Cases of trisomy 21 and trisomy 18 among historic and prehistoric individuals discovered from ancient DNA.

Aneuploidies, and in particular, trisomies represent the most common genetic aberrations observed in human genetics today. To explore the presence of trisomies in historic and prehistoric populations we screen nearly 10,000 ancient human individuals for the presence of three copies of any of the target autosomes. We find clear genetic evidence for six cases of trisomy 21 (Down syndrome) and one case of trisomy 18 (Edwards syndrome), and all cases are present in infant or perinatal burials. We perform comparative osteological examinations of the skeletal remains and find overlapping skeletal markers, many of which are consistent with these syndromes. Interestingly, three cases of trisomy 21, and the case of trisomy 18 were detected in two contemporaneous sites in early Iron Age Spain (800-400 BCE), potentially suggesting a higher frequency of burials of trisomy carriers in those societies. Notably, the care with which the burials were conducted, and the items found with these individuals indicate that ancient societies likely acknowledged these individuals with trisomy 18 and 21 as members of their communities, from the perspective of burial practice.

Targeted enrichment of whole-genome SNPs from highly burned skeletal remains.

Genetic assessment of highly incinerated and/or degraded human skeletal material is a persistent challenge in forensic DNA analysis, including identifying victims of mass disasters. Few studies have investigated the impact of thermal degradation on whole-genome single-nucleotide polymorphism (SNP) quality and quantity using next-generation sequencing (NGS). We present whole-genome SNP data obtained from the bones and teeth of 27 fire victims using two DNA extraction techniques. Extracts were converted to double-stranded DNA libraries then enriched for whole-genome SNPs using unpublished biotinylated RNA baits and sequenced on an Illumina NextSeq 550 platform. Raw reads were processed using the EAGER (Efficient Ancient Genome Reconstruction) pipeline, and the SNPs filtered and called using FreeBayes and GATK (v. 3.8). Mixed-effects modeling of the data suggest that SNP variability and preservation is predominantly determined by skeletal element and burn category, and not by extraction type. Whole-genome SNP data suggest that selecting long bones, hand and foot bones, and teeth subjected to temperatures <350°C are the most likely sources for higher genomic DNA yields. Furthermore, we observed an inverse correlation between the number of captured SNPs and the extent to which samples were burned, as well as a significant decrease in the total number of SNPs measured for samples subjected to temperatures >350°C. Our data complement previous analyses of burned human remains that compare extraction methods for downstream forensic applications and support the idea of adopting a modified Dabney extraction technique when traditional forensic methods fail to produce DNA yields sufficient for genetic identification.

PALEOEPIDEMIOLOGY OF DIPHYLLOBOTHRIOSIS: CULTURAL AND ENVIRONMENTAL FACTORS AFFECTING ADENOCEPHALUS INTENSITY AND PREVALENCE.

Peruvian and Chilean mummies and coprolites provide a source of population-based parasitological information. This is especially true of the fish tapeworm, Adenocephalus pacificus. Our analysis of Chinchorro and Chiribaya mummies and diversified coprolite samples from Chile and Peru show variation in infection. There is a statistically significant difference in prevalence between Chinchorro hunter-gatherer and Chiribaya mixed-subsistence contexts. Furthermore, the most pronounced differences occur between populations within these groups. Chinchorro differences in cemeteries at the same location can be related to El Niño-Southern Oscillation variations. Pronounced prevalence variations between 3 Chiribaya villages within 7 km of each other relate to fish distribution and preparation variation. As with other recent archaeoparasitology studies, eggs-per-gram data exhibit overdispersion.

HEAD LOUSE PALEOEPIDEMIOLOGY IN THE OSMORE RIVER VALLEY, SOUTHERN PERU.

Recent studies of louse ectoparasites from mummies have developed robust data sets that allow a true epidemiological approach to the prehistory of louse parasitism. One epidemiological principle is that the binomial of overdispersion is normally negative, meaning that in a host population, parasites are aggregated in a few individuals. We demonstrate the overdispersion of lice in 3 different prehistoric communities that differ along 3 axes or variables: environmental setting, socioeconomic status, and cultural affiliation. Distinct cultural practices could have been involved in different patterns of louse infestation. Prevalence, intensity, and abundance of infestations exhibit statistically significant differences between the communities. We also find differences in prevalence between subadults and adults that contrasted by cultural affiliation and suggest conditions different from those seen today. We show that overall prevalence was affected primarily by ecological setting, not socioeconomic status nor cultural affiliation. These findings demonstrate that statistical analysis of archaeological data can reveal the states of infestation in past populations with lifestyles not seen in modern people. Our approach paves the way for future comparisons of subpopulations within archaeological communities.

The Many Hosts of Mycobacteria 9 (MHM9): A conference report.

The Many Hosts of Mycobacteria (MHM) meeting series brings together basic scientists, clinicians and veterinarians to promote robust discussion and dissemination of recent advances in our knowledge of numerous mycobacterial diseases, including human and bovine tuberculosis (TB), nontuberculous mycobacteria (NTM) infection, Hansen's disease (leprosy), Buruli ulcer and Johne's disease. The 9th MHM conference (MHM9) was held in July 2022 at The Ohio State University (OSU) and centered around the theme of "Confounders of Mycobacterial Disease." Confounders can and often do drive the transmission of mycobacterial diseases, as well as impact surveillance and treatment outcomes. Various confounders were presented and discussed at MHM9 including those that originate from the host (comorbidities and coinfections) as well as those arising from the environment (e.g., zoonotic exposures), economic inequality (e.g. healthcare disparities), stigma (a confounder of leprosy and TB for millennia), and historical neglect (a confounder in Native American Nations). This conference report summarizes select talks given at MHM9 highlighting recent research advances, as well as talks regarding the historic and ongoing impact of TB and other infectious diseases on Native American Nations, including those in Southwestern Alaska where the regional TB incidence rate is among the highest in the Western hemisphere.

Skeletal manifestations of disease experience: Length of illness and porous cranial lesion formation in a contemporary juvenile mortality sample.

OBJECTIVES: Porous lesions of the orbit (cribra orbitalia [CO]) and cranial vault (porotic hyperostosis [PH]) are used as skeletal indicators of childhood stress. Because they are understudied in contemporary populations, their relationship to disease experience is poorly understood. This paper examines the relationship between length of childhood illness and CO/PH formation in a clinically documented sample. "Turning points," which identify the window for lesion formation for CO/PH, are defined, implications for hidden heterogeneity in frailty are considered. METHODS: Data are from 333 (199 males; 134 females) pediatric postmortem computed tomography scans. Individuals died in New Mexico (2011-2019) and are 0.5 to 15.99 years (mean = 7.1). Length of illness was estimated using information from autopsy and field reports. Logistic regression was used to estimate predicted probabilities, odds ratios, and the temporal window for lesion formation. RESULTS: Illness, single bouts, or cumulative episodes lasting over 1 month is associated with higher odds of CO; individuals who were never sick have lower odds of having PH. This relationship was consistent for fatal and incidental illnesses that did not cause death. The developmental window for CO formation appears to close at 8 years. CONCLUSIONS: Those ill for over 1 month are more likely to have CO/PH than those with acute illnesses. Some individuals lived sufficiently long to form CO/PH but died of illness. Others with lesions died of circumstances unrelated to disease. This indicates hidden variation in robusticity even among ill individuals with CO/PH, which is vital in interpreting lesion frequencies in the archeological record.

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.

Ecce Homo: Moving past labels to lives.

OBJECTIVES: We report a contemporary individual who died with advanced holoprosencephaly (HPE) to encourage recognition of rare diseases (RDs), especially congenital conditions in archaeological samples. We also explore the range of conditions associated with hydrocephalus in support of nuanced interpretations of this disease. MATERIALS: The skeleton of a 17-year-old male who died with clinically diagnosed HPE, along with an age and sex matched comparative sample of 6 individuals who suffered accidental death and who were normal. METHODS: We observed and measured all remains using standard osteological methods. The clinical records for Ecce Homo were scrutinized; his family was interviewed, and his skull was X-rayed. RESULTS: The morphology and morphometry of Ecce Homo's skeleton display irregularities along the cranial midline and the postcranial skeleton consistent with anomalies derived from HPE as well as related congenital disorders and physical anomalies. CONCLUSIONS: We have reported HPE here and developed a differential diagnosis with closely related conditions. Likewise we relate the information generated in the clinical history and interviews with the family of Ecce Homo to facilitate an understanding of the social context. SIGNIFICANCE: This case is exceptional in providing information from the life context of a contemporary individual who suffered from a rare disease (HPE), with skeletal remains could be studied extensively. The differential diagnosis is useful in identifying HPE and other closely related conditions. LIMITATIONS: This is a single example with clinical intervention. SUGGESTIONS FOR FURTHER RESEARCH: Future osteological research should occur on other cases of HPE; molecular studies may offer further clarity.

Geographically dispersed zoonotic tuberculosis in pre-contact South American human populations.

Previous ancient DNA research has shown that Mycobacterium pinnipedii, which today causes tuberculosis (TB) primarily in pinnipeds, infected human populations living in the coastal areas of Peru prior to European colonization. Skeletal evidence indicates the presence of TB in several pre-colonial South and North American populations with minimal access to marine resources- a scenario incompatible with TB transmission directly from infected pinnipeds or their tissues. In this study, we investigate the causative agent of TB in ten pre-colonial, non-coastal individuals from South America. We reconstruct M. pinnipedii genomes (10- to 15-fold mean coverage) from three contemporaneous individuals from inland Peru and Colombia, demonstrating the widespread dissemination of M. pinnipedii beyond the coast, either through human-to-human and/or animal-mediated routes. Overall, our study suggests that TB transmission in the pre-colonial era Americas involved a more complex transmission pathway than simple pinniped-to-human transfer.

Missing data in bioarchaeology II: A test of ordinal and continuous data imputation.

OBJECTIVES: Previous research has shown that while missing data are common in bioarchaeological studies, they are seldom handled using statistically rigorous methods. The primary objective of this article is to evaluate the ability of imputation to manage missing data and encourage the use of advanced statistical methods in bioarchaeology and paleopathology. An overview of missing data management in biological anthropology is provided, followed by a test of imputation and deletion methods for handling missing data. MATERIALS AND METHODS: Missing data were simulated on complete datasets of ordinal (n = 287) and continuous (n = 369) bioarchaeological data. Missing values were imputed using five imputation methods (mean, predictive mean matching, random forest, expectation maximization, and stochastic regression) and the success of each at obtaining the parameters of the original dataset compared with pairwise and listwise deletion. RESULTS: In all instances, listwise deletion was least successful at approximating the original parameters. Imputation of continuous data was more effective than ordinal data. Overall, no one method performed best and the amount of missing data proved a stronger predictor of imputation success. DISCUSSION: These findings support the use of imputation methods over deletion for handling missing bioarchaeological and paleopathology data, especially when the data are continuous. Whereas deletion methods reduce sample size, imputation maintains sample size, improving statistical power and preventing bias from being introduced into the dataset.

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.

Thundering hoofbeats and dazzling zebras: A model integrating current rare disease perspectives in paleopathology.

OBJECTIVE: The article reviews the study of rare diseases and their nomenclature, emerging government policies and initiatives, and the concerns voiced by the modern rare disease communities. An interpretive model is then presented for the bioarchaeological interpretations of individuals with paleopathological evidence of rare diseases. MATERIALS: In demonstration of the application of the proposed framework, we evaluate the skeletal remains of an adult female (EZ 3-7-1) excavated in the 1980s from the Middle Woodland (50BCE-CE400) context of the Elizabeth site (11PK512) in the lower Illinois Valley, USA. METHODS: We use macroscopic examination methods, as well as cementochronology, to put forth the osteobiographical profile. RESULTS: The skeletal manifestations observed suggests limitations of major life activities, which would have increased in severity throughout the life course of EZ 3-7-1. CONCLUSIONS: The study of EZ 3-7-1 demonstrates how an osteobiography, centering on the lived experiences and limitations throughout a life course, can allow for a deeper appreciation for life in the past. SIGNIFICANCE: By considering the perspectives of the modern rare disease community in the bioarchaeological methodology, research can include the nuanced impacts of the disease on life experiences and varying societal perceptions and attitudes, as well as raising awareness and advancing contemporary perspectives on impairment and disability. LIMITATIONS: Without ample contextual evidence, there are limitations in making conclusions regarding social identity and disability. SUGGESTIONS FOR FURTHER RESEARCH: This framework should be applied to other rare diseases in a variety of contexts to further test its functionality.

Cancers as rare diseases: Terminological, theoretical, and methodological biases.

OBJECTIVE: Was cancer a rare disease in the past? Our objective is to consider the various terminological, theoretical, and methodological biases that may affect perceptions of the rarity of cancer in the past. MATERIALS AND METHODS: We discuss relevant malignant neoplastic biomedical and paleopathological literature and evaluate skeletal data. We selected 108 archaeological sites (n = 151 cancer cases) with published malignant neoplasms and that were amenable to calculating cancer crude prevalence. Furthermore, datasets from four medieval/postmedieval Portuguese and 12 postmedieval UK sites were used to compare age-adjusted rates for metastatic bone disease and tuberculosis. RESULTS: In the literature review, mean cancer crude prevalence (1.2 %; 95 % CI = 0.96-1.4) exceeded the threshold for a rare disease (RD). Age-standardized rates of MBD and TB were not markedly different in the sites surveyed. CONCLUSIONS: Methodological, theoretical and historical factors contribute to assumptions that cancers were rare diseases. The assumption that cancers are extremely rare in the paleopathological literature was not fully supported. Cancer is a heterogeneous concept, and it is important to view it as such. If a disease is considered rare, we may fail to recognize it or dismiss it as unimportant in the past. SIGNIFICANCE: We present a re-evaluation of the idea that cancer is a rare disease. We present a more nuanced way of comparing rates of pathological conditions in archaeological contexts. LIMITATIONS: Variation in the amount of useable information in published literature on malignant neoplasms. SUGGESTIONS FOR FURTHER RESEARCH: More large-scale studies of cancer in the past alongside comparative studies of cancer prevalence with other assumed rare diseases.

Root Dentin Translucency and Forensic International Dental Database: Methodology for estimation age-at-death in adults using single-rooted teeth.

Estimation of the age-at-death in adults is essential when the identification of deceased persons with unknown identity is required in both humanitarian and judicial contexts. However, the methodologies and the results obtained can be questioned. Various efforts have been developed to adjust procedures to specific populations, always seeking the precision and accuracy of the methodologies. It is known that the estimation of the age-at-death in adults coexists with wide margins of error, due to several reasons, including but not limited to statistical problems, the size of the sample or the physiological process of aging. This research focuses on a degenerative indicator of the dentin (Root Dentin Translucency) and its combination with Periodontal Height (PH) following the Lamendin's technique for estimation of the age-at-death in adults. The main objective of this research was to demonstrate the applicability of a Bayesian model based on a Forensic International Dental Database (FIDB) that include Root Translucency Height (RTH) and PH as a method to age-at-death in adults. The conclusion of this research was that the combined both indicators become a generalizable age-at-death in adults model for all human populations, where the Bayesian method would offer optimal results in any population. In this way, those populations that do not have had the possibility of validating a specific procedure, now have the opportunity to apply a valid method for estimating age-at-death in adults to global scope.

Automontage microscopy and SEM: A combined approach for documenting ancient lice.

Human ectoparasites, including lice, have been recovered from a wide range of archaeological materials. The human head louse, Pediculus humanus capitis, has been identified from mummies and sediments for decades. Louse eggs are the body part most commonly encountered and therefore the most frequently quantified. Typically, several types of microscopy are applied for egg documentation. For studies in which quantification of infestation is a goal, counting is done with the naked eye or with the aid of handheld lenses. For determination and stage classification, stereomicroscopy is commonly used. For more detailed examination of microstructure, light microscopy, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM) can be employed. In most reports, researchers use two or more techniques to accomplish interrelated goals. Automontage microscopy is used to document prehistoric arthropods with good success. Herein, we report the results of a combination of SEM and automontage microscopy to document lice and eggs recovered from South American mummies. This combined approach allows for simultaneous examination of internal and external characteristics. Thirty automontage composite images of 2 adult lice and 16 eggs showed that egg internal morphologies were easily examined showing the within-egg anatomy of emergent nymphs. SEM imaging of 9 lice and 129 eggs was completed. In the case of two adults and several eggs, SEM imaging was accomplish after automontage image capture of the same specimens. This one-to-one image comparison of SEM and automontage shows that transmitted light of automontage reveals egg internal structures and details of the adult lice. SEM allows for high magnification examination of egg, nymph and adult microstructures. We conclude that automontage imaging followed by SEM results in efficient graphic documentation of rare louse specimens.

Examining variation in skeletal tuberculosis in a late pre-contact population from the eastern mountains of Peru.

OBJECTIVE AND MATERIALS: This research evaluates the presence and chronology of tuberculosis (TB) in the northeastern highlands of Peru (CE 800-1535) through the analysis of osseous lesions from Pre-Contact Kuelap, Chachapoyas. METHODS: We examined macroscopic lesion morphology and distribution from the skeletal series (MNI = 207). RESULTS: We determined that skeletal evidence was highly consistent with advanced multifocal and spinal tuberculosis in 13 individuals. Destructive lesions of the lower thoracic and/or lumbar vertebra bodies and sacroiliac joints are evident in most cases, but we also observed lesions within the manubriosternal, hip, and knee joints. Both adult males (n = 7) and females (n = 6) present skeletal lesions from young adult to older adults, but there is only one late adolescent. Only three individuals demonstrate similar lesion distributions. CONCLUSIONS: Variation in lesion distribution in this population-based study shows the importance of identifying extra-vertebral tuberculosis and suggests that the disease may have manifested differently than at other coastal sites. These cases confirm the presence of tuberculosis both before and after Inca occupation across this central Andean highlands region. SIGNIFICANCE: This evidence for the likely endemic presence of TB in the New World prior to European Contact furthers our understanding of the distribution of this infectious disease across the region as well as elucidating lesion distribution. LIMITATIONS: The diagnosis of tuberculosis is based on skeletal lesions and it should be confirmed by molecular analysis. FUTURE RESEARCH: Additional examination of vertebral bodies (including juvenile remains) for evidence of earlier manifestations of infection.

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.

Evidence of Skeletal Fluorosis at the Ray Site, Illinois, USA: a pathological assessment and discussion of environmental factors.

OBJECTIVE: To carefully assess skeletal lesions in close environment context in order to evaluate whether skeletal fluorosis was present in individuals living in the prehistoric Midwest, USA. MATERIALS: Skeletal remains from minimally 117 individuals recovered from the Ray Site, located in western Illinois (USA) and dated to the Middle/early Late Woodland periods (50 BC-AD 400). METHODS: Macroscopic evaluation of all recovered skeletal elements. RESULTS: Eight individuals display a constellation of abnormal bony changes, including osteosclerosis, a high frequency of fractures, and dental abnormalities. CONCLUSIONS: The osteosclerotic changes along with the naturally high fluoride content of west central Illinois soil and water suggests the presence of skeletal fluorosis. SIGNIFICANCE: This is the first report of skeletal fluorosis from archaeologically recovered human remains from North America. LIMITATIONS: The ambiguous nature of the skeletal changes associated with fluorosis, especially in the less severe stages of the disease, renders determination of the etiology difficult. SUGGESTIONS FOR FURTHER RESEARCH: The continuation of paleopathological investigations of fluoride toxicity within archaeological communities recovered from this region with emphasis on the incorporation of biomedical and environmental data. Furthermore, complementary analyses of the chemical composition and the histological presentation of the skeletons could provide support for this diagnosis.

New world origin of canine distemper: Interdisciplinary insights.

OBJECTIVE: Canine distemper virus (CDV), human measles virus (HMV), and rinderpest virus (RPV) of cattle are morbilliviruses that have caused devastating outbreaks for centuries. This paper seeks to reconstruct the evolutionary history of CDV. MATERIALS AND METHODS: An interdisciplinary approach is adopted, synthesizing paleopathological analysis of 96 Pre-Columbian dogs (750-1470 CE) from the Weyanoke Old Town, Virginia site, with historical reports, molecular analysis and morbilliviral epidemiology. RESULTS: Both measles (c.900CE) and rinderpest (c. 376 BCE) were first reported in Eurasia, while canine distemper was initially described in South America much later (1735 CE); there are no paleopathological indications of CDV in Weyanoke Old Town dogs. Molecularly, CDV is closely related to HMV, while viral codon usage indicates CDV may have previously infected humans; South American measles epidemics occurred prior to the emergence of canine distemper and would have facilitated HMV transmission and adaptation to dogs. CONCLUSIONS: The measles epidemics that decimated indigenous South American populations in the 1500-1700 s likely facilitated the establishment of CDV as a canine pathogen, which eventually spread to Europe and beyond. SIGNIFICANCE: Understanding the historical and environmental conditions that have driven morbilliviral evolution provides important insights into potential future threats of animal/human cross-species infections. LIMITATIONS: Interpreting historical disease descriptions is difficult and the archaeological specimens are limited. Molecular sequence data and codon usage analyses rely on modern viruses. SUGGESTIONS FOR FURTHER RESEARCH: Interdisciplinary approaches are increasingly needed to understand diseases of the past and present, as critical information and knowledge is scattered in different disciplines.