From Gout to Heart Disease:

 the surprising story of a secret medicine

Dorian Haskard,
Professor of Cardiovascular Medicine and Rheumatology,
Imperial College London

Professor Haskard took us through the fascinating history of gout and its treatment, to its surprising link with heart disease. He has spent a good deal of time reviewing everything written about gout and his book, simply called “The Gout”, will be published by the end of the year.

Gout is a very painful affliction which is characterised by a rapid and very painful swelling in the ball of the big toe that usually lasts between 7 – 10 days, but can recur. One of the causes of gout is drinking sugar sweetened beverages, and in the past it was port and beer that were identified as the culprits.  Early “medications” often included opium and alcohol. The cause of gout is due to excessive build-up of uric acid that then forms monosodium urate crystals. The crystals are attacked by white blood cells, thus the area quickly becomes inflamed.

Interestingly, James Parkinson (the English surgeon and geologist who first identified the symptoms of Parkinson’s disease) published a paper “Observations of the Nature of Gout” back in 1805.

The first effective medication for gout was identified by John “Fish” Crawford during a visit to Montpelier. The active ingredient of the so-called “L’eau Medicinale” was later identified to be an extract from the plant Colchicum autumnale, commonly known as autumn crocus. It was not until 1833 that Philip Geiger purified the active ingredient and named it “colchicine”.

On a macabre note, the notorious murderer Catherine Wilson, who was executed in 1862 for killing seven people, was thought to have used overdoses of colchicine on her victims.

Haskard then explained that the mechanism by which colchicine works is by preventing the chromosomes from pulling apart during cell division. In the laboratory the result of treating cells with colchicine is that both pairs of chromosomes remain in one cell after cell division. When this cell divides then colchicine can once again prevent the chromosomes from separating resulting in 4 pairs of chromosomes in a single cell.  The effects of colchicine on cell division can even lead to 8 pairs of chromosomes in a single cell.  This effect of colchicine when applied to plants led to bigger blooms and resulted in a bonanza in plant breeding.

The spindles that help in pulling apart chromosomes during cell division are also present in cilia and flagella. A radioactive form of colchicine containing tritium was seen to bind to extracts of the tails of sea urchin sperm through chromotography experiments. This led to identifying that the tubules were made up of the protein tubulin, and that colchicine interferes with the assembly of microtubules.

Since colchicine interferes with cell division it was considered as a possible treatment for cancer but it proved to be too toxic for normal cells.

It is believed that colchicine evolved in plants to act as a deterrent to aphids. But if colchicine interferes with cell division, why doesn’t it kill the host plant? The answer was identified through analysis of the DNA sequence for tubulin which over millions of years has slowly altered in this plant species to no longer bind colchicine.

Haskard then introduced the link with heart disease which is caused by the narrowing of arteries we call atherosclerosis. Atherosclerosis is also accompanied by inflammatory processes in the endothelial cells. If colchicine reduces inflammation in gout patients, might it also help with the treatment of heart disease? In 2017 a large-scale clinical trial involving patients with non-fatal heart disease showed that treatment with colchicine was equally as effective as a much more expensive antibody treatment.

It was then Haskard presented some shocking evidence from carotid artery tissue removed from patients who had partial blockages.  At the centre of these blockages were microscopic particles believed to be the cause of the inflammation. Analysis of the particles has shown them to be made of polythene and PVC. Thus microplastics now seem to be appearing within human tissue and causing harm.

Our thanks to Professor Haskard for delivering such a fascinating talk.

Charles Emes

Image Courtesy The Wellcome Collection