When social anthropologist Hanna Marie Ihlebæk interviewed nurses at a Norwegian cancer ward for her doctoral thesis, she was surprised to learn that many of them relied on their sense of smell in their work. “The urinary infection is really distinct, I can recognize that smell in the hallway!” said one of the nurses. Another claimed to be able to detect digestive bleeding and cellular necrosis. “I don’t know what I would have done without my ability to smell,” said a third.
Way back in the 5th century BC, the Greek physician-philosopher Hippocrates believed that illnesses could be identified by body odor. In modern times, we have stories of Oscar the cat who seemed to sense which residents were soon to die at a Rhode Island nursing home, and of dogs who were used to detect bladder cancer, malaria, and covid. In Africa, giant rats are used to detect tuberculosis.
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For years, scientists have studied how molecules emitted by our breath or skin could be harnessed to detect a long list of diseases – Parkinson’s disease, Alzheimer’s disease, certain cancers, the flu and the common cold. Yet the field has struggled to bring such tests to the clinic. Today, thanks to new tools capable of detecting tiny quantities of molecules, as well as advances in machine learning, this goal seems within reach. A variety of illnesses could soon be effectively diagnosed through non-invasive testing using devices as simple as breathalyzers.
“It’s really, really exciting,” says Mark Woollam, a chemical biologist at the University of Indianapolis.
Breathing tests
A handful of respiratory tests are already in use, such as one that detects a stomach infection in Helicobacter pyloria major cause of stomach ulcers. Patients drink a urea-enriched solution containing a “heavy” version of carbon; if H. pylori is present, the bacteria will use the urea to produce carbon dioxide and the test will detect this carbon-heavy CO2 in the patient’s breath. But such tests require swallowing a special substance and sending a sample to a laboratory for analysis. Today, researchers are also working to develop tests that could provide results directly at home or at a doctor’s office. They are designed to detect volatile organic compounds (VOCs). These compounds occur primarily in gaseous form at room temperature and can be emitted through breath, sweat, urine, blood, and feces.
To collect breath for analysis, for example, volunteers breathe into small laboratory-grade plastic bags that look like juice packets, or into syringe-shaped breath samplers. These samples are then analyzed in the laboratory with a technique called gas chromatography-mass spectrometry. Other tests use cheaper, more portable electronic noses, made up of a series of sensors that can detect various molecules.
Determining which molecules are significant and what conclusions can be drawn from an individual sample makes developing such tests “very, very difficult,” Woollam says. Breath can contain contaminants from the surrounding air (think pollution or cigarette smoke) and the composition of breath can vary from time to time, making it difficult to standardize tests and interpret single measurements.
“From sitting to lying down, you change your breathing pattern. You hold your breath, you change your breathing pattern. You take a medication, you change your breathing pattern. … So how do you go about fixing this?” says chemist Wolfram Miekisch of the University Medical Center Rostock in Germany.
But researchers have made progress in identifying molecules that are markers of specific diseases. For example, when tumors grow, oxidative stress in the body increases, causing fat molecules in cells to break down into smaller, volatile compounds, Woollam explains.
In one study, testing patients’ breath before and after surgery to remove lung tumors identified 16 compounds that could serve as respiratory biomarkers for lung cancer, including pentanal, the foul-smelling butyric acid, woody hexanal, and decanal, which smells like orange peel. In other research, analyzes of molecules emitted from melanoma biopsy samples suggested that compounds such as the pungent chemical called 4-methyldecane could serve as a biomarker.
Molecules in urine could also offer clues to cancer. Woollam and colleagues analyzed molecules from the urine of men undergoing prostate cancer biopsies and found that a panel of six molecules could detect the disease in 75% of cases. Although less sensitive than the prostate-specific antigen (PSA) blood test, the VOC method yielded fewer false positives, which could help patients avoid unnecessary treatment.
Some cancer tests based on volatile compounds emanating from urine could soon come to market. One such test, made by biotechnology company TOBY – named after the trail sniffing dog in the Sherlock Holmes books – is designed to detect bladder cancer. Rather than looking for a single biomarker, TOBY’s test uses AI to analyze patterns of molecules emitted by urine. It was granted Breakthrough Device designation (which can accelerate approval) by the Food and Drug Administration (FDA) in 2026, validating its potential; its developers say it will be about a year before commercial launch. The TOBY team is also working on a similar test for Alzheimer’s disease, which received Breakthrough Device designation from the FDA in May.
Sebum and Parkinson’s
Clues to the disease also lie in sebum, an oily, sticky substance produced by tiny glands located in hair follicles. Researchers are studying the link between volatile substances emanating from sebum and Parkinson’s disease, which tends to be diagnosed late, meaning patients go longer without their symptoms being properly managed.
Clues to the sebum signal emerged many years ago: a woman named Joy Milne noticed that her husband’s body odor had become unpleasantly woody and musky. Fourteen years later, Les Milne received an early diagnosis of Parkinson’s disease, and at a Parkinson’s awareness conference, Joy Milne noticed that other Parkinson’s patients seemed to have a similar smell. She connected with scientists at the University of Edinburgh, and then with Parkinson’s researcher Perdita Barran. Barran and his team conducted an experiment and found that Milne’s nose could distinguish T-shirts worn by Parkinson’s patients from those worn by healthy people.
Since then, Milne and Barran, from the University of Manchester, have worked together to identify a Parkinson’s signal in sebum molecules. “If I swabbed your back, I would find about 20,000 compounds. And if you had Parkinson’s disease, about 2,000 of them – so 10 percent – would be different from those in people without Parkinson’s disease,” says Barran. These compounds include acyl-carnitines – molecules that transport fatty acids to mitochondria for energy production – and others linked to disruptions in fatty acid metabolism.
The sebum signature can correctly identify more than 84% of people with Parkinson’s disease when the disease is well advanced. But the test can also help detect Parkinson’s disease early, before obvious symptoms appear. In a 2025 report, Barran and colleagues, including Milne, studied the sebum of people with REM sleep behavior disorder, in which they physically act out their dreams — kicking their spouse in bed while dreaming about playing soccer, for example. This condition has been strongly linked to the subsequent development of neurodegenerative diseases. VOC sebum profiles in this group fell somewhere between those with diagnosed Parkinson’s disease and healthy volunteers, the researchers reported.
Future research
And other tests could be on the horizon. For example, researchers are studying the potential respiratory signatures of influenza; a 2022 study, involving 235 patients, found that certain respiratory biomarkers could distinguish influenza from similar infections with 78% accuracy. Exhaled breath could also be used to diagnose cold infections: Another team found that concentrations of compounds such as the waxy-smelling 3,8-dimethylundecane in breath correlated with rhinovirus viral loads in the nose and throat.
“What the virus does, it goes into a cell, enters it, replicates, and then destroys the cell,” Miekisch explains. Parts of the destroyed cell can then be released into a sick person’s breath, he explains, while other biomarkers come from changes within our own metabolism in response to the infection.
Still other researchers are looking for ways to distinguish viral infections from bacterial infections. Bacteria emit their own VOCs, which can be picked up in human breath (Helicobacter pylorithe bacteria that causes stomach ulcers smell like sulfur, for example). Ilaria Belluomo, a medical biotechnologist at Imperial College London, and colleagues are leading a study of bacterial and viral signatures in the breath of children hospitalized with serious lung infections. “A test that can distinguish between the two types of infections can be completely transformative,” she says. By revealing whether an infection is bacterial, it would help determine whether taking antibiotics makes sense, potentially reducing antibiotic overuse, Belluomo says.
One of the most promising applications of research into volatile biomarkers of infection would be in intensive care, says Miekisch. This could make it possible to continuously monitor the breathing of intubated and critically ill patients to detect the first signs of danger. For example, distinguishing between sepsis, caused by bacteria, and the autoimmune reaction called systemic inflammatory response syndrome is “an important question,” he says.
Yet obstacles remain. One of them is the lack of standardization, which makes it difficult to compare results between different studies. Another obstacle is not fully understanding where these biomarkers come from, Miekisch says. And some tests that seemed promising failed in larger studies or lacked funding to go to market.
But a lot of VOCs…
Gn Health
