For 439 Years, Poison Was Suspected. The Real Killer Left Its DNA in the Medici Bones

In October 1587, Francesco I de’ Medici, Grand Duke of Tuscany, suddenly developed a severe fever. He died a few days later. His wife, Bianca Cappello, died at nearly the same time.

It happened too quickly, too conveniently, and within one of Italy’s most powerful families. Rumors of poisoning spread, and suspicion fell on Francesco’s brother, Cardinal Ferdinando de’ Medici, the duke’s political rival.

More than four centuries later, traces of the suspected killer were found not in a wineglass or an archive, but in Francesco’s own bones.

Researchers extracted ancient DNA from his remains — short fragments of genetic material that can survive in bone for hundreds or even thousands of years. Among the human DNA, they detected traces of two malaria parasites: Plasmodium falciparum and Plasmodium malariae.

The finding matched the historical record. Before his death, Francesco suffered bouts of intermittent fever. Shortly before becoming ill, he had been staying at the family villa in an area surrounded by rice fields and wetlands, where mosquitoes were abundant. Malaria remained widespread in central Italy for several more centuries.

Parasite DNA alone confirms an infection; it does not capture the exact moment of death. But combined with the reported symptoms and historical setting, it makes malaria the most convincing explanation for the duke’s death — without the need for poison or a palace conspiracy.

The researchers also examined the remains of Francesco’s younger brother, Cardinal Giovanni de’ Medici, who died in 1562 at the age of 19. His bones also contained DNA from P. falciparum. The parasite strain carried two previously unknown mutations.

The study therefore became more than an investigation into an old death. Ancient DNA can reveal which malaria strains circulated in Renaissance Europe and how the parasite changed as it spread between regions.

Bones preserve more than the human genome. Sometimes they also retain the genetic signature of the disease that accompanied a person through their final days.