She worked with researchers at the University of Manchester in England to identify volatile biomarkers for Parkinson’s disease that may lead to first noninvasive screening
Clinical pathologists and medical laboratories are used to working with certain biological indicators that drive diagnostics and clinical laboratory testing. Mostly, those biomarkers are contained within various liquid samples, such as blood and urine. But what if a person’s odor could accurately predict risk for certain diseases as well?
Far-fetched? That’s what Parkinson’s researcher Tilo Kunath, PhD, first thought when he was contacted by a woman who claimed she could “smell” Parkinson’s disease coming from her husband. Kunath is Group Leader, Reader in Regenerative Neurobiology, at the Center for Regenerative Medicine at the University of Edinburgh, and head of the Tilo Kunath Research Group, which focuses on how the protein, alpha-synuclein, causes degeneration of neurons in Parkinson’s patients, as well as on producing a cell-based therapy for Parkinson’s disease.
Joy Milne, a retired nurse from Perth, Scotland, is the women whose heightened sense of smell enabled her to detect her husband’s Parkinson’s a decade before he was diagnosed with the disease.
Of course, Milne did not know at the time that what she was smelling was in fact a disease. She told NPR that she first noticed that her husband’s smell had changed from “his lovely male musk smell,” which she’d noticed when they first met, into “this overpowering sort of nasty yeast smell.”
Frequent washing did not remove the odor and as time went on the smell became stronger. When aspects of her husband’s personality and sleep habits also began to change, Joy convinced her husband, Les Milne, an anesthetist, to seek a diagnosis, thinking he had a brain tumor. Les was diagnosed with Parkinson’s disease.
It was 20 years later, when the Milnes attended a Parkinson’s disease support group, that Joy recognized the same distinctive smell she had noticed on Les on the other members of the group. That’s when the Milnes first realized Joy’s heightened sense of smell was something quite unique and possibly unprecedented.
Dogs Can Do It, Why Not Humans?
The concept that a disease gives off an aroma that can be detected by humans or animals is not far-fetched. As far back as 2013, Dark Daily was writing about such research. For example, in “C. diff-sniffing Beagle Dog Could Lead to Better Infection Control Outcomes in Hospitals and Nursing Homes,” we wrote about one hospital’s innovative approach to early detection of Clostridium difficile (C. diff) infection using a two-year-old beagle named Cliff that was faster at detecting certain infections than standard clinical laboratory tests used daily in hospitals throughout the world.
And in, “Researchers Determine That Individuals’ ‘Breathprints’ Are Unique; May Have Potential for Clinical Laboratory Testing When Coupled with Mass Spectrometry Technology,” we reported on research that showed a person’s breathprint is as unique as a fingerprint and may be as effective as bodily fluids in diagnosing diseases. The research also showed it was feasible to combine breath specimens and mass spectrometry to accurately identify disease, possibly leading to new diagnostic assays.
Thus, when the Milnes approached Dr. Kunath about Joy’s ability to “smell” Parkinson’s, they were on solid ground. However, he was not convinced.
“It just didn’t seem possible,” Kunath told NPR. “Why should Parkinson’s have an odor? You wouldn’t think neurodegenerative conditions such as Parkinson’s, or Alzheimer’s, would have an odor.”
But Kunath reconsidered after learning of research presented during the Experimental Biology annual meeting in 2019, which showed canines can in fact effectively detect lung cancer biomarkers in blood serum.
He contacted Milne and devised an experiment in which a group of people who had Parkinson’s disease, and another group that did not, would take home t-shirts and wear them overnight. The next day the t-shirts were assigned randomized numbers and put in a box. Milne then smelled each of the 12 t-shirts and assigned each one a score.
Kunath told NPR that Milne was “incredibly accurate.” She had misidentified only one shirt worn by a person in the control group. She incorrectly diagnosed the person with Parkinson’s. However, three months later, that man was in fact diagnosed with Parkinson’s, meaning Joy’s accuracy was 12-for-12.
“She was telling us this individual had Parkinson’s before he knew, before anybody knew,” Kunath told the BBC Scotland.
In an ensuing study, “Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum,” published in 2019 in ACS Central Science, the researchers describes the “distinct volatiles-associated signature” of Parkinson’s disease, which includes “altered levels of perillic aldehyde and eicosane, the smell of which was then described as being highly similar to the scent of Parkinson’s disease by our ‘Super Smeller.’” Joy Milne co-authored the study.
The concept of the human body producing volatile chemicals that can serve as biomarkers for disease or illness is not new to clinical laboratory professionals. The urea breath test, for example, to detect the presence of active H. pylori bacteria in the stomach is a longstanding example of one such diagnostic test.
Inspired by Milne’s accuracy, Kunath enlisted the help of Perdita Barran, PhD, Director of the Michael Barber Center for Collaborative Mass Spectrometry at the University of Manchester in England, to identify the specific compounds that contributed to the smell Joy had detected on her husband and the other Parkinson’s patients.
Barran led a larger Manchester University study which was published on ChemRxiv, titled, “Sebum: A Window into Dysregulation of Mitochondrial Metabolism in Parkinson’s Disease,” which was funded by a Michael J. Fox research grant (12921). Barran and her research team, which included Milne, “found 10 compounds linked to Parkinson’s by using mass spectrometry and other techniques” on skin sebum samples, reported NPR.
“We really want to know what is behind this and what are the molecules. And then, [determine if] the molecules [can] be used as some sort of diagnostic test,” Kunath told NPR.
A Definitive, Noninvasive Test for Parkinson’s?
The UK researchers discovered in the skin sebum volatile biomarkers of Parkinson’s disease that may lead to development of the first definitive test for the disease.
“We still effectively diagnose it today the way that Dr. James Parkinson diagnosed it in 1817, which is by observing people and their symptoms,” Crawford told BBC Scotland. “A diagnostic test like this could cut through so much of that, enable people to go in and see a consultant, have a simple swab test and come out with a clear diagnosis of Parkinson’s.”
“It wouldn’t have happened without Joy,” Barran told BBC Scotland. “For all the serendipity, it was Joy and Les who were absolutely convinced that what she could smell would be something that could be used in a clinical context, and so now we are beginning to do that.”
A viable, working diagnostic test based on these new biomarkers may be years away. Nevertheless, clinical laboratory leaders will want to follow the ongoing efforts toward development of a noninvasive swab test for Parkinson’s disease. Such a breakthrough would revolutionize Parkinson’s testing and might never have come to light without the persistence of a woman with an extremely sensitive sense of smell.
—Andrea Downing Peck