Document Type


Publication Date



Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be a model for health research, with probable medical and economic benefits.


In compliance with the publisher’s copyright and archiving policies, this is a post-print version of the document. Post-print materials contain the same content as their final edited versions, but are not formatted according to the layout of the published book or journal.