䉷2008 by The Wenner-Gren Foundation for Anthropological Research. All rights reserved. 0011-3204/2008/4906-0001$10.00. DOI: 10.1086/592434
Current Anthropology Volume 49, Number 6, 2008 963
Diet, Tuberculosis, and the
by A. K. Wilbur, A. W. Farnbach, K. J. Knudson, and J. E. Buikstra
CA⫹Online-Only Material: Supplements A and B
Osseous manifestation of infectious disease is of paramount importance to paleopathologists seeking
to interpret ancient health, but the relationships among infectious agent exposure, development of
disease, and skeletal involvement are complex. The outcome of an exposure strongly depends on
multiple factors, including ecology, diet, nutrition, immune function, and the genetics of pathogen
and host. Mycobacterial diseases are often studied in ancient remains but also areespecially inﬂuenced
by these factors; individual and population differences in severity and course are apparent following
onset of active disease. The osteological record for these diseases represents the complex interplay
of host and pathogen characteristics inﬂuencing within- and among-individual skeletal lesion prev-
alence and distribution. However, many of these characteristics may be assessed independently
through the archaeological record. Here, we explore the contributions of dietary protein and iron
to immune function, particularly the course and outcome of infection with Mycobacterium tuber-
culosis. We emphasize how nutrition may inﬂuence the dissemination of bacilli to the skeleton and
subsequent formation of diagnostic lesions. We then generate models and hypotheses informed by
this interplay and apply them to four prehistoric New World areas. Finally, discrepancies between
our expectations and the observed record are explored as a basis for new hypotheses.
The interpretation of human health in prehistory has been
of interest since at least the eighteenth century (Roberts and
Manchester 1995), and modern paleopathological analyses
have provided rich resources for studies of past disease as
well as human adaptation, migration, identity, and other an-
thropological issues. A majority of paleopathological analyses
relies on the skeletal record, which presents a unique set of
problems for diagnosis of ancient infectious diseases. The
outcome of exposure to many infectious agents—including
the development of skeletal lesions—strongly depends on
multiple factors including ecology, diet, nutrition, immune
function, and genetics of pathogen and host.
In their formulation of the “osteological paradox,” Wood
and colleagues (1992) called attention to several key issues
surrounding the interpretation of skeletal lesions. While their
examples are drawn primarily from among the suite of non-
speciﬁc indicators of stress, Wood and colleagues’ admoni-
A. K. Wilbur is a postdoctoral research associate, A. W. Farnbach
is a Ph.D. candidate, K. J. Knudson is Assistant Professor, and J.
E. Buikstra is Professor and Director of the Center for Bioarchaeo-
logical Research in the School of Human Evolution and Social
Change at Arizona State University (Tempe, AZ 85287, U.S.A.
[email@example.com]). This paper was submitted 11 XII 06 and
accepted 3 IV 08.
tions are no less apt for those interpreting disease-speciﬁc
paleopathology. They write that estimations of disease prev-
alence are impossible if based solely upon skeletal lesion fre-
quency. They also argue that while many of the tangled issues
surrounding such factors as hidden heterogeneity of risk await
biomedical insight, anthropologists can contribute signiﬁ-
cantly to a better understanding of “the role played bycultural
context in determining heterogeneous frailty and the level of
selective mortality.” They further call for “a better under-
standing of the details of various pathological processes at the
cell, tissue, and organ levels” (pp. 357–8).
The improved understanding sought by Wood and col-
leagues (1992) is crucial to interpret skeletal pathology re-
sulting from the mycobacterial diseases tuberculosis and lep-
rosy. Mycobacterial diseases hold particular interest for
paleopathologists because they afford the opportunity to ex-
amine the interactions between an infectious agent and hu-
man migration and settlement patterns (Buikstra 1977; Buik-
stra and Cook 1981; Formicola, Milanesi, and Scarsini 1987;
Jankauskas 1998). The mycobacterial diseases tuberculosis
and leprosy have plagued Homo sapiens, and probably our
hominid ancestors, for millennia. Despite our long coevo-
lutionary history, however, these pathogens have not reduced
in virulence to a state of benign commensalism with humans.
The development of effective chemotherapy in the early to
964 Current Anthropology Volume 49, Number 6, December 2008
mid-twentieth century held great promise to eradicate tu-
berculosis and leprosy, but by the late twentieth century it
was clear that the relationship between pathogenic mycobac-
teria and humans would not be easily dissolved. In 1993, the
World Health Organization (WHO) declared tuberculosis a
global emergency; the disease has reemerged as a leading cause
of mortality, responsible for an estimated 1.6 million deaths
per year (WHO 2007). Devastating to human health and so-
cial systems, tuberculosis has been the subject of research
efforts throughout the world. Expression of mycobacterial
disease is especially inﬂuenced by multiple host, pathogen,
and environmental factors (Nicod 2007), some of which can
be independently assessed from the archaeological record.
We apply this knowledge of host-pathogen interactions to
clarify the development of tuberculous skeletal lesions, re-
sponding to Wood and colleagues’ (1992) call for improved
understanding of paleopathological processes. We ﬁrst review
the inﬂuence of two nutrients, protein and iron, on the course
and outcome of tuberculosis. We discuss the roles of each in
the immune response to tuberculosis, emphasizing the way
each may inﬂuence the metastasis of bacilli to the skeleton
and subsequent formation of lytic lesions. We then present
models for the formation of tuberculosis paleopathology in-
formed by this complex interplay of nutrition, immune func-
tion, and infectious disease. Finally, we compare expectations
based on our models to observed paleopathological evidence
for tuberculosis and nutritional stress from four different areas
of the New World. Our goal is to better inform interpretation
of disease in the ancient past while also more generally ad-
dressing issues of diet and health that are relevant today.
Identiﬁcation of Tuberculosis in Past
The “best” approach to understanding the prevalence of tu-
berculosis in past populations remains debated. Where his-
torical documents are extant, diagnostic imprecision and a
lack of standardization in recording cause of death can render
identiﬁcation of pulmonary tuberculosis somewhat unreliable
in medical records before the mid-nineteenth century
(McKeown and Record 1962). Tuberculosis does not occur
as a diagnosis until the late 1830s (Keers 1978), and earlier
terms like “consumption” could subsume a wide range of
conditions in addition to tuberculosis. In the United King-
dom, Morton (1720) describes consumptions resulting from
bloody ﬂux, breast⫺feeding with inadequate diet, scurvy, and
diabetes in addition to pulmonary consumptions that bear a
closer resemblance to tuberculosis. Hardy (1988) notes that
in the London Bills of Mortality, deaths from chronic bron-
chitis are misallocated to consumption from at least 1810 to
the 1830s, when the Bills ceased to be published. For many
regions of the world, such systematically recorded medical
data are not available.
Molecular methods are increasingly used to identify the
causative agents of tuberculosis—Mycobacterium tuberculosis
and other members of the M. tuberculosis complex (MTBC,
comprising M. canettii,M. microti,M. bovis, and M. afri-
canum)—in ancient remains, but these studies commonlyrely
on the preidentiﬁcation of potentially tuberculous bone sam-
ples through traditional osteological techniques or from his-
torically documented cemetery populations. The DNA from
ancient remains holds promise to identify the causative agent
in cases where skeletal or soft tissue signals are ambiguous
and even to elucidate the evolution of the infectious agent,
but there are serious limitations as well. Preservation of an-
cient DNA is variable, and even under the best conditions,
the molecules degrade (Handt et al. 1994; Ho¨ss et al. 1996;
Pa¨a¨bo 1989), leaving only very small (!500 bp) fragments.
In some aspects, tuberculosis is ideal for ancient DNA stud-
ies. Mycobacteria replicate, sometimes in large numbers,
within lesions generated by the disease’s osseous form. These
lesions are classically located in vertebral bodies but can be
present in other bones. The pulmonary form of the disease
may affect the internal aspects of ribs, but this type of lesion
is also found with other severe pulmonary infections (Buikstra
and Williams 1991; Pfeiffer 1991; Roberts, Lucy, and Man-
chester 1994; Lambert 2002) and is probably secondary to the
inﬂammatory process rather than directly due to mycobac-
terial replication at the site. However, some studies have re-
ported successful recovery of MTBC DNA from affected ribs
(Mays, Fysh, and Taylor 2002; Raff, Cook, and Kaestle 2006).
Several challenges of diagnosing ancient tuberculosis using
DNA have yet to be entirely overcome, however. Among the
most signiﬁcant of these is the abundance of nontuberculous
mycobacteria throughout nature, including burial sites.
Strong genetic similarities between species, compounded by
the small DNA fragments obtainable, make species and sub-
species identiﬁcation difﬁcult. However, the presence of re-
petitive elements unique to the MTBC genome has aided
identiﬁcation to at least the level of the complex. One of these,
the IS6110 insertion sequence (Thierry et al. 1990a, 1990b)
present in multiple copies in many strains, leading IS6110 to
be the earliest—and still the most common—ampliﬁed target
for ancient tuberculosis (Salo et al. 1994; Arriaza et al. 1995).
Subsequent studies have reported MTBC-speciﬁc DNA am-
pliﬁcation from nonpathological bones of documented tu-
berculosis cases (Baron, Hummel, and Hermann 1996) and
from skeletons with nonspeciﬁc lesions or no lesions (Haas
et al. 2000; Zink et al. 2001).
Many molecular studies of ancient tuberculosis have met
with skepticism because they lack discussion of adherence to
proper authentication procedures. Cooper and Poinar (2000)
set forth minimal criteria for scientiﬁc investigation of ancient
DNA that focus primarily upon two issues: control of con-
tamination and independent reproducibility of results. In ad-
dition, samples available for ancient DNA studies are limited,
and the small amplicons produced are difﬁcult to place in
phylogenetic context. These and practical issues such as the
expense and time necessary for analysis currently render mo-
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 965
lecular methods at best supplementary to traditional paleo-
Given our present technology, osteolytic lesions indicative
of tuberculosis may present a more reliable picture of ancient
tuberculosis morbidity and mortality than molecular meth-
ods. Nonetheless, these lesions can identify only a subset of
affected individuals in whom disease disseminated to the skel-
eton. Those who survived sufﬁciently long to develop skeletal
lesions may have had the best immunity to the disease (Wood
et al. 1992), and the sample of skeletons examined may or
may not be representative of the originalpopulation (Waldron
1994; Roberts and Buikstra 2003).
Estimates of tuberculosis prevalence from such a subset are
also problematic because risk for extrapulmonary disease is
multifactorial. Exposure to M. tuberculosis does not always
lead to infection, and infection does not always lead to active
disease. Clinical studies on modern individuals of European
ancestry indicate that only approximately 5%–10% of infected
persons develop active disease (Medical Research Council
1972), though this risk of disease is not uniform across all
modern populations (e.g., Hurtado et al. 2003). Of individuals
who develop active tuberculosis, only a portion of cases will
disseminate from the initial site of infection, and of these,
only approximately 2%–4% will experience migration of the
bacteria to osseous tissues (Cailhol, Decludt, and Che 2005;
Lee and Abramson 1996). Thus, relationships among risks of
pulmonary infection, skeletal involvement, and death are not
intuitive, and it is difﬁcult to translate prevalence of tuber-
culosis paleopathology into an explicit understanding of the
extent to which a population was affected by this disease.
Knowledge of the macroscopic and microscopic processes
of immune reaction to mycobacterial infection, especially of
tuberculosis lesion formation in bone, may lead to a more
complete understanding of which members of a population
are likely to exhibit skeletal involvement and thus the extent
to which the prevalence of skeletal indicators reﬂects theprev-
alence of tuberculosis in the living population. Many factors
determining inter- and intrapopulational differences are in-
visible in a skeletal sample; however, examination of the im-
mune response to pulmonary M. tuberculosis infection reveals
that mechanisms related to protein and iron metabolism are
likely to affect the dissemination of bacteria to the skeleton
and destruction of bone at the site of skeletal involvement.
The Human Immune Response to
Interactions between mycobacteria and the immune system
are complex and still being elucidated (Kaufmann2001; Ques-
niaux et al. 2004; Houbin, Nguyen, and Pieters 2006; Nicod
2007), but it is clear that both the innate and acquired im-
mune systems respond using a variety of interrelated signaling
mechanisms. Pathogenic mycobacteria, in turn, have evolved
strategies to circumvent host immune responses at several
steps along a progression from exposure to infection to con-
tainment (latency) to active disease. Figure 1 is a simpliﬁed
diagram of stages in the human immune response to M.
In humans, the typical route of exposure and infection with
M. tuberculosis is via inhalation of droplets discharged from the
lungs of infected individuals. Biological, social, and environ-
mental factors inﬂuence susceptibility to mycobacteria, and the
susceptible portion of a population varies. Among immune-
competent individuals of European ancestry, only 10% of ex-
posed individuals are expected to become infected (Medical
Research Council 1972); of those infected, approximately 50%
may ultimately develop active disease. However, Hurtado et al.
(2003) found that 64% of Paraguayan Ache´ became infected
following exposure, and 30% of those infected developed active
disease within 10 years of the study onset.
Following entry into the lungs, mycobacteria encounter
alveolar macrophages and monocytes such as dendritic cells
(Reddy and Anderson 1998). These phagocytic cells bear re-
ceptors to bind infectious agents, engulf them in an organelle
called a phagosome, and digest them following fusion of the
mature phagosome with a lysosome, an organelle containing
acid hydrolases. Fragments (antigens) from this digestion are
presented on the outside of the macrophage, and cell-signaling
molecules called cytokines are released (see Kaufmann 2001
for further review). The cytokines recruit T-cells, a component
of the acquired immune system, which can recognize the
antigens exhibited by the phages.
Recruited T-cells produce cytokines that activate macro-
phages, enhancing their bactericidal and antigen presentation
capacities (Cosma, Sherman, and Ramakrishnan 2003). Dur-
ing chronic M. tuberculosis infection, activated macrophages
enclose the focus of infection within a granuloma. This struc-
ture creates an environment that contains and restricts growth
of the bacilli, resulting in latency; ﬁbrotic or calciﬁed tissue
surrounds and stabilizes the granuloma over time. Most
immune-competent individuals are able to control the infec-
tion at this stage without any signs of illness, but they do not
generally eradicate the bacteria from their system (Flynn and
Sometimes, however, the bacilli evade the granuloma re-
sponse, replicate freely, and disseminate from the initial site
of infection. If the latent state is disturbed (or never attained),
the infection enters a progressive state characterized by un-
controlled bacterial replication and dissemination. The focus
of infection becomes liqueﬁed and remains exposed to oxy-
gen, providing a rich medium for bacterial growth. As the
bacteria replicate, destroying the infected tissue (McDonough
and Kress 1995), the expanding, structurally compromised
granuloma may erode into an airway, allowing infection to
spread quickly to a new host as the contents are shed. Erosion
of the liqueﬁed granuloma into blood or lymph vessels results
in metastasis of the infection to extrapulmonary sites, in-
cluding the bones and joints (Granger, Hibbs, and Broadnax
Mycobacteria have evolved mechanisms to thwart the host
966 Current Anthropology Volume 49, Number 6, December 2008
Figure 1. Simpliﬁed ﬂow chart of the human immune response to in-
halation of M. tuberculosis, and the individual effects of inadequate pro-
tein and adequate iron on that response.
immune system. During the early encounters of phagocytic
cells and mycobacteria, for example, receptor binding and
phagosome-lysosome fusion play key roles in the development
of a maximally effective host immune response. Pathogenic
mycobacteria are able to manipulate the phagosome
membrane to prevent phagosome-lysosome fusion (reviewed
in Houbin, Nguyen, and Pieters 2006; Kaufmann 2001), pre-
venting antigen presentation, blocking the Th1 response, and
barring macrophage activation.
The interplay between host innate (phagocytic cells) and
adaptive (T cells) immune cells is also intricate. The adaptive
immune response—as opposed to the innate immune re-
sponse emphasized thus far—is characterized by the differ-
entiation of precursor T-helper cells into T-helper type 1
(Th1) or T-helper type 2 (Th2) cells (Mosmann et al. 1986).
The cell-mediated Th1 response is the most effective against
intracellular pathogens such as M. tuberculosis, while the
antibody-dominated Th2 response is more effective against
extracellular pathogens such as macroparasites. Each of these
responses downregulates the other (Sander et al. 1995), but
both are necessary to maintain health.
The differentiation of T-helper cells is mediated at least in
part by Toll-like receptors (TLR), proteins on the surfaces of
phagocytic cells that recognize various types of microbial mol-
ecules. The TLR2 speciﬁcally recognizes mycobacteria (Basu
and Fenton 2004; Quesniaux et al. 2004; Houbin, Nguyen,
and Pieters 2006); recognition by TLR2 stimulates dendritic
cells to produce cytokines invoking a Th1 response. Because
M. tuberculosis lives preferentially in macrophages, the Th1
response activating these cells is key: unactivated macrophages
digest the mycobacteria much less effectively, allowing M.
tuberculosis to replicate.
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 967
Diet and Tuberculosis
Relationships among diet, nutrition, and the course of tu-
berculosis have been known since the nineteenth century and
were suspected even earlier. In his dissertation on the causes
of a predisposition to consumption, Francis Bowes Sayre
(1790) recommended a balanced diet for those displaying the
earliest stages of tuberculosis. Armand Trousseau (cited in
Murray et al. 1978) warned in 1872 against iron supplemen-
tation for recovering patients, as this had been observed to
cause a relapse of active disease. Writing to Science in 1886,
N.W. “emphatically denie(d)” that “consumption is conta-
gious in the ordinary sense of the word” and argued that “the
ultimate cause of the disease (is) impaired nutrition” (1886,
87–88). Diets were carefully controlled in tuberculosis sana-
toria (Santos 1999; Roberts and Buikstra 2003).
In the ﬁrst half of the twentieth century, the importance
of diet was conﬁrmed. Johnston (1951) examined nutrition
and tuberculosis in adolescent girls. Depressed levels of ni-
trogen (i.e., protein) storage were associated with prolonged
disease and sometimes with dissemination, while adequate
calcium was required for maintenance of the primary tuber-
culosis granuloma and prevention of reactivation. Getz, Long,
and Henderson (1951) found a statistically signiﬁcant rela-
tionship between low initial levels of vitamin A and C and
development of tuberculosis among adult males. Downes
(1950) found a clear trend toward decreasing incidence of
tuberculosis in low socioeconomic status African-American
families who received nutritional supplementation.
Today, malnutrition is the commonest cause of immune
deﬁciency in the world, and it is known to inﬂuence the course
and outcome of tuberculosis infection (Chandra 1996). Many
micro- and macronutrients affect immunocompetency, in-
cluding vitamin D, calcium, iron, and protein, which are es-
pecially important for responses to intracellular pathogens like
mycobacteria. Here, we address the inﬂuence of protein and
iron, which have the best-understood effects on mycobacterial
Protein malnutrition is linked with tuberculosis morbidity
and mortality; experimental support for these interactions is
reviewed in CA⫹online supplement A, and the effects of
insufﬁcient protein on tuberculosis are summarized in ﬁgure
1. When protein is inadequate, macrophage antimicrobial ac-
tivity decreases; furthermore, T-cell maturation is hindered,
and the Th1 response is depressed while Th2 is favored. As
a result, macrophages remain deactivated and granulomas ill-
formed, allowing mycobacterial replication and dissemi-
Thus, among protein malnourished individuals, one might
expect Mycobacterium tuberculosis infection to cause fulmi-
nant disease—characterized by extensive tissue destruction
and relatively rapid death—due to a poorly organized gran-
uloma response and ineffective induction of the Th1 immune
response. While extrapulmonary dissemination might result,
it is possible that in such a rapidly progressive disease state,
osseous manifestation would be limited to rib lesions from
CA⫹online supplement B reviews in detail the support for
iron’s inﬂuence on tuberculosis that is described brieﬂy here;
ﬁgure 1 summarizes iron’s effects on tuberculosis. Mycobac-
teria and mammalian hosts compete to obtain iron for bac-
terial use or to sequester the mineral where bacteria cannot
access it. Where mycobacteria obtain adequate iron, repli-
cation is stimulated and macrophage bactericidal activitysub-
verted, favoring bacterial dissemination. Indeed, mild host
iron deﬁciency is protective against active tuberculosis, while
iron supplementation favors reactivation of latent infections.
In sum, available iron supports Mycobacterium tuberculosis
multiplication within host macrophages, favoring active dis-
ease and dissemination from the initial site of infection. Thus,
for both iron-replete and protein-deﬁcient individuals, ful-
minant, disseminated disease is expected following infection
with M. tuberculosis.
Implications for Paleopathology:
Immunological, epidemiological, and archaeological data can
be integrated to develop predictions for tuberculosis in skel-
etal samples. These hypotheses assume that basic immune
biology is similar among all human groups throughout time,
although the possibility of host genetic differences should be
Hypothesis 1. If chronic, severe protein malnutrition leads
to high mortality from pulmonary tuberculosis, then rapid
death before osseous involvement is expected among most
members of an infected, protein-deﬁcient group. Because ful-
minant pulmonary tuberculosis may still leave porosity or
new bone formation on ribs (Roberts, Lucy, and Manchester
1994), the signature of pulmonary tuberculosis and protein
malnutrition might appear in the form of new bone formation
on visceral surfaces of ribs. Some segments of the population
may show disseminated tuberculosis, especially if there is dif-
ferential access to protein. A high carbohydrate diet deﬁcient
in protein could be inferred from presence of high rates of
caries and abscesses, indicators of carbohydrate-rich diets;
another indication could be high rates of dental enamel hy-
poplasias, nonspeciﬁc indicators of chronic stressors in early
Hypothesis 2. If dietary iron insufﬁciency restricts growth
of intracellular mycobacteria and contains the organisms, then
infection may remain latent without progression to disease
in most members of an iron-deﬁcient group. However, mem-
bers of the population with higher access to iron-rich foods
968 Current Anthropology Volume 49, Number 6, December 2008
Table 1. Expectations for Immune Status and Pott’s Disease Based on Protein and Iron Status
Category Protein Iron Immune Status Pott’s Disease? Rib Lesions
1⫹⫹Th1 immunity but iron available to mycobacteria; growth
and dissemination possible
Possible in all age
2⫹⫺Th1 immunity and no iron for mycobacteria; latent
3⫺⫹Th2 immunity, iron for mycobacteria; fulminant pulmonary
disease (rib lesions), no dissemination, or dissemination
but death before formation of osseous lesions
4⫺⫺Th2 immunity, macrophage inability to contain bacilli, but
no iron available so slow growth; chronic disease may al-
low dissemination to skeleton and fomation of characteris-
Yes, but unlikely in
Th1 immunity, some iron for mycobacteria Depends on iron
Note: Th1 pT-helper type 1; TH2 pT-helper type 2.
could experience pulmonary tuberculosis and occasionally ex-
trapulmonary tuberculosis. Porotic hyperostosis, observed as
cribra orbitalia and cribra cranii, is expected as indicative of
iron-deﬁciency anemia, but latent Mycobacterium tuberculosis
infection would leave no osseous signature.
This may be confounded in the Old World, where genetic
anemias may give the same osseous signature as iron-deﬁ-
ciency anemia, and in regions where anemia occurs second-
arily to macroparasitic infestation. Iron absorption will be
fairly high among populations with adequate dietary iron but
high parasite loads, because iron absorption ability isinversely
related to serum iron concentrations (MacPhail and Bothwell
1992). In this case, at least some serum iron is available to
mycobacteria. The tendency for parasite infection to favor
Th2 responses would favor active tuberculosis. This result is
expected to be similar to that of protein deprivation, inwhich
a Th2 response renders macrophages unable to contain bacilli,
but the ability of mycobacteria to reproduce and disseminate
will be dependent on diet and severity of macroparasitic in-
fection. If parasite infestation is endemic and ubiquitous, po-
rotic hyperostosis could develop in children and be retained
in adult crania. Dental enamel hypoplasias are expected in
children who survive serious parasite infection, but unlike
protein malnutrition, caries may not be frequent unless the
diet also contains a large amount of carbohydrates. Hereditary
anemias and malaria-induced hemolytic anemias, not incor-
porated here, are discussed below.
Table 1 presents a model of expectations for the immune
response and skeletal manifestation of tuberculosis based on
protein and iron status. For ease of reference, we divide each
possible dietary combination of iron and protein into cate-
gories 1 through 4, with category 5 representing protein and
iron repletion but parasitic loss of iron. In table 2, we in-
corporate other skeletal/dental indicators of stress.
Considering the extremes of protein and iron availability,
dissemination of M. tuberculosis to the spine is expected in
categories 1, 4, and 5. In category 1, protein and iron are
replete in the general population. This allows for Th1 re-
sponses, but availability of iron to mycobacteria also allows
for bacterial growth and dissemination to other organsystems,
including the skeleton. Response to infection and course of
disease will depend on host factors such as genetics, reduced
immunity due to trauma or other infectious agents, and in-
tensity of exposure to the pathogen. Occurrence of enamel
hypoplasias will depend on timing of other health insults.
Caries rates are assumed to be low unless the population had
a carbohydrate-rich diet. Porotic hyperostosis is unlikely to
be present. Occurrence of Pott’s disease and porosity on in-
ternal aspect of ribs will depend on the course of infection
but are possible.
Category 5 also features sufﬁcient dietary protein and iron,
but endemic and ubiquitous macroparasite infection reduces
serum iron to some degree and pushes immunity toward the
Th2 response. Thus, macrophages will be unable to contain
bacilli. If the diet contributes some iron, mycobacteria will
be able to replicate and disseminate; the course and severity
of disease will depend on the combination of diet and severity
of parasite infection. Caries frequency in the population will
depend on the amount of carbohydrates in the diet, but
enamel hypoplasias and porotic hyperostosis are expected in
the young. Porosity on internal aspect of ribs is expected due
to pulmonary tuberculosis, and Pott’s disease is possible.
Category 4 results from severe restriction of protein and
iron, making disseminated osseous tuberculosis possible.This
may seem counterintuitive, given the necessity of iron for
mycobacterial growth and dissemination, but when protein
levels are also insufﬁcient, macrophages tend to remain un-
activated and are unable to contain bacilli. Bacterial growth
is therefore expected to be very slow, but this situation may
lead to dissemination of the organism and osseous manifes-
tation over time. Because this is expected to be a slow and
chronic process, skeletal lesions would not occur until after
some time had passed, and thus are not expected in the very
young. High levels of hypoplasias, caries and porotic hyper-
ostosis are expected.
In categories 2 and 3, dissemination of mycobacteria to the
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 969
Table 2. Population Expectations for Skeletal Indicators of Stress and Tuberculosis Based on Dietary Protein and Iron
Category Protein Iron DEHs Caries
Hyperostosis Rib Porosity Pott’s Disease
1⫹⫹O.c. Low No Possible Possible
2⫹⫺Yes High Yes No No
3⫺⫹Yes High No Yes No
4⫺⫺High High Yes Yes Yes
Yes Yes Possible
Note: DEHs pdental enamel hypoplasias; O.c. pother causes possible.
Depends on diet.
skeleton is not expected. In both situations, enamel hypo-
plasias and caries are expected to be elevated due to high
dietary carbohydrates. In category 2, under conditions of pro-
tein sufﬁciency but iron deprivation, Th1 immunity is possible
and limited iron causes the mycobacteria to remain latent
unless other circumstances trigger activation. Porotic hyper-
ostosis is expected in response to iron deﬁciency, but osseous
manifestations of tuberculosis are unlikely. In category 3,
when protein is insufﬁcient but iron is replete, fulminant
pulmonary disease leading to rapid mortality may occur be-
fore dissemination and osseous reaction is possible. Only new
bone and porosity on internal aspects of ribs are expected in
reaction to the severe pulmonary infection.
The preceding discussion presents simpliﬁed scenarios in
which only the extremes of nutritional status are considered.
Our model makes assumptions on three broad—and not mu-
tually exclusive—levels: environment, pathogen, and host. At
the level of the environment, we assume that all sites have a
similar potential for animal reservoirs of tuberculosis, that
inﬂuences of climate on the pathogen and host are negligible,
and that effects of other infectious diseases (except for mac-
roparasites) are negligible. We assume that closely related spe-
cies of mycobacterium are involved and that if different strains
affect different populations or individuals within a popula-
tion, they have similar transmission, growth, and dissemi-
nation capabilities (i.e., virulence). At the level of the host,
we assume uniform exposure and transmission opportunities
for all individuals within a population, similar immune ge-
netics within and among populations, similar immune ca-
pabilities within and among populations, similar responses to
diet within and among populations, and that food preparation
techniques do not inﬂuence dietary response to protein and/
or iron. We do not incorporate age or sex of hosts into our
model. Given the complex and multifactorial nature of tu-
berculosis manifestation in human populations, our aim is to
provide a framework in which at least one archaeologically
recognizable factor, nutritional status, can be controlled. The
predicted patterns can then be used to formulate intrasite
expectations—where factors such as status may alter diet to
some degree—and populational or regional expectations,
where geography, trade routes, or other factors might also
inﬂuence diet. Discrepancies between our model-derived ex-
pectations and observations from the archaeological record
may highlight other potential paleoepidemiological factors
and lead to new hypotheses.
Diet and Pre-Columbian Tuberculosis in
The pattern of presence and absence of ancient tuberculosis
in the New World exempliﬁes how diet can inﬂuence the
paleopathological record. In this section, we develop expec-
tations for the presence of skeletal tuberculosis in the pre-
historic New World, based on archaeological and paleopath-
ological evidence of diet and nutrition. Four case studies—
the ancient Maya, Andean South America, the North Amer-
ican southwest, and the lower Illinois River Valley—are dis-
cussed. In each, population aggregation and trade routes could
have supported transmission and maintenance of tubercu-
losis. Table 3 summarizes the available isotopic and archae-
ological evidence concerning the diet of these groups.
Maize and the Maya: Why Is Evidence of Skeletal
Many convincing cases of skeletal tuberculosis have been doc-
umented throughout the pre-Columbian Americas (Buikstra
1999; Roberts and Buikstra 2003). However, ancient Mayan
skeletons present few or no convincing cases of disseminated
tuberculosis (Buikstra 1999; Roberts and Buikstra 2003), de-
spite large population aggregates and long-distance trade since
pre-Classic times (Sharer 1994). Although Maya sites are
noted for poor bone preservation, skeletons are available for
observation: the record from the site of Copa´ n includes ap-
proximately 900 skeletons, roughly 30% of which have at least
some vertebral fragments preserved and 16% of which have
more than 25% of each vertebral class preserved (K. A. Miller,
personal communication). Because Pott’s disease primarily
manifests as lytic lesions of the vertebral bodies, some dif-
ferential preservation is expected; however, it seems unlikely
that proliferative ankylosis subsequent to vertebral collapse
would not have been preserved somewhere in the Maya realm.
Published sources related to pathology and/or diet and nu-
trition deﬁne two general patterns of nutritional stress com-
mon among the ancient Maya. The ﬁrst is very high reliance
on maize agriculture during the Classic period. There was
970 Current Anthropology Volume 49, Number 6, December 2008
Table 3. Dietary Inferences from Reported Isotopic Composition of Human Bone Collagen or Bone Apatite
Fish Meat Animal Meat C
Maya Little Little Little Little High Wright and White
Chen Chen None None Moderate Moderate High Tomczak 2003
Estuquina Moderate Moderate Moderate Moderate Moderate Tomczak 2001
San Geronimo None High Little Moderate Little Tomczak 2003
El Yaral None Little High Little High Tomczak 2003
Chiribaya Alta None High Moderate Moderate Moderate Tomczak 2003
San Cristobal Little None Little Little High
Middle Woodland Moderate None Moderate High No Buikstra et al.
1987; Styles and
Early Late Woodland High None High High No Buikstra et al.
1987; Styles and
Late Late Woodland Moderate None High Moderate Moderate Buikstra and Wil-
Mississippian High None High Low High Buikstra and Wil-
plants use different photosynthetic pathways. C
plants include tropical grasses such as maize, while the majority of other Maya
dietary items were C
some temporal and regional variation (Whittington 1989;
Wright and White 1996; White 1997), though, and most sites
also show evidence of supplementation with beans and pep-
pers, as well as occasional terrestrial and aquatic resources.
The second pattern among ancient Maya sites is high prev-
alence of porotic hyperostosis (Saul 1972; Whittington 1989;
Whittington and Reed 1997a). The condition is present in
juveniles and remains unremodeled through adulthood. This
pathology is typically attributed to dietary iron-deﬁciency ane-
mia secondary to heavy reliance on maize (Whittington 1989;
Wright 1994; Wright and White 1996; Chase 1997; Massey
and Steele 1997; Saul and Saul 1997; Whittington and Reed
1997a). Maize is relatively low in bioavailable nutrients, es-
pecially iron and protein (Katz, Hediger, and Valleroy 1974;
Young and Pellett 1994; Hunt 2003; Mangels, Messina, and
Melina 2003), and experimental studies have shown that ab-
sorption tends to be very low relative to other foods (Layrisse
et al. 1969). Maize supplemented with meat, ﬁsh, or foods
with high ascorbic acid content may supply an intermediate
level of iron, which will probably meet the needs of at least
50% of adult females (MacPhail and Bothwell 1992). Limited
supplementation, however, will not increase the bioavailable
iron to a level sufﬁcient for most adults.
The elevated prevalence of dental caries at several sites in-
dicates high reliance on carbohydrates (Chase 1997; Massey
and Steele 1997), although some between- and within-site
differences are noted (Saul and Saul 1997; White 1997). Table
4 presents the observed and expected population-level rates
of skeletal indicators of stress and tuberculosis. In general,
rates of porotic hyperostosis (described separately as cribra
orbitalia and cribra cranii) are reported for juveniles only, as
it is in juveniles that marrow hyperplasia results in erosion
of the cranial vault cortex to increase oxygen levels. Evidence
for marrow hyperplasia in juveniles is fairly common in all
of the American samples examined here, perhaps because of
young children’s high iron requirements (Stoltzfus and Drey-
fuss 1998). By adulthood these lesions are often remodeled,
but many Mayan sites such as Copa´n (Whittington and Reed
1997b) show high frequencies of lesions unremodeled into
It seems clear that throughout the Classic period, a large
segment of the Maya suffered iron deﬁciency beginning in
early childhood. Maize is also limited in lysine, an essential
amino acid, but supplementation with foods containing ly-
sine—in this case, legumes—and/or certain types of process-
ing can provide complete dietary protein (Katz, Hediger, and
Valleroy 1974; Young and Pellett 1994; Mangels, Messina, and
Melina 2003). This exempliﬁes category 2 from table 2, in
which adequate protein allows Th1 immunity, while lack of
iron inhibits mycobacterial growth. Among the Maya, then,
exposure to Mycobacterium tuberculosis may have led to latent
infection among large segments of the community, but dis-
seminated tuberculosis would not be expected.
Socioeconomic differences in reliance on maize (Wright
Table 4. Observed and Expected Population Level Rates of Skeletal Indicators of Stress and Tuberculosis (TB) Compared to Diet
Area Protein Iron Category
Stress Indicators Observed (Expected) TB Indicators Observed (Expected)
(%) Caries (%)
(%) Rib Lesions
Maya Ⳳ⫺2 42.3 (yes) 1.8–24.5
No (no) No (no) No Whittington 1989; Wright 1994;
Chase 1997; Massey and Steele
1997; Saul and Saul 1997; Whit-
tington and Reed 1997a
Chen Chen ⫹Ⳳ5 58.8 (yes) 63.7 (yes) High (yes) High (possible) Low Blom et al. 2005
Estuquin˜a ⫹Ⳳ1 44.4 (no ) 45 (no) Low (possible) High (possible) Low Buikstra and Williams 1991; Tom-
czak 2001, 2003
San Geronimo ⫹⫹ 5 12.9 (diet) 56.7 (yes) 41.9 (yes) Low (yes) Medium
Medium Buikstra and Williams 1991; Tom-
czak 2001, 2003
El Yaral ⫹⫹ 1 7.2 (low) 60.5 (no) 58.1 (no) High (possible) Medium
Medium Buikstra and Williams 1991; Tom-
czak 2001, 2003
Chiribaya Alta ⫹⫹ 1 12.7 (low) 60.4 (no) 52.7 (no) Medium
Medium Buikstra and Williams 1991; Tom-
czak 2001, 2003
San Cristobal ⫹⫺ 2 6 (yes) 57 (high) 90
(yes) 8 (yes) No (no) Low (no) No Stodder 1990, 1996
Middle Woodland ⫹⫹ 1 16 (low) 0–40
(no) No (possible) No
Early Late Woodland ⫹⫹ 1 22 (low) 5–55
(no) No (possible) No
Late Woodland Ⳳ⫹1 or 3 24 (low or
(no) No (possible
Mississippian ⳲⳲ 1? 42 (medium?) 30–65
(no) High (possible) High
Note: Plus sign preplete, plus/minus pmoderate, and minus sign pdeﬁcient.
White 1997; Lamanai, classic periods.
Whittington and Reed (1997b) report that for individuals with more than 50% of cranial sites observable, 64% show evidence of anemia; lesions also remain unremodeled in adults at very high
Summarized in Wright and White (1996) from many sites.
Includes unremodeled and remodeled lesions in all age groups; most lesions remodeled by adulthood.
References for Illinois data: Cook and Buikstra 1979; Buikstra and Cook 1981; Buikstra 1984; Cook 1984.
Frequencies of cribra orbitalia were reported by infant age categories; thus, the entire range is given here.
972 Current Anthropology Volume 49, Number 6, December 2008
and White 1996; White 1997) and variation in porotic hy-
perostosis and dental enamel hypoplasia prevalence (Massey
and Steele 1997; Saul and Saul 1997) have been reported at
some ancient Maya sites. It is probable that individuals in
communities or social groups with reduced reliance on maize
or greater access to iron-rich foods may be more appropriately
placed between categories 1 and 2. In these groups, protein
access allowed for Th1 immunity, but there may have been
sufﬁcient bioavailable iron to allow mycobacterial growth; the
outcome of M. tuberculosis infection would depend largely on
other stressors such as severe trauma or concurrent illnesses,
especially those that shift immunity to Th2. In those cases,
pulmonary tuberculosis and resulting rib lesions or miliary
tuberculosis with possible osseous lesions could arise.
These expected outcomes may explain the paucity of evi-
dence for tuberculosis among the Maya. At sites exemplifying
category 2, lesions on internal rib surfaces are the most likely
osseous signature, and given these elements’ fragility, this is
unlikely to be preserved. Only a small portion of the popu-
lation at some sites is expected to have experienced pulmonary
tuberculosis; an even smaller fraction of those would have
experienced dissemination of mycobacteria to bones. These
are more likely to be found at sites that display lowerevidence
of maize reliance, and concomitant lower prevalence of stress
The South American Andes: Contrasting Ancient Diets
The long occupation history and exceptional preservation in
Andean South America, particularly on the coast, provide
another record with which to examine the relationship be-
tween paleodiet and osteological indicators of tuberculosis.
Tuberculosis has been identiﬁed in archaeological sites
throughout the Andes, particularly in Peru and Chile (Allison,
Mendoza, and Pezzia 1973; Allison et al. 1981; Buikstra and
Milner 1991; Williams 1991; Arriaza et al. 1995; Burgess
1999). We focus on well-documented cemetery populations
in southern Peru for which detailed paleopathological and
paleodietary information is available.
During the Middle Horizon (AD 500–1000) and the Late
Intermediate Period (AD 1000–1350), the Osmore Drainage,
or Ilo and Moquegua valleys, of southern Peru was home to
many different archaeological cultures. Tiwanaku-afﬁliated
sites like Chen Chen and Estuquin˜a were located in the Upper
Osmore Drainage during the Middle Horizon and Terminal
Late Intermediate periods, respectively. Chiribaya-afﬁliated
sites were located in both the Upper and Lower Osmore
Drainage: Chiribaya Alta and San Gero´ nimo were located on
the coast in the Lower Osmore Drainage, while El Yaral was
located further inland in the Upper Osmore Drainage. Al-
though these sites were occupied roughly concurrently, the
foods consumed at each site varied. This variability is further
reﬂected in the rates of skeletal tuberculosis in the human
remains from these sites.
Some of the earliest osseous evidence for tuberculosis in
the southern Andes comes from the site of Chen Chen. Al-
though only approximately 80 km from the Paciﬁc Ocean,
carbon and nitrogen isotope analysis on human remains from
Chen Chen show a dietary reliance on maize and protein
from terrestrial animals such as camelids rather than on ma-
rine or lacustrine foods (Sandness 1992; Tomczak 2001, 2003).
Data presented in table 2 indicate that protein consumption
would have been relatively high at Chen Chen, but iron intake
may have been moderate, corresponding to category 1. Table
4 shows that more than half of all juvenile skeletons evidence
porotic hyperostosis; Blom et al. (2005) report that 36.4% of
adults also displayed cribra orbitalia lesions. Evidence for ex-
tensive irrigation at Chen Chen leads Blom et al. (2005) to
suggest that macroparasites were endemic. In this case, we
expect the pattern of indicators of stress and tuberculosis to
be more similar to category 5 than to category 1, and indeed,
the observed data are consistent with category 5.
During the Terminal Late Intermediate Period, at least 10
individuals with pathologies indicative of tuberculosis were
buried at the site of Estuquin˜a (Buikstra and Milner 1991;
Williams 1991; Roberts and Buikstra 2003). Paleodietary anal-
yses at Estuquin˜a show higher within-site variability in the
amount of C
plants consumed, and unlike the in-
dividuals buried at Chen Chen, those at Estuquin˜a ate Paciﬁc
Ocean or lacustrine resources (Tomczak 2001, 2003). We in-
terpret the diet at Estuquin˜a to be high in protein and iron.
Levels of childhood porotic hyperostosis are lower than at the
other South American sites (table 4). Estuquin˜a’s diet cor-
responds closely to category 1, in which tuberculosis would
disseminate to the skeleton. Tomczak (2001) found no sta-
tistically signiﬁcant dietary differences between the sexes, but
interestingly, males at Estuquin˜a exhibit much higher prev-
alence of osseous tuberculosis. Buikstra and Williams (1991)
attribute this to occupational factors, particularly exposure to
camelids: these animals may have been a reservoir for MTBC
In contrast to individuals buried at Chen Chen and Es-
tuquin˜a, those interred at Chiribaya-afﬁliated sites had access
to goods from a variety of ecological zones within the Chi-
ribaya polity (Buikstra 1995; Lozada Cerna and Buikstra 2002,
2005; Tomczak 2003; Blom et al. 2005). Although foodstuffs
were clearly being traded, subsistence choices at each site
indicate socioeconomic specialization (Buikstra 1995; Lozada
Cerna and Buikstra 2002, 2005; Tomczak 2003; Blom et al.
2005). For example, isotopic analysis shows that individuals
buried at the coastal site of San Gero´ nimo consumed the
greatest amount of marine products (Sandness 1992; Tomczak
2001, 2003). Although physiological stress can be seen in the
presence of porotic hyperostosis (Burgess 1999), this is
thought to result from helminthic infestation (Martinson et
al. 2003) rather than dietary factors (Blom et al. 2005) and
thus exempliﬁes category 5. At San Gero´ nimo, the number
of individuals exhibiting skeletal pathologies consistent with
tuberculosis infection is lower than the Upper Osmore Drain-
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 973
age sites, but disseminated tuberculosis is present (Burgess
1999) as expected.
In contrast, individuals buried at the inland Upper Osmore
Drainage, Chiribaya-afﬁliated site of El Yaral consumed fewer
marine products and relied more heavily on terrestrial prod-
ucts including maize and animals such as camelids (Sandness
1992; Tomczak 2001, 2003). Iron and protein levels are ex-
pected to have been adequate, as in category 1. While indi-
viduals buried at El Yaral show fewer skeletal lesions in gen-
eral, the number of osseous lesions consistent with
tuberculosis is signiﬁcantly increased, and the number of skel-
etal elements affected is greater when compared to the con-
temporaneous coastal sites of San Gero´ nimo and Chiribaya
Alta (Burgess 1999). Therefore, at Chiribaya-afﬁliated sites,
there is a correlation between greater evidence of tuberculosis
and a greater reliance on maize, camelids, and other terrestrial
products rather than marine resources (Burgess 1999).
Chiribaya Alta also preserves evidence for more hetero-
geneous diets (Tomczak 2001, 2003), cranial modiﬁcation
styles, and mortuary treatments (Buikstra 1995; Lozada Cerna
and Buikstra 2002, 2005; Blom et al. 2005). We interpret the
diet of the individuals buried at Chiribaya Alta as containing
moderate to high levels of protein and iron, although we
expect within-site variability in both. In general, however, we
expect this site to resemble category 1, and disseminated tu-
berculosis is indeed present here.
Colonialism and Southwestern Pueblo Populations
Puebloan populations from southwestern North America en-
gaged in extensive maize agriculture supplemented by beans,
amaranth, and other gathered and hunted resources (Stodder
1990). An abundance of crops and game was apparent to
Europeans on ﬁrst contact, although there was probably con-
siderable local variation in availability of resources such as
pinyon nuts, waterfowl, ﬁsh, bison, and antelope (Stodder
1990). At San Cristobal Pueblo, surplus corn was traded for
buffalo meat, which provided up to 20% of protein in pro-
tohistoric times. Following the arrival of the Spanish in the
early 1500s, trade shifted to nonsubsistence items, and gov-
ernors appropriated corn surpluses. Food shortages resulted,
and a series of famines and disease epidemics swept the New
Mexico pueblo and mission communities (Stodder 1990,
1996). Stodder’s (1990) paleopathological analysis of the San
Cristobal remains found evidence for developmental arrest in
dentition and long bones, dental pathology, iron-deﬁciency
anemia, and infectious diseases including tuberculosis. In-
stances of possible tuberculosis were recently reanalyzed by
J. E. Buikstra, with the new data presented here.
Fifty-seven percent of San Cristobal adults exhibit dental
caries, and rates are somewhat higher in young to middle
adults. This age range also shows high rates of occlusal surface
wear, lending signiﬁcance to the high rate of caries given the
negative correlation between these lesions and dental attrition.
Stodder (1990) attributes early, rapid dental wear to abrasive
maize-grinding lithics and supports a general model of maize-
dominated subsistence through comparison to other south-
western precontact and protohistoric sites. Porotic hyperos-
tosis is present in 89%–90% of adult and subadult individuals;
these lesions have been attributed to iron-deﬁciency anemia,
which is a secondary effect of high reliance on maize. Skeletal
lesions that initially were thought to indicate disseminated
tuberculosis occur in areas associated with later occupation
of the site. Reanalysis, however, suggests that none of these
are unequivocally tuberculosis; only a single young female
subadult (no. 8708) has spinal lesions that may indicate
Precontact San Cristobal people are expected to have ad-
equate protein levels but moderate to severe iron-deﬁciency
anemia. This corresponds to category 2, and as in the ancient
Maya, Pott’s disease and rib porosity are not expected. Stodder
(1990) emphasizes that these skeletons are from the late pro-
tohistoric component of the cemetery and may postdate col-
onization. If so, following Spanish occupation, trade disrup-
tion, food appropriation, and repeated famines would have
resulted in protein and iron deﬁciency for many native Pueb-
loan people. In this case, the diet would instead correspond
to category 4, in which the lack of protein pushes the immune
response toward Th2 and macrophages are unable to effec-
tively inhibit the bacilli. However, the lack of iron would result
in slow growth of mycobacteria. In these situations, chronic
disease could facilitate dissemination to various organ sys-
tems, including bone. Thus osseous lesions in the form of
Pott’s disease and rib porosity are expected in a small per-
centage of individuals. Because the process is slow, skeletal
tuberculosis is not expected in the youngest individuals, al-
though other nonspeciﬁc signs of infection may occur. In-
terestingly, there are three extremely young individuals (nos.
8634, 8644, and 8648) who show nonspeciﬁc signs of systemic
infection. Based on our model, it seems more likely then that
this sample postdates Spanish occupation, but other types of
research are required in order to ascertain whether this is
indeed the case.
Dietary Change in West-Central Illinois
The lower Illinois River valley provides an excellent context
in which to examine the effects of dietary changes on health.
West-central Illinois was occupied nearly continuously from
as early as Paleoindian times, around 8000 BC (Buikstra
1984). During the Woodland period (600 BC–AD 1000), pop-
ulations were concentrated in forested areas rich in deer, tur-
key, small mammals, and edible plants. The ﬂoodplains of the
Illinois and Mississippi rivers provided ﬁsh and mussels and
supported wetlands that contained roots, tubers, and migra-
tory waterfowl (Asch, Farnsworth, and Asch 1979). Change
in subsistence patterns over time has been well documented
(Asch and Asch 1978; Asch, Farnsworth, and Asch 1979;
Buikstra 1984; Styles and Buikstra 2006); an estimation of
974 Current Anthropology Volume 49, Number 6, December 2008
Table 5. Relative Usage of Various Dietary Resources by Cultural Period
in the Lower Illinois River Valley
Terrestrial mammals Moderate Moderate Moderate Low
Aquatic animals High High High High
Nuts High High Low Moderate
Oily seeds Low Low Low Low
Starchy seeds High High High High
Maize No No Medium High
relative usage of various resources over time is shown in table
Through the Middle Woodland period (50 BC–AD 250),
subsistence focused on hunting and gathering of wild re-
sources. Various nuts provided a high-quality resource, rich
in protein and fat (Buikstra 1984). Seed cultivation, including
gourd and squash, began during the MiddleWoodland. Marsh
elder, an oily, nutritious plant gathered since Archaic times,
became domesticated during the Middle Woodland; by Early
Late Woodland, however, nuts and marsh elder become more
sparse in the archaeological record. Starchy seeds such as those
of knotweed, maygrass, and goosefoot become more prom-
inent; these seeds contain less protein and fat and more car-
bohydrate. By the Late Late Woodland period, maize culti-
vation becomes important, and consumption increases to up
to 55% of the dietary carbon through the Mississippian (AD
1000–1300; van der Merwe and Vogel 1978). During the Late
Late Woodland, terrestrial mammal protein decreases but is
replaced by aquatic resources. Thus, over time there is a trend
for plant foods rich in proteins and fats to be replaced by
those higher in carbohydrates. However, supplementation by
terrestrial mammals and/or aquatic animals provided both
protein and iron throughout all periods.
During most of the prehistoric period, the primary mor-
tuary practice was mound burial, which results in generally
excellent preservation of skeletal remains; the osteological rec-
ord for this area is thus relatively complete (Buikstra 1984).
Extensive excavation has been conducted on regional mor-
tuary sites that date from the Archaic (8000–600 BC) through
the Mississippian. Here we focus on the time period that
begins in the Middle Woodland and continues through the
Mississippian periods. During this span, subsistence shifted
from solely hunting and foraging to supplementation with
seed cultivation and on to high reliance on maize agriculture
(Asch and Asch 1977, 1978; Asch, Farnsworth, and Asch
1979). Cook (1984) examined osteological and dental evi-
dence (Cook and Buikstra 1979) for changes in health and
found that Late Late Woodland children experienced retarded
growth relative to children in earlier or later periods. Cribra
orbitalia is common only among juveniles in this region, and
frequencies are relatively low throughout the entireWoodland
period, with a modest increase during Mississippian times.
Cook (1984) summarizes the effects of change in subsistence
on health as complicated and resulting from trade-offs: hunt-
ing and foraging provided balanced nutrition and a varied
diet, but seasonality of resources led to seasonal nutritional
stresses. The development of food production and the focus
on dependable, storable items during Woodland times (Buiks-
tra 1984) buffered against seasonal stress. However, the in-
troduction of maize agriculture and increasing dependence
on it negatively impacted childhood health. Further, maize
agriculture allowed increases in population sizes and aggre-
gation and, with these, an increase in infectious disease.
From these data, indicators of stress and tuberculosis for
Middle Woodland and Early Late Woodland sites should re-
semble those expected for category 1 due to the mixed hunting
and gathering diet. During the Late Late Woodland, as in-
creasing components of the diet come from maize and other
carbohydrates while terrestrial mammal exploitation is re-
placed by exploitation of aquatic animals, adequate ironlevels
and possibly decreased protein levels should be apparent—
the assemblage should resemble a transition between category
1 and category 3. From table 5 it is apparent that the rate of
caries observed is somewhat higher than would normally be
expected under category 1; this probably reﬂects growing uti-
lization of starchy seeds, although oily seeds and nuts are still
utilized in abundance during this period. By Mississippian
agricultural periods, although there is high reliance upon
maize as a staple, supplementation with aquatic and terrestrial
animals provided some protein and iron. Although there is
no category in our simpliﬁed model for moderate levels of
protein and iron, one would expect slow growth of myco-
bacteria on infection, and it is exactly under these conditions
that osseous tuberculosis is expected.
These expectations can be compared to data from the ex-
isting paleopathological literature. In 1981, Buikstra and Cook
examined 1,403 skeletal individuals from eight lower Illinois
River Valley region mortuary sites spanning the Middle
Woodland, Late Woodland, and Mississippian time periods.
Macroscopic examination of all skeletons with two or more
observable elements was conducted, with special emphasis on
pathology characterized by vertebral body destruction in the
thoracolumbar spine with little or no proliferative response
or involvement of other elements. In children, fusiform ex-
pansion of diaphyses was also considered as possibly indicative
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 975
The eight sites were divided into Middle Woodland, Early
Late Woodland, Late Late Woodland, and Mississippian time
components. Using the above criteria, no evidence of tuber-
culosis was present in any of the 216 Middle Woodland in-
dividuals examined. A single individual in the Early Late
Woodland displayed a possible calciﬁed nodule resulting from
pulmonary tuberculosis, but no other evidence of tuberculosis
was found in this or other Early Late Woodland individuals.
Possible evidence for disseminated tuberculosis appears in
six children from the Ledders, Helton, and Schild sites’ Late
Late Woodland components, all of whom exhibit diaphyseal
modeling consistent with (but not diagnostic of) tuberculosis,
and a single adult displays a destructive lesion of the left
auricular surface of the ilium. Only one of these—the Helton
child—is considered to be a convincing case of tuberculosis
(Buikstra and Cook 1981; Roberts and Buikstra 2003). Both
Mississippian sites, however, show evidence of vertebral de-
struction and/or classic Pott’s disease, with other axial in-
volvement in adults and juveniles, and a single possible cal-
ciﬁed pleural nodule. Buikstra and Cook (1981) also
demonstrate changes in the relative frequencies of cribra or-
bitalia over time, with lower rates in Middle and Early Late
Woodland followed by increasing rates in Late Late Woodland
and generally higher rates in Mississippian individuals. An
important deviation from our expectations is the lack of tu-
berculosis found in Middle and Early Late Woodland, al-
though it should theoretically be possible. This is discussed
in detail below.
The model of expectations for paleopathological indicators of
diet and disease presented in tables 1 and 2 is based upon
experimental and epidemiological studies of the effects of
nutrition on immune function. Its utility lies in its ability to
predict when paleopathological evidence of tuberculosis
should be present, providing that the population was exposed
to the disease. Of necessity, the model is general, but its ap-
plication to the skeletal record can serve to suggest potentially
productive avenues for future research in instances when in-
dicators of disease do not match expectations based on ar-
chaeological evidence of diet. In many cases, further hypoth-
eses can be formulated, and while not all of these will be
testable in the archaeological record, more may be in the
future as technology develops.
One overall problem is the potentially limited utility of
porotic hyperostosis as an indicator of iron-deﬁciency anemia.
To some extent this is probably attributable to the age-speciﬁc
nature of porotic hyperostosis; of necessity, we used data on
juvenile rates because those data were most readily available.
The true reﬂection of long-term, population-level iron-deﬁ-
ciency anemia is more likely to be seen in the frequencies of
unremodeled porotic hyperostosis in adulthood, which is
noted at high frequencies at some Maya sites as well as at San
Cristobal. Most importantly, it is crucial to keep in mind the
osteological paradox when observing indicators of stress in
order to make inferences about the health status of the pop-
ulation. Moderate to high levels of porotic hyperostosis occur
in children from all of the New World series examined here,
and it seems reasonable to infer that these children were the
most susceptible to the diseases that killed them. However,
the interpretation of the adult skeletons showing high levels
of unremodeled porotic hyperostosis is the opposite: these
individuals seem to represent those best able to resist the
detrimental effects of anemia and other health problems. Be-
low, we provide a few further examples of factors that may
come into play when comparing observed indicators of tu-
berculosis and stress to our model’s expectations.
Categories 1 and 5
In these two categories, osseous tuberculosis can be expected
if the population was exposed to Mycobacterium tuberculosis.
When protein and iron are adequate, development of tuber-
culosis following infection, as well as dissemination to extra-
pulmonary locations in the body, largely depends on both
host and pathogen factors. Even in the absence of extreme
nutritional deﬁciencies, the host may experience immune
stressors such as trauma or other infections, and these can
affect an entire population—in war, for example. Host ge-
netics also plays an important role in susceptibility and re-
sistance to tuberculosis (Bellamy and Hill 1998). In a small,
largely endogamous population, a similar level of suscepti-
bility or resistance among all individuals is expected because
of reduced heterozygosity, while in a much larger exogamous
population, variation in susceptibility is expected.
Pathogen factors such as dose of infectious organism, num-
ber of episodes of exposure, and the pathogenic strain in-
volved also inﬂuence host susceptibility to infection and dis-
ease (Read et al. 1999) and probably the course of disease.
Exposure to high doses of mycobacteria causes inefﬁcient im-
mune responses, and it is thought that crowded living con-
ditions may be more likely to lead to infection and disease
(Power, Wei, and Bretscher 1998). The M. tuberculosis strain
also inﬂuences the course of disease following infection (e.g.,
Arvanitakis et al. 1998).
One important host factor that has not been incorporated
in our model is coinfection with Plasmodium species, the
causative agents of malaria. This is an enormous world health
problem (WHO 2002) and is caused by mosquito-borne par-
asites that are well adapted to their hosts. Malaria has a num-
ber of effects on the human immune system (Boutlis, Yeo,
and Anstey 2006; Riley et al. 2006; Coban et al. 2007), but
one commonality is that the plasmodium has evolved to live
in red blood cells. The rupture of these cells causes many
complications, including hemolytic anemia. Unlike iron-
deﬁciency anemias secondary to diet, iron is present in the
host and is released upon rupture of the red blood cells.
Incorporating this disease in a very simple way into our model
would place it into category 5, but this is probably a gross
976 Current Anthropology Volume 49, Number 6, December 2008
and misleading oversimpliﬁcation. The complicated effects of
the malaria parasite on the human immune system at various
stages in the parasitic life cycle are difﬁcult to predict, espe-
cially in conjunction with other infections (Page et al. 2005),
and may be compounded by factors such as host age, genetics,
and pregnancy status (Stevenson and Zavala 2006).
Disseminated disease is not expected in this situation, at least
not at high frequency. Pott’s disease in some individuals may
indicate dietary differences by social groups. In large numbers,
it is possible that the iron deﬁciency is in fact the result of
parasitic infections, and thus the population ﬁts into category
5. Only latent or pulmonary tuberculosis is expected in cat-
egory 2—lack of evidence for osseous tuberculosis here would
say nothing about whether the disease was present in the
In this case, Th2 immunity combined with adequate iron for
mycobacterial growth suggests that fulminant pulmonary dis-
ease will result in the large majority of individuals who be-
come infected. This should result in porosity and new bone
formation on the internal aspect of ribs (Roberts, Lucy, and
Manchester 1994), but sufﬁcient time for development of
osseous disease is not expected. If Pott’s disease is present,
especially in a large number of individuals, this may indicate
that the population was sufﬁciently healthy to withstand the
A diet poor in protein and iron provides the most likely
situation in which osseous tuberculosis will develop. In this
case, macrophages will tend to remain unactivated and unable
to contain bacilli. Although very little serum iron will be
available for the pathogens, extremely slow growth ispossible,
and this may lead over time to dissemination and osseous
manifestation of tuberculosis. If there is evidence of exposure
to M. tuberculosis and no evidence of spinal involvement, it
may be that individuals were dying of tuberculosis of other
organ systems or of something other than tuberculosis—and
with this level of malnutrition, that is not surprising.
Goodness of Fit
In our analysis of 11 New World skeletal series, we found a
reasonable ﬁt between our model-based expectations and
stress indicators among the three Chiribaya-afﬁliated sites. An
exception to the ﬁt lies in the caries level reported for San
Gero´ nimo and Chiribaya Alta, where very little maize was
consumed; the level was higher than the one at El Yaral.
Burgess (1999) ﬁnds a generally higher level of dental health
at El Yaral than at other Chiribaya sites, and she suggests
possible environmental trace mineral or behavioral differences
as the cause. Given the presence of ceramic keros and maize
at sites like El Yaral (Lozada and Buikstra 2002) and the
importance of consumption of maize beer (chicha)inthe
Andes (Isbell 1978; Weismantel 1988; Allen 2002; Jennings
2004), it is possible that maize was often consumed as chicha
in the Moquegua Valley. If most maize consumed at El Yaral
was in liquid form, it may have inhibited the deposition of
carbohydrates on the teeth, which mostly were used for chew-
ing meat products. A number of factors may contribute to
the difference in dental health between El Yaral and the other
two Chiribaya sites, but it is interesting that the caries rates
among these South American groups consuming chicha are
The model expectations and observed skeletal indicators
also ﬁt well in all but three North American series. At San
Cristobal, precontact peoples are expected to have had suf-
ﬁcient protein, with moderate to severe iron deﬁciency cor-
responding to category 2. Disseminated disease is not expected
in this situation, and indeed, no classic cases of osseous tu-
berculosis are observed. However, the presence of possible
Pott’s disease in a subadult female as well as systemic infection
in three extremely young children could indicate tuberculosis
infection with slow disease development and dissemination
due to extreme protein and iron deﬁciencies as in category
4. This discrepancy is intriguing because these skeletons are
from the late protohistoric component of the cemetery, and
could be contemporary with Spanish occupation and the ex-
treme repeated famines documented.
Perhaps an even more intriguing lack of ﬁt between our
model-based expectations occurs in the Illinois series during
the Middle and Early Late Woodland periods. Based on the
adequate dietary levels of both protein and iron, disseminated
tuberculosis should theoretically be possible, but none is ob-
served. The discrepancy noted in this small area of North
America hints at a much larger question relevant to the entire
world: why does evidence for osseous tuberculosis appear so
late in time?
Mycobacterium tuberculosis has been a human pathogen for
millennia. A comparison of differences in the DNA between
two closely related strains of modern M. tuberculosis conser-
vatively estimated a minimum age for the complex of 35,000
years (Hughes, Friedman, and Murray 2002), and phyloge-
netic evidence from molecular studies of the entire MTBC
indicates an African origin perhaps more than 2.5 million
years ago (Gutierrez et al. 2005). Although this number may
be an overestimate due to the incorporation of recombining
portions of the genes (Smith 2006), it is clear that the as-
sociation between humans and tuberculosis is ancient. Given
that the New World pathogen has also been identiﬁed as a
member of the MTBC (Arriaza et al. 1995; Braun, Cook, and
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 977
Pfeiffer 1998; Salo et al. 1994), the bacteria must have been
present in human and/or animal migrants from the Old World
during the peopling of the Americas.
It follows from our model that groups with adequate iron
and protein stores (category 1) were susceptible to dissemi-
nated tuberculosis. Certainly many hunter-gatherer popula-
tions of the New World had an adequate diet, but there is no
osseous evidence for tuberculosis anywhere in the New World
until approximately AD 300 (Allison et al. 1981; Roberts and
Buikstra 2003). This issue is not unique to a study of the
disease in the Americas, because neither does skeletal tuber-
culosis appear in the Old World until relatively late. The ear-
liest paleopathological evidence comes from 5800 BC in Neo-
lithic Italy (Canci, Minozzi, and Borgognini Tarli 1996).
How can we account for the absence of tuberculosis among
skeletal remains until 5800 BC in the Old World and AD 300
in the New World? How could the disease have been main-
tained in small populations of hunter-gatherers? Was the com-
mon ancestor of the MTBC maintained instead in animal
populations until humans began living in large, permanent
settlements? The latter seems unparsimonious, as at least two
zoonotic transmissions into human would then have to be
posited—one in the Old World, and one in the New World.
One such transmission was already hypothesized for the Old
World (Rich 1944), with M. bovis suggested as the ancestral
organism (Cockburn 1963) that gave rise to human tuber-
culosis following cattle domestication. However, strong ge-
netic evidence from multiple research groups and multiple
types of genetic polymorphisms indicates that the common
ancestor of the complex gave rise to the human pathogens
Mycobacterium canettii and M. tuberculosis, with the other
species arising later (Brosch et al. 2002; Gutacker et al. 2002;
Baker et al. 2004; Gutierrez et al. 2005).
Despite the many studies that have been conducted on M.
tuberculosis, important questions remain regarding the origin
and coevolution of humans and pathogenic mycobacteria.
Considering the complexity and antiquity of this relationship,
answers will probably come from diverse areas of research,
including phylogenetics, microbiology, immunology, epide-
miology, paleopathology, history, and mathematical model-
ing. Our purpose in this paper has been to elucidate areas of
possible future research by highlighting areas in which the
tuberculosis observed in past populations does not ﬁt with
our theoretical expectations.
We thank Anne C. Stone, Luz-Andrea Pﬁster, Osbjorn M.
Pearson, and seven anonymous reviewers for their detailed
and insightful comments on the manuscript.
Instituto de Alta Investigacio´ n, Centro de Investigaciones del
Hombre en el Desierto–Corporacio´n Regional de Desarrollo
Cientı´ﬁco y Tecnolo´ gico (CIHDE-CODECITE), Departa-
mento de Antropologı´a, Universidad de Tarapaca´ , Arica, Chile
(firstname.lastname@example.org). 21 VIII 08
Wilbur et al. propose a methodological approach to test os-
seous tuberculosis in ancient populations. The authors want
to shed light on the osteological paradox and to discover those
individuals who died of fulminant tuberculosis, leaving min-
imal osseous lesions. There is increasing evidence that dis-
semination of Mycobacterium tuberculosis is reduced by in-
terrupting iron availability (Karyadi et al. 2000; Boelaert et
al. 2007 ) and that bacterias have developed genes to collect
iron from a human host (Lensbouer et al. 2008). Thus, the
authors suggest correlating osteopathological tuberculosis
ﬁndings with stress markers, diet, and the way the immune
system responds to tuberculosis. A low protein diet will lead
to rapid death if one is infected with tuberculosis. Low iron
in the diet may decrease tuberculosis and create a Th1
cell–mediated immune response.
To develop new methodologies is a challenge. The paper
could beneﬁt by incorporating epidemiological information
on native populations and a biocultural approach as well.
Certainly, as highlighted by the authors, tuberculosis infection
and disease progression depends on multiple factors such as
the particular strain of tuberculosis and immune status. How-
ever, ancient osteological remains are not isolated ﬁndings,
and most came from well-known archaeological contexts.
Thus, key demographic and cultural variables, such as pop-
ulation density, number of habitational sites, room sizes, and
subsistence need consideration too. Many of these variables
can be inferred from the archaeological record. Thus, the
authors should debate on how social and environmental fac-
tors inﬂuence susceptibility to tuberculosis and how these
variables may increase the prevalence of this disease.
At least for the Andean region, it seems subsistence strategy
was an important factor, either minimizing or triggering tu-
berculosis. Early coastal ﬁshing-gathering populations suchas
the Chinchorro show no sign of skeletal tuberculosis. They
had a steady source of marine food resources, a low animal
reservoir (sources) for tuberculosis, and a low population
density. These early coastal populations were also endemically
affected by parasites such as Diphyllobothrium paciﬁcum caus-
ing long-term dietary iron deﬁciency anemia. In populations
infected by parasites, said the authors, tuberculosis may shift
into a state of latency, generating a Th2 antibody–mediated
response. Bioarchaeological studies undertaken using Andean
mummies are useful to debate the model. It is interesting to
highlight the absence of skeletal and soft tissue tuberculosis
978 Current Anthropology Volume 49, Number 6, December 2008
lesions in radiographs and autopsies of preceramic Andean
mummies. It seems that tuberculosis did not affect early
coastal populations at all. On the other hand, one could pre-
dict that late agropastoral populations, particularly those
showing intensive social conﬂicts and living in more enclosed
houses, for example, should have greater evidence of tuber-
culosis. This seems to be the case in the Andean region. Later
agropastoral mummies show a variety of lesions ranging from
primary healed ﬁbrous, calciﬁed lesions (Ghon complex),mil-
iary tuberculosis, and Pott’s disease. The Ghon complex and
Pott’s disease are visible on chest x-rays of mummies (Allison
et al. 1981).
The need to study those dying of tuberculosis is paramount
(Devi et al. 2003). Tuberculosis causes consumption, loss of
appetite, and wasting away. Compared with controls, tuber-
culosis patients had a signiﬁcantly lower body mass index,
reduced skinfold thicknesses (triceps and biceps), and smaller
mid-upper arm circumference (Karyadi et al. 2000). Thus,
overall robusticity and cross-sectional geometry of long bones
within a population (controlling by sex, age, and subsistence)
could be another variable to explore. Individuals dying or
suffering from tuberculosis should be emaciated and their
The authors posed the question why tuberculosis rose late
in both the New World and the Old World. Tuberculosis reigns
in crowded living conditions. The microscopic-droplet nuclei
infected with tuberculosis are catapulted by sneezing and
coughing to nearby individuals. These droplet nuclei remain
airborne for a long time and can be easily inhaled. Therefore,
given this mode of transmission, analysis of population ag-
gregation in antiquity should be an important factor to con-
sider as well. There is a good general trend between the ap-
pearance of tuberculosis in both the New World and the Old
World and population increase, nucleation of villages, and
intensive herding and farming. With those conditions, iffarm-
ers had extended families and were living in small houses,
the creation of a social milieu in which to become infected
with tuberculosis is more likely.
The authors state that the mycobacterium is ideal for an-
cient DNA studies, but perhaps they should explain a bit more
about why and in addition give the readers some recom-
mendations on how to minimize contamination and preserve
samples for future DNA testing. Perhaps it is the right time
to create an ancient tuberculosis sample collection center.
Quantifying how much protein and iron was available in
antiquity and its sources is relevant to the model. Iron from
meat is more easily broken down and absorbed than iron
found in grains. Certainly, studying isotopes and using today’s
technology, such as laser ablation inductive coupled mass
spectrometry, individuals’ dietary habits can be analyzed and
used to test the various-alternatives model proposed by the
authors. Finally, as suggested by the authors, integrating diet,
stress indicators, parasites, and mycobacterium adaptation
gives us a cultural- and ecologically oriented model to work
with and from which to debate tuberculosis in antiquity.
Department of Anthropology, University of Vermont,
Williams Hall 508, 72 University Place, Burlington, VT
05405-0168, U.S.A. (email@example.com). 4 IX 08
This welcome contribution to the ﬁeld of paleopathology is
especially exciting because it brings together decades of data
and will prove extremely fruitful for future research. The au-
thors build a theoretical model using well-documented im-
munological and epidemiological data on tuberculosis out-
come, and where the paleopathological data do not result as
expected, we are asked to reconsider initial conclusions about
the nutritional and health status of a particular group (e.g.,
the explanation of goodness of ﬁt at San Cristobal or the
suggestion that if a case that is originally designated as cat-
egory 2 does not meet the expectations, “it is possible that
the iron deﬁciency in fact is due to parasitic infections, and
thus this is truly a case of category 5”). Inherent in the model
is the assumption that the populations studied here were all
exposed to tuberculosis (i.e., a lack of lesions is the result of
disease outcome rather than lack of exposure). I am willing
to accept that assumption for now but wonder how it will
be received in general. The approach taken here, rather than
a more traditional testing and tweaking of the model, is pro-
ductive, and it, as well as the nuanced treatment of disease
outcome, will prove an invaluable example for future studies
into a wide range of paleopathological conditions.
This paper presents very relevant information about the
effect of macroparasites on iron availability and immune re-
sponse, and I think this can be developed further, especially
in building models. The authors point out that if anemia is
the result of abdominal bleeding caused by parasites, iron
may still be available to mycobacteria. However, this may not
be the case if the anemia secondary to parasites is due to
diarrhea and nutrients passing too rapidly for sufﬁcient iron
absorption to occur. As it stands, the model contains one
category (5) that incorporates some of the expectations for
populations with high parasite loads. However, we can imag-
ine categories with other iterations of the variables considered,
and the expectations generated for category 5 currently do
not to include the suggestion that we might expect a Th2
immune response in the presence of chronic macroparasites.
The effects of iron levels is important for predicting ex-
pected outcomes for many paleopathological conditions, and
the authors found porotic hyperostosis to be of limited use
for determining iron deﬁciency anemia. I agree that only using
the porotic hyperostosis prevalence in children is problematic,
but I am not yet convinced that using unremodeled lesions
in adulthood is the way to measure iron deﬁciency overall.
Many other factors could determine whether lesions will re-
model or develop in adulthood, such as plasticity ofthe cranial
vault cortex and the distribution of red marrow. In fact, many
other factors may be in play, including those involving par-
asites. Chronic disease can cause anemia, yet high iron levels
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 979
can contribute to disease. Dietary protein and iron are not
completely independent because diets deﬁcient in protein can
limit the body’s access to iron (perhaps important for category
3), and food processing techniques might raise levels of one
nutrient to the detriment of another. Consideration of these
factors may aid in the development of model to further in-
clude expectations for parasites.
A few clariﬁcations about the model and presented data
would also be helpful. For one, in the draft I reviewed, the
caries expectations presented in table 2 need more explana-
tion. Why are the expectations different across categories
when the protein dietary information is identical? Whatother
factors are being considered? Additionally, little information
on expectations or observations for prevalence of lesions is
presented in some cases. Is this a relevant and feasible aspect
to consider in the model? Finally, more information on the
unpublished South American tuberculosis data (similar to
that described for the North American sites) would be wel-
come, as would deﬁnitions for “low,” “medium,” and “high”
in the last three columns of table 4. These clariﬁcations can
only add to the worth of the paper.
In closing, I have to say again that this article is a seminal
contribution to the ﬁeld, building beautifully on Wood et al.
(1992). I look forward to seeing the wealth of scholarship
that it is certain to generate, especially on intraregional and
intrapopulation analyses of differential access to resources and
exposure/risk factors, such as population movement. The au-
thors should be congratulated.
Piers D. Mitchell
College of Medical and Dental Sciences, University of
Birmingham, Birmingham B15 2TT, UK (p.mitchell@clara
.co.uk). 14 VIII 08
The aim of this paper is to highlight the complex interplay
between infectious disease, diet, and immune function, so
allowing a more nuanced understanding of disease in past
populations. The authors chose tuberculosis as their model
infectious disease because it can be diagnosed in human skel-
etal remains, and a large amount of modern clinical research
has been undertaken on this pathogen. This article models
expectations of tuberculosis prevalence in 11 archeological
populations from the Americas that are believed to have varied
in their dietary intake of protein and iron. Modern clinical
research on people with TB suggests that protein energy mal-
nutrition reduces resistance to the infection by impairing the
immune system, while iron deﬁciency anemia may increase
resistance by reducing iron available for mycobacterial rep-
lication. The model suggests that populations with both pro-
tective factors and good protein and energy intake in their
diet but little iron should show no sign of TB, because im-
munity should be optimal. Groups with neither protective
factor, having protein energy malnutrition but normal iron
intake, should die quickly from pulmonary TB and so have
rib lesions but no dissemination to the skeleton. Communities
with just one of the protective factors should have spinal
involvement, as they would live long enough for the disease
to affect bones such as the spine. The article concludes that
the model does ﬁt the data in the majority of populations
analyzed but not all. This would suggest that both iron de-
ﬁciency and protein energy malnutrition sometimes had a
profound inﬂuence on the prevalence of TB in the past in
the way the authors expected. The sites where the data does
not ﬁt the model may imply that anthropological assessment
of past iron and protein intake are incorrect or that other
factors that inﬂuence susceptibility to TB (such as genetics or
disease comorbidity) may be more dominant in those
The authors do state that there are many limitations to
their study, and they have tried hard to allow for these. How-
ever, a major limitation to the approach used is onethat would
appear to have been correctable. There is no statistical analysis
to determine whether the prevalence of TB in each group was
signiﬁcantly different enough to actually mean anything. Stat-
ing that some cases were found at a site where the model
predicted a high prevalence of TB compared with few or no
cases found at sites where the model predicted little TB is
tantalizing but does not in itself prove much. Data is rarely
given as to how many individuals were found at each site. If
the number of individuals excavated from one site was ﬁve
times that recovered at another, then ﬁve times the number
of cases of TB found at the larger site does not signify any
difference in prevalence of the disease. Similarly, data is only
occasionally given regarding the completeness of the skeletal
material at each site. Sites with better skeletal preservation
may appear to have more cases of TB merely because more
bone has survived for us to inspect for lesions. It may be that
the number of skeletons from each region are similar and
that preservation at all sites was similar, but without knowing
that and quantifying it in a standardized way we can never
really be sure of the inﬂuence that may have on the results.
While the quality of preservation is often not given in a quan-
tiﬁable manner in excavation reports, the number of skeletons
from each site is usually available.
This study has many laudable elements, including a sensible
hypothesis, good modern biomolecular evidence, data from
a broad range of skeletal series, and a well-researched bibli-
ography. However, I would argue that the research does not
prove their hypothesis. In my mind, the important message
of the article is that expansive studies such as this do raise
exciting hypotheses and can provide supportive evidence.
However, in the absence of any statistical analysis of the data,
I feel we should stop short of claiming that anything has been
proved, just that the hypothesis is plausible.
The article closes with a number of questions left unan-
swered by this study. One of them is particularly apt for all
of us interested in disease in the past. If genetic studies suggest
that TB is at least 35,000 years old, why does the earliest case
in the Americas date to AD 300? One might suggest that it
980 Current Anthropology Volume 49, Number 6, December 2008
could well be the limited number of well-preserved skeletons
dating from before AD 300 is just too small for us to have
randomly encountered one with classic lesions. This reminds
us once again of the difﬁculties in studying the pastprevalence
of a disease in which only a small fraction of infected indi-
viduals develop skeletal lesions we can conﬁdently diagnose
Ekaterina A. Pechenkina
Department of Anthropology, Queens College of the City
University of New York, Powdermaker Hall, 314 65-30
Kissena Boulevard, Flushing, NY 11367, U.S.A. (ekaterina
.firstname.lastname@example.org). 2 IX 08
Mycobacterium tuberculosis is a curious pathogen. It is neither
as old as some tropical pathogens that have circulated among
primates for tens of millions of years (Martin 2003) nor as
recent as pathogens acquired during the Holocene from do-
mesticated animals. Members of the human lineage ﬁrst en-
countered pathogens of the tuberculosis complex as early as
2.5 million years ago, when our ancestors spread into open
habitats harboring abundant reservoirs of mycobacteria (Gu-
tierrez et al. 2005). Surprisingly, tuberculosis remained invis-
ible in the paleopathological record for almost the entirety of
its coexistence with humans. Except for a single case of Lep-
tomeningitis tuberculosa reported for a Homo erectus cranium
from Turkey by Kappelman et al. (2008), no skeletal mani-
festations of tuberculosis have been found on human remains
dating to before 8,000 years ago. Thereafter, tuberculosis-
related lesions became fairly common, although with consid-
erable interpopulation variation in their location and
Wilbur et al.’s paper is a thought-provoking meta-analysis
of the effects of diet and nutrition on the epidemiology of
tuberculosis in past populations. The authors propose amodel
linking manifestations of the disease to the levels of two di-
etary components: iron and protein. Their model postulates
that diet-related anemia would curb the progression of tu-
berculosis infection, while protein deﬁciencies would elicit an
aggressive form of the disease. Wilbur et al.’s approach has
great potential. Using the known effects of dietary compo-
sition on disease progression to construct models for paleo-
epidemiology ought to help resolve multiple conundrums in
the human skeletal record with respect to tuberculosis, as well
as to other diseases.
Their proposed model is simple by necessity: the low res-
olution of the paleopathological record prohibits addressing
variation in individual human responses to pathogens or var-
iations in the virulence of particular pathogens. Of greater
concern is whether dietary levels of iron and protein are really
the major factors affecting the progression of mycobacterial
infection and whether the effects of variation in the availability
of these two nutrients can be reduced to the tenets of the
proposed model. The relationship between iron intake and
the progression of tuberculosis infection may not be as
straightforward as the authors presume.
As Wilbur et al. suggest, extreme iron deﬁciency would
impede the reproduction of mycobacteria. However, this
shortage of iron would also compromise immune response
by diminishing respiratory burst and nitrogen oxide produc-
tion in macrophages, thus increasing the efﬁciency of initial
infection (Schaible and Kaufman 2004, 948; Ekiz et al. 2005).
Since low levels of dietary iron may produce such opposing
effects on the progression of tuberculosis, it is not clear at
what levels the beneﬁts of dietary anemia in curbing myco-
bacterial reproduction would outweigh the disadvantages of
compromised immune response.
Furthermore, chronic disease can cause anemia even when
dietary iron is sufﬁcient; this is probably a component of the
innate response restricting pathogen proliferation (Zarychan-
ski and Houston 2008). Patients suffering from tuberculosis
often develop anemia as a result of the infection, even if their
levels of dietary iron are normal. Successful treatment of these
patients for tuberculosis restores their serum iron without
iron supplementation (Lee et al. 2004; Sahiratmadja et al.
2007). Skeletal indicators of anemia interpreted as diet-linked
could be the result of anemia due to infection instead (Stuart-
Macadam 1992). It is possible that Wilbur et al. were unable
to ﬁnd a clear inverse relationship between skeletal manifes-
tations of tuberculosis and anemia evidenced by porotic hy-
perostosis, not because porotic hyperostosis is an indicator
of “limited utility” but rather because the relationship between
tuberculosis epidemiology and anemia is nonlinear.
In addition, their proposed model seems to underplay the
role of stress in the progression of tuberculosis. Persistent
stresses in general, including physiological stress caused by
malnutrition or nutrient deﬁciencies, result in immunosup-
pression by activating the hypothalamic-pituitary-adrenal
axis, increasing both susceptibility to new pathogens and the
reactivation of latent ones (Rhen and Cidlowski 2005, 1714).
With speciﬁc respect to the progression of tuberculosis, almost
any form of stress, including protein or caloric deﬁciency
(Zachariah et al. 2002), lack of vitamins (Chan 2000), or even
extreme psychological stress due to war, deprivation, migra-
tion, or natural disaster (Barr and Menzies 1994; Lerner 1996;
Pavlovic et al. 1998; Ponticiello et al. 2005), correlates posi-
tively with increased morbidity and mortality.
We should acknowledge that the epidemiology of tuber-
culosis is an outcome of complex interactions among multiple
factors having continuous variation, including levels of var-
ious nutrients, the virulence of particular strains, individual
susceptibility, and so on. With all that in mind, it may well
be that stress accounted for much of the recognized variation
in the distribution of tuberculosis-related lesions in past pop-
ulations. The transition to agriculture and population growth
during the early Holocene introduced a whole series of new
stressors into the human condition. One possible result was
that the pathogenesis of tuberculosis became aggressive
enough to cause skeletal lesions.
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 981
Department of Anthropology and School of Graduate
Studies, 65 St. George Street, University of Toronto,
Toronto, Ontario M5S 2Z9, Canada (susan.pfeiffer@
utoronto.ca). 25 VIII 08
The contribution of Wilbur and colleagues is a valuable
thought piece, presented with maturity and balance. It draws
the reader into thinking about whether their perspective en-
riches our understanding of tuberculosis patterns in geo-
graphic areas beyond those discussed. My comments apply
their insights to our understanding of tuberculosis lesions
among Iroquoian peoples of the upper Great Lakes (chieﬂy
what is now southern Ontario) from AD 1400 to 1650. The
people of this region, at that time, lived in multifamily long
houses, practiced maize horticulture, and interred most their
dead in ossuaries. Analysis of remains from these large, sec-
ondary burial pits is complex (Pfeiffer and Fairgrieve 1994;
Williamson and Steiss 2003), but probable tuberculosis is
commonly seen. I will focus on those ossuaries I have studied
myself. The Moatﬁeld (minimum nuber of individuals [MNI]
p87, ca. AD 1300) and Uxbridge (MNI p457, ca. AD
1500) ossuaries show high lesion frequencies, suggesting that
nearly all people suffered from tuberculosis, based onmodern
probabilities of osseous tissue involvement. Bone tissue from
Uxbridge has yielded DNA consistent with Mycobacterium
tuberculosis (Braun, Collins Cook, and Pfeiffer 1998).
The Uxbridge remains show osseous signs of tuberculosis
in very young children as well as adults (Pfeiffer 1984). Ver-
tebral tissue modiﬁcations akin to Pott’s kyphosis are seen in
one child aged 3–5 years; a minimum of eight of the 145
immature individuals show vertebral lesions consistent with
tuberculosis. At the smaller Moatﬁeld ossuary (Pfeiffer 2003),
there were no diagnostic vertebral lesions among juveniles,
but there were three crania (infant to 3–5 years) showing
resorptive, endocranial lesions that may have been tubercu-
lous meningitis (cf. Schultz 1999) but were not scrutinized
for those speciﬁc characteristics before their reinterment. In-
formation on cribra orbitalia is not available for Uxbridge; at
Moatﬁeld the frequency (28%) is comparable to that from
other Iroquoian ossuaries, but the proportion of affected ju-
veniles (56.5%) is the highest documented for this region.
Lesions on the pleural aspect of adult ribs are present in both
groups; they represent a higher proportion of the sample at
Uxbridge (Pfeiffer 1991) than at Moatﬁeld.
How does Iroquoian dietary information ﬁt with this pic-
ture? The presence of lesions among all age groups suggests
that they fall into category 1, that of people with dietarily
adequate protein and iron. This does not appear to have been
the case. Adults from Uxbridge as well as the Kleinburg os-
suary (MNI p561, AD 1600) have been radiographically
shown to have low bone mass, suggesting dietary inadequacy
relating to a heavy reliance on maize (Pfeiffer and King 1983).
Regional analyses demonstrate strong reliance on maize by
AD 1300 (Schwarcz et al. 1985). Stable isotopes in teeth from
the Moatﬁeld sample show this pattern (van der Merwe et
al. 2003). The spacing of d
C from collagen and enamel (7‰)
indicates an herbivorous diet. Nitrogen isotopes indicate that
Moatﬁeld people were getting protein from eating ﬁsh, es-
pecially large-bodied carnivorous ﬁsh. Some communities ap-
pear to have focused on ﬁsh (lacustrine/riverine protein), and
others on deer (terrestrial protein) during this period (Mac-
Donald 2002). Caries rates and dental health are consistent
with this picture. Caries rates for all teeth range from around
25% to over 40%, but this understates the effect of caries
because of the high levels of antemortem tooth loss through
abscessing. Moatﬁeld mandibles showed 32% antemortem
loss and 39% caries among the remaining teeth (Crinnion,
Merrett, and Pfeiffer 2003). Dietary energy was apparently
adequate and evidence for nutritional diseases is equivocal,
but both protein and iron seem to have been in short supply.
This places Iroquoians in category 4.
As noted by Wilbur et al., diet is not the only factor in-
ﬂuencing infectious disease patterns. Among Iroquoians, two
exacerbating factors deserve particular attention. On the plus
side, they may have been ingesting ﬁsh oil from species that
provide signiﬁcant health beneﬁts. The nitrogen isotope ratios
are consistent with types of ﬁsh that are not common infaunal
remains from the middens, including burbot (a type of cod).
The absence of burbot bones may indicate that the oil was a
commodity that was traded, as was observed historically (Fox
2000). Cod liver oil is an excellent source of fat soluble vi-
tamins and omega-3 fats, beneﬁtting the immune system and
bone tissue. Even a small amount of this type of ﬁsh oil could
counterbalance some of the less beneﬁcial aspects of their
diet. On the negative side of the health equation, Iroquoians
lived in smoky, crowded longhouses. Maxillary sinusitis is
ubiquitous by adulthood at Uxbridge and Moatﬁeld (Merrett
and Pfeiffer 2000; Merrett 2003). The indoor combustion of
biomass fuels (e.g., wood smoke in this case) is associated
with heightened respiratory infections and suppressed im-
mune response (Roberts 2007). Poor air quality could have
sped or ampliﬁed the course of tuberculosis.
The combination of reliance on an imperfect carbohydrate
dietary staple, a climate that is cold, damp, and cloudy for
much of the year, and life in crowded, smoky longhouses
allowed tuberculosis to spread readily. The mystery is how
Iroquoian people survived long enough to show skeletal le-
sions. Low dietary iron intake could have slowed disease
progress. Fish oil in the diet may have also had a salutary
effect. It would be interesting to study patterns of tuberculosis
from ossuaries representing groups with different protein
sources (ﬁsh versus deer). While intrigued, I am not sure
whether we will be able to differentiate categories 1 and 4 on
osteological evidence alone. Nevertheless, their work certainly
982 Current Anthropology Volume 49, Number 6, December 2008
Nancy Tayles and Judith Littleton
Department of Anatomy and Structural Biology, Otago
School of Medical Sciences, University of Otago, P.O. Box
913, Dunedin, New Zealand (email@example.com)/
Department of Anthropology, University of Auckland,
Private Mail Bag 92019, Auckland, New Zealand. 25 VIII
We applaud the approach taken by Wilbur et al. to the chal-
lenging task of attempting to determine the prevalence and
signiﬁcance of TB in prehistory. It is refreshing to see a move
beyond the traditional interpretation of the lesions to one
drawing in epidemiological and immunological knowledge
and incorporating this with nonspeciﬁc skeletal markers of
malnutrition, isotopic and archaeological evidence of dietary
composition, and archaeological evidence of subsistence and
habitat to produce a model of TB prevalence and distribution.
We do, however, have some issues with the development
of the model. Wilbur and coauthors point to the interaction
between nutrition and infection and highlight some of the
speciﬁc linkages that are hypothesiz ed to exist between TB
disease and iron deﬁciency or protein undernutrition. These
are seen acting in one direction, yet interactions between TB
infection and disease and nutritional status are two-way. For
example, a characteristic symptom of TB disease is weight
loss and a recent review suggests that the anemia seen in TB
is most frequently the anemia of chronic infection (van Lettow
et al. 2003).
The authors justify the emphasis on protein and iron on
the basis that these have the best-understood effects on my-
cobacterial infection. However, there are long-recognized
linkages between TB and other nutrients, particularly vitamin
D inadequacy (e.g., Roberts and Buikstra 2003, 54–55; van
Lettow et al. 2003). The model simpliﬁes a set of complex
relationships between nutrition and TB.
Beyond this, their identiﬁcation of protein deﬁciency in
human remains relies on two assumptions, ﬁrst, that high
caries rates are indicative of high carbohydrate consumption,
and second, that a high carbohydrate diet is of necessity low
in protein. On the ﬁrst point, although some carbohydrates
(notably maize in the New World) are cariogenic, not all are
equally so (Lubell et al. 1994; Oxenham et al. 2006). On the
second point, the inclusion of agriculture as a contributor to
subsistence does not necessarily equate to inadequate protein.
The model also privileges nutrition over the other char-
acters that inﬂuence susceptibility to TB—in particular, past
population history of TB, the age structure of the population,
other infections and immunosuppressing conditions. It could
be argued that the speciﬁc case studies examined in this paper
share a population history of tuberculosis but globally that
varies substantially. The population ratio between pulmonary
and extrapulmonary TB seems to be, at least partially, a func-
tion of population and individual life history. Populations
with a long history of TB are more likely to experience higher
rates of extrapulmonary disease than pulmonary (Farer et al.
1979; Verver and Veen 2006, 881–2).
Similarly age structure reﬂects TB mortality as well as af-
fecting TB transmission and disease location (Roberts and
Buikstra 2003, 48–50). For example, children who are sus-
ceptible to tuberculous meningitis are also the sentinel in-
dicator of active TB transmission because until they can have
a productive cough, they are not agents of transmission
(Howie et al. 2005). In this instance, the age structure of the
population and the distribution of active and inactive lesions
become important variables.
The further complicating point is the increasing recognition
of the synergistic relationship between tuberculosis and other
conditions (infectious and noninfectious). The chronicity of
TB means that it is a prime candidate for syndemic (Milstein
2002) interactions; for example, other zoonoses can inﬂuence
the presence and distribution of skeletal signs within
Such studies require a detailed analysis of context, and while
the model proposed here may be a heuristic device, the lack
of consideration of the composition and context of the sam-
ples discussed limits its interpretive power. The authors have
shown us how understanding of, for example, the immune
system, can improve interpretation. However, we also need
to accept that the interactions are complex, and despite the
appeal of a simple model, human biology is rarely that easily
Facultad de Ciencias Antropolo´gicas/Autonomous
University of Yucatan, Carr. Me´ rida Tizimı´n, km 1; CP
97305, Me´rida, Yucata´n 97305, Mexico (firstname.lastname@example.org).
Only recently have we started to understand some of the
speciﬁc mechanics involved in mycobacterial exposure, dis-
ease development, and skeletal involvement of tuberculosis
in world prehistory. A laudable effort in this direction is the
paper by Alicia Wilbur and her colleagues. Buildingon knowl-
edge of host-pathogen interaction, it explores the role of di-
etary protein and iron in the deadly spread of tuberculosis
through the Americas. To test their model, the authors discuss
the presence versus absence of skeletal indicators of tuber-
culosis in four large cultural settings with different dietary
patterns. This “cross-cultural” comparison is intended to pro-
vide viable answers on the possible role of nutrition in the
spread of the disease.
While this paper beneﬁts from a rigorous research design
that builds on a set of hypothetical predictions and observed
patterns, I think it does not escape the shortcomings that are
inherent in this type of research. One of my main concerns
in this regard is the use of nonspeciﬁc stress markers (caries,
porotic hyperostosis, dental enamel hypoplasias), which all
can have different etiologies, in order to make inferences spe-
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 983
ciﬁcally about carbohydrate intake or iron deﬁciency, a short-
coming that the authors themselves are probably well aware
of. Also their decision to employ a unifactorial approach (i.e.,
diet) to examine the decisively multifactorial mechanisms in-
volved in mycobacterial diseases naturally comes to limit any
afﬁrmative statement or causal explanation regarding the re-
lationship between dietary patterns and tuberculosis. I agree
therefore with the authors when they conclude that the pur-
pose of their study has a heuristic quality, to elucidate areas
of future research and, more speciﬁcally, to incite new ques-
tions regarding the relatively late outbreak of the disease in
I will take up this last issue here, since it is only marginally
discussed in the paper. Why have no convincing cases of
probable tuberculosis been traced before AD 300, and why is
the bulk of suggestive specimens dated to the second millen-
nium AD? This comes as a surprise especially when consid-
ering that at least two of the examined areas (parts of the
Andes and Mesoamerica) look back on a long-standing mil-
lenary trajectory of relatively unchanged subsistence patterns,
with eras of centralized geopolitical systems and high pop-
ulation densities, which would have made feasible environs
for earlier tuberculosis outbreaks. Well known arethe crowded
living conditions in the many large pre–AD 1000 urbanized
centers such as Teotihuacan in the highlands of Mexico or
Tiwanaku in the south central Andean highlands. It follows
from this that the critical bacterial thresholds for tuberculosis
dissemination had not been reached in the early times and/
or that the transmission mechanisms that did lead to the
initial outbreaks of the disease might have been different from
those operating during the second millennium, a time when
the disease had already spread over large parts of the New
World. A stronger diachronic emphasis in the research design
would surely have enriched the discussion. Alternatively,
stricter control on coetaneous populations when selecting the
cohorts to be assessed, preferably post-AD 1000, would have
been convenient when assessing the outcomes of the myco-
bacterial coevolution with humans.
As it stands, the selection of Maya skeletal series in par-
ticular is inconvenient in this respect, since the great majority
derives from precollapse populations (pre-AD 800), and some
even clearly predate the Classic period (pre-AD 150). Con-
sidering that all datable Mesoamerican specimens suggestive
of tuberculosis have been traced to the second millenium AD,
the Classic Maya world appears to be an unlikely setting for
initial outbreaks of tuberculosis that were sufﬁciently massive
enough to leave their traces in the minute fraction of pre-
served and recovered remains that have been examined by
specialized personnel. Here, instead of linking the disease’s
presence or absence to nutritional patterns, which have an-
alogs in most other parts of the pan-Mesoamerican sphere,
I would argue that factors found in the Maya Lowlands’ dense
vegetation and its particular geography should have worked
as natural barriers against disease spread. Also, the year-round
warm climate, the design of ancient Maya living spaces, and
an outdoor lifestyle all make the Maya Lowlands an improb-
able milieu for early outbreaks and along with the local ge-
ography should account for the absence of clear diagnostic
lesions in the Maya skeletal series cited by the authors.
While these thoughts potentially dismiss the relevance of
Classic Maya nutritional patterns in the development or ab-
sence of tuberculosis, they trace promising future lines of
research, at least in this area. Postclassic inland populations
that settled in the karstic plains of Yucatan during the second
millenium AD could constitute new target populations for
researchers, since the skeletal collections from this part of the
Maya world have been only partly scrutinized and are steadily
growing. Also the systematic examination for diagnostic fea-
tures of the large and relatively well-preserved Classic and
Postclassic skeletal populations of the coastal fringes should
make promising future research objects. Most of the skeletal
indicators from these populations are consistentwith category
5 (sufﬁcient dietary protein and iron but high load of infec-
tions), thus allowing a possible interpretation of tuberculosis
outbreaks and detectable skeletal signatures, to keep with the
reasoning of the authors. It is precisely this set of ideas and
agendas that the present paper encourages, and my colleagues
should be congratulated for it.
We thank the commentators for an excellent set of suggestions
and criticisms aimed at improving our model. Before ad-
dressing the comments, we think it important to reiterate the
original purpose of this paper: to better inform our under-
standing of disease in the ancient past by developing models
based upon information available that was independent of
the disease in question. Our interest was in the interplay of
diet and the immune system and how these affected the de-
velopment and course of tuberculosis in humans. Examining
the published epidemiological and experimental literature, we
ﬁrst determined the ways in which two nutrients, protein and
iron, could affect the immune response to tuberculosis. Five
dietary categories were constructed based on coarsely divided
levels of these two nutrients. Population level expectations
for disease course—and how that might or might not be seen
in the skeleton—were then posited for each category.
Following development of this model, we compiled infor-
mation on the diets of several ancient New World peoples.
The dietary information was obtained from the archaeological
record as well as being inferred from dental and osteological
nonspeciﬁc indicators of stress. We then assigned each pop-
ulation group to a dietary category and ﬁnally compared our
observations of skeletal tuberculosis indicators (i.e., rib and
vertebral lesions) to our expectations for indicators based on
the dietary category previously assigned. We do not expect
984 Current Anthropology Volume 49, Number 6, December 2008
the model to be useful as a predictor of diet from presence
or absence of tuberculosis lesions.
In general, our idea for development of such models seems
well received. Most commentators suggested potential inclu-
sion of other variables to enhance our diet and immunity
model or inclusion of other types of information that could
inform our interpretations of the paleopathological record.
Bernardo Arriaza, for example, suggested the addition of ep-
idemiologically relevant social, demographic, and cultural var-
iables that were probably as important in ancient societies as
they are today. Ekaterina Pechenkina raises an excellent issue
with our neglect of the effects of stress on the immune system
and how various emotional, physiological, and environmental
stressors can impact morbidity and mortality. Pechenkina’s
point that a variety of stressors can negatively impact health
is well taken. Of the stressors Pechenkina lists as examples,
however, many are interlinked: poor nutritionoften goes hand
in hand with war, deprivation, migration,and naturaldisaster.
Despite being interlinked, these social and physiological
stressors may act in physiologically and biochemically dis-
parate ways; separating them—or even clearly distinguishing
them in prehistoric populations—may prove extraordinarily
difﬁcult but worthwhile to attempt.
Susan Pfeiffer, Nancy Tayles, and Judith Littleton all em-
phasize other nutrients that historic, anecdotal, and modern
clinical and experimental literature suggest to be of impor-
tance in immunity to tuberculosis, in particular vitamin D.
However, the intricacies of this compound’s role in tuber-
culosis immunology render it ill-suited for the relatively sim-
ple model we aimed to generate here. While vitamin D in-
adequacy has long been linked to active tuberculosis, the
“massive” amounts of vitamin D’s active form, calcitriol, pro-
duced in tuberculosis patients (Rook 1988, 769) are strongly
implicated in immunopathology favoring bacterial dissemi-
nation and tissue destruction. Production of calcitriol in gran-
ulomas downregulates the signaling molecule interleukin-12
(Rook and Hernandez-Pando 1996), the consequences of
which are likely to include reduced induction of the Th1
response, reduced activity of bactericidal cells, andpromotion
of activated T-cell death (Gately et al. 1998), leading to im-
mune hyporesponsiveness to tuberculosis bacteria (Hirsch et
al. 1999) and probable failure to contain the bacteria at the
initial point of infection. In cells exposed to Mycobacterium
tuberculosis, calcitriol also upregulates the proinﬂammatory
tumor necrosis factor a(TNF-a), a signaling molecule re-
quired for organized granuloma formation in mice (Flynn
and Chan 2001) but also associated with fever, weight loss,
and tissue destruction, as well as liquefaction and necrosis of
pulmonary tuberculosis lesions (Rook et al. 1987).
More disturbingly for those of us attempting to link vitamin
D status with tuberculosis skeletal pathology, calcitriol can
have both mediated and direct effects on the skeleton. The
TNF-a, upregulated by the calcitriol produced at the gran-
uloma, is shown in some systems to be a paracrine suppressor
of osteoblast activity (Evans et al. 1998; Qi et al. 1999; Silvestris
et al. 2004; Vermes et al. 2004) and stimulator of osteoclast
differentiation and activity (Evans et al. 1998; Qi et al. 1999).
Although these effects were countered in one study (Vermes
et al. 2004) by addition of calcitriol itself, the rescue was only
partial. Furthermore, calcitriol has been shown to induce
osteoclast-like differentiation of progenitor cells (e.g., Clohisy
et al. 1987; Qi et al. 1999). It is further established that cir-
culating calcitriol upregulates osteoclast activity, resulting in
calcium withdrawal from the bones. It is not unlikely that
this effect may also function locally in skeletal tuberculosis,
with calcitriol overspill at the margins of bone-adjacent gran-
ulomas upregulating osteoclastogenesis and bone resorption
during tuberculosis infection. Because of these complications,
for the purposes of this paper we settled on protein and iron
as nutrients better understood with respect to tuberculosis
immunology; however, we continue to more closely examine
the role of vitamin D.
Particularly inspiring to us was Vera Tiesler’s venture into
the issue of tuberculosis cases in ancient American societies
and why the vast majority of convincing cases of skeletal TB
do not show up until after AD 1000. She advocates tighter
temporal control of samples as well as suggesting thatresearch
among the ancient Maya remains might be better informed
by climate and environment, including habitation style and
construction, rather than diet. However, she also suggests
newly analyzed ancient Maya collections from contrasting en-
vironments for such a modeling study, and it is this type of
exploration that we hope to stimulate with our paper.
Deborah Blom and Piers Mitchell both requested more
quantiﬁcation in our case studies, and we agree that this would
enable statistical comparisons that could be illuminating in
future studies. For the purpose of this paper, our aim was to
use data that were available in the published literature with
the intent of demonstrating how modeling of diet and nu-
trition information from the archaeological record can guide
expectations and generation of future hypotheses, rather than
to actually “test” a hypothesis or model in this case. This issue
does, however, highlight the need for presentation of data in
published literature so that independent testing and veriﬁ-
cation of results can be achieved by other groups, which is
one of the principle tenets of science. Indeed, some sort of
osteological database similar to Genbank would be a dream
come true for many researchers, although the feasibility of
such a project is debatable.
On the subject of databases, for now we have to disagree
with Arriaza’s suggestion of the creation of an ancient tu-
berculosis sample collection center. As we discuss in our in-
troduction, a number of serious challenges with ancient DNA
studies of disease remain. Most researchers have now adopted
the strict quality control measures necessary for ancient DNA
extraction and ampliﬁcation, but limitations of template size
and preservation necessitate analysis of very small, often non-
speciﬁc sequences whose information has been further com-
promised by the incorporation of ampliﬁcation errors. At-
tempts to identify these errors are met with the same lack of
Wilbur et al. Diet, Tuberculosis, and the Paleopathological Record 985
phylogenetic information that error-free small fragments
would confront: what are our expectations for a 1,500-year-
old M. tuberculosis fragment, for example? To develop such
expectations, it is necessary to understand the temporal and
geographical distribution of not only the M. tuberculosis com-
plex organisms of interest, but also of the closely related,
genetically similar, and environmentally ubiquitous myco-
bacterial species that are most certainly present in both the
ancient and modern burial context of the sample.
There are insufﬁcient analyses even from modern myco-
bacterial strains to inform identiﬁcation of ancient fragments
recovered by researchers, and this negatively impacts the for-
mation of an ancient tuberculosis sample collection. That is,
fragments must be securely placed phylogenetically before
they can be considered for inclusion in the collection Arriaza
suggests. What might be an excellent starting point along the
road to an ancient disease DNA database would be devel-
opment of a database with accurate genome information from
modern disease organisms and closely related species. Current
sequencing efforts by many groups are rapidly expanding the
genetic information publicly available through such sites as
Genbank, although genetic studies of disease organisms tend
to be biased in favor of economically signiﬁcant organisms
To conclude, we were delighted to see that our model was
well received and that it generated discussion of future re-
search avenues. We recognize, as did several commentators,
that such an approach is always limited, in the sense that it
must be general enough to be broadly applicable to a wide
set of situations and yet speciﬁc enough to capture the nu-
ances of each individual case examined. Our hope is that our
general approach may be useful to researchers who can add
other parameters relevant to their study areas to stimulate
further hypothesis formation and testing.
—A. K. Wilbur
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