Neanderthals left Africa 400,000 years ago and settled in Eurasia. Until they went extinct about 40,000 years ago, they coexisted for tens of thousands of years with Homo sapiens, the direct ancestors of humans. They were the same Homo genus, so why did one go extinct while the other has prospered to this day? Scientists in the United States and Australia have offered a new answer: lead poisoning.
A team led by Manish Arora of the Icahn School of Medicine at Mount Sinai and Alysson Muotri of the University of California, San Diego (UCSD) School of Medicine said in the journal Science Advances on the 15th (local time) that "hominins have been exposed to lead since 2 million years ago, and only modern humans have a genetic variation that protects the brain from lead, which is presumed to have led to the development of language and social abilities."
◇ Lethal lead levels found in hominin fossils
Lead is a deadly heavy metal that damages neural function. Until now, it was thought that humans had suffered from lead poisoning since the Industrial Revolution. Arora, an environmental epidemiologist, confirmed that lead is also present in Neanderthal fossils. Muotri, a neurologist, estimated that lead prevented language abilities from developing in Neanderthal brains, leaving them unable to properly cope with rapid environmental changes and leading to their extinction. By contrast, Homo sapiens had a mechanism to protect the brain even under the same lead exposure.
To test the lead poisoning hypothesis, Muotri formed a joint research team with dozens of collaborators, including Arora and Renaud Joannes-Boyau, a paleoanthropologist at Southern Cross University in Australia. First, they analyzed 51 fossil teeth from hominins and modern humans, as well as monkeys, across Africa, Asia, and Europe. When a laser is fired at a tooth, internal materials are ejected; analyzing these revealed the presence or absence of lead.
The samples included Australopithecus africanus and Paranthropus robustus, Neanderthals, and Homo sapiens, as well as the extinct great ape Gigantopithecus blacki, orangutans, and baboons. Lead was detected in 73% of the samples. Lead levels were highest in a 1.8-million-year-old Gigantopithecus tooth. Lead was also found in 71% of the modern human and hominin samples.
Scholars had assumed that humans were exposed to lead from the ancient Roman era, when water was carried in lead pipes, and that lead poisoning surged during the Industrial Revolution. Mining, smelting, gasoline, and paint were identified as the main causes of lead poisoning. Only in the latter half of the 20th century, after it was revealed that lead inflicts fatal damage on the nervous system, was the use of lead curbed.
Surprisingly, the lead accumulated in hominin teeth was at levels similar to those of people born between the 1940s and 1970s. The researchers inferred that hominins were exposed to lead through water, as Romans were. "Hominins would have sought caves with running water," Muotri said, adding, "An analysis of enamel, the hardest part of the teeth, suggests that lead exposure began in infancy."
◇ Mini-brain experiment confirms the effects of lead poisoning
To find out how lead influenced human evolution, the team conducted organoid experiments. Organoids are "organ-like structures," grown by culturing stem cells, which can develop into any human cell, into three-dimensional structures resembling organs.
Previously, Muotri's team had been investigating 61 genes that differ between the two human lineages. The key among them was the NOVA1 gene, which coordinates neural development and acts as a switch to turn hundreds of genes in the brain on and off. Muotri's team created brain organoids carrying the Neanderthal version and the modern human version of NOVA1, respectively.
The researchers exposed the brain organoids to lead at levels comparable to what ancient humans would have encountered in nature. Lead acted differently on the two lineages' mini-brains. In the Neanderthal-type brain organoids, the FOXP2 gene in neurons was disrupted. This gene is essential for language and vocal development. In modern human brain organoids, such disruptions barely appeared. The team explained that while Neanderthals and modern humans share the same FOXP2 gene, the way it is regulated by NOVA1 likely differs, potentially leading to differences in language ability.
"Humans organize societies, share ideas, and coordinate large-scale migrations through language," Muotri said. "Neanderthals may have engaged in abstract thinking, but without developed language abilities, they likely could not convey their thoughts to one another." In other words, Neanderthals' inferior communication abilities left them unable to adequately respond to rapid climate change, ultimately leading to their extinction.
Academia showed a reserved stance toward the claim that lead poisoning determined human evolution. Shara Bailey of New York University, an expert on hominin teeth, told Science the same day that it was "a bold and creative hypothesis," but noted that "there are still many limitations to the study." "To begin with, children and adults may have different diets, so we cannot be certain at what ages hominins were exposed to lead," Bailey said.
Takashi Namba, a neuroscientist at the University of Helsinki in Finland, likewise said, "It is very interesting in that there are not many studies that experimentally address environmental factors that influenced human evolution," while pointing out that "it is unclear whether exposing organoids to lead accurately reflects what happens in the developing brain."
References
Science Advances (2025), DOI: https://doi.org/10.1126/sciadv.adr1524