BREAKTHROUGH SCIENCE
image courtesy - Reader's Digest
Does This Dog Know Whether You Have Cancer?
The canine nose is a marvel of nature.
Science believes that a computerized model will save millions of lives.
OSA,
an athletic 28-kilo 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 leapt on to 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? Despite the remarkable success of
immunotherapy, C R I S P R 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-short comings. One
disheartening case in point: of the estimated 21,410 new cases in India, diagnosed this year with ovarian cancer, a disease that is treatable when found
early, more than 13,700 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 i.e. - the canine nose. Osa is able to
distinguish between blood samples taken from cancer patients and their healthy
peers by simply sniffing them. In fact, she's one of the
Eight cancer-detection dogs trained by
DeAngelo and her colleagues at the Penn Vet Working Dog Center, a non-profit
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 issues, 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.
"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 had been breeding could lead them to the avalanche victims buried beneath the snow.
Despite this history, science hadn't
considered whether dogs could detect cancer until the late 1980s, after a 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?
"So I rang the lady in the file up," Williams
recalls "And we had the most fascinating Conversation !"
The patient, a 44-vear-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.
A DOGS NOSE IS UP
TO A MILLION TIMES
MORE SENSITIVE
THAN A HUMAN NOSE.
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, we had the Schnau-zer, 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. 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 De- Angelo. "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 the dog 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 noise with a clicker or simply says
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.
As the dogs undergo this foundational
training, the trainers evaluate heir 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" De Angelo 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 that
nobody is allowed to approach De-
Angelo's house, unannounced (doing so, results in loud barking and pande-
monium). Upon entering the home, the
visitor, the host and the dog must all proceed immediately outside to play
ball, to set Osa at ease, before any business can be conducted. But with these, neuroic 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 out the one number
that's out of place. They really like having things very neat and controlled. they are 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. 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 com- pounds, any one of which could be capturing
the dog's attention. And that
MEDICAL DETECTION
DOGS ARE THE
ONES WITH QUIRKY
PERSONALITIES.
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 (odorants) grab 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
the two. Then they remove individual odorants 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 odorants and provide a reading of healthy,
benign, or malignant, within minutes. Another version might handle up to 10
samples at a time.
While most people would likely prefer to have what ails the 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 tue wet th Leam 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 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.
