Image Courtesy of Yale Ancient Pharmacology program.
Upon graduating from medical school, physicians often recite modern versions of the Hippocratic Oath, which famously contains the promise to “do no harm.” Today, this measure is purely ceremonial—rarely do doctors wish to hurt their patients. In Ancient Greece, however, the notions of harm and healing were often intertwined. The Greek word pharmakon captures this duality—it does not refer exclusively to prescribing remedies, but it encompasses the dual concepts of healing and hurting, poisons and cures.
Hellebore, a delicate flower famed in Greek culture, typifies this duality. While it was known to be a popular pharmaceutical product in antiquity, its exact applications and effects have now been lost. Oddly, hellebore is also a fatal poison. Implicated in the death of Alexander the Great and used by Nebros, an ancestor of Hippocrates, to poison the city of Kirrha’s water pipes, the “winter rose” has had a dubious yet unquestionably decorated history.
To investigate the nature of hellebore, the Yale Ancient Pharmacology Program (YAPP) traveled to Antikyra this summer. Led by Andrew J. Koh, the program’s director and a Museum Scientist at the Peabody Museum, YAPP is a unique research team. Aiming to study “ancient pharmacology,” the program combines a variety of methodologies, merging ethnographic observations and chemical analysis with innovative ideas from machine learning and drone technology.
Micah Gold (YC ’24) was a part of the Greek expedition and has been contributing to the technological aspects of YAPP’s research since his first year. His early work focused on recognizing and identifying pottery using multispectral imaging. “The idea is that when sunlight hits pottery, it reflects different spectra than rock,” Gold explained. “And if we use our multispectral drone at the right frequencies, we can pick out that difference.”
This summer Gold traveled to Antikyra, an ancient port city that used to be well-known for its hellebore treatments, hoping to apply his skills in the team’s search. “Historically, Antikyra seems to be a sort of sanatorium for recovering individuals. People would travel from all across the world to Antikyra to do a hellebore treatment,” Gold said.
YAPP aimed to find local hellebore specimens and figure out why the plant was so desired. It wasn’t easy: the team contacted medicine men and local farmers and hiked for miles up Mount Helicon. But after three days of searching, it happened. “We finally found this large quantity of hellebore and were able to take samples,” Gold said.
With these samples, Gold and other technicians in the YAPP team trained their drones on the multispectral and thermal signatures of hellebore. Similar to how they located pottery, they used the data to detect these plants from the sky, avoiding more arduous journeys in the future.
Coming back from this successful expedition, YAPP has more options than ever as they get ready to explore the implications of their findings. Modern drug discovery today is focused on the process of exhaustion, akin to throwing a proverbial kitchen sink at any given problem. This approach, called high-throughput screening, uses machine learning to run through millions of pharmacological tests, creating combinations of chemical compounds that just might work. YAPP’s research aims to take a different, more economical approach to drug discovery. “Why don’t we have a concerted effort to use the knowledge of past botanicals, and maybe that can be a better clue to finding the next life-saving drug?” Gold asked.
In addition to presenting us with possibilities for medical innovation, uncovering clues from the past can also help us learn about how humans used to live. Was hellebore truly used to cure madness and indigestion? Did Emperor Caligula use it during Roman times? There are many questions left unanswered. “It might be the case that the hellebore we’re studying doesn’t have any special properties because it might be the case that the hellebore we’re studying is not even the right species,” Gold said. “It could be that that species has gone extinct.” According to locals, there are at least two other types of the plant that YAPP has not yet found.
The YAPP team’s quest for hellebore will continue next year with the additional support of Yale botanists, including Patrick Sweeney from the Peabody Museum. Their efforts could potentially reveal discoveries about both the ancient world and the present day.