Galen, father of systematic medicine. An essay on the evolution of modern medicine and cardiology

International Journal of Cardiology 172 (2014) 47–58

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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard

Review

Galen, father of systematic medicine. An essay on the evolution of modern medicine and cardiology Ares Pasipoularides ⁎ Department of Surgery, Duke University School of Medicine, Durham, NC 27710, United States

a r t i c l e

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Article history: Received 25 November 2013 Accepted 30 December 2013 Available online 8 January 2014 Keywords: Galenic corpus Galen's concept of the motions of the blood Galen demonstrated that the arteries contain blood and the motor power of the heart Galen postulated arteriovenous communications or anastomoses (capillaries) Galen's ebb-and-flow was supplanted by Harvey's circulation of blood History of medicine

a b s t r a c t Galen (129–217) was the ultimate authority on all medical subjects for 15 centuries. His anatomical/physiological concepts remained unchallenged until well into the 17th century. He wrote over 600 treatises, of which less than one-third exist today. The Galenic corpus is stupendous in magnitude; the index of word-entries in it contains 1300 pages. Galen's errors attracted later attention, but we should balance the merits and faults in his work because both exerted profound influences on the advancement of medicine and cardiology. Galen admonished us to embrace truth as identified by experiment, warning that everyone's writings must be corroborated by directly interrogating Nature. His experimental methods' mastery is demonstrated in his researches, spanning every specialty. In his life-sustaining schema, the venous, arterial, and nervous systems, with the liver, heart, and brain as their respective centers, were separate, each distributing through the body one of three pneumata: respectively, the natural, the vital, and the animal spirits. He saw blood carried both within the venous and arterial systems, which communicated by invisible “anastomoses,” but circulation eluded him. The “divine Galen's” writings, however, contributed to Harvey's singular ability to see mechanisms completely differently than other researchers, thinkers and experimentalists. Galen was the first physician to use the pulse as a sign of illness. Some representative study areas included embryology, neurology, myology, respiration, reproductive medicine, and urology. He improved the science and use of drugs in therapeutics. Besides his astounding reputation as scientist-author and philosopher, Galen was deemed a highly ethical clinician and brilliant diagnostician. © 2014 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

Rien ne se perd, rien ne se crée, tout se transforme. [Nothing is lost, nothing is created, everything is transformed.] [Lavoisier, Traité élémentaire de chimie, 1789.] Galen (Gk. Γαληνός = peaceable, quiet) (Fig. 1), vir clarissimus (“most famous man”) [1,2], was an ancient Greek polymath– physician–surgeon, a universal scholar with accomplishments that arguably surpassed Leonardo's (1452–1519) [3,4]. In his clinical practice, he followed the judicious Hippocratic principle of allowing first the “vis medicatrix naturae,” the healing force of Nature (Φυσις), a chance to assert itself, and intervening only if this proved ineffective. Starting out as physician to the gladiators in Pergamos, he attained grand authority in Rome through copious energy, immense self-confidence, high moral principles, vast learning, virtually flawless logic and persuasive rhetoric, combined with remarkable practical proficiencies as an observer, a clinician dedicated to service to the ill, rich or poor, and an avid experimenter.

⁎ Tel.: +1 828 254 0279. E-mail address: [email protected]. 0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.166

Oddly enough, the incipient winding up of Galenism in the Late Renaissance (1500–1600) was owed specifically to the reawakening of Galen's own methods of research, stressing the unity of reason and experience, by Vesalius (1514–1564) and Harvey (1578–1657) [3,5–8]. As detailed by the insightful analyses of the preeminent American physician–anatomist and medical historian Prof. Charles Mayo Goss [9,10], many of the “errors” imputed to Galen are factitious and contrived, or are mistakes of copying with perpetuated defects, of translation often at third hand far from the original Greek, of interpretation, or even of understanding by the critics [9,11,12]. The last and greatest medical sage of antiquity – he died c. 217 according to Nutton [13] – Galen remains a towering founding figure for the clinical practice of medicine [14]. Medical science made no remarkable progress after Galen and the outright collapse of the Greek scientific intellect in the 3rd and 4th centuries. Until well into the 17th century, Galenic medicine was Western medicine. His medical scriptures, in the opinion of the physicians who succeeded him, fulfilled the highest demands which could be made upon their knowledge in these matters. The results which he had obtained in his morphological and functional investigations appeared to them to need neither correction nor amplification; they ascribed the same character of completeness to Galen's physiological theories. He held teleologic doctrine sacrosanct, maintaining that means do not lead to ends, but ends to means, and felt earnest awe for the omnipotence and wisdom of the Creator or Demiourgos –

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Fig. 1. Galen. Photographs of head-on-pedestal bust in the National Museum of Naples, Italy (left), and of engraving in the National Library of Medicine, Washington, DC (right).

echoed by Vesalius' Conditor rerum, Maker of things, in the Fabrica – forming a potent impression on religious scholars and leaders in ensuing ages. 2. Birth, upbringing and education Galen was born in 129 CE at Pergamos, near Smyrna in Asia Minor, at a time when the Greek city (population then, 160,000) was under Roman rule. Pergamos had been home to a Library that housed approximately 200,000 volumes, according to Plutarch — one of the most important ancient libraries [15]. Galen was the son of Aelius Nicon, a wealthy architect, mathematician, and philosopher who closely supervised Galen's education and tutored him at home, intending him to pursue philosophy or politics. However according to Galen, Nicon was visited in a dream by Asklepios – god of healing – who guided him to steer his son toward medicine. Galen subsequently began his medical studies, at age 17, as a therapeutes (θεραπευτης) at the renowned Asklepieion (medical center) of Pergamos (Fig. 2) [16]. From his earliest youth his mind was inculcated with classic reasoning and ideals as embodied in the creations of Hippocrates, Plato and Aristotle, and throughout his life he made much of his own paideia, or Greek education. His ethics and his comprehensive works embody the philosophical, scientific, and medical thinking of Greek antiquity, and are the consummation of all that had paved the way. In pursuit of knowledge Galen spent some time at Smyrna, Corinth, and Alexandria [17], where he studied anatomy in the tradition established by Herophilos (335–280 BCE), a famous Greek who practiced in Alexandria and is deemed to be the first anatomist. Pliny the Elder (23–79 CE) describes Herophilos as the “first man to search into the causes of disease” through dissection. Later, Galen deplored that Rome prohibited human dissection, and he had to invoke animal organ homology. Rome drained mainland Greece and Asia Minor of

their best; at age 30, Galen moved there and built an enviable practice [18], on the Via Sacra. He lectured in the public amphitheater and even performed his animal experiments before gripped lay audiences, defying the Hippocratic Oath. His passion to spread knowledge as widely and publicly as possible is the key to understanding Galen and his demonstrations (επιδειξεις). He swiftly rose to fame becoming Physician to the Emperor Marcus Aurelius, the Stoic philosopher and great Philhellene who wrote Meditations (Τα εις εαυτον — literally: My inner thoughts) in Greek [17], which was used as lingua franca among the Roman ruling class and intelligentsia, and to his son and successor, Commodus. Marcus Aurelius said about Galen: Primum sane medicorum esse, philosophorum autem solum — first among physicians, and unique among philosophers.

3. Galenic corpus Roman highest-circle dignitaries frequented Galen's anatomic demonstrations; the consul Boethus, of Greek background, was charmed by Galen and requested treatises (see below) on the mechanisms of voice and breath [17], launching him on his epic writing task. He created more works than any author in antiquity and may have written over 600 treatises, of which less than a third exist today [19]. Galen was not only concerned with abnormal states; he was also interested in developing theories on the functioning of the healthy organism. His surviving work runs to over 3 million words; expending his paternal wealth, he employed over 20 Greek scribes (literati). The extant Galenic corpus remained the basis of medical teaching until well into the 18th century. The industrious physician–classicist Karl Gottlob Kühn of Leipzig (1754–1840) and his staff translated 122 of Galen's treatises and his edition, comprising the Greek and its Latin translation, runs to 22 thick volumes, 676 index pages and over 20,000 text pages [20].

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library of Vlatadon in Thessalonike, where microfilms of the manuscripts of Mt. Athos are kept, by the Paris Sorbonne University researcher, Véronique Boudon-Millot [23]. As the preceding confession aptly relates, Galen had all the fervor of an energetic and inquisitive mind; he kept an eye on all branches of knowledge with astounding adeptness and enthusiasm [24,25]. He is arguably the founder of both anatomy and experimental physiology, which he considered indispensable for diagnosis, prognosis and therapy [20,21], because, although he had celebrated forerunners in both, his works endured remaining “current” for over 15 subsequent centuries! [26]. He was a gargantuan writer, preoccupied with useful teaching (χρησιμον διδασκαλιαν), on all specialties of medicine, surgery, gynecology, psychiatry, therapeutics, hygiene, preventive medicine, philosophy, logic, ethics, and many other subjects [27]. He conducted experiments on himself, such as burning his skin in several places to determine the best remedy for burns. His extant works in the original Greek – Galen did not speak Latin [17] – fill well over 20 thick volumes. The Galenic corpus is a uniquely stupendous edifice [28,29]. It erected itself into an enduring universal system through the creative power of its founder, who disclosed a vast array of facts to medical science and opened for it new avenues. Galen's experiments and the texts describing them were very meticulous and thorough. His love for teaching is the basis of written denunciations he aimed at those fashioning themselves as fake authorities and others who passed on incorrect information. He upheld his conclusions using his arsenal of logic and rhetoric, provoking the animosity of some colleagues; his ensuing sense of indignation imparts to his writings an eristic tone infused with a strong combative spirit. It should be remembered too that one of the enduring features of Greek thought is its polemical nature, with rival views on offer both on substantive questions and on methodology. Fig. 2. (Top) Ruins of the Asklepieion of Pergamos. The complex included temples, dining rooms, fountains and baths, dormitories, and other structures The eponym relates to Asklepios, the god of Medicine and son of Apollo, the physician; Asklepios' symbol was an entwined snake. Founded in the 4th century BCE, this elite Asklepieion gained its reputation during Hellenistic/Roman times; it rivaled those on Hippocrates' Kos, in Epidaurus and in Athens. (Bottom) Votive tablet from the Asklepieion of Athens. Scalpels and cups are shown. The fist-sized cups (cucurbitulae, σικυαι, κυαθοι) relieved local congestion by applying a partial vacuum created by heat. In wet cupping, the skin would be scraped allowing removal of blood or venom.

Included in the Kühn collection is a work titled Οτι αριστος ιατρος και φιλοσοφος (Quod optimus medicus sit quoque philosophus, Τhe best doctor should also be a philosopher) [20,21]. In fact, Galen's medical theory is adjoined to philosophy. He did not follow exclusively the teachings of any one philosophical school, but developed a syncretist view of Aristotle and Plato and was in complete harmony with Hippocrates, whom he regarded as the repository of medical wisdom. Unfortunately, many of Galen's books were destroyed in the fire that in 192 CE burned the Templum Pacis (Temple of Peace) on the Via Sacra in Rome, where many of his valuable possessions, manuscripts, and codices [4] were stowed in the royal storehouse (αποθηκη) [17,21]. In his newly uncovered philosophical treatise Περι αλυπιας (Peri alupias, On denial of grief), Galen, aged 63, describes his dire loss and how he suffered this loss of material wealth, books and instruments with equanimity, referring to his megalopsychia (μεγαλοψυχια, grandeur of soul) [22]: “…the fact that, after the loss of the totality of my pharmaceutical remedies, the totality of my books, as well as these recipes of reputable remedies, as well as the various editorial comments I wrote on them, in addition to so many other works, each one of which exhibits that love of work that was mine my entire life; the fact that I felt no pain shows first the nobility of my behavior and my megalopsychia.” Megalopsychia is a laudable virtue and was defined by the Stoic philosophers as the habit of mind which makes one superior to anything that happens, whether good or bad, equally; in the present context, it is Galen's psychic grace when faced with extreme adversity. This treatise had been lost and was rediscovered fortuitously in 2005 in the monastic

3.1. Gutenberg's printing press and the study of Galen in the Renaissance What the printing press did for classic scholars in the Renaissance is akin to what the steam engine did for manufactures. It allowed widespread and low-cost dissemination of mass produced – as contrasted to handwritten – works. It also changed the way that knowledge was preserved and circulated, thus allowing the elimination of persistent human error. As Nauert puts it [30], “Printing produced a standardized frame of reference, the hundreds of identical copies having exactly the same words on exactly the same lines and pages… [It] stabilized the text of a classical work… The advent of printing made textual improvements by humanist editors permanent and cumulative in a way impossible for manuscript books.” A great number of Galen's medical treatises were printed nearly straightaway after Gutenberg's invention of printing. After theology, medicine was the subject that most engaged the interest of printers, and many portions of the Galenic corpus were made available for wide reading. The patience and scholarship required for this can be appreciated properly only by pondering the labor of reading the scruffy handwriting of the old manuscripts and collating them, and the time required to elucidate degenerated text that had crept in through the carelessness, misunderstanding, or miscopying of the original Greek words by successive copyists. The world owes an immense debt to the Renaissance and later physician-scholars for this work. 3.2. Linacre and Erasmus One among them was Thomas Linacre (c. 1460–1524), the founder of the Royal College of Physicians of England, after whom Linacre College at Oxford University is named. Linacre was William Harvey's intellectual godfather, a renowned scholar and a Hellenist. He was instructor in Greek to Erasmus of Rotterdam (1466–1536), a vehement proponent of Greek in medical education, believing that [31] “It will be thought impudent to call oneself a physician without it [Greek]. It is at least far from

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negligible to be able to listen to the founder of the art, Hippocrates, and next to him Galen, Paul of Aegina, Dioscorides speaking in their own language…” In the preface to his mentor's Leonicenus translation of Galen's De motu musculorum, Linacre stated [32]: “There is nothing I desire more than to make the works of Galen – after Hippocrates the greatest benefactor of human health – available to all who use the Roman [Latin] tongue…” Remarkably, following acquisition of the first treatise translated by Linacre, Erasmus wrote in a letter [33] “Linacre's translation of Galen at last begins to be on sale here, and I like it exceedingly. After this I may even be ready to become a physician… Give my greetings to Linacre and encourage him to publish the rest of his work.” These titans of the Renaissance felt that once Greek medical science was restored in authentic published texts, once the knowledge of it was disseminated, medical practice could revive as the arts and letters had. 4. A sampler of Galen's contributions to medical science and practice The importance attributed to visible facts, or “phenomena,” explains the preeminent role of anatomical knowledge for Galen. Anatomy has, for Galen, several objectives: for clinical practice, it is indispensable, whether that involves complicated surgery or controlling a simple hemorrhage. It is necessary for physiological understanding and physical examination. And it offers access to the comprehension of pathology (viz., pathological anatomy) and to diagnosis. Galen considered pathology as antithetical to physiology and that it is necessary to know the latter to understand any pathological problem. Mastery of anatomy should prevent physicians from making mistakes not only in their procedures but also in interpreting symptomatology. To wit, applying his knowledge of myology and functional neuroanatomy, Galen cured his friend Eudemus, suffering with arm numbness and paralyzed fingers, by working on the brachial plexus in the neck rather than on the fingers themselves. He famously noted that “Leaving the affected parts alone, you will reach the spine from which you will treat the disease.” Galen conducted dissections and vivisections on all kinds of animals [8], as Harvey did centuries later [5,6]. The explicit purpose of his anatomical dissections was to map the world of knowledge normally hidden within the body, including the brain [34], and then, by showing how form followed function, to reveal the perfection of the design of the Creator (Platonic Demiourgos of the universe — Δημιουργος). His monotheism was drawn from Plato's Timaeus (Τιμαιος). Through observation and experiment Galen strived to validate a teleological view, in what he deemed as the consummate means of syncretizing the realism of Aristotle with Plato's idealism [5]. Interestingly, in his anatomical demonstrations and treatises, Galen often took the opportunity to bring in clinical cases and applications bearing on the anatomical parts described [35]. 4.1. Miscellaneous findings pertaining to renal and digestive function Galen advocated catheterization for urinary obstruction, employing the urinary catheter for the very purposes for which it is used today [36]. He proved that the kidneys – not the bladder – made urine (see below), and studied digestion on animal models [16]. He recognized the lacteals, the lymphatics conveying milk-like chyle (χυλος, thick liquid extract) from the intestine to the liver, eponymously linked with Gaspar Asellius (1581–1626). As Galen put it [37], “Each of which [lacteals] ends at a portion of spongy flesh (αδην, mesenteric lymph gland) specially associated with itself” — the lacteals, however, had already been described by Erasistratus (304–250 BCE), son-in-law of Aristotle [5,6]. Galen described the ducts of the submaxillary and lingual glands, now connected with the names of Wharton (1614–1673) and Rivinus (1652–1723).

4.2. Myology Galen described the anatomy of many muscles, deemed as the instruments of voluntary motion [11,38]. Because of its automaticity [4], he classified the heart not as a muscle but as a hard sort of flesh (σαρξ). His myology is accurate and thorough; e.g., he described the platysma myoides, the constrictor oris, the orbicularis palpebrarum, the popliteus, and the interossei and lumbrical muscles of hand and foot, and the extrinsic and intrinsic muscles of the larynx and of the tongue – an organ not of voice, but of speech – to which he accurately ascribed 16 in all. In his De motu musculorum (Περι μυων κινησεως), Galen pointed for the first time to existence of protagonist and antagonist muscles [11] causing movement in opposite directions — because return motions need muscle pairs with opposite effect (e.g., flexors–extensors), since muscles can only exert a pulling force and cannot push themselves back into their original positions. He demonstrated antagonistic pair actions by experiments involving severing individual muscles and groups, and with a mechanical lever model made of articulated bones and thongs attached in proper places to simulate muscles. He knew the effect of cutting the nerves to a muscle group on antagonist action [11,39]. He studied passive motion of muscles and related muscular to gravitational action. He termed sustained muscle activity “tonic contraction.” He explained the effect of habit on muscles and the subconscious control of voluntary muscles. In contrast to muscles, viscera and blood vessels are controlled by natural autonomic processes, not by the conscious mind [11,40]; yet, defecation/urination can be involuntary or assisted by muscles [11]. 4.3. Respiration and phonation, neuroanatomy and neurology In his De voce et anhelitu (Περι φωνης και αναπνοης, On voice and respiration) and De voce, Galen showed that the voice is tightly linked to respiration, and respiration is achieved by muscles moved by the phrenic and thoracic nerves. He ligatured the recurrent laryngeal nerves and demonstrated aphonia in his famous experiment on the squealing pig [41] (see Fig. 3). He reprimanded surgeons who, being ignorant, severed these nerves rendering patients mute after neck operations, e.g., goiter surgery [42]. In animal experiments, he found that in quiet breathing the diaphragm plays the main part and the intercostal muscles participate only in forcible respiration [11]. He studied ventilation using bellows to inflate dead animals' lungs. Galen introduced the concept of the Central Nervous System (CNS) by proposing that the spinal cord is an extension of the brain. He knew that left-side brain injury may affect the right side of the body and vice versa. He was the first to describe the autonomic nervous system [43,44]. He conceived the nerves as simply pathways for motion and sensation communication between the CNS and the muscles and sensory organs [44–47]. Just how was this accomplished? To Galen, the Mediterranean electric ray (Torpedo torpedo), sending shocks through clubs and spearing irons numbing the hands of fishermen, afforded a model of signal transmission via the nerves. The hypothesis of the transmission of pneuma through the nerve canal, adopted by others, applied for Galen just to the optic nerves, the only ones appearing to be hollow. He traced nerves responsible for the motion of particular muscles through their complex paths, and elucidated the sensory/motor functions of both cranial and spinal nerves by tying off specific nerves and checking what functions were interrupted [35,48]. He studied functional neuroanatomy in pigs, by total/partial divisions of different nerves and the spinal cord at various levels, and by transverse sections of the brain, or by pressurizing the cerebral ventricles. He described the ensuing sensory and motor disturbances, and the resulting patterns of acute paralysis and incontinence with an astonishing fidelity [49]. He showed that cord injury between 1st and 3rd vertebrae caused instantaneous death; injury between 3rd and 4th vertebrae arrested respiration; damage below the 6th vertebra caused paralysis of the thoracic muscles,

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Fig. 3. The title page of the index volume of a collection of Galen's works published by Luceantonij Iunte Florentini in Venice, in 1541–1542. In the bottom panel, Galen performs his famous squealing pig experiment [41], proving innervation of the intrinsic laryngeal muscles by the recurrent laryngeal nerves. After tying these nerves off bilaterally, the animal was rendered completely voiceless (no squeal); by loosening the ligatures, it could suddenly cry out again!

while lower lesions produced paralysis of the lower limbs, bladder, and intestines. He advocated operations for brain injuries, and was familiar with the clinical picture of cord compression and its surgical relief [50]. He found that sensory (soft) and motor (hard) nerves have separate attachments to the cord [51]; this fact was formalized in the 19th century as law of Bell (1774–1842) and Magendie (1783–1855): anterior spinal nerve roots are motor; posterior, sensory. The great cerebral vein and its malformations and the communicating branch of the internal laryngeal nerve bear Galen's eponym. He also described the meningeal layers, the cerebral ventricles containing cerebrospinal fluid [52], the calamus scriptorius, i.e., the inferior writing quill-like part of the rhomboid fossa of the 4th ventricle, and the narrow canal leading from the 3rd to the 4th ventricle, now called the aqueduct of Sylvius, after the French anatomist Jacques Dubois or Sylvius

(1478–1555), who was Andreas Vesalius' (1514–1564) teacher. Sylvius wished to reconcile the classical Galenic teachings with contemporary observations. Convinced that Galen was omniscient in all matters medical, he published in 1555 a treatise of anatomy based on Galen's anatomic works; one of the structures described in it was the “aqueduct.” 4.4. Pathophysiology and oncology Galen's genius of observation shows, e.g., in classifying fevers by their time-patterns and in the adroitness of his experiments. He saw anatomic studies as effective means of deriving understanding of (patho) physiological processes, since the form and other structural detailed characteristics of organs – including relations, texture, solidity, composition, etc. – cannot be separated from their functions. However, he

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discarded the simplistic approach of anatomical deduction, or forthright inference of function from form. Conversely, adhering to Aristotle, he deemed that a dynamic understanding of complex physiological processes, such as digestion or growth, can facilitate the understanding of particular structural characteristics of the apposite organs. His supplementary physiological investigations are just as pioneering as his anatomy. He knew of Erasistratus' αδηλος διαπνοη (perspiratio insensibilis), the invisible and intangible but weighable vapor and gaseous products given off from the lungs during exhalation and from the skin comparably to sweat but by vaporization, which was characterized further by Santorio Sanctorius (1561–1636) of Padua [53]. Galen called any benign neoplasia an oncos (ογκος, tumor), reserving Hippocrates' karkinos (Gk. for crab) for malignant tumors; the name alludes to the appearance of dark veins around the cancerous part, akin to the legs of a crab [54]. He later added -oma, (Gk. suffix connoting generalization), giving the name carcinoma (καρκινωμα). He advised operating for cancer; a wide round incision should be made around the tumor, so that the entire growth is excised. He warns the surgeon to be particularly careful because there is great danger of hemorrhage and the attempt to restrain it with ligatures may affect neighboring tissues with cancer; he also mentions cauterizing the roots of the tumor, a process that may also prove dangerous [54]. 5. Galen's views on the cardiovascular system, in nucem Galen quickly outgrew and discarded many preexisting doctrines, parts of long accepted tenets. His embrace of truth was defined by rigorous experiment and observation, rather than mere common sense, consensus, authority, or revelation. In his work On the natural faculties (see below) he gives his own precept that to be outstanding in knowledge one must love truth and must learn all that has been said by the most knowledgeable. And then he must test and prove it, observing what part agrees and what disagrees with testable fact, and should choose accordingly. And yet, some of his “tested-and-true” notions were superseded in later times, just as a meta-induction from the overall history of medicine assures us will happen to a number of currently accepted medical theories, inherently provisional and quite possibly wrong. 5.1. Arteries contain blood Sanguinary disputes entailed the doctrine that the left heart side and the arteries contained only air or an enigmatic derivative of it: a spirit (Gk. pneuma, πνευμα); after all, larger arteries were empty after death. Galen established that this belief was groundless, through experiments proving that the arteries, as the veins, contained blood [55]. On stabbing the left ventricle blood immediately sprung after withdrawal of the blade, and the scalpel was bloodstained, no matter how quickly it was withdrawn. He incised an artery between two ligatures and showed that it contained blood, which appeared promptly as it was incised (Antyllus aneurysm operation [56,57], named for the famous 3rd century Greek surgeon). He also implied the motor power of the heart by showing that the blood pulsates between the heart and a ligated artery, but not beyond [43]. As Harvey states in Chapter IX of De motu cordis [3,5,6], in another experiment Galen severed a small artery and demonstrated that the blood drained from both veins and arteries [58,59]. Galen's demonstration that the arteries contain blood is a landmark in medical scientific reasoning. The doctrine that only the veins contained blood, which Galen debunked, has particular interest because it suggested another question needing answer: passage of blood from veins to punctured arteries required pathways. Galen proposed that blood seeped through invisible arteriovenous communications or anastomoses (capillaries), which existed in both the systemic periphery and the lungs [3,6]. Through these connections, the pulsatile arteries withdraw blood from the veins when they swell, and squash it into them when they shrink. Thus, the movement of blood and pneuma is neither unidirectional nor speedy, as the contents of arterial and venous trees

move back-and-forth slowly, responding to distinct organ demands. It is intriguing that this vital inference about arteriovenous microchannels, eluding proof without the microscope, should have been deduced by Galen from arguments pertaining to an erroneous hypothesis. Marcello Malpighi's (1628–1694) [60] discovery of capillaries followed Galen's inference by about 15 centuries [3,6]; it verified the existence of the missing link in Harvey's schema, which postulated a new role for the arteriovenous communications — see Epigraph. According to Galen, typically, conduits to organs functioned on the model of the airways to the lungs in respiration (see below). If the arteries simply distended passively as blood was forced into them, the twoway exchange of material – “refined, vaporous blood” leaving the arteries to nourish the surrounding tissues, outer air drawn in through skin pores – would not be taking place [68]. The faculty transmitted through the arterial tunics from the heart, causing them to expand actively like bellows [5], allowed such an exchange [68]. 5.2. Galen's tripartite anatomical system and theory of the motions of the blood Galen could not see the circulation of blood. His theory of the movements of the blood [3,5,6] was predicated on 4 tenets (see Fig. 4): (1) the liver as the source of the veins and of purplish, sluggish blood; (2) the communication from right to left ventricle through minute and invisible foramina in the interventricular septum; (3) no unidirectional circulatory movement of blood propelled by the heart – blood slowly ebbed and flowed, being attracted by different organs; and (4) the 3 essential pneumata (πνευματα), ethereal pluripotent spirits, as developed in Plato's Timaeus. It entailed these 3 Platonic pneumata, the vital forces vivifying the body and directing it to the performance of its functions, seen variously as energies (ενεργειαι) or causes of activity. They were controlled by the tripartite system of liver–heart–brain, which represented a rational foundation for therapy. The postulate was that all organs and bodily systems functioned through faculties or drives (δυναμεις), such as attraction, assimilation, retention, and elimination, ascribed to an innate vital attribute. The organs (οργανα) are properly constituted, goal-directed, anhomoeomerous physical structures which have functions (χρειαι) contributory (and therefore teleologically posterior) to the overall functioning of the organism as a whole. Galen rejected Erasistratean mechanical ideas (e.g., viewing urinary excretion as purely a mere filtering process), less goal-oriented than his heuristic teleological and vitalistic vision. 5.3. Genesis of the idea of the essential pneumata The idea of the essential pneumata must have arisen naturally from the observation of reversible transformation processes associated with induced changes in enthalpy, such as vaporization and condensation, freezing and melting, sublimation and deposition (cf. inset in Fig. 4), by early ancient Greek craftsmen, naturalists, physicians, and thinkers. For instance, evaporative processes could be viewed as analogous to the transmutation or conversion of a component of a body (blood) into semi-material spirit (pneuma) or the release of such a pneuma from a body (blood) in which it has been trapped, whereas the reverse process of condensation as the absorption and assimilation of an ethereal pneuma into a body (blood). Observing compound liquids in a distilling apparatus, such as Galen must have used in preparing his materia medica, their movement, growth, disembodiment and reincorporation, evokes both the separation of the pneuma of material substances (blood) from its restrictive matrix, and the subsequent binding of pneuma into matter, which it rejoins within the collecting flask(s) of the apparatus. Radical changes in the colors and properties of the materials can accompany such transmutations. In this context, I am reminded of Isaac Newton's invocation of an “ethereal active fluid” (pneuma?) in attempting to explain universal attraction and gravitation—see note 11 on p. 84, Section VII, part I, in Hume, D. (1739–40): A treatise of

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Fig. 4. In Galen's tripartite schema, the venous, arterial, and nervous systems, with the liver, heart, and brain as hubs, were separate. Each distributed through the body one of 3 pneumata: respectively, the natural, vital, and psychic spirit. The idea of the essential pneumata must have arisen naturally from the observation of reversible transformation processes associated with induced changes in enthalpy (see discussion in text). Blood coursed within the venous and arterial trees. Modified from Pasipoularides [6], with permission of the American Physiological Society.

human nature. London: Oxford/Clarendon; 1973 reprinting of LA SelbyBigge's 1888 edition. 5.4. Liver, right ventricle, systemic veins and vena arteriosa, and physikon pneuma The liver attracted nutriment from veins connecting it to the GI tract; it “concocted” it into thick, dark blood endowed with physikon pneuma (φυσικον πνευμα; natural spirit, driving basic bodily functions), which was then drawn into the veins (Fig. 4); the impetus for this was the attractive force (ελκτικη δυναμις) of tissues drawing nourishment essential for sustenance. The veins dispersed (αναδoσις) this blood to tissues for maintenance and growth or healing, or to pass through as transpiration and perspiration, or eliminate as waste (αποκριτικη δυναμις). Some blood was similarly attracted by the heart, which actively dilated drawing blood from the liver into its right ventricle just as the expansion of a bellows sucks in air [5], or as the flames of a lamp suck up oil [61], then discharged it via the vena arteriosa (pulmonary artery) into the lungs, to nourish them. On expiratory contraction of the thorax, the blood in the vena arteriosa, having its backflow impeded by the pulmonic valve, could only flow forward into the arterial (in present usage, venous) system of the lungs. The arteria venosa (pulmonary vein[s]) then carried blood to the left ventricle along with some quality derived from the inspired air. Aside from cardiac propulsion, Galen had explained the accessory thoracoabdominal pumping apparatus and had clearly outlined the

mechanisms of the pulmonary circulation! In his works, William Harvey clearly and repeatedly admitted that Galen, “that father of physicians,” deserves the credit for the discovery of the flow of blood from the right heart through the lungs into the left ventricle [5,6]. It is helpful to remember that in the terminology used by Galen, all vessels that directly or indirectly (via the atria/auricles) stem from the right ventricle are “veins;” all stemming from the left ventricle are “arteries.” Furthermore, “arteries” have extra tunics and thicker walls and are stiffer than the thinner “veins.” Accordingly, our pulmonary artery is Galen's vena arteriosa (αρτηριωδης φλεψ), and our pulmonary vein [s] his arteria venosa (φλεβωδης αρτηρια).

5.5. Left ventricle, arteria venosa and systemic arteries, and zotikon pneuma By focusing on the italicized text in the preceding paragraph, it becomes obvious that the pulmonary circuit was recognized as one route through which blood was transported from the right to the left ventricle, in Galen's overall schema. As noted by Bylebyl and Pagel [62], François Umeau (1530–1594) antedated Harvey's testimonial – in Chapter VII of De motu cordis – when he averred in his De liene libellus (On the spleen), published in 1578, that Galen himself had “indicated” the idea of the pulmonary loop when he wrote that “the vein-like arteries (pulmonary veins) take up a certain portion of blood from the artery like veins (pulmonary artery branches) through subtle and invisible passages.”

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The purpose of the lungs was 2 fold: to cool the heart, source of the innate heat, and to provide zotikon pneuma, vital spirit, for arterial blood. Some blood also passed directly from right to left ventricle, through small “foramina” in the trabeculated interventricular septum, which close-up after death. Intriguingly, William Harvey made his case against the septal foramina by borrowing Galen's methodology in a different context [6,7] — see below. Blood coming through these foramina and via the pulmonary circuit was mingled in the left ventricle with zotikon pneuma (ζωτικον πνευμα, expressing itself in the heartbeat, pulse and body warmth) accessing it via the trachea (τραχεια αρτηρια, vessel for breathing and phonation), the lungs, the arteria venosa (pulmonary veins) and the left auricle. As we will see shortly, the intuition that air-like stuff (pneuma) is taken up by the blood and transported throughout the body was to prove correct, in early modern times. As the vital spirit-with-blood mixture was “concocted” by the innate heat generated by the heart, the waste vapors (λιγνυς) were expelled back to the lungs via the arteria venosa, by regurgitating through the mitral valve. The latter process was made possible by the comparative insufficiency of the mitral valve; remarkably, this was postulated as a functional attribute of the mitral valve because it has two cusps rather than three, causing it to close not quite completely. Subsequently, the modified by the breathed air, pneuma-vitalized, scarlet-colored blood was sucked out of the left ventricle through the aortic valve, by the aorta and systemic arteries (Fig. 4). Arterial blood was distributed responsively to organs having special need for such refined fluid, i.e., brain, eyes, lungs, and to the body as a whole, to give it its normal warmth and verve.

diastole, and contraction or systole — the inverse of modern terminology. The active cardiac diastole coincided with that of the central arteries, which it initiated. Galen was an expert on the pulse [20,28,29]; he was the first to use it, deducing many valid correlations between its patterns and various illnesses, and is the originator of pulse diagnosis. He wrote many semiotic treatises on the subject; Table 1 displays 18 preserved and authenticated books by him on the pulse. He advocated palpating the pulse at the wrist and stressed the importance of feeling the pulse in health, so as to have its normal, idiosyncratic in every individual, qualities in mind when judging it in disease. He described at length the variations of the pulse due to age, sex, season, exercise, sleep, pregnancy, bathing, food, and wine; among the variations in configuration are included the pulsus myurus (μυουρος σφυγμος) consisting of a series of beats of diminishing intensity, likened to the conical tapering tail of a mouse or rat, and the pulsus dicrotus (δικροτος σφυγμος) comprising a double-peaked beat. 6. Galen's ebb-and-flow supplanted by Harvey's circulation of blood As familiar analog for blood transport Galen held field irrigation: a one-way system; there are no special channels through which, after its distribution in the irrigated regions, the fluid is then collected and taken back to the reservoir to be used again and again for irrigation. Furthermore, his ebb-and-flow theory was internally self-consistent and prevailed unchallenged through the Renaissance [4,5,6,69]. It was in line with the back-and-forth motion of respiratory gases in the airways

5.6. Brain, nerves, and psychic pneuma Reminiscent of Plato, Galen placed the overseeing soul and its functions in the brain, or rather in the psychikon pneuma, which allowed for their realization, e.g., via voluntary motion [40]. The heart did play a secondary role: through the carotid arteries, it supplied the brain with the aeriferous blood that contributes to the formation of the psychikon pneuma, the one pertaining to the will and higher functions. Galen supposed that pneuma reached the brain both mixed with arterial blood and directly, via the nostrils. In the brain, it was processed into psychikon pneuma (ψυχικον πνευμα, psychic spirit), giving rise to thought and psychic phenomena, and was guided as a signal via the nerves to give rise to the senses and to sensitize and move the voluntary muscles and other structures (Fig. 4) [40–47]. From this stemmed Galen's idea of ligating or sectioning the nerves and central nervous tissues to see what impairment(s) resulted! 5.7. Galen's appraisal of the arterial pulse Erasistratus correctly held that whereas the heart fills because it is dilated, the arteries are dilated because they are filled. Galen, like Erasistratus, thought that the cardiac ventricles had a muscle that spread their walls apart after each systole, to exert a diastolic “vis a fronte” (a suction force-from-ahead) upon the fluids with access to them, a strikingly modern conception [3,63–67]. It arose from Nature's abhorrence of a vacuum (horror vacui). In his On the natural faculties, Galen wrote that the overlying ventricles, at each diastole, rob the vena cava and lungs of a sizable quantity of blood [68]. He thought, like Herophilus (325–255 BCE), that arteries had a similar faculty originating in the heart and pulsing out along their walls drawing blood along, much as a bellows, and could then contract to force it out again [5]. He had performed a famous experiment 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. Accordingly, he surmised that the arterial pulse emanates from the heart and is transmitted through the tunics of the arteries [68]. Thus, he characterized the pulse (σφυγμος) as an alternating arterial configuration, comprising wall expansion or

Fig. 5. Title page of De usu partium by Galen, avowed as “unquestionably the Prince of physicians,” translated by Nicolao Regio Calabro and published in Paris in 1528, by Colinaei.

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Fig. 6. Galen's Theriak (Θηριακη) was an electuary compound of over 70 drugs, used mainly as poison antidote and an elixir. Its wide appeal held sway for as long as Galenic medicine did!

and lungs, and the use of the gullet for back-and-forth motion of nutriments by ruminants and human swallowing–vomiting. Accordingly, Galen made the generalization that the movement of material – air, nutriment, blood, or pneuma – between every organ of the body and its connections took place in both directions within any given channel of exchange. Ebb-and-flow was eventually supplanted by the epoch-making discovery of the Circulation, as archetype for which William Harvey used the Water cycle model of Aristotle, as I have recently detailed elsewhere [3,5,6]. Harvey's concept was not accepted without controversy. To wit, Descartes (1596–1650), in the Discours de la Méthode published in 1637 [6], accepted blood's circulation but rejected Harvey's explanation

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of cardiac motion resulting from myocardial contraction. Such explanation was, for Descartes, unimaginative; he leaned – as Leonardo had done [4] – toward the thermodynamic concept of the heart as a Galenic furnace, supplying motive power to the circulation by virtue of its innate heat, rarefying blood with zotikon pneuma and forcing it into the arteries, like boiling milk overflowing a kettle. Ideas on the structure and function of what we identify today as the cardiovascular system form the keystone of any physiological doctrine, of any comprehensive explanation of vital processes or activity. Galen may have had accessible just about all the anatomical knowledge underlying the discovery of blood's circulation (with the exception of the venous valves). Yet he didn't “see” it. The assumption – in analogy patterned after one-way agricultural irrigation systems – that blood was itself nourishment was an insurmountable hindrance to any conception of circulation, since it was believed that blood, originating mostly from the liver, was carried out to the periphery by the veins to be consumed and woven onto the existing tissues, as needed by bodily organs, without leaving any residue to return to the center and circulate. As demonstrated by Harvey's inspiring progression toward his epochmaking discovery [5,6], knowledge of structural organization was not a sufficient condition for sighting the Circulation. The main epistemological obstacle to Galen seems to have been the readily available, ostensible, teleological explanations for the assumed blood movements — involving primarily nutritional and, secondarily, respiratory driving phenomena. Harvey, on the other hand, was vexed to the end by the inability to identify an Aristotelian final cause or purpose (τελος) of blood's circulation. This and the difference in color between arterial and venous blood, remained as two unresolved questions in his magnificently imaginative scheme until Richard Lower (1631–1691) and Antoine Lavoisier (1743–1794) [5,6,70] in early modern times. 7. Galen's accomplishments and influence Galen's experiential philosophic approach to clinical practice and research spans the centuries and is applicable to modern medicine. All knowledge about physiology and most about anatomy and botany were contained in a small fraction of his works, until Harvey. Even as late as 1833, the index to Prof. Karl-Gottlob Kühn's (1754–1840) compilation of the extant treatises of Galen – Claudii Galeni Opera Ornnia (Γαληνου Απαντα), encompassing volumes I–XX, of which XVII and

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XVIII comprise 2 tomes each [A and B] [20,71] – could be designed for working medical practitioners as well as for classical scholars. As observed by Prof. Nutton of University College, London, Kühn's (he was professor of Medicine, Anatomy and Surgery, Physiology and Pathology at the University of Leipzig [71], the 2nd-oldest in Germany) approach “looked back to history in seeking to pick out the most effective theories and practices from the past as a guide to the present.” Similarly motivated was Prof. Charles Daremberg's (1817–1872) – of the Collège de France – French translation of the Galenic Corpus (Oeuvres, 1854–1856). Galen's writings show medicine as part of biology. This treatment of medicine as the center of a larger whole – he was seeking to combine Hippocrates and Aristotle – signposts the Hellenic unity of science, a unity afterward to be lost, but nowadays increasingly reviving in the endeavors of multidisciplinary investigations. Galen earned his position among the few who have contributed, not merely to progress in some specialty, but to the general advancement of Medicine. Sagaciously surveying the medicine of his own time and the older teachings, he strove to make a system from his conceptions of the medical wisdom of Hippocrates and the biology of Aristotle. Furthermore, he personally gathered and built up extensive apothecary reserves of medications of superior quality. He differentiated topographic anatomy from anatomy of purpose, morphology from function, established a system of general pathology, and strived to understand medical conditions through comparative and pathological anatomy. The Corpus Galenicum, summarizing the state of medicine at the pinnacle of the Roman Empire, embraces virtually every facet of medical theory and practice; besides, it offers Galen's own important advances in anatomy, physiology, embryology — including his discovery of the fetal pulse, materia medica (Fig. 6), and general and multispecialty clinical practice [20,72,73]. Galen's philosophical discourses cannot be separated readily from his medical though [74]. Throughout his expositions on knowledge and semantics he argued that medicine, properly understood, can have the same epistemological certainty, linguistic precision, and intellectual standing that philosophy possessed in his time. Likewise his treatises on the language of medicine and his commentaries on Hippocratic texts form part of his project to recover authentic medical knowledge from the accretions of specious doctrine. His systematic treatment of all matters medical, his authoritative self-confidence, and maybe above all, his accomplished teleology (τελεολογια explaining phenomena by final causes) or conclusive proclamation of the purpose of every part and organ of the body [75–77], contributed to making his Corpus the basis or canon par excellence of medieval and Renaissance medical practice. Only those who are unaware of Galen's incalculable knowledge and understanding, his inventive common sense, and the recurring astounding anticipations of what we deem most modern, presume to disparage him. The Galenic corpus, endowed with the status of a “world classic” [13,73], has been translated in many modern languages, and one does not have to delve into Latin – if not Greek – tomes to discern what a phenomenon of medical knowledge Galen was, and how astute were his devotees, such as the visionary William Harvey, who followed him closely. The more we know of Galen, the less amazed we are at his undisputed sway over the minds of people for ages after his death. He was undeniably the successor of Hippocrates. 7.1. Galen, William Harvey, and Aristotle Galen held full sway – in various forms and attires – for roughly 15 centuries [2,6]. When Galenic precepts were eventually subjected to serious challenges in the 16th and 17th centuries, the masterminds who restructured and transformed those fields took their instruction and inspiration from their study of the restored writings of “the Prince of physicians,” “the divine Galen,” as William Harvey referred to him with tangible admiration [5,6]. Indeed, as Michael H. Shank concluded after studying the matter assiduously along Owsei Temkin's path [69], analogical reasoning suggested by the Galenic treatment of the urinary

system stands behind Harvey's insight into the Circulation [7]. Shank points out that reasoning inspired by Galen's methodology seems to underlie several of Harvey's arguments in De motu cordis. Harvey often refers to Galen as though he were a contemporary [6]; in a sense he was, for as an experimental biologist, Galen had advanced to positions from which Harvey was the first to push on further. To be sure, the relation between visionary thinkers and the giants they supersede is frequently characterized not just by sharp discontinuities, but also by underlying connections [4–6]. Several of Harvey's arguments in De motu cordis bear a striking resemblance to Galen's discussion of the urinary system in Book I of De naturalibus facultatibus (Περι φυσικων δυναμεων, On the natural faculties). In Chapter XIII of Book I [68], Galen objected first to the views of Asklepiades (129–40 BCE), who claimed that ingested fluid somehow vaporized and passed through the walls of the stomach and intestines into the bladder, where it once again condensed as urine. He contended that this account was preposterous and rebuked Asklepiades vehemently for overlooking the obvious: “One is forced to marvel at the ingenuity of a man who puts aside these broad, clearly visible routes [the ureters], and postulates others which are narrow, invisible — indeed, entirely imperceptible [68].” In quite a parallel approach, Harvey likewise protested vehemently against the postulated invisible pores in the septum of the heart, in the Introduction to De motu cordis: “And why, I ask you, do they have recourse to hidden, invisible, uncertain and obscure pores…, when there is such an open way through the pulmonary vein [vein-like artery]? Truly, it is a wonder to me that they should make, or rather invent, a way through the septum of the heart…” [78]. Galen used ligatures and sections to establish the function of the ureters – he coined the term – and the unidirectionality of urinary flow from the kidneys into the bladder. His procedure relied on vivisection and the judicious use of ligatures, and entailed a remarkable intermingling of ingenious reasoning with technical skill [68]. Completely in the footsteps of Galen, Harvey made extensive use of ligatures and sections; e.g., he showed how the ligation of the aorta at the base of the heart combined with the section of the carotid artery resulted in empty arteries and full veins. Likewise, he tied off a vein near the heart to show the vein emptying between the ligature and the heart. Harvey used the forceps in animal vivisection, or external ligatures on humans, to observe the direction and rapidity of the blood flow. These procedures served the same purpose as Galen's ligatures in the case of the slower-moving urine. As Galen noted, the oblique insertion of the ureters into the bladder yields in effect a one-way ureterovesical valve. This observation and the associated arguments were likely exploited by Harvey, in developing his understanding of the role of venous and cardiac valves. De motu cordis is inundated with lengthy citations from Galen [6,58] — an obvious consequence of Harvey's search for supportive materials in Galen's writings. Indeed, the main part of Chapter VII of De motu cordis quotes passages from Galen's De usu partium (Περι χρειας μοριων, On the usefulness of the parts, see Fig. 5). These emphasize the importance of the cardiac valves in ensuring that the blood flows unidirectionally from the right ventricle toward the lungs, passing from the branches of the pulmonary artery to those of the pulmonary vein, and that this blood reaches the left heart. Harvey subsequently “recycles,” as Shank puts it [7], Galen's argument, which “can more rightly be used… if only the names are changed [blood vs. urine flow context], for the passage of blood from the veins through the heart into the arteries” [78]. Galen conducted many measurements of urine production and compared it to the quantity of liquid ingested. Then, in Chapter XVII of Book I of De naturalibus facultatibus [68], he performed a remarkable order of magnitude analysis depending on rough measurements/estimates of urine production made not for the sake of accuracy, but to establish plausible ballpark figures. He remarks: “Now it is agreed that all parts which are undergoing nutrition produce a certain amount of residue, but it is neither agreed nor is it likely, that the kidneys alone, small bodies as they are, could

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hold four whole congii [about 3 gal], and sometimes even more, of residual matter. For this surplus must necessarily be greater in quantity in each of the larger viscera… For, if the kidneys produce in [wine] drinkers three and sometimes four congii of superfluous matter, that of each of the other viscera will be much more, and thus an enormous barrel will be needed to contain the waste products of them all. Yet one often urinates practically the same quantity as one has drunk, which would show that the whole of what one drinks goes to the kidneys.” This order of magnitude analysis is strikingly reminiscent of the wonderful counterpart argued by William Harvey in Chapter IX of De motu cordis, describing how the blood put out by the heart in half an hour amounts to a multiple of the total body weight and, thus, the incessant blood motion is readily compatible only with a circulatory system! [6]. The similarities between the lines of reasoning of Galen and Harvey are more striking than the differences [7,79]. Each involves a reductio ad absurdum based on quantitative premises. As I have recently detailed elsewhere [5], there is a remarkable order of magnitude analysis in Book I, Chapter XIII, of Aristotle's Meteorologica by which he argues against the postulate that the rivers are supplied with water by definite underground reservoirs, which fill up in the winter and then are gradually depleted during the summer. Aristotle posits that it should be clear to anyone making the rough calculation of the amount of water flowing in a day and then envisaging the size of the requisite reservoir, that it would have to be as enormous as the whole Earth (or, at least, not fall far short of it) to receive the total water flowing in a year. Since he preceded them and they were both his dedicated disciples, thoroughly familiar with his works, it appears probable that Galen and Harvey, side-by-side, had a foothold on Aristotle's shoulder, giving them an advantageous vantage point to view reality and understand physiology. 8. Conclusions Galen was the towering figure in Medicine for 15 centuries, his teachings enduring unchallenged until well into the 17th century. After Aristotle's the greatest systematization of natural knowledge, Galen's corpus, rooted in observation and experiment, was comprehensive and systematic. He may have written over 600 treatises, of which less than one-third are extant. An index of the word entries in his extant writings (in 1994) amounts to 1300 pages [29]. His errors attracted later attention, but we should balance the merits and faults in his work because both exerted profound influences on the history and advancement of all medicine, including cardiology. He based the healing art upon knowledge of disease and its causes, and pathology upon anatomy and physiology of the organism in health. He consciously modeled his medical and physiological arguments and demonstrations on geometric proof modes. Galen's writings would provide a superb guide to those who absorbed their spirit, as William Harvey did. Galen laid down the principles of scientific investigation and stressed scientific rationalism: experience and reasoning (πειραν και λογισμον). His real genius for observation/experiment stands out in his urologic and neurologic studies. He warned us that all writings must be verified by experiential testing. But the immensity of his works drew attention to his conclusions, not to his methods that had created them; it fostered fragments, abridgements, and guides that omitted his experiments and morphed gradually to the doctrinaire “Galenism” of the later Middle Ages. Already, Guy de Chauliac (1300–1368), a most influential surgeon of the 14th century who wrote Chirurgia magna partly from earlier sources, echoed this when he said speaking of the surgeons of his generation: “Let them follow the doctrine of Galen, which is entirely made up of experience and reason, and in which one investigates things and despises words.” In Galen's life-sustaining schema, the venous, arterial, and nervous systems, with the liver, heart, and brain as centers, were separate, and each distributed through the body one of the three pneumata: respectively, the natural, vital, and psychic spirit. He saw blood carried both

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within the venous and arterial systems, which communicate by invisible “anastomoses,” but circulation eluded him. Galen's writings, however, contributed to Harvey's singular ability to see mechanisms completely differently than other researchers, thinkers and experimentalists. Galen was the first to use the pulse as a sign of specific illnesses. His study areas included, among others, embryology and circulatory changes after birth, dietetics, hygiene, therapeutics, psychology, and virtually all medical and surgical specialties. He treated enslaved persons as he did their masters [17]. Besides his great reputation as scientist-author and philosopher, Galen was a highly ethical clinician and brilliant diagnostician, with vast natural powers of judgment.

Acknowledgments I am indebted to the Duke Libraries, particularly the David M. Rubenstein Rare Book & Manuscript Library, for archival materials, and illustrations.

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