From the Deputy Director for Intramural Research

Intramural Contributions to the Public Health

BY MICHAEL GOTTESMAN

I have often used this space to remind the NIH intramural community of the important role that the NIH intramural program plays in addressing urgent and compelling issues related to the public health. Three recent examples are worthy illustrations of the importance and impact of intramural involvement in mounting a rapid and effective research response to complex and difficult issues that have aroused public concern and threaten the public health: (1) the role the National Institute of Allergy and Infectious Diseases (NIAID) is playing in developing diagnostics and a vaccine that could help contain the current Zika epidemic; (2) a new protocol at the National Institute of Neurological Disorders and Stroke (NINDS) to help define, characterize, and potentially treat postinfectious myalgic encephalomyelopathy (previously known as chronic fatigue syndrome); and (3) the National Institute of Environmental Health Sciences’ (NIEHS) research related to the lead-contaminated water supply in Flint, Michigan.

NIAID Director Anthony Fauci has been a visible authority in interpreting events related to the Zika epidemic in South and Central America and the Caribbean to a concerned American and international audience. The key elements of this filovirus epidemic are the important role that mosquito vectors play (especially members of the genus Aedes); the relative mildness of the primary illness compared with its potentially devastating effects—especially microcephaly—on the developing fetus when women are infected early in pregnancy; and its cross-reactivity with dengue, another filovirus, makes antibody-based epidemiological studies difficult.

As related by Hugh Auchincloss, NIAID deputy director and acting scientific director, the NIH intramural program is contributing to studies of the pathogenesis of Zika and its potential prevention in two important ways. First, to allow Zika-specific antibody studies, NIAID is synthesizing a Zika antigen that is devoid of dengue cross-reacting epitopes. Second, a current intramural quadrivalent dengue vaccine is being modified to insert Zika open-reading frames. The production of this construct is straightforward, but the creation of a vaccine suitable for use will take at least a year. This delay, given the rapid spread of Zika in the Americas, will mean that such a vaccine will arrive after the main epidemic has passed. Most susceptible individuals will have been infected and developed natural immunity. Targeting the mosquito vector now appears to be the highest priority for prevention.

Avi Nath, NINDS clinical director, is developing a clinical protocol to study postinfectious myalgic encephalomyelopathy–chronic fatigue syndrome (ME-CFS). An important issue with this disorder is the need to carefully define the patient population that will be studied to increase the likelihood that a clear etiology can be determined. One typical pattern is the development of profound fatigue and postexertional weakness after an acute febrile illness.

Postviral asthenia, or weakness, is a well-established phenomenon, but in most people, the fatigue dissipates after a few weeks. In people with ME-CFS, however, the fatigue persists for many months or years. A reasonable hypothesis is that this weakness is the result of the activation of an immune-mediated brain dysfunction.

Nath’s protocol will explore this hypothesis through detailed phenotyping including genetic, metabolic, microbiological, neurological, immunological, and neuroendocrine studies of a pilot group of 40 ME-CFS patients and various control subjects. It is hoped that the application of the most advanced studies of this type will provide an indication as to what goes wrong in this disorder.

Finally, the NIEHS has taken a long-term leadership role for the Department of Health and Human Services in research related to the health effects of the lead-contaminated drinking water in Flint, Michigan. Linda Birnbaum, director of NIEHS, and John Bucher, scientific director of NIEHS’s National Toxicology Program, explained that Flint’s water source was changed about two years ago from the treated Detroit Water and Sewerage Department water (from the Detroit River and Lake Huron) to the highly corrosive Flint River. Because the Flint River water was not treated with orthophosphate to prevent leaching of lead from lead piping and lead soldering in public pipes and plumbing in Flint households, lead concentrations in some of the drinking water coming from some faucets reached 13,000 parts per billion (ppb); 15 ppb is the highest concentration allowed by the Environmental Protection Agency.

No level of exposure to lead is considered safe, however. NIEHS research has confirmed that blood-lead concentrations above 5 micrograms per deciliter (μg/dL) delay puberty, increase the incidence of attention deficit hyperactivity disorder (ADHD) and other problem behaviors, and decrease academic achievement and cognitive measures in children.

A full evaluation of blood-lead concentrations in children in Flint is underway, but a limited sample so far indicates a doubling or tripling of the numbers of children with concentrations greater than 5 μg/dL. Both Birnbaum and Bucher emphasized that environmental lead contamination in lower-income communities is not limited to Flint and represents an important contributor to health disparities as well as illustrating the need for environmental justice in oversight of environmental contaminants.

I think we should all be proud of these important leadership roles and contributions of our intramural colleagues to improving both global health and health within our own communities. In addition to the direct effects of developing new diagnostics and therapeutics, the trusted research that we do at NIH provides a firm foundation for important public-health policies.