Paracelsus

by Timo Tait, PhD.

One of the first scientists to introduce chemistry to medicine, Paracelsus, was a steadfast advocate for the use of inorganic salts, minerals, and metals for medicinal purposes.?His studies of medicine and the elements inclined a belief based on medieval alchemy that the nature of medicines was explained by a tripartite of sulphur, mercury, and salt – in every disease, the symptoms depended on which of these three principals caused the ailment.?This led him to hypothesise that materials which are poisonous in large doses may be curative in small doses and thus by 1537 he had established that “sola dosis facet venenum” – the dose makes the poison – accordingly, insinuating that nothing is without poison, it is merely the dose encountered which permits something not to be poisonous.?There are of course many variables that influence when a toxic dose may be reached, such as solubility of a toxic molecule in body fluids, frequency of exposure, health, age, genetic makeup, and the route of administration.??Although intravenous or intraperitoneal administration is generally more toxic than when something is taken orally, many plants and spices commonly used for culinary or other purposes contain compounds which may be hazardous, dangerous, or fatal at high enough doses.?Saffron, casava root, almonds, pomegranate, nutmeg, potatoes, and coffee all contain toxic compounds which may cause cellular or neurological effects.?Yet even though morning coffees are not likely to cause unintended demise (the LD50 in humans for the active metabolite caffeine is estimated between 150 and 200 mg/kg), several accidental poisonings and deaths have occurred following ingestion of plants or fungi by children or when a toxic specimen is mistakenly collected and eaten during foraging.??So, how do certain molecules act as poisons or toxins??Paracelsus held that organs in the body operated based on separating pure substances from impure ones and that salt, sulphur, and mercury were humours which represent stability, combustibility, and liquidity respectively.?Poisons, therefore, were causative agents which affected imbalances in these principals.?Today we know that poisons and toxic compounds negatively interfere with molecular targets within cells, with functional units embedded in the lipid membrane, or with the membrane itself.?Interaction of small molecules with protein receptors or enzymes may elicit agonistic, antagonistic, or inhibitory effects on cellular function and essential communication, while others may physically alter protein structure by covalent or non-covalent changes to the tertiary conformation, resulting in inactivation of protein function.?Moreover, several compounds may destabilise cell membranes, whilst others still can alkylate or intercalate with DNA. Still, nowadays several highly toxic compounds are routinely used in medicine at very low concentrations to control a plethora of malaise, with the use of cardiac glycosides to treat arrhythmias, injection of botulinum toxin for muscular and cosmetic reasons, and quinine derivatives to combat malaria, to name but a few, thus echoing Paracelsus’ assertion, sola dosis facet venenum.