Toxicology in the Borgias period: The mystery of Cantarella poison

Abstract

Since antiquity, poisoning has been a traditional political weapon. In Renaissance Italy, murder in political circles became so frequent that nobody believed in the natural death of popes, cardinals, and royalty. This period in history was marked by poisoning attempts of the Borgia family. It was said that they were using several kinds of poison among which cantarella a variation of arsenic, the composition of which remains unknown. In our article, we try to trace cantarella’s composition and etymology.

Since antiquity, poisoning has been a traditional political weapon and often involved in altering royal succession. Mithridates VI Eupator (132–163 BC), king of Pontus in Asia Minor who lived in constant apprehension of being poisoned by his enemies, became obsessed with poisons and tried to develop tolerance by ingesting small amounts daily along with a mixture of antidotes. Mithridates apparently obtained some degree of immunity to otherwise fatal doses of arsenic by ingesting miniscule amounts over many years. He was known to display his “immunity” to poison plots at banquets, inviting his guests to sprinkle his food and drink with deadly substances. ^1,2 Experimenting on criminals and slaves, he was one of the first to systematically study poisons in humans. The results of his experimentation were the development of a general antidote, Mithridatium, that contained 36 ingredients that were said to protect against known poisons. ^1,3 In the following centuries, several alexipharmaka or theriac (derived from the Greek therion for wild beast) were developed; the most celebrated of which was that invented by Adromachus the Elder, a Cretan who became the chief-physician to the Emperor Nero (54–68). Andromachus concoction, Galene Theriaca (tranquility theriac), was an improved version of Mithridate’s elixir, containing 65 ingredients with a higher proportion of opiates and minerals with the original lizard flesh replaced by flesh of a viper. ⁴

Centuries later, in Renaissance Italy, poisoning was at its height. Prepared by physicians, alchemists, and pharmacists, poisons were employed by wealthy families under the impulse of lust and avarice for power. Murder in political circles became so frequent that nobody believed in the natural death of popes, cardinals, and royalty. Many of these poisons originated from the so-called “three kingdoms of nature” (animals, plants, and minerals) and included snake venom, cantharides, aconite, belladonna, strychnine, corrosive sublimate, arsenic, and others. ⁵ The use of poison is also mentioned in several passages in the archives of the Venetian Council of Ten, one of the major governing bodies of the Republic of Venice from 1310 to 1797. It is of interest that the entry concerning the extermination of Sultan Mehmed II (1432–1481) contains the following: “9th July 1477. Decision—the offer made by Salamoncino and his brothers of procuring death to the Emperor of the Turks through the care of master Valcho (Mehmed’s physician) is accepted.” In the same way, the Council ordered in 1450 the poisoning of Count Francesco Sforza (1401–1466). They were planning to use a poison in the form of balls which when placed in the fire would produce toxic fumes provoking the instantaneous death of all those who were near the fireplace. ⁶

This period in history was marked by intrigue and poisoning attempts of the Borgia family, the most infamous family of Renaissance Italy. Their name became synonymous with cruelty and corruption and even if current historians are attempting to acquit them, the Borgias’ legend remains fascinating. Originating from the Borja town in Valencia, Spain, the Borgias became prominent in political and ecclesiastical cycles during the 15th and 16th centuries. Among their illustrious members were two Popes, Callixtus III (1378–1458) and Alexander VI (1431–1503), as well as, the illegitimate children of Alexander VI, Cesare Borgia (1475–1507) the major inspiration for Niccolò Machiavelli’s (1469–1527) famous work “the Prince” and the renowned political schemer Lucrezia Borgia (1480–1519). ⁷ Due to the actions of these two children, the family name remains associated with greed, power, lust, and murder.

The Borgias specialized in disposing of cardinals, bishops, and nobles by using several kinds of poisons including arsenic, strychnine, cantharidin, and aconite incorporated in drinks, clothes, gloves, book pages, flowers, and drugs. ⁷ It is said that the Borgias selected and laid down rare poisons in their cellars with as much thought as they gave to their vintage wines. The ideal poison should be reliable, effective, deceptive, and slow acting but strong enough to kill the victim ⁸ (Figure 1). It has been suggested that all these properties were accumulated in a secret poison used by the Borgias; the cantarella, a variation of arsenic, the composition of which remains unknown. A primary reason for the popularity of arsenic as a poison was that it has no flavor or odor and when mixed into food or drink, it is tasteless. It seems that cantarella was a complex mixture containing arsenic combined with alkaloids of putrefaction emitted by organic substances in the later stages of decay. ⁹ According to Nicolas Garelli (1670–1732), the chief physician of Emperor Charles VI (1685–1740), to obtain alkaloids of putrefaction, a high dose of arsenic was administered to a pig which was then suspended by the hind legs. The froth around the mouth of the dying animal was collected and kept in a bottle for use in the composition of poisons. ⁷ The Italian physician and historian Paolo Giovio (1483–1552) mentioned that cantarella was a kind of whitish powder with a pleasant taste which resembled sugar and that its efficacy was proved in several murders. ⁷ Served in a goblet of wine at dinner, it had the reputation to function with time-clock precision. According to the desire of the murder, cantarella could kill in a day, a month, or a year. It was also believed that cantarella was so powerful that no antidote existed. It was said that victims presented with a variety of symptoms including confusion, vomiting, abdominal pain, and diarrhea which could mimic several diseases. Moreover, it seems that Pope Alexander VI and his son Cesare accidentally fall victims to cantarella poisoning. Alexander died but his son recovered after entering into the body of a dead horse; an ancient belief mentioned by the Italian physician Girolamo Mercuriale (1530–1606) sustaining that entering the body of a dead animal warded off the effects of the poison. ⁵

Figure 1.

A glass of wine with Caesar Borgia (1893), painting of John Collier (1850–1934).

Another mystery surrounding cantarella is its name. Several theories have been postulated. The word arose from cantharellus, which means in Latin small cup or coming from the Greek word κάνθαρος, a kind of drinking cup. The choice of the name seems logical as cantarella was almost always mixed in liqueur or fortified wines and served in small cups. ⁷ According to another theory, the name cantarella came from the ancient Greek word κάνθαρις meaning Cantharides or Spanish fly, the insect which secretes the substance cantharidin. Cantharidin was administered in small doses as an aphrodisiac and in larger doses as a poison. The dose concentration difference has been documented by several ancient medical authors such as Dioscorides (40–90) and Pliny (23–79). ¹⁰ Probably, cantarella contained among other substances, cantharidin. In an attempt to further explain the choice of the name for such a powerful poison, it is worth mentioning that in the first edition of the famous Italian dictionary Crusca (1612), the word cantarella designates an extremely venomous insect. ¹¹

Regardless of the origin of the name of the poison and its composition, cantarella became synonymous with the murders of the Borgias, and its poisonous power is summarized in the Renaissance Italian black humor: “If you want to live, don’t dine with the Borgias and few who have dined with the Borgias have lived to tell of it.” Toxicology has evolved from an art of human poisoning to one of the basic sciences essential for improving human well-being and environmental health. ¹²