Dosage alone determines poisoning


When as a schoolboy, I never imagined that history could be interesting, let alone be an important factor in the development of the art of medicine. However, medical history has shown modern medicine the way forward. If it had not, we would still be using “laudable pus” on wounds and subscribing to the “vapors” as the cause of TB.

Take toxicology, for example. We didn’t just stumble across this very important branch of medical expertise. We were actually handed it in the 16th Century from a doctor by the name of Theophrastus Phillippus Aureolus Bombastus von Hohenheim, AKA Paracelsus.

It was Paracelsus who proposed the earth shattering concept that ‘Dosage alone determines poisoning.’ When you think about it, this was the basic principle of toxicology.

Toxicology and Applied Pharmacology covers original research pertaining to action of chemicals, drugs, or natural products to animals or humans. The Journal of Toxicology and Applied Pharmacology covers mechanistic approaches to physiological, biochemical, cellular, or molecular understanding of toxicologic / pathologic lesions and to methods used to describe these responses.

Paracelsus is credited with developing a mineral-based chemical approach to human health problems, a radical in his day who is considered elemental in the transition from mystical traditions to modern science.

The dose of any substance decides whether the substance is harmful or otherwise.

Paracelsus intended to indicate this to be a basic principle of toxicology. “All things are poison, and nothing is without poison, the dosage alone makes it so a thing is not a poison.”

This concept went across the medical thinking of the day, which dated back to Hippocrates and Galen, who contributed a substantial amount to the Hippocratic understanding of pathology. Under Hippocrates’ bodily humors theory, differences in human moods come as a consequence of imbalances in one of the four bodily fluids: blood, yellow bile, black bile, and phlegm. Galen promoted this theory and the typology of human temperaments. In Galen’s view, an imbalance of each humor corresponded with a particular human temperament (blood—sanguine, black bile—melancholic, yellow bile—choleric, and phlegm—phlegmatic). Thus, individuals with sanguine temperaments are extroverted and social; choleric people have energy, passion, and charisma; melancholics are creative, kind, and considerate; and phlegmatic temperaments are characterized by dependability, kindness, and affection.

As human dissection was not allowed in those early years (Roman law had prohibited the dissection of human cadavers since about 150 BC), Galen dissected monkeys. Galen’s principal interest was in human anatomy, but, because of this restriction, Galen performed anatomical dissections on living (vivisection) and dead animals, mostly focusing on pigs and primates. This work was useful because Galen believed that the anatomical structures of these animals closely mirrored those of humans. Galen clarified the anatomy of the trachea and was the first to demonstrate that the larynx generates the voice. In one experiment, Galen used bellows to inflate the lungs of a dead animal. Galen’s work on the anatomy remained largely unsurpassed and unchallenged up until the 16th century in Europe.

However, in the middle of the 16th century, the anatomist Andreas Vesalius challenged the anatomical knowledge of Galen by conducting dissections on human cadavers. These investigations allowed Vesalius to refute aspects of Galen’s anatomy.

Medically it was an interesting time, in the 16th century. The ‘establishment’ was being challenged by Paracelsus and Vesalius, and they fought back to retain the old teachings – no matter how incorrect they were.

There were people in the time of the plague (the Black Death) who believed that they had sinned. They believed that the only way to show their true repentance was to inflict pain on themselves. These were the so-called flagellants who whipped themselves to show their love of God and their true remorse at being a sinner. Clearly, this was no cure for the plague.

We still haven’t got all the answers, but we are a lot closer than we were in the 16th century!