A medieval manuscript makes a novel contribution to modern microbiology

Kevin Lyons

Last year, researchers at the University of Nottingham prepared a medicinal eyesalve according to instructions found in an Old English manuscript from the mid-10th century, entitled Bald’s Leechbook – or, in Modern English, Bald’s Book for Physicians (Harrison et al., 2015). The list of ingredients for this eyesalve included garlic, wine, oxgall (bovine bile) and an ambiguously-named vegetable, now thought to be either onion or leek. The eyesalve appears to have been used to treat styes (eyelash follicle infections), which are most often caused by the Gram-positive bacterium Staphylococcus aureus – commonly known by its more infamous antibiotic-resistant form: methicillin-resistant S. aureus (MRSA). Despite the fact that a previous attempt by another group to measure the efficacy of Bald’s eyesalve had been unsuccessful (Brennessel et al., 2005), the researchers at the University of Nottingham and their collaborators at the Texas Tech University found that the eyesalve was very effective in killing both planktonic and biofilm forms of S. aureus, noting that “the remedy repeatedly killed established S. aureus biofilms in an in vitro model of soft tissue infection and killed methicillin-resistant S. aureus (MRSA) in a mouse chronic wound model”.

Significance

Medical texts from the Middle Ages are often dismissed as being rife with accounts of ineffective potions, superstitious rituals, and beliefs associating the causes of disease with the supernatural. While these accusations may often prove true, this leads to the quick assumption that we have nothing of modern clinical relevance to learn from such texts. Although many of the individual ingredients of Bald’s eyesalve have been known to exhibit antibacterial activities for some time, the efficacy of the concoction was found to be largely dependent upon careful adherence to the written instructions in Bald’s Leechbook. In other words, deviation from either the recommended combination of ingredients, or the recommended preparatory method (which includes a 9-day waiting period) resulted in a reduction in efficacy. These unexpected findings provide an impetus to further explore the realm of historical medicine. Systematically sifting through the tomes of medieval hocus-pocus may help to reveal novel antimicrobial compounds, or could perhaps enable the rediscovery of other forgotten medicinal recipes which may be valuable as we enter into the post-antibiotic era.

Experiments and Results

The full translation of the recipe for Bald’s eyesalve (given by Harrison et al., 2015), is as follows:

Make an eyesalve against a wen [stye]: take equal amounts of cropleac [an Allium species – probably onion or leek] and garlic, pound well together, take equal amounts of wine and oxgall [bovine bile], mix with the alliums, put this in a brass vessel, let [the mixture] stand for nine nights in the brass vessel, wring through a cloth and clarify well, put in a horn and at night apply to the eye with a feather; the best medicine.

At first glance it appears quite promising: it constitutes an attempt to treat a supposed bacterial infection with ingredients which are individually known to have antibacterial properties. Allium species such as garlic, onion and leek produce a variety of compounds such as ajoene, allicin and flavonoids – which can have adverse effects on bacterial biofilm formation, quorum sensing (cell-cell communication) and virulence. Bile salts act as surfactants, which can disrupt lipid membranes, and are known to be antibacterial (admittedly not usually against Staphylococcus spp.). The wine in the recipe may act as a source of small, plant-derived antimicrobial molecules; or as a solvent, to release antibacterial compounds from the Allium species over the 9-day waiting period. Finally, the recipe specifies the use of a brass vessel. Given the known antibacterial properties of copper, it is possible that copper salts leaching from the brass vessel may also contribute to the activity of the eyesalve. Although the eyesalve’s principal mode of action is as-of-yet unknown, the authors speculate – based on what is known about the eyesalve’s ingredients – that multiple antibacterial mechanisms may be involved.

One of the major findings of the study was that deviation from the instructions outlined in Bald’s Leechbook reduced the antibacterial activity of the eyesalve against S. aureus biofilms in an in vitro model of soft tissue infection, suggesting that the precise combination of ingredients and the 9-day waiting period are important. Another notable observation was that Bald’s eyesalve was more effective in eliminating MRSA from a mouse chronic wound model than the last-line antistaphylococcal drug, vancomycin. This is a remarkable finding, and suggests that it may be possible sometime in the future to harness Bald’s eyesalve or its components for in vivo use to treat MRSA infections. As always, however, more work needs to be done; but it is surely exciting to see that an unusual, stand-alone, curiosity study has the potential to be developed into a full-blown drug discovery project: The AncientBiotics Project

Discussion

This is an intriguing story, and a great example of the power of co-operative, interdisciplinary research. No doubt it was the first time a researcher from the School of English and Centre for the Study of the Viking Age at the University of Nottingham has been listed among the authors of an mBio paper! Three cheers for Christina Lee (and her translating skills)!

The lead researchers first presented their work in March of last year – in Birmingham, UK – at the 2015 Annual Conference of the Society for General Microbiology (since re-named the Microbiology Society). Of course it wasn’t long before the media was churning out zippy headlines and overhyped commentary regarding the wonders of Bald’s eyesalve and medieval medicine. As one Daily Mail commenter noted, “add eye of newt and it beats cancer too”.

The British Library characterizes Bald’s Leechbook as a mid-10th century collection of “medical remedies, diagnoses and charms”, and the book provides us with many other interesting therapeutic suggestions in addition to the surprising properties of Bald’s eyesalve. It seems likely that many of these alleged treatments are not effective as cures – but what they lack in utility, they make up for in entertainment value. A modern translation of Bald’s Leechbook was published in 1865, compiled and edited by Rev. Thomas Oswald Cockayne (a Cambridge-educated philologist), and is available online.

The following is an excerpt on how to treat ‘water-elf disease’ (whatever that is), using a combination of over 20 different ingredients:

If a man is in the water-elf disease, then are the nails of his hand livid, and the eyes tearful, and he will look downwards. Give him this for a medicine; everthroat, cassuck, the netherward part of fane, a yew berry, lupin, helenium, a head of marsh mallow, fen mint, dill, lily, attorlothe, pulegium, marrubium, dock, elder, fel terrae (or lesser centaury), wormwood, strawberry leaves, consolida; pour them over with ale, add holy water and sing this charm over them thrice:

I have wreathed round the wounds, the best of healing wreaths. That the baneful sores, may neither burn nor burst, nor find their way further, nor turn foul and fallow, nor thump or throb on, nor be wicked wounds, nor dig deeply down, but he himself may hold in a way to health. Let it ache thee no more, than ear in earth acheth.

The description of the “baneful sores” suggests considerable suffering, and given the possibility that ‘water-elf disease’ was incurable at the time, not only would the sick person have had to endure an extensive illness, it seems he/she may also have had to endure the humiliation and discomfort of being cloaked in different kinds of plants; drenched in beer and holy water; and subjected to a verbal assault in the form of some nutter muttering incantations. It’s quite an image.

While reading Bald’s Leechbook it is interesting to consider whether or not ‘water-elf disease’ or any of the other ailments described, had microbiological origins. Some sources seem to suggest that the painful sores, watery eyes, itchy skin and severe fatigue of ‘water-elf disease’ are characteristic of conditions such as chickenpox and measles (Carr-Gomm and Heygate, 2010).

Bald’s Leechbook also contains details on how to repair a cleft palate, as well as alleged cures for a headache, chilblains, shingles, impotence and lustfulness (to name a few). However, it seems every Anglo-Saxon historian’s favourite passage concerns a bizarre method by which to allegedly improve a person’s mental health:

In case a man be a lunatic; take skin of a mereswine or porpoise, work it into a whip, swinge the man therewith, soon he will be well. Amen.

We laugh at this advice now – not least for its blatant stupidity, Pythonesque imagery, and obvious disregard for the as-yet-uninvented concept of political correctness. All humour aside, however, the irrationality inherent in the above quote – as well as that found in the passage concerning ‘water-elf disease’ – should serve to remind us that although Bald’s Leechbook has been found to contain a modicum of useful scientific information (in the description of Bald’s eyesalve), we would do well to proceed with caution in analysing further alleged historical remedies, lest the hyperbolic headlines surrounding Bald’s eyesalve cloud our better judgment.

References:

  1. Harrison, F., Roberts, A.E., Gabrilska, R., Rumbaugh, K.P., Lee, C. and Diggle, S.P. (2015) A 1,000-Year-Old Antimicrobial Remedy with Antistaphylococcal Activity. mBio. 6(4), e01129-15.
  2. Brennessel, B., Drout, M.D. and Gravel, R. (2005) A reassessment of the efficacy of Anglo-Saxon medicine. Anglo-Saxon England. 34, 183-195.
  3. Carr-Gomm, P. and Heygate, R. (2010) The Book of English Magic. The Overlook Press.

Featured Image: Recipe for an eye salve, from Bald’s Leechbook, England, mid-10th century, Royal MS 12 D XVII, f.12v – © The British Library (Image Source)

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