The Road to Personalized and Predictive Medicine
Authors: Greg Martin, Dean Jones
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

To the Editor:

Sznajder and Ciechanover (1) effectively summarized the long and winding road toward personalized and predictive medicine. We agree with their conclusion that “continued investments in high-quality research … will be required,” although we feel that the lessons learned from the Human Genome Project and cancer therapeutics provide an opportunity to shorten and straighten the path for discovery. The lessons provide substrata to promote fundamental changes in biomedical research to improve efficiency and to deliver affordable personalized medicine.

A first lesson is that human disease is complex; although this is obvious, the number of possible combinations for functional variations in 20,000 genes is 20,000!, which renders traditional study impractical. Because genetic variation is not equivalent to dysfunction, there is little disillusionment in the failure of gene sequencing to advance personalized medicine. However, the Human Genome Project critically advanced sequencing cost, throughput, and analytics to approach clinical use.

A second lesson is that complexity is relative. The genome project was accomplished by segmenting the project into manageable tasks, which Christopher Wild (2) proposed applying to the environmental “exposome” to complement the Human Genome Project. In principle, this can be operationalized by systematic application of surveillance and biomonitoring methods, such as the metabolome (3), where measurement of 20,000 chemicals is possible for $125. Combined with genomic information for 20,000 genes, this provides an array of information with 400 million interactions—sufficient resolution to define an individual as an individual. By having systematic assembly of exposure information, a framework for study of the impact of genetic variations on health outcomes becomes clear.

Most recently, the conceptual framework of “multimorbidity” (4) provides a universal health and disease framework for personalized medicine. Realizing that one-fourth of all people and two-thirds of people over age 65 have multiple morbidities challenges our prior single-disease paradigms and leads to further exploration of common pathways for disparate diseases.

These concepts informed the genesis of the Emory University–Georgia Tech Predictive Health Institute in 2004, which set the goal to characterize human health from the broadest perspective, from social and cultural assessments to medical testing through to genome–metabolome interactions (5). By more fully understanding health, we have the opportunity to predict human disease even before it is clinically overt. This characterizes the optimal approach to personalized medicine—the ability to predict disease in individuals and target interventions to restore and optimize health. This approach has surpassed conception and entered reality, with well-documented examples of intervening in human health earlier and more effectively than ever before (6). The path to personalized medicine is not hopelessly long, but will require thoughtful planning, coordinated efforts, and continued societal investment.