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Biological Theory

, Volume 4, Issue 4, pp 378–389 | Cite as

Making Knowledge in Synthetic Biology: Design Meets Kludge

Article

Abstract

Synthetic biology is an umbrella term that covers a range of aims, approaches, and techniques. They are all brought together by common practices of analogizing, synthesizing, mechanicizing, and kludging. With a focus on kludging as the connection point between biology, engineering, and evolution, I show how synthetic biology’s successes depend on custom-built kludges and a creative, “make-it-work” attitude to the construction of biological systems. Such practices do not fit neatly, however, into synthetic biology’s celebration of rational design. Nor do they straightforwardly embody Richard Feynman’s “last blackboard” statement (1988) that without creating something it cannot be understood. Reflecting further on the relationship between synthetic construction and knowledge making gives philosophy of science new avenues of insight into scientific practice.

Keywords

construction design engineering kludging scientific knowledge synthetic biology systems biology 

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References

  1. Alon U (2007) Simplicity in biology. Nature 446: 497.Google Scholar
  2. Andrianantoandro E, Basu S, Karig DK, Weiss R (2006) Synthetic biology: New engineering rules for an emerging discipline. Molecular Systems Biology 2: 2006.0028. Doi:  10.1038/msb4100073 Google Scholar
  3. Arkin A (2008) Setting the standard in synthetic biology. Nature Biotechnology 26:771–774.Google Scholar
  4. Arkin AP, Fletcher DA (2006) Fast, cheap and somewhat in control. Genome Biology 7: 114. Doi:  10.1186/gb-2006-7-8-114 Google Scholar
  5. Auffray C, Imbeaud S, Roux-Rouquie M, Hood L (2003) From functional genomics to systems biology: Concepts and practices. Comptes Rendus Biologies 326: 879–892.Google Scholar
  6. Bamford G (1993) Popper’s explications of ad hocness: Circularity, empirical content, and scientific practice. British Journal for the Philosophy of Science 44: 335–355.Google Scholar
  7. Barrett CL, Kim TY, Kim HU, Palsson BØ, Lee SY (2006) Systems biology as a foundation for genome-scale synthetic biology. Current Opinion in Biotechnology 17: 1–5.Google Scholar
  8. Becskei A, Serrano L (2000) Engineering stability in gene networks by autoregulation. Nature 405: 590–593.Google Scholar
  9. Benner SA, Sismour AM (2005) Synthetic biology. Nature Reviews Genetics 6: 533–543.Google Scholar
  10. Blake WJ, Issacs FJ (2004) Synthetic biology evolves. Trends in Biotechnology 22: 321–324.Google Scholar
  11. Blake WJ, Kaern M, Cantor CR, Collins JJ (2003) Noise in eukaryotic gene expression. Nature 422: 633–637.Google Scholar
  12. Botstein D (2004) Ira Herskowitz: 1946–2003. Genetics 166: 653–660.Google Scholar
  13. Boyle PM, Silver PA (2009) Harnessing nature’s toolbox: Regulatory elements for synthetic biology. Journal of the Royal Society Interface 6 (Suppl. 4): S535–S546.Google Scholar
  14. Breithaupt H (2006) The engineer’s approach to biology. EMBO Reports 7: 21–24.Google Scholar
  15. Brent R (2000) Genomic biology. Cell 100: 169–183.Google Scholar
  16. Çaǧatay T, Turcotte M, Elowitz MB, Garcia-Ojalvo J, Süel GM (2009) Architecture-dependent noise discriminates functionally analogous differentiation circuits. Cell 139: 512–522.Google Scholar
  17. Canton B, Labno A, Endy D (2008) Refinement and standardization of synthetic biological parts and devices. Nature Biotechnology 26: 787–793.Google Scholar
  18. Cello J, Paul AV, Wimmer E (2002). Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template. Science 297: 1016–1018.Google Scholar
  19. Chan LY, Kosuri S, Endy D (2005) Refactoring bacteriophage T7. Molecular Systems Biology 1:2005.0018. Doi:  10.1038/msb4100025 Google Scholar
  20. Chatterjee R, Yuan L (2006) Directed evolution of metabolic pathways. Trends in Biotechnology 24: 28–38.Google Scholar
  21. Church GM (2005) From systems to synthetic biology. Molecular Systems Biology 1: 2005. 0032 Doi: 10.1038/msb4100007 Google Scholar
  22. Costelloe T (2008) Giambattista Vico. Stanford Encyclopedia of Philosophy. http://plato.stanford.edu/entries/vico/
  23. Creager ANH, Lunbeck E, Wise MN, eds (2007) Science Without Laws: Model Systems, Cases, Exemplary Narratives. Durham, NC: Duke University Press.Google Scholar
  24. de Lorenzo V, Danchin A (2008) Synthetic biology: Discovering new worlds and new words. EMBO Reports 9: 822–827.Google Scholar
  25. de Regt HW, Leonelli S, Eigner K, eds (2009) Scientific Understanding: Philosophical Perspectives. Pittsburgh: University of Pittsburgh Press.Google Scholar
  26. Deamer D (2005) A giant step towards artificial life? Trends in Biotechnology 23: 336–338.Google Scholar
  27. Deamer D (2009) On the origin of systems: Systems biology, synthetic biology and the origin of life. EMBO Reports 10 (special issue): S1–S4.Google Scholar
  28. Delbrück M (1979) Interview with Max Delbrück. Oral history project, California Institute of Technology Archives, CA. http://oralhistories.library.caltech.edu/16/ Google Scholar
  29. Drubin DA, Way JC, Silver PA (2007) Designing biological systems. Genes and Development 21: 242–254.Google Scholar
  30. Dueber JE, Wu GC, Malmirchegini GR, Moon TS, Petzold CJ, Ullal AV, Prather KLJ, Keasling JD (2009) Synthetic protein scaffolds provide modular control over flux through an engineered metabolic pathway. Nature Biotechnology 27: 753–759.Google Scholar
  31. Eldar A, Chary VK, Xenopoulos P, Fonts ME, Losón OC, Dworkin J, Piggot PJ, Elowitz MB (2009) Partial penetrance facilitates developmental evolution in bacteria. Nature 460: 510–514.Google Scholar
  32. Ellis T, Wang X, Collins JJ (2009) Diversity-based, model-guided construction of synthetic networks with predicted functions. Nature Biotechnology 27: 465–471.Google Scholar
  33. Elowitz MB, Leibler S (2000) A synthetic oscillatory network of transcriptional regulators. Nature 403: 335–338.Google Scholar
  34. Elowitz MB, Levine AJ, Siggia ED, Swain PS (2002) Stochastic gene expression in a single cell. Science 297: 1183–1186.Google Scholar
  35. Endy D (2005) Foundations for engineering biology. Nature 438: 449–453.Google Scholar
  36. Endy D (2006) Synthetic biology Life 2.0. The Economist http://www.economist.com/science/displaystory.cfm?storyJd=7854314
  37. Endy D (2008) Synthetic biology: Can we make biology easy to engineer? Industrial Biotechnology 4: 340–351.Google Scholar
  38. Ferber D (2004) Microbes made to order. Science 303: 158–161.Google Scholar
  39. Feynman RP (1965) The Character of Physical Law. London: BBC.Google Scholar
  40. Feynman RP (1986) Personal observations on the reliability of the shuttle. In: Report of the Presidential Commission on the Space Shuttle Challenger Accident. Vol 2, Appendix F. http://history.nasa.gov/rogersrep/v2appf.htm
  41. Feynman RP (1988) Last blackboard. Photo ID 1.10-29. http://www.archives.caltech.edu
  42. Feynman RP as told to Leighton R (1988) What Do You Care What Other People Think? Further Adventures of a Curious Character. New York: Norton.Google Scholar
  43. Forster AC, Church GM (2006) Towards synthesis of a minimal cell. Molecular Systems Biology 2: 45. Doi: 10.1038/msb4100090 Google Scholar
  44. Forster MR (2007) A philosopher’s guide to empirical success. Philosophy of Science 74: 588–600.Google Scholar
  45. Francois P, Hakim V (2004) Design of genetic networks with specified functions by evolution in silico. Proceedings of the National Academy of Science of the USA 101: 580–585.Google Scholar
  46. Gardner TS, Cantor CR, Collins JJ (2000) Construction of a genetic toggle switch in Escherichia coli. Nature 403: 339–342.Google Scholar
  47. Gil R, Silva FJ, Peretó J, Moya A (2004) Determination of the core of a minimal bacterial gene set. Microbiology and Molecular Biology Reviews 68: 518–537.Google Scholar
  48. Glass JI, Assad-Garcia N, Alperovich N, Yooseph S, Lewis MR, Maruf M, Hutchinson CA3, Smith HO, Venter JC (2006) Essential genes of a minimal bacterium. Proceedings of the National Academy of Sciences USA 103: 425–430.Google Scholar
  49. Goodwin W (2009) Global climate modeling as applied science. Paper presented at Models and Simulations 3, Charlottesville, Virginia: March 5–7, 2009. http://philsci-archive.pitt.edu/archive/00004517/
  50. Gould SJ (1997) The exaptive excellence of spandrels as a term and prototype. Proceedings of the National Academy of Sciences USA 94: 10750–10755.Google Scholar
  51. Gould SJ, Vrba ES (1982) Exaptation: A missing term in the science of form. Paleobiology 8: 4–15.Google Scholar
  52. Granholm JW (1962) How to design a kludge. Datamation (Feb). http://neil.franMin.ch/Jokes_and_Fun/Kludge.html
  53. Grinnell F (2009) Discovery in the lab: Plato’s paradox and Delbrück’s principle of limited sloppiness. FASEB Journal 23: 7–9.Google Scholar
  54. Guet CC, Elowitz MB, Hsing W, Leibler S (2002) Combinatorial synthesis of genetic networks. Science 296: 1466–1470.Google Scholar
  55. Guido NJ, Wang X, Adalsteinsson D, McMillen D, Hasty J, Cantor CR, Elston TC, Collins JJ (2006) A bottom-up approach to gene regulation. Nature 439: 856–860.Google Scholar
  56. Gunawardena J (2008) Programming with models. Paper presented at Modelling Complex Biological Systems in the Context of Genomics, Lille Spring School, Villeneuve d’Ascq, France: April 7–11, 2008. http://epigenomique.free.fr/LILLE_08/en/index.php
  57. Hartwell LH, Hopfield JJ, Leibler S, Murray AW (1999) From molecular to modular biology. Nature 402 (Suppl.): C47–C52.Google Scholar
  58. Haseltine EL, Arnold FH (2007) Synthetic gene circuits: Design with directed evolution. Annual Review of Biophysical and Biomolecular Structure 36: 1–19.Google Scholar
  59. Heinemann M, Panke S. 2006. Synthetic biology: Putting engineering into biology. Bioinformatics 22: 2790–2799.Google Scholar
  60. Henkel J, Maurer SM (2007) The economics of synthetic biology. Molecular Systems Biology 3: 117. Doi: 10.1038/msb4100161 Google Scholar
  61. Hold C, Panke S (2009) Towards the engineering of in vitro systems. Journal of the Royal Society Interface 6 (Suppl. 4): S507–S521.Google Scholar
  62. Huang S, Wikswo J (2006) Dimensions of systems biology. Reviews of Physiology, Biochemistry and Pharmacology 157: 81–104.Google Scholar
  63. Isalan M, Lemerle C, Michalodimitrakis K, Horn C, Beltrao P, Raineri E, Garriga-Canut M, Serrano L (2008) Evolvability and hierarchy in rewired bacterial networks. Nature 452: 840–845.Google Scholar
  64. Issacs FJ, Dwyer DJ, Collins JJ (2006) RNA synthetic biology. Nature Biotechnology 24: 545–554.Google Scholar
  65. Jan YN, Jan LY (1998) Serendipity, the principle of limited sloppiness, and neural development. International Journal of Developmental Biology 42: 531–533.Google Scholar
  66. Katsnelson A (2009) Brick by brick. The Scientist 23(2): 42–47.Google Scholar
  67. Keasling JD (2008) Synthetic biology for synthetic chemistry. ACS Chemical Biology 3: 64–76.Google Scholar
  68. Keizer G (2009) Microsoft plans monster Patch Tuesday next week. http://www.computerworld.com/s/article/9139155/Microsoft_plan_monster_Patch_Tuesday_next_week
  69. Khosla C, Keasling JD (2003) Metabolic engineering for drug discovery and development Nature Reviews Drug Discovery 2: 1019–1026Google Scholar
  70. Knight T (2003) Idempotent vector design for standard assembly of biobricks MIT Synthetic Biology Working Group http://dspace.mit.edu/handle/1721.1/21168
  71. Koide T, Pang WL, Baliga NS (2009) The role of predictive modelling in rationally re-engineering biological systems Nature Reviews Microbiology 7: 297–305Google Scholar
  72. Koopman P, Hoffman RR (2003) Work-arounds, make-work and kludges IEEE Intelligent Systems (Nov/Dec): 70–75Google Scholar
  73. Koyabashi H, Kærn M, Araki M, Chung K, Gardner TS, Cantro CR, Collins JJ (2004) Programmable cells: Interfacing natural and engineered gene networks Proceedings of the National Academy of Sciences USA 101: 8414–8419.Google Scholar
  74. Lakatos I (1968–9) Criticism and the methodology of scientific research programmes. Proceedings of the Aristotelian Society 69: 149–186.Google Scholar
  75. Lartigue C, Glass JI, Alperovich N, Pieper R, Parmar PP, Hutchinson II CA, Smith HO, Venter JC (2007) Genome transplantation in bacteria: Changing one species to another. Science 317: 632–638.Google Scholar
  76. Lartigue C, Vashee S, Algire MA, Chuang R-Y, Benders GA, Ma L, Noskov VN, Denisova EA, Gibson DG, Assad-Garcia N, et al. (2009) Creating bacterial strains from genomes that have been cloned and engineered in yeast. Science 325: 1693–1696.Google Scholar
  77. Lazebnik Y (2002) Can a biologist fix a radio? Or what I learned while studying apoptosis. Cancer Cell 2: 179–182.Google Scholar
  78. Leffall J (2009) What Patch Tuesday’s patchy record means. http://mcpmag.com/articles/2009/10/19/patch-tuesday-patchy-record.aspx
  79. Lenhard J, Winsberg E (forthcoming) Holism and entrenchment in climate modelling. http://www.cas.usf.edu/∼ewinsb/papers.html
  80. Linden DJ (2007) The Accidental Mind: How Brain Evolution Has Given Us Love, Memory, Dreams, and God. Cambridge, MA: Harvard University Press.Google Scholar
  81. Loettgers A (2009) Synthetic biology and the emergence of a dual meaning of noise. Biological Theory 4: 340–356.Google Scholar
  82. Luisi PL, Ferri F, Stano P (2006) Approaches to semi-synthetic minimal cells: A review. Naturwissenschaften 93: 1–13.Google Scholar
  83. Marcus G (2008) Kluge: The Haphazard Evolution of the Human Mind. NY: Houghton Mifflin.Google Scholar
  84. Marguet P, Balagadde F, Tan C, You L (2007) Biology by design: Reduction and synthesis of cellular components and behaviour. Journal of the Royal Society Interface 4(15): 607–623.Google Scholar
  85. Martin VJJ, Pitera DJ, Withers ST, Newman JD, Keasling JD (2003) Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nature Biotechnology 21: 796–802.Google Scholar
  86. Mazia D (1953) Letter to Joshua Lederberg, October 23. The Joshua Lederberg Papers, National Library of Medicine. http://profiles.nlm.nih.gov/BB/A/K/T/N/
  87. Michalodimitrakis K, Isalan M (2008) Engineering prokaryotic gene circuits. FEMS Microbiology Reviews 33: 27–37.Google Scholar
  88. Miner RC (1998) Verum-factum and practical wisdom in the early writings of Giambattista Vico. Journal of the History of Ideas 59: 53–73.Google Scholar
  89. Minty JJ, Varedi KSM, Lin XN (2009) Network benchmarking: A happy marriage between systems and synthetic biology. Chemistry and Biology 16: 239–241.Google Scholar
  90. Morange M (2009) A new revolution? EMBO Reports 10 (special issue), S50–S553.Google Scholar
  91. Mukherji S, van Oudenaarden A (2009) Synthetic biology: Understanding biological design from synthetic circuits. Nature Reviews Genetics 10: 859–871.Google Scholar
  92. Muntendam R, Melillo E, Ryden A, Kayser O (2009) Perspectives and limits of engineering the isoprenoid metabolism in heterologous hosts. Applied Microbiology and Biotechnology 84: 1003–1019.Google Scholar
  93. NEST (New and Emerging Science and Technology), European Community (2005) Synthetic biology: Applying Engineering to Biology. Brussels: European Commission Directorate General for Research. http://www.univ-poitiers.fr/recherche/documents/pcrdt7/syntheticbiology.pdf Google Scholar
  94. Nicolaou KC, Vourloumis D, Winssinger N, Baran PS (2000) The art and science of total synthesis at the dawn of the twenty-first century. Angewandte Chemie (International Edition) 39: 44–122.Google Scholar
  95. Nielsen J (2001) Metabolic engineering. Applied Microbiology and Biotechnology 55: 263–283.Google Scholar
  96. Noireaux V, Bar-Ziv R, Godefroy J, Salman H, Libchaber A (2005) Toward an artificial cell based on gene expression in vesicles. Physical Biology 2: 1–8.Google Scholar
  97. O’Malley MA, Dupre J (2005) Fundamental issues in systems biology. BioEssays 27: 1270–1776.Google Scholar
  98. O’Malley MA, Powell A, Davies JF, Calvert J (2008) Knowledge-making distinctions in synthetic biology. BioEssays 30: 57–65.Google Scholar
  99. Oransky I (2008) Seymour Benzer. The Lancet 371: 24.Google Scholar
  100. Paulsson J (2004) Summing up the noise in gene networks. Nature 427: 415–418.Google Scholar
  101. Peccoud J, Blauvelt MF, Cai Y, Cooper KL, Crasta O, DeLalla EC, Evans C, Folkerts O, Lyons BM, Mane SP, Shelton R, Sweede MA, Waldon SA (2008) Targeted development of registries of biological parts. PLoS One 3(7): e2671. Doi: 10.1371/journal.pone.0002671.Google Scholar
  102. Pleiss J (2006) The promise of synthetic biology. Applied Microbiology and Biotechnology 73: 735–739.Google Scholar
  103. Popper KR (1963) Conjectures and Refutations: The Growth of Scientific Knowledge. London: Routledge.Google Scholar
  104. Pósfai G, Plunkett III G, Fehér T, Frisch D, Keil GM, Umenhoffer K, Kolisnychenko V, Stahl B, Sharma SS, de Arruda M, Burland V, Harcum SW, Blattner FR (2006) Emergent properties of reduced-genome Escherichia coli. Proceedings of the National Academy of Sciences USA 312: 1044–1046.Google Scholar
  105. Powell A, O’Malley MA, Müller-Wille SEW, Calvert J, Dupré J (2007) Disciplinary baptisms: A comparison of the naming stories of genetics, molecular biology, genomics and systems biology. History and Philosophy of the Life Sciences 29: 5–32.Google Scholar
  106. Prather KLJ, Martin CH (2008) De novo biosynthetic pathways: Rational design of microbial chemical factories. Current Opinion in Biotechnology 19: 468–474.Google Scholar
  107. Purnick PEM, Weiss R (2009) The second wave of synthetic biology: From modules to systems. Nature Reviews Molecular Cell Biology 10: 410–422.Google Scholar
  108. Radder H, ed (2003) The Philosophy of Scientific Experimentation. Pittsburgh: University of Pittsburgh Press.Google Scholar
  109. Raj A, van Oudenaarden A (2008) Nature, nurture, or chance: Stochastic gene expression and its consequences. Cell 135: 216–226.Google Scholar
  110. Ro D-K, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J et al. (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440: 940–943.Google Scholar
  111. Root-Bernstein RS (1989) How scientists really think. Perspectives in Biology and Medicine 32: 472–488.Google Scholar
  112. Serrano L (2007) Synthetic biology: Promises and challenges. Molecular Systems Biology 3: 158. Doi: 10.1038/msb4100202 Google Scholar
  113. Shetty RP, Endy D, Knight TF Jr (2008) Engineering BioBrick vectors from BioBrick parts. Journal of Biological Engineering 2:5. Doi: 10.1186/1754-1611-2-5 Google Scholar
  114. Simpson ML (2004) Rewiring the cell: Synthetic biology moves towards higher functional complexity. Trends in Biotechnology 22: 555–557.Google Scholar
  115. Smith HO, Hutchinson III CA, Pfanndoch C, Venter JC (2003) Generating a synthetic genome by whole genome assembly: ΦX174 bacteriophage from synthetic oligonucleotides. Proceedings of the National Academy of Sciences USA 100: 15440–15445.Google Scholar
  116. Sole RV, Munteanu A, Rodríguez-Caso C, Macia J (2007) Synthetic protocell biology: From reproduction to computation. Philosophical Transactions of the Royal Society London B 362: 1727–39.Google Scholar
  117. Sorger P (2005) A reductionist’s systems biology. Current Opinion in Cell Biology 17: 9–11.Google Scholar
  118. Sprinzak D, Elowitz MB (2005) Reconstruction of genetic circuits. Nature 438: 443–448.Google Scholar
  119. Stich S (2006) Is morality an elegant machine or a kludge? Journal of Cognition and Culture 6: 181–189.Google Scholar
  120. Szostak JW, Bartel DP, Luisi PL (2001) Synthesizing life. Nature 409: 387–390.Google Scholar
  121. Szybalski W (1978) Nobel prizes and restriction enzymes. Gene 4: 181–182.Google Scholar
  122. Tanenbaum AS (1988) Computer Networks. 2nd ed. New York: Prentice Hall.Google Scholar
  123. Tyo KE, Alper HS, Stephanopoulos GN (2007) Expanding the metabolic engineering toolbox: More options to engineer cells. Trends in Biotechnology 25: 132–137.Google Scholar
  124. Vaughan D (1996) The Challenger Launch Decision: Risky Technology, Culture, and Deviance at NASA. Chicago: University of Chicago Press.Google Scholar
  125. Vermuri GN, Aristidou AA (2005) Metabolic engineering in the -omics era: Elucidating and modulating regulatory networks. Microbiology and Molecular Biology Reviews 69: 197–216.Google Scholar
  126. Voigt CA (2006) Genetic parts to program bacteria. Current Opinion in Biotechnology 17: 548–557.Google Scholar
  127. Weber W, Fussenegger M (2009) The impact of synthetic biology on drug discovery. Drug Discovery Today 14: 956–963.Google Scholar
  128. Wimsatt WC (2007) Re-engineering Philosophy for Limited Beings: Piece-wise Approximations to Reality. Cambridge, MA: Harvard University Press.Google Scholar
  129. Wolf DM, Arkin AP (2003) Motifs, modules and games in bacteria. Current Opinion in Microbiology 6: 125–134.Google Scholar
  130. Yildirim MA, Vidal M (2008) Systems engineering to systems biology. Molecular Systems Biology 4: 185. Doi: 10.1038/msb2008.22 Google Scholar
  131. Yokobayashi Y, Weiss R, Arnold FH (2002) Directed evolution of a genetic circuit. Proceedings of the National Academy of Sciences USA 99: 16587–16591.Google Scholar

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© Konrad Lorenz Institute for Evolution and Cognition Research 2010

Authors and Affiliations

  1. 1.EgenisUniversity of ExeterExeterUK

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