M-LEEAD: Environmental Health in Michigan: Flint Water Crisis

Environmental Health in Michigan: Flint Water Crisis

Summary

The Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) Center, which improves our understanding of the contribution of environmental exposures toward the etiology of chronic diseases and conditions, has mobilized in response to the public health emergency currently unfolding in Flint, Michigan. The Community Engagement Core (CEC) is coordinating efforts between scientists and community partners to inform the creation of materials and messaging targeted toward Flint residents which will improve understanding of the short and long term health effects of the water crisis. Efforts to date include:

Supported Translation of existing materials into Spanish by working with a Detroit based partner organization to put the state in touch with additional translators, helping to address a delay in getting materials translated and out to the Spanish speaking Flint community.
Disseminated newly translated materials through coordinating efforts between Detroit Hispanic Development Corporation (DHDC) representatives and UM-SPH students to go door to door and speak with Flint residents in a predominantly Spanish-speaking community.
Collaborated with Center scientists to revise existing materials with up-to-date scientific information based on UM-SPH research and informed Chief Medical Executive of the Michigan Department of Health and Human Services Dr. Eden Wells of suggested revisions.
Coordinated with multiple academic, community, and government entities to build off existing community connections to coordinate on dissemination of materials and resource distribution.
Provided Expertise to multiple entities in the interest of improving understanding of health impacts of the crisis.

Currently, M-LEEaD Center leadership is in conversation about the best use of resources as we move forward, recognizing the emergent nature of the situation, and will continue to add activities to this as they are completed.

Selected Center Activities

Translation: Angela G. Reyes, Founder and Executive Director of the Detroit Hispanic Development Corporation (DHDC) and M-LEEaD Center Stakeholder Advisory Board member, reached out to UM-SPH faculty and staff for a scientific response to the water crisis, having heard from her Flint partners that materials had not previously been translated into Spanish and that members of the non-English speaking Flint community were continuing to use water in a way that was unsafe. UM-SPH faculty responded and provided a number of both English and Spanish resources that Ms. Reyes and her team compiled and translated, including the Flint Water Response Team document put together by the State of Michigan. This continues to be a developing situation and the CEC is currently in conversation with multiple groups to address this critical issue.
Dissemination: DHDC representatives called for volunteers to disseminate the newly translated materials, and UM-SPH M-LEEaD Center faculty responded by sending out a message to MPH students, several of whom were then able to join students from LaSalud (UM-SPH Latino student group) and community partners in going door-to-door. This effort was supplemented by multiple statewide coalitions (Black and Brown Coalition, Michigan Latino Group) and religious organizations (St. Mary’s Church), which has been serving as the “home base” for weekend dissemination efforts. Most recently, Latino student groups on the UM campus have begun to coordinate amongst themselves in order to better coordinate efforts.
Collaboration: Meanwhile, at the request of both community and academic partners, UM-SPH faculty and M-LEEaD Center scientist Dr. Stuart Batterman reviewed the Flint Water Response Team document put together by the State of Michigan, and provided suggested edits that would better communicate the potential routes of exposure as well as details regarding filters and other strategies for reducing exposure. This newly revised document has been sent to Dr. Eden Wells, Chief Medical Executive, Michigan Department of Health and Human Services and M-LEEaD Center scientist, who forwarded to her communications team.

CEC team members have also been working with Crossing Water, a social worker-led effort to bring relief to families in crisis in Flint, to develop a set of instructional videos related to filter usage and short- and long-term effects of lead exposure.
Coordination: CEC team members have been in conversation with multiple academic, community and government entities to coordinate efforts in Flint. We continue to coordinate with faculty at the M-LEEAD Core Center, the UM SPH’s Task Force on Flint (which is working closely with Flint community residents), and the UM SPH Prevention Research Center (PRC) at UM-SPH, which has longstanding relationships in the Flint community. PRC staff have offered to be a part of dissemination efforts through their existing networks as it is helpful. We are also in communication with community groups in Flint in both the English and Spanish speaking communities to assist with coordination of efforts.

The CEC has also been responsive to national calls for coordination from NIEHS, CDC, and EPA, and has supported efforts to coordinate action among student groups at UM-SPH to organize among themselves.
Expertise: M-LEEaD members have provided expertise through multiple venues. The CEC has worked to share information about nutrition and lead, and helped to circulate fact sheets providing information on dietary sources. For more information, see the “Selected Additional Resources” section.

One recent example of this is M-LEEaD Center and Children’s Center P30 investigators Karen Peterson and Dana Dolinoy, along with Barbara Felt, MD at U of M Mott Hospital, provided Mr. Ryan Burtka, Legislative Director to Michigan State Senator Jim Marleau information and advice on nutritional supplementation and food-based strategies for the children’s population of Flint, Michigan.

Recommendations included judicious use of multi-vitamins (MVI), recommended in the context of the medical home where a primary care provider can take into consideration other medical problems, advise appropriately and provide guidance to help avoid over use of MVI. Note: vitamin supplements should only be taken under a doctor’s supervision. A medical home would help to optimize nutrition education, immunization status, and developmental assessment, intervention and follow up. References and text describing how nutrients influences lead absorption were provided, showing in general deficiencies in calcium, iron and zinc enhance lead absorption, while vitamin D may enhance absorption and bone storage. Studies in adults have shown higher lead absorption rates when fasting.

Mr. Burtka followed up, describing preliminary conversation with DHHS regarding health assessment strategies. Specifically, Medicaid will reimburse fully for vitamins that are recommended in a medical setting. For those individuals not covered by Medicaid, Senator Marleau may want to ensure that coordinating agencies can direct people to either free or reduced cost supplements at the direction of a physician. A main goal is to pivot folks away from the need for bottled water and onto addressing long term health concerns for the Flint Population.

Media Outreach

Dana Dolinoy

Interview with UCSC Science Communication Program regarding molecular epigenetics and environmental justice, April 04, 2016
Interview with Cody Kozacek, which will be featured on Chinadialogue.net, a bilingual news site that focuses on environmental issues in China and globally
Fox2 Detroit TV Interview, "Effects of Flint water on pregnant mothers a concern” January 22, 2016
“Best of Health,” KVMR-FM Radio, Nevada City CA, January 22, 2016
Capital City Live, WILS Radio, Lansing, MI, January 26, 2016
Mom’sRising.org Twitter chat, January 27, 2016

Rita Loch-Caruso

Medpage Today: Public Health & Policy “Friday Feedback: Lead Poisoning and Other Silent Public Health Threats,” Friday, February 19, 2016
China CCTV Interview, January 20, 2016
U.S. News and World Report: Boiling water doesn't remove lead, Loch Caruso warns March 25, 2016

Other Core Activity

Our Integrated Health Sciences Core, represented by Sung Kyun Park, has invited Dr. Mona Hanna-Attisha to UM to give a talk and meet with M-LEEaD scientists and CEC representatives, with a date set for February 3, 2016. The talk was very well-attended and resulted in at least one new collaboration involving coordinating blood lead testing efforts.
Jerome Nriagu, M-LEEaD Center Scientist, has added his name to a list of experts compiled by the American Public Health Association of people who are willing to assist with the response in Flint.
Center Co-Leader Dana Dolinoy has been in conversation with the Children’s Environmental Health Network to share resources and information from the M-LEEaD Center.
We continue to work on ways our M-LEEaD scientists can engage, collaborate, and support the Flint community and regulatory stakeholders in this crisis.

Affiliated Partner Organization Efforts

A number of the CEC Stakeholder Advisory Board member organizations have been undertaking efforts of their own to respond to the developing situation.

Henry Ford Health System: For the past several weeks, Henry Ford and Health Alliance Plan (HAP) have been teaming up to coordinate a system-wide bottled water collection to assist Flint residents impacted by the water emergency. We have since been informed by emergency responders that water donations are no longer needed at this time. However, Henry Ford has been approached for nursing support and a team of nurses is being assembled to assist with health care related services. As an organization with a history of helping those in need in our community and beyond, we want to thank everyone for their spirit of collaboration to participate in this emergency. Henry Ford continues to monitor the situation in Flint, and will direct additional resources if called upon by emergency responders.

M-LEEaD Center Lead Research

Publications

“Perinatal Lead Exposure Alters Gut Microbiota Composition and Results in Sex-specific Bodyweight Increases in Adult Mice”: Members: Dana Dolinoy, Chuanwu Xi; Authors: Wu J, Wen XW, Faulk C, Boehnke K, Zhang H, Dolinoy DC, Xi C; Info: Toxicological Sciences. 2016;151(2):324-333. doi:10.1093/toxsci/kfw046; PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26962054
“A Western Diet Pattern Is Associated with Higher Concentrations of Blood and Bone Lead among Middle-Aged and Elderly Men.”: Members: Sung Kyun Park; Authors: Wang X, Ding N, Tucker KL, Weisskopf MG, Sparrow D, Hu H, Park SK; Info: The Journal of Nutrition. 2017;147(7):1374-1383. doi:10.3945/jn.117.249060; PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28592514
“Environmental Exposures to Lead, Mercury, and Cadmium and Hearing Loss in Adults and Adolescents: KNHANES 2010–2012”: Members: Sung Kyun Park; Authors: Choi YH, Park SK; Info: Environmental Health Perspectives. 2017;125(6):067003. doi:10.1289/EHP565; PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28599263
“Burden of higher lead exposure in African-Americans starts in utero and persists into childhood”: Members: Sung Kyun Park; Authors: Cassidy-Bushrow AE, Sitarik AR, Havstad S, Park SK, Bielak LF, Austin C, Johnson CC, Arora M; Info: Environ Int. 2017 Nov;108:221-227. doi: 10.1016/j.envint.2017.08.021; PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28886415
“Perinatal lead (Pb) exposure results in sex and tissue-dependent adult DNA methylation alterations in murine IAP transposons”: Members: Dana Dolinoy; Authors: Montrose L, Faulk C, Francis J, Dolinoy DC; Info: Environ Mol Mutagen. 2017 Oct;58(8):540-550. doi: 10.1002/em.22119. Epub 2017 Aug 19; PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28833526

Pilot Projects

“Single Cell Transcriptomics to Map the Effects of Developmental Lead Exposure on the Hippocampus”

Primary Investigator: Kelly Bakulski, Justin Colacino

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Abstract: Lead exposure is ubiquitous and CDC estimates that 500,000 or 2.5% of US children under the age of 5 currently have blood lead levels above the reference level for demonstrated neurological deficits (5 μg/dL). Lead is responsible for approximately 1% of the global burden of disease, primarily through permanent effects on childhood intelligence and behavior. The hippocampus is a key brain region involved in learning, memory, and response to stimuli. Both epidemiology and toxicology studies have noted changes in hippocampal function and bulk tissue molecular characteristics. Recent spatial transcriptomics work highlights the highly heterogeneous nature of the hippocampus. Toxicants can act on the hippocampus by altering gene expression and most current work investigates bulk brain tissue or composite regions, but gene regulation is tissue and cell type specific. Study of the hippocampus’ sensitivity to environmental factors, on the level of individual cells, is needed to understand biological determinants of neurodevelopment. In archived tissue from a longitudinal study of mice perinatally exposed to lead or control diet, at 5-months we test for differences in the hippocampus at the single cell level. We will perform single cell RNA-sequencing analysis on 26,000 cells from the hippocampus by lead exposure to 1) test for genome-wide gene expression differences by exposure across all cells; 2) compare cell population and subpopulation proportions by exposure; and 3) test for gene expression differences within cell populations by exposure. We will determine whether the toxic effects of lead are uniform across hippocampal cells or specific to particular sensitive cell types. This proposal is a stepping stone to future work linking cell population specific neurological changes to behavioral changes, characterizing the molecular basis by which lead influences cognition and behavior. Understanding links between cellular differentiation state and hippocampal transcription with toxicant exposure may offer mechanistic insights into the neurodevelopmental effects of lead exposure and can highlight potential interventions.
Accomplishments: Coming soon!
Policy or Public Health Impacts: Coming soon!
Publications: Coming soon!
Grant applications and grant awards resulting from Pilot Project: Coming soon!

“In Utero Lead Exposure and Neuron-specific Epigenetic Change Associated with Life-Course Neurobehavioral Phenotypes”

Primary Investigator: Dana Dolinoy, PhD

Co-Investigator: Christopher Faulk, PhD; Howard Hu, MD, ScD; Karen E. Peterson, ScD; Brisa N. Sanchez, PhD

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Abstract

Recent human post-mortem evidence indicates that frontal cortex neuronal cells have distinct DNA methylation signatures compared to non-neurons. In addition, the methylation landscape of neuronal cells varies depending on neuronal activity, based on in vivo research in adult mice. This evidence suggests that the methylome of neuronal cells may be plastic throughout the lifespan and it may be particularly sensitive to environmental conditions such as lead (Pb) exposure. Previous epigenetic epidemiology research in the brain has studied mixed cell types in whole tissue samples, but it is now clear that epigenetic analyses that target specific cell types may be more informative, particularly since neurons are known to represent approximately only a fraction of cells in CNS tissue.

Accomplishments

We are conducting a novel study of neuron-specific epigenetic signatures associated with Pb exposure in a mouse model. Using post-mortem frontal cortex tissues from 10-month old mice exposed in utero to Pb and control water, we have optimized the use of Fluorescence Assisted Cell Sorting (FACS) to separate neuronal nuclei from non-neuronal nuclei in 9 control samples and 18 Pb exposed samples. We have performed a whole-genome tiling array (Nimblegen) on DNA from neuronal nuclei from control and Pb-exposed mice. Next we will assay for differential DNA methylation in the neuronal cell population compared to non-neuronal cells in the promoter regions of four candidate genes: Adam17, Bace1, Aph1a, and Drd1a, as well as globally. This mouse work will lay the foundation for future epigenetic epidemiology studies in Alzheimer’s disease cases versus control samples, as well as ongoing studies in epigenetics, life course obesity phenotyping, and metabolic syndrome risk.

Policy or Public Health Impacts

The developmental origins of health and disease literature has emphasized perinatal environmental exposures and chronic disease in adulthood, but has failed to fully integrate life-course analysis with epigenetic approaches that carefully consider cell-type specificity. Using a well-established gestational lead exposure mouse model, this project is examining the relationship of in utero lead exposure to neuronal frontal cortex DNA methylation in four key genes involved in Alzheimer’s Disease-like pathologies and activity, as well as global methylation levels. By integrating analysis of lead exposure, frontal cortex neuronal DNA methylation patterns, and activity/energy endpoints, data from this project will illuminate mechanisms by which early environmental exposures are linked to later disease and may shed light on potential preventive approaches to reduce long-term disease risk.

Publications

Grashow R, Miller MW, McKinney A, Nie LH, Sparrow D, Hu H, Weisskopf MG. Lead exposure and fear-potentiated startle in the VA Normative Aging Study: a pilot study of a novel physiological approach to investigating neurotoxicant effects. Neurotoxicol Teratol. 2013 Jul-Aug; 38:21-8. PMID: 23603705.

Grant applications and grant awards resulting from Pilot Project

P01 ES022844 (Center PI: Peterson: Project 3 PI: Dolinoy) 04/01/13-03/31/18 NIH NIEHS/EPA “Lifecourse Exposures & Diet Epigenetics, Maturation & Metabolic Syndrome” Goals: This proposed Center seeks to understand the mechanisms by which exposures to mixtures of EDCs (bisphenol A (BPA), phthalate metabolites, lead, and cadmium) in utero and during the pubertal transition affect physical growth and maturation and lead to alterations in metabolic homeostasis, oxidative stress and contribute to risk of metabolic syndrome. R21 grant submitted for RFA: Research Linking Environmental Exposure to Neurodegenerative Disease

Selected Additional Resources

Informational Links

Fact Sheets

Other University of Michigan Lead resources

Government resources

This document was prepared by Amy Schulz and Barbara Israel, Co-Investigators, and Sharon Sand, Project Coordinator, of the Community Outreach & Engagement Core

The CEC promotes multi-directional communication among UM environmental health researchers, public health decision makers, and communities. Researchers work together to advance knowledge of environmental health issues that affect community members in Detroit and Southeast Michigan. More information can be found at mleead.umich.edu, or by contacting Sharon Sand, Project Coordinator, at (734) 615-8695 or slsand@umich.edu.