Three ribs of Francesco I de’ Medici have preserved for 439 years something much less theatrical than arsenic: the DNA of malaria parasites. A group of researchers from the Universities of Pisa and Yale found traces of in the remains of the Grand Duke of Tuscany Plasmodium falciparum And Plasmodium malariaereinforcing with genetics a diagnosis that the court doctors had already formulated in 1587.
Francesco died in October of that year after days of intermittent fever. Shortly afterwards his wife Bianca Cappello also died, suffering from a very similar illness. Malaria, however, was a decidedly less interesting explanation than a brother cardinal with an excellent dynastic motive: Ferdinand de’ Medici succeeded Francesco as grand duke and ended up at the center of rumors of possible poisoning.
After more than four centuries, the study published on iScience adds genetic evidence to a story that medicine, news and laboratory analysis have been arguing about for a long time.
The perfect suspect was his brother
Francesco I and Bianca Cappello fell ill while they were in the Medici villa of Poggio a Caiano, in an area of Tuscany where malaria was endemic. Medical sources of the time describe intermittent fevers and a course considered compatible with the disease. Francesco was also subjected to bloodletting, a treatment that certainly did not offer great advantages to an already debilitated organism.
Then there was Ferdinand. Cardinale, Francesco’s brother and successor, had enough interest in the succession to become the perfect protagonist of a Renaissance mystery. Rumors of poisoning began almost immediately and survived much better than their protagonists.
In 2006, an apparently scientific confirmation even arrived. A study published in British Medical Journal analyzed tissues attributed to Francesco and other samples linked to Bianca, finding concentrations of arsenic that the authors interpreted as compatible with acute intoxication. The conclusion was heavy: Francesco and Bianca would have died of poisoning.
Four years later, two proteins also turned up in Francesco’s bones Plasmodium falciparum. In the work published in 2010 on The American Journal of MedicineGino Fornaciari, Valentina Giuffra and the other authors considered them the first biological proof of the presence of malaria in the Grand Duke at the time of death. The poison was starting to lose several points.
This time there was DNA in the ribs
The new work looked directly for the parasite’s genetic material. The researchers analyzed four rib samples: three belonging to Francesco and one to his brother Giovanni de’ Medici, a cardinal who died in 1562 after a febrile illness.
They were recovered from Francesco’s samples 185 base pairs of mitochondrial DNA of Plasmodium falciparum and others 43 of Plasmodium malariae. They are tiny fragments, as one might expect from material that had remained in the bones for more than four centuries, but they allowed the two parasites to be genetically identified.
The simultaneous presence of the two species is compatible with cases of multiple infection observed in other European remains of the same period. The authors, however, are cautious: other samples will be needed to understand how common this co-circulation was in 16th century Tuscany.
On Giovanni the DNA was much better preserved. The researchers recovered 1,865 base pairs of P. falciparum and identified a so far uncharacterized haplogroup, with two peculiar mutations. And here the matter also comes out of the Medici mystery: those ribs tell something about the malaria that circulated in Renaissance Europe, not only about those who occupied Palazzo Pitti.
The study by the University of Pisa and Yale also compared that sequence with other ancient samples, from the Iron Age to the twentieth century. The strain found in Giovanni is close to sequences from Europe, Taiwan and the Caribbean and, according to the authors’ analysis, could derive from a demographic expansion of the parasite that occurred in Europe.
For Francesco, however, the result adds to the malarial proteins already found in 2010 and above all to the descriptions left by the doctors who saw him get sick and die. Three different pieces of the same story: documents, proteins and now DNA.
And Bianca Cappello?
Here it is best to stop CSI Firenze just before the closing credits. The new study did not analyze Bianca Cappello’s remains. The samples belong to Francesco I and Giovanni de’ Medici.
Bianca fell ill in the same place and almost at the same time as her husband, presenting similar symptoms and dying shortly after. Malaria is therefore a coherent explanation for her too and already appears in the historical reconstructions of the story. The new DNA, however, concerns Francesco. Attributing the same genetic result directly to Bianca would mean making him walk a few meters more than those allowed by the tests.
Ferdinand thus remains the brother with a dynastic motive, who became grand duke after the death of Francesco and dragged the suspicion of murder with him for centuries. In the ribs of the Grand Duke, however, the researchers found Plasmodium falciparum And Plasmodium malariae. After 439 years, poison still works great as a plot. Much less as a diagnosis.
