Her Incredible Sense of Smell Helped Scientists Develop the First Parkinson's Test
Forty years ago, Joy Milne, a nurse from Perth, Scotland, noticed a musky odor coming from her husband, Les. At first, Milne thought the smell was a result of bad hygiene and badgered her husband to take longer showers. But when the smell persisted, Milne learned to live with it, not wanting to hurt her husband's feelings.
Twelve years after she first noticed the "woodsy" smell, Les was diagnosed at the age of 44 with Parkinson's Disease, a neurodegenerative condition characterized by lack of dopamine production and loss of movement. Parkinson's Disease currently affects more than 10 million people worldwide.
Milne spent the next several years believing the strange smell was exclusive to her husband. But to her surprise, at a local support group meeting in 2012, she caught the familiar scent once again, hanging over the group like a cloud. Stunned, Milne started to wonder if the smell was the result of Parkinson's Disease itself.
Milne's discovery led her to Dr. Tilo Kunath, a neurobiologist at the Centre for Regenerative Medicine at the University of Edinburgh. Together, Milne, Kunath, and a host of other scientists would use Milne's unusual sense of smell to develop a new diagnostic test, now in development and poised to revolutionize the treatment of Parkinson's Disease.
"Joy was in the audience during a talk I was giving on my work, which has to do with Parkinson's and stem cell biology," Kunath says. "During the patient engagement portion of the talk, she asked me if Parkinson's had a smell to it." Confused, Kunath said he had never heard of this – but for months after his talk he continued to turn the question over in his mind.
Kunath knew from his research that the skin's microbiome changes during different disease processes, releasing metabolites that can give off odors. In the medical literature, diseases like melanoma and Type 2 diabetes have been known to carry a specific scent – but no such connection had been made with Parkinson's. If people could smell Parkinson's, he thought, then it stood to reason that those metabolites could be isolated, identified, and used to potentially diagnose Parkinson's by their presence alone.
First, Kunath and his colleagues decided to test Milne's sense of smell. "I got in touch with Joy again and we designed a protocol to test her sense of smell without her having to be around patients," says Kunath, which could have affected the validity of the test. In his spare time, Kunath collected t-shirt samples from people diagnosed with Parkinson's and from others without the diagnosis and gave them to Milne to smell. In 100 percent of the samples, Milne was able to detect whether a person had Parkinson's based on smell alone. Amazingly, Milne was even able to detect the "Parkinson's scent" in a shirt from the control group – someone who did not have a Parkinson's diagnosis, but would go on to be diagnosed nine months later.
From the initial study, the team discovered that Parkinson's did have a smell, that Milne – inexplicably – could detect it, and that she could detect it long before diagnosis like she had with her husband, Les. But the experiments revealed other things that the team hadn't been expecting.
"One surprising thing we learned from that experiment was that the odor was always located in the back of the shirt – never in the armpit, where we expected the smell to be," Kunath says. "I had a chance meeting with a dermatologist and he said the smell was due to the patient's sebum, which are greasy secretions that are really dense on your upper back. We have sweat glands, instead of sebum, in our armpits." Patients with Parkinson's are also known to have increased sebum production.
With the knowledge that a patient's sebum was the source of the unusual smell, researchers could go on to investigate exactly what metabolites were in the sebum and in what amounts. Kunath, along with his associate, Dr. Perdita Barran, collected and analyzed sebum samples from 64 participants across the United Kingdom. Once the samples were collected, Barran and others analyzed it using a method called gas chromatography mass spectrometry, or GS-MC, which separated, weighed and helped identify the individual compounds present in each sebum sample.
Barran's team can now correctly identify Parkinson's in nine out of 10 patients – a much quicker and more accurate way to diagnose than what clinicians do now.
"The compounds we've identified in the sebum are not unique to people with Parkinson's, but they are differently expressed," says Barran, a professor of mass spectrometry at the University of Manchester. "So this test we're developing now is not a black-and-white, do-you-have-something kind of test, but rather how much of these compounds do you have compared to other people and other compounds." The team identified over a dozen compounds that were present in the sebum of Parkinson's patients in much larger amounts than the control group.
Using only the GC-MS and a sebum swab test, Barran's team can now correctly identify Parkinson's in nine out of 10 patients – a much quicker and more accurate way to diagnose than what clinicians do now.
"At the moment, a clinical diagnosis is based on the patient's physical symptoms," Barran says, and determining whether a patient has Parkinson's is often a long and drawn-out process of elimination. "Doctors might say that a group of symptoms looks like Parkinson's, but there are other reasons people might have those symptoms, and it might take another year before they're certain," Barran says. "Some of those symptoms are just signs of aging, and other symptoms like tremor are present in recovering alcoholics or people with other kinds of dementia." People under the age of 40 with Parkinson's symptoms, who present with stiff arms, are often misdiagnosed with carpal tunnel syndrome, she adds.
Additionally, by the time physical symptoms are present, Parkinson's patients have already lost a substantial amount of dopamine receptors – about sixty percent -- in the brain's basal ganglia. Getting a diagnosis before physical symptoms appear would mean earlier interventions that could prevent dopamine loss and preserve regular movement, Barran says.
"Early diagnosis is good if it means there's a chance of early intervention," says Barran. "It stops the process of dopamine loss, which means that motor symptoms potentially will not happen, or the onset of symptoms will be substantially delayed." Barran's team is in the processing of streamlining the sebum test so that definitive results will be ready in just two minutes.
"What we're doing right now will be a very inexpensive test, a rapid-screen test, and that will encourage people to self-sample and test at home," says Barran. In addition to diagnosing Parkinson's, she says, this test could also be potentially useful to determine if medications were at a therapeutic dose in people who have the disease, since the odor is strongest in people whose symptoms are least controlled by medication.
"When symptoms are under control, the odor is lower," Barran says. "Potentially this would allow patients and clinicians to see whether their symptoms are being managed properly with medication, or perhaps if they're being overmedicated." Hypothetically, patients could also use the test to determine if interventions like diet and exercise are effective at keeping Parkinson's controlled.
"We hope within the next two to five years we will have a test available."
Barran is now running another clinical trial – one that determines whether they can diagnose at an earlier stage and whether they can identify a difference in sebum samples between different forms of Parkinson's or diseases that have Parkinson's-like symptoms, such as Lewy Body Dementia.
"Within the next one to two years, we hope to be running a trial in the Manchester area for those people who do not have motor symptoms but are at risk for developing dementia due to symptoms like loss of smell and sleep difficulty," Barran had said in 2019. "If we can establish that, we can roll out a test that determines if you have Parkinson's or not with those first pre-motor symptoms, and then at what stage. We hope within the next two to five years we will have a test available."
In a 2022 study, published in the American Chemical Society, researchers used mass spectrometry to analyze sebum from skin swabs for the presence of the specific molecules. They found that some specific molecules are present only in people who have Parkinson’s. Now they hope that the same method can be used in regular diagnostic labs. The test, many years in the making, is inching its way to the clinic.
"We would likely first give this test to people who are at risk due to a genetic predisposition, or who are at risk based on prodomal symptoms, like people who suffer from a REM sleep disorder who have a 50 to 70 percent chance of developing Parkinson's within a ten year period," Barran says. "Those would be people who would benefit from early therapeutic intervention. For the normal population, it isn't beneficial at the moment to know until we have therapeutic interventions that can be useful."
Milne's husband, Les, passed away from complications of Parkinson's Disease in 2015. But thanks to him and the dedication of his wife, Joy, science may have found a way to someday prolong the lives of others with this devastating disease. Sometimes she can smell people who have Parkinson’s while in the supermarket or walking down the street but has been told by medical ethicists she cannot tell them, Milne said in an interview with the Guardian. But once the test becomes available in the clinics, it will do the job for her.
[Ed. Note: A older version of this hit article originally ran on September 3, 2019.]
When Erika Schreder’s 14-year-old daughter, who is Black, had her curly hair braided at a Seattle-area salon two or three times recently, the hairdresser applied a styling gel to seal the tresses in place.
Schreder and her daughter had been trying to avoid harmful chemicals, so they were shocked to later learn that this particular gel had the highest level of formaldehyde of any product tested by the Washington State Departments of Ecology and Health. In January 2023, the agencies released a report that uncovered high levels of formaldehyde in certain hair products, creams and lotions marketed to or used by people of color. When Schreder saw the report, she mentioned it to her daughter, who told her the name of the gel smoothed on her hair.
“It was really upsetting,” said Schreder, science director at Toxic-Free Future, a Seattle-based nonprofit environmental health research and advocacy organization. “Learning that this product used on my daughter’s hair contained cancer-causing formaldehyde made me even more committed to advocating for our state to ban toxic ingredients in cosmetics and personal care products.”
In 2013, Toxic-Free Future launched Mind the Store to challenge the nation’s largest retailers in adopting comprehensive policies that eliminate toxic chemicals in their personal care products and packaging, and develop safer alternatives.
Now, more efforts are underway to expose and mitigate the harm in cosmetics, hair care and other products that children apply on their faces, heads, nails and other body parts. Advocates hope to raise awareness among parents while prompting manufacturers and salon professionals to adopt safer alternatives.
A recent study by researchers at Columbia University Mailman School of Public Health and Earthjustice, a San Francisco-based nonprofit public interest environmental law organization, revealed that most children in the United States use makeup and body products that may contain carcinogens and other toxic chemicals. In January, the results were published in the International Journal of Environmental Research and Public Health. Based on more than 200 surveys, 70 percent of parents in the study reported that their children 12 or younger have used makeup and body products marketed to youth — for instance, glitter, face paint and lip gloss.
Childhood exposure to harmful makeup and body product ingredients can also be considered an environmental justice issue, as communities of color may be more likely to use these products.
“We are concerned about exposure to chemicals that may be found in cosmetics and body products, including those that are marketed toward children,” said the study’s senior author, Julie Herbstman, a professor and director of the Columbia Center for Children's Environmental Health. The goal of the survey was to try to understand how much kids are using cosmetic and body products and when, how and why they are using them.
“There is widespread use of children’s cosmetic and body products, and kids are using them principally to play,” Herbstman said. “That’s really quite different than how adults use cosmetic and body products.” Even with products that are specifically designed for children, “there’s no regulation that ensures that these products are safe for kids.” Also, she said, some children are using adult products — and they may do so in inadvisable ways, such as ingesting lipstick or applying it to other areas of the face.
Earlier research demonstrated that beauty and personal care products manufactured for children and adults frequently contain toxic chemicals, such as lead, asbestos, PFAS, phthalates and formaldehyde. Heavy metals and other toxic chemicals in children’s makeup and body products are particularly harmful to infants and youth, who are growing rapidly and whose bodies are less efficient at metabolizing these chemicals. Whether these chemicals are added intentionally or are present as contaminants, they have been associated with cancer, neurodevelopmental harm, and other serious and irreversible health effects, the Columbia University and Earthjustice researchers noted.
“Even when concentrations of individual chemicals are low in products, the potential for interactive effects from multiple toxicants is important to take into consideration,” the authors wrote in the journal article. “Allergic reactions, such as contact dermatitis, are some of the most frequently cited negative health outcomes associated with the use of cosmetics.”
Children’s small body side, rapid growth rate and immature immune systems are biologically more prone to the effects of toxicants than adults.
Adobe Stock
In addition to children’s rapid growth rate, the study also reported that their small body size, developing tissues and organs, and immature immune systems are biologically more prone to the effects of toxicants than adults. Meanwhile, the study noted, “childhood exposure to harmful makeup and body product ingredients can also be considered an environmental justice issue, as communities of color may be more likely to use these products.”
Although adults are the typical users of cosmetics, similar items are heavily marketed to youth with attention-grabbing features such as bright colors, animals and cartoon characters, according to the study. Beyond conventional makeup such as eyeshadow and lipstick, children may apply face paint, body glitter, nail polish, hair gel and fragrances. They also may frequent social media platforms on which these products are increasingly being promoted.
Products for both children and adults are currently regulated by the U.S. Food and Drug Administration under the Federal Food, Drug, and Cosmetic Act of 1938. Also, the Fair Packaging and Labeling Act of 1967 directs the Federal Trade Commission and the FDA “to issue regulations requiring that all ‘consumer commodities’ be labeled to disclose net contents, identity of commodity, and name and place of business of the product's manufacturer, packer, or distributor.” As the Columbia University and Earthjustice authors pointed out, though, “current safety regulations have been widely criticized as inadequate.”
The Personal Care Products Council in Washington, D.C., “fundamentally disagrees with the premise that companies put toxic chemicals in products produced for children,” industry spokeswoman Lisa Powers said in an email. Founded in 1894, the national trade association represents 600 member companies that manufacture, distribute and supply most personal care products marketed in the United States.
No category of consumer products is subject to less government oversight than cosmetics and other personal care products. -- Environmental Working Group.
“Science and safety are the cornerstones of our industry,” Powers stated. For more than a decade, she wrote, “the [Council] and our member companies worked diligently with a bipartisan group of congressional leaders and a diverse group of stakeholders to enhance the effectiveness of the FDA regulatory authority and to provide the safety reassurances that consumers expect and deserve.”
Powers added that the “industry employs and consults thousands of scientific and medical experts” who study the impacts of cosmetics and personal care products and the ingredients used in them. The Council also maintains a comprehensive database where consumers can look up science and safety information on the thousands of ingredients in sunscreens, toothpaste, shampoo, moisturizer, makeup, fragrances and other products.
However, the Environmental Working Group, which empowers consumers with breakthrough research to make informed choices about healthy living, believes the regulations are still not robust enough. “No category of consumer products is subject to less government oversight than cosmetics and other personal care products,” states the organization’s website. “Although many of the chemicals and contaminants in cosmetics and personal care products likely pose little risk, exposure to some has been linked to serious health problems, including cancer.”
The group, which operates the Skin Deep Database noted that “since 2009, 595 cosmetics manufacturers have reported using 88 chemicals, in more than 73,000 products, that have been linked to cancer, birth defects or reproductive harm.”
But change, for both adults and kids, is on the horizon. The Modernization of Cosmetics Regulation Act of 2022 significantly expanded the FDA’s authority to regulate cosmetics. In May 2023, Washington state adopted a law regulating cosmetics and personal care products. The Toxic-Free Cosmetics Act (HB 1047) bans chemicals in beauty and personal care products, such as PFAS, lead, mercury, phthalates and formaldehyde-releasing agents. These bans take effect in 2025, except for formaldehyde releasers, which have a phased-in approach starting in 2026.
Industry and advocates view this as a positive development. Powers, the spokesperson, praised “the long-awaited” Modernization Cosmetics Regulation Act of 2022, which she said, “advances product safety and innovation.” Jen Lee, chief impact officer at Beautycoutner, a company that sells personal care products, also welcomes the change. “We were proud to support the Washington Toxic-Free Cosmetics Act (HB 1047) by mobilizing our community of Brand Advocates who reside in Washington State,” Lee said. “Together, they made their voices heard by sending over 1,000 emails to their state legislators urging them to support and pass the bill.”
Laurie Valeriano, executive director of Toxic-Free Future, praised the upcoming Washington state law as “a huge win for public health and the environment that will have impacts that ripple across the nation.” She added that “companies won’t make special products for Washington state.” Instead, “they will reformulate and make products safer for everyone” — adults and children.
You shouldn’t have to be a toxicologist to shop for shampoo. -- Washington State Rep. Sharlett Mena
The new legislation will require Washington state agencies to assess the hazards of chemicals used in products that can impact vulnerable populations, while providing support for small businesses and independent cosmetologists to transition to safer products.
The Toxic-Free Future team lauds the Cosmetics Act, signed in May 2023.
Courtesy Toxic-Free Future
“When we go to a store, we assume the products on the shelf are safe, but this isn’t always true,” said Washington State Rep. Sharlett Mena, a Democrat serving in the 29th Legislative District (Tacoma), who sponsored the law. “I introduced this bill (HB 1047) because currently, the burden is on the consumer to navigate labels and find safe alternatives. You shouldn’t have to be a toxicologist to shop for shampoo.”
The new law aims to protect people of all ages, but especially youth. “Children are more susceptible to the impacts of toxic chemicals because their bodies are still developing,” Mena said. “Lead, for example, is significantly more hazardous to children than adults. Also, since children, unlike adults, tend to put things in their mouths all the time, they are more exposed to harmful chemicals in personal care and other products.”
Cosmetologists and hair professionals are taking notice. “Safety should be the practitioner’s number one concern” in using products on small children, said Anwar Saleem, a hair stylist, instructor and former salon owner in Washington, D.C., who is chairman of the D.C. Board of Barbering and Cosmetology and president of the National Interstate Council of State Boards of Cosmetology. “There are so many products on the market that it can be confusing.”
Hair products designed and labeled for children's use often have milder formulations, but “every child is unique, and what works for one may not work for another,” Saleem said. He recommends doing a patch test, in which the stylist or cosmetologist dabs the product on a small, inconspicuous area of the scalp or skin and waits anywhere from an hour to a day to check for irritation before continuing to serve the client. “Performing a patch test, observing children's reactions to a product and adequately adjusting are essential.”
Saleem seeks products that are free from harsh chemicals such as sulfates, phthalates and parabens, noting that these ingredients can be irritating and drying to the hair and scalp. If a child has sensitive skin or allergies, Saleem opts for hypoallergenic products.
We also need to ensure that less toxic alternatives are available and accessible to all consumers. It’s often under-resourced, low-income populations who suffer the burden of environmental exposures and do not have access or cannot afford these safer alternatives. -- Lesliam Quirós-Alcalá.
Lesliam Quirós-Alcalá, an assistant professor in the department of environmental health and engineering at the Johns Hopkins Bloomberg School of Public Health, said current regulatory loopholes on product labeling still allow manufacturers to advertise their cosmetics and personal care products as “gentle” and “natural.” However, she said, those terms may be misleading as they don’t necessarily mean the contents are less toxic or harmful to consumers.
“We also need to ensure that less toxic alternatives are available and accessible to all consumers,” Quirós-Alcalá said, “as often alternatives considered to be less toxic come with a hefty price tag.” As a result, “it’s often under-resourced, low-income populations who suffer the burden of environmental exposures and do not have access or cannot afford these safer alternatives.”
To advocate for safer alternatives, Quirós-Alcalá suggests that parents turn to consumer groups involved in publicizing the harms of personal care products. The Campaign for Safe Cosmetics is a program of Breast Cancer Prevention Partners, a national science-based advocacy organization aiming to prevent the disease by eliminating related environmental exposures. Other resources that inform users about unsafe ingredients include the mobile apps Clearya and Think Dirty.
“Children are not little adults, so it’s important to increase parent and consumer awareness to minimize their exposures to toxic chemicals in everyday products,” Quirós-Alcalá said. “Becoming smarter, more knowledgeable consumers is the first step to protecting your family from potentially harmful and toxic ingredients in consumer products.”
A startup aims to make medicines in space
Story by Big Think
On June 12, a SpaceX Falcon 9 rocket deployed 72 small satellites for customers — including the world’s first space factory.
The challenge: In 2019, pharma giant Merck revealed that an experiment on the International Space Station had shown how to make its blockbuster cancer drug Keytruda more stable. That meant it could now be administered via a shot rather than through an IV infusion.
The key to the discovery was the fact that particles behave differently when freed from the force of gravity — seeing how its drug crystalized in microgravity helped Merck figure out how to tweak its manufacturing process on Earth to produce the more stable version.
Microgravity research could potentially lead to many more discoveries like this one, or even the development of brand-new drugs, but ISS astronauts only have so much time for commercial experiments.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth.”-- Will Bruey.
The only options for accessing microgravity (or free fall) outside of orbit, meanwhile, are parabolic airplane flights and drop towers, and those are only useful for experiments that require less than a minute in microgravity — Merck’s ISS experiment took 18 days.
The idea: In 2021, California startup Varda Space Industries announced its intention to build the world’s first space factory, to manufacture not only pharmaceuticals but other products that could benefit from being made in microgravity, such as semiconductors and fiber optic cables.
This factory would consist of a commercial satellite platform attached to two Varda-made modules. One module would contain equipment capable of autonomously manufacturing a product. The other would be a reentry capsule to bring the finished goods back to Earth.
“There are many high-performance products that are only possible to make in zero-gravity, which is a manufacturing capability that cannot be replicated in any factory on Earth,” said CEO Will Bruey, who’d previously developed and flown spacecraft for SpaceX.
“We have a team stacked with aerospace talent in the prime of their careers, focused on getting working hardware to orbit as quickly as possible,” he continued.
“[Pharmaceuticals] are the most valuable chemicals per unit mass. And they also have a large market on Earth.” -- Will Bruey, CEO of Varda Space.
What’s new? At the time, Varda said it planned to launch its first space factory in 2023, and, in what feels like a first for a space startup, it has actually hit that ambitious launch schedule.
“We have ACQUISITION OF SIGNAL,” the startup tweeted soon after the Falcon 9 launch on June 12. “The world’s first space factory’s solar panels have found the sun and it’s beginning to de-tumble.”
During the satellite’s first week in space, Varda will focus on testing its systems to make sure everything works as hoped. The second week will be dedicated to heating and cooling the old HIV-AIDS drug ritonavir repeatedly to study how its particles crystalize in microgravity.
After about a month in space, Varda will attempt to bring its first space factory back to Earth, sending it through the atmosphere at hypersonic speeds and then using a parachute system to safely land at the Department of Defense’s Utah Test and Training Range.
Looking ahead: Ultimately, Varda’s space factories could end up serving dual purposes as manufacturing facilities and hypersonic testbeds — the Air Force has already awarded the startup a contract to use its next reentry capsule to test hardware for hypersonic missiles.
But as for manufacturing other types of goods, Varda plans to stick with drugs for now.
“[Pharmaceuticals] are the most valuable chemicals per unit mass,” Bruey told CNN. “And they also have a large market on Earth.”
“You’re not going to see Varda do anything other than pharmaceuticals for the next minimum of six, seven years,” added Delian Asparouhov, Varda’s co-founder and president.