For nearly 500 years, historians debated a tantalizing question: Were two members of the legendary Medici dynasty victims of disease — or cold-blooded murder? Now, scientists have finally delivered a definitive answer.
Researchers from Yale University and the University of Pisa extracted and analyzed ancient DNA from the skeletal remains of Francesco I de' Medici, Grand Duke of Tuscany, and his brother Giovanni de' Medici, a cardinal. The results, published in the journal iScience, confirm that both brothers died of malaria — specifically Plasmodium falciparum, the deadliest strain of the parasite.
The finding puts to rest centuries of speculation that Francesco was poisoned, a theory that had inspired books, documentaries, and endless academic debate. The Florentine banking dynasty financed the Renaissance, produced four popes and two queens of France, making stories of betrayal and assassination seem entirely plausible.
"This genetic analysis confirms the historical accounts as well as prior research. Now we can say with scientific certainty that malaria, not poisoning, killed Grand Duke Francesco de' Medici," said study co-author Valentina Giuffra, professor of history of medicine at the University of Pisa.
The research team extracted DNA from four rib samples of the brothers, who were entombed in the Medici Chapels in Florence. The analysis revealed traces of P. falciparum in Giovanni's remains, while Francesco carried evidence of a second malaria strain alongside it.
Earlier testing by the University of Pisa had already suggested both brothers carried the malaria parasite, but scientists had never genetically analyzed their skeletal remains to confirm the findings. The suggested diagnosis was based on historical accounts describing symptoms such as intermittent fevers — consistent with malaria.
Beyond solving a historical cold case, the research offers valuable insights into how malaria has evolved over centuries. The study provides a rare genetic snapshot of Renaissance-era malaria strains, potentially helping scientists better understand the history of one of the world's deadliest infectious diseases.
"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," said Yale researcher Alexander Ochoa.
Senior author Serena Tucci, assistant professor of anthropology at Yale, described the work as "a great example of how we can use advanced ancient DNA laboratory methods to map the history of this deadly pathogen."
Malaria was widespread in Central Italy from ancient times well into the 20th century, and it remains a major global health threat. According to the World Health Organization, there were an estimated 282 million malaria cases worldwide in 2024, resulting in roughly 610,000 deaths.
The study closes the book on one of the Renaissance's most enduring mysteries — proving that truth, in this case, was not stranger than fiction. It was malaria all along.
