Mastering the Methods of the Chosen Research Area Is Essential to Make Any Progress


Professor John Jefferys’ expertise has been in the cellular physiology of neurons of the hippocampus and cortex, their organisation into functional networks, and especially how they can malfunction in chronic epilepsy. His research has led to insights into: network mechanisms of acute seizures and chronic epileptic foci, prion diseases, network mechanisms of cortical oscillations, and sensitivities of brain tissue to electric fields.

He joined the epilepsy research team of the Second Faculty of Medicine, Charles University, in 2019, after teaching at the University of Birmingham and the University of Oxford. Here he has created an experimental-clinical group that focuses on research on sudden unexpected death due to epilepsy.

Photograph: Adam Hříbal (2. LF)

You are an expert in brain research. What was the reason for you to choose and dedicate your career to this scientific field?

As a teenager I was fascinated about how brains work. I still am. Now I would say it differently: my central interest is on how the dynamics of brain activity leads to behaviours and to brain diseases, most notably epilepsy – wordier, more realistic, but still fundamentally the same motivation.

At the Second Faculty of Medicine, you focus on epilepsy research. The level of our knowledge of this disease has changed dramatically over the last decades. What do you consider to be the most significant discovery in epileptology?

In such a complex disease I don’t think there can be one “most significant discovery”. Can I offer two answers?

From the point of view of most patients, improvements in anti-seizure drugs are important, particularly in reducing undesirable side effects. Anti-seizure drugs with fundamentally new mechanisms are rather rare, but more often small changes in chemical structures can reduce adverse side effects while retaining or enhancing control of seizures. This is not radical, but it makes for considerable improvements in quality of life.

From my point of view as a physiologist, I think a really significant discovery is on our deeper understanding of electrical activities associated with epilepsy. In focal epilepsies it turns out that the brain cells responsible for driving seizures occupy a much smaller area than that where seizures are detected by traditional “EEG” or brain wave recording methods. The traditional EEG is generated by mechanisms that can be a very long way from the abnormally active brain cells that drive them. Patients who are not adequately controlled by anti-seizure drugs can be successfully treated by surgical removal of the part of the brain responsible for the seizures, but it is crucial that that part of the brain is located precisely. Prof Jiruška and I have worked together on electrical markers for “epileptogenic cortex” over many years.

What is your view of the future of epilepsy research and its treatment? Would you like to offer your predictions?

Here are two.

Developing drugs that can prevent or cure epilepsy. Current drugs act to suppress seizures, which are the defining symptoms of epilepsy. They do not alter the course of the underlying disease. Where a triggering event can be identified (like severe head injury, or some infectious diseases) it would be great to develop a treatment that could prevent the development of epilepsy months or years later. That has proved a tough challenge, but I remain hopeful.

Electrical stimulation could provide a very different class of treatment to drugs. It avoids the problem of drug resistance and can be targeted at the specific sites of seizure origin and/or at the times of seizure onset. Avoiding stimulation during the long periods between seizures reduces the risk of unintended impacts on brain function. At the moment several kinds of electrical stimulation exist that produce measurable reductions in seizure frequency, but more research is needed to improve their effectiveness to a degree that really improves quality of life.

You are a highly regarded scientist. What is your advice to those medical students who consider the path of science and research. What, in your opinion, is the key to success?

I think they should start by identifying a question, or at least a topic, that they find interesting and important. Then they need to find a good mentor and supervisor. Mastering the methods of their chosen research area is essential to make any progress. That involves attention to detail, rigor and in some cases manual dexterity. They also will need the ability to take a broader view, both to interpret their results, and to formulate new theories to frame their next experiments, and eventually their proposals for research funding. Scientific research needs careful, detailed, and highly-disciplined work to critically test theories, but that needs to be combined with the ability to switch to a creative mindset which is how you produce new theories. You also need a flexible mind to recognise the implications of unexpected results (which can be very productive – surprise results led to most of my more highly cited papers). This creative phase of the scientific cycle needs time and space for reflection, which can be in short supply in modern academic life.

A separate issue, that maybe applies more to basic science students, is to learn in detail about the impact of their chosen disease on the people affected. My current research on SUDEP (sudden death in epilepsy) was prompted by talking with fund-raisers for an epilepsy research charity, Epilepsy Research UK. It turned out that all those fund-raisers were bereaved family members of people who had died of SUDEP, and it seemed to me that we had a duty to understand SUDEP and to identify ways to reduce risk, and to prevent the final lethal stage. I should probably add that personally this meant moving from a total focus on brain circuits to thinking of the body as an integrated system, which is a personal return to a fundamentally physiological approach.

What qualities of a scientist do you consider to be the most essential?

Curiosity, integrity, and commitment to the primacy of experimental evidence. In science we must accept that our theories may turn out to be wrong, but even when that happens it should still advance the field.

You have been a member of our faculty since 2019. How do you like your current tenure, perhaps compared to your previous engagements in the UK?

I arrived not long after the Physiology department started developing epilepsy research as one of its major research themes. I believe it now is a centre of excellence in the field, particularly within the context of EpiReC Prague. I greatly enjoy working surrounded by mostly young, and always enthusiastic and very capable researchers who share my interest in epilepsy. Working with the members of the SUDEP group is a special pleasure and privilege.

The big change from the UK that comes from my working here is that I can focus almost exclusively on research, which is the aspect of academic life I enjoy the most.  My experience may well be too selective, but my impression is that Charles University (and maybe the whole Czech system) has not become as “managerial” as universities in the UK. In my opinion too restrictive top-down management damages academic initiative, and that initiative provides the basis for excellence in both teaching and research.

Created: 9. 11. 2022 / Modified: 29. 6. 2023 / Mgr. Petr Andreas, Ph.D.