The Cancer Chronicles (2 page)

After making my way north to Dinosaur (population 339), where Brontosaurus Boulevard intersects Stegosaurus Freeway, I stood at an overlook and watched Morrison stripes in a canyon reddening with the setting sun. But it was a little farther west, along the
Green River in the western reaches of
Dinosaur National Monument, that I saw the most beautiful example: a cliffside of greenish grays slumping into purples slumping into browns. It indeed resembled, as the woman at the park headquarters had told me, melted Neapolitan ice cream.

It was somewhere in these parts that a dinosaur bone was discovered that displays what may be the
oldest known case of
cancer. After the dinosaur died, whether from the tumor or something else, its organs were eaten by predators or rapidly decomposed. But the skeleton—at least a piece of it—gradually became buried by windblown dirt and sand. Later on, an expanding lake or a meandering
stream flowed over the debris, and the stage was set for fossilization. Molecule by molecule minerals in the bones were slowly replaced by minerals dissolved from the water. Tiny cavities were filled and petrified. Several epochs later dinosaurs were long extinct, their world overlaid by lakes and deserts and oceans, but this fossilized bone, encased in sedimentary rock, was preserved and carried through time.

That hardly ever happened. Most bones disintegrated before they could become fossilized. And of the fraction that survived long enough to petrify, all but a few remain buried. The specimen, now labeled CM 72656 and housed at the
Carnegie Museum of Natural History in Pittsburgh, was a survivor. Unearthed by a rushing river or exposed by tectonic forces—somehow it was delivered to the surface of our world where, 150 million years after the animal died, it was discovered by some forgotten rockhound. A cross-section was cut with a rock saw, polished, and after passing through who knows how many human hands, the fossil found its way to a Colorado rock shop where
it caught the eye of a doctor who thought he knew a case of bone cancer when he saw one.

His name was
Raymond G. Bunge, a professor of urology at the University of Iowa College of Medicine. In the early 1990s, he telephoned the school’s geology department to ask if someone would come evaluate a few prize specimens in his collection. The call made its way through the switchboard to
Brian Witzke, who on a cold autumn day bicycled to the doctor’s house and was presented with
an attractive chunk, 5 inches thick, of mineralized dinosaur bone. Viewed head-on, the fossil measured 6.5 by 9.5 inches. Lodged inside its core was an intrusion, now crystallized, that had grown so large it had encroached into the outer bone. Bunge suspected
osteosarcoma—he had seen the damage the cancer can do to human skeletons, particularly those of children. Oval in shape and the size of a slightly squashed softball, the tumor had been converted over the millennia into
agate.

The fragment was too small for Witzke to identify the bone type
or the species of dinosaur, but he was able to provide a geological diagnosis: The reddish-brown color and the agatized center were clues that it came from the Morrison Formation. Bunge remembered buying the souvenir somewhere in western Colorado—burnished pieces of petrified dinosaur bone were a favorite among collectors—but he couldn’t remember the precise location. He gave the rock to the geologist, asking that he seek an expert opinion.

Other projects intervened, and so the fossil sat almost forgotten atop a filing cabinet in Witzke’s office, until the day he sent it to Bruce
Rothschild, a rheumatologist at the Arthritis Center of Northeast Ohio who had expanded his practice to include dinosaur bone disease. He had never seen a clearer or more ancient example of prehistoric cancer. His next step was to determine just what kind of cancer it was.

The tumor, it turned out, didn’t exhibit the ill-defined margins or the
layered, onion-skin look of an osteosarcoma, the cancer Bunge had suspected, or of another malignancy called
Ewing’s sarcoma. Rothschild also felt confident in ruling out
myeloma, a cancer of
plasma cells that leaves bone with a “punched out” appearance. The fact that the tumor, gnawing its way outward, had left intact a thin shell of bone was reason to exclude the more invasive
multiple myeloma. Every skeletal disease leaves a distinct engraving and, one by one, Rothschild eliminated the possibilities: “the superficial solitary and coalescing pits of leukaemia,” “the expansile, soap bubble appearance of
aneurysmal bone cysts,” “the epiphyseal ‘popcorn’ calcifications
characteristic of
chondroblastomas,” “the ‘ground glass’ appearance of
fibrous dysplasia.”

For an outsider reading Rothschild’s observations, the medical jargon might be somewhere between translucent and opaque, words that gain a grim familiarity only as one strives to understand the sudden disruption of cancer. What is clear from the beginning is the confidence with which a specialist in the obscure discipline of dinosaur pathology can provide a likely diagnosis for a 150-million-year-old tumor. Rothschild went on to rule out the “sclerotic-rimmed lesions
of gout,” the “zones of resorption characteristic of
tuberculosis,” and the “sclerotic features of gummatous lesions of treponemal disease.” Unicameral bone cysts, enchondromas, osteoblastomas, chondromyoxoid fibromas, osteoid osteoma, eosinophilic granuloma—who would have known that so much can go wrong inside what appears to be solid bone? None of these seemed like candidates. To Rothschild’s eye the lesion had the markings of a
metastatic cancer, the deadliest kind—a cancer that had originated from cells elsewhere in the dinosaur’s body and migrated to establish a colony in the skeleton.

There had been scattered references in the journals
to other dinosaur tumors—
osteomas (clumps of overeager bone cells outgrowing their rightful bounds) and
hemangiomas (abnormal effusions of blood vessels that can form within the spongy tissue inside bone). Like cancer, these
benign tumors are a kind of
neoplasm (from the Greek for “new growth”)—cells that have learned to elude the body’s checks and balances and exert a will of their own. The cells in a benign tumor are multiplying rather slowly and have not acquired the ability to invade surrounding tissue or to metastasize. They are not necessarily harmless. Occasionally a benign tumor can press
dangerously against an organ or blood vessel or secrete
destructive hormones. And some can become cancerous. These were rare enough. But sightings of malignant dinosaur tumors were especially scarce. A cauliflower-like growth in the forelimb of an
Allosaurus
was thought for a while to be a
chondrosarcoma. But on close examination Rothschild decided that it was just a healed fracture that had become infected. Bunge’s fossil was the real thing. In a terse, five-hundred-word paper written with Witzke and another colleague and published in
The
Lancet
in 1999, he came to a bold conclusion: “
This observation extends recognition of metastatic cancer origins to at least the mid-
Mesozoic [the Age of the Dinosaurs], and is the
oldest known example from the fossil record.”

I’d first heard of Raymond Bunge’s fossil earlier that summer when I began working my way through the literature on the science of
cancer. There is something sickly fascinating about the way a single cell can break from the pack and start
multiplying, creating something alien inside you—like a new organ suddenly sprouting in the wrong place or, even more gruesome, a vicious, misshapen embryo.
Teratomas, rare
tumors that arise from misguided
germ cells (the ones that give rise to eggs and sperm), can contain the rudiments of hair, muscle, skin, teeth, and bone. Their name is from the Greek word
teras,
for “monster.” A young Japanese woman had an
ovarian cyst with head, torso, limbs, organs, and a
cyclopean eye. But these cases are very rare. Tumors almost always evolve according to their own impromptu plan. The most dangerous ones become
mobile. Once they have established themselves in the immediate vicinity—your stomach, your colon, your uterus—they move on,
metastasize, to new ground. A cancer that began in the
prostate gland can end up in the
lungs or the spinal column. There was no reason to believe that cancer hadn’t occurred in dinosaurs. But considering the tiny fraction of paleontological remains that humans have had the opportunity to examine, coming across an actual example seemed almost miraculous.

Consider the size of the field: From
Dinosaur National Monument in
Utah and
Colorado, the
Morrison Formation reaches north into Wyoming, Idaho, Montana, the Dakotas, and southern
Canada. It spreads east to Nebraska and Kansas, and south to the panhandles of Texas and Oklahoma, and into New Mexico and Arizona. It covers approximately half a million square miles. Erosion and excavation, natural or man-made, have only nicked the edges, barely sampling the 7-million-year accumulation of dinosaur bones, and only those that happened to become fossilized. If it hadn’t been for Raymond Bunge’s sharp eye, the earliest solid evidence of prehistoric cancer would have been missed. How many other cases were crushed inside those lightless layers? And among the bones that have been retrieved, how many malignancies had been overlooked? Paleontologists were hardly ever looking for cancer—few would recognize it if they saw it—and the only tumors they had a chance of finding would be
those that had tunneled their way outward to a bone’s surface or had been revealed by a random fracture or the blind cut of a lapidary saw.

One of the most elusive questions about cancer is how much is timeless and inevitable—arising spontaneously inside the body—and how much has been brought on by
pollution,
industrial chemicals, and other devices of man. Getting a rough sense of the frequency of cancer in earlier epochs might provide important clues, but only with a larger sample of data. His interest piqued by Bunge’s fossilized tumor, Rothschild began looking for more.

With a portable fluoroscope, he began x-raying his way through the
museums of North America. In people, cancers that
metastasize to the skeleton most commonly lodge in the spine, so Rothschild concentrated on vertebrae. By the time he was done he had examined 10,312 vertebrae from about seven hundred
dinosaurs collected by the
American Museum of Natural History in New York, the Carnegie Museum in Pittsburgh, the
Field Museum in Chicago, and other institutions throughout the United States and Canada—every specimen north of the Mexican border that he could get his hands on. He inspected loose vertebrae and, using ladders and a cherry picker, the soaring spines of whole skeletons. (There is
a picture of him wearing a dinosaur T-shirt and leaning backward inside the rib cage of a
Tyrannosaurus rex.
) Bones that appeared abnormal under x-rays were scrutinized more closely with a CT scan.

In the end, his diligence paid off. He found another bone metastasis, and this time it was possible to identify the victim: an
Edmontosaurus,
a duck-billed titan (the family name is
Hadrosauridae) that lived toward the end of the
Cretaceous, right after the Jurassic, when dinosaurs began to go extinct. Other Hadrosauridae also had bone tumors, all of them
benign: an
osteoblastoma, a
desmoplastic fibroma, and twenty-six
hemangiomas, but there were none among the other beasts. That perhaps was the biggest surprise. Although Hadrosauridae vertebrae made up less than one-third of the bone pile—about 2,800 specimens from fewer than one hundred dinosaurs—they were the source of all the tumors. The approximately
7,400 vertebrae that were not hadrosaurs—
Apatosaurus,
Barosaurus,
Allosaurus,
and so forth—exhibited no
neoplasms, either malignant or benign.

It was the kind of anomaly epidemiologists of human
cancer confront all the time. Why do some people get more cancer than others? Some evolutionary twist may have left
Hadrosaurus
with a genetic predisposition for tumors. Or the reason might have been metabolic. These
dinosaurs, Rothschild speculated,
may have been more warm-blooded than other ones. Warm-blooded metabolisms run faster—it takes energy to maintain body heat—and that might accelerate the accumulation of the cellular damage that leads to malignancy.

Maybe the difference was not
endemic but
environmental—something about what
Hadrosaurus
ate. Plants in an ecosystem engage in endless chemical warfare, synthesizing herbicides and insecticides to fight off pests. Some of these chemicals are
mutagens: they can change DNA. Modern descendants of the fernlike
cycads that grew in Mesozoic times produce poisons that can induce liver and kidney tumors in
laboratory rats. But why would
Hadrosaurus
eat more cycads than, say,
Apatosaurus
? Another possible source of carcinogens—needles from
conifer trees—had been discovered in the stomachs of a couple of
Edmontosaurus
“mummies,” whose remains had been buried under the right environmental conditions to fossilize instead of rot. But that wasn’t much evidence to go on.

There were other curiosities to explain. When
Hadrosaurus
tumors did occur it was only among the caudal vertebrae—those nearest the tail of the spine. What was it about the bottom of the reptile that was more susceptible than the top? If only dinosaurs could be re- created from ancient DNA as they were in
Jurassic Park
and made available for medical
research. At the great cancer centers—
Dana-Farber in Boston,
MD Anderson in Houston, and others around the world—a scientist can consume a career studying the role a single molecule plays in malignancy. Just the data from Rothschild’s survey suggested dissertations’ worth of questions. The overriding one was how to put his findings into perspective. Human bone cancer of
any kind—
metastatic or originating in the skeleton—is a rarity. Was one case among seven hundred
dinosaur skeletons a little or a lot?

In a third paper,
Rothschild considered the odds. He had been approached by two astrophysicists who were hoping to support their theory that the end of the dinosaurs’ earthly reign was hastened by a spike of radioactive cosmic rays.
Ionizing
radiation—the kind strong enough to damage DNA—can cause
cancer, and
bone marrow is particularly susceptible. If a cosmic event had unleashed unusually strong rays, the effect on the dinosaurs would have been like being
x-rayed from outer space.