Study finds ancient lead exposure shaped evolution of human brain


Colorful image of brain

Image credit: Hamdi Kandi Studio/Canva

A new international study reveals exposure to the toxic metal lead happened much earlier than previously thought. 

In an article published in Science Advances, researchers have revealed our human ancestors were periodically exposed to lead for over 2 million years, and the toxic metal may have influenced the evolution of hominid brains, behavior and even the development of language.

The study also adds a new piece to the puzzle of how humans outcompeted their Neanderthal cousins. Brain organoid models grown with Neanderthal gene variants were more susceptible to the impacts of lead than human brains, suggesting that lead exposure was more harmful to Neanderthals.

“This team of scientists combined novel fossil geochemistry, cutting-edge brain organoid experiments and pioneering evolutionary genetics to uncover a surprising story about lead’s role in human history,” said senior author Renaud Joannes-Boyau, professor at Southern Cross University in Australia and director of the Geoarchaeology and Archaeometry Research Group.

The study was also led by scientists at the Department of Environmental Medicine at the Icahn School of Medicine at Mount Sinai Hospital and the School of Medicine at the University of California, San Diego, and a paleoanthropologist from Arizona State University’s Institute of Human Origins.

Teeth expose a toxic thread

Until now, scientists believed lead exposure was a modern phenomenon, linked to human activities such as mining, smelting and the use of leaded petrol and paint.

By analyzing 51 teeth from fossil and living great ape species, fossil human relativesIncluding Australopithecus africanus, Paranthropus robustus, early Homo and Neanderthals. and Homo sapiens, the team discovered clear chemical signatures of intermittent lead exposure stretching back almost 2 million years.

Using high-precision laser-ablation geochemistry at Southern Cross University and Mount Sinai’s state-of-the-art exposomics facilities, the researchers found distinctive "lead bands" in the enamel and dentine of teeth, formed during childhood as the enamel and dentine grew. 

These bands reveal repeated episodes of lead uptake from both environmental sources — such as contaminated water, soil or volcanic activity — and from the body’s own bone stores, released during stress or illness.

 Illustration of a sectioned fossil tooth
Illustration of a sectioned fossil tooth analyzed by LA-ICP-MS (left) where a laser rasters across the sectioned surface and ejected material is transported to the mass spectrometer. The area of focus on a sectioned Gigantopithecus blacki molar from China (middle) and the resultant lead distribution (scale on far right) from that area revealing a large number of biogenic banding relating to repeated acute exposures to lead (right). Graphic courtesy of Science Advances.

“Teeth provide a treasure trove of information about all aspects of our early life experiences, health, stress and — as it turns out — exposures to environmental toxins as well,” said Gary Schwartz, a research scientist at the Institute of Human Origins and professor at the School of Human Evolution and Social Change at ASU.

“It’s that property of teeth, that they provide a window into our entire growth biology, that makes them the perfect focus for this sort of work.” 

From fossils to function: Lead and the language gene

Using human brain organoids — miniature, lab-grown models of the brain — the scientists compared the effects of lead exposure on two versions of a key developmental gene called NOVA1. This gene is known to orchestrate gene expression upon lead exposure during neurodevelopment.

The modern human version of NOVA1 is different from the version found in Neanderthals and other extinct hominids, but until now scientists were unclear why this different gene variant evolved.

When organoids carrying the archaic NOVA1 variant were exposed to lead, they showed marked disruptions in the activity of FOXP2, expressing neurons in the cortex and thalamus — brain regions that are critical for the development of speech and language. This effect was far less pronounced in organoids with the modern NOVA1 variant.

“These results suggest that our NOVA1 variant may have offered protection against the harmful neurological effects of lead,” said Alysson Muotri, professor of pediatrics and cellular and molecular medicine at UC San Diego.

“It’s an extraordinary example of how an environmental pressure — in this case, lead toxicity — could have driven genetic changes that improved survival and our ability to communicate using language, but which now also influence our vulnerability to modern lead exposure.”

Genetics, neurotoxins and the making of modern humans

The study also showed that lead exposure in archaic-variant organoids disrupted pathways involved in neurodevelopment, social behavior and communication. The altered FOXP2 activity in particular points to a possible link between ancient lead exposure and the evolutionary refinement of language abilities in modern humans.

“This study shows how our environmental exposures shaped our evolution,” said Manish Arora, professor at the Icahn School of Medicine at Mount Sinai. “From the perspective of inter-species competition, the observation that toxic exposures can offer an overall survival advantage offers a fresh paradigm for environmental medicine to examine the evolutionary roots of disorders linked to environmental exposures.”

While lead exposure today is mostly due to human industry, it remains a serious global health issue, particularly for children, according to Joannes-Boyau. The findings underscore how deeply intertwined environmental toxins and human biology have been and warn that our vulnerability to lead may be an inherited legacy of our past.

“It really is quite astonishing that we can read information embedded in fossil teeth that links almost directly to the developmental biology of human brain growth and evolution,” Schwartz said. “This sort of transdisciplinary work — bridging paleontology, geochemistry, neurobiology, environmental sciences and genetics — really opens up new vistas for the sorts of questions we can now ask about the past.”

Article adapted from Southern Cross University.

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