Mount Sinai and Military Medicine Team Up to Map Disease Years Before Symptoms

For years, a core dream of preventive medicine has been the ability to detect disease long before it announces itself through symptoms. A new multi-institution initiative is attempting to do exactly that, using one of the most extraordinary biological archives in the world: the Department of Defense Serum Repository, which holds serial blood samples from millions of U.S. service members, many collected a decade or more before any illness emerged.

The project, called ORIGIN - Omics to Characterize Preclinical Stages of Non-Infectious Diseases - was launched by the Icahn School of Medicine at Mount Sinai in collaboration with the Uniformed Services University of the Health Sciences and the Henry M. Jackson Foundation for the Advancement of Military Medicine. It brings together 10 specialties across the Mount Sinai Health System and will study more than 25 conditions simultaneously, with the goal of identifying molecular warning signals that appear years before a diagnosis.

What the DoD Repository Makes Possible

U.S. military service members undergo comprehensive health monitoring from enlistment forward. The resulting records - including regularly collected blood samples - create a longitudinal biological dataset with no civilian equivalent. For researchers, those stored samples offer a rare scientific opportunity: the ability to look backward from a diagnosis and ask what was happening in the body three, five, or ten years earlier.

ORIGIN will analyze blood from up to 13,000 active-duty service members, focusing on samples drawn years before any disease diagnosis. The analytical tools include proteomics (the study of proteins), metabolomics (metabolic byproducts), genomics (genetic variants), and exposomics (environmental exposures) - together often called "omics" technologies. By integrating these data streams, the team hopes to build what researchers describe as a molecular atlas of how disease begins.

The study timeline covers samples collected between October 2003 and September 2025. The project is expected to run for at least 10 years.

From One Disease to Twenty-Five

The scientific foundation for ORIGIN comes from earlier work by Jean-Frederic Colombel, co-director of Mount Sinai's Helmsley Inflammatory Bowel Disease Center and co-principal investigator on ORIGIN. Over more than a decade, Colombel collaborated with USU researchers to study inflammatory bowel disease in military personnel using the DoD repository. That earlier research identified molecular signals in blood samples taken years before IBD was diagnosed.

ORIGIN expands that model dramatically. Where the earlier effort focused on one disease, ORIGIN will study conditions including rheumatoid arthritis, lupus, multiple sclerosis, Crohn's disease, neurodegenerative diseases, PTSD, colon cancer, lung cancer, and heart failure - all from the same stored blood archive.

"For years, we have dreamed of being able to tell a patient: 'We see this coming, and here is what we can do about it,'" Colombel said. "ORIGIN is the realization of that dream. By studying the blood of service members years before they get sick, we can map the molecular road to disease and ultimately develop tools to change course."

Breaking the Habit of Studying One Disease at a Time

One of the structural innovations in ORIGIN is its deliberate departure from disease-siloed research. Medicine has traditionally organized itself around the organ or system that a disease affects - cardiologists study heart failure, neurologists study multiple sclerosis, oncologists study cancer. ORIGIN is designed to look across all of these simultaneously, searching for shared biological pathways that underlie apparently distinct conditions.

That work is coordinated through the Precision Immunology Institute at Mount Sinai, which was specifically built to break down barriers between medical specialties. "By uniting 10 departments and bridging the worlds of military medicine and academic research, we are creating something entirely new - a molecular atlas of how disease begins," said Miriam Merad, director of the institute and co-principal investigator for ORIGIN.

USU's data analysts will select and match cases and controls from the Military Health System Data Repository, coordinate record deidentification, and ensure data security before sharing samples with Mount Sinai for analysis.

Military-Specific Exposures Add Another Layer

The study will also examine the biological effects of military-specific environmental exposures, including burn pits and per- and polyfluoroalkyl substances - synthetic chemicals known as PFAS or "forever chemicals" - found at more than 700 U.S. military sites. These exposures have been linked to elevated cancer risk and other health conditions in veterans, but the molecular mechanisms through which they alter disease susceptibility remain poorly understood.

The scope of ORIGIN also makes it relevant far beyond military medicine. Early-onset colon cancer - a disease rising among Americans under 50 - is among the conditions targeted. So is PTSD, which affects millions of civilians as well as veterans. Findings from ORIGIN could eventually reshape clinical guidelines for how these diseases are detected and classified.

One fundamental limitation of any study using retrospective blood samples is that causal relationships are difficult to establish with certainty. Correlation between a molecular marker and a future diagnosis does not prove the marker caused the disease. Larger follow-up trials will ultimately be needed to validate any predictive biomarkers ORIGIN identifies before they can be used in clinical practice.