1700 B.C.: Hebrew Bible influences medicine x

The Bible only has a few vague descriptions of diseases, and none of these vagaries are regarding our disease asthma.  However, the Bible does provide some knowledge of what life may have been like for asthmatics in ancient Egypt, Mesopotamia, and among the early Jewish Community (Israelites, Hebrews)

The Bible is believed to have been written in the 1000 years that preceded the birth of Christ (10, page 511), although the information obtained in it is believed to go back much farther.  Some some experts have actually estimated the Biblical date for the beginning of time to be 4004 B.C., (see my post: "4004 B.C.: The beginning of Time?" to be published 8/7/14).  Since the authors of the Bible were recording legends previously relayed across generations by word of mouth, the stories had to be pithy.  For this reason, actual dates may forever remain a mystery.

Hebrew history is interesting because the people were nomads, meaning they had no home, or at least they were in search of a home.  Where they came from and why they left remains a mystery, and this is true of many of the societies that made their way to Egypt and Mesopotamia.  Because the Hebrews were nomads,  they lived among, and therefore were influenced, by the various cultures they came into contact with.  Among these cultures were those present in and around ancient Mesopotamia and ancient Egypt.

The Babylonians believed that all disease was punishment from the gods, and some speculate this is why the Jews/ Hebrews likewise believed that their God, the only God, was responsible for causing all diseases and healing all diseases.  Through priests, who acted as mediators, the Hebrew God healed, or he allowed the prophets to heal.  (5, page 28)

The Hebrew were held captive in Egypt for several centuries prior to the exodus around 1550 B.C., and they were also held captive in Babylon around 604 B.C.  So there are various references to both the Mesopotamian and Egyptians medical beliefs, providing evidence that the early Jews were influenced by both.

Fielding Hudson Garrison, in his 1922 history of medicine, explains that:

In the Old Testament, disease is an expression of the wrath of God, to be removed only by moral reform, prayers and sacrifice; and it is God who confers both health and disease: 'I will put none of these diseases upon thee, which I have brought upon the Egyptians: for I am the Lord that healeth thee.' (7, page 57)(Exodus 15:26)

After God gave Moses the laws, the Lord said, "If you will obey me completely by doing what I consider right, and by keeping my commands, I will not punish you with any of the diseases that I brought on the Egyptians.  I am the Lord, the one who heals you." (Exodus 15: 26)

The Bible also refers to the Babylonian method of diagnosing through hepatoscopy, or inspecting the liver of sacrificial animals.  It is by this means they diagnose through divination or omens:

"For the king of Babylon stood at the Paring of the ways, at the head of the two ways to use divination:  he made his arrows bright, he consulted with images, he looked in the liver." (Ezekiel 21:21)

There are many references to God's ability to cause sickness and to heal, such as is mentioned by Job:

"God bandages the wounds he makes; his hands hurt you, and his hands heal you." (Job 5: 18) 

Abraham, who was labeled as "Father of Israel" by Israel's God, and who set the Israelites off on a quest for the land of Canaan, the promised land, mentions it sometime around the 2nd century B.C.:

Because of what had happened to Sarah, Abraham's wife, the Lord had made it impossible for any woman in Abimelech's palace to have children.  So Abraham prayed for Abimelech, and God healed his wife and his slave girls, so that they could have children. (Genesis: 20:17)

The prophet Jeremiah, who lived in the later part of the 7th century B.C., mentions it:

"But I will heal this city and its people and restore them to health.  I will show them abundant peace and security.  I will make Judah and Israel prosperous, and I will rebuilt them as they were before.  I will purify them from the sins that they have committed against me, and I will forgive their sins and their rebellion.  Jerusalem will be a source of joy, honor, and pride to me; and every nation in the world will fear and tremble when they hear about the good things that I do for the people of Jerusalem and about the prosperity that I bring to the city." (Jeremiah 33: 6)

"I will make you well again; I will heal your wounds." (Jeremiah 30:17 

Moses, who lived around 1550 B.C., mentions it as he calls for the Lord to heal his wife Miriam:

So Moses cried out to the Lord, "O God, heal her!"  (Numbers 12:13) 

Isaiah, who lived in the 8th century B.C., believed that not only was Assyria a great threat to Judah, but so to was the sin of the people.  In the Book of Isaiah, the Lord said of the Israelites:

"I have seen how they acted, but I will heal them.  I will lead them and help them, and I will comfort those who mourn.  I offer peace to all, both near and far!  I will heal my people.  But evil men are like the restless sea, whose waves never stop rolling in, bringing filth adn muck.  There is no safety for sinners," says the Lord. (Isaiah 57:18-21)

The prophet Hosea, who lived sometime before the fall of Samaria in 721 B.C., mentions it:

The people say, "let's return to the Lord!  He has hurt us, but he will be sure to heal us; he has wounded us, but he will bandage our wounds, won't he? In two or three days he will revive us, and we will live in his presence.  Let us try to know the Lord.  He will come to us as surely as the day dawns , as surely as the spring rains fall upon the earth." ( Hosea 6:1-3)

According to Garrison priests were hygiene police, meaning that they made sure the people of Israel washed and purified their bodies in order to prevent the spread of disease.  Yet the priests, he says, did not act as physicians.  Instead, this task was left to the physician.  (7, page 57)

In the Bible the various references to magi, or physicians, or high priests are usually in reference to Egyptian or Babylonian healers  So there was definitely a crossover of the beliefs of the various ancient societies.

The Bible has perhaps the first recorded evidence that physicians existed in Egypt about 1,700  years before the birth of Christ.  When Jacob died, "Joseph commanded his servants, the physicians, to embalm him; and the physicians embalmed Israel, and forty days were fulfilled for him, for so are fulfilled the days of those that are embalmed." (1, page 26)(10, page 17)(7, page 57)(Genesis 50: 2)

Garrison explains that "the king Asa consulted physicians instead of the Lord and 'slept with his fathers' for his pains (II Chronicles 16: 12-13), or that if two men fight and one of them be injured to the extent of having to keep his bed, she or her 'shall pay for the loss of his time, and shall cause him to be thoroughly healed.(Exodus 21:19)" (7, page 57-58)

While the Bible makes no mention of asthma nor asthma remedies, although it does make perhaps the first reference to a narcotic: (9, page 9)

During wheat harvest, Reuben went out into the fields and found some mandrake plants, which he brought to his mother Leah. Rachel said to Leah, “Please give me some of your son’s mandrakes.”  But she said to her, “Wasn’t it enough that you took away my husband? Will you take my son’s mandrakes too?” (Genesis 30: 14-15)

Mandrakes are a member of the nightshade family (solanaceae) of plants that, when ingested, can make breathing easeir and cause a hallucinogenic effect, easing pain and suffering.  The sonanaceae family of plants will play a significant role later in our asthma history, although it's doubtful (althgough possible) this was used as a remedy for dyspnea in the Biblical age.

Further reading:

• 5000-50 B.C.: Asthma in Ancient Egypt, and Physicians
• 5000-50 B.C.: Asthma in Ancient Egypt, and Eber Papyri 
• 2700 B.C.: Imhotep invents rational medicine

References:

1. Renouard, Pierce Victor, "History of Medicine: From it's origin to the 19th century," 1856, Cincinnati, Moore, Wistach, Keys and Co., page 26, chapter 1, "Medicine of the Antique Nation."
2. "Moses," Catholic Encyclopedia, http://www.newadvent.org/cathen/10596a.htm, accessed 3/21/13
3. Puschmann, Theodor, translated by Evan H. Hare, "A history of medical education from the most remote to the most recdent times," 1891, London, H.K. Lewis
4. Dunglison, Robley, author, Richard James Dunglison, editor,  "History of Medicine from the earliest ages to the commencement of the nineteenth century," 1872, Philadelphia, Lindsay and Blakiston
5. Baas, John Herman, "Outlines in the history of medicine and the medical profession," translated by H.F. Handerson, 1889, New York, J.H. Vail and Co.
6. Wilder, Alexander, "History of Medicine: a brief outline of medical history and sects of physicians, from the earliest historic period; with an extended account of the new schools of the healing art in the nineteenth century, and especially a history of the american Eclectic practice of medicine, never before published," 1901, Maine, New England Eclectic Publishing, Co.
7. Garrison, Fielding Hudson, "An introduction to the history of medicine, with medical chronology, suggestions for study, and bibliographic data," 3rd edition, 1922, Philadelphia and London, W.B. Saunders Company
8. "The Assiatic Journal, for British adn foreign India, China and Australia," volume VIII, New Series, May-August, 1832, London, Parbury, Allen and Co.
9. Bradford, Thomas Lindsley, "Quiz questions on the history of medicine: from the lectures of Thomas Lindsley Bradford," edited by Robert Ray Roth, 1898, Philadelphia, John Joseph McVey
10. Prioreschi, Plinio, "A history of medicine: Primitive and ancient medicine," volume I, 1991, New York, The Edwin Mellen Press

1 A.D. to 1900: The first Dry Powdered Inhalers

Figure 1 -- Gilewski and Rauchfuss Insufflator for
dry powder application. A, compressing bulb ;
B, slot covering D, aperture into which the powder
 is inserted; C, shower of powder leaving the instrument. (1, page 340)

While we may think of dry powder inhalers (DPI), with their unique, complicated, and often expensive containers, as relatively new products.  We often think of the Intal Spinhaler, first produced in the 1960s, as the first DPI.  Yet we would be wrong.  

Galen described that the ancient physician Aesculapius blew "astringent powder into the larynx by means of a bent reed" in patients who presented with angina, or chest pain.  The medicines used were nutgall and myrrh.  This is according to John Solis Cohen, the expert of sorts on inhalation devices in the 19th century.  He described the device as "being considered something of a novelty, even at the present day."  His book on inhalation devices was published in 1876. (1, page 340)

The problem with this is the powder would be inhaled back into the oral cavity upon exhalation.  To remedy this "Czermak attached a rubber ball compressor to flexible tubing, which is compressed at the proper moment.  The patient may do this treatment by his self, although most often it's done by the physician, or some assistant. (1, page 340)

F1g. 2.—Powder Inhaler Or Insufflator With Interchangeable Tubes.
It was designed by  Lewin and Oertel 

Yet, according to Cohen, these two methods are called insufflation as opposed to inspiration or aspiration.  Insufflation is Latin for "blowing into." The patient must hold his breath after application of the insufflation, and resist the urge to exhale to improve deposition of the medicine.

Gilewski and Rauchfuss composed a good insuflator (Fig. 1), "which consists of a properly shaped tube, with a gum ball for the purpose of propelling the powder forwards. The powder is inserted into a slot in the tube, over which a tubular cover slides after the introduction of the medicine, which can be propelled in any direction desired by arranging the apertures of exit at the distal extremity of the tube"  There were various similar products composed, although none, according to Cohen, was better than the original. (1, page 340)

Cohen described a variety of insufflators, and so did his cohort, Paul Tissier.  Tissier would be our other expert on inhalation devices in the 19th century.

Lewin and Oertel devised an insuflator that, according to Tissier, "consists of a sort of horn furnished with an opening; through this penetrates a glass tube, to the outer portion of which is attached a rubber bulb; gentle manipulation of the bulb produces in the horn a thick cloud of dust, which is propelled toward the narrow end of the instrument, where it is directly breathed by the patient. In the United States there is sold an instrument (Fig. 2) to be used either with a hand-bulb or a current of compressed air from a reservoir." (2, page 446)

Bryant created an "auto-insufflator, consisting of a bent tube, having at one point an opening, which may be closed by a stopper. Through this opening the powder is introduced; one end is placed in the nose, the other in the mouth, and gentle blowing is performed. A simple rubber tube answers the same purpose. For insufflation into the larynx and trachea one uses special curved instruments. (Figs. 114, 115.) For insufflation into the pharynx and upon the tonsils any tube may be employed, such as a reed, quill, glass or rubber tube, or a special instrument," according to Tissier. (Fig. 116).

Various physicians provided various different recommendations for the medicine to be applied to the larynx for various disorders, such as hoarseness, inability to speak, and inflammation of the palate and throat.  Remedies included:  lycopodium, cinchona, acetate of lead, nitrate of silver, and tannin,  Other physicians recommend igniting the powder and inhaling the smoke.  (1 page 340)(page 448)

Two more old DPIs from Tissier's book

References:

1. Cohen, John Solis, "Inhalation in the treatment of disease," 1876
2. Tissier, Paul Lois Alexandre, "Pneumatherapy: including Aerotherapy and inhalation," 

1848: The Chambers dry powdered inhaler

Surely there were powders that were inhaled since the beginning of time.  People would sun dry and crush herbs, and then inhale the powder.  Sometimes they'd use a funnel.  One of my patients said he used to inhale asthma powder in the 1950s with a funnel he made with a magazine.

Thomas K. Chambers, in 1848, announced that he believed the inhalation of powder would allow for the direct application of medicine to the lungs, which are otherwise "inaccessible." For doing this he introduced a glass funnel of his own design specifically made to inhale a very fine powder of pollen of lycopodium or club moss with nitrate of silver or sulphate of copper, or both. (1) (2)

The device and how to use it was described by Chambers in the Boston Medical and Surgical Journal:

The patient should introduce into his mouth, as far as he can without choking, a well-dried glass funnel, and draw in his breath strongly, whilst he himself, or a second parly, dusts the powder in a dense cloud into the large end with an ordinary nursery puff-ball. If the dust is raised by an attendant, the patient can indicate the moment he inspires by raising his hand. 

To obviate the necessity for withdrawing the funnel after each inhalation, to prevent the dust being blown about the room, an apparatus with a double valve and a closed powder-box may be used, which allows the dust to pass inwards only; but the necessary employment of metal makes the machine less agreeable than the more awkward but cleanerlooking and less formidable glass.

Chambers describes that inhaling such a "dust" is an "inconvenience" and often induces coughing, yet it's better than "introducing a sponge to the larynx, as has been recommended." He also explains that the operation of the device is very complicated to use.

References:

1. Sanders, Mark, "Pioneers of Inhalation," Inhalatorium.com, a slideshow by Mark Sanders, http://www.ddl-conference.org.uk/files/DDL20presentations/19.Sanders.pdf
2. Chambers, Thomas, "Inhalation of Nitrate of Silver,"Boston Medical and Surgical Journal, February to August, 1849, Edited by J.V.C. Smith, Volume XL, Boston, David Clapp,  pages 394-5

225 - 200 B.C. Dogmatism is challenged

Even while the dogmatic school of medicine (rational medicine) was being formed at the school of Cos by Hippocratic writers, so to was forming the emperical school of medicine at the school of Cnidos (1, page 29) by the following triad:  (1, page 29) (3, page 68)(4, page 91)

• Herophilus:  (325-280 B.C.)  He came up with many of the theories followed by the school
• Philinus (pupil of Herophilus, around 250 B.C.):  Started empiric school of medicine
• Serapion (successor of Philinus, around 225 B.C.)  He supported empiricism

This school was basically established to counter the "extravagances" of the Dogmatic School of Medicine at the School of Cos.  (3, page 69)  A common saying of the empiracist was "It is not the cause but the cure of disease that concerns us; not how we digest, but what is digestible." (5, page xiii)

The major differences between these schools were as follows:  (1, page 29)(3, page 69) (4, page 68-9)

Dogmatists/ Rationalists/ Hippocratic Dogmatic School of Medicine	Empiricists/ Emperics Empirical School of Medicine
Supported ideas of the physician Hippocrates	Supported ideas of the philosopher Pyrrho
Were in search for causes of disease	Were not concerned with causes.  A person was ill is all they needed to know
Speculated on possible causes and remedies	Did not speculate
Created theories to explain causes and why a remedy will work.  Generally, diseases were caused by the body as a whole.	Did not create theories to explain anything.  If something was unknown, it was left at that
Cures were based on the theory postulated.	Cures were based on experience.  If something worked in the past, it will work today.  Medicine not based on experience could injure
They had few remedies, many of which were harsh, such as bleeding, purging, and vomiting	They had many remedies, and they were generally friendlier than dogmatist remedies and probably worked better
They believed anatomy was important to understand the physiology of disease	They despised anatomy and physiology.

Serapion was the most outspoken of the empirics, and "he wrote with great vengeance  (1, page 29), as he said:

"What is the use of  knowing the shape and position of the brain and liver, or whether there are such things as brains or livers at all."  (4, page 68)

Another common saying of the empirics was:

"It is not the cause, but the cure of diseases that concerns us; not how we digest, but what is digestible." (4, page 68)

Galen wrote about Serpion the empirist in his Outline of Empericism: (2, page 161)

Of the ancients, however, Hippocrates, Erasistratus, and Herophilus have stated nothing about the treatment suffering from the disease (i.e. lethargy).  But Serapion the Empericist, in Book 1 of his treaties Against the Haireseis, gave some instructions (about this) which are, however, too obscure to be reported here.

Serapion thus became an experimentalists.  He experimented to see what drugs worked best for said disease.  He recorded and made conclusions based on his own observations and experiments, as opposed to coming to speculative conclusions.  (1, page 30)

As described by Edward Withington:

"In short, they (empiricists) reduced the whole art and science of medicine to a system of therapeutics.  A person is ill, that is, he has certain unpleasant feelings or symptoms; surely the first thing to do is to find something which will remove them, and the whole duty of the physician is to discover what particular treatment, and especially what drugs, will get rid of particular sets of symptoms."  (3, page 68-9)

The way to do this is based on the "tripartite foundation" (1, page 30) of the following three methods:  (3, page 69)

1. Experience:  His own experience and observations
2. History:  Learning from the experience and observation of his contemporaries and  predisessors
3. Analogy:  Drawing conclusions based on similar situations to find remedies for new and strange cases

 And thus was formed the Empirical school of medicine.

The empirics were essential to this time because they created an important alternative to the dogmatists, some of whom (see Erasistratus) performed autopsies on live convicted criminals to see what organs did during life.  Hopefully, as some reports suggest, many such victims were given a large dose of morphine before the procedure.  Yet still it was considered inhumane and irrational by the empiricist, and reasonably so.

While the dogmatists based their remedies on speculation, the empiricists used only remedies that were shown by experience to work. This was a viable alternative to the extreme remedies of bleeding and purging used by many dogmatists.  The empiricist also added quite an array of new remedies, including opium and sulpher.

The dogmatists became known as rationalists due to their desire to rationalize diseases and their remedies.  They believed "everything must have a sufficient reason for its existence," Empirics believed what can be observed by experience is known, and what is not known is not to be speculated upon.

References

1. Meryon, Edward, "History of Medicine: comprising a narrative of its progress from the earliest ages to the present and of the delusions incidental to its advance from empericism to the dignity of a science," volume I, London, 1861,
2. Eijk, Philip J., editor, "Ancient Histories of Medicine: essays in medical doxography and histeriography in classical antiquity," 1999, Boston,
3. Withington, "Medical History from it's Earliest Times: a popular history of the healing art," 1894, London, The Scientific Press
4. Watson, John, "Medical Profession in Ancient Times: an anniversary discourse delivered before the New York Accademy of Medicine November 7, 1855," 1856, New York, Baker and Godwin
5. Brock, John, "Galen on the natural faculties," 1916, London, New York, William Heinemann, G.P. Putnam's Sons

2013: Is asthma really a neurosis?

In doing my asthma history, one of the first things I learned about the disease was that it was considered a nervous disorder, or a neurosis, for most of history.  When I learned this I was offended.  I was actually mad.

It brought me back to a time when I was a kid and my older brother called me a "useless waste of skin" because I was unable to play football one day.  Learning this also took me back to back to 1985 when I was a patient at National Jewish Health/ National Asthma Center, and instead of being discharged after 6-8 weeks as I was told, I was admitted to 2-May for further psychological evaluation.

The booklet for 2-may defined the unit as:  "'2-May is a 24 bed medical/ psychiatric floor divided into 2 units of 12 patients each. It is a patient care area for children who need extended treatment for psychological and family problems which may be related to chronic asthma.'" 

I had to read and sign a contract before being admitted to 2-May, and the following is what I agreed to:

1. Better control of my asthma
2. Work on learning to control feelings of anxiety

I had a hard time admitting the later, although I agreed to it because I wanted to avoid further debate.  Yet I really had a hard time with 2-May being referred to as a "psychiatric floor."  The irony of this is I had been seeing a psychiatrist weekly, and working with a social worker daily, and yet the transition to 2-may continued to be a major issue for me.  

In the end, though, fears don't amount to much, as I ended up liking it on 2-May.  I never accepted my psychologist, although every other part of it went rather well.  Still, when I was discharged in July of 1985, it was almost 25 years before I would talk about my time there.  I was actually embarrassed for having spent time in a psychiatric unit.  

Yet in retrospect, I see how it really benefited my life.  In retrospect, and after further studying the history of asthma, I now accept that asthma was considered a neurosis at an early age.  Scientists during the 19th century pretty much just assumed asthma was a neurosis, especially after Henry Hyde published his writings "On Asthma" in the 1950s.  Salter defined asthma as a disease of airway spasms and as a nervous disease.

As far back as the 19th century asthma physicians realized there was no permanent scarring in the lungs or anywhere else in the body of people who died of pure asthma.  There was something "invisible" going on, and the only rational way they could explain it was to call it a neurosis.  Back then, if the disease left no scars, such as epilepsy and asthma, it was a neurosis.  Even arthritis was referred to as a neurosis, because there was no underlying explanation for why it was caused.

But the immune system was not well understood until after the turn of the 20th century.  The immune system is rather invisible unless you have the ability to study and analyze the various hormones of the body, of which these physicians did not. So, in my opinion, it was fine for them to refer to it as a neurosis.  To them, any action by the immune system would simply be explained by some flaw of the mind.  

Once asthma was determined to be an auto-immune disease by the 1950s, and once it was learned that the bodies over-reaction to triggers in the environment in and around the individual, the nervous theory of asthma was disproved.  

And despite this understanding, by the 1980s it was observed by asthma physicians that poorly controlled asthma continued to effect the psychology of the person involved.  For example, if you are suffering from poorly controlled asthma and allergies, you won't be able to do things normal people do.  You won't be able to spend time with your dad in the woods.  You won't be able to participate in gym class and sports.  And when you did, you suffered as a result.  

And such suffering often results in psychological consequences.  Kids would pick on me and other asthmatics because we were different.  It was observed long ago that asthmatics tend to spend more time with women and their mothers.  It was observed asthmatics were more likely to cook and read, as opposed to do normal masculine activities.  So such hardluck asthmatics would need help catching up to his peers.

And that's what my doctors saw back in 1985.  That's what I interpret out of reading the reports of my psychologists.  Today there are much better asthma medicines, so asthma is much easier to control.  For this reason, most asthmatics shouldn't be psychologically deprived in this way.  Yet I'm sure there continue to be cases of hardluck asthma where the nervous system is involved.

For example, I continue to have anxiety.  And, based on studies that I have read, a large portion of asthmatics have anxiety.  Some studies link asthma and anxiety.  Surely the asthma attack will provoke some anxiety, but I'm talking about between the attacks.  Some modern experts believe asthma is more than just the lungs, that also involved the stomach, and the mind.  Yes, asthma continues to be a nervous disease.

So the 21st century is much like the 19th and 20th centuries where physicians and scientists continue to come up with new scientific evidence, new medicines, and new theories about the disease.  The debate as to what asthma really is may not be solved for many years to come.  

But the nervous component is obvious.  When a person is diagnosed with asthma, or has a long history of the disease, a wise physician must also consider the nervous component of the disease too.  And this is important, I think, because most people aren't open about this aspect.  Most people think of nervous disorders as bad and embarrassing, when in truth they are diseases, or, in the case of asthma, part of the disease.  If diagnosed properly, they can be treated.

Keep in mind here that this is just my opinion.  However, I base on my study of the history of this disease, the scientific evidence available up to this time, and my own experience with this disease (43 years and counting).

Today I openly discuss my experience at what is now called National Jewish Hospital.  I also have no problem with asthma being considered a nervous disease, and for the reasons as noted above.  If anything, I am now proud for my experience there.  I feel very fortunate.  I see how that place has benefited me, as I note in this post. 

Further reading:

1. 1985:  The horror that was 2-May (part II)
2. 1600:  Creation of nervous and spasmotic theories of asthma
3. 1650:  Asthma could get you absolved from crimes
4. 1800-1900: What asthma theory won the era?
5. 1850:  Asthma is a disease of the mind
6. Seven ways asthma has benefited my life

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

50-400 A.D.? Antyllus describes asthma remedy

Of his writings we have none.  Of his life we know nothing.  When he lived we know nothing.  When and where he practiced medicine we know nothing. Yet we do know he was a physician and surgeon who lived in the 2nd century, and that he wrote about asthma.  His name was Antyllus.  

Galen diligently collected the works of all medical writers who came before him, yet of Antyllus he wrote nothing.  So if he lived before Galen as some speculate, one might wonder why Galen ignored him.  So another theory is he lived after Galen.

For preserving the ideas of this surgeon we owe thanks to Oribasius of Pergamus.  He quoted many medical authorities prior to his time, including the works of physicians we would otherwise know nothing of, such as Oribasius.  (5, page 129)

Some speculate he lived as late as the Roman Emporor Velerium who ruled Rome from 260-264 A.D.  (1, page 129, (3, page 11).  Still others speculate he lived as late as the fourth century. (2, page 124-5)

Regardless, he must have held a reputable reputation in the medical community because he was written about by many writers, including Oribasis, Aetius, Rhazes and Paulus Aegineta.  Oribasis was the first to write about him, so this used as a baseline for dating his life. (2, page 125)

What he did for the medical community we can gather some hints.  Aegineta was the first to mention a technique for performing the operation of tracheotomy, and credits Antyllus for educating him on the best method of doing this.   (2, page 124)

He's also credited as being among the first to describe a method of surgically treating aneurysms.  Overall, his his "works seem to be useful and interesting, as it contains some of the most valueable surgical observations that have come down to us from antiquity." (2, page 124)

Regarding asthma we have gathered some knowledge from Antyllus, and for this we are thankful to John Watson for bringing this knowledge to us in his book, "Medical Profession in Ancient Times," as noted here:

He treated humid asthma with suffumigations, placing the patient in such a position as readily to inhale the fumes from particles of aristolochia (treats edema) or clematis (mild diuretic) previously sprinkled over burning coals in a chaffing-dish or brasier."  (4)

References:

1. Watson, John, "Medical profession in ancient times: an anniversary discourse delivered before the New York Academy of Medicine November 7, 1855," 1856, pages 128-129
2. "Biographical Dictionary of the society for the diffusion of useful knowledge," Longman, Brown, Green and Longmans, volume III, 1843, A. Spottingwood, London
3. Peters, John C., "On Sects in Medicine read before the Medico-Legal Slociety of New York, 1870," 1874, New York, J.R. McDivitt, Law Publisher
4. Watson, John, op cit, see page 129, and also see reference 3 above (Peters, John C., page 11)
5. Withington, Edward, "Medical History from it's earliest times," 1894