Ancient Lead Exposure May Explain Modern Human Brain Evolution

What made the modern human brain so different from that of our extinct relatives, such as Neanderthals? Researchers at the University of California San Diego School of Medicine, along with an international team, have discovered that ancient hominids, including early humans and great apes, came into contact with lead far earlier than previously believed — up to two million years before modern humans began mining it. This long-term exposure may have influenced how early brains evolved, possibly hindering language and social development in all but modern humans, who possess a unique protective genetic variant. The findings were published in Science Advances on October 15, 2025.

The team examined fossilized teeth from 51 hominids found across Africa, Asia, and Europe. The samples included both modern and archaic humans such as Neanderthals, early human ancestors like Australopithecus africanus, and extinct great apes including Gigantopithecus blacki.

Lead traces were present in 73% of the fossils studied,with 71% of modern and archaic human samples showing contamination. Fossils of G. blacki dating back 1.8 million years revealed the highest levels of acute exposure.

It was previously thoght that humans began facing significant lead exposure only in recorded history, especially during the Roman era, when lead pipes were used for water systems, and later during the Industrial Revolution. lead pollution declined only after the late twentieth century.

“We stopped using lead in our daily lives when we realized how toxic it is indeed,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.

To the researchers’ surprise, teeth from people born in the mid-twentieth century (the 1940s through the 1970s), when exposure to leaded gasoline and paint was widespread, showed similar lead patterns to ancient human fossils.

The scientists suggest that ancient humans and their relatives might have encountered lead through their search for water, much like the Romans did later in history.

“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 disrupts brain growth and function, impairing intelligence and emotional regulation.

faced with this evidence, Muotri and his team began to question how modern humans managed to thrive despite such toxic conditions during their evolutionary past.

A tiny genetic change

A gene known as neuro-oncological ventral antigen 1 (NOVA1) plays a major role in brain formation and synaptic development. Acting as a key regulator of neurodevelopment,NOVA1 helps determine how neural progenitor cells react to lead exposure,and disturbances in its activity are linked to neurological disorders.

Nearly all modern humans carry a version of the NOVA1 gene that differs by a single DNA base pair from the version found in Neanderthals. Earlier work from muotri’s group showed that swapping the modern NOVA1 with the older variant in miniature brain models, called organoids, caused dramatic changes in brain structure and connectivity.

“Everything about the organoids is identical except for that genetic variant, allowi