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The NIH Catalyst: A Publication About NIH Intramural Research

National Institutes of Health • Office of the Director | Volume 25 Issue 3 • May–June 2017

From the Deputy Director for Intramural Research

Population-Based Research Improving Public Health

BY MICHAEL GOTTESMAN, DDIR

Michael Gottesman

In the past I have pointed out how laboratory-based research done at the NIH has changed the practice of medicine. However, even more impact on the health of the public can be attributed to the epidemiological studies done by scientists at the NIH or as collaborations between intramural and extramural investigators. Such population-based intramural programs of various sizes have been established in about half of the institutes and centers, including the NCI, NICHD, NIAID, NIEHS, NIMH, NHLBI, NHGRI, NEI, NIA, NIDDK, and NIMHD. Epidemiologic studies provide rigorous statistical evidence of the association between human behavior or environmental circumstances and disease that may motivate more detailed mechanistic studies to enhance prevention or suggest other interventions to ameliorate disease and disability. Such studies use a wide range of research designs, often involve multidisciplinary and multi-investigator collaborations, and may generate mechanistic data that support findings from laboratory-based studies.

By way of example, allow me to cite studies that have led to changes in the practice of medicine and so have made obvious improvements in the public’s wellbeing. These studies represent a tiny percentage of the population-based studies done at the NIH and have been chosen only to illustrate how powerful such studies can be.

The focus of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), founded more than 50 years ago by Joseph Fraumeni Jr. (who has just retired but will continue as a scientist emeritus at the NIH; congratulations, Joe!), has been on genetic and environmental factors that increase the incidence of cancer. NCI scientists have discovered a substantial percentage of the human genetic syndromes that predispose one to cancer, including the eponymous Li-Fraumeni syndrome that is due to inherited p53 mutations that lead to cancers in multiple organ systems. People who carry mutations that predispose them to cancer can be counseled to undergo earlier and more frequent screening to improve the likelihood that cancer can be discovered in an earlier, more treatable stage.

DCEG scientists also did many of the early epidemiological studies that showed the relationship between human papillomavirus (HPV) infection and cervical and oropharyngeal cancer. Their work pointed to the need for an HPV vaccine, which was developed by John Schiller and Douglas Lowy in NCI.

NCI has also demonstrated associations between various environmental exposures, such as medical X-rays and computed-tomography scans, and an increased incidence of cancer. These studies have resulted in changes in medical practice that should reduce the incidence of radiation-associated cancers.

Another distinguished population-health program at the NIH is NICHD’s Division of Intramural Population Health Research, which will be celebrating its 50th anniversary soon. Epidemiologists in this program study human populations across the lifespan. Twenty-five years ago, NICHD scientists in collaboration with researchers in Ireland found an association between neural-tube defects and folate deficiency.

Today, expectant mothers take folate supplements, and bread is supplemented with folate to ensure adequate maternal concentrations for normal fetal development. As a result, there has been a dramatic drop in neural-tube defects in the United States and several other countries.

NICHD epidemiologists have made other important contributions. They were the first to show an association between maternal diabetes and poor fetal outcomes.

They also showed that participation in formal swimming lessons was associated with an 88 percent reduction in the risk of drowning in children aged one to four years old. (Drowning is a very common cause of death in childhood in many parts of the world.) That demonstration has influenced the advice that pediatricians give parents and will, we hope, lead to universal swimming lessons.

Some studies have been reassuring; for example, NICHD epidemiologists have shown that children conceived by assisted reproductive technologies have the same growth and developmental trajectories as children conceived without treatment.

NIEHS has also contributed to studies of pregnancy and human development. The observation that up to 25 percent of embryos fail to survive six weeks (before women know they are pregnant) came from an NIEHS study, as did the finding that, by age 50, up to 80 percent of black women and 70 percent of white women have uterine fibroids. For black women, especially, the earlier development of fibroids has significant public-health implications.

For NHLBI, the iconic Framingham Study represents a comprehensive effort to enumerate the risk factors that contribute to the development of atherosclerotic cardiovascular disease. Most of the seminal observations about the association among smoking, high blood pressure, lipid abnormalities, obesity, and diabetes and heart disease came from the rigorous population-based studies conducted by the intramural leaders of the Framingham study and their many extramural colleagues who contributed. Additional studies to test the role of these factors in more diverse populations are underway, but the primary methodology came from the Framingham study.

Now, with three generations of study participants, decades of clinical data, and a treasure trove of molecular and DNA-methylation data from thousands of participants analyzed by whole-genome sequencing, gene-expression profiling, microRNA profiling, proteomics, and metabolomics, the Framingham study is at the forefront of a burgeoning new field of molecular epidemiology that will provide insights into the next generation of risk factors for cardiovascular disease and many other diseases.

There are many other examples of profoundly important observations made by NIH population scientists that have improved public health. I think the ones cited here give you a flavor of the important contributions that the NIH has made to this field.

Although somewhat different in approach to laboratory- or clinic-based mechanistic studies, population-based research has had a substantial effect on public health. And, it’s important to note, that although epidemiologists are often the principal investigators for such research initiatives, the work is not possible without the team-science approach that population scientists typically use. Such research teams often include biostatisticians, health behaviorists, and clinicians.

The celebration, in May, of a half-century of studies on population health at NICHD provides us with an occasion to take stock of our many successes and to ensure that we will support rigorous and vigorous population studies at the NIH in the future.

This page was last updated on Monday, April 11, 2022

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