1213-1644: The discovery of gases and basic anatomy

Roger Bacon was perhaps the first to conceiveof the idea that a substance,
later called carbon dioxide, was in the air when cellars where grapes
were fermenting. He does not get creditfor the discovery of CO2, however.  

Even though Galen's theories about air held sway over the scientific community, there were various great minds along the way that doubted Galen, and based on their own observations, set out to perform experiments that would prove Galen wrong.

Roger Bacon (1213-1294) was born in Kilchester in Somersetshireto to a wealthy family when Henry III (1207-1272) was the King of England.  He spent 8-10,000 pounds performing his own experiments, went to Oxford, "where his great abilities were soon recognized."  He then moved to Paris, "the center of intellectual learning at the time," said historian Thomas Bradford. (14, page 112)

He was "disgusted with the superficial scholastic methods at the time, and devoted himself to the study of languages and experimental research," said Bradford.  (14, page 112)

Bradford said he ended up back at Oxford by 1250 and found himself a member of the Fransiscan order. (4, pages 112-113)

 "His fame spread at Oxford, although it was whispered that he had dealings in magic and the black arts.  Some doubts of his orthodoxy were expressed, and in 1257 Bonaventura, the General of his orders, forbade his lectures at Oxford, and commanded him to leave the town and place himself under the command of the body in Paris.  There he remained for ten years under constant supervision, suffering great privations, and not allowed to write anything the might be published." (4, pages 112-113)

During his life there was much scorn and animosity toward the medical profession and science in general, although somehow he gained the respect of Pope Clement IV (1195-1268) who "wrote to Bacon ordering him, notwithstanding the interdict of his superiors, to write out and send him a treaties on the sciences.  Previous to this he, discouraged, had composed but little; but taking heart of grace and despite of the many obstacles thrown in his way by the jealousy of his superiors and brother friars, he completed in 18 months three large treatises, the Opus Magnus, Opus Minus and Opus Tertium. In 1268, Bacon was released and allowed to return to Oxford, where he continued his labors in experimental science, and in completing his numerous treatises. He wrote a great many works on alchemy, philosophy and physics." (14, page 113)

So Bacon's life is yet another example of how hard it was for great minds in this era to perform experiments, and to get their works published.  However, he made the observation that air in cellars where grapes were fermenting was not normal, and prolonged exposure resulted in mental changes and possibly death.  He determined there was a substance in this that he called gas sylvestre.  This gas later became known as carbon dioxide.

Perhaps among the most significant contributions to science came from Nicolaus Copernicus (1473-1543), who in 1543 discovered that the planets revolve around the sun.  Out of fear of persecution, his works weren't published until after his death, although they had an astounding impact on other great minds, thus opening the door for the scientific revolution that followed.

In 1609 Galileo Galilee  (1564-1642) invented the telescope,  (11, page 255), and continued on to make astronomical observations that supported the works of Copernicus.  He had the courage to face the dogmatic Church, and published his works during his lifetime.  As a result, he was arrested for heresy and spent the rest of his life under house arrest.  His energy, courage and sacrifices, however, made him a significant player in the scientific revolution.  By history, he is considered among the fathers of modern physics and science.

Garrison notes that the works of investigators such as Copernicus and Galileo, and other such great men, also had an impact on medicine.  For example, in 1600 Galileo invented a "rude thermometer or thermoscope, and as early as 1600 (Johannes) Kepler had used pulse-counting to time his astronomic observations."  (11, page 258)

Surely investigators studied the stars and planets, they also studied plants, animals and humans, learning much about anatomy, how life is created and sustained, and about diseases.  Also investigated was the air we breathe, and its relationship with the sustenance of life.

For instance, in 1541 Paracelsus (1493-1541), a Swiss Alchemist, suggested that a substance in air was essential for sustaining life.  (6)  Another great example is Johann (Jan) Baptist van Helmont (1577-1644), a man who greatly appreciated the works of Paracelsus, and who performed tests on this substance, and he "recognized its true origin and defined its principle characteristics."  (1, page 19)

Van Helmont is also the first to use the term 'gas.' as something "distinct from air and water vapor."  (2, page 40) (1, page 19)  He believed that when God created Heaven he thus created water and air.  Van Helmont performed a variety of tests to prove that water was separate from air, and that water could not be turned into air.  He determined that air could be compressed and water could not, and he also deduced that "air could be reduced to one-half of its original volume under pressure."  (3, page 96)  

He likewise observed that water could be metamorphosed into ice, vapor and gas (his new term).  (4, page 64)  He knew he had a substance that was not water and not vapor, and he knew he had to come up with a term to describe it.  So he used the term "chaos," shortened it a bit, and came up with his new term 'gas."  He explained that "I have called this mist Gas, owing to its resemblance to the Chaos of the Ancients." (5, page 179)

Elizabeth Potter, in her 2001 book, explains that "Experimentally, we see that when the flame of a candle burning on top of a water surface and enclosed in a cylinder has consumed the air, the water rises in the cylinder and extinguishes the candle.  Helmont argued that the otherwise empty space within the air contains magnale or spirit of the air.  This Magnale is also a third thing between spirit and matter, and it, not air, keeps us alive when we breathe." (3, page 96-7)

Out of fear of persecution, van Helmont's works weren't published until after his death in 1648 by his son. Van Helmont has since become known as the founder and father of pneumatic chemistry.

Another interesting tidbit about van Helmont was that he is believed by many historians to be the first physician to oppose the Hippocratic humoral theory of disease, that diseases were caused by an imbalance of the four humors: blood, phlegm, black bile and yellow bile.  He was also the first to oppose the four elements so duly championed by Aristotle, of earth, fire, water and air.  Instead, he created some of his own theories based on his experiments.  For example, he believed the two primary elements were water and air.

Robert Hooke discovered the respiration
was not to keep the circulation of the
blood moving.

In 1553 Michael Servetus (1509?-1553) discovered that blood circulates through the body.  He accurately diagrammed the flow of blood through the body, and explained that the lungs cause the arterial blood to be a brighter red in color, and not the heart, as Galen taught.   (7, page 474)

He was also the first to speculate that blood does not cross through a septum (or invisible pores) from the right ventricle to the left ventricle as Galen had suggested, but takes another route. He described that the blood entered the left ventricle during diastole, and this is where the "vital spirit" is formed, and from there it travels to the arteries. (8, page 63-64)

In this way he was the first to suggest that the blood must go through the lungs in order to get to the heart.  For being so brave to announce his suggestions that were opposed to the mighty Galen, he was burned at the stake.  (15, page xxiii)

Severetus's pupil, Andreas Vesaleas, was the first person to publish an accurate anatomy of the body.  He performed autopsies, and had a painter paint what he saw.  He erred in believing that the  purpose of circulation was to cool the blood.  (7, page 474)(11, page 243-4)

Vesaleas also used bellows to push air into the trachea of an animal, and this experiment was later used by Robert Hooke (see below) to prove that artificial respirations could be used to keep a person alive.

Vesaleas is considered by many as the modern father of anatomy, and you can read more about him by clicking here.

Another student of Servetus  was Realdus Columbus (1516-1569).  He was a surgeon and professor of anatomy at Padua from 1544 until his death in1569. He continued Servetus's work on circulation of the blood, describing the passage of blood from the vena-cave to, through the pulmonary circulation, and then through left ventricle and aorta. (8, page 70-71) Columbus also saw that blood changes in the lungs.  (11, page 243)

Andrea Cesalpino (519-1603) was the first to describe the idea that blood circulates through the body.  But he usually doesn't get credit for this observation because he failed to prove it.

William Harvey (11, page 242)

Continuing the work of Servetus was William Harvey (1578-1657).  Bradford said he was born in 1578, at Folkestone in Kent, and by the time he was ten-years-old he was accepted at Caius College, Cambridge, in 1593.  He studied there fore five years, then traveled to France and Germany, and then studied at the "celebrated" medical school at Padua. (14, page 119)

Bradford said that he studied under some of the most renowned anatomists of the era, including Dr. Fabricius.  14 page 91)(15, page xxiii)

Hieronymus Fabricius (1537-1619) studied the venous system of the human body, and discovered membranous folds that he referred to as valves.  He speculated that these allowed blood to flow upward.  Since the blood pressure was lower the farther blood gets from the heart, these valves were necessary to prevent gravity from pulling blood on it's way back up the legs to the heart and lungs from being pulled back down to the lower legs and feet (and thus causing dropsy of the feet). (14, page 92)

In other words, his discovery of valves made Fabricus wonder if the blood circulated as opposed to moved in a to and fro motion as Galen had suggested.  But whether this was true or not would be left to one of his students to determine, and that student so happened to be William Henry. (14, page 93)(15, page xxiii)

Some say he lectured by candle light.  Perhaps it was in this "light" that William Harvey was introduced to veins and valves.  This wisdom, coupled with the enthusiasm of his instructor, inspired Henry to further investigate these veins and valves to learn more about them. "Perhaps," Harvey must have wondered, "Fabricius is right, that the blood does circulate." (14, page 119)

Bradford said he graduated from Padua in 1602 and began a practice in Cambridge in London.  Then, in he became a physician at Bartholomew's Hospital, and in 1615 became professor of anatomy and surgery at the college.  It was here began his own anatomical research.  (14, page 119)

Like Andreas before him, he wasn't satisfied with the current method of just speculating about the movement of the blood and heart, or that assuming it was knowledge only God was privy to. He studied the heart and vessels, and came to the conclusion that the heart was a pump, and it circulates the blood through the body. (9, page 168-169)

Of course, once Harvey published his discovery, his medical practice took a hit, and he was criticized by a dogmatic medical profession.  However, in the end, Harvey would be proved right, and his ideas (of course based on science as opposed to theory) would win out, and he lived long enough to see his theory become accepted, according to Fielding Hudson Garrison in his book "Introduction to the history of medicine." (11, page 246) (also see 14, pages 119-120)

Garrison describes "William Harvey" as the "greatest name in the seventeenth century... and whose work has exerted a profounder influence upon modern medicine than that of any other man save Vesalius.. it was the most momentous discovery since Galen's time." (11, )  However, his view that the purpose of breathing was to cool the blood "retarded the development of the true physiology of respiration for a long time." (11, page 242-244)

Garrison further explains that Harvey's proof that all blood passes through the lungs, and circulates around the body, made it possible for physiology to become a "dynamic science."  It was through this discovery, one that barely eluded so many other eyes, that made it possible, for one thing, later investigators to inject dyes and other solutions into the vessels that resulted in many anatomical discoveries, such as:  (11, pages 244-248)

• Lacteal Vessels by Gasparo Aspelli in 1622
• Thoracic Duct by Jean Pecquet 
• The Pancreatic Duct by Georg Wirsung in 1642
• Circle of Willis in by Thomas Willis in 1664
• Capillaries in the lungs by Marcello Malpighi in 1661 (see below)

While his comrades initially rejected his theory that blood circulates through the body, King Charles "took great interest in these discoveries and witnessed several experiments.  Several years after he made this discovery, and when he was 50 years old, he wrote a book defending his discovery.  Perhaps it was due to his friendship with the king that his ideas were accepted before his death in 1657. (14, page 119-122)

Of course each of these discoveries dispelled some ancient myth about the flow of substances through the body.  For instance, Galen believed the purpose of "veins and lymphatics of the intestines carried chyle to the liver, according to Garrison.  This theory of Galen was disproved by the above discoveries, all thanks to the discovery that blood circulates through the body by Harvey.  (11, page 246-7)

Galen believed the pulse would help determine changes in the pneuma, indicating disease.  Harvey, on the other hand, described that the beating of the heart correlates with the pulse felt at the various points on the body. As the pulse is felt, this is when blood is forced through the many vessels of the body during contraction of the heart. The heart then relaxes, and this is when the heart receives blood. The strength and force of the pulse, therefore, is a direct correlation to the strength and force of the heart.(9, page 168-169)

He generally agreed with Columbus that the right ventricle of the heart pumps blood to pulmonary artery to the lungs where the blood is nourished, and the left side of the heart pumps blood to the various arteries of the body. As quoted by Osler:  (9, page 170)

"I began to think whether there might not be A Movement, As It Were, In A Circle. Now this I afterwards found to be true; and I finally saw that the blood, forced by the action of the left ventricle into the arteries, was distributed to the body at large, and its several parts, in the same manner as it is sent through the lungs, impelled by the right ventricle into the pulmonary artery, and that it then passed through the veins and along the vena cava, and so round to the left ventricle in the manner already indicated." (10)

Marcello malpighi was the first to observe
capillary anastomosis, although he did not
attach importance to it.

While the Fabrica opened the eyes of the anatomist, the discovery that blood circulates inspired the anatomist to learn more about the physiology, or the functions of the body.  In this way, he inspired people to learn more about medicine, and how medicine affects the various organs of the body.  He therefore is referred to by many as the modern father of medicine.  (15, page xxiii)

One of the main limitations that nearly brought his research to a "standstill" was the inability to see the microscopic capillary anastomosis, which are the microscopic connections joining veins with arteries.  (11, page 245)

Marcello Malpighi (1628-1694), professor at the University of Bologna, discovered the alveoli and capillary in 1661, and observed exchange of air from the lungs to capillaries in a frog.  (7, page 474)  (14, page 142)

In 1665 he discovered blood corpuscles, (14, page 142) or what we refer to as red blood cells.  These cells are the main constituent in blood, and their main responsibility to is carry oxygen through the blood stream to the various organs of the body.

Garrison said that this was the missing link that Harvey was looking for regarding the complete circulation of blood through the body.  (11, page 247)

Malpighi's discover was verified by later observations:

• Dublin professor William Molyneux observed the capillary system in lizards in 1683.  
• Anton von Leeuwenhoeck (1632-1723) observed capillaries in the larvae and feet of frogs in 1688
• William Cowper "saw the passage of the arterial into the venous current in the mesentery (membrane that attaches the intestines to the abdominal wall) of a cat in 1687 (14, page 142)

Getting back to Harvey, there was more good than harm that came out of the brilliant mind of Harvey.  For instance, Garrison notes the following, which is significant to our history:

The most brilliant outcome of Harvey's experimental method was in the clearing up of the obscure matter of the physiology of respiration... Before Harvey's day, men still believed, with Galen (and even Vesalius), that the object of respiration was to cool the fiery heart, the purpose of the chest movements being to introduce air for generating vital spirits by the pulmonary vein, and to get rid of the heart's smoky vapors by the same channel. This Galenic notion was not a mere piece of symbolism, as in Richard Crashaw's (1612-1649) poem on St. Teresa (The Flaming Heart), but was part and parcel of actual belief about the physics of the circulation. "Before Harvey's time," says (Sir Clifford) Allbutt (1836-925), "respiration was regarded not as a means of combustion but of refrigeration. How man became such a fiery dragon was the puzzle." Harvey's demonstration showed that the blood is changed from venous to arterial in the lungs, but beyond that point, as even (Samuel) Pepys (1633-1703) has recorded in his Diary, no one could tell how or why we breathe (13, page 266)

Per Garrison, Pepy's wrote regarding respirations:

But what among other fine discourse pleased me most was Sir G. Ent about Respiration; that it is not till this day known or concluded among physicians, nor to be done either, how the action is managed by nature, or for what use it is." (13, page 266) 

Giovannin Alfonso Borelli (1608-1679) was the first to describe muscular activity, the beating of the heart, and the function of the lungs, and digestion as purely mechanical acts, thus dispelling ancient theories. He also discovered that arteries were elastic,

Conrad Victor Schneider (1614-1680) studied the membranes in the nose, and became the first to recognize that phlegm was secreted by this membrane, what is now known as the Schneiderian Memberane.  Before his discovery, it was believed that phlegm was formed in the brain during some disease processes and merely drained into the nasal cavity and into the lungs.  Schneider's observation, which was made in 1664, was among several necessary in order to slowly, ever so slowly, put an end of the age old Grecian theories holding back the medical profession.  (14, page 124)

In 1636 Robert Boyle (1627-1691) discovered the presence of gases in the blood, and is therefore perhaps the first to describe an element.  He found that "fresh defibrinated blood gave off bubbles of gas when it was exposed to the vacuum of an air pump."  A few years later John Mayow (1640-1679) thought the gas was nirto-aerial gas, or what we now refer to as oxygen.  (7, page 517)

He was, therefore, the first to prove that there was more to life than the four basic elements (Earth, Air, Water, fire) were not the only essential elements of life.  Of course Van Helmont was considered to be a madmen by the scientific community and the medical profession.  It was not appreciated during this time to oppose accepted doctrine.  (2, page 40)

Of course Boyle is also famous for a law of physics named after him called Boyle's Law.  This states that at a constant temperature the pressure of a gas has an inverse relationship to it's volume. This law would become very significant to many of the later researchers.  This law explains why we breathe, why popcorn pops, why a tea kettle whistles,  and why a balloon bursts when you blow too much air into it.  The same law would later be used by physicians to explain why inventions like Robert Hooke's bellows might cause trauma to the lungs, as you will see in a moment.

In 1665 Robert Hooke (1635-1703) invented the compound microscope, and this would ultimately play a significant role in both science and medicine.  (11, page 256).  In 1667 Hooke discovered that respiration was not to maintain circulation, as had previously been thought.  Interestingly, Hook took the trachea of a dog and connected it to a "pair of bellows, and the ribs and diaphragm were removed;  the dog was seized with convulsions and appeared to be dying, but revived when air was blown into the lungs.  Small punctures were now made into various parts of the lungs, and by means of two pairs of bellows the lungs were kept fully distended with fresh air; the dog remained quiet and its heart beat regularly. The circulation continued although there was no alternate expansion and collapse of the lungs; moreover, a further experiment showed that even when the lungs were allowed to collapse the blood continued to circulate for some time. " (7, page 474)

By his experiment, Hooke also proved that "by blowing a bellows briskly over the open thorax of a dog, that artificial respiration can keep the animal alive without any movements of either chest or lungs. The experiment, which had been performed by (Andreas) Vesalius (1514-1564), proved that the essential features of respiration is not in its intrinsic movements, but in certain blood changes in the lungs." (11, page 267)

Also in 1665 Richard Lower (1631-1691) performed the first successful blood transfusion, taking the blood of one animal and inserting it into the animal of another.  Then, in 1669, he "lower injected dark venous blood into the insufflated lungs, and concluded that its consequent bright color was due to the fact that it had absorbed some of the air passing through the lungs."  (11, 267-268)

John Mayow -- He was the first to discover
Oxygen, although never received credit because
he died at the young age of 35, before his writings
were published, and therefore his discoveries
were forgotten by history until the 20th century.  

Jan Swammerdam (1637-1680) became an expert in dissecting animals, studying them with the stethoscope, and describing their anatomy.  He was the first to describe the anatomy and life cycle of bees and other insects.  In 1658 he discovered red blood cells in the blood of frogs.  He postulated that an element (later found to be oxygen) could be carried by blood to the various muscles of the body.  (11, page 251)(12, page 366)

In 1664 he discovered that fetal lungs of mammals sink before a breath has been taken, and float after respiration has taken place. He also demonstrated that a frog leg could be made to contract, and this proved useful by later investigators.  His works were published posthumously by Herman Boerhaave in 1737. (11, page 251)(12, page 366)

Antonj van Leeuwenhoek (1632-1723) had a collection of over 247 microscopes which he used to study plant, animal and even human specimens.  He was the first to accurately describe the anatomy of a red blood cell in 1674.  He also saw the capillary anastomasis previously described by Malpighi.  It was through Malpighi and Leeuwenhoek "which finally completed Harvey's demonstration."  (11, page 251)

Antonj van Leeuwenhoek observed and
described capillary anastomosis, and in this
way finally proved that Harvey was right,
that blood circulates through the body. 

John Mayow (1664-1679) learned by his many experiments that dark bloooyd turns bright red upon taking up certain particles in the air, and he referred to these particles as "nitro-aerial gas."   He also learned that blood exposed to a vacuum gave off bubbles, and he believed this to "nitro-aerial gas."  He was right, and the substance, as later proved, was oxygen. While he did not discover oxygen, he was that close. (7, page 475) (11, page 268)

However, he did learn there was indeed a substance in the air, what he called "nitro-aerial gas," that was "necessary for all forms of life," and it was inhaled during the process of respiration.  He thus concluded that respiration was not to cool the blood as previously thought, but for the exchange of gases.  Substances in the air were were inhaled into the lungs and absorbed by the blood in the lungs (thus changing its color from dark to bright red).  Another function of respiration was "the removal of vapors arising from the blood." (7, page 475)

If that wasn't enough, he also discovered that maternal blood supplies an unborn fetus with not just food, but also with "nitro-aerial gas." While he proved that respiration was not to cool the blood, he also proved the blood is not the source of its own heat.  Instead, he proved that heat was produced by the activity of the muscles of the body.  (11, page 268)

Mayow's works were  published in 1668 and 1674, although he died at the early age of 35 before his works were published.  So he was was never recognized until the turn of the 20th century.

So while he doesn't get credit by history, Mayow may actually have been the first person to discover oxygen.  Yet, unfortunately, history doesn't give credit for the first to do something, but the first to publish their discovery or invention.  This truth will play out many times in world history.  (7, page 474-5)

By the 1750s this substance was called "fixed air."  While performing his own experiments in 1757, Joseph black proved Van Helmont was right. Ultimately Van Helmont would get true credit for his discoveries, and would be referred to as the father of pneumatic chemistry.

References:

1. Tissier, Paul Louis Alexandre, “Pneumotherapy including aerotherapy and inhalation methods and therapy,” volume x, 1903, Philadelphia, P. Blakiston’s Sons & Co., page 19
2. Lagerkvist, Ulf, "The Enigma of Ferment," 2005, Singapore, World Scientific Publishing
3. Potter, Elizabeth, "Gender and Boyle's Law of Gases," 2001, Indiana University Press
4. Newman, William R, et al, "Alchemy Tried in the Fire," 2002, University of Chicago
5. Lehrs, Ernst, "Man or Matter," 1958, Great Britain, Whistable Litho Ltd.
6. Jindel, S.K., "Oxygen Therapy," 2008, pages 5-8
7. Hill, Leonard, Benjamin Moore, Arthur Phillip Beddard, John James Rickard, etc., editors, "Recent Advances in Physiology and bio-chemistry," 1908, London, Edward Arnold
8. Hamilton, William, "A History of Medicine, Surgery and Anatomy," 1831, Vol. I, London, New Burlington
9. Osler, William Henry, "The evolution of Modern Medicine: A series of lectures delivered at Yale University on the Sillman Foundation in April, 1913," 1921, New Haven, Yale University Press
10. Osler, ibid, pages 170, reference referring to William Harvey: Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus, Francofurti, 1628, G. Moreton's facsimile reprint and translation, Canterbury, 1894, p. 48. 20 Ibid., p. 49.
11. Garrison, Fielding Hudson, "Introduction to the history of medicine," 1921, London, 
12. Baker, Christopher, editor, "The Great Cultural Eras of the Western World: Absolutism and the Scientific Revolution 1600-1720: A biographical dictionary," 2002, CT, Greenwood Publishing; Herman Boerhavve published Biblia Naturae (Bible of Nature) in 1737, which was a two volume compilation of the works of Jan Swammerdam. Can you read Latin?
13. Garrison, op cit, 266; (Samuel) Pepy's Diary, Mynors Bright's ed., London, 1900, v, 191
14. Bradford, Thomas Lindsley, writer, Robert Ray Roth, editor, “Quiz questions on the history of medicine from the lectures of Thomas Lindley Bradford M.D.,” 1898, Philadelphia, Hohn Joseph McVey
15. Brock, Arthur John, "Galen on the natural faculties," 1916, London, New York, William Heinemann, G.P. Putnam's Sons

1543: Vesalius sparks end to dark ages of medicine

So our friend Claudius Claudius Galen wrote his book of anatomy and medicine in the 2nd century, just prior to the end of the Roman era of western civilization.  For greater than a thousand years physicians amid this civilization, instead of thinking on their own and advancing medicine, worshiped Galen as a god of medicine. His writings contained all the knowledge required of medical students.

Surely over the years there were errors observed in Galen's words, although these errors were always overlooked, explained away as "probably nothing."   Medical curiosity was frowned upon, and all was forgotten as the world dipped into a dark ages. 

People were content to remain ignorant until a man by the name of Andreas Vesalius wrote a book that stunned the scientific and medical community back into existence.  

Vesalius was born in 1514, "into a world of physicians, pharmacists and royal patronage," explains Lois N. Magner.  "His father was imperial pharmacist to Charles V and often accompanied the Emperor on his travels.  As a youth, Vesalius began to teach himself anatomy by dissecting mice and other small animals."(4, page 158)

Galen's mighty reign as god of medicine ended almost as soon as Vesalius became a student at the University in Paris.  This is where we find him entering through the large doors, entering a large observatory with a podium in the front and a dissecting table with a fresh corps lying on top of it.  Vesalius seems oblivious of the stench of rotting flesh as he takes a position close to the table and waits for the professor and his assistant to enter.

Within fifteen minutes the room is crowded with students hovering to see a young assistant cut into the chest of the body. Standing behind his assistant, behind the podium which has a copy of one of Galen's books on top of it, we find professor Jacobus Sylvius, who was born in Amiens, France, who began teaching anatomy at Paris in 1531.  (7, page 200)

He reads Galen's words as his assistant displays what Galen is explaining. His voice is strong and powerful, radiating full and strong so even at the rear of the auditorium we can hear his every word.  His assistant usually dissects an animal, we know from our history lessons, but today his students are privy to an actual human dissection. This is something Sylvius did for his students only once a year.  

Historian Kerfoot D. Shute said in 1910, that Jacobus 

Sylvius (1478-1555): "was an uncompromising Galenist.  

He preached Galen in everything, and trusted Galen 

more than he did his own eyes. To him instruction in 

anatomy was reading a chapter of Galen and though he, 

on rare occasions,  made use of imperfect dissections

of the human body these dissections were simply for the 

purpose of illustrating and making the teachings of Galen

and not for the purpose of disproving Galen."(7, page 200)

As Sylvius reads, loud and clear, the one assistant does the cutting, and another points to each part of the body being described by Galen.  It's actually a neat system, and they have it down pat, as though they have done this hundreds of times before. (3, page )

After the dissection is done all the men are clear of the room except Vesaleas and Sylvius

Andreas says, "What you read and what your assistant pointed to did not agree."

Sylvius shouts, "There are no errors in the writings of Galen."

Andreas says, "Galen taught that the liver was five-lobed, that the breastbone had seven segments, that a network of blood vessels could be found under the brain.  You believe every word of it, although those features couldn't be found in the body right under your eyes.  You see exactly what Galen tells you to see!

Sylvius shouts, "Get out!" He points to the door.

"If the corpse and book don't agree, then the error is in the book!"

"If the error and book don't agree, then the error is in the corpse!"

 "God forbid you doubt Galen."

"Get out!" Sylvius points aggressively this time.

"Michelangelo and van Calcar know more about the human anatomy than you, professor!"

"GET OUT!

"Those artists need accurate description of the body!  They study it up and down so they can accurately draw the body.  You guys merely studied Galen!

"YOU ARE A MAD MAN!

"Hmph!" is the noise that escapes Vesaleus, as he rushes out through the large doors, which bang shut in his absence.  We follow his path, and catch up to him as he trudges down the middle of a dirt road, dust spewing as a horse and buggy buz past.  He coughs.

Vesalius stops in front of a fountain and says, perhaps talking to us:

I am not content to just believe everything Galen writes.  The best teacher of the human body is not Galen but the human body. I stole a skeleton and studied it, yes I did.  I learned the human breastbone did not have eight segments as Galen described, it had only three parts.  How could a teacher as magnificent as Galen have gotten it wrong?" 

Andreas Vesalius (1514-1564)

There is a long pause as Vesaleas appears to be gazing at his shadow waddles in the twinkling water. 

Then by chance one day I dissected an Ape.  It occurred to me:  Galen never even dissected a human body, otherwise he would have known the human sternum had only three parts.  For thousands of years doctors treated diseases based on the anatomy of apes not of humans."  

Vesalius turns to look our way, as tough he knows we are real, although we know he's actually looking at Sevalius as he exits the observatory.  Sevalius does not stop, perhaps pretending he does not hear the young Vesalius as he says:

"I have a mission.  I hope you read of my discovery for history's sake!"

Vesaleas smiles.

Back in the time machine we sit and think about the day's events.  To Galen's defense we must remember  in both ancient Greece and Rome it was considered sacrosanct and illegal to dissect a human body.  In fact, it was illegal to even touch a corpse except for preparing it for burial.  Even in the 16th century it was illegal without permission. While Sylvius probably obtained a legal corpse, most dissections were performed on bodies stolen from cemeteries.

By his coming out in the open with his discovery, Vesaleas came head to head with his colleagues in the medical community.  His fellow physicians ridiculed him to the point he had no choice but to leave Paris without a degree. (4, page 158)

Surely this set him back for a while,but it did not slow him down. Surely there were other men like Vesalius who had suspected Galen of being wrong, although Vesalius had access to something that none of those men had: the Gutenberg Printing Press.  It was invented in 1448 by Johannes Gutenberg, but by 1537 the press had become commonplace, and just about all great minds eager to publish a book had access to it.  Vesalius needed it big time in order to return medicine to western civilization.

Vesalius was hired as professor at the University of Padua in 1537 (3,4) and decided to dissect the bodies himself. His colleagues wondered why he would waste his time considering Galen had described the human body so perfectly.  Learning from dissecting is a waste of time, they said, and all that was needed could be learned simply by opening up one of Galen's books. (3, page)

Later that same year he becomes a medical doctor and was appointed to "lecturer-demonstrator" of anatomy and surgery.  From sun up to sun down, three days a week, he demonstrated and lectured about the human body in front of ever growing crowds of medical students.  (4, page 158)

To mark his independence from Galen, Vesalius arranged a public dissection lecture in which he demonstrated over 200 differences between the skeleton of apes and humans, while reminding his audience that "Galen's work is based on the dissection of apes."

His fellow professors, including his old instructor, cried foul.   Sylvius wrote letters explaining how crazy Vesaleas was, and even called him a "mad man." (2, page 159)

Yet despite their cries, it would be Vesaleas who laughed last.  He was the one who was noted to be correct by history. He was the one who became famous for his observation.  He would become so popular that within a few years he would have enough money to hire an artist by the name of jan Stephen van Calcar to draw the human body as it was being dissected by him.  

Andreas Vesalius published the first accurate book of anatomy on the
printing press at Basle in 1543.  While the book in and of itself was
controversial, the title page shown here shows an engraving of
the teacher and his students examining a cadaver. (6, title page)

This book was published in the year 1543 in Basle when Vesalius was only 28.  This first accurate book of the human anatomy was called De Humani Corporuis Fabrica, or "The Fabric of the Human Body." It consisted of 700 pages, and the title page consisted of the teacher and his students studying a cadaver, which in itself must have been controversial.  (5, page 89)

This was a major scientific breakthrough, and the spark that would end the dark ages of medicine and the dawn of the scientific revolution.  From this point on human anatomy would be taught based on accurate pictures and descriptions, as opposed to Galen's ignorant descriptions. 

He continued to meet fierce opposition from his fellow professors with chants such as: "You are ruining our reputation!" They shouted such filth at him in the halls of the university he worked.  They accused him of crimes.  Many wrote books against Vesalius.  Instead of completing more medical work, he spent the next 20 years fighting to get others to recognize the importance of the Fabric.

This engraving shows Vesalius displaying the the muscular system of
a human arm.  This was among many engravings displayed inside his
book that were created by jan Stephen van Calcar 

This is just the way it was in the 16th century: statements of scientific fact did not come without a fight.  Yet it was a fight worth fighting.  Thanks to the courageous acts of Vesaleas a spark was lit under the medical community that would grow into a full and flourishing flame within a few years.  

Historians like John Hudson Tiner now recognize Vesaleas's discoveries about Galen's lies as one of the top ten most important medical discoveries of all time.  Yet unfortunately Vesalius never lived to see its acceptance into modern medicine.  His later travels took him out of Europe and nothing is known about when nor how he died.

Although there are theories.  In his history of medicine, the father of modern medicine, William Henry Osler, explained one theory:  (2, page 160).

"The story is that he had obtained permission to perform a post-mortem examination on the body of a young Spanish nobleman, whom he had attended.  When the body was opened, the spectators to their horror saw the heart beating, and there were signs of life!  Accused, so it is said, by the Inquisition of murder and also of general impiety he only escaped through the intervention of the King, with the condition that he make a pilgrimage to the Holy Land.  In carrying this out in 1564 he was wrecked on the island of Zante, where he died of a fever or of exhaustion, in the fiftieth year of his life."

Regardless, Vesalius is a hero in every medical history. Actually, it wasn't Vesalius alone who saved medicine, as there is another hero in our story, and his name was Johannes Gutenberg.  Gutenberg provided the method, and Vesalius used it to create a spark.

Shortly after his death ancient Greek medicine returned west, was transcribed from Arabic back into western languages.  Yet along with the old wisdom came a plethora of new remedies and a young pharmaceutical profession. (5, page 75, 82)

Click here for more asthma history.

References:

1. The John Hopkins Hospital bulleton," (volume XV 1904), "from the epoch of the Alexandria School (300 B.C.)"
2. Osler, William, "The Evolution of Modern Medicine: A series of lectures at Yale University on the Silliman Foundation in April, 1913," New Have, Yale University Press, 1921,
3. Tiner, John Hudson, "Exploring the History of Medicine," (the conversation in this post is based on the writings of Tineralthough the actual words are made up by me). 
4. Magner, Lois N, "A History of Medicine," page 160
5. Bradford, Thomas Lindsley, writer, Robert Ray Roth, editor, “Quiz questions on the history of medicine from the lectures of Thomas Lindley Bradford M.D.,” 1898, Philadelphia, Hohn Joseph McVey
6. Vesalius, Andreas, "De Humani Corporis Fabrica Libre Septem," 1555,
7. Shute, D. Kerfoot, "The life and works of ndreas Vesalius," Old dominion journal of medicine and surgery, Tomkin, Beverly R. Tucker, Douglas Vanderhoof, Murat Willis, R.H. Wright, editors, 1910, Richmond Virginia, The Old Dominion Publishing Corporation, pages 195-211

My medicine history

Sometimes I wonder how many asthma medicines I've downed since January of 1070.  I was diagnosed with asthma in 1972, but I'm sure I had trouble even before that.  I remember mom pouring this nasty tasting medicine from a pink or purple bottle in the medicine cabinet onto a spoon and making me down it.  It tasted nasty.  Was that Sustair? or was it some form of Alupent solution?  I may never know.

The following are all the medicines I recollect taking for my asthma over the years:

1. Susphrine:  I wrote my experience with this medicine here.  
2. Terbutaline:  This was a rescue medicine.  My only memory with this was at the asthma hospital in 1985.  It made my blood pressure spike, so my experience was only temporary.  
3. Alupent inhaler:  My old buddy.  I wrote about my experience with this medicine here.
4. Alupent solution:  I was introduced to this in 1985 at the asthma hospital and used it until 1991 when I was introduced to Ventolin solution.  It made my heart pound, but boy was it a lifesaver in its day
5. Cromolyn:  This was the famous spinhaler dry powder inhaler.  The powder sometimes made me cough, and this made my asthma worse.  I used it from sometime around 1983 until around 1990 when I just quit taking it.  I don't know if it ever did any good.
6. Theodur:  I was chronically dependent on this for over 30 years, although it was an awesome bronchodilator I think doctors are now afraid of but shouldn't.  I wrote about it here.  
7. Sustair:  It's the syrup version of theophylline.  It tasted like yuck. 
8. Aminophylline:  IV version of theophylline they give you when you're admitted to the hospital.  I don't think it's used anymore, though.  
9. Atropine solution:  It's a mild bronchodilator, although it's used more as a preventative medicine because it has a slow onset of action.  It's the same medicine that used to be available in asthma powder and asthma cigarettes.  I generally mixed it into my Alupent solution and inhaled the treatment for 10-15 minutes about four times a day.  
10. Atrovent:  It's the factory made Atropine-like product that's available as an inhaler.  I took this from the late 1980s until the early 1990s when I simply quit taking it.  It was also available as a solution for my nebulizer.
11. Vanceril:  The infamous beclomethasone inhaler.  There were various brands and generic names, although Vanceril was the one I usually found in my bedroom.  
12. Azmacort:  I started taking this when I was admitted to the asthma hospital in 1985 and I took it until 1998 when I was switched to Flovent. It was a good inhaler, although 4-6 puffs 4 times a day made it so compliance was a major issue. 
13. Broncosol:  Actually the predecessor of terbutaline. Thankfully I only had to take it a few times 'cause boy did it make my heart pound.
14. Prednisone or Medrol:  Good old systemic steroids.  I have been on these so many times I cannot count the days.  I was on them most often in 1984 and 1985, so much that there were concerns of side effects.  I was on them in 1998 and 2012 for short term.
15. Solumedrol:  The IV version of systemic roids you get in the hospital.  The last time I needed it was in 1998.
16. Flovent:  This is the best steroid I started taking in 1998.  I switched to Advair in 2005, although Flovent is one of the contents.  
17. Serevent:  I also started taking this in 1998 when I started taking Flovent.  I didn't like the side effects so I was on and off it for the next seven years until I started taking Advair
18. Drixoral:  I started taking this in 1985, and my doctor wanted me to take it daily to control my 200 allergies.  When I got home from the asthma hospital my mom wouldn't let me use it because it was too expensive. 
19. Xanax:  The old mind relaxer.  It's an anxiolytic. I was first on it for about six months in 1985, and then again for a while in 1998.  These were when my asthma was the worse.  I just started on it again as needed in April of 2012.
20. Antibiotics: Many different kinds and many different times.
21. Nasal irrigation:  In 1985 I was supposed to take this salt water and drain out my nasal passages with it.  I hated it, and it was discontinued to be replaced with Ocean Spray.
22. Ocean spray:  (I was on this for a while in 1985 and 1986.  It was another medicine used to clean out my sinuses.  It was another medicine my mom didn't want to pay for.
23. Nasalide:  It was another allergy medicine I was on in 1985. 
24. Dulera:  It has Azmanex and Formoterol in it.  It's a long acting beta adrenergic I trialed in 2011.  I determined the Formoterol was was nice in that it was fast acting like Albuterol, but too strong.  It made me too jittery, so I stopped the trial
25. Symbicort:  It has Pulmicort and Formoterol in it.  I trialed it in April October of 2012.  I liked it for the same reason I like Dulera, and stopped taking it for the same reason too. 
26. Albuterol tablets:  Sometimes around 1987 or 88 I took these pills.  I never found them to be effective.  Apparently neither did anyone else, as the product was soon thereafter removed from the market

The following are asthma medicines I'm currently on:

• Advair 50/250: The combination inhaler with Serevent and Flovent.  It's been a lifesaver.  
• Advair 50/500:  I take this when my asthma is acting up, and more often I've been taking it regularly.  I usually alternate it with the other Advair
• Ventolin inhaler: The best asthma medicine ever in a handy pocket-size version
• Ventolin Solution:  Used mainly for exacerbations and when the inhaler can't be found
• Prilosec:  It's not uncommon for asthmatics to have stomach problems
• Singulair:  Liekotriene Antagonist basically used to control allergy symptoms.  Take it daily
• Claritin:  Antihistamine used to control allergy symptoms.  I now take it daily
• Ultram:  Allergies, sinusitis and asthma anxiety cause headaches, and this works

400 B.C.-200 A.D.: A history of 'vital air'

Air has existed since the beginning of our existence, that we know for sure.  Without air we wouldn't have life, and people must have figured that out at an early date.  They also must have figured out early that breathing is necessary for life, considering when people stop breathing life end.  (7, page 473)

Primitive people and ancient societies didn't know about air, let alone oxygen, per se.  However,  as far back as 1000 B.C., ancient Hindu physicians who wrote the Charaka and Sustrata recognized both the presence of the lungs and the 'prana vayu,' a substance in the air that many historians believe was oxygen. (5)

"Charaka (500 B.C.) mentions the head, the chest, the ears, the tongue, the mouth and the nose as the seat of 'prana vayu.'  Sustrata (1000 B.C) spoke of 'prana vayu' as flowing in the mouth. What else can this 'prana vayu' be identified with," writes S.K. Jindal in his 2008 book, "Oxygen Therapy." (5)

Anaximenes of Miletus (585-525 B.C.) believed that air "was the primary principle," and he referred to is at the pneuma, or "the breath of life," explains William Henry Osler, the father of modern medicine. He explains that the "pneuma was described by Anaximens as the "psychic force that animates the body and leaves it at death -- 'our soul being air, holds us together'" (9, pages 38-39)

Yet it was Empedocles (490-430 B.C.), a pre-Socratic Greek philosopher, who first conceived the idea that air contained a substance that was vital to life.  He defined air as one of the four basic elements: air, water, earth and water.  Everything that we see is made up of these substances, and health of animals and humans was determined by the equilibrium of these four substances. (9, page 40)

He was also the first to describe respiration:

"As soon as that humidity, of which there is a great store on the first formation of the foetus, begins to be diminished, the air insinuating itself through the pores of the body succeeds it; after this the natural heat, by its tendency to make its escape, drives the air out, and when this natural heat enters the body again the air follows it afresh. The former of these actions is called Inspiration, and the latter Expiration."  (1, page 47-48)

He described how with the inspiration air entered into the body, and that it was circulated through the body by the "continuous motion" of the blood, and that it nourishes the heart and the mind.  Empedocles explains that the heart "nourished in the sea of blood which courses in two opposite directions: this is the lace where is found for the most part when men call Thought; for the blood round the heart is Thought in mankind." (2, page 186)

He also may have been the first to observe of the "faetus in utero" that "respiration commenced before birth."

Aristotle (384-322 B.C.), a Greek philospher and student of Plato (and teacher to Alexander the Great), mentioned "air" as one of the essential elements of life.  He observed that air had weight when he wrote that "a bladder filled with air was heavier than an empty bladder." (6, page 19)

He did not know that there was a difference between arteries and veins, although he did know that both were filled with blood. He also knew that the heart was the key to "circulation" of the vital spirit.  He actually came up with the term vessels as he noted the vessels contained the blood as in a vase. The lungs inhaled the spirits and pneuma from the air from the trachea (which he referred to as the arteria, because it contained air. Hippocrates also referred to the trachea as the arteria. (9, page 72)

Praxagoras of Athens (born 340 B.C.) believed that "pulsation was only in the arteries, and maintained that only the veins contained blood, and the arteries air," writes William Henry Osler.  "As a rule the arteries are empty after death, and Praxagoras believed that they were filled with an aeriform fluid, a sort of pneuma, which was responsible for their pulsation."  He was among the first to study the pulse. (9, page 72)

Archimides (287-212 B.C.), a Greek mathemetician and stronomer, wrote that "air is weighed in air." (6, page 19)

In the 3rd century B.C., Erasistratos (335-280 B.C.) of the School of Alexandria, in Egypt, recognized the relationship between air and blood and that air was essential for life to exist.Around 294 B.C. Erasistratos "taught that arteries carried blood to the various parts of the body; those vessels carried air and air only, and the blood was carried in the other vessels, the veins."  (7, page 473)

He also believed the heart contained no blood (8, page 94)  In fact, Osler explains, it's for this reason arteries got their name, as the term "artery" comes from the Greek term arteria, or air.  The trachea was referred to as the windpipe, or arteria tracheia, also known as "the rough air tube." (9, page 72)

Erasistratos contested that air contained a substance (a pneuma) that, once it entered the body, it was transformed into this "vital pneuma" that was essential for life.  This transformation was performed in the "left ventricle of the heart and, together with blood, results in heat, energy, and life.... a part of the vital pneuma enters the brain where it turns into 'psychic pneuma.'  This psychic pneuma processes sensory perceptions and renders possible understanding and knowledge."  (3, page 8)

Osler adds that this "vital pneuma"  was also the cause of the heart beat, "the source of innate heat of the body, and it maintained the processes of digestion and nutrition." It's sent to the brain where an animal spirit is formed, and this spirit is sent to the nerves of the body to give the person emotion and sensation and motion. Osler explains that when we use the terms "high spirits" and "low spirits," these terms come from the views of Erasistratos and other ancient Greek philosophers.  (9, page 73)

By 70-160 A.D. Athenaeus of Cicilia opened what was called the "pneumatic school" of medicine that "flourished" for many years.  The pneumatic theory held that there was a pneuma in the air that was inhaled, transported to the heart by vessels, and then transported to the rest of the body by vessels.  This pneuma was therefore essential for good health and life, for maintaining a balance of the four humors by maintaining an appropriate level of heat and moisture. (2, page 291)

Aretaeus of Cappadocia (130-200 A.D.), a physician from ancient Greece, believed the heart was "the exciting cause or principle of respiration," according to Hamilton, "being seated in the centre of the lungs, which it inspires with a desire for fresh air. The lungs he did not believe to be susceptible of pain, from being composed of a loose sort of substance like wool; rough cartilaginous arteries, according to him, were dispersed throughout them; they were unprovided with muscles, and furnished only with some small and slender nerves, by means of which their motion was produced." (1, page 32)

Middle Ages diagram of Galen's concept of blood flow

Aelius Galen (130-200 A.D.), a famous Greco-Roman physician, studied the heart extensively  Osler notes that he "studied particularly the movements of the heart, the actions of the valves, and the pulsatile forces in the arteries.  He observed venous blood was darker, and believed it provided nutrition to the body. Arterial blood was thinner and brighter, and this was because it contained an abundance of "vital spirit," or vital air.  Arterial blood was warmed in the left ventricle, and this heat was sent to all the organs of the body.(9, page 80).

Galen also observed, as did Erasistratus, that the veins and arteries communicate by small pores and small vessels that allows for the mingling of spirits and blood. He did not, however, know the blood circulated, as he though it made it's way to the organs by small pores. However, some historians, including Osler, believe he was very close to figuring this out, and if given more time he probably would have. He did not see the heart as a pump, but as a fireplace, notes Osler. (9, page 80)

He believed the purpose of the heart was to warm the blood.  He believed the left ventricle purified the blood and sent pure blood to the vital organs, such as the liver.  (7, page 473)

It should also be known that, according to Phillip Crampton in his 1839 "Outlines of the history of medicine, nothing remains of the writings of Erasistratos, so much of what we know about his anatomical discoveries comes from the writings of Galen. Crampton said that Galen described Galen's view of the passage of blood and air through the body this way:

According to him, the air passes from the lungs to the heart, which performs the functions of a smith's bellows, attracting the air by the dilatation of the left auricle ; from the left auricle it passes by the arteries which contain air, or rather animal spirits, to every part of the body. The veins contain all the blood, and according to this supposition, fever and inflammation are the consequence of any portion of blood passing, by an error loci, from the veins into the arteries. (10, page 519)

Galen supported this view and added to it.  Crampton explains it was Galen who was perhaps the first to describe human respiration:

Some notion of the state of experimental philosophy in the time of Galen, may be formed from the account which he gives of the experiment by which he Convinced the assembled physicians and philosophers of Rome, that air was contained within the cavity of the chest, between the lungs and the pleura costalis; he says he explained to them the manner in which the air passed from the lungs through the cribriform plate of the sethmoid bone into the ventricles of the brain, in which a true respiration was performed, the organ rising and falling in correspondence with the motions of the chest, and the air escaping through the sutures and the palate (10, page 520)

So Galen supported the views of Erasistratos and then expanded upon them. He agreed with Erasistratus that some pneuma in the air was inhaled, warmed in the heart, and sent to the body by a series of vessels and cannals and pores.  He also believed something of waste was exhaled.  He actually proved by experiments Erisistratos wrong when he asserted the arteries contained air not blood.  Galen proved arteries contained blood.  (7, page 473)(9, page 82)

Arthur John Brock, in the introduction of his 1916 translation of some of Galen's works, explains Galen's thoughts on how blood and air flowed through the body:

In his opinion, the great bulk of the blood travelled with a to-and-fro motion in the veins, while a little of it, mixed with inspired air, moved in the same way along the arteries; whereas we now know that all the blood goes outward by the arteries and returns by the veins; in either case blood is carried to the tissues by blood-vessels, and Galen's ideas of tissuenutrition were wonderfully sound. (10, page xxxvi)

He also explained that the "spongy flesh of the lungs acts upon the air we inhale converting it to a subtler product, pneuma.  This refined breath passes through very find 'pores' into branches of the pulmonary vein, and thence is 'attracted,' with blood, by the attractive faculty into the left ventricle of the heart, where it encounters more hot blood and becomes metamorphosed into life giving, i.e. 'vital' pneuma." As the pneuma is 'transported' to the various parts of the body it is further metamophosed.  (4, page 45)

Why were there two sets of vessels for the same fluid? Galen wondered.  And he speculated, as historian William Hamilton notes that:

the great vein (vena cava) was the great reservoir of the blood, while the aorta was the recipient of the spirits, and that, notwithstanding the proximity of the mouths of the veins and arteries to each other, the blood, during the continuance of health, did not enter the vessels in which the spirits flow; but, when this arrangement happens to be disturbed by any violence, that the blood forces its way into the arteries, and occasions more or less disorder of the system. The only use which he assigned to the process of respiration was to supply the arteries with air (what he referred to as vital air).

Yet this is all just speculation, and there were many theories as to what this 'vital air' contained.  Regardless, Galen was so well respected by the medical community that his theory grabbed a hold and held a prominent position in the minds of physicians for the next 1,900 years.  This theory held strong even when better wisdom became available.

References:

1. Hamilton, William, "A History of Medicine, Surgery and Anatomy," 1831, Vol. I, London, New Burlington
2.  Prioreschi, Plinio, "A History of Medicine: Greek Medicine," Vol. II, 1994, 2004, 2nd ed., NE,  Horatius Press
3. Tesak, Juergen, Chris Code, "The History of Aphasia: Theories and Protagonists," 2008, New York, Psychology Press
4. Wilson, Nigel, "Encyclopedia of Ancient Greece," 2006, NY, Taylor and Francis
5. Jindel, S.K.,Ritesh Agarwal, "Oxygen Therapy," 2009,2nd ed., Jaypee Brothers, pages 5-8
6. Tissier, page 19
7. Hill, Leonard, "Recent Advances in Physiology and bio-chemistry," 1908, London, Edward Arnold
8. Garrison, Fielding H, "An introduction to the history of medicine," 3rd edition, 1922, Philadelphia and London, W.B. Saunders Company, page 95
9. Osler, William, "The Evolution of Modern Medicine: A series of lectures at Yale University on the Silliman Foundation in April, 1913," New Have, Yale University Press, 1921,
10. Crampton, Phillip, "Outlines of the history of medicine from the earliest historic period to the present time, intended to illustrate the connextion between the progress of anatomy and the improvements of the healing arts," read before the Royal College of Surgeons on November 29, 1838, published in The Dublin Journal of Medical Science, 1839, Volume 14, Dublin, Published by Hodges and Smith, pages 504-533
11. Galen, writer, Arthur John Brock, translator, "Galen: On the Natural Faculties," 1916, London and New York, William Hienemann and G.P. Putnam's Sons