William Withering: Foxglove and the Birth of Digitalis

In 1775 a Birmingham physician named William Withering (1741–1799) was asked what he thought of a family recipe for dropsy, the swelling of the legs and body that we now know is often caused by a failing heart. The recipe had been kept secret by an old woman in Shropshire and held twenty or more different herbs. Withering, who was also one of the best botanists in England, judged that the active herb could be no other than the purple foxglove, Digitalis purpurea. He spent the next ten years learning how to give it, and in 1785 he published An Account of the Foxglove, and some of its Medical Uses, a book that reported every one of his cases, “successful or otherwise”. From that hedgerow plant came digitalis, and from digitalis came digoxin and digitoxin, heart medicines still studied in clinical trials in the 2020s.

This wing tells the story in four deep-dive articles: the man himself, the book and the discovery, the plant and the chemistry of how it acts on the heart, and the two centuries of research that followed. The overview below gives the whole story on one page. It is history and science, told for curious readers; the historical doses Withering described are reported as history, and foxglove is a poisonous plant.

Table of Contents

  1. Deep-Dive Articles
  2. 1. Who William Withering Was
  3. 2. The Discovery on One Page
  4. 3. The Natural Source: Purple Foxglove
  5. 4. Dose, Titration and the Narrow Margin
  6. 5. Timeline at a Glance
  7. 6. Later Significance
  8. Key Research Papers
  9. Connections
  10. Featured Videos

Deep-Dive Articles

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William Withering: Life and Career

A Shropshire surgeon’s son who trained at Edinburgh, gave the Birmingham poor a free hour every day, botanised and named minerals with the Lunar Society, and fought tuberculosis for his last sixteen years.

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An Account of the Foxglove (1785)

The old woman’s recipe, the Mother Hutton legend, the early overdoses he admitted, 163 cases reported successful or not, and the nine inferences that closed the book.

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Foxglove: The Plant and the Science of Digitalis

The biennial hedgerow plant, folk medicine before Withering, the cardiac glycosides digitoxin and digoxin, and how blocking the sodium-potassium pump strengthens and slows the heart.

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From Foxglove to Digoxin: Legacy and Later Research

Blood-level assays, an antibody antidote, the DIG trial, RATE-AF in Withering’s own Birmingham and the 2025 DIGIT-HF digitoxin trial.

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1. Who William Withering Was

Withering was born in March 1741 in Wellington, Shropshire, the son of a surgeon. He studied medicine at the University of Edinburgh from 1762 and took his MD in 1766 with a thesis on the “malignant putrid sore throat” (De Angina Gangraenosa). In 1767 he set up in practice in Stafford, where he was physician to the county infirmary, and in 1772 he married Helena Cookes, a former patient and a botanical illustrator.

In 1775 he moved to Birmingham and took over the practice of Dr William Small. In the preface to his foxglove book he wrote that he kept up Small’s custom of giving free advice to the poor for one hour a day, and that this brought him “between two and three thousand” patients a year. He became one of the physicians of the Birmingham General Hospital, which opened in 1779, and a member of the Lunar Society, the Birmingham circle that included Erasmus Darwin, Matthew Boulton, James Watt, Joseph Priestley and Josiah Wedgwood.

He was far more than a doctor. In 1776 he published A Botanical Arrangement of all the Vegetables Naturally Growing in Great Britain, the first British flora arranged on the Linnaean system in English, a book whose 250th anniversary was marked in the BMJ in 2026. In 1784 he showed in the Philosophical Transactions that a heavy mineral from Alston Moor, which he called terra ponderosa, was not the same as barite; in 1789 the German geologist Abraham Gottlob Werner named it witherite in his honour. He was elected a Fellow of the Royal Society in 1785.

From the early 1780s he suffered from pulmonary tuberculosis and wintered in Portugal in 1792 and 1793. His house was threatened during the 1791 riots against Priestley and his friends. He died in Birmingham on 6 October 1799, aged 58, and was buried at Edgbaston Old Church under a memorial carved with a foxglove on one side and Witheringia, a plant genus named after him, on the other. The full story is told in William Withering: Life and Career.

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2. The Discovery on One Page

Withering told the story himself in 1785: “In the year 1775, my opinion was asked concerning a family receipt for the cure of the dropsy. I was told that it had long been kept a secret by an old woman in Shropshire, who had sometimes made cures after the more regular practitioners had failed.” The medicine, he was told, caused “violent vomiting and purging; for the diuretic effects seemed to have been overlooked.” Out of twenty-odd herbs he picked out foxglove.

The first years were a process of trial and correction. He admitted that at first he “gave it in doses very much too large, and urged its continuance too long”, misled by the belief, carried over from squill, that a diuretic worked best when it made the patient sick. He moved from the root, which he judged too uncertain in a biennial plant, to the leaves gathered while the plant was flowering and carefully dried; from a long-boiled decoction to an infusion; and then to the powdered leaf, so that doses could be measured. By 1779 his experience had been communicated to the Medical Society at Edinburgh, and in 1783 foxglove entered the new Edinburgh Pharmacopoeia.

The book itself numbers 163 of his own cases, from Case I to Case CLXIII, followed by letters from other practitioners. In the preface he wrote that he had “mentioned every case in which I have prescribed the Foxglove, proper or improper, successful or otherwise”, because “Truth and Science would condemn” publishing only the good results. The medical historian Ulrich Tröhler has described this as an early appeal for caution and completeness in reporting on a new medicine.

A popular story gives the old woman a name, “Mother Hutton”, and shows Withering buying her secret. That is a legend. Withering never names her or says he met her; the name and the well-known picture come from a 1928 drug-company advertising illustration, and the cardiologist and historian Dennis Krikler traced the story as “the making of a myth”. The full account is in An Account of the Foxglove (1785).

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3. The Natural Source: Purple Foxglove

Purple foxglove, Digitalis purpurea, is a biennial plant of hedgerows, heaths and woodland edges across Britain and western Europe. In its first year it forms a low rosette of soft, downy leaves; in its second it sends up a tall spike of tubular purple flowers and then dies. Withering used the leaves of the flowering plant, and his own notes show he understood that the potency of a herbal leaf depended on when it was gathered and how it was dried.

Foxglove was not new to folk medicine. Historians note that it seems to have been unknown to Greek and Roman physicians, but by the Middle Ages it was widely used in folk remedies, including the thirteenth-century Welsh tradition of the Physicians of Myddfai, and it was sometimes rubbed onto the skin, with effects that modern readers recognise as glycoside overdose. Kinne-Saffran and Kinne place Withering at the end of a long line of herbal diuretics passed down by village “wise women”. Other plants carry related heart-active compounds: sea squill, which Withering himself compared with foxglove, and the African strophanthus vines used for arrow poison.

The active compounds are cardiac glycosides. In 1930 Sydney Smith reported the isolation of digoxin, “a new digitalis glucoside”, from a foxglove species; digitoxin is its close relative. These molecules bind to and inhibit the sodium-potassium pump (Na+/K+-ATPase), the membrane enzyme Jens Skou described in 1957. In heart muscle, slowing the pump leaves more sodium inside the cell, which in turn leaves more calcium available for each contraction, so the beat grows stronger; the same drugs also slow conduction through the junction between the upper and lower chambers, which slows a rapid pulse. Withering himself believed the plant acted chiefly on the kidneys; his ninth inference noted only its “power over the motion of the heart, to a degree yet unobserved in any other medicine”. The plant and the chemistry are explained in Foxglove: The Plant and the Science of Digitalis.

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4. Dose, Titration and the Narrow Margin

Withering’s most lasting practical lesson was that foxglove works within a narrow band between too little and too much. In his chapter of “Effects, Rules, and Cautions” he listed what very large or quickly repeated doses produced: “sickness, vomiting, purging, giddiness, confused vision, objects appearing green or yellow; increased secretion of urine … slow pulse, even as slow as 35 in a minute, cold sweats, convulsions, syncope, death.” Emergency physician H. A. Bessen, reviewing the book two centuries later, noted that Withering recorded these toxic effects strikingly well even though he was largely unaware of the drug’s action on the heart.

His answer, in the language of his time, was to give small measured doses of a standardised dried leaf and stop when the kidneys responded or when the pulse slowed or sickness began. He judged that the diuretic effect did not depend on making the patient sick, and that pushing the dose to nausea could actually check the flow of urine. He also recorded that a physician cured by foxglove root had taken, by Withering’s estimate, many times the quantity a strong man ought to take — a reminder of how uncertain the plant was before dosing was measured.

Modern research has restated the same lesson in numbers. Serum digoxin assays from 1969 made the gap between therapeutic and toxic blood levels measurable, and a later analysis of the DIG trial found that, in men, lower blood concentrations were associated with lower mortality while higher ones were associated with higher mortality. Pharmacologist Alasdair Breckenridge summarised Withering’s legacy as four lessons that still apply to new drugs: preparation must be standardised, people differ in their response, effect depends on dose, and adverse effects must be recorded. Foxglove remains a poisonous plant; a 2017 case report described fatal poisoning when its leaves were mistaken for comfrey.

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5. Timeline at a Glance

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6. Later Significance

For two centuries digitalis was a mainstay of treatment for heart failure and for controlling a fast pulse in atrial fibrillation. Its standing changed as stronger diuretics and newer heart drugs arrived; cardiologist Allen Weisse described the decline in a 2010 essay titled “A fond farewell to the foxglove?”, while arguing that the drug remained useful.

Large trials have since measured what the old plant does and does not do. In the 1997 DIG trial of 6,800 patients with heart failure, digoxin did not change overall mortality compared with placebo (relative risk 0.99) but reduced hospital admissions for worsening heart failure (relative risk 0.72). A 2015 meta-analysis found the same neutral effect on death in randomised trials, and attributed the apparent harm seen in observational studies largely to sicker patients being prescribed the drug. In Birmingham, Withering’s own city, the RATE-AF trial (2020) found no difference in six-month quality of life between low-dose digoxin and bisoprolol for permanent atrial fibrillation, with fewer adverse events in the digoxin group. In 2025 the DIGIT-HF trial reported that digitoxin, another foxglove glycoside, lowered the combined rate of death or hospital admission for heart failure (hazard ratio 0.82) in patients already on modern therapy, although death alone was not significantly different.

Beyond the drug itself, Withering’s book is cited as an early model of complete, honest reporting of a new treatment, and the plant’s target, the sodium pump, led researchers to search for the body’s own digitalis-like substances. These later chapters are told in From Foxglove to Digoxin: Legacy and Later Research.

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Key Research Papers

  1. Krikler DM. The foxglove, “The old woman from Shropshire” and William Withering. J Am Coll Cardiol. 1985;5(5 Suppl A):3A-9A. PubMed PMID: 3886750
  2. Krikler DM. Withering and the foxglove: the making of a myth. Br Heart J. 1985;54(3):256-7. PubMed PMID: 3899150
  3. Silverman ME. William Withering and An Account of the Foxglove. Clin Cardiol. 1989;12(7):415-8. PubMed PMID: 2663265
  4. Buchtel L, Ventura HO. Lunar Society and the discovery of digitalis. J La State Med Soc. 2006;158(1):26-30. PubMed PMID: 16602482
  5. Aronson JK. When I use a word . . . Medical anniversaries in 2026: William Withering’s Botany. BMJ. 2026;392:s104. PubMed PMID: 41545062
  6. Tröhler U. Withering’s 1785 appeal for caution when reporting on a new medicine. J R Soc Med. 2007;100(3):155-6. PubMed PMID: 17339312
  7. Bessen HA. Therapeutic and toxic effects of digitalis: William Withering, 1785. J Emerg Med. 1986;4(3):243-8. PubMed PMID: 3543113
  8. Groves MJ, Bisset NG. A note on the use of topical digitalis prior to William Withering. J Ethnopharmacol. 1991;35(2):99-103. PubMed PMID: 1809828
  9. Kinne-Saffran E, Kinne RK. Herbal diuretics revisited: from “wise women” to William Withering. Am J Nephrol. 2002;22(2-3):112-8. PubMed PMID: 12097727
  10. Smith S. Digoxin, a new digitalis glucoside. J Chem Soc. 1930:508-510. DOI: 10.1039/JR9300000508
  11. Breckenridge A. William Withering’s legacy--for the good of the patient. Clin Med (Lond). 2006;6(4):393-7. PubMed PMID: 16956147
  12. Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336(8):525-33. PubMed PMID: 9036306
  13. Ziff OJ, Lane DA, Samra M, Griffith M, Kirchhof P, Lip GY, Steeds RP, Townend J, Kotecha D. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ. 2015;351:h4451. PubMed PMID: 26321114
  14. Bavendiek U, Großhennig A, Schwab J, Berliner D, Rieth A, Maier LS, Gaspar T, Thomas NH, Liu X, Schallhorn S, et al. Digitoxin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2025;393(12):1155-1165. PubMed PMID: 40879434

PubMed Topic Searches

  1. PubMed: William Withering foxglove
  2. PubMed: digitalis history
  3. PubMed: Digitalis purpurea cardiac glycosides
  4. PubMed: digoxin heart failure randomized trial

Further Reading

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Connections

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