International Journal of Osteoarchaeology

Int. J. Osteoarchaeol. 13: 189196 (2003)

Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/oa.671

A First Prehistoric Case of Tuberculosis

from Britain
SIMON MAYSa,* AND G. MICHAELTAYLORb
a

Ancient Monuments Laboratory, English Heritage Centre for Archaeology,

Fort Cumberland, Eastney, Portsmouth, UK
b
Centre for Molecular Microbiology and Infectious Disease, Imperial College of
Science, Technology and Medicine, London, UK

ABSTRACT

A likely case of tuberculosis in an Iron Age human burial from Dorset, England is described.
Osteological examination and biomolecular study support the diagnosis. A radiocarbon
determination indicates a date range for the burial of BC 400230. This case represents
the earliest reported case of tuberculosis from Britain, and indicates that the disease was
present here prior to the Roman invasion. Copyright 2003 John Wiley & Sons, Ltd.
Key words: tuberculosis; palaeopathology; England; ancient DNA; Iron Age

Introduction
Excavations at Tarrant Hinton, Dorset, England
have revealed 15 human burials of prehistoric
date. Burial 7, the subject of the present study, is
one of a pair of contracted inhumations which lay
within approximately 2 m of one another. These
two interments lay within an area which yielded
evidence for Iron Age occupation; the evidence
suggests this took the form of a small, undefended, agrarian settlement.

Osteological findings
The skeleton is fairly complete (Figure 1),
although a later ditch, which cut the burial, has
removed the cranium and some elements from
the upper left part of the body. Gross preservation of extant elements is good, with only minor
* Correspondence to: Ancient Monuments Laboratory, English
Heritage Centre for Archaeology, Fort Cumberland, Eastney, Portsmouth PO4 9LD, UK.
e-mail: simon.mays@english-heritage.org.uk

Copyright # 2003 John Wiley & Sons, Ltd.

post-depositional erosion of bone surfaces. All

epiphyses are fused, indicating skeletal maturity.
Pelvic morphology indicates male sex; dental
wear suggests an age at death of about 3040
years (Brothwell, 1981).
The pathological lesions are confined to the
lumbar spine. There is destruction of the superior
part of the body of the third lumbar vertebra (L3)
(Figure 2), so that in most places less than half its
height remains. On the right side of the body, a
little more of the anterior wall of the centrum
remains than is the case elsewhere and it is
pierced here by two holes which have the appearance of sinuses. There is destruction of the
inferior part of the body of the second lumbar
vertebra (L2) (Figure 3), although more of the
body height remains here than is the case with
L3. Re-articulation (Figure 4) indicates that the
destructive changes in these vertebrae would
have resulted in approximately 60
angular
kyphosis. The lytic lesions show no evidence of
bony repair, and their margins are of somewhat
sclerotic trabecular bone. Although the destructive process in L3 has extended to the pedicles,
the neural arch and facet joints are normal, as are
Received 28 February 2002
Revised 31 October 2002
Accepted 16 December 2002

S. Mays and G. M. Taylor

190

Figure 2. Third lumbar vertebra, superior view. The vertebral body

shows destructive changes with negligible bone regeneration.

Figure 3. Second lumbar vertebra, inferior view.There is superficial

destruction of the inferior surface of the vertebral body.The surface
of the lytic area is of similar character to that in the third lumbar vertebra. Note also the ligamentous ossification visible on the lateral
sides of the body.

osteophytes exist on the right side; these are not

ankylosed but interdigitate.

Diagnosis

Figure 1. Surviving elements, burial 7. Stippling indicates diseased

areas.

those on L2. There is a little reactive bone on the

lateral surfaces of the bodies of the first three
lumbar vertebrae, and the bodies of the first
lumbar vertebra (L1) and L2 are united on the
left side by a paravertebral osteophyte. Similar
Copyright # 2003 John Wiley & Sons, Ltd.

A number of competing diagnoses were considered. The discussion which follows draws upon
the palaeopathological diagnostic criteria of
Steinbock (1976), Kelley & El Najjar (1980),
Ortner & Putschar (1985), Aufderheide &
Rodriguez-Martin (1998) and Ortner (1999).
Although disease of non-infectious origin,
such as aortic aneurysm or metastatic carcinoma
may cause bony destruction in the spine, the
lesions in burial 7 do not resemble those seen
in these conditions; on the contrary, their
Int. J. Osteoarchaeol. 13: 189196 (2003)

A First Prehistoric Case of Tuberculosis from Britain

Figure 4. Re-articulation of the first three lumbar vertebrae to illustrate angular kyphosis due to destructive lesions in vertebral
bodies.The hole visible in the lateral side of the body of third lumbar
vertebra probably represents a sinus.

morphology is suggestive of an infectious process. The nature of the changes led us to consider
as the principle diagnostic options pyogenic
osteomyelitis, brucellosis, actinomycosis, various
fungal infections, and tuberculosis.
Pyogenic osteomyelitis may result in bony
destruction and vertebral collapse with kyphosis.
However, neural arches are often involved and
bony repair of destructive foci is generally a
prominent feature. Although brucellosis may
cause destruction of vertebral bodies, spinal disease is often polyfocal, bony repair is often
prominent and kyphosis is not usual. Occasionally, actinomycosis may affect the spine, but it
tends to involve posterior parts of the vertebrae,
the disc space is often spared and spinal collapse
is rare. Although a variety of fungal infections
may affect the spine, there is generally a predilection for involvement of posterior parts of the
vertebrae.
Copyright # 2003 John Wiley & Sons, Ltd.

191
Our favoured diagnosis is tuberculosis. The
following observations are consistent with this.
When tuberculosis affects the skeleton, the spine
is a common site for lesions. Spinal tuberculosis is
generally monofocal. Fewer than five vertebrae
are generally affected. The lower thoracic and
upper lumbar spine are most commonly involved.
Spinal collapse with angular kyphosis is frequent.
Lytic foci show negligible bony regeneration.
Vertebral bodies are favoured sites for lesions.
Involvement of neural arches is uncommon.
The pattern by which there are lesions on the
parts of two adjacent vertebral bodies flanking a
disc-space, as seen in the present example, is
frequent in skeletal tuberculosis. This may reflect
direct extension of infection from one vertebra to
another across the disc space or the fact that the
halves of two vertebral bodies flanking a discspace share a common blood supply (Aufderheide & Rodriguez-Martin, 1998: 122). Although
bony regeneration at lytic lesions is negligible in
the present case, there is sub-periosteal bone
deposition on walls of adjacent centra. This
pattern has been observed in documented examples of spinal tuberculosis (Kelley & El-Najjar,
1980), and presumably reflects local irritation of
the periosteum. Bony ankylosis may occur in
about 10% of cases of vertebral tuberculosis
(Steinbock, 1976: 182). As in the present example, this characteristically involves ossification of
paravertebral ligaments and seems most frequent
in the lumbar spine (Steinbock, 1976).

Biomolecular study
The principle causative agents of tuberculosis in
man are two bacteria of the Mycobacterium tuberculosis complex, Mycobacterium tuberculosis and Mycobacterium bovis. M. tuberculosis is almost exclusively a
human pathogen. M. bovis causes disease in diverse animal species, especially cattle, as well as
in man, and is naturally transmissible between
animals and humans.
Analysis of human remains from archaeological sites has indicated that Mycobacterium tuberculosis complex DNA may survive for several
millennia in bones from infected individuals
(references in Mays et al., 2001). Because ancient
DNA characteristically survives only in miniscule
Int. J. Osteoarchaeol. 13: 189196 (2003)

192
amounts an initial amplification step, using polymerase chain reaction (PCR) is required. This
technique enables amplification of specific regions of interest, permitting subsequent separation and visualization of DNA products on
agarose gels. Sequencing is normally carried out
to confirm the identity of the PCR product.
For palaeopathological cases of tuberculosis,
analyses for ancient DNA potentially provide a
biomolecular means of confirming diagnosis. In
addition, because genomic differences exist between M. tuberculosis and M. bovis, DNA study may
also permit identification of the species responsible for tuberculous infection in individual cases.
It was with these twin aims in mind that biomolecular work was undertaken on the present
material.
Three separate DNA extracts were prepared
from vertebrae adjacent to the pathology (twelfth
thoracic vertebra, L1 and L2). A fourth extract
was prepared from bone powder sampled from a
rib. Two other adult burials from Tarrant Hinton
with no indications of skeletal infection (burials 2
and 6) were sampled to act as controls. Extraction
of DNA, PCR methodology, and measures to
counter contamination have been previously reported (Taylor et al., 1997; Mays et al., 2001). In
an attempt to confirm the diagnosis of tuberculosis, nested PCR for the multi-copy element
IS6110 was performed. Depending upon the
tuberculosis strain, this element may be present
in up to 20 copies in the mycobacterial genome,
making it an ideal candidate for PCR amplification from archaeological remains where the state
of DNA preservation may be poor. In nested
PCR, as used here, a second round of amplification is performed using two additional oligonucleotide primers which anneal to and amplify a
smaller segment of the first round product. Three
out of the four extracts from burial 7 (L1, L2 and
rib) were positive using this procedure, whereas
the control burials were consistently negative
(Figure 5). The extract from L1 was tested twice
by nested IS6110 PCR, the extracts from L2 and
the rib were tested three times. Figure 6 shows
the results from one of these assays. The samples
always exhibited a single band of the expected
size with negative template and extraction
blanks. A re-extraction of the rib and vertebra
L2 were PCR negative (Figure 6), suggesting all
Copyright # 2003 John Wiley & Sons, Ltd.

S. Mays and G. M. Taylor

Figure 5. Gel electrophoretic analysis of nIS6110 PCR products

on 3% agarose. Lane 1: 100bp DNA size markers. Lane 2: water
blank, 2nd round. Lane 3: water blank,1st round. Lane 4: positive
control, H37Rv tuberculosis DNA. Lane 5: extract from control specimen burial 6. Lane 6: burial 7 extract 1. Lane 7: burial 7, extract 2.
Lane 8: extract from control specimen burial 2. PCR polymerase
chain reaction.

Figure 6. Gel electrophoretic analysis of nIS6110 PCR products

on 3% agarose. Lane 1: 100bp DNA size markers. Lane 2: positive
control, H37Rv tuberculosis DNA. Lane 3: water blank. Lane 4: extraction blank. Lane 5: second extraction of bone powder from rib
sample. Lane 6: second extraction of bone powder from vertebral
sample. Lane 7: first extraction of rib sample. Lane 8: first extraction
of vertebral sample.

persisting DNA had been recovered by the first

extraction. The products from the L2 and rib
samples were purified on 2% low melting point
agarose and recovered from the gel using a DNA
Clean kit (Hybaid Ltd). Cycle sequencing of
PCR products using the internal IS6110 primers
IS-3 and IS-4 was performed on a Perkin-Elmer
GeneAmp 2400 PCR machine with a Dye Terminator Ready Reaction kit (Applied Biosystems
Int. J. Osteoarchaeol. 13: 189196 (2003)

A First Prehistoric Case of Tuberculosis from Britain

ABI), according to the manufacturers protocol.
This was followed by analysis on an ABI 310
Genetic Analyser.
In an endeavour to distinguish M. tuberculosis
from M. bovis, the three positive extracts from
burial 7 were further tested for a polymorphism in
the oxyR pseudogene which distinguishes M. bovis
from M. tuberculosis species (Sreevatsan et al., 1996)
and for the RD7 deletion (Gordon et al., 1999;
Mays et al., 2001). This particular deletion event,
comprising the loss of approximately 12.7 Kb of
DNA, is restricted to some strains of M. africanum,
M. microti and classic M. bovis isolates. The
samples were also examined for polymorphic
sites in the gyrase A and catalase G genes
( gyrA95, and katG 463 and katG 203) to provide
information on genotypic group (Sreevatsan et al.,
1997; Frothingham, 1999). The primer sequences
and other parameters of these PCR methods
have been described recently (Sales et al., 2001).
Finally, as brucellosis was one of the differential
diagnoses, hemi-nested PCR for IS6501 was also
undertaken as described (Mays et al., 2001).
IS6501 is a multi-copy insertion element
present in variable number (535) in the Brucella
genome dependent upon the species (Ouahrani
et al., 1993). However, of all the PCR methods
tried for tuberculosis and brucellosis, only that
for IS6110 was positive. Cycle sequencing with
both forward and reverse IS6110 primers confirmed the identity of the 92bp product. Figure 7
summarizes the results of the IS6110 sequencing
runs.

Dating
Two radiocarbon determinations were undertaken in 2001 by the Oxford Radiocarbon Accelerator Unit on bone from burial 7. The samples
were processed according to the methods described by Bronk-Ramsey et al. (2000) and BronkRamsey & Hedges (1997). The results from the
two samples (OxA-10864-5) were not statistically different, so a weighted mean was taken
before calibration. The maximum intercept
method of Stuiver & Reimer (1986) was used to
calculate the calibrated date range. The weighted
mean of 2286  25 BP gives a calibrated date
range of BC 400230 at 95% confidence.
Copyright # 2003 John Wiley & Sons, Ltd.

193
Weighted mean 13C and 15N values are
19.5  0.2% and 7.9  0.4%. These are indicative of a mainly terrestrial diet that is not
likely to affect the radiocarbon date.

Discussion
The osteological diagnosis of tuberculosis in
burial 7 is supported by the biomolecular evidence of positive nIS6110 PCR and sequencing
of the products from both the vertebral and rib
extracts. Nested PCR for this multi-copy element
is the most sensitive of the tuberculosis methods
available, permitting in theory detection of only
15fg of DNA or three genome copies (Mays et al.,
2001). The other tuberculosis genotyping PCRs
targeting single copy genes or the RD7 deletion
have sensitivities ranging from 501000 genome
copies. Additionally, the length of surviving
template required for successful amplification of
IS6110 is just 123bp, whereas the other assays
require fragment lengths ranging from 131 to
211bp (Sales et al., 2001). Considered together,
these observations imply a generally poor state of
DNA survival in this burial. Although the positive
IS6110 assay supports the diagnosis of tuberculosis it is particularly regrettable that it could not
be determined whether M. bovis or M. tuberculosis
was the causative species.
The earliest British palaeopathological cases of
tuberculosis currently in the literature come from
the Roman period, from whence 13 cases have, to
our knowledge, been described (Harman et al.,
1981 (one case); Cox, 1989 (two cases); Stirland
& Waldron, 1990 (three cases); Molleson, 1993
(three cases); Steele & Mays, 1999 (one case);
Conheeney, 2000 (two cases); Anderson, 2001
(one case)). Although none have published radiocarbon dates, the earliest appears to be from the
first century AD (Steele & Mays, 1999). The
Tarrant Hinton case predates this by at least
three centuries.
Earlier cases than the present one are known
from mainland Europe. Formicola et al. (1987) and
Canci et al. (1996) report convincing cases from
Neolithic (fourth millennium BC) Italy. Further
cases of a similar date are known from Egypt
(Strouhal, 1999) and the Near East (Ortner,
1979).
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194

S. Mays and G. M. Taylor

Figure 7. Summary of automated DNA sequencing of IS6110 polymerase chain reaction (PCR) products obtained from burial 7. a) Consensus sequences (using forward and reverse primers) obtained from vertebra and rib extracts aligned with the published sequence of
IS6110. Bordered sequences depict primer binding sites. b) Sequence EditorTM layout of PCR product from vertebra obtained with forward
(upper panel) and reverse primers (lower panel). c) Sequence EditorTM layout of rib PCR product obtained with forward (upper panel)
and reverse primers (lower panel).TH Tarrant Hinton; Vert. vertebra.

Given the existing evidence, it seems reasonable to suppose that tuberculosis was originally
transmitted to human populations in Britain from
Continental Europe. The current example indicates that this must have occurred in prehistoric
Copyright # 2003 John Wiley & Sons, Ltd.

times. Sporadic finds of imported items indicate

links between Britain and Continental Europe as
far back as the Neolithic age (Darvill, 1987: 72).
In later prehistory, the evidence becomes more
plentiful, and by the first millennium BC it seems
Int. J. Osteoarchaeol. 13: 189196 (2003)

A First Prehistoric Case of Tuberculosis from Britain

that communities in southern England were involved in regular cross-channel trade (Cunliffe,
1995: 1114). These contacts would doubtless
have facilitated the spread of disease.

Acknowledgements
Thanks are due to the Priest House Museum,
Wimborne, for permission to sample the skeletal
material. We are grateful to Alan Graham for
providing background information on the site
and to Alex Bayliss for help in interpreting the
radiocarbon date.

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