Medici family mystery may be solved after more than 400 years

Ever since the mysterious deaths of a husband and wife from the Medici family, a powerful Italian dynasty that ruled Florence and Tuscany almost uninterruptedly from 1434 to 1737, rumors have swirled about what led to the couple’s untimely demise. Now scientists believe they have found an answer; This was not murder, it was malaria.
In 1587, Grand Duke Francesco I de’ Medici and his wife Bianca Cappello died within hours of each other after days of agony.
Logic at the time suggested that malaria was the culprit because the couple showed symptoms of the disease, including intermittent fever. But rumors of an assassination immediately spread, pointing to Ferdinando, Francesco’s younger brother and rival, as the perpetrator.
Ferdinando was heir to the throne but was at risk of being ousted in favor of Francesco’s illegitimate son Antonio. Moreover, the fact that Ferdinando visited the grand duke and his wife at their home just before he fell ill further strengthened the suspicion that he had poisoned them with arsenic to ensure his rise to power.
The couple fell ill at the Medici villa at Poggio a Caiano, near Florence; a region of swamps and rice paddies – ideal habitats for mosquitoes that can carry malaria. However, rumors of murder persisted, possibly aided by the Medici family’s history. murder and assassination attempts.
Since 2004, exhumation of 49 Medici family tombs and analysis of their skeletal remains have begun. Medici Project, various studies They confirmed that the cause of Francesco’s death was malaria. However, other studies Published as recently as 2006 used toxicological studies to determine that the couple were indeed victims of arsenic poisoning,
The remains of Francesco I de’ Medici. – Courtesy of the Department of Palaeopathology, University of Pisa
A new study led by Serena Tucci, an assistant professor of anthropology at Yale University’s School of Arts and Sciences, and conducted jointly by Yale and the University of Pisa in Tuscany. He used DNA taken from the skeletal remains of Francesco and another brother, Giovanni, in an attempt to settle the dispute once and for all.
“In recent years, we have tried to solve this mystery by carrying out some special analyses, in particular paleo-immunological analyzes that confirmed the presence of malaria in the remains. But the rumors would not end, because paleo-immunology is not a definitive solution and only ancient DNA can give an answer with a high degree of certainty,” said Valentina Giuffra, professor of medical history at the University of Pisa and one of the authors of the study. to workIt was published in the journal iScience in June.
Paleo-immunology uses antigens, substances or proteins that trigger an immune response, to check for traces of disease in ancient ruins. A newer approach, DNA analysis, is more accurate because it looks for direct genetic signatures of a disease.
Giuffra and colleagues found genetic traces of plasmodium, the parasitic protozoa responsible for malaria, in samples of bone material taken from Francesco’s ribs. “DNA is definitive,” Giuffra said. “It solves the problem and the doubts. I think this is a definitive answer.”
Two types of malaria
Malaria is one of history’s biggest killers of humanity and 610,000 deaths in 2024 alone, according to the World Health Organization. The name of the disease, which manifests itself with fever, headache and chills, comes from the Medieval Italian expression “mal aria”, meaning bad weather. The name derives from the idea that the disease was contracted by breathing foul-smelling air near swamps or stagnant waters.
Giuffra said historical sources support the assumption that malaria killed Francesco and Bianca. Documents written by the court physicians of the Medici family described symptoms consistent with the disease. They also detailed some of the treatments administered to patients, such as bloodletting – deliberate bloodletting. While these treatments were thought at the time to cure the patient of an illness, they actually made their condition worse.
The genetic analysis was done on small bone samples that were set aside when the Medici tombs were opened in 2004 before the rest of the remains were reburied. Giuffra said that scientists were not able to perform a similar analysis at that time because the technique was not sufficiently developed.
The new study found not just one but two strains of the malaria parasite – Plasmodium falciparum and Plasmodium malariae – in Francesco’s remains, suggesting he may have been a victim of double infection. Researchers also analyzed the remains of Francesco’s younger brother, Cardinal Giovanni de’ Medici, who died after a trip to the Tuscan coast with two other family members 25 years ago. Malaria was also found in the form of a previously unknown strain of Plasmodium falciparum in Giovanni’s sample.
Portraits of Cardinal Giovanni di Cosimo I de’ Medici by Agnolo Bronzino (left) and Francesco de’ Medici attributed to Alessandro Allori (right). – G. Nimatallah/De Agostini/Getty Images; Heritage Images / Getty Images
“Francesco and Giovanni, a younger member of the family, traveled 25 years apart to parts of Tuscany known for malaria,” Giuffra said.
“Court physicians tried to dissuade some members of the Medici family from making these trips, especially in the autumn, a particularly favorable season for malaria. But they went anyway, and a few days after the trip they began to develop the first symptoms, including the intermittent fever associated with malaria infection.”
Detecting different types of malaria also helps track the evolution of the disease. “Our study contributes to filling a historical gap for the Renaissance and space period in central Italy, where very limited knowledge exists about the evolution and spread of malaria,” Alexander Ochoa, an assistant research scientist at Yale and first author of the study, said in an email.
So, is there any guarantee that Francesco wasn’t poisoned too?
“Perhaps not,” Ochoa said, “but the genetic evidence presented in our study reduces the margin for speculation.”
Gisella Caccone, a senior research scientist also at Yale and one of the study’s authors, agrees. “We can say they had malaria, but we can’t say they weren’t poisoned,” Caccone said in an email. he said.
“It was already assumed at the time that they had contracted malaria, based on the symptoms they had and the fact that they had traveled to the malaria-infested swamps of southern Tuscany; and if someone decided to hasten their departure by poisoning them, we would never know. So how likely is that?”
Are skin rashes a sign of poisoning?
Donatella Lippi, a professor of medical history at the University of Florence and co-author of the 2006 study supporting the assassination hypothesis, said she still believes Francesco was poisoned. “Getting malaria does not mean dying from it, and this research supports what I have always advocated,” Lippi, who was not involved in the study, said in an email. he wrote.
He added that in the case of Francesco’s death, records in the Vatican Library mention skin rashes, fever and swelling – all symptoms of acute arsenic poisoning.
“I believe Francesco contracted malaria, but he was poisoned and died from the poison. His grave was exhumed 300 years after his death; his hands were clenched as if in pain and his body was well preserved; arsenic may explain both.”
Giuffra stated that Lippi’s findings were not based on the skeletal remains exhumed from Francesco’s grave, but on biological tissue found in a different location where some of Francesco’s organs were supposedly placed after the autopsy, according to historical records used by Lippi. Francesco was known to be a alchemist Giuffra added that she was experimenting with chemicals that could explain the skin rashes.
Researchers are studying remains recovered from the Medici Tombs in Florence. – Courtesy of the Department of Palaeopathology, University of Pisa
Anne Stone, Regents Professor at Arizona State University’s School of Human Evolution and Social Change, said the study is interesting from both a historical and ancient pathogen perspective. Stone, who was not involved in the study, suggests that the brothers died due to malaria infection, but toxicological analyzes need to be done to understand whether poison played a role.
“Recovering pathogen DNA from centuries-old human remains is technically very challenging,” David Caramelli, an anthropology professor at the University of Florence who was not involved in the study, said in an email.
“Although the study provides evidence consistent with malaria infection, I do not think it definitively resolves the long-standing debate about malaria or poisoning. The presence of pathogen DNA is not necessarily equivalent to indicating cause of death, and genetic evidence should always be interpreted in conjunction with historical, archaeological and pathological data.”
Still, Caramelli concluded that the new research represents a significant step forward and shows how. paleogenomics can contribute to answering long-standing historical questions.
EDITOR’S NOTE: This story has been updated with additional information.
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