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Multi-Level Complexities in Technological Development: Competing Strategies for Drug Discovery

  • Matthias Adam
Chapter
Part of the Boston Studies in the Philosophy of Science book series (BSPS, volume 274)

Abstract

Drug development regularly has to deal with complex circumstances on two levels: the local level of pharmacological intervention on specific target proteins, and the systems level of the effects of pharmacological intervention on the organism. Different development strategies in the recent history of early drug development can be understood as competing attempts at coming to grips with these multi-level complexities. Both rational drug design and high-throughput screening concentrate on the local level, while traditional empirical search strategies as well as recent systems biology approaches focus on the systems level. The analysis of these strategies reveals serious obstacles to integrating the study of interventive and systems complexity in a systematic, methodical way. Due to some fairly general properties of biological networks and the available options for pharmaceutical intervention, drug development is captured in an obstinate methodological dilemma. It is argued that at least in typical cases, drug development therefore remains dependent on coincidence, serendipity or plain luck to bridge the gap between (empirical and/or rational) development methodology and actual therapeutic success.

Keywords

Drug Development Drug Discovery Virtual Screening Pharmaceutical Intervention System Biology Approach 
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.

References

  1. Adam, M. 2005. Integrating research and development: The emergence of rational drug design in the pharmaceutical industry. Studies in History and Philosophy of Biological and Biomedical Sciences 36:513–537.CrossRefGoogle Scholar
  2. Adam, M. 2007. What to expect from rational drug design. Expert Opinion on Drug Discovery 2:773–776.CrossRefGoogle Scholar
  3. Adam, M. 2008a. Zwischen wissenschaftlichem Verständnis und therapeutischer Wirksamkeit. Pharmaforschung aus wissenschaftsphilosophischer Sicht. In Bittere Arznei. Wirtschaftsethik und Ökonomik der pharmazeutischen Industrie, eds. P. Koslowsi, and A. Prinz, 45–56. München: Fink.Google Scholar
  4. Adam, M. 2008b. The changing significance of chance experiments in technological development. In Selected Contributions to GAP.6, eds. H. Bohse, K. Dreimann, and S. Walter (CD-ROM), 1–14. Paderborn: Mentis.Google Scholar
  5. von Ahsen, O., and O. Bömer. 2005. High-throughput screening for Kinase inhibitors. ChemBioChem 6:481–490.CrossRefGoogle Scholar
  6. Belleau, B. 1970. Rational drug design: Mirage or miracle? Canadian Medical Association Journal 103(8):850–853.Google Scholar
  7. Böhm, H.-J., G. Klebe, and H. Kubinyi. 1996. Wirkstoffdesign. Heidelberg: Spektrum.Google Scholar
  8. Buchheit, K.-H., R. Gamse, R. Giger, D. Hoyer, F. Klein, E. Kloppner, H.-J. Pfannkuche, and H. Mattes. 1995. The Serotonin 5-HT4 receptor. 1. Design of a new class of agonists and receptor map of the agonist recognition site. Journal of Medicinal Chemistry 38:2326–2330.CrossRefGoogle Scholar
  9. Burch, R.N., and D.J. Kyle. 1991. Mass receptor screening for new drugs. Pharmaceutical Research 8:141–147.CrossRefGoogle Scholar
  10. Butcher, E.C. 2005. Can cell systems biology rescue drug discovery? Nature Reviews Drug Discovery 4:461–467.CrossRefGoogle Scholar
  11. Carrier, M., and P. Finzer. 2006. Explanatory loops and the limits of genetic reductionism. International Studies in the Philosophy of Science 20:267–283.CrossRefGoogle Scholar
  12. Chabner, B.A., and T.G. Roberts, Jr. 2005. Chemotherapy and the war on cancer. Nature Reviews Cancer 5:65–71.CrossRefGoogle Scholar
  13. Cockburn, I.M., R. Henderson, and S. Stern 1999. The diffusion of science driven drug discovery: Organizational change in pharmaceutical research. National Bureau of Economic Research Working Paper 7359, http://www.nber.org/papers/w7359 (last accessed 29 February 2008).
  14. Congreve, M., C.W. Murray, and T.L. Blundell. 2005. Structural biology and drug discovery. Drug Discovery Today 10:895–907.CrossRefGoogle Scholar
  15. Cushman, D.W., and M.A. Ondetti. 1991. History of the design of specific inhibitors of angiotensin converting enzyme. Hypertension 17:589–592.Google Scholar
  16. Drews, J. 1995. Intent and coincidence in pharmaceutical research. The impact of biotechnology. Arzneimittelforschung/Drug Research 45:934–939.Google Scholar
  17. Drews, J. 1999. In Quest of Tomorrow’s Medicines. New York, NY: Springer.Google Scholar
  18. Erlanson, D.A. 2006. Fragment-based lead discovery: A chemical update. Current Opinion in Biotechnology 17:643–652.CrossRefGoogle Scholar
  19. FDA. 2007. 2007 CDER Update.http://www.fda.gov/cder/present/galson/2007/2007CDERUpdateWCBPJan292007.pdf (last accessed 29 February 2008).
  20. Good, A.C., S.R. Krystek, and J.S. Mason. 2000. High-throughput and virtual screening: core lead discovery technologies move towards integration. Drug Discovery Today 5(12, Suppl.):S61–S69.CrossRefGoogle Scholar
  21. van der Greef, J., and R.N. McBurney 2005. Rescuing drug discovery: In vivo systems pathology and systems pharmacology. Nature Reviews Drug Discovery 4:961–967.CrossRefGoogle Scholar
  22. Hardy, L.W., and A. Malikayil. 2003. The impact of structure-guided drug design on clinical agents. Current Drug Discovery 3(December):15–20.Google Scholar
  23. Hitchings, G.H. 1969. Chemotherapy and comparative biochemistry: G.H.A. Clowes memorial lecture. Cancer Research 29(11):1895–1903.Google Scholar
  24. Horrobin, D.F. 2003. Modern biomedical research: an internally self-consistent universe with little contact with medical reality. Nature Reviews Drug Discovery 2:151–154.CrossRefGoogle Scholar
  25. Kitano, H. 2007. A robustness-based approach to systems-oriented drug design. Nature Reviews Drug Discovery 6:202–210.CrossRefGoogle Scholar
  26. Klebe, G. 2006. Virtual ligand screening: Strategies, perspectives and limitations. Drug Discovery Today 11:580–594.CrossRefGoogle Scholar
  27. Kubinyi, H. 1999. Chance favors the prepared mind. From serendipity to rational drug design. Journal of Receptor and Signal Transduction Research 19:15–39.CrossRefGoogle Scholar
  28. Kubinyi, H. 2003. Drug research: Myths, hype and reality. Nature Reviews Drug Discovery 2:665–668.CrossRefGoogle Scholar
  29. Kuhn, P., K. Wilson, M.G. Patch, and R.C. Stevens. 2002. The genesis of high-throughput structure-based drug discovery using protein crystallography. Current Opinion in Chemical Biology 6:704–710.CrossRefGoogle Scholar
  30. Lipinski, C., and A. Hopkins. 2004. Navigating chemical space of biology and medicine. Nature 432:855–861.CrossRefGoogle Scholar
  31. Maxwell, R.A., and S.B. Eckhardt. 1990. Drug Discovery. A Casebook and Analysis. Clifton, NJ: Humana Press.Google Scholar
  32. Nightingale, P., and P. Martin. 2004. The myth of the biotech revolution. Trends in Biotechnology 22:564–569.CrossRefGoogle Scholar
  33. PDB. 2008. Yearly Growth of Total Structures. http://www.rcsb.org/pdb/home/home.do (last accessed 10 March 2008).
  34. Pitt, J.C. 2001. What engineers know. Techné 5(3):17–29.Google Scholar
  35. Ratti, E., and D. Trist. 2001. Continuing evolution of the drug discovery process in the pharmaceutical industry. Pure and Applied Chemistry 73:67–75.CrossRefGoogle Scholar
  36. Schmid, E.F., and D.A. Smith. 2004. Is pharmaceutical R&D just a game of chance or can strategy make a difference? Drug Discovery Today 9:18–26.CrossRefGoogle Scholar
  37. Schwardt, O., H. Kolb, and B. Ernst. 2003. Drug discovery today. Current Topics in Medicinal Chemistry 3:1–9.CrossRefGoogle Scholar
  38. Shaffer, C. 2005. Drug discovery veers off target. Drug Discovery Today 10:1489.CrossRefGoogle Scholar
  39. Thomke, S., E. von Hippel, and R. Franke. 1998. Modes of experimentation: an innovation process – And competitive – Variable. Research Policy 27:315–332.CrossRefGoogle Scholar
  40. Van Regenmortel, M.H.V. 2004. Reductionism and complexity in molecular biology. EMBO Reports 5:1016–1020.CrossRefGoogle Scholar
  41. Vincenti, W.G. 1990. What Engineers Know and How They Know It. Baltimore, MD: Johns Hopkins University Press.Google Scholar
  42. Williams, M. 2004. A return to the fundamentals of drug discovery? Current Opinion in Investigational Drugs 5:29–33.Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Technische Universität DarmstadtDarmstadtGermany

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