(Stories in the History of Medicine)

AdamBlatner, M.D.

February 16, 2009. (I plan to revise and polish this a bit yet, but thought I'd get it posted just to get the ball rolling.)
: This is the fourth in a series of presentations given to the February, 2009 session of our local lifelong learning program, Senior University Georgetown.)
Other lectures in this series include: 1. Introduction and Germ Theory, plus supplementary webpages on a brief overview of the history of medicine before 1500,
   a brief overview of the history of medicine after 1500, and the history of microscopy.
    2: Contagion, Infection, Antisepsis ;          3: The Early History of Immunology  ;     5:  Recognizing Nutritional Deficiencies
    6:  Hygiene: Sanitation, Hookworm, Dental Floss, & Summary

The focus of this presentation is mainly the stories associated with the pains of surgery, dentistry, and obstetrics, though some later applications to the treatment of chronic pain may be addressed. Of course, there could be two other tracks, one dealing with stories associated with the histories of opium and its compounds, such as laudanum and paregoric, of aspirin and other pain medicines; and a third track would be the stories of recreational drug use, using various substances  for intoxication and release—including cannabis, alcohol, and a variety of other recreational drugs. Of course, there is some overlap, but I'll try to stay with the subject. Also, the focus is mainly on developments in the 19th century, and though I touch lightly on further developments in the 20th century, I make no claim to offering a thorough treatment, because ther are so many and their histories are complicated by the inter-disciplinary complexity of fields that characterize our own increasingly postmodern world.

The Need for Anesthesia

Many efforts at alleviating pain and discomfort have been a part of humanity's story since the beginning, and to this end our better-known responses have been the use of alcoholic beverages and the leaves and flowers of the cannabis plant (i.e., marijuana). (The psychedelic drugs derived from plants were strong enough so that where and when they were used, such substances, such as the peyote cactus buds, generally were ingested as part of a cultural ritual, a spiritual container of the visions that would ensue. Such substances were not at all  used as anesthetics.) There were other herbs that were used that might add to a person's sense of drowsiness, but when the issue was not just pain but the acute pain of surgery, these anodynes would not suffice.

The pain of surgery was torture! Celsus, a Roman physician, wrote around 100 AD:
     "Now a surgeon should be youthful or at any rate nearer youth than age; with a strong and steady hand which never trembles, and ready use the left hand as well as the right; with vision sharp and clear, spirit undaunted; filled with pity, so that he wishes to cure his patient, yet is not moved by his cries, to go too fast, or cut less than necessary; but he does everything just as if the cries of pain cause him no emotion."

Indeed, the necessary brutality of the process---and it also extended to those who extracted teeth---made this activity less attractive, drew significantly less status, than the more quiet and dignified work of  the physician. Surgeons were at or below the level of the apothecary---indeed, they as a profession had only begun to emerge from the even lower-status "barber-surgeon." But the sciences of anatomy and pathology, described in previous lectures, as they emerged into culture, raised the status of the surgeon somewhat. Indeed, when anesthesia brought quiet instead of screams into the operating theatre, and antisepsis and then asepsis brought a measure of ritual to the process, surgeons actually transformed into having more status in the early 20th century than non-specialist "family practice" doctors!

Another quote, from the satirical play by George Bernard Shaw, The Doctors' Dilemma, in which a composite successful old codger, Sir Patrick, reminisces:

    "He's a clever operator, is Walplole, though he's only one of your chloroform surgeons." [Walpole is a young and perhaps overly-self-confident young man whose mission is to remove some organ--the "nuciform sac"-- that in actually---not in the play---doesn't exist.] Sir Patrick contines: "In my early days, you made your man drunk; and the porters and students held him down; and you had to set your teeth and finish the job fast. Nowadays you work at your ease; and the pain doesn't come until afterwards, when you've taken your cheque and rolled up your bag and left the house. I tell you, Colly, chloroform has done a lot of mischeif. It's enabled every fool to be a surgeon."
In many surgeries, several burly men were needed to hold down patients and surgeons had to make themselves numb to patients’ pleas for mercy, coping by seeking to work as rapidly as possible. Alcohol and opium were used at times, as well as mandragora and some other herbs, which worked a little, but not terribly well. In large doses they also had secondary problems and might make the patient throw up and if sufficiently sedated, possibly inhale some of the vomit, causing a kind of pneumonia called aspiration pneumonitis. Ether had that problem too at heavy doses.

Another approach to anaesthsia was what later came to be called hypnosis, earlier called “animal magnetism” by Anton Mesmer in the late 18th century; but "mesmerism" weas not found to be terribly valid. Nevertheless, there were a few physicians who found that it worked with some of their patients in surgery—one fellow, James Esdaile, used it successfully in India in the 1830s -- but it didn’t work for him in the less suggestible Scotland when he returned to the British Isles.

The Invention of Ether

The small organic molecule of ether was first created in 1275 by Spanish chemist Raymundus Lullius (shown on the left), as a product of the action of sulfuric acid on alcohol. (Back then sulfuric acid was called vitriol—some of you have heard the word “vitriolic” to describe a very harsh, acidic manner of speaking or a political diatribe.) Re-distilling the product of vitriol and alcohol generated what Lullius called "sweet vitriol."  Yet no mention was made of its psychotropic qualities or anesthetic potential.

History is full of this, precursors, someone working with some aspect of the problem. To say again, though, it’s not really an invention until—what? When it’s recognized and put to use? Like the joke that the fellow who invented the wheel was clever, but the guy who invented the other three and attached them to a wagon—he was a genius!  Or should the credit go to the guy who invented the wheel? Well, we’ll go into that story later.

So ether was noted if one read carefully in the literature again in 1540, its synthesis being described by German scientist Valerius Cordus (shown at the right); and at about the same time, Swiss physician and alchemist Paracelsus commented briefly on the hypnotic effects of ether. Later, in 1730, German scientist W.G. Frobenius changed the name of sweet vitriol to “ether.” And thus it remained until the early 1800s when gradually people realized that the vapors could generate a pleasant “high” as a recreational drug. But application as an anesthetic awaited four more decades.

The Invention of Nitrous Oxide

Now let’s turn to another anesthetic, nitrous oxide, laughing gas. This simple chemical was first manufactured in 1772 by Joseph Priestly in England. Priestly was a pioneer of chemistry—drawing away from the less scientific alchemy a century earlier—and he also discovered the gases nitrogen and oxygen, though he didn’t really appreciate the significance of this latter discovery.

A slight digression: Burning and respiration were explained as an action of phlogiston—which, though never detected, was assumed to be there. Nowadays we assume several things like this—dark matter and dark energy, which are said by astronomers to make up 93% of the stuff of the universe; strings which are unimaginably small but their configurations in 10 or 11 dimensional space account for the various sub-atomic particles. Sometimes stuff is theorized and then later the underlying theory is replaced by another one.

In this case, three years later, the great French chemist Anton Lavoisier, in 1775, isolated and defined oxygen and re-conceptualized the nature of oxidation and oxygenation or respiration in living beings. Lavoisier also described the nature of an acid and the way in respiration Oxygen was exchanged for carbon dioxide.

The idea that gases might have therapeutic possibilities became fashionable. A pneumatic medicine institute was started in a spa south of London.

Humphrey Davy
Thomas Beddoes
 In 1799 Humphrey Davy discovered anesthetic properties of nitrous oxide (N20)---also known as "laughing gas."  He had recently joined Thomas Beddoes’ Pneumatic Institution (established 1798) for treatment of disease by inhalation. Beddoes (1760-1808) had picked up on the idea that inhalation of the different kinds of gasses that were being created might have a wide variety of therapeutic applications. (A recent example of a similar fashion was the use of bottles of oxygen that were fashionable in I think the 1990s  at some Japanese and European bars for refreshment.) Beddoes was an interesting and multi-faceted character. Because his sympathy for the French revolution made him politically unappreciated in certain cirlces, it was expedient that he resign from his faculty position at Oxford even though his classes were among the most popular.

Davy himself was an exuberant young man who later looked back on this phase of his life with a bit of chagrin; he became a noted scientist who discovered the elments potassium and sodium, invented a miner's lamp, and so forth. Around 1799, though he first experimented with nitrous oxide on animals, then himself, and was most taken with the experience, writing about it with enthusiasm.

There ensued in America and England a bit of a fashion, the idea of enjoying intoxication

with nitrous oxide or ether. In the cartoon to the right, the caricaturist Gillray shows a demonstration, dated around 1802, featuring probably Davy as an assistant. The cartoonist is stretching the truth to weave in a bit of broad humor: Breathing a gas may make you high, but it won’t make you fart. Still, it was a topic for satire.

Anyway, people enjoyed getting high, as seen below in another  1808 cartoon of a nitrous oxide gathering:

A wide variety of reactions would come with the breathing of laughing gas---a suffusion of insight, occasional grandiosity, sometimes belligerence, quasi-mystical experiences, but the problem is that attempts to write down these experienced insights didn't work: the idea or feeling slips away like a dream

The point to make here is that the two gasses that were to become important anesthetic were first viewed as merely recreational in nature, and in some places made illegal, the way marijuana or MDMA ("Ecstasy") has been more recently treated.

Here are some other pictures of ether parties in the 1830s:

In the 1820s, a newspaper suggested a way to have one's wife become more tractable and mellow.
 Let's get stoned: Young men trying ether in the 1830s.

But it hadn't yet mad inroads to the medical profession. Rather, there was a pride in operating quickly. For example, Robert Liston in London

was a “hot shot” surgeon who was strong and well practiced, and enjoyed high status because of his skill. He could be charitable and kind to the poor, or gentle in the sick-room, but tended to be contentious with peers. A number of anecdotes attend the rapidity of his surgeries—we’re talking about finishing the main part of a procedure in less than 2 minutes!

The Discoverer(s) of Anesthesia.

Four professionals later claimed to have been the main one who discovered anesthesia! Their fight went all the way to Washington DC and to the French Academy, and various public figures and later historians tended to support this or that figute.

The first one---who, alas, held back his publication until later!---was Crawford Williamson Long (1815-1878), an established small-town (Danielsville) Georgia physician who

claimed to have used ether for surgery in 1842. He had apprentices---four young gentlemen---Long being around 29 and they around 20. As was common, all held occasional nitrous oxide parties, and one time they had run out of nitrous and Long reminded them that ether might also serve as an intoxicant. This led to his noticing that high spirits during such frolics might result in injury without the person seeming to feel pain. So finally he tried it on a patient, and then several.

His later excuse was that he felt that he needed more of a peer-group consensus and felt intimidated by his small-town status. After anesthesia was publicized, he made his claim that he had tried if four years earlier.

 The next candidate was Horace Wells (1815-1848) . He was also a young man  who had contact and dealings with the next two people to be mentioned. He was a dentist who, at an exhibition of the use of nitrous oxide, also witnessed analgesia under the influence.

 Wells  went home and tried it on himself: he had an impacted molar and asked a colleague to extract it, Wells first having inhaled deeply of nitrous oxide. This was successful, so he tried it first on a patient, then several more. Emboldened, he spoke to Jackson, who pooh-poohed the idea, but nevertheless proposed to the nearby medical school that this substance could be a possible anesthetic.

The appointment was set up in 1844, the experiment engaged, but nitrous is too short-acting, and one must also inhale it for quite a while. Even then, possibly breaths need to be taken fairly frequently to maintain analgesia---it wears of fairly rapidly, too. For whatever reason, this demonstration failed: The patient groaned and grimaced as the surgery neared completiong, and the observers jeered. Wells was humiliated and left. What was more galling is that Wells thereupon obtained a great deal of documentation that his approach worked---he used nitrous oxide with many patients who were profoundly grateful. But the opportunity to demonstrate the potential for anesthetic passed to another--William Thomas Green Morton (1819-1868):

Morton was another dentist---and a one-time partner with Wells!---also living in the greater Boston region. He had studied with a man named Charles Jackson (about whom we'll hear more) and who suggested that Morton try using ether.

Morton tried this on some animals and finally approached the cheif surgeon at the Massachussets General Hospital where earlier Wells had failed. On October 16, 1846 the demonstration again was held---Morton actually came in late, delayed by last-minute adjustments to the ether inhaler in the picture to the right:

       The scene that ensued has been painted and shown by a number of artists:

The same surgeon who had given Wells a chance finally was able to operate without a screaming patient. At the end, Dr. Warren said, "Gentlemen, this is no humbug." Many who witnessed it said that they were profoundly moved!

The third fellow, Charles T. Jackson,  is an interesting character, a man not afraid of claiming to have influenced matters—he  claimed to have given the idea of morse code to Morse of the telegraph fame. In this case, he may have been somewhat active in suggesting to both Wells and Morton the potential for anesthesia in these gases—Jackson was in a role to do this; and he claimed to have done it; but didn’t demonstrate it or write it up early. Historians are mixed about his priority. A few give him credit, others consider him a scoundrel and probable a bit of a sociopath

The fourth man is Thomas Morton, who has been given the main credit by many medical historians because he stuck with it and demonstrated the effectiveness of ether—that was what he used—at the Massachusetts Hospital— and the one who brings the method to the public gets the real credit. But there are several catches and circumstances.

Oliver Wendell Holmes, Senior—the pioneer against unwashed hands in the prevention of childbed fever mentioned in the second lecture—also lived in Boston area, heard about the demonstration, and wrote Morton, commending him and suggesting the use of the term “anesthesia.”

Subsequently, all four of them or their surviving family members and associates battled in congress and up to the Supreme Court as to who deserves official recogniton! Wells appealed to the French Academy.  Money was a hoped-for side benefit, the claimants wishing they could get something additional along with that recogniton. It went on for years and various notables took sides.

A few side issues: Morton was not entirely forthcoming about the formula: He had added a bit of artificial fragrance to a fairly widely known and common substance, and re-named it Letheon. He hoped to patent it and profit from it, but the chief of the hospital held out until he admitted it was simple ether. Now there’s another historical note here: Ever since there was a bit of a scandal about some docs in the previous century who kept back as a secret gimmick only they could use—the word for that is “proprietary”— the use of a more effective design for obstetrical forceps—which could have saved thousands of lives—the ethos was reinforced that this kind of patenting of what everyone should be able to use is unethical.

At any rate, this indeed was a true breakthrough of the first order, and it rightly swept the civilized world within a year or two. In contrast to the slower and more contested growth ofvaccination or germ theory, I guess the squeeky –or perhaps, a more appropriate word is screaming—wheel gets the grease. Nevertheless there was wariness among medical men and clergy, some of whom thought that pain was good, right, just, natural, and should not be interfered with.

So, then, who is to get the credit?

C. Long
H. Wells
Wm T. Morton
Chas T. Jackson
It's really a rather sad story. Wells sought justification, but interestingly, a few years later, discovered chloroform, which is a rather seductive substance, and became habituated. He went downhill, also using alcohol, and finlly killed himself in jail! Morton and Jackson also  struggled and also had unhappy ends. Long died of natural causes.

England and James Simpson

Within a year people had been incorporating ether into their surgical practice in England and Western Europe. The aforementioned Robert Liston had amputated a leg with the patient anesthetized and announced, "This Yankee dodge, gentlemen, beats Mesmerism hollow!"

 In January, 1847, James Young Simpson (1811-1870) used ether as an aid to reduce pain in a difficult childbirth in Edinburgh, Scotland, which, at the time, had one of the top medical schools in the world. Ether, however, was by no means an ideal anesthetic. It tended to make people cough, could feel stifling and generate struggling in those who didn't trust the method, and sometimes made people throw up. It took a while to get them to sleep and smelled funny. It wasn't easy to use. Therefore, Simpson undertook to explore the range of other possible anesthetic agents. Finally he came upon chloroform, which he tried a few times not only on himself, but also on some friends.


He hit upon chloroform, which knocked him out, made his friends act weird, but it was a pleasant type of unconsciousness and it smelled better than ether.

Simpson tried it on some patients and then on some obstetric patients. It became accepted in many circles because Simpson was associated with high status faculty and there didn't seem to be much problem. Again clergy and some doctors objected, but Simpson responded with reason and good arguments.

The use of chloroform became even more mainstream when Queen Victoria used it in 1853 to help with the birth of her son Leopold. John Snow (1813-1858) had become better known for his work on a cholera epidemic---we'll talk about that more in the last lecture. Her Majesty recorded in her journal, "The effect was soothing, quieting & delightful beyond measure."   

Even some doctors objected, such as the old codger described jokingly in Bernard Shaw’s “The Doctors’ Dilemma,” noting the old days when you had to be fast, and now with chloroform anyone can do it and take their time.

An interesting thing about chloroform, though: It is good, but not as safe as some originally thought. If there’s any adrenaline in the system, people tend to get cardiac arrest and die. Also, there are occasional late complications of severe and fatal toxicity to the liver, which leads to a distinctly uncomfortable death. Happens a bit more in kids.

It took 30 years to really run the numbers but it became ever-more clear that ether was safer, with something like 3 per 1000 occasions of mortality versus 14 or so for chloroform.

Technological Developments

Codman ether inhaler
Codman nitrous oxide inhaler
Ormsby Inhaler

Allis Inhaler 1880s
Drip inhaler
Junker's inhaler
In the wake of the new technology of the gaseous anesthetics, a variety of inhalant systems were invented and revised in an attempt to promote the easiest, smoothest, most comfortable, most convenient, and in other ways a better way to use these substances.

Some of the questions asked might include the following: What can ensure adequate air or oxygen supply while breathing nitrous? How about compressing the gas so that it need not fill large bags? That requires the building of metal bottles and compressing equipment, and also valves so all doesn’t go into mouth or lungs and blow them up with compressed air. (That’s one of the functions of that little side non-inflatable bag you see.)
Further Developments: Endo-Tracheal Anaesthesia
This is where they put the patient to sleep with an intravenous anaesthesia, then put in a topical spray on his  vocal cords so they don't go into spasm, and slip a tube down his windpipe a bit. There's an inflatable cuff so no fluid (saliva, vomit) can get down into the lungs. It's needed so they can breathe for you.

The first problem was that going into the chest broke a kind of vacuum that's needed for effective breathing. They needed this technology so they could "bag" the patient, breathe for him, even if the diaprhagm muscle can't expand the lungs. This allows the surgeon to operate on the lungs, esophagus, heart or anything else within the chest cavity.
         Another need for this kind of breathing is that  if they do deep abdominal surgery, they need to counteract the tendency of the abdominal muscles to contract. It's more than difficult to retract and keep it open with this spasm. Either they must increase the depth of the anesthesia to dangerous levels or pharmacologically relax the muscles.

In the 1940s they discovered the active ingredient in South American Amazon Indian arrow poison: It's Curare. They synthesized it. The only problem with using this stuff is that you are so relaxed you can't breathe or swallow---but you're fully awake. So what needs to happen is to put you out deeply, then relax your muscles, and then time it so that the relaxant wears off before the anesthesia---which is one reason why you need a specialist!  (I suspect they don't need to do this with the more recent laparoscopy procedures.)

Topical, Local, and Regional "Block" Anaesthetic

Almost everyone has experienced their dentist putting an injection of novocaine or something like that into their gum area before working on a tooth.That process requires a number of developments that emerged in the mid-late 1800s. First, they needed the invention of the hypodermic syringe, which with improvement became possible to go intravenously and even into the spinal canal.

Second, you need a liquid anesthetic to inject. In the early 1800s some chemists had brought back the leaves of the coca plant from South America and began to extract and identify the active ingredient that they named "cocaine." Gradually its properties became a little more known, and one physician who was especially interested in its energizing properties was a general practitioner with some background in neurology, named Sigmund Freud. Age 29, Freud tried drinking a fluid extract of cocaine and was very pleased---enough to encourage his fiancee at the time, Martha Bernays, to, well, warm up a bit.

Freud also turned his friends on to cocaine, and was dismayed to discover that some of them became addicted. This he hadn't anticipated. Indeed, for a while cocaine was actually used as a treatment for morphine addiction, which had become not uncommon by that time in Europe and America.

Freud shared his enthusiasm for the potential of this new medicine with a friend, the eminent (in Vienna, anyway) ophthalmologist, Carl Koller.

Dr. Koller also noticed the way cocaine numbs the skin and mucous membranes, and from there Koller experimented and found cocaine to be a good local anesthetic for the eyes. Others discovered that it was also good for surgery or other procedures on the nose, inserting catheters into the urethra, and other procedures for which a topical anesthetic is indicated.

In the United States, the idea of local anesthesia appealed to up-and-coming surgeon William Stewart Halstead (1852-1922) who also experimented on himself and with some friends and found that it could work. Alas, he also became addicted!

Hypodermic needles had been invented in the 1850s and improved thereafter. Halstead tried not only topical anesthesia, but putting this numbing agent around nerves, and found again that it worked in depth. He is the pioneer then of what is called “conduction” anesthesia.

An interesting side problem: It turned out cocaine was addictive, and a few years later, Halstead went into a hospital and was treated with morphine to counter the withdrawal symptoms from cocaine, whereupon he became addicted to morphine instead of cocaine, and in spirt of a few efforts to conquer this addiction, relapsed several times. An interesting point is that except for Halstead not being terribly social, he was for the most part able to function, be maintained on his morphine, and adjusted to that maintenance dose, was quite alert—enough to function as perhaps the most outstanding surgeon in the United States at the time! This went on for at least a decade or more!    This story has implications for our views of what are the necessary consequences of addiction and how much is due not to the substance or addiction so much as the illegality of the whole process, and when is something to be called a disease?

Back to anesthesia: So now we have two types of anesthesia, inhalation of certain gases and hypodermic. A third route, intravenous, came with the continuing development of better needles, finer and more flexible, less likely to break off— and also the invention of the chemical, barbituate, and its derivatives. Old phenobarbital was developed in the early 1900s, but it was too long-lasting. Around 1915 someone invented some shorter-acting meds.

Another thing about cocaine and morphine, for your interest. They had invented another type of opiate that would be helpful in countering morphine addiction: In 1895 Heinrich Dreser working for The Bayer Company of Elberfeld, Germany, finds that diluting morphine with acetyls produces a drug without the common morphine side effects. Bayer begins production of diacetylmorphine and coins the name "heroin." In 1898 the Bayer Company introduced heroin as a substitute for morphine. In the early 1900's the philanthropic Saint James Society in the U.S. mounts a campaign to supply free samples of heroin through the mail to morphine addicts who are trying give up their habits. In 1902 in various medical journals, physicians discuss the side effects of using heroin as a morphine step-down cure. However, several physicians would argue that their patients suffered from heroin withdrawal symptoms equal to morphine addiction! And by 1903 heroin addiction rises to alarming rates.   (Interestingly, around 1946 Demerol (meperidine or pethidine) was introduced with a similar claim of being less addicting, but by the 1980s it became clear that this medicine was no better than morphine in its effectiveness and no better than morphine also in its addictive potential— and in some ways worse in its side-effect profile.


For a while several served mainly as recreational drugs—which leads me to state right now that there are several drugs developed more in the last fifty years that have been made almost impossible to explore regarding serious medical applications, psychiatric applications—LSD being one, MDMA also known as ecstasy another—although they may offer correspondingly significant benefits. So what is considered recreational and naughty and worthy of suppression may need to be re-thought—that’s one of the first morals to this story.