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Malaria was "the killer" of Francesco I de' Medici (1531-1587).

  • January 2009
Authors:
Raffaella Bianucci at Ronin Institute
Raffaella Bianucci
Gino Fornaciari at Università di Pisa
Gino Fornaciari
Valentina Giuffra at Università di Pisa
Valentina Giuffra
Ezio Ferroglio at Università degli Studi di Torino
Ezio Ferroglio
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MEDICAL HUMANITIES PERSPECTIVES
Helle Mathiasen, CandMag, PhD, Section Editor
Malaria Was “the Killer” of Francesco I de’ Medici
(1531-1587)
Gino Fornaciari, MD,
a
Valentina Giuffra, PhD,
a
Ezio Ferroglio, DVM, PhD,
b
Raffaella Bianucci, PhD
c,d
a
Division of Paleopathology, History of Medicine and Bioethics, Department of Oncology, Transplants and Advanced Technologies in
Medicine, University of Pisa, Italy;
b
Laboratory of Parasitology and Parasitic Diseases, Department of Animal Production,
Epidemiology and Ecology, University of Turin, Grugliasco Torino, Italy;
c
Laboratory of Anthropology, Department of Animal and
Human Biology, University of Turin, Torino, Italy;
d
UMR 6578 CNRS-EFS (Biocultural Anthropology), University of Marseille,
France.
The sudden deaths of Francesco I de’ Medici (1531-1587),
Second Grand Duke of Tuscany (Figure 1a), and his wife,
Bianca Cappello (1548-1587), have been shrouded in mys-
tery, and the cause of death has been debated for the past 4
centuries.
Francesco was the first child of Cosimo I de’ Medici
(1519-1574), First Grand Duke of Tuscany, and his wife,
Eleonora of Toledo (1522-1562). He became Grand Duke of
Tuscany in 1564, ruling until his death. Francesco was not
interested in political affairs, which he delegated to his
functionaries. Instead, he became a patron of the arts and
sciences and a passionate alchemist. In 1565, he married
Joan of Austria (1548-1578), and they had 7 sons. During
this marriage, Francesco began a relationship with a Vene-
tian noblewoman, Bianca Cappello, whom he married in
1579 after the death of his wife.
In October 1587, the Grand Duke and his wife died
unexpectedly within 24 hours of each other. Contemporary
medical documents attributed the deaths to tertian malarial
fevers.
1
Rumors soon spread that Francesco and Bianca had
been poisoned with arsenic by Francesco’s brother, Cardi-
nal Ferdinando I (1549-1609) (Figure 1b).
2
The rumors
were apparently instigated by courtiers who knew of the
long-standing disagreements between the brothers.
Ferdinando I never tolerated the presence of the new
Grand Duchess at the Medici court. The Cardinal also re-
sented Bianca’s meddling in court affairs and accused his
brother of behaving in a manner unbecoming his ducal role.
Two weeks before their deaths, on September 25, 1587,
Ferdinando, Francesco, and Bianca met at the Medici villa
in Poggio a Caiano, where they were thought to have at-
tempted a reconciliation.
Francesco I’s skeleton was unearthed from the topsoil of
the Medici Chapels in San Lorenzo Church (Florence, Italy)
in 2004.
3
Bianca Cappello’s remains have not been recov-
ered; her burial site remains unknown. Recently, the ancient
rumors of murder have received apparent support from a
toxicologic study that excluded malaria as the cause of
Francesco’s death.
4
Malaria was endemic in Central Italy, especially Tus-
cany, from the 2nd and 3rd centuries BC to the end of World
War II. To determine whether the original death certificates
might have been correct and the rumors false, we carried out
an immunologic investigation to determine whether Plas-
modium falciparum malaria might have caused the death of
Francesco I.
Cancellous bone was harvested from a vertebra of
Francesco I. Bone samples of Cosimo I de’ Medici, who
died of pneumonia, and his daughter-in-law, Joan of Aus-
tria, who died in childbirth, were used as negative controls.
1
In addition, 2 medieval bone samples from 2 sites known to
be free from malaria (Briançon, France, 17th century; Augs-
burg, Germany, 14th century) also were used as negative
controls.
Extracts prepared from spongy bone samples were ex-
amined for the presence of P. falciparum histidine-rich
protein 2 and P. falciparum lactate dehydrogenase using 2
commercial qualitative double-antibody immunoassays:
Malaria Antigen RAPYDTEST and Malaria Detect RAPYDTEST
(DiaSys, Waterbury, Conn).
5
Positive results were obtained from both dipstick assays.
We therefore provide the first biological evidence of the
Funding: None.
Conflict of Interest: None of the authors have any conflicts of interest
associated with the work presented in this manuscript.
Authorship: All authors had access to the data and played a role in
writing this manuscript.
Requests for reprints should be addressed to Gino Fornaciari, MD,
Department of Oncology, Transplants and Advanced Technologies in Med-
icine, Division of Paleopathology, University of Pisa, Via Roma 57, 56126
Pisa, Italy.
E-mail address: g.fornaciari@med.unip.it
0002-9343/$ -see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2009.12.020
presence of both P. falciparum ancient proteins (P. falcipa-
rum histidine-rich protein 2 and P. falciparum lactate de-
hydrogenase) in the skeletal remains of Francesco I de’
Medici. No mixed falciparum infections or non-falciparum
infections were identified. Bone samples from Cosimo I,
Joan of Austria, and control samples were all negative, as
expected.
Our recent findings support the detailed medical docu-
ments recorded by court physicians who carefully described
the different stages of the sudden illness that affected the
Grand Duke Francesco I until his demise.
1
Muscle has, thus far, been considered the best tissue for
the detection of P. falciparum malaria because of its abun-
dant red cell content.
6
We now show that malaria antigens
also can be detected in ancient bone samples.
With the use of modern methods, we provide robust
evidence that Francesco I had falciparum malaria at the time
of his death. Our immunologic results confirm the archival
sources that described the onset, course, and fatal outcome
of the disease. Our findings also absolve Ferdinando I from
the shameful allegation of being the murderer of his brother
and sister-in-law.
References
1. Pieraccini G. La stirpe de’ Medici di Cafaggiolo: saggio di ricerche
sulla trasmissione ereditaria dei caratteri biologici. Firenze: Nardini
Editore; 1986.
2. Saltini GE. Della morte di Francesco I de’ Medici e di Bianca Cappello.
Archivio storico italiano, Nuova serie. 1863;XVIII:21-81.
3. Fornaciari G, Vitiello A, Giusiani S, et al. The “Medici Project”: first
results of the explorations of the Medici tombs in Florence (15th-18th
centuries). Paleopathol Newsl. 2006;133:15-22.
4. Mari F, Polettini A, Lippi D, Bertol E. The mysterious death of
Francesco I de’ Medici and Bianca Cappello: an arsenic murder? Br
Med J. 2006;333:1299-1301.
5. World Health Organization. The role of laboratory diagnosis to support
malaria disease management. Focus on the use of rapid diagnostic tests
in areas of high transmission. Report of WHO Technical Consultation.
Geneva 25-26 October 2004;1-32.
6. Bianucci R, Mattutino G, Lallo R, et al. Immunological evidence of
Plasmodium falciparum infection in a child mummy from the early
dynastic period. J Archaeol Sci. 2008;35:1880-1885.
Figure 1 Portraits of Francesco I de’ Medici (Scipione Pulzone, Uffizi) (a) and Ferdi-
nando I de’ Medici (Scipione Pulzone, Uffizi) (b). (With permission from the Ministry of
Cultural Heritage.)
569Fornaciari et al Malaria of Francesco I
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Medici di Cafaggiolo: saggio di ricerche sulla trasmissione ereditaria dei caratteri biologici. Firenze: Nardini Editore
  • Jan 1986
  • G Pieraccini
  • La
  • De
Pieraccini G. La stirpe de' Medici di Cafaggiolo: saggio di ricerche sulla trasmissione ereditaria dei caratteri biologici. Firenze: Nardini Editore; 1986.
Della morte di Francesco I de' Medici e di Bianca Cappello. Archivio storico italiano, Nuova serie
  • Jan 1863
  • 21-81
  • G E Saltini
Saltini GE. Della morte di Francesco I de' Medici e di Bianca Cappello. Archivio storico italiano, Nuova serie. 1863;XVIII:21-81.
The role of laboratory diagnosis to support malaria disease management. Focus on the use of rapid diagnostic tests in areas of high transmission. Report of WHO Technical Consultation
  • Nov 2004
  • 1-32
  • Health World
  • Organization
World Health Organization. The role of laboratory diagnosis to support malaria disease management. Focus on the use of rapid diagnostic tests in areas of high transmission. Report of WHO Technical Consultation. Geneva 25-26 October 2004;1-32.