2. The concept of a universal antidote
The first universal antidote was mithridate, in which after taking it an increasingly strong dose response was induced [4]. In the 1st century AD, its composition was modified by Andromachus the Elder, Nero’s physician, who added dozens of new ingredients to mithridate, including viper meat, which was commonly considered as an antidote to snake venom [5]. This is how Theriac Andromachi was made, the first anti-venom antidote, used for people bitten by snakes and other wild animals (Greek θηριακός, thēriakós, means ‘concerning venomous beasts’) living in the vast territory of the Roman Empire [6].
Galen’s observations of the victims of venomous animals shaped the paradigm of poison, a substance that can cause a deterioration of health or even death when absorbed or introduced into the human body [7]. In the treatise entitled ‘De antidotes’, he noticed the dual nature of plants. Some of them, such as cowbane and hellebore, were food for animals, but were harmful to humans, thus endangering their lives. Theriac, the ‘cleansing fire’ produced from cowbane, aconite and black henbane, among others, was a remedy for the most dangerous poisonous plants and animal venoms. Due to the similarities between the violent reaction of the human body to animal venoms and symptoms of the plague, Galen treated contagion victims with theriac. He argued that as poison entered the body through the mouth, the evil entered from the air with the breath, therefore the administration of a universal antidote was justified. Theriac had to be taken constantly to ensure resistance to various diseases [8]. Arab doctors practising in medieval Europe did not bring new content to the knowledge of antidotes, limiting themselves to copying Galen’s thoughts, including those about theriac as a means of preventing a plague [9]. Even in the 17th century, diseases caused by poisons and contagions were combined into one category and treated with theriac [10]. Until the mid-18th century, recipes for theriac, and also for mithridate, were in all official dispensatories and pharmacopoeias [1,10].
The first lectures on poisons and their effects in the human body were given by Girolamo Mercuriale (1530-1606) at the University of Padua, based on the treatises of Galen, Aetius, Scribonius the Elder, Pliny, Avezoar and Avicenna. The systematizing of knowledge on poisons was such pioneering work, that Mercuriale asked Wojciech Szeliga (in Latin: Albert Scheliga, died 1585), a medicine student from Warsaw, to write down and compile the lectures, and in accordance with the then customs published them under his own name. This is how the textbook ‘De venenis et morbis venenosis tractatus locupletissimi’ was created in 1584 by Szeliga. He described the effects of poisons patterned on Mercurialis, i.e., in terms of the humoral pathology as systemic diseases caused by poisoning one of the humours, usually blood. The methods of the chemical identification of poisons were not known yet and they were recognized on the basis of a heart rate test. Unlike the plague, the effect of a poison manifested itself in an uneven pulse that gradually weakened until blood circulation finally ceased. Among less characteristic symptoms were vomiting, tremors, hiccups, and abdominal pain. At first, a doctor would remove a poisoned humour by administering emetic, diaphoretic, laxative, and diuretic agents. Additionally, a doctor could recommend mithridate or theriac, viper scorpion, toad or lizard oil, simple medicines with absorbing properties, such as Armenian clay, deer horn (Cornu Cervi) and bezoar, or emerald, topaz and hyacinth, or magic stones to protect against the hidden poison [9].
In the 17th century, poisoning was described from the perspective of iatromechanics. According to Sebastian Śleszkowski (1576-1648), in Latin called Slescovicus, the author of the book entitled ‘Incomparabilis thesaurus alexitericus’, the characteristic features of poisons were disorganisation and a change in body composition and nerve irritability, often with fatal consequences. He used the criterion of the toxic action strength to classify, one of the strongest which was ethanol. He emphasised that the same pharmaceutical agent can be a medicine, poison or antidote, such examples were: mugwort (Artemisia), agaric (Agaricus) or periwinkle (Vinca pervinca). However, he was uncritical of medical superstitions. Among effective antidotes, he mentioned lamb’s blood, diamond, emerald and a picture of a snake that allegedly gave protection against a viper bite [11].
The problem of poisons and counteracting their harmful effects was also taken up by John Jonston (1603-1675), a Scottish physician who settled in Poland [12]. In the treatise ‘Syntagma universae medicinae practicae’, he described in detail eight mineral poisons (including copper, considered an antidote by Mercuriale and Szeliga), eight animal poisons (including leeches commonly used to let blood) and thirteen plant poisons, including monkshood (Aconitum napellus), henbane (Hyoscyamus niger), black hellebore (Helleborus niger), overseas strychnine tree (Strychnos nux vomica) and mandrake (Mandragora officinarum). Almost all poisonous plants have been known since antiquity [8].
In the 18th century, it was discovered that animal venoms reach the brain through the bloodstream. Instead of administering antidotes, it was necessary to limit the spread of the poison by burning or cauterising the wound after the bite, applying ligatures, cupping without scarification, applying cold compresses of diluted hydrochloric acid, amber oil mixed with musk, or scorpion oil with rue, chamomile and Peruvian balm. From then on, theriac became only an additive in camphoric vinegar or vesicants (patches causing irritation) when applied to the puncture wound [13]. William Heberden (1710-1801) contributed to the complete rejection of theriac by proving that behind the traditional name there were medicines produced by pharmacists according to various recipes, having incomparable effects and containing a multitude of ingredients inhibiting each other’s biological activity [14].