Abstract
Recent research advances in modifying and controlling DNA have created a booming field of biological engineering called synthetic biology. In synthetic biology engineers manipulate and modify living organisms to change (and produce entirely novel) functionality, which has led to new fuel sources or the ability to mitigate pollution. Synthetic biology research is also expected to lead to methods of intelligent drug delivery. In synthetic biology, designs are first built using biological programming languages and then implemented in a laboratory. These synthetic organisms can be considered living programs that will sense, respond and interact with humans while they persist in the natural environment. We argue that we should view these as safety critical devices which can be both regulated and certified. Since the synthetically engineered organisms follow a regular cycle of reproduction and replication that involves mutations, they will eventually adapt and evolve new behavior over time. In this paper we propose the use of an assurance case for synthetically engineered organisms, and present an orthogonal dimension, an assurance timeline, that can be used to reason about the dynamic, evolving aspects of these systems. We present a case study based on a real application to illustrate our ideas.
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References
Adam, L., Kozar, M., Letort, G., Mirat, O., Srivastava, A., Stewart, T., Wilson, M.L., Peccoud, J.: Strengths and limitations of the Federal guidance on synthetic DNA. Nat. Biotechol. 29(3), 208–210 (2011)
Anderson, J., Strelkowa, N., Stan, G.-B., Douglas, T., Savulescu, J., Barahona, M., Papachristodoulou, A.: Engineering and ethical perspectives in synthetic biology. EMBO Rep. 13(7), 584–590 (2012)
Attwood, K., Kelly, T.: Controlled expression for assurance case development. In: Proceedings of the 23rd Safety-Critical Systems Symposium on Engineering Systems for Safety, pp. 143–165 (2015)
Baldwin, G.: Synthetic Biology: A Primer. World Scientific, London (2016)
Benenson, Y.: Biomolecular computing systems: principles, progress and potential. Nat. Rev. Genet. 13, 455–468 (2012)
Bereza-Malcolm, L.T., Mann, G., Franks, A.E.: Environmental sensing of heavy metals through whole cell microbial biosensors: a synthetic biology approach. ACS Synth. Biol. 4(5), 535–546 (2015)
Chapman, R.: Assurance cases for external infusion pumps. U.S. Food and Drug Administration (2010). www.fda.gov/downloads/medicaldevices/newsevents/workshopsconferences/ucm219685.pdf
David, A., Larsen, K.G., Legay, A., Mikučionis, M., Poulsen, D.B., Sedwards, S.: Runtime verification of biological systems. In: Margaria, T., Steffen, B. (eds.) ISoLA 2012, Part I. LNCS, vol. 7609, pp. 388–404. Springer, Heidelberg (2012)
Denney, E., Pai, G.: A lightweight methodology for safety case assembly. In: Ortmeier, F., Lipaczewski, M. (eds.) SAFECOMP 2012. LNCS, vol. 7612, pp. 1–12. Springer, Heidelberg (2012)
Denney, E., Pai, G., Habli, I.: Dynamic safety cases for through-life safety assurance. Int. Conf. Softw. Eng. 2, 587–590 (2015)
Denney, E., Pai, G., Pohl, J.: AdvoCATE: an assurance case automation toolset. In: Ortmeier, F., Daniel, P. (eds.) SAFECOMP Workshops 2012. LNCS, vol. 7613, pp. 8–21. Springer, Heidelberg (2012)
Denney, E., Pai, G., Whiteside, I.: Formal foundations for hierarchical safety cases. In: IEEE 16th International Symposium on High Assurance Systems Engineering (HASE), pp. 52–59. IEEE (2015)
Ellis, S.J., Henderson, E.R., Klinge, T.H., Lathrop, J.I., Lutz, J.H., Lutz, R.R., Mathur, D., Miner, A.S.: Automated requirements analysis for a molecular watchdog timer. In: International conference on Automated software engineering (ASE), pp. 767–778 (2014)
Galdzicki, M., Clancy, K., Oberortner, E., Pocock, M., Quinn, J., Rodriguez, C., Roehner, N., Wilson, M., Adam, L., Anderson, J., Bartley, B., Beal, J., Chandran, D., Chen, J., Densmore, D., Endy, D., Grünberg, R., Hallinan, J., Hillson, N., Johnson, J., Kuchinsky, A., Lux, M., Misirli, G., Peccoud, J., Plahar, H., Sirin, E., Stan, G., Villalobos, A., Wipat, A., Gennari, J., Myers, C., Sauro, H.: The synthetic biology open language (SBOL) provides a community standard for communicating designs in synthetic biology. Nat. Biotechnol. 32(6), 545–550 (2014)
Graydon, P.J.: Formal assurance arguments: a solution in search of a problem? In: 45th Annual IEEE/IFIP International Conference on Dependable Systems and Networks (DSN), pp. 517–528. IEEE (2015)
Hendriks, E., van Lente, T., Raaphorst, R., Purwanto, A., Poljakova, W., Parrish, J., Daszczuk, A., Dessalegne, Y., Jo, E., Oldebesten, A., Drenth, I., Kuipers, O., Veening, J., Herber, M.: iGEM: team groningen: food warden (2012). http://2012.igem.org/Team:Groningen
Hölzl, M., Rauschmayer, A., Wirsing, M.: Engineering of software-intensive systems: state of the art and research challenges. In: Wirsing, M., Banâtre, J.-P., Hölzl, M., Rauschmayer, A. (eds.) Soft-Ware Intensive Systems. LNCS, vol. 5380, pp. 1–44. Springer, Heidelberg (2008)
iGEM Parts Registry. http://parts.igem.org/
Jaradat, O., Graydon, P., Bate, I.: An approach to maintaining safety case evidence after a system change. arXiv preprint (2014). arXiv:1404.6846
Kahl, L.J., Endy, D.: A survey of enabling technologies in synthetic biology. J. Biol. Eng. 7(1), 13 (2013)
Kelle, A.: Beyond patchwork precaution in the dual-use governance of synthetic biology. Sci. Eng. Ethics 19(3), 1121–1139 (2013)
Kelly, T., Weaver, R.: The goal structuring notation-a safety argument notation. In: Dependable Systems and Networks Workshop on Assurance Cases (2004)
Kis, Z., Pereira, H.S., Homma, T., Pedrigi, R.M., Krams, R.: Mammalian synthetic biology: emerging medical applications. J. Roy. Soc. Interface 12(106), 20141000 (2015)
LaVan, D.A., Marmon, L.M.: Safe and effective synthetic biology. Nat. Biotechnol. 28, 1010–1012 (2010)
Lee, E.J., Tabor, J.J., Mikos, A.G.: Leveraging synthetic biology for tissue engineering applications. Inflamm. Regen. 34(1), 015–022 (2014)
Lin, C.-L., Shen, W.: Generation of assurance cases for medical devices. In: Lee, R. (ed.) CIS. SCI, vol. 566, pp. 127–140. Springer, Heidelberg (2015)
Lin, H., Wu, J., Yuan, C., Luo, Y., van den Brand, M., Engelen, L.: A systematic approach for safety evidence collection in the safety-critical domain. In: Annual IEEE International on Systems Conference (SysCon), pp. 194–199. IEEE (2015)
Lutz, R.R., Lutz, J.H., Lathrop, J.I., Klinge, T.H., Mathur, D., Stull, D.M., Bergquist, T., Henderson, E.R.: Requirements analysis for a product family of DNA nanodevices. In: IEEE International Requirements Engineering Conference (RE), pp. 211–220, September 2012
Nair, S., de la Vara, J.L., Melzi, A., Tagliaferri, G., de-la-Beaujardiere, L., Belmonte, F.: Safety evidence traceability: problem analysis and model. In: Salinesi, C., Weerd, I. (eds.) REFSQ 2014. LNCS, vol. 8396, pp. 309–324. Springer, Heidelberg (2014)
Rossello, R.A., David, H.: Cell communication and tissue engineering. Commun. Integr. Biol. 3(1), 53–56 (2010)
Sarpeshkar, R.: Analog synthetic biology. Philos. Trans. A Math. Phys. Eng. Sci. 372, 20130110 (2014)
Slusarczyk, A., Lin, A., Weiss, R.: Foundations for the design and implementation of synthetic genetic circuits. Nat. Rev. Genet. 13(6), 406–420 (2012)
Sujan, M.A., Habli, I., Kelly, T.P., Pozzi, S., Johnson, C.W.: Should healthcare providers do safety cases? lessons from a cross-industry review of safety case practices. Saf. Sci. 84, 181–189 (2016)
Weinstock, C.B., Goodenough, J.B.: Cmu/sei-2009-tn-018: towards an assurance case practice for medical devices. Software Engineering Institute, Technical report, Carnegie Mellon (2009)
Whitaker, W.B., Sandoval, N.R., Bennett, R.K., Fast, A.G., Papoutsakis, E.T.: Synthetic methylotrophy: engineering the production of biofuels and chemicals based on the biology of aerobic methanol utilization. Curr. Opin. Biotechnol. 33, 165–175 (2015)
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This work was supported in part by NSF grants CCF-1161767 and MCB-1449014.
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Cohen, M.B., Firestone, J., Pierobon, M. (2016). The Assurance Timeline: Building Assurance Cases for Synthetic Biology. In: Skavhaug, A., Guiochet, J., Schoitsch, E., Bitsch, F. (eds) Computer Safety, Reliability, and Security. SAFECOMP 2016. Lecture Notes in Computer Science(), vol 9923. Springer, Cham. https://doi.org/10.1007/978-3-319-45480-1_7
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