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South African Journal of Science
http://www.sajs.co.za Volume 112 | Number 7/8
July/August 2016
Research Article Primary osteogenic tumour in Australopithecus sediba
Page 1 of 7
© 2016. The Author(s).
Published under a Creative
Commons Attribution Licence.
Osteogenic tumour in Australopithecus sediba:
Earliest hominin evidence for neoplastic disease
AUTHORS:
Patrick S. Randolph-Quinney1,2*
Scott A. Williams2,3
Maryna Steyn1
Marc R. Meyer4
Jacqueline S. Smilg2,5,6
Steven E. Churchill2,7
Edward J. Odes1,2
Tanya Augustine1
Paul Tafforeau8
Lee R. Berger2,9
AFFILIATIONS:
1School of Anatomical Sciences, University of
the Witwatersrand, Johannesburg, South Africa
2Evolutionary Studies Institute, School
of Geosciences, University of the
Witwatersrand, Johannesburg, South Africa
3Center for the Study of Human Origins,
Department of Anthropology, New York
University, New York, New York, USA
4Department of Anthropology, School of
Social & Behavioral Sciences, Chaffey
College, Rancho Cucamonga, California, USA
5School of Radiation Sciences, University of the
Witwatersrand, Johannesburg, South Africa
6Department of Radiology, Charlotte Maxeke
Academic Hospital, Johannesburg, South Africa
7Department of Evolutionary Anthropology,
Duke University, Durham, North Carolina, USA
8European Synchrotron Radiation Facility,
Grenoble, France
9DST/NRF South African Centre of Excellence
in Palaeosciences, University of the
Witwatersrand, Johannesburg, South Africa
*Current address: School of Forensic
and Applied Sciences, University of
Central Lancashire, Preston, Lancashire,
United Kingdom
CORRESPONDENCE TO:
Patrick Randolph-Quinney
EMAIL:
prandolph-quinney@uclan.ac.uk
POSTAL ADDRESS:
School of Forensic and Applied Sciences,
University of Central Lancashire, Preston,
Lancashire, PR1 2HE, UK
DATES:
Received: 11 Dec. 2015
Revised: 16 Mar. 2016
Accepted: 17 Mar. 2016
KEYWORDS:
Malapa; palaeopathology; neoplasia;
taphonomy; osteoma; malignant
HOW TO CITE:
Randolph-Quinney PS, Williams SA, Steyn M,
Meyer MR, Smilg JS, Churchill SE, et al.
Osteogenic tumour in Australopithecus sediba:
Earliest hominin evidence for neoplastic
disease. S Afr J Sci. 2016;112(7/8), Art.
#2015-0470, 7 pages. http://dx.doi.
org/10.17159/sajs.2016/20150470
We describe the earliest evidence for neoplastic disease in the hominin lineage. This is reported
from the type specimen of the extinct hominin Australopithecus sediba from Malapa, South Africa,
dated to 1.98 million years ago. The affected individual was male and developmentally equivalent
to a human child of 12 to 13 years of age. A penetrating lytic lesion affected the sixth thoracic
vertebra. The lesion was macroscopically evaluated and internally imaged through phase-contrast
X-ray synchrotron microtomography. A comprehensive differential diagnosis was undertaken
based on gross- and micro-morphology of the lesion, leading to a probable diagnosis of osteoid
osteoma. These neoplasms are solitary, benign, osteoid and bone-forming tumours, formed from
well-vascularised connective tissue within which there is active production of osteoid and woven
bone. Tumours of any kind are rare in archaeological populations, and are all but unknown in
the hominin record, highlighting the importance of this discovery. The presence of this disease
at Malapa predates the earliest evidence of malignant neoplasia in the hominin fossil record by
perhaps 200 000 years.
Introduction
A neoplasm (‘new-growth’ or tumour) is defined as a mass of localised tissue growth, the cellular
proliferation of which is no longer subject to the effects of normal growth-regulating mechanisms.1-3
A neoplasm may be benign or malignant. Malignant tumours are often referred to colloquially as cancer,
although the term ‘malignant neoplasia’ is more clinically appropriate.1 In the developed world, death from
malignancy is second only to cardiovascular disease and is often perceived as a disease of modernity.4
Neoplastic disease would have been prevalent in the past (e.g. Odes et al.5), but most likely occurred
at much lower levels of incidence than today, given the shorter life expectancy for victims1,6,7 and the
differing environmental context. Both these factors strongly influence the incidence and prognosis of any
cancer.3,8 The preserved signatures of neoplasms of any kind are rare in archaeological populations, and
are all but unknown in the hominin record. Here we present the earliest fossil evidence for neoplastic
disease in the human lineage, with a detailed description and diagnosis of a tumorous lesion affecting
the spine of a juvenile male Australopithecus sediba, Malapa Hominin 1 (MH1).9,10 This species has been
postulated as a possible ancestor of the genus Homo.9 The clinical and evolutionary implications of the
diagnosed condition are discussed.
The Malapa hominin site
The Malapa site is one of several hominin-bearing Plio-Pleistocene cave deposits located within the
Cradle of Humankind World Heritage Site to the northwest of Johannesburg, South Africa. The region
includes sites such as Sterkfontein11, Swartkrans12, Kromdraai13, Gladysvale14 and Rising Star15. The
fossil deposits in these caves were formed in roughly similar fashion as debris cone accumulations
deposited beneath vertical cave openings, which formed phreatically within the dolomites of the Malmani
Subgroup.15,16 At Malapa, the main hominin-bearing deposits have been dated using uranium-lead dating
of flowstones, combined with palaeomagnetic and stratigraphic analyses of flowstones and underlying
sediments, to 1.977 ± 0.002 million years ago (Ma).17 The cave deposits comprise five sedimentary
facies, termed A to E, from stratigraphically lowest to highest.
Facies A and B occur below a central flowstone sheet, and are overlain by an erosion remnant (facies C),
which in turn is overlain by the main hominin-bearing breccia, facies D. This has yielded well-preserved
macro- and micro-mammal fossils (such as carnivores, equids and bovids18), including the fossilised
remains of at least six hominins. Two of these, MH1 and MH2, have been reported in the literature as
representatives of a new hominin species, Australopithecus sediba9. Taphonomically the site has been
interpreted as a complex cave system with open deep vertical shaf ts that operated as death traps for animals
on the surface of the landscape. This death-trap scenario might have been the process by which the Malapa
hominins entered the cave system17,18, as evidenced by peri-mortem damage on the skeletons of MH1
and MH2, consistent with a fatal fall19. Furthermore, both skeletons present partial anatomical articulation
consistent with rapid incorporation into the cave sediments early in the decomposition process.18
Case study: Vertebra U.W. 88-37
A pathological lesion affects the spine of Malapa Hominin 1 (MH1), the type specimen of
Australopithecus sediba. This individual (Figure 1) was male, and at death he was at a developmental
stage equivalent to that of a human child aged 12 to 13 years9. The pathological specimen (U.W. 88-37)
is a complete vertebra originally assigned to T5-T710, now considered to represent the sixth thoracic
vertebra10. The dorsal surface of the right-side lamina exhibits a rounded penetrating defect (Figure 2),
measuring approximately 6.7 mm supero-inferiorly and 5.9 mm medio-laterally.
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South African Journal of Science
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July/August 2016
Figure 2: Vertebra U.W. 88-37. Photographs of surface morphology of
U.W. 88-3 showing position of lesion on right side of vertebral
lamina: (a) right lateral aspect, (b) left lateral aspect, (c) inferior
aspect, (d) superior aspect, (e) posterior aspect, (f) anterior
aspect. Note that apertures seen on lateral aspects of the
vertebral body in images (a), (b) and (f) represent normal vascular
foramina infilled with residual breccia matrix. Images produced by
Peter Schmidt.
The defect presents as a lytic lesion that extends ventrally into the
lamina for much of its length, the most anterior portion of which remains
infilled with breccia matrix (Figure 3). On the surface, the lesion has
well-rounded edges with a somewhat sclerotic appearance. There is no
evidence of periosteal or reactive bone formation on the cortex of the
specimen. Viewing the right lamina from above, it appears thicker than
the left lamina and bulges laterally over the lesion, indicating a reactive
remodelling response to the presence of the defect.
Figure 3: Vertebra U.W. 88-37. Multi-focus (composite image stack)
micrograph of surface morphology of U.W. 88-37 showing
sub-angular penetrating defect on the right vertebral lamina.
The lesion has well-rounded edges with lateral bulging of
the cortex over the lesion, indicating a reactive remodelling
response to the presence of the defect. Note that anterior
portion of defect remains infilled with breccia matrix.
Micrograph taken with Olympus SZX Multi-focus microscope,
magnification 7x. Scale bar = 10 mm. Image courtesy of
Alexander Parkinson.
The lesion initially widens directly under the oval opening, but then
narrows as it progresses anteriorly. The base of the lesion appears
smooth and sclerotic under microscopic evaluation insofar as the
presence of residual breccia allows. The spinous process deviates
slightly to the right, but appears in keeping with slight asymmetry
noted elsewhere in the surviving thoracic vertebrae. This deviation falls
within normal variation; we do not consider it significant enough to
cause scoliosis or other vertebral misalignment, and it is unlikely that
this asymmetry was related to the pathology.
Figure 1: Surviving skeletal elements attributed to Malapa Hominin 1 (at time of writing).
Research Article Primary osteogenic tumour in Australopithecus sediba
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Because of the presence of breccia within the lesion, the internal
morphology of the specimen was assessed using phase-contrast
X-ray synchrotron microtomography (performed at the European
Synchrotron Radiation Facility, ESRF) and a specific acquisition
protocol applied for high-quality imaging of large fossils (see
Supplementary Appendix materials and methods). From the
microtomographic volume, the maximum long axis of the lesion in
the transverse plane measures 11.8 mm x 4.9 mm along the minor
axis, with a cross-sectional area of 45.6 mm, and in the sagittal
plane the lesion measures 14.7 mm x 7.9 mm, with a cross-sectional
area of 68.6 mm. The internal linear dimensions are consistently
less than 20 mm in diameter, which has important implications for
final diagnosis.
Figure 4: Vertebra U.W. 88-37. Sixth thoracic vertebra of juvenile
Australopithecus sediba (Malapa Hominin 1). Partially trans-
parent image volume with the segmented boundaries of
the lesion rendered solid pink. Volume data derived from
phase-contrast X-ray synchrotron microtomography. (a) left
lateral view, (b) superior view, (c) right lateral view. Images
produced by P.T.
Figure 4 shows the microtomographic imaging, with a semi-trans-
parent volume-rendered image row. The imaging indicates that the
lesion is highly penetrative and extends ventrally within the right-side
of the spinous process, penetrating the lamina before terminating
at the approximate level of the superior articular facet. The internal
morphology shows no involvement of the transverse process or
pedicle, and the lesion does not penetrate the vertebral canal. No
mineralised focal point or nidus was discerned. The edges of the first
two-thirds of the lesion (moving dorsal to ventral) display sclerotic
characteristics, with circumscribed margins of well-integrated
cortical bone, abutted and intersected by trabecular striae (Figure 5
and Supplementary Appendix). This pattern is indicative of a slow-
forming bony process, with remodelling and reorganisation of
posterior aspects of the lesion. The shape of a lesion is indicative of
its growth rate, with lesions that are long and oriented with the long
axis of a bone indicating a nonaggressive benign process. The ventral
third of the lesion, however, displays a geographic pattern of bone
destruction, showing a sharp non-sclerotic margin and evidence
of active osteolytic processes, with sharply-defined transection
of individual trabeculae, and active osteolytic penetration into the
anterior portion of the lamina. A volume-rendered negative surface
model of the lesion (Figure 6) demonstrates the clear distinction
between the dorsal sclerotic zone and the ventral lytic zone within the
body of the active lesion.
Key: S – quiescent sclerotic zone, O – active osteolytic zone, B – remaining breccia
matrix infill.
Figure 5: Transverse slices through vertebra U.W. 88-37 derived from
phase-contrast X-ray synchrotron microtomography. Relative
position and anatomical orientation of orthoslices (a), (b)
and (c) shown on the volume-rendered model. The posterior
portion of the lesion is sclerotic with circumscribed margins
of well-integrated cortical bone, abutted and intersected
by trabecular striae, with remodelling and reorganisation
of the cortex. The anterior portion of the lesion displays a
geographic pattern of bone destruction, showing a sharp non-
sclerotic margin and evidence of active osteolytic processes,
with sharply defined transection of individual trabeculae
and active osteolytic penetration into the anterior portion of
the lamina. Image produced by P.S.R.Q.
Research Article Primary osteogenic tumour in Australopithecus sediba
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Figure 6: Surface rendered image volume of the U.W. 88-37 lesion
derived from phase-contrast X-ray synchrotron microto-
mography. Images show isosurface derived from segmented
boundaries of the lesion (remaining breccia infill removed).
The arrow denotes the interface between the smoother dorsal
sclerotic zone and the disorganised ventral lytic zone within
the body of the lesion. (a) right lateral view, (b) medial view.
Images produced by P.T.
Differential diagnosis
Diagnosis was undertaken using palaeopathological and clinical
diagnostic criteria1,2,20-34. The accumulated evidence for osteolytic and
osteosclerotic processes indicates that the disease process was both
chronic and active at the time of death of MH1 (as mentioned, at a
developmentally equivalent stage to a modern human child of 12 to 13
years of age). The lesion was less than 15 mm at the largest diameter,
extending deep into the right side of the spinous process and involving
only the vertebral lamina. The presence of reorganised sclerotic bone
indicates a reactive ante-mortem process, and the lesion can therefore
not be attributed to taphonomic, diagenetic or pathology-mimicking
effects or processes1.
The morphology of the lesion externally and internally is inconsistent with
vertebral osteomyelitis. The absence of a proliferative cor tical inflammatory
response (such as periosteal and/or endosteal bone hypertrophy) or
secondary lytic lesions across both the U.W. 88-37 vertebra and the
surviving cranial and post-cranial elements of MH1 excludes a diagnosis
of specific or non-specific systemic infection, such as brucellosis, non-
specific osteitis, haematogenous osteomyelitis or treponemal osteitis.
There is no evidence of deformation or callus formation associated with
skeletal trauma such as a healed fracture, and the lesion does not present
morphology consistent with post-traumatic processes such as cortical
hypertrophy or the development of a cloaca. It is therefore most likely
that this condition represents a primary osteogenic or osseous tumour
of the spine. These are rare lesions with a much lower incidence than
metastases, multiple myeloma or lymphoma.1,2,20,21,23,27,32 Based on age
at death, sex, anatomical location of the lesion, and specific patterns of
expression and skeletal involvement, conditions such as osteosarcoma,
chondrosarcoma or Ewing’s sarcoma can be excluded; these neoplasms
are often more aggressive, with destruction of the cortex1,21,23.
Included in the differential diagnosis as the most likely cause of
the observed lesion are osteoid osteoma, osteoblastoma, giant
cell tumour and aneurysmal bone cyst. A number of secondary
diagnoses are possible, specifically enostosis (compact bone island),
fibrous cortical defect (fibroxanthoma), plasmacytoma, eosinophilic
granuloma, and hydatid cyst infection. The range of possible differential
diagnoses and primary diagnostic criteria are detailed in Table S1
(Supplementary Appendix).
Based on the observed pathological, morphological, and life-history
criteria, the two most likely diagnoses are osteoid osteoma and
osteoblastoma. Taking the demographic data for these two tumour
types into account, both options seem possible: both are primary bone-
forming tumours, osteoblastic in nature; benign; have a predilection for
males; and show the highest prevalence in juveniles and adolescents.
Osteoid osteoma resembles the observed lesion in terms of size, as
these tumours are usually less than 20 mm in diameter, with well-
circumscribed margins and being round or oval in form23.
McCall22 notes that computed tomography is the most valuable method
to investigate this type of lesion. Under CT imaging of osteoid osteoma
a small lucency is often recorded, which may have a central high
attenuation as a result of mineralisation, and surrounding sclerotic bone
is noted with some thickening of the lamina or pedicle. These are features
seen in MH1 (Figure 4). On plain radiographs, most osteoid osteomas
are osteosclerotic, with or without a visible nidus. By contrast, Kan and
Schmidt35 suggest that osteoblastomas are predominantly lucent or
lytic in roughly 50% of cases, sclerotic in 30% of cases, and mixed in
the remaining 20% of cases. On plain radiographs, osteoblastomas are
typically expansile with a scalloped or lobulated appearance, and their
margins are well-defined, with a sclerotic rim evident in approximately
30% of patients. A sclerotic rim is therefore much more common in
osteoid osteomas than in osteoblastomas. The smooth, sclerotic, well-
defined posterior margins of the lesion we studied are fully consistent
with a resolving osteoid osteoma. However, the skeletal distribution
of osteoid osteoma might argue against this being the most likely
diagnosis, as osteoid osteomas are most commonly found in the lower
extremities; occurrence in the spine is less likely than that exhibited
in osteoblastoma22.
To quantifiably assess the differential diagnosis, we applied Bayes
Theorem of conditional probability to the diagnosis of osteoid osteoma
and osteoblastoma. Using absolute clinical incidence data of osteoid
osteoma36-38 and osteoblastoma25,37-42 to calculate prior and conditional
probabilities of the disease expression in the vertebral column (as
opposed to elsewhere in the skeleton), a conditional probability of
0.214 was derived for the likelihood of osteoid osteoma, and 0.068
for osteoblastoma. These results indicate a 3.75-fold higher likelihood
that osteoid osteoma was represented in this case than osteoblastoma
(see supplementary online material Table S2 for discussion of Bayes
parameters and probability functions used). Given the morphological
and pathological similarities between the two tumour types, and the
age and nature of the specimen under analysis, the results suggest
osteoid osteoma firstly and osteoblastoma secondly as the most likely
diagnoses of what was clearly a benign entity of abnormal nature.
Research Article Primary osteogenic tumour in Australopithecus sediba
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Discussion
MH1 suffered from a primary osteogenic tumour, which affected the
right lamina of the sixth thoracic vertebra. The neoplastic lesion was
chronic and was still active at the time of his death. From modern
clinical studies36-38 it is likely that osteoid osteoma may have taken
months, rather than years, to develop. This neoplastic condition may
involve neurological deficits, although this is unlikely as the lesion did
not penetrate the neural canal, and no scoliosis was noted. However, the
position of the lesion may have affected normal musculoskeletal function
and movement of both the shoulder-blade and the upper right quadrant
of the back. The tumour may have invoked a number of physiological
responses including acute or chronic pain, muscular disturbance
and pain-provoked muscular spasm, as discussed in clinical case
studies.21,36-38,40 A close association exists between the affected region
and overlaying or closely inserting muscles such as trapezius, erector
spinae, and rhomboid major, and this might have led to limitations on
normal movement, given the likely arboreal component in the locomotor
repertoire of A. sediba.9,43
The presence of a primary bone-forming tumour of the spine presents
a number of considerations with regard to both the life-history of
Australopithecus sediba, and evidence for neoplasia elsewhere in the
deep past. Evidence for neoplastic disease is not unknown in the fossil,
archaeological and historical records1,8,44. However, preservational
factors limit the study of neoplasms to the skeleton (with the rare
exception of naturally and artificially mummified bodies that may
preserve pathological soft tissues) from which the confident diagnosis
of tumours has been problematical45. The earliest skeletal evidence for
neoplastic disease comes from pre-Cenozoic contexts, with purported
cases of neoplasm found in fossil fish from the Upper Devonian. The
earliest unequivocal case dates from 300 Ma, with evidence of benign
osteoma with focal hyperostosis affecting the skeleton of Phanerosteon
mirabile from the North American Lower Carboniferous3. Later terrestrial
cases include diagnoses of benign haemangioma and eosinophilic
granuloma in Jurassic dinosaurs; benign osteoma in mosasaurs;
and haemangioma, metastatic cancer, desmoplastic fibroma and
osteoblastoma in Cretaceous hadrosaurs.46,47 In the more recent past,
benign osteoid osteoma and osteoblastoma have been identified in
European mammoths dating from 24 000 to 23 000 years ago (ka).48
The presence of neoplastic disease in the hominin fossil record is highly
contentious. Until recently, the earliest purported evidence was suggested
to be from a mandible of archaic Homo from Kanam, Kenya. This fossil
is generally thought to derive from the Lower or Middle Pleistocene, and
expresses pathological growth in the symphysial region. The lesion has
been attributed to osteosarcoma, bone keloid, or Burkitt’s lymphoma,
although some researchers have diagnosed it as osteomyelitis resulting
from a facial fracture49-52. The first substantive evidence for malignant
neoplasia in hominins is derived from the SK7923 metatarsal fragment,
dated to 1.8 to 1.6 Ma, from the site of Swartkrans, South Africa; a bony
cortical exostosis together with osseous infilling of the medullary cavity
of the shaft of the bone has been attributed by Odes and colleagues to
osteosarcoma5.
The next significant evidence for near-human neoplastic disease is
suggested by Monge and colleagues, who present a case of fibrous
dysplasia in a rib of Homo neanderthalensis dated to 120 ka from the
European site of Krapina.53 The Middle Pleistocene site of Atapuerca
(Sima de los Huesos) evidenced small benign osteoid osteomata
affecting the orbital roof of crania AT-777 and the endocranial surface
of Cranium 4.54 Other evidence comes from the Vogelherd (Stetten) II
parietal bone, initially thought to represent a 35-ka-old Neanderthal,
but now known to be Neolithic in origin55; in this specimen new bone
formation has been linked to a possible meningioma although the
final diagnosis remains equivocal56. The most significant evidence for
neoplastic disease in antiquity derives from the bio-archaeological
record of the recent Holocene (and the last four millennia in particular)
and is detailed in a number of historical reviews and texts1-3,46 to which
the reader is directed.
As noted above, neoplastic disease in various forms, including osteoid
osteoma and osteoblastoma, is an ancient phenomenon. It first appeared
during the Palaeozoic and Mesozoic in extinct fish and members of the
Dinosauria respectively.3,46,47 However, the fact that reports of cancers
or neoplasms remain exceedingly rare in the fossil record of almost
any geological epoch1,3,8,46,47,53 may be due to a number of factors,
exacerbated by the relative disjunction between osseous tumours and
all other forms of neoplasms. Primary bone tumours are rare compared
with other neoplasms and account for around 7% of all soft and hard
tissue cancers.22 Neoplasms are historically reported to be rare in wild
living mammals, with only 1.8% of deaths in chimpanzee communities
reportedly resulting from cancer.3 A mere handful of neoplastic cases
have been recorded based on observational studies of camels, deer,
gibbons, tigers, kangaroos, pacaranas, fur seals, ferrets, killer whales,
harbour seals, sea lions and harp seals.3 However, recent reviews of
neoplasms in wild non-human primates57 have shown that neoplastic
disease might be far more widespread than previous studies suggest,
in both monkeys and great apes; however, the vast majority of such
cases involve benign soft tissue rather than malignant tumours. When
bone tumours have been noted, they have tended to present as small
benign growths such as button osteomata, which have been observed in
both gorilla subspecies but have not been seen in either chimpanzees or
orangutans57. An isolated case of benign osteochondroma was observed
in the Gombe chimpanzee ‘Old Female’.58 Whilst these rare cases of
neoplasia in non-human primates share morphological homology with
human disease expression, it is unclear whether they share a common
genetic basis or evolutionary history.
With regard to osteoid osteoma in humans, cytogenetic chromoso-
mal studies indicate some degree of a genetic basis. This includes
the involvement of chromosome 22, 22q monosomy and trisomy
aberrations59; aberrant expression of transcription factors Runx2 and
Osterix, both of which are master regulators of osteoblastic lineage
differentiation60; and duplications and deletions at 22q13.159, the
locus of which reflects genes that play a role directly in osteogenesis
(PDGF-B and ATF-4). The involvement of the latter suite of genes may
suggest a degree of evolutionary conservatism, which warrants further
investigation across primate taxa. As noted by Odes et al.5, whilst the
expression of neoplasia is rare in prehistory, the capacity for neoplastic
disease (as evidenced by both fossil evidence and oncogenes) was
present in deep-time.
It is no surprise that metastatic bone tumours are rare or absent in the
archaeological and fossil records, because of the limited life expectancies
of our ancestors6,7 and the low incidence generally of skeletally forming or
affecting neoplasms1,3,20,23,46. It is well known that primary bone tumours
mostly occur in younger individuals1,20,21,27,37,40, and it can therefore
be expected that such tumours would have been present and have a
similar prevalence to what is observed among modern individuals. It
seems likely that neoplastic disease was as prevalent in ancient hominin
populations as that expressed today in wild primate groups, but for
various reasons it left little fossil trace. One reason might be the sheer
paucity of individuals recovered from the hominin record, which would
represent an issue of epidemiological sampling6.
With regard to the earliest evidence for neoplastic disease in the hominin
fossil record reported here, the fact that primary bone neoplasms
are so rare makes this an important discovery. Whilst we consider it
unlikely that neoplastic disease would have played a major role in the
evolutionary forces operating on the Homininae, this case provides
a unique glimpse into the individual life experience of a single extinct
hominin. MH1 provides a window onto the expression and evolution
of neoplastic disease in the human lineage, and highlights the utility
of multidisciplinary clinical studies applied to the understanding of the
evolution and development of disease in the human lineage.
Acknowledgements
We would like to acknowledge the assistance and help of the
following people in the production of this research: Bonita de Klerk,
Wilma Lawrence and Jennifer Randolph-Quinney. S.A.W. would like
to acknowledge the help of Morgan Hill and Eric Mazelis from the
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Microscopy and Imaging Facility, and Neil Duncan and Eileen Westwig
of the Department of Mammalogy at the American Museum of Natural
History. Further support in scanning time was given by the European
Synchrotron Radiation Facility and by the Department of Radiology at
Charlotte Maxeke Academic Hospital in Johannesburg. The research
was funded by grants to L.R.B. from the National Geographic Society,
the National Research Foundation of South Africa and the DST/NRF
South African Centre of Excellence in Palaeosciences. Additional direct
support for E.J.O. was received from the National Research Foundation
of South Africa and the DST/NRF South African Centre of Excellence
in Palaeosciences. M.S. was supported by the National Research
Foundation of South Africa.
Authors’ contributions
P.S.R.Q. coordinated the research and wrote the original draft of the
manuscript, incorporating additional case notes and observational data
on U.W. 88-37 as provided by S.A.W., M.S., M.R.M., J.S.S., S.E.C.
and L.R.B. Detailed discussion of oncogenetics was provided by T.A,
and E.J.O. provided detailed discussion of the historical data on early
hominin palaeopathology. P.T. undertook the synchrotron scanning of
the specimen, and primary reconstruction, segmentation and imaging.
All authors contributed equally to data acquisition and analysis, and
to editing.
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