Reflections
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Sertürner moved to Einbeck, just north of Göttingen, in1806. It was only in 1817, while there, that he unequivocallyreported the isolation of pure morphine
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. He prepared it byextracting opium with hot water and precipitating morphine with ammonia. He obtained colorless crystals, poorly soluble in water, but soluble in acids and alcohol.In order to establish that his crystals carried thepharmacological activity of raw opium, Sertürner tested themon himself and three boys, “none older than seventeen.” It wasa near-catastrophe. He writes:In order to test my earlier experiments strictly, Iencouraged three persons, none older than seventeen years, to take morphine with me simultaneously. Warned by the previous effects, however, I merelyadministered half a grain dissolved in half a drachmaof alcohol and diluted with several ounces of distilled water.
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This produced a generalized redness of cheeksand eyes [perhaps due to the alcohol] and the vitalfunctions appeared generally enhanced. After half anhour, another half-grain was taken; the condition wasaggravated markedly, while a transient tendency to vomiting and a dull pain in the head with narcosis was felt. After another 15 minutes, we swallowed anotherhalf-grain of morphium, undissolved, as a coarsepowder, with 10 drops of alcohol and a half-ounce of water. The outcome with the three young men wasdecidedly rapid and extreme. It presented as pain in theregion of the stomach, exhaustion, and severe narcosisthat came close to fainting. I also was subject to thesame fate. Being in the supine position, I fell into adream-like state and sensed in the extremities,particularly the arms, a slight twitching whichaccompanied the pulse beats. These distinct symptomsof true intoxication, particularly the frail condition of thethree young men, caused me so much concern that I,half unconscious, drank more than a quarter of a bottle(6 to 8 ounces) of strong vinegar and also had the othersdo the same. This led to such severe vomiting that,several hours later, one who was of a particularlydelicate constitution and whose stomach had alreadybeen emptied completely, found himself in a continuousstate of a most painful and highly alarming retching. Inthis condition, I gave him carbonated magnesia, upon which the vomiting subsided instantly. The night passedunder deep sleep. Although the vomiting recurred in themorning, it immediately subsided after a strong dose of magnesia. Lack of opening of the body, loss of appetite,narcosis, and pain in the head and body disappearedonly after several days. Judging from these highlyunpleasant experiences, I deduce that morphine, evenin small quantities, acts as a strong poison. . . . As noneof the other components of opium possesses effects suchas those described here, the important medicinalproperties of opium probably result from puremorphine, which I have to leave to the physicians to test.In this and other experiments, Sertürner showed that hiscrystalline material had the pharmacological actions of opiumby testing it both on animals and humans. Importantly, he alsodemonstrated that other preparations from opium were devoidof activity. As a consequence of his studies, Sertürner estab-lished the principle that plants contain active substances that,on isolation, carry the therapeutic properties of the plant.Sertürner further concluded that morphine would soon replaceopium. We are left feeling uneasy about the experiment on theteenaged boys. Although scientifically important, theexperiment is ethically dubious. Sertürner was not a physicianand also took part in the experiment, with a near-disastrousloss of judgment as a result. A modern Human SubjectsCommittee would not approve. Indeed, such an experiment today would open the investigator to criminal prosecution. Was Sertürner’s experiment acceptable by 1817standards? There should perhaps have been a physicianpresent who was not an experimental subject. If the experiment was morally or ethically reprehensible, the transgression isinsignificant compared to the slaughters being wrought byNapoleon. One has only to think of the 200 amputationscarried out (without anesthesia) in one day by the French armysurgeon, Larrey, at the battle of Borodino, to place Sertürner’sexperiments in context. However, other experiments on humansin Germany, a century or more in the future, would reach backto shadow reflections on Sertürner’s achievement.Claims of priority in the discovery of morphine have beenmade for two other investigators. Jean-Francois Derosne
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prepared a crude extract of opium (with alcohol and water),and obtained, by potassium carbonate precipitation, what hecalled “sel de Derosne.” Derosne’s alkaloidal fraction lackednarcotic properties, and was probably largely narcotine (alsoknown as noscapine), perhaps with meconic acid, bothabundant in opium. Armand Seguin read a paper to theInstitute of France in 1804, but only published it in 1814
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.He described the isolation of a principle, but did not report anyanimal or human experiments.The relationship between toxicity and therapy was anancient concept. Walter Raleigh wrote, in 1614
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, “Theskillful and learned chemist could draw helpful medicines out of poison, as poison out of the most helpful herbs and plants.”Shakespeare refers to the same principle more poetically in
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In other words, he gave about 32 milligrams of material,comparable to a 60-milligram average oral adult dose of amorphine salt
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.
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