This past Saturday, physicians and academics from around the world gathered in Germany to mark the bicentennial of a medical breakthrough considered as important as the discovery of ether, X-rays and blood types–although the man who made that breakthrough is far from being a household name.
Freidrich Wilhelm Adam Serturner was a 20-year-old pharmacist’s assistant when he set out to satisfy his curiosity about the medicinal properties of opium, used by physicians for millennia to relieve pain.
With little equipment or formal training, working in his spare time, he succeeded in crystallizing an organic alkaloid compound from the opium poppy’s resinous gum. Not only that, he demonstrated that the compound he had isolated was opium’s active ingredient: opium with the alkaloid removed had no effect on animals, but the alkaloid itself had 10 times the power of processed opium.
His first paper, published in 1805, was ignored. He continued experimenting for another dozen years, doping dogs (and himself, and his friends), and when he published another paper, he gave his compound a catchy name: morphine, after Morpheus, the Greek god of dreams.
This time, the scientific world noticed. Serturner was the first to isolate a plant alkaloid, and his success sparked a new field of chemistry and helped give birth to the modern pharmaceutical industry. Other alkaloids were isolated in quick succession: strychnine in 1817, caffeine in 1820, nicotine in 1828. Had it existed then, Serturner surely would have won a Nobel Prize.
In 1818 a French physician, Francois Magendie, published a pape describing how morphine had relieved the pain of a sick young girl and helped her sleep, and morphine soon became a favored treatment for a host of ailments. Once reliable syringes were developed mid-century, injectable morphine became a standard method of reducing pain during and after surgery. It was widely used during the American Civil War (although perhaps as much for one of its side-effects, severe constipation, as for its pain-relieving capabilities: one of the big killers in Civil War camps was dysentery). It also found its way into numerous patent medicines, like Mrs. Winslow’s Soothing Syrup, which, needless to say, was remarkably effective at quieting teething infants.
Some doctors thought morphine might cure opium addiction, but it soon became apparent morphine itself could be addictive (although it’s not as addictive as people tend to think). In 1874, in one of the most ironic developments in science, C. R. Alder Wright, a chemist at a London hospital, came up with an even more potent narcotic, diacetylmorphine, which he hoped would be a non-addictive alternative to morphine. Bayer began marketing the new drug for pain relief and as a sedative for coughs in 1898–and, since it worked so heroically, they gave it the brand name “Heroin.”
It soon became obvious Wright had not exactly succeeded at his goal. Bayer wisely ended production of heroin in 1913 and concentrated on aspirin instead.
Today, morphine is still the gold standard of pain relief. Like other opiates, it works on the nervous system, inserting molecules of itself like keys into the keyhole-like receptors on the outside of cells in the brain (and elsewhere). The results depend on the receptor, the type of cell, and other variables. Nerve cells, for instance, might fire more quickly–or less quickly. Morphine fits into the same receptors as the body’s own built-in pain-mediation and euphoria-producing substances, such as endorphin, and thus produces the same kind of effects.
However, it also has side-effects–not just the aforementioned constipation, but nausea and itching. The late Leon Goldberg, a University of Chicago pharmacologist, wanted to find a way to end those side-effects for a friend of his who was on morphine (often prescribed to patients with advanced cancer). He modified naltrexone, already known to block morphine, into methylnaltrexone (MNTX). The difference is that MNTX cannot pass through the blood-brain barrier–leaving morphine free to relieve pain, while stopping it from affecting other parts of the body.
MNTX has already undergone clinical testing, and could be on the market for the treatment of opioid-induced constipation within a year or two. Meanwhile, it’s showing promise in alleviating other opiate-induced side-effects, such as post-operative bowel dysfunction (the shutting down of the gastrointestinal tract after surgery, a serious complication), itching and urinary retention.
If morphine’s side-effects can be reduced, then as it enters its third century of use, it may yet live up to the title grandly bestowed upon it by renowned 19th-century Canadian physician Sir William Osler: “God’s own medicine.”
