The dogs that are helping us beat cancer

Osa, an athletic yet stubborn 62-pound German shepherd with a long fluffy tail and a fondness for red bandanas, seems an unlikely superhero. But the six-year-old pooch has mastered the art of sniffing out cancerous tumours and is key to a research project that has the potential to revolutionise oncology.

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.

Case in point: an average of 75 Canadian women are diagnosed each day with breast cancer, a disease that is treatable when found early. Yet each day, some 14 Canadians die from breast cancer.

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 in the world: 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 five cancer-detection dogs trained by Annemarie DeAngelo and her colleagues at the university’s Penn Vet Working Dog Centre, a non-profit X-Men academy of sorts that breeds and trains “detection dogs.”

Prior, one of the sniffer dogs, photograph by Jason Varney

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 US.

And cancer is only one possible target. This type of system could lead to similar devices for other major health issues too, such as bacterial infections, diabetes and epilepsy. Some dog trainers and university researchers have also set their sights on developing a method of detecting COVID-19 infections based on skin odour.

It all starts with the canine nose. Our own schnozz doesn’t even come close. The average human is equipped with 6 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—50 times more than humans.

Dogs also devote considerably more neural real estate to processing and interpreting these signals than humans do—the part of the dog’s brain devoted to smelling is 40 times greater than ours. Add it all up, and the dog nose is about 10,000 to 100,000 times more sensitive than the human nose.

Dogs are taught to detect traces of ovarian cancer on a scent wheel, photograph by Jason Varney

“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 the sniffing abilities of dogs 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 victims buried beneath the snow from avalanches and snowstorms.

Despite this history, scientists hadn’t considered whether dogs could detect cancer until the late 1980s, after Hywel Williams, a 30-year-old medical resident at King’s College Hospital in London, stumbled upon scientific gold.

After arriving at King’s 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 actually smelled cancer?

Osa (above) is another dog that works at the centre, photograph by Jason Varney

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

The patient, a 44-year-old woman, told Williams that Baby Boo, her border collie-Doberman mix, 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 pants. Baby Boo finally tried to bite the lesion off, at which point she visited her doctor. When doctors excised the mole, they found it was a 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, one of the world’s most respected and widely read medical journals. Suddenly, dog lovers across the globe 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 also 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.

In 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.

Osa arrived at the Penn Vet Working Dog Centre 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 has learned 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.

Annemarie DeAngelo with her star pupil, Osa, photograph by Jason Varney

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 specialisation.

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.

Penn’s medical-detection dogs are the ones with quirky personalities and an ability to narrow their focus. Cynthia Otto, the founding director of the centre, calls them the centre’s “sensitive souls.”

They dislike noisy and crowded environments like 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 large enough to hold two separate containers—one containing plasma from a woman with metastatic ovarian cancer and the other with 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.

“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 out which of the hundreds of potential aromatic chemical compounds (odorants) grabs their attention.

A similar approach is used to train the device. The engineers start with two separate samples consisting of many odorants mixed together and make sure the machine can distinguish between them. Then they remove individual odorants from each sample, training the machine to distinguish increasingly subtle differences that are more difficult to detect.

Say hello to Grizzly, photograph by Jason Varney

The goal is to eventually place a vial of plasma inside a microwave-sized electronic sniffer that can analyse its odorants and provide a reading of healthy, benign or malignant within minutes. Another version might handle up to ten samples at a time.

Most people would prefer to have what ails them sniffed out by a sympathetic nose rather than a machine, but that’s not in the cards, according to Bruce Kimball, a chemist at the Monell Chemical Senses Centre in Philadelphia.

The number of dogs and handlers that would have to be deployed to the various hospitals and medical facilities around the US is neither practical nor feasible, 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. That team has also correctly detected different types of cancer, and is building a cancer-detecting device for the National Institutes of Health. 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—it’s expected that commercial prototypes for the cancer-sniffing device will be complete within nine months—it will be one of the most important victories yet in the war against cancer. Of course, the dogs have no idea what all the fuss is 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 since, after all, Osa’s nose could potentially save thousands of lives one day soon. 

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