For 440 years, one of history's most persistent murder theories held that Cardinal Ferdinando de' Medici poisoned his brother Grand Duke Francesco I and Francesco's wife Bianca Cappello in October 1587 to seize power in Florence.
A 2006 toxicological study even reported elevated arsenic levels in their remains. A new study published in iScience by Yale University and the University of Pisa has settled the debate with something none of the earlier investigations could produce, the parasite's own DNA.
Researchers extracted ancient DNA from Francesco's ribs and found molecular evidence of two malaria species: Plasmodium falciparum and P. malariae. The symptoms recorded in 1587, recurring fevers, chills, rapid decline over back-to-back days, match malaria precisely.
The couple had recently visited the Medici villa at Poggio, which sat near swampy rice fields where mosquitoes thrived. It was malaria, not Cardinal Ferdinando. The cardinal was innocent. He became Grand Duke anyway.
The bonus discovery may matter more to modern medicine than to Renaissance history. In the bones of Cardinal Giovanni de' Medici, who died of malaria 25 years earlier at 19, researchers found a previously unknown strain of Plasmodium falciparum with two unique genetic mutations.
The strain is closely related to lineages that spread across Italy, France, Spain and beyond. Scientists say understanding how the parasite has evolved over centuries gives researchers better tools to model and combat its continued evolution today, including its growing resistance to the frontline drug artemisinin.