Q&A: Benoît Duc on MD-Phds, a thirst for knowledge and demonstrating impact
In the second of our 3-part feature series, we discover another member of our ECR community - who they are, what inspires them to pursue a career in life sciences, and their role in our research in Lausanne.
His interest in the biology of cancer awakened by an inspirational lecturer in his second year of medical studies, Benoît Duc is now part of the University of Lausanne's MD-PhD programme. One year into his PhD under the direction of Prof Johanna Joyce, he discusses choices made and yet to come, and the scientists and the science he has encountered along the path to becoming a "good clinican and good researcher".
What were you like in high school?
I really enjoyed maths and was very interested in all things technical, like construction and micro-engineering. When it came to senior high, the natural choice was the maths-physics stream with an IT option, and in my mind I was heading for the EPFL to study engineering.
So, what led you to choose medicine?
We actually have several doctors in the family, both of my grandfathers, an uncle – and my father who is a practicing pathologist, in Sion. My parents never tried to influence me but the fact that I saw my father enjoy his profession undoubtedly played its part. A year into my Maturité studies, it just dawned on me that what I actually wanted to study was medicine.
What made you realise that you were equally drawn to research?
In our second year, the more fundamental courses like molecular biology, pathology or the basics of cancer biology, make up a major part of the lectures and this part of the syllabus was taught to us by Pr Ivan Stamenkovic. His enthusiasm and charisma – legendary in the student community! – meant I greatly enjoyed his subjects; the torch he carried for research clearly sparked my interest. His way of teaching drew me to think about the biology of cancer, and made me realise that I wanted to know more. Up to then, I wasn't even aware of the FBM’s MD-PhD programme.
How did you gain your first experience of basic science?
I approached Pr Stamenkovic who put me in touch with one of his mentees, Dr Nicolo Riggi. During that second year’s summer break, I spent a few weeks in the Riggi lab working on rare paediatric sarcomas, which I found fascinating. Later, opting to do my master’s project in fundamental research (medical students can choose between clinical or fundamental research), I went back to Nicolo’s lab to do my thesis.
What is the MD-PhD programme and how easy is it to join it?
The purpose of the programme is to train doctors who close the gap between the bench and the bedside- who become both good clinicians and good researchers.
Med students branch off to this programme typically in the third or fourth year of their degree. The formal process involves reaching out to the MD-PhD commission who then put students in touch with different principal investigators who we can meet and discuss with. These exchanges allow to pinpoint mutual interests with a view to undertaking your PhD in their lab. You then present your project to the MD-PhD commission to solicit potential funding.
Did many others in your year go down this path?
Out of 200 students, roughly 15 submitted projects and 6 or 7 were awarded a grant. It must be said that to decide to enrol you need to be in it for the long haul. Bearing in mind that clinical specialisations alone can add a further 5 years to your medical studies, it's understandable that many want to train for their specialist title and simply “get to work”. It's perhaps a reflection of the Department of oncology’s calibre that it has numerous MD-PhDs, the Joyce Lab alone having had three such!
How did you join Johanna Joyce's lab?
I first discovered Pr Joyce’s fascinating research on brain tumors during my medical studies, through a great presentation she gave at a Swiss Cancer Centre Léman retreat in Lausanne. I then contacted her to potentially join the lab, but unfortunately there were no openings at that time.
For my sixth year research internship, I spent three months with Mario Suvà at the Massachusetts General Hospital, in Boston. His lab addresses important questions around the biology of glioblastomas, the most common malignant tumors arising in the brain. When I was looking for a lab for my PhD, as luck would have it, Johanna was now looking to recruit an MD-PhD; the Joyce lab is very translational, and Johanna always aims to have several clinical scientists in the group to help drive this research. I was actually on my military service when the opportunity came up! But, I managed to take a day off to visit the lab, and Johanna proposed a few of the ongoing projects including the one I'm currently working on. We then submitted the project to the ISREC Foundation - who graciously awarded its Grant for Translational Oncology to support my position!
Tell us a little about Joyce lab's work?
As part of the Department of oncology and the Ludwig Lausanne branch, we study the microenvironment of brain tumors, by which we mean all the cells in a tumor in addition to the cancer cells e.g. the immune cells, stromal cells, the blood vessels. Johanna’s research has shown in the past how this context is key to the survival of cancer cells, and that strategies targeting the tumor microenvironment might improve cancer therapy in patients.The lab extensively studied the biology of breast and pancreatic cancer, but now focuses on primary brain tumours and brain metastasis in particular, given the often poor prognosis for these patients. Of note: metastases of the brain are the most frequent type of malignant brain tumors, mainly from primary lung and breast cancer.
What is your favourite aspect of this part of your MD-PhD?
The clinical aspects can occasionally be a little formalistic, which is of course fundamental to the rigour of medical practice. Within that context, enigmas and a sense of discovery do naturally arise. But, in science you get to experience having an idea, testing it, finding that it leads to another approach, which in turn you find you also need to test. I really like this experimental, evolutionary process, where your own ideas have an impact, and where you also have to take responsibility for them.
Does this mean you have regrets at not having gone straight into research?
Absolutely none. It’s really beneficial to have a background in medicine. Of course, it means having to catch up on technical laboratory aspects. But, at the level of…asking one’s self the right questions, I think medical studies bring a unique set of tools and a specific way of thinking about cancer.
When you first arrived in the Joyce lab, how did you deal with not having that basic science experience?
Mainly by working with the other PhD and post-doc students in the lab who, day in day out, have generously shared their experience and taught me the different experimental approaches that I now use routinely in my own project. I'd also prepared by following additional online courses, such as in bioinformatics, during my medical studies. It was a challenge fitting them in but it gave me extra motivation to get through the medical syllabus, which calls for a huge amount of pure rote learning. Those courses pushed me to ask myself more questions, and reflect more deeply. Even for the medical aspects of my training, it helped me to be more analytical.
What do you really enjoy about research?
The translational aspect clearly, but I'm also really intrigued by the fundamental research - the quest to determine how mechanisms act in a tumour. Our project’s objective is to identify one of these mechanisms, and to test it in a preclinical model to determine if such an approach might ultimately improve patients’ survival rates. The preclinical impact can be quite swift. As for the clinical impact, that all depends. If a suitable molecule is already being used in clinical trials in other pathologies, things are simpler since its toxicity will already have been tested. From there, a pharmaceutical company has to see an interest and push its development. In all, we’re looking at at least ten years before it becomes a standard treatment…That’s a long journey.
Does that make you impatient?
Initially it did, yes, because in the clinic you can get to witness results more quickly. As scientists, we give our all to projects – but with the premise that they may only have an impact at some point down the road. I would say that the ability to deal with that is also an important part of what you learn as a researcher.
How do you see cancer research evolving?
Single-cell technologies are changing how we do research, and they're evolving so quickly. We used to look only at genes, then we studied the proteins; now we’re scrutinising the spatial organisation of the tumor, and its environment. All this represents an explosion in terms of the volume of data to work with.
Beyond identifying different types of cells and describing them in detail, the next big step will be to show what are their critical functions within a living tumour. This is precisely the “translational” aspect, often the most difficult: supporting the importance of a finding by demonstrating its impact. With single cell technology, we now demonstrate that: in a given cancer type, in one sub-population of immune cells, X, Y and Z genes are expressed, which appear to attack the tumour. This in itself constitutes the subject of an entire scientific paper. But, what can we actually bring, through this knowledge? Can we target this population of cells with a drug?
And, where do you see yourself after your MD-PhD?
I’m currently considering two options. I could pursue with a post-doc and continue full-time in research. But, this would mean foregoing any clinical practice in the future. I feel that I might lean towards obtaining my clinical (FMH) specialisation, most likely in pathology. The field brings me a little closer to the laboratory than most, is closely involved in the problematic of oncology and - importantly - would be easier to combine with continued research activities.
This interview was conducted in French. All images, including @Twitter, are courtesy of Benoît Duc and Joyce Lab.
On being a PhD in Joyce Lab...
My PhD project addresses challenges in the field of lung cancer metastasis in the brain, representing the final stage of cancer progression when tumor cells have successfully spread to a new organ and colonised it. This is highly relevant from a clinical perspective. First, because they are associated with an extremely poor outcome and second, because they cause deaths in patients in which the disease outside the brain is under control. The project was of interest to Johanna as it builds on existing work by Ángel Alvarez-Prado, a current post-doc in the lab. Ángel performed a study on patient samples demonstrating that depending on the mutations that are present in the cancer cells, the TME differs, particularly in brain metastasis of a lung cancer. What we've yet to determine is whether it’s simply a correlation (down to other reasons), or if the mutations themselves provoke this change in the TME.
This could have an important impact on the clinic; the Lausanne University Hospital’s pathology unit is now testing all tumor resections for specific mutations. We found that tumors harbouring some of these mutations result in a potentially stronger immune reaction against the tumor. It would be intriguing to determine if these patients react better to immunotherapy. Our intent is to evaluate, using preclinical models, whether different versions of these tumours, with different mutations, respond differently to treatments.
In a separate project, I’m also studying how normal cells intermingling with the cancerous cells are controlled i.e. the epigenetic regulation of the TME. I’d read a great paper on the subject, by Robert Bowman when he had done his PhD with Johanna, focusing on gliomas, when her lab was at MSKCC in New York. I was of course able to reach out to him personally, and benefit from his input on some of the important questions that my project aims to address.