Tag: smell

We Can Now Predict Disease With Smell

In 2015, Joy Milne made waves when it was revealed that she had an amazing talent – she could smell Parkinson’s Disease. And now she’s helping develop tests that could diagnose Parkinson’s long before symptoms begin to show.

TRANSCRIPT:

Maybe start with some details about how accurate dogs’ sense of smell can be. And then segue into the fact that some people have a similar ability – and now that ability could save lives.

Zoe Sketch?

In a recent video, I talked about some superhuman senses that some animals have, and in it, I talked about the fairly well-known fact that dogs can actually smell some kinds of cancers.

So now you have a new anxiety when a dog buries its nose in your crotch.

The problem is dogs can’t talk, so it’s hard to figure out exactly what chemicals they’re smelling. And even the most accurate dogs were still in the 80% range.

But imagine if a person could have that ability, and could talk and could help discern exactly what chemicals they were smelling. That is exactly what’s happened in the case of Joy Milne, and thanks to her super smeller, we could be on the verge of a whole new suite of diagnostics tools that could save millions of lives.

Joy Milne is a retired nurse from Perth, Australia, who has kind-of had a superpower her whole life. And she had no idea.

Joy has something called hyperosmia, basically a superhuman sense of smell, her nose has more olfactory receptors than the rest of us.

Which kinda makes me think of tetrachromacy, where some people are born with 4 types of cones in their retinas instead of 3, so they have the ability to see colors a little more clearly than the rest of us.

So you could say Joy could smell in colors the rest of us can’t smell.
And this is something she never really thought about, you know, we all just assume that others perceive the world the same way we do.

Which is why it probably drove her crazy when about 10 years into her marriage, she started to notice a smell coming off her husband.

His name was Les, he was a doctor, and yeah, she started noticing a musky, yeasty smell coming off of him, and she assumed it was from something at work.

He of course couldn’t smell it, which isn’t unusual, we tend to go nose blind to our own smells, but to her it was just pungent, especially on his neck and upper back.

So she started telling him he needed to wash himself better. He did his best to oblige her but she kept complaining about it. I can only imagine the fun little arguments that that created.

Marriage.

She eventually just learned to live with it and tried to let it go because it was driving him crazy and besides, nobody else could smell it so… what can you do.

But a few years after that, she noticed his personality began to change.

As Joy told NPR in 2020:

“He was more moody. He wasn’t as tolerant.”

They began to fight more. All the good qualities she admired in him – patience and thoughtfulness – began to slip away.

By his early 40s, she saw her husband as a completely different person.

And then one night, she woke up to Les attacking her.

She told NPR:

“He was sort of screaming and shaking me… but he was totally oblivious of it.”

He was clearly just having a nightmare, but this was the breaking point. I’m sure getting attacked in the middle of the night could do that.

So Joy demanded he visit a doctor. She thought he might have a brain tumor.

Turns out, 45-year-old Les Milne had Parkinson’s disease.
Most of us know Parkinson’s disease as a brain disorder that can cause uncontrollable or unintended movements like shaking, stiffness, and difficulty with balance and coordination.

But people with Parkinson’s may also develop behavioral and mental changes, depression, and memory problems. And that was the case with Les.

The disease occurs when nerve cells in the basal ganglia are damaged or die. But scientists don’t know exactly what causes that.
Joy and Les made the best of things over the next 20 years, but as his condition deteriorated, it put a strain on their marriage, so they decided to join a Parkinson’s support group.

So they show up to this meeting, they actually got there kinda late. But when Joy walked in the room, a wave of that familiar smell came over her.

It took her a minute to realize that that smell was coming from the other people in the room.

Joy told NPR:

“And then I realized for some people it smelled stronger and for other people it didn’t smell so strong.”

She realized that maybe this thing that she’d been smelling this whole time was Parkinson’s disease.

And she’d been smelling it way before Les started showing any symptoms.

Both being healthcare workers, she and Les realized the implications of this. Because if you could start treating Parkinson’s before the nerve damage starts, you could save a lot of lives.
This was an amazing revelation. But what exactly are you supposed to do with that?

Well Joy reached out to a Parkinson’s researcher at the University of Edinburgh named Tilo Kunath.
And his initial reaction was probably exactly what you’d expect.
Wow, that is weird… Yeah… Well, I hate to cut this short but I’ve got a guy on the other line that can hear diabetes so thanks for calling, bye bye then.

Needless to say, it sounded a little crackpot to him at first but then he thought about the research that had shown that dogs could smell cancer – and he figured it couldn’t hurt to give it a look.

So he had her visit his lab for a special test. What he did was he took two groups of people, one group that had Parkinson’s and one that didn’t, and he had them wear white T-shirts for a night and seal them in boxes.

He then had Joy smell the shirts to see if she could identify the people who had Parkinson’s.

And the results were pretty mind-blowing. She got all of them right except for one – she had a false positive, she thought someone had Parkinson’s who didn’t.

But still, like 95/98% accurate, it was crazy.

Except that actually wasn’t true. Because a few months later that guy, that false positive guy… was diagnosed with Parkinson’s. She smelled it before he had any symptoms, and before it showed up on medical tests.

100% accurate. More accurate than established diagnostic tests.

So yeah, Dr. Kunath was on board at this point and continued to work with Joy. Unfortunately it was right about this time that Les’s health started to go downhill.

Les passed away in 2015. Before he died, he made Joy promise to continue researching and find a way to help others.

Joy and Dr. Kunath published their findings in ACS Central Science in March 2019. This spawned a lot of articles and specifically got the attention of a researcher named Perdita Barran.

Barran is a researcher from the University of Manchester Department of Chemistry and she wanted to see if they could figure out exactly which chemicals Joy was smelling.

So she and Joy started working together and they found several chemicals in the sebum, which is an oily discharge that we all have in our skin.

It’s often overproduced in people with Parkinson’s disease.

The research showed elevated levels of compounds like eicosane, hippuric acid, and octadecanal.

Using that info, Joy and a team of scientists from the University of Manchester developed a new skin swab test.

It works by swabbing the back of a person’s neck and back to collect sebum. Then a mass spectrometer analyzes it.

It can detect Parkinson’s disease with 95 percent accuracy under lab conditions.

The scientists sampled 79 people who had the disease and 71 healthy people.

They identified 500 compounds that were different between people with Parkinson’s and those without it.

Barran told the Hull Daily Mail:

“What we are now doing is seeing if (hospital laboratories) can do what we’ve done in a research lab in a hospital lab. Once that’s happened then we want to see if we can make this a confirmatory diagnostic that could be used along with the referral process from a GP to a consultant.”

The testing is still in the early stages, with a lot of refining still to be done.

Joy is also working with other scientists around the world to see if she can smell other diseases like cancer and tuberculosis.

By the way, Joy describes her super smell as a gift and a curse because, well for one thing a lot of perfumes and candles are overwhelming to her, I can imagine that’s annoying but also… it creates some ethical issues.

Because sometimes when she’s walking down the street or shopping in the supermarket, she’ll walk past somebody… And she can smell Parkinson’s on them.

So what do you do in that situation? Do you say something? How would that go?

“Excuse me, ma’am, can you hand me that box of Corn Pops? Thanks. Oh, you probably have an undiagnosed terminal illness, okay bye…”

Like seriously, what are you supposed to do?

Joy consulted with medical ethicists and said she probably shouldn’t say anything. For now anyway.

Because the research is still new, it’s not in laboratory conditions and there are also privacy issues involved.

Besides, what are they supposed to do, go to their doctor and demand a test because some random lady at the store said they smell like Parkinson’s?

But maybe in the future the smell test will pass the… smell test. We’ve known that different diseases have different smells for a long time.
The ancient Indian medical text Sushruta Samhita even includes the line:

“By the sense of smell we can recognize the peculiar perspiration of many diseases, which has an important bearing on their identification.”

 

In Chinese medicine, there’s a practice called Listening and Smelling, or Auscultation and Olfaction.

They basically assign sounds and smells to the different organs in the body. And changes in those smells could indicate problems in those organs.
And the same is true to a lesser extent in Western medicine. Smells have often been a diagnostic tool.

For example, if a patient had a fruity aroma of decomposing apples, an experienced diagnostician would know they probably have diabetic ketosis.

Back in the day the smell of baked bread coming off a person was a sign of typhoid fever.

hyperaminoaciduria – dried malt or hops
scrofula – stale beer

And Yellow Fever apparently smells like a butcher shop. So good luck getting a date when you smell like that! And you know, the yellow fever.

Now at this point you might be asking me,  “Why Joe? How exactly do diseases make different smells?” To which I would respond by saying why are you talking like that?

To put it simply, our bodies are basically chemical factories, and diseases alter those factories, and the chemicals it creates.

For example, a pathogen could alter the level or types of microbes, which expirate different chemicals that we can pick up through smell.

Or, the activation of our immune system could change the excretion of metabolic byproducts from our hormonal system.

And there is one smell test that has made its way into the clinic, it’s a test for asthma.

When the airways in our lungs are infected, they release nitric oxide in a person’s breath. And those levels are higher in people with asthma.

Well, after two decades of development, the FDA approved a handheld device that doctors now use to help make a diagnosis.

This is a cool first step, but now they’re working on similar technology for personal use that could let you monitor medication effects and or even give advance warnings of asthma attacks.

It could even plug into a mobile phone, with an app reporting on nitric oxide levels.

As Raed Dweik, a physician and professor at the Cleveland Clinic, told Scientific American in 2016:

“Your phone would become the device. That’s the future.”

So it is possible in the not too distant future that you could take a scent sample as part of your yearly physical exam.

And that sample could be analyzed to find everything from Parkinson’s to cancer, Alzheimer’s, heart disease, you name it.

And with those early warnings you could start treating and fending off the disease long before they actually become a problem.

And along with that, devices that work with your phone to give you early warnings of problems in your daily life.

It really could be the beginning of a whole new way to see disease, far earlier than our eyes could detect.

All because of one woman and her superhuman sense of smell. Really cool stuff.

How Scientists Accidentally Created The World’s Worst Smell

Thioacetone is a chemical whose smell is so bad, it’s almost impossible to believe. Weirdly, it was created from a chemical that you can find in candy. But it opens up questions about how smell works and why we react to smells the way we do.

TRANSCRIPT:

We’ve all kinda gotten used to COVID-19 at this point and we’ve heard all the weird effects it can have on the body but one of the weirdest has to be that it makes you lose your sense of smell.

Remember when it was still new and we were learning new things about it all the time, how weird that was? Remember panicking if you thought you weren’t smelling something at the level you thought you should?

We only have 5 senses, and this disease, for reasons we still don’t understand two years later, turns one of them off.

Imagine if it made you blind temporarily, or deaf, or you couldn’t feel anything you touched?

I guess there are other diseases that do that actually.

But the point is, everybody who lost their sense of smell talks about how weird it makes everything, how it makes it hard to eat because food all tastes like Elmers glue.

Don’t know what you got till it’s gone I guess.

But there are some instances where not having a sense of smell would probably be a good thing. For example if you were ever to run across a certain chemical called Thioacetone; considered by many to be the worst smell in the world.

What’s the worst thing you’ve ever smelled? Really, think about it, put it in the comments. I bet just thinking about it brings you back to a vivid memory of some kind. Probably not a great one. Maybe it’s even something that traumatized you. And you’re now spiraling into a dark abyss of pain you thought you had escaped. A door you thought you had permanently shut. And now you’re back inside of it, trapped, screaming into the uncaring void…

…Sorry I just made you do that.

But that’s the power of smell, it’s wired directly into our emotional centers, it’s our most primal sense. And yet, we still don’t really know how it works.

I know that sounds like clickbait, but it’s true, there’s no single agreed-upon theory of smell.

What we do know is that a smell happens when an odor molecule binds to a receptor within the nasal cavity.

That smell is then interpreted by the glomerulus which gets a bunch of information from other receptors in the nose called olfactory receptor neurons, and then combines all that info together into what we call smell.

And that is about how deep our understanding goes, we’re still struggling to figure out how exactly our olfactory receptors detect the molecules in the first place.

There are competing theories.

Docking theory of olfaction: Purposes a very 1:1 match. It’s kind-of a lock and key situation where a molecule key fits into a receptor lock. Each receptor is either on or off and the number of different receptors tells the brain how to interpret it.

Odotope theory: Is similar to docking theory except that molecules can fit several types of receptors and vice versa. It’s more of a matter of processing the signal through the noise.

Vibration theory of olfaction: That the molecules fit into receptors but the receptors are actually interpreting the vibrations of the molecules at the atomic level.

This one is pretty controversial, it also posits that quantum tunneling is involved which is totally nuts, so it’s heavily debated. I just think it’s funny that smelling science has drama.

But because we don’t know exactly how it works, it turns out you can’t really measure stink.

Or I should say you can measure the concentration of a smell but good or bad is rather subjective. One person’s stinky cheese or dripping gasoline odor is someone else’s bouquet of roses. Noses are weird.

So there is no objective scale of smells like, say scoville units that measure spiciness by the level of capsaicin in a food.

What we can gather is people’s reactions to the stink and see just how universally hated it is. Then we can look at how much this chemical can disperse and still be detected. And from that, of course, we can create a weapon.

Because humans gonna human.

Yes, the US Department of Defense studied smell in order to create a non-lethal stink bomb to use against the enemy.

One person who consulted on the stink bomb project was a cognitive psychologist named Pamela Dalton.

She said that the DOD had created a lot of different smelly chemicals and gave her access to their stink inventory.

She zeroed in on one that the government used to simulate large military latrines to test cleaning products on.

From this base of stink Dalton went on to create what she dubbed the “stench soup” she described the soup as smelling like “Satan on a throne of Onions” and that she couldn’t imagine a worse smell.

Well, she might not be able to imagine it, but there is a worse smell. FAR worse.

In the year 1889, German scientists were working with a chemical called Trithioacetone, which today is used as a flavorant in candy. So fairly harmless chemical, but as they were experimenting with it, they “cracked” that molecule.

Turning Trithioacetone into just thioacetone. And it turns out that while good things may come in threes, one is the loneliest number.

Because this compound smells in a profound way.

Almost supernatural.

Okay, so let me take a second and tell you what I really wanted to do with this video.

I heard about thioacetone and my YouTuber clickbait brain took off I was like, I’m gonna get my hands on some of this stuff. I’m gonna take just a tiny bit of it and go down to the park and rub it on a tree and then shoot people reacting to it as they walked by.

I mean I’m not really into prank videos but smell is a difficult thing to get across visually so I really wanted to show someone reacting to it, either other people or myself, I’d title it, “I Smelled The Worst Thing In The World” And I’d even do the whole Thumbnail wow face, put a red circle in there, I was ready to sell out big time.

…But then I read some of the stories about thioacetone.

And yeah… That’s not going to happen.

When the German chemists accidentally made a small amount of thioacetone, they also accidentally spilled a little of it.

And apparently one little quirk of thioacetone is it spreads through the air so fast that the people standing right next to it don’t actually smell it right away.

And by the time they picked up on the smell in their lab, people were literally passing out and vomiting in the streets of Friberg.

A newspaper at the time described it as “an offensive smell which spread rapidly over a great area of the town causing fainting, vomiting and a panic evacuation.”

They literally tipped over a beaker and it caused people to evacuate their homes and businesses up to a half a mile away in all directions in a matter of seconds.

That’s some fast stank.

Thioacetone popped up again in England in 1967.

British researchers Victor Burnop & Kenneth Latham were using thioketones to synthesize new polymers, and made a terrible mistake.

They left a bottle of residue open for a moment. In that time a building filled with people 200 yards away started to become overwhelmed by an unspeakable odor and nausea soon followed.

Just having a bottle open for a few seconds caused people to get sick in another building two football fields away.

At around that same time Professor Mayer at Dresden University of Technology stumbled upon it while experimenting with chemical compounds called thioketones.

He had heard about thioacetone and wanted to experience it for himself. And even though he was fully prepared to smell something awful, he was still blown away by it. Saying…

He calls it red. I’ve heard it described as brown and orange as well.

Oh, and another thing about thioacetone – it lingers.

As if the pungent smell wasn’t bad enough, apparently it’s described as “sticky” and will get embedded in your clothes and hair.

There was a story of some chemists that were exposed to thioacetone in a lab and even though they followed all the protocols and washed it off and everything, later that day when they went to a restaurant, the other patrons complained about their smell to the manager so much he literally sprayed deodorant on them at their table.

There’s Stench, And Then There Is Thioacetone, the World’s Stinkiest Chemical

But all of these stories are from a long time ago, it’s actually hard to find modern accounts of scientists working with Thioacetone, because I think they did enough research.

It doesn’t seem to have any other uses, it just stinks, really bad, really really bad. Enough said.

It’s literally like a WMD of smell, and it’s just not worth messing with it.

Because smelly spills happen all the time.

One of these spills happened in the city of Rouen (row-on) in Normandy, France.

There they have a chemical plant run by Lubrizol. And in 2013 they had a large chemical spill.

That chemical was heated by the air and evaporated, filling the air with the smell of rotten eggs that the wind carried for hundreds of miles, as far away as London.

People in Rouen reported feeling nauseous and having migranes from it.

The chemical spilled? Wasn’t Thioacetone actually but its baby brother mercaptan which is often put into natural gas lines to detect gas leaks.

Yeah, the use of mercaptan in gas lines goes back to… you guessed it… The Victorians!

I mentioned in one of my many Victorian videos that when gas lines first started appearing in homes, lots of people died of gas leaks, because natural gas is odorless and they didn’t know there was a leak. So they started adding mercaptan to it.

The human nose can detect 1.6 parts per billion of mercaptan, so you can imagine just how intense the odor must have been when pure mercaptan was floating over Europe.

The reason is the sulphur in the molecule, and the human nose is so good at detecting sulphur it is thought even a single molecule can even be detected.

Fun Fact:

The human nose is also really good at detecting the scent of vanilla (scientifically known as Vanillin). Vanillin has an even lower detection threshold of 2.0×10-7 mg/m3.

Yeah, apparently if you took an oil tanker full of pure vanillin and poured it out, it would literally make the whole planet smell like vanilla. The whole planet.

Which would kinda turn the whole planet into Disneyland. They pipe in vanilla scent through vents along main street Disneyland.

But back to thioacetone, why? Why is this stuff so bad? Especially when you consider it was derived from something that goes in candy? Chemistry is weird.

Thioacetone is derived from the Thiol group aka sulfur family.

Thiols are sulfur analogues of alcohol (Thi = Sulfur ol=alchol)

Humans evolved to avoid them because rotten things tend to release sulfurs. And rotting things tend to also contain you know, death and disease; stink, saving lives.

After a couple thousand years of evolutionary pressures, and now we are grossed out by dumpsters on breezy summer nights. Looking at you South Dallas.

Ultimately that is really what our human perception of stink is supposed to do. It’s what all of our senses are supposed to do, keep us alive.

Thioacetone really shows just how powerful chemistry can be and arguably dangerous, I can’t imagine what two oil trucks of thioacetone being tipped over would smell like. International smells like death day…week?

But luckily that’s very unlikely to happen. It doesn’t seem to have any use so there’s not a lot of factories making the stuff.

Like it’s so bad that you can’t even weaponize it, which is why the DOD was experimenting with other things. Try to smoke out some bad guys or disperse a crowd with thioacetone and all your guys will pass out in their own vomit too.

So even though my original plan for this video was kinda thwarted, maybe some things are best just left as a mystery.

Perhaps shelving thioacetone for good is the wise thing to do.

Researching into this episode made me appreciate my nose, as silly as that may sound.

I found myself taking time to really smell things around me, because most of our surroundings we grow used to and “smell blind” to but taking time to take deep breaths allowed me to appreciate new scents in my home and outside.

Smell is also powerfully tied to our memories and our emotions on an almost animal instinctual level. Most people can remember a smell, be it the smell of their grandmother’s house or their favorite flower.

It is very integral to who we are as humans, it enriches the world around us. Smell keeps us safe, and also leads us to food or water. One of the lowest concentrations of smell humans can detect is the scent of rain.

That scent, geosmin, can be as faint as 400 parts per trillion and still be detected, which really speaks to just how ancient and well tuned our booger factory is.

So it’s not all horrible. I asked you earlier to think of the worst thing you’ve ever smelled, how about I leave you on an upbeat, what’s your favorite smell? What’s a smell that takes you to your happy place?

And maybe as you go about your day, take a minute from time to time to focus on your nose and the smells around you. You might find it gives you a more rounded out experience, besides, it just helps you live in the moment, which is always good.

 

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