Zoobiquity (6 page)

As veterans streamed home from Asia and Europe after World War II, doctors in the United States were battling a deadly threat on the home front.
Five times the number of Americans who died at Iwo Jima and Omaha Beach were dying every year of heart disease. In response, the National Heart Institute launched what became the gold standard in long-term medical investigations: the Framingham Heart Study.
Every two years, starting in 1948 and continuing today, thousands of men and women from that Massachusetts city go to special doctors. They give blood and other lab samples, have comprehensive physicals, and answer question after question about their eating, exercise, work, and leisure habits.

As the data piled up over decades, researchers began to discern patterns. High blood pressure and smoking led to heart disease. Age and gender influenced risk. It’s hard to believe that this information we now accept as routine was ever unknown. Even today, Framingham’s half century (and counting) of statistics is paying dividends as researchers mine the data for long-term trends in stroke and dementia, osteoporosis and arthritis. The iconic study is now in its third generation, having enrolled many of the children and
grandchildren
of the original participants.

Longitudinal medical studies—those with large populations and elongated time frames—are hard to pull off. What makes them so valuable is exactly what can make them so frustrating. Even when lots of people sign up, many drop out. Participants lose interest. They forget to go to their physicals. They move away and don’t leave a forwarding address. They blow off the third or thirteenth or thirty-third questionnaire.

But the challenge hasn’t daunted Dr. Michael Guy.
In 2012 he began enrolling three thousand participants in what is perhaps the most ambitious new longitudinal study in more than a decade. Its focus is cancer in a population that has a staggering 60 percent risk of dying from the disease.

And his research team knows for sure that their test subjects aren’t likely to cheat or fib or flee. They won’t fudge answers on their surveys or tell a researcher only what she wants to hear. They’ll be loyal and enthusiastic and obedient. The researchers know this because they chose their participants deliberately and wisely. They are all golden retrievers.

Before you start picturing a floppy-eared puppy in a sterile wire lab cage, let me explain. The dogs enrolled in the Canine Lifetime Health Project—a long-term cancer study Guy sometimes calls “Framingham for Dogs”—are beloved pets. Recruited from normal homes all over the United States, they live in yards and bedrooms, romp with children and other dogs, eat the food their owners carefully select and prepare for them. They walk neighborhood sidewalks and play fetch in local parks.

Like the human participants in the Framingham study, each dog in the Canine Lifetime Health Project will be followed for the rest of its life. As the data roll in, epidemiologists, oncologists, and statisticians will scrutinize the dogs’ diets to see if nutrients or portion sizes contribute to developing cancer. They will pore over environmental exposures—from secondhand smoke to household cleansers. They will measure how far the dogs live from power lines and freeways to determine whether any cancers cluster in significant ways. The researchers will analyze the genetic code of each dog, comparing it to the others and to the complete canine genome (
completed in 2005 on the DNA of a female boxer named Tasha).

This unprecedented study, undertaken by the nonprofit Morris Animal Foundation, could radically shift our approach to cancer in dogs. And the effort may yield knowledge that will benefit not only future generations
of pets but also the animals at the other end of the leash. Dog cancer has many stories to tell about human cancer: where it comes from, why it migrates, and, possibly, how to stop it in its tracks. A multispecies take on cancer research means our special relationship with man’s best friend is about to get even closer.

Except for some grizzling on her muzzle, Tessa’s fur was glossy black—a striking contrast with her streetlight-yellow vest. The bright garment, as snug as a Partridge Family costume, was covered with embroidered patches. A few advertised dog food companies. One identified Tessa as a “Dock Dog,” an elite animal athlete whose jumping and fetching prowess makes the average pet look like a Little Leaguer going up against Derek Jeter. But the most noticeable feature of Tessa’s vest were the two words stitched in black thread across her midriff: “Cancer Survivor.”

Tessa is a black Labrador retriever I met in the spring of 2010 at a gathering of pet patients who had battled illnesses and won. Although a brown lesion on the gum behind her lower left fang was still visible, her mouth cancer had been in remission for two years.
As I patted Tessa’s furry, wedge-shaped head, her owner, Linda Hettich, explained how she had discovered her dog had the disease. They were playing fetch and Tessa brought back a bloody tennis ball. A trip to the vet confirmed a cancer diagnosis, and Tessa went into treatment. Although Hettich’s distinct alto voice (she’s the noon anchor for a Los Angeles news radio station) conveyed gratitude that Tessa’s cancer had not returned, her face betrayed a certain grim anxiety. Tessa was not her first dog to have cancer. A few years earlier, her beloved mutt, Kadin, had died of it. Hettich admitted in a whisper that she sometimes wonders why two of her dogs have fought the disease.

“With Kadin, there was a tremendous amount of guilt,” she told me. Now that Tessa has had cancer, she said, there are moments when she wonders, “I’m two for two—what did I do?”

That didn’t surprise me a bit. I’d heard “What did I do?” before; that question frequently plagues many human cancer patients, too.

One of my roles at UCLA involves caring for people who’ve developed heart problems as a side effect of their cancer treatments. Sometimes they share with me their personal theories for why they drew the cancer
card. Often, it’s something they did:
My cell phone. My deodorant. My char-grilled salmon. My microwave. My lipstick. My plastic Evian bottle. My years as a flight attendant
. Or something they didn’t do:
Missing church. Not exercising. Skipping mammograms
. Something that was done to them:
My father’s nicotine addiction. The fluoride in my water. The new carpet at my office
. Or general stress:
A lingering lawsuit. A mountainous credit card balance. Caring for an aging parent
.

I understand that these narratives allow patients to feel a modicum of control in the face of a terrifying diagnosis. Because that in itself can be healing, I usually just listen quietly as I measure their blood pressure, check their pulses, and place my stethoscope over their heart. But some seem to be seeking medical absolution, so I gently remind them of something they’ve surely heard before: cancer has many causes. Within the DNA we inherited from our parents, from our great-great-great-grandparents, and from ancient animal ancestors lie the blueprints and machinery that instruct cells to create and maintain our body parts. But when this machinery contains errors and then malfunctions, the out-of-control growth we call cancer can develop.

Here’s what I mean. Living, growing organisms must constantly replace old and dying cells with fresh, new ones. Making a new cell requires copying every single one of the almost three billion building blocks (called nucleotides) in the cell’s DNA. This provides the daughter cell with the exact same information as its parent. When all goes well (and, astonishingly, it usually does), the DNA is copied exactly. But occasionally, about once every ten thousand nucleotides, a mistake is made. Chemical codes can be left out, duplicated, or put in the wrong place.

Much of the time, these slipups—called mutations—are caught by the cell’s chemical “proofreaders” and fixed before they wind up in a new cell. Often, a “typo” sneaks through but it’s not significant and the cell can continue along normally, even with the misprint. Sometimes these mistakes occur in critical regions of the DNA and actually enhance cell function. These minor changes, over time, can produce new traits, new behaviors, and even new species. For example, alterations or mutations are responsible for size differences in dog breeds. Slight variations in the genes that direct skeletal growth create the most obvious difference between a Chihuahua and a Great Dane.

However, some mutations harm the cell’s function. For example, normal
cells carry “suicide codes” in their DNA. When a cell gets old or is damaged beyond repair, these codes spring into action and cause the cell to self-destruct in a process called apoptosis. But cells can develop mutations in the very genes that direct the destruction. When the destruction instructions go awry or malfunction, the damaged cells will stay alive. They then can replicate—mistakes and all. When that happens, the new defective cell, like its parent, lacks normal cell death instructions. Now there are two cells, each with DNA mistakes and missing the appropriate controls. When these faulty cells replicate, they become four, then eight, then sixteen. Soon an entire population of immortal cells has grown without restraint. This is cancer: initially normal cells, grown out of control, now with different DNA instructions.

When the out-of-control, mutation-containing cells cluster together, they form a tumor. Sometimes the mutated cells find their way into the bloodstream or lymph system, which are essentially superhighways with mass access to the rest of the body. When the cells travel far from their origins and then replicate in the new location, that’s metastasis. Some cancers, like melanoma, metastasize readily. Others, like chordomas found on the base of the skull, are less ambitious and grow primarily in one region. (By the way, this is the most basic difference between the cancers we call “benign” and those we say are “malignant.” Any mass of abnormal cells is a tumor, but benign growths tend to remain in the same location and refrain from invading nearby tissues.)

But whether a cancer is sluggish or fleet, a homebody or an adventurer, tumor-forming or what we call “liquid,” what underlies its enormous burden of suffering and death is nothing but errors in the genetic code. Many behaviors and factors in the environment promote these errors and lead to cancer.
Smoking, sun exposure, excess alcohol consumption, and obesity have all been linked to DNA damage and to various cancers.

There’s also a catalog of known, toxic substances that, given adequate exposure, can almost certainly trigger cancer: naturally occurring radon (and other radioactive substances), asbestos, chromium-6, formaldehyde, benzene, and others. The National Institutes of Health (NIH) flags fifty-four documented carcinogens implicated in human cancers. More research will surely add to this list.

With so many toxins in our environment and so many cancer diagnoses in our communities, it’s easy to point to our polluted surroundings
and connect the cancer-causing dots to our neighbors’ suffering. Cancer, many people believe, is unnatural—a disease of our own making. In fact, cancer prevention has become a marketing tool. The simple act of choosing milk or deodorant or tuna fish can feel like a high-stakes exercise in cancer avoidance. Sorting out what’s Madison Avenue from what’s medically accurate has become a challenge for patients and a responsibility for their doctors.

But cancer can also develop in people who didn’t smoke, drink, or tan and who avoided microwaving food in plastic and cooking on Teflon. It strikes yoga practitioners, breast-feeders, and organic gardeners; infants, five-year-olds, fifteen-year-olds, fifty-five-year-olds, and eighty-five-year-olds. And, pointedly, it’s not uncommon to see elderly patients who have done everything “wrong” … but show no trace of the disease.

The impulse to blame ourselves or our cultures for our diseases is not unique to modern society or to cancer. As the medical historian Charles Rosenberg has pointed out, “
The desire to explain sickness and death in terms of volition—of acts done or left undone—is ancient and powerful.”

What insights can a species-spanning approach bring? Even the briefest survey of cancer in other animals sheds light on a critical but overlooked truth: where cells divide, where DNA replicates, and where growth occurs, there will be cancer. Cancer is as natural a part of the animal kingdom as birth, reproduction, and death. And, as we’ll see, it’s as old as the dinosaurs. Literally.

Tessa was just one of the million or so dogs who get diagnosed with cancer each year.
Intriguingly, many canine cancers behave very similarly to human cancers. Lethal prostate cancer runs a similar clinical course in men and male dogs. Breast cancer may seek bone tissue in female dogs, just as it can preferentially metastasize to the skeleton in women. Osteosarcoma, which tends to hit human teenagers during their growth spurts, strikes with similar ferocity in many large and giant-breed dogs.

Sadly, many outcomes are similar, too. As in people, many cancers in dogs become resistant to therapy. And in both species they can recur, even after a patient has been given the all clear.

Dogs aren’t the only animals in our lives who get cancer. When a
cat presents with fever and jaundice, the vet must consider
leukemia or lymphoma, leading feline killers in the United States.
And when a cat’s owner discovers a lump in her pet’s breast, it may turn out to be a highly aggressive form of breast cancer also diagnosed in many women. For some cats with breast cancer, lumpectomy may suffice. For others, radical mastectomy of the entire chain of all eight mammary glands must be performed.

Rabbit hysterectomies are commonly recommended due to the high risk of uterine cancer as these pets age.
Parakeets are prone to developing tumors on their kidneys, ovaries, or testes. And cancer patients can also be reptiles.
Zoo veterinarians have reported on leukemia in pythons and boa constrictors, lymphoma in death adders and hognose snakes, and mesothelioma in rattlesnakes.

Pediatricians of fair-skinned children aren’t the only doctors who worry about skin cancer in their patients.
Equine sunburn is thought to cause skin cancer in light-colored horses, although this “gray horse melanoma”
may connect more to a genetic issue in the breed than to too many hours spent basking in the sun. Still, because as many as 80 percent of gray horses will get skin cancer of some kind, their concerned owners, along with those of horses with white “socks” on their legs or blazes on their noses, sometimes apply zinc oxide sunscreen to exposed skin areas. Others, like the parents of towheaded toddlers, insist that their horses wear a hood when out of the stable.