The Medici family evokes wealth and power for those who are familiar with the lasting imprint this famous family left on their native city - Florence, Italy. They transformed Florence from a prosperous medieval republic into the cultural and financial heart of the Italian Renaissance. The Medicis’ patronage provided opportunities for art and science to flourish. Their support of Galileo enabled his astronomical discoveries, and four members of the family served as Pope. From the decoration of the famous ceiling of the Santa Maria del Fiore Cathedral, known as the Duomo, to the enduring cultural legacy of iconic artists such as Botticelli, Leonardo da Vinci, Raphael, and Michelangelo, they helped shape European culture and science.
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400-Year-Old Question: Poison or Disease?
One of the Renaissance's most enduring mysteries centers on the deaths of Francesco I de' Medici and his second wife, Bianca Cappello, who died within hours of each other in October 1587. For more than four centuries, historians have debated whether they succumbed to disease or were murdered with poison as part of a dynastic power struggle. This mystery has now been concluded by modern investigation techniques.
A Sudden Double Death
In October 1587, Francesco and Bianca were staying at the Medici villa in Poggio a Caiano, after several days of fever, vomiting, and weakness, Francesco died on October 19, and Bianca died the next day. Two deaths of prominent people at the same time with the same symptoms sparked suspicion, as neither was old nor weak, and neither was in poor health. Francesco was only 46 years old.
Suspicion Falls on Ferdinando
The accusation focused on Francesco's younger brother, Ferdinando I de' Medici, as the most likely suspect. Rumors swirled that he had poisoned the couple’s food with arsenic–a preferred weapon of the Renaissance. No evidence of his guilt was produced at the time, but it was reasonable to think the deaths were political. Ferdinando opposed Bianca’s influence at court, and succession depended on Francesco’s death. The cause of death being arsenic was the popular option until modern science shifted the debate.
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Fernando I de’ Medici. (Public Domain)
Modern Science Intervenes
In the early 2000s, scientists examined remains believed to belong to Francesco and Bianca. Some chemical analyses reported elevated arsenic levels, which seemed to confirm theories of poisoning. However, historians pointed out that arsenic was also used as medicine during the Renaissance. It might even have entered the remains through later contamination.
A recent investigation published in 2026 analyzed ancient DNA and proteins recovered from Francesco's remains. Researchers detected clear molecular evidence of infection by the malaria parasite Plasmodium falciparum, along with biological signs consistent with a severe malarial illness. It is one of the deadliest forms of malaria.
Infographic relating how DNA damage found in the Medici brothers’ samples revealed malaria as cause of death. ((Ochoa et al., iScience/CC BY 4.0)
The symptoms described in 1587—including fever, chills, weakness, and declining health—are better explained by malaria than by arsenic poisoning. The testing also provided clues about the spread of the disease across Europe centuries ago.
The study, originally published in iScience, examined the skeletal remains of Francesco and his younger brother, Cardinal Giovanni de' Medici. Both men’s deaths are now linked to their repeated fevers, a symptom that has been linked to malaria within historical records. Researchers, principally from Yale and Pisa Universities, extracted DNA from the rib bones of these two brothers - three from Francesco, one from Giovanni. Their remains have rested inside the Medici Chapel within the Basilica di San Lorenzo in Florence.
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Ancient DNA damage patterns were used to authenticate Plasmodium DNA recovered from the skeletal remains of Grand Duke Francesco I de' Medici and Cardinal Giovanni de' Medici during the study of Renaissance malaria infections. (Ochoa et al., iScience/CC BY 4.0)
The Surprise Inside Giovanni's DNA: A Previously Unknown Malaria Strain
Giovanni’s DNA sample held another surprise. His P. falciparum DNA belonged to a previously unseen genetic type. The particular sequence contained unique mutations. When researchers compared the DNA samples with other ancient malaria genomes dating back to the Iron Age and as far as the 1940s, they found close links with samples from Europe, Taiwan, and the Caribbean. Their results suggest that this strain spread during a period of population growth in Europe. These findings also add another layer to this chapter in the long history of malaria. The DNA itself helped scientists trace how malaria parasites changed over time and how different strains of this disease spread across several regions. Those genetic records from the Medici brothers can now fill certain gaps in the historical record.
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Did Bianca also die of malaria?
Researchers are not as confident about Bianca’s cause of death, but most historians believe she also suffered from a malaria infection. Their villa was located in a marshy area where malaria was common. Fewer biological samples are available from Bianca, so there is less evidence in her case.
Cardinal Giovanni di Cosimo I de' Medici. (Baccio Lomi/Public domain)
Malaria, Not Murder
Historical accounts match the DNA evidence. In 1562, Giovanni was traveling with his mother, Eleonora of Toledo, and his younger brother, Garzia, to the Tuscan Coast. Marshes in this area were unfortunately full of malaria-carrying mosquitoes. All three developed a terrible fever and died within a month. Giovanni was only 19 years old.
Meanwhile, Francesco fell ill 25 years later after visiting the Medici family’s villa in Poggio with his wife, Bianca. They decided to walk through swampy rice fields where mosquitoes were abundant. Mosquitos had the motive and opportunity to kill.
Why Renaissance Doctors Couldn't Identify — or Treat — Malaria
The new DNA findings match reports written by court doctors during the 16th century. These same reports described repeated fevers known in central Italy at the time as “febbre terzana,” the local name for malaria. The records also mention bloodletting, a common medical practice used if a doctor believed the patient was suffering from a lethal element that could not be seen from the outside. Thus, it must be released from the inside. Unfortunately, the remedy could be far worse than the original ailment. Earlier studies have also found immune markers directly linked to P. falciparum in the brothers' DNA.
This study is the first time scientists have confirmed these findings with genetic evidence from the subjects’ remains. These results resolve one of the Renaissance’s longest-running medical debates while also adding new data to the history of malaria. Malaria was finally eradicated in central Italy during the 20th century, following numerous disease control campaigns. Today, the illness still affects numerous people across many regions of the globe. The World Health Organization (WHO) estimates that about 282 million cases of malaria caused 610,000 deaths in 2024 alone. Fortunately, ongoing research like this study on two Renaissance brothers can yield evidence of transmission and mosquitoes’ adaptations over time.
Top image: Left; Portrait of Francesco I de' Medici, Right; Bianca Cappello. Source: Left; Alessandro Allori/Public domain, Right; Alessandro Allori/Public domain
By Ramsey Hardin
References
Alexander Ochoa et al., “Ancient DNA Analyses of Remains of the Medici Family (16th Century CE) Provide Insights into the Genetic Variation of Plasmodium falciparum " iScience 29 (2026): 116371, Available at: https://www.cell.com/iscience/fulltext/S2589-0042(26)01746-3
Cummings, M. “Genetic Analysis of Medicis’ Remains Reveals Renaissance-Era Malaria Strains—and Closes Book on a Murder Mystery.” Yale News. June 30, 2026.https://news.yale.edu/2026/06/30/genetic-analysis-medicis-remains-reveals-renaissance-era-malaria-strains-and-closes-book.
Radley, Dario. “Ancient DNA Reveals Malaria Killed the Medici Brothers, Not Poison.” Archaeology Magazine. July 2, 2026.https://archaeologymag.com/2026/07/malaria-killed-the-medici-brothers-not-poison/
Killgrove, Kristina . “Ancient-DNA Analysis Solves 500-Year-Old Mystery of What Killed 2 Medici Brothers.” Live Science. July 1, 2026.https://www.livescience.com/archaeology/ancient-dna-analysis-solves-500-year-old-mystery-of-what-killed-2-medici-brothers.
University of Pisa. “Malaria Killed the Medici Brothers: Parasite DNA Reveals a Previously Unknown Strain.” June 2026.https://www.unipi.it/en/news/malaria-killed-the-medici-brothers/.
World Health Organization. World Malaria Report 2025. Geneva: World Health Organization, 2025.https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2025
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