Lead: a heavy metal toxin that is deeply connected to our ancestors’ neurodevelopment and historical evolutionary processes
By EMILIA ROSE— science@theaggie.org
In 1921, an American chemist named Thomas Midgley Jr. developed a new method to reduce engine knocking, a process in which fuel ignites unevenly and produces a shockwave. When Midgley added a small amount of tetraethyl lead (lead-based fuel) to his test engine, nearly all engine knocking vanished.
From this point on, leaded fuel became the new norm for all cars for most of the 20th century, and the chemical byproducts were then pumped into our atmosphere. However, lead is a heavy metal toxin, and by comparing lead levels in the atmosphere with neurodevelopment patterns, researchers have found that long-term exposure to it — like what was seen for nearly a century — has had severe, unintended consequences.
In a 2024 paper, Duke scientists Michael J. McFarland, Aaron Reuben and Matt Hauer estimated the effects of the widespread use of tetraethyl lead in common automobile fuel. They estimated that mental illness in the general population significantly increased during the era of tetraethyl lead.
At the molecular level, lead can pass through the blood-brain barrier (the lining around blood vessels in the brain that filters certain molecules in or out of the cells). This is mainly because lead can mimic certain calcium ions, which pass through the blood-brain barrier regularly. Think of it like the wrong key to a lock: it is just right enough to get inside, but then everything gets jammed up.
These calcium ions play a critical role in our brain chemistry. When lead takes its place, it messes up the concentration of calcium ions and cell communication, which can lead to central nervous system damage, gene expression challenges and loss of protection from free radicals, which are unstable, reactive and damaging molecules.
More importantly, it can damage certain regions of the brain — like the prefrontal cortex, cerebellum and hippocampus — and lead to many types of neurological disorders, especially during childhood development.
But interestingly, lead may not just affect us in our lifetimes, but it may have also affected our species over millions of years. Despite the harmful effects lead has on our bodies, something unexpected arrives when we zoom out from the molecular level and look deeper into humanity’s evolutionary history; to a time when coexisting species of humans walked the Earth.
We tend to imagine evolution as a story of physical survival: stronger bodies, better tools and protection against predators and the climate. But back then, could our survival have also depended on something much smaller in scale?
Professor Andrew Whitehead of the UC Davis Department of Environmental Toxicology briefly commented on the idea that evolution is more than visible interactions.
“No matter what kind of creature you’re talking about, if there are changes in the environment that threaten fitness, then that sets the stage for adaptive or evolutionary trajectories being altered,” Whitehead said. “Whether you’re talking about heavy metals or other kinds of poisons, there’s a long […] history of life […] adapting to chemical changes in their environment.”
A variety of researchers at Southern Cross University, including scientist Renaud Joannes-Boyau, demonstrated this idea, experimentally linking lead exposure in our ancient ancestors to the type of brain function that persists in us today.
“Organoids carrying the Neanderthal-like NOVA1 variant showed substantial disruptions […] in the cortex and thalamus when exposed to lead,” Joannes-Boyau said. “These brain regions are essential for language and speech development. Organoids with the modern human NOVA1 gene showed far less disruption.”
Simply put, scientists used organoids, which are small, lab-grown representatives of larger organs, and subjected them to lead. Each organoid contains a special gene called NOVA1, which helps regulate the expression of other genes when exposed to our metal toxin culprit. The difference was that one organoid had a Neanderthal version of the gene, and the other had our common ancestor’s version.
What they found was that ancient homosapiens evolved a variant of the NOVA1 gene compared to our evolutionary cousins. Our version of the gene showed greater resilience to lead exposure during neurodevelopment, the period in which our brain grows and develops.
Significantly, ancient lead exposure in volcanic eruptions, polluted water and soil may have subtly influenced which of our ancestors survived to shape our species. Rather than changing genes directly or leading to physical changes in our bodies, lead likely acted as a sort of filter, favoring neural gene variants that were more resilient and gradually became part of the human blueprint.
However, an important distinction is that lead itself did not shape our species; it was not the mastermind giving us the brains we have today.
Professor Roberta Millstein of the UC Department of Philosophy outlined the distinction of causation.
“It would be more accurate to say that […] when there is a new environmental factor, there can be genetic mutations in populations that turn out to be advantageous for the survival and/or reproduction of members of the population,” Millstein said via email. “If that variation confers enough advantage, it will tend to spread through the population and be passed from generation to generation.”
Lead did not give us our brains. The notorious poison is, in no doubt, toxic to us. In reality, it merely existed throughout history, and in existing, filtered what survived. Indirectly, our brains are the way they are because lead — at least in part — has been part of our evolutionary story for all these millions of years.
Written by: Emilia Rose— science@theaggie.org
