TITLE PAGE
Did Giovanni dalle Bande Nere become a legendary condottiero because of his MAOA gene?
Pellegrini S, Ph.D.a, Mariotti V, Ph.D.a, Di Nunzio C, Ph.D.b, Palumbo S, Ph.D.c, Ricci P, M.D.b, Fornaciari G, M.D.d, Pietrini P, M.D., PhD.e.
aDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa (Italy);
bDepartment of Medical and Surgical Sciences, Legal Medicine, Magna Graecia University,
Catanzaro (Italy);
cDepartment of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa,
Pisa (Italy);
d Department of Civilisations and Forms of Knowledge, University of Pisa, Pisa (Italy); eIMT School for Advanced Studies, Lucca (Italy).
Corresponding author: Pietro Pietrini, IMT School for Advanced Studies, Piazza San Ponziano 6, 55100, Lucca (Italy)
e-mail: pietro.pietrini@imtlucca.it
KEY WORDS: MAOA, violent behavior, gene-environment interaction, Giovanni Dalle Bande Nere
ACKNOWLEDGMENTS
CORRESPONDENCE
The interplay between genes and childhood environment in modulating human behavior has recently encountered a renewed interest (Chang et al., 2018; Iofrida et al., 2014; Palumbo, et al., 2018). In particular, a VNTR (Variable Number of Tandem Repeats), located in the promoter of the monoamine oxidase A (MAOA) gene in the X chromosome has been found to modulate adulthood control of aggressive behavior in relation to childhood environment ( Caspi et al., 2002). Specifically, the
alleles with 2, 3 and 5 repeats, named the MAOA Low-activity alleles, decrease MAOA expression and are associated with a higher risk of aggressive and antisocial behavior - to the point that MAOA has been nicknamed “the Warrior gene” - as opposed to the alleles with 3.5 and 4 repeats which are
High–activity alleles ( Caspi et al., 2002).
While the first report of severe antisocial behavior due to a genetically dysfunctional MAOA activity dates back only 25 years (Brunner et al., 1993), we questioned whether such genetic variants could
be detected in ancient cases known because of their aggressive and violent behavior.
To this aim, we investigated the legendary Reinassance condottiero Giovanni Dalle Bande Nere (1498-1526) by extracting DNA from a fragment of his left femur, obtained by one of the authors (GF), who performed the body exhumation and examination (Fornaciari et al, 2014). MAOA genotyping was performed by Polymerase Chain Reaction (PCR) amplification. The size of the product was estimated by comparison with two samples with known genotypes.
Giovanni dalle Bande Nere carried the MAOA 2-repeat Low-activity allele (fig.1), a very rare variant, found only in 0.1% of Caucasian males (Beaver et al., 2014).
Males with the 2-repeat allele show levels of violence approximately twice greater than males with any of the other MAOA variants(Guo et al., 2008); these individuals are significantly more
likely to engage in shooting and stabbing behaviors than subjects with the other genotypes (Beaver, Barnes, and Boutwell 2014). The 2-repeat allele exhibits in vitro a promoter activity equal to 25– 30% of the promoter activity of the High-activity 4-repeat allele (Guo et al., 2008).
Furthermore, Giovanni was raised in an affectively poor and neglecting environment, with no father - Giovanni de’ Medici, “il Popolano” (1467-1498), died just five months after the baby was born - and was raised only by his mother, Caterina Sforza (1463-1509), famous as the “warrior lady” of Renaissance, who mostly neglected Giovanni, as she spent her life strenuously fighting against Cesare Borgia (Pieraccini, 1924).
Giovanni was only 12 y/o when he mortally wounded a boy of his same age and thus he was banished from Florence. By age of 20 years, something like 8 to 10 murders for futile reasons were attributed to him, including the killing of two emissaries of Camillo Appiano, lord of Piombino, for which he was banished again from Florence for five years. At 28 years, in his last year of life, he killed in Pavia a noble from Lucca, supposedly for an old insult. A reckless troop leader, Giovanni would get explosively angry with his soldiers and would not hesitate to kill them personally, often for little or no reasons. The Medici historian Gaetano Pieraccini defined him “an innate criminal” (Pieraccini, 1924).
We propose that the association between the rare genetic variant resulting in a reduced MAOA activity and the neglecting childhood environment may have significantly contributed to Giovanni's impressive aggressive behavior.
The main limitation of this work is that it is a retrospective evaluation of a single case. On the other hand, this is also the peculiar and innovative aspect of this study that, to our knowledge, is the first to provide an evaluation of a notorious case of abnormally violent behavior in light of the modern behavioral genetics acquisitions.
In the last decade, genetic and neurobiological factors that (may) affect control of behavior have been taken into consideration in Courts, in cases of individuals who committed impulsive crimes, including homicides, as one of the reasons to claim mental insanity in the defendant, both in Europe and in the United States(Feresin, 2009; Iofrida et al., 2014; Scurich and Appelbaum, 2017).
insights on the mechanisms that subtend human behaviour, including those acts that violate moral and social norms, like the killing of another human being.
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Figure 1. Electophoretic pattern of PCR products obtained from Giovanni Dalle Bande Nere’s DNA and from two control samples with known genotypes (C1 and C2). Lane 1: negative control without DNA (C-). Lane 2: GeneRuler 50pb DNA Ladder. Lane 3: Giovanni Dalle Bande Nere’s DNA. Lane 4: 2/4-repeat positive control. Lane 5: 3/4-repeat positive control.
