What 21st century medicine should be—history, vision, implementation, and opportunities

P4 medicine will employ longitudinal, high-dimensional analyses of individuals, integrating molecular, digital, electronic health record, and self-monitoring data. This will classify patients, diseases, and drugs, and continually convert data into knowledge through iterative hypothesis testing to inform systems approaches to both wellness and disease. Two preliminary trials have been carried out to validate this approach, one involving 100 individuals over nine months in 2014 and a second recruiting 5,000 individuals over four years from 2015 until 2019. These trials (i) validated scientific (quantitative) wellness, using personal, high-dimensional data to improve one’s wellness, and (ii) demonstrated the power of longitudinal data clouds to bring fundamental new insights into wellness and disease. These led to a vision of 21st century n = 1 medicine which optimizes the health trajectories of each individual. Each health trajectory has three states: (1) a wellness state that will be extended and optimized through scientific wellness and healthy ageing; (2) a wellness-to-disease transition state where early biomarkers will be identified and used to design therapies employing the identification of the earliest disease-perturbed networks to reverse disease before it manifests as a clinical entity; and (3) a progressive disease state for which physicians and scientists will use data-driven systems approaches to find therapies that ameliorate or reverse disease. This chapter discusses the promotion of a million person genome/phenome project with a major healthcare system to initiate the implementation of 21st century medicine in the US healthcare system. The challenges and opportunities associated with the realization of 21st century medicine are also discussed.