How your pet can save your life
HOW MEDICAL SCIENCE IS TURNING TO ROVER AND FLUFFY AS A SUPERIOR ALTERNATIVE FOR CLINICAL TRIALS
There are none of the usual padded chairs and IV poles in the chemo room, just black gym mats on the floor and doggy treats at the ready. Eight-year-old Bosco is lying on his side, a catheter inserted into a hind leg. His handlers, wearing protective masks and gowns, are on the floor with him. One gently holds him down while the other checks to make sure the catheter is well inside the vein, so that the toxic chemo doesn’t spill into the surrounding tissue.
“I’m in,” she says, then injects a syringe filled with the cancer drug doxorubicin.
Bosco’s owners, Alex Magditsch and Lynda McCarthy, first noticed a fatty lump on the dog’s left side at Christmas, and soon after that, another small mass on his lower jaw. Their vet then discovered enlarged lymph nodes in his groin and neck. By February, a biopsy came back cancer: aggressive multicentric lymphoma.
They were devastated by the news, so on their vet’s advice they turned to the Ontario Veterinary College’s Mona Campbell Centre for Animal Cancer. Bosco was immediately scheduled for 25 rounds of chemo at the facility, part of the University of Guelph. The family also agreed to enrol their mixed-breed rescue in several clinical trials, including one exploring whether a special molecular test can predict early enough how well dogs with advanced lymphoma are responding to their chemo, so they can be switched to a more effective drug if needed.
All this might sound extreme. The price tag for canine cancer treatments can run $10,000 to $20,000. But Bosco’s treatment could save not only his life, it may save yours.
Vets are collaborating with researchers in human medicine to study the genetics of a fatal heart disorder shared by dogs and humans. They’re working on epilepsy, and stem-cell therapy for spinal cord injuries.
“To me, it’s one medicine. It always has been,” writes veterinarian Stephen Withrow on the website for the Flint Animal Cancer Center, one of the world’s largest, which he founded at Colorado State University. “One medicine. One cancer. One cure.”
But selling this to funding agencies and industry has been difficult, he says, “convincing big drug companies that we have relevant models that can be studied so much cheaper than human trials.” There’s also a risk that any adverse event that might be species-specific — “on rare occasions,” he says, “cats don’t behave like people” — would slow down progress on human drug development.
So labs continue to use mice — not sweet, mixed-breed family dogs — for research.
The thing is, when researchers succeeded in mapping the first full genome of a dog in 2005 — Tasha, a female Boxer — they discovered humans share more of their ancestral DNA with dogs than with mice.
In fact, studies suggest that 85 per cent of drugs that appear promising when tested on the lowly lab rodent fail spectacularly when moved into humans. Cancer drugs are the ones most likely to flop.
Dogs and humans, on the other hand, coevolved. We live in the same homes, not sterile cages, we breathe the same air and are exposed to the same pollutants and pathogens that might trigger mutant cells that morph into cancer.
Dogs are genetically diverse, just like humans, and have intact immune systems. Companion animals also develop tumours naturally and spontaneously, the same way we do. Some shared tumours can be so functionally identical it’s hard to know “dog” from “human” when looking at a biopsy.
Given the leap between mice and humans, the thinking now is, “maybe there’s a better stepping stone,” says Brian Lichty, of McMaster University’s Immunology Research Centre, who is collaborating with Ontario Veterinary College (OVC) researchers testing a breast cancer vaccine in cats.
The cardiovascular systems of dogs and people are also remarkably similar, veterinarians say. Canine dilated cardiomyopathy, a deadly disease that causes the heart to weaken, dilate and swell like a balloon near bursting can lead to congestive heart failure. DCM is the second most common form of heart disease in dogs — and the third most common in humans.
Yet dogs age and die five to eight times faster than humans, meaning the outcomes to studies testing new therapies can be known that much sooner, and at far less cost.
All this may give some animal lovers pause. “We understand why people may have this visceral and immediate reaction,” says Dr. Alka Chanda, chief of laboratory case management for PETA. But while her organization is categorically opposed to experimenting on dogs and cats in labs, these animals are not being used as “test tubes with tails,” she says.
Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, says dogs with cancer are treated as compassionately, maybe “sometimes even nicer,” than people. “Nobody is taking a dog and putting him in a kennel in a room somewhere, never to be seen again, and experimenting on them,” he says. “These are pets that are getting genuine care.” “Has she been out to pee? “I sound like such a mom.” Dr. Fiona James bends down to stroke Vallie, a “Shorkie,” or Shih tzu-Yorkie mix. Vallie has been having seizure-like episodes for more than a year. She sometimes goes limp, like a noodle, other times rigid and dazed. “You can call her name, but you can tell she’s not with it,” her owner, Cheryl Parker, says.
Today, Vallie is lying on a blanket, James, her residents and students huddled in a circle around her, their heads nearly touching. “There’s no personal space in neuro,” James quips as she inserts the first of 15 electrode needles into Vallie’s scalp, just beneath the skin.
When the dog flinches with the first poke, then the second, James orders “happy juice,” a quick-acting, but also quick-reversing sedative. “She’s conscious,” James says, as the team resumes attaching the electrodes to Vallie’s scalp, cheekbones and the base of her ears. “She just doesn’t care.”
These electrodes will feed brain wave data wirelessly to a camera and laptop. James has created an EEG backpack worn by the dogs, modified from those worn by children, that allows the veterinary neurologist and professor at OVC to monitor a dog’s epilepsy while it is moving, even chasing a ball across a field, instead of trying to diagnose epilepsy with the dog heavily sedated or under anesthesia — which can abolish the very behaviours, the twitches or seizures, she’s trying to catch.
Epilepsy is five times more common in dogs than in people and affects many breeds. The classic seizure for a dog is a generalized tonic clonic seizure. But dogs, like humans, also suffer absence seizures, where they blank out briefly, or partial seizures, “where you might have a little twitch, similar to the twitch you might get in an eyelid when you get tired and stressed,” James explains. It can be difficult to distinguish these seizures — like the Boxer James once treated who would shake his head vigorously from side to side — from a behavioural issue, like an obsessive-compulsive disorder.
Working with her predecessor, Dr. Roberto Poma, James decided to see whether they could record animals awake. “And we did that with a little chihuahua who wore the cables when he was confined to a baby crib.”
His nose twitches turned out to be absence seizures, the first time such seizures were recorded in a dog. After their paper was published, in 2010, James wondered, “Maybe we can go one step further. Maybe we can cut the cable.”
She looked to the Hospital for Sick Children in Toronto, working with researchers in pediatric epileptology. She got a grant, and started recording brain activity in dogs suspected of having epilepsy.
Now she’s giving back. Working with the mobile backpack on Rhodesian ridgebacks, James and an international team have discovered a new gene mutation in dogs that may help better diagnose and treat myoclonic epilepsy, one of the most common forms of epilepsy in children and adults. The disease causes rapid, jerk-like movements of the face, limbs or muscles, like the sudden spasms that jolt us awake at night.
Vet Lynne O’Sullivan, an expert on dilated cardiomyopathy, or DCM, is also making critical discoveries applicable to humans. DCM makes it difficult for the heart to pump blood around the body. In dogs, like people, it causes coughing and difficulty breathing from fluid retention.
Recently, O’Sullivan collaborated with researchers at the University of Washington, providing heart muscle samples from dogs that have died of DCM. The Washington team has identified a molecule involved in muscle contraction. In heart cells from dogs with DCM, it restored normal function. The same molecule improved muscle function in human cells.
For all this progress, it’s comparative oncology that holds out the most hope. Despite hundreds of billions of dollars of research worldwide, cancer still ranks among humanity’s most lethal killers.
“These people who are looking for breakthroughs aren’t interested in whether the breakthrough comes from a dog or a zebra fish,” Dr. Larry Glickman, professor emeritus at Purdue University said in a PBS documentary on comparative oncology released last year. “Just give us something we can work with that will help speed up the process of drug development, which is so long and expensive.”
The OVC in Guelph is among the leaders in animal-to-human medicine and the only international member of a U.S. National Cancer Institute consortium of comparative oncology trials.
The college offers advanced cancer surgery — among other feats, Dr. Michelle Oblak is removing tumours burrowed deep into the brain cavity and rebuilding skulls with titanium mesh. Vets are also testing treatments for the same bone cancer that killed Terry Fox, and immune therapy for melanoma.
Dogs and cats are the most common patients, but the centre has also treated horses, rabbits, ferrets, birds, and even bearded dragons.
The prevalence of certain cancers among pets and humans is different. Humans tend to get carcinomas, tumours that arise from the epithelial cells like prostate, lung and breast cancers. Dogs and cats tend to get sarcomas, tumours that arise from tissue like bone, muscle, cartilage and fat.
“And so you could say, well, that means the dog is not a useful model for human disease,” says Brenda Coomber, co-director of the Institute of Comparative Cancer Investigation at the OVC.
But as she points out, for those people who do have sarcomas, “we haven’t really had anything better to offer them in the last 30 or 40 years. And it turns out some of the pathways that are disrupted in some of these tumours are not unique to sarcomas.”
Comparative oncology is clearly bearing fruit: Last year, the U.S. Food and Drug Administration fast-tracked an immunotherapy vaccine for osteosarcoma after a study in dogs showed those treated with the vaccine had a median survival of 956 days — double the rate from the standard treatment of amputation and chemo alone. Testing Imbruvica on dogs gave the drug company behind it the confidence to move into human trials. It is now used to treat people with certain leukemias and lymphomas.
Funding is catching up as well. The trial testing genetically modified viruses to attack mammary tumours in cats was supported by money from the Canadian Breast Cancer Foundation. The Terry Fox Research Institute is funding a vaccine trial for canine osteosarcoma.
“One of the fundamental challenges facing us in human oncology is the fact that we are learning so much more about cancer — the structure of cancer cells and how they behave,” says Lichtenfeld, of the American Cancer Society, but there aren’t enough people enrolling in studies of experimental drugs.
“By including our pets in clinical trials, we might get some very valuable clues,” he says, clues that can never come quickly enough.
Bosco’s people are certainly hoping for time. After six months of chemo, he’s doing well, the early fatigue and weight loss no longer an issue. But his family has been told that the median life for a dog once cancer treatments are over is 12 months.
“We’re really hoping he pushes that year,” Lynda says, but even if “biology and the gods” should will that he doesn’t, “how cool that humans and dogs developed this relationship 30,000 years ago, and they might end up saving our lives?”
(THEY) AREN’T INTERESTED IN WHETHER THE BREAKTHROUGH COMES FROM A DOG OR A ZEBRA FISH.