by Martin Booth
One hole in the act was that patent medicines containing opium were not covered. Inevitably, their sales soared as the act started to bite and a new campaign against these began amongst doctors in the 1880s, criticism of the opium trade which was being carried on with China adding to the climate of opinion in favour of further opium regulation. The main force of the attack was against chlorodyne – Dr J. Collis Browne’s Chlorodyne alone earned its makers £31,000 in 1891. The next year, legislation brought patent opiate medicines under the umbrella of the 1868 act: sales from Dr J. Collis Browne’s Chlorodyne fell slightly to £25,000 by 1899.
The new legislation was quickly turned to advantage by the patent medicine industry which continued to market its brands but without an opiate content. Surveys by the British Medical Association in 1909 and 1912 discovered that most remedies were free of opium, the makers keenly advertising the fact. Liquifruita Medica gives a good example, its advertising claiming it was ‘free of poison, laudanum, copper solution, cocaine, morphia, opium, chloral, calomel, paregoric, narcotics or preservatives’. Quite what good it might do was not questioned: many former opiate medicines were now little more than syrups laced with foul-tasting herbs. The common dictum was the worse it tasted, the more good it must do.
By the end of the nineteenth century, opium was firmly in the domain of the doctor rather than the kitchen cupboard and, with new specific drugs being developed, it was no longer needed as a cure-all. Opiates became controlled substances, improvements in the medical profession reduced the degree of self-medication and opiates were prescribed for a more limited range of illnesses than before.
Yet, by now, opium’s throne was under threat. Where opium itself had ruled in the past, its crown was being passed to its stronger, more powerful and seemingly more miraculous constituent parts.
5
Heroic Substances
Early in the eighteenth century, pharmacists and physicians began to hunt for the core substances of opium which produced its miraculous properties. There was an awareness – arrived at as much by guesswork as by scientific analysis – of there being what was called the ‘basic principle’ of opium, otherwise referred to as its ‘essence’: Rousseau’s ‘Black Drop’, having three times the potency of any other opium mixture, was considered to have a super-abundance of this elusive compound, yet what it was was unknown and, as doctors were always requesting even stronger potions, there was created a growing demand for the knowledge. It was believed that, if this substance could be isolated, the potency of opium could be vastly increased by getting rid of the ineffective material in its make-up. It goes without saying the financial rewards of discovery were an added incentive.
Of course, what the hunters did not realise was they were drawing inexorably closer to the discovery of the alkaloids of opium, the organic chemical compounds at its very heart.
Several men worked independently to investigate the poppy and its products, one of the earliest being an American, John Leigh of Virginia, who published his Experimental inquiry into the properties of opium in 1786. Seventeen years later, a French pharmacist called Derosne succeeded in separating out a salt from opium which, in experiments on animals, proved to be more powerful than raw opium. He promptly announced he had discovered opium’s essence, publishing his findings in the Annales de Chimie in February 1804, and immodestly naming the salt ‘Sel narcotique de Derosne’. Not surprisingly, it quickly gained popularity as a medicine.
What Derosne had discovered was one of opium’s constituent parts, a substance today known as noscapine (formerly called narcotine), although his was not a pure sample.
In December 1804 another French chemist, Armand Seguin, presented a paper, entitled ‘Sur l’opium’, to the Institut de France, in which he outlined a technique for obtaining another substance from opium. His discovery was not published for a decade, by which time he was in disgrace for embezzling drug supplies from the French army, and his work was dismissed. Seguin did not know it but he was on the trail of one of the most far-reaching medical discoveries of all time.
The first real breakthrough is generally credited to a 21-year-old German pharmacist’s assistant from Paderborn in Westphalia, Friedrich Wilhelm Adam Sertürner. Born in Neuhaus in June 1783, he received no scientific education or training but he was apprenticed to a pharmacist for five years. Although his laboratory equipment was inadequate and rudimentary, his patience and precise scientific observation were not and, curious about opium, he spent much of his spare time investigating it. Working initially in Paderborn and later at Einbeck in Hanover, he was to alter the future of medicine. His painstaking experimentation has saved millions of lives: it might also be argued to have instigated the scourge of modern society.
In 1806, Sertürner published the results of fifty-seven of his experiments in the Journal der Pharmacie, twenty of which dealt with meconic acid which he termed poppy acid. He discovered pure poppy acid had a different effect on blue plant pigment than raw opium in solution did, deducing this was caused by something in the acid. He then studied the precipitates of chlorates in an infusion of opium and arrived at the conclusion that he had found a new, independent, chemical substance. What he had isolated for the first time was a pure medicinal compound which he proved to be basic as opposed to acidic. This was a revelation for up until then all organic compounds were thought to be acids. The new compound was to be known as an alkaloid – that is, an organic compound with alkaline properties.
Sertürner experimented with his alkaloid on animals. Opium with the alkaloid removed showed no effect but the substance itself had ten times the power of processed opium. He knew he had arrived at the secret of opium which he referred to as its ‘principium somniferum’, or sleep-making principle. He named his discovery ‘morphium’ after Morpheus, the Greek god of dreams or sleep although, since then, it has variously been known as morphia, morphinum and morphin. We know it today as morphine.
For years after his initial work, Sertürner experimented on himself, looking to perfect his morphium, passing through its various states of euphoria, depression and nausea, learning of its therapeutic effects as well as its dangers of which he prophetically wrote, ‘I consider it my duty to attract attention to the terrible effects of this new substance in order that calamity may be averted.’
At first, his work was ignored: his lack of qualifications condemned him to obscurity although he knew in his heart that what he had achieved was ground-breaking. ‘I flatter myself,’ he wrote in 1816, ‘that Chemists and Physicians will find that my observations have explained to a considerable extent the constitution of opium, and that I have enriched chemistry with a new acid (meconic) and with a new alkaline base (morphium), a remarkable substance which shows much analogy with ammonia.’ However, in 1817 the French chemist, Joseph Louis Gay-Lussac, drew attention to it although it was fourteen years before the Institut de France awarded Sertürner a 2000-franc prize and a citation for having ‘opened the way to important medical discoveries by his isolation of morphine and his exposition of its character’. His achievement also sparked considerable research into the hunt for alkaloids of other organic substances: in 1817, strychnine was discovered, in 1820 caffeine, with nicotine following in 1828.
Once Sertürner’s work was widely known, others built upon it. Two French chemists, Joseph Cavento and Pierre Joseph Pelletier, evolved a process for producing morphine and, in 1818, a French doctor, François Magendie, published a paper entitled Formulary for the Preparation and Mode of Employing Several New Remedies, the subject of which was the medical application of the alkaloid. Magendie described the case of a young girl with an aortic aneurysm who had sought in vain for a cure for insomnia produced by the pain from physicians and ‘gossips, charlatans, pharmacists, magnetizers’ and ‘herbalists’. Claiming she could not take opium, Magendie prescribed her two types of pills, one strong and the other weak, containing the acetate and sulphate of morphine. These calmed her symptoms and he went on to prove their efficacy with o
ther patients.
Although morphine did not catch the attention of addicts in the first decade after its discovery, it was otherwise misused for, being of considerable strength, it was taken by a large number of suicides. So many people used it to end their lives (or as an implement of murder) that it was included with gunpowder and other man-made tools of destruction in Balzac’s Comédie du Diable, published in 1830: the Devil himself claimed it was a primary cause for the sudden population increase in Hell.
By the early 1820s, morphine was commercially available in Western Europe: in Britain and America, its popularity as an anodyne rapidly increased after the translation of Magendie’s paper. It was cheap to produce and, more importantly, was sold with a standardised measure of strength. For the first time, doctors could prescribe accurate doses. Being far more potent than opium, only ¼ grain of morphine had the same effect as 1– 1½ grains of opium. By 1840, morphine was widely accepted and used for almost as many medical conditions as opium, and the application of pure alkaloids rather than simple opium preparations was becoming commonplace.
Other opium alkaloids had been found: Robiquet identified codeine, its name originating from the Greek for poppy-head, in 1832: Pelletier found narceine in the same year: thebaine was discovered by Thiboumery, working with Pelletier, in 1835: papaverine was separated out by Merck in 1848.
Despite the arrival of morphine, opium was still popular. Dr Jonathan Pereira’s standard British text on therapeutics, published in 1854, still described opium as the most important, valuable remedy available to doctors and recommended it because its effects were ‘immediate, direct, and obvious; and its operation is not attended with pain or discomfort’
It is little wonder opium was so highly regarded for the main aim of doctors was not to cure illness but to combat pain. Other painkillers existed but these could have side-effects whilst opium did not, at least in the short term. Throughout the first half of the nineteenth century, some doctors argued about the dangers of opium although, generally speaking, they side-stepped the issue of addiction through prolonged administration. The situation was still confused when, early in the 1850s, a new means was invented of introducing a measured dose of purified drug into the body. It was a turning-point in not only medical but sociological history.
For some time, doctors had been hunting for a way of administering drugs without ingesting them. Ever since William Harvey proved, in the early seventeenth century, that blood circulates through the body to all tissue, doctors had pondered how to get it to transport drugs.
A number of methods were attempted. Monsieur Pomet used a clyster (enema), writing that ‘given in clysters opium operates quicker than when taken by mouth.’ Suppositories made of morphine and coated with wax and animal fat were also invented. Inhalation was tried but was too time-consuming and made the patient nauseous. Epidermatic methods using skin patches and the direct smearing of opium ointment on to raw flayed flesh were also used, but they caused blistering. Clearly, something else was needed.
The subcutaneous introduction of drugs was not new. In 1656, Sir Christopher Wren injected opium into dogs using a hollow quill attached to a bulb. He even experimented on humans but little interest was taken in the process. It was not until the 1830s that the process was reconsidered when a Dr Lafargue, of St Emilion, wrote of his method of admitting morphine into the bloodstream. It was crude: a lancet was dipped into morphine solution, pushed horizontally under the skin and left there for some seconds. He later refined the process by suggesting tiny pills of morphine could be inserted under the skin with a blunt needle. Very gradually, the principle of the needle came together with the concept of the syringe, which was already known, having been invented by Hero of Alexandria, the mechanical genius of the classical world.
Who actually invented the medical hypodermic syringe is uncertain for a number of doctors began independently injecting drugs around the same time, using a glass syringe and tube with a sharpened point. Some argue a French doctor, Charles-Gabriel Pravaz, was the instigator in 1851, although Dr Isaac Taylor, practising in America, was introducing drugs into an incision by means of a blunt-nozzled syringe as early as 1839. In 1845, a Dublin practitioner, Dr Francis Rynd, injected drugs with a gravity-fed bottle attached to a hollow needle. It was, however, Dr Alexander Wood of Edinburgh, using a syringe he had ordered from an instrument maker called Ferguson in London, who perfected the hypodermic syringe in 1853. Important modifications on Wood’s design were made by Dr Charles Hunter of St George’s Hospital, London. He became the first advocate of what he termed the ‘ipodermic’ method and widely preached its use in Britain. It caught on. Within two years, it was widely used in Europe and, by 1856, Dr Fordyce Barker was giving the first hypodermic injections in America.
Wood’s technique was to inject his patient’s arm, gaining a rapid effect, an advantage being the avoidance of the unpleasant gastric side-effects of oral administration. However, he and many others made an incorrect assumption: they thought injection, as opposed to ingestion, would not lead to an appetite for the drug – the noun ‘appetite’, meaning a craving or addiction, comes from the belief that one got hungry for the drug just as one did for food, alcohol or anything else which was eaten. Remove the act of swallowing, they reasoned, and hunger would be assuaged. With this belief, Wood injected morphine widely. A good many of Wood’s patients became morphine addicts. Ironically, his wife was to die of an overdose of injected morphine, the first-ever recorded drug death by hypodermic needle.
Morphine injections were used to treat everything from inflammation of the eyes, menstrual pains and rheumatism to delirium tremens. The rapid effect of injected morphine and the invention of early anaesthetics, such as chloroform, also meant surgery was more readily carried out and post-operative pain easily controlled.
The widespread use of the new syringe, allied to the belief injected morphine was not addictive, lead to what became known as ‘morphinism’. Many misguided doctors provided morphine and syringes for those patients rich enough to purchase them and taught them how to self-inject. Typically, morphine addicts were from the middle and upper classes: morphine, precision-made syringes and needles cost money, so most addicts were middle-aged professionals and business people. The poor, who could seldom afford a doctor’s fees, rarely saw morphine. Entire families became addicted because of the ready supply, the lack of legal controls on prescriptions and the fact a prescription, having been paid for, was the rightful property of the patient who could re-use it ad infinitum.
Encouraged by medical conviction that morphine was benign, its use became a casual pastime amongst the well-to-do of Europe and the USA: even when the dangers became apparent, many ignored them, took their daily injections and went about their everyday lives not realising the truth until they were habituated. As with opium, no social stigma was attached to morphinism which it was assumed the addict had acquired through medical treatment.
Another factor causing morphinism was that larger doses were being taken than had been the case with laudanum or opium pills. One ounce of laudanum contained approximately 1 grain of morphine, so even laudanum addicts taking 2 ounces a day were dosing on far less morphine than an injecting addict. Although some kept their daily intake to 6 grains, many took over 10, with some taking up to 40 grains a day, the equivalent of 40 ounces of laudanum. When one considers a very high laudanum dose such as Coleridge’s, of 38 ounces (2 pints) a week, one can see how terrible morphinism was compared to opium addiction.
Morphine’s anodyne properties, however, appeared a godsend in the many wars which raged in the nineteenth century. For the first time, soldiers’ wounds could be treated under anaesthetic and the subsequent pain relieved. As the fighting increased, so did the demand for opium and morphine.
In the American Civil War, poppies were cultivated across both Union and Confederate territories, with Virginia, Tennessee, South Carolina and Georgia being the main growing states. The opium was used to cure the dysentery endemic in bo
th armies, with morphine being refined as a painkiller. A large number of wounded Civil War veterans became morphine addicts as a result: opiate addiction was so common it was known as the ‘army disease’ or ‘Soldier’s Disease’.
Opium was administrated orally to a massive extent in both armies, troops routinely dosed on a daily basis against malaria and diarrhoea. To say administration was casual is an understatement. Union Surgeon Major Nathan Mayer did not even dismount from his horse to dispense opium. He poured out what he termed ‘exact doses’ into his hand and let the recipients lick it from his glove. Morphine injections were also given as syringes became more commonplace. Over ten million opium pills and two million ounces of opiates in powder form and tinctures (mostly morphine) were issued in the army of the Union. One may reasonably assume a similar dosage amongst Confederate troops.
The war had another detrimental effect. More than 63,000 soldiers returned home with lingering gastric upsets for which they continued to take opium: and they brought with them a knowledge of morphine. In his book The Opium Habit, published in 1868, Horace Day wrote:
The events of the last few years [the Civil War] have unquestionably added greatly to [addict] numbers. Maimed and shattered survivors from a hundred battlefields, diseased and disabled soldiers released from hostile prisons, anguished and hopeless wives and mothers, made so by the slaughter of those who were dearest to them, have found, many of them, temporary relief from their suffering in opium.
The American soldier was not unique. British troops in the Crimean War injected morphine to escape the terrible conditions in their camps and, in the Franco-Prussian War, both French and Prussian soldiers drowned their sorrows in not only alcohol but also in morphine.