A Brief History and 21st Century Challenges

Chapter 2

A Brief History and 21st Century Challenges Jane E. Buikstra Arizona State University Sharon DeWitte, University of South Carolina

In this chapter, we consider the history of paleopathology and a few of the fundamental issues faced by practitioners in the development of this field. We then turn to a discussion of the current state of paleopathology, reviewing methodological and theoretical issues encountered in 21st century paleopathology. In this regard, we discuss the differential diagnosis of pathological conditions in archeological skeletal remains, suggesting avenues by which paleopathologists may pursue more rigorous diagnosis. Finally, we discuss the important contribution of paleoepidemiology in the advancement of this field, as well as considering the ramifications of the osteological paradox in such work.

A BRIEF HISTORY OF PALEOPATHOLOGY Paleopathology has been defined in recent decades as the study of disease, both human and nonhuman, in antiquity using a variety of different sources, including human mummified and skeletal remains, ancient documents, illustrations from early books, painting and sculpture from the past, and analysis of coprolites (Ortner, 2003: 8) More recently, this definition has been reevaluated and expanded to reflect the crucial interplay of biomedical and social sciences and the humanities in the development and future of the field (Buikstra et al., 2017). A comprehensive history of paleopathology has recently been written (Buikstra and Roberts, 2012), and there are several other older summaries of this history that readers who have a specific interest in the subject may wish to consult (e.g., Jarcho, 1966; Angel, 1981; Ubelaker, 1982; Armelagos, 1997; Aufderheide and Rodriguez-Martin, 1998). Thus, a detailed history of paleopathology that includes research using all the varied sources of potential information is beyond the scope of this book. Here, we offer a brief summary of the history of paleopathology,

highlighting some of the issues and major developments in the field over the past 200 years. The history of paleopathology in many ways parallels the development of most other scientific disciplines. The early publications consist of a body of descriptive literature in which abnormalities encountered by an observer are described against the background of what is normal. Much of this early research was no more than an anatomical account of these abnormal conditions with little if any attempt to explore the biological or pathological significance of what was being described. The earliest work focused on nonhuman paleontological specimens (e.g., Esper, 1774; Cuvier, 1820). Warren (1822) included a discussion of artificial cranial deformation in human skulls of indigenous North Americans in his book titled, A Comparative View of the Sensorial and Nervous Systems in Man and Animals. In 1861 in Paris, Gosse published another study of artificial cranial deformation. In the following decades, the question of the origin of syphilis began to be debated with intensity (e.g., Jones, 1876; Virchow, 1898). This debate marks one of the earliest attempts to use archeological human remains to resolve an important biomedical problem. And toward the end of the 19th century, R.W. Shufeldt proposed that the term “paleopathology” be used to describe “all diseased or pathological conditions found fossilized in the remains of extinct or fossil animals” (Shufeldt, 1892: 679). As the term “paleopathology” began to be used in the early 20th century, this period witnessed a marked expansion of published reports on ancient disease. Particularly notable is the work of Sir Marc Armand Ruffer (1910) on Egyptian mummies, and the studies on Nubian skeletal material by Wood-Jones (1908, 1910) and Elliot-Smith and Wood-Jones (1910). In the United States, Aleˇs Hrdliˇcka (1914) published some observations on the pathology of ancient Peruvian skulls. In 1923, Moodie’s

Ortner’s Identification of Pathological Conditions in Human Skeletal Remains. DOI: https://doi.org/10.1016/B978-0-12-809738-0.00002-8 © 2019 Elsevier Inc. All rights reserved.

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introduction to the study of ancient disease, which emphasized nonhuman paleontological specimens, appeared. A brief, general review of human paleopathology was published by Williams in 1929. This review included observations on bones and teeth as well as on mummy tissue and ancient art. Pales (1930) followed with his book on paleopathology and comparative pathology. Most of his cases and discussions concerned European human specimens. In the same year, Hooton (1930) published his classic study of North American Indian skeletal material from Pecos in which he included an extensive description of pathological specimens. Hooton’s study is notable in its descriptive detail, in the statistical treatment of different types of disease in the skeletal population, and in his efforts to show trends in disease frequency through the time period of human occupation at the site. In the 1960s, Wells (1964) published a review of evidence of human paleopathology from skeletal material, mummies, and art that brought paleopathology to the attention of a more general audience. But in the preceding decades, paleopathological studies had fallen into a pattern of inclusion in archeological research as descriptive addenda or appendices. Thus, calls for further advances in the field of paleopathology were made (Jarcho, 1966; Brothwell and Sandison, 1967; see also Grmek, 1983/1989), resulting in the establishment of professional organization, international journals, and professional meetings and training seminars (Buikstra and Roberts, 2012). Throughout the development of human skeletal paleopathology as a scholarly discipline there have been recurring problems in both theory and methodology. In the early stages of paleopathology, most of the research was conducted by physicians who had little knowledge of archeology, thus context often was overlooked. As studies of pathological skeletal specimens began to be conducted primarily by biological anthropologists, whose formal training and experience in skeletal pathology and radiology may be deficient, pathological conditions were at risk of being attributed incorrectly to the wrong time period by those unfamiliar with the complexities of archeological dating. Further, bone lesions were incorrectly diagnosed through ignorance of anatomy and the total range of diseases that affect bone (see Stewart’s comments on this problem in Jarcho, 1966: 43). These problems were complicated further due to the slow formulation of a theoretical context for interpreting the meaning of paleopathological data. [See, e.g., the debate (Wood et al., 1992; Goodman, 1993) about what can and cannot be said about prevalence data and the inferences made about the health of past human populations.] In 1988, Ortner and Aufderheide (1991) organized a symposium held as part of the International Congress of Anthropological and Ethnological Sciences in Zagreb,

Yugoslavia (now Croatia) that attempted to assess (1) how far paleopathology had developed as a scientific discipline, (2) some of the theoretical and methodological problems that needed to be resolved, and (3) directions that research might take in the future. Methodological issues included an inconsistent descriptive terminology that precluded comparison between published reports, and the lack of diagnostic criteria that fully utilized the information available in archeological human skeletons (Ortner, 1991). Theoretical issues included the need for greater understanding of what skeletal disease meant in terms of the general morbidity that existed within the living population in which the person with skeletal disease lived (Ortner, 1991). Much of the emphasis in paleopathology until fairly recently has been on descriptions of pathological specimens, and there had been little effort to relate the evidence of disease to the broader problems of human adaptation. Early hints of such an emphasis exist in Hooton’s Pecos Pueblo monograph (1930), in the consideration of epidemiological factors in evaluating the data on pre-Columbian tuberculosis in the New World (Morse, 1969), and in discussions on the origin of treponemal diseases (Hackett, 1963; Hudson, 1965). But not until recently has the trend toward population studies of ancient disease become a significant part of the literature on paleopathology as these methodological and theoretical problems are resolved (e.g., Larsen, 1997). Much of the descriptive literature in skeletal paleopathology depended upon the scholar’s knowledge of gross bone pathology. Unfortunately, where this knowledge was inadequate there were few reference sources that could be of assistance. Jarcho (1966) organized a symposium on human paleopathology that addressed this problem, among others. The participants called for the establishment of a paleopathology registry and improved diagnostic methodology to partially correct these problems. Steinbock’s reference book (1976) on diagnosis of ancient bone disease represented the first integrated attempt to establish diagnostic criteria for the paleopathologist that addressed the broad range of diseases that affect the human skeleton. The first two editions of this volume (Ortner and Putschar, 1981 and slightly revised in 1985; Ortner, 2003) provided a complimentary treatment of skeletal disease. Both these reference works represented important steps in improving the knowledge regarding the types of diseases that affect bone and the morphological features associated with the disease. Since the publication of the first two editions of this book, there has been a substantial increase in research on broader scientific problems, particularly those related to paleoepidemiology, as we will review later in this chapter. There has also been significant progress made on several crucial methodological problems. One of the most

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important of these has been the improvement in our application of differential diagnosis, which we will discuss in detail in the following section. As we face a new suite of issues and advances in the 21st century, we argue that paleopathology should be an interdisciplinary endeavor, incorporating expertise from the humanities, the social sciences, and the biomedical sciences (Buikstra et al., 2017).

21ST CENTURY PALEOPATHOLOGY Our vision of 21st century paleopathology is of a profoundly interdisciplinary endeavor, drawing knowledge and professionals from the biomedical and social sciences, as well as the humanities. We use knowledge about past health to address the coevolution of humans and pathogens, and we anticipate much more knowledge about both human and animal disease will soon be reviewed through molecular study. This volume therefore is meant to be an entry point for knowledge that necessarily extends well beyond these pages. First of all, we must recognize that paleopathology proceeds primarily through scientific methods. Our observations of ancient remains should be drawn carefully, follow standard descriptive terminology, and be designed to minimize both intra- and interobserver error. A general overview of terminology appears on the Paleopathology Association’s website (https://paleopathology-association. wildapricot.org/Nomenclature-in-Paleopathology). While this overview generally follows medical terms, methodological and application issues arise due to the fact that most of our observations are made upon materials that emerged from a burial environment. Taphonomic changes are frequently described in terms also used for vital processes, “abraded” and “eroded” being two apt examples. Therefore, when using such terms, the observer should be careful to indicate whether the process occurred ante- or postmortem. We continue to follow Ragsdale and colleague’s (1981) descriptions of periosteal bone reactions (see also Weston, 2012), familiar to those of us who have been humbled during Ortner/Ragsdale and Ragsdale workshops at the annual meetings of the Paleopathology Association. It is crucial not only to describe, but also to understand, the processes that have led to the observed change. As we consider our observations, we should report whether or not the process was active at the time of death, or quiescent. There are published standards (Buikstra and Ubelaker, 1994) and freely available databases (Osteoware) for recording pathological changes in human bones. Whatever system is used, an explicit key that explains the coding system is crucial. While this issue may not seem so important to those starting their research careers, its

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significance will become apparent as the need for consistency across years of data collection and comparative approaches emerge. Observing pathological changes and distinguishing these from postmortem alterations is one crucial step in assessing ancient disease (see Chapter 5: Abnormal Bone: Considerations for Documentation, Disease Process Identification, and Differential Diagnosis). Once these have been coded by individual, and then across a skeletal sample, the identification of a condition assumes significance. Remembering that observations may be complicated by comorbidities, i.e., that two or more diseases may affect a given individual, the survey of possible conditions should begin. In most cases, this assessment can begin with this volume, but it should not necessarily end here. To fully appreciate the manner in which bones (and other tissues) may react to a given insult requires an appreciation of the variable manner in which a person may be affected and the fact that the person may have died prior to the most extreme manifestation of the disease, as recorded here or in the clinical literature. Certainly medical interventions, especially antibiotics and chemotherapy, have changed the course of disease over the past century profoundly. Earlier medical procedures, such as treating venereal syphilis with mercury or malaria with high-temperature baths, may or may not have altered the course of disease. Such treatments, however, may have introduced their own diagnostic sequelae. Earlier editions of this volume have recommended clinical diagnoses found in books and medical museums between 1750 and 1930. We are inclined to a more conservative perspective, particularly in reference to infectious diseases. The most reliable sources, in our experience, have been clinical reports from the period following the identification of the pathogen causing the condition and prior to the development of effective interventions. In the absence of documented collections, of course, autopsies and radiographic records are seldom sufficiently complete to provide the desirable, complete skeletal record. Even those practitioners using documented collections should be careful to read all the supporting documentation to discern the degree to which the “diagnosis” was based upon clinical observations rather than posthoc skeletal observations. Again, we emphasize that, in most cases, this book should be considered a secondary source. Anyone wishing to develop a definite differential diagnosis should consult the primary literature, which engages the clinical literature. Web-based searches are important, especially in discovering primary source documents from an earlier era. Identifying a disease process in archeologically recovered human remains is only part of the process of interpreting past lives. A practitioner of paleopathology needs to appreciate concepts drawn from the social sciences

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(Buikstra et al., 2017; Chapter 3: Themes in Paleopathology) and the humanities (Mitchell, 2011, 2012, 2017). Given the myriad branches of knowledge required for most studies of ancient disease, collaborations are crucial and training in professional cooperation and respect are important for paleopathologists. Among other essential considerations are ethical issues relating to patients and descendent groups (Lambert, 2012). These are an essential part of any training program and any development of a project involving peoples from the past. In closing, we will more closely examine the potential contribution of paleoepidemiology to 21st century paleopathology research.

PALEOEPIDEMIOLOGY Epidemiology and Paleoepidemiology Epidemiology is the study of the distribution of healthrelated states or events (including, but not limited to, disease) within populations and of the factors that affect them, and the application of this information in efforts to control diseases and other health problems (WHO, 2018). Paleoepidemiology is the study of population-wide patterns of human health and disease in the past, typically done using data derived from skeletal or mummified remains excavated from archeological sites or from documented skeletal collections. For many populations, skeletal data provide the only remaining evidence of health in the past, and paleoepidemiology thus provides invaluable insights into how human health has varied within and between populations or subpopulations throughout human prehistory and history. Hooton’s (1930) examination of pathology in Pecos Pueblo is often credited as the first paleoepidemiological study, providing a model for the application of quantitative analyses of paleopathological data that became more widely used in bioarcheological research beginning in the 1960s (Armelagos, 2003; Mendonc¸a de Souza et al., 2003). Since then, paleoepidemiologists have addressed such topics as the Neolithic and the second epidemiological transitions (e.g., Armelagos and Cohen, 1984; Wilson, 2014; Zuckerman, 2014), the effects of European contact on indigenous populations (e.g., Klaus and Tam, 2009; Larsen et al., 2001), and mortality patterns during and health patterns following infectious disease epidemics (e.g., DeWitte, 2018; DeWitte and Wood, 2008). Though the ultimate goal of paleoepidemiology— understanding how and why health-related states vary within a population—is shared with epidemiology, and though both fields focus on groups rather than individuals as the fundamental units of analysis, the data and analytical methods available to scholars in these fields are quite different. Epidemiologists use experimental or

observational data derived from longitudinal or crosssectional studies of living populations; however, only cross-sectional data are available to paleoepidemiologists. Because paleoepidemiologists work with samples of the dead, they cannot follow individuals over time to determine how their health-related states change in response to exposure to a particular variable. It is possible for paleoepidemiologists to examine the within-individual effects of variables over time (i.e., the life course) in a typical archeological skeletal sample by assessing later-life outcomes associated with developmental stress markers or isotopic signature of diet or mobility that form relatively early in life and can be assigned ages-at-formation. Alternatively, paleoepidemiologists can study documented skeletal collections for which they have information both about exposures early in life and later health or mortality outcomes. With respect to the former approach, there are unfortunately a limited number of developmental skeletal stress markers (e.g., enamel hypoplasia, neural canal dimensions, tooth size, cribra orbitalia, stature), and they generally suffer from low specificity. Further complicating paleoepidemiological studies is the fact that skeletal samples are typically accumulated over multiple generations, and often it is difficult or impossible to determine more precisely, within the general period of use of a cemetery, the date of death of each individual in the sample (Mendonc¸a de Souza et al., 2003). This is even further complicated by the lack of accuracy and precision associated with adult skeletal age-estimation methods (BocquetAppel and Masset, 1982; Milner and Boldsen, 2012). As a consequence of these issues, paleoepidemiologists rarely examine true cohorts of individuals (a cohort is a group of individuals who all experience a particular event at the same time; e.g., a birth cohort is a group of people who were all born at the same time) as is possible for epidemiologists. Thus, paleodemographic studies might be confounded by temporal changes in exposure variables that cannot be detected and thus which cannot be controlled for. Epidemiologists are interested in and generally capable of measuring health-related states and disease outcomes relative to a particular population at risk. That is, epidemiologists can identify not only those individuals who have the specific conditions of interest, but also those alive at the same time (and at the same age) who do not have those conditions or who do not develop them over the course of a study. Combined with good temporal control, information about the population at risk allows epidemiologists to better contextualize, among other things, the incidence and prevalence of conditions. Incidence is the number of new or newly diagnosed cases of a condition within a specified period of time, and prevalence is the actual number of individuals with the condition alive at a particular point or during a particular

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period of time. In theory, paleoepidemiologists share an interest in these phenomena with respect to past populations. However, paleoepidemiologists have much more limited information about past populations at risk, as they observe only those individuals who died and ultimately became part of excavated skeletal samples (see more about selective mortality below), not the actual onceliving populations to which they originally belonged. Paleoepidemiological reconstructions of past populations at risk, incidence, prevalence, and other measures are thus, at best, biased. Epidemiologists are also better able to identify healthrelated states or diseases of interest because they have at their disposal data collected from living people using a variety of diagnostic tools (the nature of which depends on the condition of interest), including physical examinations of living patients or decedents, health history and behavior questionnaires, immunoassays, histological analyses, and cell cultures. Diagnostic criteria or tests for identifying diseases or conditions are typically described in terms of their sensitivity and specificity. Sensitivity, which is also referred to as the true positive rate, is the proportion of people with a condition who are correctly identified by a test as having the condition, i.e., the extent to which true positives are not overlooked by the test (Boldsen, 2001; Waldron, 2007). Diagnostic tests with high sensitivity produce few false negatives, so if people test negative for the disease of interest, it is likely that they do not, in fact, have that disease. Specificity (also called the true negative rate) is the proportion of people without a condition who are correctly identified by the test as not having it (Boldsen, 2001; Waldron, 2007); i.e., specificity is the extent to which people who test positive really represent the condition of interest. Diagnostic tests with high specificity produce few false positives, so if people test positive for a condition, it is likely that they actually have the condition. Because of controlled laboratory and field experiments, it is possible to accurately assess the sensitivity and specificity of diagnostic criteria used in living populations, so epidemiologists know how confident they can be in their diagnoses and research findings based thereon. Though epidemiologists often work with data derived from tests having relatively low sensitivity and specificity, they are at an advantage in knowing something about the level of uncertainty they face in their research. Paleoepidemiologists, on the other hand, most often rely solely upon skeletal lesions or stress markers to assess health-related states, which provide relatively limited information about health and disease (compared to the data available to epidemiologists) and for which there is often limited, if any, information about sensitivity and specificity. The specificity of skeletal lesions for diagnostic purposes is limited in large part by the fact that bone

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can respond to disease and trauma in just a few general ways: bone is deposited, removed, or deformed in response to these deviations from normal physiology or structural integrity. Paleoepidemiologists are faced with the dilemma that many diseases can lead to the production of skeletal lesions that look similar, if not identical, across those etiologies. For example, Weston (2008) assessed periosteal new bone formation macroscopically and using radiographs from individuals with known metabolic, infectious, and other conditions, such as chronic osteomyelitis, fracture, syphilis, and rickets. She did not identify any location, size, shape, or form characteristics of the lesions that were specific to those conditions, which indicates that responses to diseases are determined by the nature of the affected bone and the periosteum rather than by the diseases themselves (Weston 2008: 56). Even in cases of diseases that produce pathognomonic lesions (many examples of which are provided in this volume), differential diagnosis can be severely hampered if the preservation of the relevant elements is poor. The sensitivity of skeletal lesions is limited because not everyone with conditions that have the potential to affect the skeleton will, in fact, develop skeletal lesions in response (Milner and Boldsen, 2017). For example, tuberculosis can cause the production of diagnostic bony lesions, but only approximately 3% 5% of people with untreated tuberculosis develop such lesions (Resnick and Niwayama, 1995). This low proportion means that many people with tuberculosis in skeletal samples will not be diagnosed based on skeletal pathology alone. As has been discussed elsewhere (see, e.g., Mays, 2018; Zuckerman et al., 2016), few paleoepidemiological studies have estimated the sensitivity and specificity of skeletal lesions. For example, Smith-Guzma´n (2015) assessed the sensitivity and specificity of a suite of skeletal lesions with respect to malaria-associated anemia using clinical samples of individuals with known cause of death or malaria exposure. Boldsen (2001) estimated the sensitivity and specificity of skeletal indicators of leprosy based, in part, on samples drawn from medieval cemeteries associated with lepers’ hospitals. Konigsberg and Frankenberg (2013) illustrate the general approach to estimation using a hypothetical example. Often, however, paleoepidemiologists face an unquantified level of uncertainty regarding how many false negatives and false positives with respect to a particular condition exist within their samples. As emphasized in Chapter 8, it is increasingly possible to use ancient biomolecular approaches to identify diseases such as bubonic plague, tuberculosis, leprosy, malaria, hepatitis, and enteric fever (Salmonella) in skeletal or mummified tissue samples (Bos et al., 2011, 2014, 2016; Donoghue et al., 2015; Marciniak et al., 2016; Patterson Ross et al., 2018; Va˚gene et al., 2018).

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However, these approaches are not without their own problems; e.g., they are expensive (prohibitively so for many scholars) and destructive, and it can be difficult to interpret negative findings given the myriad factors that interfere with DNA and other biomolecule preservation, extraction, or amplification. As a result, ancient biomolecule studies tend to yield small sample sizes of individuals who test positive for the pathogens of interest, and thus, to date, few paleoepidemiological studies have been based solely on ancient bimolecular data. Despite the issues associated with identifying specific conditions in skeletal samples, paleoepidemiological studies have examined a variety of specific infectious, metabolic, and degenerative conditions in past populations, including leprosy (Boldsen, 2001), syphilis (Harper et al., 2011), tuberculosis (Buikstra, 1999), vitamin D deficiency (Snoddy et al., 2016), developmental dysplasia (Blatt, 2015), and degenerative joint disease (Klaus et al., 2009). The existence of documented historical plague burials has also facilitated paleoepidemiological studies of bubonic plague in the absence of diagnostic skeletal pathology (DeWitte and Wood, 2008; Kacki, 2017). By choice or necessity, however, rather than attempt to diagnose specific etiologies, many paleoepidemiologists use skeletal lesions as general (i.e., nonspecific) indicators of exposure to physiological stress or developmental disturbance. Thus, many paleoepidemiological studies focus on the general health of populations using nonspecific indicators rather than attempt to assess health in the context of specific diseases. This approach skirts some of the issues associated with low sensitivity and specificity, but still must contend with the fundamental issue that skeletal samples are inherently biased and that the presence or absence of lesions can be difficult to interpret (as framed by the osteological paradox, described below).

The Relationship Between Paleoepidemiology and Paleopathology With its focus on skeletal pathology, paleoepidemiology is clearly aligned with its sister discipline, paleopathology. Both fields focus on health, disease, or well-being in the past, and both make use of the same skeletal pathologies and stress markers (and thus both ultimately grapple with the same limitations associated with these data). However, paleopathology is primarily concerned with the differential diagnosis of pathologies in individual skeletons, establishing the antiquity of specific diseases, or documenting the presence of particular conditions in past populations via case studies of one or a few individuals (Boldsen and Milner, 2012). Paleoepidemiology, as detailed above, focuses on populations as the unit of analysis, and though some practitioners might not entirely

agree with Goodman’s (1993: 282) claim that “paleoepidemiologists are rarely interested in individuals,” it is certainly true that from an analytical and interpretive perspective, individuals are of interest because they contribute to the observed aggregate patterns (Milner and Boldsen, 2017). Because of these different scales of focus, paleopathology and paleoepidemiology typically use different analytical approaches. Paleopathology tends to be more descriptive, whereas paleoepidemiology applies quantitative analyses to a greater extent (indeed, quantitative analyses are impossible to apply to paleopathological case studies involving isolated individuals). Like epidemiology, paleoepidemiology is inherently comparative; in order to interpret the broader implications of the presence of pathologies, rates of pathological lesions are compared in paleoepidemiological studies between groups, such as male versus female, urban versus rural, or high status versus low status. Paleopathology, however, can be successfully done without the application of a comparative framework. Milner and Boldsen (2017) emphasize the unique paleoepidemiological focus on estimating the risks of death associated with skeletal pathologies. Their definition of paleoepidemiology is inherently demographic. Informative paleopathological research does not necessarily require information beyond the presence (or absence) of pathology, and thus paleopathology can be done independently of demographic data.

Paleoepidemiology and the Osteological Paradox The focus on population-level health and disease dynamics in paleoepidemiology provides scholars in the field the opportunity to actively engage with and attempt to resolve some of the issues associated with the osteological paradox, which was described over 25 years ago by Wood et al. (1992). The osteological paradox centers around two important phenomena: heterogeneous frailty and selective mortality. Frailty, in this context, refers to the age-standardized relative risk of death (Vaupel et al., 1979). Variation in frailty (i.e., heterogeneous frailty) exists in populations because of a variety of factors, such as differences in immune competence (associated with nutritional status, genetic variation in regions of the genome associated with immunity or disease susceptibility, the effect of sex hormones, etc.), differences in risktaking behavior (e.g., smoking or heavy drinking) or exposure to occupational hazards, or variation in exposure to disease vectors or environmental pollution. Wood et al. emphasized the potential for “hidden” heterogeneity in frailty to complicate reconstructions of health from skeletal samples. Epidemiologists, because they have access to

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observational, interview, and clinical data from living people, can potentially identify and control for numerous factors known or suspected to influence frailty. However, even in living populations, not all sources of variation in frailty are known and thus controlled for in studies of population health. This problem of hidden heterogeneity is exacerbated when we rely on biased samples of the dead for whom behavioral and clinical information is nearly or (more often) totally nonexistent. Without the ability to control for many potential sources of variation in frailty in skeletal samples, we cannot be certain that the aggregate patterns we observe in these samples accurately represent the health or disease experiences of all of the subgroups that comprise the larger sample. Heterogeneous frailty strongly influences the composition of the skeletal samples. With respect to many causes of death, mortality does not behave indiscriminately, killing all individuals at each particular age at the same rate. Instead, mortality is often selective: disproportionately affecting individuals with the highest frailty at each particular age. It is these individuals, with the highest frailty, who are most likely to become part of the skeletal samples that are eventually available to paleoepidemiologists. This phenomenon makes it difficult, if not impossible, to estimate the prevalence of conditions in once-living populations based on the observed frequencies of associated pathologies in a skeletal sample, particularly if those conditions are associated with elevated risks of mortality. Using this approach would tend to result in the overestimation of the prevalence of the causative conditions. Because of the potential effects of heterogeneous frailty and selective mortality, Wood et al. urge caution in the interpretation of health from observations of skeletal pathologies or stress markers, particularly avoiding the conventional assumption that the presence of skeletal pathologies is an indicator of poor health and a lack thereof reflects good health. As had previously been addressed by Angel (1975), Ortner (1991,1992), and Harpending (1990), Wood et al. discussed the relationship between skeletal lesion formation and survivorship. Specifically, they raise the possibility that because skeletal pathologies take time to form, they might, at least in some cases, indicate relatively good health rather than high frailty. That is, the presence of a skeletal pathology reflects survival, at least temporarily, with or beyond the causative condition. The absence of pathology might indicate relatively poor health if individuals without skeletal lesions succumbed to illness, trauma, or malnutrition and died before the lesions could form. Wood et al. (1992) do not argue that stress markers are necessarily or even typically reflective of good health; instead they urge scholars to consider multiple, equally plausible, interpretations rather than uncritically hewing to conventional interpretations that might not be appropriate.

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One way to address these fundamental difficulties is to leverage aggregate demographic data to assess the effects of skeletal pathologies (Milner and Boldsen, 2017). Rather than making assumptions about how pathologies reflect health, paleoepidemiologists can establish whether (in a particular context) a positive association exists at the population level between a skeletal pathology and risk of death (or a negative association exists between the pathology and survival). Such an association would support interpretations of the pathology as an indicator of poor health. This approach reduces uncertainty about what skeletal pathologies indicate about health at the population level, but we must still be cautious about the inferences we make for individuals in the sample. Estimation of survivorship or the risk of death associated with pathologies is only possible using paleoepidemiological data; it cannot be done using isolated individuals. This approach requires a comparative approach and access to information about the demographic outcomes for people with and without pathologies. With structured aggregate data, paleoepidemiologists are also in a position to directly assess heterogeneous frailty, as least with respect to those factors that are detectable in the skeleton or burial context, such as age, sex, social status, or nutritional status. Being able to compare mortality outcomes across these and similar categories does not entirely alleviate the problem of hidden heterogeneity in frailty, but at the very least, paleoepidemiologists can, with large enough samples, control for some sources of heterogeneity that might otherwise confound reconstructions of population health. Examples of paleoepidemiological research that have addressed the osteological paradox include Boldsen’s (2005) study of the association of skeletal indicators of leprosy and risk of mortality in medieval Denmark; Wilson’s (2010, 2014) assessment of the health and demographic effects of the intensification of maize agriculture, the adoption of Mississippian lifeways, and increased interpersonal violence and warfare in Illinois; and DeWitte and colleagues’ evaluation of selective morality during the medieval Black Death in London (DeWitte and Hughes-Morey, 2012; DeWitte and Wood, 2008).

REFERENCES Angel, J., 1975. Paleoecology, paleodemography and health. In: Polgar, S. (Ed.), Population, Ecology, and Social Evolution. The Hague, Molton, pp. 167 190. Angel, J.L., 1981. History and development of paleopathology. Am. J. Phys. Anthropol. 56 (4), 509 515. Armelagos, G., 1997. Paleopathology. In: Spencer, F. (Ed.), History of Physical Anthropology, 2, M-Z. Garland, New York, pp. 790 796. Armelagos, G., 2003. Bioarchaeology as anthropology, Archaeological Papers of the American Anthropological Association, vol. 13. pp. 27 40.

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Armelagos, G.J., Cohen, M.N., 1984. Paleopathology at the Origins of Agriculture. Academic Press, Orlando, FL. Aufderheide, A.C., Rodrı´guez-Martı´n, C., 1998. The Cambridge Encyclopedia of Human Paleopathology. Cambridge University Press, Cambridge, UK. Blatt, S.H., 2015. To swaddle, or not to swaddle? Paleoepidemiology of developmental dysplasia of the hip and the swaddling dilemma among the indigenous populations of North America. Am. J. Hum. Biol. 27, 116 128. Bocquet-Appel, J.P., Masset, C., 1982. Farewell to paleodemography. J. Hum. Evol. 11, 321 333. Boldsen, J.L., 2001. Epidemiological approach to the paleopathological diagnosis of leprosy. Am. J. Phys. Anthropol. 115, 380 387. Boldsen, J.L., 2005. Leprosy and mortality in the medieval Danish village of Tirup. Am. J. Phys. Anthropol. 126, 159 168. Boldsen, J.L., Milner, G.R., 2012. An epidemiological approach to paleopathology. In: Grauer, A.L. (Ed.), A Companion to Paleopathology. Wiley-Blackwell, Oxford, pp. 114 132. Bos, K., Schuenemann, V., Golding, G., Burbano, H., Waglechner, N., Coombes, B., et al., 2011. A draft genome of Yersinia pestis from victims of the black death. Nature 478, 506 510. Bos, K.I., Harkins, K.M., Herbig, A., Coscolla, M., Weber, N., Comas, I., et al., 2014. Pre-Columbian mycobacterial genomes reveal seals as a source of new world human tuberculosis. Nature 514, 494 497. Bos, K.I., Herbig, A., Sahl, J., Waglechner, N., Fourment, M., Forrest, S. A., et al., 2016. Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus. eLife 5, e12994. Brothwell, D.R., Sandison, A.T. (Eds.), 1967. Diseases in Antiquity: A Survey of the Diseases, Injuries and Surgery of Early Populations. Springfield, Ill.: C. C. Thomas. Buikstra, J.E., 1999. Paleoepidemiology of tuberculosis in the Americas. In: Pa´lfi, G., Dutourk, O., De´ak, J., Hu´tas, I. (Eds.), Tuberculosis Past and Present. Golden Book Publishers and Tuberculosis Foundation, Budapest/Szeged, pp. 479 494. Buikstra, J.E., Ubelaker, D. (Eds.), 1994. Standards for Data Collection from Human Skeletal Remains: Proceedings of a Seminar at the Field Museum of Natural History. Arkansas Archaeological Survey Press, Fayetteville. Buikstra, J.E., Roberts, C.A. (Eds.), 2012. The Global History of Paleopathology: Pioneers and Prospects. Oxford University Press. Buikstra, J.E., Cook, D.C., Bolhofner, K.L., 2017. Scientific rigor in Paleopathology. In: Buikstra, J.E. (Ed.) Rigor in Paleopathology. pp. 80-87. Special Issue of the International Journal of Paleopathology, 19, 80 141. Cuvier, G., 1820. Recherches sur les Ossemens Fossiles, vol. 4. Dufour, Paris. DeWitte, S.N., 2018. Stress, sex, and plague: patterns of developmental stress and survival in pre- and post-black death London. Am. J. Hum. Biol. 30. Available from: http://dx.doi.org/10.1002/ ajhb.23073. DeWitte, S.N., Hughes-Morey, G., 2012. Stature and frailty during the black death: the effect of stature on risks of epidemic mortality in London, A.D. 1348 1350. J. Archaeol. Sci. 39, 1412 1419. DeWitte, S.N., Wood, J.W., 2008. Selectivity of black death mortality with respect to preexisting health. Proc. Natl. Acad. Sci. U.S.A. 105, 1436 1441. Donoghue, H.D., Spigelman, M., O’Grady, J., Szikossy, I., Pap, I., Lee, O.Y.C., et al., 2015. Ancient DNA analysis—an established

technique in charting the evolution of tuberculosis and leprosy. Tuberculosis 95, S140 S144. Elliot-Smith, G., Wood-Jones, F. (Eds.), 1910. The Archaeological Survey of Nubia Report for 1907-1908, Vol II: Report on the Human Remains. National Printing Department, Cairo. Esper, J. 1774. Ausfu¨hrliche Nachricht von Neuentdeckten Zoolithen, Unbekannter Vierfu¨ssiger Thiere, und denen sie Enthaltenden, so wie Verschiedenen Andern Denkwu¨rdigen Gru¨ften der Obergebu¨rgischen Lande des Marggrafthunis Bayreuth. Nu¨rnberg. Goodman, A., 1993. On the interpretation of health from skeletal remains. Curr. Anthropol. 34, 281 288. Gosse, L.A., 1861. Pre´sentation d’un Crane de´ferme´ de Nahoa. Bulletins de la Socie´te´ d’Anthropologie de Paris 2, 567 577. Grmek, M.D., 1983/1989. Diseases in the Ancient Greek World. Johns Hopkins University Press, Baltimore, Maryland. Hackett, C., 1963. On the origin of the human treponematoses (pinta, yaws, endemic syphilis and venereal syphilis). Bulletin of the World Health Organization 29, 7 41. Harpending, H., 1990. Review of “health and the rise of civilization” by MN Cohen. Am. Ethnol. 14, 799 800. Harper, K.N., Zuckerman, M.K., Harper, M.L., Kingston, J.D., Armelagos, G.J., 2011. The origin and antiquity of syphilis revisited: an appraisal of old world pre-Columbian evidence for treponemal infection. Am. J. Phys. Anthropol. 146, 99 133. Hooton, E.A., 1930. The Indians of Pecos Pueblo: A Study of Their Skeletal Remains. Yale University Press, New Haven, CT. Hrdliˇcka, A., 1914. Special notes on some of the pathological conditions shown by the skeletal material of the ancient Peruvians. Smithsonian Miscellaneous Collections 61, 57 69. Hudson, E., 1965. Treponematosis and man’s social evolution. American Anthropologist 67, 885 901. Jarcho, S., 1966. Human Paleopathology. Yale University Press. Jones, J. 1876. Explorations of the aboriginal remains of Tennessee. In Smithsonian Contributions to Knowledge, 259. Kacki, S., 2017. Influence de l’e´tat sanitaire des populations du passe´ sur la mortalite´ en temps de peste: Contribution a` la pale´oe´pide´miologie. BMSAP 29, 202 212. Klaus, H.D., Tam, M.E., 2009. Contact in the Andes: bioarchaeology of systemic stress in Colonial Mo´rrope, Peru. Am. J. Phys. Anthropol. 138, 356 368. Klaus, H.D., Spencer Larsen, C., Tam, M.E., 2009. Economic intensification and degenerative joint disease: life and labor on the postcontact north coast of Peru. Am. J. Phys. Anthropol. 139, 204 221. Konigsberg, L.W., Frankenberg, S.R., 2013. Bayes in biological anthropology. Am. J. Phys. Anthropol. 152, 153 184. Lambert, P.M., 2012. Ethics and issues in the use of human skeletal remains in paleopathology. In: Grauer, A.L. (Ed.), A Companion to Paleopathology. Wiley-Blackwell, Chichester, West Sussex, UK, pp. 17 33. Larsen., C.S., 1997. Bioarchaeology: Interpreting Behavior from the Human Skeleton. Cambridge University Press, Cambridge, UK. Larsen, C.S., Griffin, M.C., Hutchinson, D.L., Noble, V.E., Norr, L., Pastor, R.F., et al., 2001. Frontiers of contact: bioarchaeology of Spanish Florida. J. World Prehistory 15, 69 123. Marciniak, S., Prowse, T.L., Herring, D.A., Klunk, J., Kuch, M., Duggan, A.T., et al., 2016. Plasmodium falciparum malaria in 1st 2nd century CE Southern Italy. Curr. Biol. 26, R1220 R1222. Mays, S., 2018. How should we diagnose disease in palaeopathology? Some epistemological considerations. Int. J. Paleopathol. 20, 12 19.

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Mendonc¸a de Souza, S.M.F., Carvalho, D.Md, Lessa, A., 2003. Paleoepidemiology: is there a case to answer? Mem. Inst. Oswaldo Cruz 98, 21 27. Milner, G.R., Boldsen, J.L., 2012. Transition analysis: a validation study with known-age modern American skeletons. Am. J. Phys. Anthropol. 148, 98 110. Milner, G.R., Boldsen, J.L., 2017. Life not death: epidemiology from skeletons. Int. J. Paleopathol. 17, 26 39. Mitchell, P.D., 2011. Retrospective diagnosis and the use of historical texts for investigating disease in the past. Int. J. Paleopathol. 1, 81 88. Mitchell, P.D., 2012. Integrating historical sources with paleopathology. In: Grauer, A.L. (Ed.), A Companion to Paleopathology. WileyBlackwell, Chichester, West Sussex, UK, pp. 310 323. Mitchell, P.D. 2017. Improving the use of historical written sources in paleopathology. In Rigor in Paleopathology: Perspectives from across the Discipline, J. E. Buikstra, ed., International Journal of Paleopathology 19, 88 95. Moodie, R., 1923. Paleopathology: An Introduction to the Study of Ancient Evidences of Disease. University of Illinois Press, Urbana. Morse, D., 1969. Ancient disease in the Midwest. Springfield, Illinois State Museum Reports of Investigations, No. 15. Ortner, D.J., 1991. Theoretical and methodological issues in paleopathology. In: Ortner, D.J., Aufderheide, A.C. (Eds.), Human Paleopathology: Current Syntheses and Future Options. Smithsonian Institution Press, Washington, DC, pp. 5 11. Ortner, D.J., 1992. Skeletal paleopathology: probabilities, possibilities, and impossibilities. In: Verano, J.W., Ubelaker, D.H. (Eds.), Disease and Demography in the Americas. Smithsonian Institution Press, Washington, DC, pp. 5 13. Ortner, D.J., 2003. Identification of pathological conditions in human skeletal remains. Academic Press, San Diego, CA. Ortner, D.J., Aufderheide, A. (Eds.), 1991. Human Paleopathology: Current Syntheses and Future Options. Smithsonian Institution Press, Washington, D. C. Ortner, D.J., Putschar, W.G.J., 1981. 1985 Identification of pathological conditions in human skeletal remains. Smithsonian Institution Press. Pales, L., 1930. Paleopathologie et Pathologie Comparative. Masson et Cie, Paris. Patterson Ross, Z., Klunk, J., Fornaciari, G., Giuffra, V., Ducheˆne, S., Duggan, A.T., et al., 2018. The paradox of HBV evolution as revealed from a 16th century mummy. PLoS Pathog. 14, e1006750. Ragsdale, B.D., Madewell, J.E., Sweet, D.E., 1981. Radiologic and Pathologic Analysis of Solitary Bone Lesions, Part II: Periosteal Reactions. Radiologic Clinics of North America 19, 749 783. Resnick, D., Niwayama, G., 1995. Osteomyelitis, septic arthritis, and soft tissue infection: organisms. In: Resnick, D. (Ed.), Diagnosis of Bone and Joint Disorders, third ed. W. B. Saunders, Edinburgh, pp. 2467 2474. Ruffer, M., 1910. Remarks on the histology and pathological anatomy of Egyptian mummies. Cairo Sci. J. 1 5. Shufeldt, R.W., 1892. Notes on paleopathology. Popular Science Monthly 42, 679 684. Smith-Guzma´n, N.E., 2015. The skeletal manifestation of malaria: an epidemiological approach using documented skeletal collections. Am. J. Phys. Anthropol. 158, 624 635. Snoddy, A.M.E., Buckley, H.R., Halcrow, S.E., 2016. More than metabolic: considering the broader paleoepidemiological impact of vitamin d deficiency in bioarchaeology. Am. J. Phys. Anthropol. 160, 183 196.

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Steinbock, R., 1976. Paleopathological Diagnosis and Interpretation. Charles C. Thomas, Springfield, IL. Ubelaker, D.H., 1982. The Development of Human Paleopathology. In: Spencer, F. (Ed.), A History of American Physical Anthropology 1930-1980. Academic Press, New York, pp. 337 356. ˚ .J., Herbig, A., Campana, M.G., Robles Garcı´a, N.M., Va˚gene, A Warinner, C., Sabin, S., et al., 2018. Salmonella enterica genomes from victims of a major sixteenth-century epidemic in Mexico. Nat. Ecol. Evol. 2, 520 528. Vaupel, J.W., Manton, K.G., Stallard, E., 1979. The impact of heterogeneity in individual frailty on the dynamics of mortality. Demography 16, 439 454. Virchow, R., 1898. Knochen aus Alten Gra¨bern von Tennessee. Verhandlungen der Berliner Gesellschaft fu¨r Anthropologie 30, 342 344. Waldron, T., 2007. Paleoepidemiology: The Measure of Disease in the Human Past. Left Coast Press Inc, Walnut Creek, CA. Warren, J., 1822. A Comparative View of the Sensorial and Nervous Systems in Man and Animals. Ingraham, Boston. Wells, C., 1964. Bones, Bodies and Disease. Thames and Hudson, London. Weston, D.A., 2008. Investigating the specificity of periosteal reactions in pathology museum specimens. Am. J. Phys. Anthropol. 137, 48 59. Weston, D.A., 2012. Nonspecific Infection in Paleopathology: Interpreting Periosteal Reactions. In: Grauer, A.L. (Ed.), A Companion to Paleopathology. Wiley-Blackwell, Chichester, West Sussex, UK, pp. 492 512. Williams, H.U., 1929. Human paleopathology, with some original observations on symmetrical osteoporosis of the skull. Arch. Pathol. 7, 839 902. Wilson, J.J., 2010. Modeling Life Through Death in Late Prehistoric West-Central Illinois: An Assessment of Paleodemographic and Paleoepidemiological Variability [PhD]. Binghamton University, SUNY, Binghamton, NY. Wilson, J.J., 2014. Paradox and promise: Research on the role of recent advances in paleodemography and paleoepidemiology to the study of “health” in Precolumbian societies. Am. J. Phys. Anthropol. 155, 268 280. Wood-Jones, F., 1908. The pathological report. Archaeological Survey of Nubia Bulletin 2, 55 69. Wood-Jones, F., 1910. Anatomical variations, and the determination of the age and sex of skeletons. In: Elliot-Smith, G., Wood-Jones, F. (Eds.), The Archaeological Survey of Nubia Report for 1907 1908, Vol II: Report on the Human Remains. National Printing Department, Cairo, pp. 221 262. Wood, J.W., Milner, G.R., Harpending, H.C., Weiss, K.M., 1992. The osteological paradox: Problems of inferring prehistoric health from skeletal samples. Curr. Anthropol. 33, 343 370. World Health Organization, 2018. Health Topics: Epidemiology. ,http://www.who.int/topics/epidemiology/en/. (accessed 15.01.18.). Zuckerman, M.K., 2014. Modern Environments and Human Health: Revisiting the Second Epidemiological Transition. Wiley-Blackwell, Hoboken, NJ. Zuckerman, M.K., Harper, K.N., Armelagos, G.J., 2016. Adapt or die: three case studies in which the failure to adopt advances from other fields has compromised paleopathology. Int. J. Osteoarchaeol. 26, 375 383.