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Infectious Disease Part 1: Treponemal Disease & Smallpox

5 Oct

The following two posts deal with biomolecular approaches and research studies in detecting the presence of infectious diseases in human bone from archaeological material.  The recent coming of age of biomolecular techniques, as applied to archaeological material, has provided a rich and complex source of information in helping to uncover how infectious diseases spread in the historic and prehistoric past.  Whilst it has help clear some mysteries up, it has unleashed others.  The first post, here, describes recent research focused on Treponemal diseases (including Yaws, Syphilis and Pinta) and Smallpox.  The second post can be found here.


Treponemal Diseases

Roberts & Manchester (2010: 216) note that infectious diseases are ‘not solely microbiological entities but are a composite reflection of individual immunity, social, environmental, and biological interaction’.  The study of treponemal disease, in particular, is fraught with controversy and stigma, both in the modern and historical contexts (Lucas de Melo et al. 2010: 1, Roberts 2000), and in the nature of its spread and transmission.  However the combination of molecular pathology, phylogenetics, and palaeopathological studies, are helping to produce a clearer genetic origin of the disease and the impacts that this disease had, and continues to have, on the world at large (Hunnius et al. 2007: 2092).  Typically the bacterial diseases of the genus Treponema are split into different forms; pinta (T. carateum), yaws (T. pallidum subspecies pertenue), endemic syphilis (T. pallidum subspecies edemicum) and venereal/congenital syphilis (T. pallidum subspecies pallidum) (Table 1; Lucas de Melo et al. 2010: 2).  The four forms were, until recently, indistinguishable in physical and laboratory characteristics (Roberts & Manchester 2010: 207), whilst the pinta strand does not affect bone (Waldron 2009: 103).  DNA analysis of the bacteria of venereal syphilis has shown a difference between it and the non-venereal types; although it is noted that there is no change in the clinical presentation of the disease (Roberts & Manchester 2010: 207).

Table 1. Geographic location, transmission and whether bone is affected for treponemal disease (after Waldron 2009: 103).

Yaws was likely the first disease to emerge, probably from an ape relative in Central Africa, whilst the endemic form of syphilis derived from an ancestral form in the Middle East and the Balkans at a later date, whilst T. pallidum was the last to emerge, probably from a New World progenitor, although the issue is still highly contentious (Roberts & Manchester 2010: 212, Waldron 2009: 105).  Gaining virulence at a dramatic rate in the 15th and 16th centuries AD in Europe, venereal syphilis affected a large section of the population due to its mode of transmission.  It should be noted, however, that bone changes in syphilis are rare in the early stages but common in the tertiary stage of the disease (Roberts & Manchester 2010).  It has also been noted that there could be a back and forth transmission, from one treponemal disease to another, within intra-population groups changing from one environment to another; that ultimately it’s possible that each social group, or population, has its own treponemal disease suited to its ‘geographic and climatic home and its stage of cultural development’ (Roberts & Manchester 2010: 213).

However, this infectious disease, in its venereal form, is particularly hard to locate and identify in archaeological populations; the limitations of biomolecular palaeopathology have become clear (Bouwman & Brown 2005: 711, Hunnius et al. 2007, Lucas de Melo et al. 2010: 10).  Bouwman & Brown’s (2005) experiment, and Hunnius et al. (2007) subsequent paper, have highlighted the difficulties in amplifying T. pallidum subspecies T. pallidum, even in highly suspected bone samples.  Bouwman & Brown (2005: 711) tested 9 treponemal samples using the Polymerase Chain Reaction (PCR) tests, optimized to highlight ancient treponemal DNA.  This resulted in poor amplification of  treponemal ancient DNA (aDNA) from human bone, even with bone of varying origins (geographic, social and climatic samples).  3 outcomes where postulated; the bones were either not suitable for aDNA retrieval, treponemal aDNA was present but the PCR was not sensitive enough to be pick it up, or there was no treponemal DNA in the bones (Bouwman & Brown 2005: 711-712).  Subsequent investigations and phylogenetic approaches have highlighted that the disease invades different parts of the body at impressive rates, but in the later stages of the disease, the organism’s DNA is not present in the actual bone itself, just at the stage when an osteologist can identify it macroscopically (Hunnius et al 2007: 2098).  Phylogenetic evidence supports evidence of variations in the virulence of syphilis, and the support of a more distant origin, possibly around 16,500 to 5000 years ago, but where exactly remains unsolved (Lucas de Melo et al. 2010: 2).  Interestingly, in the early 20th century P. Vivax (the main causer of malaria) was used as a treatment for patients with neurosyphilis in a procedure by the physician Julius Wagner-Jauregg; it was injected as a form of pyrotherapy to introduce high fevers to combat the late stage syphilitic disease by killing the causative bacteria (Wagner-Jauregg 1931).


The Smallpox virus is particularly devastating and disfiguring disease, but thankfully no longer an active infection in the modern world (Manchester & Roberts 2010: 180).  Although kept only in laboratory samples now, there is an ongoing concern regarding whether it could be a danger to modern archaeologists dealing with infected material (Waldron 2009: 110).  The disease, once contracted, either leads to recovery with lifelong immunity or death.  The severe form is called variola major and is documented in the Old World with a 30% death rate once contracted, whilst its less virulent form, named variola or alastrim minor, is found in Central America and has a mortality rate of 1% (Hogan & Harchelroad 2005, Li et al. 2007: 15788).  Smallpox, the strictly human variola virus pathogen, is found in literature and documentary records during the last 2000 years (Larsen 1997), yet an osteological signature is not present or identifiable in infected individuals (Waldron 2009: 110).  Therefore to find out the origins of the disease, Li et al. (2007) used correlated variola phylogenetics with historical smallpox records to map the evolution, origin and transportation of smallpox between human populations.

Li et al. (2007: 15787) state that no credible descriptions of the variola virus have been found on the American continent or sub-Saharan Africa before the advent of westward European exploration in the 15th century AD; suggesting that with European exploration and expansion came the virulent waves of smallpox that helped to decimate the existing Native American populations, who previously had no contact or natural immunization with such a highly virulent disease.  It is worth noting here the disease has been used in warfare as a chemical weapon surprisingly early.  During the 18th century American colonial wars between the French, British and the Native Americans, the British forces stationed in America actively infected items of clothing that were given to the Native population to help aid the spread of the disease among the Native Americans , who at that time were largely allied to the French.  This weakened the Native American population dramatically during the various colonial wars and subsequent colonial expansion westward; it’s estimated nearly half of the American Native population died from smallpox alone and its naturally rapid commutable spread of smallpox through human populations (Hogan & Harchelroad 2005).

Li et al. (2007: 15787) note that there are ambiguous gaps in the evolution of smallpox disease itself however.  Li et al. (2007) initiated a systematic analysis of the concatenated Single Nucleotide Polymorphisms (SNP’s) from the genome sequences of 47 variola major isolates from a broad geographic distribution to investigate its origins.  Variola major has a slowly evolving DNA genome, which means a robust phylogeny of the disease is possible (Hogan & Harchelroad 2005).

Firstly, the results showed that the origin of variola was likely to have diverged from an ancestral African rodent–borne variola like virus, either around 16,000 or 68,000 thousand years ago dependent on which historical records are used to calibrate the molecular clock (East Asian or African) (Li et al. 2007: 15791).  Taterapox virus is associated with terrestrial rodents in West Africa, and provides a close relationship with the variola virus.  It is entirely possible that variola derived from an enzootic pathogen of African rodents, and subsequently spread from Africa outwards (Li et al. 2007: 15792).  Secondly, evidence points towards two primary clades of the variola virus, both from the same source as above, but each represent a different severity and virulence of the variola virus.

The first primary clade is represented by the Asian variola major strains, which are the more clinically severe form of smallpox;  the molecular study of its natural ‘clock’ suggests it spread from Asia either 400 or 1600 years ago (Li et al. 2007: 15788).  Included in this first primary clade is the subclade of the African minor variation of the main Asian variola major disease.  The second primary clade compromises two subclades, of which are the South American alastrim minor and the West African isolates (Li et al. 2007: 15788).  This clade had a remarkably lower fatality rate in comparison to the above clade.  The importance of phylogeny analysis is that it highlights areas of disease prevalence and virulence that can be missed, or indeed entirely absent, from the osteological and archaeological record (Brown & Brown 2011).


Bouwman, A. S. & Brown, T. A. 2005. The Limits of Biomolecular Palaeopathology: Ancient DNA cannot be used to Study Venereal Syphilis. Journal of Archaeological Science. 32: 703-713.

Brown, T. & Brown, K. 2011. Biomolecular Archaeology: An Introduction. Chichester: Blackwell Publishing.

Hogan, C. J. & Harchelroad, F. 2005. Smallpox. Emedicinehealth. Accessed at on the 29th of April 2012.

Hunnius, T. E., Yang, D., Eng, B., Waye, J. S. & Saunders, S. R. 2007. Digging Deeper into the Limits of Ancient DNA Research on Syphilis. Journal of Archaeological Science 34: 2091-2100.

Larsen, C. S. 1997. Bioarchaeology: Interpreting Behaviour from the Human Skeleton. Cambridge: CambridgeUniversity Press.

Li, Y., Carroll, D. S., Gardner, S. N., Walsh, M. C., Vitalis, E. A. & Damon, I. K. 2007. On the Origin of Smallpox: Correlating Variola Phylogenics with Historical Smallpox Record. Proceedings of the National Academy of Science. 104 (40): 15787-15792.

Lucas de Melo, F., Moreira de Mello, J. C., Fraga, A. M., Nunes, K. & Eggers, S. 2010 Syphilis at the Crossroad of Phylogenetics and Palaeopathology. PLoS Neglected Tropical Diseases.4 (1): 1-11.

Mitchell, P. 2003. The Archaeological Study of Epidemic and Infectious Disease. World Archaeology. 35 (2): 171-179.

Roberts, C. & Manchester, K. 2010. The Archaeology of Disease. Stroud: The History Press.

Wagner-Jouregg, J. 1931. Verhutung und Behandlung der Progressiven Paralyse durch Impfmalaria.  Handbuch der Experimentellen Therapie, Erganzungsband Munchen.

Waldron, T. 2009. Palaeopathology. Cambridge: Cambridge University Press.

The Origins of Tuberculosis & Smallpox

3 Jun

The following articles cited were brought to my attention by the good work of Confusedious: A Science Blog, and his entries on TB and its  possible origin.

Surprising Origins of Tuberculosis & Smallpox

Recent genetic investigations into the origin of the above diseases, of the chromosomes in TB and the study of smallpox’s ‘biological clock’, has revealed interesting information regarding their origin.   TB and Smallpox were previously thought caused or at least had its early origins during the domestication of animals, and by the dense urbanisation of human populations, first seen during the Mesolithic to Neolithic transition (Tuberculosis- Barnes et al 2011, Larsen 1997, Roberts & Manchester 2010, Smith et al 2009, Smallpox- Li et al 2007, Waldron 2009).

Compression Of Vertebrae As An Effect Of TB

Tuberculosis was originally thought to be spread from bovine at the period of domestication, with the strains M. Tuberculosis and M. Bovis to be considered the main organisms for TB infection in humans.  New genetic research has led to distinguish that M. Tuberculosis did not evolve from M. Bovis at the time of domestication of animals as a direct zoonosis; however it must be remembered that ‘it is probable that a necessary condition for its transference from animal to human is the close association between the two’ (Roberts & Manchester 2010: 184, Smith et al 2009).  I’d imagine the intensification of the Neolithic domestication undoubtedly led to higher rates of cross-species infection.  Research has also shown that the Mycobacterial Tuberculosis strain appeared some 15,300-20,400 years ago, well before the domestication of the earliest animals (Roberts & Manchester 2010: 185).  However there is no doubting the record that during the Neolithic, and up to the present day, that TB has damaged numerous lives.  The effects of TB on the human body can produce results found in osteological remains (Waldron 2009).  This will be discussed in a later blog entry on diseases found in human bones.

The threat of smallpox, a unique infectious disease to humans, was wiped out in AD 1980, but its origins are mysterious.  As Roberts & Manchester (2010: 181) note smallpox (Variola major or minor) ‘would obviously need highly populated urban areas for its success…and it is unlikely it was a problem until urbanization occurred’.  Recent genetic investigations into the origin of the Variola major/minor have discovered that it likely diverged from an ancestral African rodent-borne Variola-like virus either 68,000 to 16,000 BP (Li et al 2007).  However, it is well known that in its most virulent form in humans as smallpox, it has ravaged human urbanised populations for at least 2000 years, and is definitely dated to 10,000 BP.  Curiously, from documentary data and archaeological data, it seems there is a particular lacking of recorded smallpox cases in ancient Greece and ancient Rome (Roberts & Manchester 2010).

The Effects of Smallpox Decimated The Americas When The Europeans Helped Spread the Disease in the 16th Century, As Depicted In This, The Florentine Codex.

New genetic data is providing the backdrop for how infectious diseases spread, and more about their origin.  It is also helping scientists develop past population pathways for infection routes and rates (Jurmain et al 2011).It is apparent that new genetic data has opened up a whole raft of new research potentials into the origins and evolution of tuberculosis, and the relationship before, during and after the domestication of animals.


Barnes, I.Duda, A. Pybus, O. G. Thomas, M. G. 2011. ‘Ancient Urbanization Predicts Genetic Resistance To Tuberculosis’. In Evolution. 65 (3): 842-848. Blackwell Publishing: London.

Jurmain, R. Kilgore, L. & Trevathan, W.  2011. Essentials of Physical Anthropology International Edition. London: Wadworth.

Li, Y. Carroll, D. S. Gardner, S. N. Walsh, M C. Vitalis, E. A. & Damon, I. K. 2007. ‘On The Origin of Smallpox: Correlating Variola Phylogenics with Historical Smallpox Record’. In PNAS. 104 (40). October 2nd.  15,787-15,792.National Academy of Sciences: Wisconsin.

Roberts, C. & Manchester, K. 2010. The Archaeology of Disease Third Edition. The History Press: Stroud.

Smith, N. H. Hewinson, R. G. Kremer, K. Brosch, R. & Gordon, S. V. 2009. ‘Myths and Misconceptions: The Origin and Evolution of Mycobacterium tuberculosis’. In Nature Reviews: Microbiology. Vol 7. 537-544. Macmilan Publishers Limited: London.

Waldron, T. 2009. Palaeopathology: Cambridge Manuals in Archaeology. Cambridge:Cambridge University Press.