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“At first there is the experimental research“

“At first there is the experimental research“

Foto: Doctor Ulf Glade spoke with Dr. Glade, who works as a certified biologist at the University of Bremen and did his doctorate on the history of anesthesia, about the first medical means for “anesthetizing“ people and about the beginnings of anesthesia. Doctor Glade, all through the history of man and already 150 years ago – the “official discovery of anesthesia“– patients had to be treated for severe injuries. Early anesthetic aids were already known in antiquity. What important methods were incorporated in medical treatments during those times? What did we already know back then?

Ulf Glade: Physicians in the ancient world, in Mesopotamia, Egypt, Greece and Rome were already very capable and able to perform a wide array of surgeries – they already had medical instruments, similar to the ones we use today. Admittedly, we cannot talk about real anesthetic means here. But there were already different substances, mostly plant-based ecstasy drugs that had a calming effect on consciousness. For example, henbane seeds, mandrake and the mandragora potion that’s extracted from it or poppy, meaning opiates were used. Certain alkaloids that have an analgesic effect are referred to as opiates. These substances were usually administered to the patient in a solution. –What happened then was not actual anesthesia in our present day sense, but rather a subduing of the patient, he calmed down and in some instances fell into some type of narcotic sleep. Let’s go one step further. In the Middle Ages there were so-called sleeping sponges. What should we picture here?

Glade: Sleeping sponges were based on similar calming, herbal substances. A sponge that was dipped into warm water beforehand was placed on the patient’s mouth and nose. The sponge was soaked in a liquid that was mainly based on plant compounds like mandrake, henbane or water hemlock. Since the patient inhaled these substances in vapor form, he was said to have fallen into some type of reversible anesthesia. In the early Middle Ages this method was particularly common in the Arabic and European regions. A waking sponge accompanied the sleeping sponge, which allegedly was fennel-based and was used to wake the patient up again. However, that still was not a safe solution. Reports about fatalities, accidents and warnings about the addictive character of this treatment mounted. This probably eventually led to the fact that this type of anesthesia disappeared during the course of the Middle Ages. During the following centuries all books on surgery focused on the awake patient. Apparently early forms of anesthesia were available, but then were abandoned.

Prior to that, ancient writings also always assumed a patient is awake when operated on. In general, suffering pain was considered “natural“ and accepted as inevitable. In earlier times until well into the 19th century, a great surgeon therefore was someone who was able to operate quickly. There are also reports about Dominique Jean Larrey, Napoleon’s personal physician during the Russian Campaign, who was able to amputate an entire leg in several minutes or even seconds. Modern medicine or the modern view of the human body and its functions is introduced in the 19th century. What kinds of anesthetics were used in those beginnings?

Glade: The substances that were used were gaseous anesthetics, ether, chloroform and laughing gas, meaning nitrous oxide. Chloroform was used very often. The use of ether was also very common until well into the 20th century. Nitrous oxide was temporarily not used as often, but is the only original gaseous anesthetic that also is clinically used today.
Later on, around the 30s of the 20th century, liquid, intravenous anesthetics were being used.

At the end of the 19th and the beginning of the 20th century, those were already the anesthetic group of elements that we are still using today. Needless to day they are not the exact same elements, but similar, related substances. From which point onward can we talk about a successful reversible turning off of consciousness in connection with analgesia (indolence)?

Glade: There were several successful attempts in the beginning of the 19th century, but they were forgotten, because they often weren’t presented with a high-publicity effect.

But there is one definite date: On October 16, 1846 William Thomas Green Morton performed the first successful public anesthesia during surgery. For all intents and purposes, this marks the hour of birth of modern anesthesia. From this moment on, there are officially surgeries without pain.

Yet it’s important to differentiate: You can turn off pain with the aid of three methods. You can either administer a pain reliever to the patient who has suffered a fracture or a deep cut. During a physical injury, so-called pain mediators are being released in the human organism, which in turn activate neurons. The “pain” information then is being transmitted. If you block this mechanism via a pain killer, you inhibit pain perception.
Secondly you have local anesthetics, like the ones you get at the dentist for example. Here the transmission of neural impulses of the particularly affected nerves is being blocked out. The result: The pain signal does not reach the brain.

We are talking about anesthesia during a temporary, reversible functional inhibition of the brain, by which a loss of consciousness is produced and thus leads to a turn off of pain perceptions (analgesia). Unlike a person who is asleep, the person who is anesthetized cannot be awakened. In reality we are in pain. For all intents and purposes, all processes of incurring pain, transmission and pain processing take place. This is a proven fact, but we are not conscious of it. Anesthesia is simultaneously also closely tied to amnesia, so that the patient forgets in case he had actually experienced pain after all. Which scientists significantly contributed to the development of surgery with modern anesthesia methods and what anesthetics were being used?

Glade: The anesthetics for instance were chloroform, ether and nitrous oxide. The entire successes in surgery in the following decades, meaning after 1846, were based on anesthesia. Because of the fact that a patient could be anesthetized, even surgeries that took longer could be performed. There are many famous names which contributed to this development – from Lister to Sauerbruch. If we take a look at the origins of anesthesia, two names are important: William Thomas Green Morton and Horace Wells. Wells like Morton was a dentist who happened to see a man who had breathed in nitrous oxide and hit his shinbone, but showed no signs of pain. Wells was so intrigued by this observation that he tried to prove this phenomenon with his assistant. Sedated by laughing gas, his assistant pulled Mr. Well’s tooth. This was the first successful modern anesthesia, though it was not done in public.

Wells wanted to demonstrate this phenomenon in public one year before Morton. Unfortunately there were some adverse conditions due to –among other things- the patient being obese and an alcoholic, and Wells was not successful. During this failed public attempt, William Morton sat in the auditorium and picked up the subject. However, he used ether, which he produced with a friend who was a chemist. Just one year later he performed the first successful public anesthesia.

Foto: Anesthesia bottle
The diversity of theories is primarily due to the fact that there are
many different anesthetics with different chemical structures;
© Müller The history of modern anesthesia is also closely tied to the development of anesthesia theories. After all, one wanted to gain more knowledge about the effectiveness of individual anesthetics. What important results did scientists gather at the end of the 19th and the start of the 20th century?

Glade: This is still a mystery. Thus far there is no generally accepted anesthesia theory. There are several different theories that describe the effects of different anesthetics very well and how they reversibly turn off consciousness. But there are none that actually exactly explain for all anesthetics on how they precisely turn off the critical regions of the brain, thereby causing loss of consciousness.

The feasible scientific insights were of course always dependent on the current medical and scientific level of knowledge. Not until the mid-19th century cell theory, which stated that all living creatures are made up of cells, was introduced. I am thinking for instance about Claude Bernard here, who researched the effects of anesthetics on yeast cells. His first theory was that anesthetics generally are cell poisons. The further natural science advanced and the further the brain was being researched, the more detailed the theories on anesthetics became. The Meyer-Overton Theory developed, which describes that anesthesia is produced by lipid-solvent, i.e. fat-dissolving substances.

According to the theory, the effects of anesthetics are based on them penetrating the cell membranes of nerve cells as a result of their solvent chemical affinity toward fats. The more liposoluble an anesthetic is, the better it works. This is the so-called Lipid Theory at the beginning of the 20th century. However, it does not explain why olive oil for instance, which is particularly liposoluble, does not work as an anesthetic.

And then the synapse, the connection between two neurons, was discovered. This happened in about 1911. The new anesthesia theories focused on the interaction inside the synapse and the linked blockade or activation of neurons.
Currently for about the past 30 years receptors, the docking points for transfer agents between neurons, are better and better researched and understood and are being favored as possible contact points for anesthetics. Several receptors play an essential role in turning off consciousness.

The diversity of theories is primarily due to the fact that there are many different anesthetics with different chemical structures, which cause consciousness to turn off. And of course also the following applies: If you find out how and where anesthetics work, you can then also make the converse argument that these factors play a role in the generation of consciousness. When did we intentionally distinguish between clinical and experimental anesthesia?

Glade: At first there is the experimental research, which continues to further develop today. Already in 1846 the first anesthesia took place in America, one year later it happened in England and in 1847 chloroform was already adopted in medical practices. Actually you can already talk about clinical anesthesiology a mere two years later. Of course there were also attempts to incorporate the theories of anesthesia into medical studies, but that took quite a long time. Yet you can talk about the establishment of the subject quite early on, even if it did not enjoy the official status at that point. From that point on, was there also a lesser risk of dying due to anesthesia during a surgical intervention?

Glade: Apart from anything else, this is also a track record on experience. The more frequently medically experienced people performed anesthesia, the better their experiences were in terms of risks. The progress happened very fast. Nonetheless, there were always accidents that were very much regretted. This caused two different opinions to form among physicians. One side wanted to research the ideal anesthetic, which rendered accidents impossible. The other side believed that the education of physicians which chose to perform anesthesia as a full-time profession, needed to be improved.

It took until the first third of the 20th century until full confidence that is comparable with today’s standard set in, after which there continued to be accidents much like today. When did physicians start to concentrate in one specific field? And since when do we have anesthesiologists as a profession?

Glade: In the 80s of the 19th century there were two names that are synonymous for the specialization as an anesthetist in the medical profession: John Snow and Frederic Hewitt. They were sort of the first anesthesiologists.

The Society of Anesthetists was already founded in 1893 in England, the first professional association of anesthetists. A specialization happened very early on in this case. In Germany the anesthesiologist profession was introduced in 1953 and the same year the German Society of Anesthesiology was founded. Until then, the anesthetist did not have a steady job. There were physicians who specialized in it without have a specialized education in medical studies. This was publically deplored. What did a surgical team at the beginning of the 19th century look like? When did the first “modern surgeries“ take place?

Glade:In essence at that time you already had a fairly mature surgical team, just like we have today. You had the surgeon and the assistant, the nurse and then you had somebody who took care of anesthesia and monitored the patient during the surgery. Relatively quickly checklists were developed, detailing how a person reacted during anesthesia or what type of reflexes failed upon reaching the stage of complete anesthesia during which surgery could be performed. And so we were already able to talk about “modern surgery” at the end of the 19th century. All important basic principles for surgical interventions we also deem important today, anesthesia, the importance of hygiene and antisepsis were already known.

The interview was conducted by Diana Posth

(Translated by Elena O'Meara)


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