1628: William Harvey discovers circulation, and proves it

Robert Hooke discovered the respiration
was not to keep the circulation of the
blood moving. In 1553 

A book published by Andreas Vesaleas inspired physicians to investigate the human body. But, it was a book published by William Harvey that empowered physicians to truly understand the human body, and how changes in the body caused diseases. And so it is Harvey who is credited as paving the way for modern medicine.

Galen alluded to the idea that blood circulated through the body in the 2nd century. Yet in his many writings, he described blood as moving back and forth between organs in a to and fro motion. Whether he had a notion it circulated is left to speculation.

Vesaleas was the first person to publish an accurate anatomy of the body. He performed autopsies and had a painter paint what he saw, and this was published in a book, De humani corporis fabrica, in 1543. However, he erred in believing that the purpose of circulation was to cool the blood. (7, page 474)(11, page 243-4)

A contemporary of Vesaleas was Realdus Columbus (1516-1569).  He was a surgeon and professor of anatomy at Padua from 1544 until his death in 1569. He continued Servetus's work on the circulation of the blood, describing the passage of blood from the vena-cave through the pulmonary circulation, and then through the left ventricle and aorta. (8, page 70-71)

Columbus also saw that blood changes in the lungs.  (11, page 243)

Andrea Cesalpino (1519-1603) 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.

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 to the legs and feet. This is what prevented diseases like dropsy of the feet. Today, we would refer to this as pedal edema. (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. This students name was William Harvey. (14, page 93)(15, page xxiii)

Michael Servetus discovered circulation. He discussed it in his 1553 book, although he also failed to prove it.  So the door was still wide open for a major breakthrough in science, and just the man to accomplish this task was William Harvey, who essentially took over the work of Servetus.

William Harvey (1578-1657)(11, page 242)

Medical Historian Thomas Bradford said Harvey 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 for 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)

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, he became a physician at Bartholomew's Hospital, and in 1615 became a professor of anatomy and surgery at the college.  It was here he 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 a knowledge that only God was privy to. He studied the heart and vessels in animals and came to the conclusion that the heart was a pump, and it circulates the blood through the body. (9, page 168-169)

How he discovered blood circulates is quite interesting. At the time it was believed blood was created by the liver. Veins and arteries pulsated to move the blood through the body. It was then absorbed by tissues.

Harvey used math to prove this was not possible. He studied how much blood went through the heart in an hour. He calculated that three times a person's weight in blood passed through the heart per hour. So, if it was produced by the liver as previously suspected, a person would simply explode.

While his comrades initially rejected his theory that blood circulates through the body, Bradford said:

King Charles took great interest in these discoveries and witnessed several experiments. He appointed Harvey his physician in 1643.  In 1633 he accompanied the king and his court to Scotland.  When "Old Parr" died the king gave the body to Harvey to dissect.  (14, page 120)

Several years after he made this discovery, and when he was 50 years old, he would publish, in 1628, Exercitatio anatomica de Motu Cordis et Sanguinis (An Anatomical Exercise on the Motion of the Heart and Blood in Living Beings).  (14, (page 119-122)

Of course, once Harvey published his discovery in his 1628 book  his medical practice took a hit, and he was criticized by a dogmatic medical profession.  (11, page 246)(14, pages 119-120)(17)

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, said Garrison. (11, page 246) (also see 14, pages 119-120)

Perhaps it was due to his friendship with the king that his ideas were accepted before his death in 1657. (14, page 119-122)

Garrison said William Harvey "was 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, )

Charles Auffray and Denis Noble, in a 2009 article in International Journal of Molecular Science, said that Harvey may even have come close to discovering how the heart may continue beating even after it is removed from the body.  They quote Harvey as saying:

The heart of an eel and of certain other fish and animals, having been taken out of the body, beats without auricles.  Furthermore, if yo ucut it in pieces, you will see the separate pieces each contract and relax, so that in them the very body of the heart beats and leaps after the auricles have ceased to move. (17)

Auffray and Noble said:

He (Harvey) could not, in his day, take this dissection further down to discover that the rhythmic mechanism was integrated at the level of individual cells, since the cell theory was formulated by Matthias Schleiden (1804-1881) and Theodor Schwann (1810-1882) two centuries later based on observations with the microscope introduced  in practice in the life sciences of Anton van Leeuwenhoek (1632-1723) only after Harvey's death.  However, he was the first to realise that rhythmicity was a property of the smallest structures he could discern. (17)

Had he had access to the microscope, perhaps Harvey would have made similar discoveries.  Yet he did not need to make any further discoveries, considering his discovery of circulation, and his proving it, was enough to secure his spot in history books.

Despite his accomplishments, Harvey's 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)

However, 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."  (11, pages 244-248)

It was through this discovery  that made it possible for 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)

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, said 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 the pulmonary arteries and then 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.

Garrison added:

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 (including Vesalius and Harvey), 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) 

While the Fabrica of Vesalias 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. Harvey, therefore, is often referred to by many as the modern father of medicine.  (15, page xxiii)

References:

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
16. "History of Chemistry," historyworld.net, http://www.historyworld.net/wrldhis/PlainTextHistories.asp?ParagraphID=kpt, accessed 7/6/14
17. Affray, Charles, Denis Noble, "Origins of Systems Biology in William Harvey's masterpiece on the Movement of the Heart and the Blood in Animals," April 17, 2009, International Journal of Molecular Sciences, 10(2), pages 1658-1669, found online at ncbi.nlm.hih.gov, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680639/, accessed 7/8/14
18. Strathern, Paul, " A Brief History Of Medicine:  from Hippocrates to Gene Therapy," 2005, London, Robinson, page

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1668: Leeuwenhoick completes Harvey's work

Anton van Leeuwenhoik (1632-1723)

William Harvey proved blood circulated through the body in 1628, although he could not see where veins and arteries connected. Marcello Malpighi observed where arteries and veins connected, although he considered it to be of little significance.  It wasn't until 1668, when Antony Leeuwenhoek observed these same connections, that the work of Harvey had been completed.

Anton (Antony) van Leeuwenhoek was born in Delft, Holland, on October 24, 1632.  His father was a basket maker, and his mother was from a family of "well-to-do" brewers, and so he had "an easy going life, said Garrison, "the greater part of which was devoted to the study of natural history."  (11, page 251)rcu

He was well educated a a child, and, in 1648, he left Delft to live with his uncle at  Benthuizen, where he was apprenticed in a linen-draper's shop (made linen products). In 1654 he returned to Delft and set up his own shop as a draper, although he also worked as a surveyor, a wine assayer, and as a minor city official. (18)

Leeuwenhoek's microscope

was a very powerful magnifying glass

It was a very simple device

that used only one lens,  

that is mounted in a tiny hole

in the brass plate that makes up 

the body of the instrument. 

The specimen was mounted 

on the sharp point that sticks up 

in front of the lens.  

Its position and focus could be adjusted

by turning the two screws.

The instrument was 3-4 inches long,

and had to be held up close to the eye.

It required good lighting and great patience.

This was a significant accomplishment

considering the compound microscope

was invented in 1595,

and had already been used 

by Robert Hooke

and Jan Swammerdam.

(18)

He was not well off financially as an adult, and there were no signs he would become one of the most significant scientists of his era.  However, perhaps inspired by Robert Hooke's book Micrographia,  by 1668 he had learned to grind lenses, and he made simple microscopes, using them to investigate plants and animals.  Over time he would end up with a collection of over 247 microscopes with 419 lenses, most of which he made himself.  (11, page 251)(18)

A neat thing about his microscope was that it was a simple microscope that used one lens. This was significant because a compound microscope similar to the one used today had been invented in 1595 and had been used by Robert Hooke and Jan Swammerdam to make significant discoveries.  (18)

However, compound microscopes were complicated to make, and it was not possible to magnify objects greater than twenty or thirty times their natural size. Due to Leeuwenhoek's skill at grinding lenses and adjusting lighting, he became skilled at observing microscopic structures up to 200 times their natural size. (18)

Perhaps for this reason alone, became such a significant investigator of the microscopic unknown, so significant that the director of the East India Company, said Garrison, sent him specimens, and even Peter the Great visited his collection in 1689.  He even donated 26 of his microscopes to the London Royal Society, of which he later became a member. (11, page 251)

Garrison said:

Leeuwenhoek was a strong man of marvelous industry, and during his long life he sent as many as 375 scientific papers to the Royal Society and 27 to the French Academy of Sciences.  (11, page 251)

He ended up "with skill, diligence, an endless curiosity, and an open mind free of t scientific dogma of his day."  This allowed him to become one of the most significant physicians and scientists of his era, making many of the "most important discoveries in the history of biology." (18)

He was the first person to visualize, or at least the first to report seeing: (11, page 251)

• Sperm cells (1674)
• Striped character of voluntary muscle (1675
• Protazoa (1675)
• Microorganisms (bacteria) in the teeth (1683)  (11, page 251)

By finding microorganisms in the teeth, he became the first person to accurately describe the "chains and clumps"associated with bacteria.  (11, page 251)

His most significant observation, at least for our history, was his observation of red blood cells in 1664 and capillary anastomosis connecting arteries and veins in 1668.  (11, page 252)

He was not the first to observe either, as Swammerdam was the first to describe red blood corpuscles and Malpighi also described them.  Malpighi was the first to describe capillary anastomosis connecting where arteries and veins came together, although he did not consider it a significant find.

Leeuwenhoek was the first to give a complete account of red blood cells, and he was the also first to consider capillary anastomosis as being a significant find. 

Garrison said:

It was Malpighi's discovery and Leeuwenhoek's thorough work on the capillary circulation which finally completed Harvey's demonstration. (11, page 252)

So while Galen might have suspected blood circulates as far back as the 2nd century, it wasn't described until the 16th century by Servetus, and proved until the 16th century by Harvey.  Yet with the observations of Malpighi and Leeuwenhoek, for the first time the circulation of blood could be traced through the entire body. 

References:

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
16. "History of Chemistry," historyworld.net, http://www.historyworld.net/wrldhis/PlainTextHistories.asp?ParagraphID=kpt, accessed 7/6/14
17. Affray, Charles, Denis Noble, "Origins of Systems Biology in William Harvey's masterpiece on the Movement of the Heart and the Blood in Animals," April 17, 2009, International Journal of Molecular Sciences, 10(2), pages 1658-1669, found online at ncbi.nlm.hih.gov, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680639/, accessed 7/8/14
18. "Antony van Leeuwenhoik (1632-1723)," ucmp.berkeley.edu, http://www.ucmp.berkeley.edu/history/leeuwenhoek.html

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1661: Malpighi completes Harvey's work

Marcello Malpighi (1628-1694)

So William Harvey proved that blood circulates through the body and published his proof in 1628.  Yet one thing that limited his research, almost causing it to come to a "standstill," was his inability to see where the arterial system connects with the venous system.

However, this problem would be resolved, thanks to the microscope, and thanks to the investigations of Marcello Malpighi.  He was the first to observe and report capillary anastomosis, which are the microscopic connections joining arteries and veins. (11, page 245)

Malpighi was professor at the University of Bologna.

By using a microscope in 1661, he observed the exchange of air from the lungs to capillaries in a frog.  He therefore was the first person to see the alveoli and capillary system. However, said Garrison, he did not apply much significance to this discovery (7, page 474)  (14, page 142)(11, page 252)

Garrison said that this was the missing link that Harvey was looking for regarding the complete circulation of blood through the body. However, considering Malppighi applied little significance to it, the discovery was not well regarded.  It would be left to a later investigator to complete Harvey's work. (11, page 247, 252)

A few years later, 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.

Malpighi's discover was verified by later observations:

• Dublin professor William Molyneux observed the capillary system in lizards in 1683.  
• 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 
• Anton von Leeuwenhoeck (1632-1723) observed capillaries in the larvae and feet of frogs in 1688 (14, page 142)

References:

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
16. "History of Chemistry," historyworld.net, http://www.historyworld.net/wrldhis/PlainTextHistories.asp?ParagraphID=kpt, accessed 7/6/14
17. Affray, Charles, Denis Noble, "Origins of Systems Biology in William Harvey's masterpiece on the Movement of the Heart and the Blood in Animals," April 17, 2009, International Journal of Molecular Sciences, 10(2), pages 1658-1669, found online at ncbi.nlm.hih.gov, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680639/, accessed 7/8/14
18. "Antony van Leeuwenhoik (1632-1723)," ucmp.berkeley.edu, http://www.ucmp.berkeley.edu/history/leeuwenhoek.html

1628: William Harvey discovers circulation, and proves it

Robert Hooke discovered the respiration
was not to keep the circulation of the
blood moving.In 1553 

While a book published by Andreas Vesaleas began a quest to learn about the human body, the discovery that the blood circulates by William Harvey would was a revolutionary breakthrough that allowed scientists and physicians to truly understand te human body, and how changes within caused disease.

Galen alluded to the idea that blood circulated through the body in the 2nd century. Yet in his many writings he described blood as moving back and forth between organs in a to and fro motion. Whether he had a notion it circulated is left to speculation.

Vesaleas was the first person to publish an accurate anatomy of the body. He performed autopsies, and had a painter paint what he saw, and this was published in a book, De humani corporis fabrica, in 1543. However, he erred in believing that the purpose of circulation was to cool the blood. (7, page 474)(11, page 243-4)

A contemporary of Vesaleas was Realdus Columbus (1516-1569).  He was a surgeon and professor of anatomy at Padua from 1544 until his death in 1569. He continued Servetus's work on circulation of the blood, describing the passage of blood from the vena-cave through the pulmonary circulation, and then through the left ventricle and aorta. (8, page 70-71)

Columbus also saw that blood changes in the lungs.  (11, page 243)

Andrea Cesalpino (1519-1603) 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.

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, one of whom was William Harvey. (14, page 93)(15, page xxiii)

Michael Servetus discovered circulation to the publication of his 1553 book, although he also failed to prove it.  So the door was still wide open for a major breakthrough in science, and just the man to accomplish this task was William Harvey, who essentially took over the work of Servetus.

William Harvey (1578-1657)(11, page 242)

Medical Historian Thomas Bradford said Harvey 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 for 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)

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 he 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 in animals, and came to the conclusion that the heart was a pump, and it circulates the blood through the body. (9, page 168-169)

While his comrades initially rejected his theory that blood circulates through the body, Bradford said:

King Charles took great interest in these discoveries and witnessed several experiments. He appointed Harvey his physician in 1643.  In 1633 he accompanied the king and his court to Scotland.  When "Old Parr" died the king gave the body to Harvey to dissect.  (14, page 120)

Several years after he made this discovery, and when he was 50 years old, he would publish, in 1628, Exercitatio anatomica de Motu Cordis et Sanguinis (An Anatomical Exercise on the Motion of the Heart and Blood in Living Beings).  (14, (page 119-122)

Of course, once Harvey published his discovery in his 1628 book  his medical practice took a hit, and he was criticized by a dogmatic medical profession.  (11, page 246)(14, pages 119-120)(17)

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, said Garrison. (11, page 246) (also see 14, pages 119-120)

Perhaps it was due to his friendship with the king that his ideas were accepted before his death in 1657. (14, page 119-122)

Garrison said William Harvey "was 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, )

Charles Auffray and Denis Noble, in a 2009 article in International Journal of Molecular Science, said that Harvey may even have come close to discovering how the heart may continue beating even after it is removed from the body.  They quote Harvey as saying:

The heart of an eel and of certain other fish and animals, having been taken out of the body, beats without auricles.  Furthermore, if yo ucut it in pieces, you will see the separate pieces each contract and relax, so that in them the very body of the heart beats and leaps after the auricles have ceased to move. (17)

Auffray and Noble said:

He (Harvey) could not, in his day, take this dissection further down to discover that the rhythmic mechanism was integrated at the level of individual cells, since the cell theory was formulated by Matthias Schleiden (1804-1881) and Theodor Schwann (1810-1882) two centuries later based on observations with the microscope introduced  in practice in the life sciences of Anton van Leeuwenhoek (1632-1723) only after Harvey's death.  However, he was the first to realise that rhythmicity was a property of the smallest structures he could discern. (17)

Had he had access to the microscope, perhaps Harvey would have made similar discoveries.  Yet he did not need to make any further discoveries, considering his discovery of circulation, and his proving it, was enough to secure his spot in history books.

Despite his accomplishments, Harvey's 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)

However, 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."  (11, pages 244-248)

It was through this discovery  that made it possible for 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)

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, said 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 the pulmonary arteries and then 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.

Garrison added:

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 (including Vesalius and Harvey), 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) 

While the Fabrica of Vesalias 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. Harvey, therefore, is often referred to by many as the modern father of medicine.  (15, page xxiii)

References:

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
16. "History of Chemistry," historyworld.net, http://www.historyworld.net/wrldhis/PlainTextHistories.asp?ParagraphID=kpt, accessed 7/6/14
17. Affray, Charles, Denis Noble, "Origins of Systems Biology in William Harvey's masterpiece on the Movement of the Heart and the Blood in Animals," April 17, 2009, International Journal of Molecular Sciences, 10(2), pages 1658-1669, found online at ncbi.nlm.hih.gov, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2680639/, accessed 7/8/14

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1664: Sylvius improves medical image

Sylvius started a medical clinic at Leyden in 1658.
A future successor of his was Herman Boerhaave,
who re-established respect for the profession by
having his students learn at the bedside, and focusing
on studying the patient before regarding theories.
Methods used at the clinic were so popular that
they quickly spread to other clinics in Britain, and
then throughout the whole of Europe. 

Francois de la Boe, also known as Sylvius, was among the first physicians who helped transform alchemy into chemistry, and improve the image of the medical profession.  

He was born in Hanau in the Netherlands in 1614, was educated at Paris, Sedan, Leyden and Basle, and earned his medical degree from Basle at the age of 23. He opened a practice at Hanua, and later moved it to Leyden and then Amsterdam.  He quickly became a very successful physician.  (1, page 115)

In 1660 he was hired as professor at Leyden, and in 1664 he opened the first medical clinic at Leyden. He also started what is believed to be the first university chemical laboratory.  (1, page 115)(2, page 68)

Bradford said: 

Here he had many pupils on account of the clinical method of instruction and his convenient system with its therapeutics. 

He was, therefore, among the first to take the student to the bedside of the patient in order to get the best medical education. This was an idea adapted and perfected by a future student and professor at Leyden by the name of Herman Boerhaave. This model of educating medical students would be later adapted by medical schools throughout Britain, all of Europe, and eventually the United States. (2, page 68)(3)

Bradford said Sylvius was a firm user of chemistry, and in this way transitioned the profession from alchemy to chemistry. His main ideas about medicine mainly follow the Hippocratic model, that diseases are caused by an imbalance of the humours. Although, like most physicians, he ads his own elements to the theory. Of this, Bradford said: (1, page 116)

There were three cardinal fluids—the saliva, the pancreatic fluid and the bile. The majority of diseases are caused by excess of acidity in the system or alkalinity. Health consisted in the undisturbed performance in the body of the process of fermentation; the saliva was thought to give rise to hectic fevers because there was some fever after eating. (1, page 116)

Bradford said the diagnostics of Sylvius can be summed up by the following passage by Sylvius:

As often as the whole blood appears black, it indicates that the acidity predominates; if the blood is redder, it shows that the bile in it is overabundant. In the first case the acid in the body and in the blood must be diminished; in the second, the bile must be lessened and its power broken. If the blood which is normally free from odor and of a sweetish taste, tastes salty, the alkali in the body is too pure, and when brought into contact with the acid spiritus engenders a humor of a saline taste which is prejudicial to the body. Fever is diagnosed by the pulse and not by the heat of the body. (1, page 116) 

In blending chemistry and medicine, britannica.com says that he "held that all phenomena of life and disease are based on chemical action."  Britannica also says that he blended William Harvey's proof that blood circulated through the body with the Hippocratic and Galen humoral theory. (3)

Regarding the view of Sylvius on the respiratory system, late 18th and early 19th century asthma expert Robert Bree said the following about Sylvius:

According to Sylvius, the parenchyma of the lungs is sometimes dense and corrugated, occasioning dyspnoea. He attributes this state to the restringent quality of the blood, but it may be assigned perhaps, with more reason, to preceding inflammation. (4, page 32)

Bradford said "his therapeutics were simple. We must get rid of the acids or the alkalies. When the acid is in excess give an alkali, when the alkali is in excess give an acid.  (1, page 116)

Bradford continued "(the) general object of therapeutics was to keep up the strength of the patient, remove diseases, mitigate symptoms, and remove their causes."  He listed the following as the remedies of Sylvius:

• Heating methods
• Absorbants
• Emetics
• Etc. 

Unlike most physicians of his era, he did not recommend bleeding.

Bradford said his ideas regarding medicine earned him many followers, although of his remedies, on the other hand, "it has been said that his therapeutics cost as many lives as the thirty years' war." (1, page 116)

Overall, like various other physicians from the 18th century (such as Boerhaave), and even while he was an ardent supporter of older theories, his contributions helped transform medicine away from "mythical speculation to a rational application of universal laws of physics and chemistry." (3)

References:

1. 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
2. Foucault, Michael, "The Birth of the Clinic," 2003, Great Britain, Routledge Classics 
3. Franciscus Sylvius, britannica.com, http://www.britannica.com/EBchecked/topic/577670/Franciscus-Sylvius, accessed 11/12/13
4. Bree, Robert, "A practical Inquiry into Disordered Respiration," 1810, London,  

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