The leading scientific breakthoughs that led to a correct understanding
This page about the history of gout was last reviewed or updated, on 31 August 2011
The history of gout goes back over 4,000 years. Gout is a very old, and distinguished, disease known to the ancient Egyptians, Greeks and Romans. The name of the disease, gout, from the Latin Gutta (drop) was first christened with a variety of additional names depending on where in the body the attack took place. Podagra, if it was the joint connecting the big toe to the foot; gonagra in the knees; chiagra in the hands.
To-day these more specific terms have gone out of frequent usage, and the all encompassing term “gout” is normally used, irrespective of the location of the attack, although different adjectives may be placed in front of the word “gout,” to be more specific about the kind of gout being described –acute, chronic, tophaceous etc.
THE ANCIENTS AND THEIR CAUSES OF GOUT - The humours (humors) that were not funny.
Around 400 B.C. Hippocrates (466-377 B.C.), thought its cause was connected to the four humours (humors) which, if in balance in the body delivered health, and if out of balance delivered illness. The humours (humors) were blood, black bile, yellow bile and phlegm. The cause of gout he thought, was that an excess of one of these humours “dropped” or “gutta-d”, into a joint and hence the pain and inflammation therein. Tophi were accumulations of unbalanced humours (humors) in the affected body area such as an elbow joint.
Hippocrates was the first known physician to attempt to describe what causes gout
Claudius Galen, (129 - 199-217 AD), physician to five Roman Emperors in the 2nd century AD, believed in an annual bleeding to re-balance the out-of-balance humours that had or would develop as a consequence of over eating and drinking, or of too much sexual activity (if you were a man – they didn’t think women got gout until later in life, and generally that's correct).
Claudius Galen, a Greek in Rome, was an early luminary in the history of gout
Antoni Van Leeuwenhoek was the first person in the history of gout to see gout's needle shaped crystals
With this microscope, Antoni Van Leeuwenhoek was the first human to see that tophi was not chalky but crystallised.
But no one followed up this breakthrough and it was not until 1776, nearly 100 years later, the year of the publication of Adam Smith’s famous treatise on economics “The Wealth of Nations,” and of the outbreak of the American revolution, that the next true step forward in the history of gout was taken.
Carl Wilhelm Scheele a Swedish-German scientist who may have discovered oxygen before Joseph Priestley, worked at the University of Uppsala in Sweden, the same university, and at the same time, as the famous gout sufferer Carl Linnaeus who was its professor of Natural History. In 1776 Scheele examined what he called urinary concretions (solid matter) and discovered a new acid, which he named lithic acid. It later became known as uric acid, most of which in the body is in the form of urate. In the same year his fellow countryman, Tobern Bergman analysed a bladder stone and found the same acid in it.
Carl Wilhelm Scheele. He discovered uric acid in a urinary concretion (solid matter).
GOUT AND URIC ACID - URIC ACID'S ROLE IS DISCOVERED BY SIR ALFRED GARROD
But the connection between uric acid and the chalky tophus crystals Leeuwenhoek had seen was not made. This would be the next major breakthrough in the history of gout, in fact a crucial breakthrough, and it came from Britain. In 1797, William Hyde Wollaston learnt that the same acid Scheele had found (lithic/uric acid) in urinary concretions was also found in tophi – taken from his own ear.
"Gouty matter is lithiated soda” declared Dr.Wollaston, or as we would put it today, monosodium urate crystals. The link between gout and uric acid been learnt but where was uric acid in the body apart from the tophi? And was its presence the cause of the crystals or the consequence of them?
It had been known that uric acid was found in the blood for some time - not just in tophi, or kidneys stones or urinary concretions - but was it the cause of gout? In 1848 a British physician, Sir Alfred Garrod, who had made gout and rheumatism just about his life’s work, declared in a lecture that an excess of uric acid in the blood was the cause of gout. Garrod had developed what he called his “Uric Acid Thread Experiment”, which others have since renamed his “Thread Test.”
Garrod's test for uric acid Garrod secured one or two 1” long linen thread or threads in blood treated with acetic acid, the central ingredient in vinegar, for 36 – 60 hours. He would then be able to see, under a polarising lens microscope, the urate of soda crystals accumulate on the thread. In some extraordinary way, the crystals were attracted to the thread like candy floss (aka cotton candy or fairy floss) to a candy stick. He noted that if the blood under test held a lot of uric acid the crystals were formed, and if it didn’t, they weren’t.
For the first time in the history of gout here was a very plausible explanation of an immediate cause of gout, but it took decades for Garrod’s explanation to be completely accepted despite the fact that he had also noted or observed around 150 gout patients with large amounts of uric acid in their blood.
In 1859 Garrod, completed “The Nature and Treatment of Gout and Rheumatic Gout”. One of his ten propositions in this book stated firmly and clearly that the gout inflammation was caused by the deposited urate of soda (uric acid). Another, that an excess of uric acid (today we’d call it hyperuricemia) led to crystallisation and inflammation.
And that the excess of uric acid was caused by over-production, or under excretion by the kidneys. The kidneys excreted uric acid, they did not produce it as many had thought.
It's from purines Gout had been associated with dietary excesses and a lack of exercise since at least Roman times, but did uric acid somehow come from foods and drinks, and were there other sources? As eloquent and definitive as Garrod had been about uric acid and its serum measurement by his Uric Acid Thread Experiment, and of other features of gout, he had not identified where uric acid came from.
And thus one of the major causes of uric acid, and in excess, still remained to be learnt. In 1898, again about 100 years since William Wollaston had linked uric acid and gout tophi crystals, and about 25 years after the last edition of Garrod’s book, the next major piece on the gouty jigsaw was slotted into place. It was, perhaps, the last of the major breakthroughs, although there have been many other breakthroughs since then. The fact that uric acid came from purines in foods and drinks was proved by the German scientist Emil Fischer. His Nobel Prize was partly awarded for this proof. It had taken over 4,000 years of gout history to get to this point.
Emil Fischer proved that purines structured uric acid.
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