How has one woman gained the incredible ability to smell Parkinson’s Disease? Photo credit: Rollz International via Unsplash
Throughout the history of science, many things have changed beyond recognition, but one thing that has stood the test of time is the scientific process itself: create a hypothesis and run experiments to test it. Nonetheless, sometimes, breakthroughs can come from the most unexpected of places and can overturn this traditional foundation of scientific discovery. One such unexpected scientific development came in the form of a nurse from Scotland called Joy Milne.
Joy Milne can smell the presence of Parkinson’s disease in patients. The realisation that she possesses this highly unusual skill came about during the course of her husband Les’ battle with Parkinson’s disease. Around 12 years before his diagnosis at age 45 in 1986, Joy noticed a change in her husband’s scent, in particular a musky smell that persisted over years. But it was not until she attended events with the Parkinson’s UK charity that she noted the same distinctive smell in other Parkinson’s patients.
What is Parkinson’s Disease (PD)?
Parkinson’s disease is a progressive neurodegenerative disease in which aggregates of the protein alpha-synuclein accumulate in the brain and cause the death of dopaminergic neurons. Dopamine is a crucial neurotransmitter which allows the transmission of electrical signals within the brain and therefore the loss of dopamine results in a wide range of motor and non-motor symptoms.
Joy’s incredible skill gained interest from many scientists…
Joy’s incredible skill gained interest from many scientists, and in 2012, Dr Tilo Kunath of Edinburgh University decided to investigate further. In order to test Joy’s ability to distinguish Parkinson’s patients from healthy patients, the research team enlisted 6 healthy volunteers and 6 Parkinson’s patients to take part in a trial. Each participant wore a t-shirt for a day and these t-shirts were then given to Joy, whereupon she had to decide which t-shirts belonged to Parkinson’s patients and which to the healthy controls. Her accuracy was astounding, she identified all 6 Parkinson’s patients in the group. But it is important to note that she did also “incorrectly” identify one healthy volunteer as being a Parkinson’s patient. This investigation then became even more astounding 8 months later, when the “incorrectly” identified participant contacted the research group having just been diagnosed with Parkinson’s. Joy had identified that individual as having Parkinson’s before the patient himself was even aware!
Joy had identified that individual as having Parkinson’s before the patient himself was even aware!
How can Joy ‘smell’ Parkinson’s?
Joy has a condition known as hereditary hyperosmia, which means that she was born with a heightened sense of smell. The condition causes a lower threshold for the detection of odour, which is the source of her ability to detect subtle changes in scent that others cannot.
Joy’s ability to detect the scent of Parkinson’s relies on an oily substance called sebum which is produced in the skin. The overproduction of this fluid (seborrhoea) is known to be one of the non-motor symptoms of Parkinson’s and it has been identified that the change in smell in Parkinson’s patients is occurring due to changes in the composition of sebum.
Specifically, altered levels of certain volatile substances within sebum, including perillic aldehyde and icosane, are believed to result in the scent identified by Joy. These changes in certain molecules in the sebum could be due to a number of factors. One example is that changes in the activity of the skin microbes affect the bacteria present on the skin surface and hence leads to changes in the metabolites present in the skin sebum. Another potential cause could be that the seborrhoea results in increased trapping and retention of these lipid-like metabolites on the skin surface.
When measuring the sebum metabolites, drug naïve PD and medicated PD were indistinguishable, but PD and non-PD were distinguishable. This suggests that the lipid profile identified is specific to PD and can subsequently be used to formulate a diagnostic biomarker test.
What are the implications of this research?
…diagnosis of this condition has an error rate of up to 30% even when conducted by the most experienced neurologists.
Parkinson’s is difficult to diagnose due to its plethora of motor and non-motor symptoms, complex presentation, and symptom overlap with other similar conditions. It has been shown that diagnosis of this condition has an error rate of up to 30% even when conducted by the most experienced neurologists. Having identified the molecules whose altered levels indicate Parkinson’s disease, it could now be possible to diagnose the disease by use of a skin swab—a technique currently under development by institutions such as the University of Manchester. This is a groundbreaking development for a huge number of reasons. Most crucially, this would give a definitive diagnosis for Parkinson’s. Currently diagnosis is given based on clinical symptoms, but there is no definite test, and the condition can only be confirmed post-mortem.
Secondly, as demonstrated by Joy’s ability to smell Parkinson’s before symptoms develop, it is clear that these volatile molecule changes occur years before onset of symptoms. This sebum detection would allow for much earlier diagnosis, which is currently a very rare occurrence in the field of neurodegenerative disease (renowned for late diagnosis). This will subsequently improve the lives of many patients as their treatment can be introduced to manage their condition much earlier. Finally, this test would allow a quick, non-invasive, and potentially inexpensive test for the disease in contrast to other potential tests—which require a sample of cerebrospinal fluid and hence are much more painful and invasive.
It is also crucial to consider the further implications of Joy’s unique talent, outside of Parkinson’s. Joy has also identified distinctive scents in many other conditions such as cancer, Alzheimer’s, and tuberculosis. Hence, the molecular changes in these conditions can also be explored for potential biomarker tests.
What is it like to live as a ‘super-smeller’?
Joy describes how living with a heightened sense of smell can also present challenges, as well as benefits. Aside from the everyday struggles of finding the scent of cleaning chemicals in the supermarket or other people’s perfumes overwhelming, there is a more sombre side to having such a skill. Joy discusses how, often, she can smell Parkinson’s on individuals she interacts with in public but is prohibited from telling them by the advice of medical ethicists.
Joy discusses how, often, she can smell Parkinson’s on individuals she interacts with in public but is prohibited from telling them by the advice of medical ethicists.
The future:
In the UK alone there are already over 150,000 people living with Parkinson’s disease and in an ageing society, that number is set to rise to around 172,000 by 2030. With Joy’s help the changes in sebum composition were isolated and now promising steps are being made in developing a clinical skin swab test, which will totally revolutionise the way we can manage the ever growing problem of Parkinson’s disease.
The story of Joy Milne and her incredible skill is the perfect example of how scientific developments can spring from the most unexpected and diverse sources, and how something as simple as a good sense of smell can revolutionise a field. This case serves as a reminder that sometimes, to break out of the mould is to change the world, and that scientific innovation cannot always be defined by a set of traditional procedures.
