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Potions & Poisons: Alchemy to Pharmacology

What is Pharmacology?

Definition: The Greek word for drug, pharmakon means a drug, remedy, and a poison. Drugs can be either toxins or antidotes.
General Points: Most therapies were discovered by empirical means—observation, accident, trial and error. The empirical discovery of therapies depends on two conditions: 1) what constitutes the disease; and 2) an opportunity to observe outcomes.
Origins: In the first century BC, King Mithridates VI of Pontus in Asia Minor feared that he was going to be murdered by the Romans. He experimented by immunizing against poisons by drinking the blood of ducks who had been fed toxins—thus the universal term for a universal antidote, mithridates.
Another ancient antidote was theriac, which was developed to counteract animal poisons. This term is from the Greek word therion (‘wild beasts’), and there were a great variety of recipes for this treatment, some involving up to 70 ingredients, including the flesh of vipers.
Both mithridates and theriac were used to treat infectious diseases, conceived as ‘pests’ or ‘poisons’.

Page from Early Modern Text of Materia Medica, in Latin

Faith & Placebos; and Medicine in the Ancient World

Doctors, or healers, have always used therapeutic treatments. Ancient remedies included both magic and prayer in addition to herbal treatments.
The usefulness of a spiritual factor is not limited to the ancients, however, as pilgrims with a variety of ailments continue to flock to healing shrines such as Lourdes in France, Fatima in Portugal, and Ste-Anne-de-Beaupré in Quebec.
The spiritualistic or vitalistic aspect of treatment is a an important element in the concept of a placebo (from the Latin for ‘to please’). The term refers to the administration of harmless but inert compounds to treat a patient. However, before discounting the placebo, clinical trials have demonstrated that they are effective in virtually form of intervention against almost all diseases.
Greek Therapeutics: In the Greco-Roman world disease was thought to be caused by an imbalance in the humours—thus treatment tried to restore the balance. Key to treatment was the modification of diet and lifestyle. Most Hippocratic treaties refer to non-drug therapies such as bloodletting, special diets, baths, exercise or rest, and applications of heat or cold. However, more than 300 medications are also cited—most of plant origin that were applied either externally or internally. Hippocratic doctors believed in the healing power of nature, and that medicine was to help the body heal itself; it was not supposed to hurt (although sometimes it could). Primum non nocere (‘first, do no harm’)!

Pottery Votives Found in Greek Healing Temples

Galen, in the second century AD was a successful therapist. He utilized a wide variety of medications, most of which were vegetable derivatives, that came to be known as galenicals, or simples.
Roman-era pharmacopoeia embraced the therapies of much of the Classical age, and relied on an assortment of medical botany—more than 600 plants, animals and their derivatives. Remedies were classified by their physical qualities: oils, animals, cereals, herbs, roots, and wines.
The most famous text was by Dioscorides, a first-century Greek physician, whose writing on materia medica (‘medical substances’) was the standard for more than 1,400 years.
Many of the herbal treatments first discovered by the Greeks were ‘saved’ by the Arab physicians in the early medieval period, and then reintroduced to Europe during the late Middle Ages where they were they translated into Latin.
A problem for European physicians consulting these works was that no ancient illustrations survived, and most descriptions of plants were difficult to related to known species.

Early Modern Woodcut Portrait of Galen

Therapeutics in the Age of Galen

Medieval Pharmacology: The Alchemists & Botany

In medieval Europe Churchmen, such as the Venerable Bede (672-735) in England, and fellow monks had extensive knowledge of plant remedies. Unschooled healers often used chants and charms to cure certain diseases that they believed were caused by bad luck, darts shot by elves, or evils of the ‘great worm’—a term applied to snakes, insects and dragons.
Amulets, magic numbers, astrology, and meteorological ‘research’ also demonstrated the instability of much of society, how much had been lost of past knowledge, and that the torch of medicine had moved from Galen’s Rome and Western Europe to the Arab empire in the East.
One of the most famous botanical ingredients was the mandrake root (mandragora) which was used to make both love potions and as an anesthetic—often mixed with wine. The Mandrake’s anthropoid appearance led to the development of a rich mythology that claimed that humans who pulled it from the ground would be killed by its screams (even in Harry Potter), and that a dog should therefore be tied to the root and tempted to harvest it by placing a dish of meat nearby that the dog would have to dig up.

Medieval Illustration of the Mandrake Root

Early Modern Alchemist’s Workshop (Early 16th Century)

Metals and Therapeutics

While the ancient Greeks knew about copper and did use it in some treatments, it was not until the late 1400s that metals came to be widely used in medical therapies. By the Renaissance, the Greco-Roman concept of the ‘earth’ element, had been expanded to include the new elements of salt, antimony, mercury and sulfur.
By the 16th century mercury was being recommended as a treatment for the new European disease of syphilis. Mercury causes gastrointestinal disturbances, gum swelling, salivation, and neurological toxicity, but also was an effective treatment for syphilis.
Antimony compounds produce nausea, vomiting, purging and cardiovascular collapse, but in a tartar emetic is was one of the most popular therapies of the early modern period (17th-18th centuries), and despite calls for its prohibition, was used as a ‘cure’ for typhoid fever and pneumonia.

Medieval Couple in a Mercury Bath

A Canadian Story: Banting, Best and Treating Diabetes

Frederick Banting (1891-1941), a physician in London, Ontario, was convinced from his research that a pancreatic disorder was the cause of diabetes mellitus. In the summer of 1921, he borrowed laboratory space from J.J.R. Macleod a professor of physiology (who was away on a fishing holiday in Scotland) at the University of Toronto to work with Charles Best (a medical student) on experimentally induced diabetes in dogs. They isolated and purified the hormone insulin, using extracts from the Islets of Langerhans in the pancreas (along with J.B. Collip). They injected the extract into a diabetic dog who was near death, but who then made a rapid recovery. The result of this work was that insulin was the first hormone to be developed as a specific replacement therapy for this common, and previously fatal disease. On 11 January 1922, they gave injections to a 14-year old boy, Leonard Thompson, who was dying of diabetes in the Toronto General Hospital. Thompson’s blood-sugar level fell, and within days he was out of bed, and in weeks returned home where he could now live (albeit dependent on insulin injections). The 1923 Nobel committee presented the prize to Banting and Macleod, who shared it with Best and Collip. The Eli Lilly Company in Indianapolis, who had helped to solve the technical problems with producing insulin, then went into large-scale production of this life-saving cure.

Frederick Banting and Charles Best at University of Toronto

Frederick Banting (1891-1941)

Top Treatments Used or Sold in Various Medical Practices, 1795-1930s

1795	1850s	1880s	1930s
Opium	Quinine	Cupping	Codeine
Blisters	Opium	Opium	Acetylsalicylic acid
Senna	Venesection	Tartar emetic	Sodium bicarbonate
Aloes	Tartar emetic	Chloroform	Acetphenetidin
Tartar	Calomel (mercury)	Bromide	Elixir pepsin
Cinchona	Blisters	Aconite	Sodium bromide
Licorice	Ipecac	Chloral hydrate	Glycerin
Enemata	Cupping	Enemata	Sodium salicylate
Mercurials	Iron	Milk	Nux vomica
Jalap	Jalap	Ammonium Clorate

A Pharmaceutical’s Life Cycle: The Jawetz Curve

Graph of Phases in a Drug’s Use (Jawetz in Annual Review of Medicine (1954)) [below]

Ernest Jawetz (b. 1916) [right]

The Jawetz model, first proposed in the mid 1950s closely fits the history of most new remedies: First, the use rises quickly during a period of optimism, then some side effect is noted, and the approval drops rapidly (based on fear and mistrust), and then its use stabilizes at a moderate level. These swings have been called: “from panacea to poison to pedestrian.”
While rigorous drug testing attempts to eliminate the huge drops due to unexpected side-effects, some dips are the result of other factors such as which disease is fashionable, and who the target audience is.
While most used/sold drugs have changed dramatically over the past 200 years, the problems they were/are meant to treat is consistent: heart disease, lung disease, stomach ailments, mental disorders—in short chronic problems, many of which are related to diet and lifestyle. Were the ancient Greeks therefore far off the mark?