Sniffing out disease

Someone with a truly amazing sense of smell is retired nurse Joy Milne. Incredibly, Joy can sniff out Parkinson's disease. Katie Haylor spoke to Joy, and mass spetrometry expert Perdita Barran from the University of Manchester, to find out more...

Joy - My husband was 31, 32 and I began to smell a change in his basic male musk smell became quite different, it changed. I put it down to the fact he was a consultant anaesthetist in an enclosed environment, sweating and that and really he wasn't pleased about me going on about it so I was quiet and we just put up with it.

Katie - But now, University of Manchester scientist Perdita Barran and her colleagues have, using Joy's impressive nose, been able to identify a handful of biomarkers for Parkinson's disease which currently has no conclusive diagnostic test. First off, Perdita told me how her and Joy met.

Perdita - Well, Joy found us as she approached colleague of mine, Tila Kunar, at the University of Edinburgh, who's a basic scientists like me working on Parkinson's disease, and she told him that he should find out why people have Parkinson's disease smell differently. I have to say, we didn't really believe her at first. We thought that perhaps it was just an associated sense with the disorder movement of people with Parkinson's but we thought we better prove it, and we thought we'd better divorce the smell from the person and the motor symptoms. So we devised a test which got people who had Parkinson's and people who didn't to wear T-shirts and then the T-shirts were cut up and put into bags for Joy to smell way away from any patient. And, well Joy, you can say, she was right!

Joy - And yes, as a parting gesture I said you've cut them in half and I don't know which witch is which, will I put them back together again to the person? And I did.

Katie - Joy smelled 12 T-shirts: six were worn by people with Parkinson's and six were controls. And she got them all correct. What's more, she identified one control subject as having Parkinson's. This was labelled as a false positive but they actually got in touch later to say they'd received a diagnosis. So I asked Joy, what exactly does Parkinson's smell like?

Joy - It is a quite deep animal musk and it has quite a rancid smell in it when it's a little bit stronger.

Katie - Lovely. So having controlled for variables like sex or diet that could be separating the T-shirt wearers, and confirming that Joy really could smell Parkinson's, Perdita and the team took a closer look at where on the T-shirts these odours were actually coming from.

Perdita - So you might think it will be under the armpits; that's where we think people smell, but it wasn't. It was in the middle of the back underneath the hairline, and that's a region of our bodies where we excrete a lot of the oily substance called sebum. That's the place where when you're a teenager you get spots - face as well. So we then had to develop a test that could be applied to patients that would extract sebum from them and we would then waive volatile molecules from the sebum - that means the ones that go through the air - and so that's what we did.

Katie - Once Joy's sense of smell told them which molecules to look for the team were then able to put the sebum in a machine that essentially weighs different molecules, called a mass spectrometer, in order to define what molecules are there and in what abundance.

Perdita - We've been able to pinpoint four compounds, which are three of them upregulated and one of them is actually down regulated in people who have Parkinson's, and those molecules have been given back to Joy and she smells them and she smells the smell. So we now have four biomarkers that tell us whether someone has Parkinson's or not just from swabbing their skin.

Katie - The four markers in question are eicosine, hippuric acid, octadecanal and perillic aldehyde - quite a mouthful. These compounds are normally found in sebum but it's the quantities that could, the team hopes, mean these could form a diagnostic tool for Parkinson's disease. But could looking for the quantities of these compounds in sebum reveal anything about the severity of someone's condition?

Perdita - That's a really good question and I can't answer that now. There are definitely some patients who have a much stronger smell and much stronger signal than others. Definitely people at late stage Parkinson's the smell is stronger and the signal is stronger and we've really focused on people who are called "drug naïve". That means that they haven't yet been put onto medication for Parkinson's disease because we want to see how early we can diagnose it and actually those cohort have a very strong smell as well. So we think we will be able to go even earlier and that's where our research is taken us now, to see if we can diagnose people before the motor symptoms.

Katie - We don't currently have a cure for Parkinson's disease, but if we can pick up on it earlier the hope is that we might be able to make interventions to prevent the condition from spreading. But why should Parkinson's disease smell at all?

Perdita——我们真的不知道答案。What we do know is that people who have Parkinson's do produce more sebum, and sebum is a nice oily environment which bacteria would certainly like to eat and colonise on. So it may well be that this is a signature based on the change in the microflora on the skin of people with Parkinson's, but why that smells I don't know.

Katie - And now to Joy. What's it actually like to have this ability?

Joy - It can be a curse but it in this instance it's a superb gift I’ve been given. And I feel that I really do have to use it because having lived with Parkinson's for so long I think now is the time. We have the science, we have the research, and with those together we could diagnose Parkinson's earlier and then look at the inflammatory process far before the motor symptoms come in. And I think that's so important.