Transctriptional Science aims to re-evaluate existing data in the context of the translational sciences paradim in order to secure reliability and validity of data used for hypothesis generation, project design and decision making at a highest possible level of confidence

1. Transcriptional Science: an essential prerequisite to enable translational sciences developed by: Thomas Wilckens, MD, PhD

2. “ Science Business”, Gari P. Pisano, Harvard Business School Press, 2007 Can Science be a business? It would appear that the answer, based on the experience to date would be no. This answer is, however, only correct, if we take existing organizational and institutional arrangements and existing management technologies as given. Transcriptional Sciences: a building block for Symbiotic Innovation: Reshaping value creation in concert with Translational Sciences Academia cannot replace early stage R&D but must establish essential fundaments. Lessons from biotech should guide the creation of novel anatomies. Symbiotic Innovation - © Sandrine Shepard Thomas Wilckens

4. Translational research connecting basic research to patient care: The wealth of data need rigorous evaluation by putting human biology back in the center of discovery Translational Research - © Dr. Thomas Wilckens Cells/animals molecules genes Health Clinical Research Basic Research human research Participants Populations Societies Heal care systems Mechanism Markers Drugs Devices Interventions T1 or TR T2 or TM1 Bench to Bedside Laboratory to Human Bedside to Community Experience to Practice Caveat: Research & funding need to be arranged around and along scientific/medical problems rather then aligning existing infrastructures and organisations in order create increased revenue to academic institutions; i.e. disease areas, pathologies, target-families T3 or TM2 Barriers Feasibility Strategy Effectiveness Safety Post-marketing Obeservatios Off-label-use GP obeservations

6. On-Ko-Chi-Shin “ The new idea resides within the old.” What about the old data & overcome experimental designs ; i.e. compare the “cortisol story” In consequence a third field for research seems required to enable Translational Sciences . Translational Sciences (Research & Medicine): forward directed measures A critical analysis of our approach to science should allow optimal use of old and emerging studies and data Transcriptional Science: Securing contemporary experimental designs and data’s reliability and validity Symbiotic Innovation - © Sandrine Shepard Thomas Wilckens

10. Cortisol: the master of homeostasis and host defence : Cortisol exploits complex receptor interactions to assure optimal adaptation to “stress” Cortisol follows a circadian rhythm superimposed by adaptations to stressors occupying GR and MR, A, B, C Aldosterone shows no circadian rhythm and reacts to changes in volume and/or minerals Cort/Aldo undulation is not synchronous like sinus/cosinus resulting in complex dynamic GR/MR interactions MR activation is associated with tissue damage in CVD, stroke and related inflammation (activation of NfkB) 11- β -HSD-1 11- β -HSD-1/2 catabolism activation

11. Chaos & control of cortisol actions: stochastic induction of disease non-linear dynamics impact on biological systems and side effect potential Linear correlation analyses may not translate to real world biology and therapeutic constellations Mathematic models support the identification of “ therapeutic windows ” and experimental designs Circadian rhythms of GR and MR ligands interfere with “natural stress” responses Symbiotic Innovation - © Sandrine Shepard Thomas Wilckens Homeostatic model” without” perturbations; i.e. equally long parts of a pendulum result already in a highly complex pattern; the animation shown represent individual variations

15. TS: reduces risks, costs, time and increases the chance for success Successful product development will require sustainable support combined with iterative project evaluation ‘ It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change’ Charles Darwin Imagine, what happened, if we additionally used our intelligence and resources optimally to adopt? P. Talaga in Drug Discovery Today 9/2009, Share or die!: Symbiotic Innovation - © Sandrine Shepard Thomas Wilckens

16. Thank you for your attention: Could anybody please ask why I am convinced that SI works! I have a nice slide! Can Science be a business? Facing the opportunities of the www, the transitions that take place, innovation & value creation for society and industry appears a feasible goal SI: Fostering Transcriptional & Translational Sciences Symbiotic Innovation - © Sandrine Shepard Thomas Wilckens Transcriptional Science Translational Medicine Translational Research Symbiotic Innovation