Taking the Medicine: A Short History of Medicine’s Beautiful Idea, and our Difficulty Swallowing It

by Burch, Druin

  Inasmuch as the dried willow bark actually did reduce fevers, Stone’s discovery was a success. He had no way of knowing, given the limitations of the world he lived in, that fever was not itself the disease, but the body’s method of trying to fight its way back to health. What he potentially could have grasped, but did not, was that what mattered was not whether patients were feverish and uncomfortable for a few days, but whether, in the end, they survived.

  Part of what stopped Stone from thinking about this was that, to his mind, he could see the treatment working. The fevers subsided, the patients generally got better. When someone got worse instead, there was always a reason to hand.

  The ancient use of willow had fallen out of favour and none of the books that Stone looked in said much about it. The Egyptians said they used it to give strength to the heart, which it was incapable of doing. They put it on infected ears and aching muscles, into neither of which it was easily absorbed. Dioscorides in AD 100 mentioned the use of willow – but dealt only with the leaves, not the bark that was the rich source of the active ingredient. So the use of willow went back a long way, but in the same style as the medical use of celery and lettuce and watermelon. Stone’s achievement was to note a real effect of the bark – its ability to bring down fevers – even though he mistook this for a guarantee of its helping provide a cure.

  By the end of the eighteenth century, as Stone had hoped, willow bark was a widespread medication. William White, an apothecary, spoke gratefully about its use. ‘Since the introduction of this bark into practice, in the Bath City Infirmary and Dispensary, as a substitute for the Cinchona, not less than 20 pounds a year have been saved to the Charity.’ He worked to develop extracts of the bark. When the Napoleonic war made imports more difficult, efforts to replace cinchona increased even further. Willow, which did not cure malaria, thus partly replaced cinchona, which did. Doctors felt pleased at their advance.

  6 Beetroots, Mesmerism and Organic Chemistry

  IGNORANCE IS A great spur to questioning, and to progress. The physical scientists from the Royal Society onwards were excited to realise how much they did not know, and how much remained to be discovered. Perhaps no group were more enchanted, more enthralled, or more full of promise to the world, than the chemists.

  Chemistry had developed from medieval and Renaissance alchemy. The ethos of alchemy was that of the conspiracy theory. Someone, somewhere, had discovered how to turn lead into gold. It was an alchemist’s task to uncover the information that others were keeping secret, to root out the heart of the mystery. Clues were to be found everywhere – in coded messages hidden within books, in signs from the heavens. What all alchemists understood was that the knowledge was already out there, squirrelled away. Paranoia went together with a belief in magic: the natural world felt to alchemists like something already fully explored, where the best bits had been hidden by those who had got there first.

  Chemistry was born, in the seventeenth and eighteenth centuries, out of a different feeling. Nature was open and honest, its practitioners believed, there for all to explore. Anyone able to devise the right method could be rewarded with understanding. Her mysteries need not be approached secretively. The greater the intelligence you came to her with, the more she would reveal.

  It was not until the middle of the eighteenth century that chemistry was able ‘to free itself from these delusions, and to venture abroad in all the native dignity of a useful science’. So wrote Thomas Thomson, Regius Professor of Chemistry at Glasgow, in 1830, reviewing the development of his discipline from its alchemical roots. By the middle of the preceding century, he believed, chemists had finally begun ‘to be useful to man, by furnishing him with better and more powerful medicines than the ancient physicians were acquainted with’.

  Thomson was writing at a time when the realisation of medicine’s uselessness had not really dawned. His belief that chemists had extended the range of effective medicines was inaccurate, as was his assumption that there had ever been a substantial range to extend. The ancients had possessed opium, and now there was cinchona and willow bark. None could be credited to chemistry.

  Advances, however, had been made, like that of Paracelsus dissolving opium in alcohol rather than water. The next breakthrough came in the unlikely shape of the beetroot. In the middle of the eighteenth century the German Andreas Sigismund Marggraf found that he could use brandy to extract crystals from this undistinguished root vegetable. They tasted sweet. Marggraf showed that they were the same substance as that which gave the sweetness to sugar cane. Efforts to breed sweetness into beetroot began. The importance of Marggraf’s innovation was his demonstration that what mattered was not where a molecule (in this case sugar) had come from, but the nature of the molecule itself. It was a move towards the idea that a chemical’s structure, rather than its heritage, determined its function.

  The next step was taken by Antoine François Fourcroy, the son of an apothecary in the service of the Duc d’Orléans. He qualified as a doctor in 1780 and turned his attentions to chemistry, taking up a lecturer’s post in the subject four years later. With cinchona bark still in demand, and still exceedingly expensive, efforts were being made to find both replacements and counterfeits. Fourcroy was well connected but from a poor background; his evident talent led the French Société Royale de Médecine to sponsor his medical education. Even before it was finished they were employing him to help analyse mineral waters. Fourcroy responded by developing reagents, substances that reacted with what was in the water, allowing analyses that were not only newly accurate but also did not require the water to be boiled down in order to measure the solids dissolved within it. Impressed by the great French chemist Lavoisier, Fourcroy worked not only to advance his own experiments in chemistry, but also to help others to do the same.

  In 1784 Lavoisier was temporarily distracted from his other researches by a request from Louis XVI of France. Franz Mesmer was obtaining impressive medical results by a process that seemed difficult to understand. By sitting close and touching people, he appeared able to heal a range of problems. He felt his healing utilised ‘animal magnetism’, a heretofore undiscovered physical fluid, one that was simply not apparent to other observers but that connected him with his patients. The king wanted to know if it was real. He set up a commission to investigate, appointing four doctors (including Guillotin, later the inventor of the ‘humane’ and ‘democratic’ machine) and five leading scientists, among them Lavoisier and Benjamin Franklin. The commission decided that Mesmer’s ‘animal magnetism’ was a fantasy. This was Lavoisier’s opinion:

  The art of concluding from experience and observation consists in evaluating probabilities, in estimating if they are high or numerous enough to constitute proof . . . The success of charlatans, sorcerers, and alchemists – all those who abuse public credulity – is founded on errors of this type of calculation.

  Lavoisier was being a bit unfair, since the greatest dangers to public credulity were not from those who set out intentionally to fool people, but from those who had already fooled themselves. Some of those were mesmerists; many more were doctors.

  Lavoisier’s language is interesting. Reaching conclusions was an ‘art’, relying on ‘experience and observation’ rather than experiment. Probabilities came not by calculation, but by estimate. It was an inadvertently accurate summary of the way even members of the king’s commission decided what medical effects were real, and what were not. Irrationality, Lavoisier concluded, was most likely when it came to those things ‘that touch the most’. People wanted to know what the future held, and they wanted to prolong their lives. Their desires made them unable to think clearly on those subjects.

  In the meantime, Fourcroy’s experience in analysing mineral water made him well qualified to approach more solid matters. He undertook an analysis of bark from trees that were being used as alternatives to cinchona. Cinchona floribunda, also called Quinquina of St Domingo, was one: its name neatly combining the actions of a hope and a
n advertisement. Fourcroy published his analysis of the bark’s chemical components in 1791. It came to be regarded as a model way of exploring a vegetable substance, but Fourcroy was able to say very little about the bitter-tasting residue that was putatively the bark’s active ingredient, and got nowhere in actually isolating an anti-malarial compound.1 His success in breaking the bark down into constituent substances, however, prompted interest from others in continuing his approach. Fourcroy encouraged these interests, as did the French government. These early efforts at chemical analysis were driven by concerns over the dilution and adulteration of medical compounds, in particular of opium and cinchona. Commercial interests also pushed development. Once the Napoleonic War was blocking trade between France and the tropical British colonies, extracting sugar from beetroot suddenly became financially profitable. It made people think about the value of the chemical processes involved. If you could replace expensive sugar cane imports with something so simple as beetroot, what else could you do? Solvent extraction, the chemist’s method for separating and thereby concentrating particular parts of a fluid (or a vegetable), began to seem like a technique with more than academic interest.

  From the early years of the nineteenth century, the successful isolation of active drug principles began. At first it was haphazard. In 1803 Charles Derosne, a Parisian pharmacist, while attempting to devise a way of measuring concentrations of opium, ended up with a substance he did not understand and that he found to be peculiarly alkaline. Chemists had learnt to expect that the constituent parts they derived from plants would be acid. Derosne mistakenly put the oddity down to his having contaminated the crystals with potash, and thought no more of it. Around the same time Friedrich Sertürner, a young Austrian apothecary, made a similar discovery. He published on the subject repeatedly from 1805, attracting little attention. Then in 1817 he managed to get his paper into the journal edited by France’s leading chemist, Gay-Lussac. Annales de Chimie had been founded in 1789 by Lavoisier and continued to attract general interest. Its readers realised these alkaline crystals were something strikingly special.

  Gay-Lussac’s editorial pointed out that Sertürner had isolated what appeared to be the active ingredient of opium. (Sertürner and three volunteers convincingly demonstrated their case by accidentally overdosing themselves with it.) Sertürner had called it morphium: Gay-Lussac, wishing to make the name reflect the odd fact that the substance was alkaline, altered that to morphine. Yet it was not the achievement of this specific isolation that Gay-Lussac felt was of chief importance. He was more excited by the principle it established, that plants contained something more than the organic acids heretofore isolated. If the first-ever organic alkali was morphine, what else might it be within the power of plants to provide?

  Cinchona was an obvious target for this sort of hopeful interest. A few half-successful efforts had been made in the years before Gay-Lussac’s editorial, but only after its publication did people begin looking for alkaline substances. Once they knew what they were after, progress was quick. In 1820 the Frenchmen Pelletier and Caventou isolated quinine. It turned out to be one of a number of substances in cinchona bark that had anti-fever and anti-malarial properties. Pelletier and Caventou understood that these newly uncovered plant ingredients might be of wider use. They recommended that they be properly investigated for their direct medical uses.

  To an extent, the discovery of what came to be called alkaloids helped medicine take its ignorance more seriously. Chemistry was developing new drugs, different from anything that had gone before. You did not have to suggest that your teachers and your idols might have been mistaken in order to believe that the effects of these novel medicines might not be fully worked out.

  The development of pharmacopoeias whose ingredients were chemicals rather than plants was a boon. The properties of plants varied so much, between seasons and climates and even plots of earth, that notions of testing were handicapped by the difficulty of obtaining consistent drugs. Quinine was a lot more palatable and a lot less noxious than the cinchona bark which contained a lot of other alkaloids as well. People swallowed quinine with more success than cinchona, and vomited it up again less frequently. Our modern fantasy of the gentle benevolence of plants, and the acrid artificiality of drugs, was inconceivable to these early pioneers, who saw things very much the other way around. The birth of the modern pharmaceutical industry began with efforts to convert ever-increasing amounts of the natural bark to the gentler and more effective sulphate of quinine.

  In the ten years from 1828, progress was made in isolating active compounds that could replace willow bark. In Germany, Italy and in France salicin (from the Latin name for willow, Salix) and then salicylic acid were developed. They, too, quickly became used as substitutes for the continually expensive cinchona and its modern derivative of quinine. Like willow bark, neither salicin nor salicylic acid had any anti-malarial activity.

  It was in 1828, also, that Friedrich Wöhler synthesised urea. The molecule by which humans get rid of nitrogen, urea is an essential part of the way our bodies handle proteins, and a key waste molecule in urine. It also contains carbon and is therefore organic. Yet Wöhler made it out of ammonium cyanate, an entirely inorganic compound. For the first time chemists knew that they were able to artificially construct a molecule that previously had existed only as the product of a living creature.

  * * *

  1 The tree was later renamed Exostemma floribundum, correctly dismissing any notion that it was a form of cinchona.

  7 New England and New Ways of Thinking

  MENTAL TECHNIQUES AS well as chemical ones were advancing.

  Born in Cambridge, Massachusetts, at the start of the nineteenth century, Oliver Wendell Holmes contemplated abandoning medicine for poetry. At the age of twenty-one, his poem ‘Old Ironsides’ won him national attention. It was written to celebrate the wooden-hulled American warship, a veteran of the 1812 war against the British, built from American live oaks and clad in copper by the Revolutionary hero Paul Revere. The success of the poem touched Holmes’s imagination; he spoke of the ‘lead poisoning’ that entered his soul on seeing his own words in print.

  Against his inclination to art, however, was the Calvinist devotion to work in which he had been raised. Poetry was an admirable talent for a cultured man, but a suspect occupation for his entire career. After a thoroughly American elite education – Phillips Academy followed by Harvard – Holmes went to Paris in 1833, at the age of twenty-four. For a while he spent his time at the races and the theatre. Then, his puritan side winning through, he concentrated on his studies at the École de Médecine. There he came under the influence of the nation’s leading teacher, Pierre Charles Alexandre Louis.

  Louis harboured an unusual scepticism about the value of existing medical knowledge. The accepted theory was that a fever resulted from inflammation, from an excess of blood: attaching leeches closest to the inflamed bit of the body drew this away, easing the fever; in pneumonia, for example, the leeches were put on the patient’s chest. In addition to their own indigenous supply, in the year that Holmes arrived in Paris the French medical industry imported an extra forty-two million leeches. Hungary and the Ukraine, Turkey, Romania, Russia and North Africa were exporters. And with a lifespan of almost a decade, the leeches were highly reusable.

  Seemingly it was inconceivable for anyone to consider that all bleeding was useless or, worse, harmful. Yet Louis questioned the way in which people were bled, and came up with new ideas as well as, more significantly, setting out thoughtfully to test them. ‘What was to be done,’ he asked, ‘in order to know whether blood-letting had any favourable influence on pneumonia, and the extent of that influence?’ It was a question much on his mind during the time that Holmes studied under him. Louis’s first attempt to write on the subject was an 1828 article, which led to a full-blown book in 1835. What Louis wanted to clarify was when patients should be bled. Was it best to attach the leeches to their chests on the day they fell ill
? The day after? The day after that? What troubled him was the knowledge that each patient was different, and that their fitness and their age and the severity of their infection could all vary. How, he wondered, could he avoid mistaking the influence of these factors for the influence of his leeches?

  The gradual development of our ability to think clearly about such issues is not a sequence of precisely linked events. Louis did not think as he did because he read Van Helmont, nor were Holmes’s later thoughts the direct products of his time in France. These inventive thinkers, arriving at ways of seeing the world that were more correct and useful than what had come before, advanced the progress of human culture with ideas that were partly their own and partly not. Ideas about truth, about experimental method and how science could best discover Nature were bubbling under, bursting forth now in one person’s way of looking at the world and now another’s.

  For any particular disease, wrote Louis,

  let us suppose five hundred of the sick, taken indiscriminately, are subjected to one kind of treatment, and five hundred others, taken in the same manner, are treated in a different mode; if the mortality is greater among the first than among the second, must we not conclude that the treatment was less appropriate, or less efficacious, in the first class than in the second?

  What had been only carelessly implied in Van Helmont’s description in 1662 was thoughtfully exposed in Louis’s. The natural differences between one patient and another, between this instance of infection and that, could be prevented from biasing a test’s results by simply including a large enough group of people and spreading them randomly. As Louis acknowledged: