3S - Systematic, systemic, and systems biology and toxicology

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SMIRNOVA, Lena, Nicole KLEINSTREUER, Raffaella CORVI, Andre LEVCHENKO, Suzanne C FITZPATRICK, Thomas HARTUNG, 2018. 3S - Systematic, systemic, and systems biology and toxicology. In: Alternatives to Animal Experimentation : ALTEX. 35(2), pp. 139-162. ISSN 1868-596X. eISSN 1868-8551. Available under: doi: 10.14573/altex.1804051

@article{Smirnova2018Syste-42273, title={3S - Systematic, systemic, and systems biology and toxicology}, year={2018}, doi={10.14573/altex.1804051}, number={2}, volume={35}, issn={1868-596X}, journal={Alternatives to Animal Experimentation : ALTEX}, pages={139--162}, author={Smirnova, Lena and Kleinstreuer, Nicole and Corvi, Raffaella and Levchenko, Andre and Fitzpatrick, Suzanne C and Hartung, Thomas} }

Hartung, Thomas Kleinstreuer, Nicole Smirnova, Lena 3S - Systematic, systemic, and systems biology and toxicology Fitzpatrick, Suzanne C 2018-05-08T14:15:06Z eng Levchenko, Andre Kleinstreuer, Nicole Fitzpatrick, Suzanne C Smirnova, Lena terms-of-use Corvi, Raffaella Hartung, Thomas Levchenko, Andre 2018 Corvi, Raffaella 2018-05-08T14:15:06Z A biological system is more than the sum of its parts – it accomplishes many functions via synergy. Deconstructing the system down to the molecular mechanism level necessitates the complement of reconstructing functions on all levels, i.e., in our conceptualization of biology and its perturbations, our experimental models and computer modelling.<br /><br />Toxicology contains the somewhat arbitrary subclass “systemic toxicities”; however, there is no relevant toxic insult or general disease that is not systemic. At least inflammation and repair are involved that require coordinated signaling mechanisms across the organism. However, the more body components involved, the greater the challenge to reca­pitulate such toxicities using non-animal models. Here, the shortcomings of current systemic testing and the development of alternative approaches are summarized.<br /><br />We argue that we need a systematic approach to integrating existing knowledge as exemplified by systematic reviews and other evidence-based approaches. Such knowledge can guide us in modelling these systems using bioengineering and virtual computer models, i.e., via systems biology or systems toxicology approaches. Experimental multi-organ-on-chip and microphysiological systems (MPS) provide a more physiological view of the organism, facilitating more comprehensive coverage of systemic toxicities, i.e., the perturbation on organism level, without using substitute organisms (animals). The next challenge is to establish disease models, i.e., micropathophysiological systems (MPPS), to expand their utility to encompass biomedicine. Combining computational and experimental systems approaches and the chal­lenges of validating them are discussed. The suggested 3S approach promises to leverage 21st century technology and systematic thinking to achieve a paradigm change in studying systemic effects.

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