A medieval potion, described in a 1000 year-old manuscript kept at the British Library, has recently been shown to have 'astonishing' antibiotic properties, capable of defeating the 'superbug' MRSA. Boudewijn Dominicus looks at the science behind this 'ancientbiotic'.

Medieval medicine is often seen as a bit of an oxymoron. With practices such as bloodletting commonplace¹, many would say this reputation is deserved. Indeed the word for ‘leech’, a creature synonymous with medicine of the era, is derived from the Anglo-Saxon word for physician ‘laece’².

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Although many treatments were ineffective or even harmful, careful analysis of Old English medical texts has revealed that not all of them were as backwards as we imagine. For example, there is evidence that honey was used as an antiseptic – its high sugar content and low levels of hydrogen peroxide destroying bacterial cells³.  Another example was the use of the herb marrabium vulgare (horehound) to treat coughs – horehound is still used today in some throat lozenges⁴. Some of these treatments required specific identification of herbs, careful preparation and appropriate administration. Such examples show that Anglo-Saxon physicians were willing to experiment, see what worked and from that, occasionally, find an effective cure – formulating simple compound drugs using a prototypical scientific method.

But now, researchers from the University of Nottingham have discovered a medieval treatment for eye infections which puts even some modern medicines to shame. The eye salve described in Bald’s Leechbook, a 9^th century medical manuscript held by the British Library, was tested by a team of microbiologists at Nottingham University’s Centre for Biomolecular Sciences and was shown to kill one of today’s most notorious antibiotic-resistant bacteria: Methicillin-resistant Staphylococcus aureus (MRSA).

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Dr Christina Lee, an Anglo-Saxon expert from the University’s School of English, translated the recipe which was made from a mixture of garlic, onions, wine, and bovine bile salts, all of which were then brewed in a brass cauldron and let sit for nine days:

“take cropleek and garlic, of both equal quantities, pound them well together, take wine and bullocks’ gall, of both equal quantities, mix with the leek, put this then into a brazen vessel, let it stand nine days in the brass vessel, wring out through a cloth and clear it well, put it into a horn, and about night time apply it with a feather to the eye.”

The microbiologists made three batches and tested them on cultures of three commonly found and hard to treat bacteria, Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa in both synthetic wounds and in infected wounds in mice. The results were then compared to a control treatment using the same recipe, but without the vegetable compounds. On their own the ingredients had no measureable effect, but when combined the mixture was startling effective: only about one in a thousand bacteria survived application. Vancomycin, the current antibiotic of choice against MRSA, has approximately the same level of antibacterial activity.

The scientists then diluted the eye salve, investigating its effectiveness at different concentrations and exploring its possible mechanism of action. Interestingly, they found that when the medicine was too dilute to kill Staphylococcus aureus, it interfered with bacterial cell-cell communication (quorum sensing). Quorum sensing is essential to the formation of biofilms; a means by which bacteria aggregate together to form a cell colony. Biofilms can promote bacterial antibiotic resistance by forming a dense outer film around a colony which is impervious to antimicrobials such as antibiotics and detergents. As such, many microbiologists think that blocking this behaviour could be a means of combatting antibiotic resistance. 

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Bald’s remedy certainly confirms that this approach is promising. Many of the microbiologists involved were surprised by the efficacy of the treatment. Dr Freya Harrison, who led the work in the laboratory at Nottingham, commented that they were “hopeful that Bald’s eyesalve might show some antibiotic activity, because each of the ingredients has been shown by other researchers to have some effect on bacteria in the lab – copper and bile salts can kill bacteria, and the garlic family of plants make chemicals that interfere with the bacteria’s ability to damage infected tissues. But we were absolutely blown away by just how effective the combination of ingredients was.”

The next step is to investigate why the combination confers such powerful antibiotic activity; in isolation each individual ingredient has little effect. Understanding how and why these ingredients interact may inform the development of new drugs which could help us combat the ‘evil that is antibiotic resistance’.

 

Boudewijn Dominicus

References

¹http://britishlibrary.typepad.co.uk/digitisedmanuscripts/2013/10/anglo-saxon-medicine.html

²http://bjgp.org/content/bjgp/20/97/63.full.pdf

³http://europepmc.org/abstract/MED/23569748

⁴http://www.vikingsofmiddleengland.co.uk/surgery-medicine.html