A 21st-century roadmap for biomedical research
JRC scientist contributes to the definition of a 21st-century roadmap for biomedical research which proposes the use of human-specific models and innovative in vitro technologies instead of animals.
Toxicological testing is undergoing a paradigm shift, away from observing adverse effects in whole-animal models and towards the measurement of subtle effects that a compound can have on human derived cells and tissue tested in vitro. However this new non-animal approach to toxicology relies heavily on being able to interpret these in vitro responses to reliably predict possible adverse effects in a human. This in turn requires sufficient understanding of the relevant toxicological processes at play and the possibility to systematically apply that understanding in the testing and assessment of new compounds. Such mechanistic knowledge can be represented as an Adverse Outcome Pathway (AOP) that describes a logical sequence of causally linked biological events that lead from the first action of a compound to an eventual adverse effect on human health.
In view of continuing failures in health research, drug discovery, and clinical translation, a central recommendation of this publication is to utilise the AOP concept to facilitate a better understanding and representation of disease pathways at multiple biological levels and consequently improve drug development in biomedical research. Furthermore, it is proposed that using human-specific models and novel technologies can help deal with the uncertainty in biomedical research results due to the biological variation between species.