A Drop of History 121

The history of aspirin
When the famous drug was rejected by Bayer as useless

The woman writhed in the throes of labour, crying out as though she was being torn asunder. By her side, the father of medicine, Hippocrates, could do nothing to ease her pain except give her to chew strips of willow bark, one of the commonest trees around. Don’t laugh at this primitive cure, because the great Hippocrates gave the labouring woman exactly what a modern doctor would give today: aspirin. The famous drug was born out of salicylic acid, the basic component of willow bark.

Hippocrates had noted the analgesing effect of the tree’s bark in the 5th century BCE, but several more centuries had to pass before the most famous painkiller of all time was created and developed in the form we all know today. The next reference to salicylic acid was made by a British clergyman: in 1763, Edmund Stone advised his parishioners to chew on willow bark when they were in pain. Later, scientists would discover that salicylic acid is an effective analgesic, at the same time capable of protecting one’s system from infection. Unfortunately, the acid is highly corrosive to the stomach, and not few of those who used it would vomit. Until the 19th century, many attempts were made to use the particular acid in medicine and find ways to avoid its side effects.

Completely by chance, in 1853, French chemist Charles Frédéric Gerhardt mixed salicylic acid with acetyl chloride. He had just created aspirin, without even knowing it, but he lost the title of “father of aspirin”, because he did not continue producing it, considering the procedure exceedingly complex. The title went, a few years later, in 1897, to German chemist Felix Hoffmann, who worked for the Bayer pharmaceutical research facility.

Hoffmann’s father suffered from rheumatoid arthritis and took salicylic acid to ease the pain. Hoffmann senior, however, could not cope with the drug’s side effects, so his son tried to find a way to make its administration more tolerable. In fact, young Hoffmann did what Gerhardt had, the only difference being that salicylic acid could be synthesised in the laboratory and not extracted from the trees, so the resulting chemical compound was more stable. After his success, Hoffmann proudly presented the result of his research to the company management, but Heinrich Dreser rejected it as useless and potentially dangerous. That was the very same drug that was to turn the little pharmaceutical company into a giant.

Besides, around the same time, Hoffmann, being very productive, had discovered another compound, diacetylmorphine, which had some amazing effects. According to contemporary studies, the new discovery created a unique sense of euphoria and made workers feel like heroes, that is why the compound was later named heroin. Because of heroin, whose first application was in cough syrup, Bayer had no interest to spare for Hoffmann’s lesser discovery, aspirin.

Hoffmann, however, did not stay idle; instead, he took his new discovery to Berlin hospitals. Recognition for the drug came from the patients themselves. Only then did Bayer deign to look at aspirin again. Soon Hoffmann saw his discovery go into mass production, but the poor man had not thought of patenting it, so aspirin brought profit to the company instead of himself. Bayer patented the drug in March 1899 and Hoffmann did not receive a single penny of the profit; instead, he retired and studied art history in Switzerland.

Until the end of World War I, Bayer had a monopoly on the manufacture and distribution of the drug, but after Germany lost the war, Britain, Russia, France and the USA claimed part of the rights. Not a bad move at all, considering that aspirin is in mass production even today. It is estimated that eighty billion tablets are consumed in the USA every year, and fifty billion in Europe.

© Dimitris Kambourakis 2003, All Rights Reserved
Translation from the Greek © M.A.K. 2008, All Rights Reserved

A Drop of History 116

Yellow fever
The disease that exterminated five million people

In 1894, renowned French developer Ferdinand de Lesseps, after some rest on the laurels of the Suez Canal construction, started the second great project of his life: the construction of another canal, this time in Panama, that would join the Atlantic and Pacific Oceans. But the Sinai desert had nothing on the jungles of Central America. An epidemic broke out on the huge construction site, killing two-thirds of the workmen and, shortly afterwards, Lesseps himself. That was the infamous yellow fever. The project was abandoned, and was finished much later by the Americans, only after a way to fight the disease had been found.

Yellow fever was first mentioned in 1648, and is up there with the greatest and most lethal infections that humankind has known, like the plague of the Peloponnesian War, the disease that Mark Antony’s legions brought to Rome from Mesopotamia, the Black Death of the Middle Ages, the Great Plague of London. Yellow fever was considered a disease of the New World, because that is where it was first noted, but, as it was proven much later, it had existed long before in Africa.

The particular disease was awful and its symptoms horrible. It started with pain in the stomach, the joints and bones, followed by convulsions and black viscous vomit, and continued with rashes all over the body, fever, coma and death. That development unfolded within five days and its mortality rate was almost 100%. It first appeared in Guadelupe in 1648, before moving to Cuba, New York, South Carolina, Boston. Wherever it arrived, people died in droves. All the traditional defence methods – quarantines, isolations, disinfections – proved useless. For two centuries, yellow fever appeared out of the blue and killed people without anyone knowing how it was transmitted. In the tropics it was endemic. In temperate places it appeared in spring and summer. Neither the cremation of the dead nor the disinfection of houses and ships could stop it.

In 1741, yellow fever exterminated three-quarters of the English troops at the siege of Cartagena. In 1799, it killed 31,000 people around the Caribbean. In 1878, another 25,000 victims followed suit. The disease was terrifyingly contagious. In 1781, a frigate sailed from the Honduras towards Port Royal, in Jamaica; it never arrived, and, when found drifting aimlessly, some time later, it was revealed that the entire crew had died of yellow fever.

Years went by, the fever claimed more and more victims, but medicine could not find a cure. The English and French sugarcane plantation owners, to save themselves, abandoned Jamaica and Martinique and returned to their cooler countries, leaving their properties and slaves in the hands of their halfbreed overseers. Medicine, wrapped in a cocoon of conservatism, refused for decades to adopt new ideas in order to find the cause of the disease. Yellow fever had been classified as a contagious miasma, an incurable disease of the New World, and was persistently ignored, despite its lethality. Two of its worst outbreaks occurred in New Orleans in 1853 and in the American Southwest in 1878, with 25,000 victims.

On 14 August 1881, a pioneer doctor named Carlos Finlay overcame traditional beliefs and, in a speech before the Royal Academy of Havana, expressed for the first time the view that yellow fever was transmitted by mosquitoes of the genus Aedes Aegypti. The Academy doctors laughed and rejected Finley’s theories, branding them ridiculous. Twenty more years passed, and the disease kept killing. An eminent bacteriologist, Giuseppe Sanarelli, based on the old views, claimed that the fever was caused by a bacillus that he called “icteroid”. His theory was immediately accepted and acclaimed, while the unknown doctor’s view had been ridiculed.

Three decades later, the Americans who occupied Cuba, seeing that the disease would not abate, remembered Carlos Finlay, who was old by that time. Finlay helped, despite his bitterness, and the appointed committee concluded that the fever was spread by the mosquitoes. So, in order to fight it, they had to disinfect the standing waters in the marshes and cisterns and destroy the mosquitoes’ eggs. The American military accomplished that by putting fish in the cisterns, that ate the floating eggs. Yellow fever receded from Cuba.

In the rest of America, however, civilian doctors refused to accept the conclusions of their military colleagues; the usual medical rivalries. So, while the problem was solved in Cuba, there was a new outbreak in the mainland, which was not treated, as yellow fever was still considered an incurable disease. Only when the epidemic crossed over to Cuba again and was repelled once more did they deign to check the new method and adopt it. After 1910, yellow fever was practically eradicated, after exterminating an estimated five million people in two centuries.

I am left with the impression that, in the end, history allows medicine to cure a grave disease only when the conditions are ripe for the surfacing of another, much more lethal, one which will also be considered incurable for a long time.

© Dimitris Kambourakis 2003, All Rights Reserved
Translation from the Greek © M.A.K. 2008, All Rights Reserved

A Drop of History 114

The history of alchemy (2)
The charlatans of science

The heyday of alchemists spanned the Middle Ages and the Renaissance, but their idiosyncratic kind existed since ancient times. Every advanced culture had its own secretive caste of scientists who, in one way or another, devoted their lives to seeking answers to the mysteries of nature, as much as to the satisfaction of one of mankind’s most primordial desires: fast, unlimited wealth.

There were alchemists in ancient Egypt and ancient China, while their European colleagues, much later, claimed that they had derived the basic laws of their craft from the god Hermes’ famous Emerald Tablet. Go figure. Christianity, magic and the 12 Olympians, all rolled into one. Towards the end, in the 16th and 17th centuries, alchemy fell into the hands of frauds and charlatans. Sovereigns, merchants and feudal lords had so much need of gold to fund their wars and trade journeys, that they were ready to accept any swindler who assured them he could make them roll in it.

The trap alchemists set was the assurance that the philosopher’s stone, which they sought, could, on contact with any base metal, transmute it into ten, a hundred, or even a thousand times as much gold. One can understand the dizzy dreams of any lord faced with such promises, especially when such promises were given by mysterious people shrouded in the stuff of legends, who spoke ancient languages, wrote in arcane symbols and worked with peculiar metals, liquids and powders, whose deepest and most dangerous secrets they were familiar with.

A lord had to fund the laboratory and procure the materials, but also to hand over the initial gold for the procedure to begin. Part of that would belong to the fraudulent alchemist, but such a one, with his superior knowledge of metals, could provide gold in greater quantity but inferior purity, as long as it was bright enough to fool anyone. Of course, many such alchemists did not make it to the end, despite the sonorously mysterious terms they used to cozen their sponsors, like the eagle-lion’s eggs, the raven’s return, the earth’s thickness, and other such. Dozens of them were lynched by enraged peasants who had lost their few gold pieces, or were sent to the stake or the gallows by deceived nobles.

Even more numerous, though, were the nobles who were deceived by crafty alchemists. In 1589, the Venetians gave the alchemist Bragantini the royal treatment because he offered the city two vials of a liquid that would progressively transmute two loads of mercury into gold, worth six million ducats. As long as the supposed transmutation went on, Bragantini lived like a king; then he scarpered before the fraud was revealed. It is interesting that, although those were the times when witch-hunting was rife, alchemists were never targeted by the Inquisition. The philosopher’s stone was supposedly distilled from the source of divine creation itself, so it was a wholesome substance, not diabolical at all.

The depiction of the legendary philosopher’s stone was incredibly convoluted, and purely allegorical. It was cube-shaped, with seven flowers on its sides, which represented the seven known planets and their respective metals. Above the cube was the symbol of mercury, flanked by the moon (symbol of silver) and the sun (symbol of gold). Above those was the symbol of sulphur and a phoenix. And above all was the king, with fire on one side and the pelican’s blood on the other. A composition able to terrify anyone during those dark times.

Alchemy died out in the 18th century, but the real contribution of alchemists to chemistry and metallurgy was huge. Constant experimentation and mixing of chemical elements for centuries were bound to create an accumulation of knowledge on the subjects. Besides, there were many discoveries made accidentally. Gunpowder, for example, was known to the Chinese centuries earlier, but the Europeans did not get it from them. It was concocted by accident, in the cauldron of an alchemist who, seeking the philosopher’s stone, ended up creating the black explosive powder.

© Dimitris Kambourakis 2003, All Rights Reserved
Translation from the Greek © M.A.K. 2008, All Rights Reserved