A call for a Human Exposome Project.

Four decades of the Human Genome Project and its consequences have shown how the entrepreneurial state, through significant investment into science, can drive scientific progress and advance biomedicine. A certain fraction of diseases can now be explained as caused by genetics, and a more significant fraction as impacted by genetics. Besides another fraction caused by pathogens, the third and probably largest impactor is exposure, i.e., the many physicochemical and lifestyle factors. This article makes the case that it is time to start a Human Exposome Project, which systematically explores and catalogs the exposure side of human health and disease. The envisioned Human Exposome Project needs to be more than a scaled exposomics approach, aiming to assess the totality of relevant exposures through ~omics of human body fluids and forming exposure hypotheses. Exposomics is increasingly complemented by exposure science and biomonitoring to measure exposure, mechanistic understanding, human-relevant microphysiological systems, big data, and artificial intelligence (AI) to mine these data and integrate pieces of evidence. The potential impact of AI on a possible Human Exposome Project is so substantial that we should speak of exposome intelligence (EI) because this allows us to expand our limited current knowledge to the big unknown unknowns of threats to human health.