The Mummified, Sudden Death Case Of Digitalis Poisoning

Several palynological studies, which were carried out over the past decades on the graves of important historical personages have helped obtain valuable information on the intake of vegetable food and beverages consumed before death, the ingestion of toxic or poisonous substances, use of particular aromatic substances in funerary rites, the origin of the clothes found in the burial and vegetation of a particular range. In the case of Cangrande della Scala, palynological spectra, although at low concentration values, revealed the intake of vegetal components by the Prince in the last moments of his life. In particular, they showed the ingestion of foxglove leaves and flowers.

Some articles are published on the significance of low taxa pollen spectra and low values of entomophilous plants in archaeobotanical and paleo forensic cases. In the case of Cangrande della Scala the prevalent ingestion of foxglove leaves instead of flowers could explain the low concentration values of pollen grains as toxicological analyses have shown the presence of two active principles of Digitalis, digoxin and digitoxin, in liver and faeces samples. The concentrations of Digitalis glycosides determined in these experiments after the rehydration of samples in a ratio of fifty/fifty are in the toxic range. However, taking into account a reasonably high loss of the compounds during the seven centuries elapsed since Cangrande della Scala’s death, it is possible to infer that the digoxin and digitoxin concentrations measured in the tissues of the Prince at the time of death were well above the lethal concentrations.

An integrated evaluation of the experimental data provided by the palynological and toxicological study clearly suggests an intoxication through the oral administration of an infusion or decoction of leaves and flowers of Digitalis. An autopsy could not reveal any alteration referable to Digitalis intoxication because acute poisoning does not leave traces at a macroscopic level. Nevertheless, Digitalis poisoning is characterised by gastrointestinal symptoms including nausea, vomiting, diarrhoea, abdominal pain; central nervous manifestations, in particular, somnolence, hallucinations, delirium and severe headache; effects on the heart like abnormal rhythms, the most serious of which is ventricular tachycardia, that can cause heart blockage.

The gastrointestinal symptoms manifested by Cangrande della Scala in his last hours of life and described by historical sources are compatible with the early phase of Digitalis intoxication. The symptomatology of Cangrande della Scala includes vomiting and diarrhoea with acute pain (“fluxus ventris,” “fluxu obiit,” and “corporeus fluxus stomachique dolor acutus”); sometimes there is a reference to fever (“fluxum et febrem continuam ob laborem exercitus”).

It is difficult to ascertain whether the Digitalis fatal intoxication of Cangrande della Scala was an intentional murder or a terrible mistake. The therapeutic properties of foxgloves were discovered in the second half of the eighth-century, but the toxic effects of the plant must have been known much earlier. Unfortunately, there is a gap in the documentary sources, since references to foxglove as a poison were not found before Renaissance times. Even if foxglove grew over the most part of Europe, it was never mentioned by Dioscorides, Theophrastus or other ancient writers.

One of the first historical sources on the Digitalis is a manuscript copy of the Herbarium Apuleii Platonici, written at Bury St Edmunds around 1120, where the English word foxglove appears along with the names of other plants prescribed to compose topical ointments for the treatment of wounds. According to the medical and botanical literature from Roman to Modern age, all these plants are described and defined as poisonous, and employed as analgesics, hypnotics and narcotics only in small doses.

The sudden disappearance of a powerful and relatively young man probably favoured the circulation of rumours about this death. Although some diseases are occasionally mentioned, such as the imprecise illnesses of 1315 and 1325, Cangrande della Scala was healthy, despite the great physical efforts during the military campaigns of the last twenty years of his life. The hypothesis of poisoning is mentioned by some local historical sources, even if the documents are not anterior to the second half of the fourteenth-century. A vernacular Venetian chronicle was written soon after 1354 and the chronicler Galeazzo Gatari in the last part of the fourteenth-century report that Cangrande della Scala was poisoned. The Veronese notary Boninsegna da Mizzole, author of a local chronicle between the fourteenth and fifteenth-century, and the notary and historian Torello Saraina in the fifteenth-century claimed that the poison had been hidden in a fruit. On the other hand, poisoning was a diffused practice in the European Middle Ages.

Some details about poisoning modalities are reported in the fifteenth-century by a Treviso chronicler, who claims that the physician accused of poisoning had been imprisoned and hung after the confession. This dubitative and late version seems to be confirmed by a more authoritative source, the jurist and chronicler Guglielmo Cortusi, who was ambassador in Verona in 1328 and close to the environment of Alberto II della Scala (1306-1352), co-ruler of Verona after the death of Cangrande della Scala together with his brother Mastino II della Scala (1308-1351); according to Guglielmo Cortusi, who is silent about the causes of Cangrande della Scala’s death, his physician died on the gallows.

Considering that the therapeutic properties of Digitalis were recognised only in Modern times, in the case of Cangrande della Scala accidental ingestion of a vegetal mixture including flowers and leaves of Digitalis should not be excluded; glycoside ingestion probably occurred as a result of an erroneous identification of leaves, not always easy to distinguish from those of other edible plants, as occurs also today. Accidental poisonings consequent to ingestion of herbal concoctions containing foxglove leaves are reported in modern clinical literature.

But the most likely hypothesis is that of a deliberate administration of a lethal amount of Digitalis; the poison may have been masked in a decoction containing chamomile and black mulberry, prepared for some indisposition of Cangrande della Scala. Although several cases of poisoning through the use of organic substances are known from historical sources, no other direct shreds of evidence are documented in the palaeopathological literature.

The multidisciplinary study performed on the natural mummy of Cangrande della Scala supports the hypothesis that he was a victim of digitalis poisoning. Palynological analyses demonstrated the presence of foxglove as pollen grains in the rectum content and toxicological analyses confirmed the presence of two active principles of Digitalis, digoxin and digitoxin, present in a toxic concentration in the liver and faeces. Although it is not possible to totally rule out an accidental intoxication, the most likely hypothesis is that of a deliberate administration of a lethal amount of Digitalis. It is more problematic to detect the instigator of the murder. The principal suspects are the neighbouring states, the Republic of Venice or Ducate of Milan, worried about the new regional power of Cangrande della Scala and Verona; at the death of Cangrande della Scala also his ambitious nephew Mastino I della Scala, who became ruler of Verona in association with his brother Alberto II della Scala, cannot be totally excluded as an instigator.

The case of Cangrande della Scala represents the unique direct evidence of poisoning through the use of organic substances in paleopathological literature.