Monday, March 18, 2013

5000-50 B.C.: Asthma in Ancien Egypt: the Ebers Papyri

Facsimiles from the Ebers Papyrus in Egyptian Hieratic characters,
the upper containing three, the lower eleven dental prescriptions.
From Walter Libby's 1922 book on the history of medicine (12, page 6)
In the early 19th century an old scroll was discovered between the legs of a mummy in Assasif, which is in the necropolis of Thebes on the west bank of the Nile River in Egypt. It was soon noted to be one of the longest medical papyri known to history, and it is very well preserved, and even includes the notes of the owner in the margins.  (1, page 1517)  It is from this ancient text we find our first known description of asthma-like symptoms, and our first asthma remedy.

This old Egyptian scroll was purchased in Luxor in 1862 by Edwin Smith, who also purchased another famous scroll, the Edwin Smith Papyrus, at about the same time. It is unknown to history by whom Smith purchased it from.  It's also a mystery what tomb it came from considering the person who found it had passed away before it was learned the significance of it.  However, it's believed to be from the tomb of a doctor, and some speculate it came from the same tomb as the Smith Papyrus (3, page 30)(10)

The scroll was purchased by Egyptologist George Ebers in 1873.  When he came into possession of it, "it consisted of a single, tightly rolled piece of the finest yellow-brown papyrus. The width of the document was 30 centimeters, and the length of the written part 20.23 meters. No other papyrus known to Egyptologists is better preserved." (10)  He had it translated and published, and from here on out it has been referred to as the Georg Ebers Papyrus. (3, page 30)  Ebers gave the original scroll to the University of Leipsic "for safe keeping," and where it an be observed by anyone who visits the museum.    (10) It remains there to this day (at least as of 3/17/13).

The 20.32 meter long scroll consists of 108 neatly organized columns of 20-22 lines written in hieratic*. This text is printed in black ink.  Each column is numbered (the rubrics) and printed in red ink (that contained red lead).  (4, page 49)(5, page 311)(10)

Unlike other ancient Egyptian texts which were only fragments of larger texts, the Ebers Papyrus is believed to be a complete text.  (4, page 49)(5, page 311)  Fielding Hudson Garrison, in his 1922 book, "An introduction to the history of medicine," explains that the  papyrus appears to be written "edition de luxe, as it is prepared for some great temple." (4, page 49)

Yet by the time it was translated and determined to be the most important ancient medical texts of all time, (2, page 17) the person who found it was dead. Even the person who sold it to Edwin Smith remained a mystery, so where the document was actually found may never be known.  (3, page 30)

Translating the text proved to be complicated, as many of the Egyptian descriptions of ailments and remedies proved hard to translate into modern languages.  Dr. Joachim translated it into German in 1890, and this was translated into English in 1930 by Dr. Cyril Bryan.  Later, in 1937, Dr. Ebbell attempted another English translation and he appeared to be bolder in his translation, and it is from here that we come to our belief that this great document describes symptoms of modern diseases such as diabetes, angina, jaundice and asthma.  Other experts have criticized Ebbell for overly using his imagination in his interpretations. (3, page 30)

Some passages in the text refer to past Egyptian Pharaohs going all the way back to the First Dynasty of around 3400 B.C., wrote Dr. Elliot Smith in his introduction to Bryan's translation.  Although, he says, the mentioning of such names is unreliable in dating because tying script with known names was common among ancient societies in order to garnish credibility.  The document was ultimately dated thanks to experts who were adept at dating the methods of Egyptian writings. (9, page xii, xv)

So the document is dated to about 1550 B.C.  Considering there is a description on the back side of the scroll of Amenhotep I, (1, page 1517)  who lived around 1500 to 1526 B.C., these dates are also frequently noted.  

Either way, due to passages that date back to the First Dynasty, it is clear that the content dates farther back than when the scroll was written.  It was this observation, perhaps, that inspired the imagination of Georg Eber to speculate that the document might have been a copy of the last six of the Hermetic texts, which are thought to contain medical wisdom from the god Thoth (referred to as Hermes by the ancient Greeks).

Thoth was the moon god, and he had a significant role in medicine (similar to Apollo in ancient Greece).  It is believed he talked to an Egyptian priest (or priests) during the early ages of Egypt, and this priest wrote down the wisdom he learned from the god.  There are various references to these documents by various physicians, although the original texts have long disappeared.  (2page 19)(4, page 49)

However, this theory, and others like it, were ultimately believed to be untrue, as experts now figure the document to be an encyclopedia of sorts of medical wisdom from various ancient documents. Smith Quotes Warren R. Dawson from his 1929 book "Magician and Leech" as saying the Ebers Papyrus is basically a compilation of recipes for the various ailments of that time taken from various other books that are "many centuries older."  Dawson says the Ebers Papyrus "is not a book in the proper sense of the word: it is a miscellaneous collection of extracts and jottings collected from at least forty different sources. It consists mainly of a large collection of prescriptions for a number of named ailments, specifying the names of the drugs, the quantities of each, and the method of administration."  And, as noted above, a few sections deal with diagnosis, symptoms and anatomy. (9, page xv)

This theory may be supported by the fact the papyrus has scribbles in the margins, such as  "this is a genuine remedy," or "Excellent.  I have often made it, and also proved it," according to Withington.  (2, page 17)  Perhaps notes similar to these were scribbled next to our description of our first inhaler:
Thou shalt fetch 7 stones and heat them by the fire, thou shalt take one therof and place (a little) of these remedies on it and cover it with a new vessel whose bottom is perforated and place a stalk of a reed in this hole; thou shalt put thy mouth to this stalk, so that thou inhalest the smoke of it.  Likewise wit all stones.  Thereafter thou shalt eat something fat, of fat meat or oil." (6, page 9
It is unclear exactly what herbal preparations were used, although its' probable that they used stramonium, belladona, henbane, and bitumen to "alleviate catarrh and coughs, and ease breathing," according to Mark Jackson in his article, "'Divine Stramonium': The Rise and Fall of Smoking for Asthma." (14, page 174)

One major difficulty with interpreting these old documents, or so the experts say, is that it can sometimes be difficult to translate Egyptian writing into our modern language. This in mind, I think, therefore, I can honestly say there is scanty evidence this Egyptian "inhaler" was used for anything more than a priest-physicians's trick to fool a patient into thinking something was being done, perhaps by the magic of the gods.

Henry Sigerist, in his 1951 book "A History of Medicine: Primitive and Archaic Medicine," notes that "Fumigations were not infrequently used in the treatment of anus and vagina and a recipe of the Berlin Papyrus (and Ebers Papyrus) tells us what the technique was.  Seven bricks were heated, and the cold drug was poured over one after another while the patient was held over the developing fumes."

My point here is we must be careful in thinking any inhalers or fumigation used by the ancient Egyptians was anything more than just something that was not' understood being used for an ailment that was not understood.  According to Mark Jackson, in his 2009 book "Asthma: A Biography:"
While Ebell's specific interpretation has been challenged by other translators, the papyrus certainly appears to list remedies to remove phlegm, alleviate catarrh, coryza, and coughs, and to ease breathing.  Significantly, Egyptian treatments for respiratory conditions included not only the oral consumption of a variety of concocted vegetable, mineral, and animal products but also the delivery of active substances directly to the lungs by inhalation."  (13, page 38)
So, as you can see, we could easily use our imaginations here as it comes to the treatment of asthma in ancient Egypt.  You are short of breath, you call for a physician, and a specialist comes to your house.  You hope he's an Internist who specializes in diseases of the chest, and you hope he has knowledge to this primitive inhaler, and that he also has a medicine called Belladonna that he tosses on those heated bricks.  Belladonna would take the edge of by easing both your breathing and your mind.

According to Sigerist the teeth where food enters and the anus where food exits were highly regarded by the ancient Egyptians.  Sigerist even notes various references to "the holy anus," and "shepherd of the Anus."  These shepherds were probably physicians who specialized in ailments of the anus, such as "hemorrhoids, prolapsus recti, inflammation and pruritus of the anus."  The pharaoh had his very own anal physician to take care of it, and perhaps this physician recommended this inhaler for hemorrhoids, a remedy we might think of as purely irrational, although to the Egyptians it was most surely rational.  (Sigerist, page 317, 335)

We must realize that Egyptian physicians had scanty knowledge of anatomy, and this is true despite the fact they prepared animals for food and sacrifice, and humans for mummification.  They knew about the inner organs, and they knew about vessels and blood, but they didn't know about the relationship with these and ailments of the body.  They did not make that connection.

So they would have no idea about diseases like asthma, nor other diseases that would make a person short of breath.  Basically, all physicians could do was note the symptoms -- chest pain, short of breath, wheezing -- and what remedies seemed to work.  And, according to

Likewise, it must be understood here that Egyptian medicine was based on myth, and ailments were caused by the wrath of gods, particularly the god Isis.  So remedies, in a sense, were believed to be gifts from the gods of health and healing, such as Thoth.  They worked by magical means.  So while these remedies may seem irrational to the modern reader, they were quite rational given the medical wisdom of the time.

Once translated, the Ebers Papyrus scroll was learned to contain over 700 magical formulas as remedies for the most common ailments of that time, with various incantations randomly assorted through the text.  Some of the remedies included pills in the form of dough, herbs and minerals that were put into beer and wine, salves and oils to rub onto the skin and wounds, a salve made from honey was put over wounds, and gargles and inhalations.

If you had complained of an ailment, a physicians would be summoned.  Egyptian physicians specialized in particular symptoms, so you would see a physician who specialized in treating your symptoms. If your specialist was an internist, perhaps you would be provided with the remedy above, which may actually contain breathing relief, considering Belladonna was later proven to contain a mild bronchodilator component.

Yet, more than likely, your treatment would be a general treatment, treated the same way as any other ailment.  Since the Egyptians were among the first society to attribute sickness to good health, he might suggest something simple to cleanse your body, which may involve any of the following::
  • Enemas (the stomach was believed to be a cause of most diseases breathing problems)
  • Emetics (to vomit out the poisons)
  • Animal excreta (including crocodile and camel)
  • Herbs such as squill and henbane
  • Fumes of burned sundried and crushed Belladonna leaves and roots (as noted above)
  • Eating foods such as figs , grapes, frankincense, cumin and juniper fruit
  • Drinking wine and sweet beer 
Along with the above treatments, the following were considered routine in order to keep your body clean: (11, page 18, 23)
  • Daily baths
  • Abstinence from certain foods (like cow flesh, pigs, flatulent beans, etc.)**
  • Gymnastics
  • Linen clothing worn for cleanliness
  • Purgatives and emetics every three months to cleans body***
  • Friction and inunction of the body (basically involves rubbing certain parts of the body)
  • Fumigations (usually during epidemics to "purify the air."  
  • Inhaling steam from inhalations 
  • Careful system of nurturing from childhood
  • Incantations (magic words)
  • Amulets (to wear or keep close to you and or your home to ward off spirits and for healing)
Or, if your asthma was diagnosed as being caused by witchcraft, the following remedy may be used:
"Against all kinds of witchcraft -- a large beetle; cut off his head and wings, boil him, put him in oil, and apply to the part. Then cook his head and wings, put them in serpent's fat, warm it, let the patient drink it." (2, page 18)
If your physician didn't heal you you might consult a priest or magician who would provide you with an amulet or incantation to say each morning.  Or he might place his gentle palm over your throat or chest and chant an incantation to induce healing and scare away the evil demons that were causing you to breathe heavy.  Perhaps the good feeling of hope by this method was more healing to you than what your physician might recommend.

Another neat thing to note here is that by dating the Ebers Papyrus to around 1500 or 1550 B.C., this would place it as being written about the time of the Exodus.  That means it was probably written around the time Moses walked the earth, and the wisdom it contained was available to him.  So the Bible may provide us with another good source for learning what life was like for Asthmatics in Ancient Egypt. (see link below)

Further reading:
*Hieratic is a form of Egyptian cursive, and was used "chiefly on sacred and medical papyri and on wooden coffins... the characters are written from right to left... about 300 A.D. all knowledge of the meaning of the characters had died out, and it was not until the discovery in 1799 of the Rosetta stone (by Boussard, a French artillery officer) that any real progress was made in the decipherment." (10)

** Note that the upper classes of Egypt did not eat pig, and despite this, historians note a high incidence of hardened arteries.  One study of Egyptian mummies found hardened arteries in three fourth of the mummies studied.  While this was a recent study, some historians noted this as far back as the 1930s. You can read more about this here. Also see the comments to this post for reference. 

***While many historians noted the Egyptians to drink to excess, more modern historians think the beer and wine drank with most meals was more watered down and less potent than those of which we drink today. 

 References: 
  1. Selin, H., "Encyclopedia of the History of Science, Technology and Medicine in Western Cultures," 2nd edition, 2008, Springer
  2. Withington, Edward Theodor, "Medical History from its earliest times," 1894, London, Aberdeen University Press
  3. Nunn, John F, "Ancient Egyptian Medicine," 1996, University of Oklahoma Press
  4. Garrison, Fielding Hudson, "An introduction to the history of medicine," 1922, Philadelphia and London, W.B. Saunders Company
  5. Sigerist, Henry E, "A History of Medicine," vol II, "Primitive and Archaic Medicine," 1951, New York, Oxford University Press
  6. Ebell, B.,  translator, "The Papyrus Ebers: The Grea)test Egyptian Medical Document," 1937, Copenhagan, page 67.  I found references to this passage by Mark Jackson (Asthma: A biography," 2009, New York, Oxford University Press, page 39), and Henry E. Sigerist (see reference immediadely above, page 339).  Sigerist says that a similar passage can also be found in the Berlin Papyrus.  
  7. Reference Pending
  8. Osler, William Henry, "The evolution of modern medicine," 1921, New Haven, Yale University Press
  9. Smith, G. Elliot, introduction to Cyril, Bryan,s book, "The Papyrus Ebers," 1930, London, The Garden City Press, Bryan's book was an English translation of the German translation of the papyrus. 
  10. Von Klein, Carl H., "The Medical Features of the Papyrus Ebers," The Journal of the American Medical Association, December 23, 1905, Volume 45, page 1928, George H. Simmons, editor, volume XLV, July - December, 1905, Chicago, American Medical Association Press.  This article provides a fuller story of how the document ended up in the hands of Georg Ebers, how it came to existence, etc.  
  11. Baas, Johann Herman, author, Henry Ebenezer Sanderson, translator, "Outlines of the history of medicine and the medical profession," 1889, New York
  12. Libby, Walter, "The history of medicine in its salient features," 1922, Boston and New York, Houghton Mifflin Commpany
  13. Jackson, Mark, Asthma: A biography," 2009, New York, Oxford University Press
  14. Jackson, Mark, "'Divine Stramonium': The Rise and Fall of Smoking for Asthma," Medical History, 2010, 54: 171-194

Sunday, March 17, 2013

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:
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

Friday, March 15, 2013

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," 



Thursday, March 14, 2013

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

Tuesday, March 12, 2013

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

Sunday, March 10, 2013

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:

Saturday, March 09, 2013

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