Position paper From the digital twins in healthcare to the Virtual Human Twin: a moon-shot project for digital health research.

The idea of a systematic digital representation of the entire known human pathophysiology, which we could call the Virtual Human Twin, has been around for decades. To date, most research groups focused instead on developing highly specialised, highly focused patient-specific models able to predict specific quantities of clinical relevance. While it has facilitated harvesting the low-hanging fruits, this narrow focus is, in the long run, leaving some significant challenges that slow the adoption of digital twins in healthcare. This position paper lays the conceptual foundations for developing the Virtual Human Twin (VHT). The VHT is intended as a distributed and collaborative infrastructure, a collection of technologies and resources (data, models) that enable it, and a collection of Standard Operating Procedures (SOP) that regulate its use. The VHT infrastructure aims to facilitate academic researchers, public organisations, and the biomedical industry in developing and validating new digital twins in healthcare solutions with the possibility of integrating multiple resources if required by the specific context of use. Healthcare professionals and patients can also use the VHT infrastructure for clinical decision support or personalised health forecasting. As the European Commission launched the EDITH coordination and support action to develop a roadmap for the development of the Virtual Human Twin, this position paper is intended as a starting point for the consensus process and a call to arms for all stakeholders.