Edward Stone and the willow bark

Great discoveries do not always announce themselves in laboratories. Sometimes they begin in a country lane, in a parson's idle gesture, when a man with no instruments but his own attention tastes a piece of bark and finds it bitter in a way he has tasted before. The age of chemistry has not yet arrived in the Cotswold valleys in 1757. What there is, instead, is a clergyman with a habit of looking, and an old country doctrine that the cure for a fever grows where the fever grows.

THE PARISH AND THE FEVER

Edward Stone was born at Princes Risborough in Buckinghamshire in 1702, schooled on the King's Foundation at Eton from 1717, admitted to Wadham College Oxford in 1722, taking his BA in 1726 and his MA in 1729, ordained deacon the same year. By 1745 he was vicar of Chipping Norton in north Oxfordshire, a wool town set above the Glyme, with damp meadows below the church and willows along the stream. The ague was the affliction of the valley parishes. Every late summer the marsh fevers came up out of the low ground, and the burial register thickened. The Peruvian bark, the Jesuits' bark, was the one known remedy, but it came across two oceans, cost what a labourer could not pay, and the supply was uncertain. The vicar buried his parishioners and noted, in the manner of a man trained to observe causes, where they had lived and how the water lay.

A TASTE BY THE GLYME

One day about the year 1757, walking the meadow path below the church, Stone broke a piece of bark from a white willow and put it on his tongue. It was, he wrote afterwards, very like that of the Peruvian bark. The resemblance struck him with a force he could not at once account for. He stood with the bitter taste in his mouth and the slow brown water of the Glyme moving past, and what came into his mind was the old doctrine of signatures, the country pharmacist's article of faith: that a Providence which set the disease in the marsh had set the cure in the marsh also. As this tree, he would write, delights in a moist or wet soil, where agues chiefly abound, the general maxim, that many natural maladies carry their cures along with them, or that their remedies lie not far from their causes, was so very apposite to this particular case, that I could not help applying it.

SIX YEARS OF QUIET TRIAL

He gathered a pound of the bark in the summer, dried it for more than three months on the outside of a baker's oven, pounded it to a fine powder, and began. He gave it first to himself, then, cautiously, to feverish parishioners who had no other recourse. Twenty grains, three times a day, in any common vehicle: water, tea, small beer. He kept count. He kept count for six years. In the diary of a country incumbent, with no apparatus, no chemist, no laboratory, no university chair, he conducted what was in plain truth a clinical trial. About fifty patients passed under his hand. Of those, perhaps forty came clear of the ague within five to fourteen days. Ten did not. He noted the failures as carefully as the successes, because he was a country parson and the parish register did not flatter. He varied the dose, mixed it with the Peruvian bark in scarce times to stretch the supply, observed that the willow alone would carry the work. He told nobody outside the parish for six years. He was waiting to be sure.

THE LETTER TO MACCLESFIELD

On the twenty-fifth of April 1763, in the upstairs study of the Chipping Norton rectory, in the pale spring light through the south casement, the vicar sat to a piece of quarto paper and addressed himself to George Parker, second Earl of Macclesfield, President of the Royal Society. The handwriting was the careful clerk's hand of an Oxford man of his generation. My Lord, he began, Among the many useful discoveries, which this age hath made, there are very few which, better deserve the attention of the public than what I am going to lay before your Lordship. He set out the bark, the dose, the patients, the six years. He set out the country reasoning that had brought him to the tree, and he did not pretend it was more than it was. He did not claim to know the chemical principle. He claimed only what a country observer could claim: that he had given the willow bark to about fifty persons sick of the ague, and that it had answered. Five pages, no more. He folded the letter, sealed it, and put it on the hall table for the Wednesday post to London. He was sixty-one. He did not know that he had written the founding document of the most-consumed manufactured medicine in human history. He knew only that the bark worked, that the parish needed it, and that the Royal Society was the only address at which such a thing might be properly entered.

CRANE COURT, JUNE 1763

The letter was read at the Society's meeting at Crane Court off Fleet Street on the second of June 1763. Stone was not present. The Fellows heard the paper through, in the dry committee manner of that house, and passed it to the editors of the Philosophical Transactions. It was printed in Volume 53 of that year, pages 195 to 200, under the title An Account of the Success of the Bark of the Willow in the Cure of Agues, by the Rev. Mr Edward Stone, of Chipping-Norton in Oxfordshire. The Transactions were, in the 1760s, the one scientific journal in the English language with serious circulation on the Continent. The paper went out, in due course, to Edinburgh, to Leiden, to Paris, to the German university towns, and it lay on the shelves of medical libraries for the next sixty years, waiting for the chemists to catch up to the country parson.

WHAT THE CHEMISTS FOUND

They caught up slowly. In 1828, at Munich, the pharmacist Johann Andreas Buchner isolated the active glycoside from willow bark and gave it the name salicin, from Salix, the willow. In 1838, at Pisa, Raffaele Piria broke salicin down to salicylic acid. In 1859 Hermann Kolbe at Marburg synthesised salicylic acid from coal-tar phenol, and the substance entered industrial production. In 1897, in the Bayer laboratories at Elberfeld, Felix Hoffmann produced the stable acetylated form, acetylsalicylic acid, and in 1899 the Bayer company put it on the market under the name Aspirin, a for the acetyl, spir for the meadowsweet Spiraea ulmaria in which the related acid had also been found, in for the pharmacist's habitual ending. The parson's bitter bark, tasted by the Glyme in 1757, had become a white powder pressed into tablets and shipped by the ton. It is by every careful count of the twentieth-century historians the most-consumed manufactured drug in the history of the species. About one hundred and twenty billion tablets were swallowed in the year 2024.

THE WILLOWS BELOW THE CHURCH

Stone died at Chipping Norton on the twenty-sixth of November 1768, in his sixty-seventh year, five years after the letter and thirty years before the German chemists began the work that would carry his observation forward. He is buried at St Mary the Virgin, the parish church above the Glyme. The rectory is a private house now. In 2003 the Bayer company placed a bronze plaque on the porch of the parish church, naming him plainly: the Reverend Edward Stone, vicar of this parish 1745 to 1768, discoverer of the anti-pyretic properties of willow bark, 1763. Great moments in science are usually claimed afterwards by the institutions that finish the work, and the country observer who began it is usually forgotten. Stone was nearly forgotten. What kept his name was the precision of his five pages, the count of fifty patients honestly tallied, and a single sentence in a letter to a London earl, written in good plain English on a Monday afternoon in April. Below the church, on the slow water of the Glyme, the willows still stand. The parish holds, without proof and without needing it, that they are the daughters of the trees the vicar walked among.