Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541-750).

The first historically documented pandemic caused by Yersinia pestis began as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although paleogenomic studies have previously identified the causative agent as Y. pestis, little is known about the bacterium's spread, diversity, and genetic history over the course of the pandemic. To elucidate the microevolution of the bacterium during this time period, we screened human remains from 21 sites in Austria, Britain, Germany, France, and Spain for Y. pestis DNA and reconstructed eight genomes. We present a methodological approach assessing single-nucleotide polymorphisms (SNPs) in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis on the eight reconstructed genomes reveals the existence of previously undocumented Y. pestis diversity during the sixth to eighth centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as the parallel occurrence of multiple derived strains in central and southern France, Spain, and southern Germany. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45-kb genomic region in the most recent First Pandemic strains affecting two virulence factors, intriguingly overlapping with a deletion found in 17th- to 18th-century genomes of the Second Pandemic.

The prevalence of cancer in Britain before industrialization.

BACKGROUND: To plan for cancer services in the future, the long view of cancer prevalence is essential. It might be suspected that cancer prevalence before tobacco and industrial revolution pollutants was quite different to today. METHODS: To quantify the degree to which cancer prevalence may be changing over time, the authors analyzed 143 skeletons from 6 cemeteries from the Cambridge area (6th-16th centuries). Visual inspection coupled with screening using both plain radiographs and computed tomography scans was used to detect malignant lesions. RESULTS: A total of 3.5% of individuals showed evidence for metastases. Factoring in modern data for the proportion of those with cancer that die with bone metastases, this suggests a minimum prevalence of all cancers at the time of death in medieval Britain to be approximately 9% to 14% of adults. CONCLUSIONS: This figure compares with a 40% to 50% prevalence of cancer at the time of death for modern Britain. The difference may be explained by the effects of modern carcinogens, the spread of viruses that trigger malignancy, industrial pollutants, and longer life expectancy. LAY SUMMARY: Until now, no one has been able to work out how common cancer was before the time people were exposed to tumor-inducing chemicals from tobacco and industrial factories. In this novel study, the authors have determined the percentage of people living in medieval Britain who had cancer metastases to bone at the time of their death and then compared that with modern data. It was found that cancer was approximately 25% as common in medieval times as it is today. This article suggests cancer was much more widespread in medieval times than was previously realized.

Medieval injuries: Skeletal trauma as an indicator of past living conditions and hazard risk in Cambridge, England.

OBJECTIVE: To explore how medieval living conditions, occupation, and an individual's role within society impacted their risk of skeletal trauma. MATERIALS: The skeletal remains of 314 individuals from medieval Cambridge that were buried in the parish cemetery of All Saints by the Castle (n = 84), the Augustinian friary (n = 75), and the cemetery of the Hospital of St John the Evangelist (n = 155) were analyzed. METHODS: Macroscopic examination and plain radiographs were used to classify fracture type. The causative mechanisms and forces applied to a bone were inferred based on fracture morphology. RESULTS: The skeletal trauma observed represents accidental injuries, likely sustained through occupational or everyday activities, and violence. The highest prevalence rate was observed on the individuals buried at All Saints by the Castle (44%, n = 37/84), and the lowest was seen at the Hospital of St John (27%, n = 42/155). Fractures were more prevalent in males (40%, n = 57/143) than females (26%, n = 25/95). CONCLUSIONS: Skeletal trauma was highest in All Saints parish burial ground, indicating that the poor, whether working urban or rurally, had the highest risk of injury. The pattern and types of fractures observed suggests that males experienced more severe traumatic events than females. However, females that were routinely involved in manual labor were also at increased risk of injury. SIGNIFICANCE: This article enhances our understanding of how traumatic injuries differed by age, sex, and burial locations in the medieval period. FURTHER RESEARCH: Additional comparative studies in different geographical regions are needed to determine how representative these findings are.

Intrapopulation variation in lower limb trabecular architecture.

OBJECTIVES: Trabecular structure is frequently used to differentiate between highly divergent mechanical environments. Less is known regarding the response of the structural properties to more subtle behavioral differences, as the range of intrapopulation variation in trabecular architecture is rarely studied. Examining the extent to which lower limb trabecular architecture varies when inferred mobility levels and environment are consistent between groups within a relatively homogenous population may aid in the contextualization of interpopulation differences, improve detectability of sexual dimorphism in trabecular structure, and improve our understanding of trabecular bone functional adaptation. MATERIALS AND METHODS: The study sample was composed of adult individuals from three high/late medieval cemeteries from Cambridge (10th-16th c.), a hospital (n = 57), a parish cemetery (n = 44) and a friary (n = 14). Trabecular architecture was quantified in the epiphyses of the femur and tibia, using high resolution computed tomography. RESULTS: The parish individuals had the lowest bone volume fraction and trabecular thickness in most regions. Multiple sex differences were observed, but the patterns were not consistent across volumes of interest. DISCUSSION: Differences between the three groups highlight the great variability of trabecular bone architecture, even within a single sedentary population. This indicates that trabecular bone may be used in interpreting subtle behavioral differences, and suggests that multiple archaeological sites need to be studied to characterize structural variation on a population level. Variation in sex and group differences across anatomical locations further demonstrates the site-specificity in trabecular bone functional adaptation, which might explain why little consistent sexual dimorphism has been reported previously.

East Anglian early Neolithic monument burial linked to contemporary Megaliths.

In the fourth millennium BCE a cultural phenomenon of monumental burial structures spread along the Atlantic façade. Megalithic burials have been targeted for aDNA analyses, but a gap remains in East Anglia, where Neolithic structures were generally earthen or timber. An early Neolithic (3762-3648 cal. BCE) burial monument at the site of Trumpington Meadows, Cambridgeshire, UK, contained the partially articulated remains of at least three individuals. To determine whether this monument fits a pattern present in megalithic burials regarding sex bias, kinship, diet and relationship to modern populations, teeth and ribs were analysed for DNA and carbon and nitrogen isotopic values, respectively. Whole ancient genomes were sequenced from two individuals to a mean genomic coverage of 1.6 and 1.2X and genotypes imputed. Results show that they were brothers from a small population genetically and isotopically similar to previously published British Neolithic individuals, with a level of genome-wide homozygosity consistent with a small island population sourced from continental Europe, but bearing no signs of recent inbreeding. The first Neolithic whole genomes from a monumental burial in East Anglia confirm that this region was connected with the larger pattern of Neolithic megaliths in the British Isles and the Atlantic façade.

Histotaphonomic analysis of bone bioerosion reveals a regional framework of diverse deathways in the Neolithic of Southeast Italy.

The wide diversity of Neolithic funerary practices is increasingly recognised. In Southeast Italy, recent studies have drawn attention to the co-existence of multiple ways of treating the dead within single sites and across the region. In this study, we address how such diverse deathways form a regional framework of ritual practice through histotaphonomic analysis of bone bioerosion. Samples were obtained from articulated, semi-articulated and disarticulated remains from four sites in Apulia which each presented different modes of treatment and disposal of the dead. Bone thin sections were analysed by light microscopy to characterise microstructural preservation through features including bacterial bioerosion, staining, inclusions, and Wedl tunnelling. We investigate the early post-mortem histories of individuals whose remains ended up in various states of dis/articulation and diverse depositional contexts. Disarticulated remains frequently displayed arrested or extensive bacterial bioerosion, which was also found in articulated and semi-articulated skeletons. Additionally, remains deposited in similar contexts, as well as articulated and disarticulated remains deposited together in the same context, often showed different histotaphonomic characteristics, suggesting diverse early post-mortem trajectories. As a result, we argue that Neolithic deathways in southeastern Italy incorporated a high level of diversity in the early post-mortem treatment of the body. A framework for funerary practices emerges, whereby disarticulated remains probably originated from bodies which had been buried previously and subjected to varying extents of shelter, exposure to invertebrates, and duration of burial. However, we acknowledge the ongoing research into the origins of bacterial bioerosion and the problem of equifinality, which leaves open the possibility for further scenarios of early post-mortem treatment.

Genetic history of Cambridgeshire before and after the Black Death.

The extent of the devastation of the Black Death pandemic (1346-1353) on European populations is known from documentary sources and its bacterial source illuminated by studies of ancient pathogen DNA. What has remained less understood is the effect of the pandemic on human mobility and genetic diversity at the local scale. Here, we report 275 ancient genomes, including 109 with coverage >0.1×, from later medieval and postmedieval Cambridgeshire of individuals buried before and after the Black Death. Consistent with the function of the institutions, we found a lack of close relatives among the friars and the inmates of the hospital in contrast to their abundance in general urban and rural parish communities. While we detect long-term shifts in local genetic ancestry in Cambridgeshire, we find no evidence of major changes in genetic ancestry nor higher differentiation of immune loci between cohorts living before and after the Black Death.

Tuberculosis before and after the Black Death (1346-1353 CE) in the Hospital of St John the Evangelist in Cambridge, England.

This research explores how the prevalence of tuberculosis (TB) in a medieval hospital was affected by the demographic and social changes that following the Black Death (1346-1353 CE), the initial years of the Second Plague Pandemic. To do this, skeletal remains of individuals buried at the Hospital of St John the Evangelist in Cambridge, England, that could be dated to living before (n = 77) or after (n = 55) the Black Death were assessed for evidence of TB (indicated by destructive lesions of the spine, ribs, large joints, and other recognised criteria). Overall, the odds of females having skeletal lesions caused by TB were over four times higher than males. No significant difference was detected in the prevalence rates in those who lived before and after the Black Death (7.8%, 6/77 before and 11.0%, 6/55 after). However, the odds of females having skeletal evidence of TB were over five times greater after the Black Death than they were before. These findings indicate that women may have been 1) more susceptible to TB, 2) surviving longer post-infection than men, and/or 3) that women with TB were more likely to be admitted to the Hospital especially following the Black Death. It is also possible that impairment due to TB infection may have been a contributing factor for entry into the Hospital for women but not men.

Caring for the injured: Exploring the immediate and long-term consequences of injury in medieval Cambridge, England.

OBJECTIVE: To combine paleopathological and biomechanical analysis to reconstruct the impact that a severe skeletal injury had on an individual's ability to function and participate in medieval society. MATERIALS: Three medieval individuals from Cambridge, England with ante-mortem fractures to the lower limb were analyzed. METHODS: Plain X-rays were used to determine the degree of malunion, rotation and overlap of each fracture. Cortical bone architecture of the injured individuals and 28 uninjured controls were analyzed using micro-computed tomography (µCT). Clinical and functional consequences were examined using the Bioarcheology of Care framework. RESULTS: The mechanism of injury, the secondary complications, and the extent of the care received was reconstructed for each individual. Bilateral asymmetry in the cortical bone architecture revealed the long-term alterations to each individual's gait. CONCLUSION: Each of these individuals survived a severe injury resulting in chronic physical impairment, though not all would have been considered 'disabled'. SIGNIFICANCE: This research contributes to the discussion about medieval care provision and social constructions of disability by illustrating how an interdisciplinary approach provides insight into the experiences of those with physical impairments. The integration of µCT imaging within the Bioarcheology of Care model is a novel approach with great potential for application across the field. LIMITATIONS: Biomechanical analysis was restricted to cortical geometry. SUGGESTIONS FOR FUTURE RESEARCH: Further study of bilateral asymmetry in trabecular architecture could complement our understanding of altered loading modalities in past societies.

Assessing the relative benefits of imaging with plain radiographs and microCT scanning to diagnose cancer in past populations.

OBJECTIVE: To determine the degree to which plain radiographs (x-rays) and microCT scans can improve accuracy in the diagnosis of cancer in human remains from past populations. MATERIALS: The skeletal remains of 143 individuals from medieval Cambridgeshire, dating from 6th-16th century CE. METHODS: Visual inspection of the skeletons for lesions compatible with malignancy, coupled with plain radiographs and microCT scans of the pelvis, femora and vertebra. RESULTS: Three individuals had visually apparent metastases on their skeletons. Plain radiographs did not identify further individuals with cancer, but did show further lesions in bones with normal external appearance. MicroCT scans identified cancer in two further individuals with normal visual appearance and normal plain radiographs. CONCLUSIONS: Imaging human skeletal remains increases the detection rate of cancer in human skeletal remains. We found microCT scanning to be a much more sensitive imaging modality than plain radiography. It improved our diagnostic accuracy and enabled us to more reliably distinguish between malignant lesions and taphonomic change. SIGNIFICANCE: Future studies investigating the prevalence and nature of malignancy in past populations would benefit from systematic microCT scanning of pelvis, femora and vertebrae of skeletons to optimise their diagnostic accuracy. LIMITATIONS: MicroCT scanning is more expensive than plain radiographs, and may not be easily accessible to biological anthropologists. SUGGESTIONS FOR FURTHER RESEARCH: To apply this approach to skeletal series from different time periods and geographical regions, where the types of cancer existing in the local population may differ from those we studied in medieval Britain.

An invasive Haemophilus influenzae serotype b infection in an Anglo-Saxon plague victim.

BACKGROUND: The human pathogen Haemophilus influenzae was the main cause of bacterial meningitis in children and a major cause of worldwide infant mortality before the introduction of a vaccine in the 1980s. Although the occurrence of serotype b (Hib), the most virulent type of H. influenzae, has since decreased, reports of infections with other serotypes and non-typeable strains are on the rise. While non-typeable strains have been studied in-depth, very little is known of the pathogen's evolutionary history, and no genomes dating prior to 1940 were available. RESULTS: We describe a Hib genome isolated from a 6-year-old Anglo-Saxon plague victim, from approximately 540 to 550 CE, Edix Hill, England, showing signs of invasive infection on its skeleton. We find that the genome clusters in phylogenetic division II with Hib strain NCTC8468, which also caused invasive disease. While the virulence profile of our genome was distinct, its genomic similarity to NCTC8468 points to mostly clonal evolution of the clade since the 6th century. We also reconstruct a partial Yersinia pestis genome, which is likely identical to a published first plague pandemic genome of Edix Hill. CONCLUSIONS: Our study presents the earliest genomic evidence for H. influenzae, points to the potential presence of larger genomic diversity in the phylogenetic division II serotype b clade in the past, and allows the first insights into the evolutionary history of this major human pathogen. The identification of both plague and Hib opens questions on the effect of plague in immunocompromised individuals already affected by infectious diseases.

Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia.

Human herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, infects a majority of adults globally. Phylogeographic clustering of sampled diversity into European, pan-Eurasian, and African groups has suggested the virus codiverged with human migrations out of Africa, although a much younger origin has also been proposed. We present three full ancient European HSV-1 genomes and one partial genome, dating from the 3rd to 17th century CE, sequenced to up to 9.5× with paired human genomes up to 10.16×. Considering a dataset of modern and ancient genomes, we apply phylogenetic methods to estimate the age of sampled modern Eurasian HSV-1 diversity to 4.68 (3.87 to 5.65) ka. Extrapolation of estimated rates to a global dataset points to the age of extant sampled HSV-1 as 5.29 (4.60 to 6.12) ka, suggesting HSV-1 lineage replacement coinciding with the late Neolithic period and following Bronze Age migrations.

Fancy shoes and painful feet: Hallux valgus and fracture risk in medieval Cambridge, England.

OBJECTIVE: Hallux valgus, the lateral deviation of the great toe, can result in poor balance, impaired mobility and is an independent risk factor for falls. This research aims to compare the prevalence of hallux valgus in subpopulations of medieval Cambridge, England, and to examine the relationship between hallux valgus and fractures to examine the impact of impaired mobility and poor balance caused by this condition. MATERIALS: 177 adult individuals from four cemeteries located in Cambridge, England. METHODS: Human remains were macroscopically and radiographically assessed. RESULTS: Hallux valgus was identified in 18 % of individuals and was significantly more common during the 14th-15th centuries than the 11th-13th centuries. The highest prevalence was observed in the friary (43 %), followed by the Hospital (23 %), the rurban parish cemetery (10 %), and the rural parish cemetery (3%). Fractures from falls were significantly more common in those with hallux valgus than those without. CONCLUSION: The increased prevalence of hallux valgus identified in individuals from the 14th to 15th centuries coincided with the adoption of new footwear with pointed toes. Those that adopted this fashion trend appear to have been more likely to develop balance and mobility problems that resulted in an increased risk of falls. SIGNIFICANCE: This is the first study to explore the relationship between foot problems and functional ability by studying hallux valgus in archaeological assemblages. LIMITATIONS: Falls are complex and determining the mechanism of injury in human skeletal remains is not always possible. FURTHER RESEARCH: Fracture prevalence rates may have been affected by biological factors and underlying pathological conditions.

Gout and 'Podagra' in medieval Cambridge, England.

OBJECTIVE: To estimate the prevalence rate of gout and to explore the social factors that contributed to its development in the various sub-populations in medieval Cambridge. MATERIALS: 177 adult individuals from four medieval cemeteries located in and around Cambridge, UK. METHODS: Lesions were assessed macroscopically and radiographically. Elements with lytic lesions were described and imaged using micro-computed tomography (µCT) to determine their morphology. RESULTS: Gout was identified in 3 % of the population. Individuals buried in the friary had highest prevalence (14 %), with low prevalence rates in the Hospital (3 %) and town parish cemetery (2 %), with no cases in the rural parish cemetery. Gout was more prevalent during the 14th-15th centuries than the 10th-13th centuries. CONCLUSION: The high prevalence rate of gout in the friary is at least partly explained by the consumption of alcohol and purine-rich diets by the friars and the wealthy townsfolk. Medieval medical texts from Cambridge show that gout (known as podagra) was sometimes treated with medications made from the root of the autumn crocus. This root contains colchicine, which is a medicine that is still used to treat gout today. SIGNIFICANCE: This is one of the first studies to assess the epidemiology of gout in medieval England and suggests that gout varied with social status. LIMITATIONS: Our sample size precludes statistical analysis. SUGGESTIONS FOR FURTHER RESEARCH: Additional studies that assess the epidemiology of gout in medieval Europe is needed in order to be able to fully contextualize these findings.

Phylogeography of the second plague pandemic revealed through analysis of historical Yersinia pestis genomes.

The second plague pandemic, caused by Yersinia pestis, devastated Europe and the nearby regions between the 14th and 18th centuries AD. Here we analyse human remains from ten European archaeological sites spanning this period and reconstruct 34 ancient Y. pestis genomes. Our data support an initial entry of the bacterium through eastern Europe, the absence of genetic diversity during the Black Death, and low within-outbreak diversity thereafter. Analysis of post-Black Death genomes shows the diversification of a Y. pestis lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. In addition, we show the loss of a genomic region that includes virulence-related genes in strains associated with late stages of the pandemic. The deletion was also identified in genomes connected with the first plague pandemic (541-750 AD), suggesting a comparable evolutionary trajectory of Y. pestis during both events.