LITMIR.BIZ

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and described how he ‘had an opportunity of observing the fever acting as a slow poison. ‘[Victims] felt out of sorts only, but gradually became pale, bloodless and emaciated, then weaker and weaker, till at last they sank more like oxen bitten by tsetse than any disease I ever saw.’

      In India, where vast swathes of the country remained uncultivated because of malaria, the British Army were sending back reports of human devastation. It was suggested that the disease acted as a natural form of population control. Amongst adults, about 25 million struggled with the chronic nature of the disease, and about 2 million died annually. Horrified army officers reported grim symptoms. Patients suffered from chills, convulsions, burning temperatures, muscle pains, nausea, vomiting and delirium. Many died in a coma; many more found that their illness returned intermittently. The British naturally blamed the natives, despite the fact that their own policy of serfdom and the land policy of the East India Company compounded the severity of the problem.

      Even in the 1850s, no one was sure what caused this disease. There were plenty of theories, most involving marshlands and airborne infection, but, despite vague hunches from Livingstone and others no one had yet made the scientific link with mosquitoes.

      Treatment for malaria was more straightforward, although often difficult to secure. Up until 1820, when the French chemist–pharmacists Pelletier and Caventou isolated quinine from cinchona bark, many physicians still proffered such remedies as three days of blood-letting, or treatment with mercury, or three bottles of brandy. The superstitious believed that carrying a spider in a nutshell, or eating one, would cure the disease.

      But this was the era of the new alkaloid. Cinchona bark (and roots and leaves) contained not only quinine (named after the Spanish spelling of ‘kina’, the Peruvian word for bark), but also cinchonine, and in the next two decades, two more alkaloids were isolated from the tree, quinidine and cinchonidine. Each had a slightly different molecular structure, and none was quite as effective against malaria as pure quinine (but nonetheless sold as such). In the same period, the two Frenchmen also isolated the strychnine from St Ignatius’s beans, and other chemists found other alkaloids – caffeine in coffee beans and codeine in opium.

      Quinine was in limited supply, and thus expensive. The cinchona tree is about the size of a plum tree with leaves like ivy, and was found almost exclusively in Bolivia and Peru. By 1852, the Indian Government was spending more than £7,000 annually on cinchona bark, and £25,000 for supplies of pure quinine. The East India Company was spending about £100,000 annually. Predictably, this was not intended to treat the poor, and still bought nothing like the 750 tons of bark required by the British army in India alone.

      The clamour for quinine from the great European imperialists was immense, and Britain and Holland mounted costly attempts to grow cinchona seeds in India and Java; the British tried to grow the tree for commercial use in Kew Gardens. The initial planting missions failed, as explorers would often plant the wrong seeds in the wrong place. Some did get rich on the disease, the most notorious being John Sappington who marketed Dr Sappington’s Pills in the Mississippi valley by persuading local churchmen to ring their bells in the evening to remind people to take them. Sappington had capitalised on the one fundamental property of quinine – its scarcity – and had added other worthless substances to his pills to make his supplies go further. In London and Paris, the cost of bark was about £1 per pound, but as it took approximately 2 lb of bark to treat each person, only the well-off got better. When, in the 1840s and 1850s, hundreds of thousands began demanding quinine as a prophylactic, it was clear that it had become the most desirable drug in the world.

      In his room in Oxford Street, August Hofmann had a theory as to how quinine might be made in the laboratory. To his credit, he seems not to have been interested primarily in the fortune to be made by such a discovery. He had noted how naphtha, which he called the ‘beautiful’ hydrocarbon, produced in great quantities in the manufacture of coal-gas, may be converted by a relatively straightforward process into a crystalline alkaloid known as naphthalidine. This substance was found to contain 20 equivalents of carbon, nine of hydrogen and one of nitrogen.

      Coal-gas contains more than 200 different chemical compounds, although only a few of them were known to Hofmann and his students in 1850. These are split between hydrocarbons (which include naphthalene, benzene, and toluene) and those compounds containing oxygen (the most important being phenol or carbolic acid).

      Hofmann believed that, as the formula for quinine differed from that for naphthalidine by only two additional molecules of hydrogen and oxygen, it might be possible to make quinine from the existing compound just by adding water. ‘We cannot, of course, expect to induce the water to enter merely by placing it in contact,’ he wrote. ‘But a happy experiment may attain this end by the discovery of an appropriate metamorphic process.’

      William Perkin was only eleven when Hofmann published this theory, and he read it only after he was admitted to the Royal College in 1853. He soon recognised the importance of the idea. ‘I was ambitious enough to want to work on this subject,’ he recalled, and was motivated further three years later by Hofmann’s chance remark that artificial quinine was now surely within their grasp. What he had not grasped was that the apparent simplicity of quinine’s constituent parts would so thoroughly conceal the hidden complexity of their architecture. The ‘happy experiment’ desired by his mentor would not be forthcoming, or at least not in the way he had anticipated.

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       * On another visit Hofmann found one of his students making good use of the gas fires to cook his meals. ‘At lunch time he used to grill sausages in the empty, scoured dish of the sand-bath . . . or bake ham and eggs for him and his friends,’ Hofmann’s student Volhard recalled. ‘Hofmann had often observed the not-quite chemical-smelling scent; one day he followed it and appeared quite unannounced in the makeshift kitchen . . . He dealt with his English pupil in masterly manner. No word of reproach, but he kept him busy until the last sausage was wholly charred.’

       Chapter Four

      The Recipe

      She said she was going to do it, and by golly, on Thursday, she did it. Because she is the first female secretary of state of Missouri, Judi Moriarty changed the color of the state manual to . . . mauve.

      For those who don’t know, mauve is a delicate shade of purple.

      ‘I wanted a color that represents me and made a statement,’ Moriarty said when introducing the new state manual. ‘It’s in good taste, and it has a lot of beauty.’

      St Louis Post-Dispatch, 1994

      In the first months of 1856, Gustave Flaubert began Madame Bovary, Karl Bechstein opened his piano factory, the plans for the bell Big Ben were drawn up at a foundry in Whitechapel and Queen Victoria instituted the Victoria Cross. During the Easter holidays of that year, August Hofmann returned briefly to Germany, and William Perkin retired to his laboratory on the top floor of his home in the East End of London. Perkin’s domestic workplace contained a small table and a few shelves for bottles. He had constructed a furnace in the fireplace. There was no running water or gas supply, and the room was lit by old glass spirit lamps. It was an amateur’s laboratory, an enthusiast’s collection of stained beakers and test tubes and rudimentary chemicals. The room smelled of ammonia. The table on which he worked was stained with spillage from previous efforts, and probably of ink as well. He was surrounded by landscape paintings and early photographs, and by jugs and mugs and other domestic trinkets that were as alien to a laboratory as delicate soda crystals were to any other house in this smoky residential neighbourhood. It was an unexpected setting for one of chemistry’s most romantic and significant moments.

      Looking back, Perkin adopted a rather nonchalant tone to describe his actions. ‘I was endeavouring to convert an artificial base into the natural alkaloid quinine, but my experiment, instead of yielding the colourless quinine, gave a reddish powder. With a desire to understand this particular result, a different base of more simple construction was selected, viz. aniline, and in this case obtained a perfectly black product. This was purified and dried, and when digested with spirits of wine gave the mauve dye.’

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