Superstuffs: Aspirin

250 years ago, in 1763, the President of the Royal Society in London received a letter from Rev. Edward Stone, a clergyman in Oxfordshire.  The story told in Stone’s letter began in 1758 when at the age of 56 he took a walk in the country.  He reported that he had chewed some willow bark and felt that it might have reduced various aches and pains, or “agues” as he called them.  He decided to do some careful experiments.

He collected a kilogram or so of the bark, dried it and then crushed it into a powder.  Then he started to take measured quantities at intervals of four hours and noted whether there was any change to his symptoms.  Over a few days he slowly increased the dose until he found that about 2.5g was successful.  During the next five years Stone tried out his remedy on about fifty of his neighbours and found that they too felt relief of pains and fevers.  

Stone was not the first to notice the analgesic or pain-relieving effects of willow bark although he does not seem to be aware of his predecessors.  In fact the ancient Greek physician, Hippocrates had recorded its use and people around the world used the various species of willow that grew in their vicinity.   Nevetheless, the publication of Stone’s letter in the Philosophical Transactions of the Royal Society inspired new interest across Europe in the properties of willow bark.

In 1838, Joseph Buchner, a German, isolated the active material from willow bark.  He called it salicilin after the Latin name for the willow, salix.  Two years later  Johann Pagenstecher, a Swiss found the same substance in a wild flower called meadowsweet (Latin name, spiraea) which was much more common.  In 1838 Raffaele Pirea, an Italian, broke salicin down to salicylic acid or 2-hydroxybenzenecarboxylic acid to give it its modern name.

Salicylic acid was found to have all the medicinal benefits of willow bark but it irritated the stomach sometimes causing more discomfort to patients than their original symptoms. The solution to this problem was found in 1853 by Charles Gerhardt, a Frenchman.  He added an extra chemical group to the salicylic acid to make it acetylsalicylic acid.  Unfortunately Gerhardt’s preparation was not very efficient.  It was another 44 years before the story was taken further.

In 1863, 100 years after Stone’s paper, Friedrich Bayer, a German, founded a company to make dyes.  By the 1890s the Bayer company had become large and successful and was manufacturing a range of chemicals including medicines.

A team of chemists searched for new drugs that could be sold profitably. One such drug, derived from the opium poppy, they called “heroin”.  One of the team, Felix Hoffman, found a much better, cheaper, method of making acetylsalicylic acid.  At first Bayer weren’t certain that the new drug was worth manufacturing but in 1899 they decided to market it with the name “aspirin”.

Almost immediately, aspirin was a great success and particularly during the great flu epidemic of 1918, when millions died and many more fell ill, aspirin gained popularity.  During the next century nearly everyone swallowed an aspirin tablet to cure a headache or reduce the fever of colds and flu.

Although tons and tons of aspirin had been manufactured no-one really understood how it worked until 1971 when John Vine, in London, discovered its action in cells.  Vine’s research won him a Nobel prize but it also suggested some other uses for aspirin.  It was found to reduce the chance of blood clots forming in blood vessels.  Today aspirin is recommended to anyone suffering or likely to suffer from heart or circulation problems.  Further research has shown that it may also have a role in fighting cancer.

Aspirin’s various medicinal properties mean that it is still an important product for Bayer and many other pharmaceutical companies and there is probably a packet of the tablets or powders in most homes.  The title of “superstuff” is certainly justified.

Activities

1.     Discuss whether Edward Stone was a good scientist in his work on willow bark.

2. Some years after Stone, Edward Jenner tested his smallpox vaccination on one subject, and William Withering tried out the heart drug, digitalis, on dozens of his patients.
Compare Stone’s and these other eighteenth century experiments with modern clinical tests involving placebos and double blind trials.

3. Why did the Bayer company give acetylsalicylic acid the trade name “aspirin”?  There are some clues in the article.

4. Explain why Buchner and Pirea’s discoveries were an improvement on using willow bark as a remedy

5.(A level) Hoffman’s method of making aspirin involved reacting salicylic acid with acetic anhydride.  The other product is ethanoic acid. Find out the structure of acetic anhydride, salicylic acid (2 hydroxybenzenecarboxylic acid) and aspirin (acetyl salicylic acid) and write a structural formula equation for the reaction.

Peter Ellis

Peter Ellis taught science (mainly chemistry) in secondary schools to GCSE and A level for 35 years and was a head of department for twenty years.  He is now a freelance writer of educational materials in science and dabbles in writing fiction.