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Extramural Research

Harvard Center for Children's Environmental Health and Disease Prevention Research (2004-2011)

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Harvard Center for Children's Environmental Health and Disease Prevention

Principal Investigator: Joseph Brain
Co-Principal Investigator: Robert Wright

Joseph Brain

Overview Exposures and Outcomes
Research Projects Key Findings
Community Partners Publications (2004 - 2011)

Harvard University study areas - Tar Creek, Oklahoma
Harvard University study areas - Tar Creek, Oklahoma


The Center for Children's Environmental Health and Disease Prevention Research at the Harvard School of Public Health was established in June, 2004 to address the concerns of people living in and around the Tar Creek Superfund site in northeastern Oklahoma. This area is highly contaminated by metals from mining waste (including lead, cadmium, iron and manganese) and populated by many residents of Native American descent.

The overall goal of the Harvard Children's Center is to take a highly innovative and integrated approach to addressing a "real world" problem, i.e., the potential of the mixtures of metals that are present in "chat" (mining waste) to interact with each other in terms of exposure, absorption, dose, and adverse effects on child health and development.

Harvards Core Diagram

Environmental Exposures and Health Outcomes

Primary Exposures: Mining waste, including heavy metals such as lead, manganese, cadmium and iron
Primary Outcomes: Neurobehavioral development, growth, psychological stress

Research Projects

The Harvard Children’s Center is pursuing four research projects, two of which involve community-based field research with partners at Tar Creek, with the support of four Cores.

Project 1: Metals, Nutrition, and Stress in Child Development is a community-based participatory epidemiologic study that examines biological markers of fetal and early childhood exposure to metals (lead, manganese, cadmium, and iron), their impact on measures of mental development, and their response to a quasi-experimental randomized trial of nutritional and behavioral interventions.

Project 2: Exposure Assessment of Children and Metals in Mining Waste: Composition, Environmental Transport, and Exposure Patterns is assessing the utility of size fractionation and sequential extraction studies for characterizing chat, conducting a nested case-control study of the determinants of high versus low burdens of metals amongst children participating in Project 1, and will produce standardized “homogenized chat” for Projects 3 and 4. 

Project 3: Manganese, Iron, Cadmium, and Lead Transport from the Environment to Critical Organs During Gestation and Early Development in a Rat Model is investigating the expression of binding and transporter molecules for metal transport and the corresponding pharmacokinetics of metals from the lung and gut to the blood, CNS and other organs as they relate to pregnant rats and their weanlings. 

Project 4: Metals Neurotoxicity Research Project is examining the effect of pre- and neo-natal exposure to metals on neurochemical changes and neurobehavioral outcomes in rats.  The effect of simple mixtures of metals will be compared with the effect of “homogenized chat” in both Projects 3 and 4.

Key Findings

  • Exposure to iron oxide has been demonstrated to cause a reduction in transport of manganese and iron in rats, and results suggest that the potential toxicity of these metals can be modified by the level of iron present (Brain et al. 2006).
  • Tests in a group of children ages 11-13, from the Tar Creek area have shown that their general intelligence scores, particularly verbal IQ scores, were lower as the levels of manganese (Mn) and arsenic (As) in their bodies increased.  Scores on tests of memory for stories and a word list were also inversely related to the level of Mn and As.  In some cases, a significant Mn-by-As interaction was found (Wright et al. 2006).

Community Partners

Harvard Community Partners
Harvard Community Partners

The Community Outreach and Translation Core (COTC) of the Harvard Center for Children's Environmental Health and Disease Prevention Research is working with the investigators from each of the Projects and Cores as well as an active COTC Advisory Board to translate and apply the scientific findings of the Center into information for the public, policy makers, and clinical professionals to protect the health of children.

L.E.A.D. Agency, Vinita, Oklahoma
Integris Baptist Regional Medical Center, Miami, Oklahoma

Centers Funded By:
Centers Funded by Epa and NIEHS

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