Linking isotope analysis and paleopathology: An andean perspective.

This paper reviews the significant advances in isotopic investigations in Andean South America and directs scholars to explore new theoretical and analytical directions, specifically the applicability of isotope data to paleopathology. Excellent preservation and large skeletal collections of human remains make the Central Andes ideal for biogeochemical reconstructions and advancements in isotopic methods. Our aims are twofold: first, we present a meta-analysis of stable and radiogenic isotope research in the Central Andes since 1985, and highlight those that combine analyses of isotope ratios and pathological conditions. Second, we discuss useful directions for incorporating stable isotope analysis more explicitly in studies of paleopathology in the Andes more in the future. Principle research foci have described dietary variation and regional population mobility since the 1980s, where early methodological explorations identified significant trends in isotopic variation. For the years 1980-2017, we identified 96 scholarly publications through a meta-data analysis of major peer-reviewed journals, book chapters, and conference proceedings. These demonstrate specific trends in topical and methodological preferences across the Andean region and a shift from 10 publications pre-1997 to 67 in the last 10 years. However, combined isotope and paleopathology studies in this region remain sparse; given the ecological, geological, and cultural complexity of the Central Andes, analyses of pathological conditions in different regions would significantly benefit from the information on diet, mobility, and local ecology that isotope ratios provide. Isotope analysis requires destruction of archaeological tissues, and interpreting isotope data can be complex, but it can also provide unique insights into the pathogenesis of multifactorial conditions and assist differential diagnosis. Therefore, we also discuss research designs for pairing isotopic and paleopathological variables that will allow researchers to better capture disease ecologies in archaeological samples and their variation across different regions, within related sites, and within individual lifespans.

An introduction to advances in Andean South American paleopathology.

In the 20 years since the publication of John Verano's foundational paper "Advances in Paleopathology of Andean South America," paleopathological and bioarchaeological investigations of human skeletal remains in the region have increased dramatically. Today, primary foci have grown to span the identification of disease, detailed reconstructions of biocultural interactions, embodied social experiences, and ancient living worlds. In this special issue, more than a dozen scholars reflect on the state of developments in the scientific analyses of ancient disease, life, and society across the region. For this introductory article, we frame the current state of Andean paleopathology by reviewing key historical contributions beginning in the last century. More recent trends since 1997 are defined via a meta-analysis of the literature. We then highlight current innovations and consider future directions of study. We then close with an overview of the papers comprising this special issue. Each article explores major theoretical, topical, and methodological advances that have transpired since 1997 and charts the course for the next two decades of work - with implications and insights that transcend the Andes and speak to key paleopathological issues around the world.

Advances in the molecular detection of tuberculosis in pre-contact Andean South America.

Andean paleopathological research has significantly enhanced knowledge about the geographical distribution and evolution of tuberculosis (TB) in pre-Columbian South America. In this paper, we review the history and progress of research on ancient tuberculosis (TB) in the Andean region, focusing on the strengths and limitations of current approaches for the molecular detection of ancient pathogens, with special attention to TB. As a case study, we describe a molecular screening approach for the detection of ancient Mycobacterium tuberculosis in individuals from Late Intermediate Period (1000-1400 CE) contexts at the site of Huari, Peru. We evaluate 34 commingled human vertebrae and combine morphological assessments of pathology with high throughput sequencing and a non-selective approach to ancient pathogen DNA screening. Our method enabled the simultaneous detection of ancient M. tuberculosis DNA and an evaluation of the environmental microbial composition of each sample. Our results show that despite the dominance of environmental DNA, molecular signatures of M. tuberculosis were identified in eight vertebrae, six of which had no observable skeletal pathology classically associated tuberculosis infection. This screening approach will assist in the identification of candidate samples for downstream genomic analyses. The method permits higher resolution disease identification in cases where pathology may be absent, or where the archaeological context may necessitate a broad differential diagnosis based on morphology alone.

Osteoarthritis, entheses, and long bone cross-sectional geometry in the Andes: Usage, history, and future directions.

Akin to approaches encouraged by Verano (1997) in the Andes, and Ortner (2011, 2012) for general paleopathological studies, this article focuses on accurate descriptions and definitions of osteoarthritis, entheses, and long bone cross-sectional geometry. By evaluating these conditions as part of biological responses to abnormal skeletal changes and biomechanical stress, this research discusses each condition's pathogenesis. Further, this article emphasizes a "small data" approach to evaluating these conditions in ancient culturally and biologically related human populations, where the study samples must have good skeletal preservation, where estimates of age and sex need to be included as major factors, and where abnormalities need to be described and evaluated. This article also discusses global clinical and osteological research on ways scholars are currently trying to establish industry-wide methods to evaluate osteoarthritis, entheses, and long bone cross-sectional geometry. Recent studies have focused on rigorous evaluation of methodological techniques, recording protocols, and inter- and intra-observer error problems. Additionally, scholars have focused on physical intensity of movement using biomechanics, evaluated burials of known occupation, and used complex statistical methods to help interpret skeletal changes associated with these conditions. This article also narrows to focus on these conditions within thematic "small data" areas throughout the Andes. This research concludes with describing future directions to understand skeletal changes, such as more multidisciplinary studies between osteologists and pathologists, collaborations with living people to collect CT, x-rays, or computer-aided motion capture, and a stronger focus on how these conditions correlate with intense biomechanical changes in younger individuals.

Cranial modification and the shapes of heads across the Andes.

This broad literature review considers advances in the study of cranial vault modification with an emphasis on investigations of Andean skeletal remains over the last two decades. I delimit three broad categories of research, building on Verano's synthesis of the state of Andean paleopathology in 1997. These are associations with skeletal pathological conditions, classification and morphology, and social identity. Progress is noted in each of these areas with a particular emphasis on methodological advances in studying morphology as well as the growth of contextualized bioarchaeology and the incorporation of social theory in the consideration of cranial modification as a cultural practice. The article concludes with avenues for future research on head shaping in the Andes specifically and paleopathology more broadly.

Developmental anomalies and South American paleopathology: A comparison of block vertebrae and co-occurring axial anomalies among three skeletal samples from the El Brujo archaeological complex of northern coastal Peru.

Though developmental anomalies have been noted for over a century in South American paleopathology, they have received less attention than other pathological conditions. When anomalies are reported, they tend to be unusual case studies or incidental findings. Paleopathological research should also consider anomalies from a population perspective, to broaden our understanding about the frequency of specific anomalies, and potentially offer insight into genetic relationships, cultural behavior, or environmental factors. This investigation compared block vertebrae and co-occurring postcranial axial anomalies among three skeletal samples reflecting an occupational sequence at the El Brujo Archaeological Complex of Peru. Block vertebrae demonstrate both considerable antiquity and persistence through time, though frequencies, vertebral level, and co-occurring anomalies varied by sex and cultural period. Among the Late Preceramic sample, the frequency of C2-C3 block vertebrae was highest and only seen among females, which may suggest familial influence, genetic isolation, and potentially matrilocality. The Moche sample demonstrated a moderate frequency of blocks, which in combination with the frequencies of other developmental anomalies, may suggest population continuity paired with an influx of new genes, demographic expansion, and possible cultural change with regard to postmarital residence. The Lambayeque sample demonstrated the lowest frequency of blocks and the highest frequency and greatest diversity of anomalies, which may suggest genetic continuity from the Moche, an expanded gene pool, broader opportunities for mate choice, and cultural change. It is hoped that this investigation will provide data for future comparisons and call attention to the need for the broader study of developmental anomalies in South America.

Metabolic diseases in Andean paleopathology: Retrospect and prospect.

John Verano's 1997 synthesis of Andean paleopathology guided two decades of research and was instrumental in establishing modern Andean paleopathology. This paper reviews the current state and new directions in the study of skeletal metabolic disorders in the Central Andean archaeological record. Key historical, ecological, methodological, and contextual issues intersect with the study of metabolic bone diseases in Andean paleopathology. This paper further examines known temporal and spatial distribution of these disorders, as well as the strengths and weaknesses of the record of linear enamel hypoplasias, cribra orbitalia, porotic hyperostosis, scurvy, and rickets. Many other metabolic bone diseases have yet to be documented such as pellagra, hypophosphatasia, osteomalacia, and mucopolysaccharidosis among others. This work closes with considerations in the search for these undocumented diseases, but such an effort is only one part of new wave of advancements just on the horizon. The study of metabolic diseases in Andean paleopathology can lead the development of more sophisticated approaches to data collection, analysis, and interpretation - especially regarding theoretical interpretations from various bodies of social theory to the Developmental Origins of Health and Disease hypothesis, life history approaches, and phenotypic adaptive plasticity and constraint.

Spatial paleopathology: A geographic approach to the etiology of cribrotic lesions in the prehistoric Andes.

OBJECTIVE: The ubiquity of cribra orbitalia in skeletal samples has led to rigorous debate over their etiology, with most concluding that nutrition, physiological stressors, and environmental disease vectors synergistically contribute to lesion development. To parse the relative contributions of these etiological factors in the prehistoric Andes, this spatial paleopathological meta-analysis investigates the relationship between population-wide prehistoric Andean cribra orbitalia rates and geographic, climatic, and hydrological variables. METHODS: Crude prevalence patterns of cribra orbitalia from 61 archaeological sites were plotted and analyzed with geostatistical methods to explore spatial patterns in the distribution of anemia-associated lesions. Multiple linear regression modeling was performed on 19 spatial variables suspected to contribute to various forms of anemia that result in cribrotic lesions. RESULTS: Spatially-clustered high cribra orbitalia rates exist around the Central Peruvian coast, but are paradoxically low on the Ecuadorian coast. Multiple regression shows that elevation, temperature, and precipitation were not predictive of lesion rates. Multiple regression models show that aridity and seasonal variability in freshwater supply, together, explained a third of the variation in lesion rates. CONCLUSION: While cribra orbitalia has long been tied to coastal proximity, these results suggest environmental constraints such as the need for water storage could have promoted malnutrition and pathogenic infection more than mere coastal proximity. LIMITATIONS OF THIS STUDY: This analysis is limited by the paucity of data from highland sites and by the assumption that burials are local to the excavation site. SUGGESTIONS FOR FUTURE RESEARCH: Future studies will integrate isotopic and remotely-sensed data into models to explore links between water security, nutrition, and disease.

Advances in paleopathology in context: A focus on soft tissue paleopathology.

Skeletal and mummified remains from South America have had a significant impact on the progress of paleopathological research. In 1997, John Verano synthesized the state of paleopathological research, identifying trends and highlighting future potentials. The goal of this contribution is to consider Verano's observations on advances in soft tissue paleopathology within the context of the development of the field of mummy studies. As his article was published near the midpoint between the present and the early 1970s, when the modern form of mummy studies began to form, considering his observations in this context allows researchers the opportunity to consider how the field has progressed since the late 1990s.

Paleopathology and children in the Andes: Local/situated biologies and future directions.

In the decades since Verano (1997) published his foundational piece on Andean paleopathology, scholars have recognized the importance of the bioarchaeology of childhood. Yet, scholarship on ancient childhood in the Andes deemphasizes paleopathology. Nonadult paleopathological data are often employed in large-scale, biocultural studies focused on environmental or political adaptations; however, they can also elucidate children's individual lived experiences and roles in society. To generate culturally-meaningful paleopathological data, we must take a contextualized approach to our analyses and interpretations. Disparate use of chronological age in published datasets makes synthesis across studies problematic, and ethnohistorical and ethnographic data on Andean children demonstrate that developmental age categories, rather than chronological age ranges, are most appropriate. Further, paleopathological data can best inform our investigations when they are combined with related datasets such as those on sex, diet, activity, and mobility. With that in mind, we use the theoretical framework of "local biologies" (and the related "situated biologies"), where biology is viewed as heavily contingent on culturally-specific beliefs and practices and local physical, sociocultural, and political environments (Lock, 1993, 2001; Niewöhner and Lock, 2018). Local biologies approaches can enrich social bioarchaeology and paleopathology to by specifically situating children and their experiences within the ancient Andean world.

Patterns of trauma across Andean South America: New discoveries and advances in interpretation.

In his review article John W. Verano covered trauma, warfare, trophy taking, and human sacrifice, but his discussion mostly focused on the results of studies of museum or private collections and the recent discovery of the mass human sacrifice from Huaca de la Luna. Due to the renewed interest in the paleopathology of South America, a trend which Verano observed, these types of investigations have grown exponentially in the past twenty years since his initial publication. Here we synthesize the published data on the study and interpretation of traumatic injuries across time and space and we tease out some of the themes that have emerged in the twenty odd years since the seminal paper written by Verano. We searched and analyzed publications from 1997 to 2017 that pertained specifically to Andean South America through the review of library databases and then narrowed our search to trauma-related topics. In our literature review and meta-analysis of published studies on traumatic injuries, we found that nearly one-third of publications related to the field of paleopathology in Andean South America dealt with subjects we classified under trauma (N = 116/378), such as trephination, violence, sacrifice, warfare, etc. Large sample sizes, population-focused research, advances in methods of analysis, and hypothesis driven investigations have led to sophisticated and nuanced interpretations along a wide range of themes so that we understand a great deal more about violence, sacrifice, trephination, warfare and their sociopolitical and environmental contexts in prehistoric and early colonial Andean South America.

Looking back, looking forward: Paleopathology in Andean South America.

Over the past twenty years, the field of Andean paleopathology has advanced significantly thanks to a new generation of scholars who have been attracted to this region and whose innovative research has expanded our knowledge substantially. The papers in this special issue demonstrate how the field of Andean paleopathology has diversified and grown to become what is today a truly interdisciplinary enterprise involving archaeology, ethnohistory, biological anthropology, geochemistry, medical imaging, and genetics. These studies apply theoretical approaches to research questions that are increasingly innovative and nuanced as well as analytical methods that were in their infancy when I wrote my 1997 survey of the field.

Advances in regional paleopathology of the Southern Coast of the Central Andes.

Because of a rich cultural history and excellent preservation of archaeological materials the south coast of the Central Andes is a region where many anthropological questions can be explored, using the latest methods and techniques. Over the last 20 years, multidisciplinary paleopathological studies have revealed interesting and unanticipated perspectives regarding the lives and cultures of the peoples who inhabited this region in pre-Hispanic times. This paper presents a panorama of these recent investigations, beginning with a review of the data sources - the collections of human remains - available for study, their numbers, preservation, accessibility, strengths and weaknesses. Then follows a revision of recent investigations, presenting new knowledge about temporal trends in human health in the region, including mortality curves, stature achieved in adulthood, porotic hyperososis, cribra orbitalia, linear enamel hypoplasias, dental caries, biochemical analysis, trauma, and violence. This review shows how the knowledge of the history of this region has increased but also the many new questions that have emerged. Hopefully this paper will encourage more investigation, as the collections of human remains from this region are abundant, well documented and well preserved.

Exploring oral paleopathology in the Central Andes: A review.

This targeted review of oral paleopathology in the Central Andes explores research that focuses on a set of interrelated, multifactorial processes: dental caries, macrowear, alveolar abscess, antemortem tooth loss (AMTL), periodontal disease, and the presence of dental calculus. These conditions help characterize oral health because they result from the culturally mediated interaction of individuals' oral cavity with their external environment. To better understand how osteologists working in the Central Andes have interpreted the frequencies of these conditions, I review the etiology of each, as well as discuss the important issues in their analyses. I then highlight studies that integrate of a number of oral paleopathological conditions, that examine associations between oral conditions and other skeletal indicators of health, or that use multivariate statistical techniques to analyze conditions. In the Central Andes, these proxies for oral health have generally focused on several key research themes including the introduction of domesticated foods may have occurred earlier than expected, but that populations may have maintained mixed subsistence strategies for a significant period. Researchers have also identified that changes accompanying Inca imperialism were likely not as detrimental to local populations as was Spanish colonialism. Finally, the long-practiced, culturally important, activity of chewing coca has been shown to create an identifiable pattern of oral paleopathological conditions.

Paleo-oncology: Taking stock and moving forward.

This article serves as an introduction to the International Journal of Paleopathology's special issue, Paleo-oncology: Taking Stock and Moving Forward. Reflecting the goals of the special issue, this paper has been designed to provide an overview of the current state of paleo-oncology, to introduce new and innovative paleo-oncological research and ideas, and to serve as a catalyst for future discussions and progress. This paper begins with an overview of the paleo-oncological evidence that can be found in ancient remains, followed by a summary of significant paleo-oncological findings and methodological advances to date. Thereafter, challenges in estimating past prevalence of cancer are highlighted and recommendations are made for future advancements in paleo-oncological research. The ground-breaking studies included in the special issue and referenced throughout this introduction embody the many ways in which progress can be made in the field of paleo-oncology.

Molecular paleopathology and paleo-oncology-State of the art, potentials, limitations and perspectives.

This paper reviews the current knowledge on molecular paleopathology with respect to oncological information. This covers both the information on the protein level (proteome) as well as the gene level (genome) and includes data on carcinogenic factors - such as molecular evidence for oncogenic viral infections. Currently, relatively little data is available for neoplastic disease in paleopathology. Likewise, few studies describe the biochemical or immunohistochemical analysis of tumors - a tool to potentially classify the tumor type and the underlying primary tumor in metastases. On the gene level, two studies described distinct molecular mutations in either a tumor-driving oncogene or a tumor suppressor gene, both being excellent examples for paleo-oncological studies. The paucity of historic tumor material - particularly when only osseous remains are available - represents the most hindering factor for molecular paleo-oncology. This can only be overcome in future by both the thorough investigation of mummified archaeological biomaterial and the improvement of analytical assays in order to trace even minute amounts of tumor material in osseous lesions.

Old World tuberculosis: Evidence from human remains with a review of current research and future prospects.

The evidence for TB in archaeological human remains for the Old World is reviewed in published and some unpublished sources. The evidence of Pott's disease was considered specific for TB, with other bone changes, such as rib lesions, as non-specific. Limitations of the data are discussed. Most evidence for TB comes from skeletons from the northern hemisphere, particularly in Europe in the late Medieval period (12(th)-16th centuries AD), but there is early evidence in the Near/Middle East and Egypt. Many parts of Africa, Asia and Australasia have very little or no evidence. aDNA analysis has provided data on species and strains of the Mycobacterium tuberculosis complex organisms affecting people in the past. The extant data suggest the first epidemiological transition (Neolithic agriculture and permanent settlements) led to an increase in TB, with later increases in urban environments of the late Medieval period. A number of causative factors were at play. Future research, particularly using biomolecular analysis, has the potential to further contribute to our understanding of the origin and evolution of TB, thus merging the disciplines of palaeopathology and evolutionary medicine.

Screening ancient tuberculosis with qPCR: challenges and opportunities.

The field of ancient DNA (aDNA) has rapidly accelerated in recent years as a result of new methods in next-generation sequencing, library preparation and targeted enrichment. Such research is restricted, however, by the highly variable DNA preservation within different tissues, especially when isolating ancient pathogens from human remains. Identifying positive candidate samples via quantitative PCR (qPCR) for downstream procedures can reduce reagent costs, increase capture efficiency and maximize the number of sequencing reads of the target. This study uses four qPCR assays designed to target regions within the Mycobacterium tuberculosis complex (MTBC) to examine 133 human skeletal samples from a wide geographical and temporal range, identified by the presence of skeletal lesions typical of chronic disseminated tuberculosis. Given the inherent challenges working with ancient mycobacteria, strict criteria must be used and primer/probe design continually re-evaluated as new data from bacteria become available. Seven samples tested positive for multiple MTBC loci, supporting them as strong candidates for downstream analyses. Using strict and conservative criteria, qPCR remains a fast and effective screening tool when compared with screening by more expensive sequencing and enrichment technologies.