Where are they now? Prof John McGrath
Prof John McGrath – A Past Recipient of the Lions Medical Research Fellowship.
Lions members know that important projects often take a long time. Medical research requires continued investment over many decades – this is especially the case for severe mental disorders like schizophrenia. This poorly understood group of brain disorders affects about one in a hundred individuals. Symptoms include hearing voices and having strange beliefs (i.e. delusions). Affected individuals have poor concentration and a lack of drive. The onset of the disorder is often in the prime of life – in the second and third decade of life. Despite our best efforts at treatment, a sizeable subgroup of those with schizophrenia have a persistent or intermittent pattern of symptoms that can extend over many decades. Just as disorders like diabetes and osteoarthritis are chronic disorders of adulthood, mental disorders are the chronic disorders of the young.
I was a proud recipient of a grant from the Lions Kidney and Medical Research Foundation in 1995. At this time, much of our research was linked with Professor Sue Pond, at the Princess Alexandra Hospital, in labs supported by the Lions Medical Research Foundation. We have very fond memories of these early days. I recall talking to participants in the Miss Personality Quests about our research, sharing the platform with the now legendary Ian Frazer.
Our first grant was in collaboration with someone who would be well known to Lions members across Australia – Professor Alan Mackay-Sim – the Australian of the Year in 2017. Alan and I were interested in the hypothesis that schizophrenia was a disorder of early brain development – something may have gone wrong in how the brain was wired up during development (e.g. before birth), that then increased the risk of later schizophrenia. However, this research question is hard to assess in adults. However, Alan’s team had recently started research related to the special nervous tissue that is inside our nose and that is used for the sense of smell. First in animals, and then in people with mental disorders, we explored this research over 10-15 years. The seed grant from Lions allowed us to prepare pilot data for an application to the Australian National Health and Medical Research Council (NHMRC). Subsequently, Alan’s team made landmark discoveries about how this tissue might help repair spinal trauma. This is a good example of how investments in research may have unexpected ‘by catch’. A grant related to unravelling the cause of schizophrenia then led to a possible treatment for spinal trauma.
Working with Alan we became world leaders in culture neurons from nasal biopsies and then using this tissue to explore differences between subjects with schizophrenia versus healthy controls. We also started to explore a new hypothesis related to the causes of schizophrenia. It had been known for nearly 100 years that people born in winter and spring had a slightly increased risk of later developing schizophrenia. The evidence suggested that some early life event that fluctuated across the seasons may be a causal risk factor for schizophrenia. We examined possible infectious agents (e.g. influenza) but also started a program of research related to vitamin D – the sunshine hormone. Again, in collaboration with Alan Mackay-Sim, and with Dr Darryl Eyles, we developed an animal model to explore this innovative research question. After 20 years of research, we now have built a solid body of research based on animal studies that proved that low prenatal vitamin D does alter brain development in rodents. In addition, we have shown in Danish studies that new born babies with low vitamin D have an increased risk of later developing schizophrenia. This is a tantalizing hypothesis, but it suggests that a simple, safe intervention (i.e. the use of vitamin D supplements) may reduce the risk of schizophrenia. Just as folate supplements can reduce the risk of spina bifida, we wonder if vitamin D supplements could reduce mental disorders.
20 years later, we are still working on this hypothesis in collaboration with colleagues in Denmark, Sweden, the Netherlands and the US. More work needs to be done, but we still believe that this risk factor warrants further study. Our work has been supported by the NHMRC and funding agencies from the US and Denmark. This is an example of how small investments from agencies like the Lions Medical Research Foundation can leverage discoveries for many decades.
My family has a long history with Lions. My parents, Brian and Betty McGrath, have held high office in local Lions Districts. In 1971 Lions supported me as an exchange student to New Zealand. The early grant in 1995 was a key stepping stone in my career. Over the decade I am proud to have trained many of the researchers of the future and contributed to a better understanding of schizophrenia. I have a special place in my heart for Lions – I would like to express my heartfelt appreciate for the support that Lions provides to the local research community.