What if doctors could tell you a disease was coming years before you felt a single symptom-and stop it in its tracks? That is the goal of a sweeping new research initiative launched by the Icahn School of Medicine at Mount Sinai in collaboration with the Uniformed Services University of the Health Sciences (USU) and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF).
The project, called "ORIGIN: Omics to Characterize Preclinical Stages of Non-Infectious Diseases," brings together 10 specialties across Mount Sinai Health System in an ambitious multidisciplinary disease-prevention study.
The study will analyze stored blood samples from up to 13,000 active-duty U.S. service members, drawn years before any diagnosis, using advanced molecular "omics" tools such as proteomics, exposomics, metabolomics, genomics, and more. By identifying risk factors and early warning signals, ORIGIN aims to lay the groundwork for predicting and ultimately preventing some of today's most common and devastating diseases.
A decade of partnership, now expanded to a global scale
"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,'" said Jean-Frédéric Colombel, MD, Professor of Medicine (Gastroenterology) and Co-Director, The Helmsley Inflammatory Bowel Disease Center, Icahn School of Medicine at Mount Sinai, and Co-Principal Investigator, ORIGIN. "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. This is medicine at its most proactive, and it could benefit not just military families, but every American."
For more than a decade, Dr. Colombel has partnered with USU researchers to study inflammatory bowel disease (IBD) in military personnel using the Department of Defense Serum Repository (DoDSR), which contains millions of longitudinal blood samples. Their research identified molecular signals in the blood years before IBD was diagnosed.
ORIGIN dramatically expands that model. Where the earlier effort focused on one disease, ORIGIN will study more than 25 conditions simultaneously, including rheumatoid arthritis, lupus, multiple sclerosis, Crohn's disease, neurodegenerative disease, post-traumatic stress disorder (PTSD), colon cancer, lung cancer, and heart failure. The effort is powered by the Precision Immunology Institute at Mount Sinai (PrIISM), whose cross-disciplinary model is specifically designed to break down the walls that traditionally separate medical specialties-enabling cardiologists, immunologists, neurologists, oncologists, and environmental and data scientists to work as one team.
Why the military? A unique window into human health
U.S. military service members receive comprehensive, routine health monitoring from the moment they enlist, creating an extraordinary long-term medical record that is unlike anything available in the civilian world. The DoDSR holds serial blood samples from millions of service members, many collected a decade or more before any illness emerged. For researchers, this is a scientific treasure.
ORIGIN will use this resource to answer questions that have never been answerable before, including:
- What is happening in the body five years before someone is diagnosed with lupus?
- What molecular changes precede early-onset colon cancer-a disease on the rise in younger adults-by three years?
- How do military-specific environmental exposures like burn pits and per- and polyfluoroalkyl substances (PFAS, aka "forever chemicals," which are found at more than 700 U.S. military sites) alter the body's biology and raise disease risk?
USU's data analysts will select and match cases and controls from the Military Health System Data Repository, coordinate with the Armed Forces Health Surveillance Division to deidentify all records, and ensure the proper governance and security of the data and serum before it is shared with the Mount Sinai research team for analysis.
The men and women warfighters of this country deserve cutting-edge medical care. Our collaboration with Mount Sinai directly advances our USU mission to support the readiness, health, and well-being of our military community, using the unparalleled resource of the DoD Serum Repository to decode the early biology of chronic diseases. The insights from ORIGIN will help us protect service members today and advance medicine for decades to come."
Daniel J. Adams, MD, Associate Professor of Pediatrics at USU and USU's Principal Investigator for ORIGIN
Breaking medical silos: The PrIISM approach
One of the most exciting aspects of ORIGIN is the way it is structured. ORIGIN is designed to break from the traditional model of studying one disease at a time. Instead, 10 departments across Mount Sinai Health System are collaborating under PrIISM to look for shared biological pathways across different conditions.
Using advanced "omics" technologies, researchers will analyze proteins, metabolites, environmental exposures, and immune responses from blood samples, integrating these data through sophisticated computational modeling. By uncovering common molecular roots of disease, the team hopes to develop treatments and prevention strategies that work across multiple conditions-and ultimately reclassify illness based on molecular biology rather than the organ it affects.
"ORIGIN is exactly the kind of bold, boundary-breaking science that PrIISM was built to support," said Miriam Merad, MD, PhD, Director, PrIISM, and Mount Sinai's Co-Principal Investigator for ORIGIN. "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. The potential to prevent illness before it starts, and to rewrite how we classify and treat dozens of conditions, is truly transformative for patients everywhere."
A study with real-world impact
The study timeline covers samples collected between October 2003 and September 2025, and the project is expected to run for at least 10 years-with findings that could reshape clinical guidelines, drug development, and public health policy for generations.
Diseases targeted by ORIGIN include conditions that are increasingly common among younger Americans, such as early-onset colon cancer, PTSD, and Crohn's disease, making its findings urgently relevant far beyond the military community.
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