UNMET MEDICAL NEEDS - CONCEPTS AND REALITIES IN THE RATIONAL DRUG DESIGN
Gerd Folkers, Martin Boyer, Collegium Helveticum, UZH/ETH Zurich
Both, the drug development strategies as well as the conception of health have changed considerably during the last century.
Through the advances in informatics, chemistry and biology the «rational drug design approach» was established in the 1960s. It was supposed to complement or even replace the classical »trial-and-error« methodology by implementing Nobel Laureate Paul Ehrlich’s early 20th Century vision of the «personal pill» (1901). Nowadays a ligand can be developed by computer-aided molecular design to fit and bind strongly to the 3D shape of the protein’s active or binding side and as such influences its target specifically. This approach works fine in vitro, but nevertheless, in practice just a couple of these drugs have reached the market. Lack-of-efficiency, next to toxicity, is regarded as the main reason for failure of rationally designed drugs in medical trials. Does therefore the lack-of-efficiency represent a lack-of-causality in the conception of diseases in phenomenological and molecular terms? How can a reductionistic linear model be applied to a non-linear dynamic system? Which is the relevant level of comprehension? Isn’t a system exposed to a drug different from the system alone? Probably the designation «rational» already gives us a hint elucidating the problem: ratio aims at proportion, which in the case of «rational drug design» means that just «negligible» fraction of the system lays within the focus. New initiatives in the integrative system biology, as the Swiss System-X, are expected to tackle such questions in a brother context. Consequently, in the search for alternatives the focus shifts slowly back on «drugs with a rich pharmacology», or as they were formerly pejoratively called «dirty drugs» – as opposed to the rationally developed «clean drugs». The former actually represent the overwhelming part of known drugs.
The latter change lays in the comprehension of health, which can be summarised in a transition from pathogenesis to salutogenesis. This manifests through an increased demand of products and services of complimentary medicine as well as of prevention (functional food). Thus it may be argued that the altered definition of disease and health as well as the altered self-conception influences the use and range of a pharmaceutical product. The definition of health, the consequences of the demographic trend (older population) and the «diseases of civilisation» (obesity) influence the medical demand and the «unmet medical needs» respectively and an understanding of needs in current society (consumer vs. producer).
The aim of the study is to track the concepts of biological systems applied to various levels of the drug development process, as there are amongst others software engineers of drug design applications, pharmacologists, research officers and marketing strategists. Through interviews and field studies a broad fundament will be established addressing the relation of theoretical concepts and practical acting. This basis of evidence is to be used to sensitize these actors concerning their now hypothesised conceptual shortcomings.