Authors: Martin Booth
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 â 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
âprincipium somniferum',
or sleep-making principle. He named his discovery âmorphium' 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, âI 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. âI flatter myself,' he wrote in 1816, âthat 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 âopened 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 âgossips, charlatans, pharmacists, magnetizers' and âherbalists'. 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 other 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 1â 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 âimmediate, 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 âgiven 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 âipodermic' 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 â the noun âappetite', 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 âmorphinism'. 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 both 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 âarmy disease' or âSoldier'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 âexact 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.
It was not long before case studies were being published about the collapse of morphine addicts' health, far worse than anything engendered by opium. The symptoms were soon recognised: a haggard appearance and emaciation, loss of sexual ability or desire and, as with opium, constipation. Attempts to break habituation led to what were described as severe flu-like symptoms.
Warnings about the power of hypodermically injected morphine started to be published. A British physician, Dr T. Clifford Allbutt, reported in 1870 a lack of caution against morphine by injection, observing there were too many doctors for whom âthe syringe and phial are as constant companions as was the lancet to their fathers.' He went on to comment: