Multi-Level Complexities in Technological Development: Competing Strategies for Drug Discovery
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.
KeywordsDrug Development Drug Discovery Virtual Screening Pharmaceutical Intervention System Biology Approach
- 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
- 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
- Belleau, B. 1970. Rational drug design: Mirage or miracle? Canadian Medical Association Journal 103(8):850–853.Google Scholar
- Böhm, H.-J., G. Klebe, and H. Kubinyi. 1996. Wirkstoffdesign. Heidelberg: Spektrum.Google Scholar
- 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).
- 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
- Drews, J. 1995. Intent and coincidence in pharmaceutical research. The impact of biotechnology. Arzneimittelforschung/Drug Research 45:934–939.Google Scholar
- Drews, J. 1999. In Quest of Tomorrow’s Medicines. New York, NY: Springer.Google Scholar
- FDA. 2007. 2007 CDER Update.http://www.fda.gov/cder/present/galson/2007/2007CDERUpdateWCBPJan292007.pdf (last accessed 29 February 2008).
- 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
- Hitchings, G.H. 1969. Chemotherapy and comparative biochemistry: G.H.A. Clowes memorial lecture. Cancer Research 29(11):1895–1903.Google Scholar
- Maxwell, R.A., and S.B. Eckhardt. 1990. Drug Discovery. A Casebook and Analysis. Clifton, NJ: Humana Press.Google Scholar
- PDB. 2008. Yearly Growth of Total Structures. http://www.rcsb.org/pdb/home/home.do (last accessed 10 March 2008).
- Pitt, J.C. 2001. What engineers know. Techné 5(3):17–29.Google Scholar
- Vincenti, W.G. 1990. What Engineers Know and How They Know It. Baltimore, MD: Johns Hopkins University Press.Google Scholar
- Williams, M. 2004. A return to the fundamentals of drug discovery? Current Opinion in Investigational Drugs 5:29–33.Google Scholar