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The Analytical Chemistry of the Smell of Parkinson’s


Over the last few years, there has been lots of media coverage of a remarkable lady called Joy Milne, who has an unusually acute sense of smell and is able to identify victims of Parkinson’s disease from a characteristic odour on their clothes. Currently, there is no clinical test for the disease and so Joy’s ability has excited a great deal of interest.

This has led to a recent BBC documentary about Joy, and the quest to find a way of detecting Parkinson’s early using the chemical signature of volatile organic compounds in sebum (the oily substance secreted from the skin). You can watch a brief trailer for the program here.

Much of the action in the documentary takes place in our laboratory, however, since the program is directed at the general public, it is understandably light on scientific detail.  This is a shame, as the story of Anatune’s involvement is an interesting one, especially if you are an Analytical Chemist!

Since Joy lives in Perth, her story has received the greatest coverage in Scotland and one of our customers, having seen a program on the topic, telephoned the BBC and said that he knew how the science could be taken forward (GC-MS with Olfactometry). He recommended that someone should contact Anatune, as we had a laboratory well equipped for the task.

Shortly afterwards, Anatune’s Phine Banks had a meeting with Professor Perdita Barran of the Manchester Institute of Biotechnology (MIB), it transpired that MIB were already working with Joy Milne, and Professor Barran asked if we could help with a short feasibility study to see if GC-MS-Olfactometry had anything to offer.

Anatune is a relatively small commercial organisation and we don’t have much uncommitted resource to play with.  However, in this case, we were almost certainly unique in having both the knowledge and the instrumentation to do what was required.  At times like this social responsibility counts and it’s a privilege to do something that can really make a difference.

Joy can identify a distinctive odour and it was easy to establish that the sebum of Parkinson’s sufferers contains a distinctive pattern of volatile organics.  If the biomarkers could be identified, then a practical instrumental test could be envisaged.

By using a high-resolution, accurate mass, GC-MS with an odour port, we could separate the volatile compounds from the sebum, split the column effluent between the MS and the odour port and present the separated components for Joy to smell.  We could then see if she could identify any regions of the chromatogram as having odours that Joy could associate with the smell of Parkinson’s disease. If Joy was successful in this, then the mass spectrometer would give us accurate mass data on the corresponding peaks, that would help identify the compounds responsible for the smell.

The Agilent GC/Q-TOF we were using also enabled us to export data files to Mass Profiler Pro (MPP), a chemometrics software package that would give the best chance of spotting differences between the different classes of samples.

MIB provided us overall guidance and also clothing samples from both Parkinson’s patients and control subjects. Since we were analysing for unknown compounds, we recommend the use of dynamic headspace sampling (GERSTEL MultiPurpose Sampler with DHS), since this provided us with the best recovery of volatiles from the fabric.

Joy had to travel to our lab in Cambridge from Perth in Scotland, and could only be in the lab for a total of two days.  In that time, we had to train Joy to work with the odour port for the first time and then get through a batch of samples, with a GC run time of 30 minutes.

Fortunately, Joy was trained by Dr Kathy Ridgway.  Kathy has great experience in the analysis of taints and odours and knows a great deal about olfactometry, and this got Joy off to the best possible start.

Camilla Liscio was responsible for method development and time constraints meant that she had to come up with an instrumental method quickly. This took her just a couple of days and resulted in a very robust method that worked perfectly when used on a batch of 60 real samples for the chemometrics study.

There are plenty of ways in which the project could have failed, but in the event, there were two valuable outcomes from this short, well planned, well executed project.

Firstly, Joy Milne was indeed able to identify peaks in the chromatogram as being components of the characteristic odour of Parkinson’s disease and this, together with the GC/Q-TOF, enabled tentatively identities to be assigned to the components that Joy had identified.

Secondly, the chemometrics study, showed that it is possible to clearly distinguish between control samples and different patient samples.

Together, both outcomes point to an interesting avenue of research in the search for a way of diagnosing Parkinson’s at an early stage.  This work will form part of a paper MIB will submit for publication in ‘The Lancet’.

I was hanging around the lab on the days this was happening and I remember being aware that I was witnessing something rare and special.  A moment when a team of remarkable people, with different affiliations and diverse talents work together to achieve a breakthrough of great value.

Rarer still, the moment was captured for posterity by an (unassuming) BBC cameraman.

Watch the full documentary, which is available on BBC iPlayer until the 18th January 2018.

 



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