Zoobiquity (7 page)

If your dermatologist reminds you to remove your nail polish before coming in for your yearly mole scan, that’s because she wants to check not only for melanoma but also for squamous cell carcinoma, a common form of skin cancer and the same kind Tessa had. Tessa’s was in her mouth, but it can also start under a toenail. That’s similar to what happened to a zoo rhinoceros I once examined.
Her cancer grew under her horn—which is made from keratin, exactly the same protein that makes up our finger- and toenails.
Cattle also develop squamous cell carcinomas in the pale skin encircling their eyes. Some Herefords have been intentionally bred for darker pigmentation around the eyes, which gives them a little more protection from the sun and seems to reduce the incidence of cancer.

Strike-branding livestock with sheet-metal strips heated to 300° to 600°F can cause tumors to grow around these permanent markings. Like
branded cattle, humans who modify their bodies with branding are at increased risk of cancer at the sites of these injuries. Even tattooing may be associated with a rare form of skin cancer.

Cancer strikes across ecosystems and throughout the animal kingdom.
Osteosarcoma, the cancer that forced Ted Kennedy’s son, Ted Junior, to undergo an amputation in the early 1970s, attacks the bones of wolves, grizzly bears, camels, and polar bears. Paul Allen, the cofounder of Microsoft, successfully battled Hodgkin’s lymphoma.
Sadly, a killer whale from Iceland succumbed to this cancer of the immune system after months of fever, vomiting, and weight loss.
And the neuroendocrine cancer that claimed the life of Apple cofounder Steve Jobs, while rare in humans, is a fairly common tumor of the domestic ferret and has been diagnosed in German shepherds, Cocker spaniels, Irish setters, and other dog breeds.

Wild sea turtles around the world are dying in large numbers from cancerous tumors possibly triggered by a herpes virus.
Genital cancers have become rampant in marine mammals, from North American sea lions to South American dolphins to open-ocean sperm whales. Many of these cancers are brought on by rampaging strains of the papilloma virus, which in humans can cause cervical cancers and genital warts.

So severely is the disease assailing some animal groups that three wild species are facing extinction because of cancer.
Tasmanian devils, found only on their namesake island off mainland Australia, are in the midst of an epidemic of devil facial tumor disease, a cancer that spreads when they fight. Deaths from cancer are hindering conservation of endangered
Attwater’s prairie chickens, which used to thrive across Texas, and
Western barred bandicoots, an Australian marsupial.

Cancer can grow in insects, including fruit flies and cockroaches.
The disease can even be destructive in the plant world, although plant tumors, sometimes called “galls,” cannot metastasize and so, for plants, cancer is a chronic condition, not a leading killer. Although cancer rarely kills the plant, it does decrease its vigor.

One thing is clear: cancer is not unique to humans. And neither is it a product of our modern times.
More than 3,500 years ago, before soup cans were lined with bisphenol A–laced plastic, before hormones were pumped into meat, and before methylparabens were added to shampoos, Egyptian physicians described human breasts with “bulging tumors.”
Ancient Greek doctors, including Hippocrates, explicated cancer in their medical texts (and coined the term
karcinos
, which means “crab”). The disease appears in ancient Indian Ayurvedic and Persian medical books and in Chinese folklore. Galen, the renowned second-century Greek physician who practiced in Rome, said breast cancer was the most common of the many cancers he saw. In fact, as James S. Olson writes in
Bathsheba’s Breast
, “
Among ancients, breast cancer
was
cancer,” primarily because it was the one they could easily see.

In the last few decades, paleopathologists have used X-rays and other methods to survey Egyptian mummies.
They’ve examined Bronze Age skeletons from Britain and preserved corpses from Papua New Guinea and the Andes. While their data is admittedly limited—no soft tissue, DNA degradation—the researchers widely agree that cancer did indeed exist in human antiquity. But it’s even older than that.

In 1997, amateur fossil hunters happened upon the fossilized remains of a female meat eater known as
Gorgosaurus
, a lanky cousin of
T. rex
. The paleontologists from the Black Hills Institute of Geological Research who examined her became intrigued by a puzzling finding. In spite of her fearsome, five-inch-long serrated dagger teeth and impressive twenty-five-foot height, this
Gorgosaurus
was riddled with injuries: a lower-leg fracture, fused vertebrae in her tail, a shattered shoulder, broken ribs, and a raging, pus-filled jaw infection. Examining the fossils with electron microscopes and plain radiographs revealed a possible explanation for these multiple injuries. The scans showed evidence of a mass in the dinosaur’s skull. While paleontologists have argued over the nature of this mass, some experts believe it to be the fossilized remains of a brain tumor.

A tumor positioned in the ancient animal’s skull would have pressed on her cerebellum and brainstem. These areas are critical regulators of motor activity, balance, memory, and autonomic functions like heart rate. What this meant for the dinosaur is written into her injured skeleton. Researchers suggest that the burgeoning tumor likely affected her daily life.

“
As the tumor grew, the dinosaur—a female perhaps three years old—would have forgotten where she left her last kill, and then she would have forgotten to go to the bathroom,” said one. A tumor in that position meant she wouldn’t have been able to move quickly or make
rapid predatory decisions. Like many humans with brain tumors, this ancient creature might have had pain—excruciating headaches upon waking and when bearing down for a bowel movement or any time she bent her head lower than her heart, perhaps to drink or feed or mate.

Other paleo-oncologists have found tumors in hadrosaurs, the duckbilled prey favored by
T. Rex
.
At the University of Pittsburgh, medical students learn about cancer by studying a 150-million-year-old diseased dinosaur bone on loan from the Carnegie Museum of Natural History.
And evidence of probable metastatic cancer has been found in the bone of a Jurassic dinosaur that lived some 200 million years ago.

Because dinosaur DNA would have been subject to transcription errors similar to those humans face, it’s not surprising that tumors formed in prehistoric creatures. On the other hand, environmental factors may have played a role as well. For most of us, “carcinogens” is synonymous with “man-made toxins.” In fact, however, many mutation triggers are as natural as flowers, plants, and sunshine.

At times, even the most pristine, “natural” corners of our planet can become as polluted as a Superfund site. A couple of million years ago, for example, you wouldn’t have wanted to be living in what is now Yellowstone National Park’s unspoiled Hayden Valley. That’s when the region’s supervolcano spewed ash over an area that would now cover sixteen states.
About sixty-five million years ago, in an area of west-central India called the Deccan Traps, a monster volcano belched more than a quarter of a million cubic miles of lava over the landscape and filled the air with toxic gases like sulfur dioxide.
Ionizing radiation, toxic volcanic spew, or even Mesozoic food sources may have wreaked havoc with the DNA of the living creatures inhabiting the Earth in these areas and during these periods.
In fact, cycads and conifers, the oldest living seed-bearing plants, and staples of dinosaurs’ diets, contain potent carcinogens. This means that we are not the first (or only) species on Earth whose diet or environment has been infiltrated with carcinogenic substances.

“Jurassic cancer” demonstrates that while we humans may have coined the term “cancer,” we certainly didn’t create the condition. In fact, the sheer ubiquity of cancer makes it an intrinsic part of life. Yes, toxic exposures created by humans have amplified the risk, in some cases greatly. Several examples of cancer in animals I named earlier have been linked to environmental poisons (more on that in a moment). But the
potential
to get cancer is simply part of being a living creature on Earth, an organism with cells containing replicating DNA.

The vulnerability of DNA to mutation means that cancer “
becomes a statistical inevitability in nature—a matter of chance and necessity,” as Mel Greaves wrote in
Cancer: The Evolutionary Legacy
.

While nothing is likely to dull the devastation a patient feels upon hearing the dreaded words “You have cancer,” perhaps there’s a small measure of solace to be found in the knowledge that the disease is at least as old as the dinosaurs and as universal among today’s animals as hearts and blood and bones. But a zoobiquitous approach to cancer research could promise more than psychological balm. It could lead to breakthroughs in treatments, therapies, and our understanding of the risks. In fact, it’s already starting to do just that.

Imagine two animals: a tiny bumblebee bat (weight: .07 of an ounce, the size of a penny) and an enormous blue whale (weight: 420,000 pounds, the size of twenty-five elephants). The huge whale has vastly more cells in its body than the tiny bat and trillions more cell divisions over its longer life. Which animal would you predict would be more likely to get cancer? Because we know that cancer stems from a single cell’s faulty replication, you might think that animals with more cells, more replications, and more mutations would have more cancer.

Genomics researchers at the University of Pennsylvania tested this hypothesis by calculating the number of cells in the human colon and comparing it to the number of cells in the colon of a giant blue whale. They concluded that if cell division and “proofreading” were identical across species, all whales ought to have colorectal cancer by the time they hit their eightieth birthday.

But as far as we know, they don’t. In fact,
larger species, overall, seem to get cancer less often than smaller species. This fascinating observation is called Peto’s paradox, after the British cancer epidemiologist Sir Richard Peto, who recognized and first described this biologically surprising reality.

To be clear, Peto wasn’t talking about the size differences between large and small members of the
same
species—say, seven-foot, six-inch basketball player Yao Ming and four-foot, eight-inch gymnast Kerri
Strug. Rather, the paradox describes cancer rates
between
species—like bats and whales. In fact, within species, larger individuals may actually have a greater susceptibility to some tumors. Osteosarcoma, for example, a malignant bone cancer seen in adolescence, occurs more commonly in tall teens. Similarly, osteosarcoma in dogs is seen most frequently in larger, long-limbed breeds like Great Danes, Dobermans, and Saint Bernards.

The implication of Peto’s paradox is that there’s something special about DNA replication in large animals—something that may protect them from cancer. Large-animal DNA might be more effective at repairing itself. Perhaps the cells of megafauna divide with greater fidelity to the original and so are less susceptible to cancer-causing mutations. Or maybe they contain better DNA proofreaders and lower mutation rates. Larger animals might have better tumor-suppression genes. More efficient immune systems. Or maybe their cells are just better at programmed cell suicide—apoptosis.

If nothing else, Peto’s paradox shows that unexpected hypotheses can emerge from a comparative approach. But human cancer specialists don’t read the
Journal of Cetacean Research and Management
. And marine biologists don’t regularly attend the American Society of Clinical Oncology’s annual meeting. Important clues about the nature and behavior of cancer across species remain unconnected.

Making matters more difficult, obtaining truly accurate statistical information about cancer rates in wild species is challenging at best. Doing a necropsy on every dead animal in the wild is a practical impossibility. And human-style cancer screening for wild animals is equally implausible. If regular colonoscopies were possible in wild whales, we might find clues to their cancer-protection mechanisms.

Bringing together experts in wildlife biology, human oncology, and veterinary medicine could expand our understanding of cancer itself. Academics are increasingly recognizing the benefits of an interdisciplinary approach. The National Cancer Institute’s Comparative Oncology Program and enterprises like the Center for Evolution and Cancer at the University of California, San Francisco, are expanding research on cancer. The next major cancer breakthrough might not come from a basic scientist working on a genetically engineered mouse in a sterile lab, but from a veterinary oncologist thinking about bumblebee bats, blue whales, and Saint Bernards.

Perhaps one of the most promising places to look for cancer clues among our fellow species is the disease that ranks among the top killers of female humans: breast cancer. Breast cancer strikes mammals from cougars, kangaroos, and llamas to sea lions, beluga whales, and black-footed ferrets. Some breast cancer in women (and the occasional man) is connected to a mutation of a gene called BRCA1. All humans have a BRCA1 gene. It’s on our seventeenth chromosome. But some of us (about 1 in 800) are born with a mutated version. For Jewish women of Ashkenazi descent, it’s as high as 1 in 50.

BRCA1 appears to be an especially skilled molecular copy editor. When it’s working right, it catches mistakes in the DNA every time a cell divides. It corrects typos and restores deletions. Like a great editor, BRCA1 keeps the DNA elegant, supple, concise, and true to its original intentions. But when BRCA1 is or becomes mutated, the DNA codes can get garbled and confused. Over generations of division this can lead to cancerous cell replication.

Many organisms have vulnerable BRCA1 genes. And in some animals, its malfunction seems to result in breast cancer, just as it does in humans.
In one Swedish study, the presence of a BRCA1 mutation made English springer spaniels four times more likely to develop breast cancer. Jaguars in zoos in the United States that were on progestin-based birth control showed patterns of breast cancer that were very similar to those of women with BRCA1 mutations.
^*
Zoo veterinarians report high incidence in other big cats, too, including tigers, lions, and leopards.