Translational Medicine

Translating science into medicine: Q&A with international experts

Elsevier’s Berlin Translational Dialogue provided a forum for exchange on future avenues for clinical translation of basic science discoveries

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 <strong>Berlin Translational Dialogue speakers with Elsevier colleagues.</strong> Back row from left: Profs. Kenneth Chien, Erwin Böttinger, Stefan Kaufmann, Thomas Sommer, Werner Müller-Esterl, Michael Teitell. Front row from left: Adriaan Klinkenberg; Dr. Nick Fowler, Helen Habernickel and Dr. Thomas Schwarz-Romond (Elsevier); Dr. Michaela Frye; Prof. Karl Einhäupl; Dr. Emilie Marcus (Cell Press); Prof. Ulrich Dirnagl; and Dr. Michiel Kolman (Elsevier). (Photos by Sascha Radke)

Efficient and effective translation of basic research findings into clinical practice improves patients’ quality of life and adds value to healthcare systems around the world. These are strong incentives for governments and societies to invest in basic research and foster translational efforts. However, it can take years – and numerous unexpected turns – before new research finds its way into patient care.

Environments that foster science translation

Panelists said the following conditions were important to support the translation of basic research into clinical applications:

  • Adequate organizational culture and mindsets towards a common goal
  • Mutual respect in focused translational research units
  • New incentive schemes that bridge current gaps in basic versus clinical training/career tracks
  • Engaging all relevant stakeholders (translational scientists, patient groups, funders, governments and regulators)

Several elements are crucial for effectively navigating this journey: suitable infrastructures, organizational commitment, a transformative research culture, training and education (particularly of younger scientists), the collaboration of every stakeholder along the translational path, and robust and reproducible publication.

These subjects, and many more, were discussed at the Berlin Translational Dialogue November 8. Organized by Elsevier, and paying tribute to the many translational efforts in Berlin’s biomedical research institutions, this initiative was prompted by the recent foundation of the Berlin Institute of Health and the arrival of its new chairman, Prof. Erwin Böttinger, who brings his vast experience from the Icahn School of Personalized Medicine at Mount Sinai Hospital in New York to Berlin.

The Berlin Translational Dialogue connected more than 60 leading scientists, research administrators, heads of core facilities, and pharma representatives with executives from Elsevier. The positive, open and science-focused atmosphere enabled fruitful conversation and an honest assessment of Berlin’s position in the global translational space.

Some highlights

  • Prof. Nikolaus Rajewsky directs the highly innovative research program at the Berlin Institute for Medical Systems Biology.Dr. Kenneth Chien, Professor at the Karolinska Institute in Stockholm, and Dr. Erwin Böttinger crystalized their views on successful science translation.
  • Dr. Ulrich Dirnagl, Professor at the Charité & German Center for Neurodegenerative Diseases, emphasized the importance of robust and reproducible research for accelerating science translation, cutting losses early, and focusing efforts on truly promising projects.
  • Dr. Nikolaus Rajewsky, Professor and Founding Director of the Berlin Institute for Medical Systems Biology, advocated a systems-view on biological/disease principles and shared his institutional vision of combining best-in-class bioinformatics with experimental research to advance medicine.
  • Dr. Michaela Frye is group leader at the Stem Cell Institute, University of Cambridge.Dr. Michaela Frye, Group Leader at the Cambridge Stem Cell Institute, and Dr. Michael A. Teitell, Director of Basic/Translational Research at UCLA’s Jonsson Comprehensive Cancer Center, echoed Dr. Rajewsky’s call for filling translational pipelines with basic research. They both emphasized the power of interdisciplinary cooperation with academic and commercial partners to validate disease relevance and examine the translational value of basic findings.
  • Dr. Stefan Kaufmann chaired an interactive panel discussion that was joined by Dr. Thomas Sommer, Professor at the Charité & Humboldt University Berlin and Acting Director of the Max-Delbrück Center, and Dr. Karl Max Einhäupl, Professor at the Charité & Humboldt University in Berlin and Chairman of the Executive Board Charité, where they explored how to shape the translational environment in Berlin and possibly beyond.

After the event, the organizers interviewed some of the speakers and panelists about their impressions of the event and Berlin’s potential as future hub for systems/personalized medicine.

Q: What do you see as the primary challenge in translating basic science discoveries?

Prof. Erwin Böttinger, PhD, is the new Chairman of the Berlin Institute of Health.

Erwin Böttinger: A primary challenge is certainly the successful integration of the different research worlds and cultures of basic science and medical care. It depends on our ability to communicate, share data, and function as a collaborative entity. It is also important to keep in mind that innovative translational biomedical research has to address a clear clinical need, and at the same time requires deep understanding of biological mechanisms.

Karl Max Einhäupl: The main hurdle faced by From left: Profs. Clemens Schmitt and Ulrich Dirnagl talk with Prof. Karl Max Einhäupl (Chairman of the Charitè Executive Board) during the event.translational medicine today is that of bridging the gap between basic and clinical studies and the subsequent implementation into the healthcare system. A second obstacle relates to the segmentation of research groups and the lack of relevant incentives for cooperative research. The consequence is that publications in high ranking basic research journals tend to forge academic careers and makes clinical research less professionally attractive. To confound the matter further, Germany’s public health scientific community remains underdeveloped, and industrial partners tend to view research cooperations as being molded by marketing forces, whereas academia perceives such cooperations as being sponsorship driven. This results in a fragmented and wasteful research landscape that undermines science translation efforts.

Q: Does the increasing pressure for immediate application restrict academic freedom and the space for unbiased scientific curiosity?

Prof. Michael A. Teitell is Director of Basic/Translational Research at UCLA’s Jonsson Comprehensive Cancer Center.

Michael Teitell: The push to applications is a double-edged sword. There are finite resources available to governments, institutions and philanthropies, and simply the growing scale of funding applications may limit resources. By necessity, available funds to support basic studies will shrink, and those interested in working in science will migrate to translation or even another occupation, perhaps not immediately but over time. This is already happening to some extent in the US, in part caused by the NIH funding patterns. Since so much of our actionable foundation for translation comes from fundamental studies, at first unrelated to disease, often in model organisms, in test tubes, or on computer screens, this may become a concern. It should become an area for active management of resources and their intelligent allocation.

It’s also a risk to force scientists or organizations that are superb in one area. such as fundamental discovery, to now branch into another area in order to secure funds. In general, it is my impression at an individual level that passion leads to advances, and being forced to allocate time and effort in an area that is not one’s passion will dilute and even subvert the actual work and advances produced.

I guess in sum, the issue will be one of balance — balancing the need for fundamental discovery with the need to advance progress against disease and aging-related problems, etc. Each country and each institutional entity, maybe each individual, will have to define what balance works in that setting, and there is probably no right or perfect answer to this issue.

With science translation being a truly global endeavor, is there sufficient room for region-specific approaches, unique local infrastructures, or collaborative expertise? Should Berlin aim to identify and focus on such elements to distinguish itself from other global science centers?

Kenneth Chien, Professor at the Karolinska Institute in Stockholm and biotech entrepreneur at Moderna Therapeutics, fostered an inspiring, high-level discussion, here with Prof. Thomas Sommer, acting Director of the MDC, Berlin.Kenneth Chien: I think there has to be a sharper focus than simply collecting huge patient data and sending them for analysis elsewhere. Thinking carefully on certain expertise for functional validation is key. Furthermore, a focus on intelligent exploitation of the most recent technologies — or even better, identify their limits and innovate to overcome them. I do not think it wise to try and do the exact same type of work that the Broad Institute and Wellcome Trust are already engaged in, as they have critical mass for much of this type of work. That being said, the approach could be extended to a specific area of expertise that Berlin already has or could generate unique strengths. This is how strategic global partnerships are of pivotal importance.

Ulrich Dirnagl: There is no doubt that science is an international endeavor. Good scientists pick their collaborators because of their expertise. The reason that we team up locally has most often to do with convenience and not to forget the need to appeal to certain funding schemes. I personally think that local proximity also pays off, since a good coffee or sometimes a good beer can help quite a lot to foster translation as well as scientific debate in general.

Pharma companies are opening their pre-clinical pipelines, moving research capacity close to academic research hubs (Cambridge, Stockholm, Singapore, etc.). Is this mixing of academic and professional worlds a temporary trend or essential to accelerate science translation?

Erwin Böttinger: The mixing of worlds is certainly no recent trend. Science translation can only be successful if teams with different expertise work closely together. A multidisciplinary approach is necessary, where teams meet and transfer knowledge and know-how. Clinical scientists and researchers in biomedical sciences need to collaborate with partners such as healthcare providers, patent agents, and industrial partners, aiming for effective transfer of basic findings to preclinical models and later to early clinical validation.

Kenneth Chien: In my opinion, partnerships with the private sector are absolutely essential. Academic institutions should not try to morph into drug development or pharma companies, with regulatory, toxicologic, dosing, formulation, scalability expertise. This would distract from the core innovation and discovery aspect that is the coin of the realm of academia at the highest level. But exploring new ways to integrate all efforts in real time could be a game-changer.

Do you see future medical progress as being inevitably coupled to the data (and -omics) or stem cell revolution, irrespective of a more systems-level view on homeostasis and diseases?

Ulrich Dirnagl: I totally agree. Still, it is on smart scientists, serendipity, intelligent hypotheses, computers, high-resolution imaging, novel techniques to study cell biology at a molecular level, disease models with high external validity, among many others. Omics, on the other hand, are just techniques, and to state that we need data is trivial. To imply that -omics and big data will fundamentally change the way knowledge progresses, I would say no. It is a current trend that will be absorbed into our future procedures, as with other technologies before.

Reflecting on the Berlin Translational Dialogue, have you learned anything surprising? Did any of the interactions change your opinion about Berlin’s approach to science translation?

Kenneth Chien: I came away from this focused, small meeting with leaders of biomedical science in Berlin with a clear appreciation of the commitment, vision and considerable potential in the arena of translational medicine. At the same time, it will be important to identify a strategic focus to unlock this potential. The leadership in the area, particularly the recruitment of Dr. Bottinger, bodes well for the overall effort. Berlin is an attractive place for a young, talented work force and trainees that are all essential for the field at the bench and bedside. That being said, there are core challenges we all face in the translational space, some of these are conundrums that are yet to be fully solved. For those, it might be important or indeed fun to approach them together.

Ulrich Dirnagl: To be honest, I was a bit skeptical in the beginning. But the spotlight on the BIH and its new leadership was definitely helpful. We had a number of discussions during and after the meeting relating to the future focus and philosophy of the BIH, which were helped by the fact that some of the participants normally do not interact due to the fact that they work in different areas or institutions.

Michael Teitell: I was impressed by the commitment of many of Berlin’s leading institutions and their senior leadership at establishing an inter-institutional focus on translation; this is an important dialogue that will require significant action and resources to be achieved. Many key issues going forward include recruitment, training the next generation, establishing teams and teamwork, and providing details for the vision espoused by all leaders on the dialogue panel. The measure for eventual success of Berlin’s endeavor will be (a potentially new) approach to overcome many of the outlined barriers.

Elsevier Connect Contributor

Thomas Schwarz-Romond, PhD, MBADr. Thomas Schwarz-Romond serves as Executive Publisher - Journals in Elsevier’s Berlin office. During his PhD and postdoctoral research, Thomas investigated the molecular and structural mechanisms of Wnt-signaling at the Max Delbrück Center for Molecular Medicine (MDC-Berlin) and the Medical Research Council Laboratory of Molecular Biology (MRC-LMB Cambridge). From 2006 to 2015, he worked as Scientific Editor for The EMBO Journal. He acquired managerial skills during an MBA leadership program and joined Elsevier in April 2015.

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