Can dogs sniff out cancer patients as accurately as they can detect drugs and bombs?

Produced by: Science Popularization China

Author: Ning Jueyin (Pet Health Research Institute, Huazhong Agricultural University)

Producer: China Science Expo

Editor's note: In order to unveil the mystery of scientific work, the China Science Popularization Frontier Science Project launched a series of articles called "Me and My Research", inviting scientists to write articles themselves, share their scientific research experiences, and create a scientific world. Let us follow the explorers at the forefront of science and technology and embark on a journey full of passion, challenges, and surprises.

Huanglongbing, which can cause yellowing of leaf stems and mottled yellowing of leaves, and then turn into "red nose" fruit, not only makes citrus fruits of poor quality and lose their economic value, but also spreads rapidly, endangering the entire orchard. This disease, caused by bacteria and spread by psyllids, is always "wanton" in the face of traditional monitoring methods because of its secrecy and destructiveness. It has always been the number one enemy of the global citrus economy. However, no one expected that the "citrus cancer" that has affected the ups and downs of the citrus industry for decades could be diagnosed by a dog's nose .

Golden Labrador Retriever

(Photo source: veer photo gallery)

Recently, in the Gannan Navel Orange Industrial Park in Jiangxi Province, a new monitoring method for Huanglongbing, which consists of a trainer and a Labrador Retriever, has greatly improved the detection rate of Huanglongbing by virtue of the dog's excellent olfactory "diagnostic" ability. The incidence of Huanglongbing in the park has once dropped from 29% to 3%. Since dogs can smell the disease of fruits, can they also identify cancer patients? The answer is of course they can.

Why can dogs detect cancer by smelling it?

Compared to humans, who have only 5 million odor receptors, dogs have 44 times more odor receptors than humans, and the number has exceeded 220 million. The flat surface area of ​​olfactory receptors is 690 times larger than that of humans. Steve White, a doctor of animal behavior research, once made a vivid metaphor in his research report "Basics of Police Dog Operations - Smell": The surface area of ​​olfactory receptors of German shepherd dogs and humans is the comparison between one square yard (0.83 square meters) and a postage stamp (0.0012 square meters).

Plaque-like structures on the nasal plane

(Image source: Unsplash)

The dog's nose plane is the part of the nose without hair, and the patchy structure covers it and extends from the nose plane to the nostrils and nasal cavity. This allows the dog's nose, which has a sniffing power of up to 3.3m/s, to quickly inhale more volume of fresh air while expelling more volume of "old" air from the gap on the side of the nose.

After the air enters the nasal cavity, the odor molecules first pass through the vomeronasal organ located below and then go to the olfactory area at the back. The remaining air flows from the lower channel of the tail along the pharynx to the lungs to participate in breathing.

Schematic structure of the canine and human olfactory systems

(Image source: Reference 7)

The vomeronasal organ is a special olfactory organ that humans do not have. It is located in the tissues on both sides of the nose and the piriform bone, and is in the form of "pairs of small blind tubes". As a chemical receptor for pheromones, it not only has bipolar olfactory cells, but is also directly connected to the olfactory lobe and the brain through 608 vomeronasal nerve bundles. It is more sensitive to specific chemical sensing signals (i.e. pheromones) within a small range and is considered to be an auxiliary structure of the main olfactory system.

The olfactory area is the core area of ​​the dog's olfactory system and the place where the main olfactory system works. It contains a large number of olfactory organs such as nasal concha, sinus, ethmoid bone, olfactory mucosa and olfactory bulb. Here, dogs can identify chemical odors in the environment, which is also an important physiological reason why they can identify cancer.

The lowest concentration that most animals can distinguish for odors is 10^-6 to -10^-9 molar, for humans it is 10^-4.5 molar, and dogs can smell odors as low as 10^-17 molar concentration. That is to say, on a football field that is 120 meters long and 90 meters wide, a dog can easily smell the scent of an apple. Similarly, on this football field, a dog can also easily smell a cancer patient.

Why Can Dogs Smell Cancer?

Let's first take a look at how the "citrus cancer" Huanglongbing can be smelled. Timothy Gottwald, a plant protection expert in Florida, USA, found that when bacteria infect citrus trees, citrus trees will release some extremely small and special chemicals. It is by capturing these chemicals that dogs can determine whether a citrus tree has Huanglongbing. Similarly, cancer also releases extremely small and special chemicals - this is the fundamental reason why dogs can identify cancer patients.

As we all know, Chinese medicine emphasizes "observation, smell, questioning, and palpation". This "smell" is the concrete manifestation of physical illness accompanied by smell - when a person is sick, the mouth, saliva, urine, sweat, etc. will have abnormal smells. Take the typical smells that people can smell as an example. When a diabetic patient has diabetic ketoacidosis, excessive acetone will be exhaled from the body, and it smells like rotting apples; the exhaled gas of patients with renal failure contains a certain concentration of dimethylamine and trimethylamine substances, which smells similar to urine.

An old Chinese doctor diagnoses a patient

(Photo source: veer photo gallery)

When we culture colon cancer cells, lung cancer cells and other cancer cells in vitro, we will find that they also produce different "smells", but the concentrations are very low and humans cannot smell them.

Where does the smell of cancer come from?

In order to meet their own needs for continued growth, cancer cells will have typical metabolic characteristics such as: ① dysregulation of glucose, fat and amino acid metabolism; ② changes in metabolite-driven gene regulation; ③ metabolic interactions with the microenvironment. In other words, compared with healthy cells, cancer cells have completely different metabolic levels and produce unique metabolites.

3D images of cancer cells

(Photo source: veer photo gallery)

Some of these metabolites exist in the body in a non-volatile form (such as genes, cancer antigens, growth factors, interleukins, etc.), and the other part exists in a volatile form (such as alkanes, alkenes, alcohols, aldehydes, ketones, benzene series, as well as oxygen-containing compounds, nitrogen-containing compounds and sulfur-containing compounds) through blood circulation, and are excreted from the body through breathing, saliva, urine, feces, skin radiation and blood release into the surrounding air - this part of the volatile metabolites is called VOCs (volatile compounds).

The concentration of VOCs released by cancer patients through exhaled breath is in the microgram to picogram range, while the concentration of VOCs released through blood and urine is in the microgram to nanogram range. How many micrograms, nanograms, and picograms are there?

If a paper clip weighs about 1 gram and a sesame seed weighs about 1 milligram, then one thousandth of a sesame seed is a microgram, which is about the weight of a dust particle that is invisible to the naked eye. Cut the dust into 1,000 pieces, each of which is 1 nanogram. Take 1 nanogram and cut it into 1,000 pieces, and you get 1 picogram per piece.

It can be seen how low the concentrations of VOCs are at the microgram, nanogram and picogram levels, but fortunately, dogs' noses are strong enough that these concentrations are just within their olfactory range - this is why almost no one can smell cancer, but dogs can.

How good are dogs at sniffing out cancer?

In 1989, a dog that had never been trained kept barking at a "black mole" on its owner's leg. Confused, the owner went to the hospital for a checkup and found that the "black mole" was actually a malignant melanoma. After this incident was published in The Lancet, the number of related research reports abroad increased dramatically. The dog training program has also expanded from sniffing melanoma to a series of common human cancers such as bladder cancer, ovarian cancer, breast cancer, prostate cancer and lung cancer.

According to relevant foreign literature, research on dogs' ability to sniff out cancer is still in the laboratory stage. Their sensitivity and specificity for cancer generally reach over 90%, a result that has also been verified by Zhao Qintao's team in China .

Currently, the team's research has stepped out of the laboratory and into the hospital. According to the preliminary double-blind test results of the hospital, the dogs' detection rate for new and different stages of myeloma is 94%, the detection rate for early lung cancer is 93%, and the detection rate for recurrence during and after treatment is 98%.

Maybe in the near future, dog-loving families will really have a small cancer-detecting radar that can act cute and interactive! Of course, I still want to wish everyone good health!

References:

[1] Huang Jiaquan, Li Li, Wu Fengnian, et al. Proliferation and pathogenicity of Huanglongbing bacteria carrying different prophages in citrus psyllids[J]. Chinese Agricultural Science, 2022, 55(4): 719-728.

[2] Xinnongcai. Unbelievable! Can a dog “cure” the “citrus cancer” Huanglongbing? [OL]. Xinnongcai, 2024-08-09.

[3] Wang Shuang, Zhang Peng. Research on the test of dog's "sniffing power"[C]. Proceedings of the 2012 National Working Dog Technology Seminar, 2012: 410-416.

[4] Yi Maoxiu. Spatial expression differences and evolutionary analysis of olfactory receptor genes in domestic dogs[D]. Qufu: Qufu Normal University, 2013.

[5] Yoder AD, Larsen P A. The molecular evolutionary dynam-ics of the vomeronasal receptor (class 1) genes in primates: agene family on the verge of a functional breakdown[J]. Olfactory subsystems in mammals: morphology, genetic and evolution, 2015.

[6] Huang Yong, Li Meiyi, Li Yuxia, et al. Research progress on canine sense of smell and taste[J]. Contemporary Animal Husbandry, 2013, 12(4): 719-728.

[7] Wang Ziling, Wang Xiaowen, Zhao Qintao. Clinical feasibility study of dog's sniff diagnosis of human cancer[J]. Jiangxi Journal of Animal Husbandry and Veterinary Medicine, 2023(05):44-47.

[8] Fang Shaoqin, Xu Hu, Li Jie, et al. Research progress on using dogs to sniff volatile organic compounds to screen cancer patients[J]. Journal of Community Medicine, 2023, 21(15):810-816