Zoobiquity (8 page)

And yet, having a BRCA1 mutation doesn’t automatically lead to breast cancer. BRCA1-related breast cancer results when genetic predisposition meets something that activates it—including hormonal and environmental exposures. Researchers call these triggers “second hits.” And studying a variety of animals could help pinpoint which combination of genes and triggers leads to cancer.

This leads to the counterintuitive possibility that when it comes to breast cancer, a jaguar originating in South America and an English springer spaniel living in Sweden might be medically more relevant to an Ashkenazi Jewish woman than her next-door neighbor is. In medical jargon, we call these spontaneously occurring cancers “natural animal
models,” and they’re prized by scientists for their power to expose the true biology of disease.

Unlike the jaguars and spaniels who carry an increased risk of breast cancer, some groups of mammals, intriguingly, may be protected from it.
^†
The latte you sipped this morning contained milk from an animal sorority that very rarely gets breast cancer.
Professional lactators—the dairy cows and goats that make milk for a living—have rates of mammary cancer that are so low as to be statistically insignificant. That animals who lactate early and long seem to have some protection against breast cancer is not only fascinating; it parallels human epidemiologic data that tie breast-feeding to reduced mammary cancer risk.

The species-spanning protective power of breast-feeding—or the hormonal states associated with it—could hint at a new form of prevention. For example, if induction of lactation, a few times a year, could be shown to dramatically reduce a woman’s lifetime risk of developing the leading lethal cancer among females, it could transform preventive medicine. This may sound odd, but it’s just one step stranger than many other health-maintenance routines we take for granted. Women have their cervixes swabbed and their breasts X-rayed. For many, taking hormone-altering daily birth control pills has become standard, quelling endometriosis, suppressing acne, or even guaranteeing a period-free honeymoon. We have our colons scoped, our skin scanned for moles. You might not wrinkle your nose at the idea of scheduling a preventative, induced lactation if you knew that your risk of breast cancer might plummet to the level enjoyed by professional animal lactators.

It may also be that lactation is protective because it decreases the exposure to estrogen a breast receives with every menstrual cycle. An approach suggested to me by Chris Bonar, the chief veterinarian of the Dallas World Aquarium, could help clarify exactly what it is about breast-feeding that seems to be protective. He noted that female mammals have different numbers of reproductive cycles per year.
Some wild bats, for example, have vaginal menstrual bleeding every thirty-three days, a monthly cycle similar to that of some primates, including
humans. In contrast, sheep and pigs are polyestrus and ovulate only several times a year. Female ring-tailed lemurs, bears, foxes, and wolves usually cycle just once a year. But breast-feeding disrupts reproductive cycles in mothers. So by comparing breast cancer rates in female animals with different cycle frequency—and different hormone exposures—comparative oncologists could home in on an important distinction: how much breast-feeding’s power to protect comes from lactation itself and how much from disrupting the hormones that accompany reproductive cycles.

Another thing we can learn from animal cancer is the extent to which it’s caused by outside invaders: viruses. Veterinary oncologists see this all the time. Lymphomas and leukemias among cattle and cats are quite frequently viral. Many of the cancers sweeping sea creatures from turtles to dolphins are rooted in papilloma and herpes viruses.

As we know, cancer starts as a cell with mutated DNA. Few things in nature rival viruses for their skill at tinkering with DNA. But human physicians tasked with fending off and treating so-called lifestyle cancers, such as those caused by smoking, drinking, or overeating, tend to think “infectious trigger” only when it comes to a narrow range of malignancies. Every oncologist and many patients, for example, know that viruses are responsible for Kaposi’s sarcoma, some leukemias and lymphomas, and some liver cancers. “Cancer à deux” (cervical and penile cancers shared by sexual partners) is spread by the human papilloma virus.

In fact, worldwide, about 20 percent of human cancers are viral. In Asia, the leading cause of liver cancers is viruses: hepatitis B and C.
Across Africa’s “lymphoma belt,”
^‡
the Epstein-Barr virus is a known driver of Burkitt’s lymphoma. Human papilloma virus and hepatitis B and C are on the NIH’s list of known carcinogens. The idea that cancers spread virally has led some epidemiologists to call for treating cancer as an infectious disease. This is something veterinarians already do.

Peto’s paradox, Jews and jaguars, professional lactators, viral triggers—in these cases, a zoobiquitous approach can help us generate new hypotheses about the causes of cancer. But animals may be able to help us in a
more urgent or timely way. They may be able to warn us of impending disease—before it actually strikes us.

In 1982, dead beluga whales began drifting ashore along the St. Lawrence Estuary in northeastern Canada. The leading cause of death was a grim list of cancers. Intestinal. Skin. Stomach. Breast. Uterine. Ovarian. Neuroendocrine. Bladder.

The St. Lawrence belugas, it turned out, were saturated with heavy metals, as well as other industrial and agricultural contaminants, including dichlorodiphenyltrichloroethane (DDT), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). Researchers from the University of Montreal didn’t have to look far for the source of these artificial intruders. Lining the coast were aluminum smelters. Every year for decades, these factories pumped tons of PAHs into the water and released other contaminants into the air. Day after day, these compounds had drifted through the water and accumulated on the ocean floor. Mussels and other sea-dwelling organisms absorbed them. When the belugas scooped into the sediment to feed, they received a double dose of toxins—in the sand and silt as well as in their food.

The contaminants were linked to the whale cancers and the die-off. Significantly, another group of animals living around the St. Lawrence Estuary at the same time shared the whales’ unusual cancer patterns: humans.

When animals die in clusters, we’re wise to pay attention. Emerging infectious diseases like SARS and avian influenza often show up first in animals. Endocrine-disrupting chemicals may manifest in animals before they affect human fertility.
Animals even forewarn us of biological attacks or chemical leaks; when anthrax escaped from a Soviet military facility in 1979, for example, the first to die were nearby livestock.

Sometimes the animal warnings point to cancer.
Although PCB production and DDT use have been banned in the United States for more than thirty years, researchers now suspect that the toxins may be contributing to a significant increase in the outbreak of sea lion cancers off California. For thirty years, starting in the 1940s, manufacturing companies used this part of the Pacific to dump millions of pounds of those
chemicals. Although the Environmental Protection Agency instituted a clean-up in 2000, there’s one reservoir that’s hard to get at: the animals’ own bodies. Through gestation and lactation, up to 90 percent of a mother’s contaminant load can be “dumped” into her first-born pup. Veterinary oncologists believe that either repeated “hits” of the toxins are causing the animals’ cells to mutate or they’re suppressing the animals’ immune systems so much that the herpes virus that causes the cancer has a better chance to replicate. If that’s true, these animal cancers could be warnings to humans living in areas polluted by similar chemicals that the dangers of toxins might go beyond direct exposure. They may be passed down through generations (meaning their presence can be felt long after a toxic site is cleaned up) and/or have secondary effects on the immune system.

Industrial pollutants are causing animals to suffer and die. Responsibility for these animal illnesses lies squarely with our species. Indeed, if animals could lawyer up, we humans would probably find ourselves as the defendants in any number of class-action lawsuits. Beluga whales shouldn’t have to die terrible deaths from cancer because we allow our industries to foul the waters where they eat and breed.

So with the proviso that in an ideal world we wouldn’t give animals cancer for the convenience and greed of certain industries (many of which we all partake in, whether petroleum or plastic or pesticides), the sad fact that animals get cancer can be helpful to humans if we think of them as sentinels. And one way to honor their sacrifice is to do something about it. Not pretend it doesn’t affect us. As governments, as societies, as a species, we need to act when we see disease emerging in clusters of animals—to save them and to save ourselves.

As humans, we don’t live in the waters of the St. Lawrence Estuary or the Pacific kelp beds off California. We live in condo complexes and single-family homes, studio apartments, farmhouses, and trailers. And in all of those places, who lives with us? Dogs.

Hundreds of millions of dogs around the world coexist with us as pets. At the simplest, most expedient level, this means they can serve as in-house sentinels to warn about or confirm cancer risks.
One study of nose and sinus cancers in dogs, for example, found a strong correlation
with the use of indoor coal or kerosene heaters. The longer the dog’s nose, the greater its chance of getting this cancer, possibly because of a greater exposed nasal surface area.
Bladder cancer and lymphoma, both linked to pesticides, have been reported in pet dogs, with a higher risk for bladder cancer found in female dogs that were obese.
And military dogs who served in Vietnam had higher-than-usual rates of testicular cancer, possibly because of their exposure to a variety of chemicals, infections, and medications during their tours of duty.
^§

Where we don’t overlap might be telling, too. Dogs rarely get colon cancer. Lung cancer is also atypical, although short- and medium-nosed dogs living in homes with smokers are susceptible. Canine breast cancer is rare in countries that promote spaying but quite common where most female dogs remain reproductively intact. In humans, too, oophorectomy (removal of the ovaries) and premature ovarian failure dramatically reduce breast cancer risk.

But beyond their possible use as canine canaries in our domestic coal mines, dogs may be ideal proxies for studying the actual biology of how cancer works in our own bodies.
Currently, the vast majority of cancer studies are done on mice. So-called humanized mice have been specially bred to mimic our gene patterns. Often their immune systems have been altered to allow the cancer to grow. Most lab mice are “given” cancer; usually it doesn’t arise spontaneously in their bodies. For decades, this “artificial” cancer has yielded useful insights into tumor biology—how cells divide, how tumors form, how they metastasize and spread to other parts of the body. But the genesis of the disease, its complexity, how it becomes resistant to therapy, and how it recurs are really not answerable in mouse models. Even side by side, under a microscope, mouse tumors are very different from human tumors.

Our human tumors, it turns out, are remarkably similar to those of the animals with whom we live: our pet dogs.
Dog cancer cells and human cancer cells are nearly indistinguishable. Dogs live longer than mice, so researchers can observe the cancer—and the treatments—over the long term. And, unlike most lab mice, pet dogs’ immune systems are intact, allowing oncologists to study how a cancer acts when challenged
by natural defenses. Dogs are also simply much bigger than mice. This has implications, both practical—the tumors are physically easier to see—and philosophical (think of Peto’s paradox).

Here I must pause to make absolutely clear that I’m
not
talking about experimenting on dogs in labs. I’m talking about the opposite. Observing cancer while caring for companion animals—pets—who develop cancer spontaneously and receive treatment from veterinarians.

This novel approach is known as comparative oncology. Recognizing that studying naturally occurring cancers in the animals that share our homes might unlock some of cancer’s mysteries, the National Cancer Institute launched the Comparative Oncology Program (COP) in 2004. One of the COP’s early innovations was to pool the brain trusts of twenty top-tier veterinary teaching hospitals in the United States and Canada. This network, called the Comparative Oncology Trials Consortium, conducts clinical trials in pet dogs, searching for new anticancer drugs and treatments for human patients. (The trials are sponsored by pharmaceutical companies hoping to bring new human therapies to market.) But while pet health may not be the intended goal of the program, some of the advances that benefit humans will come back full circle to enhance the health of animals, too.

Comparative oncology has already improved the health of many animals, including us. It’s not a stretch to say that new cures have come out of cross-species cancer comparisons (although physicians and veterinarians alike tend to manage expectations with more clinical terms like “novel therapeutic strategies” and “positive survival rates”).
For example, the limb-sparing technique that human doctors use today to save teenagers with osteosarcoma from amputations was pioneered in dogs by a veterinary oncologist, Stephen Withrow, and his team at Colorado State University, working jointly with physicians. And a potential cure for malignant lymphoma using transplanted stem cells was first successful in twelve pet dogs under treatment at Fred Hutchinson Cancer Research Center in Seattle, paving the way for this technique to be used in human beings.

Veterinary gene chasers are currently looking at DNA for molecular clues to canine lymphoma, bladder cancer, and brain cancer. And here’s why genes are relevant: picture a Great Dane looming over a Chihuahua or a Saint Bernard sniffing a pug. Members of
Canis lupus familiaris
,
although belonging to the same species, can look and act extremely different from one another. But those desirable differences—traits honed over centuries of selective breeding and codified in the American Kennel Club Blue Book—carry an ironic and sometimes tragic Trojan horse. As
Kerstin Lindblad-Toh, the MIT molecular biologist who led the canine genome-mapping project, explained to me, breeding for desirable traits inadvertently selects for and transmits other mutations, some of which can cause cancer.