Early-stage academic drug discovery in Europe following the Covid-19 crisis: Quo Vadis?
Published on June 8th, 2022
Bruno Villoutreix
PhD, director of research within the INSERM Unit 1141, Hospital Robert Debré in Paris.
The global death toll from the Covid-19 pandemic reached 5.5 million in early 2022, but demographers, data scientists, and public-health workers all suggest that this number is a significant underestimate—not to mention the undefined number of people who continue to become infected by SARS-CoV-2 and long-Covid patients. Further, pandemic-related deaths have resulted in well over a million young orphans (1). The Covid-19 crisis has raised many questions about other infectious diseases and ailments that still lack appropriate medical treatments. Many of these questions involve drug discovery and development, both in the private sector and in academic settings. It is common to see questions on social networks and blogs such as, “Is it possible to develop affordable new drugs quickly?”, “Why do so many new drugs seem to come from non-EU countries?” and “What lies ahead?”
Commentary
Bruno O. Villoutreix
The global death toll from the Covid-19 pandemic reached 5.5 million in early 2022, but demographers, data scientists, and public-health workers all suggest that this number is a significant underestimate—not to mention the undefined number of people who continue to become infected by SARS-CoV-2 and long-Covid patients. Further, pandemic-related deaths have resulted in well over a million young orphans (1). The Covid-19 crisis has raised many questions about other infectious diseases and ailments that still lack appropriate medical treatments. Many of these questions involve drug discovery and development, both in the private sector and in academic settings. It is common to see questions on social networks and blogs such as, “Is it possible to develop affordable new drugs quickly?”, “Why do so many new drugs seem to come from non-EU countries?” and “What lies ahead?”
Indeed, in the face of a crisis of such magnitude, scientists and citizens alike were expecting stimulating debates about what went wrong in terms of European drug discovery, what went right, and how European countries could emerge stronger. Many scientists anticipated democratic, publicly supported changes and novel actions aimed at boosting European academic drug-discovery research. Unfortunately, at the time of this writing, such debates do not seem to be taking place or are entirely in the hands of a small number of experts, various lobbyist groups, and some government authorities. The last few decades have shown that early-stage drug discovery has never been properly considered in most European countries (but UK as indeed significant efforts took place to strengthen academic drug discovery these recent years). Is this finally going to change?
I will discuss drug discovery in the academic system for several reasons. First, well-funded, coordinated, and efficient academic drug-discovery research should ultimately lead to win-win public-private partnerships (2, 3). Further, as observed by numerous researchers and economists, the pharmaceutical sector is becoming more dependent upon academic organizations as sources of innovation for new medicine (4). In other words, it is important for academic drug discovery to become a major topic in the post-Covid-19 era. Drug discovery and development involve numerous complex processes, highly integrated, non-siloed interdisciplinary research, and collaborations between academia and the private sector (5, 6). Over the years, several success stories have emerged from academic groups (7–9) but, in general, academic drug discovery in Europe and its member states remains fragmented. While know-how and skills are clearly present, Europe’s academic drug-discovery process lacks recognition, coordination, and appropriate financial support. Strategies or workflows to quickly translate pioneering research findings from bench/computer to bedside are either missing or could be significantly enhanced. Additionally, the scientists working in this field lack clear career tracks. If drug discovery success is measured by the number of approved drugs on the market, many European countries are declining and/or could certainly perform much better if they received appropriate support and consideration (10).
There are numerous obstacles to academic drug discovery. It is time- and resource intensive, requires many unique skills, and is politically risky. In Europe and its member states, one major reason for the lack of appropriate financial support is that “one-size-fits-all” grant calls are written with preconceived ideas about excellence and innovation—as if drug discovery were a typical research discipline. Recently, funding has been primarily dedicated to the development of technologies or to the investigation of molecular mechanisms involved in the health and disease states. While these topics are obviously important, funding has seldom gone directly toward the discovery of therapeutic agents or drug candidates. There is a lack of incentive for developing drug discovery as an academic field of research. Government officials and policy/decision-makers typically have limited training in drug discovery and therefore seek advice from experts. Yet, these experts do not seem interested in developing early-stage drug discovery in academia, or they tend to approach the field from a therapeutic angle, focusing on a specific biological system or organ or on a single condition. When the budget is tight, it might be much more efficient to actively develop disease-agnostic platforms so as to avoid reinventing the wheel for every single disease or single therapeutic target. The current way of functioning also contributes to “silo” mentality. Year after year, some policy makers/government officials and scientific experts form an intriguing network that appears to be trapped into an echo chamber—an environment in which people only encounter opinions that reflect and reinforce their own—causing the system to get stuck for decades. Finally, because academic drug discovery and development is a vast field involving many stakeholders with potential conflict of interest, it is politically risky. Officials and decision makers tend to avoid promoting this topic in Europe or its member states because years of efforts are needed to make a significant impact, and the initial rewards and results to report to citizens are minimal.
We need a shift in academic culture, whereby evaluating committees view the effective translation of research into novel treatments as essential, not as a distraction from academic research and realize the efforts of researchers working at the interface between different disciplines. Many academic scientists in Europe are highly interested in drug discovery but feel they have been shut out of policy/decision making and underline the lack of transparency surrounding this field. A simple analysis of the processes at play supports this impression. Initiating discussions and debates within the scientific community, with citizens, and with policy/decision makers is urgent (even more so in the era of “genomic medicine”), as is reinforcing unbiased training and education about the various aspects of drug discovery and development. We must be proactive and delay no longer. Our efforts will require years, given that drug discovery and development are inherently long-term, costly processes, but such a project will ultimately create a mindset and ecosystem that could strengthen European research, encourage entrepreneurship, and favor novel, win-win public-private partnerships. It is thus my hope that the devastating Covid-19 crisis will serve as a catalyst for fundamental changes in the field of academic drug discovery in Europe and its member states, and will stimulate novel types of partnerships with the private sector.
References:
1. Hillis, S. et al., (2021). Lancet. 398:391–402. doi: https://doi.org/10.1016/S0140-6736(21)01253-8
2. Kinch, M. et al., (2020). Drug Discov. Today. 25: 1905–1909. doi: https://doi.org/10.1016/j.drudis.2020.09.004
3. Gold, A. and Edwards, A., (2021). Front. Drug. Discov. doi: 10.3389/fddsv.2022.898654
4. Mazzucato, M., (2018). The Entrepreneurial State, Penguin, New York.
5. Villoutreix, B.O., (2021). Front. Drug. Discov. doi: 10.3389/fddsv.2021.728469
6. Dahlin, J. et al., (2015). Nat. Rev. Drug Discov. 14:279–94. doi: 10.1038/nrd4578
7. Tralau-Stewart, C. et al., (2014). Nat. Rev. Drug Discov. 13:15–16. doi: 10.1038/nrd4200
8. Everett, J., (2015). Expert. Opin. Drug Discov. 10:937–44. doi: 10.1517/17460441.2015.1059816
9. Frye, S. et al., (2011) Nat. Rev. Drug Discov. 10: 409–10. doi: 10.1038/nrd3462
10. Patridge, E. et al., (2015). Drug Discov. Today. 20:1182–7. doi: 10.1016/j.drudis.2015.06.006
Bruno Villoutreix, PhD, is director of research within the INSERM Unit 1141 (Hospital Robert Debré), in Paris. He has a background in molecular biology, structural bioinformatics and chemoinformatics and has been working for over 20 years in different countries, in the private and academic sectors. He has over 240 publications, several book chapters and patents. He has contributed strongly to the development of several chemical probes and drug candidates with one anti-metastatic molecule designed in silico presently in phase II clinical trial. He also worked on the development of more stable therapeutic proteins in the field of blood coagulation (e.g., hemophilia A), on monoclonal antibodies in the field of cancer (prostate specific antigen) and on drug repositioning with applications in several therapeutic areas.
