A new analysis of the centuries-old skeletal remains of two Medici brothers has confirmed malaria as the cause of their deaths, resolving a historical mystery that has persisted for nearly 500 years. Researchers utilized advanced ancient DNA laboratory methods to detect the presence of Plasmodium falciparum, the parasite responsible for the deadliest form of malaria, in the remains of Giovanni de' Medici and his brother Francesco de' Medici, the former Grand Duke of Tuscany.
The findings, published in the journal iScience, were the result of a collaboration between Yale researchers and paleopathologists from the University of Pisa in Italy. The team analyzed DNA extracted from four rib samples from the brothers, which were entombed in the Medici Chapels in Florence. This genetic evidence provides the strongest scientific confirmation to date that Francesco de' Medici died from malaria rather than poison, a theory that had long fueled historical debate.
For generations, historians suspected foul play within the powerful Medici dynasty, a Florentine banking family instrumental in financing the Renaissance and producing popes and queens. The persistent theory of Francesco's poisoning inspired numerous books, documentaries, and extensive discussion, partly because the family's influence made tales of betrayal seem plausible.
While earlier testing by the University of Pisa had suggested malaria based on reported symptoms such as intermittent fevers, the new genetic analysis definitively confirms these historical accounts. "Now we can say with scientific certainty that malaria, not poisoning, killed Grand Duke Francesco de' Medici," said study co-author Valentina Giuffra, full professor of history of medicine at the University of Pisa.
The study also offers valuable insights into the evolution and spread of malaria species. "The study of ancient DNA offers us an opportunity not only to diagnose malaria in the remains of individuals from the past, but it also offers us a window for understanding the evolution of malaria species," stated Yale researcher Alexander Ochoa. Malaria was prevalent in Central Italy from ancient times through the 20th century and remains a significant global health issue, with an estimated 282 million cases worldwide in 2024.
This research demonstrates the power of ancient DNA analysis in solving historical enigmas and provides a clearer understanding of the past impact of infectious diseases.