The study -- published in Science Advances -- also offers a new angle on why modern humans ultimately surpassed Neanderthals. Lab-grown brain organoids with Neanderthal genetic variants reacted more strongly to lead than organoids with human genetics, hinting that Neanderthals may have been more vulnerable to lead's neurological effects.

Researchers from the Geoarchaeology and Archaeometry Research Group (GARG) at Southern Cross University (Australia), the Department of Environmental Medicine at the Icahn School of Medicine at Mount Sinai Hospital (New York, USA), and the School of Medicine at the University of California San Diego (UCSD, USA) combined fossil chemistry, brain organoid experiments, and evolutionary genetics to uncover how lead factored into hominid history.

Evidence of Ancient Lead Exposure in Fossil Teeth

For many years, lead toxicity was assumed to be closely tied to human industry, including smelting, mining, and the use of leaded petrol and paint. That view shifted when researchers analysed 51 fossil teeth from a range of hominids and great apes, including Australopithecus africanus, Paranthropus robustus, early Homo, Neanderthals, and Homo sapiens. The teeth showed clear chemical traces of intermittent lead exposure that stretch back nearly two million years.

High-precision laser-ablation geochemistry performed at Southern Cross University's GARG Facility (located in Lismore, NSW) and at Mount Sinai's Exposomics laboratories revealed distinct 'lead bands' in the enamel and dentine. These bands formed during childhood and indicate recurring periods of lead intake from environmental sources (such as polluted water, soil, or volcanic activity) or from lead stored in the body's bones and released during times of stress or illness.

"Our data show that lead exposure wasn't just a product of the Industrial Revolution -- it was part of our evolutionary landscape," said Professor Renaud Joannes-Boyau, Head of the GARG research group at Southern Cross University.

"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."

How Lead Interacted With Early Brain Development

To understand the functional impact of this exposure, the team studied human brain organoids, which serve as simplified, lab-grown models of early brain development. They tested how lead affected two versions of a key developmental gene known as NOVA1, which regulates gene expression under lead exposure during neurodevelopment. The modern human version of NOVA1 differs from the variant seen in Neanderthals and other extinct hominids, although the reason for this evolutionary change was previously unclear.

Organoids carrying the Neanderthal-like NOVA1 variant showed substantial disruptions in FOXP2-expressing neurons in the cortex and thalamus when exposed to lead. These brain regions are essential for language and speech development. Organoids with the modern human NOVA1 gene showed far less disruption.

"These results suggest that our NOVA1 variant may have offered protection against the harmful neurological effects of lead," said Professor Alysson Muotri, Professor of Pediatrics/Cellular & Molecular Medicine and Director of the UC San Diego Sanford Stem Cell Institute Integrated Space Stem Cell Orbital Research Center.

"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."

Genetic Insights Into the Rise of Modern Humans

Genetic and proteomic data from the study showed that lead exposure in organoids with archaic gene variants disrupted multiple pathways tied to neurodevelopment, communication, and social behavior. The FOXP2 disruptions are especially noteworthy because of FOXP2's well-established role in speech and language. These results suggest that long-term pressure from environmental toxins may have nudged cognitive and communicative traits along different evolutionary paths in modern humans and Neanderthals.

"This study shows how our environmental exposures shaped our evolution," said Professor Manish Arora, Professor and Vice Chairman of Environmental Medicine.

"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."

What Ancient Lead Exposure Means for Us Today

Although modern lead exposure is mostly linked to industrial activities, it continues to pose a serious health threat, especially for children. The new findings show that human susceptibility to lead may be deeply rooted in our evolutionary past and shaped by interactions between genes and environmental conditions.

"Our work not only rewrites the history of lead exposure," added Professor Joannes-Boyau, "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."

The research drew on fossil teeth from Africa, Asia, Europe, and Oceania, using detailed geochemical mapping to trace childhood episodes of lead intake. In parallel, brain organoids containing either modern or archaic NOVA1 genes were used to study how lead affected brain development, with particular attention to FOXP2, a gene central to language. Genetic, transcriptomic, and proteomic analyses were combined to build a broad understanding of how lead may have influenced the evolution of hominid cognition and social behavior.

The significance of this discovery became clearer when a Japanese study on supercentenarians, meaning individuals who live well past 100, found that this same T helper cell subset was abundant in their immune systems. Prof. Monsonego now believes these cells may help maintain an immune response that is suitable for a person's stage of life.

The team's findings, led by Dr. Yehezqel Elyahu in collaboration with Prof. Valery Krizhanovsky of the Weizmann Institute of Science, were recently reported in Nature Aging.

Aging, Senescent Cells, and the Immune Response

Scientists describe aging as a process in which cells gradually lose the ability to repair routine damage. When this occurs, the body shows signs of aging. Senescence cells, which naturally appear when regulated properly, become harmful if they accumulate, since they can trigger inflammation and tissue injury.

The researchers discovered that a portion of the T helper cells that increase with age unexpectedly have killing capabilities. These cells help remove senescence cells, thereby limiting their negative effects. Prof. Monsonego's work showed that reducing the number of these T helper cells in mice caused the animals to age more quickly and shortened their lifespan.

This unusual and highly specialized subset of T helper cells continues to rise in number with age and appears to play an important role in slowing the aging process.

Tracking Biological Age and Rethinking Immune Resetting

Because T helper cells shift as people age and appear central to how aging unfolds, Prof. Monosonego and his team suggest monitoring these immune patterns in individuals beginning in their 30s. Such tracking could reveal how quickly someone is aging biologically and help guide early steps to support healthy aging. Differences of decades can develop between biological and chronological ages.

"People say that to reverse aging and "rejuvenate," we need to reset their immune system like the immune systems of people in their 20s. However, our research shows that this might not be the case. People don't need a super-charged immune system; they need one that is working properly and appropriate for their stage in life. So, one of the "axioms" of how to reduce aging may be incorrect," says Prof. Monsonego.

In addition to offering new insight into aging, the newly identified cells may also be useful in diagnostics and future treatments addressing dysregulated aging, longevity, and diseases linked to aging.

Research Team and Support

Prof. Monsonego is part of The Shraga Segal Department of Microbiology, Immunology and Genetics in the Faculty of Health Sciences at BGU, and is also affiliated with TheSchool of Brain Sciences and Cognition.

Contributors to the research included Ilana Feygin, Ekaterina Eremenko, Noa Pinkas, Alon Zemer, Amit Shicht, Omer Berner, Roni Avigdory-Meiri, Anna Nemirovsky, and Keren Reshef from BGU, along with Lior Roitman from Weizmann.

The work received support from the Israel Ministry of Science and Technology (Grant no. 3-16148) and the Litwin and Gural Foundations.