The ABCs of Anaesthetic History – Alcohol, Beer and Cocktails

Louis Pasteur. Etching by L. Orr after A. G. A. Edelfelt, 1885 
©https://wellcomecollection.org 

Alcohol and humanity have shared an interwoven relationship throughout history. Since prehistoric times, alcohol has played a significant role in human civilisation, and its importance has been noted in several ancient texts including the Christian Bible, on medical papyri of the Egyptians, and even on clay tablet prescriptions of Sumerian physicians [1]. The influence of alcohol has been observed in several aspects of civilisation - socially, politically, and scientifically. In ancient Egypt the pyramid-builders received their payment in the form of beer and bread [1]. Rum was at the centre of the triangular trade between New England, Africa, and Europe and would act as the kindling that sparked the American Revolution of 1775 in the United States [2]. Within the scientific community alcohol has played a momentous role in numerous discoveries, however its role in the implementation of anaesthesia in modern medicine has been somewhat lost to history.

Prior to its use in anaesthesia, alcohol had been the subject of interest of French biologist, microbiologist, and chemist Louis Pasteur (1822-1895). Pasteur had been asked by Mr Georges Bigot for help with his souring beetroot alcohol. Pasteur determined that the souring was the result of lactic acid production and that microscopic cells of fermenting yeast were the culprits. He extended his studies and discovered that microorganisms in the air were responsible for soured beer, wine, and milk. Pasteur found that by heating these substances the felonious microorganisms could be destroyed and the product sterilised – thus the advent of Pasteurisation [3]. This concept of microscopic life contaminating wine led to his proposition that other microorganisms could manifest in disease. This ideology, later known as Germ Theory, inspired the esteemed British surgeon Joseph Lister (1827-1912), who became a strong advocate for asepsis in surgery and his novel approach resulted in a substantial decline in post-operative infection and deaths [4]. The brewing industry itself would help advance scientific understanding with the development of the infamous student’s t-test - a revolutionary statistical tool that will be familiar to most Anaesthetists. Its origin is also steeped in alcohol. Student’s t-test was developed by William Sealy Gosset (1876-1937) who spent his career working for the Guinness brewery in Dublin. Gosset was tasked with improving the brewing process, and during his time at Guinness, he developed his test to assess the quality of stout using only small sample sizes. He published his theory in the journal Biometrika under the pseudonym of “Student” – the source of the test’s name [5]. There are numerous other discoveries where alcohol has had an influential factor, and anaesthesia is no exception, alcohol has helped to shape the science and practice of anaesthesia.

Carlsberg don’t make blood gas analysers, but if they did… - blood gas analysis

In 1952, Copenhagen was in the midst of the polio epidemic which had a devastating effect on its population with over 300 people requiring artificial ventilation. This massive ventilation effort was led by Dr Bjørn Ibsen who was the first to suggest the use of positive pressure ventilation. Ibsen is seen by many as the father of intensive care medicine. He utilised medical and dental students to continuously hand ventilate patients day and night – at the peak, about 450 students. He identified that patients had died from an excess of blood CO₂ secondary to inadequate ventilation and used pH and pCO₂ analysis to guide ventilation. During this epidemic, medical devices which provided accurate blood gas analysis of pH, pCO₂ and pO₂ were urgently required to help guide clinicians. The development of such instruments began in Copenhagen with the beer brewing company Carlsberg [6]. Søren Sørensen (1868-1939) was a chemist who worked for the Carlsberg Laboratory. Like Gosset at Guinness, Sørensen was employed to apply a scientific method to the beer industry to advance biochemical knowledge related to brewing.

Building on the work of physical chemists from the previous century he developed the pH scale in 1909 – an easier way to visualise the concentration of hydrogen ions in solution [7]. His use of the pH scale was employed to improve the quality of Carlsberg beer, but this development would have benefits beyond brewing. Gotfred Haugaard (1894-1969) was another employee of the Carlsberg’s lab and assistant to Sørensen. In 1937 he approached the technology company Radiometer A/S and requested support in producing a device that could measure the pH of liquids. Radiometer built on the work of Max Cremer (1865-1935) who in 1906 discovered that glass electrodes could produce an electrical potential that was proportional to the concentration of hydrogen ions in solution [8]. Their result was the production of the Radiometer pH meter [9] and in the initial 1952 polio epidemic of Copenhagen, their pH meter was used alongside the cumbersome and time-consuming technique of Van Slyke pCO₂ measurements to successfully guide treatment of patients [10].

Richard Stow of Columbus, Ohio was also struggling to care for polio patients at the same time and developed a pCO₂ electrode based on the pH electrode. He was able to measure pCO₂ but had difficulty in stabilising his results. He was approached by John Severinghaus (b. 1922) who was able to stabilise the electrode by modifying a glass pH electrode and surrounding it in sodium bicarbonate (NaHCO₃). This modification not only stabilised the electrode but doubled its sensitivity and allowed for rapid analysis [9]. The Clark pO₂ electrode was developed by Leland Clark (1918-2005) in 1954 and it was combined with the pH and pCO₂ electrode by Severinghaus and his technician Freeman Bradley to develop the first three-function blood gas analyser in 1959 [9]. These devices helped to revolutionise clinical medicine and were commercially produced by separate companies in California, Massachusetts and in Copenhagen by Radiometer, who supplied the original Radiometer pH meter to Dr Ibsen in 1952 [9].

And so, the story had come full circle. It started with the Danish brewing company Carlsberg and their scientific approach to the beer brewing business that led to Sørensen’s development of the pH scale. Radiometer A/S, another Danish company, would develop the electronic pH meter for Carlsberg lab which would be utilised during the Copenhagen polio pandemic. Severinghaus would combine his and others’ technology to create the first blood gas analyser that would be built by a Danish company and used by Danish doctors to treat polio patients in a brand-new field of medicine – Intensive Care Medicine.

Inhaled anaesthetic agents

Prior to the popular use of inhaled anaesthesia, surgery was a terrifying ordeal of pain and suffering, although some relief could be found with the anaesthetics of antiquity. The Egyptians would compress the carotids to induce a loss of consciousness and, while seemingly primitive, the use of physical methods was continually employed into the 18th Century with the surgeon James Moore (1763-1834) using the compression of nerves to induce peripheral anaesthesia of limbs. Natural products such as the milk of the poppy, the mandrake plant, cannabis leaves, and even alcohol itself, were heavily exploited for their pharmacological properties and often mixed with wines as tinctures or soporific sponge to induce inebriation or sleep [11]. Psychotherapy in the form of mesmerism was also used to induce a hypnotic state in patient to help them deal with their pain [12]. While these methods may have helped provide pain relief, they were unpredictable, unreliable, and risked endangering patients’ lives.

By the mid-19th century, the dawn of modern anaesthesia, had replaced many of these traditional concoctions, and patients could have procedures performed painlessly and somewhat safely. The deep anaesthesia provided permitted surgeons to operate beyond surface-level procedures and enabled the advancement of complex surgical techniques. The discovery of these inhaled anaesthetic agents had been the result of incremental information gathering from many individuals and their origin can be traced by the guiding hand of alcohol.

From the bubbling of beer – nitrous oxide

Joseph Priestley (1733-1804) was an accomplished chemist, natural philosopher, theologian, and educator [13]. The “airs” that he discovered (which included oxygen, nitrous oxide and other gases) would become a cornerstone of modern anaesthesia. In 1767 Priestley was working as a minister in Leeds, and it was a nearby brewery that would spark his lifelong affair with “airs”. The local brewery provided Priestley with a plentiful supply of bubbling fermenting gases to experiment with. He called these gases “fixed air” - which would come to be known as carbon dioxide (CO₂). In his experiments he combined these fermenting gases with water and developed the process of carbonation. This led to his subsequent publication in 1772 of “Impregnating Water with Fixed Air” [14]. He furthered his experiments on airs in 1774 by heating mercuric oxide (HgO) with a burning lens and found the air emitted was “five or six times as good as common air”. He called this “dephlogisticated air” - what was later characterised by Antoine Lavoisier (1743-1794) as oxygen (O₂). In the years following, he continued experimenting and produced, characterised, and identified gases including sulphur dioxide (SO₂), nitric oxide (NO), ammonia (NH₃) and, of particular relevance to anaesthesia, nitrous oxide (N₂O) [15].

In the late 18th century, at the age of 19, Humphry Davy (1778-1829) was appointed as superintendent of the Pneumatic Institute in Bristol – a society that was established to study the medical potential of gases. Davy began self-experimenting with Priestley’s nitrous oxide alongside friends and colleagues at parties. Davy coined the well-known term of “laughing gas” because of these parties. These celebrations were reserved for the elite of society and included many doctors and medical students. Davy published his findings in 1800 with “Researches, Chemical and Philosophical, chiefly concerning Nitrous Oxide, or Dephlogisticated Nitrous Air, and its Respiration”. This work however only briefly mentioned the possible benefit of using nitrous oxide in surgery, and it would be another 44 years, before nitrous oxide would be used in dental surgery by the dentist Horace Wells in Hartford, Connecticut [16][17].

The use of nitrous oxide alongside alcohol became very fashionable because of its euphoric effects and relaxant properties. Tickets were sold for individuals to attend demonstrations and exhibitions of nitrous oxide at “laughing gas” parties. Dr Horace Wells (1815-1848) attended one of these exhibitions held by Dr Gardner Colton - whose sole occupation had become “laughing gas” demonstrator. During this performance, Wells witnessed a friend, Sam Cooley, inhale nitrous oxide and injure his leg without experiencing any pain. This act inspired Wells to use nitrous oxide at his dental practice and he invited Colton to his surgery the next morning. Colton administered nitrous oxide to Wells and, Dr John Riggs (a colleague and student of Wells) extracted a molar from Wells’ jaw painlessly [18]. Recent evidence from letter correspondence between Wells’ and his wife suggests that he may have even encountered and used nitrous oxide prior to Colton’s visit [19].

Following this initial success and after a month and a half of experimentation, Wells sought permission to publicly trial his form of anaesthesia in 1845 in Boston, Massachusetts. Wells administered his anaesthetic to a patient using unfamiliar equipment and as a consequence it is likely an inadequate dose was delivered. Unfortunately, the patient let out a scream of pain during their tooth extraction. Wells, humiliated and defeated, was booed and jeered from the operating theatre and left the hospital ashamed. He never returned to experimenting with nitrous oxide and its brief use as a general anaesthetic was largely abandoned owing to the discovery of ether the following year [18]. The 1870s saw a revival in its use and its popularity grew and remained the mainstay of dental anaesthesia until the 1960s. It also found its place as an effective obstetric analgesic in the 1930s [16].

And so, it was Priestley’s fascination with the fermenting “airs” from a nearby brewery that lead to his discovery of nitrous oxide, oxygen and other gases. Despite Wells’ unsuccessful demonstration of nitrous oxide, this once recreational gas became one of the most commonly used anaesthetic agents today. Nitrous oxide has helped countless women through childbirth, provided a coping strategy for pain control and provided pain relief for those in the dental chair.

A controversial cocktail – ether

Ether is an anaesthetic agent whose historical use has been shrouded in controversy and personality clashes. In 1540 German physician and botanist, Valerius Cordus, discovered ether after distilling it from sulphuric acid and wine. Cordus referred to it as his “sweet oil of vitriol” and its instructions for preparation are comparable to a modern cocktail recipe:

“Take six ounces of strong, very biting, thrice purified wine, and the same quantity of sour oil of vitriol. Mix in a Venetian glass, and place in a small gourd with a narrow mouth, and seal the mouth with clay. Set aside thus for a whole month, or two.”[20]

This “cocktail” would later become known as “ether” by August Siegmund Frobenius whilst presenting the substance to the Royal Society in February 1730, however, it was not until the early 19th century that medicinal use of ether was exploited [20]. After Davy’s writings on nitrous oxide in 1800, Michael Faraday (1791-1867) drew a comparison to the effects of ether, which had become popular for its intoxicating effects. In a similar fashion to nitrous oxide, the early use of ether was limited to its recreational use in “ether frolics”, which proved popular in the United States and would set the scene for early ether enthusiasts [21]. Travelling lecturers would invite volunteers from the audience to come on stage and inhale the ether; amusing the spectators as they witnessed semi-conscious antics on stage. In Ireland, during the temperance movement of the 1800s, ether served as a substitute for alcohol - it produced similar inebriating effects, left little hangover, and fulfilled their temperance pledge. This caused particular problems in the North of Ireland and eventually led to banning its recreational use 1891 after it was branded a poison [22].

While the first use of ether as an anaesthetic agent has been classically attributed to William TG Morton (1819-1868) in 1846, there were others in the United States who used ether before him including William Clarke and Crawford Long [23]. William Clarke (1819-1898) was a keen recreational user of ether and would be the first to use ether as a form of dental anaesthesia whilst a student at Vermont Medical College. Clarke successfully administered ether to a young lady in Rochester, New York for painless dental extraction, but his Professor was sceptical and convinced Clarke that her hysterical reaction to pain was the cause for her unconscious state, not the ether, and so Clarke abandoned any further use [23]. Crawford Long (1815-1878) was the next to investigate the potential of ether as surgical anaesthesia and in 1842 in rural Jefferson, Georgia, he was able to painlessly remove two small tumours from the neck of a patient. He continued to use this method on his patients, but his results were not published until 1849 [23] and it would be Morton who was credited for the introduction of ether anaesthesia.

Morton was a man full of confidence and it was this confidence that helped him to promote his method of ether administration. Morton had a meandering start to his life. He had tried his hands at a business in Baltimore, fraudulently obtaining goods on forged letters of recommendation and eventually joined the Baltimore College of Dentistry but left without a diploma. Morton had been a student of the previously humiliated Dr Wells in advanced techniques of prosthetic dentistry, and later they would become colleagues with a joint business in Boston. It was during this short-lived business venture that Morton was introduced to Charles Jackson (1805-1880). Acting on Jackson’s advice, Morton practised and honed the technique of his new ether anaesthetic on several patients in private. Eventually, Morton demonstrated this new technique publicly in Boston. It was on 16 October 1846 in the Massachusetts General Hospital that Morton provided ether vapour via an inhaler of his own design to Gilbert Abbott. Abbott was able to have a tumour removed from the angle of his jaw without pain, distress or screams of agony [24][25] - Morton was successful! News of his accomplishment quickly spread across the United States and eventually arrived at Great Britain in December 1846. The first UK ether anaesthetics were given in private in Dumfries and London on 19 December 1846 [26] and the first public demonstrations of ether anaesthesia was undertaken in University College Hospital, London on 21 December 1846, when the surgeon Robert Liston famously exclaimed “This Yankee dodge beats mesmerism hollow” [25].

Knowing the impact of his demonstration, Morton tried to do what no other physicians of the era had attempted before - patent his anaesthetic. He tried to mask his anaesthetic by mixing the ether with orange oil and marketed it as “Letheon”. However, the smell of ether was instantly recognised, and his illusion did not last. His colleagues and previous teachers Wells and Jackson did not take kindly to his claim and fame. Wells claimed that he had been the true pioneer of inhaled anaesthesia with his use of nitrous oxide and Jackson claimed that it was he who provided Morton with the idea that ether would provide superior anaesthesia compared to nitrous oxide. Alongside the rural Georgian practitioner Crawford Long, they disputed his “discovery”. William Clarke did not join in with the emerging disagreement and never lay his own claim to the discovery. In an attempt to gain monetary profit from his popularisation of ether, Morton petitioned Congress to award him for his discovery. He received little financial gain and was instead rewarded with praise, medals and even received an honorary MD from Baltimore in 1852 [24].

The fate of Wells, Jackson, and Long were not as glorious or bountiful. Wells, frustrated by the lack of recognition, travelled to France to seek support and on his return home, his life took an unfortunate downward spiral. He returned to the United States and moved to New York where he began to abuse ether and chloroform. He was eventually arrested and imprisoned after throwing sulphuric acid over two prostitutes. He convinced the prison officer to allow him to leave to collect personal belongings and used this an opportunity to dose himself with chloroform and sadly ended his life by lacerating his femoral artery [27]. Jackson spent his days fighting against Morton for the credit behind the discovery of ether. His efforts made their way to the US Congress and the courts, but interest waned with the ongoing struggle of the American civil war, and no recognition was given. Years later, whilst visiting a cemetery in Cambridge, Massachusetts, Jackson overheard mention that the discoverer of anaesthesia, WTG Morton, was buried in that Cemetery. This sent Jackson in a fit of rage and a neuropsychiatric disability of which he would never recover, he eventually died in August 1880 in the McLean Institute of the Insane in Massachusetts [27]. Long was the least affected by this controversy. He spent some time arguing his case but eventually returned to his practice in rural Georgia and died of a stroke in June 1878 shortly after providing ether anaesthesia to a labouring patient [27]. In the following years, the use of ether would dwindle with the discovery of chloroform’s anaesthetics properties.

Guthrie’s sweet whiskey – chloroform

The synthesis of chloroform occurred independently and simultaneously around 1831 in America, France, and Germany by Samuel Guthrie (1782-1848), Eugène Soubeiran (1797-1859) and Justus von Liebig (1803-1873) respectively. The method for the synthesis of ether included alcohol and a form of chloride. In Guthrie’s case, this was mixing whiskey with chloride of lime to create what was known as Guthrie’s Sweet Whiskey [28]. His recipe was:

“Into a clean copper still, put three pounds of chloride of lime and two gallons of well flavoured alcohol of sp. Gr. .844 and distil. Watch the process and when the product ceases to come highly sweet and aromatic, remove and cork it up closely in glass vessels.” [28]

Chloroform would not be availed as an anaesthetic agent until 1847 when it came into the hands of Dr James Young Simpson (1811-1870). Simpson was an extremely gifted individual, having graduated from medicine at the University of Edinburgh at just 21 years old, he specialised in obstetrics and became Professor of midwifery in 1840 at the age of 28 [29]. Simpson observed Robert Liston perform surgery under ether anaesthesia, and this inspired him to administer his first ether anaesthetic in January 1847 to a labouring woman against both the religious and medical doctrine of his time. However, he noted that ether had its limitations as it required large doses during labour, had a slow onset, and increased patient produced secretions. He needed a better anaesthetic and would find his solution in Guthrie’s Sweet Whiskey – chloroform [29][30].

His search for an ideal anaesthetic agent took place not on the laboratory bench but at the dinner table with colleagues. Simpson opened his home to friends and colleagues for dinner and, according to his daughter Eve Simpson, held regular “anaesthetic séances” [31]. Dr George Keith and Dr Mathews Duncan would partake in these dinner party experiments and would be presented with tumblers, glasses, and saucers each filled with untested narcotics. It was on the fateful evening of 4 November 1847, after several unsuccessful brews were tried, that Simpson presented the men with chloroform from a brandy decanter hidden under heaps of wastepaper. After their tumblers were filled, the liquid’s vapours were deeply inhaled, and each man fell into a deep sleep. The party members awoke on the floor “under the mahogany” [31]. It was clear to Simpson that he found his answer and four days later he successfully put the concoction to use. He quickly published his results on 20 November 1847. He continued to be a strong proponent for chloroform, but his main interest lay with midwifery and obstetrics [30]. The individual who would bring chloroform to the fore and become the first anaesthetic specialist was Dr John Snow.

John Snow (1813-1858) practiced as a surgeon and general practitioner in Soho, London before focusing on anaesthesia. While Snow is best known for his epidemiological work in mapping the outbreak of cholera in London, his contribution to anaesthesia is equally remarkable. Snow had a keen interest in respiration and gas chemistry and the advent of ether anaesthesia allowed him to combine these interests with his clinical work. Those before Snow had practised anaesthesia as an art and Snow would bring a quantitative and scientific approach to the new speciality [32][33]. Snow would grow to become an expert in the delivery of anaesthesia and would be the first doctor to specialise as an anaesthetist with more than 5000 procedures in 12 years of practice working alongside surgeons such as Robert Liston. In 1847 he published “On the Inhalation of Ether”, a guide to administering ether and designed an inhaler in 1847 that would allow for the accurate and controlled delivery of ether whilst accounting for temperature fluctuations [32].

The death of 15-year-old Hannah Greener in 1848 and the subsequent deaths of others, were all attributed to chloroform toxicity. It prompted a necessity to quantify its dosing, and Snow in his usual scientific approach recommended that the administration of vapours needed to be accurately delivered via engineered vaporizers [32]. Snow always sought to improve his practice through true scientific approach by experimentation and keeping detailed notes on his patients. His attention to detail would elevate him in medical circles to be seen as a true expert in anaesthesia. His expertise would be called upon in 1853 to provide chloroform anaesthesia to Queen Victoria to aid her in the delivery of her eight child, Prince Leopold [34]. It has been widely believed that this royal treatment was the catalyst to the change in public perception towards obstetric analgesia but it is more likely that it was the careful and meticulous approach of Snow combined with his clinical skills that converted his professional colleagues rather than a sway in public opinion [35]. Snow would go on to establish his epidemiological work, before his sadly premature death at the age of 45 following a stroke [34].

If it’s good enough for the pope… - cocaine

The stimulant effects of coca leaves were long understood by the ancient Incan people thousands of years before the Spanish arrival in South America. For the Andean people it had two uses - firstly, as a cultural symbol reserved for the societal elite and secondly for its medicinal properties, providing pain relief when chewed, used for gastrointestinal upset as a tea, and as a stimulant for work. Europeans were introduced to the coca leaf with the arrival of the Spanish to South America in the 16th century[36]. The first mention of its local anaesthetic benefits was from a Spanish Jesuit missionary Bernabé Cobo (1582-1657) who was persuaded to chew on coca leaves to successfully alleviate his toothache instead of extracting the healthy tooth [37]. Coca leaves were mixed with chalk or shell ash and chewed [36], but the actual amount of cocaine extracted from chewing coca leaves was about 0.5% - this “dose” was not overly potent but was released gradually. The recognised medical benefits of coca leaves and its potential commercial applications led to an increased appreciation of the leaves and there was a desire to extract the active component and refine it [36].

With the use of ethanol as an extraction solvent, the tropane alkaloid, cocaine can be successfully extracted from raw coca leaves. The compound was first isolated in 1855 by Friedrich Gaedcke (1828-1890) terming it “erythroxyline”. This compound would later be purified by Albert Niemann (1834-1861) in 1860 and he published his findings in his PhD dissertation “Über eine neue organische Base in den Cocablättern” and called the substance “cocaine” [36][38]. Unfortunately, Niemann would die the following year from lung injuries that he likely sustained from his experimentation with mustard gas. A commonality for anaesthetic agents is that their medical applications are not initially recognised, and cocaine was no exception to this. The main use of cocaine until this point was as a stimulant and in the form of the popular tincture – Coca wine.

Angelo Mariani (1838-1914), a Corsican, was the world’s first cocaine millionaire with his coca wine. He came from a long line of doctors and chemists and was a habitual user of coca - convinced of its potential health benefits. Mariani found that the most bitter leaves were the most potent and would mix them with Bordeaux wine to improve their taste. Mixing the leaves with wine furthered the ethanol extraction of the active alkaloid cocaine creating a more potent solution! [38] His “Vin Mariani” was sold all over the world and received endorsements from world figures such as Pope Leo XIII, Queen Victoria, and even Thomas Edison. Mariani even supplied the coca in the form of lozenges, pastilles, and tea. Medical professionals would recommend its use for depression, digestive disorders, alcoholism, and Sigmund Freud would prescribe it as a cure for opium addiction [36].

Sigmund Freud (1856-1939), a recent Vienna graduate, experimented with coca on himself as a means to alleviate his opium addiction. He found the results to be so effective that he prescribed it liberally to himself and his patients and in 1884 published his paper “Über Coca” in which he recommended its use for opium addiction, headaches, and fatigue [39]. He noted the numbing effects on his tongue but did not utilise these anaesthetic effects himself and instead suggested its use to his colleague and friend Karl Koller (1857-1944). Encouraged by Freud, Koller experimented on animals, then on himself, and eventually performed his first surgery with cocaine as a local anaesthetic on 11 September 1884 to treat a patient’s glaucoma [37]. Koller presented his results to the Viennese Medical Society in October 1884 and published his results later that month. The impact of his discovery was instantly recognised and by late 1885 there were 60 publications from the United States and Canada about local anaesthesia and cocaine [37]. The era of regional and local anaesthesia for surgery had begun.

The excitement for this newly described anaesthesia would continue to flourish, and by 16 August 1898 August Bier (1861-1949) would perform the first spinal anaesthesia through an intrathecal injection of cocaine in what he called “cocainisation of the spinal cord”. Bier had attended Kiel University Germany and was a student of Heinrich Quincke (1848-1922). Quincke was known for introducing the technique of lumbar puncture into clinical practice and collaboration between the two is likely [40]. Bier’s first patient was a 34-year-old labourer with tuberculosis who required a foot amputation but could not undergo general anaesthesia. Bier suggested spinal anaesthesia to him and injected 3ml of 0.5% cocaine solution. After 20 minutes Bier was able to complete the surgery without the patient experiencing any pain. He performed a similar technique to five other patients before embarking on self-experimentation with the help of his assistant Dr August Hildebrandt [41].

Hildebrandt performed a spinal anaesthetic on Bier using the same technique that Bier had developed for his own patients. However, in the process Hildebrandt had difficulty attaching the syringe to the needle hub which led to Bier losing a significant amount of cerebrospinal fluid. Most of the cocaine was lost before being injected and Bier had no anaesthetic effect from the spinal cocainisation. Dr Hildebrandt volunteered to swap places with Bier as the subject for experimentation and Bier successfully injected 0.5mls of 1% cocaine into Hildebrandt’s intrathecal space. Bier produced a detailed summary of the effects of his spinal in a publication [41]. The anaesthetic lasted over 45 minutes and during this time Bier tested the efficacy of his block through a series of bizarre checks that included burning a cigar on Hildebrandt’s legs, avulsion of his pubic hairs, striking his shin with a hammer, and strong pressure and traction of the testicles. Delighted with their success the men proceeded to “dine and drink wine and smoke cigars” [41]. After the effects of the spinal wore off both men initially felt fine but the following day, they both developed severe headaches lasting 8 days for Bier and 4 days for Hildebrandt. Bier described these as “unpleasant after-effects” and attributed the severity of their symptoms to the fact they “drank and smoked more than was good for us” [38]. Both men suffered from post-dural puncture headaches and in his report, he described the classic symptoms, but Bier misattributed this to his wine “hangover” rather than the large amount of cerebrospinal fluid they both lost.

Alcohol is ubiquitous in the story of cocaine, firstly through its role as an extraction solvent which enabled Niemann to isolate the cocaine alkaloid from the coca leaf, and then in the popularisation of Mariani’s “Vin Mariani” with its increased potency, which eventually would lead to Koller’s discovery of its anaesthetic potential and Bier’s development of the new field of neuraxial anaesthesia.

Conclusion

Alcohol has played a pivotal role throughout human civilisation, and its influence in the advancement, enlightenment, and practice of both modern medicine and anaesthesia is clearly evident. From the bubbling of fermented beer in Leeds, to the cocktails of Sweet Oil of Vitriol, and the spirits of Guthrie’s Sweet Whiskey, the foundations of modern anaesthesia were given life. These various alcoholic concoctions provided the deep sedation and unconsciousness that enabled patients to have pain-free surgical procedures and forever changed the face of obstetric analgesia, dentistry, and surgery. The widespread utilisation of ether, chloroform, and cocaine was not through collective medical experience alone, and its recreational use and abuse at parties and frolics undoubtedly played a pivotal role in the popularisation of these agents. It was the collective effort of key individuals and clinicians who recognised and utilised their medical value that paved the way for the creation of the speciality of Anaesthesia.

The Danish chemist, Søren Sørensen, at the Carlsberg brewery laboratory, with the support of Radiometer A/S, would establish the pH meter for blood gas analysis - a crucial technology in the treatment of polio patients in 1952 in newly established Intensive Care Units. A brewery in Leeds would kindle Joseph Priestley’s fascination with “airs” eventually leading to his discovery of nitrous oxide. Humphrey Davy and his companions would indulge in laughing gas parties before Dr Horace Wells found its use as a procedural analgesic and sedative. The mixing of wine and sulphuric acid would give Cordus his Sweet Oil of Vitriol. While ether would be abused in the same way as nitrous oxide, it would be William Morton with support of Wells and Jackson, who would popularise ether for its medical potential. Ether would pique the medical world’s interest in inhaled anaesthetic agents and encourage Simpson to search for an alternative with his anaesthetic seances. He found this in Guthrie’s Sweet Whiskey, chloroform, in 1847. Dr John Snow would go on to become the first anaesthetic specialist and bring a structured and scientific approach to the art of anaesthetics. Pure alcohol was an ideal extraction solvent for the discovery of cocaine when Albert Niemann extracted the alkaloid from coca leaves in 1860. Antoine Mariani would use wine to improve the taste of the bitter and potent coca leaves and in the process create a more potent solution via ethanol extraction with his Vin Mariani. The Royal and Holy endorsement of Vin Mariani eventually witnessed cocaine achieve medical recognition. Sigmund Freud would prescribe cocaine to his patients to treat opium addiction and inspired his friend Karl Koller to eventually provide the first operation under local anaesthetic on 11 September 1884.

And so, we have the ABCs of anaesthetic history – Alcohol, Beer and Cocktails. The alcohol-based solvents involved in the extraction of coca leaves, the Danish beer brewery’s involvement in the first commercially available pH analyser, and the cocktails which caused both controversy and the popularisation of ether. The course was set, and today the science of anaesthesia is key to modern medical practice, a world without anaesthesia is unthinkable. We give our thanks to all those individuals involved whose remarkable work led to these discoveries and, of course, to alcohol itself. Cheers! Sláinte! Prost!

John Thompson
CT3 Anaesthetics
University Hospital North Durham

Twitter: @JackHThom

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