A Medieval Cow Bile Stew Could Teach Us How to Fight Modern Infections

Everything old is new again. Nowhere is that more true than in the research of a multidisciplinary team of scientists and medieval scholars who discovered that by replicating a treatment for a sty (an eyelash follicle infection) from a medical text from Anglo-Saxon times, they created a potent antibiotic for Methicillin-resistant Staphylococcus aureus (MRSA).

Christina Lee, a professor of Viking studies at the University of Nottingham in the UK, never thought she would be part of a team that discovered a new antibiotic. "Never in my wildest dreams," she says, with a laugh. The formula in the 10th century medical text, called "Bald's Leechbook," involves mixing garlic, onion, wine, and cow bile in a brass vessel before letting the mixture sit for nine days to ferment. The resulting concoction, brewed up by the researchers in a modern glass container with a brass square placed in it to replicated a brass vessel, proved 90 percent effective in killing MRSA in laboratory testing, says Kendra Rumbaugh, a professor at Texas Tech University Health Sciences Center. Rumbaugh, who was part of the scientific team testing the formula the medieval scholars concocted, noted that vancomycin, the current treatment for MRSA, proved to be less effective a treatment in the team's experiment in a mouse chronic wound model.

While Lee was surprised by how well the recipe worked, she was not surprised that a medical text written well before the Enlightenment would prove useful. "I have always believed in people being rational. I have always believed that people in the Middle Ages were far more rational than we think," she says. While recipes involving virgins gathering water at dawn exist in medical texts from the time, they are far less common than people think, Lee points out. Most medieval recipes involve carefully selected ingredients mixed in a very logical and deliberate manner.

The research made a splash when it was published in 2015, but work has not progressed as fast as Lee would like since. The next steps would involve identifying the active ingredients in the leechbook formula for modern medical use. Rumbaugh thinks the formula's efficacy can be improved from 90 percent, bringing it closer to the accepted 99 percent effective standards for an FDA approved antibiotic. 'What we were dealing with in these first experiments was a very crude solution, yet it still did better than vancomycin," Rumbaugh says. Identifying the active ingredients and creating an optimal formulation could create a new antibiotic for hospital use that would save lives.

MRSA, which is resistant to most antibiotics, can cause skin and bloodstream infections, pneumonia, and sepsis. It is often acquired in hospitals but has increasingly also been seen outside a hospital setting. In addition to MRSA, years of overuse of antibiotics have created a number of drug-resistant bacteria which doctors are now struggling to treat. At the same time, drug companies have not made major strides in discovering new antibiotics. While some new antibiotics have entered the market, a new class of antibiotics has not been discovered since 1987. This year, the World Health Organization (WHO) has called for renewed research into antibiotic-resistant bacteria, listing MRSA as a "high" priority. "We are in such dire need for new antimicrobials that thinking outside the box is exactly what we need to do," Rumbaugh says.

The next step is to do clinical trials, Lee tells me. But thus far funding for continuing the research has proven elusive. The research of the interdisciplinary team, made up of microbiologists and medieval scholars, does not fit perfectly into any one category of funding. While they keep applying for new grants, Lee has gotten emails asking if she can provide people with the antibiotic remedy the team made from the leechbook. She sadly can't share the concoction, as "it is unethical, we say 'don't try this at home,'" Lee says.

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In fact, trying it at home might not be very feasible even with the exact recipe listed in the team's study. The same formula was previously tested in 2005, and failed to yield anything useful. To test it again, Lee and her colleagues sought to replicate the recipe as exactly as possible in modern times. "Agriculture is very different from the Anglo-Saxon period," Lee says. The exact translations of some of the ingredients were also lost to time. The type of onion used in the recipe was unclear, so after many long discussions around alliums, they made several batches, some of which used leeks, while others used onion, both of which, interestingly, worked. Finding wine made in the same methods, with the same grapes as used in medieval times was another challenge. The researchers lucked out and found a vineyard with a charter from the 10th century, whose wine they used for their formula. In an effort to at least somewhat minimize modern pollutants, the researchers used only organic produce for their medieval antibiotic. Not exactly something you can whip up on the weekend.

While the team tries to secure more funding for their leechbook antibiotic, only time and more research will tell if there are other useful drugs hiding in surviving medieval medical texts. One of Lee's former PhD students, Ellen Connolly, is currently working on creating a database from a later medical work, called the "Lylye of Medicynes," from the 15th century. The book contains 360 recipes for medications. By creating the database and examining the relationship between ingredients and the diseases they treat, Connolly hopes to find other antibiotic candidates for testing.

There is every indication that it is possible that more useful recipes are waiting to be discovered. A pharmacist in China, Tu Youyou, won the Nobel Prize for Medicine in 2015 for her work on a treatment for malaria that used an herbal medication from a Chinese medical work written in 340. Medieval medical practitioners "were much more meticulous and better practitioners of scientific method than we previously thought," Rumbaugh says. "The formulation loses efficacy if it does not steep for as many days as they specify, or if you remove some of the components. This suggests they were performing empirical tests, recording results and systematically improving their recipes." It would be a shame to let all of their careful years of research go to waste.

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