Friday, January 11, 2013

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 Movement, As It Were, In 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.

  1. Tissier
  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

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