heart of classical humorism, finishing
what Paracelsus had started in Basel more than three hundred years earlier.
Cancer fit neatly into Virchow’s ideas about the cellular nature of disease, and his close observations of malignant cells helped him form his theories. In 1845, two years out of medical school, he was the first to observe that some sick patients had far too many white cells in their blood and too few platelets and red blood cells. He coined the word
leukemia
to describe their condition because it meant “white blood” in Greek. Later, he noticed that a swollen lymph node above the left collarbone—now known as Virchow’s node—was often an early sign of cancer, an indicator still used by physicians today. Virchow poured all of his ideas and observations about cancer into an eighteen-hundred-page, three-volume work entitled
Die Krankhaften Geschwülste
(The Malignant Neoplasms), published in 1863. Many of his core beliefs have been vindicated, including the cellular nature of cancer, the central role of rapid cell division in its development, and the importance of an initiating event, an “irritation,” to begin the process by disrupting a previously healthy cell. As Virchow aged, his irritation theory fell out of favor and researchers drifted toward competing theories of carcinogenesis. He died in 1902, at age eighty—too soon to see his ideas return to vogue, and in variations that even someone with Virchow’s remarkable foresight could not have anticipated.
One of the many reasons the discovery of a malignant tumor in a child is so emotionally wrenching is that it is so surprising. Cancer is, in the main, an affliction of the elderly. In any given year, a person over age sixty-five in the United States is almost ten times more likely to be diagnosed with cancer than someone younger.
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In fact, between ages five and sixty-nine, the likelihood of getting cancer in any particular year rises with each year of life, and it does so in increasingly large intervals: from about one in nine thousand in the fifth year of life to about one in fifty-seven in the sixty-ninth year. There seem to be many reasons for this: complex molecular changes that occur in the cells of older organisms, immune deficiencies associated with aging, and the many years and intricate biochemical steps required before some types of tumors (prostate lesions, for example) can begin growing.
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And yet, about thirty-eight times a day in the United States, and perhaps eight hundred times elsewhere on Earth, a child is diagnosed with cancer. That is still a rare occurrence, with fewer than one in six thousand American children diagnosed per year, but not as rare as it used to be. Childhood cancer incidence jumped by more than one-third between 1975 and 2005—more than twice as much as overall cancer incidence.
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Improved case reporting and earlier diagnosis explain some portion of the overall increase but do not explain why cancer cases among children are rising at a much faster pace than cancers in adults. Nor has science credibly explained why a child would get an old person’s disease in the first place.
For Michael Gillick’s parents, the diagnosis of neuroblastoma, a cancer of the nervous system, was a thunderbolt from a cloudless sky, a sucker punch from the blind side. They were on the floor before they even knew what hit them. A week after his father discovered the first lump, three-month-old Michael was strapped down on an operating table at New York Hospital in Manhattan. A surgeon made an incision from his neck to his groin and tried to remove a softball-sized tumor that had enveloped Michael’s left kidney and adrenal gland and the blood vessels near his heart. When the discouraged surgeon realized that the tumor was far too large to be safely cut out, especially in light of Michael’s sky-high blood pressure (170 over 100, instead of the normal 70 over 50 for an infant), the doctor sewed him back up, noting on his way out that the cancer had spread to the liver and lymph nodes. Michael, the surgeon told his stunned parents, had a 50 percent chance of reaching his first birthday. A cure was unlikely (at the time, the long-term survival rate for metastatic neuroblastoma was only about 5 percent), but aggressive chemotherapy might buy him some time.
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Michael’s cancer, like most others, was named for the cells where the malignant transformation began. Neuroblasts are one of the everyday miracles of fetal development, primitive stem cells that form during the first days of an embryo’s existence and gradually transform into neurons, or nerve cells. In most of us, neuroblasts do their job and then quietly retire, occasionally stirring again to supply additional neurons when needed. But Michael’s neuroblasts never
stopped running at top speed. While he was still in the womb, they started to divide frenetically, clumping together in fast-growing tumors that first formed in his adrenal glands but could appear in any organ with nerve cells, including his eyes, spine, and brain. The cancer was named in 1910 after its origin in neuroblasts was confirmed, but Rudolf Virchow was the first to describe it, in 1864, based on a case description of a child with a large abdominal tumor. Michael’s cancer probably began in the first weeks of his mother’s pregnancy. A year later, the tumors were large enough to compress many of his vital organs, including his heart, lungs, spine, bowels, eyes, and brain. They also distorted Michael’s facial features, transforming his countenance from Raphaelite cherub to something much more abstract.
By themselves, the symptoms of neuroblastoma were more than sufficient to kill Michael, but now he also had to face the horrific side effects of chemotherapy and high-dose steroid treatments, including chronic diarrhea and vomiting, severely stunted growth, a hypersensitive stomach, pounding headaches, brittle bones, and collapsed veins. It was all too much for the Gillicks, and after weeks of chemotherapy failed to slow the growth of the main abdominal tumor, they decided to take Michael home. When he turned six months old, his family celebrated Michael’s first birthday, assuming that it would be their only opportunity to do so. Linda Gillick called funeral parlors and even purchased an infant-sized coffin so that she would not have to go through the agony of buying one when the time came. Her son had been given the medical equivalent of a death sentence; he was trapped in a prison from which there was no realistic chance of escape.
Michael Gillick did not escape his cell, but he did not die either. He made it to Christmas, then to his real first birthday and then to another Christmas, and another. His tumors did not spontaneously disappear, as sometimes happens with neuroblastoma, but their growth slowed. Contrary to the doctors’ predictions, the malignancies did not crush any of his vital organs, though there were many terrifying emergency hospitalizations. Radiation therapy cost Michael his golden locks without eliminating the facial tumor that damaged his hearing, blurred his vision, and several times even temporarily blinded him—an especially terrifying experience for a child.
Three types of chemotherapy similarly failed. At Michael’s insistence, the grueling treatments stopped when he was eight. Other than morphine, one of the few helpful drugs his ravaged body could tolerate was a blood pressure medication called Regitine. But that drug was no longer being produced in pill form by its manufacturer, a company the Gillicks had heard of because
everyone
in Toms River had heard of it: Ciba-Geigy, the Swiss corporation that owned the local chemical plant. Michael was slowly working through his stockpile of the pill.
Several of Linda Gillick’s neighbors worked at the chemical plant, but she was far too preoccupied with Michael to pay attention to the occasional articles in the local papers about pollution there and at the nearby egg-farm-turned-dumpsite known as Reich Farm. Like most residents of Toms River, the Gillicks lived east of the chemical plant—downwind, since the prevailing winds came from the west. And like many other families in town, their water came primarily from two well fields operated by the Toms River Water Company: the Holly wells, just downstream from the chemical plant, and the Parkway wells, a mile south of Reich Farm. In the early 1980s, those geographic proximities had no particular resonance to the Gillicks or anyone else in Toms River. The air smelled all right, and the tap water looked fairly clear—even if the water pressure was annoyingly low during the summer. So many people were moving into town that the water company always seemed to be struggling to keep up.