In Focus pubs.acs.org/acschemicalbiology
Chemical Biology Consortium Sweden Lars G. J. Hammarström* and Annika Jenmalm Jensen Chemical Biology Consortium Sweden, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden
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weden has a long and proud history of biomedical and pharmaceutical research, contributing to an increased understanding of disease and spawning generations of small molecule therapeutics over the past 100 years. It is in stark contrast to this tradition that the Swedish research community in recent years has seen the closing of Pharmacia R&D after its acquisition by Pfizer, closing of AstraZeneca research sites in Södertälje and Lund, and the down-sizing or termination of a large number of small and midsized biotech companies in the country. In the wake of the global pharma R&D crisis, a similar trend has affected nearly all top pharmaceutical companies worldwide.1−3 In response to the retreat of big pharma away from discovery sciences, the global academic community has stepped up to the challenge of extending basic research from university laboratories further toward applied and translational clinical application.4−6 This transition has largely been an organic evolution resulting from the “down-sizing” of pharma research investments. However, it has also partly been facilitated by the migration of experienced drug hunters from industry into academia, where they now often play key roles as supervisors and scientific experts in university screening facilities and chemical biology platforms. Unlike the U.S. and most of the rest of Europe, Sweden has seen a notable increase in governmental funding of science during the years following the global financial crisis,7 including the launch of a new research infrastructure within academic small molecule discovery, sponsored by the Swedish Research Council. Based at Karolinska Institutet in Stockholm, Chemical Biology Consortium Sweden (CBCS, www.cbcs.se; Figure 1) was established in 2010, effectively consolidating a majority of the chemical biology activities in Sweden at the time. CBCS coordinates and enables a powerful network of academic facilities in Sweden for the discovery, development, and validation of small molecules as pharmacological tools (chemical probes) within the realm of academic research. CBCS’s mission is to facilitate the use of small molecules and chemical biology toward advancing knowledge within fundamental aspects of biology. The organization is home to a highly multidisciplinary faculty encompassing biochemists, cell biologists, medicinal chemists, computational chemists, in vitro pharmacokineticists, and informaticians. In other words... a typical chemical biology lab. CBCS today comprises three major nodes, at Karolinska Institutet in Stockholm, Umeå University, and Uppsala University, establishing a geographical presence at three of the largest research institutions in Sweden, each contributing with different areas of expertise. The Laboratories for Chemical Biology Umeå (LCBU), headed by Prof. Mikael Elofsson, are equipped to focus on projects within plant physiology and infectious diseases. Prof. Per Artursson, head of the Uppsala © 2013 American Chemical Society
Figure 1. CBCS headquarters, housed in the recently established Science for Life Laboratory (SciLifeLab) at Karolinska Institutet in Stockholm.
University Drug Optimization & Pharmaceutical Prof iling Platform (UDOPP), is a renowned authority in drug pharmacokinetics and transport and offers collaborative services in pharmaceutical profiling of small molecules. The Laboratories for Chemical Biology at Karolinska Institutet (LCBKI), headed by CBCS director Dr. Annika Jenmalm Jensen, houses an extensive compound collection and platform for assay development, screening, medicinal chemistry, cell-based phenotypic analysis, and target identification. CBCS utilizes a biannual peer-review process to triage project proposals that are submitted to the consortium. Today, 3 years after its inception, CBCS has over 70 projects completed or in progress with academic researchers at every major research university in Sweden. With experience gained from similar initiatives in other countries, CBCS has chosen to establish a working model that builds upon a few fundamental philosophies that we consider essential to the success of the infrastructure: 1. We do NOT do Drug Discovery. The enormous effort, resources, and finances required to bring a therapeutic all the way to the market cannot be understated. Thus, in most cases, drug development is better suited confined to the strict principles and deep financial pockets of the pharmaceutical industry. Science and basic discovery research, on the other hand, are not product developments but rather organic processes that rarely benefit from strict rules, filters, and predefined notions of what is wrong or right. This is the area in which academic research excels, and this is where CBCS has its Published: December 20, 2013 2605
dx.doi.org/10.1021/cb400858v | ACS Chem. Biol. 2013, 8, 2605−2606
ACS Chemical Biology
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focus. The refinement of knowledge within disease-related biology will result in better validated protein targets, more refined disease models, and a better understanding of pathophysiology and human disease. Inevitably, this will benefit drug discovery, the pharmaceutical industry, and in the end, patients. 2. Collaboration is key. CBCS is not a CRO, nor is it a charity. Collaborating PIs are expected to be proactive participants in all projects and shoulder a portion of the costs, thus guaranteeing commitment and accountability. Additionally, fully internalizing projects would quickly deplete available resources and limit productivity. Thus, it is mandatory that all collaborating PIs contribute to the project with, at minimum, equal resources as those allocated from CBCS. CBCS maintains a core staff of about 25 individuals spread across the three nodes. However, with the network of collaborating scientists involved, the number of individuals currently working on CBCS projects is well over 100. 3. No one knows everything. As a wise man once said: “If you’re the smartest guy in the room, get a bigger room.” CBCS does not maintain a disciplinary focus toward any specific disease area, technology, or scientific philosophy. The collaborating PI is always the expert of his or her area of focus, providing an invaluable source of knowledge in the assay, technique, molecule, or cell/tissue/organism/model being studied and developed. In contrast, most academic groups are relatively unfamiliar with basic principles of microtiter-based assay formats for small-molecule screening, handling of large data sets (i.e.. informatics), and the caveats of pharmacological modulation with small molecules (i.e., medicinal chemistry, pharmacokinetics, and ADME). Thus, in the face of the profound complexity of human biology, it is essential to maintain a pragmatic, percipient, and humble communication throughout the project life-span. 4. Follow it through. In many respects due to the inadequate knowledge and capabilities on both parts mentioned above, many facilities that operate through an “open-access” philosophy or dedicate themselves to only very limited aspects of a chemical biology project quickly find their data disappearing into a “black hole” of neglect or taking undesirable turns that do not always leverage the full impact of the data generated. Thus, from the first informal meeting to the final drafts of publication, CBCS strives to remain an active partner, advisor, and contributor to project developments. In the autumn of 2013, the Karolinska Institutet node of CBCS moved into the Science for Life Laboratory in Stockholm, a collaborative effort between Stockholm University, The Royal Institute of Technology, and Karolinska Institutet aimed at advancing technology-driven, high-throughput molecular bioscience and translational medicine. In its newly furbished laboratories, CBCS will gain access to additional expertise and facilities in its arsenal of technology, including advanced genomics, proteomics, and advanced bioimaging technology. These additional capabilities will strengthen CBCS’s ability to further assist Sweden’s academia in the advancement of disease-related science and perhaps help to breathe new life into Sweden’s drug discovery industry.
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In Focus
REFERENCES
(1) Sams-Dodd, F. (2013) Is poor research the cause of the declining productivity of the pharmaceutical industry? An industry in need of a paradigm shift. Drug Discovery Today 18, 211−217. (2) Scannell, J. W., Blanckley, A., Boldon, H., and Warrington, B. (2012) Diagnosing the decline in pharmaceutical R&D efficiency. Nat. Rev. Drug Discovery 11, 191−200. (3) Pammolli, F., Magazzini, L., and Riccaboni, M. (2011) The productivity crisis in pharmaceutical R&D. Nat. Rev. Drug Discovery 10, 428−38. (4) Jorgensen, W. L. (2012) Challenges for academic drug discovery. Angew. Chem., Int. Ed., 2−7. (5) Frye, S., Crosby, M., Edwards, T., and Juliano, R. (2011) US academic drug discovery. Nat. Rev. Drug Discovery 10, 409−10. (6) Kotz, J. (2011) Small (molecule) thinking in academia. Nature 410, 409−410. (7) Smaglik, P. (2013) Swedish success story−Institutions shake off rivalries to build scientific collaborations and hire world-class talent. Nature 502, 711−712.
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dx.doi.org/10.1021/cb400858v | ACS Chem. Biol. 2013, 8, 2605−2606
