RICERCA ITALIANA     

DISEASES, ENVIRONMENT AND SOCIETY AT THE GRAND DUKE COURT OF FLORENCE: AN HISTORICAL, ARCHAEOLOGICAL AND PALAEOPATHOLOGICAL STUDY OF THE MEDICI FUNERARY DEPOSITIONS (XVI-XVIII CENTURIES)

Università di Pisa

Abstract

The reseach project aims to perform a historico-medical and palaeopathological research on the 49 funerary depositions of the Medici Grand Dukes, from Giovanni delle Bande Nere (+1526) to Anna Maria Luisa (+1743), buried in the famous Medici Chapels of the Basilica of San Lorenzo in Florence.
The historico-medical research will be structured on two levels:
individuation and classification of written sources, both published and unpublished, delineating the relationship between lifestyle, illness and therapies specific of the age to which the Medici individuals belong; reconstruction of the evolution of contemporary medical knowledge and therapeutical treatments for the pathologies diagnosed by the paleopathological équipes.
The aim is to integrate biomedical data with the chronological perspective of biographical data, and vice versa.
The palaeopathological research will include: funerary archaeology, anthropology, palaeonutrition (by spectroscopy and atomic absorption, infrared spectroscopy (for the study of macromolecules), parasitology, pathological anatomy, histology, histochemistry, immunohistochemistry, electron microscopy, molecular biology (study of ancient DNA) and identification of the different types of ancient pathogens.
We intend also to perform a molecular screening on the mummified and skeletal remains of the Medici for the presence of residual human, bacterial and viral DNA.
To obtain information on genetic relationships between mummies, ancient DNA from the Medici family will be investigated through the study of the mitochondrial DNA control region.
Since historical record indicates that several members of the dynasty died of infectious diseases such as tuberculosis, syphilis, plague and smallpox, the aims of the palaeo-DNA investigation are to confirm the paleopathological diagnosis performed on the basis of the macro- or microscopic examination of the remains, and to detect the infectious diseases also in the absence of anatomical or histological evidence.
In conclusion, all the most recent biomedical techniques will be adopted for a global biological reconstruction in order to obtain as much information as possible about the environment, style of life and diseases (Pathocenosis) regarding these important personages of the Italian Renaissance.
Finally, the research will be involved in the creation of a centralized ancient human remains bio-repository to address the need of permanent preservation of ancient biological samples of historical and cultural relevance. <<<

Principal Investigator

Gino FORNACIARI Università di PISA

Research Objectives

About 50 bodies of the Medici Grand Dukes, in most cases embalmed and buried in the crypts of the Medici Chapels in Florence, are still in good state of preservation and have never been examined systematically. Only at the end of the 40's the corpses were submitted to a brief anthropological study.
The project entails a systematic palaeopathological research, carried out on the remains of the members of the Medici Family of the Grand-ducal branch and on the iconographic and literary-historical sources.
The historical and palaeopathological study will include the identification of all the stigmata that have left a sign on ancient human remains, both skeletonized and mummified, or that are documented by archive data.
The research will involve a number of specialistic approaches, including:
- a study of iconographic, archivistic and literary-historical sources;
- a study by means of imaging techniques so as to evidence morpho-structural alterations on bone segments, related to congenital and/or acquired modifications, or related to presumed diseases. The diseases diagnosed will be subdivided into two different classes. One will include "real diseases", defined as important pathologic conditions (tumours, tuberculosis, leprosy and some major infectious diseases that may have left a trace on the remains); the other will group "minor" pathologies, showing less severe features, but still conditioning the life of the person affected (osteo-articular diseases, diseases due to various deficiencies). The influence of lifestyles and of environmental conditions will be studied in depth.
The objectives are ample and articulated as described below:
- reconstruction of the life styles with specific reference to the dietary habits, physical activity, daily life activities of the Medici family;
- retrospective interpretation of the historical sources in the light of the evidence provided by the paleopathological study;
- correlation between the data of traditional iconography and the findings of imaging iconography;
- reconsideration of the nosography of past centuries in the light of current palaeopathological findings.
We intend also to perform a screening of the skeletal remains of a series of member of the Medici family of the XVI - XVIII centuries for the presence of residual bacterial and viral DNA. Actually, the historical record indicates that several members of the dynasty died of infectious diseases such as tuberculosis, syphilis, plague and smallpox.
The aims of the palaeo-DNA investigation are different: 1) to confirm a palaeopathological diagnosis performed on the basis of the macro- or microscopic examination of the remains; 2) to clarify controversial diagnoses; 3) to detect infectious diseases in the absence of anatomical or histological evidence.
With regard to infectious diseases we will focus on molecular analysis of Treponema pallidum, causative agent of venereal syphilis, and Plasmodi, causative agents of malaria.
We will examine also the mitochondrial control region HVRI, which may provide data not only on DNA preservation, but also on the maternal genetic variability of the mummies examined.
The palaeopathological study of the bodies would increase considerably the knowledge currently available about the diseases and life habits, as well as the personality of the members of that dynasty, fundamental for the Italian Renaissance.
This is one of the objectives of the Medici project, which is aimed at performing a deep and diversified study, at various levels, starting from the anthropological, palaeopathological, radiological and endoscopic examination of the mummies.
The laboratory analyses will include: anthropology, palaeonutrition (by spectroscopy and atomic absorption, infrared spectroscopy (for the study of macromolecules), parasitology, pathological anatomy, histology, histochemistry, immunohistochemistry, electron microscopy, molecular biology (study of ancient DNA) and identification of the different types of ancient pathogens.
In conclusion, all the most recent biomedical techniques will be adopted for a global biological reconstruction in order to obtain as much information as possible about the environment, style of life and diseases regarding these important personages of the Italian Renaissance.
We plan to create a centralized ancient human remains biorepository in order to collect, preserve and analyze biological samples from the Medici family. Each sample will be characterized with accompanying provenance information including historical data. This objective provides a basic tool for implementing the upstream objectives, and represents an important goal in itself, as it will entail development of an advanced International facility that will be extremely valuable as a resource for furthering studies also beyond the present scopes. Moreover, ethical and legal issues related to collection, storage and distribution of biomaterials from human remains will be carefully considered. <<<

Timescale

24 months

National and international background

Palaeopathology, which studies the morphological remains of ancient diseases, has over the past decades become an independent discipline comprising history, archaeology, physical anthropology and pathological anatomy. Therefore, palaeopathology is different from the history of medicine, mainly concerned with the history of physicians, from both a biographical and theoretical point of view, and of the therapies, and based exclusively on historical and literary sources. Palaeopathology studies the diseases of a more or less recent past, through direct examination of ancient skeletal or mummified human remains. As concerns those periods for which written documentation is available, palaeopathology also resorts to historical sources, but only as an aid to the interpretation of pathological patterns obtained directly from the human remains.
Although a relatively recent science, a considerable number of researches and studies have given important results.
Palaeopathology has both a historical and medical interest:
1. Historical, because from the features and incidence of the different pathologies it is possible to go back, indirectly, to the habits and life-styles of ancient populations;
2. Medical, because study of the onset of some important present-day diseases, such as cancer and atherosclerosis, and the reconstruction of the origins and early diffusion of infectious diseases, have aroused a strong interest in the field of medicine.
Over the past thirty years the study of ancient diseases has had great international development. Recent international meetings have shown all the new technologies applied in this research field, with a better understanding of bone tissue pathology. Radiological techniques such as computerized tomography (CT) and 3-D CT have been adapted to the study of ancient human remains. Dietary reconstruction, using trace elements analysis and stable isotope ratios, have made palaeonutrition a more exact science. During the last ten years, development of the polymerase chain reaction (PCR) has produced remarkable discoveries on ancient DNA (aDNA), changing the physiognomy of palaeogenetics and our knowledge of infectious disease in ancient times.
In Italy, the series of mummies and in particular the single mummies are relatively numerous. Depositions are generally of the Renaissance, modern, but also medieval periods, and all constitute precious palaeopathological material.
The palaeopathological study of the Italian mummies has a strong scientific interest for the large number of specimens, perfect state of preservation of the bodies, and importance of historical personages. The numbers vary from a few dozens to several thousands, as in the case of the Capuchin Catacombs in Palermo, Sicily.
The project concerns the study of a series of mummies very important from the historical and palaeopathological point of view: that of the famous Medici Chapels of the Basilica of S. Lorenzo in Florence.
Mummies of the Medici family represent an important sample of Italian lifestyle and pathologies in the era of the "long" Renaissance (1450-1700). The historical meaning of the Medici in Italian political and cultural history cannot be downplayed. Their lives, diseases and illnesses, together with the remains of their bodies, allow meaningful generalizations on material and cultural history - as well as on epidemiology and nosology. Aragonese mummies, conserved in the Basilica of S. Domenico Maggiore, Naples, have already been studied and no doubt useful comparisons will be drawn with the Medici mummies.
The project aims at identifying and studying historical, archival and other documentary evidences that can prove useful in studying the mummies.
Plague, syphilis, smallpox, malaria, tuberculosis, typhus, were all to be found in Tuscany, and particularly in Florence, from the 15th to the 18th centuries. We know from medical and literary ancient texts that many important epidemics described by classical authors were in fact typhus; that malaria was already endemic in central Italy in Roman imperial age; that bubonic plague was endemic in Europe during the Middle Age; that syphilis has been first described in Europe at the end of the 15th century, and immediately understood as coming from the New World.
Such a historiographic approach is easily related to the study of the genetic evolution of specific pathogen micro organisms (viruses, vibrios, bacteria) aiming at the reconstruction of the social and environmental factors that favoured the spreading of the infectious diseases, causing epidemics and pandemics.
Data gathered from medical history analyses can be compared and implemented with the results of palaeomicrobiological research. The latter, using up-to-date techniques - histology, chemical histology, immunochemical histology - allows retrospective diagnoses of infectious diseases. Microbiological findings in human remains allow the gathering of essential epidemiological information on the history of diseases, of the evolution of pathogens, of their interaction with the environment.
In the early 20th century, beginning with the French Annales historiography, historical research has developed new methods for the reconstruction of material everyday life, taking into account archival and biographical sources.
An interdisciplinary approach is thus required - also in the field of the history of medicine - as testified by studies performed using both bibliographical and archival sources and paleopathological findings (skeletal remains and mummies) in order to assess the relationship between lifestyle and illness during the Middle and Modern Ages.
New biochemical and molecular technologies offer a new approach for the study of genetic information contained even in a small amount of DNA, molecule that, under specific conditions, can be preserved in ancient human remains. Palaeogenetics and molecular palaeopathology of mummified tissues and skeletal remains open new prospectives for a retrospective and more precise diagnosis of diseases, their occurrence, frequency and interactions with environmental factors in historic times and population.
For this reason, the ancient remains of the Medici family represent an important sample with cultural and historical relevance; if adequately studied these remains might provide direct data on ancient diseases that arose in individuals assigned to precise historical and social contexts.
Historiography on infectious diseases in Italy indicates that syphilis and malaria were present in Central Italy and in particular in Tuscany from the 15th to the 18th centuries. A review of the medical history suggests that syphilis originated in the Old World. Although rare, human treponematosis was indeed endemic in the pre-Columbia New World before contact. With the help of molecular methods which now allow a positive identification of Treponema pallidum, causative agent of venereal syphilis, in palaeopathological material, it seems possible to elucidate the matter of origin and spread of syphilis further and to evaluate previous diagnoses of treponemal disease. We know from medical and literary ancient text that malaria was already endemic in Central Italy in Roman Imperial age. Indeed, molecular studies conducted on ancient skeletal remain from an infant cemetery of the 5th century in Lugnano in Teverina (Umbria) revealed the presence of DNA sequence of Plasmodium falciparum, one of the four species of protozoan that cause malaria. Plasmodium falciparum is the most virulent species and is cause of mortality and morbidity in sub-Saharan Africa. Most geographically widespread and prevalent in some region (Asia, Central and South America, Middle East) is Plasmodium vivax. The detection of different ancient Plasmodi DNA is of great relevance taking into account that residual anophelinae population capable of Plasmodi transmission pose a permanent risk for the (re)emergent of malaria where it currently does not exist, as observed in Tuscany, Central Italy. The detection of ancient microbial DNA offers a new approach for the study of infectious diseases, their occurrence, frequency and host-pathogen interaction in historic times and populations. Moreover, data obtained from skeletal and mummified tissues may represent an important completion of contemporary phylogenetic analyses of pathogens. A new field of "ancient pathogens" is making an impact on our concepts of the evolution of infectious diseases, and it will eventually alter the practice of public health in their control.
Palaeo-oncology is the study of carcinomas and sarcomas in ancient human populations. These populations are informative concerning the possible influences on cancer of morphologic and functional evolution, diet, lifestyle, and other environmental factors. Tumours arise from the clonal expansion of somatic cells carrying genetic mutations often due to the interaction with environmental mutagens, including infectious agents and physical or chemical carcinogens.
For this reason, the molecular study of tumours identified in ancient mummies could contribute to shed light on the history of neoplasms and on the relationships between mutations, lifestyle, and environmental risk factors through time.
In this respect, studies conducted in the last years allowed the discovery of smallpox particles in a 16th century mummies, the identification of a K-ras mutation in a carcinoma that affected Ferrante I of Aragon, king of Naples, at the end of 15th century and the demonstration of human papillomavirus (HPV) in a Renaissance mummy.
The important assemblages of late Medieval to Early Modern age mummies represent a scientific and cultural heritage of the utmost importance. In fact, if adequately preserved and studied with a multidisciplinary approach, these mummies might provide direct data on ancient diseases that arose in precise historical and social contexts.
The analysis of ancient pathogen DNA represents one of the most recent and promising fields of molecular palaeopathology. This type of quest can have different goals: 1) to confirm, through the identification of the DNA of the etiological agent, a paleopathological diagnosis made on the basis of a macro- and microscopic examination of the remains; 2) to solve controversial cases; 3) to show a (palaeo)pathological state in the absence of anatomical or histological evidence.
Reports, covering all the above listed situations, are now available on the scientific literature.
The first case is well exemplified by the paleopathological diagnosis of tuberculosis. Its bony manifestations potentially enable its identification in early skeletal remains, and indeed palaeopathologists have been studying tuberculosis in excavated material for over 100 years. The quest for Mycobacterium tuberculosis DNA has therefore the aim to confirm the diagnosis made on morphological grounds. In the recent past it has been applied, for example, to remains showing calcified soft (lung) tissue or spine deformity (kyphosis).
An example of the second situation is given by the molecular investigation performed on a skeleton from Bet Guvrin, Israel, dating from Byzantine period (IV-VII century A.D.). There were pathological changes in the lower extremities, which presented significant diagnostic problems. The original diagnosis was of Madura foot (a local, chronic disease caused by opportunistic bacteria or fungi). This conclusion, however, was later challenged by MANCHESTER (1993) who suggested leprosy as the cause of bone alteration. The controversy remained unresolved until Spigelman and Donoghue were able to demonstrate the presence of residual Mycobacterium leprae DNA in a bone specimen from the Bet Guvrin skeleton.
A particularly promising sector of the studies on ancient bacterial DNA is the third, i.e. the identification of pathogens that produce no bone lesion. The most authoritative example is given by the studies about the nature of the etiological agent of the medieval pandemic known as Black Death. Through the molecular analysis of remains of dental pulp, obtained from XIV century mass graves, they were able to identify the DNA of Yersinia pestis, the plague agent. At the same time they were able to exclude alternative etiologic agents such as Bacillus anthracis and Rickettsia prowazekii.
The important assemblages of late Medieval to Early Modern age mummies represent a scientific and cultural heritage of the utmost importance. In fact, if adequately preserved and studied with a multidisciplinary approach, these mummies might provide direct data on ancient diseases that arose in precise historical and social contexts. On this purpose, creation of a centralized human ancient tissues biorepository designed to collect, process, and distribute large numbers of high quality research specimens quickly and efficiently is a relevant issue. <<<