(12/17/20) From January 2018 to January 2020, Dr. Mridul Agrawal conducted a life sciences research project in the field of hematology and oncology as a DFG fellow at the Dana-Farber Cancer Institute, Harvard Medical School. He spoke to the DFG Office North America about the outstanding climate of innovation in Boston, the underlying conditions for successful research in the group led by Prof. Benjamin L. Ebert, planning versus coincidence, music and art – and his skill level at table tennis.

Through its research fellowship program, the DFG supports laying the foundation for academic careers by funding an independent research project abroad and, since 2019, in Germany too. A large proportion of these fellowships are awarded in the USA and, to a lesser extent, in Canada, reflecting the belief – still prevalent in the natural sciences, and life sciences in particular – that for a career in research you have to have “been once in America.”

Today we would like to give you an impression of who is behind DFG funding number AG 252.

DFG: Mr. Agrawal, many thanks for taking the time to talk to us. Your curriculum vitae is packed full of fascinating connections and awards, as well as a whole array of career and education stages. Hopefully we’ll be able to explore some of these. On paper, it all looks carefully planned and executed. Were there any career moves that were less a result of your own planning?

Mridul Agrawal (AG): First of all, many thanks to the DFG not only for enabling me to do research in the US in the first place but also for giving me this opportunity to reflect and talk about it in a pleasant format. When all this is condensed on paper, it looks much more like planning or even strategy than is actually the case. I don’t really think biographies can be planned or predicted: up to now I've simply had the privilege of being able to follow my interests – and frequently these have led me down paths whose twists and turns I wouldn’t necessarily have been able to predict. I’ve also been lucky enough to find companions and mentors who have inspired me and given me confidence, support and freedom, encouraging me to carry on pursuing my own path. This initial assistance in a number of very different situations has certainly helped me find the courage at other points in my life to make decisions that may seem unconventional at first sight, such as studying health economics parallel to medicine or – as was recently the case – founding a start-up in the field of digital health. My Indian roots certainly have some part to play in my being able to approach the new and unknown with a certain degree of composure, while my German background helps me remain consistent in sticking to a path once chosen.

DFG: You completed your medical studies at the Mannheim Medical Faculty of the University of Heidelberg, received your doctorate with an award-winning thesis in the field of hematology and oncology, and then went on to do a Master of Science in Health Economics (M.Sc.) dealing with the distribution of responsibilities within the German health system. How did the move come about from this to translational research, and why oncology in particular?

AG: Actually, that emerged from my doctoral thesis. I was working in the field of leukemia research when I was doing my doctorate. Due to a health event in my family, I had to postpone my first state examination at short notice, and I started work on my doctoral thesis with Prof. Andreas Hochhaus, who was in Mannheim at the time, now in Jena. This series of events turned out to be a blessing in disguise because Professor Hochhaus became an important mentor to me. He instilled in me an enthusiasm for translational research at an early age, giving me a scientific compass and introducing me to clinical medicine. Oncology fascinates me because it gets you very close to the patient, takes a holistic view of people and is in a constant state of change due to the push for innovation. For me, it’s the subject that best allows me to combine my passion for practical medicine with my interest in science.

DFG: You went to Boston on a DFG research fellowship to study resistance mechanisms in leukemia caused by chemotherapy. Your project is now based at Benjamin L. Ebert’s laboratory at Harvard Medical School’s Dana-Farber Cancer Institute. Why this group in particular?

AG: I changed my original research project after arriving in Boston, having quickly realized after a few pilot experiments that it wouldn’t be possible to answer the research question unambiguously from a methodological point of view. It was a key lifetime experience for me personally to pluck up the courage to end a project and re-establish my bearings. Professor Ebert gave me all the freedom I needed and actively supported me. I deliberately chose his research group because it has made a major contribution towards understanding clonal hematopoiesis as a potential precursor stage of cancer, and it is involved at the interface of basic research and clinical application. I had the opportunity to meet Professor Ebert in person at an international congress in 2015. In the course of the conversation I quickly realised that he’s an extraordinary scientist as well as a very personable individual. The way he embraces science by persistently pursuing fundamental questions is both enthralling and inspirational. He encourages you to strike out on untrodden paths in pursuit of new insights. In doing so, you also learn how to ask the ‘right’ scientific questions in the first place. This approach is highly ambitious of course, but it also offers enormous opportunities for personal development. In pursuing this journey, Professor Ebert takes his role as mentor very seriously but he also creates a very pleasant atmosphere within the working group where we help each other and openly engage in an exchange of ideas.

DFG: If you had to present your current research topic to an audience of non-experts in a three-minute science slam, what would the highlights be?

AG: For my postdoc I’m looking into the influence of acquired gene mutations in blood cells on the inflammatory process. In recent years, our laboratory has made a significant contribution to detecting certain gene mutations, previously known mainly from malignant blood disorders; these even occur in healthy, aging people without any abnormalities in their blood. This phenomenon is called clonal haematopoiesis of indeterminate potential (CHIP). So clonal hematopoiesis is a potential precursor stage of malignant blood disorders such as leukemia: it involves the acquisition of gene mutations, even though there are no changes in the blood count and bone marrow.
In leukemias, all cancer cells usually originate from a diseased stem cell which, unlike healthy stem cells, is capable of clonal proliferation. Interestingly, our research group observed that the risk of people with clonal hematopoiesis developing a blood malignancy is low, at just one percent per year, but is associated with increased mortality from cardiovascular disease. In further experiments we were able to show that in mice with clonal haematopoiesis, the inflammatory process is intensified by the release of various messenger substances that favor plaque formation in blood vessels. This is where my research project comes in: I’m currently investigating the extent to which certain gene mutations in blood cells can have an impact on the inflammatory process – including in ways not related to cardiovascular disease.

DFG: You are now 33 years old. Professor Ebert is probably in his early to mid-50s. Do you feel you would be capable of rising to that level in the next 20 years, i.e. become head of a fairly large research group or even director of a Max Planck Institute, and do you have the ambition it would take to do so?

AG: I very much enjoy my work and I’m certainly ambitious, but my primary aim right now is to successfully complete my postdoc and the scientific projects I’m involved in. Following this, I’d like to continue my academic career as a physician-scientist and establish my own research group. I’m also looking forward to working as a doctor again, because I’ve missed being involved with patients. I’m not driven by any particular title or position, but I do want to continue to pursue my interests and get involved in hematology/oncology so as to contribute to improving the diagnosis and treatment of cancer based on a more detailed understanding of the pathophysiology. For me, the journey is more important than the final destination.

DFG: That almost obviates one of the questions we normally ask regarding career alternatives. I see from your CV that you were accepted onto a Boston Consulting Group (BCG) talent program. Didn’t they want to recruit you? Are there any other alternatives you have in mind?

AG: That was during my studies a long time ago. I wanted to gain my own impression of different job profiles. The question of career alternatives isn’t relevant right now. I’m very happy I stayed in medicine. I remain curious and open, and medicine offers lots of opportunities for development – whether as a doctor, scientist or entrepreneur. I derive great pleasure from working at the interface between basic research and medicine; as an entrepreneur I’m excited at the opportunity to measure ideas against reality and be a driving force behind change.

DFG: The DFG is based in Bonn. Ludwig van Beethoven was born in Bonn 250 years ago. You used to play the oboe. In other words: Music is a subject we can talk about here. Beethoven’s medical record is long and ended with his death at the age of just 57. To put the question to you as both a physician and a musician: if Beethoven had been happier, would he have left us different music?

AG: The question as to how happiness or misfortune influences an artist’s work is a fascinating one. Unlike science, art and music are forms of expression, so I do believe that artists’ joys and sorrows are conveyed through their works to some extent. Your question about Beethoven is a difficult one for me to answer, but it reminds me of a contemporary musician whom I admire very much and have also had the pleasure of meeting: Augustin Hadelich, an exceptionally gifted violinist who suffered severe burns in his youth and had to reacquire his skills on the instrument. I find his music incredibly expressive, clear and emotional – perhaps also influenced by this biographical event.

But back to Beethoven: last year I had the pleasure to attend a performance of the Kreutzer Sonata by pianist Evgeny Kissin and violinist Itzhak Perlman at Boston Symphony Hall. The music and the interplay between these two virtuoso artists touched me deeply, but I can get just as excited about Zakir Hussain on the tabla or electronic ambient music à la Aphex Twin.

DFG: In your CV you also mention your membership of ‘ARTgenossen,’ the young patrons’ association of the modern art museum Kunsthalle Mannheim. Can you tell us about this and explain where you see possible overlaps between art and science?

AG: The reason might seem rather trivial – or the result of coincidence if you like. Karl-Friedrich-Gymnasium, the secondary school I attended, is right across the road from Kunsthalle Mannheim, so I had always had a view of the museum from my classroom window. Obviously I was curious enough to pop in and take a look now and again, too – and it was very worthwhile. The ARTgenossen have a small budget which they can use to organie museum zand studio visits, lectures and small-scale events at the Kunsthalle. The opportunity of a behind-the-scenes look at a museum was particularly interesting for me, as was engaging in dialogue about it with my peers.

I believe art and science are both concerned with the search for truth, albeit in very different ways. Both require and promote creativity. Whether they overlap or simply co-exist is not so important in my opinion. Simply put: art is capable of being provocative and perhaps should be; but science shouldn’t – more than anything it has to be verifiable.

DFG: You list table tennis as being one of your hobbies, which you probably wouldn’t if your level was just enough for a family knockabout. If there was a top-ranking table tennis player in an in-house DFG sports club, would they stand a chance against you? Are you more of an attacking or a defensive player and what is your racket-holding technique?

AG: Even though my first name means “gentleness” and was certainly chosen by my parents in the hope of influencing the development of my character accordingly, when it comes to table tennis, I’m a passionate attacking player. My preferred racket position is the handshake grip – an appropriate term because I always like to say goodbye properly after the match and thank the opponent for a fair game. I’d love to join in a DFG table tennis championship!

DFG: Thank you very much for the interview! We will keep our fingers crossed that your plans come to fruition as anticipated and that anything unplanned has a happy outcome – as has obviously been the case quite frequently in your life.

Go to Webseite:

• https://connects.catalyst.harvard.edu/Profiles/display/Person/165261

Contact

• E-Mail: Mridul_Agrawal@DFCI.Harvard.edu
• Linkedin: www.linkedin.com/in/mridulagrawal/
• Twitter: @Agrawal_Mri