Journal of Thrombosis and Haemostasis, 9 (Suppl. 1): 118–129
INVITED REVIEW
Discovery of the cardiovascular system: from Galen to William
Harvey
W. C. AIRD
The Center for Vascular Biology Research, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston,
MA, USA
To cite this article: Aird WC. Discovery of the cardiovascular system: from Galen to William Harvey. J Thromb Haemost 2011; 9 (Suppl.1): 118–129.
Summary. The goal of this review is to examine the events that
led to discovery of blood circulation. The Ancient Greeks,
including Hippocrates and Galen viewed the cardiovascular
system as comprising two distinct networks of arteries and
veins. Galen claimed that the liver produced blood that was then
distributed to the body in a centrifugal manner, whereas air or
pneuma was absorbed from the lung into the pulmonary veins
and carried by arteries to the various tissues of the body.
Arteries also contained blood, which passed from the venous
side via invisible pores in the interventricular septum and
peripheral anastomoses. This was an open-ended system in
which blood and air simply dissipated at the ends of veins and
arteries according to the needs of the local tissue. Blood was not
seen to circulate but rather to slowly ebb and flow. This view
would hold sway for 15 centuries until 1628 when William
Harvey published his momentous 72-page book, On the Motion
of the Heart and Blood in Animals. Harvey employed experiment
and deductive logic to show that arteries and veins are
functionally, if not structurally, connected in the lung and the
peripheral tissues, and that blood circulates. The mechanical
force of the heart replaced GalenÕs elusive attractive powers.
Ultimately, Galenism would collapse under the weight of
HarveyÕs evidence, and a new paradigm of blood circulation
would prevail.
Keywords: biology, cardiology, history, vascular.
Correspondence: William C. Aird, 330 Brookline Avenue, Boston MA
02215, USA.
Tel.: +1 617 667 1031; fax: +1 617 667 1035.
E-mail: waird@bidmc.harvard.edu
1
An argument is said to be deductive ÔIf it draws a conclusion from certain
premises on the grounds that to deny the conclusion would be to
contradict the premisesÕ.
2
Bloodletting would persist as a common therapy for many medical
conditions into the early 19th century. Harvey himself was a great bleeder.
In fact, he thought his circulation explained why bloodletting worked. If
blood is going around the body in a circle, then removing blood may
reduce blood pressure and remove the blood of toxins.
DOI: 10.1111/j.1538-7836.2011.04312.
Introduction
Imagine opening the chest cavity of an animal such as a
mouse and – without any prior knowledge of the circulation
– trying to make sense of the movement of the heart and
blood. For those readers who have had occasion to observe
the beating heart during open-heart surgery, or the rapid
motion of the heart in the living animal, they will appreciate
it rises and falls in the chest as it beats. How does this
alternating motion correlate with contraction (systole) and
dilatation (diastole) of the heart? Is diastole a passive state or
an active dilatation? It will also be noted that the arteries
pulsate. How does the pulsation relate to the cardiac cycle?
Knowing that the arteries contain blood, in what direction is
the blood flowing? Cutting open the artery gives little clue
about directional flow. Is the system open-ended or closed?
This is a difficult question to answer given that the
connections between the arteries and veins cannot be seen
with the naked eye. The Ancient Greeks had no prior
knowledge about the structure and function of the cardio-
vascular system. Even worse, by the 1600s investigators were
working with incorrect prior information. One cannot see the
circulation of blood. Thus, its discovery – a turning point in
the annals of biomedical history – depended on inference
through clever experimental approaches, as pioneered by
William Harvey.
Why is the discovery of the circulation considered to be so
important? Prior to Harvey, the physiology of the body was
essentially a question of the refinement of ingested food. Food
was transformed in the liver into blood and distributed in veins
throughout the body where it was assimilated to restore the
tissues gradually lost. In addition to blood, veins also contained
other humors, including yellow and black bile. Part of the
venous blood was diverted to the heart where it was mixed with
air in the left ventricle to form arterial blood imbued with vital
spirits. The latter was distributed to tissues of the body through
the arteries, providing heat, life and motion. (Some of the
arterial blood was sent to the brain for further refinement into
psychic spirits). The humors, spirits and heat ebbed and flowed
around the body, according to the needs of the tissues. Disease
was attributed to an imbalance of humors or a shift in the
patterns of flow within the body. Treatment was directed at
 2011 International Society on Thrombosis and Haemostasis

restoring the balance or controlling the movement of fluids.
Bloodletting (venesection) was a common remedy, as was the
use of ligatures (tourniquets) to redirect or divert the flow of
blood from one part of the body to another. The system made
sense. It was internally cohesive. However, fifteen centuries
later, HarveyÕs finding that blood circulates implied that blood
was not constantly being consumed in the periphery and
replenished by ingested nutrients, but rather that blood was
conserved. From a therapeutic standpoint, the rationale for
bloodletting – a mainstay of treatment for virtually every
disease –was cast into doubt. In short, the new theory of blood
circulation changed the intellectual system and worldview of
physiology, disease and therapy.
As modern-day clinician-scientists, why should we care
about the history of the circulation? For one, the historical
account reminds us that investigators from different eras
should be judged in the context of their own times. It is difficult
to put ourselves into the position of those who did not have our
answers. However, Galen was a brilliant researcher and
thinker, no less driven by a search for the truth than was
William Harvey. The Ancient Greeks did their best to generate
sound conceptual systems based on data available to them.
They did not know that their system was flawed. We can only
hope that our current models of the vascular system will be
judged fairly and sympathetically by future generations who
look back at the errors of our ways. Second, progress in science
does not occur in a vacuum, but rather builds on a foundation
of scholarship. As Harvey pointed out: Ôthere is no science
which does not spring from pre-existing knowledgeÕ. Science
did not begin with the molecular revolution, the germ theory or
the cell theory. Rather, science began when the Ancient Greeks
began searching for non-divine natural causes. Galen inherited
and built on the work of the Ancients, Harvey overhauled
Galenic doctrine, and we continue to build incrementally on
HarveyÕs model. Third, the fact that science fell dead for
centuries after GalenÕs death teaches us that scientific reasoning
is fragile and can be suppressed under certain political,
theological and cultural conditions. Progress in science contin-
ues to be hampered by such barriers, as evidenced by the recent
debate over human stem cell research. Fourth, the narrative
provides insights into the evolution of epistemological thinking,
or ways we go about acquiring knowledge and truth about the
natural world. One reason to study history is to understand
why people thought the way they did, what assumptions did
they make and why did they make them? This should remind
us to do the same about ourselves. Finally, the story teaches us
the importance of questioning existing dogmas when the
evidence calls for it. Harvey, while respectful of and deferential
to his predecessors, was not afraid to carve his own path.
HarveyÕs warnings about the power of authority and dogma
are equally pertinent today as they were in his time.
Before galen
Since the golden age of Greece (around 400 BC), it was
appreciated that all animals, including humans, must be
 2011 International Society on Thrombosis and Haemostasis
Discovery of the cardiovascular system 119
nourished, and that the nourishment must somehow be
distributed from the intestines to all parts of the body. During
this process humors are formed. Hippocrates and his contem-
poraries were the first to offer sophisticated reasoning in
medicine, rejecting a role for divine causation. They maintained
that health is associated with a balance of the humors, disease
with an imbalance. Thus, disruption of the nutritive process
plays a key pathogenic role in disease. Aristotle (384 BC)
believed that the heart is the center of the physiological
mechanism, the seat of the soul and the source of all blood
vessels. Praxagoras (340 BC) was the first to differentiate
between arteries and veins. He theorized that arteries begin in
the heart and carry pneuma, while veins originate in the liver
and carry blood. Herophilus (3rd century BC) recognized that
arteries have thicker coats than veins (noting the exception in
the lung). Erasistratus (3rd century BC) considered the heart to
be the source of both veins and arteries. He believed that
arteries normally contain air alone (Fig. 1). He observed that
when punctured, an artery bleeds. To explain this paradox, he
suggested that blood moves from veins to arteries through
invisible anastomoses when the arteries are emptied of air. In
summary, Galen inherited a flawed knowledge base from the
Ancient Greeks on which to build.
Galen
Galen the man
Galen was born in 129 AD in Pergamum, Asia Minor
(presently Bergama, western Turkey) during the height of the
Roman Empire. He began his medical studies at the age of 16.
His education spanned many years and geographical locations,
including Alexandria in Egypt. In 157 AD, at age 28, Galen
returned to Pergamum where he was appointed to the post of
surgeon to the gladiators. In this role, Galen received on-the-
job training as doctor, surgeon, trainer, and nutritionist. In 162
AD, Galen traveled to Rome, where he quickly established a
reputation as a leading medical authority. He was ultimately
appointed as Physician to the Emperor. Galen carried out the
bulk of his experimental work in the form of public demon-
strations. He wrote a vast number of works in subjects ranging
from medicine, through logic, philosophy, and literary criti-
cism. It is believed that Galen lived well into his 80s, dying
between 207 and 216 AD.
GalenÕs sources and methodology
Galen inherited from the Ancients an intelligible working
system of physiology and medicine. He set Hippocratic
medicine within a broader anatomical-physiological frame-
work, codifying, systematizing and building on existing
knowledge [1,2]. Galen carried out many of his own exper-
iments. He was not allowed access to human bodies (but he did
see inside humans in surgery and by chance). Thus, his studies
were largely confined to dead or living animals. In addition to
experimental evidence, Galen relied heavily on teleological
120 W. C. Aird

Fig. 1. Schematic of the cardiovascular system over time. (A) According to Erasistratus, arteries and veins are separate. Veins contain blood (blue color),
while arteries contain air (white color). Food is taken up in the intestines by the portal veins, delivered to the liver (black color), transformed into blood and
then transported to the vena cava by way of the hepatic vein. From the vena cava, venous blood is delivered to all parts of the body. Some of the blood is
diverted to the right ventricle (blue colored chamber in the heart), from where it enters the pulmonary artery to nourish the lungs. Air is taken up in the
lungs by the pulmonary veins, transferred to the left ventricle and distributed to the tissues via the arteries. Fuliginous vapors (waste) are excreted by
retrograde flow through the mitral valve and pulmonary vein. (B) Galen demonstrated that arteries normally contain blood (red color), not air.
Arterial blood is derived from the passage of venous blood through invisible pores in the interventricular septum (shown as interrupted septal wall). (C)
Colombo described the pulmonary circuit, in which venous blood in the right ventricle passes through the lungs into the left ventricle and arteries.
However, Colombo maintained the Ancient Greek view that blood flow in veins is centrifugal (away from the liver and towards all tissues), with only a
small amount entering the right heart. Thus, ColomboÕs system is a hybrid between closed (pulmonary) and open (systemic). (D) Harvey discovered
that blood circulates not only in the lung, but also around the whole body. An important clue was the presence of valves in the veins (two of them are shown
in white). The liver is no longer the source of veins. Rather, the system is driven by the mechanics of the heart (now shown in black). Transfer of blood from
arteries to veins in the lung and periphery may occur through direct connections or anastomoses (as shown) or through porosities in the flesh (the
latter mechanism being favored by Harvey).

arguments (Nature does nothing in vain) to explain the
structure and function of the human body. Galen repeatedly
stressed the unity of reason and experience. Some 400 years
earlier, Aristotle had introduced formal logic as a means of
generating scientific knowledge. In keeping with AristotleÕs
teachings, Galen employed deductive logic to arrive at many of
his conclusions .1 An example is his demonstration that arteries
contain blood, but not air:
1 If arteries contain blood, then they are not filled with
pneuma from the heart.
2 But arteries do contain blood.
3 Therefore, arteries are not filled with pneuma from the
heart.
However, as noted by the Galenic historian, Vivian Nutton,
Ô[GalenÕs] conclusions are almost always correctly derived from
his premises: it is the premises themselves that are disputableÕ
[3]. For example, consider the following demonstration:
1 If the heart is hotter than other organs, then it is the source
of innate heat.
2 But the heart is hotter than other organs.
3 Therefore, the heart is the source of innate heat.
Here, Galen bases the second premise on what he considered
to be clearly evident to the senses, namely that the heart is
hotter than other parts of the body. This erroneous premise
would go unchallenged for centuries until the invention of the
thermometer.
GalenÕs view on Nature
Galen accepted the ancient doctrine that the four elements
(earth, wind, fire, and water) embody the four primary
irreducible qualities (the hot, cold, dry and wet). These
corresponded to the four essential humors of the body (blood,
black bile, yellow bile, and phlegm) [1,4,5]. The humors, in
turn, took their origin from the elements found in food. Indeed,
GalenÕs physiology started with nutrition. As we will see, food
was ultimately transformed into blood, and blood in turn was
somehow transmutated into the flesh of tissues. But the human
body was more than a series of hungry organs. It had warmth
and vitality, it moved voluntarily, it had thoughts. Thus,

 2011 International Society on Thrombosis and Haemostasis


overlaid on the nutritive or natural spirits (the blood) was a
vital spirit. While the natural spirit had its origin in food and
drink, the vital spirit was derived from atmospheric air. Natural
spirits were carried by veins, vital spirits by arteries. At the
center was the heart, which mediated exchange between blood
in the veins and air in the arteries. Like a burning cauldron, the
heart also provided the body with innate heat. The heart was a
smelterÕs furnace and factory, not a pump. This industrial
model of the heart reflected existing technology in Roman
society. The analogy of the heart to a force pump was only
really made possible when such devices became commonplace
in the 16th century.
The body parts and their actions resulted from different
combinations of the four elements, qualities, and humors.
Galen proposed a theory of natural faculties, according to
which every part of the body has the power to attract, retain,
and concoct or alter its nutritive humors as well as to expel its
excrements. At any point in time, the flow of material (e.g.,
nutriment, pneuma or waste) between body parts seems to
follow a gradient of attractive and expulsive powers.
Galen agreed with Hippocrates and Aristotle that the heat of
the body is innate and inexorably linked to life and the soul.
Innate heat is required for alterative processes and is thus
indispensable for digestion, nutrition, and the generation of
humors. The innate heat derives from the heart (especially the
left ventricle) and the arteries. Galen rejected AristotleÕs brain
as a cooling device, claiming instead that it is the lungs that
refrigerate the heart.
In addition to his vitalism, Galen accepted certain mecha-
nistic explanations. For example, he agreed with some of his
predecessors that nature abhors a vacuum and that there is a
tendency for a vacuum to become refilled. For Galen, this is a
mechanical law that explains how active dilatation of body
cavities (such as the heart and arteries) creates traction and
draws neighboring matter into itself. In contrast to the
powerful vital attractive power of all body parts that operates
at small distances, the mechanical vacuum effect can exert
traction even across large distances.
GalenÕs view on the cardiovascular system
Veins contain blood According to Galen, the liver is the
source of all veins and the principle instrument of
sanguification [4–7] (Fig. 1). In the stomach, food is
concocted into chyle, which is then delivered to the small
intestine and absorbed into veins. The chyle is carried in the
portal vein to the liver, where nutriment becomes actual blood,
which is charged with natural spirits. Blood is purified in the
liver and then enters the hepatic vein through invisible
connections between branches of the portal and hepatic
veins. The blood moves from the hepatic vein to the inferior
vena cava, which through its branches supplies all the parts of
the body above and below the liver. In other words, blood
moves centrifugally from the center (the liver) to the periphery.
This is an open-ended system designed to provide one-time
distribution of food. Each part of the body attracts and retains
 2011 International Society on Thrombosis and Haemostasis
Discovery of the cardiovascular system 121
only enough blood for its immediate requirements. Blood that
is assimilated into tissue is ultimately lost though invisible
emanation. The parts receive fresh supplies from the liver as
needed. As such, movement of blood was subsumed under the
theory of nutrition according to which each body attracts,
retains, and assimilates food, and expels its superfluities.
A portion of blood nourishes the lung via the right
ventricle A small amount of blood entering the vena cava
is diverted to the right auricle, which is considered an
outgrowth of the caval system. From the right auricle blood
enters the right ventricle. Dilatation of the right ventricle draws
in blood from the vena cava. The right ventricle further
elaborates and attenuates the blood, rendering it fine and thin.
Some of this refined blood enters the pulmonary artery. Blood
in the pulmonary artery nourishes the lung. A small portion of
the blood (the thinner part) in the pulmonary artery is squeezed
through invisible anastomoses into the pulmonary veins, from
which it too is absorbed by the lungs, providing them with vital
spirits. Finally, some blood in the right ventricle passes into the
left ventricle through invisible pores in the interventricular
septum.
The heart intrinsically pulsates Galen recognized that both
ventricles pulsate even when their nerves are severed or the
heart is removed from the thorax. Thus, the power of pulsation
has its origin in the heart itself. The heart dilates during diastole
and contracts during systole. Diastole is an active process
during which the heart snatches up or sucks in the inflowing
blood like a smithÕs bellow or sponge. The filling of the heart in
diastole causes the heart to twist and the apex to rise and strike
the chest wall. Systole serves to expel residues from the left
ventricle into the pulmonary vein.
Respiration cools the innate heat and yields vital
spirits The outer air is concocted in the lung to form
pneuma. Pneuma is then transmitted by the pulmonary veins
into the left ventricle where it cools the innate heat and where it
meets the venous blood received through the septum. Together,
these conditions result in further concoction into vital spirits,
which are then distributed to tissues in arteries. Noxious
vapors, generated as a byproduct of the innate heat are expelled
into the pulmonary vein during systole and ultimately expired
through the airways. Retrograde movement in the pulmonary
vein is made possible because the mitral valve has only two
outgrowths (valves), which cannot be accurately closed. Thus,
the pulmonary veins serve as ventilating ducts, inhaling cool air
into the left ventricle, and exhaling heated air and smokey
vapors. Stated another way, the left ventricle ventilates itself by
inhaling and exhaling through the pulmonary veins. The lungs
also serve to aid the flow of blood by their rise and fall, as well
as to provide physical protection to the heart.
Arteries contain air and blood Erasistratus had argued that
arteries normally contain air or pneuma alone. Galen proved
experimentally that all arteries in the body contain a portion of
122 W. C. Aird
blood. This was demonstrated by ligating an artery in two
places, slicing open the intervening segment, and finding blood,
but no air. If arteries contain blood, how does it get there from
the veins? Galen suggested that blood permeates from
pulmonary arteries to pulmonary veins through invisible
channels. However, the resulting blood in the pulmonary
veins does not reach the left ventricle, but rather is used by the
lungs as nourishment. In other words, there is no pulmonary
circuit. Instead, blood in the left ventricle (and hence the
systemic arteries) is derived directly from the right ventricle,
through invisible pores in the interventricular septum.
Arteries vs. veins Galen noticed that certain properties
differed between arteries and veins. For example, veins are
located in both superficial and deep locations, whereas
arteries are always deep. Arteries pulsate, veins do not. The
tunic of arteries is denser than that of veins. The blood in
arteries and veins is qualitatively different. Compared with
veins, the blood contained in arteries is hotter, thinner and
more spirituous.
The arterial pulse is an intrinsic property of the blood
vessel The arterial pulse is an inherent property of the blood
vessel. It is a vital power that springs from the heart and is
transmitted through the coats of the arteries. GalenÕs claim was
based on a famous experiment (later criticized by Harvey) in
which he placed a hollowed reed into a severed artery. When he
tightened a ligature around the vessel wall over the hollow tube,
he noted that the distal arterial segment stopped pulsating.
The whole body breathes in and out Arteries are not
expanded because they are filled. Rather, they are filled because
they are expanded. When expanded, the arteries draw in from
all sides. When contracted, they squeeze out on all sides.
Exchange occurs through pores or vents in the coats of the
arteries or through mouths that open into the gut of outer skin.
GalenÕs model amounts to a type of skin breathing, where
arteries on the surface of the body draw in airy substance that
surrounds us (during diastole), and eliminate smoky, vaporous
residue derived from the burning up of the juices (during
systole) throughout the whole animal. The intake of air into
dilated arteries serves to cool the natural heat, whereas the
expulsion of smoky, vaporous residue serves to purge
the innate heat. In short, the arterial pulse and respiration
serve the same ends.
All is in all None of the parts of the body is absolutely pure.
Everything shares in everything else. Thus, while arteries are
primarily instruments of the pneuma, they have their share of
thin, pure spirituous blood. Veins are primarily instruments of
the blood or other nutriment, but contain a little mistlike air.
All over the body, arteries and veins communicate with one
another by common openings and exchange of blood and
pneuma occurs through certain invisible and extremely narrow
passages or inosculations. Through these junctions, the arteries
draw from the veins, when they expand, and squeeze into them
when contracting. Thus, the movement of blood and air is
neither directional nor rapid. Rather, the contents of blood
vessels move slowly, hither and thither.
Medical implications of GalenÕs theory Many internal and
external factors were thought to interfere with nutrition and
blood flow, and thus produce disease. In external
hemorrhages, blood is attracted to the wound. Internally,
an abnormal flux of blood to one site of the body may
produce swelling and inflammation. Alternatively, there may
be larger scale movements of blood, for example from the
center to the periphery (outward movement, or expansion) or
from the periphery to the center (inward movement, or
concentration). Therapies were designed to alter or correct a
harmful flux of humors. These included the application of
heat, massages, ligatures, or venesection in strategic, specific
sites of the body.
GalenÕs legacy Galen was faced with a bewildering array of
facts. He knew that the heart moved and tapped against the
chest wall, that breathing was essential to life, that heat was
extinguished in death, that the valves of the heart functioned,
that arteries and veins were connected with the heart, and that
these two blood vessel types were structurally different and
contained blood of different color. Determining the various
movements of the living heart must have been extremely
challenging. Nonetheless, Galen developed a system of
remarkable internal coherence, one that provided an
explanation for digestion, the production of blood, the
distribution of nourishment around the body, and the
generation and conveyance of heat. In short, the functions of
the liver, veins and right heart were to deliver the products of a
healthy diet to the various parts of the body, while the
functions of the lung, left heart and arteries were to deliver fresh
air and to cool the body. All of this was consistent with
NatureÕs intent. More importantly, the system provided a
rational foundation for therapy.
GalenÕs most significant contribution was to synthesize
existing knowledge, including the Ancient Greek heritage of
humoral medicine. However, he also made original observa-
tions. He was to the first to convincingly demonstrate that
arteries contain blood. His argument that blood must normally
pass from veins to arteries via anastomoses in the lung and
periphery was novel as was his misguided reference to
imaginary holes in the interventricular septum. The question
of how blood got from the right ventricle of the heart to the left
ventricle would challenge investigators for the next 1500 years.
Its answer would provide an important clue about the
circulation of blood.
The dark ages, middle ages and the Renaissance
The fall of the Roman Empire was followed by a long period of
time (500–1400 AD) in which the scholarly tradition was
closely intertwined with – and controlled by – the Church [8–
11]. There was no interest in acquiring new knowledge through
 2011 International Society on Thrombosis and Haemostasis

experimentation. Rather the focus – on the part of philosophers
and the clergy – was to preserve and organize Ancient Greek
teachings and to reconcile these with theology. GalenÕs
teleological leanings fit well with Christian doctrine. His work
became scripture and its theological status rendered it immune
to reasoned challenge. Any new findings or anomalies were
made to fit GalenÕs physiology and anatomy.
Compared with the Latin West, the intellectual conditions in
Byzantium and the Islamic world were far superior. Arabic
authors had access to many more works of the Ancient Greeks
than did the West. In the mid-13th century, Ibn al-Nafis of
Damascus provided the first description of the pulmonary
circulation. He wrote that blood does not permeate the
interventricular septum, but rather circulates in the lungs via
invisible connections between the pulmonary arteries and veins.
In 1547, Ibn al-NafisÕs work was translated into Latin.
However, there is no evidence that his ideas were known to
Servetus and Colombo who rediscovered the pulmonary
circulation in the 1500s.
In the 12th century, animal dissection was initiated in
Salerno for the first time since Antiquity. Dissection of human
bodies appears to have begun in the late 13th century at the
University of Bologna. Over the next 2 centuries, the objective
of dissections was not to investigate, but rather to study and
teach the works of Galen. In the 1400s, the Renaissance in Italy
ushered in a new era of learning and discovery. With the
emergence of the polymath, art and science began to inform
each other in important ways. Leonardo da Vinci (1452–1519),
who was interested in the link between form and action of the
human body, was the first to make accurate drawings of the
heart, including its valves. In a departure from Galen, who
claimed that the heart was not a muscle, Leonardo wrote: Ôthe
heart is a vessel made of thick muscle, vivified and nourished by
artery and vein as are other musclesÕ. Leonardo was the first to
identify the atria as heart chambers, and to provide a
description of atherosclerotic coronary arteries. These discov-
eries notwithstanding, Leonardo – like everyone else in his time
– was an avowed Galenist.
Andreas Vesalius (1514–64), a Flemish professor of anatomy
at Padua, carried out his own dissections (unlike Galen, he had
access to human corpses) and began to point out errors in
GalenÕs work. In particular, he questioned the existence of
pores in the interventricular septum. One of VesaliusÕs great
contributions was his use of detailed, realistic illustrations of
the human body in what amounted to the first modern
textbook of anatomy.
Michael Serveto (also known as Servetus, 1511–1553), a
Spanish philosopher-theologian, published a treatise in which
he proposed that blood is driven from the right ventricle to the
lungs, where it mingles with inspired air and is ultimately drawn
into the left ventricle. There is no evidence that Serveto actually
carried out his own experiments.
Realdo Colombo (also known as Columbus, 1516–1559),
an Italian anatomist and student of Vesalius bred in the
Galenic tradition, provided an anatomical account of the
pulmonary transit of blood (Fig. 1). He based his theory on
 2011 International Society on Thrombosis and Haemostasis
Discovery of the cardiovascular system 123
three observations. First, he noted that the pulmonary vein is
full of blood, which would not be the case if the vessel were
constructed solely for conveying air and vapors. Second, he
was unable to demonstrate pores in the interventricular
septum. Third, he recognized that the heart valves are
competent and thus vital blood cannot return to the lungs.
Since all organs of the body are in need of vital spirits, how
else could the lung receive them except by the aorta and
pulmonary circuit (apparently, Colombo did not identify the
bronchial arteries, though Leonardo had described them
some years earlier)? His observations were reported in a
posthumous publication in 1559. Colombo made no reference
to the work of Ibn al-Nafis or Servetus, and was probably
unaware of their contributions (indeed, Harvey would later
allude only to the work of Colombo). It is important to point
out that neither Servetus nor Colombo overthrew Galenic
doctrine. Both continued to maintain that only a small
amount of the venous blood was diverted to the right heart
(and hence the left ventricle). Most of the blood remained in
the vena cava and was distributed centrifugally to the
periphery. The pulmonary circuit simply replaced the septal
pores as a means of transferring blood from the right to left
ventricles.
Girolamo Fabrizio (also known as Fabricius, 1537–1619),
professor of anatomy at Padua when Harvey studied there,
identified venous valves in 1574 and published a description of
them in 1603. As an adherent of Galenism, Fabricius proposed
that the valves function to slow the centrifugal flow of blood to
the periphery. In other words, they serve to prevent forceful,
excessive outward movement of blood due to gravity and
peripheral attraction to the lower part of the limbs at the
expense of under-nourishing the upper parts. This was only a
minor departure from Galen, who believed that the flow of
blood was controlled by the attractive power of the parts,
which drew blood as needed.
In 1571, Andrea Cesalpino (also known as Caesalpinus,
1519–1603), a former student of ColomboÕs and now a
professor of medicine at Pisa, confirmed the existence of the
pulmonary circuit. In a departure from his predecessors, he
posited that the heart, and not the liver, is the main source of
nutriment. Cesalpino envisioned that veins carry some (but
not all) of the nutriment from the gut and liver to the heart
where it receives its final perfection and is then distributed to
the body through the arteries. The rest of the venous blood
moved centrifugally from the liver to tissues. Caesalpinus
envisioned that (only under certain circumstances, such as
with the use of a ligature or tourniquet) blood would pass
from the arteries to the veins in the periphery. Although he
came close to describing the circulation, Caesalpinus still
viewed the system as providing one-way delivery of nutri-
ment to the tissues.
In 1627, Cesare Cremonini developed a quantitative argu-
ment implicating a role for arteries not just as a vehicle for heat
and spirit but also as an instrument of nutrition. He pointed
out that arterial blood, once generated is diffused in Ôgreat
quantityÕ to the entire body. He asked what becomes of it if it is
124 W. C. Aird
always generated but not consumed as nutrient. Surely it would
grow to infinity, he concluded.
In summary, the revival of experimental investigation in the
1500s, while opening the door to progress, did not lead to the
downfall of GalenÕs system of physiology. So persuasive was
GalenÕs theory that these new findings were simply integrated
as small modifications into the ancient scheme.
William harvey
Harvey the man
William Harvey was born in 1578 AD in Kent, England. In
1593, he matriculated as a student at Gonville and Caius
College, Cambridge, where he studied classics, rhetoric and
philosophy. After receiving his Bachelor of Arts degree in 1597,
Harvey studied medicine at Padua in Italy, the greatest medical
school of the time. The curriculum at the time revolved around
GalenÕs physiology and anatomy and AristotleÕs physiology. In
Padua, Harvey studied under Fabricius, and it is likely that he
saw a demonstration of the venous valves well before their
discovery was published in 1603. It is noteworthy that while
Harvey was at Padua, Galileo occupied the chair of mathe-
matics. The extent to which Galileo influenced HarveyÕs
approach to experimental research is debated. Harvey returned
to England in 1602, and in 1604 was appointed Assistant
Physician at St. BartholomewÕs Hospital. In 1615, Harvey was
appointed Lumleian Lecturer (a lifetime appointment) at the
Royal College of Physicians. In this capacity, Harvey lectured
twice a week at the College in anatomy and surgery in 6-year
cycles. HarveyÕs lecture notes from 1616, which have been
preserved, attest to the early seeds of his theory of the
circulation. In 1628, Harvey published his findings in a modest
72-page book written in Latin, entitled Exercitatio Anatomica
de Motu Cordis et Sanguinis in Animalibus (which translates as
Anatomical Exercises on the Motion of the Heart and Blood in
Animals). He published two rebuttals to his critics in 1649.
Harvey served as Physician to the King (initially James I, then
Charles I). He married but had no children. He died in 1657 at
the age of 79.
HarveyÕs sources and methodology
Harvey realized that observation, while key to the scientific
method, must be followed by the formulation of a hypothesis
[9,12]. The validity of that hypothesis, in turn, requires
repetitive, directed experiments. In this respect, Harvey was a
modern thinker. However, he remained partly embedded in the
ancient doctrine. He was a great admirer of Aristotle, adopting
his teleological ideas, his program in comparative anatomy and
some of his views on the natural world, including its vitalistic
core. Like Aristotle, Harvey saw the unity of various circular
motions in the universe and parallelism between microcosm
and macrocosm. Circular movement symbolized perfection,
perpetuity and preservative qualities. Indeed, this analogy may
have been critical to HarveyÕs reasoning. Harvey inherited
AristotleÕs use of observations and deductive logic to acquire
new knowledge. Consistent with his hypothetical-deductive
approach, Harvey did not use teleology as final proof, but
rather as a means to establish testable premises. That being
said, he did not shy away from occasional teleological
arguments. For example:
1 If Nature does nothing in vain, she would not have added the
right ventricle for the sole purpose of nourishing the lungs.
2 But Nature did add a right ventricle.
3 Therefore, Nature added the right ventricle for another
purpose.
Early in his career, Harvey did not outright discard Galenic
doctrine. Indeed, much like his Renaissance predecessors, he
initially aimed to advance or push forward the work of the
Ancient Greeks. Although Harvey would eventually replace
the Galenic system of physiology with a new model, he
continued to espouse an essentially vitalistic and qualitative
picture of the human body. However, it is important to point
out that Harvey was careful to distinguish what he considered
fact (e.g., the circulation of blood) from what he considered
speculation (e.g., the purpose of the circulation of blood).
Finally, Harvey leveraged his rhetorical skills, social standing,
and his connection with the Royal College and the Court to
promulgate his new theory.
HarveyÕs view on Nature
Like the Ancient Greeks, Harvey viewed the body as being
moved by vital forces and comprising humors. In contrast to
Galen, who assigned primary importance to formed organs,
Harvey believed in the primacy of the blood. For Harvey,
blood was not only nutriment, but also the ultimate repository
of heat and spirits. He believed that the spirits in the veins and
arteries were not distinct from the blood Ôany more that the
flame of a lamp is distinct from the inflammable vapor that is
on fireÕ. The blood is imbued with spirit much like wine
contains spirit. ÔFor a wine, when it has lost all its spirit, is no
longer wine, but a vapid liquor or vinegar, so blood without
spirit is not blood, but something elseÕ.
Harvey rejected mechanical explanations that were emerg-
ing as part of the Scientific Revolution, led by such contem-
poraries as Galileo, Rene Descartes and Francis Bacon. The
scientific revolution rejected the Ancients wholesale, and
ushered in an era of mathematics, mechanization and an
atomic theory. The world was no longer seen in qualitative
terms but rather in mathematical terms. For example, the
terms ÔhotÕ or ÔcoldÕ were represented by numbers on a
temperature scale. According to the atomic theory, matter
could be broken up into discrete entities, which were not cold,
hot, dry or wet, but rather possessed quantities of length,
breadth, depth and motion. These elements interacted with
one another in a mechanical manner. Particles interacted and
reacted according to laws of physics, not according to a final
cause. As such, the human body came to be seen as complex
machine. These uncompromising views contrasted with Har-
veyÕs vitalistic leanings.
 2011 International Society on Thrombosis and Haemostasis

HarveyÕs description of the movement of the heart and arteries
Against skin breathing As pointed out earlier, the Ancient
Greeks believed that arteries suck in air during diastole and
expel fuliginous vapors during systole through the pores of
the flesh and skin [10,13–16]. Harvey argued that if arteries
are filled in diastole with air, then why when one plunges
into a bath of water or oil, does the arterial pulse not become
smaller or slower, since the bath will interfere with the
uptake of air? Moreover, how do those arteries that lie deep
within tissues absorb air during diastole? How does the fetus
draw air into its arteries through the abdomen of the
motherÕs abdominal wall, and how do deep diving mammals
absorb air through the infinite mass of water? How is it that
during systole, arteries expel vapors, but not vital spirits? If
arteries attract blood from the left ventricle during arterial
diastole, how can they at the same time attract air from the
body surface?
Arterial pulse is due to impulses of the blood from the left
ventricle Harvey criticized GalenÕs experiment with the
reed, even doubting that the experiment was ever carried
out. Indeed, we learn later (in his letters published in 1649)
that Harvey repeated the experiment and found the opposite,
namely that the artery distal to the ligatured segment
containing the tube continues to pulsate. When an artery is
cut, blood spurts out and escapes with force, alternately in
jets, with the jets corresponding to arterial systole (when the
arteries are dilated). The jets occur only from the orifice
closest to the heart. If arterial dilatation serves to suck in air,
as Galen would have it, the severed artery should not Ôthrow
blood to such a distanceÕ. Just because the arterial wall is
thick does not mean that the pulsatile property proceeds
along them from the heart. In fact, we observe a normal
pulsation in arterial aneurysms, where the coat is attenuated.
(In a communication that was published in 1649, Harvey
tells us about the case of a patient of his who had evidence
of a calcified aorta at autopsy yet who had demonstrated a
pulse in the legs and feet during life). Contraction of the
ventricles occurs at the same time as the arteries are
distended. When the heart stops beating, the arteries lose
pulsation. Blood spurts from a severed artery at the same
time that the heart contracts. Thus, in contrast to what the
Ancients believed, contraction (systole) of the heart occurs
simultaneously with dilatation (systole) of the arteries. ÔThe
arteries, therefore, are distended, because they are filled like
sacs or bladders, and are not filled because they expand like
bellowsÕ. The arterial pulse can be compared to Ôblowing into
a glove and producing simultaneous increase in volume of all
its fingersÕ. Harvey attributed arterial diastole to an inherent
property of the vessel wall (which we know today to involve
elastic recoil). ÔThus the arteries are dilated by the heart, but
subside of themselvesÕ. Clinical evidence for this conclusion
was provided by the observation that patients with
compression or infarction of the artery results in reduced
pulsation distally.
 2011 International Society on Thrombosis and Haemostasis
Discovery of the cardiovascular system 125
Arteries and veins contain the same blood The Ancient
Greeks believed in a dual system of veins and arteries. Galen
proposed that veins contain blood, whereas arteries contain
blood imbued with vital spirits. Harvey believed that both
arteries and veins contain the same blood. Indeed, arterial and
venous blood, when removed from the body and allowed to sit
in a basin, demonstrate the same color, similar consistency in
the coagulated state, and the same height (volume) when
cooled. Harvey wrongly attributed the redder color of freshly
removed arterial blood to the fact that the thick arterial coats
render the outlets smaller and that these smaller orifices act like
a sieve, allowing escape of the lighter, thinner part of blood. He
even claimed that in obese patients, subcutaneous fat
compresses the veins so that phlebotomy yields thinner, more
florid blood, not unlike that of an artery. Although arteries and
veins contain the same blood, Harvey acknowledged that
arterial blood is more spirituous and Ôpossessed of higher vital
forceÕ. The blood and spirits do not flow in the arteries
separately but as one body.
Against the right ventricle serving merely to supply
nourishment to the lungs In the Galenic system, the right
ventricle serves a Ôprivate functionÕ, namely to provide the lung
with nourishment (blood). In contrast, the left ventricle is
designed for the egress of vital spirits and regress of fuliginous
vapors. However, both ventricles are structurally similar and
display comparable action, motion and pulse. How, Harvey
asked, can we explain the dichotomy in function of identically
structured right and left ventricles? Moreover, the pulmonary
artery and vein are roughly the same size, and so it seems
unlikely that the former serves a private function (providing
nourishment to the lung) and the latter a public function
(providing pneuma to the left ventricle). If only a portion of
blood from the vena cava reaches the right ventricle (the rest
proceeding to the superior vena cava), then why is the
pulmonary artery so large, in fact of greater capacity than both
iliac veins? Why was ÔNature reduced to the necessity of adding
another ventricle for the sole purpose of nourishing the lungsÕ?
Why does the lung require so much nourishment and why does
the nutriment for this organ (but not others such as the brain
and eyes) require additional concoction in the right ventricle?
Against the left ventricle serving for egress and regress of
spirits Harvey called into question GalenÕs claim that the
left ventricle draws in air and expels vapors through the same
blood vessel (the pulmonary vein). If the mitral valve allows
retrograde flow of such vapors, how can it prevent the escape
of air? If the pulmonary artery has the single purpose of
delivering blood to the lungs, why should we presume that
the pulmonary vein (which is almost as large and has the
coats of a vein) has multiple functions (e.g., air passing from
the lungs into the left ventricle and vapors passing from the
left ventricle into the lungs)? Why would Nature construct a
single vessel for opposing flow of air and vapors? If the
pulmonary vein serves as a conduit for air and vapors, why
when it is cut does one only see blood? If the pulmonary
126 W. C. Aird
artery was designed for conveyance of air, then why is it
structured as a blood vessel, and not like the annular
bronchi?
Against the transit of blood from the vena cava to aorta
through holes in the interventricular septum Galen held
that vital spirits require both air and blood and that blood
entered the left ventricle via hidden porosities in the
interventricular system. Like Vesalius and Colombo, Harvey
could not demonstrate these septal pores. He went a step further
and claimed that they simply did not exist. He pointed out that
the septum is denser and more compact than most parts of the
body. Moreover, given that the right and left ventricles contract
and dilate simultaneously, how can one ventricle extract
substances from the other? Why should these foramina permit
exchange of blood from right to left sides, but not of air from left
to right? Why do we need to invoke invisible channels when the
pulmonary vein and the lax, soft, spongy substance of the lung
offer an open route? There are examples in nature whereby
blood is transferred from veins to arteries through visible open
passages. For example, in fish, the heart consists of a single
atrium and ventricle through which blood readily passes from
the venous trunk to aorta. In the mammalian fetus, blood is
transferred from the venous to arterial side through visible,
conspicuous patent channels, namely the foramen ovale and the
ductus arteriosus. When these close postnatally, why would
Nature replace them with invisible pores in the septum? Why
not accomplish the same though the substance of the lungs?
Finally, if blood permeates the septum, why then is the septum
supplied by coronary vessels?
In favor of pulmonary transit of blood from vena cava to
aorta In addition to the points outlined above, Harvey
argued that if the whole of nutritive juices pass through the liver,
then surely the whole of blood can pass though the lungs. After
all, the liver is dense, while the substance of the lung is loose and
spongy. Moreover, in contrast to the liver, which has no
impelling power, the lung receives blood under force from the
right ventricle. Finally, the pulmonary valves prevent blood
from returning to the heart from the pulmonary artery. Harvey
concludes that Ôblood is continually permeating from the right
to left ventricle, from the vena cava into the aorta, through the
porosities of the lungsÕ. (Marcello Malpighi would later use light
microscopy to identify these porosities as capillaries). Nature
added the right ventricle not to nourish the lungs, but to propel
blood through the lungs into the cavity of the left ventricle.
The intrinsic motion of the heart is systole, not
diastole The heart is erected and rises upwards and strikes
the chest wall when contracted. When grasped in the hand, the
heart becomes harder during contraction, creating a tension
that is similar to contracting skeletal muscle. A contracted
heart becomes paler in color. When the ventricle is pierced,
blood is forcefully projected outwards when the heart is
contracted. Thus, Harvey states: Ôone action of the heart is the
transmission of the blood and its distribution, by means of the
arteries, to the very extremities of the bodyÕ. In addition to this
action, Harvey speculates that there may be other functions,
including adding heat, spirit or perfection to the blood, but
decides not to address these questions.
Quantity of blood is too great to be explained by open system
of blood vessels A major obstacle that Harvey faced as he
collected his data was that any findings could be interpreted as
an artifact of the system, as an unusual or pathologic pattern of
blood flow. Any outside influence on the system could alter the
rate and/or direction of normal blood flow. He needed
quantitative proof in the intact organism. Harvey asked
himself: Ôwhat might be the quantity of blood which was
transmittedÕ by the heart? He carried out what amounted to a
thought experiment. He had found that the left ventricle
contained up to 2 ounces of blood. He then assumed different
ejection fractions (1/4, 1/5, 1/6 or 1/8) and multiplied the
resulting stroke volume by the heart rate (which he estimated as
only 33 per min). In this way, he arrived at a cardiac output
that exceeded the total volume of blood in the whole body
(between 3.9 and 31 kg per 30 min, values that vastly
underestimate the true cardiac output, but nonetheless exceed
the total volume of blood in the body). Importantly, more
blood passes through the heart than can be supplied by the
food consumed or that can be contained in veins at the same
moment. Moreover, the quantity of blood must be far greater
than that required for nutrition (a process by which blood is
assimilated, becomes coherent and transforms into the
substance of the tissue). In an open-ended system of arteries,
this large quantity of blood would cause the arteries to rupture.
Thus, Ôit is matter of necessity that the blood perform a circuit,
that it return to whence it set outÕ. Stated another way, blood
must continually return to the heart to provide for the
quantitative requirements of the heartbeat. To prove this
point, Harvey tied or used his fingers to constrict the veins
entering the heart of fish or a snake and noted that the space
between the constriction and the heart, as well as the heart itself
became empty and pale (Fig. 2). On the other hand,
compression of the aorta caused the heart to become
distended and blue-purple in color. These changes were
reversed with loosening of the constriction.
Blood enters a limb by arteries and returns from it by
veins Harvey employed two types of ligatures (tourniquets)
on the arm (Fig. 3). The first was a tight ligature that
compresses both the arteries and veins, resulting in loss of
pulsation beyond the ligature. The tight ligature was used
clinically to stem the flow of blood during amputations, for the
castration of animals and for the ablation of tumors. The other
was a ligature of medium tightness, which compresses the veins
but not the arteries. The arterial pulse can still be palpated
distally. This type of ligature was used clinically in bloodletting.
The Ancient Greeks believed that with the medium-tight
ligature, more blood was attracted to the distal arm via the
veins (a similar argument was made for heat, pain and a
vacuum drawing blood). Hippocrates wrote: Ôligatures set the
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 Discovery of the cardiovascular system 127

Fig. 2. Proof that arteries receive blood from veins by transmission through the heart. (A) Tying the veins below the 2-chambered heart of a fish,
Harvey recognized that the space between the ligature and the heart quickly becomes empty, thus indicating that blood returns to the heart. (B)
Harvey described seizing the vena cava of a live snake (laid open) between the finger and thumb. He found that the part that intervenes between the
fingers and the heart almost immediately becomes empty, while the heart becomes smaller and paler in color. The size and color of the heart return to
normal when the impediment to flow is removed. On the contrary, if the aorta is compressed, the heart becomes inordinately distended and assumes a deep
purple or even livid color. These changes are reversed when the obstacle is removed. Harvey concluded: ÔHere then we have evidence of two kinds of death:
extinction from deficiency, and suffocation from excessÕ. (C) Harvey claimed that if the aorta of a dog or a sheep be tied at the base of the heart, and
the carotid or any other artery be opened, the artery will be empty and the veins Ôreplete with bloodÕ. This is consistent with the notion that Ôarteries
receive blood from the veins in no other way than by transmission through the heartÕ.

blood in motionÕ. In the case of the tight ligature, Harvey noted
that not only is the distal pulse lost, but also the artery proximal
to the tourniquet rises higher with each systole, throbs more
violently and seems fuller. When the ligature is loosened so that
it is of medium tightness, the pulse can now be felt. The hand
and arm become deeply colored and distended, engorged with
blood. The subject reports a sensation of warmth. In contrast,
the veins above the ligature are not swollen. Based on his
observations with ligatures, Harvey concluded that blood
enters the arm by the arteries and leaves by the veins. Blood
must pass from arteries into veins through anastomoses or
porosities of the flesh. According to Harvey, blood is forced
upwards through the veins by virtue of muscle action in the
extremities.
Venous valves promote centripetal flow of blood from the
lesser to the greater veins Fabricius discovered that veins
contain valves. The valves of veins are directed upwards or
towards the trunks of veins. Fabricius believed that the valves
serve to hinder gravity-dependent outward flow of blood.
Harvey commented that even veins that are not subjected to
gravity effects in the upright, erect position contain valves.
Moreover, if blood flows centrifugally, why would its passage
from larger to smaller veins not be sufficient to retard flow?
Harvey was unable to pass a probe through a large vein into a
smaller vein, whereas he readily passed a probe in the opposite
(outer to inner) direction. Harvey then used a series of ligature
experiments to prove that the venous valves prevent retrograde
centrifugal flow of blood in the veins.

 2011 International Society on Thrombosis and Haemostasis

128 W. C. Aird

Fig. 3. Schematic of HarveyÕs experiments with ligatures. Harvey employed tight ligatures (top) to compress the arteries and veins leading to the hand
or medium-tight ligatures (bottom) to compress the veins only. The tight ligature results in reduced arterial blood flow to the extremity (denoted by
dotted red line), loss of pulse at the wrist and a cold hand. The arteries proximal to the ligature become distended (denoted by thickened red line). The
medium-tight ligature results in unimpaired arterial flow of blood to the extremity, but impaired venous drainage. Thus the arterial pulse at the wrist is
intact, while the distal veins are distended (denoted by the thickened blue line). The hand becomes swollen and deeply colored. V, vein; A, artery.

Blood is transferred from veins to arteries by way of
porosities in the tissue Harvey stated his belief that blood
moves from the right to left ventricle via minute inosculations
of vessels or hidden porosities in the lung. Similarly, in the
extremities, Harvey considered that the blood passes from
arteries to veins either through arterial-venous anastomoses or
by the porosities of the flesh that are permeable to blood.
Harvey would later write: ÔI have never succeeded in tracing
any connection between arteries and veins by a direct
anastomoses of their orificesÕ. Rather, the blood is ÔurgedÕ
from the porosities into the small veins by virtue of the impulse
of the blood. Thus, contrary to popular belief, Harvey did not
favor the existence of a direct connection (i.e., capillaries)
between veins and arteries.
HarveyÕs legacy Today, HarveyÕs theory of blood
circulation is widely recognized as the foundation for modern
medicine [17,18]. However, at the time, his discovery was met
with skepticism. The theory was controversial because it ran
counter to the existing dogmas of the time. Anticipating the
opposition to his revolutionary theory, Harvey wrote in his
book: Ô… not only do I fear danger to myself from the malice of
a few, but I dread lest I have all men as enemiesÕ. Many of
HarveyÕs detractors were invested in ancient doctrine. What was
the purpose of the circulation when the whole process would
lead to re-cooking of the blood and its conversion to bile? In
fever, wouldnÕt the circulation repeatedly deliver putrid material
to the whole body? Where were the arterial-venous
anastomoses in the tissues that HarveyÕs theory demanded?
DidnÕt Harvey vastly overestimate the cardiac output, because
blood was boiled in the heart and thus was volumetrically
expanded? Perhaps the violent, painful deaths suffered by
research animals interfered with natural conditions. Could
HarveyÕs findings in animals be rightly extrapolated to humans?
What was the divine rationale for the circulation? Beyond the
intellectual realm, it would take even longer for HarveyÕs
discovery to have a practical impact. Part of the reason was that
Harvey was most interested in reporting the facts, without
speculating on their therapeutic implications. Some argued that
the new theory lacked any clinical relevance. What were they to
tell their patients, whose expectations were based on a doctor-
patient relationship steeped in ancient doctrine? Like alternative
medicine today, humoral medicine had the advantage that it
was tailored to the individual patient. Was it reasonable to
abandon longstanding successful therapies simply because of a
change in the underlying theoretical rationale? The controversy
surrounding HarveyÕs model for the circulation of blood would
persist until MalpighiÕs discovery of capillaries in 1661. Its
impact on clinical practice would not be realized until well after
HarveyÕs death.2
Conclusion
In todayÕs world it seems unfathomable that there was ever a
time when blood was not known to circulate. Yet the circulation
of blood eluded investigators until the 1600s. Both Galen and
Harvey were brilliant thinkers, far ahead of their time. Both
received the best education in their day. Both were clinician-
scientists, driven by a search for the truth. They understood the
value of anatomical dissection and comparative anatomy. True,

 2011 International Society on Thrombosis and Haemostasis


Harvey had access to human corpses, whereas Galen did not.
But the discovery of the circulation was in no way contingent
upon human dissection. From a technological standpoint, there
was little to separate the two. Both had access to dissecting
instruments and tourniquets. Neither one had the benefit of a
microscope. So what did Harvey possess that Galen lacked?
First, he inherited a different knowledge base. Galen took as his
starting point the work of the Hippocratic investigators as well
as that of Herophilus and Erasistratus. He set out to synthesize
and build on established models of physiology and disease.
Harvey benefited from key observations (i.e., clues) on the part
of his predecessors, including VesaliusÕs insistence that he could
not find pores in the interventricular system, FabriciusÕs
demonstration of the venous valves, and ColomboÕs ÔdiscoveryÕ
of the pulmonary transit. However, rather than integrate these
findings into a Galenic framework, Harvey leveraged them to
support a new theory of blood circulation. Second, unlike so
many of his predecessors, Harvey was prepared to challenge
dogma and authority. Although deferential to the Ancient
Greeks, he was willing to reject their doctrines. Third, Harvey
benefited from an emerging intellectual environment that
stressed the importance of experimental reproducibility and
quantitation. Harvey was far more interested in proximate,
mechanical explanations than he was in teleological causes.
Finally, in their use of analogies to represent the cardiovascular
system, Galen and Harvey may have been influenced by the
technologies of their day. Galen was interested in comparisons
with smithÕs bellows. In contrast, Harvey was likely to have
been informed by force pumps, which were common in his time.
In the final analysis a confluence of circumstances – largely out
of their control, and apparent only with the benefit of hindsight
– is responsible for Harvey being ÔrightÕ and Galen being
ÔwrongÕ. In contrast to HarveyÕs pro-Galenic critics, it is
tempting to speculate that had Galen himself read HarveyÕs
little book of 72 pages, he would have embraced its conclusions
with uncommon fervor and praise.
Galen was keen to observe and understand. He recognized
differences in the structure of blood vessels in different parts of
the body. He saw that arteries and veins contain different kinds
of blood. For Galen there was a dynamic complexity in the
system whereby the delivery of blood (with its humors and
spirits) matched the needs of the underlying tissue. GalenÕs
system was ÔaliveÕ and vital. By contrast, HarveyÕs circulation
was more mechanical, being centered on a force pump, the
heart, which delivered a relatively constant amount of blood
around and around the body through a series of conduit vessels.
There was a certain monotony and periodicity to his system.
Arterial and venous blood was identical and there was little
reference to vascular diversity, save for the venous valves.
Today, a fuller understanding of the vasculature and its
endothelial lining points to something far more complex than
HarveyÕs system. Venous and arterial blood is indeed different.
Blood does not simply circulate around and around the body,
but is dynamically regulated in content and flow. The structure
and function of the vasculature differs between different organs.
Sometimes the reason to study history is not to learn to avoid
 2011 International Society on Thrombosis and Haemostasis
Discovery of the cardiovascular system 129
past mistakes but in fact to return to past questions. Perhaps
GalenÕs complexity gets at something that is really right.
Acknowledgements
The author wishes to thank Vivian Nutton and Jane
Maienschein for critically reviewing the manuscript and for
their helpful suggestions. See [19–22] for additional recom-
mended reading.
Disclosure of Conflict of Interest
The author states that he has no conflict of interest.
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