by Mary Gearing
figures by Krissy Lyon

Imagine being a parent in Flint, Cleveland, or another city with high lead levels, constantly wondering about the effects of lead on your children’s health. You’d keep asking the same questions: if we lived somewhere else, would they be smarter? Will they have trouble in school or later in life because of lead? The sad truth is that there is no safe level of lead exposure. You’ve probably heard that lead is linked to lower IQs, aggressive behavior, criminal activity, and neurological disease, but news reports rarely discuss the biology behind lead poisoning. In fact, lead’s danger lies in its ability to mimic and disrupt essential molecules in our bodies, with devastating effects on the brain and other organs.

How does lead enter and affect the brain?

Lead is a true poison that has no necessary role in the body. Because it looks like a lot like calcium, an essential player in brain chemistry, lead can sneak into the otherwise well-protected brain. Lead then disrupts the movement and storage of calcium inside cells, increasing cell stress, which can lead to the death of neurons and other brain cells.

Lead also hijacks calcium’s roles in the brain, including communication between neurons. When a neuron is activated, calcium enters the neuron and stimulates the release of chemicals called neurotransmitters. Neurotransmitters carry the activation signal from this first neuron across a small gap to the next neuron, thus passing the signal. This process repeats until the signal reaches its target.

By mimicking calcium, lead fundamentally changes how neurons pass these signals, as shown in the figure below. First, lead competes with calcium movement into a neuron – when lead is present, less calcium can enter the neuron. As a result, the neuron releases less neurotransmitter, sending a weaker signal to the following neuron. Lead can also cause spontaneous neurotransmitter release in non-activated neurons, so later neurons receive inappropriate signals (Figure 1). Neurotransmitter signaling is especially important for learning and memory, and lead exposure impairs these processes.

Figure 1: Lead alters neurotransmitter release. When calcium (Ca2+) enters a neuron, the neuron releases neurotransmitter (green diamonds) to send a signal to the next neuron. Lead (Pb2+) can interfere with this process in two ways. When lead blocks calcium entry into the neuron, the neuron releases less neurotransmitter and sends a weaker signal to the next neuron. Lead can also cause aberrant neurotransmitter release when calcium is not present.
Figure 1: Lead alters neurotransmitter release. When calcium (Ca2+) enters a neuron, the neuron releases neurotransmitter (green diamonds) to send a signal to the next neuron. Lead (Pb2+) can interfere with this process in two ways. When lead blocks calcium entry into the neuron, the neuron releases less neurotransmitter and sends a weaker signal to the next neuron. Lead can also cause aberrant neurotransmitter release when calcium is not present.

Lead is associated with decreased brain volume

Humans are most vulnerable to lead before birth and early childhood, because the brain and other systems are growing and developing rapidly. Since lead changes the way neurons interact and causes cell death, it irreversibly alters the delicate process of development. Moreover, lead levels in children are often higher than in adults exposed to the same environment, because children consume more food and water relative to their size than adults. Children also chew and eat objects around them, including paint chips or lead-containing toys, increasing their lead exposure.

To calculate the impact of childhood lead exposure, researchers from the Cincinnati Lead Study recruited pregnant women living in Cincinnati neighborhoods with high levels of lead. They recruited women from 1979-1984 and monitored their children closely up to 6.5 years of age, then again at 10, 15-17, and 19-24 years.

Researchers examined how lead exposure altered total brain size, as well as the size of specific brain regions. Using magnetic resonance imaging (MRI), they found that higher lead exposure was associated with a smaller prefrontal cortex in young adults (Figure 2). Since the prefrontal cortex is responsible for attention, complex decision-making, and regulating social behavior, differences in its size and function could explain the cognitive and behavior problems seen with lead exposure.

Figure 2: Lead exposure is associated with decreased brain volume. Brain scans were compiled/averaged from 157 subjects in the Cincinnati Lead Study and overlaid on a standard brain template. Red and yellow areas indicate regions of volume loss. The first row of images shows prefrontal cortex volume loss. Figure from Cecil et al., 2008, licensed under a Creative Commons Attribution License.
Figure 2: Lead exposure is associated with decreased brain volume. Brain scans were compiled/averaged from 157 subjects in the Cincinnati Lead Study and overlaid on a standard brain template. Red and yellow areas indicate regions of volume loss. The first row of images shows prefrontal cortex volume loss. Figure from Cecil et al., 2008, licensed under a Creative Commons Attribution License.

Lead increases the risk of heart disease

Lead also affects other parts of the body, notably the cardiovascular system. Lead’s effects on the heart and blood vessels put people at higher risk for high blood pressure, coronary artery disease, and stroke later in life.

Blood vessels are more than just tubes that carry blood; they contain muscle cells that help them adjust to a changing environment. For example, if you’re dehydrated, the muscle contracts, decreasing the space for blood to flow, and increasing your blood pressure so you don’t faint. Constant high blood pressure is bad for vessel health, and the body has numerous signals to regulate blood pressure. Unfortunately, lead affects a number of these signals.

One culprit of lead in blood vessels should be familiar: calcium. Just as in the brain, lead can be transported like calcium in vessel cells and take over some of calcium’s normal activities. In vessels, calcium promotes vessel narrowing to increase blood pressure, so lead does the same, damaging vessels over time. Lead also increases vessel muscle cell stress, further stiffening vessels and increasing blood pressure (Figure 3).

When blood vessels become smaller, the heart must work harder to pump blood around the body. To get an idea of these demands, imagine drinking water through a normal-sized straw, and then compare that effort to drinking the same amount of water through a small coffee straw. As the heart struggles to cope with these increased demands, it actually becomes weaker. Many years after initial lead exposure, a weakened heart and blood vessels can lead to a heart attack, stroke, or other complications.

Figure 3: By mimicking calcium and increasing cell stress, lead causes vessels to constrict, limiting the space for blood to flow (compare the size of the red circles.) This narrowing increases blood pressure, forcing the heart to work harder. Lead causes both the blood vessels and the heart to weaken, increasing a person's risk of heart disease.
Figure 3: By mimicking calcium and increasing cell stress, lead causes vessels to constrict, limiting the space for blood to flow (compare the size of the red circles.) This narrowing increases blood pressure, forcing the heart to work harder. Lead causes both the blood vessels and the heart to weaken, increasing a person’s risk of heart disease.

We can stop lead exposure – but we must take action

In the 1970s, the government banned lead from paint and began phasing it out of gasoline, two major public health successes that lowered blood lead levels by about 80%. But the war has not yet been won. Forty years later, the CDC estimates that 500,000 children in the United States have blood lead levels above 5 ug/dl, the threshold for public health intervention.

It’s clear that lead is still a major public health concern, but the response to the latest lead crisis in Flint was sorely lacking. We now know that children under 6 drinking Flint River water were 46% more likely to have blood lead levels above 5 ug/dl. State and local officials used misdirection to minimize this situation, refusing to acknowledge the problem. These actions were not merely negligent – they were criminal, and multiple individuals have been indicted for these activities.

In failing to take action to reduce lead exposure, we are allowing children to encounter a poison that irreversibly damages their bodies. Lead exposure sets children up for every disadvantage in life. Even worse, it is most common in children already disadvantaged due to low socioeconomic status. It is unconscionable to allow this poison to continue to threaten human health – in Flint, across the United States, and around the globe.

Despite these sobering problems, there is hope for the future. A 2009 analysis suggests that every dollar spent on lead removal may have an economic benefit of $17-$220, including increased economic productivity and decreased education and health care costs. This cost-benefit ratio is similar to that of vaccines, a major public health triumph. Since a diet rich in calcium, iron, and vitamin C can lower children’s absorption of lead, hunger prevention programs like SNAP and local food banks also reduce the negative effects of lead exposure.

What can you do to fight lead and environmental pollutants? The American Academy of Pediatrics has excellent resources on lead in the home, including how to screen your water for lead. Blood lead testing is recommended for children under 6 and is commonly covered by insurance. Numerous nonprofit organizations have made lead poisoning a policy priority, and the World Health Organization holds International Lead Poisoning Prevention Week each October. To finally win the war on lead, we must use our voices to advocate for a healthier future.

Mary E. Gearing is a PhD candidate in the Biological and Biomedical Sciences program at Harvard. Follow her on Twitter @megearing.

For more information:

Due to space constraints, some of lead’s biological effects were not covered in this piece. For a more complete picture of lead’s impact on children, please see the WHO guide and other resources listed below. To learn more about the effects of very high lead levels, please see the histories of lead poisoning in the United States.

The Effects of Lead on Children

A Guide to Childhood Lead Poisoning – World Health Organization
Lead Exposure in Children – American Academy of Pediatrics

History of Lead Poisoning in the United States

Lead: America’s Real Criminal Element – Mother Jones
An American History of Lead Poisoning – The Atlantic
Current State of Lead in the United States
The Flint Water Study
Unsafe Lead Levels in Tap Water Not Limited to Flint – New York Times
In Some Zip Codes, 1 in 7 Children Suffer from Dangerously High Blood Lead Levels – Washington Post

Lead Exposure Prevention/Advocacy

Massachusetts Childhood Lead Poisoning Prevention Program – Mass. Health and Human Services
International Lead Poisoning Prevention Week of Action – World Health Organization
Lead Poisoning Prevention Week – Environmental Protection Agency
Lead Prevention Tips – Centers for Disease Control

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11 thoughts on “The Deadly Biology of Lead Exposure

  1. I appreciate this article. It gave me a basic understanding of the biological effects of lead and other published articles, to learn more.

  2. It’s great that you pointed out how lead is a true poison that has no necessary role in the body. I was reading a health magazine earlier and I saw some warnings about the effect of lead paint. It seems lead paint is quite dangerous, and you could even get a landlord lead paint safety certificate because of it.

  3. i found this article very interesting, that has a lot of great info it’s the first time to know it, thanks for sharing

  4. The major source of paint-related exposure in the home is not eating paint chips. It is the ingestion of very fine dust that accumulates in and from window sills. This means every parent (and clinician) can play a role immediately: vacuuming out window sills and floors with a HEPA filter/bag, and washing floors clean of dust. https://www.who.int/news-room/fact-sheets/detail/lead-poisoning-and-health

    This distinction matters very much as it invites more actionable remedies–to a more insidious mechanism.

  5. Wow, it never would have occurred to me that lead can cause cell death in the brain. My brother is thinking of purchasing an older home but he is worried that the paint in the home might contain lead. It seems like it would be a good idea for him to have an inspection service test the property for lead so that he can know if it is safe or not.

  6. I had lead when I was a little girl I got treated and it went away I know it did some type of effect but I got a test done in my adult hood it don’t show , so seeing this since I don’t have any more lead it can’t affect the calcium going into my neuron anymore. So at this point the effect of my calcium is no more.

  7. Preventing further exposure and buildup of lead in the body is critical. Removing the existing lead from a young person’s brain tissue may not reverse the damage already done. So is removing the existing body burden of lead as soon as possible is essential. For most people, modified citrus pectin will work well. A number of studies have shown its effectiveness.

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