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Today, lead exposure directly correlates to a post-industrialized world. However, new evidence indicates that exposure to the poisonous element is not necessarily a new issue. Based on an interdisciplinary approach to geoarchaeological analysis, Homo sapiens and our hominid ancestors have struggled with the lead for over two million years. According to a study published on October 15 in Science Advances, lead’s influence is so pervasive that it may have affected the evolution of human brains, behavior, and even our language. What’s more, our ability to withstand some of the metal’s worst impacts may also partly explain how we outlasted our cousins, the Neanderthals.

The state of lead today

Lead exposure remains a public health issue around the world, even after decades of remediation efforts. According to the Institute for Health Metrics and Evaluation, the toxic metal contributed to over 1.5 million deaths globally in 2021. It also continues to negatively affect the physical and neurological development of children, often leading to lower test scores, behavioral issues, hearing problems, and anemia.

Despite this knowledge, lead is still used to manufacture many vehicle batteries, ceramics, cosmetics, and other everyday items. Meanwhile, even drinking water can be susceptible to contamination due to lead leaching into water supplies through outdated plumbing systems.

Laboratory experiments with brain organoids carrying either modern or archaic NOVA1 genes examined the effects of lead on brain development, with a focus on FOXP2, a gene central to speech and language. Credit: University of California San Diego

Teeth tell a different story

For years, experts largely agreed that lead exposure is a modern crisis almost entirely tied to industrial projects including smelting, mining, and the longtime use of leaded gasoline. While this is partly true, an international team of archaeologists, geneticists, and chemists are confident that hominids have ingested the metal at various times over millions of years.

The evidence comes from 51 fossilized teeth from Homo sapiens and Neanderthals, as well as great ape species such as Australopithecus africanus and Paranthropus robustus. After analyzing the teeth with a technique known as high-precision laser-ablation geochemistry, the researchers identified clear “lead bands” formed inside the teeth as their dentine and enamel grew during each specimen’s childhood.

“Our data show that lead exposure wasn’t just a product of the Industrial Revolution–it was part of our evolutionary landscape,” Renaud Joannes-Boyau, head of the Geoarchaeology and Archaeometry Research Group (GARG) at Australia’s Southern Cross University, said in a statement.

Instead of lead paint or gasoline, exposure millions of years ago would have come from soil and water contamination sometimes exacerbated by volcanic activity. The metal is even occasionally released by a body’s own bone stores during times of sickness or stress.

“This means that the brains of our ancestors developed under the influence of a potent toxic metal, which may have shaped their social behavior and cognitive abilities over millennia,” added Joannes-Boyau.

Using human brain organoids (miniature, lab-grown models of the brain), the team compared the effects of lead on two versions of a key developmental gene called NOVA1, a gene known to orchestrate gene expression upon lead exposure during neurodevelopment. The modern human version of NOVA1 is different from that found in Neanderthals and other extinct hominids. Credit: University of California San Diego

Brain organoids and NOVA1

To test how lead exposure may have affected evolutionary cognitive development, Joannes-Boyau and colleagues turned to experts in brain organoids. Formed by directing stem cell growth in a lab, brain organoids function as miniature models of the mind that scientists can use as a proxy for studying the human brain. In this case, researchers grew organoids to test lead’s influence on two variants of a gene tied to neurodevelopment called NOVA1. Scientists have long known Homo sapien’s version of *NOVA1 *differs from the NOVA1 in Neanderthals and our other extinct relatives, but lacked an explanation for this feature.

One possible reason showed itself soon after the brain organoids were exposed to lead. In the older examples of NOVA1, the metal disrupted neurons in the cortex and thalamus—two brain regions largely responsible for speech and language development. But this disruption wasn’t as severe an issue in organoids displaying modern human NOVA1 genes.

“Our work not only rewrites the history of lead exposure, it also reminds us that the interaction between our genes and the environment has been shaping our species for millions of years, and continues to do so,” said Joannes-Boyau.

With a more solid understanding of humanity’s genetic journey, researchers may be able to better mitigate the worst effects of lead exposure, particularly during childhood development. According to UC San Diego pediatric cellular medicine researcher Alysson Muotri, the findings suggest an “extraordinary example” of environmental pressure driving evolution.

“In this case, lead toxicity could have driven genetic changes that improved survival and our ability to communicate using language,” the study co-author explained before cautioning that those very changes “now also influence our vulnerability to modern lead exposure.”

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