The Academic Pill: How Academia Contributes to Curing Diseases

Abstract

This special issue of SLAS Discovery showcases academic screening centers and not-for-profit translational drug discovery centers. Historically, high-throughput screening was developed by the pharmaceutical industry and until the end of the 20th century was mainly carried out within its walls. After the sequencing of the human genome, academic institutions started creating screening centers to either find tool compounds or carry out RNA interference screens to study the genome. In 2003, the U.S. National Institutes of Health (NIH) Roadmap set out a plan for creating screening centers and chemical libraries, further strengthening the trend of academic screening.1Zerhouni E. The NIH Roadmap.Science. 2003; 302: 63Google Scholar Although many academic screening centers aim to discover tool compounds for chemical biology, an appetite has always existed for more translational projects; academic screening would hopefully produce therapeutic molecules that could be used in the clinic. The desire for novel therapeutic molecules was particularly strong for neglected and rare diseases, where a lack of economic incentive meant that therapies were not available. Like many trends, after an initial enthusiasm there came a realization that developing new drugs was challenging and that academic screening centers, while facing different difficulties compared with industrial screening laboratories, also struggled to bring drugs into the clinic. The reasons for this struggle are numerous, but I would like to underline two major reasons. First, there is a lack of funding opportunities for bringing hit compounds forward and developing lead candidates into drug candidates. Public research funds typically do not finance such work, since it is not basic research, and the projects are at too early a stage for applying for translational grants to spin out a company. It is equally hard to find pharmaceutical partners at this stage. Typically, the pharmaceutical industry invests in projects where a proof of principle has been obtained in animals, and the effects of the molecule of interest are better understood. Second, academic screening centers typically lack the infrastructure to host, curate, and process very large, high-quality chemical collections. Given the importance of the quality of compounds entering the screening process, it is perhaps not surprising that many projects did not materialize into lead molecules that could be brought forward into the clinic. To fill the gap between academic research and drug development, translational drug discovery centers were established. These centers were created to help bridge academia and industry; to have the critical mass in terms of people, instruments, compounds, and chemistry; and to form private–public partnerships (PPPs) to bring innovative compounds forward into the clinic. This special issue of SLAS Discovery offers a snapshot of the research being conducted in academic screening laboratories and in translational drug discovery centers. We invited many centers to contribute and 15 laboratories answered the call. As to be expected, the 15 manuscripts submitted cover a wide range of topics. The first three manuscripts, by Franke et al.,2Franke R. Hinkelmann B. Fetz V. et al.xCELLanalyzer: A Framework for the Analysis of Cellular Impedance Measurements for Mode of Action Discovery.SLAS Discov. 2019; 24: 213-223Google Scholar Warchal et al.,3Warchal S.J. Dawson J.C. Carragher N.O. Evaluation of Machine Learning Classifiers to Predict Compound Mechanism of Action When Transferred across Distinct Cell Lines.SLAS Discov. 2019; 24: 224-233Google Scholar and Janosch et al.,4Janosch A. Kaffka C. Bickle M. Unbiased Phenotype Detection Using Negative Controls.SLAS Discov. 2019; 24: 234-241Google Scholar describe analytical methods for phenotypic profiling of cellular responses. Using phenotypic signatures for discovering the mode of action of compounds is a very active research field, and it is not surprising