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William Withering (1741-99)
Engraved plate of the foxglove, from the first edition of Withering’s Account of the Foxglove (1785)
William Withering and the Purple Foxglove: A Bicentennial Tribute Jeremy M. Norman
Reprinted from the Journal of Clinical Pharmacology 25, no. 7 (Oct. 1985)
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. I was informed also, that the effects produced were violent vomiting and purging; for the diuretic effects seemed to have been overlooked. This medicine was composed of twenty or more different herbs; but it was not very difficult for one conversant in these subjects, to perceive, that the active herb could be no other than the Foxglove.1Withering W: An Account of the Foxglove and Some of Its Medical Uses: With Practical Remarks on Dropsy and Other Diseases. Birmingham, U.K., M. Sweeny 1785;
So began William Withering’s description of his clinical experience with the purple foxglove, which was published 200 years ago. In this book, Withering discussed 158 patients whom he treated with the foxglove. Of these, 101 patients with congestive heart failure experienced relief following administration of the drug, today known as digitalis after the Latin name for the plant, Digitalis purpurea. An analysis of Withering’s individual case reports published by Estes and White2Estes JW, White PD: William Withering and the purple foxglove. Scientific American 1965; 212 (6):110-119. suggests that many of the 57 other cases, such as those with pulmonary tuberculosis, did not involve diseases amenable to treatment with digitalis. Withering himself was aware that these factors might be affecting his results and warned against generalizing on the basis of his cases.
Estes and White consider Withering’s observations on the clinical use of digitalis to be remarkably thorough for his time. Withering investigated the traditional use of the drug and found that the dosage was generally excessive. He experimented with the various forms of its traditional preparation-as foxglove tea, as a decoction, and as an infusion. He preferred to use the “beautiful green powder” made from the dried leaves gathered just before blossoming time. Withering derived the optimum quantity of the drug to be administered as a single dose. Estes and White point out that the amount of digitalis he prescribed had only slightly less activity than the tablet used in contemporary practice. Furthermore, the incidence of side effects of the drug declined as Withering gained clinical experience over the ten years of his research. Estes and White observed that “it appears that the overall incidence of side effects attributable to digitalis in Withering’s patients approximates the incidence recorded by physicians today. One could learn to use digitalis effectively and safely if one had no other text than Withering’s Account of the Foxglove.”
Few statements underline the utility of medical history more effectively than Estes and White’s statement that Withering’s classic still has scientific use 200 years after its initial publication. Equally extraordinary might be the fact that 110 years after Johann Schmiedeberg’s isolation of the principal active constituent of digitalis, the glycoside digitoxin,3Schmiedeberg JEO: Untersuchungen ueber die pharmakologische wirksamen Bestandtheile der Digitalis purpurea. L Arch Exp Path Pharmak 1875;3:16-43. pharmaceutical companies still find it most economic to produce digitalis directly from the plant, essentially following Withering’s methods, but on a vastly greater scale. Thus, one of the most widely used drugs today is still intimately tied to one physician and to a beautiful wild flower indigenous to his region. That Withering was the first to elevate this traditional folk remedy into scientific medical practice reflects his extraordinary perspicacity as a physician and botanist.
The purple foxglove grew like a weed throughout the English midlands of Withering’s boyhood, but we do not have any evidence that the youthful Withering paid any special attention to this wild flower, which sometimes rises five feet or higher, like a spire of large purple bells above ferns and copses and along hedges. The name of the plant seems to have evolved as a corruption of “folk glove,” with folk here referring to the “little folk” or fairies. The name may also be traced to the Anglo-Saxon Foxes-glees or “fox music.” This refers to an ancient musical instrument that consisted of bells hung on an arched support. The Latin scientific name was coined by the 16th century Bavarian physician Leonhard Fuchs (1501-1566) as a translation of the German word for the plant-- fingerhut or thimble, which accurately describes the shape of the flower. In his De historia stirpium commentarii, published in 1542, Fuchs described the plant as a purgative and an emetic. Estes and White also suggest that Fuchs may have observed the value of the foxglove, in treating dropsy (edema), a property sometimes described by later herbalists, who typically also recommended it for diseases it could not affect. Without any scientific understanding of its properties, the drug seems to have gone in and out of vogue over the centuries until it developed a strong reputation for toxicity, which was around the time Withering set out to study its effects in great detail.
Biography
Born in 1741, the only son of a prosperous Shropshire apothecary and nephew of two physicians, Withering entered the University of Edinburgh in 1762, and received his M.D. degree in 1766. At the time, Edinburgh was the leading medical school in Britain, if not the world, and Withering studied there under such luminaries as Alexander Monro (1733-1817, anatomy), Joseph Black (1728-1799, chemistry), Robert Whytt (1714-1766, neurology), and William Cullen (1710-1790, clinical medicine). Cullen, distinguished clinician and teacher, was said to have been especially influential in Withering’s development as a physician. Following the practice of British students, Withering spent his spring and summer holidays traveling, and during one vacation, he attended the medical lectures of William Hunter (1718-1788) at Great Windmill Street, London. Withering chose to write his M.D. dissertation on malignant-putrid sore throat, more commonly called scarlet fever. As was required in 1766, he published the thesis in Latin under the title De angina gangraenosa.4O’Malley CD: De angina gangraenosa. (English translation), in J Hist Med Allied Sci 1953;8:16-45. When an epidemic of scarlet fever hit Birmingham in 1778, Withering returned to the subject of his initial research, publishing An Account of the Scarlet Fever and Sore Throat, or Scarlatina Anginosa; Particularly as it Appeared at Birmingham in the Year 1778 (1779). This was sufficiently appreciated to be translated into German (1781), and a second edition appeared in 1793.
Withering started his general practice in the small town of Stafford in southern Staffordshire, near his family home in Wellington, Shropshire. He became physician to the newly built Stafford Infirmary, and although he was well-liked, rural communities in England, then as now, were slow to accept newcomers; he had plenty of leisure time, and he became one of England’s most eminent botanists. Though he had a disagreeable experience with the subject at Edinburgh, he was drawn to botany by his friend Richard Pulteney (1730-1801), who later became the historian of English botany and the first biographer of Linnaeus.7Fulton IF: The place of William Withering in scientific medicine. J Hist Med Allied Sci 1953;8:1-15. Another explanation for Withering’s interest in botany is given in a book by Henrey.5Henrey: British Botanical and Horticultural Literature Before 1800, vol 1. Oxford, Oxford University Press, 1975; 22. Quoting a Withering letter dated 1787 to Sir Joseph Banks, the great patron of science, Henrey argues cogently that it was the inspection of Banks’ British herbarium circa 1768 that stimulated Withering to study botany.
Withering’s botanic interests were further stimulated during the spring and summer of 1768 when he treated a young patient named Helena Cooke, who happened to be an amateur painter of flowers. During her long convalescence, Withering searched the countryside “to supply subjects for the highly finished drawings” (Henrey;5Henrey: British Botanical and Horticultural Literature Before 1800, vol 1. Oxford, Oxford University Press, 1975; 22.) she might create. From all of this intense mutual study of flowers a budding romance blossomed, and in 1772, Cooke married Withering.
After his marriage, Withering found himself spending much time collecting the rich flora of the Stafford area for systematic classification and study. He eventually extended his herbarium to include plants from all parts of Great Britain and, in 1776, issued his first major publication, A Botanical Arrangement of all the Vegetables Naturally Growing in Great Britain (1776). This was the first Great Britain flora classification using Linnaean binomial nomenclature, and the first complete scientific classification and description of British plants in the English language. By including information on the natural places of growth of the plants described, their time of flowering, their economic uses as foods and drugs,. and their poisonous properties, together with the methods of botanic investigation and preservation of specimens, Withering filled a real need. The book eventually passed through four editions, each incorporating Withering’s increasing botanic knowledge and experience. In the last edition published in his lifetime (1796), Withering effected a number of important taxonomic changes in the Linnaean system. He also surveyed the British cryptogams, a class of plants imperfectly described by Linnaeus. After Withering’s death, his son saw the work through four more editions between 1805 and 1830.
With a family to support, Withering began in 1772 to search for a more profitable practice. In 1775, he received a letter from Erasmus Darwin (1731-1802), a rotund physician/poet/scientist and educational reformer who may be best remembered today as the eccentric genius grandfather of Charles Darwin. The letter suggested that Withering apply for the successful Birmingham practice of the recently deceased Dr. William Small. Withering acquired the practice and immediately became successful in this new environment. Not only was he taken into social and intellectual circles, but his practice quickly grew, providing an income of £1,000 per annum, later increasing to £2,000, which were vast sums in Withering’s day. Withering was said to have the largest medical practice in Birmingham, and some said it was the largest outside of London. At Birmingham General Hospital, he held a daily clinic for the poor and is supposed to have treated 2,000 to 3,000 cases annually without charge. In 1785, he calculated that he traveled 6,303 miles on professional visits--an immense effort in those days of bad country roads and horse-drawn vehicles.
In spite of his enormous practice, Withering continued to devote his spare time to botany and also to mineralogy and chemistry, about which he published several papers in the Philosophical Transactions of the Royal Society. His chemical interests were nourished by his friendship with Joseph Priestley (1733-1804), who was the first to isolate oxygen in 1772. Both Priestley and Withering were fellow members of the informal but very important Lunar Society of Birmingham, a small group of no more than 14 scientists and intellectuals that met at members’ homes monthly on the Monday nearest the full moon-in order, as Dr. Priestley recorded, “to have the benefit of its light in returning home.”(Fulton;7Fulton IF: The place of William Withering in scientific medicine. J Hist Med Allied Sci 1953;8:1-15.) Other members included Erasmus Darwin, the engineer Matthew Boulton (1728-1809), and his partner James Watt (1736-1819), inventor of the first practical and widely used steam engine. Withering worked together with his fellow members of the Lunar Society to seek solutions to the social, economic, political, scientific, and technologic problems of the midlands during a period of rapid industrialization.8Schofield R: The Lunar Society o f Birmingham: A Social History of Provincial Science and Industry in 18th Century England. Oxford, Oxford University Press, New York, 1963. While politically more moderate than Priestley, Withering shared his views in support of the French Revolution, and during the celebrated Birmingham Riots of July 14-17, 1791, when Priestley’s house, library, and laboratory were destroyed, Withering’s home was ransacked.
In 1783, Withering translated Torbern Bergman’s Sciagraphia regni mineralis as the Outlines of Minerology, to which he added notes. He also chemically analyzed the mineral waters at various spas in England and Portugal. That year, Withering contracted tuberculosis, which was the cause of his eventual death in 1799. Through awareness of his physical limitations and skillful planning, Withering was able to accomplish much more than many men who enjoy robust health. The enforced rest periods required by bouts of illness may have actually stimulated his scientific research. For both scientific and personal reasons, Withering became especially interested in the effects of different climates on patients suffering from consumption (tuberculosis). He also maintained an extensive meteorologic journal.
Yet for all of his diverse scientific accomplishments, Withering will be longest remembered for assuring the place of digitalis in scientific medicine. His first published reference to the foxglove appears in his Botanical Arrangement (1776; 376): “A dram of it taken inwardly excites violent vomiting. It is certainly a very active medicine, and merits more attention than modern practice bestows upon it.” In view of the fact that he had already spent a year studying the effects of the foxglove, this understatement indicates the caution that characterizes his work.
Having undertaken what might be called a ten-year clinical trial of digitalis, he published his results not with any special claim to fame but to guard against the misuse of the drug by the medical profession, which had naturally become intensely interested in it following rumors of Withering’s success. He wrote in his Account of the Foxglove: “The use of the Foxglove is getting abroad and it is better the world should derive some information, however imperfect, from my experience, than that the lives of men should be hazarded by its unguarded exhibition, or that a medicine of so much efficacy should be condemned and rejected as dangerous and unmanageable.”
Apart from a German translation (1785), Withering’s Account of the Foxglove underwent only one edition, and an autographed letter by Withering that recently passed through my hands indicated that the edition was still not sold out as late as 1798. This may partially explain why Withering was far better known in Europe for his contributions to botany and mineralogy than for his monumental contribution to medicine. The French botanist l’Heritier de Brutelle named a genus of plants of the Solanacea family Witheringia. In 1796, Abraham Gottlob Werner also commemorated Withering’s name when he called barium carbonate “witherite.” In 1782, Withering had first demonstrated that naturally occurring barium carbonate is a compound distinct from other barium salts.
Withering continued to work and see patients until the day before he died of consumption. A friend who observed him gravely ill during that last working day was said to be responsible for the now celebrated pun: “The flower of English physicians is indeed withering.”(O’Malley;4O’Malley CD: De angina gangraenosa. (English translation), in J Hist Med Allied Sci 1953;8:16-45.)
Withering himself possessed a caustic wit, sometimes expressed in his letters. Witness this brilliantly concise response to a duelling challenge:
Sir,
I received your note; the purport of which if I am not mistaken, is a request that I would fix upon a time and place that you may have the opportunity to kill me. But it further implies that I may also have the opportunity of killing you; and this you call satisfaction. It may be so to you. Permit me, however, to assure you that it would be no satisfaction to me to kill you, or any other man; therefore, until our ideas can be more properly adjusted, you must allow me to decline to meet you.9Roddis LH: William Withering: The Introduction of Digitalis into Medical Practice. New York, Harper, 1936; 118.
An artist known to me only as S.H. turned the medical properties of the foxglove into a moderately bad, but frequently quoted, poem published in late editions of Withering’s A Botanical Arrangement. Cushny, himself an authority on digitalis, saw fit to include it in his tributes:6Cushny AR: William Withering, M.D., F.R.S., in Cope Z (ed): Sidelights on the History of Medicine. 1957; 202.
The foxglove’s leaves, with caution given,
Another proof of favouring Heav’n
Will happily display;
The rapid pulse it can abate;
The hectic flush can moderate
And, blest by Him whose will is fate,
May give a lengthen’d day.
In his painstaking clinical trial of digitalis, Withering exemplifies the objectivity and thoroughness characteristic of the greatest scientific research. He was fully and eloquently aware that far more research would be required before the true value of the foxglove as a remedy in scientific medicine would be fully known. “In spite of opinion, prejudice, or error,” he wrote, “Time will fix the real value upon the discovery and determine whether I have imposed upon myself and others or contributed to the benefit of science and mankind.”10Peck TW, Wilkinson KD: William Withering of Birmingham.1950.
NOTE: For a more extensive biography of Withering, see Peck and Wilkinson.10Peck TW, Wilkinson KD: William Withering of Birmingham.1950. For a more recent history of digitalis, which was widely misperceived to be a panacea during much of the 19th century, see Ackerknecht.11Ackerknecht EH: Aspects of the history of therapeutics. Bull Hist Med XXXVI 1962;36:389-419.
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