The Joy of the Smell Test

If actionable knowledge can come for several sources, but we forbid action based on some of those sources, we will limit our effective action. In the case of health, unnecessary suffering and death will result. In previous entries I highlighted cases where dogs’ advanced ability to smell can diagnose and warn of human maladies more accurately, quicker, and cheaper than other methods. Dog-detectable maladies include Covid, epileptic seizures, and cancer. But the medical establishment underuses this source of knowledge because it is not viewed as scientifically respectable. (And perhaps also because those who practice scientifically respectable ways of knowing, benefit from limiting competition?) The passages quoted below sketch the story of a “hyperosmic” nurse who can smell a distinct odor that identifies those who have and who will have Parkinson’s. Note that follow-up research on this outside-the-box diagnostic method was not funded by governments or universities but by a private foundation founded and funded by Parkinson’s patients and their families and friends. Having a terrible disease sometimes leads to despair, sometimes to a sense of urgency.

(p. 30) As a boy, Les Milne carried an air of triumph about him, and an air of sorrow.  . . .  “We were very, very much in love,” Joy, now a flaxen-haired 72-year-old grandmother, told me recently. In a somewhat less conventional way, she also adored the way Les smelled, and this aroma of salt and musk, accented with a suggestion of leather from the carbolic soap he used at the pool, formed for her a lasting sense of who he was. “It was just him,” Joy said, a steadfast marker of his identity, no less distinctive than his face, his voice, his particular quality of mind.

Joy’s had always been an unusually sensitive nose, the inheritance, she believes, of her maternal line. Her grandmother was a “hyperosmic,” and she encouraged Joy, as a child, to make the most of her abilities, quizzing her on different varieties of rose, teaching her to distinguish the scent of the petals from the scent of the leaves from the scent of the pistils and stamens. Still, her grandmother did not think odor of any kind to be a polite topic of conversation, and however rich and enjoyable and dense with information the olfactory world might be, she urged her granddaughter to keep her experience of it to herself.

. . .

Les spent long hours in the surgical theater, which in Macclesfield had little in the way of ventilation, and Joy typically found that he came home smelling of anesthetics, antiseptics and blood. But he returned one August evening in 1982, shortly after his 32nd birthday, smelling of something new and distinctly unsavory, of some thick must. From then on, the odor never ceased, though neither Les nor almost anyone but his wife could detect it.  . . .

Les had lately begun to change in other ways, however, and soon the smell came to seem almost trivial. It was as if his personality had shifted. Les had rather suddenly become detached, ill-tempered, apathetic. He ceased helping out with many household chores; he snapped at his boys.

. . .

When he began referring to “the other person,” a shadow off to his side, she suspected a brain tumor. Eventually she prevailed upon him to see his doctor, who referred him to a neurologist in Manchester.

Parkinson’s disease is typically classed as a movement disorder, and its most familiar symptoms — tremor, rigidity, a slowing known as bradykinesia — are indeed motoric. But the disease’s autonomic, psychological and cognitive symptoms are no less terrible and commonly begin during the so-called prodrome, years before any changes in movement.

. . .

(p. 31) Feeling desperate, Joy eventually persuaded Les to go with her to a meeting of local Parkinson’s patients and their caregivers.

The room was half full by the time they arrived. Near the coat stand, Joy squeezed behind a man just as he was taking off his jacket and suddenly felt a twitch in her neck, as if some fight-or-flight instinct had been activated, and she raised her nostrils instinctively to the air. She often had this reaction to strong, unexpected scents. In this case, bizarrely, it was the disagreeable odor that had hung about her husband for the past 25 years. The man smelled just like him, Joy realized. So too did all the other patients. The implications struck her immediately.

For nearly all the recorded history of medicine and until only quite recently, smell was a central preoccupation. The “miasma” theory of disease, predominant until the end of the 19th century, held that illnesses of all kinds were spread by noxious odors. By a similar token, particular scents were understood to be curative or prophylactic. More than anything, however, odor was a tool of diagnosis.

The ancients of Greece and China confirmed tuberculosis by tossing a patient’s sputum onto hot coals and smelling the fumes. Typhoid fever has long been known to smell of baking bread; yellow fever smells of raw meat. The metabolic disorder phenylketonuria was discovered by way of the musty smell it leaves in urine, while fish-odor syndrome, or trimethylaminuria, is named for its scent.

. . .

(p. 33) Most diseases can be identified by methods more precise and ostensibly scientific than aroma, however, and we tend to treat odor in general as a sort of taboo. “A venerable intellectual tradition has associated olfaction with the primitive and the childish,” writes Mark Jenner, a professor of history at the University of York. Modern doctors are trained to diagnose by inspection, palpation, percussion and auscultation; “inhalation” is not on the list, and social norms would discourage it if it were.

During her time as a nurse, Joy had done it anyway, reflexively, and learned to detect the acetone breath that signaled an impending diabetic episode, the wet brown cardboard aroma of tuberculosis — “not wet white cardboard, because wet white cardboard smells completely different,” she explained — or the rancidness of leukemia. The notion that Parkinson’s might have a distinctive scent of its own had not occurred to her then, but when it did occur to her years later, it was hardly exotic.

She and Les worried that the normosmics of the world, unfamiliar with medical smells and disinclined to talk about odor in general, might not take her discovery very seriously. They searched for an open-minded scientist and after several weeks settled on Kunath, the Parkinson’s researcher at the University of Edinburgh. In 2012, Joy attended a public talk he gave. During the question-and-answer session, she stood to ask, “Do people with Parkinson’s smell different?” Kunath recalls. “I said, ‘Do you mean, Do people with Parkinson’s lose their sense of smell?’” (Smell loss is in fact a common early symptom of the disease.) “And she said: ‘No, no, no. I mean, Do they smell different?’ And I was just like, ‘Uh, no.’” Joy went home. Kunath returned to his usual work.

Six months later, however, at the urging of a colleague who had once been impressed by cancer-sniffing dogs, Kunath found Joy’s name and called her. She told him the story of Les’s new smell. “I think if she’d told me that, as he got Parkinson’s, he had a change in smell, or if it came afterwards, I probably wouldn’t have followed up any more,” Kunath told me. “But it’s this idea that it was years before.”

He called Perdita Barran, an analytical chemist, to ask what she made of Joy’s claims. Barran suspected Joy was simply smelling the usual odor of the elderly and infirm and misattributing it to Parkinson’s. “I knew, because we all know, that old people are more smelly than young people,” says Barran, who is now a professor of mass spectrometry at the University of Manchester. Still, Barran was personally acquainted with the oddities of olfaction. Following a bike accident, she had for several years experienced various bizarre distortions to her own sense of smell. The idea that Joy might be capable of experiencing odors that no one else could did not strike her as entirely outlandish.

She and Kunath ran a small pilot study in Edinburgh. Through Parkinson’s UK, they recruited 12 participants: six local Parkinson’s patients and six healthy controls. Each participant was asked to wear a freshly laundered T-shirt for 24 hours. The worn shirts were then cut in half down the center, and each half was placed in its own sealed plastic bag. Kunath oversaw the testing. Joy smelled the T-shirt halves at random and rated the intensity of their Parkinsonian odor. “She would find a positive one, and would say, ‘There — it’s right there. Can you not smell it?’” Kunath recalled. Neither he nor the graduate student assisting him could smell a thing.

Kunath unblinded the results at the end of the day. “We were on a little bit of a high,” he recalled. Not only had Joy correctly identified each sample belonging to a Parkinson’s patient, but she was also able, by smell, to match each sample half to its partner. Barran’s skepticism evaporated. Still, Joy’s record was not perfect. She had incorrectly identified one of the controls as a Parkinson’s patient. The researchers wondered if the sample had been contaminated, or if Joy’s nose had simply gotten tired. By Barran’s recollection, Kunath’s response was: “It’s fine! It’s one false positive!” Barran herself was slightly more cautious: Joy had mislabeled both halves of the man’s T-shirt.

Of more immediate interest, though, was the question of what was causing the smell in the first place. The odor seemed to be concentrated not in the armpits, as the researchers had anticipated, but at the neckline. It took them several weeks to realize that it perhaps came from sebum, the lipid-rich substance secreted by the skin. Sebum is among the least studied biological substances. “It is actually another waste disposal for our system,” Barran says. “But no one had ever thought that this was a bodily fluid we could use to find out about disease.”

Barran set out to analyze the sebum of Parkinson’s patients, hoping to identify the particular molecules responsible for the smell Joy detected: a chemical signature of the disease, one that could be detected by machine and could thus form the basis of a universal diagnostic test, a test that ultimately would not depend on Joy’s or anyone else’s nose. No one seemed to be interested in funding the work, though. There were no established protocols for working with sebum, and grant reviewers were unimpressed by the tiny pilot study. They also appeared to find the notion of studying a grandmother’s unusual olfactory abilities to be faintly ridiculous. The response was effectively, “Oh, this isn’t science — science is about measuring things in the blood,” Barran says.

Barran turned to other projects. After nearly a year, however, at a Parkinson’s event in Edinburgh, a familiar-looking man approached Kunath. He had served as one of the healthy controls in the pilot study. “You’re going to have to put me in the other category,” he said, according to Kunath. The man had recently been diagnosed with Parkinson’s. Kunath was stunned. Joy’s “misidentification” had not been an error, but rather an act of clairvoyance. She had diagnosed the man before medicine could do so.

Funding for a full study of Joy, the smell and its chemical components now came through. “We saw something in the news, and we thought, Wow, we’ve got to act on that!” says Samantha Hutten, the director of translational research at the Michael J. Fox Foundation. “The N.I.H. is not going to fund that. Who’s going to fund it if not us?”

. . .

(p. 51) Joy has enjoyed her fame, but the smell work also radicalized her, in its way, and she has a reputation for being a bit intransigent in her advocacy. The initial scientific skepticism toward her was of a piece, she thought, with what she already held to be the medical corps’s hopeless wrongheadedness about Parkinson’s disease. For Joy, as for many caregivers, the psychological aspects of the illness were by far the most difficult to manage, much less accept, and these happened to be precisely the symptoms neurologists seemed least interested in acknowledging, let alone addressing.  . . .

To Joy’s mind, still more proof of this medical obstinacy came from the discovery that she was not alone in her ability to smell Parkinson’s disease. When the research first began to attract attention in the media, Barran and Kunath received messages from around the world from people reporting that they, too, had noticed a change in the smell of their loved ones with Parkinson’s.
  . . .  But for the smell taboo, Joy thought, someone somewhere might have taken these people seriously, and the importance of the odor might have been realized decades sooner.

For the full story see:

Scott Sayare. “The Smell Test.” The New York Times Magazine (Sunday, June 16, 2024): 28-33, 51 & 53.

(Note: ellipses added; bold in original.)

(Note: the online version of the story has the date June 3, 2024, and has the title “The Woman Who Could Smell Parkinson’s.”)

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