The fall and rise of pharmacology--(re-)defining the discipline?
Pharmacology is an integrative discipline that originated from activities, now nearly 7000 years old, to identify therapeutics from natural product sources. Research in the 19th Century that focused on the Law of Mass Action (LMA) demonstrated that compound effects were dose-/concentration-dependent eventually leading to the receptor concept, now a century old, that remains the key to understanding disease causality and drug action. As pharmacology evolved in the 20th Century through successive biochemical, molecular and genomic eras, the precision in understanding receptor function at the molecular level increased and while providing important insights, led to an overtly reductionistic emphasis. This resulted in the generation of data lacking physiological context that ignored the LMA and was not integrated at the tissue/whole organism level. As reductionism became a primary focus in biomedical research, it led to the fall of pharmacology. However, concerns regarding the disconnect between basic research efforts and the approval of new drugs to treat 21st Century disease tsunamis, e.g., neurodegeneration, metabolic syndrome, etc. has led to the reemergence of pharmacology, its rise, often in the semantic guise of systems biology. Against a background of limited training in pharmacology, this has resulted in issues in experimental replication with a bioinformatics emphasis that often has a limited relationship to reality. The integration of newer technologies within a pharmacological context where research is driven by testable hypotheses rather than technology, together with renewed efforts in teaching pharmacology, is anticipated to improve the focus and relevance of biomedical research and lead to novel therapeutics that will contain health care costs.
Department of Pharmacology, Vertex Pharmaceuticals Inc., Cambridge, MA, United States.
Raymond J
RJ
Winquist
Profectus Pharma Consulting Inc., San Jose, CA, United States.
Kevin
K
Mullane
Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States. Electronic address: Rivoli1635@comcast.net.
Michael
M
Williams
D000818:Animals; D003001:Cloning, Molecular / Q000379:methods; D006801:Humans; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000378:metabolism*; D010597:Pharmacogenetics / Q000193:education / Q000379:methods / Q000639:trends; D010600:Pharmacology / Q000193:education / Q000379:methods / Q000639:trends*; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D011956:Receptors, Cell Surface
Drug discovery; Pharmacology; Receptors; Systems biology