Clues to creating new antibiotics may be hidden in a 15th-century medical text, now being studied by a medievalist at Penn.

Erin Connelly, a Penn Libraries fellow in digital manuscript studies, is creating a database of the ingredients used in medieval medical recipes, analyzing not only what they are, but how they are used in combination.

As a member of an “ancientbiotics” team, she is working with an interdisciplinary group—including pharmacists, microbiologists, chemists, medievalists and data experts in the United States and the United Kingdom—to test the efficacy of the medieval medical treatments, and their relevance to modern medicine.

“The past could inform the future,” says Connelly, the CLIR-Mellon Fellow for Data Curation in Medieval Studies in the Libraries’ Schoenberg Institute for Manuscript Studies.

The ancientbiotics team was formed at University of Nottingham in England in response to the emergence of antibiotic-resistant pathogens and the lack of new drugs currently in development to treat antibiotic-resistant infections, Connelly says, noting that the World Health Organization warns antimicrobial resistance is an increasingly serious threat.

“The team believes that novel routes to antibiotic discovery are necessary,” she says, “and that present-day research may also reveal something about the methodology of medieval practitioners.”

Connelly joined the team while pursuing her doctorate in Medieval English at the University of Nottingham in England. For her dissertation, she produced the first edition of the early 15th-century Middle English translation of Bernard of Gordon’s “Lilium medicinae,” which is known as the “Lylye of Medicynes.” The Middle English translation is surviving in one manuscript, “Ashmole 1505,” held by Oxford’s Bodleian Library.  

Connelly is scheduled to discuss her work on the project at the Library of Congress in Washington, D.C., on Tuesday, March 7. The talk will detail the initial findings of the pilot study performed by the ancientbiotics team on a 1,000-year-old recipe known as Bald’s Eyesalve for eye infection.

The research, published in 2015, showed the recipe repeatedly killed established Staphylococcus aureus biofilms in an in vitro model, and killed Methicillin-resistant Staphylococcus aureus (MRSA) in a mouse chronic wound model. Subsequent research has shown that the recipe could have potential for treating a range of antibiotic-resistant soft tissue pathogens and a non-bacterial parasite infection (leishmaniasis). The recipe has been replicated by six independent researchers, Connelly says.

During her two-year fellowship at Penn, Connelly is compiling a database of ingredients from the “Lylye of Medicynes” for a pilot analysis of non-random associations. For example, plantago, honey, pomegranate, and vinegar consistently co-occur as ingredient combinations from the recipes of the “Lylye.”

The “Lylye” is notable for its pharmaceutical content: There are nearly 6,000 individual ingredients in the text, 3,500 of those contained in 360 specific recipes representing more than 110 disease states.

“Once we create a large enough database and can identify the patterns and how the ingredients relate to each other, it could inspire new recipes, with an aim toward informing laboratory research for new antimicrobials,” she says.

The Bald’s Eyesalve recipe was chosen by the ancientbiotics team for research and testing because many ingredients have natural anti-microbial properties: garlic, leeks, onions, wine, oxgall.

“Following the exact specifications of the Anglo-Saxon recipe is crucial,” she says, including a nine-day activation period. “It is only when all ingredients are combined together that you get a very potent anti-Staphylococcal effect.”

The idea of pre-modern ingredients working in combination is exciting to scientists studying the powerful compound at the molecular level, she says, and to herself as a student of history.

“I have a strong interest in pre-modern medicines and plant products and treatment of illness, and the possibility of deriving antibiotics from those sources,” says Connelly, who received her undergraduate degree in biology from Calvin College in Michigan. She even worked briefly in a molecular oncology laboratory after graduation.

As a medievalist, she says this research throws light on what is popularly, and she believes erroneously, known as the Dark Ages.

“Something from the past, it seems, could be helpful, but we’re not there yet,” Connelly says. “It takes a lot of time and a lot of research.”