8. Neuroepigenetics of Lead: The Flint Water Crisis

8. Neuroepigenetics of Lead: The Flint Water Crisis


            In April of 2014 Flint, Michigan changed its water supply from the Detroit-supplied Lake Huron water to the Flint River while waiting on a new pipeline from Lake Huron in order to save money. Residents were immediately alarmed by this news, as the pollution of the Flint River was common local knowledge. Soon after this change, residents found that the water from their faucets was discolored brown and smelly. For months the government trivialized the issue and even went to far as to alter evidence. As the problem persisted, they issued notices for residents to boil the water before consumption without making any serious changes. (Debucquoy-Dodley, D., 2016)

Pediatrician Dr. Mona Hanna-Attisha, now a local hero, noticed symptoms in her patients such as skin rashes, stomach pain, and fatigue, which are seen after lead poisoning. Scientists from Virginia Tech contacted her to inform her of increased lead levels they had found in the local water. When researchers looked at the amounts of lead in the blood of Flint residents, they saw that the blood levels nearly doubled after the water source changed. Because young children regularly have their blood tested for lead as a safety precaution, Dr. Hanna-Attisha looked through the medical records and found that more than one out of ten children in the Flint neighborhoods had elevated blood lead levels (Hanna-Attisha et al. 2015).

 

Screen Shot 2016-06-19 at 5.59.28 PM(Hanna-Attisha et al., 2015)

For 17 months, the residents of Flint complained about their water while lead exposure persisted. Flint residents continued reporting symptoms such as skin rash, hair loss, and memory and vision loss. It was not until LeeAnn Walters, a nurse and a mother of four children affected by the high levels of lead in the water, researched further into the situation that the Flint water problem became a national scandal. Walters became suspicious when she noticed that something was wrong when her three year olds developed red bumps after a bath. When she got her children’s blood tested, the results confirmed what she had been afraid of all along; her children had been exposed to dangerous levels of lead. (Lurie, 2016) This is just one of the many victims who unjustly harmed by Flint’s water situation.

After months of ignoring the concerns of Dr. Hanna-Attisha and the complaints of the residents, the government officials finally admitted that the water had more levels of lead than what is safe or normal. It was revealed that in order to save money, the city did not add the anti-corrosives that would prevented the acidic Flint River water from slowly eating away at the pipes. Since the pipes were old and contained lead, the lead began leaking into the water supply and into the bodies of Flint locals who consumed the water. Why is this a grave health concern? Lead is a metal that causes damage to the brain during development and can lead to long-lasting learning and behavioral disabilities in young children. Therefore, the exposure of the people of Flint to lead is likely to have serious health consequences. This article will focus on how lead can affect the brain of children throughout childhood, adolescence and adulthood.

Children and adults can become exposed to lead by inhaling lead particles in the air of homes in which lead-based paint is used or by ingesting it from drinking water coming from corroded pipes as well as lead-based plated faucets. When lead is breathed in through the nose or mouth, about 30-50% of lead particles are absorbed into the mucus of the lungs. The smaller lead particles can spread to many organs of the body (including kidneys and brain) while larger lead particles can reach the digestive tract when the mucus is swallowed. When lead reaches the digestive system of adults, only 10-15% of lead is absorbed. However, when children or pregnant women swallow lead, they absorb half of the lead! Usually, most of the lead leaves the body within a couple of months, but some of it can be stored in the bones or teeth for 10 years or longer (ATSDR, 2011).

This topic is of great interest and importance in light of the current devastating water crisis in Flint— an avoidable man-made disaster. Perhaps what is most horrifying about this is the criminal neglect of government officials, and the social implications this carries due to Flint being a majority black and low-income community. As young scientists in training, we feel that our job is to present this information about how lead exposure works to those who have loved ones affected by this tragedy. Educating the public may help get these affected children the long-term health and educational care that they deserve.

NATURE VERSUS NURTURE

The concept referred to as “nature” versus “nurture” helps to explain the science of who we are. Each cell in the body has a set of instructions called the DNA, which is the blueprint for life. Each segment of the DNA expressed different instructions for making different products. These products are called proteins, substances in the body that help build, maintain, and replace the tissues in your body. Every cell in a person’s body has the same exact set of instructions, or DNA. However, not the same set of instruction is read, or “transcribed”, from every cell. There are tiny tags that are added onto the DNA to control if a gene is turned on (transcribed) or not. They can be thought of as seal or a lock with a key that determines whether a particular cookbook recipe, or close set of genes, will be read from the library of recipes book, or our genome. The function of some of these genes, or recipe books, is to make a usable product or dish, called proteins. “Proteins” are substances in the body that help build, maintain, and replace the tissues in your body, and “genes” are the locations in the DNA that hold the instructions for how to make that protein.

There are two types of tags: ones that we are born with and ones that are added later in life due to experience, including environmental pollutants such as lead or stress. The tags that are added due to experience are also referred to as epigenetic modifications. These “epigenetic modifications” are changes made to the instruction guide for our cells, or our DNA, that turn a gene on by “unlocking” or off by “locking” the cookbook. The recipes, or genes, are still there, but locks are either added so they can’t be read and their product (the proteins) can’t be made, or locks are removed so the recipe can be read and the product can be made. Thus, the concept of “nature”— what we’re born with— versus “nurture” — changes made to us by the environment is important to keep in mind when learning about the effects of lead exposure on our brains.

PRENATAL EXPOSURE

While an estimated three out of seven children were affected by the water drinking supply in Flint, around the Detroit community, thousands of children younger than five years still have blood lead levels that are higher than (Senut et al. 2012) the greatest “safe” lead level acceptable to the U/S. Agency for Toxic Substances and Disease Registry (ATSDR, 2012). In a 2015 study by Sen et al., researchers found that 564 particular recipes, or gene locations, coming from the “DNA book library”, that had a particular type of lock, called the DNA methyl marks. There were different levels of these DNA methyl marks, or “locks,” on the 564 genes, or “recipe books,” in the animals exposed to lead. This means that lead might be changing the locks to either close or open the recipe book, which would change the amounts and types of protein products being made. The researchers found that lead exposure during pregnancy affects the “recipe book lock” even in a woman’s egg cells, where these changes can be passed on to the grandchildren. The interactions between environmental and life experiences and our genetic makeup can influence who we are and how we behave in stressful, social, and in novel situations.

Lead exposure during pregnancy can have major negative effects on how we respond to stressful experiences. A study found that when mouse mothers are given low levels of lead before pregnancy, their babies experience greater stress in response to scary situations. This happens when there are changes in levels of hormones we use to respond to stress. A hormone is a secreted substance that travels to organs or tissues and affects their functions. In this study, the levels of the hormone that is used to “tone down” our stress response, or corticosterone, were lower in the children of the mothers that were given lead before becoming pregnant. This changed how the mothers’ babies responded to stressful or scary situations in the long-term (Virgolini et al, 2006). These possible long-lasting changes in the response to stress are seen in both female and male babies of mothers exposed to lead and stressed two months before pregnancy (Cory-Schleta et al. 2004), suggesting that both girls and boys are can be negatively affected by early pregnancy lead exposure.

More recent studies have also tried to understand what could contribute to the changes in social behaviors as well as learning and memory. A study has shown that when mothers exposed to lead early during pregnancy gave birth to babies that were less social than the babies of the unexposed mothers (Hill et al. 2015). This suggests that lead exposure before birth could also affect children’s motivation to socialize. Another study by Sanchez-Martin et al. (2015) has shown that lead exposure during the time right before and after birth can influence how information gets passed on from the parent to the child. The information passed on affects the cortex, which is important for decision-making, awareness, language, and attention, as well as the hippocampus, which is important for learning and memory. The authors looked at the presence of DNA methyl marks, or cookbook locks, in the brains of 2-month old mice that were either exposed or not exposed to lead before birth. They observed over 1,000 particular sites along the DNA that contained the addition of the DNA methyl marks in the learning and memory center of the brain, the hippocampus. The lead exposure prevented the genes, or “recipes”, from being read, so the instructions needed for learning and memory could not be followed. This includes genes that are important for the functioning of the area where new neurons, or cells of the brain, are born every day to create memories, producing long-lasting decreases in the information that can be retained (Sánchez-Martín et al, 2015). Together, these findings suggest that lead exposure before birth alters learning and memory, social behavior, and/or stress responses by changing the types and amounts of genes, or recipe books, that are being transcribed into usable information.

EARLY LIFE EXPOSURE

Girls and boys exposed to lead during childhood or early adolescence can also develop long-lasting changes in mental performance. The factors that help cause these changes in behaviors include DNA methylation. Recently, 43 children (25 boys and 18 girls; ages from 3 months to 5 years) from Detroit had their DNA samples taken to see how lead exposure from the local water supply affected DNA methylation (Sen A. et al, 2016). The researchers found that lead exposure in boys and girls affected methylation of 75 genes, or locations in the DNA that contain different instructions to make the usable products called proteins. Given that these proteins are important for increasing cell’s activity, also referred to as metabolism, it could be possible that lead exposure during childhood or early adolescence negatively affects mental performance by slowing down activity of cells important for these processes.

Lead has also been shown to affect DNA methylation by changing levels of special proteins that add the methyl marks, or “recipe book locks” to particular sites on the DNA, or recipe book library, in mouse brains. Researchers have found that early life lead exposure decreases levels of the protein called the methyl binding protein 2 (MeCP2) (refer to Sam Cusimato’s podcast) that can determine how many of the genes, or recipe books, contain the methyl marks, or locks. This results in reduced passing on of “recipe” information that help brain cells survive and are needed for brain functioning and learning and memory (Senut et al, 2012). Together, these findings suggest that lead exposure can potentially cause gender-specific changes in marking patterns along the DNA “recipe book” that could contribute to long-lasting changes in passing of information important for many brain functions (Sen A. et al, 2016).

LATE LIFE EFFECTS

Scientists have recently discovered that high lead levels in the blood may increase the risk of developing neurodegeneration and related problems like Alzheimer’s disease— a condition in which mental decline beings at an earlier age and increases as people age. “Neurodegeneration” is when the cells of your nervous system, such as neurons, become damaged and do not function properly. This can cause memory loss, confusion, and difficulty in decision-making, which are all seen in Alzheimer’s disease. Scientists have found specific genes that are affected by lead. As discussed earlier, DNA methylation at a gene prevents it from being turned on, so that the “recipe” can’t be read and the body is now lacking that particular function.

Lead increases DNA methylation for a protein that helps keep brain cells healthy so they can form new memories and recall old ones. This protein that helps brain cells to grow that keeps brain cells alive when they are stressed is called the brain-derived neurotrophic factor, or BDNF (Sen et al., 2015). If DNA methylation is blocking these “recipes” from being read, the cells will be less healthy and it will be more difficult to make new memories and remember old ones. But you can also have the opposite problem where less-than-normal DNA methylation was also found in children of mothers with high blood levels of lead. In this case, too much proteins were made from the genes that did not have the methyl tags. One of these proteins is called the nerve injury induced protein 2 (NINJ2). It helps cells bind to other cells or its surroundings and is needed to repair injured nerves. It also helps neurons to wire together during development and helps them rewire together in the right location after injury (Sen et al, 2015). Too much of this protein may make the neurons improperly rewire together after injury. Thus, lead exposure could cause our brains to age faster.

CONCLUSION

Together, these studies suggest that environmental toxins like lead can have an effect on the babies’ development and children early in life that could be important for producing long-lasting changes in mental performance. Understanding how these changes happen could help to prevent these problems, and also help treat children who have been permanently affected by these changes. With the community becoming aware of the contaminated lead water, there are some steps that concerned parents can take to help their children. Special diets have been shown to help prevent and even reduce the damaging effects of lead exposure (Guillarte et al. 2003). These special diets include foods like green vegetables, salmon, cheese, yogurt, and oranges that are healthy, low-fat, and high in substances like iron, calcium, folate, thiamine, zinc, and vitamin C. (Burke & Miller, 2011) A useful guide of good foods and recipes from the Lead Prevention Program can be found here: https://www.epa.gov/sites/production/files/2014-02/documents/fight_lead_poisoning_with_a_healthy_diet.pdf (US EPA, 2001).

Educating communities about lead exposure can help encourage local governments to provide support for a specialized educational system as well as healthcare benefits for individuals with serious mental impairments. The Health and Human Services Department has issued $3.6 million to give affected Flint residents transportation to get bottled drinking water as well as to doctors’ visits. Also, charities such as the Convoy of Hope and the Flint Child Health & Development Fund have been donating clean water to Flint residents. However, additional funds could not only help secure lead-free water but also help local schools in Flint to host parental informational sessions regarding solutions to prevent or potentially diminish the toxic effects of lead exposure. Given that many of these heavy metals are not only found in the water of the Flint residents, but also in the drinking water of millions of children worldwide, finding a solution to the Flint water crisis will also be very useful for helping the international community to prevent the behavioral and mental impairments associated with lead.

References

Agency for Toxic Substances and Disease Registry. (2011) Lead. Centers for Disease Control and Prevention. Retrieved from http://www.atsdr.cdc.gov/substances/toxsubstance.asp?toxid=22

Burke, M. G., & Miller, M. D. (2011). Practical guidelines for evaluating lead exposure in children with mental health conditions: molecular effects and clinical implications. Postgraduate medicine, 123(1), 160-168.

CNN Library. (2016). Flint Water Crisis Facts. Cable News Network. Retrieved from http://www.cnn.com/2016/03/04/us/flint-water-crisis-fast-facts/

Cory-Slechta, D. A., Virgolini, M. B., Thiruchelvam, M., Weston, D. D., & Bauter, M. R. (2004). Maternal stress modulates the effects of developmental lead exposure. Environmental health perspectives,112(6), 717.

Debucquoy-Dodley, D. (2016) Did Michigan officials hide the truth about lead in Flint? Cable News Network. Retrieved from http://www.cnn.com/2016/01/14/us/flint-water-investigation/

Guilarte, T. R., Toscano, C. D., McGlothan, J. L., & Weaver, S. A. (2003). Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Annals of neurology, 53(1), 50-56.

Hanna-Attisha, M., LaChance, J., Sadler, R., and Schnepp, A. (2015) Elevated Blood Lead Levels in Children Associated With the Flint Drinking Water Crisis: A Spatial Analysis of Risk and Public Health Response. American Journal of Public Health, 106(2): 283-290.

Hill, D. S., Cabrera, R., Wallis Schultz, D., Zhu, H., Lu, W., Finnell, R. H., & Wlodarczyk, B. J. (2015). Autism-Like Behavior and Epigenetic Changes Associated with Autism as Consequences of In Utero Exposure to Environmental Pollutants in a Mouse Model. Behavioural neurology.

Lurie, J. (2016) Meet the Mom Who Helped Expose Flint’s Toxic Water Nightmare. Mother Jones. Retrieved from http://www.motherjones.com/politics/2016/01/mother-exposed-flint-lead-contamination-water-crisis

Sánchez-Martín, F. J., Lindquist, D. M., Landero-Figueroa, J., Zhang, X., Chen, J., Cecil, K. M., … Puga, A. (2015). Sex- and Tissue-Specific Methylome Changes in Brains of Mice Perinatally Exposed to Lead. Neurotoxicology, 46, 92–100.

Sen, A., Heredia, N., Senut, M. C., Hess, M., Land, S., Qu, W., … & Ruden, D. M. (2015). Early life lead exposure causes gender-specific changes in the DNA methylation profile of DNA extracted from dried blood spots.Epigenomics, 7(3), 379-393.

Senut, M. C., Cingolani, P., Sen, A., Kruger, A., Shaik, A., Hirsch, H., … & Ruden, D. (2012). Epigenetics of early-life lead exposure and effects on brain development. Epigenomics, 4(6), 665-674.

United States Environmental Protection Agency. (2001) Lead and a Healthy Diet: What You Can Do to Protect Your Child. United States Environmental Protection Agency. Retrieved from https://www.epa.gov/sites/production/files/2014-02/documents/fight_lead_poisoning_with_a_healthy_diet.pdf

Virgolini, M. B., Bauter, M. R., Weston, D. D., & Cory-Slechta, D. A. (2006). Permanent alterations in stress responsivity in female offspring subjected to combined maternal lead exposure and/or stress. Neurotoxicology,27(1), 11-21.

One thought on “8. Neuroepigenetics of Lead: The Flint Water Crisis

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