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Chapter Three

Floating in the Air

Wandered in the town, to the Museum and

Zoo . . . Reconstructions of Hausa and Sanghay villages – combination of indigo and pale calabash. Hunchback boy with staff and bowl and mauve purple jumper stretched like a landscape over his totally deformed body . . . A restaurant in a garden. I drank a beer on a red spotted cloth-covered table. Mosquitoes bit the hard parts of my fingers.

Bruce Chatwin in Niger, 1971, from Photographs and Notebooks

When Perkin left the Royal College every evening and walked along Oxford Street, his journey was illuminated by gas light. London was ablaze with gas: houses, factories and streets had been lit this way since the beginning of the century, and Perkin’s laboratory work had begun to rely on gas for other fiery uses.

But this demand brought some terrible problems. Gas derived from the distillation of coal, and millions of tons were processed each year to meet demand. The process – which involved the highly combustible method of heating coal in closed vessels without oxygen – also yielded several useless and dangerous by-products: foul-smelling water, various sulphur compounds and a large amount of oily tar.

For many years these were regarded as waste; the problem was not how to utilise them but how to get rid of them. The sulphur was found to be removable with lime and sawdust, while the gas-water and tar were abandoned in streams, where they poisoned the water and killed the fish. Anyone who requested any of these by-products was given them without charge in huge barrels. Some hopeless experiments were conducted with them, and then they were again thrown away into streams. But gradually, in the years leading up to Perkin’s birth, new uses were uncovered.

The gas-water was found to be rich in ammonia, and the sulphur compounds would be used in the manufacture of sulphuric acid. In Glasgow in the 1820s, Charles Macintosh found a use for the coal tar, developing a method of waterproofing cloth. He used it to prepare a special solution of rubber, applied it to two pieces of coat fabric, and called it a raincoat, but other people soon began calling it a macintosh. It was also used as a protective coating on timber, and was widely employed on the new railway system. Its combination with creosote also afforded a thick coating for wood and metals, and it was used as a disinfectant in sewage. Some patents from the 1840s even suggested the early use of tar and coal-tar pitch on road surfaces.

At the opening of the Royal College of Chemistry, coal-tar was already recognised as an immensely complex material. The first students understood that it consisted of the elements carbon, oxygen, hydrogen, nitrogen and a little sulphur, and they knew that from these combinations an inviting list of substances could be formed.

The study of modern chemistry was still in its infancy – it was only in 1788 that Antoine Lavoisier demonstrated that air was a mixture of gases which he called oxygen and nitrogen – and important advances were being made every year. Molecules such as the solvent naphtha had already been isolated in coal-tar in the 1820s, but the great challenge was now to reveal its constituent atoms, and to show how these may be modified to form other compounds. Naphtha was found to contain benzene, and, by a painstaking process of fractional distillation, this in turn was found to contain such materials as toluidine and aniline. The chemists often knew the atomic combination of each molecule – how many elements of carbon, how many of oxygen or hydrogen – but not how they fitted together. Their precise chains and points of attachment – those knobbly bead-and-metal constructions that (in the days before three-dimensional computer software) proud chemists liked to pose beside for photographs – would not be fully understood for several decades.

The research students at the Royal College thus conducted much of the exploratory work without map or compass, and some paid the price. Charles Mansfield, one of Hofmann’s most enterprising students, had been discouraged from setting up dangerous large-scale coal-tar experiments at the Royal College, and yet persevered with his project in a building near King’s Cross railway station. While preparing large quantities of benzene for an international exhibition in 1855, a fire broke out which consumed both him and his assistant.

It was aniline that most fascinated Professor Hofmann. He had spent much of his laboratory time in Germany investigating its possibilities, and continued his researches in Oxford Street. Crucially, he managed to impart this enthusiasm to his students.

‘As a teacher he was singularly interesting and lucid,’ Lord Playfair explained in a memorial lecture given in Hofmann’s honour in 1893, the year after his death. ‘He marshalled his arguments with great care, and as he brought them towards the conclusion, he increased in his persuasiveness and seemed to each individual student to take him into his special confidence.’

Frederick Abel, the joint-inventor of cordite, once asked himself, ‘Who would not work, and even slave, for Hofmann?’ Before he tackled explosives, Abel conducted an analysis of the mineral waters of Cheltenham and researched the effects of various substances on aniline (one of which was the poisonous gas cyanogen, from which his eyes suffered permanent damage). Another of his students established the composition of the air on Mont Blanc.

Strangely for a chemist, Hofmann was a rather clumsy man, once explaining to Abel that when he was younger he could hardly handle a test tube without ‘scrunching’ it. ‘There was an indescribable charm in working with Hofmann,’ Abel remembered, ‘in watching his delight at a new result or his pathetic momentary depression when failure attended the attempt to attain a result which theory indicated. “Another dream is gone,” he would mutter plaintively, with a deep sigh.’

One of Hofmann’s principal talents appeared to be choosing the right student for the right job, and in selecting a huge variety of avenues for research. In his first five years, some thirty-six different projects were undertaken. The Queen and the Prince Consort were frequent visitors to his laboratories, and Hofmann delivered several lectures at Windsor Castle. At the Royal Institution in 1865, Hofmann delighted Prince Albert and other notables with a demonstration involving croquet balls and rods. The royals may have enjoyed his quaint English literal translations from German idioms; they were certainly interested in his students’ work on soil and plants – in fact, they were keen on anything which might lead to practical applications.

William Perkin noted how his mentor used to tour the laboratories several times a day and talk to his students as if each piece of their work was of phenomenal importance. Occasionally their work did indeed carry genuine significance; most often it was mundane and doomed. And almost all the time Hofmann seemed to have done it before by himself. ‘I well remember one day,’ Perkin said, ‘when the work was going on very satisfactorily and several new products had been obtained, he came up and commenced examining a product of the nitration of phenol one of the students had obtained by steam distillation. Taking a little of the substance in a watch glass, he treated it with caustic alkali, and at once obtained a beautiful scarlet salt. Looking up at us in his characteristic and enthusiastic way, he at once exclaimed, Gentlemen, new bodies are floating in the air!’*

Another tour was less fruitful. Once, Hofmann was holding a glass bottle containing a little water, and invited a student to pour sulphuric acid into it. The heat cracked the glass, and the acid splashed from the floor into Hofmann’s eyes. ‘Hofmann was sent home in a cab,’ Perkin remembered, ‘and had to be kept in bed in a dark room during several weeks.’ Despite this hardship, he was so anxious about his work that his students were asked to visit him in his murky bedroom to report progress and receive new instructions.

Predictably, Perkin was a formidably diligent student, and found the preliminary coursework rather easy. He sat near a window overlooking Oxford Street’s horsedrawn carriages, and spent some time sharing common interests with a man called Arthur Church seated opposite him. ‘We were both given to painting and were amateur sketchers,’ Church remembered. ‘I was introduced to his home and we began painting a picture together. This must have been soon after the Royal Academy exhibition of 1854, when I had a picture hung.’

Church had created his own domestic laboratory by converting a small aviary at his home, so was keen to see Perkin’s makeshift chemistry room on the top floor at King David Fort, where he worked in the evenings and at weekends. Perkin liked to take his work home with him, particularly when, after the completion of his basic syllabus in 1855, Hofmann had honoured him by making him his youngest assistant. ‘The students working at research seemed to me to be superior beings,’ Perkin observed.

Perkin’s earliest tasks concerned the formation of organic bases from hydrocarbons, but he was more interested in the results of his next assignment which led to one of his earliest published papers. At the beginning of February 1856 he submitted to the Proceedings of the Royal Society a brief report ‘On some new Colouring Matters’ he had found with Arthur Church. ‘This new body presents some remarkable properties,’ they wrote. That substance, which they named nitrosophenyline, was the result of a experiment with hydrogen and a distillation of benzol. It produced a bright crimson colour, it dissolved in alcohol with an orange-red tint, and it changed to a yellowish-brown when diluted with alkali. They concluded that it had ‘a lustre somewhat similar to that of murexide’, the rich purple originally made from guano.

Although August Hofmann was keen to see his students publish (and had in fact communicated the above findings to the journal himself), he believed the colourful discovery was of little value. In one sense he was right, for Perkin and Church could suggest no practical application for their new colour, and so they resumed other work. But it is significant that the pair, both painters, should be alert to what others might consider merely a pretty coincidence.

Hofmann faced other dilemmas. Many of the wealthier patrons of his college were concerned that chemistry was not producing results that would be beneficial to their well-being. And every landowner who had been excited by Justus Liebig’s crusade was soon disappointed that the institution they supported was not, after all, their salvation. Subscriptions dwindled, and the college was forced to merge with the School of Mines; some students in Perkin’s third year gained entry with the sole aim of improving coal extraction.

Even in 1856, there was much debate, and much disquiet, about the true virtues of pure chemistry. Triumphant practical men simply distrusted men of science. The success of the Great Exhibition of 1851, at which the magnificent Crystal Palace in Hyde Park hosted the most impressive display of booming mechanics that anyone had seen, suggested that progress would be forged merely by the continued application of cheap and copious steam power.

The problem with studying pure chemistry, on the other hand, was that the endeavour seldom produced anything remotely useful.

In the annual report of the Royal College published in 1849, August Hofmann revealed that one of his most cherished ambitions was to show how well the study of chemistry could produce the artificial synthesis of natural substances. He admitted that this involved an uncertain mix of supremely patient application and great good fortune. Indeed, Hofmann and his students were simply grasping for great things in the manner of skilled artists painting with untried materials. ‘Perhaps we will be lucky,’ Hofmann said.

By about 1830 it was becoming clear that all the substances isolated from plant and animal sources contained the elements carbon, hydrogen and oxygen, and often nitrogen and sulphur (the science of organic chemistry is essentially the chemistry of carbon compounds). A simple chemical compound was described by the combination of its elements. At school, Perkin would have learnt the basics: the elements were represented by chemical symbols such as C (carbon), H (hydrogen), O (oxygen) and S (sulphur), where an element is a substance that combines with others to form compounds, but which cannot be broken down into any simpler substance itself. When two or more elements combine, it is the atoms of the different elements that join together, forming molecules. Each molecule of a compound contains the same number of atoms as every other molecule of the compound. In the most rudimentary example, H2O, the chemical symbol for water, thus contains two hydrogen atoms and one oxygen atom. It was not yet known that in some elements – such as the oxygen in the air – the atoms can join together to make molecules without other elements being involved.

One substance Hofmann wished to make in the laboratory was quinine. Quinine was the only treatment found to be effective against malaria, and in the middle of the nineteenth century malaria was a problem that determined the size and prosperity of an empire.

Malaria is an ancient disease, and perhaps the ruin of ancient civilisations. The fortunes of Rome and the Campagna have been tracked against its prevalence. It became widespread after the Second Punic War at about 200 BC, and declined during the days of the Roman Empire until the end of the fourth century AD. But it then reached epidemic proportions, and hampered colonisation until its decline shortly before the Renaissance.

The term malaria – the misleading literal translation of the Italian ‘bad air’ – was probably first used in English in the 1740s, when Horace Walpole described ‘a horrid thing called the mal’aria that comes to Rome every summer and kills one’. Before this, its presence was defined by the catch-all diagnosis of fever or ague.

In Hofmann’s day, malaria was the grave concern not just of Asia and Africa. France, Spain, Holland and Italy were still intensely malarious, although, as elsewhere in this period, it was not always possible to define precisely how many deaths were due to other fevers such as cholera. It was common in Russia and the Western Territory of Australia, and in America the disease was prevalent in the swamplands of the Carolinas, Florida and New Orleans. During the Civil War, malaria was the chief cause of death in the Southern States, and there were hundreds of thousands of cases in New York and Philadelphia – the situation only improving with the clearing and development of land.

In England, where, it was believed, malaria had been responsible for the deaths of James I and Cromwell, the disease was still rampant in the 1850s.The worst areas were the Cambridgeshire Fens and Essex marshes, and in Great Expectations Dickens depicted the marsh agues around Pip’s home in Medway, Kent. Between 1850 and 1860, tens of thousands of people were admitted to St Thomas’s Hospital diagnosed with ague (malarial fevers), and in 1853 it accounted for almost 50 per cent of all admissions.

British imperialists found malaria to be the greatest hindrance to colonisation. In Kilimane, for example, David Livingstone found the mosquitoes ‘something dreadful’, 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.

_________________________________

* 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.’

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