The sufferings of humanity are manifold. Yet, as the saying goes, there’s a remedy for everything (but death). The Pharmacognostic Collection at D-CHAB is filled with such remedies and objects, and each has an intriguing story. One such substance is morphine: a groundbreaking drug that heralded the age of modern pharmacy, finding its way into nurseries and wartime trenches, with profound and lasting consequences.
A groundbreaking discovery
It was certainly an exhilarating moment for the young Friedrich Wilhelm Sertürner when, after passing his examinations in 1803, he began his work as an assistant apothecary in Paderborn, Germany. The small provincial town was hardly a place where one would expect a scientific breakthrough, and yet it was there that Sertürner made a discovery that would help lay the foundations of modern pharmaceutical science.
At the beginning of the 19th century, processes in pharmacy were still interpreted through the lens of alchemy. Apothecaries were craftsmen rather than academics. They sourced their remedies from the mineral, animal, and plant kingdoms, distilling and extracting substances to produce oils, tinctures, and other medicinal preparations. Why these remedies worked, however, was largely unknown. As a result, their effectiveness could not be exactly predicted or controlled. Not even the exotic turtle shells and stuffed crocodiles that were exhibited in many apothecaries, including those in Switzerland, to serve as symbols of broad medical expertise, could disguise this uncertainty.
Apothecaries were eagerly searching for the underlying, quantifiable active ingredients, also in long-established painkillers such as opium, the milky sap of the opium poppy. After all, patients were supposed to drift gently and painlessly into sleep, not accidentally into the afterlife. The prevailing view was that all active substances must be acids, but the attempts to find the active ingredients proved largely unfruitful.
The breakthrough is widely credited to Sertürner. In 1804, working in the relative isolation of Paderborn, he succeeded in isolating the principal active ingredient of opium through a process involving 57 steps. To the surprise of the scientific community, chemically, the substance was not an acid but a base, belonging to what would later become known as the alkaloids, an entirely new class of compounds.
A deadly sleeping draught
To make sure the crystalline substance was indeed what he believed it to be, Sertürner tested its effects on animals, including dogs (one of which died in the process). He later went a step further, experimenting on himself and several friends (which nearly proved fatal as well). Clearly, some fine-tuning was still required – the dose makes the poison – but the active ingredient had been found, marking a scientific milestone, even though widespread recognition of the achievement was still nearly a decade away.
By the middle of the nineteenth century, “morphium” – Sertürner had named it after Morpheus, the god of sleep – was beginning its remarkable rise. Soon studied more thoroughly, the newly renamed morphine found widespread use as a medicine and even made its way into children’s nurseries. This may sound shocking today. At the time, however, opium-based tinctures had long been sold over the counter as universal remedies, including in Switzerland, and soon the catalogue of remedies broadened further, featuring hashish (recommended against corns) and cocaine (marketed for conditions such as toothache and hay fever).
As for morphine, it became fashionable to quiet a fretful or teething child with remedies such as Mrs Winslow’s Soothing Syrup (a mixture of morphine and alcohol). Around 1900, the ETH professor Carl Hartwich remarked with irony in his book on human stimulants that educated Europeans are astonished when told that Chinese parents calmed their children by blowing opium smoke into their faces. Yet, he observed, the poppy-based syrups “with which unscrupulous mothers in our own countries quiet crying children are not a whit better.” Indeed, not every child awoke from that soothing sleep.
The soldier’s disease
At the same time, the invention of the hypodermic syringe by Pravaz and Wood accelerated morphine’s use as a powerful painkiller in the wars of the nineteenth century. For wounded soldiers, it was both a blessing and a curse. While it brought unprecedented relief from pain, many veterans returned home dependent on the drug, victims of what became known as the “soldiers’ disease.”
Just as an opium smoker constantly turns back to the pipe to escape the symptoms of withdrawal, so too does the morphine addict, upon leaving the sanatorium, return to the Pravaz syringe, Hartwich observed. As a pharmaceutical scientist at ETH – yes, pharmacy had established itself as a scientific discipline – Hartwich was deeply engaged in the study of opium at that time and collected various objects, many of which are preserved today in the D-CHAB Pharmacognostic Collection.
Today we know that opioids bind to opioid receptors in the brain, suppressing pain signals, while simultaneously activating the brain’s reward system. The resulting surge of dopamine produces feelings of euphoria. With prolonged use, the brain adapts, creating a craving for the drug and a need for ever higher doses. The consequence can be a devastating and ultimately fatal addiction.
Sertürner’s Legacy
There is a sad irony in the fact that the search for a safe morphine substitute led to the adoption of an opium-derived substance that proved even more addictive: heroin. Introduced by Bayer, the drug was, like morphine before it, marketed with great enthusiasm. Heroin was promoted as a cough suppressant for children, an excellent sedative, and an effective aid for overcoming morphine addiction. The next crisis soon followed. By 1940, Bayer had ceased production.
Opium and heroin have survived into the present day as hard drugs, while morphine and other opium-derived compounds and opioids still rank among the most indispensable and reliable drugs for the treatment of severe pain. Modern medicine also benefits from a vast range of other plant-derived alkaloids. This, too, is part of Sertürner’s legacy: he was the first to unlock an entirely new class of biologically active compounds.
What would Sertürner have thought of all these developments? Perhaps he would simply have observed that his hopes had come true. As he wrote (1806), physicians would no longer have to contend with “uncertainty and approximation” but could rely on remedies whose effects were consistent. He also hoped that “other substances might be separated from various plants, for example the so-called poisonous plants, in which their effects are concentrated.”
Further information
Barop H. (2021): Mohnblumenkriege – Die globale Drogenpolitik der USA 1950 – 1979. Helena Wallstein Verlag. S. 29-30
Brook et al. (2017): The Chemical History of Morphine: An 8000-year Journey, from Resin to de-novo Synthesis. Journal of Anesthesia History, Volume 3, Issue 2. doi.org/10.1016/j.janh.2017.02.001
Hartwich C. (1911): Die menschlichen Genussmittel. Ihre Herkunft, Verbreitung, Geschichte, Anwendung, Bestandteile und Wirkung. Chr. Herm. Tauchnitz. Leipzig. S. 219
John Oxley Library (2016): The Baby Killer – Mrs Winslow’s Soothing Syrup (Patent medicine in Queensland). State Library Queensland. URL: https://www.slq.qld.gov.au/blog/baby-killer-mrs-winslows-soothing-syrup-patent-medicine-queensland
Listos J. et al. (2019): The Mechanisms Involved in Morphine Addiction: An Overview. Int. J. Mol. Sci.20(17), 4302; doi.org/10.3390/ijms20174302
Meyer K. (2004): Dem Morphin auf der Spur. Pharmazeutische Zeitung. URL: https://www.pharmazeutische-zeitung.de/titel-16-2004/
Sertürner F. W. (1806): Darstellung der reinen Mohnsäure (Opiumsäure) nebst einer chemischen Untersuchung des Opiums. Journal der Pharmacie 14. 47-93.
Sertürner F.W. (1817): Ueber das Morphium, eine neue salzfähige Grundlage, und die Mekonsäure, als Hauptbestandteile des Opiums. Annalen der Physik 55: 56-89.
Wetterau J. (2022): 125. Jahrestag: Als Heroin noch ein „heroisches“ Arzneimittel war. Gesellschaft Deutscher Chemiker. URL: https://www.gdch.de/my/article/125-jahrestag-als-heroin-noch-ein-heroisches-arzneimittel-war