Luigi Capasso

Antiquity of cancer

Cancer’s relationship with the genetic characteristics of the hosts and environmental conditions has been demonstrated convincingly in modern populations. Environmental conditions and the genetic characteristics of human populations have changed markedly over our long history, and these changes have inevitably caused changes in the epidemiology of cancer. From a genetic standpoint the changes are so important as to seem banal. The first representatives of our genus, for example Homo habilis, which lived in East Africa roughly 2 million years ago, were phenotypically characterized by small body size (maximum stature 1.20 m), relatively low cranial capacity (about 400 cc), perfectly erect posture and bipedal gait. They likely used some sort of primordial articulate, symbolic language, and were surely able to produce artefacts, such as stone and wood utensils, which represent the first technology on Earth. Beginning at this time technology assumed an important role in human evolution, with humans furthering their evolution not just through slow biological modifications but also through rapid technological advances. This is a unique development in the history of life on Earth. These primordial humans differed considerably from modern humans in terms of biology, cultural capabilities and social organization, and it is quite obvious that these differences must have produced variations in their ability to contract, develop and spread diseases, including the types and prevalences of neoplasms. In conclusion, it would seem likely that genetic changes in humans caused biological variations, including susceptibility to cancer over time, and socio-cultural changes also changed the patterns of human cancer. The role of paleopathology is to detect these variations, extending the research to pre-humans, and obviously nonhuman animals, observing the presence and prevalence of neoplasms in fossil animals, comparing ancient and modern evidence and creating a comparative pathology not limited to differing extant species, but that also extends to individual species during their evolution. The environment also changed markedly over time, as did the relationship between humans and the ecosystem, which itself changed during our evolution, in part because of our changing lifestyles. The first humans were nomadic, obtaining the food they needed by hunting and by gathering spontaneous vegetables. Only about 12,000 years ago did humans introduce farming and herding, developing sedentary habits, and then and gathering into densely populated communities. Environmental and ecological changes can also be linked to human activities, especially those that have occurred recently in the more developed countries. All these environmental changes and the tremendous changes in human habits may have modified human cancer in terms of both the types of neoplasms and their prevalence. Paleopathology must also determine the history of the relationships between human cancer and environmental, cultural and socio-economic changes. Only through the paleopathologic analysis of both pre-human remains (including the non-human fossil record) and ancient human remains we can reconstruct (i) the existence of cancer in antiquity, for example the evidence for cancer in the fossil record (also before the relatively recent origin and rise of our species), (ii) the type and prevalence of cancer in both pre-human and ancient human populations, (iii) the relationship between cancer prevalence and the demographic structure of human populations and its variations over time, (iv) the variations in type and prevalence of cancer as related to the genetic or environmental changes that occurred during biological, social, cultural and economic human evolution and (v) the general biological significance of cancer with respect to life on the Earth over a very long interval of observation (i.e., millions of years). These analyses can only be made if one considers cancer as a phenomenon strictly linked to life, studying the pathologic events comparatively and (vi) considering the types and prevalences of cancer with respect to the systematic relationships of the animals that this disease affects today.

Possible brucellosis in an early hominin skeleton from sterkfontein, South Africa.

We report on the paleopathological analysis of the partial skeleton of the late Pliocene hominin species Australopithecus africanus Stw 431 from Sterkfontein, South Africa. A previous study noted the presence of lesions on vertebral bodies diagnosed as spondylosis deformans due to trauma. Instead, we suggest that these lesions are pathological changes due to the initial phases of an infectious disease, brucellosis. The macroscopic, microscopic and radiological appearance of the lytic lesions of the lumbar vertebrae is consistent with brucellosis. The hypothesis of brucellosis (most often associated with the consumption of animal proteins) in a 2.4 to 2.8 million year old hominid has a host of important implications for human evolution. The consumption of meat has been regarded an important factor in supporting, directing or altering human evolution. Perhaps the earliest (up to 2.5 million years ago) paleontological evidence for meat eating consists of cut marks on animal remains and stone tools that could have made these marks. Now with the hypothesis of brucellosis in A. africanus, we may have evidence of occasional meat eating directly linked to a fossil hominin.

Odontometric sex discrimination in the herculaneum sample (79 AD, Naples, Italy), with application to juveniles

Sex determination of subadult skeletal remains with satisfactory accuracy represents one of the most important limitations of archaeological research and forensic practice. Teeth are one of the most durable physical elements of an individual that remain after death, and constitute a potential source of information about the biological sex of that individual. This study was based on the skeletal remains of 117 individuals from the ancient city of Herculaneum (Naples, Italy), victims of the eruption of the nearby volcano Vesuvius on 24/25 August, 79 AD. It has been possible to develop discriminant function formulae based on dental dimensions of adult individuals whose sex had previously been determined based on descriptive osteologic criteria. These formulae were subsequently applied to the permanent dentitions of immature individuals of the same population in order to estimate their sex. The results show that the canine is the tooth with the greatest sex dimorphism in adults, providing percentages of correct assignment of sex between 76.5% and 100% depending on the dimension used. Of the 30 subadult individuals in the target sample, estimation of sex was possible for 22 individuals. Sex assignments matched those determined from descriptive characteristics of the ilia and mandible in 73.33% of the cases. The results provide some optimism that this method may be applicable to juvenile archaeological samples.

Micro-biomechanics of the Kebara 2 hyoid and its implications for speech in Neanderthals.

The description of a Neanderthal hyoid from Kebara Cave (Israel) in 1989 fuelled scientific debate on the evolution of speech and complex language. Gross anatomy of the Kebara 2 hyoid differs little from that of modern humans. However, whether Homo neanderthalensis could use speech or complex language remains controversial. Similarity in overall shape does not necessarily demonstrate that the Kebara 2 hyoid was used in the same way as that of Homo sapiens. The mechanical performance of whole bones is partly controlled by internal trabecular geometries, regulated by bone-remodelling in response to the forces applied. Here we show that the Neanderthal and modern human hyoids also present very similar internal architectures and micro-biomechanical behaviours. Our study incorporates detailed analysis of histology, meticulous reconstruction of musculature, and computational biomechanical analysis with models incorporating internal micro-geometry. Because internal architecture reflects the loadings to which a bone is routinely subjected, our findings are consistent with a capacity for speech in the Neanderthals.

Brucellosis at Herculaneum (79 AD)

The author describes vertebral lesions observed in the skeletons of 16 adults who fled to the ancient beach at Herculaneum during the eruption of Mount Vesuvius, where they were buried alive. In all cases the lesions present as the osteolysis of the superior vertebral angle. Though it is true that this region is generally affected by osteolytic activity in all the haematogenous vertebral osteomyelitises, because of the particular arterial circulation patterns of the vertebrae, several distinctive features of these lesions indicate they were caused by brucellosis. Of particular significance are the strong, frequent sclerotic reactions below the osteolytic areas and the non-involvement of the small posterior intervertebral articulations. The sclerotic reactions are primarily due to endosteal activation, with thickening of the trabecular network produced by both an increase in the volume of the trabeculae and an increase in their number, which results in a consequent reduction of the marrow spaces. There is also periosteal activation due to the involvement of the periosteum; the anterior faces of the vertebrae struck by chronic phlogosis. Finally, there are ossifications at the centres of the anterior faces of the affected vertebral bodies that form as a result of the osseous metaplasia of the anterior longitudinal vertebral ligament, which is also involved in the progression of the disease. The bone neoformations attributable to these varying pathogenetic origins (endosteal, periosteal and metaplastic) combine to produce a sclerotic hemi-ring, known as the brucellar sclerotic vertebral hemi-ring, which can be quite dense, and surrounds the area of the osteolysis of the antero-superior somatic angle from below and behind. The vertebral lesions are also restricted to characteristic sections of the spinal column (the dorso-lumbar traict), the vertebrae (the antero-superior angle) and the upper plate (the region below the impression of the anulus fibrosus). In 68.7% of the cases the vertebral lesions are associated with rib alterations that are likely attributable to the micronodular brucellar pleurisy that commonly strikes brucellosis victims. Vertebral lesions that correlate with melitococcic spondylitis were found in 16 subjects (about 17.4% of the adults) and are more common in men than in women (M/F ratio=3:1). The high frequency of the disease is supported by historic evidence; indeed, written sources mention that the Romans made considerable use of milk from sheep and goats. It was consumed directly, without cooking or other forms of treatment, and also as milk derivatives, including ovine-milk yogurt and an impressive variety of fresh cheeses. The important role of ovine milk in the Roman diet could be behind the great frequency of brucellosis at the time. The data from the Herculaneum population provide the first concrete evidence in favour of a milk-related source for the disease. Copyright

Herculaneum victims of the volcanic eruptions of Vesuvius in 79 AD

Evidence from the excavation of Herculaneum, which began in 1738, has led archaeologists to conclude that the population, unlike that of Pompeii, where many died as they were undertaking their daily tasks, escaped the tremendous volcanic eruption of 79 AD. Only six victims have been found in the town, a number that is consistent with sudden deaths that typically occur in mass panic situations. In 1982 the archaeological excavation of Herculaneum’s ancient beach began, and we discovered that notwithstanding the near-perfect evacuation of the town there were victims of the eruption. Indeed, the skeletons of about 250 people were found, some on the ancient beach, and some inside sheds built on the beach that had probably been used to store boats (figure 1). This discovery opened many new, unexpected paths for research; in particular it throws light on the paleobiology of an ancient Roman population whose habits and culture are well known to archaeologists. At the same time, the discovery leads to unsettling questions: why was the city fully evacuated, and why, despite the evacuation, did some of the population die? When, and how, was the evacuation carried out, and when, and how, did death occur? Over the past 5 years I have used taphonomy (study of fossilisation) and compared archaeological and anthropological data, and my findings help to answer these questions. Foremost, we know the precise chronology of the volcanic eruptions from both historical sources and geological data. Pliny the Younger 1,2 wrote an account of the eruption, and volcanologists have studied in detail the sequence of eruptive phases. The eruption was preceded by a series of earthquakes, and began in the afternoon of Aug 24, 79 AD. However, the inhabitants of Herculaneum were unimpressed by events; at least some remained in the town, and only by nightfall was the exodus concluded, as is shown by the volcanic rock strata, and as is suggested by the oil lamps some of the victims had in their hands. 3

Osteoma: palaeopathology and phylogeny

Osteoma is a poorly understood benign bone tumour, the truly neoplastic origin of which has been debated by several authors. Some scientists underline its relationship with hyperostosis. Other authors deny the existence of osteoma as an autonomous nosographic entity. Cranial osteoma, single or multiple, is frequently found in ancient human bones from archaeological excavations. To clarify the true nature of this pathologic osseous neoformation, the author examines the occurrence of osteomata in other extant vertebrates. Comparative pathology shows that it is particularly frequent in fishes. Palaeopathological examination of fossil animals documents the great antiquity of this pathology: in fact osteoma was demonstrated on the body of a cervical vertebra from a Cretaceous mosasaur. The author found evidence of osteomata in many fossil fishes of the Miocene and the Pliocene, and also in some mammal remains. Histologic and radiographic analyses demonstrate the presence of common morphologic characteristics in the lesions in different species and different time period. In conclusion, the study shows that human osteomata (mainly cranial) have a long history and are a pathology found in many other vertebrates.

Use of a multiplex polymerase chain reaction assay in the sex typing of DNA extracted from archaeological bone

We developed an original method that allows the simultaneous molecular amplification and analysis of human chromosome X- and Y-specific sequences from cortical compact bone using the polymerase chain reaction (PCR). The strategy is based on sequential amplification using external and internal primers. The targeted loci are SRY for chromosome Y and DXZ4 for chromosome X. Internal and external primer pairs for both loci were selected in order to allow the simultaneous amplification of short sequences of distinct molecular weight in the same reaction. Ethidium bromide stained PCR products were analysed on 2 per cent agarose gels. The presence of two distinct amplification bands permitted the fast and unequivocal identification of male bones, whereas female bones were identified by the presence of a single band. The technique was validated by comparative analysis of modern human DNAs of known sex and of DNAs from medieval bone samples whose sex could be determined using conventional anthropological methods. We then analysed bone samples from 40 burials found under the Church of St Maria Aprutiensis in Teramo, Abruzzo. These burials were dated to AD 800–1200 by 14C accelerated mass spectrometry radiometric analysis. Molecular analysis allowed the unambiguous identification of sex in all the samples studied. These results indicate that molecular techniques represent useful and often critical additions to anthropological studies of ancient human remains.

Odontometric sex estimation on three populations of the Iron Age from Abruzzo region (central–southern Italy)

BACKGROUND In archaeological contexts, sex identification is a necessary step for a complete reconstruction of the biological profile of the individuals and to know demographic patterns of the population, nutritional stress, diseases, growth and development, and distribution of pathological conditions. METHODS This study is based on the skeletal remains of 149 individuals from three protohistoric populations in close temporal and geographic proximity in Abruzzo region (central-southern Italy): Opi, Alfedena and Bazzano. It has been possible to develop logistic regression equations based on dental measurements of permanent teeth of adult individuals whose sex had previously been estimated based on pelvic and cranial features. These equations were subsequently applied to the permanent dentition of immature individuals and adult individuals whose sex was estimated as uncertain or unknown in order to estimate their sex. RESULTS The mandibular canine is the tooth with the greatest sexual dimorphism in adults, followed by both maxillary and mandibular first and second molars, providing a correct assignment of sex ranging from 83.7% and 95.9% of cases, depending on the dimensions used for the construction of these equations. Of the 29 individuals in the target sample (14 adultus, 10 juvenilis and 5 infans), sex estimation was possible for 23 (10 adultus, 8 juvenilis and 5 infans), representing an applicability rate of 79.31% of the individuals. CONCLUSIONS The results indicate that odontometrics is a useful tool for sex estimation and allows to increase the data to perform more complete paleodemographic studies on archaeological populations.

The Heart of Santa Rosa

Santa Rosa is a well preserved mummy dating back to the 13th century AD. It is conserved in the monastery of the same name, Santa Rosa, located in Viterbo, near Rome. In 1995, the Section of Anthropology of the State University “G d’Annunzio” of Chieti was entrusted with the preservation of the mummifi ed body. Scientifi c examination provided an opportunity to obtain anthropological and pathological data with modern techniques. Examination has confi rmed that Santa Rosa was a gracile girl, who died at the age of 18–19 years. Investigations showed total agenesis of the sternum–a variant of Cantrell’s syndrome. We examined the heart of Santa Rosa, which was removed from her chest in 1921. The heart of Santa Rosa is a mummifi ed specimen of small dimensions lacking the great arteries and systemic and pulmonary veins (fi gure A). External and internal inspections with a lens and stereomicroscope, and radiography were done (fi gure B). Although the posterior walls of the atria had already been removed, the appendages suggest situs solitus of the atria, and the morphology of the ventricles indicate atrioventricular concordance with d-loop of the ventricles. The apex of the heart is bifi d due to a diverticulum of the left ventricle. The low intensity radiograph shows a right deviation of the ventricular septum and the presence of a mass, probably a thrombus, between the apex of the left ventricle and the entry of the diverticulum. Ventricular diverticulum is one of the most common heart defects described in patients with Cantrell’s syndrome and is frequently associated with development of thrombus and subsequent embolisation. One theory is that Santa Rosa died of tuberculosis. However, biomolecular and paleopathological analyses of the mummy showed no evidence that an infectious chronic disease occurred in vitam. The present data suggest that a cardiac embolism could have been the cause of her death.