The Right Chemistry: Cleopatra, cobras and the birth of psychopharmacology
Love can sometimes be deadly. Just ask Cleopatra. Of course you can't, unless you are someone like John Edward or James Van Praagh, psychics who claim to be able to talk to the dead.
The famed Egyptian queen committed suicide in 30 BC after hearing of the death of her great love, the Roman general Mark Antony.
After the assassination of Julius Caesar, with whom Cleopatra had a relationship and a child, she had teamed up with Antony to fight Octavian, Caesar's designated heir, in a battle to see who would rule Rome. Their joint armies were defeated by Octavian, and when Antony heard a false report that Cleopatra had been so devastated by the news that she committed suicide, he decided to follow suit.
When Cleopatra learned of Mark's death, she made up her mind to kill herself, but to do it without suffering. Supposedly, she tested various poisons on condemned prisoners and concluded that the bite of the Egyptian cobra was lethal without inducing spasms of pain. It was also an appropriate way to go, because the snake was an Egyptian symbol of divine royalty. The Egyptian cobra is often referred to as an "asp," an anglicization of "apsis" an ancient term that referred to poisonous snakes found in the Nile region.
The queen had a servant smuggle the snake into the royal chambers in a basket of figs and allowed herself to be bitten on the breast, at least so goes the story. If that's the way it really went down, it was not in a painless fashion. The cobra bite induces tremendous swelling with excruciating pain as the skin stretches uncontrollably. The venom of the cobra has at least three different toxins, all three are proteins that either destroy cells or impair transmission of information from one nerve cell to another. Today antivenoms are available, produced by injecting a non-lethal dose of venom into a horse or sheep and then collecting the animal's blood to isolate the antibodies formed.
Just about the only animal that will tangle with a cobra successfully is the mongoose. This ferret-like animal supposedly prepares for its battle with cobras by dining on Rauvolfia serpentina, commonly known as Indian snakeroot. Legend has it that in India this plant was once used as an antidote for snakebite after people observed that it was a big part of the mongoose's diet. Unfortunately the legend has no basis in fact. Mongooses do suffer bites from snakes, however not often, because the fangs of the cobra may not be able to reach the skin of the animal due to the thick fluffed fur. Furthermore, the mongoose is very quick and is highly skilled at attacking cobras and avoiding their strike. People are not that successful at avoiding bites. About 35,000 to 50,000 people die of snakebite every year in India.
Folkloric accounts often stimulate research to see whether there is any validity to them, and sometimes, of course, there is. Ethanolic extracts of Rauvolfia serpentina do indeed neutralize cobra venom in the test tube, but there is no evidence that consuming the plant has any effect on snakebites. It can, however, have an effect on the mental state of a person. Rauvolfia is traditionally linked with the holy men and mystics of India, including the great spiritual leader Mahatma Gandhi. Such spiritual men have reportedly chewed the root of the plant to help them achieve a mental state of complete philosophical detachment during the meditation process. In Sanskrit, the plant is known as "chandrika," which translates as "moonshine plant" because it was supposed to be a treatment for "moon disease," or mental illness thought to be related to the lunar phases. In this case, there actually is something to the folklore.
Plants contain numerous compounds with potential biological activity, and snakeroot is no exception. Some 50 compounds with such potential have been identified, but the most interesting one is reserpine, first isolated in 1952. It made its mark in medicine mostly through the work of Dr. Nathan S. Kline, (1916–1983), a graduate of the New York University School of Medicine. Kline is the only two-time winner of the Albert Lasker Award for Clinical Medical Research, an award sometimes referred to as "America's Nobel Prize." In 1952, he headed a research unit at Rockland State Hospital, N.Y. (later the Rockland Psychiatric Center) at a time when traditional therapies seemed inadequate to treat the growing number of mentally ill patients.
Kline and his colleagues took the unusual step of investigating reserpine, which was already being used in the United States to treat high blood pressure. He was intrigued by stories from India about the calming effects of snakeroot. Trials with hospitalized patients found that approximately 70 per cent of those suffering from schizophrenia were markedly relieved of their symptoms, earning Kline his first Lasker Award.
Reserpine holds a place in history as "the original tranquilizer," and at one time was the only such medication employed as a calming drug on seriously disturbed psychiatric patients. But reserpine also comes with some undesirable side effects that can include edema and psychological problems like nightmares and despondency, which can give rise to suicidal ideation. It has now been replaced by better drugs.
Encouraged by his success with this tranquilizer, Kline focused his research on drugs with a potential to treat mental illness. In 1964, he earned his second Lasker Award for the study and subsequent introduction of iproniazid, a "monoamine oxidase inhibitor" for the treatment of severe depression. The successful use of drugs for two major categories of psychiatric illness led to the release of thousands who were able to rejoin society. Kline's work has been acknowledged as a major factor in opening a new era in psychiatry, namely psychopharmacology. And it all started with the folklore about the snakeroot plant, the mongoose, and the cobra.
Joe Schwarcz is director of McGill University's Office for Science & Society (mcgill.ca/oss). He hosts The Dr. Joe Show on CJAD Radio 800 AM every Sunday from 3 to 4 p.m.
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