This Dog's Nose Is So Good at Smelling Cancer That Scientists Are Trying to Build One Just Like It
Claire Guest, co-founder of Medical Detection Dogs, with Daisy, whom she credits with saving her life.
Daisy wouldn't leave Claire Guest alone. Instead of joining Guest's other dogs for a run in the park, the golden retriever with the soulful eyes kept nudging Guest's chest, and stared at her intently, somehow hoping she'd get the message.
"I was incredibly lucky to be told by Daisy."
When Guest got home, she detected a tiny lump in one of her breasts. She dismissed it, but her sister, who is a family doctor, insisted she get it checked out.
That saved her life. A series of tests, including a biopsy and a mammogram, revealed the cyst was benign. But doctors discovered a tumor hidden deep inside her chest wall, an insidious malignancy that normally isn't detected until the cancer has rampaged out of control throughout the body. "My prognosis would have been very poor," says Guest, who is an animal behavioralist. "I was incredibly lucky to be told by Daisy."
Ironically, at the time, Guest was training hearing dogs for the deaf—alerting them to doorbells or phones--for a charitable foundation. But she had been working on a side project to harness dogs' exquisitely sensitive sense of smell to spot cancer at its earliest and most treatable stages. When Guest was diagnosed with cancer two decades ago, however, the use of dogs to detect diseases was in its infancy and scientific evidence was largely anecdotal.
In the years since, Guest and the British charitable foundation she co-founded with Dr. John Church in 2008, Medical Detection Dogs (MDD), has shown that dogs can be trained to detect odors that predict a looming medical crisis hours in advance, in the case of diabetes or epilepsy, as well as the presence of cancers.
In a proof of principle study published in the BMJ in 2004, they showed dogs had better than a 40 percent success rate in identifying bladder cancer, which was significantly better than random chance (14 percent). Subsequent research indicated dogs can detect odors down to parts per trillion, which is the equivalent of sniffing out a teaspoon of sugar in two Olympic size swimming pools (a million gallons).
American scientists are devising artificial noses that mimic dogs' sense of smell, so these potentially life-saving diagnostic tools are widely available.
But the problem is "dogs can't be scaled up"—it costs upwards of $25,000 to train them—"and you can't keep a trained dog in every oncology practice," says Guest.
The good news is that the pivotal 2004 BMJ paper caught the attention of two American scientists—Andreas Mershin, a physicist at MIT, and Wen-Yee Yee, a chemistry professor at The University of Texas at El Paso. They have joined Guest's quest to leverage canines' highly attuned olfactory systems and devise artificial noses that mimic dogs' sense of smell, so these potentially life-saving diagnostic tools are widely available.
"What we do know is that this is real," says Guest. "Anything that can improve diagnosis of cancer is something we ought to know about."
Dogs have routinely been used for centuries as trackers for hunting and more recently, for ferreting out bombs and bodies. Dogs like Daisy, who went on to become a star performer in Guest's pack of highly trained cancer detecting canines before her death in 2018, have shared a special bond with their human companions for thousands of years. But their vastly superior olfaction is the result of simple anatomy.
Humans possess about six million olfactory receptors—the antenna-like structures inside cell membranes in our nose that latch on to the molecules in the air when we inhale. In contrast, dogs have about 300 million of them and the brain region that analyzes smells is, proportionally, about 40 times greater than ours.
Research indicates that cancerous cells interfere with normal metabolic processes, prompting them to produce volatile organic compounds (VOCs), which enter the blood stream and are either exhaled in our breath or excreted in urine. Dogs can identify these VOCs in urine samples at the tiniest concentrations, 0.001 parts per million, and can be trained to identify the specific "odor fingerprint" of different cancers, although teaching them how to distinguish these signals from background odors is far more complicated than training them to detect drugs or explosives.
For the past fifteen years, Andreas Mershin of MIT has been grappling with this complexity in his quest to devise an artificial nose, which he calls the Nano-Nose, first as a military tool to spot land mines and IEDS, and more recently as a cancer detection tool that can be used in doctors' offices. The ultimate goal is to create an easy-to-use olfaction system powered by artificial intelligence that can fit inside of smartphones and can replicate dogs' ability to sniff out early signs of prostate cancer, which could eliminate a lot of painful and costly biopsies.
Trained canines have a better than 90 percent accuracy in spotting prostate cancer, which is normally difficult to detect. The current diagnostic, the prostate specific antigen test, which measures levels of certain immune system cells associated with prostate cancer, has about as much accuracy "as a coin toss," according to the scientist who discovered PSA. These false positives can lead to unnecessary and horrifically invasive biopsies to retrieve tissue samples.
So far, Mershin's prototype device has the same sensitivity as the dogs—and can detect odors at parts per trillion—but it still can't distinguish that cancer smell in individual human patients the way a dog can. "What we're trying to understand from the dogs is how they look at the data they are collecting so we can copy it," says Mershin. "We still have to make it intelligent enough to know what it is looking at—what we are lacking is artificial dog intelligence."

The intricate parts of the artificial nose are designed to fit inside a smartphone.
At UT El Paso, Wen-Yee Lee and her research team has used the canine olfactory system as a model for a new screening test for prostate cancer, which has a 92 percent accuracy in tests of urine samples and could be eventually developed as a kit similar to the home pregnancy test. "If dogs can do it, we can do it better," says Lee, whose husband was diagnosed with prostate cancer in 2005.
The UT scientists used samples from about 150 patients, and looked at about 9,000 compounds before they were able to zero in on the key VOCs that are released by prostate cancers—"it was like finding a needle in the haystack," says Lee. But a more reliable test that can also distinguish which cancers are more aggressive could help patients decide their best treatment options and avoid invasive procedures that can render them incontinent and impotent.
"This is much more accurate than the PSA—we were able to see a very distinct difference between people with prostate cancer and those without cancer," says Lee, who has been sharing her research with Guest and hopes to have the test on the market within the next few years.
In the meantime, Guest's foundation has drawn the approving attention of royal animal lovers: Camilla, the Duchess of Cornwall, is a patron, which opened up the charitable floodgates and helped legitimize MDD in the scientific community. Even Camilla's mother-in-law, Queen Elizabeth, has had a demonstration of these canny canines' unique abilities.

Claire Guest, and two of MDDs medical detection dogs, Jodie and Nimbus, meet with queen Elizabeth.
"She actually held one of my [artificial] noses in her hand and asked really good questions, including things we hadn't thought of, like the range of how far away a dog can pick up the scent or if this can be used to screen for malaria," says Mershin. "I was floored by this curious 93-year-old lady. Half of humanity's deaths are from chronic diseases and what the dogs are showing is a whole new way of understanding holistic diseases of the system."
The Cellular Secrets of “Young Blood” Are Starting to Be Unlocked
Fabrisia Ambrosio (center) surrounded by her lab staff.
The quest for an elixir to restore youthful health and vigor is common to most cultures and has prompted much scientific research. About a decade ago, Stanford scientists stitched together the blood circulatory systems of old and young mice in a practice called parabiosis. It seemed to rejuvenate the aged animals and spawned vampirish urban legends of Hollywood luminaries and tech billionaires paying big bucks for healthy young blood to put into their own aging arteries in the hope of reversing or at least forestalling the aging process.
It was “kind of creepy” and also inspiring to Fabrisia Ambrosio, then thousands of miles away and near the start of her own research career into the processes of aging. Her lab is at the University of Pittsburgh but on this cold January morning I am speaking with her via Zoom as she visits with family near her native Sao Paulo, Brazil. A gleaming white high rise condo and a lush tropical jungle split the view behind her, and the summer beach is just a few blocks away.
Ambrosio possesses the joy of a kid on Christmas morning who can't wait to see what’s inside the wrapping. “I’ve always had a love for research, my father was a physicist," she says, but interest in the human body pulled her toward biology as her education progressed in the U.S. and Canada.
Back in Pittsburgh, her lab first extended the work of others in aging by using the simpler process of injecting young blood into the tail vein of old mice and found that the skeletal muscles of the animals “displayed an enhanced capacity to regenerate.” But what was causing this improvement?
When Ambrosio injected old mice with young blood depleted of EVs, the regenerative effect practically disappeared.
The next step was to remove the extracellular vesicles (EVs) from blood. EVs are small particles of cells composed of a membrane and often a cargo inside that lipid envelope. Initially many scientists thought that EVs were simply taking out the garbage that cells no longer needed, but they would learn that one cell's trash could be another cell's treasure.
Metabolites, mRNA, and myriad other signaling molecules inside the EV can function as a complex network by which cells communicate with others both near and far. These cargoes can up and down-regulate gene expression, affecting cell activity and potentially the entire body. EVs are present in humans, the bacteria that live in and on us, even in plants; they likely communicate across all forms of life.
Being inside the EV membrane protects cargo from enzymes and other factors in the blood that can degrade it, says Kenneth Witwer, a researcher at Johns Hopkins University and program chair of the International Society for Extracellular Vesicles. The receptors on the surface of the EV provide clues to the type of cell from which it originated and the cell receptors to which it might later bind and affect.
When Ambrosio injected old mice with young blood depleted of EVs, the regenerative effect practically disappeared; purified EVs alone were enough to do the job. The team also looked at muscle cell gene expression after injections of saline, young blood, and EV-depleted young blood and found significant differences. She believes this means that the major effect of enhanced regenerative capacity was coming from the EVs, though free floating proteins within the blood may also contribute something to the effect.
One such protein, called klotho, is of great interest to researchers studying aging. The name was borrowed from the Fates of Greek mythology, which consists of three sisters; Klotho spins the thread of life that her sisters measure and cut. Ambrosio had earlier shown that supplementing klotho could enhance regenerative capacity in old animals. But as with most proteins, klotho is fragile, rapidly degrading in body fluids, or when frozen and thawed. She suspected that klotho could survive better as cargo enclosed within the membrane of an EV and shielded from degradation.
So she went looking for klotho inside the EVs they had isolated. Advanced imaging technology revealed that young EVs contained abundant levels of klotho mRNAs, but the number of those proteins was much lower in EVs from old mice. Ambrosio wrote in her most recent paper, published in December in Nature Aging. She also found that the stressors associated with aging reduced the communications capacity of EVs in muscle tissue and that could be only partially restored with young blood.
Researchers still don't understand how klotho functions at the cellular level, but they may not need to know that. Perhaps learning how to increase its production, or using synthetic biology to generate more copies of klotho mRNA, or adding cell receptors to better direct EVs to specific aging tissue will be sufficient to reap the anti-aging benefits.
“Very, very preliminary data from our lab has demonstrated that exercise may be altering klotho transcripts within aged extracellular vesicles" for the better Ambrosio teases. But we already know that exercise is good for us; understanding the cellular mechanism behind that isn't likely to provide additional motivation to get up off the couch. Many of us want a prescription, a pill that is easy to take, to slow our aging.
Ambrosio hopes that others will build upon the basic research from her lab, and that pharmaceutical companies will be able to translate and develop it into products that can pass through FDA review and help ameliorate the diseases of aging.
Podcast: Should Scientific Controversies Be Silenced?
The recent Joe Rogan/Spotify controversy prompts the consideration of tough questions about expertise, trust, gatekeepers, and dissent.
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
The recent Joe Rogan/Spotify backlash over the misinformation presented in his recent episode on the Covid-19 vaccines raises some difficult and important bioethical questions for society: How can people know which experts to trust? What should big tech gatekeepers do about false claims promoted on their platforms? How should the scientific establishment respond to heterodox viewpoints from experts who disagree with the consensus? When is silencing of dissent merited, and when is it problematic? Journalist Kira Peikoff asks infectious disease physician and pandemic scholar Dr. Amesh Adalja to weigh in.

Dr. Amesh Adalja, Senior Scholar, Johns Hopkins Center for Health Security and an infectious disease physician
Listen to the Episode
Kira Peikoff is the editor-in-chief of Leaps.org. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.


