DNA cracks centuries-old murder mystery involving one of history's most famous families

Researchers at Yale University believe they've solved a centuries-old mystery over how a member of one of Italy's most famous families died.

In a study published in the journal iScience, researchers analyzed ancient DNA from Grand Duke Francesco I de' Medici, the Renaissance ruler of Tuscany, who died suddenly in 1587.

Francesco I de' Medici and his wife, Bianca Cappello, died a day apart after falling ill with intermittent fevers following a stay at a mosquito-filled villa — fueling centuries of rumors that they had been poisoned.

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Working with paleopathologists from the University of Pisa in Italy, the team analyzed DNA extracted from the ribs of Francesco I de' Medici, as well as Giovanni de' Medici, his younger brother who died of malaria 25 years earlier.

The research was led by Serena Tucci, assistant professor of anthropology at Yale University, whose work was publicized in a university press release on June 30.

Researchers found genetic traces of Plasmodium falciparum, the parasite responsible for the deadliest form of malaria — effectively debunking the longstanding poisoning theory.

The team "found a novel strain of Plasmodium falciparum, the species that causes the deadliest form of human malaria, in the bones of Giovanni de Medici," the release said.

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"The researchers also discovered molecular traces of P. falciparum and a second species, P. malariae, in the remains of Francesco de Medici," the statement added.

While malaria was endemic to central Italy during the Renaissance, the lack of definitive scientific evidence allowed theories to persist.

"Their quick deaths spawned rumors that Francesco’s brother and rival, Cardinal Ferdinando de Medici, had them poisoned with arsenic," said the statement.

It marks the first time researchers have genetically analyzed the brothers' skeletal remains, confirming earlier evidence they had malaria.

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The results are "scientific proof to dispel persistent speculation that Francesco de Medici was poisoned to death," Yale officials said.

Archival sources, including contemporary reports from court physicians, describe the symptoms the brothers suffered that are consistent with malaria, which was called "febbre terzana" by residents of Central Italy at the time.

"The reports also describe the treatments to which the stricken were subjected, including bloodletting, a common practice that likely did patients more harm than good," the release said.

Although historical records described symptoms consistent with malaria, rumors that Francesco had been poisoned persisted for centuries, Tucci told Fox News Digital.

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Asked why the rumors persisted, Tucci said, "We do not know."

The professor added, "Probably because it was still plausible, given that up to now, there were no conclusive reports that indeed they had malaria. Our study is the first one to genetically confirm it."

Tucci added that while the researchers cannot completely rule out poisoning, "malaria remains the most likely explanation for his cause of death."

She also noted that "the hypothesis of poisoning doesn't seem to be well-supported from a scientific perspective — it's very speculative."

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"We can only say that we found the pathogen that causes malaria in this specimen, confirming that he had malaria," Tucci said.

The same genetic approach could "certainly" help solve other historical mysteries, said Gisella Caccone, a senior research scientist in Yale's Department of Ecology & Evolutionary Biology and a co-author of the study.

"[It's possible if] there is a clear hypothesis to address and one can address it using genomic-based approaches," added Caccone. "It depends on the questions and the tools we have."

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The DNA recovered from centuries-old remains can do more than solve historical mysteries, Caccone pointed out: The newly identified malaria strain could help researchers better understand how the parasite has evolved over time.

"The more we know about how fast it can change, the better our methods and models to control will be," she noted.

"Using historical specimens can not only help us understand our past better, but also it can help build a better future."