Arjune Sen, Professor of Global Epilepsy, Founding Director of the Centre for Global Epilepsy and Director of the Oxford Martin Programme on Global Epilepsy, talks to Head of the Nuffield Department of Clinical Neurosciences Professor Kevin Talbot about his career so far, the challenges of working in global health and his next steps in epilepsy research on Purple Day.

Kevin: Let’s start with some simple questions about you Arjune, as a clinician, a professor of neurology. What drew you to medicine?

Arjune: What drew me to medicine, is that when I was younger - and this sounds a little contrived - my brother and I used to be very affected by asthma and we used to be quite ill. One year we spent more time in hospital than we did in school. So, we could see the benefits of medicine there, getting us through those things, and that sort of set us both on the trail into medicine. What perhaps is a more interesting story, is why I ended up in neurology...

Kevin: That’s my next question!

Arjune: I was a medical student here in Oxford. And as you know, the summers are super long, so you have to do something with your summer. I remember going to the library and thinking, ‘Well I'll just call up all of these journals and see if they've got a placement, because I've always had an interest in writing’. So I called up Nature, Scientific American, Science, New Scientist etc, and they all said ‘what are you talking about? We don't do internships for 18 year-olds for two and a half months’. But eventually someone asked, ‘what are you doing next year?’ So I said, ‘the second year, it’s all neuroscience.’ And they said, ‘well, there's this place called the Institute of Neurology in central London, why do you call them?’ So I called them and they eventually said there’s one person who might help, he’s called Simon Shorvon. I wrote to Simon, who set up the Epilepsy Research Group back in the 1970s/ 80s, and he said, ‘Yes, okay, we'll find something for you to do’. We had some family friends with a house that was between tenants, so I rented that house for £50 a week and then spent eight weeks that summer in London.

Kevin: Are you saying that contact with a senior figure was inspirational? Was that important to you in your career development?

Arjune: I think it's essential. Simon and I are still in touch. And I have to say that it wasn't that I did that and it was clear that I would then end up doing epilepsy. But it was clear when I came back at the start of second year that I wanted to do neurology.

Kevin: So how did you move into epilepsy?

Arjune: When I completed basic medical training, I wanted to then do a PhD in something that incorporated molecular neuroscience and clinical benefit, so that there would be lots of therapeutic options. Neurology has changed from the time that I was doing the PhD. But epilepsy already had a lot of therapeutic options available, so it had that aspect to it. With the Epilepsy Research Group at Queen Square I managed to create a project that had all of those elements in it. That then led to doing epilepsy clinics and the epilepsy interest seeded from there.

Kevin: You have been providing an epilepsy service for way more than a decade now in Oxford, seeing huge numbers of patients. Epilepsy is one of the commonest neurological conditions and yet it is under-resourced. At what moment in that journey did you start thinking more globally?

One of the things about global conditions - and all conditions to a degree are global - is that if you can make a small difference for a million people, that's probably better than making a larger difference for ten people.

Arjune: I often say that like my life feels like one long anecdote, so this is the anecdote that led to global health. And it speaks for the huge advantage of actually being in Oxford. In 2017 I received an email from someone who works in history here, Dr Sloan Mahone, who had been looking at psychiatric illness in Africa for a long time. The email basically said, ‘I've been looking at psychiatric illness and there's a lot of overlap with epilepsy. Psychological illness can be very stigmatising, epilepsy is as well. I looked up who does epilepsy in Oxford and your name came up. Do you want to meet?’ So we met. And Sloan’s brother, who’s a Catholic priest in America, had a connection to Zimbabwe because he would host Zimbabwean nuns there. Through those nuns he knew someone in Zimbabwe who had epilepsy. He then came over to Oxford and so he, Sloan and I all met together.

Kevin: This is a very Oxford kind of yarn isn’t it really? And, it's interesting because you realise that you might think someone sits down and plans out their career as a researcher, but serendipity always plays a part. Because Oxford has a global brand, this is the kind of thing that happens, you get interesting connections like this.

Arjune: I think Oxford in particular does global health very well. And the people who are really instrumental in global health in Oxford have a very different approach to many universities. It is a very utilitarian approach that you're not doing this for the grants or the publications, but you are doing a lot of it for the nonacademic impacts to make a step change difference on the ground.

Kevin: Eventually, as a scientist and a clinician, you become progressively uncomfortable when you start to realise that what you're doing is very focused on either one disease or certainly one disease played out within one population. In my own area of MND we have an international symposium every year and what is very striking is that two thirds of the world are not attending - there’s no one from China, India, or Africa - and that's a problem. That's especially a problem for genomics, since human migration in history is a key determinant of the genetic architecture of disease in specific populations. So I was thrilled when I saw you developing this area of interest, but obviously it comes with a whole set of challenges?

Arjune: Yes it does. Speaking to your point about representation and real engagement is crucial. One of the huge problems in epilepsy genetics, for example, is that 80-85% of people with epilepsy live in low resource settings. Almost all of the genetics is done in the UK, the US, and in Western Europe, so it's a very rarified cohort. And that may be part of the reason why epilepsy genetics hasn't yet delivered on its full potential. So yes, there are enormous challenges, but we have this approach where we start with colleagues, who become collaborators, but then we actually want people to become friends. And friends should be able to tell you when you're not doing something correctly and be able to tell you that with great equity. If you're going to make the change, you need to understand the problem in country, and allow the people in country to really shape what you do and have a very equitable conversation with you about that. I think that's done very, very well in Oxford.

Kevin: Obviously a lot of the things we're dealing with here are about macro economic or global political issues that are not going to be solved by individual researchers. How do you approach this and say ‘here are some practical targets and goals that you can achieve’, so you can feel you really do something to make an impact?

Arjune: Again, I think one of the things about global conditions - and all conditions to a degree are global - is that if you can make a small difference for a million people, that's probably better than making a larger difference for ten people. And you can make a big difference with actually just good coordination, good team infrastructure, good team players and colleagues that work and collaborate well. We've also partnered with other organizations. We work very closely with the World Health Organisation (WHO) and with the International League Against Epilepsy. So you can then leverage from all of that expertise. The WHO seems so remote, but actually their objectives are the same. They can be constrained in the same way in terms of budgets and so on and so forth. You have to work with them, and they're very keen to do that.

Representation and real engagement is crucial. One of the huge problems in epilepsy genetics, for example, is that 80-85% of people with epilepsy live in low resource settings

Kevin: When people think about global health, they think about infectious disease and broader public health issues. Neurology is usually pigeonholed as something to do with rare conditions. But epilepsy is the best example maybe of something which does not in any way obey borders or social conditions. Also, I haven’t given you the opportunity to say what you're actually going to do over the next few years - why don’t you tell us?

Arjune: I would say that that's exactly right. The WHO did say in 2019 that epilepsy is a public health imperative, and it is a public health imperative, not a neurology or even, just a general medicine imperative.

What we're trying to do with the next phase of work is in fact integrate a lot of things that I used to do. My PhD looked at molecular basis of neurodegeneration in epilepsy. Epilepsy is common anyway, but it gets more common after the age of 50 as it intersects with dementia and stroke. What we're going to be doing in a new project is actually branching out a little bit, to looking at epilepsy and how it intersects with stroke and how it intersects with Alzheimer’s disease, predominantly in African populations. We're going to do some large-scale studies to track people after stroke, to look at people with dementia and how likely they are to develop epilepsy, how we can collate all of those things together and then really try and use epilepsy, exactly as you said Kevin, as a segue into brain health more broadly. We hope that this can really make a difference and we are always very welcome to collaborations. If you are interested in our work please do get in touch.