Meet the Dogs That Can Sniff Out Cancer

The canine nose is a marvel of nature. Science believes that a computerized model will save millions of lives.

Osa, an athletic 62-pound German shepherd with a long fluffy tail and a fondness for red bandannas, seems an unlikely superhero.

She chews on the couch when she’s bored and isn’t above making a scene to get attention. On a recent day when her foster mother and trainer Anne­marie DeAngelo stepped outside their New Jersey home while chatting with a visitor, Osa bounded up and barked for attention; when that failed, she leaped onto the patio table, stuck her snout in DeAngelo’s face, and began whining.

“You are unbelievable,” DeAngelo growled before cracking a smile.

But if Osa wants to play the diva, she’s entitled. After all, how many six-year-old pooches do you know who have mastered the art of sniffing out cancerous tumours and are involved in a research project that has the potential to revolutionize oncology?

trainer Annemarie DeAngelo with OsaPhoto: JASON VARNEY FOR READER'S DIGEST
Annemarie DeAngelo with her star pupil, Osa

Despite the remarkable success of immunotherapy, CRISPR gene editing, and other recent breakthrough treatments, oncologists’ inability to detect some cancers in their early stages remains one of the field’s most ­intractable—and fatal—shortcomings. One disheartening case in point: of the estimated 3,100 women in Canada expected to be diagnosed this year with ovarian cancer, a disease that is treatable when found early, almost 1,900 are likely to die from it.

Osa might soon help improve those odds. She is part of an ambitious effort launched five years ago at the University of Pennsylvania that aims to reverse engineer one of the most powerful scent detection machines ever discovered—the canine nose. Osa is able to distinguish between blood samples taken from cancer patients and their healthy peers simply by sniffing them. In fact, she’s one of eight cancer-detection dogs trained by DeAngelo and her colleagues at the Penn Vet Working Dog Center, a nonprofit X-Men academy of sorts that breeds and trains “detection dogs.” The ultimate goal is to develop an “electronic sniffer” that can approximate the cancer-­sniffing super­powers of Osa and her pals. Such a machine could then be deployed to thousands of doctors’ offices and medical diagnostic facilities around the nation.

And cancer is only one possible target. This type of system could lead to similar devices for different health conditions, such as bacterial infections, diabetes, and epilepsy. Some dog trainers have even begun setting their sights on ­COVID-19. “It’s basically the exact same approach,” says Cynthia Otto, the founding director of the centre.

It all starts with that wondrous invention of nature: the canine nose. Our own schnoz doesn’t even come close. The average human is equipped with five million olfactory receptors, tiny proteins capable of detecting individual odour molecules. These receptors are clustered in a small area in the back of the human nasal cavity, meaning a scent must waft in and up the nostrils. In dogs, the internal surface area devoted to smell extends from the nostrils to the back of the throat and comprises an estimated 300 million olfactory receptors, 60 times more than humans.

Dogs also devote considerably more neural real estate to processing and interpreting these signals than humans do. Compared with a paltry 5 per cent for humans, 35 per cent of a dog’s brain is dedicated to smelling. Add it all up, and the dog nose is up to a million times more sensitive than the human nose.

Osa with trainers at the training facilityPhoto: DANIEL PETERSCHMIDT/SCIENCE FRIDAY
For Osa, here with DeAngelo and Cynthia Otto, cancer research is not all work.

“Sniffing is how dogs see the world,” explains Marc Bekoff, professor emeritus of ecology and evolutionary biology at the University of Colorado, Boulder. “That’s how they pick up information about who has been there, are they happy, are they sad, is the female in heat, are they feeling well or not. Their nose leads the way—dogs sniff first and ask questions later.”

Humans have always appreciated the potential of the canine snout. In the Middle Ages, authorities in France and Scotland relied on dogs and their sniffing abilities to hunt down outlaws. Search-and-rescue dogs emerged in the 18th century when the monks of the Great St. Bernard Hospice in the Swiss Alps discovered that the canines they’d been breeding could lead them to avalanche victims buried beneath the snow.

Despite this history, science hadn’t considered whether dogs could detect cancer until the late 1980s, after 30-year-old medical resident Hywel Williams stumbled on scientific gold.

Upon arriving at King’s College Hospital in London to begin his training as a dermatologist, Williams was tasked with reviewing every case of melanoma seen at the hospital over the previous 20 years. It was an eye-glazing assignment, recalls Williams. But one after­noon, he came across a four-word notation in a file that caught his attention. It read simply: “Dog sniffed at lesion.” What did that mean? Was it possible the dog in the file actually smelled cancer?

text: A dog’s nose is up to a million times more sensitive than a human nose.

“So I rang the lady in the file up,” Williams recalls. “And we had the most fascinating conversation!”

The patient, a 44-year-old woman, told Williams that her border collie-Doberman mix named Baby Boo had become fixated on a curious mole on the woman’s left thigh, sniffing it often. The ritual continued every day for several months, with Baby Boo nuzzling the woman’s leg through her trousers. Baby Boo finally tried to bite the lesion off, at which point the woman visited her doctor. When doctors excised the mole, they found it was malignant melanoma.

“Something about that lesion fascinated the dog,” Williams recalls. “And it literally saved this woman’s life.”

Williams and a colleague published their findings in the Lancet, a well-respected medical journal. Suddenly, dog lovers around the world were reaching out to Williams and sharing similar experiences. There was the 66-year-old man who developed a patch of eczema on the outer side of his left thigh—a lesion that became the obsession of his Labrador retriever until he went to the doctor. It was found to be basal cell carcinoma. There was George the schnauzer, trained by a Florida dermatologist. George “went crazy” when he sniffed out a suspicious mole on the leg of a patient. It turned out to be malignant.

a dog learning to detect traces of cancer on the scent wheelPhoto: COURTESY PENN VET WORKING DOG CENTER
DeAngelo and Otto were moved to tears when the dogs learned to detect traces of ovarian cancer on the scent wheel.

Over the years since, a growing body of evidence has emerged suggesting that dogs can sniff out bladder cancer, prostate cancer, diabetes, and even malaria, among other conditions. But not just any Chihuahua, corgi, or beagle can do the job.

Like most of the dogs, Osa arrived at the Penn Vet Working Dog Center from a breeder at two months of age. “We look at their genetics,” says De­Angelo. “We look at their work ability. They have to come from working lines, not show or pet lines, but one that has that hunt/prey drive.” Osa began taking obedience and agility training (walking a plank, climbing a ladder, gliding over a rubble pile) and quickly advanced to basic odour detection skill training.

During these sessions, the dogs are introduced to a universal detector calibrant, a potent, distinct odour developed by a veterinary scientist to train dogs. The trainer places the ­calibrant—a powder contained within a Mylar bag with a tiny hole to let the odour out—on the floor or on a wall or holds it in hand. As soon as the dog sniffs at the odour to investigate it, the trainer “marks” the smell by making a noise with a clicker or simply saying yes, and then rewards the dog with a treat. This process is repeated until the dog learns that when it finds this odour, it gets rewarded.

Next, the trainer begins offering the dog choices—for instance, placing two distinct odours in identical containers, only one of which produces a click and a treat when sniffed. Once that is mastered, the trainer begins withholding the treat until the dog freezes in front of the container of choice and stares.

dogs Grizzly and PriorPhoto: JASON VARNEY FOR READER'S DIGEST
It’s a family affair! DeAngelo’s dogs, Grizzly (left) and Prior, also work at the centre.

As the dogs undergo this foundational training, the trainers evaluate their skill sets and temperaments and use the data to choose a particular area of specialization. Dogs that demonstrate a passion for running on rubble enter search-and-rescue training. Those that don’t enjoy rubble but have strong noses might become narcotics or bomb dogs. Dogs who think that lightly “biting people is a fun game,” DeAngelo jokes, end up as police dogs.

Penn’s medical-detection dogs are the ones with quirky personalities and narrow focuses. Otto calls them the centre’s “sensitive souls.” They dislike noisy, crowded environments, such as airports or disaster recovery sites. Osa is very suspicious of people she doesn’t know—so much so that nobody is allowed to approach De­Angelo’s house unannounced (to do so results in loud barking and pandemonium). Upon entering the home, visitor, host, and dog must all proceed immediately outside to play ball to set Osa at ease before any business can be conducted. But with these neurotic traits also comes an uncommon focus.

“I often refer to our medical-­detection dogs as the CPAs,” Otto says. “They would love to just look at the spreadsheets and find the one number that’s out of place. They really like having things very neat and controlled. They’re the detail dogs.”

While Osa had all the qualities that make up a great sniffer dog, that didn’t guarantee that she’d be able to master the most essential task of all. To find out if she could, DeAngelo and her team put Osa in front of a scent wheel, a stationary metal contraption with multiple arms, each one of which is large enough to hold two separate containers—one containing plasma from a woman with metastatic ovarian cancer and the other plasma from a healthy volunteer. When Osa stopped in front of the correct sample, pointed her nose at it, and froze, DeAngelo and her colleagues hugged and cried.

Osa in a training tunnelPhoto: DANIEL PETERSCHMIDT/SCIENCE FRIDAY
Training a dog like Osa to sniff out cancer can take a year to 18 months.

“You don’t know if it’s going to work, so you train it, and you train it,” she says. “You’re actually now going to put the real cancer in the wheel, in the plasma, and see if the dogs can identify it and ignore the other samples. And it worked! The very first time! It was very emotional.”

And yet that’s only half the challenge. To transform Osa’s remarkable abilities into something replicable—an electronic nose—researchers have to figure out what it is precisely that Osa and her friends are reacting to. De­Angelo says the blood samples she has trained her dogs with contain hundreds of different organic compounds, any one of which could be capturing the dog’s attention. And that is why the Penn team includes not just the physicists and engineers designing the instrumentation for their electronic nose but also chemists to help figure out what exactly that electronic nose needs to be calibrated to smell. The group has been breaking the cancer samples down into progressively smaller constituent parts and presenting them to the dogs to winnow down which of the hundreds of potential aromatic chemical compounds (odourants) grab their attention.

A similar approach is used to train the device. The engineers start with two separate samples consisting of many odourants mixed together and make sure the machine can distinguish between the two. Then they remove individual odourants from each sample, training the machine to distinguish increasingly subtle differences that are more and more difficult to detect. The goal is to eventually place a vial of plasma inside a microwave-sized electronic sniffer that can analyze its odourants and provide a reading of healthy, benign, or malignant within minutes. Another version might handle up to ten samples at a time.

text: Medical-detection dogs are the ones with quirky personalities.

While most people would likely prefer to have what ails them sniffed out by a sympathetic (if wet) nose rather than a cold machine, that’s not in the cards, according to Bruce Kimball, a chemist at the Monell Chemical Senses Center in Philadelphia. “The sheer numbers of dogs and handlers that would have to be deployed” to the various hospitals, labs, and medical facilities around the country “is not practical,” he says.

An electronic nose prototype has been built, and it’s successful in sniffing out cancer 90 to 95 per cent of the time. As impressive as that sounds, researchers say there’s still more work to be done. Right now, they have a good idea of what compounds or chemicals create the odour, but the team wants more specificity. One objective is to be able to distinguish between early- and late-stage cancer. “It would be incredible to identify people at an early stage and really have an impact on saving lives,” says Otto. “The dogs have been able to detect that.” With that ability, a blood test could be sent to a central lab—or, ideally, performed in a doctor’s office—and rolled in as part of one’s annual checkup, making some hidden cancers a thing of the past.

If it all works as DeAngelo and Otto hope—and Otto is confident that a working device is “on the horizon”—it will be one of the most important victories in the war against cancer yet. Of course, neither Osa nor any of her furry friends have much idea what the fuss is all about.

“To them, it’s just a game,” says DeAngelo. “Osa just knows that, I was trained and when I find this odour and I indicate on it, then I get rewarded.”

Osa prefers that reward to be a piece of cheese. It’s a small price to pay. After all, Osa’s nose is potentially revolutionizing how and when we detect countless types of cancer and saving thousands of lives along the way.

Next, find out how one Ontario doctor is helping breast cancer patients prepare for treatment.

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