Did lead limit brain and language development in Neanderthals and other extinct hominids?

(Press-News.org) What set the modern human brain apart from our now extinct relatives like Neanderthals? A new study by University of California San Diego School of Medicine and an international team of researchers reveals that ancient hominids — including early humans and great apes — were exposed to lead earlier than previously thought, up to two million years before modern humans began mining the metal. This exposure may have shaped the evolution of hominid brains, limiting language and social development in all but modern humans due to a protective genetic variant that only we carry. The study was published in Science Advances on October 15, 2025.

The researchers analyzed fossilized teeth from 51 hominids across Africa, Asia and Europe, including modern and archaic humans such as Neanderthals, ancient human ancestors like Australopithecus africanus, and extinct great apes such as Gigantopithecus blacki.

They detected lead in 73% of the specimens, including 71% of modern and archaic humans. Notably, G. blacki fossils dating back 1.8 million years showed the most frequent acute lead exposure.

It’s long been assumed that humans have been exposed to harmful amounts of lead since antiquity — when the Romans used lead pipes to transport water — and that lead contamination increased significantly during the Industrial Revolution, only to be curtailed during the late twentieth century. 

“We stopped using lead in our daily lives when we realized how toxic it is, but nobody had ever studied lead in prehistory,” said corresponding author Alysson Muotri, Ph.D., professor of pediatrics and cellular & molecular medicine at UC San Diego School of Medicine, associate director of the Archealization Center and director of the Sanford Integrated Space Stem Cell Orbital Research Center.

Surprisingly, teeth from people born between the 1940s and 1970s — when children were exposed to leaded gasoline and paint — showed similar patterns of lead exposure to fossilized human teeth.

The team hypothesizes that, like the Romans, ancient humans and other hominids may have been exposed to lead because of their need for water.

“One possibility is that they were looking for caves with running water inside,” Muotri said. “Caves contain lead, so they were all contaminated. Based on the tooth enamel studies, it started very early in infancy.”

Lead exposure impedes brain development, leading to deficits in intelligence and difficulties with emotional regulation.

Given these findings, Muotri and his team wondered how the modern human brain had flourished despite exposure to lead during our evolution.

A tiny genetic change

A gene called neuro-oncological ventral antigen 1 (NOVA1) plays a central role in human brain development and synapse formation. Considered the master regulator of neurodevelopment, NOVA1 controls how neural progenitor cells respond to lead. Disruption of NOVA1 activity is linked to several neurological disorders. 

Most modern humans have a variant of NOVA1 gene that differs by a single DNA base pair from the ancestral version that was present in Neanderthals. Previous work by Muotri and his colleagues showed that replacing the human NOVA1 variant with the archaic variant resulted in significant changes to the architecture and synaptic connectivity of tiny stem-cell-derived models of human brains called organoids.

“Everything about the organoids is identical except for that genetic variant, allowing us to ask whether that specific mutation between us and Neanderthals is giving us any advantage,” said Muotri. The archaic variant accelerated brain maturation but resulted in less complexity over time. “If all humans have this newer mutation in all corners of the world, very strong genetic pressure must have selected for it in our species.”

To explore whether environmental lead exposure influenced this selection, the team created brain organoids with both the human and archaic NOVA1 variants and exposed them to lead. They then compared the development of their cortical and thalamic neurons.

Lead exposure altered NOVA1 expression in both variants, affecting genes linked to neurodevelopmental disorders such as autism and epilepsy.

However, only the archaic NOVA1 variant changed the expression of FOXP2, a gene essential for language and speech development. People with certain FOXP2 mutations cannot produce sophisticated language.

“These type of neurons related to complex language are susceptible to death in the archaic version of NOVA1,” said Muotri. “ The FOXP2 gene is identical between us and the Neanderthals, but it's how the gene is regulated by NOVA1 that likely contributes to language differences.”

Evolutionary implications

The findings suggest that the acquisition of the modern NOVA1 variant may have protected us from the detrimental effects of lead, promoting complex language development and social cohesion. This could have given modern humans a significant evolutionary advantage over Neanderthals, even in the presence of lead contamination.

Muotri believes these results have important implications for understanding how environmental stressors shaped brain development during human evolution. He speculates that lead exposure may have contributed to the extinction of Neanderthals around 40,000 years ago.

“Language is such an important advantage, it’s transformational, it is our superpower,” said Muotri. “Because we have language, we are able to organize society and exchange ideas, allowing us to coordinate large movements. There is no evidence that Neanderthals could do that. They might have had abstract thinking, but they could not translate that to each other. And maybe the reason is because they never had a system to communicate that was as efficient as our complex language.”

Understanding how NOVA1 gene variants can affect FOXP2 expression helps elucidate the relationship between lead contamination and brain development and also sheds light on neurological conditions related to language, including speech apraxia — a condition that makes it difficult to produce speech sounds correctly — and autism.

The study's co-authors included Janaina Sena de Souza, Sandra M. Sanchez-Sanchez, Jose Oviedo, University of California San Diego; Marian Bailey and Matthew Tonge at Southern Cross University; Renaud Joannes-Boyau, Southern Cross University and University of Johannesburg; Justin W. Adams, University of Johannesburg and Monash University; Christine Austin, Manish Arora, Icahn School of Medicine at Mount Sinai, Kira Westaway, Macquarie University; Ian Moffat, Flinders University and University of Cambridge; Wei Wang and Wei Liao, Anthropology Museum of Guangxi; Yingqi Zhang, Institute of Vertebrate Paleontology and Paleoanthropology; Luca Fiorenza, Monash University and Johann Wolfgang Goethe University; Marie-Helene Moncel, Museum National d'Histoire Naturelle; Gary T. Schwartz, Arizona State University; Luiz Pedro Petroski and Roberto H. Herai, Pontifícia Universidade Católica do Paraná; Jose Oviedo, University of Arizona; and Bernardo Lemos, Harvard T. H. Chan School of Public Health.

The study was funded, in part, by the National Institutes of Health (grants R01 ES027981, P30ES023515, R01ES026033), the Australian Research Council (grant DP170101597), the National Science Foundation (grant BCS 0962564), and the The Leakey Foundation.

Disclosures: Muotri is the co-founder of and has an equity interest in TISMOO, a company specializing in genetic analysis and human brain organogenesis. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict-of-interest policies.

More information, including a copy of the paper, can be found online at the Science Advances press package at https://www.eurekalert.org/press/vancepak/.

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