Local Anesthesia - Koller's Gift to Mankind


Local anesthetics are among the most widely used medications prescribed and used by many physicians, dentists and non MD personnel worldwide. The story of the discovery of local anesthetics is one of the most fascinating in the history of medicine and it occurred just 126 years ago this year. How did this great advance come about?

Was this discovery just a chance happening or was it just a matter of time before someone added up all of the evidence? We’ll let you decide that. The discovery of general anesthesia is also a very interesting story and there are many similarities to the discovery of both of these great advances in medicine. The story of the discovery of general anesthesia is widely known my many doctors but few are familiar with the details about local anesthesia.
Advances in Medical Science : General Anesthesia
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Robert C. Hinckley's oil painting " The First Operation Under Ether". Francis A. Countway Library of Medicine
General anesthesia was widely used all over the world following Morton’s (1) dramatic public demonstration of etherisation in the Massachusetts General Hospital on October 16th 1846. That great day is now remembered by doctors in many parts of the world and is often referred to as ‘Ether Day’.

The excitement about this great advance in medical science continued for some time until it became evident that the process of inducing unconsciousness was not as simple as it appeared and indeed even young healthy people died from it. The first official anesthetic death was reported in England in 1847. The patient was a young 15 year old girl who presented for removal of an ingrown toe nail. She succumbed quickly to chloroform before the surgeon even started the operation. Hannah Greener (
2) was the name of this young lady.

There were other problems with inhalation anesthesia. The induction process was quite often prolonged and patients remained unconscious for hours afterwards and when they regained consciousness they frequently vomited for hours and sometimes days afterwards. Some operations were not at all suitable for general anesthesia because of the protracted nausea and vomiting postoperatively. Cataract surgery was particularly hazardous under general anesthesia to the extent that many ophthalmologists conducted that operation without any anesthesia at all. Following is a description of cataract surgery before the introduction of local anesthetics:

‘It was like a red-hot needle in yer eye whilst he was doing it. But he wasn’t long about it. Oh no. If he had been long I couldn’t ha’ beared it. He wasn’t a minute more than three quarters of an hour at the outside’- an old man’s description of his cataract operation to Thomas Hardy and his wife on their visit to Dorsetshire in 1882. (Hardy Florence Emily:
Early Life of Thomas Hardy. 1840-1891. NY. MacMillan Co.1928.
An Alternative to General Anesthesia : Incas and Conquistadors
From this information one can readily surmise that there was a great interest in finding an alternative to general anesthesia for some surgeries and particularly ophthalmology. Great efforts were made to relieve mankind’s suffering during these operations including ‘mesmerism’ and hypnosis but most were very unsatisfactory.
Cocaine was used by the Incas long before the conquest of Peru by Pizarro in 1532. The Incas considered cocaine to be a divine gift from Manco Capac. The leaves were used by the ruling chiefs to reward the upper classes for their good work. The Conquistadors changed that ruling at the second Council of Lima in 15693 thereby allowing commoners to use cocaine. Since that time cocaine became a very important part of Spain’s colonial trade. For centuries the indigenous people of the Andes have chewed the leaves of the coca plant mixed with lime. This mixture, referred to as a cucada was well known for its stimulating effects and ability to ward off tiredness and hunger.

Singer and Underwood (
4) published a report in 1962 in which they stated the following: “From early times the natives of Peru knew about the anesthetic qualities of the Coca plant, and they used to chew leaves and allow the saliva to run over part of the body, which had to be cut.”Other reports suggest that shamans used the cocaine in wounds during trephining procedures which were performed up to as recently as the early 1900s.

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Erythroxylum coca, the coca plant, native to north-western South America. Its leaves contain many alkaloids including cocaine.
The chemical nature of cocaine was first studied by Gaedcke in 1855 when he extracted an amorphous substance from the coca shrub which he called an alkaloid and named it erythroxyline. Dr.Sherzer a chemist on board the Austrian ship Novarra brought back some coca shrubs to Europe and his friend Niemann (5) extracted cocaine from the erythroxyline in 1860. Niemann observed that cocaine numbed his tongue.
In 1868 a Peruvian army surgeon named Thomas Moréno y Maiz (
6) published a book describing the effects of cocaine and alluded to the local anesthetic properties of cocaine and perhaps was the first to describe seizures induced by cocaine. He actually conducted animal experiments using cocaine.
In 1879 von Anrep observed that a solution of cocaine injected into the skin caused numbness and he even dropped cocaine into the eye and noted that it dilated the pupil. Despite all the evidence pointing to the local anesthetic effects of cocaine the vital connection was not made for another 5 years very much like the story of general anesthesia.
An Epiphany : Psychoanalysis and Eye Surgery
Koller was very motivated to find a way to anesthetize the eye. Koller and Freud were colleagues. The initial excitement among academics about the pharmacological properties of cocaine was dwindling rapidly. But Freud was still interested in the potential central effects of the drug and encouraged Koller to continue with his experiments. Koller was an ophthalmologist in training. Freud went on leave to Germany for a few months and asked Koller to continue with his experimental work on cocaine. In order to continue Freud’s work Koller needed some cocaine and Freud had left some cocaine for him to experiment with.
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In Koller’s papers (7), discovered after his death, he describes the exact moment when he made the connection that had been so obviously missed by many before him. He describes the occasion as follows: “Upon one occasion another colleague of mine, Dr.Engel, partook of some (cocaine) with me from the point of his penknife and remarked, “How that numbs the tongue.” I said “Yes, that has been noticed by everyone that has eaten it.” And in the moment it flashed upon me that I was carrying in my pocket the local anesthetic for which I had searched some years earlier. I went straight to the laboratory, asked the assistant for a guinea pig for the experiment, made a solution of cocaine from the powder which I carried in my pocketbook, and instilled this into the eye of the animal.’
There was a witness to Koller’s discovery and his name was Dr.Gaertner who was the young assistant in Stricker’s laboratory where Koller worked. Following is Gaertner’s description of what happened that day: One summer day in 1884, Dr.Koller, at that time a very young man, was engaged in a piece of embryological research. He stepped into Professor Strickers laboratory, drew a small flask in which there was a trace of white powder from his pocket, and addressed me, Professor Stricker’s assistant, in approximately the following words:

' "I hope, indeed I expect that this powder will anesthetize the eye" "We’ll find out that right away", I replied. A few grains of the substance were thereupon dissolved in a small quantity of distilled water, a large, lively frog was selected from the aquarium and held immobile in a cloth, and now a drop of the solution was trickled into one of the protruding eyes. At intervals of a few seconds the reflex of the cornea was tested by touching the eye with a needle…After about a minute came the great historic moment, I do not hesitate to designate it as such. The frog permitted his cornea to be touched and even injured without a trace of reflex action or attempt to protect himself- whereas the other eye responded with the usual reflex action to the slightest touch'.

With the greatest, and surely considering its implications , most justifiable excitement the experiment continued. The same tests were performed on a rabbit and a dog with equally good results.
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Vienna General Hospital, where Koller and Freud were contemporaries in in the early 1880's
‘Now it was necessary to go one step further and to repeat the experiment upon a human being. We trickled the solution under the upraised lids of each other’s eyes. Then we put a mirror before us, took a pin in hand, and tried to touch the cornea with its head. Almost simultaneously we could joyously assure ourselves, “I can’t feel a thing”. We could make a dent in the cornea without the slightest awareness of the touch, let alone any unpleasant sensation or reaction. With that the discovery of local anesthesia was completed. I rejoice that I was the first to congratulate Dr.Koller as a benefactor of mankind’ (8)

Koller was just 25 years of age when he made this discovery. He immigrated to the United States in 1888 on the ship SS Saale and worked as an ophthalmologist in private practice in New York until his death in 1944.
Written by Brendan T. Finucane MB, Professor Emeritus, University of Alberta , Edmonton.
References
1. Morton WTG Remarks on the Proper Mode of Administering Sulphuric Ether By Inhalation. Boston, Dalton & Wentworth, Printers, 1847. 44pp.

2. Meggison TN Death from Chloroform (Letter). London Medical Gazette 1848; 6: 255-6

3. Vandam LD: Some aspects of the history of local anesthesia. Handbook of Clin. Pharmacol 81:1-19, 1987

4. Musto DF: Opium, cocaine and marijuana in American History, Scientific American July 1991 pp 40-47

5. Koller C
History of cocaine as a local anesthetic, JAMA 117: 1284, 1941

6. Von Oettingen WF
: The earliest suggestion of the use of cocaine for local anesthesia. Ann Med Hist (NS)5: 275-280, 1933

7. Hortense Koller Becker- Carl Koller and Cocaine. The Psychoanalytical Quarterly
Vol xxx11: 309-373,1963

8. Gaertner J Die Entdeckung der Lokalandasthesie.
Vienna: Der Neue Tag 1919 (Also in Neue Freie Presse under Unterhaltung und Wissen, 1919)