Montreal Gazette


Anesthesio­logist changed surgeries with curare

- JOE SCHWARCZ The Right Chemistry

The history of surgery is often divided into an era described as “before Griffith” and one as “after Griffith” based on Dr. Harold Griffith's introducti­on of curare in 1942 as a muscle relaxant in surgery. This solved a problem that had plagued surgeons since the discovery of anesthesia 100 years earlier.

The dose of ether, cyclopropa­ne or chloroform that rendered a patient unconsciou­s had little effect on the autonomic nervous system, which meant that when an incision was made, muscles would twitch and even go into spasm, creating difficulti­es for the surgeon. Use of a higher dose of anesthetic was a workaround, but that had problems of its own. Sometimes the patient wouldn't wake up.

Working as an anesthesio­logist at Montreal's Homeopathi­c Hospital, Griffith was aware of curare's recent introducti­on as a treatment for the seizures that were a side-effect of the drug Metrazol used to treat depression.

Curare controlled seizures by impairing muscular activity but notably had no effect on the heart. Lewis Wright, a physician at the Squibb pharmaceut­ical company in charge of marketing curare as Intocostri­n for seizures, suggested to Griffith that the drug could be useful as a muscle relaxant in surgery.

Griffith administer­ed curare without first doing any animal experiment­s or seeking permission from an ethics committee. It is a different world today and a surgeon could not introduce a drug on a whim. However, it should be mentioned that Griffith was aware that an antidote for curare overdose was available and he had it on hand should it be needed.

Physostigm­ine, isolated from the Calabar bean, had been found by Austrian physiologi­st Jacob Pal to counter the effects of curare, though its mechanism of action was not known. That was only discovered after English pharmacolo­gist Sir Henry Dale determined that curare produces paralysis by blocking the receptor on nerve cells for acetylchol­ine, the neurotrans­mitter needed for muscular activity. It is this activity that physostigm­ine counters by inactivati­ng acetylchol­inesterase, the enzyme that normally breaks down acetylchol­ine. As a result, the concentrat­ion of acetylchol­ine is increased and it displaces curare from the receptor.

Once the molecular structure of curare's active ingredient, tubocurari­ne, was determined in 1948, chemists were able to produce a number of analogs that performed better and eventually replaced tubocurari­ne.

Griffith was a Mcgill University graduate in medicine and had spent a year at the Hahnemann Homeopathi­c College in Philadelph­ia. Whether he ever practised homoeopath­y isn't clear, but certainly his position as an anesthesio­logist did not involve the use of non-existent molecules, the hallmark of homoeopath­y. The name Homeopathi­c Hospital was also a curiosity since it actually functioned as a regular hospital. Perhaps some homeopathi­c remedies were used, but certainly not in surgical cases.

The path of curare from the jungles of South America to the operating room is a fascinatin­g one.

As early as 1516, Europeans learned about the use of poisoned arrows by South American natives from the writings of Peter Martyr d'anghiera, an Italian who chronicled stories he had heard from travellers to the New World. He described how the Spanish Conquistad­ores had been attacked with poison arrows and gave a fanciful, but fabricated account of the preparatio­n of the poison from plants by women and the determinat­ion of its potency by how many of the women were found “half dead” from the toxic vapours.

In 1745, French explorer Charles Marie de La Condamine brought the first sample of curare back to Europe after seeing natives hunt small animals using a blowpipe and poisoned darts. He gave some of the poison to physicians at Leiden University in the Netherland­s who injected it into a cat and found that it produced paralysis. British naturalist Charles Waterton had also encountere­d curare on his South American travels, and in 1825, together with surgeon Benjamin Brodie, performed a classic experiment that actually laid the foundation for the use of curare in surgery.

Brodie and Waterton injected a female donkey with curare whereupon it quickly stopped breathing and collapsed as its respirator­y muscles became paralyzed. The animal's heart, however, kept beating. At this point, Brodie made an incision in the windpipe and used bellows to pump air into the animal's lungs. He kept this up for two hours, when much to his surprise the donkey raised its head and proceeded to get up, apparently none the worse for wear.

The experiment had demonstrat­ed that at a sublethal dose, curare was capable of producing paralysis that lasted until the effect of the drug wore off. Clearly, curare had therapeuti­c potential, but further experiment­s were hampered by the scarcity of the drug.

That problem wasn't solved until American Richard Gill found a job as a salesman for a rubber company that led to his settling in Ecuador where he learned about curare from the native tribesmen he befriended. Unfortunat­ely, a fall from a horse left him partially paralyzed, suffering from painful bouts of muscle spasms. When he returned to the U.S., his physician, Walter Freeman, mentioned that muscle spasms were amenable to treatment with curare. This was the same Freeman who would become infamous for introducin­g the “ice pick lobotomy” to treat mental illness, a procedure he performed on President John F. Kennedy's sister Rosemary with frightful consequenc­es.

Motivated to gather a sufficient quantity of curare, Gill returned to Ecuador and put together an expedition to seek out the plants from which curare could be extracted. After five months in the jungle and watching natives prepare the arrow poison, he returned with 12 kilograms of crude curare.

Curiously, there is no historical record of Gill using curare to treat himself, but Nebraskan psychiatri­st Abram Bennett heard about Gill's exploits from Freeman and contacted him for a sample. He had in mind to mitigate the side-effects of Metrazol that he had been prescribin­g. When this was successful, the Squibb pharmaceut­ical company bought all of Gill's curare, and Horace Holaday, one of its chemists, found a way to produce a standardiz­ed version that was then marketed as Intocostri­n, the drug that Griffith used. He reported that “within one minute it made the abdomen as soft as dough.”

The rest, as they say, is history.

Joe Schwarcz ( is director of Mcgill University's Office for Science & Society ( He hosts The Dr. Joe Show on CJAD Radio 800 AM every Sunday from 3 to 4 p.m.

 ?? JOHN MAHONEY ?? Dr. Harold Griffith was a Mcgill University graduate in medicine who introduced curare in 1942 as a muscle relaxant in surgery while working as an anesthesio­logist at Montreal's Homeopathi­c Hospital. Curare produces paralysis by blocking the receptors on nerve cells for acetylchol­ine.
JOHN MAHONEY Dr. Harold Griffith was a Mcgill University graduate in medicine who introduced curare in 1942 as a muscle relaxant in surgery while working as an anesthesio­logist at Montreal's Homeopathi­c Hospital. Curare produces paralysis by blocking the receptors on nerve cells for acetylchol­ine.
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