by Burch, Druin
It is impossible to appreciate each case with mathematical exactness, and it is precisely on this account that enumeration becomes necessary. By so doing, the errors (which are inevitable) being the same in the two groups of patients subjected to different treatments, mutually compensate each other, and they may be disregarded without materially affecting the exactness of the results.
In other words, it doesn’t matter that everyone is different so long as you take a large enough group of people and divide them randomly. Some will be sicker than others, some healthier. Take enough of them and the differences will balance out. Louis had discovered the cure for the mental error that the Chinese had made almost a millennium before, racing one man dosed with ginseng against another who was not and concluding that the drug accounted for all the differences between them.
Louis went on to make a stronger point. Given that people are different, and the diseases that grip them also vary, what alternative is there to averaging out those differences with large numbers? The alternative is to pretend that your own judgement is capable of noticing and correctly accounting for all the differences that exist, and pretending none of them can bias your intuitions or undermine your conclusions. Avoiding numbers did not mean that you avoided being misled by the natural differences between patients, only that you avoided acknowledging them. Race two people against each other, or even ten, and one group might be naturally faster than the other. Race a random 500 against a random 500 more and you could reasonably expect the groups to have a similar performance.
Like Van Helmont’s, however, Louis’s ideas were better than his practice. He never did take 500 of the sick, and allocate one portion of them to one treatment and the rest to another. Instead he took the records of seventy-seven patients previously diagnosed with pneumonia, then looked at what happened to them relative to the length of the delay before bleeding was begun. Louis’s study, for all his good qualities, was woefully limited. The patients were not spread by chance, nor allocated to different approaches. They were selected after the event, and compared to others that Louis thought looked pretty similar. His conclusions, as a result, were not useful, and his failure to make the most of the methods he suggested limited his influence for good.
It was no coincidence, though, that Louis’s belief in testing went along with a scepticism about the value of medical interventions. Oliver Wendell Holmes returned to Boston soaked in both of these new beliefs. At Harvard he became both Professor of Anatomy and Professor of Physiology (less of a chair, he commented, and more of an entire settee). He also took up a more informal position as one of the nation’s leading intellectuals, a Boston Brahmin and friend of men like Henry Wadsworth Longfellow, William Cullen Bryant, John Greenleaf Whittier and James Russell Lowell. In their company he continued writing, regularly publishing poems and prose in the Atlantic Monthly and in books like The Autocrat at the Breakfast Table.
From February 1843 Holmes helped pioneer the idea that puerperal fever, then a leading cause of maternal death, was actually spread to women by their medical attendants. Puerperal fever was a wound infection, the result of bacteria taking hold in the raw lining of the womb after a woman’s child was born. Holmes was not the first to notice that it was chiefly spread by doctors, but he was one of the first to publicly argue his case. It was a conclusion that doctors could have reached far sooner, if only they were not so wedded to their belief in their own benevolence. ‘Doctors are gentlemen’, said Charles Meigs, a leading obstetrician who was too appalled by Holmes’s suggestion to take it seriously, ‘and gentlemen’s hands are clean.’ Meigs was neither stupid nor ill-meaning, just reliant on his belief that well-educated and compassionate doctors must, by their virtues, bring their patients health and healing.
Holmes thought differently. ‘In my own family,’ he wrote, ‘I had rather that those I esteemed the most should be delivered unaided, in a stable, by the mangerside, than that they should receive the best help, in the fairest apartment, but exposed to the vapors of this pitiless disease.’ Having been schooled in uncertainty, he found the idea that doctors could sometimes cause harm perfectly reasonable.
In May 1860, Holmes addressed the Massachusetts Medical Society. He gave them a blunt verdict on the value of their mutual practices. ‘I firmly believe that if the whole materia medica, as now used, could be sunk to the bottom of the sea, it would be all the better for mankind, and all the worse for the fishes.’
‘Materia medica’ meant all the drugs that mankind possessed. In Holmes’s view doctors were better off leaving well alone. Their job was to support the patients emotionally, to encourage them in sensible and healthy habits, and to admit that all the ‘cures’ and ‘treatments’ that civilisation had so far devised amounted, when put together, to poisons.
He spoke about what he thought were the causes of the situation. His descriptions of mental errors were similar to Bacon’s, and he quoted Bacon while talking of them. As well as the errors of thought in reasoning about human health, though, Holmes also spoke of the culture of medicine-taking. ‘Somebody buys all the quack medicines that build palaces for the . . . millionaires [who make them]. Who is it? These people have a constituency of millions. The popular belief is all but universal that sick persons should feed on noxious substances.’ A society, he was saying, gets the doctors it deserves. If people cry out for medical attendants who will drug them at every opportunity, that is what they get. And Americans were even more gullible than citizens of quieter and less successful nations. Americans, said Holmes, loved extravagance
. . . in remedies and trust in remedies, as in everything else. How could a people which has a revolution once in four years [i.e. an elected change of government], which has contrived the Bowie-knife and the revolver, which has chewed the juice out of all the superlatives in the language in Fourth of July orations . . . which insists on sending out yachts and horses and boys to out-sail, out-run, out-fight, and checkmate all the rest of creation; how could such a people be content with any but ‘heroic’ practice? What wonder that the stars and stripes wave over doses of ninety grains of quinine, and that the American eagle screams with delight to see three drachms of calomel given at a single mouthful?
Doctors, wishing to be successful as much as they wished to be helpful, played up to it all, ‘loving to claim as much for our art as we can’. Holmes’s feeling that medicine did more harm than good was not unique. Here is Samuel Hahnemann, a German physician fifty years older than Holmes, describing his feelings on realising that the treatments available to him at the end of the eighteenth century were harmful:
My sense of duty would not easily allow me to treat the unknown pathological state of my suffering brethren with these unknown medicines. The thought of becoming in this way a murderer or malefactor towards the life of my fellow human beings was most terrible to me, so terrible and disturbing that I wholly gave up my practice in the first years of my married life and occupied myself solely with chemistry and writing.
Hahnemann’s desperation to get out of this situation, ‘so terrible and disturbing’, led him to seek for certainties. Overdosing himself with cinchona, in an experiment that began with no hypothesis, Hahnemann made himself so ill that his symptoms resembled those of malaria. His conclusion was that a drug ‘which can produce a set of symptoms in a healthy individual, can treat a sick individual who is manifesting a similar set of symptoms’. Combined with a fantasy that water could contain the ‘memory’ of a substance that had once been in it, Hahnemann invented homeopathy.1
Oliver Wendell Holmes devoted a considerable portion of his mental and literary energy to attacking homeopathy, a way of thinking that angered him. Replacing mistakes with delusions, said Holmes, was not a valiant way of facing up to the uncertainties, mysteries and doubts with which mankind was surrounded.
Towards the end of his life, Oliver Wendell Holmes was asked a curious question. It came from William Osler, the Canadian physician who rose, largely on the charisma of his personality,
to become the most popular doctor of the nineteenth century. Osler wanted to know what had given Holmes more satisfaction – his medicine or his poetry. In other words, had he made the right decision, abandoning his ambitions to become a poet in order to practise physic?
With puritan grace, Holmes answered that undoubtedly his medicine mattered most. He had tried to save lives, if only by educating doctors about the harms they were inflicting on their patients. But he quickly turned to his memories of writing poetry. ‘I was filled with a better feeling, the highest state of mental exaltation and the most crystalline clairvoyance that had ever been granted to me – I mean that lucid vision of one’s thought and all forms of expression which will be at once precise and musical.’
Being useful to your fellow men was what an elite member of the nineteenth-century Boston intelligentsia knew should matter most. All the same, it was never quite where Holmes’s heart lay.
Osler’s own greatest achievement was to spur doctors into a belated sense of their own inadequacies. His textbook, The Principles and Practice of Medicine, a bestseller around the start of the twentieth century, pointed out that understanding of diseases had developed tremendously, but the medical ability to intervene had not. By then the world was readier to hear such messages, and Osler’s view of the world was greeted as exciting and full of promise. The Rockefeller Foundation, later to sponsor huge amounts of clinically useful medical research, was set up partly in response to the opportunities highlighted by Osler’s book.
The advances of Holmes and of Louis, the mental methods that they successfully popularised, led to no immediate new therapies. But they paved the way for doctors to begin understanding the limitations of those they possessed, and the need to improve. And the next innovation, when it came, arrived from an unexpected direction: dyestuffs.
* * *
1 I am using the word ‘fantasy’ deliberately, to signify that what Hahnemann developed was not a theory. It was not a theory becuase it was not something that he attempted to test or could conceive of disproving.
8 Dyes, Stains and Antibiotics
THE ORIGINS OF modern drugs are profoundly mixed up with our interest in brightly coloured cloths and fabrics, and with the dyes that produced them. These dyes, in turn, derived from an accidental by-product of a new invention: gaslight.
In the 1790s, the inventor William Murdoch, working to help industrialise the Cornish tin mines, found that if coal was heated within an enclosed space, it gave off a flammable gas, one that ‘burnt with great brilliancy’. By 1794 his house in Redruth was being lit by this ‘gaslight’. By 1807 so was Pall Mall in London. Westminster Bridge followed in 1813, then the city of Baltimore in 1816, then Paris in 1820. Over the next few years Murdoch’s gaslight began shining out from the world’s most developed towns.
England, rich in coal, was not alone in finding that this wonderful new process had an unwanted consequence: a sticky, smelly waste residue called coal tar.
The German chemist Friedrich Runge, in 1834, was working with benzene. Benzene was one of the constituents of coal tar, by that stage a rapidly multiplying and unwanted commodity. Runge treated benzene with chloride of lime and produced a colour so blue that he named the substance cyanol. Other chemists made similar discoveries, giving them different names. In 1855 the German chemist August Wilhelm von Hofmann, looking at all these compounds, realised that they were the same thing. He called them aniline.
Possibly the implications of their colour should have occurred to him, as it also should have to Friedrich Runge. Hofmann admired the colour of his coal-tar-derived aniline, then moved on to studying more important aspects of it than its prettiness.
Brought to England in 1845 at the behest of Prince Albert, Hofmann was the founding director of London’s new Royal College of Chemistry. His chemical ‘first love’ was aniline. The nature of it fascinated him, partly because of the way in which related chemicals had shared properties. This raised the tantalising possibility that their molecular structures – if such things could be worked out – would show similarities that corresponded to and explained their external and chemical ones. Benzene, derived from coal tar by one of Hofmann’s English students, was at the core of the family of molecules that included aniline, and which Hofmann called ‘aromatic’. He gave them the name because they smelt sweet.
Techniques for determining the structure of molecules were primitive, but chemists were effective at figuring out the elements that composed them. Benzene, for example, was C6H6, although the way those carbons and hydrogens fitted together was a mystery.1 Hofmann, like many before him, wanted to synthesise quinine. In an 1849 report to the Royal College of Chemistry, he suggested that:
. . . it is obvious that napthalidine, differing only by the elements of two equivalents of water, might pass into [quinine] simply by an assumption of water. We cannot, of course, expect to induce the water to enter merely by placing it in context, but a happy experiment may attain this end . . .
Four years after this, a fifteen-year-old boy named William Perkin came to study under Hofmann at the Royal College. For a youngster fascinated by the possibilities of chemistry, there was no mentor better. Not only was Hofmann brilliant, full of love for colleagues and chemicals alike, but his love and his brilliancy were catching. ‘Who would not work, and even slave, for Hofmann?’ recalled another student. ‘There was an indescribable charm in working with Hofmann, 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.’
The natural world that Hofmann lived in was full of wonders. Perkin remembered him wandering around the laboratory happily, admiring the new compounds that were everywhere being derived for the first time, and joining in his students’ explorations. ‘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!’
It is difficult, living in a world that holds ‘artificial’ as a pejorative, to imagine how fresh and wonderful these colours seemed, the extent to which ‘artificiality’ meant a fertile combination of human talents and Nature’s richness. Chemistry had the potential to offer compounds of power, and the attractions for the chemists were aesthetic as well as intellectual. Perkin and a friend, Arthur Church, were both keen painters. Colours attracted them and aroused their curiosity. While Hofmann viewed colour as something interesting for its chemical implications, Perkin and Church saw it as important in itself. In 1856 they submitted to the Royal Society a report ‘On Some New Colouring Matters’. Distillations gave them oranges and crimsons and dark yellows, ‘with a lustre somewhat similar to that of murexide’.
Murexide was a curious substance. The original source was a cone-shaped marine snail of the genus Murex, which could be crushed to release tiny quantities of a precious purple dye. (An old myth told of Hercules walking his dog on the shore of the Mediterranean and the dog chewing snails and staining its mouth.) The Romans treasured it, not least because of its rarity – over 10,000 snails were needed to colour a single toga. The German chemist Carl Wilhelm Scheele described making murexide artificially in 1776 from the uric acid of human kidney and bladder stones. Then the doctor William Prout, much interested in the medical problems such stones caused, found that an even richer source for uric acid was the excrement of boa constrictors. (Reptiles, like birds, excrete their protein waste in a more concentrated form than mammals.) By chemical transformation Prout arrived at ammonium purpurate, and he called it murexide for the purple colour that so resembled that of the Phoenician sea snails. By analogy, he suggested that murexide might be useful as a dye – but that was as far as the idea went.
‘I was ambitious enough to want to work on this subject,’ said Perkin, about Hofmann’s dream of making quinine from t
he coal tar residue napthalidine. He spent his spare hours during the spring and summer of 1856 in a room on the top floor of his father’s East End house. Wreathed in the stink of ammonia, surrounded by his experiments in painting and photography, on a desk stained by all his various efforts, he changed the world.
Attempting to produce quinine, which was known to be colourless, Perkins ended up with something red. Wanting to understand where he had gone wrong, he tried a similar experiment using aniline as his starting material. This time he got something that was impressively black, then, after rinsing out the flask he had made it in, he noticed that the alcohol wash left a colour of startling hue and radiance. Perkin had produced mauve.
He found that his colour stained silk, and that the newly mauve fabric kept its appearance despite being washed and hung up in the sun. At the end of August he filed a patent, and started to explore the potential for his discovery as a commercial dye. It exploded.
Queen Victoria wore mauve to her eldest daughter’s wedding in 1858, then again in 1862 when she swept into the Great London Exhibition. In between, Charles Dickens’s All the Year Round said Perkin’s mauve made Tyrian purple look ‘tame, dull and earthy’. It was part of a craze for the colour that made Perkin’s fortune, stimulating the development of a synthetic dye industry that aimed to take advantage of the rainbow of colours hidden within coal tar. Perkin himself went on to develop Britannia Violet, Perkin’s Green, and a method for commercially producing a brilliant red. Others rushed in with yellows and violets, blues and browns and blacks and every shade around them. By 1863 there was even a range of different magentas, named for their inventor: the Hofmann Violets, a belated contribution by the man who had initially failed to see the commercial importance of colourings. This was the new and wholly unexpected world of chemistry; imperial and potent and pregnant with synthetic power.
