William Withering

William Withering (1741-1799) was an English physician best known for his use of extracts of foxglove (Digitalis purpurea) to treat dropsy (edema), a condition associated with heart failure and characterized by the accumulation of fluid in soft tissues.[1] Withering's insights on the medical uses of foxglove proved crucial to modern understanding of heart failure, and today drugs containing the active compound, known as digitalis, are still prescribed.[1]

Early Life and Education

William Withering was born in 1741 during the reign of George II in the market town of Wellington, Shropshire. His father Edmund was an apothecary there, and his mother Sarah was the sister of Dr Brooke Hector, a prominent physician in Lichfield.[2] William was privately educated by the Reverend Henry Wood of Ercall.[2]

Influenced by his father, Edmund, who worked as an apothecary, and by his uncle, Brooke Hector, who worked as a physician in Lichfield, Withering enrolled at the University of Edinburgh in 1762, following four years of medical apprenticeship.[1] 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).[7] Cullen, distinguished clinician and teacher, was said to have been especially influential in Withering's development as a physician.[7]

In 1766, having shown little interest in botany, which formed a large part of the medical curriculum at the time, he prepared his thesis on malignant sore throat, titled De Angina Gangraenosa.[1] 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.[7]

Early Career and Personal Life

Withering soon relocated to Stafford, where he attended private patients and served as a founding physician of the Stafford General Infirmary.[1] He began to enjoy botany and met Helena Cookes, who sketched the plants he collected. They were married on Sept. 12, 1772, and had three children.[1] During this period, he was not overly busy, was able to indulge in amateur dramatics and met Helena Cookes, his future wife, who cultivated his interest in botany.[2]

Move to Birmingham and Professional Development

Seeking a more substantial income, Withering decided to move to Birmingham to fill a vacancy created by the death of physician and Lunar Society cofounder William Small in 1775. The move to Birmingham was suggested to Withering by Lichfield physician Erasmus Darwin.[1] 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.[7]

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.[7] Together with fellow physician John Ash, Withering served as a founder of the Birmingham General Hospital, which opened in 1779. There he treated several thousand patients each year, many of whom were impoverished and received their care gratis.[1]

Botanical Contributions

Withering gained renown for his botanical writings, the first of which, following in the tradition of English naturalist John Ray, was A Botanical Arrangement of All the Vegetables Growing Naturally in G. Britain (1776).[1] Withering's later work, An Arrangement of British Plants (1787–92), was designed to show amateur botanists, many of whom were young women, the utility of the Linnaean classification system. In addition, this work introduced his specially designed field microscope, which subsequently became known as the Withering botanical microscope.[1]

His first major publication, A Botanical Arrangement of all the Vegetables Naturally Growing in Great Britain (1776), was little more than a translations of the portions of linnaeus' writing relevant to English botany. As Withering acquired more botanical experience, however, his Botanical Arrangement became increasingly based on his first-hand observations.[5] In the last edition published during 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.[5]

Although Withering's botanical interests were confined principally to indigenous British plants, his reputation on the Continent was such that the French botanist L'Héritier de Brutelle named a genus of plants (of the Solanaceae family) Witheringia.[5] Subsequently the plant Witheringia solanacea was named in his honour, and he became known on the continent of Europe as "The English Linnaeus".[10]

The Discovery of Digitalis

In 1775 Withering learned a secret herbal treatment for dropsy from an old woman in Shropshire. He determined that among the twenty or so herbs she concocted, purple foxglove (digitalis purpurea) was the active ingredient.[6] 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.[22]

For ten years Withering carefully studied it, then presented his results in An Account of the Foxglove and Some of its Medicinal Uses with Practical Remarks on Dropsy and Other Diseases (1785).[6] Withering's lasting reputation lies primarily with his publication An Account of the Foxglove, and Some of Its Medical Uses (1785). Though foxglove (Digitalis purpurea) had been used in folk medicine for centuries, Withering drew upon 156 of his own cases to objectively demonstrate its efficacy in treating dropsy, the edematous bodily swelling that typically accompanied heart failure.[1]

This book is a model of sober, empirical medical writing. He reported the failures as well as the successes of digitalis therapy, developed guidelines to avoid overdosage and underdosage, and documented his findings with case histories.[6] Single case reports were the most widespread way of publishing original observations in Withering's time, but although he had collected records of nineteen cases of "dropsy" treated with digitalis before 1779, he decided not to report on the treatment until he had assembled all the 156 cases seen in his private practice, and seven whom he had treated at the Birmingham Hospital: It would have been an easy task to have given select cases, whose successful treatment would have spoken strongly in favour of the medicine, and perhaps been flattering to my own reputation. But Truth and Science would condemn the procedure. I have therefore mentioned every case… proper or improper, successful or otherwise.[23]

Lunar Society of Birmingham

Seeking a more substantial income, Withering decided to move to Birmingham to fill a vacancy created by the death of physician and Lunar Society cofounder William Small in 1775. (The Lunar Society was a gathering of naturalists and inventors who met monthly in the Midlands of England, traveling under the light of the full moon.)[1] He was active in Birmingham's vigorous Lunar Society, other members of which included Joseph priestly, Erasmus Darwin, Josiah Wedgwood, Matthew Boulton, and James Watt.[5]

William Withering, another doctor, moved to Birmingham in 1776 and became a member.[13] The society gained its name as its monthly meetings were always scheduled for the Monday nearest to the full moon, the better light helping to ensure the members a safer journey home along the dangerous, unlit streets.[14] The Dining Room at Soho House is also known as the Lunar Room and it is where the Lunar Society met. The meetings held here were lively affairs, where all the latest ideas and inventions were discussed and scientific experiments carried out.[11]

An exclusive club, it never had more than fourteen core members, and each member was noted for their special area of expertise including the greatest engineers, scientists and thinkers of the day.[14] The original "Lunarmen" comprised a select club, gathered together monthly for lively exchange of ideas over dinner. Members were often referred to as "Lunaticks": Galton's butler's term which the Lunaticks themselves embraced.[16] A crucial element in the "Midlands Enlightenment," they were pioneering natural philosophers (scientists), physicians, mechanical engineers, and manufacturers—"the fathers of the industrial revolution." It was an informal body with no membership list, officers, or minutes.[16]

Meanwhile, Boulton's toy business triggered his interest in metallurgy, shared by William Withering and James Keir to produce many industrial applications.[16] Medical doctor also a noted botanist and major interest in chemistry and metallurgy.[19] The Society brought together leading figures of the Industrial Revolution, fostering collaboration between scientific theory and practical application.

Scientific and Medical Achievements

Beyond his work with digitalis, Withering contributed to the clinical distinction of scarlet fever and to the medical use of lead and rum.[1] In 1796 the German mineralogist Abraham Gottlob Werner also commemorated Withering's name when he called barium carbonate "witherite." Withering had in 1782 first demonstrated that naturally occurring barium carbonate is a compound distinct from other barium salts, such as the sulfite and the oxide.[5]

Withering was elected a fellow of the Royal Society in 1784. He was also a fellow of the Linnean Society and a foreign corresponding member of the Royal Academy of Sciences of Lisbon.[5] Withering also published several other chemical and mineralogical papers, chiefly in the Philosophical Transactions, including "Experiments on Different kinds of Marl" (1773) and "An Analysis of Two Mineral Substances, Viz. the Rowley Rag-Stone and the Toadstone" (1784).[5]

Later Life and Death

Following the Birmingham riots of 1791, he left England and went to Portugal, where, as he had done in Stafford and Birmingham, he analyzed the mineral content of spa waters.[1] He visited Portugal twice in search of a salubrious climate which would slow the progressive deterioration of the chronic pulmonary condition (probably tuberculosis)from which he suffered the last fifteed years of his life. It ultimately caused his death at the age of fifty-eight.[5]

In 1794 Withering returned to Birmingham, where he died following complications of tuberculosis. He was buried at Edgbaston Old Church in Edgbaston, Birmingham, where his memorial tablet is marked by the staff and snake of Asclepius, the Greco-Roman god of medicine, and sprigs of Digitalis and Witheringia.[1] Withering died on 6 Oct. 1799, it being wittily said during his long illness that 'the flower of physicians is indeed Withering.'[4]

Legacy and Impact

Today digitalis continues to serve as the active ingredient of the cardiac glycoside drugs digoxin and digitoxin.[1] The introduction of digitalis into medical practice represents a milestone in the therapy of heart disease and especially congestive failure, and its impact continued to be felt until relatively recent times.[26] 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.[7]

Withering's publication created considerable furor with fellow Lunar Society member Erasmus Darwin, who claimed priority in having published on foxglove's therapeutic use in managing dropsy. This was not the first conflict between Withering and Darwin.[1] Despite this controversy, Withering's approach was more detailed and systematic, and he clearly deserves the credit for studying, developing, and popularizing this form of therapy.[26]

Withering's scientific methodology established important precedents for clinical research. Withering also showed that he was aware of positive bias by the 'discoverers' of new medicines—what we would refer to today as reporting bias—and the means to minimize it.[21] His careful documentation of both successes and failures in treating patients with digitalis represented an early example of systematic clinical observation that would influence medical practice for centuries to come.