When I use a word . . . Medicines regulation—poisons

Paracelsus’s dictum

The Swiss-born physician and alchemist who called himself Paracelsus (1493–1541) was born Philippus Aureolus Theophrastus Bombastus von Hohenheim. His self-adopted nickname was a pun. The name Hohenheim literally means “high home,” implying heaven, or at least somewhere nearby.

The Greek prefix πᾰρά means beside or near, or in some instances over and above. And in Latin, celsus means high or lofty. The Roman encyclopaedist Aulus Cornelius Celsus (ca. 25 BC to ca. 50 AD) was revered as the author of De medicina, a major source of information about various aspects of medical practice in his time.1 Its several sections cover the history of medicine, pathology, descriptions of diseases, anatomy, pharmacology, surgery, and orthopaedics. “Para/celsus” is therefore not only a paraphrase of Hohenheim; it also means equal to or beyond Celsus.

Paracelsus’s Septem Defensiones was published posthumously in 1564.2 In the third defence in that work Paracelsus spelt out his view that all therapeutic substances are potential poisons, in what has become a famous, much quoted dictum: “Was ist das nit gifft ist? Alle ding sind gifft und nichts ohn gifft. Allein die dosis macht das ein ding kein gifft ist.” In English: “What is there that is not a poison? Every thing is a poison and nothing is not a poison. Only the dose determines that a thing is not a poison.” Paracelsus also included a Latin translation in the margin of the first edition: “Nil sine veneno praesertim dosi non servari” or “nothing lacks poison[ous effects] especially if the dose is not heeded.”

Instead of the traditional medical system, based on the four humours, the four elements, and Aristotle’s four qualities, Paracelsus proposed a tripartite system, reflecting the Trinity and threefold human nature, consisting of the soul, the spirit, and the body.3 The three educational pillars on which he built his system were astronomy, natural philosophy, and alchemy, reflecting the heavens, the earth, and human biology. Seeking a name for the elements of his new philosophy, and wanting to avoid the word “elements” itself, he rejected words such as the Latin terms corpora (bodies), essentiae (essentials or essences), and species (classes), and the German words ersten (first things), and stücke (pieces), and finally settled on the more non-committal word, “dingen,” things.

Paracelsus’s tripartite scheme involved the use of “drei dingen” as therapeutic principles: mercury, sulphur, and metallic salts, such as those of antimony, arsenic, copper, iron, lead, magnesium, mercury, and potassium, particularly potassium nitrate. He used as remedies, which he called arcana (secret remedies), things that he considered to be the prime sources of all the matter in the universe, the causes of diseases, and at the same time possible cures.

However, the word “ding,” as used by Paracelsus in his dictum “alle ding sind gifft,” is potentially ambiguous. He might have been specifically referring to the drei dingen, his three therapies, the implication being that while he recognised that the use of large doses of such substances could be harmful, the doses that he was accustomed to using were purely beneficial. However, he may have been referring to all substances. When criticised by others for using poisons in his therapeutic practice, Paracelsus protested that the poisons in nature were put there by God, and when used properly they did not have to be poisonous. Even food and drink is poisonous, he suggested, if taken in too great quantities.

We do not know if Paracelsus understood the concept of the dose-response curve, graded effects of medicines, in which for each outcome that a medicine produces there is a no-effect level, an increasing effect as the dose increases, and no further effect as the dose is increased beyond the maximum effective. It is possible, for example, that he thought that there was a dose or range of doses that was beneficial and a separate dose or range of doses that was poisonous. This opinion would have been reinforced by his knowledge that different salts of the same metal could have different actions, beneficial and harmful.

Indeed, it was not until Guldberg and Waage formulated what we now call the Law of Mass Action, in 1864,4 that the theoretical foundations of dose-responsiveness were laid, paving the way for mathematical analyses of the phenomenon and the formal recognition of the mechanisms of drug toxicity.

Poisons

Notwithstanding Paracelsus’s view that all things are [potentially] poisons, the modern attitude to poisons is restricted to certain substances that cause “illness or death when introduced into or absorbed by a living organism, esp[ecially] when able to kill by rapid action and when taken in small quantity,” as the definition in the current, second edition, of the Oxford English Dictionary (OED) puts it.5 Of course, although the OED gives citations dating back to the early 13th century, it is by no means certain that the modern definition is relevant to the earlier examples cited.

In fact, the current definition differs in one important respect from that given in the first edition of the OED: “Any substance which, when introduced into or absorbed by a living organism, destroys life or injures health, irrespective of mechanical means or direct thermal changes. Popularly applied to a substance capable of destroying life by rapid action, and when taken in a small quantity.” However, in order to contrast popular use with scientific use, the lexicographers added, “But the more scientific use is recognized in the phrase slow poison, indicating the accumulative effect of a deleterious drug or agent taken for a length of time.” This definition was coined in around 1907, when the fascicle Piper–Polygenistic was first published. I suspect that the dictionary’s scientific adviser in this case may have been William Osler.

Going further back, we see Samuel Johnson, in his 1755 dictionary, also adopting what the OED later called the popular approach in defining a poison: “That which destroys or injures life by a small quantity, and by means not obvious to the senses.”

Origins

The words that have come down to us from the basic IndoEuropean root of the word poison, PŌ(I), tend to support Paracelsus’s view. All simply involve some form of drinking.

The Latin verb potare meant to drink, from which we get potable, potation, and potatory. The related noun potio meant a drink, giving us potion and poison.

The Greek noun, πότης, a drinker, gives συμπότης, a fellow drinker, from which συμπόσιον, a symposium, comes. Originally, a symposium was “a drinking-party; a convivial meeting for drinking, conversation, and intellectual entertainment.”6 The word entered English at the start of the 18th century and before long also came to mean “a meeting or conference for discussion of some subject.”6

If you nasalise the original IndoEuropean root, you get the Greek verb πίνειν, to drink, from which we derive pinocytosis, a term that was first suggested in the 1890s by the Russian born microbiologist, G Gabritschewsky, by then working in l’Institut Pasteur in Paris. He suggested the term in a French paper in 1894,7 as reported in English a year later, referring to the original French paper8: “[Gabritschewsky ] also deals with the diphtheritic toxin which impedes the phagocytic action of the leucocytes by its necrotic power, and suggests the probability that phagocytes are not only capable of seizing and assimilating solid bodies, but of imbibing and absorbing liquid substances, and of rendering them harmless to the organism. For this action the term pinocytosis is suggested.” [In the original French, “c’est ce que l’on pourrait appeler la pinocytose.”]

As we shall see, medicines such as morphine were at one time described as poisons in English legislation.

The 1868 Pharmacy Act

The power struggle between the physicians and the apothecaries9 was a long running one. With the founding of the Pharmaceutical Society in 1841, and after it obtained its royal charter of incorporation in 1843, its members sought to combine the affairs of dispensing apothecaries with those of the chemists and druggists, to create a new profession of pharmaceutical chemists, independent of the control of the physicians and separately regulated. The society defined two levels of pharmacist, chemists and druggists, who had passed a minor examination, and pharmaceutical chemists, who had passed a higher examination. The aim of all this was to establish a monopoly, restricting the sales of medicaments to their members, whose educational qualifications they oversaw.

This led to the 1852 Pharmacy Act, whose long title was “An Act to regulate the Sale of Poisons, and alter and amend the Pharmacy Act 1852.”10 The act was primarily concerned with regulating the affairs of the Pharmaceutical Society, and although it introduced a register of qualified pharmacists and restricted use of the title to members of the Pharmaceutical Society, it did not give them exclusive rights to sell drugs or poisons and did not provide a legal definition of the trade and practice of pharmacy. It did, however, specifically bar members of the medical profession from being registered under the act.

During the 1850s the Pharmaceutical Society opposed bills that were intended, under the jurisdiction of an independent board, to control the sales of poisons. At the same time, the General Medical Council, which had been newly formed under the 1858 Medical Act, sought to bring pharmacy practice back under the aegis of the medical profession. Indeed, at that time, and until much later, about 90% of all dispensing of doctors’ prescriptions was done by the doctors themselves.11

Matters were further complicated by the formation of a splinter group, The United Society of Chemists and Druggists, impatient with the inability of the Pharmaceutical Society to achieve their aims.

Eventually, after a considerable amount of lobbying by both groups, the 1868 Pharmacy act was passed. It ratified the Pharmaceutical Society’s rules for registration both of pharmaceutical chemists and of chemists and druggists. At the same time it protected others, such as legally qualified apothecaries and members of the Royal College of Veterinary Surgeons, who also had the right to retail and dispense poisons.

During the 1850s and 1860s public disquiet about the frequency of cases of poisoning had increased. Of particular concern were so-called patent medicines, such as chlorodyne, the main constituent of which was morphine. The upshot of this was the inclusion in the schedule to the 1868 Act of a list of substances that included opiates, the list itself defining what were considered to be the most important and dangerous poisons. The list was in two parts:

Part I
Arsenic and its preparations
Prussic acid
Cyanides of potassium, and all metallic cyanides
Strychnine, and all poisonous vegetable alkaloids and their salts
Aconite and its preparations
Emetic tartar
Corrosive sublimate
Cantharides
Savin and its oil
Ergot of rye and its preparations

Part II.
Oxalic acid
Chloroform
Belladonna and its preparations
Essential oil of almonds, unless deprived of its prussic acid
Opium, and all preparations of opium or of poppies

The last item is surprisingly imprecise. It cannot have been the intention to ban all preparations of poppies that were not opium poppies, such as poppy seeds from Papaver rhoeas for culinary purposes.

Opium as a poison

The inclusion of opium in the list of poison in the schedule to the 1868 Act, along with chloroform and belladonna may seem Paracelsian in its definition of a poison. However, it was driven by what was to become a test case following the failure of the Society of Chemists and Druggists to have their proposed 1884 Patent Medicine Bill adopted.

The medicine that was the subject of the test case was one of several formulations that contained opiates, and particularly Dr Collis Browne’s chlorodyne, which contained chloroform, morphia, tincture of Indian hemp, and prussic acid, and which had been responsible for a large number of cases of poisoning.

In the terms of the act, it did indeed seem that “everything is a poison and nothing is not a poison.”