Editorial pubs.acs.org/crt
Systems Toxicology II: A Special Issue momentum gathered in the field, its cutting-edge approaches, and the potential benefit to real-world risk assessments and the efficient protection of human health suggest they have potential to blossom if cultivated. We hope that activities such as the Systems Toxicology meetings and the ensuing special issue will raise awareness of the state of the science and the need to continue support for this field to realize such advances. The research presented in the Systems Toxicology II issue includes studies involving perturbations of biological pathways and biomarker identification. Multiomics data collections using human primary cells, cell lines, stem cells, and animal models are used in the research described in the issue, including investigation of disturbances in gut microbiome development. Among the toxicological processes explored are oxidative stress, DNA damage, steroid receptor activation, and even complex physiological processes such as secondary palate fusion. Finally, important concepts center on understanding the transition from adaptive responses to adverse effects. These articles address highly relevant topics in toxicology and set the stage for the further growth of efforts in Systems Toxicology.
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n this issue, Chemical Research in Toxicology ventures for the second time to gather a collection of articles around the topic of Systems Toxicology. The field has emerged as a result of the dramatic shift of modern Toxicology to identify and understand biological perturbations from a molecular perspective, with the goal of establishing a predictive basis for promoting chemical safety. The first Systems Toxicology special issue published in 2014 included diverse examples of current research and ideas driving the science forward. It presented new high-content bioanalysis strategies and cellbased test systems, data curation, analysis, and integration strategies to enable the solution of mechanistic network models to describe toxicity pathways. As the field has moved forward, the contributions to the Systems Toxicology II issue contained herein strive to take a further step toward better integrating multidisciplinary facets: gathering large sets of experimental data by high-dimensionality bioanalytical technologies, creating and solving mathematical models to describe these large data sets, and assessing the quality of the model by comparing predictions with experimental data. The Systems Toxicology special issues have originated from the International Systems Toxicology meetings held in Switzerland in 2013 and 2016. ACS Publications and Chemical Research in Toxicology were supporters of these meetings, and the theme of the 2016 meeting was Real World Applications and Opportunities. The objectives were to discuss real-world examples of how systems toxicology can be applied to elucidate toxic modes of action and influence realistic exposure and biological impact assessments, learn how experimental and computational elements can be integrated in systems toxicology-based approaches, and reveal recent advances in complementary and multidisciplinary research areas with the potential to enhance further developments and applications of Systems Toxicology. From the presentations at the Systems Toxicology meeting and the research articles that make up the Systems Toxicology II special issue, emerge a daunting but encouraging view. It demonstrates how far the science has progressed, yet showing considerable limitations that remain. While bioanalysis capabilities have exploded, it becomes evident that the quality and reproducibility of data, as well as the biological relevance of model systems, require careful attention. Ideally, systems toxicology studies involve experimentation at multiple levels of biological organization using a variety of bioanalytical techniques over scales of both dose and time in order to reveal the full spectrum of chemical−biological interactions. This idealized view is counterbalanced by the sheer complexity of such studies, difficulties of interdisciplinary research, and funding requirements to support such endeavors. Even with a solid experimental protocol and good data in hand, the capacity to make sense of large data sets by understanding biological pathways and establishing quantitative models can often fall short, and perhaps most neglected is the systematic validation of such predictive models. Thus, advanced and comprehensive system toxicology studies remain rare. Nonetheless, the © 2017 American Chemical Society
Thomas Hartung† Robert Kavlock‡ Shana J. Sturla*,§
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† Center for Alternatives to Animal Testing (CAAT), Johns Hopkins University, Baltimore, Maryland 21205, United States ‡ Office of Research and Development, United States Environmental Protection Agency, Washington, D.C. 20460, United States § Department of Health Sciences and Technology, ETH Zürich, Zürich 8092, Switzerland
AUTHOR INFORMATION
Corresponding Author
*Department of Health Sciences and Technology, ETH Zürich, Schmelzbergstrasse 9, Zürich 8092, Switzerland. Phone: +41 44 632 32 98. E-mail:
[email protected]. ORCID
Thomas Hartung: 0000-0003-1359-7689 Shana J. Sturla: 0000-0001-6808-5950 Notes
Views expressed in this editorial are those of the authors and not necessarily the views of the ACS. The views expressed in this editorial are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency.
Special Issue: Systems Toxicology II Published: April 17, 2017 869
DOI: 10.1021/acs.chemrestox.7b00038 Chem. Res. Toxicol. 2017, 30, 869−869
