What Does It Take to Synergistically Combine Sub-Potent Natural Products into Drug-Level Potent Combinations?

10.1371/journal.pone.0049969PLoS ONE711

The Problem with Science

This book tells the story of how a cadre of dedicated, iconoclastic scientists raised the awareness of a long-recognized preference for publishing positive, eye-catching, but irreproducible results to the status of a genuine scientific crisis. Most famously encapsulated in 2005 by John Ioannidis’s iconic title, “Why Most Published Research Findings Are False,” awareness of the seriousness of the crisis itself was in full bloom sometime around 2011–2012, when a veritable flood of supporting empirical and methodological work began appearing in the scientific literature detailing both the extent of the crisis and how it could be ameliorated. Perhaps most importantly were a number of mass replications of large sets of published psychology experiments (100 in all) by the Open Science Collaboration, preclinical cancer experiments (53) that a large pharmaceutical company considered sufficiently promising to pursue if the original results were reproducible, and 67 similarly promising studies upon which an even larger pharmaceutical company decided to replicate prior to initiating the expense and time-consuming developmental process. Shockingly, less than 50% of these 220 study results could be replicated, thereby providing unwelcomed evidence that John Ioannidis’s projections (and others performed both earlier and later) that more than half of published scientific results were false and could not be reproduced by other scientists. Fortunately, a plethora of practical, procedural behaviors accompanied these demonstrations and projects that were quite capable of greatly reducing the prevalence of future irreproducible results. Therefore the primary purpose of this book is use these impressive labors of hundreds of methodologically oriented scientists to provide guidance to practicing and aspiring scientists regarding how (a) to change the way in which science has historically been both conducted and reported in order to avoid producing false-positive, irreproducible results in their own work and, (b) ultimately, to change those institutional practices (primarily but not exclusively involving the traditional journal publishing process and the academic reward system) that have unwittingly contributed to the present crisis. For what is actually needed is nothing less than a change in the scientific culture itself to one that will prioritize conducting research correctly in order to get things right rather than simply to get published. Hopefully this book can make a small contribution to that end.</p