On St. Andrews beach on Scotland's east coast, you might run across a solitary woman on occasion, walking close to the water where the sand is wet and firm. The North Sea wind blows her gray hair over her ears as the woman closes her eyes and holds her nose into the wind. Her nose quivers and lifts, as though she's about to sneeze.
The woman's name is Joy Milne. She spent 26 years working as a nurse, raised three sons and cared for her ailing husband. Now, she is widowed. She spends her time traveling and enjoys taking long walks. She is 69 years old.
Her nose is a bit crooked perhaps, neither particularly big nor particularly small, and when she takes her glasses off, which she does to look out at the sea, you can see two dimples where they usually rest. But Milne's nose is special: She has a much better sense of smell than most people.
She can smell coffee even before she opens the door of a café and registers the scent of her grandchildren before she wraps them up in a hug. But she can also smell things during the day that she doesn't necessarily want to smell.
Exhaust fumes, butcher shops, perfume stores, the air in airplane cabins: Joy Milne's nose runs and bleeds when the world around her stinks. Not only that, but unpleasant odors make her cold. Her escape is the North Sea.
The scientific term for her extremely acute sense of smell is hyperosmia, from the Greek word "osme," meaning "odor." It is a condition associated with epilepsy, psychosis and pregnancy, but Milne has had an elevated sense of smell since childhood. Of herself, she says: "When it comes to my sense of smell, I'm somewhere between a person and a dog."
Something Monumental
For the last several years, scientists have taken an acute interest in her nose. Milne, after all, is also able to smell diseases. People with Alzheimer's smell to her like rye bread, diabetes like nail polish, cancer like mushrooms and tuberculosis like damp cardboard. Having provided care to thousands of sick people in her life, she has had plenty of contact with various illnesses. Milne, though, is most familiar with the smell of Parkinson's. It's the disease that killed her husband Leslie and his mother, who she also cared for during her illness.
Every few weeks, she shaves the tiny hairs off her upper lip that disturb her sense of smell, jumps into her white Honda Jazz and drives from her home in the Scottish town of Perth, where she lives in a small house with a garden, to Manchester. The drive takes five to six hours, and each time Milne passes through the revolving door at the Manchester Institute of Biotechnology, located on 131 Princess Street, she feels as though she is part of something monumental.
Parkinson's has been around from time immemorial, with an ancient Egyptian papyrus from the 12th century B.C. describing the suffering of a drooling ruler. But there is still no cure. Nobody even knows how exactly the disease originates.
Researchers recently began warning of a "Parkinson's pandemic," saying that the number of patients worldwide will have doubled to around 14 million by 2040. Life expectancy is on the rise and along with it, so too is the risk of coming down with Parkinson's.
The disease kills brain cells, and patients gradually lose control of their own bodies, their movements and their speech. It is a long, slow slide.
The last three nights before her husband died, Milne lay next to him in the dark and spoke with him, saying they spoke more openly than at any time during their 42 years of marriage. Les, as she called him, apologized to her for what the illness had made of him.
Enemy in the Brain
Evidence suggests that the enemy in the brain is called alpha-synuclein, a protein that for unknown reasons becomes destructive in Parkinson's patients. Normally, alpha-synuclein regulates dopamine production, and without dopamine, a person likely wouldn't even be able to lift a coffee cup: The signal from the brain would never reach the hand.
Daniel Etter/ DER SPIEGEL
A sebum swab from the Manchester Institute of Biotechnology.
In Parkinson's patients, though, the protein apparently begins killing precisely those nerve cells that produce dopamine. The process takes place in the midbrain, an area known as the substantia nigra, or black substance. It is a darker color than the rest of the brain and in cranial cross-sections, it looks not unlike a black ribbon around a brightly colored hat. Parkinson's nibbles its way forward in hiding -- until the motoric symptoms begin appearing: slow movement, tremors, muscle stiffness. By the time a doctor is able to diagnose the disease, between 50 and 70 percent of the cells have already been destroyed.
Ever since the British doctor James Parkinson published his "Essay on the Shaking Palsy" in 1817, generations of patients have had the same experience: "So slight and nearly imperceptible are the first inroads of this malady," wrote Parkinson, "and so extremely slow its progress, that it rarely happens, that the patient can form any recollection of the precise period of its commencement."
In Manchester, a team of researchers is exploring the question as to whether it might be possible to diagnose Parkinson's at an earlier stage before clear symptoms begin appearing. Pharmaceutical companies have spent years developing medicines, but what good are even the best drugs if they can only be prescribed after the brain cells have already been destroyed?
'A Strong, Masculine, Musky Smell'
The team in Manchester is led by Perdita Barran, a woman who likes to wear jeans and sneakers, with her sunglasses pushed up into her hair. She could be Joy Milne's daughter. When Milne comes to Manchester, she spends the night at Barran's home.
Barran is a chemist, not a Parkinson's researcher, but ever since Milne told medical professionals eight years ago that she is able to smell Parkinson's, Barran has spent quite a bit of her time on the disease.
Milne claims to be able to smell Parkinson's in the disease's early stages and Barran is hoping to develop an early-stage diagnostic test with Milne's help. The project is called NoseToDiagnose.
Odors are made up of molecules and molecules can be measured, heated and accelerated in tubes. In Manchester, Barran is trying to teach a machine to smell what Joy Milne is able to smell. But what exactly does Joy Milne smell? She didn't know herself for quite some time.
Daniel Etter/ DER SPIEGEL
Joy Milne conducting a smell test in the office of Perdita Barran.
For many years, she loved Leslie's bodily odor, describing it as "a strong, masculine, musky smell." Joy and Leslie Milne had their first, somewhat awkward discussion about body odor in 1981. Les was in his early 30s at the time, a successful anesthesiologist and head physician at a large hospital. One evening when he came home from work, Milne recalls, he smelled like a teenager who hadn't washed his PE clothes in a while. You should shower more often, she told him. Come to bed, he answered, let's do the crossword.
Les and Joy first met at school in the coastal city of Dundee, where the River Tay flows into the North Sea. She was 16 and he was 17, the captain of the water polo team. Joy had planned to move to Paris to study French, but because of Les, she stayed in Dundee.
The town smelled of jute back then, with Dundee being Britain's largest grower of the plant, which is used to produce burlap and rope. Milne likes to take visitors to the top of Law Hill, a green, 170-meter (560-foot) high hill in Dundee with a view of the Tay. "Les and I came up here often," she says. "Now, it smells of cowslip."
Deep Purple
When Milne closes her eyes, she smells in color. If she puts a flower up to her nose, a "kaleidoscope," as she puts it, begins spinning in her head. The medical term for this overlapping of sensory perception is synesthesia, and the color of the scent rarely has anything to do with the color of the object in question. Coffee smells "swirly gray" to her, while the smell of the North Sea is emerald green.
People, too, have colors. Dr. Perdita Barran in Manchester -- Milne calls her Perdi -- smells green to her, sometimes orange, going on red when Perdi laughs. Les, she says, was "deep purple."
She smelled her Les in the same way that other people might gaze at a painting or listen to a symphony, though Les himself could smell nothing. He lost his sense of smell in his late 20s. Not everyone who loses their sense of smell, of course, will later be diagnosed with Parkinson's. A head injury, tumors or a heavy cold can also weaken the sense of smell. But those who come down with Parkinson's usually can no longer rely on their sense of smell. Today, it is considered an early symptom of Parkinson's.
Another warning sign that they knew nothing about was bouts of constipation. Milne would cook vegetable stew for her husband to provide him relief.
Privat
Leslie Milne together with his family before his death
He also had a restless sleep, dreaming of hunting excursions, shooting at blackberry bushes in his sleep, startling awake and pointing his imaginary weapon at his wife. One time, he lost a tooth crown. Difficulty sleeping, as she now knows today, is also a possible symptom.
What happens in the body of a Parkinson's patient before diagnosis is different from person to person, depending on genetics, on nutrition and on whether and how much one exercises. Joy Milne, though, now believes that much of what transformed her Les into a different Les was the result of Parkinson's. The halitosis he began developing in his 30s, the earwax on the pillow. The oily skin on his back and face. His complaints that food tasted bland. At the time, of course, neither of them was thinking about Parkinson's. Les would clean his ears, brush his teeth and add increasing amounts of salt and pepper to his food.
The two of them had three children.
Irreversible at Age 40
According to one hypothesis, Parkinson's doesn't start in the brain, but in the stomach. The theory holds that alpha-synuclein mutates in the bowels and makes its way to the brain via the vagus nerve. The manner in which the protein then settles in the brain was described by the German anatomist Heiko Braak. In 2003, 12 years before Leslie Milne died, Braak published his six-stage model, a theory based on the dissection of hundreds of brains.
In the first stage, the vagus nerve -- the 10th cranial nerve, which controls most of our internal organs -- is afflicted in the brainstem. This is where the first aggregates appear, and it is from here that the illness spreads via the brainstem into the entire brain. The dopamine-producing substantia nigra is only afflicted in stage three. And that stage is the critical one.
Heiko Braak wrote: "Were it possible to diagnose PD already in the early, presymptomatic stages 1 or 2, and were a causal therapy to become available, the subsequent destruction of the substantia nigra could be prevented."
For Leslie Milne, the process likely became irreversible as he approached the age of 40.
The strange smell for which Joy had no explanation grew stronger and became creamier, fattier. She had stopped mentioning it to Les. He also began suffering from erectile dysfunction.
From that point on, there were essentially two Leslies. The one was attentive, hard-working and an excellent father. The other was moody, distant and weak. His bodily odor became increasingly foreign to Joy, with his nice deep purple growing increasingly brown.
Illnesses affect metabolism. Even Hippocrates and Avicenna used their noses to make diagnoses. The stool of cholera patients has a fishy odor, the urine of those suffering from diabetes smells sweet. When Milne tries to capture the smell of Parkinson's in words, she has to think for a bit. "Musky," she says. "Seabum musky."
Relying on Comparisons
Musk, though, is a sought-after scent, the basis for many perfumes. Didn't she use that word to describe her husband's body odor prior to the illness?
Milne promises to think about it a bit more. It's not easy to describe odors to people who are unable to smell them. That difficulty has to do with the human body's complex olfactory system, in contrast to, for example, our sense of taste. Humans can only taste sweet, bitter, salty, sour and umami (the taste of meat broth). Our noses, by contrast, can pick up approximately 400 different odors, as opposed to the 800 dogs can smell. Because our vocabularies don't have the necessary adjectives for those odors, we rely on comparisons instead.
Our scent receptors are located on the mucous membrane inside the nasal cavity. They are protein compounds that are each responsible for only a single odor molecule and they become active when their molecule comes through the nose and binds perfectly. Odorant molecules come in different shapes and sizes and the entire system functions according to the lock-and-key principle.
from Hacker News https://ift.tt/351c61X
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.