Happy to Investigate Malaria Parasite Biology

The ISGlobal Malaria Epigenetics Lab team (including members who left the team recently). From left to right, Núria Rovira Graells, Harvie Portugaliza, Anastasia Pickford, Oriol Llorà Batlle, Elisabet Tintó Font, Carla Sánchez Guirado, Alfred Cortés Closas, Cristina Bancells Bau, Lucas Michel Todó and Sofía Mira Martínez. Illustration: Lara Sànchez Guirado (larades86@gmail.com).

About nineteen years ago I finished a PhD on single-stranded DNA binding proteins of the fruit fly Drosophila melanogaster and asked myself: what do I want to do in the future? I had deeply enjoyed all aspects of my life as a PhD student, including my research project, but I felt I needed some changes.

My decision was to continue working in basic research (...): I wanted to move from deeply studied model organisms into investigating organisms on which there were still big things to be discovered; and I wanted to perform research that could potentially have an impact on people’s wellbeing

My decision was to continue working in basic research, but with two main differences from what I had done so far: first, I wanted to move from deeply studied model organisms into investigating organisms on which there were still big things to be discovered; second, I wanted to perform research that could potentially have an impact on people’s wellbeing in a relatively short term, while still being hypothesis-driven basic research rather than applied research.

When I had an offer to start working as a malaria investigator, I didn’t need to think twice before accepting it: this was just what I wanted to do. Some fundamental aspects of malaria parasites still remained unknown, and this disease produces enormous human suffering in low income countries. The salary would be in a foreign currency for which I did not even bother checking the exchange rate before accepting the offer (money is an unlikely driving force for a basic scientist).

When I had an offer to start working as a malaria investigator, I didn’t need to think twice before accepting it: this was just what I wanted to do

To become a molecular malariologist, I first worked for four years in a malaria endemic region of Papua New Guinea and then for two years and a half in the UK, in addition to shorter stays in Switzerland and Australia. After this, I felt I could start calling myself a malariologist and I started a malaria research team in Barcelona.

Now I am at a point of life at which I often look back into the key decisions of my life (call it midlife crisis if you want, but midlife balance may be more appropriate). I don’t ask myself whether or not I took the right decision because the answer would always be yes: if I did what I gut-felt that I had to do, this was a correct decision at that moment.

However, I do ask myself if the expectations were fulfilled. As for the idea of moving into a research field in which big things remained to be discovered, my answer is a big yes: there were fundamental questions in the biology of malaria parasites that waited to be discovered, and indeed in these almost twenty years the malaria research community has provided answers to some of them. I am proud of having contributed to providing some of these answers, together with my team. Other big questions are still unresolved, warranting excitement for the coming years.

When I ask myself about my second motivation to move into malaria research, the answer is less straightforward. Have my efforts really contributed to ameliorating human suffering? To be fair, here I have to answer myself a no or a not yet. Perhaps twenty years ago I didn’t appreciate entirely the temporal scale at which research progresses and potentially translates into practical applications, even when studying a human pathogen rather than a model organism. Starting to unravel a new mechanism by which malaria parasites adapt to fluctuations in their environment, or understanding how they convert from disease-producing forms into transmission forms are formidable tasks that take many years. The eventual application of this knowledge to develop new strategies to fight the disease will still take many more years.

Perhaps twenty years ago I didn’t appreciate entirely the temporal scale at which research progresses and potentially translates into practical applications

It is sometimes tempting to think that just by screening millions of chemical compounds to develop new drugs, or applying brute force approaches to combat the disease (e.g. mass drug administration), we may be able to defeat malaria, without needing to put efforts into understanding parasite biology. However, operational research is showing us again and again that defeating malaria in some regions of Africa is an almost impossible task with the tools currently available; empirical test and error approaches have failed to deliver a highly efficacious antimalarial vaccine, which would be a game-changer in the fight against the disease; and the development of new drugs not susceptible to drug resistance is unlikely to succeed unless it is accompanied by a deep mechanistic understanding.

While product-oriented or empirical approaches clearly need to continue being pursued, these examples tell us that defeating a complex pathogen such as malaria parasites requires more than this, as they are a formidable enemy equipped with multiple mechanisms to survive in spite of our efforts to eliminate it.

I still have a deeply rooted belief that the research from our team, together with findings from many other teams around the world, has the potential to have a major impact on the production of better tools or strategies to combat malaria. When, how, or where this will happen is completely unpredictable, as unpredictability is at the very heart of basic research. Who could have predicted that research on electrons could ever deliver such a key tool for medicine as the X-ray machine? So while I reckon that my efforts have not had an impact on human health yet, I feel we are on a right track.

I still have a deeply rooted belief that the research from our team (...) has the potential to have a major impact on the production of better tools or strategies to combat malaria

Of course there are also drawbacks when making balance of almost twenty years as a malaria researcher, but I am afraid this would require another full post.