The Cancer Chronicles (3 page)

But how would you do the epidemiology? In an earlier study
Rothschild and his wife, Christine, had x-rayed bones at the
Hamann-Todd Human Osteological Collection at the
Cleveland Museum of Natural History, a repository of three thousand skeletons from medical school cadavers—homeless souls who would otherwise be in pauper’s graves. Thirty-three of them had metastatic bone tumors, which amounts to 1.14 percent.
Autopsies at the
San Diego Zoo suggested that reptiles have a
bone cancer rate about one-eighth that of humans, or about 0.142 percent. One cancerous
Edmontosaurus
among seven hundred fluoroscoped dinosaurs yields almost precisely the same number. One would have to look elsewhere for evidence that cancer had been a factor in the extinction.

For months factoids like this had been accumulating in my notebook and metastasizing through my mind. Every question raised about cancer inevitably spawned more. How representative was the Hamann-Todd Collection of the overall cancer rate? The indigents whose bones were there may have suffered from poor nutrition and haphazard diets, possibly increasing their susceptibility. Yet many of them probably had comparatively short life spans, dying from violence or infectious diseases before there was time for a cancer to grow. Maybe it all balanced out. And maybe not. The study of the animals in the San Diego Zoo raised more questions. Animals in captivity tend to get more cancer than those in the wild, maybe because they are exposed to more pesticides or food additives, or
maybe just because they survive longer, get less exercise, and eat more. Of all the risk factors associated with human
cancer two that are seldom disputed are obesity and old age.

The most troubling question was how much one can extrapolate about
dinosaur cancer—and the ultimate origins of the disease—from what little evidence has survived. If you included in the sample only the one hundred tumor-prone
hadrosaurs,
their bone cancer rate would be 1 percent, about the same as for the human skeletons. But you have to wonder how many other specimens are waiting to be discovered. Just one more with a malignant tumor would double the cancer rate. Finally there was the question of how many cancers might have spread to unexamined parts of the skeleton or to softer organs—cancers that never reached bone. Once the tissues decomposed the evidence would be gone.

There are reports of a possible exception. In 2003, the year the Rothschild survey appeared,
paleontologists in South Dakota announced the discovery of what might be a dinosaur brain tumor. They were preparing the skull of a 72-million-year-old
Gorgosaurus,
a close relative of
Tyrannosaurus rex,
when they found “
a weird mass of black material in the brain case.” Analysis with x-rays and an electron microscope indicated that the rounded lump had consisted of bone cells, and veterinary pathologists diagnosed it as an “extraskeletal
osteosarcoma,” a bone-cell-producing tumor that had taken up residence in the cerebellum and brainstem. Maybe that explains why the
Gorgosaurus
appeared to be so battered, as though the animal, suffering from a loss of motor control, had stumbled and fallen repeatedly. “
It certainly would take a bizarre event to have created this appearance,” Rothschild speculated at the time. “The position and character may well be a tumor, but it still needs to be
proven that this is not simply broken skull fragments that fell in.”

Continuing along the Dinosaur Diamond Highway, thinking about cancer, I made my own rare sighting: a Sinclair gasoline station with
its
green dinosaur logo—another relic of earlier times. Along the road, rocking oil wells pumped the fossil fuels derived, as best we know, from prehistoric organic matter, a puree of tiny plant and animal life, perhaps with some oil of dinosaur splashed in.

It was almost dusk when I reached the
Yampa Plateau in northern
Colorado, a
300-million-year pile of geology. Eons of seismic turmoil—the thrusting and tilting, the slipping and sliding of great crustal masses—had made a mess of the timeline. For miles the road skimmed the surface of rock laid down in the
Jurassic and
Cretaceous, mid to late dinosaur time. Then without so much as a bump of the tires, the mesa top abruptly changed to
Pennsylvanian—whole epochs sheared off to expose an older world, 150 million years before the
Morrison dinosaurs, when primitive cockroaches crawled the land. Crushed a couple of strata beneath the Pennsylvanian would have been the
Devonian, a 400-million-year-old countryside. In Devonian rock 1,600 miles east of the Yampa, a
jawbone of a primitive armored fish was discovered near what became Cleveland, Ohio. It is pitted with what some scientists take to be a tumor and others dismiss as an old battle wound.

The road ended at Harpers Corner—the far tip of the plateau. I walked to the edge where deep below me the Green and Yampa Rivers come together, having sawed though all that hardened time. I stood there flummoxed by the thought of all that vanished past. After the disappearance of the dinosaurs came the
Laramide orogeny, when the peaks that became the
Rockies soared from the earth, reaching as high as 18,000 feet, only to become buried to their necks in their own debris. With the Exhumation of the Rockies (these names sound almost biblical), the infill began washing away. In early
Pleistocene time, just 2 million years ago, the great glaciations followed, leaving behind the geography we know today. Throughout all of these cataclysms life kept evolving. Stowing away on the journey was this interloper called
cancer.

Hints of
benign neoplasms have been found in the fossilized bones of
ancient elephants, mammoths, and horses.
Hyperotosis, or
runaway bone growth, appears in fish from the genus
Pachylebias,
which seem to have put the
tumors to good use. With the ballast provided by the increased bone mass, the fish could graze deeper in the salty Mediterranean waters, giving them an edge over their competitors. What began as a pathological growth may have been adopted as an
evolutionary strategy.

Malignant tumors have been suspected in
an ancient buffalo and an ancient ibex. There is even a report from 1908 of
cancer in the mummy of an ancient Egyptian baboon. The examples are scant and sometimes controversial. But as with the dinosaurs, absence of evidence is not evidence of absence. Maybe cancer was a great rarity before man began messing with the earth. But a core amount of cancer must have existed all along. For a body to live, its cells must be constantly dividing—splitting into two cells, which split into four, then eight, doubling again and again. With each division the long threads of DNA—the repository of a creature’s genetic information—must be duplicated and passed along. Over the course of time mechanisms have evolved to repair errors. But in a world awash with entropy that is naturally an imperfect process. When it goes wrong the result is usually just a dead cell. But under the right circumstances the errors give rise to cancer.

Even a lone single-celled
bacterium can spawn a mutation that causes it to replicate more vigorously than its neighbors. When that happens to a cell within a tissue the result is a neoplasm.
Plants and animals—two variations on the theme of multicellularity—ultimately sprang from the same primordial
source. Plants are our very distant cousins, and they do get something resembling cancer.
A bacterium called
Agrobacterium tumefaciens
can transfer a fragment of its own DNA into the genome of a plant cell, causing it to multiply into a tumor called
crown gall.
A remarkable paper published in 1942 demonstrates that in sunflowers these tumors can spawn secondary tumors—a primitive analog of metastasis. In the insect world
larval cells can give rise to invasive tumors—the same phenomenon, perhaps, that carried over to the vertebrates.

Cancer (
sarcomas,
carcinomas,
lymphomas, these clinically depressing names) has been described in
carp, codfish, skate rays, pike, perch, and other fishes.
Trout, like people, get liver cancer from a carcinogen,
aflatoxin, produced by the fungus
Aspergillus flavus.
Rumors that
sharks don’t get cancer led to a mass slaughter by entrepreneurs hawking cancer-fighting shark cartilage pills. But
sharks do get cancer. None of the classes of the animal kingdom are exempt. Among reptiles, there are cases of
parathyroid adenoma in turtles and of sarcoma, melanoma, and lymphatic leukemia in snakes.
Amphibians are also susceptible to neoplasms, but some offer
a strange variation on the theme. When injected with carcinogens, newts rarely develop tumors. They are more likely to react by sprouting a new, misplaced limb. This ability to regenerate body parts has been all but lost by other animals over the course of evolution.
Could this be another clue to the origins of cancer—damaged tissues trying frantically to regrow themselves, only to find that they no longer know how?

None of these creatures walk, swim, or slither to a clinic seeking care. But from the haphazard sightings of naturalists and zoologists, patterns have emerged.
Mammals appear to get more cancer than reptiles or fish, which in turn get more cancer than amphibians.
Domesticated animals seem to get more cancer than their cousins in the wild. And people get the most cancer of all.

One afternoon during my roadtrip, I stopped for a while at the
Dinosaur Journey Museum. Given the current state of science museums—so much show biz—I expected the place to be infested with animatronic dinosaurs and hands-on exhibits resembling video games. But plenty of good science was there. I peeked through the picture windows of the Paleo Lab, where live men and women sat on display, leaning over worktables and chipping embedded fossils from surrounding stone. I walked among reconstructed skeletons towering toward the ceiling—
Allosaurus,
Stegosaurus.
I saw a neck vertebra
from an
Apatosaurus
so large that without the label I wouldn’t have guessed the rocky mass had once been living tissue. It was all impressive, but over the years I had seen enough dinosaur skeletons to feel a little jaded. It wasn’t until I stopped at a display with a full-
size outline of a
Brachiosaur
’s heart standing as high as my chest that I really felt how enormous these beasts had been.

I thought again about
Rothschild’s survey of dinosaur tumors. There is
a close relationship between size and life span. Though there are exceptions, larger species tend to live longer than smaller ones, and by some reckonings, the largest dinosaurs had very long life spans—so much time and space for mutations to collect. Wouldn’t that have made them highly susceptible to
neoplasms? At least in the mammalian world the issue is not clear-cut, an observation that goes by the name of
Peto’s paradox. It was named for Sir
Richard Peto, an Oxford epidemiologist. He was puzzled that large long-lived creatures like elephants don’t get more
cancer than small short-lived creatures like mice.
The mystery was succinctly posed in the title of a paper by a group of biologists and mathematicians in Arizona: “
Why Don’t All
Whales Have Cancer?” Except for belugas in the polluted St. Lawrence estuary, whale cancer appears to be uncommon. For mice the cancer rate is high.

At first that didn’t seem so strange. There is an inverse correlation between life span and
pulse rate. During a typical lifetime an elephant and a mouse will each use up
roughly a billion heartbeats. The mouse will just do it much faster. With a metabolism on so high a burn, it seems
sensible that mice might get more cancer. But what is true for the mouse is not true for other tiny mammals.
Birds, despite their frenzied metabolic rate (a
hummingbird’s heart can beat more than a thousand times a minute) appear to get very little cancer. If you graph mammalian size against cancer rate there is no telltale sloping line, just a scattering of dots. In our ignorance, each species seems like an exception.

Scientists have proposed several reasons for why cancer doesn’t correlate smoothly with size. While larger animals may indeed get more mutations, they might also have evolved more effective means
for
repairing DNA, or for warding off tumors in other ways. The authors of the Arizona paper suggested how that might occur:
hypertumors. Cancer is a phenomenon in which a cell begins dividing out of control and accumulating
genetic damage. Its children, grandchildren, and great-grandchildren go on to spawn broods of their own—subpopulations of competing cells, each with a different combination of traits. The stronger contenders—those that have evolved an ability to grow faster than the others or to poison their neighbors or to use energy more efficiently—will gain an upper hand. But before they can dominate, the authors proposed, they might become susceptible to “hypertumors”: clusters of weaker cancer cells opportunistically trying to latch on for a free ride. These parasites would sap energy continuously, destroying the tumor or at least keeping it in check. In large, long-lived animals cancer develops gradually enough for the leeches to form. They may indeed get more tumors, but they are much less likely to grow to a noticeable size. Cancer that can get cancer. For all the time I’d spent immersing myself in the literature, this was the first I had heard of that.

That still left me wondering about the hummingbirds, and a footnote in the paper about Peto’s paradox led me to yet another of cancer’s mysteries. It is well known to zoologists that virtually all
mammals, no matter how tall or short, have precisely seven vertebrae in their necks: giraffes, camels, people, whales. (Manatees and sloths are exceptions.) Birds, amphibians, and reptiles are not bound by the rule—a swan can have twenty-two to twenty-five neck vertebrae. They also appear to get less cancer.
Frietson Galis, a Dutch biologist,
thought there must be some kind of connection. She considered what happens in rare instances when fetuses sprout an extra rib right where the seventh vertebra would normally be. As a result, children born with the defect have only six vertebrae in their necks. They are also more likely to die from
brain tumors,
leukemias,
blastomas, and
sarcomas. Galis suggests that it is why variation in the number of neck vertebrae is slowly being weeded out of the mammalian population.