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Woman Who Can Smell Parkinson’s Disease in Patients Even Before Symptoms Appear May Help Researchers Develop New Clinical Laboratory Test

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.  

Retired nurse Joy Milne of Perth, Scotland
Retired nurse Joy Milne (above) of Perth, Scotland, has an uncanny ability to diagnose Parkinson’s disease based on her highly sensitive sense of smell. Before her husband was diagnosed with the disease, she noticed a change in his smell. When she later recognized the same distinct odor among participants in a Parkinson’s support group, the Milnes asked scientists to investigate. (Photo copyright: NPR.)

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.

Katherine Crawford, Scotland Director of Parkinson’s UK, aka the Parkinson’s Disease Society of the United Kingdom, said a noninvasive diagnostic test for Parkinson’s would be game changing.

“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

Related Information:

Her Incredible Sense of Smell Is Helping Scientists Find New Ways to Diagnose Disease

Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum

Parkinson’s Smell Test Explained by Science

Scientists Sniff Out Parkinson’s Disease Smell

The Woman Who Can Smell Parkinson’s Disease

Sebum: A Window into Dysregulation of Mitochondrial Metabolism in Parkinson’s Disease

Accuracy of Canine Scent Detection of Lung Cancer in Blood Serum

C. diff-sniffing Beagle Dog Could Lead to Better Infection Control Outcomes in Hospitals and Nursing Homes

Researchers Determine That Individuals’ ‘Breathprints’ Are Unique; May Have Potential for Clinical Laboratory Testing When Coupled with Mass Spectrometry Technology

University of Edinburgh Study Finds Antimicrobial Bacteria in Hospital Wastewater in Research That Has Implications for Microbiologists

The highly infectious bacteria can survive treatment at local sewage plants and enter the food chain of surrounding populations, the study revealed

Researchers at the University of Edinburgh (UE) in Scotland found large amounts of antimicrobial-resistance (AMR) genes in hospital wastewater. These findings will be of interest to microbiologists and clinical laboratory managers, as the scientists used metagenomics to learn “how abundances of AMR genes in hospital wastewater are related to clinical activity.”

The UE study sheds light on the types of bacteria in wastewater that goes down hospital pipes to sewage treatment plants. The study also revealed that not all infectious agents are killed after passing through waste treatment plants. Some bacteria with antimicrobial (or antibiotic) resistance survive to enter local food sources. 

The scientists concluded that the amount of AMR genes found in hospital wastewater was linked to patients’ length-of-stays and consumption of antimicrobial resistant bacteria while in the hospital.

Using Metagenomics to Surveille Hospital Patients

Antimicrobial resistance is creating super bacteria that are linked to increases in hospital-acquired infections (HAIs) nationwide. Dark Daily has reported many times on the growing danger of deadly antimicrobial resistant “super bugs,” which also have been found in hospital ICUs (see “Potentially Fatal Fungus Invades Hospitals and Public Is Not Informed,” August 26, 2019.)

In a paper the University of Edinburgh published on medRxiv, the researchers wrote: “There was a higher abundance of antimicrobial-resistance genes in the hospital wastewater samples when compared to Seafield community sewage works … Sewage treatment does not completely eradicate antimicrobial-resistance genes and thus antimicrobial-resistance genes can enter the food chain through water and the use of [processed] sewage sludge in agriculture. As hospital wastewater contains inpatient bodily waste, we hypothesized that it could be used as a representation of inpatient community carriage of antimicrobial resistance and as such may be a useful surveillance tool.”

Additionally, they wrote, “Using metagenomics to identify the full range of AMR genes in hospital wastewater could represent a useful surveillance tool to monitor hospital AMR gene outflow and guide environmental policy on AMR.”

AMR bacteria also are being spread by human touch throughout city subways, bus terminals, and mass transportation, making it difficult for the Centers for Disease Control and Prevention (CDC) to identify the source of the outbreak and track and contain it. This has led microbiologists to conduct similar studies using genetic sequencing to identify ways to track pathogens through city infrastructures and transportation systems. (See, “Microbiologists at Weill Cornell Use Next-Generation Gene Sequencing to Map the Microbiome of New York City Subways,” December 13, 2013.)

Antimicrobial stewardship programs are becoming increasingly critical to preventing the spread of AMR bacteria. “By having those programs, [there are] documented cases of decreased antibiotic resistance within organisms causing these infections,” Paul Fey, PhD, of the University of Nebraska Medical Center, told MedPage Today. “This is another indicator of how all hospitals need to implement stewardship programs to have a good handle on decreasing antibiotic use.” [Photo copyright: University of Nebraska.]

Don’t Waste the Wastewater

Antibiotic resistance occurs when bacteria change in response to medications to prevent and treat bacterial infections, according to a World Health Organization (WHO) fact sheet. The CDC estimates that more than 23,000 people die annually from two million antibiotic-resistance infections.

Wastewater, the UE scientists suggest, should not go to waste. It could be leveraged to improve hospitals’ detection of patients with antimicrobial resistance, as well as to boost environment antimicrobial-resistance polices.

They used metagenomics (the study of genetic material relative to environmental samples) to compare the antimicrobial-resistance genes in hospital wastewater against wastewater from community sewage points. 

The UE researchers:

  • First collected samples over a 24-hour period from various areas in a tertiary hospital;
  • They then obtained community sewage samples from various locations around Seafield, Scotland;
  • Finally, they complete the genetic sequencing on an Illumina HiSeq4000 System.

The researchers reported these findings:

  • 181 clinical isolates were identified in the samples of wastewater;
  • 1,047 unique bacterial genes were detected across all samples;
  • 19 genes made up more than 60% of bacteria in samples;
  • Overriding bacteria identified as Pseudomonas and Acinetobacter environmental samples (Pseudomonas fluorescens and Acinetobacter johnsonii) were most likely from hospital pipes;
  • Gut-related bacteria—Faecalibacterium, Bacteroides, Bifidobacterium, and Escherichia, were more prevalent in the hospital samples than in those from the community;
  • Antimicrobial-resistance genes increased with longer length of patient stays, which “likely reflects transmission amongst hospital inpatients,” researchers noted. 

Fey suggests that further research into using sequencing technology to monitor patients is warranted.

“I think that monitoring each patient and sequencing their bowel flora is more likely where we’ll be able to see if there’s a significant carriage of antibiotic-resistant organisms,” Fey told MedPage Today. “In five years or so, sequencing could become so cheap that we could monitor every patient like that.”

Fey was not involved in the University of Edinburgh research.

Given the rate at which AMR bacteria spreads, finding antibiotic-resistance genes in hospital wastewater may not be all that surprising. Still, the University of Edinburgh study could lead to cost-effective ways to test the genes of bacteria, which then could enable researchers to explore different sources of infection and determine how bacteria move through the environment.

And, perhaps most important, the study suggests clinical laboratories have many opportunities to help eliminate infections and slow antibiotic resistance. Microbiologists can help move their organizations forward too, along with infection control colleagues.  

—Donna Marie Pocius

Related Information:

Secrets of the Hospital Underbelly: Abundance of Antimicrobial-Resistance Genes in Hospital Wastewater Reflects Hospital Microbial Use and Inpatient Length of Stay

Antibiotic-Resistance Genes Trouble Hospital Water; Study Emphasizes Importance of Antibiotic Stewardship Programs, Expert Says

Fact Sheet: Antibiotic Resistance

United States Gathers 350 Commitments to Combat Antibiotic Resistance, Action Must Continue

Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenemase Resistance

Dark Daily E-briefings: Hospital-Acquired Infections

NIH Study Reveals Surprising New Source of Antibiotic Resistance that Will Interest Microbiologists and Medical Laboratory Scientists

Venter’s Research Team Creates an Artificial Cell and Reports That 32% of Genes Are Life-Essential but Contain Unknown Functions

Understanding the unknown functions of these genes may lead to the creation of new diagnostic tests for clinical laboratories and anatomic pathology groups

Once again, J. Craig Venter, PhD, is charting new ground in gene sequencing and genomic science. This time his research team has built upon the first synthetic cell they created in 2010 to build a more sophisticated synthetic cell. Their findings from this work may give pathologists and medical laboratory scientists new tools to diagnose disease.

Recently the research team at the J. Craig Venter Institute (JCVI) and Synthetic Genomics, Inc. (SGI) published their latest findings. Among the things they learned is that science still does not understand the functions of about a third of the genes required for their synthetic cells to function. (more…)