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.

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes.

BACKGROUND: Hansen's disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease's complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period. RESULTS: Here, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae's genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria. CONCLUSIONS: Our findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease's global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy's global history and can contribute to current models of M. leprae's worldwide dissemination, including interspecies transmissions.

Advancing the understanding of treponemal disease in the past and present.

Syphilis was perceived to be a new disease in Europe in the late 15th century, igniting a debate about its origin that continues today in anthropological, historical, and medical circles. We move beyond this age-old debate using an interdisciplinary approach that tackles broader questions to advance the understanding of treponemal infection (syphilis, yaws, bejel, and pinta). How did the causative organism(s) and humans co-evolve? How did the related diseases caused by Treponema pallidum emerge in different parts of the world and affect people across both time and space? How are T. pallidum subspecies related to the treponeme causing pinta? The current state of scholarship in specific areas is reviewed with recommendations made to stimulate future work. Understanding treponemal biology, genetic relationships, epidemiology, and clinical manifestations is crucial for vaccine development today and for investigating the distribution of infection in both modern and past populations. Paleopathologists must improve diagnostic criteria and use a standard approach for recording skeletal lesions on archaeological human remains. Adequate contextualization of cultural and environmental conditions is necessary, including site dating and justification for any corrections made for marine or freshwater reservoir effects. Biogeochemical analyses may assess aquatic contributions to diet, physiological changes arising from treponemal disease and its treatments (e.g., mercury), or residential mobility of those affected. Shifting the focus from point of origin to investigating who is affected (e.g., by age/sex or socioeconomic status) and disease distribution (e.g., coastal/ inland, rural/urban) will advance our understanding of the treponemal disease and its impact on people through time.

Inflammatory periosteal reaction on ribs associated with lower respiratory tract disease: A method for recording prevalence from sites with differing preservation.

OBJECTIVES: Inflammatory periosteal reaction (IPR) on the visceral surfaces of the ribs has been used in bioarchaeology as an indicator of lower respiratory tract disease. This article presents a detailed method for recording IPR on the ribs, even those in severely fragmented states, with the objectives of increasing the consistency of recording and producing true prevalence rates for skeletons so as to improve data comparability between future bioarchaeological studies of lower respiratory tract disease. MATERIALS AND METHODS: The presence and prevalence of respiratory-related IPR were recorded from three different Sudanese cemetery sites using a detailed method for identifying and recording IPR. Sites with variable preservation were chosen to test the applicability of the method. A flowchart to aid in identification of bony changes is presented. The method requires the recording of IPR on three separate sections of the rib (neck, angle, and shaft) and the allocation of ribs into rib cage regions of upper, upper-middle, middle, lower-middle, and lower. RESULTS: Results demonstrate differences in the distribution of IPR between sites and verify the method's applicability to archeological sites with various levels of skeletal preservation. DISCUSSION: While crude prevalence rates can indicate the number of individuals experiencing lower respiratory tract disease within a site, this method can provide information about the distribution of IPR within the rib cage. This should lead to new ways of distinguishing respiratory diseases within archeological populations. This method also allows for comparability between well-preserved and lesser-preserved sites by accommodating for rib fragmentation.

Genotype of a historic strain of Mycobacterium tuberculosis.

The use of ancient DNA in paleopathological studies of tuberculosis has largely been restricted to confirmation of disease identifications made by skeletal analysis; few attempts at obtaining genotype data from archaeological samples have been made because of the need to perform different PCRs for each genetic locus being studied in an ancient DNA extract. We used a next generation sequencing approach involving hybridization capture directed at specific polymorphic regions of the Mycobacterium tuberculosis genome to identify a detailed genotype for a historic strain of M. tuberculosis from an individual buried in the 19th century St. George's Crypt, Leeds, West Yorkshire, England. We obtained 664,500 sequencing by oligonucleotide ligation and detection (SOLiD) reads that mapped to the targeted regions of the M. tuberculosis genome; the coverage included 218 of 247 SNPs, 10 of 11 insertion/deletion regions, and the repeat elements IS1081 and IS6110. The accuracy of the SOLiD data was checked by conventional PCRs directed at 11 SNPs and two insertion/deletions. The data placed the historic strain of M. tuberculosis in a group that is uncommon today, but it is known to have been present in North America in the early 20th century. Our results show the use of hybridization capture followed by next generation sequencing as a means of obtaining detailed genotypes of ancient varieties of M. tuberculosis, potentially enabling meaningful comparisons between strains from different geographic locations and different periods in the past.

Genotyping of ancient Mycobacterium tuberculosis strains reveals historic genetic diversity.

The evolutionary history of the Mycobacterium tuberculosis complex (MTBC) has previously been studied by analysis of sequence diversity in extant strains, but not addressed by direct examination of strain genotypes in archaeological remains. Here, we use ancient DNA sequencing to type 11 single nucleotide polymorphisms and two large sequence polymorphisms in the MTBC strains present in 10 archaeological samples from skeletons from Britain and Europe dating to the second-nineteenth centuries AD. The results enable us to assign the strains to groupings and lineages recognized in the extant MTBC. We show that at least during the eighteenth-nineteenth centuries AD, strains of M. tuberculosis belonging to different genetic groups were present in Britain at the same time, possibly even at a single location, and we present evidence for a mixed infection in at least one individual. Our study shows that ancient DNA typing applied to multiple samples can provide sufficiently detailed information to contribute to both archaeological and evolutionary knowledge of the history of tuberculosis.

Biomolecular identification of ancient Mycobacterium tuberculosis complex DNA in human remains from Britain and continental Europe.

Tuberculosis is known to have afflicted humans throughout history and re-emerged towards the end of the 20th century, to an extent that it was declared a global emergency in 1993. The aim of this study was to apply a rigorous analytical regime to the detection of Mycobacterium tuberculosis complex (MTBC) DNA in 77 bone and tooth samples from 70 individuals from Britain and continental Europe, spanning the 1st-19th centuries AD. We performed the work in dedicated ancient DNA facilities designed to prevent all types of modern contamination, we checked the authenticity of all products obtained by the polymerase chain reaction, and we based our conclusions on up to four replicate experiments for each sample, some carried out in an independent laboratory. We identified 12 samples that, according to our strict criteria, gave definite evidence for the presence of MTBC DNA, and another 22 that we classified as "probable" or "possible." None of the definite samples came from vertebrae displaying lesions associated with TB. Instead, eight were from ribs displaying visceral new bone formation, one was a tooth from a skeleton with rib lesions, one was taken from a skeleton with endocranial lesions, one from an individual with lesions to the sacrum and sacroiliac joint and the last was from an individual with no lesions indicative of TB or possible TB. Our results add to information on the past temporal and geographical distribution of TB and affirm the suitability of ribs for studying ancient TB.

Heterogeneity in experiences of vitamin D deficiency in an early to mid-19th century population from Montreal, Quebec.

OBJECTIVE: To use the prevalence of prenatal/infancy interglobular dentine (IGD) as a proxy for suboptimal vitamin D status and explore its link to mortality, biological sex, cultural behaviours and environmental factors during the end of the pre-industrial/ beginning of the industrial period. MATERIALS: 50 skeletons from the St. Antoine cemetery (1799-1854), Montreal, Quebec with a well-preserved first mandibular molar. METHODS: Thin sections were prepared for histological examination of IGD in crown dentine. RESULTS: IGD prevalence was 74 % (37/50) and not significantly correlated statistically to sex and age-at-death. Most IGD occurred at birth and up to 3 years-old, six individuals were affected in utero, 54 % of the sample (27/50) presented longstanding IGD and six individuals displayed multiple IGD episodes. CONCLUSIONS: Prenatal IGD episodes revealed suboptimal maternal vitamin D levels, which, alongside a high frequency of IGD episodes around birth/from birth until a certain age, suggest cultural influences. Multiple and longstanding IGD episodes might also reflect suboptimal seasonal vitamin D attainment. SIGNIFICANCE: This study provides in-depth data on IGD within a relatively large archaeological North American sample, proving relevant to epidemiological studies on suboptimal vitamin status in 19th century Montreal. LIMITATIONS: The total number of IGD episodes is underestimated due to methodological biases; first-generation migrants in this study could not be identified and excluded from the sample. SUGGESTIONS FOR FURTHER RESEARCH: Use of a larger sample with a wider age-at-death range; further research on infants and children to investigate links between growth and lesion formation and visibility.

First archaeological evidence for ginger consumption as a potential medicinal ingredient in a late medieval leprosarium at St Leonard, Peterborough, England.

Leprosy was one of the most outwardly visible diseases in the European Middle Ages, a period during which leprosaria were founded to provide space for the sick. The extant documentary evidence for leprosy hospitals, especially in relation to diet, therapeutic, and medical care, is limited. However, human dental calculus stands to be an important source of information as it provides insight into the substances people were exposed to and accumulated in their bodies during their lives. In the present study, microremains and DNA were analysed from the calculus of individuals buried in the late medieval cemetery of St Leonard, a leprosarium located in Peterborough, England. The results show the presence of ginger (Zingiber officinale), a culinary and medicinal ingredient, as well as evidence of consumption of cereals and legumes. This research suggests that affected individuals consumed ingredients mentioned in medieval medical textbooks that were used to treat regions of the body typically impacted by leprosy. To the authors' knowledge, this is the first study which has identified Zingiber officinale in human dental calculus in England or on the wider European continent.

Vertebral morphology influences the development of Schmorl's nodes in the lower thoracic vertebrae.

Schmorl's nodes are the result of herniations of the nucleus pulposus into the adjacent vertebral body and are commonly identified in both clinical and archaeological contexts. The current study aims to identify aspects of vertebral shape that correlate with Schmorl's nodes. Two-dimensional statistical shape analysis was performed on digital images of the lower thoracic spine (T10-T12) of adult skeletons from the late medieval skeletal assemblages from Fishergate House, York, St. Mary Graces and East Smithfield Black Death cemeteries, London, and postmedieval Chelsea Old Church, London. Schmorl's nodes were scored on the basis of their location, depth, and size. Results indicate that there is a correlation between the shape of the posterior margin of the vertebral body and pedicles and the presence of Schmorl's nodes in the lower thoracic spine. The size of the vertebral body in males was also found to correlate with the lesions. Vertebral shape differences associated with the macroscopic characteristics of Schmorl's nodes, indicating severity of the lesion, were also analyzed. The shape of the pedicles and the posterior margin of the vertebral body, along with a larger vertebral body size in males, have a strong association with both the presence and severity of Schmorl's nodes. This suggests that shape and/or size of these vertebral components are predisposing to, or resulting in, vertically directed disc herniation.

Squatting, pelvic morphology and a reconsideration of childbirth difficulties.

: Childbirth is commonly viewed as difficult in human females, encompassed by the 'Obstetrical Dilemma' (OD) described by early palaeoanthropologists as an evolved trade-off between a narrow pelvis necessitated by bipedalism and a large-brained fetal head. The OD has been challenged on several grounds. We add to these challenges by suggesting humans likely squatted regularly during routine tasks prior to the advent of farming societies and use of seats. We suggest that habitual squatting, together with taller stature and better nutrition of ancestral hunter-gatherers compared with later Neolithic and industrial counterparts, obviated an OD. Instead, difficulties with parturition may have arisen much later in our history, accompanying permanent settlements, poorer nutrition, greater infectious disease loads and negligible squatting in daily life. We discuss bioarchaeological and contemporary data that support these viewpoints, suggest ways in which this hypothesis might be tested further and consider its implications for obstetrical practice. Lay Summary: Human childbirth is viewed as universally difficult. Evidence from physical therapies/engineering and studies of living and ancestral humans illustrates habitual squatting widens the pelvis and could improve childbirth outcomes. Obstetrical difficulties emerged late in prehistory accompanying settled agriculture, poorer nutrition and less squatting. Specific physical exercises could improve obstetrical practice.

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.

Time to be nosy: Evaluating the impact of environmental and sociocultural changes on maxillary sinusitis in the Middle Nile Valley (Neolithic to Medieval periods).

OBJECTIVE: To investigate the prevalence of maxillary sinusitis in people who lived in the Middle Nile Valley across different periods, cultures, and environmental conditions. MATERIALS: 481 skeletons from 13 sites, curated at the British Museum, London, were analysed. The sites ranged in date from the Neolithic to Medieval periods (c. 4900 BCE-CE 1500). METHODS: Bony changes within the maxillary sinuses, associated with sinusitis and oroantral fistulae were systematically recorded according to pre-established criteria. RESULTS: There were significant differences in the prevalence of maxillary sinusitis between time period/subsistence economy groups. The Neolithic hunter-gatherer/early agricultural group had the lowest prevalence, whilst the urban group demonstrated the highest frequency of the disease. CONCLUSIONS: Factors involved in the development of maxillary sinusitis are manifold and complex. However, the results indicate that increased aridity in Sudan in later periods and intensification of agricultural practices may have played a role in increasing prevalence of the disease. Urban environments, including crowding, poor sanitation, and industrial air pollution, could also have influenced susceptibility to maxillary sinusitis. SIGNIFICANCE: Prior to this paper, the impact of arid environments on respiratory health in the past had received little attention despite growing clinical research on the topic. Both arid and urban environments are predicted to expand in the future. This paper provides a deep-time perspective on an issue of increasing concern today. LIMITATIONS: Poor preservation of skeletons and a lack of archaeological settlement data for some sites. FUTURE RESEARCH: Investigation of a greater range of populations from different environments/climates.

Tuberculosis and leprosy in perspective.

Two of humankind's most socially and psychologically devastating diseases, tuberculosis and leprosy, have been the subject of intensive paleopathological research due to their antiquity, a presumed association with human settlement and subsistence patterns, and their propensity to leave characteristic lesions on skeletal and mummified remains. Despite a long history of medical research and the development of effective chemotherapy, these diseases remain global health threats even in the 21st century, and as such, their causative agents Mycobacterium tuberculosis and M. leprae, respectively, have recently been the subject of molecular genetics research. The new genome-level data for several mycobacterial species have informed extensive phylogenetic analyses that call into question previously accepted theories concerning the origins and antiquity of these diseases. Of special note is the fact that all new models are in broad agreement that human TB predated that in other animals, including cattle and other domesticates, and that this disease originated at least 35,000 years ago and probably closer to 2.6 million years ago. In this work, we review current phylogenetic and biogeographic models derived from molecular biology and explore their implications for the global development of TB and leprosy, past and present. In so doing, we also briefly review the skeletal evidence for TB and leprosy, explore the current status of these pathogens, critically consider current methods for identifying ancient mycobacterial DNA, and evaluate coevolutionary models.

A male adult skeleton from the Han Dynasty in Shaanxi, China (202 BC-220 AD) with bone changes that possibly represent spinal tuberculosis.

Bioarchaeological data for tuberculosis (TB) have been published very sporadically in China or the rest of East Asia. To explore the history of TB in this area, 85 skeletons excavated from the Liuwei Cemetery in Shaanxi, China (202 BC-220 AD) were macroscopically examined to record TB related bone changes. These skeletons represented inhabitants of Maolingyi, an urban area that had a high population density during the Han Dynasty (202 BC-220 CE). Seventeen of the 85 skeletons had spines that were well enough preserved to observe evidence of spinal disease. Among them, a male skeleton aged around 30 years (M34-E) manifested multiple lytic lesions in the eleventh thoracic to second lumbar vertebral bodies (T11 to L2). TB was considered a possible diagnosis for the spinal lesions observed, with differential diagnoses of brucellosis and typhoid. The dense population and overcrowding in urban Maolingyi were considered the potential social risk factors for TB found at this site. The findings of this study contribute to limited knowledge about the history of TB in East Asia and suggest a relationship between population density and the spread of TB in Maolingyi at that time. However, the lack of published bioarchaeological data of TB in East Asia hinders understanding the transmission of TB within Asia and its link to the rest of the world. Further intensive review of archaeological skeletons in Asia is urgently needed. 。, 。85, 17, 。, 30、、。, 。, 。、, , 。, 。, 。.

A 6500-year-old Middle Neolithic child from Pollera Cave (Liguria, Italy) with probable multifocal osteoarticular tuberculosis.

Clear skeletal evidence of prehistoric tuberculosis (TB) is rare, especially in children. We describe and differentially diagnose the pathological changes displayed by a five-year-old child, Pollera 21 (PO21) dated to the Middle Neolithic of Liguria (Italy), or 5740±30 BP (Beta-409341; 6635-6453cal BP, 2σ, OxCal 4.2). PO21 shows a number of osteoarticular lesions, mainly of a lytic nature with very little bone proliferation: the vertebral column, the shoulder and pelvic girdles, and the ribcage are involved. Given the nature and pattern of the lesions, we propose a diagnosis of multifocal (or multiple) bone TB. Attempts to detect TB aDNA through molecular analysis gave negative results, but this alone is not sufficient to prove that PO21 was not infected with TB. The lesions observed in PO21 share similarities with other published evidence, such as spinal and joint involvement, and disseminated cyst-like lesions. Conversely, PO21 does not show diffuse bone deposition, such as hypertrophic osteoarthropathy (HOA) or endocranial modifications such as serpens endocrania symmetrica (SES). PO21 adds to our knowledge of patterns of TB manifestation in archaeological skeletal remains, which is especially important considering the variability in types and patterns of osteoarticular lesions seen today in people with TB.

'Til Poison Phosphorous Brought them Death': A potentially occupationally-related disease in a post-medieval skeleton from north-east England.

This paper describes the pathological changes observed on the skeleton of a c.12-14 year old person buried in a north-east England Quaker cemetery dated to AD 1711-1857. Bone formation (woven and lamellar) and destruction are present mainly on the mandible, clavicles, sternum and scapulae, long bones of the right arm, left ribs, spine, ilia, and the femora and tibiae. Differential diagnoses of tuberculosis and other pulmonary diseases, smallpox, actinomycosis, neoplastic disease, and "phossy jaw" are considered. While the pathological changes could represent all previously described diseases and thus be associated with the insalubrious conditions in which this person lived, it is also possible that this person worked in the matchmaking industry known to be present in the region at the time. Attention is drawn to the previously overlooked condition "phossy jaw" caused by phosphorus poisoning, which was strongly associated with this industry. While matchstick making was an industry often associated with women and girls, DNA analysis of a bone sample from the skeleton did not successfully identify biological sex. Two dental calculus samples from this person were analysed for phosphorus, and comparisons were made with samples from the same and a different site; the levels did not indicate the person was more exposed to phosphorus than any of the other people at Coach Lane. However, the pathological lesions described also have relevance in a clinical context, because "phossy jaw" has been observed in living populations, arising as a consequence of ingesting phosphorous contained within some pharmaceuticals used for treating neoplastic disease and osteoporosis.

Insights on the paleoepidemiology of ancient tuberculosis from the structural analysis of postcranial remains from the Ligurian Neolithic (northwestern Italy).

The aim of this research is to gain insights on the progression timeline of osteoarticular tuberculosis (TB) in people from the Neolithic period by using skeletal traits that are independent of the bony lesions. The body proportions and postcranial mechanical strength of bones from two individuals from Liguria in northwestern Italy (Arene Candide 5, adolescent, and Arma dell'Aquila 1, adult), were compared with the rest of the Ligurian Neolithic skeletal series (45 individuals). If TB led to wasting of the skeleton and lack of normal function that endured for years, as often happens today, a clear signature of postcranial gracility and disruption of development should be apparent. Conversely, rapid progress of the disease would leave little systemic macroscopic change in the skeleton, except for the bony lesions directly caused by the TB pathogen, suggesting a different level of bacterial virulence in the past. The extreme biomechanical gracility observed in the lower limb of Arene Candide 5 suggests a period of compromised diaphyseal periosteal apposition during ontogeny due to metabolic disturbances likely linked to TB. Results suggest that, in Neolithic Liguria, TB in humans saw a slow, chronic progression, which is characteristic of diseases with long histories of host-pathogen co-evolution.

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.