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Center for Children's Environmental Health and Disease Prevention at the Harvard School of Public Health, Boston
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Principal Investigator: Joseph Brain
Co-Principal Investigator: Robert Wright
| Overview | Community Partners |
| Summary | Results |
| Exposures and Outcomes | Selected Publications |
| Research Projects |
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.
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.
Unlike many studies that investigate the health effects of a single chemical, the Center is studying how exposure to metal mixtures affects health – reflecting more accurately reflecting the nature of toxic waste dumps where multiple chemicals are present.
The Center will enroll more than 1,000 children and includes epidemiologic studies involving biological monitoring of heavy metals among pregnant women and their children. Studies will also include periodic evaluations of the children as they grow using standardized, observational cognitive tests. A novel component of these studies is examining psychological stress associated with living near a toxic waste dump.
Research includes field testing to identify environmental, nutritional, behavioral and other lifestyle factors for elevated exposure to metals. Interventions will seek to educate parents on how to reduce exposure risks.
The projects also include two laboratory-based animal studies of metal mixtures found at Tar Creek to address the biology of metals absorption from the gastrointestinal and respiratory tracts and to gauge the effects of these metal mixtures on neurobehavioral development.
The Center draws on a group of over 20 scientists and trainees from many disciplines and the work is being conducted in close collaboration with a community-based organization, Local Environmental Action Demanded (L.E.A.D.) Agency, and the Integris Baptist Regional Hospital in Miami, Oklahoma.
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 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 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 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 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.
The potential effect of stress from living near toxic waste is being explored in Project 1 and the potential modifying effect of stress on metals neurotoxicity is being explored in Project 4.
The Administrative, Analytical Chemistry, and Biostatistics Cores enable the Harvard Center to fully integrate and support the research, and the Community Outreach and Translation Core utilizes an innovative portfolio of outreach activities developed in conjunction with a broadly-based Community Advisory Board to develop awareness and influence behaviors and health practices in order to prevent adverse health effects in children from exposure to metals in mining waste.
Primary Exposures: Mining waste, including heavy metals such as lead, manganese, cadmium and iron
Primary Outcomes: Neurobehavioral development, growth, psychological stress
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
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).
Brain JD, Heilig E, Donaghey TC, Knutson MD, Wessling-Resnick M, Molina RM. Effects of iron status on transpulmonary transport and tissue distribution of Mn and Fe. American Journal of Respiratory Cell and Molecular Biology 2006;34(3):330-337. PubMed
Hu H, Shine J, Wright RO 2007. The challenge posed to children's health
by mixtures of toxic waste: the Tar
Creek superfund site as a case-study. Pediatric Clinics of North
America. 2007 Feb;54(1):155-75. PubMed
Oken E, Wright RO, Kleinman KP, Bellinger D, Amarasiriwardena CJ, Hu H, Rich-Edwards JW, and Gillman MW. Maternal Fish Consumption, Hair Mercury, and Infant Cognition in a US Cohort. Environ Health Perspect 2005; 113(10):1376-80. Abstract | Full-Text (PDF) (120KB, 5pp, About PDF) | PubMed
Wright RO, Amarasiriwardena C, Woolf AD, Jim R, Bellinger DC. Neuropsychological correlates of hair arsenic, manganese, and cadmium levels in school-age children residing near a hazardous waste site. Neurotoxicology 2006;27(2):210-216. Abstract | Full-Text (PDF) (220KB, 7pp, About PDF) | PubMed
For more information about research on the
effects of metal exposure on human health: The Metals
Epidemiology Research Group (MERG) was
created at the Harvard School of Public Health in 1991 by
Howard Hu, M.D., as a collaboration between a number of environmental
health scientists who were interested in applying new techniques
to study the impacts of lead and other heavy metals on human
health. The Children’s Center and MERG are part
of the Harvard University Exposure, Epidemiology, and
Risk Program , which provides the overall
structure to investigate health issues such as cognitive
and cardiovascular effects of lead exposure, the effects
of air pollution on respiratory and cardiovascular health,
airborne infection transmission and health effects of bioaerosols,
the effects of infectious agents and disinfection by products
in drinking water, biomarkers of environmental exposure,
and genetic susceptibility to environmentally induced malignancies.
Full List of Publications |
Publications List from NIEHS PubMed Database
Centers Funded By: 