Researchers at Yale University have addressed a longstanding mystery concerning the death of a notable Italian historical figure. The study, published in the journal iScience, evaluates the DNA of Grand Duke Francesco I de’ Medici, a Tudor ruler who died unexpectedly in 1587.
The sudden deaths of Francesco I de’ Medici and his wife, Bianca Cappello, within a day of each other sparked rumors of poisoning. Their illness began after staying in a mosquito-infested villa, leading many to suspect foul play.
The Yale team collaborated with paleopathologists from the University of Pisa. They extracted DNA from Francesco I de’ Medici’s ribs and those of his younger brother, Giovanni de’ Medici, who died of malaria 25 years before. Under the direction of Serena Tucci, assistant professor of anthropology, the researchers discovered evidence of malaria parasites in Francesco’s remains. This discovery contradicts the previous theory of arsenic poisoning.
The researchers identified a novel strain of Plasmodium falciparum, which causes severe malaria. They also detected traces of P. malariae. These findings suggest malaria’s role in the brothers’ deaths, historically misdiagnosed as “febbre terzana” in Central Italy.
Historical sources, including reports from court physicians, had described symptoms aligned with malaria, yet rumors of poisoning persisted. Tucci explains that the study provides the first genetic confirmation of malaria as the cause of death, emphasizing the speculative nature of the poisoning hypothesis.
Gisella Caccone, senior research scientist at Yale, notes that such genetic approaches may resolve other historical uncertainties. The discovery of this particular malaria strain could also aid in understanding the parasite’s evolution and improving control methods in the future.

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