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A woman who can smell Parkinson's is inspiring research into diagnosis (2020) (npr.org)
244 points by lvnfg on Feb 13, 2024 | hide | past | favorite | 75 comments



According this 2022 piece from the University of Manchester, it seems there have been some notable updates on the research.

By using mass spectrometry, a technique that measures the weight of molecules, they have found that there are distinctive Parkinson’s markers in sebum – an oily substance secreted from the skin.

This breakthrough has led them to develop a non-invasive swab test that can, in conjunction with the onset of early Parkinson’s symptoms, identify Parkinson’s disease with around a 95% accuracy. What’s even more astounding is the speed with which the test can return a result; around 3 minutes under lab conditions.

https://www.manchester.ac.uk/discover/news/a-nose-to-diagnos...


That's pretty awesome!

I was reading along and thinking to myself "why aren't we taking these tee-shirts to a mass spectrometer?!" I figured maybe mass spectroscopy wasn't quite the end all be all tool I was imagining.

Since she could also smell TB, Alzheimer's, cancer, and diabetes it seems like those should be (especially cancer since dogs can smell some of that too) the next high value targets to determine the relevant smells.


> But Joy's superpower is so unusual that researchers all over the world have started working with her and have discovered that she can identify several kinds of illnesses — tuberculosis, Alzheimer's disease, cancer and diabetes.

The story for diagnosing Parkinson’s sounded plausible until this sentence. With Parkinson’s, you could imagine that she had some sort of sensitivity in her smell to a certain biomarker.

Now with a plethora of vastly different diseases (even cancer is really a myriad of diseases grouped together), the suspicion of a confounder goes way up.

Perhaps instead of diagnosing Parkinson’s, she is actually sensing some signal that indicates inflammation or some other distress signal.

Or else people, prior to the manifestations of these diseases tend to make subtle, unconscious changes to their hygiene.


That is not how i read that sentence.

It sounds like you are assuming that every one of those illneses smell the same to her. That is that she can tell that someone has Parkinson’s or tuberculosis, or Alzheimer's, or cancer or diabetes, but she can’t tell which one they have.

The way i read it is that she can identify which one people have based on how they smell. Totaly made up example: tuberculosis smells peppery, while Alzheimer minty, and so on and so on. (Admittedly this also assumes that the journalist was sloppy about cancer. Probably she was only tested on specific types of cancers. It is very unlikely that all cancers would smell the same. But this is something which is very easy to get jumbled up by the journalist.)

Ultimately it doesn’t matter. If it verifies through a properly designed test protocol they will publish a paper about it. If not, they won’t. So if it matters we will hear about it.


If you read the report OP linked, it says they did a blind test where she was given shirts that had been worn by a variety of people some of who had Parkinsons for differing length of time, and some who had not, and she was able to get them all, including what they though was a false positive until that person came back months later to say they had developed it (similar to how she's been able to smell it on her husband before he was symptomatic).


Why should she not be able to detect some kinds of cancers? Some dogs can.

In the end, all this should not be so difficult. Take the head space, then do MS of a bunch of people with these diseases and the head space and MS of healthy people as a comparison. The delta gives the disease.


I'm not sure any of today's mass spectrometers yet can match human smell in sensitivity, at least to some scents with larger more complex molecules.


"with larger more complex molecules."

What are "larger, more complex, molecules"? Without trolling, I think scent cuts off at a MW 330 or something.


But it's not as good with distinguishing complex organic molecules one from another, no? I.e. between various proteins of a similar size.


Mass spectrometry gives results that are a bit like the ingredient lists for food. Tells you precious little about the actual product.


You don't smell proteins.


Mass specs can detect down to the ten thousands? IIRC or so molecules.


But I don't think they can do that at the same time as having trillions of some other uninteresting molecule like water in them.

It's basically a dynamic range problem.


Mass specs would have this problem, yes. That's why they are usually paired with chromatography of some sort (usually GC/MS or LC/MS). The GC or LC more or less reduce a mixture into components, which are fed into the mass spectrometer to analyze what those components are.


Yep the Ms that does this is tethered to chromatography first (sometimes even 2 or 3 different separation schemes in tandem)


I bet most (type 1) diabetics could smell other diabetics if they were trying. High blood sugar especially changes your body odor a ton. You sweat a lot more sugar for your skin bacteria to digest.

Not to discount the woman or the article, we should totally be researching this stuff


Anybody can learn pretty quick to smell diabetics. Low blood sugar leaves one's breath bitter and metallic, high blood sugar causes fruity, sweet breath. It's extremely obvious if you're at all close to them.


Wow, til.

Is there anything they can do about the breath? (ditto people on keto diet)


On a ketogenic[diet] ... your body uses fat instead of carbohydrates for energy. This shift causes a major spike in ketones, the source of acetone breath. ... Sweet-smelling breath may be a short-term side effect of this type of diet.[0]

[0] https://www.webmd.com/diabetes/acetone-breath-diabetes

So low blood sugar causes sweet breath.


Ketones are the "metallic" smell. I wouldn't describe it as sweet.


It's literally the homeless alcoholic smell.


They used to diagnose it by tasting urine.


I read the article as saying she can tell them apart, not merely sorting them into healthy/sick.

And I wouldn't be surprised if things like "cancer" were actually a confounder (I'm thinking along the lines of detecting the body's reaction rather than the tumor itself)--but it's still useful information. They've already used her information to find a albeit imperfect test for Parkinsons. What if you had a similar test for cancer? It would tell the doctor to start looking in fashions they would not do for the general population.


If the goal is early diagnosis and the separate detections aren't getting confounded, why does it matter what parallel chain of causation leads to Parkinson in the patient and a correlating reading in the nose or other test?

If no one in a normal state has the same mix of fear, anger and confusion and this leads to a microbial change around sweat glands, then that is a valid test of greater accuracy than many existing medical tests.


In the tests, she's presumably smelling people known to have the disease or not, and maybe she can pick up on that knowledge through subtle social cues.

Impressive in itself, but that's useless for diagnosing people who don't know they have a disease, which would be the medical breakthrough.


No presuming necessary. In the article, it describes a test involving smelling t-shirts in boxes.


This would be totally necessary for a robust conclusion-trust me, the social cues of having PD are not subtle ;)


She was able to detect a person who they thought was a false positive and turned out several months later did have Parkinson's. She detected her husbands before he had signs as well.

They also found the molecule she was smelling which was expressed with sebum. This isn't entirely unfounded as they already knew about dogs smelling cancers and other various diseases.


But what if, for example, she's just sensitive to the smell of fecal matter and these people tend to have loser poops? Now is she detecting parkinson or is she detecting IBS or someone that ate something spicy or drank milk while being lactose intolerant.

The issue is the one of the false positive and bayesian statistics. If she's detecting something that has a bunch of common causes then it's not really helpful to run a suite of tests to find an underlying problem on everyone that smells the same.

A fever can be a sign of cancer, but it's also a sign of the flu. Should we check everyone with a fever for cancer?


I'm not an expert, but a very quick search showed a meta analysis[1] which considers the false positives of using volatile biomarkers as a diagnosis. The original paper[2], of which Joy is co-author has a much smaller sample size, but also has a control group to measure false positives.

Again, I'm not an expert, but from personal experience I know that Parkinson's can be hard to diagnose definitively until there are serious symptoms. This test may be relatively poor but still be useful as a piece of evidence.

[1]: https://www.sciencedirect.com/science/article/abs/pii/S03038...

[2]: https://pubs.acs.org/doi/full/10.1021/acscentsci.8b00879


The science direct link isn't working for me.

But here's the problem as I see it. Parkinsons has an occurrence rate in the population of 0.1%. If there are conditions which cause the same smells as Parkinsons and they are more common in the population (1%, 5%, 10%) then this test all the sudden becomes very not useful because even at 1% occurrence rate in the population it's already 10x more likely that you have that condition rather than Parkinsons. That's the confounding problem. And a different comment here pointed out there are conditions that also seem to have exhibited the same smells.

Who knows, perhaps this is still worth it, but for an n=30 study, this is basically nothing to consider. The group size is simply way too small.

BTW, Medical media reporters really should have a "No reporting on studies with n < 500" rule. These sensational studies are always preliminary on really low population groups. I'd love to see the meta analysis to know how many studies it's lumped in and how big those are, though.


If it helps, the meta analysis is called: Volatile organic compounds analysis as promising biomarkers for Parkinson’s disease diagnosis: A systematic review and meta

Absolutely, it may not be useful as a screening test on the general population, but it may be useful as a piece of evidence for diagnosis alongside other pieces of evidence. Even for a test with a lot of false positives, the P(Parkinson's|positive) > P(Parkinson's|negative).

I generally agree that a lot of media doesn't accurately portray uncertainty in medical advancements, buts it's not as simple as having a sample size threshold. It really depends on the significance and the strength of the effect. Also, I want to hear about the exciting preliminary stuff, provided that it's properly caveated. There's just a lot of incentives to sensationalise.


That might be just an imprecise formulation by the journalist.

Smelling tuberculosis seems plausible to me, it is a disease of the lungs.

General cancer probably no, but I have repeatedly read comments by oncologists that sarcoma, specifically, has a distinct smell.


Makes me realise there is no real way to notate a smell.

How do people even get a handle on what a smell is, and how personal an experience is it.


This is a great observation! Indeed, most languages have very few words for smells.

- https://www.theatlantic.com/science/archive/2015/11/the-voca... - https://www.wired.com/2014/11/whats-up-with-that-smells-lang...


Aroma and smell training kits exist for people into wine, beer and so on: https://aromaster.com/


Yes, but is there a notation, like there is for music?

There's a whole pyramid scheme for perfumery, of course.


Notes are for frequency and there are marks for intensity, but you still have to write down what instrument is used.

In general in the vocabulary of smells you try first to understand the instrument (certain fruit, manure, sea, etc) and then the intensity of it.

I'm not very familiar how the intensity and variations are described but I presume that it is not as formal as in the case of music.

But it has no help if you can't smell it (the frequency is out of the hearing limit) or you can't recognize the instrument from the noise.


My sister worked in urology and could smell bladder cancer


Would it be so surprising if she just has an unusually adept sense of smell?


I think the surprising thing to a lot of people, even doctors, was the fact that a disease like Parkinson’s even had a “smell” in the first place. It sounds like now we understand a lot more about this as a result of these individuals ability to smell it!


Advanced lung cancer has a strong, very distinctive smell.


This seems consistent with research from the University of Alabama that demonstrates substantial differences between Parkinsonian gut microbiome and control subjects- very plausible (IMO) that this might result in smell differences.

The Alabama paper is open access and well worth reading if you’re interested in Parkinson’s

https://www.uab.edu/news/research/item/13280-new-study-puts-...


My grandfather had Parkinson's and always had a distinctive smell... when this finding first came out oh, maybe a decade ago, I knew exactly what they were talking about. Had another friend in adulthood - yup, same smell, and yes she was found to have Parkinson's. I don't have a particularly great nose, but it's a super distinctive smell.


Holy ^&*(!!!!

I've always wondered why my grandfather smelled a certain way. Your comment made me realise that this was probably a side effect of Parkinsons.


Could you describe the smell?


Eggplant overdrive. Woodsy musk. It’s not body odor smelling exactly, nor is it cologne-like. It just hangs on them. With Joanne (family friend) I remember how distinctive it was post-diagnosis and how it triggered the memory of my grandfather. She didn’t smell that way previously and so it was very noticeable that something had changed.


People with the common cold smell like dying flowers about 2-3 days before any symptoms appear.

It took me until my 30s to discover other people didn't know/realise/detect this. But since I've shared it with people as an interesting party trick type thing I've found many people who could smell onset of a cold.

It's not surprising to me that people can smell so much more, as all of our senses differ from person to person, the range, intensity, sensitivity.

What does surprise me is turning that into a useful application that could be used by others without the same sensory capabilities, that's neat.


How do you do this socially?

You're probably not sniffing random people to chat them up with "you'll have a cold in 3 days", right?


Not random people, no, but it's a useful signal for "that person is probably contagious right now so I'll give them a wide berth".

I have got into the habit of telling people close to me, and it gives them a chance not to avoid getting a cold, but to mitigate the impact by treating the symptoms before they've really emerged.


My father had Parkinsons. And was an engineer that used degreaser, i.e. trichloroethylene. And had 'the smell'. I think it's actually more common for people to detect this smell than perhaps is implied by these articles. I suppose the lady in question was just the first to notice and bring it to the attention of the medical community.

https://www.science.org/content/article/widely-used-chemical...


They appear to be training dogs to detect PD.

https://www.medrxiv.org/content/10.1101/2023.11.01.23296924v....


They didn't mention looking for other people with the same ability. Maybe other or many or most people can do it, if they know what to look for. If I smell something bad, I never consider that it might be a disease.


If a human can do it, a dog can too, since their noses are so much more sensitive than any human's. I can imagine dogs reliably sniffing out many diseases, then this becoming a standard lab assay, or at least a component thereof.


When you feel sick, go get a "Lab" test.


And then do we query results with What's pup, doc??


Also, assays cost less money than dogs which cost less money than human specialists.


It seems safe to assume she has an especially good nose -- I figure she's the olfactory version of a tetrachromat[1] or supertaster[2]. She also had a relatively rare coincidence where she married somebody before his Parkinson's presented, and she witnessed its progression. I would assume that she isn't globally unique in her ability, but finding others with it is a bit of a chicken-and-egg problem: how do you efficiently screen for this without knowing the precise compounds are to be targeted?

[1] https://en.wikipedia.org/wiki/Tetrachromacy

[2] https://en.wikipedia.org/wiki/Supertaster


> It seems safe to assume she has an especially good nose

I wouldn't assume anything. And it might not be related to sensitivity in general, but sensitivity to a particular chemical. (Also, is the perception of smell tied only to sensory aparatus in the nose?)

> finding others with it is a bit of a chicken-and-egg problem: how do you efficiently screen for this without knowing the precise compounds are to be targeted?

Expose them to people with Parkinson's; based on her experience, it seems like a quick test. In her case, they tested it with t-shirts worn by people with Parkinson's.


> Expose them to people with Parkinson's; based on her experience, it seems like a quick test. In her case, they tested it with t-shirts worn by people with Parkinson's.

I guess, a nice impact of this story is that people with Parkinson's are gonna see it and ask their friends, "do I have a smell?" If she's not rare, we'll find out.



Thanks! Macroexpanded:

A Woman Who Can Smell Parkinson's - https://news.ycombinator.com/item?id=21532937 - Nov 2019 (87 comments)

A woman who can smell Parkinson's disease - https://news.ycombinator.com/item?id=10434974 - Oct 2015 (114 comments)


This discovery (if true) is as improbable and wonderful as luis pasteur and bacteria or fleming and penicilin


I love this story. But every time I read it I wonder why we don't have electronic noses. Obviously dogs learn a lot by smelling. Why can't scientists have some. Am I too naive?


There's a lot of people working on similar things, I don't know much but it's pretty hard because the scope is large: https://en.wikipedia.org/wiki/Electronic_nose


The first thing that came to mind when reading the title was to call James Randi for a $1 million dollar paranormal challenge.


I know several nurses that can smell C diff colitis infections. They also use dogs to find C diff infections.


There’s an association between seborrheic dermatitis and Parkinson’s. Seborrheic dermatitis gives a fairly distinct odour. It will be interesting to see whether she can detect PD among patients without extensive seb. derm.


If a human can discern the scents so well can animals like dogs be trained to do the same and maybe much more?


It was 4 years ago, is there any more news to this story ?


Anecdote : i can totally smell when my testosterone level is high (under doping) because my feet's start emitting a (different than usual) disgusting smell. Definitely less useful than smelling Parkinson, but still kinda interesting !

Edit: might be related to all (or some) those different esters in sustanon


I would hate to have that ability.

The temptation to use it as a curse would be too great.

You spilled water on my shoe! sniff I curse your grandfather with dementia!

And when grandad got dementia they would think of me and hate me and wonder if evil magic was real.


Are you a bad person then? I looks like this woman was able to put her ability into noble use. Why couldn't you?


Yes, I am a terrible person because people can't seem to understand what might be construed as a "vague attempt at humor" as such.

Jesus, laugh a little.


> Jesus, laugh a little.

I did, but then I got worried about humanity.




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