What it will take to cross the Valley of Death: Translational Systems Biology, “True” Precision Medicine, Medical Digital Twins, Artificial Intelligence and In Silico Clinical Trials

I assert that the greatest methodological challenge to improving human health is increasing the efficiency in translating the output of basic biomedical research into effective clinical therapeutics, specifically the translation from ostensibly effective drug candidates from pre-clinical studies to clinical application: the Valley of Death. This talk provides a background for the concept of Translational Systems Biology, the explicit use of mechanism-based dynamic computational models in clinically-relevant contexts, and how this term is linked with and to a great degree encompasses subsequent developments in biomedical research, such as personalized/precision medicine, digital twins, biomedical application of machine learning/artificial intelligence and in silico trials. Translational Systems Biology and its manifestation through the design and execution of in silico clinical trials, has an explicit aim of representing and overcoming key features of clinical populations that form the basis of the Valley of Death. I present three Grand Challenges for the community that I believe are critical if we are to substantively enhance the ability to effectively and efficiently evaluate drug candidates (this includes both new therapeutic agents and drug repurposing for diseases in which they were not already tested) in a clinically relevant fashion. This talk will also emphasize the cognitive/mental/academic/political barriers that mechanism-based dynamic computational modeling, a fundamental tool that underpins nearly all advances in every other technological field other than biomedicine by allowing for the practice of engineering, faces in biomedicine, and how it is subject to the tyranny of terminology. Moderator: James A. Glazier, PhD, Indiana University, Bloomington To learn more see: An, Gary, Michael Döllinger, and Nicole YK Li-Jessen. "Integration of machine learning and computer simulation in solving complex physiological and medical questions." Frontiers in Physiology 13 (2022): 949771. https://www.frontiersin.org/articles/10.3389/fphys.2022.949771/full To view the slides in this video, visit: https://docs.google.com/presentation/d/1E0pxPPVrfzwW75CEax27JBVn5xZnlfun/ *Contents* 0:00 - Introduction: J Glazier 2:11 - Coming Up 4:07 - Gary An: What it will take to cross the Valley of Death: Translational Systems Biology, “True” Precision Medicine, Medical Digital Twins, Artificial Intelligence and In Silico Clinical Trials 1:02:36 - Q&A Session If you found this video useful, please check out our other videos on computational modeling, infection and immunology: https://tinyurl.com/GLIMPRINTVideos Please consider joining our IMAG/MSM WG on Multiscale Modeling and Viral Pandemics: https://www.imagwiki.nibib.nih.gov/content/msm-viral-pandemics-meetings Please also consider joining the Global Alliance for Immune Prediction and Intervention: http://glimprint.org/