Integrating research and development: the emergence of rational drug design in the pharmaceutical industry

Adam, Matthias

doi:10.1016/j.shpsc.2005.07.003

Cited by 33 publications

(28 citation statements)

References 42 publications

(35 reference statements)

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“…Recent research has drawn attention to the fact that even the recent history of research in pharmaceutical industry, so often scathed for its prosaic methods of high throughput screening, can in fact provide examples of imaginative and innovative science. The so-called "method of rational drug design" integrates the epistemic aim of understanding fundamental physiological mechanisms and the practical aim of developing new pharmaceuticals (Adam 2005). …”

Section: Discussionmentioning

confidence: 99%

Design Rules: Industrial Research and Epistemic Merit

Wilholt

2006

Philos. of Sci.

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A common complaint against the increasing privatization of research is that research that is conducted with the immediate purpose of producing applicable knowledge will not yield knowledge as valuable as that generated in more curiosity-driven, academic settings. In this paper, I make this concern precise and reconstruct the rationale behind it. Subsequently, I examine the case of industry research on the giant magnetoresistance effect in the 1990s as a characteristic example of research undertaken under considerable pressure to produce applicable results. The example permits one to arrive at a more optimistic assessment of the epistemic merits of private, application-driven research. I attempt to specify the conditions that, in this case, advanced the production of interesting and reliable knowledge. ________________ Instrumental Research and the Concerns about Epistemic DeclineWhat epistemic consequences ensue when scientific research is taken over by corporate interests? In this paper, I will examine one important recent example of such a takeover. Among other things, I will describe the role of a certain kind of local model that figures importantly in connecting research efforts with product development and whose occurrences are sometimes aptly called 'design rules'. It is often feared that these and all other results of application-driven research are inevitably pragmatic, provisional or otherwise inferior to the knowledge achieved by curiosity-driven academic science. The ambiguity of this paper's title alludes to these worries: It is reasonable to assume that in industrial research, design rules. Might the demands of successful product design even threaten to overrule the traditional epistemic values of academic science?Quite a few players in public debates about science evidently fear so, and have expressed their concern that the gradual privatization of research will eventually prove detrimental for the epistemic merits of science as a whole.

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Section: Discussionmentioning

confidence: 99%

Design Rules: Industrial Research and Epistemic Merit

Wilholt

2006

Philos. of Sci.

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“…Adam, 2005). While pharmacological research is motivated primarily to design better pharmacological treatments for schizophrenia in clinical contexts, the drugs that are developed often play a crucial role in assisting researchers to expand and revise existing neurobiological theories of mental disorders in research contexts.…”

Section: Revising Neurobiological Theoriesmentioning

confidence: 99%

Intervention, causal reasoning, and the neurobiology of mental disorders: Pharmacological drugs as experimental instruments

Tsou

2012

Studies in History and Philosophy of Science Part C: Studies in

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Abstract:In psychiatry, pharmacological drugs play an important experimental role in attempts to identify the neurobiological causes of mental disorders. Besides being developed in applied contexts as potential treatments for patients with mental disorders, pharmacological drugs play a crucial role in research contexts as experimental instruments that facilitate the formulation and revision of neurobiological theories of psychopathology. This paper examines the various epistemic functions that pharmacological drugs serve in the discovery, refinement, testing, and elaboration of neurobiological theories of mental disorders. I articulate this thesis with reference to the history of antipsychotic drugs and the evolution of the dopamine hypothesis of schizophrenia in the second half of the twentieth century. I argue that interventions with psychiatric patients through the medium of antipsychotic drugs provide researchers with information and evidence about the neurobiological causes of schizophrenia. This analysis highlights the importance of pharmacological drugs as research tools in the generation of psychiatric knowledge and the dynamic relationship between practical and theoretical contexts in psychiatry.

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“…Such discussions were inspired by some (at their time) exceptional cases in which a more targeted, knowledge-driven development process was claimed to have been realized (Hitchings 1969, Belleau 1970, Adam 2005). …”

Section: Rational Drug Design and Its Limitsmentioning

confidence: 99%

“…Repeatedly, targeted screening remains important for these purposes. If the inferential relations are sufficiently close, the fundamental knowledge can both contribute to the development process and be supplemented or confirmed through empirical testing (Adam 2005).…”

Section: Rational Drug Design and Its Limitsmentioning

confidence: 99%

“…For instance, the developers of captopril could not make use of direct structural information on their protein target ACE (angiotensin converting enzyme), but used the available information on a related bovine enzyme instead (Cushman and Ondetti 1991). Already in the mid-1980s, however, the development of the first next-generation antihypertensive drug, losartan, included direct structural information on its target angio-tensin II (Adam 2005), while in 1989, the complete structure of HIV protease became accessible and was subsequently used for the development of HIV protease inhibitors (Congreve et al 2005) Rational drug design raised high expectations among drug researchers in the 1980s. It was hoped by many that it could substantially reduce the dependence on chance or serendipitous findings, paving the way to a much more orderly and predictable development process (Drews 1999, 121-122).…”

Section: Rational Drug Design and Its Limitsmentioning

confidence: 99%

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

Adam

2010

Science in the Context of Application

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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. An obstinate dilemma in early drug developmentFor the successful development of technology, it is often crucial to pay close attention to a number of different complex circumstances. Development can be particularly demanding if the complexities lie on different levels of a system. For instance, the design of a technology can require, first, that the technological artifact intervenes in a highly sophisticated way on a specific part of a system. Second, this intervention might have to produce effects in the system as a whole that are mediated by complex systems mechanisms. In such a case, complexities on two levels have to be dealt with: complexity of (local) intervention and complexity of systems effects (or systems complexity).For drug development, both types of complexity play a major role. Pharmaceuticals typically act on target proteins, such as enzymes, receptors or ion channels. The interaction between (potential) drugs and these molecular targets is often highly complex and subject to comprehensive theoretical modeling, chemical design and empirical testing in drug development. This problem is local in nature, being associated with specific proteins and their manipulation by drug molecules. At the same time, the intended and unintended effects of pharmacological interventions lie on the level of entire systems such as cells, organs or the organism

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Integrating research and development: the emergence of rational drug design in the pharmaceutical industry

Cited by 33 publications

References 42 publications

Design Rules: Industrial Research and Epistemic Merit

Design Rules: Industrial Research and Epistemic Merit

Intervention, causal reasoning, and the neurobiology of mental disorders: Pharmacological drugs as experimental instruments

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

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