Asthma History: Introduction

According to my mother I was diagnosed with asthma at the age of two, which would be in the year 1972.  Considering she said I was sniffling, sneezing and wheezing even before that, chances are I developed asthma and allergies close to my birth on January 4, 1970.  Despite the claims of my doctors, I never outgrew my asthma.

When I was about ten-years-old, which would be in 1980, my asthma, already bad enough, took a turn for the worse.  While other kids were able to run around and have fun during recess, I was forced to sit on the bench.  While other kids were living normal lives, I was asking the Principal to call my mom because I couldn't breathe.

I remember my mother taking me to many unscheduled visits to Dr. Gunderson, and many more to the emergency room, and most of these for asthma.  Sometime in 1980 Dr. Gunderson introduced me to a small, pocket-sized device that gave me my breath back instantly.  It was an inhaler.  I quickly became great friends with this new object, taking it with me wherever I went.

One day as I was puffing on my inhaler I wondered what life would be like for asthmatics prior to modern medicine.  As I started to investigate this, I ended up on a journey that took me all the way back to the beginning of human existence 2.5 million years ago, and then all the way back to the current world.

I learned that for most of history (perhaps 99.9 percent of it) the asthmatic had to choice but to suffer through an attack.  Once I realized this I likewise realized how privileged I was to have been born in 1970, as compared with 1870 or, worse, 1870 B.C.

I also quickly learned that, as with the warpath of mankind, the path of disease can be traced back to the beginning of human existence.  In fact, disease may go back farther than war itself, as diseases exists regardless of the desires of mankind.  Although, as we learn from the Biblical Cain, fighting began early enough in a quest for selfish gain.

So while most histories follow the path of war, this history follows the path of health and healing, with an emphasis on asthma.  In order to organize this history I will use the following definitions:

• Prehistory (prehistoric):  Time prior to the first written language, or recorded history, which is generally considered to be around 2700 B.C. 
• Ancient:  Time after written language, or time with recorded history.  This period lasted from around 2700 B.C. until the fall of Rome in 476 A.D. 
• Time:  After the birth of Christ people developed a need to keep track of time, and so the birth of Jesus was chosen as the date to begin time.  The date of his birth was estimated and this was chosen as 1 A.D. When a child is born we usually refer to the first year as zero.  With time the first 100 years is considered the first century, and therefore the years 100-199 were referred to as the 2nd century.  It's for this reason why the years 1900 to 1999 were referred to as the 20th century.  This is just how it is.  

This system was created to help people study history and keep track of dates and time.  Whether accurate or not, this is how history is recorded.  I will use this system to categorize this history of asthma:

• Beginning to 5000 B.C.: Prehistoric people (prehistory)
• 5000-2700 B.C.: Ancient Societies (Before History and Time)
• 2700 B.C.-1 A.D.: Ancient Societies (During History, Before Time)
• 1 A.D.-276 A.D.:  Ancient Societies (Beginning of Time)
• 276 -1600 A.D.: Middle Ages (The Dark Ages of Medicine)
• 1600-1800:  Age of Reason (The Age of Enlightenment)
• 1800-1900:  The Scientific Revolution (the Age of Progress)
• 1900-2000: The Age of Results
• 21st Century:  The presents
• My asthma story

Each chapter in this history is one blog post, and each will focus on one thought.  In this way I am able to keep each chapter pithy and, therefore, easy to read.  While I have done some of my own research, I try to tell this history through the eyes of those who lived it, or those who spent hours studying it.  This will, I think, give you a more complete picture of the history of asthma.  

However, considering the vastness of our history, and the brief time each person lived among it, this history is but a small glimpse of the past.  Most of our history is told by the select few privileged to be able to read and write, so it is nearly impossible to impress upon what life was like among the common folk.

Still, there was just enough evidence to draw a picture of what life must have been like for those who suffered from asthma over the years.

So what was it like to live with asthma in fill in location and year?  To best answer this question, I make a gallant effort to describe the the various cultures.  This, I think, should should allow us to gain a more complete understanding what it would be like to be sick if you lived among them.  

However, I would like you to consider the following quote from historian Henry E. Sigerist:

"We have no evidence whatsoever of any paleolithic medicine." (1, page 107)

I say this because there will be times throughout this history when we must use our imaginations to gain an understanding of what it was like to live with asthma in fill in the year and place.

So what was life like for asthmatics 2.5 million years ago?  Let's go!

Reference:

1. Sigerist, Henry E "History of Medicine," volume I: Primitive and Archaic Medicine, 1951, New York, Oxford University Press

1808: Corvisart re-introduces chest percussion to medicine

Jean Nicolas Corvisart (1755-1821) was the
mentor and teacher of two men who would go
on to gain fame studying diseases of the chest,
such as asthma: Matthew Baillie and Rene Laennec.
He also earned fame for himself when he
re-introduced chest percussion to medicine.
Another pupil of his was Marie-Francois-
Xavier Bichat, the founder of biology. 

Joseph Auenbrugger introduced the medical community to chest percussion in 1761, although his idea was flat out rejected and rarely used.  Yet it would be another 53 years before his idea would be accepted, and it would take the efforts of a famous physician by the name of Jean Nicolas Corvisart des Merets (1755-1821). 

J.F. Halls Dally, in a 1941 article, said Corvisart was born February 15, 1755, to Pierre Corvisart, an advocate and attorney to the Parliament of Paris. For part of his childhood he lived with an uncle who was a priest at Vimille.  He then started college at Sainte-Barbe at the age of 12, where he was a "mediocre pupil who favored of outdoor sports. (1, page 239)

Of his childhood education, Dally said: 

He is said to have left the college almost as ignorant as when he went in, with no reputation but that of an incorrigible idler. Thus the childhood of Corvisart gave no promise gave no promise of his brilliant future. (1, page 239)

Later on he started as a law student, but after spending time at medical clinics of Paris he became interested in medicine. He became particularly interested in the speeches of Dr. Anthony Petit, a professor of anatomy and medicine. It was this reason "the young Corvisart recognized the profession for which he was designed. He longed to study the animal economy, and for this purpose he determined to be a physician," said Baron Cuvier in his 1830 memoir of Corvisart. (2, page 81) (1, page 23)
Surreptitiously, as he didn't want his father to be disappointed, he attended the lectures of the most famous physicians of the day, including Petit and Pierre Joseph Desault, said Cuvier. His father ultimately found out and approved of his transfer to the medical profession. (2, page 81)

Dally said he paid his way through medical school by becoming a male nurse at at Hotel Dieu, the oldest hospital in Paris.  It was here he became greatly influenced by the surgeon Pierre Joseph Desault, chief surgeon of the Hotel Dieu. Corvisart observed diseases with him and and examined bodies.  He also delivered his own lectures on anatomy and physiology, and these were well received.  He soon became well liked by his fellow students and physicians. (1, page 239)(2, page 81)

He was offered a job as physician at Necker, although he declined this position because all who held it had to wear a particular wig that had been handed down for decades.  Other clinics had given up this tradition, but it was still alive at Necker.  When he was offered a choice of taking the job and wearing the wig, or keeping his hair, he said he'd prefer to keep his hair.  This was a minor set back, however, because other opportunities awaited him. (1, page 240)(2, page 81)

It's interesting to note that while medicine in other areas of Europe had moved forward by leaps and bounds, Cuvier said medicine in France remained much as it was in the middle ages when the Faculty of Paris was formed. He said:

Besides, there were no public lectures at the beds of the sick. In order to see a few patients, the students accompanied the elder physicians in their visits; afterwords, when these physicians were unwell, or too much busied with practice, they acted for them, and thus they continued, till at length they, too, slowly attained their professional rank. (2, page 81)

In 1788 he became elected as physician at Necker hospital. His predecessor was Desbois de Rochfort (1750-1786), (Rochfort had passed away) chief physician at Le Charite, who was the "real creator of clinical medicine in France.  The pupil thus succeeded the master, and the glory of the master gained added lustre.  Corvisart took over the clinical teaching and from that moment his reputation, already established among his colleagues and students, began to spread outside the confines of the hospital." (1, page 240)(2, page 81)

However, unlike his predecessors, he believed it was best to diagnose diseases by their signs and symptoms and pathological anatomy, as opposed to guessing what might be found on autopsy.  (1, page 240)

Then things change for the worse in France. Although the end result would benefit the medical profession of France.  Dally said:

In 1793 the Reign of Terror began.  The medical schools were shut, anyone could call himself a doctor and treat the sick.  Medical education was three centuries behind the times. But out of the Revolution grew modern medical education.  In the new schools of Paris laboratories were instituted for scientific study; students were taught at the bedside in hospital after the manner of Sydenham.  And it was Corvisart -- formerly rejected because he wore no wig, who taught, who for he had now become the leading professor in France. He acquired the natural history of disease by collecting observations, and when possible, following the example of Morgagni, he noted from dissection and from autopsy the changes in the body that caused symptoms of disease.  His chief lectures were given at the Necker hospital, and subsequently over a term of fifteen years at Cochin Hospital." (1, page 240)

Corvisart, whose reputation increased daily, lived in close contact with the most illustrious men of the time.  In 1795, on the criterion of the first school of medicine in Paris, he was unanimously elected to fill the Chair of Clinical Medicine, for the first time included as part of public education in France. Two years later, in 1797, he was made Professor of Medicine at the College de France. (1, page 240-241) 

While Corvisart was professor of medicine at the Charite Hospital in Paris, he studied the works of Auenbrugger and found the technique of percussion useful in diagnosing his own patients.

He championed for percussion when he re-published Abenbrugger's booklet about percussion Inventum Novum  in 1808.  While he didn't have to, he humbly gave credit for the discovery of percussion to Avenbrugger.

He wrote:

"I could have raised myself to the rank of an author by remodeling the work of Auenbrugger and publishing a work on percussion.  But by that I would sacrifice the name of Auenbrugger to my own vanity; that I do not wish to do: it belongs to him, it is his beautiful and rightful discovery which I wish to bring to life." (1, page 242-243)

While Corvisant supported Avenbrugger's general technique, he adjusted it slightly so that "he used the palmar surface of the extended and approximated fingers," said Alex Sakula. (6, page 576)

Corvisart used the technique to help diagnose patients with tuberculosis and other diseases of the chest.  Based on the sounds emitted he would be able to tell how large or small the tubercles inside a patient were, along with their locations. (3)

Corvisart and his students -- one of whom was Rene Laennec -- were believed to be the only physicians in the world who used percussion. Perhaps this was because Corvisart was among the few physicians who studied Auenbrugger's work.

The use of percussion was among the diagnostic techniques used by Corvisart.  He used percussion, took a pulse, listened to the patients lung sounds by placing his ear on his patient's chest, watched the patient's breathing, felt for a temperature, observed sputum and perspiration, color of the patient's skin, changes in the voice, etc.  (2, page 81)

This was the new medical diagnostic practice that had already engulfed the medical profession throughout much of Europe, all but for the exception of chest percussion and, maybe also, vocal fremitis.

The Catholic Encyclopedia  notes that Corvisant may have been the first to describe the technique of vocal fremitis, which is where a hand is placed over the patient's chest, and the patient is asked to make a sound, such as "a" or "e."  The physician then notes the vibratjions (fremitis) felt as the person made these sounds. Corvisart found this to be another very useful procedure in diagnosing diseases of the chest.  (5)

So, in this way, Corvisart was able to add to the list of diagnostic tools used by other European physicians of his era.  By using these tools, Corvisart, and based on his studies of bodies, he was able to match changes on the outside of the body with changes that might be occurring inside the body.  He was, therefore, able to use observation and science to diagnose.

In this way, he was able to use observation and science to diagnose patient, as opposed to using theory and just guessing.  Perhaps it was this that most impressed the emperor of France.

Napoleon Bonaparte was a famous military leader and
emperor of France.  

The technique of chest percussion may not even have been adapted by the medical profession at all if not for Emperor Napolean Bonaparte (1769-1821) selecting Corvisart as his own personal physician.  (4)

Dally said Corvisart was recommended as physician to Bonaparte because he was impressed that Corvisart used a scientific technique instead of simply guessing what was wrong, as other physicians of his era did.

Some speculate it was Boneparte who convinced Corvisart to write his first book, a treaties on diseases of the heart.  This work was significant to our history of asthma because it was among the essential steps needed for future physicians to pluck cardiac disorders that caused dyspnea out from under the umbrella term asthma. (1, page 243)

Of this, Dally said:

It is said that cardiology as such did not exist prior to Corvisart's work. He really created cardiac symptomatology, and established differential diagnosis between cardiac and pulmonary disease, as well as between functional and organic heart disease." (1, page 243)

Corvisart later wrote his commentaries on Auenbrugger, which was also well received by his peers. (1, page 241)(2, page 82)

Thanks to the writings of Corvisart, and later Rene Laennec, Auenbrugger's discovery would become readily accepted shortly after his death in 1807, and Auenbrugger would eventually go down as one of the great minds in medical history.

Auenbrugger did, however, live "just long enough to witness the beginning of a proper recognition of his discovery," said Dally. (1, page 243)

Of course Corvisart himself would also go down as one of the great minds in medical history, not just because he re-introduced chest percussion to medicine, but because was a great physician overall who left an indelible impression on the medical profession.

He developed apoplexy (stoke symptoms) that took away his ability to perform his job, but not his mind.  He then suffered a cardiac arrest on September 18, 1821. He left behind no family, although he left much to his family of physicians.  (2, page 82)

Further reading:

1. Laennec, the inventor of the stethoscope
2. Auenbrugger introduced chest percussion to medical profession

References:

1. Dally, J.F. Halls, "Life and times of Jean Nicolas Corvisart (1755-1821)," Proc R Soc Med., March, 1941, 34 (5), pages 239-246
2. Baron, Cuvier, "Biographical Memoir of M. Corvisart," Literary Port Folia, Thursday, March 18, 1830, No. 11, Philadelphia, pages 81-82
3. "The Catholic Encyclopedia, "Leopold Auenbrugger," http://www.newadvent.org/cathen/02072a.htm
4. Williams, Henry Smith, "The Century's Progress in Scientific Medicine," Harper's Magazine, 1899, page 3
5. "The Catholic Encyclopedia, "Leopold Auenbrugger," http://www.newadvent.org/cathen/02072a.htm
6. Sakula, Alex., "Pierre Adolphe Piorry (1794-1879): pioneer of percussion and pleximetry," October, 1979, Thorax ( 34(5): 575–581).  

10000 B.C. Opium discovered

Back in the 19th century physicians realized opium and Morphine benefited asthmatics suffering from air hunger (dypnea).  Since such opiates relax the mind, physicians back then used this as evidence asthma was a nervous disorder.

Today various opiates are used to help take the edge off when a person is suffering from air hunger caused by a variety of diseases, such as asthma, chronic bronchitis, emphysema and lung cancer.  The medicine relaxes the mind, eases pain and suffering, and is a mild bronchodilator.

Yet opiates are by no means a modern remedy.  As a matter of fact, opium was one of the first medicines ever discovered by humans, if not the first.
It was also the first cultivated medicine.  It benefited many suffering from disease, and it also brought great suffering.  It was the first recreational drug, and it was even responsible for a war.
An opiate is basically any medicine that is derived from opium, which is a medicine derived from the opium poppy, or Papaver somniferum.  

It was probably discovered by a random person in the prehistoric world, probably long before alcohol was discovered.  (11, page 15) Perhaps the person was in a frantic search for food and ingests the bulbs of the plant.  He soon forgets his hunger.  Some say it was discovered around 10,000 B.C., although some speculate it was discovered much earlier.

Perhaps a young man, in a jolly mood, during a month later known as February, in a frantic search for something jolly to show a girl, finds the pretty flower in an open, sunny field.  He breaks off a variety of bulbs or capsules and takes them home to show her. He sets them in the woods where only he would find them.   (1)(2, page 4)

The next day he walks a girl to that spot, and together they study the bulbs.  By accident, the young man pokes a stick into one of the bulbs, and a white milky juice pours out.  Several days, weeks, months or maybe even years later, further studies are performed on these interesting flowers, and in one the juice was set in a bowl over night.  By the end of the next day, which was hot and sunny, the juice turned into a dark brown mass.  This, it would be learned later, was the crude form of a drug later to be named poppy or opium.  (8)

The dark brown mass was ingested by a man who was grieving the loss of his wife. It tasted bitter, yet he forced it down. H no longer felt agony.  He credited the juice from the poppy, and told all his friends of the paradise created.  He told them the flower was a gift to him from the spirit of his grandfather.  He ingested the opium every day for a week, having no idea how much he ingested.  In was now April.  He had now become a nervous wreck, with headache and constant tremors.  He yearned for more opium.

A friend of his happened upon the flower, and he admired the plant.  He picked it and took it back to his clan.  He prepared the plant later that night, and shared it during story time around the fire the next night.  That night was especially pleasant, and a new dance emerged out of spontaneous celebration.  Those who drank of the mass seemed to make contact with parts of their mind previously un-visited.

So the benefits of ingesting the plant were quickly learned.  Soon the no more poppies were in the woods, and a young man was presented to the lady members of the clan as a physical wreck.  He was diaphoretic, anxious, restless, had a raging headache, and had horrible tremors.  He yearnedf for more of the juice.  He was taken to the medicine man who said the young man must be suffering from the curse of a mad man.  But who was the mad man?  A frantic search was on.

A few days later the medicine man found he had some of the plant in his possession, and he prepared it in a drink and gave it to the young man.  Almost immediately his symptoms dissipated.  It was here the side effects of the opium poppy were learned.  The plant allowed visitation with the white spirits, yet used too frequently resulted in possession of black spirits.

This was the first apparent overdose of opium.  The medicine man took charge.  He dissected the plant.  He found the plant contained a dark brown soft, gummy mass.  He decided the poppy must be used wisely, and so he kept the formula to himself.  He did not share it until he was on his deathbed, when he shared it with his grandson.

His grandson became the next medicine man. The new medicine man prescribed opium to an elderly man who was suffering from gout.  The formula he prepared had a strong smell, and was given in an amount just enough to take the edge off.  He put it on the sick man's tongue, who winced at it's bitter taste.  (1)

The new medicine man grew old, and became ill and on his deathbed told his grandson of the opium remedy.  The grandson prescribed it many times in his life, and before he grew too old he told of it to his son in the form of a poem to make the recipe easy to remember.  His son grew to be an old and wise member of the clan, and his grandson became among the first physicians.  He, like his great grand father, believed opium to be a gift from the gods.

Over time medicine men must have experimented with this medicine, learning of its ability to take the edge off life.  It must have become one of the first and best remedies in his repertoire. Whenever he had a patient who was ailing, be it from a broken bone or an ailment causing dyspnea, poppy seeds were prepared in a potion, and once injested would have taken the edge off the pain and suffering. It would have created an "artificial paradise" of sorts. (10, page 30)

By word of mouth the effects of the medicine made its way to ancient civilizations of Sumeria, and is written about in 5000 B.C. on stone tablets.  It was known then as Hul Gil, which meant the "joy plant."  It was also written about in the Assyrian medical tablet arat pa pa.   It was also used in Europe at this time too, including what would later become known as Italy.   (1)  This is significant, because many believe from here it made its way into ancient civilizations of Greece and Rome.

Many experts estimate the Biblical beginning of time to be about 4004 B.C., so it must have been shortly thereafter that Adam and Eve walked the Garden of Eden.  The use of a "soporific medicine" was mentioned in Genesis, and it's easy to speculate the medicine might have been opium: (10, page 29)

And the Lord caused a deep sleep to fall upon Adam, and he slept; and he took one of his ribs, and closed up the flesh instead therof."

It was soon cultivated for it's ability to relieve pain, dull the senses, and induce sleep.  It may also have been cultivated for its perceived ability to cause peace and calmness and creativity, or what otherwise may have been perceived as pleasure.  It brought upon a relaxed state of mind induced by the spirits or gods.

It was prepared in wine, which was sweetened with pepper and other aromatics.  Ancient Roman texts note how the Egyptians yearned for it, and were addicted.  It was given to sooth children who were teething as early as 2000 B.C., and the recipe is mentioned in the Eber Papyrus of about 1550 B.C.  

Around 1300 B.C. cultures started cultivation of the poppy in poppy fields.  "The opium trade flourished during the reigns of Thutmose, Akhenaton and King Tutankhamen. The trade route included the Phoenicians and Minoans who move the profitable item across the Mediterranean Sea into Greece, Carthage, and Europe."  (7)

The Hebrews learned about it, perhaps when they spend time as slaves in Egypt, and it's therefore alluded to in the Hebrew Bible.  It was called rosh, which means head, perhaps alluding to the head of the poppy.  It was also referred to as me-rosh, or juice of the poppy.

Ancient Roman and Greek physicians new of it.  The Greeks referred to is as apyun.  (2, page 5) While Homer doesn't necessarily write a medical book, he alludes to ailments and wounds from time to time, although there would be little known of specific diseases when Homer walked the earth around 800 B.C. Many historians speculate Homer was a surgeon, and so from his experiences he describes battle wounds and treatments, one of which may have been opium to sway away pain and suffering. (3, page 22-23)

In his epic poem Odyssey, Homer writes that an arrow aimed at Hector missed him and hit another son of Priam.  Homer writes, "Just as a poppy in a garden hangs on one side, its head laden with fruit and with the dew of spring, so he bent on one side his head, made heavy by his helmet."  (2, page 3-4)

The Odyssey has other allusions to opium, such as described by historian Henry Sigerist: "the drug given to Helen by the Egyptian lady, Polydamna, had strong euphoric properties so that whoever took it forgot all unpleasant memories and would not shed a tear even if his closest relative died; this drug might be opium, or hashish.  But it could just as well be the kind of miracle drug found in many fairy tales." (3)

Very little is mentioned about opium by Hippocrates, the father of Medicine, who lived around 400 B.C., although he is given credit for the first mention of poppy juice. While he wrote little of it, it must certainly have been known to him, especially considering he was one of the most noteworthy and prominent physicians of his time.  (2, page 4)

It most certainly would have been used at healing temples, such as those of Apollo or his son Aesclepeons.  The sick would sleep in the Aesclepeons and, supposedly, the god would appear in a dream with a remedies.  Success stories were recorded at the temple, and some believe Hippocrates had access to the the recordings at the Temple at Cos.

Perhaps this is why Hippocrates had knowledge of the "juice of the poppy," and that it has soporific effects.  Although mentioned by him, it was barely by by physicians until the Arabs started studying Greek medicine, including the works of Hippocrates.  (6, page 280)

Pedanius Dioscorides, who lived 40-90 A.D., may have been the "first to give a detailed account of opium and its uses in medicine.  Treating of the cultivated poppy, he says, that it's juice is very congealing (solidified), incrassative (thick), and desiccative (preserved), when taken in small quantity, to the size of a vetch, is anodyne (relieves pain), soporific (induces sleep), concoctive (mixed with food or drink), and is useful in coughs, and caeliac affections.  Taken in greater quantity, it proves injurious, inducing lethargy and death. (6, page 280)

He is the first to describe the best time of year to prepare the opium, and he wrote about a technique the involved finely incising the capsules to release a white milky juice.  It was set out overnight, and by the end of the next day, after sitting in the hot sun, the contents turn into a dark brown gummy mass.  This method of preparation was basically unchanged through the 19th century.  

Dioscorides noted that it benefits:  (6, page 280)

• Headache when rubbed in with rose oil
• Earache when injected  with almond oil, saffron, and myrrh
• Inflammations of the eyes with the roasted yelk of an egg and saffron
• Erysipelas and wounds with vinegar
• Woman's milk and saffron
• Inducing sleep when applied as a suppository per anum

Dioscorides recommends the following preparation of opium: (6, page 280-81)

The best kind is that which is dense, has a heavy stupefying smell, is bitter to the taste, readily incorporating with water, smooth, white, not rough, nor grumous, nor moulding like wax in the process of straining; when laid in the sun softening, and when applied to a lamp not burning with a smoky flame, and after being extinguished preserving its powers in its smell. He then mentions several modes of adulterating it which were practised in his time, and then adds, it is roasted for ophthalmic medicines upon a recent shell until it becomes soft and of a tawny colour

Dioscorides also described the method that

Themison of Laodicea, who lived in the century before the birth of Christ, wrote of opium and other narcotics, and he used "confection of poppies, which he employed in the diseases of the respiratory organs (John Watson, page 110).  This may be the first allusion of the medicine to relieve the suffering from dyspnea, such as that caused by diseases later referred to as heart failure, kidney failure, bronchitis, emphysema, and asthma.  Although please note these diseases were not defined until much later, so to Laodicea they would have been all lumped under "diseases of the respiratory organs."

In the century after the birth of Christ, Galen was one of the many who warned that while opium has benefits, it should be used sparingly as it can do more harm than good.  For this reason Galen more often recommended simple things like good eating, cleansing and exercise as opposed to drugs, and many other physicians did the same.   (4, page 61)

In the second century Celsus describes a drug called "pavaverus lacryma" and many historians seem to think this was opium, or the juice of the poppy. He described various remedies, both internal and external, where it was used as part of the formula.  One formula used it in an emollient plaster to rub on arthritic joints, and in another it was part of an injection for ear ache, or salve for the eyes.(6, page 28)

Paulus Aegineta, who lived from 625-690 A.D., did not specifically write of the analgesic effects of opium, although he does allude to "counteracting it's toxicity:"

When one has drunk from the juice of the poppy, drowsiness comes on, with coldness and intense itching, so that often when the medicine takes effect such an itching comes on that the person is roused by sleep thereby.  The smell of the medicine too is emited from the whole body.  The remedies in such cases after rejecting the substance taken by vomiting with oil and evacuating downward by a stimulant clyster and oxymel drunk with salts, or honey with warm rose-oil and much undiluted wine with wormwood and cinnamon, and warm vinegar by itself, and natron with water, and marjoram with wine.  We must also arouse by aromatics, put the person into a hot bath, and foment on account of the pruritus which supervenes; and after the bath we may use fat broths with wine and must.  Marrow also drunk with oil is useful." (5, page 75)

During his quest to conquer the world, Alexander the Great introduced the Persians and Indians to Opium.  (6)  By the founding of Baghdad in 763 A.D. the Arabs were studying the medical texts as written by the ancient Greeks and were applying opium for their own medical purposes, and writing about it in their own texts.  The medicine was referred to as afyun, mainly because the Semitics had a habit of mispronouncing p's with f's.  The Persians referred to it as apyun or abyun, although it is from the former that the term opium is derived.  (2, page 5)

They Arabs and Persians started trading with the Chinese, and one of the products of trade was opium and other drugs, as well as precious stones, brocades, and rose water.  So it's believed opium was introduced to China during the Tang dynasty (618-907) by the Arabs. They used the Arabic formulas for the poppy seed in treatment of ailments.  (2, page 5)

It was written about in the first half of the 8th century during the reign of Tang Ming Huang by Chen Tsang Chi in a work called "Supplement to the Pentsao."  His quotes on opium were from a earlier Chinese author named Sung Yang-tzu, who wrote that "the poppy has four petals.  It is white and red.  Above them is a pale red rim.  The seeds are in a bag, which is like one of those arrow heads which have air-holes to make a sound as the arrow cuts through the air. Within these are seeds like those of millet." (2, page 7)

So the Chinese now had opium, and the ability to make it themselves, and so they did.  They made it and used it as did people of the rest of the civilized world.  In 973 the Emperor Sung Tai-tsu instructed nine men to write a book in which is written: "It's seeds have healing powers.  When men have been taking the stone that confers immortality, feel it powerfully operating, and cannot eat with appetite, they must be benefiting by mixing these seeds with bamboo juice boiled into gruel and taking this." (2, page 8)

Opium is also mentioned in a poem by Su Tung Po (1036-1101): "The Taoist advises yon strongly to partake of the drink chi-su-shui.  The boy may prepare for you the broth of the ying-su." Ying-su is the name given to opium during the Tang Dynasty, and it means "jar millet," because the poppy head resembles a jar (ying). (2, page 8-9)

Avicenna (980 A.D.) was among the most prolific Arabic medical writers during the dark ages of medicine, and he wrote that opium should be treated as a poison, and if given in doses higher than two drachmas can prove deadly, with the "proper dose the size of a tare.  Around 1020 he calls it narcotic and sedative of all pains, whether taken internally or rubbed in." (6, page 282)

Narcotic is your prototypical term that gives reference to the effects of drugs like opium, reducing pain, inducing sleep, and dulling the senses.  To ancient physicians it must have been a very nice drug for physicians to know about, as life can bring about great pains and sufferings.  Physicians wanting to alleviate such sufferings may have prescribed opium.  Although, as Avicenna notes, it must be used carefully because it is a poison.

He said it was useful for (6, page 282):

• Apostemes (Abcess):  It dries up the ulcers
• Gout:  It must be mixed with the yelk of an egg to form a linemint (lotion)
• Anxiety/ suffering:  Soak a cloth smeared with it below the head
• Ear pain:  Inject it into the ear, along with myrrh and saffron
• Chronic head pain:  Soak a cloth in it can relieve suffering, and may cure it
• Opthalmy:  Eye pain can be remedied (mix with the milk of a woman)

Warning:  placing opium in the eyes may induce blindness.  Yes, Avicenna warns, if your eye pain is bad enough you cannot bare it any more, you may try this remedy.  Yet you must do so knowing the risks of this poison.  All of you who use it must know it is a poison, as well as a possible remedy and cure.  It must be used with caution.

 It also known to allay or improve: (6, page 282)

• Incessant coughs, and often cures that kind which is noisy
• Stomach peculiarities
• Diarrhoea
• Dysentery (diarrhoea with mucous and blood)
• Ulcerations of intestines

However, one must be careful, because excessive use can "impairs digestion."  Although by observing this side effect, it became among the first effective treatments to stop diarrhoea. 

Again, however, as did other physicians, he observed that "it proves fatal, he says, by congealing the vital powers and extinguishing the innate heat; and its antidote is castor. He concludes by saying, that three times the amount of the seed of hyoscyamus, or double of the seed of mandragora may be given as a substitute for it." (6, page 282)

The Arabs were also among the first to perform surgeries, and opium must have proven a useful anaesthetic.  So it's uses were varied.  Yet a plant that was once found to be a beautiful flower, and randomly used for by primitive people, was eventually cultivated and used as a potent option for physicians.

The Chinese became addicted to the medicine, and it became very valuable to them.  However, they were unable to cultivate as much of it as was needed or desired.  So the resulted in a trade route between England, India and China.  It also resulted in a war, as we'll learn in my next post.

References:

1. Aggrawal, Anil, Dr., "The story of opium," from "Narcotic Drugs," 1995, National Book Trust of India
2. Edkins, Joseph, "Opium: historical note: or the poppy in china," 1898, American Presbyterian Mission Press
3. Sigerest, Henry, E., "History of Medicine," Volume II, "Early Greek, Hindu, and Persian Medicine," 1961, Oxford University Press, page 23
4. Prioreschi, Plinio," A History of Medicine: Byrzantine and islamic medicine," 2004, Horatius Press, page 
5. Prioreschi, page 61, quoted by Prioreschi from "The Seven Books of Paulus Aegineta," V, xlii, translated by Francis Adams, London, The Sydenham Society, 3 volumes,  1844-1847, 2, page 213
6. Paulus Aegineta, translated by Francis Adams, "The Seven Books of Paulus Aegineta," V, xlii, 1847, The Sydenham Society, 3 volumes, (1844-1847), volume 2, page 279-283; here we find a good discussion of opium use by the ancients as recommended by Plinio Prioreschi (see reference 5 above)
7. "Opium Timeline", http://www.opioids.com/timeline/, accessed 12/20/12
8. Allan, Nathan, "The Opium Trade," 1853, 2nd edition, Lowell
9. Kane, Harry Hubbell, "Opium-smoking in America and China," 1882, New York, G.P. Putnam's Sons
10. Garrison, Fielding Hudson, "An introduction to the history of medicine," 1922,
11. Booth, Martin, editor, "Opium: a history," 1996, Great Britain, Simon and Schuster Ltd.

1893-1933: How does epinephrine (adrenaline) work? x

After epinephrine (adrenaline) was isolated in 1901 the quest continued to find better medicines from hormones for asthma and other diseases.  Almost as important was the quest to  to learn about how these medicines worked once they entered the body, and how to synthesize them.  While slow getting off, the quest ultimately lead to the medicines available to us today.  

The adrenal gland, which sits atop the kidneys, controls the autonomic nervous system, which is responsible for all the things inside your body you do not directly control by yourself. It gets its name from adrenaline, one of the hormones it produces. 

The autonomic nervous system has two divisions: 

• Sympathetic: It reacts to stressful situations in your life, and is often referred to as flight or fright.  For example, if someone points a gun to your head, your adrenal gland increases hormones that cause vasoconstriction. This causes your heart rate to increase in rate and force, resulting in an increase in blood pressure. It also dilates your bladder so you don't pee your pants. It also causes bronchodilation so you can breathe deeper. 
• Parasympathetic: It basically does just the opposite, and acts as a thermostat to turn your body functions back to normal.  For example, the gun now unloaded, your adrenal gland increases hormones that cause vasodilation. This causes your heart rate to decrease in rate and force, resulting in a decrease in blood pressure. It has a calming effect on your body. 

The basic anatomy of the adrenal gland and its effect on the sympathetic nervous system was understood by the middle of the 19th century. (6, page 5)  It was from this gland that various physicians in the last few years of the 19th century extracted hormones to perform experiments to learn what effect they caused. They tested the extracts on animals, on patients who volunteered, on their own children, and on themselves. 

Once they realized the vasoconstricting qualities of adrenal extracts, they tested it on various diseases, like hay fever and allergies. They did not know why it made breathing easier, although the initial theory was that asthma was caused by vasodilation that caused blood to congest in the chest. So the vasoconstricting properties of the extracts would relieve this congestion, making breathing easier.

Further testing found this theory to be false, that epinephrine mimics the sympathetic nervous system, and that it makes breathing easier because of it's bronchodilating qualities. It attaches to beta 2 receptors lining smooth muscles lining airways, and causes them to relax. This results in bronchodilation, making airways open. This made breathing easier, and it worked fast, particularly if injected. 

Later norepinephrine (noradrenaline) was isolated.

From here various experiments were performed and conclusions drawn.  Among the first was by John Newport Langley in 1901, who noticed that extracts containing epinephrine and norepinephrine caused a reaction similar to "sympathetic nerve stimulation." (1) 

In 1904  Thomas Rendon Elliot (1877-1961), working in Langley's laboratory, postulated the idea that a "chemical stimulant" was released when a nerve impulse was sent to a nerve synapse.  A nerve synapse is the space between a nerve and a muscle, and Elliot believed a chemical stimulant released by the synapse allowed an impulse to travel from the brain to that muscle cell.  (2)(6, page 65)  Then, in 1905, Langley postulated that adrenaline acted as such a "chemical stimulant." (2)

British Pharmacologist Henry Dale (1875-1968), who reported use of adrenaline as an inhalent, coined the term "sympathiomimetic amine" in reference to medicines like adrenaline that mimic the sympathetic nervous system's response, and in 1907 Paul Erlich came up with the idea that hormones that act as neurotrasmitters (such as epinephrine, norepindrugs and the drugs that mimic them) bind to receptors that sit on cells along vessels and smooth muscle, and he called these receptors chemoreceptors.(2)

Elliot ended up dropping his research to go back into clinical training due to "lack of interest in his work exhibited by the elite by the scientific establishment." Dale and Langley did not persue it, and Langley went as far as to note lack of interest because he didn't like to persue "speculative theories." (2)

In 1907 Cambridge Pharmacologist Walter Dixon "extended Elliots findings by arguing that parasympathetic nerves similarly liberate a neurotransmitter to activate effector sites" (sites where the receptors sit along smooth muscle and vessels) through the synaptic space between a nerve and the effector site.  (2)

Dale later hypothesized that the neurotransmitter Dixon wrote about was probably choline.  It was ultimately learned that medicines like Atropine, strammonium, and belladonna block the effects of choline, and were therefore referred to as anticholinergic.  Strammonium and Belladonna were already used for thousands of years for their hallucinogenic effect and to make breathing easier. Atropine was used since the early 19th century for breathing and to increase heart rate.  Now physicians knew why these drugs work. (2)

Yet the work of Elliot, Langley, Dixon and Dale was ultimately stalled due to both lack of interest by the scientific community and due to "limitations in methodology" that made it "difficult, if not impossible, to employ a more direct experimental approach to the problem at this time.  However, Elliot, Dixon and Hunt did not possess the burning interest and passion needed to overcome the obstacles presented by this fundamental biological problem."

It would be another 15  years before this line of research was picked up again. (2) So this is yet another example of the medical community initially ignoring something that would revolutionize the medical profession.  The profession had also initially rejected the watch, the germ theory, and the stethoscope)

In 1920 Otto Loewi came up with an idea to prove the the works of the above men.   (2) Loewi placed two frog hearts into a single bath, the vagus nerve of one heart was stimulated, thereby slowing it, while causing the rate of the second heart to also diminish. From this experiment, Loewi reached the conclusion that a substance liberated from the first heart was responsible for causing inhibition of the second heart.

He termed the unknown substance vagus-stoff.  Subsequent articles by Loewi provided additional evidence favoring the similarity of this substance to ACh, including its characteristic sensitivity to destruction by an esterase that Loewi had extracted from heart muscle. The substance was later identified as the neurotransmitter acetylcholine.

Loewi also proved both the SNS and the PNS response. Yet despite Loewi's research, and despite Dale's arguments in favor of the neurotransmitter theory, many continued to argue against it throughout the 1930s.  Although this work was vindicated in 1933 when Wilhelm Feldberg and Otto Krayer demonstrated "difinitively that the stimulation of the vagus nerve liberated ACh into the coronary vasculature of mammals." (2)

As a reward for their hard work, Dale and Loewi received the noble prize in 1936 "for their work on chemical transmission of nerve impulses."  (2) Despite all this research and improved wisdom of how drugs work, the next effective synthesized version of adrenaline was not available until 1949 when Isoproterenol was synthesized.  It ultimately would become the most popular asthma drug during the 1950s through the 1970s.

Further reading:

1. 1901: Epinephrine (adrenaline) discovered
2. 1833-1957: Research leads to asthma rescue medicine
3. 1900-present: The evolution of rescue medicine
4. How does respiratory medicine like epinephrine, albuterol, levalbuterol work? (The updated wisdom)

References:

1. "Sympathetic Nervous System," sciencedaily.com,, accessed 3/7/13 
2. Rubin, Ronald P., "A Brief History of Great Discoveries in Pharmacology: In Celebration of teh Centennial Anniversary of the Founding of the American Socieity of Pharmacology and Experimental Therapeutics," Pharmacological Reviews, December, 2007, vol. 59, no. 4, pages 289-359 (This article provides a good history of the discoveries of the sympathetic nervous system, the neuromuscular synapse, and how hormones such as adrenaline work)
3. McFadden, E.R., "A Century of Asthma," American Journal of Respiratory Critical Care, August 1, 2004, volume 170, no. 3, pages 215-221
4. Sneader, Walter, "Drug Discovery: A History," 2005, Wiley, Great Britain,  page 155-157. (Sneader provides a very thorough history of the discovery of hormone therapy in the later portion of the 19th century.)
5. Sander, Mark, "Inhalation Therapy: An Historic Review," Primary Care Respiratory Journal, 2007,  16 (2), pages 71-81
6. Valeri, Andrea, Carlo Bergamini, Rocco Bellantone, Celestino Pio Lombardi, editors, "Surgery of the Adrenal Gland," 2013, New York, London, Springer