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The Cancer Chronicles

Page 6

by George Johnson


  With Galen the references become even sharper. He wrote an entire book about tumors and included malignancies in a category of growth called “praeter naturam”—preternatural, meaning outside of nature. Carcinoma, he wrote, is “a tumor malignant and indurated, ulcerated or non-ulcerated.” He found breast cancer to be the most common and especially prevalent after menopause. (In contradiction to what modern oncologists believe, he wrote that women who regularly menstruate don’t get cancer.) He writes about uterine, intestinal, and anal cancer, and cancer of the palate. Sometimes he, like other Greek writers, uses the word therioma, “wild beast,” to mean malignant. “The early cancer we have cured, but the one that rose to considerable size, without surgery, nobody has cured.”

  The medieval surgeon Abu al-Qasim al-Zahrawi was no luckier: “When a cancer has lasted long and is large, you should not come near it. I have never been able to save any case of this kind, nor have I seen anyone else who has been successful.”

  It is not so different now.

  There is something comforting about knowing that cancer has always been with us, that it is not all our fault, that you can take every precaution and still something in the genetic coils can become unsprung. Usually it takes decades for the micro damage to accumulate—77 percent of cancer is diagnosed in people fifty-five or older. With life spans in past centuries hovering around thirty or forty years, finding cancer in the fossil record is like sighting a rare bird. People would have died first of something else. Yet in spite of the odds, cases continue to be discovered, some documented so vividly that you can almost imagine the ruined lives.

  After my visit to London I received from the Natural History Museum photographs of the Saxon skeleton whose tumorous femur I had hoped to examine. I had read that the growth was large—10 inches vertically by 11 inches horizontally—but I was astonished to see what looked like a basketball grafted onto the young man’s leg. The tumor shows a sunburst pattern that pathologists recognize as a sign of osteosarcoma. They see it most often in adolescents whose limbs are undergoing hormone-induced spurts of growth—more evidence for one of cancer’s few established rules: The more frequently cells are dividing, the more likely mutations will occur. The right combination will lead to a malignancy. Osteosarcoma is so rare that one would have to comb through the bones of tens of thousands of people to find a single example. Yet ancient cases continue to turn up.

  There were signs of the cancer in an Iron Age man in Switzerland and a fifth-century Visigoth from Spain. An osteosarcoma from a medieval cemetery in the Black Forest Mountains of southern Germany destroyed the top of a young child’s leg and ate into the hip joint. Bony growths inside the roof of the eye sockets indicated anemia, which may have been an effect of the cancer. The authors of the report speculated on the cause: contamination from a nearby lead and silver mine. Cancer is especially hard to accept in children, even in one from nine centuries ago, and the paper ended with a poignant note: “The tumour would certainly lead the child to die a painful death.” Though child mortality was very high in those days, the authors noted, children who made it past the first few years might live into their forties. But not this time. “The flame of life in the affected child was extinguished just when the child had survived the first years of infant excess mortality.”

  Maybe it helped to believe there was a reason—metallic poisoning from a mine. But no one knows what causes osteosarcoma. Then, as now, a few cases probably were hereditary, traced to chromosomal abnormalities. In modern times speculation turned for a while to fluoride-treated water and, more plausibly, radiation—therapeutic treatments for other disease or exposure to radioactive isotopes like strontium-90, which is spread by nuclear fallout. Strontium sits just below calcium in the periodic table of elements and imitates its behavior, incorporating itself tightly into bone. But most often osteosarcoma strikes for no apparent reason, leaving parents grasping to understand what remains as inexplicable as a meteor strike.

  Another malignancy, nasopharyngeal carcinoma, which affects the mucous membrane in the nose, can scar adjacent bone, and signs of it have been found in skeletons from ancient Egypt. One woman’s face had been all but obliterated, and I tried to imagine her stumbling through life. “The large size of the tumor, which caused such extensive destruction, suggests a relatively long-lasting process,” observed Eugen Strouhal, the Czech anthropologist who documented the case. “The patient seems to have survived for a considerable time, and doubtless had pain and other symptoms. Survival would be impossible without the help and care of the patient’s fellow-men.” Here was another case where the horrors of cancer punched through the flat veneer of scientific prose.

  Multiple myeloma, a cancer of plasma cells in bone marrow, can leave skeletal marks. Traces were found in the skull of a woman who lived in medieval times. Plasma cells are part of the immune system and when behaving normally they produce antibodies called immunoglobulins. In multiple myeloma, one type is generated at the expense of the others. A chemical test found antibodies that the researchers considered confirmation of the disease.

  Osteosarcoma, nasopharyngeal carcinoma, multiple myeloma—these are primary cancers, those found at the site of origin. They are debilitating enough. Most skeletal cancers by far come from metastases originating elsewhere. They also show up with greater frequency in the fossil record—and with devastating results. Metastatic bone cancer has been discovered in Egyptian tombs, in a Portuguese necropolis, in a prehistoric grave in the Tennessee River valley, in a leper skeleton from a medieval cemetery in England. Buried near the Tower of London the skeleton of a thirty-one-year-old woman was marked with metastatic lesions. We even know her name from a lead coffin plate: Ann Sumpter. She died on May 25, 1794.

  In 2001 archaeologists excavated a 2,700-year-old burial mound in the Russian republic of Tuva, where nomadic horsemen called the Scythians once thundered across the Eurasian steppes, their leaders exquisitely dressed in gold. Digging down through two wooden ceilings, the scientists came upon a subterranean chamber. Its floor, covered with a black felt blanket, cushioned two skeletons. Crouched together like lovers, both man and woman wore what remained of their royal vestments. Around the man’s neck was a heavy band of twisted gold decorated with a frieze of panthers, ibex, camels, and other beasts. Near his head lay pieces of a headdress: four gold horses and a deer. Golden panthers, more than 2,500 of them, bedecked his cape. His riches couldn’t save him. When he died—he appeared to have been in his forties—his skeleton was infested with tumors. A pathological analysis, including a close look with a scanning electron microscope, concluded that the nature of the lesions and the pattern of their spread were characteristic of metastatic prostate cancer. Biochemical tests revealed high levels of prostate-specific antigen, or PSA. For all the false positives these tests can produce, this result was apparently genuine.

  Metastasizing prostate cancer has been diagnosed in the partially cremated pelvis of a first-century Roman and in a skeleton from a fourteenth-century graveyard in Canterbury. While prostate cancer tends to be osteoblastic, adding unwanted mass to the skeleton, breast cancer is osteolytic, gnawing mothlike at the bone. Of all cancers, prostate and breast show the strongest appetite for skeletal tissue. Depending on the gender of the victim they are the first choice for diagnosis when bone metastases are found.

  A middle-aged woman with osteolytic lesions was excavated from the northern Chilean Andes where she had died around 750 A.D. Her desiccated body was buried in a mummy pack along with her possessions: three woolen shirts, some feathers, corncobs, a wooden spoon, a gourd container, and a metal crucible. She was no Scythian queen. Her hair reached down her back in a long braid tied with a green cord. There were lesions in her spine, sternum, pelvis. On top of her skull, cancer had chomped a ragged hole 35 millimeters across. Cancer had feasted on her right femur, shortening her leg.

  Osteolytic lesions are also found in men. They had spread throughout the skeleton of a Late Holocene hunter-gatherer exhumed in t
he Argentine Pampas. Men do get breast cancer, but only very rarely. Lung cancer can also leave osteolytic marks, but it is believed to have been exceedingly uncommon before cigarettes. His diagnosis was left hanging. It was another case of what oncologists call “primary unknown.”

  Those words still haunt me when I think about the weeks that passed before finding the source of Nancy’s metastasis. Like 90 percent of human cancers it was a carcinoma. It makes sense that these would be the most common. Carcinomas arise in the epithelial tissues that line the organs and cavities of the body and envelop us with skin. As the layers are worn by the passage of food and waste or exposure to the elements, the outer cells are constantly dying. The cells beneath must divide to form replacements. And with every division there will be mistakes in the copying of genes—spontaneous mutations or ones caused by carcinogens in food, water, and air. For children, who are just beginning to withstand life’s wear and tear, only a fraction of cancers are carcinomas.

  When it comes to hunting ancient cancer, primary carcinomas would almost always be lost with the decomposing tissues. And those that had metastasized would have often spread first to the lung or liver, killing the victim before a record was left in bone. Egyptian medical papyruses make ambiguous references to “swellings” and “eatings,” and some evidence has survived in mummies. A rectal carcinoma in a 1,600-year-old mummy was confirmed with a cellular analysis of the tissue. Another mummy was diagnosed with bladder cancer. Elsewhere in the world, a rare muscle tumor called a rhabdomyosarcoma was found on the face of a Chilean child who lived between 300 and 600 A.D. In Peru, two pathologists reported metastatic melanoma in skin and bone tissue of nine pre-Columbian Incan mummies. In a whimsical digression, they quote an eighteenth-century ode in praise of female beauty marks and then wryly remark: “Whereas [the poet] was inflamed, as were his contemporaries, by the beauty of a lady’s moles, we—some 240 prosaic years later—are romantically unmoved by any of them. They have given us nothing but trouble.”

  Other evidence of ancient cancer may have been destroyed by the invasive nature of Egyptian embalming rituals. To prepare a pharaoh for passage to the afterlife, the first step was removing most of his organs. The brain was pulled out though the nostrils. The torso was sliced open to take out the abdominal and chest organs (with the exception of the heart, which was believed necessary for the ethereal voyage). Each organ was wrapped in resin-soaked linen and then placed back into the body or in what was called a canopic jar. There were other variations. To slow the process of decay a turpentine-like solution was sometimes injected as an enema to dissolve the digestive tract.

  But embalmed tumors can survive. Treated more gently, the mummified body of Ferrante I of Aragon, who died in 1494 in his early sixties, harbored an adenocarcinoma that had metastasized to the muscles of his small pelvis. Some five hundred years after his death, a molecular study revealed a typographical error in the DNA code that regulates cell division—a G had been flipped to A—a genetic mutation associated with colorectal cancer. Maybe this was caused, the authors speculated, by an abundance of red meat served in the royal court. Or, for all we know, by an errant cosmic ray.

  Altogether I counted about two hundred suspected cancer sightings in the archaeological record. As with the dinosaurs, I was left to wonder how big an iceberg lay floating beneath the tip. Mummies are a curiosity, and most skeletal evidence is stumbled on by chance. Only recently have anthropologists really begun looking for cancer—with CT scans, x-rays, biochemical assays, and their own eyes. What they will never see, even in bone, are clues lost through what anthropologists call taphonomic changes. In digging and transporting skeletal remains, markings can inadvertently be erased. Bone-eating osteolytic lesions can cause a specimen to crumble and disappear. Through erosion, decomposition, and the gnawing of rodents, taphonomic changes might also create the illusion of metastasis—pseudopathology—a possibility that must be taken into account along with alternative diagnoses like osteoporosis and infectious disease. But on balance it seems likely that the evidence of ancient cancer is significantly underreported. Most skeletons, after all, are incomplete. Metastases are more likely to appear in certain bones like the vertebrae, pelvis, femur, and skull. Others rarely are affected. No one can know if a missing bone happened to be the one that was cancerous.

  Hoping to cut through the uncertainty, Tony Waldron, a paleopathologist at University College London, tried to get a feel for how much cancer archaeologists should be expected to find. First he had to come up with an estimate, no matter how crude, of the frequency with which primary tumors might have occurred in earlier times. There wasn’t much to go on. The oldest records that seemed at all reliable were from the registrar general of Britain for causes of death between the years 1901 to 1905. Using that as his baseline, he took into account the likelihood that various cancers would come to roost in the skeleton, where they might be identified. The numbers, a range of approximations, came from modern autopsy reports. For colorectal cancer the odds were low, 6 to 11 percent, as they were for stomach cancer, 2 to 18 percent. On the high side were cancer of the breast (57 to 73 percent) and prostate (57 to 84 percent).

  From these and other considerations, Waldron calculated that (depending on age at death) the proportion of cancers in a collection of old bones would be between 0 and 2 percent for males and 4 and 7 percent for females. No matter how hard you looked, cases of ancient cancer would be sparse—even if the rate had been as high as that of industrial Britain. To test if his numbers were plausible, he tried them out on the remains of 623 people who had been placed in a crypt at Christ Church, Spitalfields in the East End of London between 1729 and 1857. Relying solely on visual inspection, he found one case of carcinoma among the women and none among the men. That was within the range of his formula, encouragement that it was not wildly wrong.

  The next step was to try the predictions on much older and larger populations: 905 well-preserved skeletons buried at two sites in Egypt between 3200 and 500 B.C. and 2,547 skeletons that had been placed in a southern German ossuary between 1400 and 1800 A.D. (The church cemetery was so small and crowded that remains, once they had decomposed, were periodically removed and put into storage.) Using x-rays and CT scans to confirm the diagnoses, pathologists in Munich found five cancers in the Egyptian skeletons and thirteen in the German ones—about what Waldron’s calculations predicted. For all the differences between life in ancient Egypt, Reformation Germany, and early twentieth-century Britain, the frequency of cancer appeared to be about the same.

  Since then the world has grown more complex. Longevity has soared along with the manufacture of cigarettes. Diets have changed drastically and the world is awash with synthetic substances. The medical system has gotten better at detecting cancer. Epidemiologists are still trying to untangle all the threads. Yet running beneath the surface there is a core rate of cancer, the legacy of being multicellular creatures in an imperfect world. There is no compelling evidence that this baseline is much different now than it was in ancient times.

  While still immersed in the arcana of paleo-oncology, I had dinner with a friend, a scientist in her thirties who had recently been treated for breast cancer. Like many people she suspected that there is far more cancer now than in the past, and a few weeks later she sent me a reference to an article that had just appeared in Nature Reviews Cancer in which two Egyptologists concluded that there is “a striking rarity of malignancies” in ancient times. In a news release from her university, one of the authors, A. Rosalie David, made this claim:

  In industrialised societies, cancer is second only to cardiovascular disease as a cause of death. But in ancient times, it was extremely rare. There is nothing in the natural environment that can cause cancer. So it has to be a man-made disease, down to pollution and changes to our diet and lifestyle.

  …We can make very clear statements on the cancer rates in societies because we have a full overview. We have looked at millennia, not one hundred years, and have mass
es of data.

  Across the Internet, news reports jumped on the information: “Cancer Is a Man-Made Disease.” “Cure for Cancer: Live in Ancient Times.” By now I thought I had become familiar with the literature. Was there some important new evidence that had resolved the ambiguities? It was flat out wrong to say that nothing in the natural environment can cause cancer. What about sunlight, radium, aflatoxin, hepatitis virus, human papillomavirus? I kept checking the university website assuming there would be a correction. None ever came.

  The paper itself turned out to be more sober and qualified, and as I went through it line by line, I saw that nothing there was new. The authors had taken the same body of research I’d been wading through all winter and given it their own spin. While two hundred serendipitously documented cancer cases seem like a significant amount to most paleopathologists, some take the number at face value, envisioning an idyllic cancer-free past: a world where it was far less likely for children to get osteosarcoma or for even the very aged to get breast, prostate, or any of the cancers we worry about today. A world free from the attack of modern times. One can find consolation in fatalism, the idea that cancer is an inevitable part of the biological process. But there is also comfort in believing that humans, through their own devices, have increased the likelihood of cancer. What free-willed creatures have created can conceivably be undone. Failing that, there is at least a culprit to blame.

 

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