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Scientists discover the chemicals behind the unique Parkinson’s smell (economist.com)
277 points by jkuria on Mar 30, 2019 | hide | past | web | favorite | 63 comments

This is exciting for two reasons. First, we could develop a measurable diagnosis based on this. Second, we can now search for the source of these chemicals and use them to better understand this illness, and that might lead to a cure.

I love when people use these small time superpowers for tho good of everyone.

Does anyone know how close are we at the moment from being able to say "we're getting X smell, so here are the genes producing X producers"? I know we can (most of the time) say, here are the sites producing a specific protein. But are we able to find sites for second and higher order results yet?

It's luck of the draw. We understand perhaps 15-20% of the genes/proteins in the human genome fairly well. We have fairly general notions of what the rest are but lack specific understanding. We also discover novel functions for genes/proteins we thought we knew well.

One way to discover function is to what's called a "genetic screen": Assuming one develops a robust way of measuring those chemicals; we fix that as the "phenotype" we're looking for. We can then disable each gene (with CRISPR, or RNAi, or chemical mutagenesis..) and see if the chemicals get produced (or stop getting produced); and then sift through those. This strategy is far from being exhausted; and people keep coming up with cool phenotypes to measure.

One idea I've been excited for some time is using ML to robustly annotate behaviors from mice by using wide-range microphones and 24/7 video as the phenotype; and use a combinatorial genetic screen to rigorously discover genetic contributors to behavior (aggression, mobility, curiosity, socializing behavior etc.) The ML algorithm can be initially trained by hand-annotated behaviors (annotated by post-docs etc.)

EDITED: She can also smell Alzheimer's, even before a person is about to develop it.


But her sensitivity to smell means she is unable to enter the cleaning products aisle in supermarkets. To most people, the plastic packaging has no odour; to Joy, it is so intense she starts to retch.

Is that even remotely true that people can't smell that aisle? I don't think I have an extraordinary sense of smell and I think of the smell of that aisle as "rank" or something like that.

I think I can smell that aisle, but it's from the detergent, not the plastic.

I think that distinction in the text was not the intended point. With 'the plastic' they mean the products, not the plastic packaging. Because of it was the packaging, made of common materials, entire supermarkets would be off limits.

And no, I don't think most people feel no smell in the cleaning aisle.

I guess they mean that most people can smell freshly sprayed cleaning products but think the products don't smell of much when still in the bottles.

The aisle has a faintly bleachy/detergenty smell to me, but not usually oppressive, more just pleasantly clean, I suppose.

But I have noticed my hands/sweat smell different when I have a cold, and sometimes a day or two before I feel ill. I usually only get close enough to notice it on my own body, but I have a couple of times entered someone else's room/office and smelt the same smell before hearing confirmation from their croaky voice, snuffling, or them just telling me they have a cold.

(And no, it's not the smell of cough sweets or lemon/honey-based cold remedies, but it might be partly the smell of damp tissues and stale phlegm and other such nice things. Subtle but sickly sweet.)

Obviously this is neither particularly useful nor a superpower, but I'm glad research is going on into more useful applications of similar phenomena.

It's interesting that she's not becoming de-sensitized to all the smells. I think we all have the capability to discriminate between many colors, smells, sounds, etc, but most people normally would de-sensitize and filter out the noise over time.

Yeah, I can't really smell it. I have to get very close to the products. But, I have a bad sense of smell.

I always sort of hold my breath and hurry past everything in that aisle.

The diseases are already there, but can't be detected by standard tests and/or have no visible symptoms yet.

Much better read, definitely recommend over the other article

This is the same Joy.

EDIT: oops, missed the Alzheimer’s reference. Nonetheless, the title appears wrong, unless her husband had both Parkinson’s and Alzheimer’s.


I suspect that’s just a mistake in the headline. The article doesn’t say anything about Alzheimer’s.

It does mention that she can smell cancer and tuberculosis, however.

She says Alzheimer’s smells like “vanilla, with a dark side” while tuberculosis smells “harsh”.

November 15, 2018 publication:

Discovery of volatile biomarkers of Parkinsons disease from sebum

https://doi.org/10.1101/469726 (free full-text PDF link on site)

From the abstract:

We have serendipitously identified a hyperosmic individual, a Super Smeller that can detect Parkinson's Disease(PD) by odor alone, and our early pilot studies have indicated that the odor was present in the sebum from the skin of PD subjects.

Thanks for the actual paper. No authentic standards were used to validate the assignments. These are being identified by low-resolution single-quad mass alone. The chances that these compounds, if they exist, are correctly identified is very small. For point of comparison, they also found artemisinic acid, an antimalarial drug precursor that is not typically administered in the UK -- and not as the precursor.

> perillic aldehyde, hippuric acid, eicosane and octadecanal

It's tantalizing to see the names fixed in print. To make a software dev analogy, it's like finally reproducing a heisenbug and knowing it's very likely you'll find the root cause soon.

What is a heisenbug?

It’s a riff on Heisenberg’s uncertainty principle — a bug that changes behaviour when you try to observe it, typically the sort of bug that you can’t reproduce under debug conditions. Often they’re race conditions or other timing-sensitive bugs, and the debugger changes timings enough that the bug doesn’t trigger.

I fondly remember a bug that only appeared when print statements were removed. The i/o of the system out was just long enough for some buffer to clear, making the app work. That was very annoying.

earlier today I had a problem with Xcode always opening the wrong file, a README

Turns out I am not the only one: https://stackoverflow.com/questions/53132398/xcode-10-1-open...

half a year old at least, as long as the first file is a readme it will open that one instead of the actually clicked file in a new window no matter what. Only fix is to remove the file

but if Xcode is instead set to open as new tab instead of new window, instead everything works just fine.

This is a very common one with concurrent code. I've seen many cases where something works most of the time until a log statement is removed.

> It’s a riff on Heisenberg’s uncertainty principle — a bug that changes behaviour when you try to observe it...

As an aside, the Heisenbug is erroneously named because the phenomenon being described is actually the observer effect ( https://en.wikipedia.org/wiki/Observer_effect_(physics) ). The uncertainty principle refers to something entirely different.

A bug that this one customer keeps reporting and no developer in the team can replicate, until it happens one day and it happens constantly, until you try to debug it, because then the bug will never happen again. ️


To me, it's a bug which disappears when a debugger is attached... by observing it you're modifying the behaviour. I see the other comment here, I'd not heard of that explanation..

It doesn't have to involve a debugger. I had a sporadic bug once that couldn't be reproduced, which turned out to only appear when one performed an action quickly. When debugging, one tends to perform the steps to reproduce carefully, and hence slowly...

First epilepsy (dogs), now Parkinson's. Leads me (retired neurosurgical anesthesiologist) to wonder if ALL pathology has an olfactory component that, with sufficient sensitivity of instrumentation, can be detected. Perhaps we won't require a "Star Trek"-type imaging device: just stand still and let the mass spectrometer do its thing.

I'd expect you'd still need the imaging devices for many things. An olfactory test might tell you that there is a tumor in there somewhere, for example, but to treat it you probably need precise location, size, and shape.

Years ago I saw a case study go by. Despite negative tests, an elderly wife was sure something was wrong with her husband. He turned out to have a lung abscess. I no longer recall details, but the hypothesis was she could smell the rot on his breath in bed.

Would you find that with a low dose CT scan?

See, for example, Maple syrup urine disease: https://en.wikipedia.org/wiki/Maple_syrup_urine_disease

Many early medical texts routinely used smell in diagnosis.

The right question to ask is "why wouldn't it".

The only way this wouldn't work is if there is a smell your body makes that never leaves your body. But otherwise it seems pretty reasonable that you could read offgassing as a way of detecting underlying effects.

I'm right there with you though, I bet the tricorder has a nose not a eye.

Wow so 2 whole things are able to be identified by volatile chemicals and this leads to all?!

And I wonder how people like Holmes are able to survive for >10 years. We can deliver nicotine via patch, so obviously all drugs should be delivered that way. We can measure glucose from a drop of blood so obviously it follows that all blood tests run that way.

Where is the evidence that even a small fraction of the most common diseases have such a characteristic?

Curiosity is the entire point of this site. Cross-examining someone on fraud charges is way over the top! Could you please review https://news.ycombinator.com/newsguidelines.html and stick to the rules when posting to HN? These include:

"Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith."

This is needlessly antagonistic. Though all pathology may be a stretch, the evidence for these two was only recently convered and all new fields start somewhere. Indeed, this line of thought brought us Theranos, but also brought us so much else.

He was just speculating. Also, dogs can smell cancer in humans.

> Also, dogs can smell cancer in humans

...and the impending onset of dangerously low blood sugar, well before the person realizes that something is wrong. There are diabetes assist dogs available for this [1].

[1] https://www.mayoclinic.org/diseases-conditions/diabetes/expe...

Dogs have been shown to detect certain cancers at later stages (which greatly limits use as a screener.. not to mention how does the sensitivity/specificity compare to state of the art). This is not surprising since as cancers advance they cause gross biochemical changes.

The further issue diagnosing cancer/no cancer or epilepsy/no is an easy problem. But train a dog/machine on 1000 or more rare diseases. Now selectivity is an actual issue. And unless you manage to overcome that, how is all this scent stuff clinically useful?

So the original "sniffer dog" study (The Lancet 8640)[0] pretty much covers a dog sniffing out a melanoma BEFORE it got to a later stage, and saved a woman's life.

I also dont understand how training a machine would have selectivity issues. Machines dont "get trained" on one thing.

0: https://www.sciencedirect.com/science/article/pii/S014067368...

That is not a study. That is a case report written as a letter to the editor. That meets no scientific rigor at all and no generalizable conclusions can be drawn from it, it provides an anecdote for further research. It also doesn’t suggest that sniff tests would fare better compared to any other screening system for melanoma.

"We know Earth revolves around the Sun, so obviously all planets revolve around the sun? Ridiculous!"

Last count I saw was that we know of 4016 planets, and only 8 revolve around the sun, so...

In future job interviews, you will be surreptitiously sniffed by electronic devices that estimate whether you might be a liability to the health insurance group plan or a frequent absentee who uses up all the paid sick days.

To get around the paywall; https://outline.com/8M4RL7

Parkinson's, Alzeimers and other neurological disorders will be cured in the future. What bothers me is that people from past and present will continue to suffer until then. We need to support scientists more.

Within the next 150 years, we’ll probably turn most diseases into something treatable as we slowly acquire knowledge.

Of course, imagine if we started rapidly acquiring knowledge, I’d be saying within 75 years.

Your choice.

I wonder if "science" generally suffers the same plight that is discussed in The Mythical Man Month. I suspect it does.

If you know what you need to do you can only split the tasks to a certain granularity without losses. But if you don't know what you need to do, then you can have large number of independent teams trying different things with no penalty.

So, you think science one big problem that we’re trying to solve?

Personally, I’d say it’s more like millions of smaller problems.

It's not clear that doubling the research funding from the NIH results in twice as much qualitative output. That's all I mean.

Similar to yesterday's news: "Dogs demonstrate the existence of an epileptic seizure odour in humans" https://news.ycombinator.com/item?id=19521835

Smell represents an entirely new approach to medical diagnosis and in the next decade god knows how many tests we'd be able to develop using this approach. I am truly excited!

> Smell represents an entirely new approach to medical diagnosis

It's not new at all. Traditional Chinese medicine has used it for a long time, among others.

Any examples of TCM / smell patterns?

It calls for some company to create an efficient electronic nose. Build a database of disease markers, save lives, and say farewell to the health condition privacy.

It would be interesting to see whether this smell is caused by the same thing that results in Parkinson's or just associated with it.

Maybe smell detection will bring us the future Theranos imagined.

Odd... The page doesn't load for me and I end up at a Facebook error page...

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