Acta Biotheoretica

, Volume 67, Issue 1, pp 1–18 | Cite as

Design Methodologies and the Limits of the Engineering-Dominated Conception of Synthetic Biology

  • Tero IjäsEmail author
Regular Article


Synthetic biology is described as a new field of biotechnology that models itself on engineering sciences. However, this view of synthetic biology as an engineering field has received criticism, and both biologists and philosophers have argued for a more nuanced and heterogeneous understanding of the field. This paper elaborates the heterogeneity of synthetic biology by clarifying the role of design and the variability of design methodologies in synthetic biology. I focus on two prominent design methodologies: rational design and directed evolution. Rational design resembles the design methodology of traditional engineering sciences. However, it is often replaced and complemented by the more biologically-inspired method of directed evolution, which models itself on natural evolution. These two approaches take philosophically different stances to the design of biological systems. Rational design aims to make biological systems more machine-like, whereas directed evolution utilizes variation and emergent features of living systems. I provide an analysis of the methodological basis of these design approaches, and highlight important methodological differences between them. By analyzing the respective benefits and limitations of these approaches, I argue against the engineering-dominated conception of synthetic biology and its “methodological monism”, where the rational design approach is taken as the default design methodology. Alternative design methodologies, like directed evolution, should be considered as complementary, not competitive, to rational design.


Synthetic biology Engineering Design Rational design Directed evolution 


  1. Agapakis CM (2014) Designing synthetic biology. ACS Synth Biol 3(3):121–128. CrossRefGoogle Scholar
  2. Agapakis CM, Silver PA (2009) Synthetic biology: exploring and exploiting genetic modularity through the design of novel biological networks. Mol Biosyst 5(7):704–713. CrossRefGoogle Scholar
  3. Andrianantoandro E, Basu S, Karig DK, Weiss R (2006) Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol 2:1–14. CrossRefGoogle Scholar
  4. Arkin AP, Fletcher DA (2006) Fast, cheap and somewhat in control. Genome Biol 7(8):114. CrossRefGoogle Scholar
  5. Bechtel W, Richardson RC (1993) Discovering complexity: decomposition and localization as strategies in scientific research. Princeton University Press, PrincetonGoogle Scholar
  6. Blake WJ, Isaacs FJ (2004) Synthetic biology evolves. Trends Biotechnol 22(7):321–324. CrossRefGoogle Scholar
  7. Boudry M, Pigliucci M (2013) The mismeasure of machine: synthetic biology and the trouble with engineering metaphors. Stud Hist Philos Biol Biomed Sci 44(4):660–668CrossRefGoogle Scholar
  8. Bujara M, Panke S (2010) Engineering in complex systems. Curr Opin Biotechnol 21(5):586–591. CrossRefGoogle Scholar
  9. Cambray G, Mutalik VK, Arkin AP (2011) Toward rational design of bacterial genomes. Curr Opin Microbiol 14(5):624–630. CrossRefGoogle Scholar
  10. Cameron DE, Bashor CJ, Collins JJ (2014) A brief history of synthetic biology. Nat Rev Microbiol 12(5):381–390. CrossRefGoogle Scholar
  11. Cardinale S, Arkin AP (2012) Contextualizing context for synthetic biology—identifying causes of failure of synthetic biological systems. Biotechnol J 7(7):856–866. CrossRefGoogle Scholar
  12. Craver CF (2007) Explaining the brain: mechanisms and the mosaic unity of neuroscience. Oxford University Press, OxfordCrossRefGoogle Scholar
  13. Dougherty MJ, Arnold FH (2009) Directed evolution: new parts and optimized function. Curr Opin Biotechnol 20(4):486–491. CrossRefGoogle Scholar
  14. Elowitz MB, Leibler S (2000) A synthetic oscillatory network of transcriptional regulators. Nature 403(6767):335–338. CrossRefGoogle Scholar
  15. Endy D (2005) Foundations for engineering biology. Nature 438(7067):449–453. CrossRefGoogle Scholar
  16. ERASynBio (2014) Next steps for European synthetic biology: a strategic vision from ERASynBio. Technical report, ERASynBio/European CommissionGoogle Scholar
  17. François P, Hakim V (2004) Design of genetic networks with specified functions by evolution in silico. PNAS 101(2):580–585. CrossRefGoogle Scholar
  18. Giese B, Koenigstein S, Wigger H, Schmidt JC, von Gleich A (2013) Rational engineering principles in synthetic biology: a framework for quantitative analysis and an initial assessment. Biol Theory 8(4):324–333. CrossRefGoogle Scholar
  19. Guimaraes JC, Liu CC, Arkin AP (2013) From biological parts to circuit design. In: Zhao H (ed) Synthetic biology: tools and applications. Elsevier, Amsterdam, pp 63–78CrossRefGoogle Scholar
  20. Güttinger S (2013) Creating parts that allow for rational design: synthetic biology and the problem of context-sensitivity. Stud Hist Philos Biol Biomed Sci 44(2):199–207. CrossRefGoogle Scholar
  21. Haseltine EL, Arnold FH (2007) Synthetic gene circuits: design with directed evolution. Annu Rev Biophys Biomed 36:1–19. CrossRefGoogle Scholar
  22. Heinemann M, Panke S (2006) Synthetic biology—putting engineering into biology. Bioinformatics 22(22):2790–2799. CrossRefGoogle Scholar
  23. Heinemann M, Panke S (2009) Synthetic biology: putting engineering into bioengineering. In: Fu P, Panke S (eds) Systems biology and synthetic biology. Wiley, New York, pp 387–409CrossRefGoogle Scholar
  24. Holm S (2015) Is synthetic biology mechanical biology? Hist Philos Life Sci 37(4):413–429. CrossRefGoogle Scholar
  25. Houkes W, Vermaas PE (2010) Technical functions: on the use and design of artefacts. Springer, DordrechtCrossRefGoogle Scholar
  26. Hutchison CA, Chuang RY, Noskov VN, Assad-Garcia N, Deerinck TJ, Ellisman MH, Gill J, Kannan K, Karas BJ, Ma L, Pelletier JF, Qi ZQ, Richter RA, Strychalski EA, Sun L, Suzuki Y, Tsvetanova B, Wise KS, Smith HO, Glass JI, Merryman C, Gibson DG, Venter JC (2016) Design and synthesis of a minimal bacterial genome. Science 351(6253):aad6280. CrossRefGoogle Scholar
  27. Jäckel C, Kast P, Hilvert D (2008) Protein design by directed evolution. Annu Rev Biophys 37:153–173. CrossRefGoogle Scholar
  28. Knuuttila T, Loettgers A (2013a) Basic science through engineering? synthetic modeling and the idea of biology-inspired engineering. Stud Hist Philos Biol Biomed Sci 44(2):158–169. CrossRefGoogle Scholar
  29. Knuuttila T, Loettgers A (2013b) Synthetic modeling and mechanistic account: material recombination and beyond. Philos Sci 80(5):874–885. CrossRefGoogle Scholar
  30. Knuuttila T, Loettgers A (2014) Varieties of noise: analogical reasoning in synthetic biology. Stud Hist Philos Sci 48:76–88. CrossRefGoogle Scholar
  31. Kroes P (2012) Technical artefacts: creations of mind and matter—a philosophy of engineering design. Springer, HeidelbergCrossRefGoogle Scholar
  32. Kuorikoski J, Pöyhönen S (2013) Understanding nonmodular functionality: lessons from genetic algorithms. Philos Sci 80(5):637–649. CrossRefGoogle Scholar
  33. Lewens T (2013) From bricolage to biobricks™: synthetic biology and rational design. Stud Hist Philos Biol Biomed Sci 44(4):641–648. CrossRefGoogle Scholar
  34. Marguet P, Balagadde F, Tan C, You L (2007) Biology by design: reduction and synthesis of cellular components and behaviour. J R Soc Interface 4(15):607–623. CrossRefGoogle Scholar
  35. Marliere P (2009) The farther, the safer: a manifesto for securely navigating synthetic species away from the old living world. Syst Synth Biol 3(1–4):77. CrossRefGoogle Scholar
  36. Oftedal G, Parkkinen VP (2013) Synthetic biology and genetic causation. Stud Hist Philos Biol Biomed Sci 44(2):208–216. CrossRefGoogle Scholar
  37. O’Malley M (2011) Exploration, iterativity and kludging in synthetic biology. Comptes Rendus Chim 14(4):406–412. CrossRefGoogle Scholar
  38. O’Malley M, Powell A, Davies JF, Calvert J (2007) Knowledge-making distinctions in synthetic biology. Bioessays 30(1):57–65. CrossRefGoogle Scholar
  39. Packer MS, Liu DR (2015) Methods for the directed evolution of proteins. Nat Rev Genet 16(7):379–394. CrossRefGoogle Scholar
  40. Porcar M (2010) Beyond directed evolution: darwinian selection as a tool for synthetic biology. Syst Synth Biol 4(1):1–6. CrossRefGoogle Scholar
  41. Porcar M, Peretó J (2016) Nature versus design: synthetic biology or how to build a biological non-machine. Integr Biol 8(4):451–455. CrossRefGoogle Scholar
  42. Purnick PEM, Weiss R (2009) The second wave of synthetic biology: from modules to systems. Nat Rev Mol Cell Biol 10(6):410–422. CrossRefGoogle Scholar
  43. Romero PA, Arnold FH (2009) Exploring protein fitness landscapes by directed evolution. Nat Rev Mol Cell Biol 10(12):866–876. CrossRefGoogle Scholar
  44. Roosth S (2017) Synthetic: how life got made. University of Chicago Press, ChicagoCrossRefGoogle Scholar
  45. Schmidt M (2010) Xenobiology: a new form of life as the ultimate biosafety tool. Bioessays 32(4):322–331. CrossRefGoogle Scholar
  46. Schmidt JC (2015) Synthetic biology as late-modern technology. In: Giese B, Pade C, Wigger H, von Gleich A (eds) Synthetic biology, risk engineering. Springer, Heidelberg, pp 1–30Google Scholar
  47. Simon HA (1996) The sciences of the artificial, 3rd edn. MIT Press, CambridgeGoogle Scholar
  48. Torres L, Krüger A, Csibra E, Gianni E, Pinheiro VB (2016) Synthetic biology approaches to biological containment: pre-emptively tackling potential risks. Essays Biochem 60(4):393–410. CrossRefGoogle Scholar
  49. Wagner A (2005) Robustness and evolvability in living systems. Princeton University Press, PrincetonGoogle Scholar
  50. Wimsatt WC (2007) Re-engineering philosophy for limited beings: piecewise approximations to reality. Harvard University Press, CambridgeGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Practical PhilosophyUniversity of HelsinkiHelsinkiFinland

Personalised recommendations