Biology & Philosophy

, Volume 27, Issue 2, pp 179–213 | Cite as

Waddington redux: models and explanation in stem cell and systems biology

Article

Abstract

Stem cell biology and systems biology are two prominent new approaches to studying cell development. In stem cell biology, the predominant method is experimental manipulation of concrete cells and tissues. Systems biology, in contrast, emphasizes mathematical modeling of cellular systems. For scientists and philosophers interested in development, an important question arises: how should the two approaches relate? This essay proposes an answer, using the model of Waddington’s landscape to triangulate between stem cell and systems approaches. This simple abstract model represents development as an undulating surface of hills and valleys. Originally constructed by C. H. Waddington to visually explicate an integrated theory of genetics, development and evolution, the landscape model can play an updated unificatory role. I examine this model’s structure, representational assumptions, and uses in all three contexts, and argue that explanations of cell development require both mathematical models and concrete experiments. On this view, the two approaches are interdependent, with mathematical models playing a crucial but circumscribed role in explanations of cell development.

Keywords

Stem cells Systems biology Epigenetic landscape CH Waddington Models Mechanistic explanation 

Notes

Acknowledgments

Thanks to Amy Wagers, Irv Weissman, Oleg Igoshin, Elihu Gerson and two anonymous reviewers for Biology and Philosophy for discussion and comments. The paper has also benefited from comments by session participants at the 2010 meeting of &HPS3 (Indiana University), the Workshop on Modeling and Simulation (Pittsburgh, March 2011), the 2011 meeting of the Society for Philosophy of Science in Practice (University of Exeter), and the EFS Systems Biology Workshop at Aarhus University in August 2011. Funding for this research was generously provided by the Humanities Research Center at Rice University’s Collaborative Research Fellowship (2009–2010), and Faculty Innovation Fund (2010–2012).

References

  1. Alon U (2007) An introduction to systems biology: design principles of biological circuits. Taylor and Francis, Boca RatonGoogle Scholar
  2. Bechtel W (2008) Mental mechanisms: philosophical perspectives on cognitive neuroscience. Routledge, New YorkGoogle Scholar
  3. Bechtel W (2010) The cell: locus or object of inquiry? Stud Hist Philos Biol Biomed Sci 41:172–182Google Scholar
  4. Bechtel W, Abrahamson A (2005) Explanation: a mechanist alternative. Stud Hist Philos Biol Biomed Sci 36:421–441Google Scholar
  5. Boogerd FC, Bruggeman FJ, Hofmeyr J-HS, Westerhoff HV (eds) (2007) Systems biology: philosophical foundations. Elsevier, AmsterdamGoogle Scholar
  6. Brandt C (2010) The metaphor of “nuclear reprogramming”: 1970s cloning research and beyond. In: Barahona A, Suarez-Díaz E, Rheinberger, H-J (eds) The hereditary hourglass: genetics and epigenetics, 1868–2000. Max Planck Institute for History of Science, pp 85–95Google Scholar
  7. Buchanan M, Caldarelli G, de los Rios P, Rao F, Vendruscolo M (eds) (2010) Networks in cell biology. Cambridge University Press, CambridgeGoogle Scholar
  8. Conrad ED, Tyson JJ (2010) Modeling molecular interaction networks with nonlinear ordinary differential equations. In: Szallasi Z, Stelling J, Periwal V (eds) Systems modeling in cell biology: from concepts to nuts and bolts. The MIT Press, Cambridge, pp 97–123Google Scholar
  9. Craver C (2007) Explaining the brain: mechanisms and the mosaic unity of neuroscience. Oxford University Press, OxfordGoogle Scholar
  10. de los Rios P, Vendruscolo M (2010) Network views of the cell. In: Buchanan M, Caldarelli G, de los Rios P, Rao F, Vendruscolo M (eds) Networks in cell biology. Cambridge University Press, Cambridge, pp 4–13Google Scholar
  11. Enver T, Pera M, Peterson C, Andrews P (2009) Stem cell states, fates, and the rules of attraction. Cell Stem Cell 4:387–397CrossRefGoogle Scholar
  12. Fagan MB (2011) Social experiments in stem cell biology. Perspect Sci 19:235–262CrossRefGoogle Scholar
  13. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114CrossRefGoogle Scholar
  14. Gilbert S (1991) Epigenetic landscaping: Waddington’s use of cell fate bifurcation diagrams. Biol Philos 6:135–154CrossRefGoogle Scholar
  15. Glennan S (2002) Rethinking mechanistic explanation. Philos Sci 69:S342–S353Google Scholar
  16. Graf T, Enver T (2009) Forcing cells to change lineages. Nature 462:587–594CrossRefGoogle Scholar
  17. Haraway DJ (1976) Crystals, fabrics, and fields: metaphors that shape embryos. Yale University Press, New HavenGoogle Scholar
  18. Hochedlinger K, Plath K (2009) Epigenetic reprogramming and induced pluripotency. Development 136:509–523CrossRefGoogle Scholar
  19. Huang S (2009) Reprogramming cell fates: reconciling rarity with robustness. BioEssays 31:546–560CrossRefGoogle Scholar
  20. Huang S, Guo Y-P, May G, Enver T (2007) Bifurcation dynamics in lineage-commitment in biopotent progenitor cells. Dev Biol 305:695–713CrossRefGoogle Scholar
  21. Huang S, Ernberg I, Kauffman S (2009) Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective. Seminars Cell Dev Biol 20:869–876CrossRefGoogle Scholar
  22. Ichida J, Kiskinis E, Eggan K (2010) Shushing down the epigenetic landscape towards stem cell differentiation. Development 137:2455–2460CrossRefGoogle Scholar
  23. Jablonka E, Lamb M (2005) Evolution in four dimensions: genetic, epigenetic, behavioral, and symbolic variation in the history of life. The MIT Press, CambridgeGoogle Scholar
  24. Kitano H (2002) Systems biology: a brief overview. Science 295:1662–1664CrossRefGoogle Scholar
  25. Klipp E, Liebermeister W, Wierling C, Kowald A, Lehrach H, Herwig R (2009) Systems biology: a textbook. Wiley-VCH, WeinheimGoogle Scholar
  26. Machamer P, Darden L, Craver C (2000) Thinking about mechanisms. Philos Sci 67:1–25CrossRefGoogle Scholar
  27. Maherali N, Hochedlinger K (2008) Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell 3:595–605CrossRefGoogle Scholar
  28. Noble D (2010) Biophysics and systems biology. Philos Trans R Soc A 368:1125–1139CrossRefGoogle Scholar
  29. O’Malley M, Dupré J (2005) Fundamental issues in systems biology. BioEssays 27:1270–1276CrossRefGoogle Scholar
  30. Pourquié O (2011) Steering a changing course. Development 138:1–2CrossRefGoogle Scholar
  31. Qu K, Ortoleva P (2008) Understanding stem cell differentiation through self-organization theory. J Theor Biol 250:606–620CrossRefGoogle Scholar
  32. Sareen D, Svendsen CN (2010) Stem cell biologists sure play a mean pinball. Nat Biotechnol 28:333–335CrossRefGoogle Scholar
  33. Szallasi Z, Stelling J, Periwal V (eds) (2010) Systems modeling in cell biology: from concepts to nuts and bolts. The MIT Press, CambridgeGoogle Scholar
  34. Takahashi S, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676CrossRefGoogle Scholar
  35. Trounson A (2009) Why stem cell research. In: Lanza R, Gearhart J, Hogan B, Melton D, Pederson R, Thomas ED, Thomson J, Wilmut I (eds) Essentials of stem cell biology, 2nd edn. Academic Press, San Diego, p xixCrossRefGoogle Scholar
  36. Van Speybrock L (2002) From epigenesis to epigenetics: the case of C. H. Waddington. Ann N Y Acad Sci 981:61–81CrossRefGoogle Scholar
  37. Waddington CH (1939) An introduction to modern genetics. MacMillan, New YorkCrossRefGoogle Scholar
  38. Waddington CH (1940) Organisers and genes. Cambridge University Press, CambridgeGoogle Scholar
  39. Waddington CH (1956) Principles of embryology. MacMillan, New YorkCrossRefGoogle Scholar
  40. Waddington CH (1957) The strategy of the genes. Taylor & Francis, LondonGoogle Scholar
  41. Waddington CH (ed) (1968) Towards a theoretical biology. IUBS and Edinburgh University Press, EdinburghGoogle Scholar
  42. Yamanaka S (2009) Elite and stochastic models for induced pluripotent stem cell generation. Nature 460:49–52CrossRefGoogle Scholar
  43. Zhou Q, Melton DA (2008) Extreme makeover: converting one cell into another. Cell Stem Cell 3:382–388CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Department of PhilosophyRice UniversityHoustonUSA

Personalised recommendations