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Species-Spanning Medicine
When it comes to remedying diseases and disorders, dogs and people are in it together

Call it a movement, a philosophy, a revelation or a revolution.

Call it “one medicine,” “one health” or “zoobiquity.”

Call it something new, or—given that the “aha” moment on which the concept is based came in the 19th century—call it something old that’s been remembered and repackaged amidst the growing awareness that solving the mysteries of animal diseases and disorders, from injured spinal cords to cancer, can lead to possibly curing our own.

Over at least the past five years, there has been a rekindled recognition of the species-spanning nature of diseases, and of the value of species-spanning research. About 75 percent of recently emerging infectious diseases that affect humans have their origins in animals, according to the Centers for Disease Control.

On a theoretical level, the concept of “zoobiquity,” a term coined in the 2012 book of the same name, suggests that, no matter our species, we’re all in this together, subject to most of the same infirmities, capable of passing a lot of them back and forth, and more likely to find cures and treatments if we look at the big picture—at the earth and all its creatures —as opposed to focusing solely on humans.

On a practical level, species-spanning thinking—referred to by various monikers—has led in recent years to veterinary schools reinventing themselves; to a heightened spirit of cooperation between doctors and veterinarians; to new sources of funding for research; and to the realization that, when it comes to diseases shared by humans and animals, the latter may provide a quicker and less expensive route to a cure for all.

Where do dogs fit in? Right at the top. No other animal—if not physiologically, at least in terms of sharing our genetic markers and our home environment—is as close to us.

That’s why Texas A&M veterinarians and University of California, San Francisco, medical researchers have teamed up to study spinal problems in Dachshunds and other dwarf breeds and to test a new drug that blocks secondary infections. The research, which is funded by the Department of Defense, has potential application to battlefield injuries

That’s why, in New York, veterinarians with the Animal Medical Center have joined forces with physicians and researchers at the Memorial Sloan-Kettering Cancer Center to set up trials in which electrical impulses are used to treat tumors of the urinary tract in canines, with an eye toward possible human application.

That’s why the Mayo Clinic has partnered with two veterinary schools, a medical school and a private corporation to study the effectiveness of a device aimed at predicting and controlling epileptic seizures in both dogs and humans. While traditionally, research into canine epilepsy has been funded primarily by the American Kennel Club’s Canine Health Foundation and breed clubs, the Mayo Clinic collaboration received a $7.5 million grant from the National Institutes of Health.

That’s why Tobi, a paralyzed Golden Retriever, is getting stem-cell treatments that may help him walk again as part of a clinical trial headed by Dr. Natasha Olby, veterinarian and neurologist at North Carolina State University’s (NCSU) College of Veterinary Medicine. The trial will involve as many as 30 dogs over three years.

And that’s why Peggy, a Chihuahua from Albuquerque who was born with three legs, is being outfitted with a “bionic” paw at NCSU. Implanting the prosthetic device, which will have electrodes that connect to her nerves, will allow her to run and scratch, and could add to the growing use of comparable technology in humans.

Similarities between dogs and humans, especially when it comes to genes, are also the basis for Dr. Matthew Breen’s research into the most common cancer in dogs, non-Hodgkin’s lymphoma, at NCSU’s College of Veterinary Medicine. Breen and fellow researchers have, with help from the canine genome map, developed a test that can accurately predict how long a dog treated with chemotherapy will remain in remission. In collaboration with the Mayo Clinic and others, they’re in the process of converting the canine test to a human one.

“If that happens, it will be big news,” says Breen, a geneticist and professor of genomics. Breen lost his first dog to cancer when he was 12 and, as an adult, played a role in the mapping of the canine genome—a game-changing achievement that helped place dogs front and center when it comes to health research.

“It’s likely that we will learn more about cancer by looking at what happens in our dogs over the next five to 10 years than we will in the next 20 to 30 of looking solely at cancer in people,” he predicts.

But the key, he emphasizes, is looking at both at the same time.

“If we consider dogs as dogs, we’ll be able to do so much. If we consider people as people, we’ll do so much. But if we consider them both as mammals, and look at what’s common between them, we will find some intriguing answers.”

The possibilities extend well beyond non-Hodgkin’s lymphoma, and well beyond cancer. Dogs, long our antidote for loneliness, may hold the most promise of all animals when it comes to solving medical mysteries and curing what ails us.

“The answer to some of nature’s puzzles about genetics and disease,” Breen says, “has been walking right beside us for the last few hundred years.”

***

In reality, we’ve been turning to dogs for thousands of years, sometimes quite cruelly, to try to solve our human ills: from the time of Aristotle, who conducted experiments on live animals, and the era of Galen, whose second-century experiments earned him the title “the father of vivisection,” to the period of Pavlov, whose 19th-century experiments included severing the esophagi of living dogs to better study their digestion and, as a sideline, bottling and selling their gastric juices to the public as a cure for dyspepsia.

Many of the medical treatments we now take for granted were either discovered through the use of dogs or tried on dogs first.

In England during the 1600s, the first administration of medication intravenously was accomplished in a dog, via tubes and a pouch made of an animal bladder. In the 1920s, experiments on dogs led to Frederick Banting’s discovery of insulin. Banting and fellow researcher Charles Best surgically stopped the flow of nourishment to a dog’s pancreas and, after it degenerated, removed it, sliced it up, froze the pieces then ground them up. They named the extract “isletin.” When it was injected into another dog in which they’d induced diabetes, the dog’s blood glucose level dropped.

In the 1960s—long before they were ever slipped into clogged human arteries—stents were inserted into those of dogs. When a ballooning version was developed in the 1980s, it too was first tested on dogs.

Currently, as humans wait to take full advantage of its purported promise, stem-cell therapy is becoming more common—though expensive, at around $2,500 per treatment—in treating dogs with arthritis, hip dysplasia and spinal-cord injuries. Removing, treating and reinjecting stem cells (and even differentiated cells) have led to some miraculous recoveries.

Dogs may have access to novel cures and treatments yet to be made widely available to humans, but there’s a trade-off. They are still, in a way, being used as guinea pigs. The difference is—compared to Pavlov’s day, compared to some of the unsavory experimentation on dogs that still goes on—they’re not healthy dogs, or dogs in whom diseases have been induced. Most often, they’re patients, sick dogs who have run out of alternatives and whose owners have enrolled them in clinical trials in hopes of, if not curing their own pet, furthering research that might help other dogs.

The canine cancer samples from around the country that end up in Breen’s lab come from willing donors, or at least willing owners, many of whom see contributing to such research as a way their dogs can leave a lasting mark.

“By providing that data point, it’s almost a legacy for their own dog,” Breen says. “Every dog we recruit, we ask the owner for a picture to put on our wall of honor. We have hundreds and hundreds of pictures of dogs. It helps ground people in the lab, and makes them realize what they’re dealing with is not just a piece of tissue but somebody’s beloved companion that needs to be treated with the same kind of respect.”

Under microscopes, Breen studies chromosomal changes within cancer cells, changes that have been shown to duplicate those that occur in humans. “If we look at what overlaps, it’s those shared genes that highlight the major drivers in the cancer process,” he says.

The aberration of particular chromosomes allows Breen to identify which therapies will offer maximum survival chances. In lymphoma cases, up to 90 percent of dogs respond to chemotherapy and go into remission, but only about half live longer than nine months. By looking at the genetic differences between the dogs who survive for short times and those who survive longer, Breen’s team has developed a test that determines how long a dog will stay in remission; this test will, it is hoped, eventually be available for use with humans.

Experts estimate that one in four dogs will develop cancer in their lifetime. About 50 percent of those over age 10 will die from it. The types, incidence and outcomes aren’t always identical to those in humans, but even in those differences, other clues and opportunities may be found.

Bone cancer, or osteosarcoma, for example, affects a whopping 60,000 dogs a year. In humans, there are only about 900 cases a year and, as a result, its research has never received the kind of funding awarded to work being done on more widespread cancers.

By looking at the disease itself, as opposed to its effect on a singular species, some less high-profile diseases (in humans) can get more attention, and progress can be made more quickly, Breen says.

“We ignore whether it’s in dogs or people, focus on the cancer and get to the biology faster.”

Down the road, such research might keep someone else from hearing those five fateful words Breen remembers hearing as a child, when his own Border Collie cross was stricken with cancer: “There’s nothing we can do.”

***

Rudolph Virchow, though he wasn’t credited for it in his lifetime, is considered the father of “one medicine.” The 19th-century pathologist coined the term “zoonosis” and created the field of comparative pathology.

“Between animal and human medicine there is no dividing line—nor should there be,” he said. “The object is different but the experience obtained constitutes the basis of all medicine.”

Two centuries later, a variety of factors breathed new life into his old idea. Recently identified zoonotic diseases, like swine and avian flus and West Nile virus, became major public health concerns. At the same time, dissatisfaction was mounting with research studies involving mice, primarily because their findings often weren’t transferable to humans. There was a growing recognition that all animals, both wild and domestic, serve—like the canaries once used in British mines—as sentries for environmental hazards.

Dogs, while at the forefront of much modern research, also played a large role in reviving the species-spanning way of thinking. On top of the tremendous diagnostic and research value it held for dogs, the successful completion of the canine genome map in 2005 showed how similar dog genes are to our own. It also reinforced how much more quickly canine health research can progress. Mapping the sequence of the canine genome cost about $50 million and took one year, while mapping the humane genome cost more than $3 billion over 15 years.

It was one year after that benchmark, in 2006, that the American Medical Association and the American Veterinary Medical Association issued a joint declaration encouraging more partnerships and information sharing between the two branches of medicine.

For far too long, doctors of human medicine and doctors of veterinary medicine—and researchers in the two fields—operated on separate planes. By coming together and sharing their findings, proponents of one medicine held, new opportunities could be realized and new cures, possibly, found.

To those involved with treating and researching animal diseases, the increased respect from those in the world of human medical research is palpable. Dr. Jorge A. Piedrahita, geneticist and professor in the Department of Molecular Biomedical Sciences at NCSU’s College of Veterinary Medicine, remembers a time when overtures from the veterinary medical community to the human one would result in “blank stares, as if they were thinking, What would we want with you?

“The human medicine field in the past has looked at us [veterinary schools] as technicians,” he says. “They came to us if they needed a pig or a dog, but they never saw us as partners. Now we sit with them really as equals.”

Piedrahita serves as director of the Center for Comparative Medicine and Translational Research, which was created seven years ago. Based at NCSU, one of the first vet schools in the country to fully jump on the one-medicine bandwagon, the center includes 116 researchers at five colleges. The thinking behind the center, he says, is “if we help one species, we’re helping all of them.”

Since then, Piedrahita says, the road between veterinary practitioners and doctors has become much more of a two-way street. “There have been an amazing number of new interactions, and we’re still a very young center. It’s really becoming almost like a partnership.”

Doctors and vets are not the only two cultures the movement has brought closer together, he notes. It has also led to “increased sharing between clinicians, or those working with patients, and researchers, who are confined to labs.” The result, he says, is faster and more efficient research, capable of reaching solutions sooner.

Breen’s cancer research is one example of that. Another is a project Piedrahita is involved with in conjunction with Wake Forest University’s Center for Regenerative Medicine, which is seeking a solution to urinary incontinence.

While it’s a significant issue for women, especially elderly ones, one might not think that dogs—generally a less-prone-to-embarrassment species—would rank it too high, even the spayed ones, in which it is most common. Piedrahita is quick to correct that thinking.

“It’s a very big deal,” he says. “It’s the reason many of them end up in shelters, or being returned to shelters. For the dog, it may not be that big of a deal, but for the owner, it is.”

Throw in its human applications, and it becomes even bigger.

Using cells from the patient—for now, canine patients—the treatment involves reinjecting cells, usually taken from a leg muscle, into the urethral sphincter itself, where they regenerate and build new muscle. The project has received funding from the American Kennel Club’s Canine Health Foundation, and clinical trials involving as many as 40 dogs were expected to begin in January.

***

Of all the microscopic matters detected in a typical veterinary research lab, irony is not usually among them. But here’s one that has surfaced.

Among purebreds, breeding for certain traits, and to get a certain look—most often accomplished by using dogs who are closely related—has led to recessive disorders, more than those found in any other animal except humans.

It’s believed to be why Boxers are prone to mast-cell cancer and brain tumors, Scottish Terriers to bladder cancer, and Bernese Mountain Dogs to histiocytic sarcoma. It’s why one in five Golden Retrievers is diagnosed with hemangiosarcoma.

But the limited genetic diversity that has led to cancer-causing mutations in many purebreds is also what has led to dogs becoming such a valuable tool in studying disease. Breen compares it to tuning in a radio station. With the dog genome, there’s none of the noise and static from competing frequencies—just a clear signal.

Pointing fingers is useless, Breen says. “I don’t blame anybody.” But he’s among the first to admit that limiting the gene pool has made purebred dogs “a very powerful tool for simplifying genetics.”

With their “less noisy” genetic make-up, purebred dogs offer a speedier research route. It takes thousands of human patients with cancer to identify risk factors, he notes, but the same can be accomplished with as few as 100 canine patients.

***

In the book Zoobiquity: What Animals Can Teach Us about Health and the Science of Healing, Barbara Natterson-Horowitz, a cardiologist who consults with the Los Angeles Zoo, delves into the many sicknesses we share with animals. (Editor’s note: For a review of Zoobiquity, see the October 2012 issue of Bark.)

Co-authored by Kathryn Bowers, the book points out that not only humans get breast cancer, but kangaroos, beluga whales, wallabies and sea lions—to name a few—do as well. Rhinos get skin cancer; gorillas get depressed; horses suffer from erectile dysfunction; and sexually transmitted diseases plague the non-human world as well, from syphilis in rabbits to chlamydia in koalas.

By looking at the big picture, we’re likely to further our understanding of species-spanning diseases, of the planet and of the environmental factors that contribute to ill health. Two annual conferences on zoobiquity have urged medical practitioners to do just that.

In terms of the latter, dogs, once again, serve as prime examples and perfect models. They sleep in our beds, share our food, lie on our flame-retardant-treated couches and frolic on our insecticide-treated lawns. When we go for a walk, it’s usually with them at our sides or pulling us along behind them.

They may soon lead the way in science as well, as rodents take a back seat when it comes to research examining the role environmental factors, such as secondhand smoke and household chemicals, play in causing disease. While much of it was going on years before the AMA-AVMA declaration was announced or the term “zoobiquity” was coined, research involving dogs (and cats) is increasingly looking at the link between pollutants and cancer.

On top of the fact that the canine genome is 80 to 90 percent similar to that of the human, dogs are constantly at our sides, making them perfect candidates for studying not just cures but also, causes.

Since dogs are such accessible and efficient, not to mention friendly, models, the question arises (or at least ought to): should one health/one medicine/zoobiquity—and more particularly, the view of dogs and other animals as sources of solution to our own diseases—raise animal welfare concerns?

Despite their all-inclusive, holistic and harmonious sounding names, none of the calls for a species-spanning approach to medicine state that all animals are our equals, or that their value parallels that of humans. Only that they get many of the same diseases we do.

As cures come closer and as dogs are increasingly seen as the road to such cures, could our zeal lead to what animal-welfare advocates might see as reckless driving?

The book Zoobiquity points out that in virtually all of the examples it uses, animals involved in the research were already sick. When, on ABC’s “Nightline,” Natterson-Horowitz was asked if the concept could lead to testing on healthy animals—if the Hippocratic Oath of “do no harm” should apply, for instance, to hippos—she replied, “I can’t give you a simple answer, because it’s a very complicated, nuanced question.”

Breen, for his part, doesn’t hesitate. “We don’t induce cancers in dogs. The key issue about cancers, and many genetic diseases in our dogs, is that these are all spontaneous conditions … All the dogs in our study are part of a family, sharing their homes and their lives. The path to discovery involving cancer and our dogs is one we walk along side-by-side with the owners.

“We have access to state-of-the-art technologies to ask key questions, but these are worthless without the willingness of the dog-owning community to collaborate by submitting cancer specimens from their dogs. By building a strong relationship with pet owners, and realizing that their pets are like family members, like a child … it actually means the chances of ever inducing disease are less. I just can’t see it happening; it wouldn’t happen in my lab, let’s put it that way.”

Breen’s bigger fear, when comes to biomedical research, “is that all this will raise people’s hopes too high and too soon.”

That applies to the owners of afflicted pets as well as those who are afflicted themselves, or have human loved ones suffering from a disease. We’re eager to find cures. Dogs, being such perfect models for study, provide what may be one of the quickest routes to them. While a resurgence in the use of otherwise healthy dogs in intrusive experiments isn’t likely, the future (which seems to be getting here faster and faster) isn’t crystal clear.

This much is, however: fairly early in their domestication—and in what was perhaps one key component leading to it—dogs exhibited their ability to stand sentry, to serve humans by warding off dangerous, life-threatening intruders.

In a way, thousands of years later, they’re doing it again.

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This article first appeared in The Bark,
Issue 73: Spring 2013

John Woestendiek is a Pulitzer Prize–winning journalist, editor of the website Ohmidog! and author of Dog, Inc.: How a Collection of Visionaries, Rebels, Eccentrics and Their Pets Launched the Commercial Dog Cloning Industry.

ohmidog.com

Photograph by Wendy Savage, North Carolina State University College of Veterinary Medicine
Illustrations by Tim Carpenter

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