Imagine a tall, thin, aging cross between Jimmy Stewart and John Wayne—I think he was wearing cowboy boots—ambling in and taking charge. He was reassuring in his casualness, someone who had seen it all. He leafed through the test results. “There’s nothing here really.” He said it was unlikely that an ovarian cancer would metastasize to an inguinal lymph node. He was puzzled by the order for a barium enema, which was scheduled for a few days later. “It’s a useless test,” he said. We explained about the long wait for a colonoscopy. He picked up the phone, called one of the physicians who owned the clinic, and we had an appointment two days later. “We are going to cure you,” he said. That at least is my memory. Oncologists are not supposed to say that. It was encouraging that he didn’t give a damn.
The results of the colonoscopy were negative, and the final step was a PET scan. Santa Fe had just gotten its own machine—it was no longer necessary to drive an hour south to Albuquerque—and Nancy was almost first in line. PET stands for positron emission tomography, a triumph of medical technology from the recondite world of particle physics. The patient fasts the night before so the body’s cells are starving. When radio-tagged glucose is injected it is eagerly consumed. Malignant, rapidly dividing cells are especially voracious, concentrating the radioactive molecules. As these decay they shoot out positrons, particles of antimatter that collide with electrons and produce bursts of gamma rays. They strike a scintillator, which responds by emitting flashes of light. Nancy’s lower uterus was glowing from the feasting of hyperactive endometrial cells, descendants of a single cell gone mad, a cell that had forgotten it was part of a community, that began running its own show—an isolated act of betrayal that has been played out again and again since the first archaic cells grudgingly agreed to surrender their autonomy for the advantages of living in a collective.
In the days after the diagnosis, I began reading about how this might have happened. To carry on in harmony, our cells constantly exchange chemical signals, conferring on when to start multiplying and creating new tissue. As each cell receives this information it responds by sending instructions to its nucleus, the central controller, for activating the appropriate combination of genes—pressing the right buttons, hitting an arpeggio of piano keys. A cancer cell is one that has cut itself out of the discussion, solipsistically deciding on its own. Random events—triggered by a cosmic ray, a carcinogenic chemical, or just plain dumb luck—must have altered the DNA inside one of Nancy’s cells, causing it to lose touch. The trouble might have begun with a mutation to a gene that sends signals telling the cell that it is time to divide. Another mutation might have modified the molecular receptors that respond to the signals, causing them to become hypersensitive. Set on a hair trigger they fire prematurely. Either way, the cell begins multiplying more rapidly than its neighbors.
In fact these kinds of errors happen all the time. We usually don’t get cancer because other genes react to sudden bursts of activity by reining in growth. But another mutation can cause that safeguard to fail. The nucleus of a cell is constantly receiving messages, weighing the evidence and deciding what to do next. The calculations depend on a tangle of molecular cascades—more things that can go wrong. And they do. All the time. The mistakes are caught and corrected. The DNA is repaired. If that fails, a cell can sense the inner turmoil and send itself suicide signals, killing itself for the common good. But another mutation can undermine that defense.
This is all usually described as though a single cell was sitting motionless and accumulating these defects over the years. I tried to imagine the process as it really is, unfolding dynamically. One hit causes a cell to start dividing repeatedly. Then one of its many progeny acquires another mutation, and its progeny acquire still more. The longer a lineage of cells has lived the more likely it is to have mutated to the brink. That still leaves another barrier against runaway growth: a counter that monitors and limits how many times a cell can divide. With the right mutation a cell can learn to continually reset the count and become immortal. Copying itself again and again, it produces a mass of mutant offspring, a tumor.
And that is still not enough to give you cancer. It takes more mutations for the cell to learn how to invade surrounding tissues, to become malignant rather than benign. Even so, the tumor can grow only so large—the size of the tip of a ballpoint pen—before it’s starved for food or drowns in its own waste. For the tumor to continue expanding it must find a way to reach into the circulatory system and suck like a vampire.
With this infusion of nutrients the cells multiply more aggressively than ever, increasing the probability of more mutations—or adaptations, from the point of view of the evolving cancer cell. The phenomenon is what computer scientists call “random generate and test.” With all the restraints removed, the genome spins out one variation after another—hopeful monsters trying to gain an upper hand. Some might learn to consume energy more efficiently, others to tolerate harsher environments or to suppress the immune system. Finally the fittest will set sail in the bloodstream or the lymphatic ducts and explore new ground.
As I thought about this I was pulled in opposite directions. With so many checks and balances, a person must be extraordinarily unlucky to get cancer. Then again, with so many things that can go wrong, it is amazing that cancer doesn’t happen all the time.
Chapter 3
The Consolations of Anthropology
When Louis Leakey sat down to recount the discovery of what may be the earliest sign of cancer in the genus Homo, the first thing he remembered was the mud. It was March 29, 1932, midway through the third East African archaeological expedition, and it had rained so long and so hard that it took an hour to drive the four miles from the campsite in Kanjera, near the shore of Lake Victoria, to the Kanam West fossil beds. By the time he and his crew had slogged their way through they were covered with mud, and before long Leakey, who was just beginning an illustrious career as an anthropologist, was on hands and knees scouring the ground for newly exposed bones.
He was coaxing the remains of an extinct pig from the muck when one of his Kenyan workers, Juma Gitau, walked over with a broken tooth he had just extracted from a cliffside. Deinotherium, Leakey noted, a prehistoric elephant-like creature that roamed Africa long ago. Gitau went back to look for more, and as he was scratching away at the cliff face, a heavy mass of calcified clay broke loose. He chopped it with his pick to see what was inside: more teeth, but not Deinotherium. These looked like what a dentist might recognize as human premolars, still set in bone, yet they came from a layer of sediment deposited, Leakey believed, in Early Pleistocene time, about a million years ago.
Back at Leakey’s home base at Cambridge University the Kanam mandible quickly became a sensation—“not only the oldest known human fragment from Africa,” he proclaimed, “but the most ancient fragment of true Homo yet discovered anywhere in the world.” It was radical enough in those days to claim that man had originated in Africa, rather than Asia, where primordial ancestors like Java man and Peking man had been discovered. They may have been of approximately the same age as Kanam man, but Leakey found their features to be more apelike in appearance. The Kanam mandible, to his eyes, showed more modern characteristics including remnants of a human-like chin—evidence that Homo sapiens, not just its slack-jawed cousins, was far older than previously believed. Differences in the shape of the teeth led Leakey to consider Kanam man a slightly different species: Homo kanamensis. It was, he insisted, the direct precursor of us all.
Like many of Leakey’s enthusiasms this one proved controversial. One of his detractors thought the specimen looked too modern, that it was a more recent jawbone that had washed into much older surroundings. In later years anthropologists speculated that what Leakey called Homo kanamensis might actually be a more distant relative like Australopithecus, Neanderthal man, or Homo habilis. More recently others have come to believe that the specimen may be Middle to Late Pleistocene, which would make it no more than about 700,000 years old. Wh
atever its pedigree or precise age, Kanam man is no longer considered remarkable for its antiquity but for an abnormal growth on the left side of the jaw.
At the time of the discovery, it had seemed like a bother, detracting from Leakey’s find. He was working in his rooms at St. John’s College, Cambridge, carefully cleaning the specimen, when he felt a lump. He thought it was a rock. But as he kept picking he could see that the lump was part of the fossilized jaw. He sent it to a specialist on mandibular abnormalities at the Royal College of Surgeons in London, who diagnosed it as sarcoma of the bone.
There was also a thin fracture in the jaw, one that had occurred long enough before death to heal. That, the doctor surmised, may have been how the cancer had begun. Sensing the trauma, as bone cells somehow do, they had begun rapidly dividing, replacing dead tissue. And somewhere along the way—the odds are vanishingly small—this carefully controlled process had gone askew. More than enough new cells had been produced to heal the wound, but they didn’t know when to stop. Because of some biological miscalculation, cells kept dividing and dividing, overflowing the crack. Plausible as it sounded, this was just speculation. Bone fractures have not been established as a trigger for osteosarcoma. Usually there is no obvious cause. However the cancer begins it often spreads to the lungs. If the diagnosis is correct—some have had their doubts—that may be what killed Kanam man.
I first came across a mention of the Kanam jaw in a history of cancer timeline somewhere on the Web. That sent me digging into Leakey’s old books and papers, and after several e-mail exchanges I tracked down the fossil at the Natural History Museum in South Kensington, London, where it had been in storage for decades. As far as I could tell it had never been on display. The specimen had been removed from the shelf now and then to be examined. The anthropologist Ashley Montagu studied it in 1956, reporting that the tumor was so large and disfiguring that it was impossible to tell what Kanam man’s chin had been like. Other anatomical details persuaded him, however, that the fossil was clearly human-like. Another anthropologist disagreed, concluding that what Leakey thought was a chin was part of the tumor.
And so the disputes began. A London oncologist, George Stathopoulos, ventured that the tumor might not be osteosarcoma but an entirely different cancer, Burkitt’s lymphoma, a malignancy of the lymphatic system endemic among children today in central Africa, one that often damages bone. Others were not so certain. Osteomyelitis, a chronic infection, can also generate bony growths. But in his book Diseases in Antiquity, a standard reference on ancient pathology, Don Brothwell concluded that Kanam man’s abnormality was too thick and extensive to be from an infection. Like Leakey’s colleagues, he leaned toward a diagnosis of bone cancer. As recently as 2007, scientists scanning the mandible with an electron microscope concluded that the crack had indeed resulted in “bone run amok” while remaining neutral on the nature of the disease.
I wanted to see the specimen for myself, and on a spring day I arrived, as previously arranged, at the museum’s staff and researcher entrance on Exhibition Road. The man at the guard desk called ahead to Robert Kruszynski, curator of vertebrate paleontology. “He asks that you meet him by the giant sloth.” It was easy enough to find. Hunched on its hind legs, the creature’s plaster cast skeleton towered over the heads of museumgoers as it prepared to chomp at the top of an artificial tree. It had been standing that way for 161 years, when it was assembled from the bones of two or more South American specimens and put on display. Behind me was a wall of Ichthyosaurus fossils, mounted in glass cases. As I examined them, marveling at how the same bony architecture runs throughout the vertebrate world, a door opened in the corner of the hall. Mr. Kruszynski came out to greet me and then led me into the museum’s inner sanctum.
Waiting for me on a table by a window was the brown cardboard box he had retrieved from the museum stores. The handwritten label identified the contents:
M 16509
KANAM MANDIBLE.
“M” stood for “mammal.” In the upper right-hand corner of the label were two colored stickers—a red sunlike symbol and below that a blue star—indicating that the specimen in the box had been analyzed at various times by radioassay and x-rays. Mr. Kruszynski carefully removed the lid. Inside was a smaller box, fashioned from balsa wood and cardboard and covered with a glass lid, and inside that was the Kanam jaw.
He placed it on a padded mat, two layers thick to cushion it from the hard surface of the table. “All yours to look at,” he said, and went off to search for another fossil I hoped to see: a femur retrieved from an early medieval Saxon grave in Standlake, England, with an enormous growth that had also been diagnosed as a cancerous bone tumor.
I had thought I would be content just glimpsing the Kanam jaw. I never expected to be left alone with it and to be able to hold it in my hand. It was dark brown and unexpectedly heavy and dense. That shouldn’t have been surprising. It was a rock really, petrified bone. Once it had been part of a prehistoric man, or a protoman. Two yellowed teeth were still in place, and there was a deep hole where the root of another tooth had been.
Just below that, on the left inside curve of the jaw, was the tumor. It was bigger than I had expected, reminding me perversely of a type of candy from my childhood called a jawbreaker. There was also a slight swelling on the outside of the jaw, and I could understand how people might argue endlessly over whether it was part of a tumor or a chin. I could see where Leakey had sliced through the mass (some of his colleagues considered this sacrilege) to remove a section for further analysis. I could almost picture the rest of the head, its vacant eyes pleading for relief from inexplicable pain.
Mr. Kruszynski returned half an hour later to see how I was doing with the fossil. “Don’t bring it too close to the edge,” he warned. I suddenly realized that the protective pad on the table was sloping toward my lap and how easily a sudden movement might have sent the Kanam mandible dropping onto the linoleum floor.
In the end Mr. Kruszynski was unable to find the cancerous femur I’d inquired about. “For another time,” he said. The museum stores were undergoing a renovation, he explained, and the bone had apparently been mislaid along with the rest of the skeleton—all except for the skull. He pulled it from its box and let me hold it for a minute—so lightweight compared to petrified bone—then escorted me back across the barrier to the public portion of the museum. Hundreds of visitors of all ages coursed through the hallways. Some of them inevitably would get cancer, or they would love somebody who did. I wondered if anyone had been there for Kanam man.
Not much has been written about the obscure discipline of paleo-oncology. Although research had gone on sporadically for decades, the word was introduced to literature only in 1983 when a small group of Greek and Egyptian oncologists (from the Greek onkos, meaning “mass” or “burden”) began planning a symposium on human cancer in earlier times. The gathering took place the following year on a voyage between the island of Rhodes and the island of Kos, where Hippocrates was born. What emerged was an elegantly published, sparsely printed little book, Palaeo-Oncology. I felt lucky to find a copy on the Internet for one hundred dollars. Its fifty-eight pages are bound in a blue cover with gilded print, and below the title is a drawing of a crab. “Crab” in Greek is karkinos, and Hippocrates, in the fifth century B.C., used the word—it became the root of “carcinogen” and “carcinoma”—for the affliction whose Latin name is cancer.
It is not clear exactly why he chose the name. Some six hundred years later, Galen of Pergamon speculated on the etymology: “As a crab is furnished with claws on both sides of its body, so, in this disease, the veins which extend from the tumour represent with it a figure much like that of a crab.” The story is repeated in almost every history of cancer. Very few tumors, however, look like crabs. Paul of Aegina, a seventh-century Byzantine Greek, suggested that the metaphor was meant to be taken more abstractly: “Some say that [cancer] is so called because it adheres with such obstinacy to the part it seizes that, like th
e crab, it cannot be separated from it without great difficulty.” The word karkinoi was also applied to grasping tools like calipers.
All but forgotten is a very different derivation from Louis Westenra Sambon, a British expert on parasitology who, before his death in 1931, turned his attention to the study of cancer. There is a parasite, Sacculina carcini, that feasts on crabs in a manner eerily similar to the feasting of a cancerous tumor. The process was described in 1936 in a report by the pathologist Sir Alexander Haddow to the Royal Society of Medicine:
[I]t attaches itself to the body of a young crab, and casts off every part of its economy save a small bundle of all-important cells. These penetrate the body of the host and come to rest on the underside of the latter’s intestine, just beneath the stomach. Here, surrounded by a new cuticle, they shape themselves into the “sacculina interna,” and like a germinating bean-seedling, proceed to throw out delicately branching suckers which, root-like, extend through every portion of the crab’s anatomy to absorb nourishment. Growing in size, the parasite presses upon the underlying walls of the host’s abdomen, causing them to atrophy, so that when the crab moults, a hole is left in this region corresponding in size to the body of the parasite. Through this opening the tumour-like body finally protrudes and becomes the mature “sacculina externa,” free to deliver the active young into the open waters.
Long before the days of Galen, disciples of Hippocrates, dining on crabs, may have noticed the similarities between the way the parasite overtakes its host and the way a cancer metastasizes.
Whatever the reason for the name, ancient Greek texts describe what sound like cancer of the uterus and the breast. Driven by a belief in sympathetic magic, some physicians would treat a tumor by placing a live crab on top of it. They also recommended powders and ointments (sometimes made from pulverized crabs) or cauterization (burning closed the ulceration). As for patients with internal tumors, Hippocrates warned that they might best be left alone: “With treatment they soon die, whereas without treatment they survive for a long time.” The principle is part of the Hippocratic oath: First do no harm.
The Cancer Chronicles Page 5