Pest Anatomized

Lindsey’s post on plague doctors spurred me to go look through the Wellcome library for plague graphics. Here is a neat one I found:

The Wellcome library lists the title as: Loimotomia, or, The pest anatomized : an historical account of the dissection of a pestilential body by the author. Together with the author’s apology against the calumnies of the Galenists, and a word to Mr. Nath. Hodges, concerning his late Vindiciae medicinae …

They did believe in long descriptive titles in the 17th century. It was written by George Thomson, MD (1629-1677) and published in 1666 during the Great London Plague. Something tells me I need to learn more about Dr Thomson!

Mapping Malaria in Anglo-Saxon England

Guthlac at Croyland in the marshes of the Wash.

England once looked very different. Much of southern Britain was marshland for most of the island’s occupied history. These bogs, fens, and marshes ensured that areas of virtual wilderness persisted  from before Roman Britain through the Norman period and beyond. Despite the difficulties of using fenlands, these areas were not only occupied throughout the Anglo-Saxon period, but important centers like Croyland, Bardney, and Ely eventually developed in the marsh.

The largest fenland region was known as ‘the Wash’.  This low-lying region drained four rivers into  a square bay of the North Sea that forms the corner between Lincolnshire and Norfolk. In Anglo-Saxon times, this tidal marsh and bog was a vast border region between the region of Lindsey and East Anglia.  Places like Croyland and Ely were islands in the wetlands.  The eighth century Life of Guthlac describes the environment of Croyland when Guthlac arrived:

There is in the Midland district of Britain a most dismal fen of immense size, which begins at the banks of the river Granta not far from the camp which is called Gronte (Cambridge) and stretches from the south as far north as the sea. It a very long tract, now consisting of marshes, now of bogs, sometimes with black waters overhung by fog, sometimes studded with woodland islands and traversed by the windings of tortuous streams. (Hill, 1981:11 cited in Gowland & Western, 2011).

These marshes are ideal for malaria, but evidence of malaria in Anglo-Saxon England has been lacking. It is supposed that malaria would have been brought to Britain with the Romans (1). Unfortunately, there is no evidence that I know of that malaria became endemic in Roman Britain much less lasted into the early medieval (Anglo-Saxon) period. It has also been speculated that ‘spring fever’ (lecten adl) found in Anglo-Saxon leechbooks is the spring manifestation of tertian malaria (1) caused by Plasmodium vivax. This would fit the pattern of malaria in cool or cold climates like that found in Finland discussed in a recent post. Indoor transmission in Anglo-Saxon earthen floored, open structured wooden homes with thatched roofs would be an ideal way to concentrate malaria in a thinly populated marsh.  (Without chimneys homes had to open enough to allow smoke to escape from a central hearth.)

Incidence of Malaria in England, 1840-1910 (2)

It has long been known that Britain can environmentally support endemic malaria. Malaria was fairly wide-spread in 19th century Britain when it was first mapped (figure to left) (2). The upper black area on the map includes much of ‘the Wash’. However, proof of malaria is more tenuous for the medieval period.  Together with the unhealthy reputation of the brackish marshlands there is at least enough evidence to suggest that endemic malaria reached back into the late medieval period.

Malaria went by a variety of local names before the early modern period. Malaria-like fevers are mentioned in literature from Geoffrey Chaucer to William Shakespeare (2, 3). Terminology for malaria was not settled upon the Italian ‘malaria’ until the early modern period. Before then, it went by a variety of terms the most universal being ‘ague’, meaning the shakes, and sometimes  ‘fever and ague’ referring to the cyclic breaking of a fever.

Gowland and Western (2011) took a new approach to finding evidence of malaria in Anglo-Saxon England (400-1100 AD) (4). Malaria caused by Plasmodium vivax causes chronic hemolytic anemia that may result in cribra orbitalia due to expansion of the bone marrow in the cranium. Gowland and Western correlated the presence of cribra orbitalia in Anglo-Saxon skeletal remains with the presence of the malarial vector Anopheles atroparavus and reports of ‘ague’ in 19th century England.

The Anglo-Saxon cemeteries used in their study are mapped in the figure below on the left. Note that not many cemeteries are located near the modern coastline of ‘the Wash’. This area would have likely been too wet for settlement.

Anglo-Saxon cemeteries (4)

Map of A. atroparvus with 19th century "ague" records. (4)

Gowland and Western  determined areas capable of sustaining malaria by mapping the presence of A. atroparvus from a 1900 AD British Museum survey (shown above on the right) (4).  The darker the shading the more reports of mosquitoes. This survey was reported to not have been systematic, so they augmented it with 19th century ‘ague’ reports (triangles).  There are some notable areas with high levels of mosquitoes that lack ague reports. This map was use to determine malarial regions for correlation with either cribra orbitalia or the poor nutrition control enamel hypoplasia. It also roughly correlates with the 1840-1910 malaria incidence in the color map above by Kuhn et al (2).

An inverse distance map showing A. atroparus incidence vs. hot and cold spots for cribra orbitalia. (4)

In this last map, malarial areas are plotted with hot and cold spots for cribra orbitalia.  Purple and blue areas on the map indicate the highest areas of A. atroparvus in 1900, while red and orange circles indicate the cribra orbitalia ‘hot’ spots. Areas of cribra orbitalia correlate very well with malarial areas around the Wash.  Cribra orbitalia ‘cold’ spots (blue circles) correlate with areas of low A. atroparvus. They found no correlation between enamel hypoplasia with either ‘malarial’ or ‘non-malarial’ areas (4).

If this cribra orbitalia is due to malaria, it is likely an underestimate of the amount of malaria in the English wetlands. Cribra orbitalia forms in children so it will not indicate adults who contract malaria. Communities like Ely, Croyland and Peterborough were large monasteries who probably drew many into the marsh as adults.

Confirmation of malaria in Anglo-Saxon England will have to wait for molecular evidence, but this skeletal evidence strengthens the hypothesis that it was endemic in early medieval Britain. It also should be informative for the areas to concentrate efforts to find molecular evidence.

References:

(1) Cameron, M.L. (1993, repr. 2006) Anglo-Saxon Medicine. Cambridge University Press.

(2) Kuhn, K., Campbell-Lendrum, D., Armstrong, B., & Davies, C. (2003). Malaria in Britain: Past, present, and future Proceedings of the National Academy of Sciences, 100 (17), 9997-10001 DOI: 10.1073/pnas.1233687100

(3) Reiter P (2000). From Shakespeare to Defoe: malaria in England in the Little Ice Age. Emerging infectious diseases, 6 (1), 1-11 PMID: 10653562

(4) Gowland RL, & Western AG (2011). Morbidity in the marshes: Using spatial epidemiology to investigate skeletal evidence for malaria in Anglo-Saxon England (AD 410-1050). American journal of physical anthropology PMID: 22183814

Pausing for Peace

Christmas is supposed to be a time of peace and good will toward all men. The Christmas spirit can be found in the most unlikely of places. Perhaps it is in the middle of these places that Christmas is yearned for more than anywhere else. Such was the case on Christmas eve 1914 when both sides agreed to pause for peace and fellowship in the midst of No Man’s Land during the war to end all wars.  Let us commemorate that remarkable event with a you-tube that I hope becomes a classic.

DNA of the Black Death at East Smithfield, London

It seems as though every couple of months a new paper is published reporting Yersinia pestis DNA from ancient remains. This week brought the latest installment from London’s East Smithfield Black Death cemetery. This cemetery holds a special place in the scientific investigations of the Black Death because it is so well documented as being specifically for the first wave of plague in 1348-1350 and the  recovery of so many well-preserved skeletons. This cemetery has been the subject of several bioaracheological studies, primarily by former plague skeptic Sharon DeWitte, making this one of the best characterized set of Black Death victims yet to be discovered. DeWitte is also one of the co-authors of this study.

Using a new method of ‘targeted enrichment’  and high through-put sequencing an international group led by Hendrik Poinar was able to clone and sequence relatively long stretches of Yersinia pestis DNA from recovered remains. They were given access to 100 samples (53 bones and 47 teeth) from which they found 20 positive results for Y. pestis. Unfortunately they don’t indicate how many individuals these samples represent. Although the bone yielded more aDNA, the teeth had far more positive results; 37% of teeth to only 5.7% of bones. Poinar’s group believes this is consistent with a blood-borne pathogen because the tooth pulp is more vascular than bone.

Poinar’s group has reconstructed more of the ancient genome than any group to date. They had the advantage of knowing that this burial pit was open for only a short time and specifically for plague victims. They worked under the assumption that all victims of the plague died from the same strain and were therefore able to construct a composite organism. They could not have made this assumption in a churchyard cemetery that could be open for centuries. They were able to reconstruct 99% of the pPCP1 plasmid (95% with five fold coverage) and showed that its sequence matches 11 of 14 known strains today. They were also able to reconstruct a portion of the pMT1 plasmid that contains genes for the F1 antigen and a small portion of the bacterial chromosome. The Black Death strain seems to be a variant of the Medievalis biovar, but its exact placement is unclear. This has led to premature claims that the Black Death strain is extinct. Given that they haven’t shown a single mutation/polymorphism that makes a functional change, there is no evidence yet that the medieval strain was intrinsically more virulent than modern strains.

They took great pains to close all of the possible technical questions. They obtained human remains from the cemetery of St Nicholas Shambles also in London that dates from about a century earlier to serve as negative controls. These 10 specimens remained negative throughout. They analyzed the types of DNA damage found in human mtDNA from both East Smithfield and St Nicholas Shambles, and compared the level and types of damage to the Y. pestis aDNA to prove the Y. pestis DNA was original to the remains. They followed all of the isolation and contamination prevention procedures recommended for aDNA and sent their clones to two independent high-throughput sequencing facilities to confirm the sequence. By comparing the sequences of the two facilities they were able to resolve DNA damage from true polymorphisms/point mutations.

Why is this study important? First and foremost, it confirms that a well-known Black Death burial pit was due to Yersinia pestis. They developed a method to reconstruct more of the ancient genome than has been done before that should improve our phylogenetic analysis of Y. pestis. They answered all of the technical questions  that should finally bring consensus on the cause of the plague. This does not mean that other pathogens didn’t co-circulate or that every epidemic labeled as the plague really was. Now its time to dig into the epidemiology and get to the really important questions!

Schuenemann, V., Bos, K., DeWitte, S., Schmedes, S., Jamieson, J., Mittnik, A., Forrest, S., Coombes, B., Wood, J., Earn, D., White, W., Krause, J., & Poinar, H. (2011). PNAS Plus: Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia pestis from victims of the Black Death Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1105107108

DNA Detective Work Identifies Black Death Culprit, NPR: Science Friday, September 2, 2011. Ira Flatow interviews Hendrik Poinar and Michael McCormick. (podcast)

Holly Tucker’s Blood Work

Holly Tucker, Blood Work: A Tale of Murder and Medicine in the ‘Scientific Revolution’. Norton, 2011.

I picked up this book at just the right time. I read it a few weeks ago just before I started teaching my summer anatomy course. Its always a good to be reminded of all of the work and drama that went into what seems like dull facts and standard procedures today. In this case there really was a lot of blood, sweat and tears by the medical establishments of two countries intensely throughout the 1660s before the work was banned for over a century. Holly Tucker’s Blood Work is centered on the century when the quest to understand blood went from counter-productive procedures based on medieval philosophy to the beginning of scientific understanding and experimentally based medicine.

Pride and glory drove the main protagonists of the story. For Jean-Baptiste Denis, the physician at the center of Blood Work,  the need to overcome his humble origins by proving his worth and more to the gentlemen physicians of France was a driving force. His benefactor Henri-Louis Habert de Montmor wanted to be the patron of the most brilliant, the most significant scientists of France, to be the Lorenzo de’ Medici to a scientific Michaelangelo. Add in an Anglo-French medical society rivalry and some pirates for good measure, and you have a page-turner of a history. I have to admit chuckling every few pages. Some of their experiments were like watching a train-wreck in slow motion. Holly Tucker is no doubt right that they were saved from causing much more damage by their inefficiency at transfusion.

I won’t give away any of the main plot or the murder, but there were some memorable sidelines. This description of ‘heroic medicine’ will stay with me for a while.

Claude arranged for a barber-surgeon to administer numerous bleedings to his brothers arms and legs. When bleeding seemed no longer to have any effect, they tried to place leeches behind Jean’s ears, but blistering there from other treatments with warming salves kept the leeches from doing their work. Bouillons, enemas, and purgings accompanied each bleeding in a desperate attempt to save Jean’s life. And to these were added chest rubs with concoctions of ground pearls mixed with extracts of hyacinth bulbs to warm Jean’s blood, as well as placement of gutted pigeons on his scalp to create heat to stave off the shivering. Despite Claude’s heroic attempts to save his brother (or perhaps because of them), Jean died a few weeks later. (p. 105-6)

Claude Perrault was one of the best trained physicians in France, and  a founding member of King Louis XIV’s Academy of Science. He held a prominent position in the Paris Faculty of Medicine and he used all learning to try to save his brother Jean. The idea of keeping your brother warm with a gutted pigeon on his head is priceless.

If you think that today’s publish or perish environment is tough, you should read what it did to Henry Oldenburg, who nearly single-handed published the Philosophical Transactions for the Royal Society of London. He volunteered his own time and talent, published at his own considerable expense for printing and postage, was accused to treason for gathering scientific news from France, and landed in the Tower of London for his troubles (where he had to pay rent for his prison cell). He then got out and worked even harder for the Royal Society (still for free) to reestablish his reputation. His treatment is enough to keep freelance science writers, bloggers, and researchers up nights.

I do have to say that I’m not bothered by the fact that the transfusion experiments were stopped. While Holly Tucker is no doubt right that other equally dangerous experiments and treatments were being done at the same time, the paradigm shift from blood letting to blood transfusion was too great, too fast. They didn’t understand even the basics of what they were transfusing and they were doing it for the wrong scientific and philosophical reasons. Simply stopping the blood letting would have improved survival significantly!

As memorable as the information and stories in Blood Work will be, perhaps more importantly it has made me think about the importance of narrative in books on history. So many of the history books I read are organized and written like textbooks, academic in their boredom as much as their content. I read them for their information rather than for entertainment. Its nice to have both!

Kalamazoo prep begins

The program for this year’s International Congress on Medieval Studies in Kalamazoo Michigan was released last week. I’ll be giving a talk on plague references in the Venerable Bede’s Prose Life of Cuthbert (c. 720). It is the earliest substantial plague text from Anglo-Saxon England. Cuthbert survived a case of bubonic plague as a young adult and went on to become a bishop during the second major wave of plague. I hope this will be the first component in a comprehensive study of the plague in the works of the Venerable Bede, one of the best sources for the later waves of the first plague pandemic.

Session 170

The Sacred and the Secular in Medieval Healing IV: Texts, Plagues, and Religious Healing

Sponsor: Medica: The Society for the Study of Healing in the Middle Ages and AVISTA: The Association Villard de Honnecourt for the Interdisciplinary Study of Medieval Technology, Science, and Art

Organizer: Linda Migl Keyser, Univ. of Maryland, and Barbara S. Bowers, Ohio
State Univ.

Presider: William H. York, Portland State Univ.

• Plague in Bede’s Prose Life of Cuthbert, Michelle Ziegler, St. Louis Univ.
• Religious and Medical Interpretations of Pestilence in the Late Middle Ages, Ottó Gecser, Eötvös Loránd Univ./Central European Univ.
• The Lytell Boke of the 24 Stones, Tom Blaen, Univ. of Exeter
• Hope and Heat: Secular Medicine and Human Faith in Two Late Medieval Resurrection Miracles, Leigh Ann Craig, Virginia Commonwealth Univ.