Medici family murder mystery may be solved after over 400 years with new DNA analysis - CNN

Since the mysterious deaths of a husband and wife in the Medici family, a powerful Italian dynasty that ruled Florence and Tuscany almost uninterruptedly from 1434 to 1737, rumors have swirled about what led to the couple’s untimely demise. Now, scientists believe they have an answer — it wasn’t murder, but malaria.

In 1587, Grand Duke Francesco I de’ Medici and his wife, Bianca Cappello, died within hours of each other after days of agony.

At the time, logic dictated the culprit to be malaria because the couple had shown symptoms of the illness, including a telltale intermittent fever. But rumors of an assassination immediately spread, pointing to Francesco’s younger brother and rival, Ferdinando, as the perpetrator.

Ferdinando was next in line to the throne, but he was at risk of being passed over in favor of Francesco’s illegitimate son, Antonio. What’s more, Ferdinando had visited the grand duke and his wife at their residence just before they fell ill, further bolstering the suspicion that he poisoned them with arsenic to ensure his own rise to power.

The couple fell ill in a Medici villa in Poggio a Caiano, near Florence, an area dotted with marshes and rice fields — ideal habitats for mosquitoes that can carry malaria. Nonetheless, the murder rumors endured, likely aided by the Medici family’s history of murder and assassination attempts.

Since 2004, when exhumation and analysis of skeletal remains began for 49 Medici family tombs as part of the Medici Project, various studies have confirmed malaria as the cause of Francesco’s demise. However, other studies published as recently as 2006 used toxicological investigations to determine that the couple were indeed victims of arsenic poisoning,

A new study led by Serena Tucci, an assistant professor of anthropology at Yale University’s Faculty of Arts and Sciences, and jointly conducted by Yale and the University of Pisa, Tuscany, used DNA extracted from the skeletal remains of Francesco and another one of his brothers, Giovanni, in an attempt to settle the debate once and for all.

“In recent years, we tried to solve this mystery by performing some specific analysis, in particular paleo-immunological analysis, which attested to the presence of malaria in the remains. But the rumors would not stop, because paleo-immunology is not resolutive, and only ancient DNA could give an answer with a high degree of certainty,” said Valentina Giuffra, a professor of history of medicine at the University of Pisa and a coauthor of the study, published in June in the journal iScience.

Paleo-immunology uses antigens, substances that trigger an immune response, or proteins to check for traces of disease in ancient remains. DNA analysis, which is a more recent approach, is more definitive because it looks for direct genetic signatures of a disease.

Giuffra and her colleagues found genetic traces of plasmodium, the parasitic protozoa responsible for malaria, in samples of bone material from Francesco’s ribs. “DNA is certain,” Giuffra said. “It solves the problem and the doubts. I think this is a definitive answer.”

Malaria is one of the great historical killers for humanity, causing 610,000 deaths in 2024 alone, according to the World Health Organization. It manifests with fever, headaches and chills, and its name comes from the medieval Italian phrase “mal aria,” meaning bad air — a moniker derived from the idea that the disease was contracted by breathing foul-smelling air near swamps or stagnant water.

Historical sources supported the assumption that malaria killed Francesco and Bianca, Giuffra said. Documents written by court physicians of the Medici family described symptoms consistent with the disease. They also detailed some treatments administered to the patients, such as bloodletting — deliberate blood withdrawal, which at the time was thought to release a patient from an illness but in fact worsened their condition.

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The genetic analysis was performed on small bone samples kept aside when the Medici tombs were opened in 2004 before the rest of the remains were buried again. Scientists could not perform a similar analysis at the time because the technique wasn’t developed enough, Giuffra said.