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?
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 (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.
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.
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.
Only 3% of histopathology departments that responded to the Royal College of Pathologists’ workforce census reported enough staff to meet clinical demand
There is a chronic shortage of histopathologists in the United Kingdom (UK) and it is being blamed for cancer treatment waiting times that now reach the worst-ever levels, as National Health Service (NHS) training initiatives and other steps fail to keep pace with growing demand for diagnostic services.
For US anatomic pathologists and clinical laboratory managers, headlines from the UK reveal the impact a shortage of trained histopathologists (UK’s version of anatomic pathologists) and support technical staff can have on patient care when longer wait times for pathology support and diagnosis become the norm.
Royal College of Pathologists Report
The extent of the UK-wide histopathology staff shortages was highlighted in a recently released 2017 workforce census by the Royal College of Pathologists (RCPath). Of the 103 histopathology departments that responded to a survey, only 3% said they had enough staff to meet the current clinical demand! And 45% of departments had to outsource work, while half of the departments were forced to use more expensive temporary workers.
“The cost of staff shortages across histopathology departments is high for both patients and for our health services,” Jo Martin, PhD, President of the Royal College of Pathologists, noted in a statement announcing the survey results. “For patients, it means worrying delays in diagnosis and treatment. For NHS hospitals, it means spending more resources on [temporary] doctors to fill staffing gaps, or outsourcing services. We estimate this cost [to be] £27 million ($35.2 million) each year across the UK health service—money that could be better invested in staff and new diagnostic equipment.”
Royal College of Pathologists President Jo Martin, PhD, is calling on the National Health Service to take additional steps to increase the number of pathologists working in the United Kingdom, including more funded training places. That’s following the release of a Royal College of Pathologists workforce survey, which reported only 3% of histopathology departments in the UK have enough staff to meet clinical demand. (Photo copyright: Twitter.)
According to iNews, NHS England recorded its worst cancer treatment waiting times on record in July 2018, with more than 3,000 people waiting longer than two months for cancer treatment to begin. NHS’ target is for 85% of patients to begin cancer treatment within 62 days of being referred by their general practitioner.
Anatomic pathologists in the United States should consider how the UK’s average delay in starting cancer treatment affects patients in that country. It is a metric that patients in the US would not tolerate. However, in the UK’s single payer system, the government’s National Health Service sets the budgets for training new physicians, including histopathologists. For many years, the pathology profession in the UK has regularly advocated for increasing the number of histopathologists trained each year by the medical schools in that country.
In July, the number of patients waiting for treatment longer than 60 days fell to 78.2%, the 31st month in a row the target was breached, iNews reported.
“We know that histopathology consultant shortages contribute to at least part of that problem,” Martin told iNews.
The RCPath report highlights the intense pressures on histopathologists—most of whom working in understaffed laboratories—face from increased workloads, as new NHS cancer screening initiatives, an aging population, and a shift toward precision medicine result in a rising number of cases being referred to labs.
“Demand for pathology services has grown significantly in recent years and continues to grow,” Martin noted in the RCPath statement. “The pathology workforce has not increased in line with this demand. If this trend continues unchecked, clinical services could be in jeopardy. Making sure pathology services can cope with current and future demand is essential if we are to ensure early diagnosis and improve outcomes for patients.”
Lack/Loss of Trained Histopathologists an Ongoing Problem
In its most recent workforce report, The Royal College of Pathologists is reiterating its call for:
Increased funding for training;
Better information technology (IT) for day-to-day work;
Capital investment to implement digital pathology more widely; and,
Development of advanced clinical practitioner apprenticeships to help more biomedical scientists become independent practitioners who would work alongside medically-qualified histopathologists.
Long-term, the organization is calling for additional training slots for pathologists in universities as well as other changes to draw more scientists into the field.
Aging Pathology Staff Means Shortages in US a Possibility
The NHS has stopped short of declaring the pathologist shortage a crisis. Instead, a Department of Health and Social Care spokesperson in an interview with the BBC highlighted recent initiatives taken in response to the shortage. “There are hundreds more pathologists in the NHS compared to 2010 and hospitals have reduced spending on temporary agency staff by over half a billion pounds in the last year,” the spokesperson noted. “We are listening to staff, encouraging more flexible working, and have increased medical training places for home-grown doctors by 25%, to ensure the NHS has the workforce it needs for the future.”
Despite those steps, the NHS may have more work to do. According to the Royal College of Pathologists workplace survey, a quarter of all histopathologists in the UK are 55 or older, adding an approaching retirement crisis to the existing shortage.
US anatomic pathology groups and clinical laboratories should monitor these events with a keen eye. The American pathology industry is challenged by many of the same trends, such as an aging workforce and lackluster replacement initiatives. Time will tell if the US learns from the UK’s experience.
Pathologists should note that this agreement is not without controversy as the question over who owns patients’ DNA information sparks warnings from legal experts
Did you ever wonder which lab does all the genetic testing for Ancestry as it offers to help consumers learn more about their family histories? Also, were you ever curious about the actual number of genetic tests that Ancestry has generated? After all, its advertisements for these genetic tests are ubiquitous.
To the second question, the number of individual samples in the Ancestry repository and database is now four million, according to information on its website.
AncestryDNA (Ancestry) and Quest Diagnostics (Quest) now collaborate to help consumers learn about their family histories and unlock secrets in their DNA. Since August of 2016, Quest has performed the genomic testing for home DNA kits ordered through Ancestrydna.com. What impact might this have on medical laboratories that perform DNA testing for health and medical reasons?
DNA Testing Reveals Who We Truly Are
“We are very excited to be partnering with Quest Diagnostics to offer our consumer DNA test to more consumers around the world,” stated Tim Sullivan, President and CEO at Ancestry in a news release that announced the genetic testing agreement between the two companies.
To utilize the AncestryDNA service, consumers must first order a DNA kit online through the Ancestry website. The cost of the kit is $99. This includes instructions, a saliva collection tube, and a pre-paid return mailer.
DNA collection kits like the one shown above let people at home do much of the work normally performed in clinical laboratory settings. Though it’s inexpensive compared to standard DNA testing, there is controversy over privacy and ownership of the DNA information. (Photo copyright: BBC/Getty Images.)
After collecting a saliva sample, the customer sends it in for processing. Once the test is completed, an e-mail notification informs the patient that the results can be viewed on AncestryDNA’s website. Typically, a test is completed within six to eight weeks.
The DNA test uses microarray-based autosomal DNA testing, analyzing as many as 700,000 changes in an individual’s genome. These changes (or variations) are called single-nucleotide polymorphisms, or SNPs for short. They are useful in identifying a person’s true ethnicity and can distinguish possible relatives from among people who have previously taken the AncestryDNA test.
“Our focus is on helping consumers around the world take advantage of the latest technology and science to help them learn more about themselves, their families, and their place in the world,” stated Sullivan in another news release.
Managing One’s Health with DNA Information
As noted earlier, AncestryDNA has collected more than four-million DNA samples. Remarkably, its genetic testing service is currently available in more than 30 countries around the globe, according to Ancestry’s website.
The two companies hope to expand their relationship to include the development of applications to explore valuable medical and health information for consumers.
“People are very interested in their family history, and knowing one’s family health history is very important in helping us manage our health,” noted Stephen Rusckowski, Chairman, President and Chief Executive Officer of Quest Diagnostics.
The actual genetic testing is being performed at Quest Diagnostics’ 200,000 square foot facility located in Marlborough, Mass. Quest Diagnostics was chosen for the collaboration after Ancestry requested proposals from several laboratory organizations.
“Adding a second diagnostic partner is a critical step forward as we work to continue to meet the consumer demand we’re seeing for our DNA tests in the US and markets around the world,” stated Ken Chahine, PhD, JD, Executive Vice President at Ancestry and professor at University of Utah S. J. Quinney College of Law in Salt Lake City, in a press release. “We’ll also now be able to move toward an East-West logistical approach, testing kits closer to where our consumers live and, ideally, reducing the time they need to wait to receive their results.”
Concerns Over Patient Privacy and DNA Ownership
Ancestry’s genetic testing program is not without its critics. There are concerns regarding privacy issues and DNA ownership for consumers who use AncestryDNA. Joel Winston, Esq. is a New York attorney who specializes in consumer protection law and commercial litigation. In an article, Winston claimed that Ancestry’s privacy policy and terms of service gave the company complete ownership and control of submitted DNA.
“There are three significant provisions in the AncestryDNA Privacy Policy and Terms of Service to consider on behalf of yourself and your genetic relatives: (1) the perpetual, royalty-free, world-wide license to use your DNA; (2) the warning that DNA information may be used against “you or a genetic relative”; (3) your waiver of legal rights,” Winston wrote.
He claims that Ancestry customers are relinquishing their genetic privacy when they agree to the terms online. Winston urged consumers to fully read, consider, and understand the terms before agreeing to them.
Ancestry responded to the claims by releasing updated terms and conditions for clarity regarding ownership of DNA and information sharing. The company maintains they do not claim ownership rights to DNA submitted to them for testing, and that they do not share DNA testing results with other entities and organizations without customer permission.
In an interview with BBC Radio 4, a spokesperson for Ancestry stated, “We do not share user data for research unless the user has voluntarily opted-in to that sharing.” Adding, “We always de-identify data before it’s shared with researchers, meaning the data is stripped of any information that could tie it back to its owner.”
Nevertheless, Ancestry also stated they would be removing the “perpetuity clause” in AncestryDNA’s online terms and agreements.
The controversy continues and has sparked much debate and reportage from outlets that follow trends in DNA testing and medical laboratories. One such report by the debunking site Snopes attempts to clarify the issues.
Regardless of the debate over ownership of a person’s DNA, this collaboration between Ancestry and Quest Diagnostics is an example of a company relying on diagnostic industry vendors and clinical laboratories to perform services for its customers. It illustrates the need for clinicians and laboratory professionals to remain current on industry trends in ways that might help their labs to increase profits and provide value-added services to consumers. Ancestry’s growing volume of consumer testing demonstrates that there is a potential market for medical laboratories that make themselves available to consumers to answer questions and concerns about DNA testing.
EarlyCDT-Lung test followed by X-rays and CT scans proves up to five times more likely to detect cancer than current standard of care
Encouraging preliminary results from a 12,000-person clinical trial into the effectiveness of a non-invasive medical laboratory blood test for the early detection of lung cancer could signal an advance that leads to creation of similar anatomic pathology screening tests for the early detection of other cancers.
Initial skin test research shows promise but larger clinical studies needed before diagnostic tool could be ready for use by medical laboratories and pathologists
Researchers in Mexico developed a skin test that could lead to the early diagnosis of Alzheimer’s disease and pave the way for new therapies to treat a disease ranked as the sixth leading cause of death in the United States.
