When you think of ancient medicine, what comes to mind? Potions? A concoction of herbal ingredients bubbling away? Old books full of recipes? Before modern medicine, people have been creating ways to treat various ailments. So in today’s blog post, we see how one of these recipes holds up scientifically.
I came across a recent paper from the lab of microbiologist Freya Harrison. It turns out that her lab at the University of Warwick has been working on the historical remedy, Bald’s eyesalve, for over a decade as part of a team of scientists and humanities scholars from several universities.
What is Bald’s eyesalve?
Bald’s eyesalve is a remedy from a 10th century Anglo-Saxon leechbook. This medical textbook (that’s unrelated to leeches), holds the remedies for various ailments including microbial infections. You can see what it looks like in Figure 1 from the lab’s first paper on this topic. A translation of the text showed that the salve was intended to treat a “wen” or a lump in the eye, which the team interpreted as most likely a sty, an infection in an eyelash follicle that today is most likely caused by Staphylococcus aureus.
The ingredients of Bald’s eyesalve: garlic, a second Allium species, wine, and bovine bile. For the second Allium species, the exact species couldn’t be identified in the translation but was likely a leek or an onion. The book doesn’t give quantities of each ingredient. Once combined, the mixture sits in a vessel for 9 days before it can be used.
Bald’s eyesalve vs. S. aureus
In 2015, the lab published their first paper on Bald’s eyesalve. When tested against S. aureus, the team found that the full recipe, either with onion or leek, killed S. aureus cells suspended in lab cultures. This was a good start but S. aureus often grows in biofilms, a community of microbes that can stick to each other and on surfaces, which makes it harder to kill. So, the researchers tested this on S. aureus growing as biofilms on synthetic wounds, finding that both of these full recipes reduced the number of bacteria. “It was giving a seven or eight log drop in viable bacteria,” Harrison says. “You just don’t see that even with a lot of modern antibiotics [against biofilms].”
To put it into a more modern-day context, the team reached out to their colleague Kendra Rumbaugh at Texas Tech University. Her lab tested whether Bald’s eyesalve killed methicillin-resistant S. aureus (MRSA) in tissue from mice with wound infections and compared it to how they did against the last-line antibiotic vancomycin. Vancomycin had no effect but Bald’s eyesalve, both with leek or onion, reduced bacteria significantly.
Putting Bald’s eyesalve to the test against biofilms
Five years later, the lab published another paper on Bald’s eyesalve, this time showing that the concoction was effective against common wound pathogens in biofilms including Acinetobacter baumannii, an emerging opportunistic bacteria with high antibiotic resistance rates. One thing that Harrison noted was that Bald’s eyesalve couldn’t kill Pseudomonas biofilms. She called this finding “reassuring” because it meant that there was something specific going on. “We didn’t make something that is just basically bleach,” she says.
Better together: Combining ingredients for synergistic effects
The team found that they needed all four ingredients together to kill biofilms. “We noticed that individual ingredients don’t really give very good activity, but when you combine them, they give excellent activity,” says Orababa.
If you’re familiar with clinical microbiology and antimicrobial resistance, microbiologists in this field often use the term “synergy” to describe antimicrobials. When antimicrobials are synergistic, this means that the effect of the two antimicrobials together is greater than the sum of the activity of the two antimicrobials alone. Many historical remedies do exactly this, by combining multiple ingredients together.
How does Bald’s eyesalve work? Insights into mechanism of action
In the lab’s most recent paper, published this year in mSphere, they showed that Bald’s eyesalve has multiple mechanisms of actions:
- Disrupting the membranes of bacteria. One cool way the researchers tested this was to use a dye that doesn’t cross the membrane unless the membrane becomes damaged. This way, they could track the location of the dye as it binds to nucleic acids inside cells and increases fluorescence.
- Inhibiting expression of specific genes. Genes related to bacterial adhesins, which are needed to stick to other cells, and virulence factors, which cause damage to its host, were decreased with exposure to Bald’s eyesalve. Treatment with Bald’s eyesalve also decreased the expression of genes for efflux pumps, which bacteria use to remove molecules, including those that can be potentially harmful.
- Inhibiting quorum sensing. Quorum sensing is the process where cells can detect and respond to other bacteria nearby. The population density of the bacteria causes changes in gene expression and can regulate activities like biofilm formation. By inhibiting this, Bald’s eyesalve could reduce biofilm formation.
What I found interesting about this paper was that they showed how these multiple mechanisms of action make it difficult for the bacteria to become resistant to Bald’s eyesalve. The researchers did a selection experiment for two weeks where they grew bacteria for 24 hours in the presence of a lower concentration of either Bald’s eyesalve or an antibiotic. If the bacteria grew at a specific concentration, they would passage it to higher and higher concentrations of antibiotic. After two weeks, they showed that bacteria growing on antibiotics evolved resistance, growing at up to 256 times the minimum concentration that would initially inhibit the bacteria while bacteria with Bald’s eyesalve could only evolve resistance that was twice as much as the original minimum concentration needed to inhibit its growth.
What’s next for Bald’s eyesalve as an antimicrobial?
While this work shows that Bald’s eyesalve has antimicrobial properties, pinpointing the exact molecules with antimicrobial activity can be difficult. “What we’ve got in this remedy is a database of a few hundred natural compounds,” says Harrison. Orababa adds, “The complexity will be a major challenge. It needs to be well standardized before it can be used in clinical settings.”
For the last few years, Harrison says that her lab has been focusing on these compounds and testing what concentrations and ratios lead to better antimicrobial activity. “We’ve been able to extend the spectrum of activity beyond the original Bald’s eyesalve by playing with the concentration of these molecules,” Harrison says. “We now don’t have an undefined mixture of vials and vegetables.”
If you’re interested in antimicrobials, be sure to check out these articles as well:
- Curbing Antibiotic Resistance Through Off-Target Antibiotic Removal
- Do You Really Need to Finish That Course of Antibiotics?
Featured image: Bald’s eyesalve causes outer membrane deformations in Acinetobacter baumannii. Source: Orababa et al. 2026. CC BY 4.0.