Did This Duke Poison His Brother? A New DNA Analysis May Solve the Centuries-Old Medici Mystery

Researchers found evidence of malaria in Francesco I de’ Medici’s bones, leading them to argue “with scientific certainty” that it was disease, not arsenic, that led to his death in 1587

Meilan Solly | Senior Associate Digital Editor, History

July 8, 2026 1:05 p.m.

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When Francesco I de’ Medici, the second grand duke of Tuscany, died within a day of his wife in October 1587, some observers suspected foul play. Who stood to benefit from the couple’s deaths? Ferdinando, Francesco’s estranged younger brother, was next in line for the throne, making him the most likely culprit. Rumors speculated that Ferdinando had poisoned his unsuspecting brother and sister-in-law during a hunting trip.

The truth, as it turns out, is far more mundane. A new study published in the journal iScience debunks this dramatic narrative, attributing Francesco’s death to malaria. The genetic analysis suggests that the disease, which ran rampant in central Italy until its eradication in the region centuries later, also killed a third Medici brother, Giovanni.

“At the time, both were diagnosed with symptoms, such as intermittent fevers, consistent with malaria,” says co-author Valentina Giuffra, a historian at the University of Pisa, in a statement. “This genetic analysis confirms the historical accounts as well as prior research.”

For the study, researchers extracted DNA from the rib bones of Francesco and Giovanni, who are interred alongside other members of the dynasty at the Medici Chapels in Florence. (The location of the grand duchess’ grave is unknown, so her remains weren’t available for analysis.) The team identified Plasmodium falciparum, a parasite responsible for the deadliest strain of human malaria, in the bones of both brothers. Francesco’s remains also bore traces of a second parasitic species called P. malariae.

The findings demonstrate “how we can use advanced ancient DNA laboratory methods to map the history of this deadly pathogen,” senior author Serena Tucci, an anthropologist at Yale University, says in the statement. Giovanni was infected with a previously uncharacterized strain of P. falciparum that included two unique genetic mutations. This strain may have evolved from a similar one that spread across Europe at the time, but further research is needed to confirm that hypothesis.

Twenty-five years before Francesco’s death, in 1562, his mother, Eleonora of Toledo, and two of his brothers, 19-year-old Giovanni and 15-year-old Garzia, died unexpectedly. Although the Medici family maintained that all three had contracted malaria while traveling to Pisa, rumors of violence persisted, with gossip suggesting that Garzia had murdered Giovanni after a falling-out, leading their father, Cosimo I, to kill him in retribution.

A 2010 study co-written by Giuffra cast doubt on this version of events, confirming “the clinical diagnosis of the court physicians using modern methods,” specifically immunological investigations. The paper’s authors pointed out that the Medici family’s villas and hunting grounds were located in coastal or marshy areas that held a high risk of exposure to mosquito-borne diseases like malaria.

Francesco caught malaria under similar circumstances, falling violently ill while hunting in Tuscany. According to a 19th-century account of the duke’s death, doctors treated Francesco’s high fever, vomiting and convulsions with bloodletting. He refused other treatments, including enemas, and “ignored the precepts of physicians, drank and gargled with water and wine cooled with snow, and even cooled his syrups with snow.” The duke died 11 days later, with his second wife, Bianca Cappello, following him to the grave the next day.

Ferdinando’s presence at his brother’s deathbed immediately prompted whispers of wrongdoing. “It has been suggested that death rode from Rome in company with Cardinal Ferdinando … who had everything to gain by the event and who at once succeeded to the duchy,” a 20th-century chronicler wrote. Ferdinando’s well-known distaste for Bianca, who’d been Francesco’s mistress before the death of his first wife, further fueled the rumors. The cardinal had “resented Bianca’s meddling in court affairs and accused his brother of behaving in a manner unbecoming his ducal role,” the 2010 study noted. But the brothers apparently reconciled just two weeks before Francesco’s death.

The new genetic analysis solves the mystery of the grand duke’s demise, allowing researchers to pin the blame “with scientific certainty” on malaria rather than poison, Giuffra says. As first author Alexander Ochoa, a research scientist at Yale, explains in the statement, “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, Plasmodium falciparum in this case, which can help scientists better understand how the pathogen adapts over time.”

Meilan Solly | Read More

Meilan Solly is a senior associate digital editor at Smithsonian magazine, where she oversees the online history section. Solly's specialties are Tudor England, medieval Europe and World War II.