Interest in newborn health, ignited at Yale, leads to major discovery
Ofer Levy ’88, professor of pediatrics at Harvard Medical School and director of the Precision Vaccines Program at Boston Children’s Hospital, can trace his lifelong interest in infectious diseases to the research he did at Yale under the mentorship of I. George Miller, Jr., the John F. Enders Professor of Pediatrics. “In his lab, we studied the mechanisms by which Epstein-Barr virus causes disease,” Levy says. “It was my introduction into doing bench research at a sophisticated level.” In the Molecular Biophysics & Biochemistry (MB&B) program at Yale, he says he learned from and emulated former MB&B majors who pursued physician-scientist paths through M.D./Ph.D programs, and he took a deep interest in global health. He also relished his political science classes and was drawn to how research could be used “as a tool to improve the human condition.”
“Newborns do not vote, and they can’t speak,” he says. “Yet the majority of deaths due to infectious disease are in early life — especially in resource-poor countries.”
These concerns led Levy to a career as both a pediatric infectious disease specialist and researcher. Specifically, he’s looking for an answer to a question that has long eluded scientists: How exactly does the human body change — at the molecular level — in early life? And might we exploit these changes to better defend infants against infectious disease?
This past week, Levy and researchers from the University of British Columbia and the London School of Hygiene and Tropical Medicine announced a breakthrough that provides the first clues. In a study published in Nature Communications, scientists showed that they were able to extract detailed data from a small amount of newborn blood that could be used as a baseline for better understanding newborn health and the impact of medical interventions such as vaccines in early life. They drew samples from two infant groups — one in The Gambia in West Africa and one in Papua New Guinea —and found similar developmental trajectories.
“It’s the first-ever analysis of the first week of human life at the molecular resolution,” Levy says. “We were able to recruit cohorts of newborns at two different resource-poor settings across the globe, fractionate the blood, and ship frozen samples to endpoint labs to do systems analysis.”
From the day of birth to one week, researchers saw dramatic changes taking place. “Thousands of analytes [bio-chemical markers] changed in the first week of human life,” Levy says. “It gives us new insight into the molecular changes and demonstrates increases in host defense systems in early life.”
Using these common molecular changes as a baseline, Levy and other researchers can now go one step further, to discover how to use vaccines most effectively in early life to prevent disease. “These days, vaccines are given to infants at any time,” Levy says. “But maybe there’s a big difference if they are given at day zero as opposed to another day.” This next-stage vaccine research is being funded by the National Institutes of Health’s Human Immunology Project Consortium program.
Levy and another of the article’s co-senior authors Hanno Steen, an expert in proteomics (the measurement of the inventory of proteins in a biosample) are also collaborating with Yale Professor of Medicine Albert Shaw to examine newborn blood for biomarkers of influenza, and with Ruth Montgomery, assistant dean for scientific affairs at Yale, for Lyme Disease biomarkers.
While it’s currently too expensive to test every baby’s blood for the thousands of biomarkers they’ve identified, Levy can imagine a future in which researchers can identify a few predictive molecules that impact diseases and use their technology to test for those in all babies. The implications for the technology are in the early stages, but far-reaching for the possible impacts on global newborn health.