Paracelsus and the Dose Makes the Poison: The 1538 Third Defence

Table of Contents

1. The Seven Defences of 1538
2. The Original Words of the Third Defence
3. A Physician Accused of Prescribing Poisons
4. Dose and Preparation in His Reasoning
5. Mercury as the Test Case
6. From the 1564 Cologne Printing to Sola Dosis Facit Venenum
7. What the Dictum Did and Did Not Say
8. Why He Is Called the Father of Toxicology
9. Timeline of the Text
10. Key Research Papers
11. Connections
12. Featured Videos

1. The Seven Defences of 1538

By 1538 Paracelsus was in his mid-forties and had spent most of his adult life on the move. He had held a post as town physician of Basel with the right to lecture at its university in 1527, lectured in German instead of the customary Latin, publicly burned a copy of Avicenna’s Canon at a student bonfire, and left the city abruptly in early 1528 after a dispute over a fee. Over the following decade he wandered through southern Germany, Switzerland and the Tyrol, writing a great deal but seeing little of it printed. (His life story is told in full on the Life and Times page.)

In 1538 he was back in Carinthia, the Austrian region where he had grown up in the town of Villach. There he wrote what historians call his “Carinthian writings”. Two of them are direct replies to his critics. One is Labyrinthus medicorum errantium, “The Labyrinth of Erring Physicians”. The other is a set of seven short defences, known in German as the Sieben Defensiones and later in Latin as the Septem Defensiones: the Seven Defences.

The Seven Defences are, in effect, a professional self-defence written by a man who felt misunderstood and persecuted. Each one takes up a charge that had been laid against him and answers it. The Zurich Paracelsus Project, which studies and edits his works, lists them among the writings of his last years. They are not a calm treatise on pharmacology; they are polemic, and that matters for how the famous sentence in the third of them is read.

The title of the Third Defence

The third defence has a plain descriptive title: Die dritte Defension wegen des Schreibens der neuen Rezepte, roughly “The third defence, concerning the writing of new recipes”. In the language of the time, a Rezept was a prescription, the written formula for a medicine. The “new recipes” were Paracelsus’s own medicines, many of them made from metals and minerals rather than from the plant ingredients of the traditional pharmacy. The Third Defence is his answer to the accusation that these new prescriptions were dangerous.

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2. The Original Words of the Third Defence

The sentence that became famous is short. In the spelling of the first printed edition of 1564, as quoted by the clinical pharmacologist Jeffrey Aronson in a 2019 essay on the history of the phrase, it reads:

“Was ist das nit gifft ist? alle ding sind gift und nichts ohn gifft. Allein die dosis macht das ein ding kein gifft ist.”

In the English translation given by the environmental health researcher Philippe Grandjean in his 2016 review of the dose concept, this is:

“What is there that is not poison? All things are poison and nothing is without poison. Solely the dose determines that a thing is not a poison.”

The same opening question gave its title to the main scholarly study of the passage, the 1986 paper by Deichmann, Henschler, Holmstedt and Keil in Archives of Toxicology, “What is there that is not poison? A study of the Third Defense by Paracelsus”. Their study is the standard reference for anyone who wants to go back to the text itself rather than the slogan.

Reading the German

The sixteenth-century spelling is uneven — gifft and gift appear side by side, and nit is the southern German form of nicht (“not”). In modern German the passage is usually quoted in a smoothed form: “Alle Ding sind Gift und nichts ohn’ Gift; allein die Dosis macht, daß ein Ding kein Gift ist.” The modernised version drops the opening question, which is a loss, because the question carries the argument. Paracelsus is not starting from “these substances are safe”; he is starting from “name me anything that cannot harm”.

Three steps in three sentences

• The question. “What is there that is not poison?” — a challenge to his critics to name one remedy, food or substance that is harmless in every amount.
• The claim. “All things are poison and nothing is without poison.” — the capacity to harm is not a special property of metals or minerals; every substance has it.
• The turn. “Solely the dose determines that a thing is not a poison.” — what separates a poison from a non-poison is how much is given.

Notice the direction of the last sentence. In the original, the dose is what makes a thing not a poison. The slogan most people know, “the dose makes the poison”, turns this around. Both say the same thing about the relationship between amount and harm, but Paracelsus’s own wording is a defence of his medicines: given in the right amount, a dangerous substance stops being a poison and becomes a remedy.

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3. A Physician Accused of Prescribing Poisons

Medicine in Paracelsus’s day was dominated by the teaching of the ancient Greek physician Galen and his medieval interpreters, Avicenna above all. Its pharmacy was built mainly on plants, compounded into mixtures according to the theory of the four humours, together with purging, sweating and bloodletting. Mineral and metallic substances were not unknown — mercury, for instance, had long been used in ointments mixed with fats — but they sat at the edge of respectable practice.

Paracelsus pushed them to the centre. He prepared medicines from mercury, antimony, arsenic and other minerals, often in forms he had worked over with the methods of the alchemist’s laboratory. To many academic physicians this looked reckless. These were substances everyone knew could kill. A doctor who wrote prescriptions for them could be painted as a poisoner. Michaleas and colleagues, writing on his place in toxicology in 2021, describe his mineral-based remedies as controversial in his own time.

The Third Defence is his reply. The gist of his answer, as Aronson and others summarise it, is that his critics were drawing the line in the wrong place. They treated “poison” as a fixed category of substances, with mercury and arsenic on one side and herbs and foods on the other. Paracelsus denied that such a category existed. Everything, he said, can poison; the question for a physician is never whether a substance is a poison in the abstract, but how much of it is given and in what form.

An argument that turned the charge around

The rhetorical force of the passage is that it turns the accusation back on the accusers. If all things are poison, then the herbal mixtures of the traditional pharmacy are poisons too, and so are the strong purges of Galenic practice when given carelessly. The margin note printed next to the passage in the 1564 edition, discussed below, makes exactly this point about purges. The traditional physician has no special safe ground to stand on; every prescriber, old school or new, is handling substances that can harm, and every prescriber depends on getting the dose right.

That is why the passage belongs to a defence rather than a textbook. Paracelsus was not setting out to found a science of toxicity. He was trying to show that his new medicines were no more “poisonous” in principle than the old ones, and that the real skill of medicine lay in measure and preparation.

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4. Dose and Preparation in His Reasoning

Read on its own, the famous sentence seems to say that only quantity matters. Read alongside the rest of his work, it is clear that for Paracelsus the amount given was one half of the answer and the preparation of the substance was the other.

Separating the remedy from the poison

Paracelsus approached minerals and plants as an alchemist as well as a physician. He believed that each natural substance contained a hidden healing power — which he called its quinta essentia (quintessence) or arcanum — mixed together with harmful or useless matter. The art of the physician-chemist was to separate the one from the other: to break a raw substance down by distillation, dissolving, burning and similar operations, and to keep the active virtue while discarding the dross. The historian Walter Pagel, in his entry on Paracelsus in the Dictionary of Scientific Biography, describes this search for the quintessence as central to his pharmacy. The historian E. K. Hunter, in a 2022 study of dangerous substances in early modern sleep medicine, shows how this Paracelsian idea of separating a medicine from its poison carried on into later debates.

The three principles behind the chemistry

Behind the laboratory work lay his theory of the tria prima, the three principles: sulphur (the principle of burning), mercury (the principle of fluidity and volatility) and salt (the principle of solidity). The toxicologist M. F. Wilks summarises the practical consequence: because matter could be broken down into these principles, their properties could be harnessed to prepare specific medicines, and poisons could become medicines because it is the dose that determines toxicity. The Minerals, Herbs and Spagyric Extracts page explains this chemistry in detail.

Two levers on one outcome

Put together, his reasoning gave the physician two ways to turn a dangerous substance into a medicine:

• Preparation — change the substance itself, so that what reaches the patient is the “corrected” active part rather than the raw mineral.
• Dose — give that prepared substance in an amount small enough to help rather than harm.

Modern pharmacology would recognise both levers, though it explains them very differently. Chemistry now speaks of different compounds and forms of an element having very different toxicity, and of how a drug is absorbed, distributed and removed by the body. Paracelsus had none of that vocabulary. What he had was the conviction, unusual for his time, that harm and benefit were not fixed in the name of a substance but depended on what was done with it and how much of it was given.

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5. Mercury as the Test Case

If one substance stood behind the charge of poisoning, it was mercury. Mercury had been used in medicine before Paracelsus, in preparations mixed with fats. According to Michaleas and colleagues, Paracelsus expanded its use to treat syphilis and dropsy (the old name for swelling caused by fluid retention).

Syphilis was the defining new disease of his generation. It had spread explosively across Europe from the 1490s, the decade of his birth, and physicians argued fiercely over how to treat it. One rival treatment was a sweating cure built around guaiac wood imported from the Americas. Paracelsus wrote critically about the guaiac cure in 1529 in Nuremberg; that controversy is told on the Minerals, Herbs and Spagyric Extracts page.

Why mercury made the dictum necessary

Mercury illustrates both halves of the Third Defence at once. On one side, it was plainly a poison: its harmful effects on the body were well known. On the other side, Paracelsus and his followers believed that mercury, properly prepared and given in measured amounts, could act against diseases the old pharmacy could not touch. The dose principle was his justification for keeping mercury in the medicine chest. Without it, every mercury prescription was an act of poisoning; with it, a mercury prescription was a question of measure.

What the test case also showed

Mercury is also the clearest reminder of the limits of a sixteenth-century dose principle. Physicians of the era had no means of measuring how much mercury a patient absorbed, no understanding of how it built up in the body, and no reliable way to compare outcomes. The signs of mercury poisoning that toxicologists now document — heavy salivation, sore gums and loosened teeth, tremor, changes in mood and kidney damage — were frequently part of the experience of mercury treatment for centuries afterwards. The Zurich Paracelsus Project suggests that Paracelsus himself probably died of chronic mercury intoxication, though this is not certain.

Mercury nevertheless stayed in use against syphilis for nearly four hundred years after him, until the arsenical drug arsphenamine (Salvarsan) developed in Paul Ehrlich’s laboratory and, later, penicillin replaced it — the arc traced in Stephenson’s 2025 history of syphilis treatments. Grandjean’s 2016 review notes that mercury compounds remain a central concern of toxicology today. The site’s Mercury page describes what is now known about mercury exposure and health.

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6. From the 1564 Cologne Printing to Sola Dosis Facit Venenum

Paracelsus did not see the Seven Defences in print. Like most of his writings, they existed only in manuscript when he died in Salzburg on 24 September 1541. Only a few of his major works — among them the Grosse Wundarznei (Great Surgery Book) of 1536 — were printed during his lifetime.

The first printings

Interest in his work revived in the 1560s, and printers began to bring out his manuscripts. According to Aronson’s account, the Seven Defences were first printed in Cologne in 1564, in their original Swiss-German, and a Latin translation under the title Septem Defensiones followed in 1566. Latin was the shared language of European scholarship, so the 1566 edition carried the argument to physicians who could not read his German. The great collected edition of his works prepared by Johannes Huser followed in ten volumes in 1589–1591.

A margin note about purges

The 1564 printing carries a Latin note in the margin beside the passage. Aronson gives it as “Omnis purgatio venenum, si non servetur dosis” — in plain English, “every purge is a poison if the dose is not kept to”. Aronson describes it as a Latin translation set in the margin, rendering Paracelsus’s answer to his own question “What is a purge?” It is worth noticing what it picks out: purges were a staple of conventional medicine, so the margin applies the principle squarely to the traditional pharmacy, not only to Paracelsus’s new mineral remedies.

Where the Latin slogan came from

The Latin phrase that is now attached to his name, sola dosis facit venenum (“the dose alone makes the poison”), does not appear in the Third Defence. Careful accounts of the text treat it as a later condensation — a neat Latin summary that grew out of the German text and its translations, not a quotation from Paracelsus. It is a fair summary of his idea in one respect, but it is not his wording, and its form shifts the emphasis from “the dose makes a thing not a poison” to “the dose makes the poison”.

Early reception

In the decades after the printings, followers of Paracelsus — the “Paracelsians” — took up his chemical medicines and his arguments for them, and their opponents attacked both. The historian Allen Debus has traced this movement of “chemical philosophers” from Paracelsus to the Flemish physician Jan Baptist van Helmont in the seventeenth century. Hunter’s study of early modern England shows Paracelsian ideas about poisons and their correction feeding into English discussion of strong sleep-inducing remedies. The longer story of the Paracelsians belongs on the Legacy and Later Research page.

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7. What the Dictum Did and Did Not Say

Because the phrase is so often quoted, it is often stretched to mean things Paracelsus never said. Reading the original wording closely gives a clearer picture.

What it did say

• Harm is not a fixed category. No substance is a poison by nature and no substance is harmless by nature; “all things are poison and nothing is without poison”.
• Amount is decisive. Whether a given substance acts as a poison depends on how much is given.
• Medicines and poisons are the same kind of thing. A medicine is a potentially harmful substance given in a measure that helps; the physician’s job is to find that measure.
• The same rule binds every prescriber. The critics’ herbal and purging remedies were subject to the same law as his mineral ones.

What it did not say

• It did not say small amounts are always safe. The passage claims that a correct dose turns a substance into a non-poison; it says nothing about how that dose is found, and it does not claim that every small amount of every substance is harmless.
• It did not say amount is the only thing that matters. In the wider body of his work, preparation — the alchemical separation of the active part from the dross — mattered as much as quantity. The Latin tag sola dosis (“dose alone”) is sharper than his own thinking.
• It did not give a method for measuring doses. Paracelsus had no standardised dose tables in the modern sense, no concept of dosing by body weight and no trials. Toxicologists later supplied the method; Paracelsus supplied the principle.
• It did not address time, sensitivity or mixtures. Questions such as how long an exposure lasts, why some people are more sensitive than others, or how several substances act together lie outside the text. Modern toxicology has had to add these, a story told on the Legacy page.

The result is a principle that is both more modest and more radical than the slogan. It is modest because it is an argument in a quarrel, not a worked-out theory. It is radical because it erased the old line between “poisons” and “medicines” and replaced it with a question of measure.

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8. Why He Is Called the Father of Toxicology

Paracelsus did not use the word “toxicology”, and toxicology as an organised science took shape centuries after him. Yet modern toxicologists regularly name him as its founder. The titles of papers about him tell the story: J. F. Borzelleca called him the “herald of modern toxicology” in an essay in Toxicological Sciences in 2000; Michaleas and colleagues described him in 2021 as “the eminent physician and pioneer of toxicology”; and Wilks wrote in 2020 of his contribution to modern toxicology through “bringing chemistry to medicine”.

Three reasons historians give

• The dose principle itself. The core idea of toxicology is that the effect of a substance depends on the amount. Grandjean writes that Paracelsus’s dictum paved the way for the modern threshold concept and the “no-adverse-effect level” — the idea that for many substances there is an exposure below which no harm is seen.
• Chemistry in medicine. By treating minerals and their prepared forms as medicines, he made the chemical identity and preparation of a substance a medical question — the ground on which both pharmacology and toxicology later stood.
• Observation of chemical harm. He wrote about the diseases of miners and metal workers, including the effects of mercury, in a work printed after his death as Von der Bergsucht (1567). That occupational work is described on the Legacy and Later Research page.

A title worth holding loosely

Historians of medicine have also pointed out how hard Paracelsus is to pin down. Owsei Temkin’s classic 1952 essay is titled “The elusiveness of Paracelsus”, and the quincentenary assessments of 1993 by Charles Webster in the BMJ and A. Davis in the Journal of the Royal Society of Medicine marked his five-hundredth anniversary with fresh looks at his reputation. He mixed careful observation with alchemy, astrology and theology that modern science does not share, and most of his writings reached readers only through later editors and followers. “Father of toxicology” is best read as a statement about the lasting power of one idea from the Third Defence, rather than a claim that he practised toxicology as it is practised now.

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9. Timeline of the Text

• 1493 (or early 1494) — Theophrastus von Hohenheim is born near Einsiedeln, Switzerland.
• 1527–1528 — Town physician and lecturer in Basel; leaves abruptly in early 1528 after a dispute.
• 1529 — In Nuremberg, publishes on syphilis, including a critique of the guaiac wood cure.
• 1536 — Die grosse Wundarznei printed in Augsburg, one of the few major works published in his lifetime.
• 1538 — In Carinthia, writes the Seven Defences, including the Third Defence “concerning the writing of new recipes”, and the Labyrinthus medicorum errantium.
• 24 September 1541 — Dies in Salzburg; the Defences remain in manuscript.
• 1564 — First printing of the Seven Defences in Cologne, in German, with the Latin margin note “Omnis purgatio venenum, si non servetur dosis”.
• 1566 — Latin translation printed as Septem Defensiones.
• 1567 — Von der Bergsucht, his book on miners’ diseases, printed posthumously.
• 1589–1591 — Johannes Huser’s ten-volume collected edition of his works.
• Later centuries — The Latin summary sola dosis facit venenum comes into circulation as a condensed form of the idea.
• 1986 — Deichmann, Henschler, Holmstedt and Keil publish their study of the Third Defence in Archives of Toxicology.
• 2000 — Borzelleca’s essay “Paracelsus: herald of modern toxicology”.
• 2016 — Grandjean’s “Paracelsus Revisited: The Dose Concept in a Complex World”.

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Key Research Papers

1. Deichmann WB, Henschler D, Holmstedt B, Keil G. What is there that is not poison? A study of the Third Defense by Paracelsus. Arch Toxicol. 1986;58(4):207-13. PubMed PMID: 3521542
2. Borzelleca JF. Paracelsus: herald of modern toxicology. Toxicol Sci. 2000;53(1):2-4. PubMed PMID: 10653514
3. Grandjean P. Paracelsus Revisited: The Dose Concept in a Complex World. Basic Clin Pharmacol Toxicol. 2016;119(2):126-32. PubMed PMID: 27214290
4. Wilks MF. Bringing Chemistry to Medicine - The Contribution of Paracelsus to Modern Toxicology. Chimia (Aarau). 2020;74(6):507-508. PubMed PMID: 32560760
5. Michaleas SN, Laios K, Tsoucalas G, Androutsos G. Theophrastus Bombastus Von Hohenheim (Paracelsus) (1493-1541): The eminent physician and pioneer of toxicology. Toxicol Rep. 2021;8:411-414. PubMed PMID: 33717994
6. Hunter EK. 'To Cause Sleepe Safe and Shure': Dangerous Substances, Sleep Medicine and Poison Theories in Early Modern England. Soc Hist Med. 2022;35(2):473-493. PubMed PMID: 35558657
7. Stephenson J. The Centenary Series - STIs Through the Ages: From mercury to penicillin-a brief history of syphilis treatments. Sex Transm Infect. 2025;101(3):141-143. PubMed PMID: 40234009
8. Debus AG. The chemical philosophers: chemical medicine from Paracelsus to Van Helmont. Hist Sci. 1974;12(4):235-59. PubMed PMID: 11609994
9. Temkin O. The elusiveness of Paracelsus. Bull Hist Med. 1952;26(3):201-17. PubMed PMID: 14935443
10. Webster C. Paracelsus, and 500 years of encouraging scientific inquiry. BMJ. 1993;306(6878):597-8. PubMed PMID: 8461804
11. Davis A. Paracelsus: a quincentennial assessment. J R Soc Med. 1993;86(11):653-6. PubMed PMID: 8258802

PubMed Topic Searches

1. Paracelsus and toxicology
2. Paracelsus (title) and history
3. “Dose makes the poison”
4. Mercury, syphilis and history

Further Reading

• Aronson J. “When I use a word… Nothing is not a poison.” BMJ opinion blog, 9 August 2019. blogs.bmj.com
• Pagel W. “Paracelsus.” Complete Dictionary of Scientific Biography. encyclopedia.com
• Zurich Paracelsus Project, University of Zurich: Life and Works. paracelsus.uzh.ch
• Huser J (ed.). Paracelsus’s collected works, ten volumes, Basel, 1589–1591.

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Connections

• Paracelsus: The Dose Makes the Poison and the Birth of Chemical Medicine
• Paracelsus: Life and Times of a Renaissance Rebel Physician
• Paracelsus’s Medicines: Minerals, Herbs and Spagyric Extracts
• Paracelsus’s Legacy: Miners’ Disease, the Paracelsians and Modern Toxicology
• Pharmacology: Notable Doctors
• Paul Ehrlich: The Magic Bullet and Salvarsan
• Mercury Toxicity
• Arsenic
• Antimony
• Heavy Metals in Food
• Syphilis
• Toxins

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