Why and How to Expand the Role of Systems Biology in Pharmaceutical Research and Development

  • Robert D. PhairEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 736)


Seen from the perspective of funding organizations, investors, and the general public, the productivity of our world-wide biomedical research enterprise is declining despite increased investment. This opinion piece suggests a cause and a solution. The cause is the enormous complexity of human biology and pathophysiology. The unsolved human diseases involve so many interacting variables that single research laboratories headed by skilled principal investigators doing innovative experimental work cannot be expected to assemble the reductionist pieces into an integrated working model. Systems biology offers a solution, but it will require teamwork. Co-equal teams of experimental and computational biologists can construct multiscale differential equation models and test them against experimental data. A successful model provides actionable evidence-based guidance to the entire research and development team. These integrative biology teams may, for historical and cultural reasons, be unsustainable in academia, but they seem naturally suited to modern pharmaceutical research and development. One way to organize such teams and their workflow is described in detail.


Pharmaceutical Development Pharmaceutical Firm Integrative Biology Mechanistic Diagram Innovative Small Company 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Beard DA, Kushmerick MJ (2009) Strong inference for systems biology. PLoS Comput Biol 5(8):e1000459. doi:10.1371/journal.pcbi.1000459PubMedCrossRefGoogle Scholar
  2. 2.
    Phair RD, Misteli T (2001) Kinetic modelling approaches to in vivo imaging. Nat Rev Mol Cell Biol 2(12):898–907PubMedCrossRefGoogle Scholar
  3. 3.
    Teusink B, Westerhoff HV, Bruggeman FJ (2010) Comparative systems biology: from bacteria to man. Wiley Interdiscip Rev Syst Biol Med 2(5):518–532. doi:10.1002/wsbm.74PubMedGoogle Scholar
  4. 4.
    Lelandais G, Devaux F (2010) Comparative functional genomics of stress responses in yeasts. OMICS 14(5):501–515PubMedCrossRefGoogle Scholar
  5. 5.
    Chuang H-Y, Hofree M, Ideker T (2010) A decade of systems biology. Annu Rev Cell Dev Biol 26:721–744PubMedCrossRefGoogle Scholar
  6. 6.
    Greene CS, Troyanskaya OG (2010) Integrative systems biology for data-driven knowledge discovery. Semin Nephrol 30(5):443–454PubMedCrossRefGoogle Scholar
  7. 7.
    Kohl P, Crampin EJ, Quinn TA, Noble D (2010) Systems biology: an approach. Clin Pharmacol Ther 88(1):25–33PubMedCrossRefGoogle Scholar
  8. 8.
    Kitano H (2002) Systems biology: a brief overview. Science 295(5560):1662–1664PubMedCrossRefGoogle Scholar
  9. 9.
    Auffray C, Imbeaud S, Roux-Rouquié M, Hood L (2003) From functional genomics to systems biology: concepts and practices. C R Biol 326(10–11):879–892PubMedCrossRefGoogle Scholar
  10. 10.
    Dobson PD, Smallbone K, Jameson D, Simeonidis E, Lanthaler K, Pir P, Lu C, Swainston N, Dunn WB, Fisher P, Hull D, Brown M, Oshota O, Stanford NJ, Kell DB, King RD, Oliver SG, Stevens RD, Mendes P (2010) Further developments towards a genome-scale metabolic model of yeast. BMC Syst Biol 4(1):145. doi:10.1186/1752–0509–4–145PubMedCrossRefGoogle Scholar
  11. 11.
    Snow CP (1959) Two cultures. Science 130(3373):419Google Scholar
  12. 12.
    Le Novère N, Hucka M, Mi H, Moodie S, Schreiber F, Sorokin A, Demir E, Wegner K, Aladjem MI, Wimalaratne SM, Bergman FT, Gauges R, Ghazal P, Kawaji H, Li L, Matsuoka Y, Villéger A, Boyd SE, Calzone L, Courtot M, Dogrusoz U, Freeman TC, Funahashi A, Ghosh S, Jouraku A, Kim S, Kolpakov F, Luna A, Sahle S, Schmidt E, Watterson S, Wu G, Goryanin I, Kell DB, Sander C, Sauro H, Snoep JL, Kohn K, Kitano H (2009) The systems biology graphical notation. Nat Biotechnol 27(8):735–741PubMedCrossRefGoogle Scholar
  13. 13.
    Freeman TC, Raza S, Theocharidis A, Ghazal P (2010) The mEPN scheme: an intuitive and flexible graphical system for rendering biological pathways. BMC Syst Biol 4:65–65. doi:10.1186/1752–0509–4–65PubMedCrossRefGoogle Scholar
  14. 14.
    Kohn KW, Aladjem MI, Weinstein JN, Pommier Y (2006) Molecular interaction maps of bioregulatory networks: a general rubric for systems biology. Mol Biol Cell 17(1):1–13. doi:10.1091/mbc.E05–09–0824PubMedCrossRefGoogle Scholar
  15. 15.
    Wimalaratne SM, Halstead MDB, Lloyd CM, Cooling MT, Crampin EJ, Nielsen PF (2009) A method for visualizing CellML models. Bioinformatics 25(22):3012–3019PubMedCrossRefGoogle Scholar
  16. 16.
    Le Novere N, Bornstein B, Broicher A, Courtot M, Donizelli M, Dharuri H, Li L, Sauro H, Schilstra M, Shapiro B, Snoep JL, Hucka M (2006) BioModels database: a free, centralized database of curated, published, quantitative kinetic models of biochemical and cellular systems. Nucleic Acids Res 34(Database issue):D689–D691Google Scholar
  17. 17.
    Lloyd CM, Lawson JR, Hunter PJ, Nielsen PF (2008) The CellML model repository. Bioinformatics 24(18):2122–2123PubMedCrossRefGoogle Scholar
  18. 18.
    Hucka M, Finney A, Sauro HM, Bolouri H, Doyle JC, Kitano H, Arkin AP, Bornstein BJ, Bray D, Cornish-Bowden A, Cuellar AA, Dronov S, Gilles ED, Ginkel M, Gor V, Goryanin II, Hedley WJ, Hodgman TC, Hofmeyr JH, Hunter PJ, Juty NS, Kasberger JL, Kremling A, Kummer U, Le Novere N, Loew LM, Lucio D, Mendes P, Minch E, Mjolsness ED, Nakayama Y, Nelson MR, Nielsen PF, Sakurada T, Schaff JC, Shapiro BE, Shimizu TS, Spence HD, Stelling J, Takahashi K, Tomita M, Wagner J, and Wang J (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19:524–531PubMedCrossRefGoogle Scholar
  19. 19.
    Lloyd CM, Halstead MDB, Nielsen PF (2004) CellML: its future, present and past. Prog Biophys Mol Biol 85(2–3):433–450PubMedCrossRefGoogle Scholar
  20. 20.
    Popper KR (1965) The logic of scientific discovery, vol 479. Harper & Roy, New YorkGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Integrative Bioinformatics Inc.Los AltosUSA

Personalised recommendations