Medieval monastic health: Variation in skeletal signs of inflammation and developmental stress between religious orders in London.

OBJECTIVES: Previous bioarchaeological analyses of medieval monastic and nonmonastic cemeteries in London revealed evidence of lower risks of mortality, and thus better health, in the monastic settings. However, comparison of the two monastic communities, Bermondsey Abbey and Merton Priory, which adhered to different religious ideals, suggested lower risks of mortality in the former. This study examines patterns of skeletal biomarkers, which reflect developmental stress or inflammation, in an attempt to clarify the possible underlying mechanisms producing apparent health differences in these monastic communities. MATERIALS AND METHODS: This study uses skeletal data on age-at-death, periosteal new bone formation (PNBF), and cribra orbitalia from 558 adults (18 years of age and older) estimated to be male from Bermondsey Abbey and Merton Priory. Biomarker age patterns are assessed via Kaplan-Meier survival analysis and binary logistic regression. Differences in frequencies of biomarkers between the monastic sites are evaluated using Chi-square and hierarchical log-linear analyses. RESULTS: In general, PNBF is positively associated with age, and cribra orbitalia is negatively associated with age. The frequency of PNBF formation is significantly higher and that of cribra orbitalia is significantly lower in Bermondsey Abbey compared with Merton Priory. CONCLUSIONS: The differences in frequencies of these skeletal biomarkers support previous findings suggesting that health conditions were better in Bermondsey Abbey than in Merton Priory. The age patterns of cribra orbitalia suggest that these differences reflect conditions and the greater health-promoting effects of religiosity or isolation from the lay community in Bermondsey Abbey rather than differences in selective admissions processes.

Frailty and survival in the 1918 influenza pandemic.

One of the most well-known yet least understood aspects of the 1918 influenza pandemic is the disproportionately high mortality among young adults. Contemporary accounts further describe the victims as healthy young adults, which is contrary to the understanding of selective mortality, which posits that individuals with the highest frailty within a group are at the greatest risk of death. We use a bioarchaeological approach, combining individual-level information on health and stress gleaned from the skeletal remains of individuals who died in 1918 to determine whether healthy individuals were dying during the 1918 pandemic or whether underlying frailty contributed to an increased risk of mortality. Skeletal data on tibial periosteal new bone formation were obtained from 369 individuals from the Hamann-Todd documented osteological collection in Cleveland, Ohio. Skeletal data were analyzed alongside known age at death using Kaplan-Meier survival and Cox proportional hazards analysis. The results suggest that frail or unhealthy individuals were more likely to die during the pandemic than those who were not frail. During the flu, the estimated hazards for individuals with periosteal lesions that were active at the time of death were over two times higher compared to the control group. The results contradict prior assumptions about selective mortality during the 1918 influenza pandemic. Even among young adults, not everyone was equally likely to die-those with evidence of systemic stress suffered greater mortality. These findings provide time depth to our understanding of how variation in life experiences can impact morbidity and mortality even during a pandemic caused by a novel pathogen.

Survivorship and the second epidemiological transition in industrial-era London.

OBJECTIVES: The second epidemiological transition describes a shift in predominant causes of death from infectious to degenerative (non-communicable) diseases associated with the demographic transition from high to low levels of mortality and fertility. In England, the epidemiological transition followed the Industrial Revolution, but there is little reliable historical data on cause of death beforehand. Because of the association between the demographic and epidemiological transitions, skeletal data can potentially be used to examine demographic trends as a proxy for the latter. This study uses skeletal data to examine differences in survivorship in London, England in the decades preceding and following initial industrialization and the second epidemiological transition. MATERIALS AND METHODS: We use data (from n = 924 adults) from London cemeteries (New Churchyard, New Bunhill Fields, St. Bride's Lower Churchyard, and St. Bride's Church Fleet Street) in use prior to and during industrialization (c. 1569-1853 CE). We assess associations between estimated adult age at death and time period (pre-industrial vs. industrial) using Kaplan-Meier survival analysis. RESULTS: We find evidence of significantly lower adult survivorship prior to industrialization (c. 1569-1669 and 1670-1739 CE) compared to the industrial period (c. 1740-1853 CE) (p < 0.001). DISCUSSION: Our results are consistent with historical evidence that, in London, survivorship was improving in the later 18th century, prior to the recognized beginning of the second epidemiological transition. These findings support the use of skeletal demographic data to examine the context of the second epidemiological transition in past populations.

Reply to Barton et al: signatures of natural selection during the Black Death.

Barton et al.1 raise several statistical concerns regarding our original analyses2 that highlight the challenge of inferring natural selection using ancient genomic data. We show here that these concerns have limited impact on our original conclusions. Specifically, we recover the same signature of enrichment for high FST values at the immune loci relative to putatively neutral sites after switching the allele frequency estimation method to a maximum likelihood approach, filtering to only consider known human variants, and down-sampling our data to the same mean coverage across sites. Furthermore, using permutations, we show that the rs2549794 variant near ERAP2 continues to emerge as the strongest candidate for selection (p = 1.2×10-5), falling below the Bonferroni-corrected significance threshold recommended by Barton et al. Importantly, the evidence for selection on ERAP2 is further supported by functional data demonstrating the impact of the ERAP2 genotype on the immune response to Y. pestis and by epidemiological data from an independent group showing that the putatively selected allele during the Black Death protects against severe respiratory infection in contemporary populations.

Emergence, continuity, and evolution of Yersinia pestis throughout medieval and early modern Denmark.

The historical epidemiology of plague is controversial due to the scarcity and ambiguity of available data.1,2 A common source of debate is the extent and pattern of plague re-emergence and local continuity in Europe during the 14th-18th century CE.3 Despite having a uniquely long history of plague (∼5,000 years), Scandinavia is relatively underrepresented in the historical archives.4,5 To better understand the historical epidemiology and evolutionary history of plague in this region, we performed in-depth (n = 298) longitudinal screening (800 years) for the plague bacterium Yersinia pestis (Y. pestis) across 13 archaeological sites in Denmark from 1000 to 1800 CE. Our genomic and phylogenetic data captured the emergence, continuity, and evolution of Y. pestis in this region over a period of 300 years (14th-17th century CE), for which the plague-positivity rate was 8.3% (3.3%-14.3% by site). Our phylogenetic analysis revealed that the Danish Y. pestis sequences were interspersed with those from other European countries, rather than forming a single cluster, indicative of the generation, spread, and replacement of bacterial variants through communities rather than their long-term local persistence. These results provide an epidemiological link between Y. pestis and the unknown pestilence that afflicted medieval and early modern Europe. They also demonstrate how population-scale genomic evidence can be used to test hypotheses on disease mortality and epidemiology and help pave the way for the next generation of historical disease research.

Ancient pathogens provide a window into health and well-being.

This perspective draws on the record of ancient pathogen genomes and microbiomes illuminating patterns of infectious disease over the course of the Holocene in order to address the following question. How did major changes in living circumstances involving the transition to and intensification of farming alter pathogens and their distributions? Answers to this question via ancient DNA research provide a rapidly expanding picture of pathogen evolution and in concert with archaeological and historical data, give a temporal and behavioral context for heath in the past that is relevant for challenges facing the world today, including the rise of novel pathogens.

Climate change, human health, and resilience in the Holocene.

Climate change is an indisputable threat to human health, especially for societies already confronted with rising social inequality, political and economic uncertainty, and a cascade of concurrent environmental challenges. Archaeological data about past climate and environment provide an important source of evidence about the potential challenges humans face and the long-term outcomes of alternative short-term adaptive strategies. Evidence from well-dated archaeological human skeletons and mummified remains speaks directly to patterns of human health over time through changing circumstances. Here, we describe variation in human epidemiological patterns in the context of past rapid climate change (RCC) events and other periods of past environmental change. Case studies confirm that human communities responded to environmental changes in diverse ways depending on historical, sociocultural, and biological contingencies. Certain factors, such as social inequality and disproportionate access to resources in large, complex societies may influence the probability of major sociopolitical disruptions and reorganizations-commonly known as "collapse." This survey of Holocene human-environmental relations demonstrates how flexibility, variation, and maintenance of Indigenous knowledge can be mitigating factors in the face of environmental challenges. Although contemporary climate change is more rapid and of greater magnitude than the RCC events and other environmental changes we discuss here, these lessons from the past provide clarity about potential priorities for equitable, sustainable development and the constraints of modernity we must address.

Evolution of immune genes is associated with the Black Death.

Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.

Sexual stature difference fluctuations in pre- and post-Black Death London as an indicator of living standards.

OBJECTIVES: The degree of sexual stature difference (SSD), the ratio of male to female height, is argued to be an indicator of living standards based on evidence that physical growth for males is more sensitive to environmental fluctuations. In a resource-poor environment, the degree of SSD is expected to be relatively low. The aim of this study is to comparatively assess SSD in medieval London in the context of repeated famine events and other environmental stressors before the Black Death (BD) and the improved living conditions that characterized the post-Black Death period. METHODS: To test the hypothesis that a poor nutritional environment resulted in decreased SSD in medieval London, this study compares adult individuals from early pre-Black Death (c. 1000-1200), late pre-Black Death (c. 1200-1250) and post-Black Death (c. 1350-1540) cemetery contexts from London. Maximum tibial,femoral, and lower limb lengths were used as a proxy for stature, and SSD was calculated using the Chakraborty and Majumber index. RESULTS: Compared to the late pre-BD period, we find a slighter higher degree of SSD in the post-BD period for all three stature proxies used. This increase is attributed to more exaggerated increases in stature for estimated males post-BD. CONCLUSIONS: This study demonstrates the importance of examining variables that are considered indicators of living standards in light of factors like selective mortality, catch-up growth, and urban migration patterns. Future research needs to further investigate how cultural and biological processes influence the mechanisms that produce adult stature.

Twenty-first century bioarchaeology: Taking stock and moving forward.

This article presents outcomes from a Workshop entitled "Bioarchaeology: Taking Stock and Moving Forward," which was held at Arizona State University (ASU) on March 6-8, 2020. Funded by the National Science Foundation (NSF), the School of Human Evolution and Social Change (ASU), and the Center for Bioarchaeological Research (CBR, ASU), the Workshop's overall goal was to explore reasons why research proposals submitted by bioarchaeologists, both graduate students and established scholars, fared disproportionately poorly within recent NSF Anthropology Program competitions and to offer advice for increasing success. Therefore, this Workshop comprised 43 international scholars and four advanced graduate students with a history of successful grant acquisition, primarily from the United States. Ultimately, we focused on two related aims: (1) best practices for improving research designs and training and (2) evaluating topics of contemporary significance that reverberate through history and beyond as promising trajectories for bioarchaeological research. Among the former were contextual grounding, research question/hypothesis generation, statistical procedures appropriate for small samples and mixed qualitative/quantitative data, the salience of Bayesian methods, and training program content. Topical foci included ethics, social inequality, identity (including intersectionality), climate change, migration, violence, epidemic disease, adaptability/plasticity, the osteological paradox, and the developmental origins of health and disease. Given the profound changes required globally to address decolonization in the 21st century, this concern also entered many formal and informal discussions.

Toward a bioarchaeology of urbanization: Demography, health, and behavior in cities in the past.

Urbanization is one of the most important settlement shifts in human history and has been the focus of research within bioarchaeology for decades. However, there have been limited attempts to synthesize the results of these studies in order to gain a broader perspective on whether or how urbanization affects the biology, demography, and behavior of humans, and how these potential effects are embodied in the human skeleton. This paper outlines how bioarchaeology is well-suited to examine urbanization in the past, and we provide an overview and examples of three main ways in which urbanization is studied in bioarchaeological research: comparison of (often contemporaneous) urban and rural sites, synchronic studies of the variation that exists within and between urban sites, and investigations of changes that occur within urban sites over time. Studies of urbanization, both within bioarchaeology and in other fields of study, face a number of limitations, including a lack of a consensus regarding what urban and urbanization mean, the assumed dichotomous nature of urban versus rural settlements, the supposition that urbanization is universally bad for people, and the assumption (at least in practice) of homogeneity within urban and rural populations. Bioarchaeologists can address these limitations by utilizing a wide array of data and methods, and the studies described here collectively demonstrate the complex, nuanced, and highly variable effects of urbanization.

Medieval menarche: Changes in pubertal timing before and after the Black Death.

OBJECTIVES: Bioarcheological evidence suggests stature increased in males but decreased in females after the Black Death (1348-1350 CE). Because tradeoffs between growth and reproduction can result in earlier ages at menarche and lower limb length, we assess menarcheal age between 1120 and 1540 CE to better understand the health of medieval adolescent females before and after the plague. MATERIALS AND METHODS: Our sample comprises 74 adolescent females from St. Mary Spital, London (1120-1540 CE) within the age range during which menarche occurs (10-25 years). They were assessed as being pre- or post-menarcheal and divided into three groups: Early Pre-Black Death (n = 13), Late Pre-Black Death (n = 38), and Post-Black Death (n = 23). Changes in the ages of pre- and post-menarcheal females were assessed using Mann-Whitney tests. RESULTS: The average age of post-menarcheal females increased from the Early- to Late Pre-Black Death periods and declined after the Black Death. CONCLUSIONS: Short stature can reflect unfavorable growth environments, while younger menarcheal age indicates improved living conditions. The paradoxical pattern of female, but not male, stature reduction after the Black Death might reflect the association of early menarche with lower limb length and signal that adolescent females experienced improved health conditions after the epidemic. Our focus on pre- and post-menarche within a limited age span provides a novel approach for inferring average ages of menarche over time. Pathways to skeletal development and reproductive investment are part of an integrated system, providing a bridge between life history research in bioarchaeology and human biology.

Assessment of nutritional stress in famine burials using stable isotope analysis.

OBJECTIVES: We compared δ15 N and δ13 C values from bone and dentine collagen profiles of individuals interred in famine-related and attritional burials to evaluate whether individuals in medieval London who experienced nutritional stress exhibit enriched nitrogen in bone and tooth tissue. Dentine profiles were evaluated to identify patterns that may be indicative of famine during childhood and were compared with the age of enamel hypoplasia (EH) formation to assess whether isotopic patterns of undernutrition coincide with the timing of physiological stress. MATERIALS AND METHODS: δ15 N and δ13 C isotope ratios of bone collagen were obtained from individuals (n = 128) interred in attritional and famine burials from a medieval London cemetery (c. 1120-1539). Temporal sequences of δ15 N and δ13 C isotope profiles for incrementally forming dentine collagen were obtained from a subset of these individuals (n = 21). RESULTS: Results indicate that individuals from attritional graves exhibit significantly higher δ15 N values but no significant differences were found between burial types for the sexes. Analyses of dentine profiles reveal that a lower proportion of famine burials exhibit stable dentine profiles and that several exhibit a pattern of opposing covariance between δ15 N and δ13 C. EH were also observed to have formed during or after the opposing covariance pattern for some individuals. CONCLUSIONS: The results of this study may reflect differences in diet between burial types rather than nutritional stress. Though nutritional stress could not be definitively identified using bone and dentine collagen, the results from dentine analysis support previous observations of biochemical patterns associated with nutritional stress during childhood.

Sex differences in adult famine mortality in medieval London.

OBJECTIVES: Recurrent famine events during the medieval period might have contributed to excess mortality during the Black Death in London, England (c. 1349-1350). Previous research using conventional methods of age estimation revealed that adult males experienced lower risks of mortality under "normal" (attritional) but not famine mortality conditions following the Black Death. However, given the biases inherent in conventional age estimation methods, this study reassesses sex differences in risks of medieval adult famine mortality using ages estimated via transition analysis, which avoids some of the limitations of conventional age estimation methods. MATERIALS AND METHODS: We apply hazards analysis (the Gompertz model of adult mortality) to ages estimated for human skeletal remains (n = 1245) from London cemeteries dated to the pre-Black Death (c. 1000-1250 CE) and post-Black Death (c. 1350-1540 CE) periods. RESULTS: The results reveal no sex differences in risks of mortality before the Black Death but indicate that adult males faced lower risks of mortality after the Black Death during conditions of normal and famine mortality. CONCLUSIONS: These findings largely support those of our previous research, which suggested that selective mortality during the Black Death or sex-biased improvements in standard of living following the epidemic reduced risk of mortality for adult males in the post-Black Death period under normal mortality conditions. However, the use of transition analysis age estimates also revealed a reduced risk of mortality for post-Black Death adult males under famine conditions.

Genetic resiliency and the Black Death: No apparent loss of mitogenomic diversity due to the Black Death in medieval London and Denmark.

OBJECTIVES: In the 14th century AD, medieval Europe was severely affected by the Great European Famine as well as repeated bouts of disease, including the Black Death, causing major demographic shifts. This high volatility led to increased mobility and migration due to new labor and economic opportunities, as evidenced by documentary and stable isotope data. This study uses ancient DNA (aDNA) isolated from skeletal remains to examine whether evidence for large-scale population movement can be gleaned from the complete mitochondrial genomes of 264 medieval individuals from England (London) and Denmark. MATERIALS AND METHODS: Using a novel library-conserving approach to targeted capture, we recovered 264 full mitochondrial genomes from the petrous portion of the temporal bones and teeth and compared genetic diversity across the medieval period within and between English (London) and Danish populations and with contemporary populations through population pairwise ΦST analysis. RESULTS: We find no evidence of significant differences in genetic diversity spatially or temporally in our dataset, yet there is a high degree of haplotype diversity in our medieval samples with little exact sequence sharing. DISCUSSION: The mitochondrial genomes of both medieval Londoners and medieval Danes suggest high mitochondrial diversity before, during and after the Black Death. While our mitochondrial genomic data lack geographically correlated signals, these data could be the result of high, continual female migration before and after the Black Death or may simply indicate a large female effective population size unaffected by the upheaval of the medieval period. Either scenario suggests a genetic resiliency in areas of northwestern medieval Europe.

Calculus and survivorship in medieval London: The association between dental disease and a demographic measure of general health.

OBJECTIVES: Dental plaque is associated with a variety of systemic diseases and mortality risks in living populations. However, bioarchaeologists have not fully investigated the mortality risks associated with plaque (or its mineralized form, calculus) in the past. This study examines the relationship between survivorship and calculus in a medieval skeletal sample. MATERIALS AND METHODS: Our sample (n = 1,098) from four medieval London cemeteries, c. 1000-1540 CE, includes people who died under attritional (normal) and catastrophic (famine and plague) conditions. The associations between age and the presence of dental calculus on the permanent left first mandibular molar are assessed using binary logistic regression and Kaplan-Meier survival analysis. RESULTS: The regression results indicate a significant negative relationship between age and calculus presence for individuals of all ages who died under normal mortality conditions and for adults who died under both normal and catastrophic conditions. Survival analysis reveals decreased survivorship for people of all ages with calculus under normal mortality conditions. Similarly, during conditions of catastrophic mortality, adult males with calculus suffered reduced survivorship compared to males without it, though there was no difference in survivorship between adult females with and without calculus. CONCLUSIONS: These results suggest that, as in modern populations, calculus accumulation in the inhabitants of medieval London reflects a greater risk of premature death. The evaluation of calculus, a potential measure of underlying frailty, in the context of a demographic measure of general health suggests that it might provide insights into health in past populations.

Patterns of frailty in non-adults from medieval London.

Famine has the potential to target frail individuals who are at greater risk of mortality than their peers. Although children have been at elevated risk of mortality during recent famines, little is known about the risks posed to children during the medieval period. This study uses burials from the St. Mary Spital cemetery (SRP98), London (c. 1120-1540) to examine the relationships among non-adult age at death, burial type (attritional or famine), and four skeletal lesions (porotic hyperostosis, cribra orbitalia, linear enamel hypoplasia [LEH], and periosteal new bone formation). Hierarchical log-linear analysis reveals significant associations between famine burials and LEH, independent of age. Significant associations also exist between age and the presence of cribra orbitalia, porotic hyperostosis, and periosteal lesions, with all three lesions present in greater frequencies among older children and adolescents, independent of burial type. The LEH results suggest that early exposure to stressors increased frailty among non-adults in the context of famine. The associations between age and the other skeletal indicators suggest that, in both famine and non-famine conditions, frailer individuals died at younger ages and before skeletal lesions could manifest, while their less frail peers survived multiple physiological insults before succumbing to death at older ages.

Stress, sex, and plague: Patterns of developmental stress and survival in pre- and post-Black Death London.

OBJECTIVES: Previous research revealed declines in survivorship in London before the Black Death (c. 1346-1353), and improvements in survivorship following the epidemic. These trends indicate that there were declines in general levels of health before the Black Death and improvements thereof afterwards. This study expands on previous research by examining whether changes in survivorship were consistent between the sexes, and how patterns of developmental stress markers changed before and after the Black Death. MATERIALS AND METHODS: This study uses samples from London cemeteries dated to one of three periods: Early Pre-Black Death (1000-1200 AD, n = 255), Late Pre-Black Death (1200-1250 AD, n = 247), or Post-Black Death (1350-1540 AD n = 329). Temporal trends in survivorship are assessed via Kaplan-Meier survival analysis, and trends in tibial length (as a proxy for stature) and linear enamel hypoplasia (LEH) are assessed using t-tests and Chi-square tests, respectively. RESULTS: Survivorship for both sexes decreased before the Black Death and increased afterwards. For males, LEH frequencies increased and stature decreased before the epidemic, and LEH declined and stature increased after the Black Death. For females, the only significant change with respect to developmental stress markers was a decrease in stature after the Black Death. CONCLUSIONS: These results might reflect variation between the sexes in sensitivity to stressors, the effects of nutrition on pubertal timing, disproportionate access to dietary resources for males in the aftermath of the Black Death, the disproportionate deaths of frail individuals during the epidemic, or some combination of these factors.

Do leprosy and tuberculosis generate a systemic inflammatory shift? Setting the ground for a new dialogue between experimental immunology and bioarchaeology.

It is possible that during long lasting chronic infections such as tuberculosis (TB) and leprosy individuals who generate a stronger immune response will produce a chronic shift in the systemic levels of inflammatory proteins. Consequently, the systemic immunological shift could affect inflammatory responses against other persistent pathogens such as Porphyromonas gingivalis associated with periodontal disease (PD). OBJECTIVE: To determine if in vitro exposure to Mycobacterium tuberculosis or M. leprae lysates impacts subsequent immune responses to P. gingivalis; and to propose a new dialogue between experimental immunology and paleopathology. MATERIAL AND METHODS: We sequentially (2 days protocol) exposed peripheral blood mononuclear cells (PBMCs) from healthy donors to bacterial lysates either from M. tuberculosis, or M. leprae, or P. gingivalis. After collecting all supernatants, we measured the expression of immune proteins TNFα and IFNγ using an enzyme-linked immunosorbent assay. RESULTS: Early exposure (day 1) of PBMCs to M. leprae or M. tuberculosis lysates induces an inflammatory shift detected by the increase of TNFα and IFNγ when the same cells are subsequently (day 2) exposed to oral pathogen P. gingivalis. DISCUSSION: By extrapolating these results, we suggest that chronic infections, such as TB and leprosy, could generate a systemic immunological shift that can affect other inflammatory processes such the one present in PD. We propose that the presence and severity of PD should be explored as a proxy for inflammatory status or competence when reconstructing the health profile in past populations.