A groundbreaking study from the University of Oxford’s Nuffield Department of Medicine heralds a transformative advance in palaeoproteomics, unveiling a novel method to extract and identify proteins from ancient soft tissues. For decades, such tissues—brains, muscles, and internal organs—have remained elusive to molecular analysis due to their fragile nature and the challenges involved in protein recovery. This pioneering approach not only cracks open this biological vault but also illuminates the molecular intricacies and health statuses of individuals who lived centuries ago, redefining our understanding of human history at a biochemical level.
Traditional investigations into ancient proteins have predominantly focused on mineralized tissues such as bones and teeth, which, despite their durability, offer only a partial and often limited biological narrative. Soft tissues, conversely, contain a richer and more nuanced repertoire of biological information, including proteins linked to disease, metabolism, and neurological function. However, the absence of reliable extraction protocols has confined these tissues to a ‘black box,’ leaving vast molecular stories untold. The Oxford research team, led by Alexandra Morton-Hayward, has shattered this barrier by developing and validating the first fully robust workflow designed specifically for ancient soft tissue proteomics.
Central to their challenge was overcoming the resilience of cell membranes, notoriously difficult to breach after centuries of degradation and biochemical crosslinking. After meticulous experimentation involving ten distinct chemical and mechanical disruption techniques on human brain samples excavated from a Victorian workhouse burial site, the team identified urea—a simple organic compound commonly found in urine—as the key agent. Urea’s unique properties effectively disintegrated the membranes, releasing proteins that, until now, were locked away within cellular confines, unavailable for mass spectrometric analysis.
Once liberated, these proteins undergo separation with state-of-the-art liquid chromatography, a technique that isolates molecules based on their chemical interactions during flow through a specialized column. Subsequently, mass spectrometry, a powerful analytical method that sorts proteins based on their mass-to-charge ratios, identifies the protein species with exceptional sensitivity. The study further enhances this process by integrating high-field asymmetric waveform ion mobility spectrometry (FAIMS), a cutting-edge technology that discriminates ions in an electric field based on their mobility. This additional separation step increased protein identifications by approximately 40%, a colossal leap in analytical depth allowing unprecedented molecular resolution from minuscule sample amounts.
This refined methodology empowered the researchers to uncover an astonishing breadth of over 1,200 ancient proteins from only 2.5 milligrams of archaeological brain matter. This represents the richest and most diverse palaeoproteome recovered from any ancient tissue reported to date, capturing a molecular snapshot of both healthy brain function and pathological markers. Among their findings were proteins implicated in neurological conditions including Alzheimer’s disease and multiple sclerosis, diseases whose signatures are invisible in skeletal remains but discernible through soft tissue proteomics. These revelations signify a tremendous advancement in reconstructing the health profiles of past populations, historically inaccessible due to the absence of soft tissue biomarkers.
The implications of this technique extend far beyond archaeology. Proteins, unlike DNA, display remarkable longevity in the fossil record, often outlasting nucleic acids by significant timescales. As molecular time capsules, they encode nuanced information about an individual’s physiological status and environmental adaptations, offering key insights into evolutionary biology, ancient disease epidemiology, and even paleonutrition. By enabling the recovery of a far broader array of proteins, particularly those only expressed in internal organs—estimated at around 75% of all human proteins compared to under 10% in bone—this approach dramatically expands the horizons of molecular paleontology.
Moreover, by capturing proteins specific to neurological tissue, the method opens a window onto aspects of ancient human life previously hidden, such as cognitive health and neurodegenerative conditions. The detection of potential biomarkers for psychiatric illness and mental health disorders—conditions that historically have left no physical trace in bones—provides an extraordinary new dimension to archaeological and evolutionary studies. This could revolutionize understandings of how disease and environment shaped human populations over the past millennia.
The research team’s location within Oxford’s Centre for Medicines Discovery facilitated interdisciplinary innovation, blending molecular biology, analytical chemistry, and archaeological science. Senior author Professor Roman Fischer highlights how this technique “transforms our ability to understand the health of past populations” by moving beyond skeletal remains and delving into soft tissue pathology. The method’s outstanding sensitivity and adaptability promise diverse applications ranging from mummified remains to bog bodies, and from antibodies to peptide hormones, marking it as an indispensable tool for future palaeobiological research.
External experts underscore the significance of this advancement. Dr. Christiana Scheib from the University of Cambridge’s Department of Zoology lauds the study for setting a fundamental experimental benchmark, enabling researchers to extract meaningful protein data from rare and precious soft tissue archaeological samples. The ripple effects of such fundamental progress are poised to resonate through evolutionary biology, anthropology, paleomedicine, and beyond.
As scientists grapple with the immense complexity inherent in ancient biological materials, this study’s approach to multidimensional molecular separation—akin to sorting Lego pieces first by color, then shape, then size—exemplifies the power of combining sophisticated analytical technology with ingenious chemical treatments. In essence, this layered discrimination enhances the probability of recovering and confidently identifying elusive protein molecules that would otherwise remain buried beneath background noise, degraded signals, or complex molecular mixtures.
Looking forward, the potential of this breakthrough method is vast. It heralds a new era where the internal biology, disease history, and molecular ecology of ancient humans can be directly studied at an unprecedented scale and resolution. This will enrich narratives of human evolution, migration, and health, weaving molecular threads into the archaeological and anthropological tapestry. The facility to chart soft tissue protein signatures in ancient specimens thus upends previous limitations, catalyzing a renaissance in palaeoproteomic exploration.
The study titled “Deep palaeoproteomic profiling of archaeological human brains” is slated for publication in the journal PLOS One on 28 May 2025. Its data and methods promise to inspire numerous follow-up investigations and technological refinements, ultimately expanding the depths to which ancient life is probed molecularly. For historians, scientists, and the public alike, it signals a remarkable leap toward reading the intimate biological stories encoded in the soft tissues of our ancestors, long obscured yet now within reach.
Subject of Research: Extraction and identification of proteins from ancient soft tissues, specifically archaeological human brain samples.
Article Title: Deep palaeoproteomic profiling of archaeological human brains
News Publication Date: 28 May 2025
Web References: http://dx.doi.org/10.1371/journal.pone.0324246
Image Credits: Alexandra Morton-Hayward
Keywords: palaeoproteomics, ancient proteins, soft tissues, archaeological brains, mass spectrometry, FAIMS, protein biomarkers, neurodegenerative diseases, ancient diseases, molecular archaeology, Victorian cemetery, urea extraction, protein identification
