Dr. Crivellato is an associate professor of human anatomy at the University of Udine Medical School (UUMS), Udine, Italy. His research interests are in the areas of cell degranulation and the history of anatomy.
Dr. Ribatti is a professor of human anatomy at the University of Bari Medical School, Bari, Italy. His primary interest is the study of angiogenesis in several physiological and pathological conditions.
Diogenes of Apollonia was a pre-Socratic philosopher. We have no direct evidence as to his date of birth or death but a testimony from Diogenes Laertius, the famous doxographer of the 3rd century AD, informs us that he was a contemporary of Anaxagoras. From this and other sources, we can reasonably infer that Diogenes of Apollonia lived during the second half of the 5th century BC, with a floruit around 440–430 (Kirk et al.,1983). The same Diogenes Laertius refers that he was a renowned “natural philosopher.” With this term, we indicate scholars who were principally interested in explaining the constitution of all matter in terms of specific basic substances. These scientists were also engaged in exploring the different aspects of the physical and biological world, from cosmology to astronomy, from earth sciences to climatology, from agriculture to physiology of living organisms. Such people initiated what was defined as the Western scientific tradition insofar as they made the first attempt to interpret natural phenomena rejecting supernatural causations or mythical explanations and introducing a new critical spirit of rational discussion (Lloyd,1970).
Diogenes of Apollonia was a follower of Anaximenes of Miletus, the great Ionic philosopher who had lived 100 years earlier. Like Anaximenes, he postulated air be the original principle ('αρχη) and the basic substance of both animate and inanimate world. Air is infinite and eternal. All comes into being from air through a mechanism of condensation and rarefaction. Air is endowed with intelligence and divine attributes, and even the soul is constituted by air. Human beings acquire air through the breath and thus they become capable of thinking, reasoning, and perceiving sensations. It is the inner air (o εντoς αηρ) that is “man's soul and thought” (DK 64 A 19) (Diels and Kranz,1966).
Diogenes was an eclectic spirit who attempted at a reconciliation of the old philosophical tradition with the new empirical observations. According to Diogenes Laertius, he wrote numerous books. Simplicius, the neo-Platonist philosopher of the 6th century AD who made long and accurate quotations from Diogenes' work, mentioned four of these books: On Nature (Περι ϕυσεoς), Against Physicists, Meteorology, and On the Nature of Man. Only the first one was known to him and could be partly conveyed to us.
DIOGENES' ACCOUNT OF VASCULAR ANATOMY
In this book, we find the primary systematic description of the vascular system in man. Before reporting Diogenes' account, we will first address a linguistic trouble. Diogenes used the term “ϕλεβες” to indicate the vascular structures he was dealing with. This expression is usually translated with the word veins (Kirk and al.,1983), or Adeln in German (Diels and Kranz,1966) and vene in Italian (Giannantoni et al.,1969). However, ancient Greek scientists had no notion of veins in the modern sense. Both Democritus (DK 68 B 120) and Aristotle (De Vita 26, 480 a 11) (Carbone,2002), for instance, spoke about pulsating veins, obviously indicating arteries. The distinction between veins (ϕλεβες) and arteries ('αρτηριαι) came later. It was Praxagoras of Cos (born about 340 BC) who was credited to be the first who made a general distinction between arteries and veins and recognized different functions to them (von Staden,1989). For this reason, we will translate the term “ϕλεβες” as “blood vessels,” “vessels,” or “vascular channels.”
Diogenes opens his presentation with this sentence: “Blood vessels in man are as follows.” He first mentions “two vessels, which are outstanding and run through the abdomen along the backbone, one to the right side and the other to the left, each directed downward to the corresponding leg and upward to the head.” We are inclined to suppose that here Diogenes is referring to the inferior and superior vena cava (to the right) and aorta (to the left). This vascular architecture relies in part on animal dissections, in particular ovine and bovine dissections. Remarkably, it resembles a series of Leonardo da Vinci drawings, one of which is exemplified in Figure 1, which also depend on necropsies of these mammals (Siraisi,1990). In their route to the head, maintains Diogenes, “these vessels pass near the clavicles through the throat.” Here, Diogenes is likely reporting on the internal jugular veins. “From these [two large] vascular channels, blood vessels expand all over the body; from the right one, those [vessels] that run to the right side and, from the left one, those that run to the left side. Two [other] great vessels reach the heart near the backbone and two others, running a little higher up through the chest underneath the armpits, are directed toward the hands, each on its own side of the body. One is called the splenetic vessel, the other the hepatic vessel.” This last sentence does not seem to make any sense because splenetic and hepatic vessels do not run through the axillary region. But if we interpret the former as the vascular channel running along the splenetic (left) side of the body and the latter as the blood vessel directed to the hepatic (right) side, we find ourselves before a fairly good description of the vessels of the upper limb. This assumption is supported by the following sentences: “Each of them subdivides at its extremity. One [vessel] runs to the thumb, the other to the palm of the hand. From these vessels others lead off, thin and ramified, directed to the rest of the hand and fingers.” Despite its very schematic design, this is a substantially truthful piece of regional anatomy.
Diogenes continues with a rather vague description of splancnic vessels and the vessels of the lower limb. “From the principal blood channels [the supposed descending aorta and inferior vena cava], other tinier [vessels] branch off; from the right one, those directed to the liver and, from the left one, those directed to the spleen and kidneys.” “Numerous thin channels split off from the great vessels and are directed to the abdominal cavity and ribs.” “Those that extend to the legs ramify into two branches at the root of the limb and run through the whole thigh. The largest of them runs along the posterior part of the thigh and appears outstanding; the other, which runs along the middle part of the thigh, appears a little less prominent. Thereafter, both extend past the knee directed to the shin and the foot, like those that run to the hands. They reach the sole of the feet and from here they extend to the toes.” Although uncertain and to some extent incorrect, this early anatomical representation has the precious value of an archetype account.
Diogenes then proceeds to the description of the vessels of the neck and head. “Those [two vessels] that extend to the head through the throat appear large in the neck.” As previously mentioned, Diogenes' report is here most likely concerning the internal jugular veins. “From the extremity of each of them, many vessels branch off in the direction of the head. Those originating from the right one find their way to the left and those that come from the left one extend to the right. And both sets [of vessels] terminate near the ear.” This appears to be a depiction of the course of the internal jugular vein, which presents an apparent origin in the parotid region by confluence of veins coming from the ipsilateral parts of head and neck. Diogenes proceeds with an interesting observation: “There is another vessel that runs nearby the large one, on either side of the neck, but it is a little smaller and the majority of vessels coming from the head converge in it. And these [two vessels] extend inward through the throat and from each of them [other] vessels branch off, passing underneath the shoulder blade in the direction of the hands; and these appear alongside the splenetic and hepatic vessels [the putative axillary vessels] as another, a little smaller pair.” We conjecture that Diogenes is here speaking, first, about the common carotid artery, which runs close to the internal jugular vein on its inner side, and about the external carotid artery that gives off many branches in the upper region of the neck. The last sentence seems to deal with the sublcavian artery and the axillary artery, which run close to the venous subclavian-axillary trunk (which has been previously described) and present a smaller size than the parallel veins. This part is, in our opinion, one of the most significant of the whole account because Diogenes seems aware of the paired arrangement of axillary vessels, with one vascular channel (the artery) being tinier than the other (the vein). Then he continues: “Other vascular channels derive from these vessels and reach the region below the breast.” Here, Diogenes is likely speaking about internal and external mammary vessels. At last, Diogenes refers to genital vessels: “A pair of delicate vessels originates from each of these [the two large vessels] and run through the spinal marrow to the testicles. Another pair extends to the kidneys running under the skin through the flesh. These terminate at the testicles in men and at the uterus in women. They are called the spermatic blood vessels.” He concludes his vascular description with an enigmatic sentence: “The blood vessels that come from the abdomen are broad at first and then they become narrower until they change from right to left and from left to right.” The anatomical architecture of the vascular system as conceived by Diogenes is schematically illustrated in Figure 2.
VIEWS OF DIOGENES' CONTEMPORARIES
In Historia Animalium, Aristotle informs us that Diogenes conceived the vascular system as a sequence of blood channels originating from the head (Peck,1965). Although there is no trace of this notion in the extant fragment we have here translated, the concept that the source of blood vessels was in the head or brain can be found in two other scientists of the fifth century BC, roughly contemporary of Diogenes: Syennesis and Polybus. Comparison of Diogenes' account with the testimonies of these two scientists gives the magnitude of Diogenes' contribution to the comprehension of the anatomy of the vascular system in man. Syennesis of Cyprus was a physician. According to Aristotle, he wrote as follows: “The nature of the stout blood vessels is this: from the eye across the eyebrow, along the back, past the lung, below the breasts; one runs from right to left, the other from left to right: the latter runs through the liver to the kidney and the testicle, the former to the spleen and kidney and testicle, and thence to the penis” (HA III, 2, 511 b 24 foll.; translated by Peck,1965). This passage, with an addition, occurs also in the Hippocratic treatise De Natura Ossium (On Bones).
Polybus was the pupil and the son-in-law of Hippocrates. He described the vascular system in man as composed by four pairs of blood vessels originating from the head: one posterior, two lateral, and one anterior (HA III, 3, 512 b 12 foll.) (Peck,1965). Remarkably, one of the two pairs of lateral vessels is described as traversing the middle sagittal plane and extending to the opposite side of the body. Both Syennesis' and Polybus' vascular accounts appear extremely primitive and inconsistent with the architecture of blood vessels in man. Their descriptions provide a useful yardstick for assessing Diogenes' contribution to the knowledge of vascular anatomy. His report indeed largely surpasses the standard of his time and achieves a much greater approximation to the truth. It also justifies Simplicius' comment on Diogenes' account: that Diogenes provided indeed a “precise anatomy of the blood vessels” (DK 64 B 6).
DIOGENES' CONTRIBUTION TO VASCULAR PHYSIOLOGY
Diogenes contributed not only to the initial definition of the anatomy of blood vessels in man but also to the formulation of an early functional view of the vascular system. As previously mentioned, it was Praxagoras of Cos, the teacher of the great Alexandrian anatomist Herophilus of Chalcedon (335–280 BC), who first made a general distinction between arteries and veins more than a century and a half after Diogenes. According to Praxagoras, arteries emerged from the left ventricle of the heart, had a thick wall, and exhibited pulsation while veins originated from the right ventricle, had a thinner wall, and did not pulsate. He explicitly recognized different functions to them inasmuch as arteries, in his opinion, would carry the pneuma while veins would convey blood and nourishment to all parts of the body.
Greek biologists indeed envisaged the arteries as channels for the passage of pneuma or a mixture of blood and pneuma. This notion deserves a short comment because it was destined to play an enormous influence on the subsequent development of human physiology. “Pneuma” was equivalent to soul or life and was identified with air and breath (Singer,1957). The term “'αρτηρια” actually indicates a duct for the passage of air (αηρ), and Plato, Aristotle, and also some Hippocratic authors used this term to designate the windpipe or bronchial tubes (von Staden,1989). The idea that arteries contain air probably originates by the observation that they are empty in dead animals. We find for the first time the word “'αρτηρια” indicating the aorta artery in the Hippocratic treatise De Carnibus (On Fleshes) (von Staden,1989).
The concept of a double vascular organization, an arterial system filled with air (pneuma) or a mixture of blood and air, and a venous hematic (nourishing) system replenished only by blood, first formulated by Praxagoras, was later accepted by Erasistratus of Ceos (310–250 BC), who made of this distinction the basis of his pneumatic physiology (Singer,1957). Erasistratus maintained that arteries were filled exclusively by air but his contemporary Herophilus held a different view because, in his opinion, arteries contained blood mixed with air (Harris,1973). According to Galen of Pergamon (129 to c. 216 AD), arteries transported a special kind of refined blood, called the vital spirit or vital pneuma, which was elaborated in the left ventricle. Here the blood, derived from the right ventricle through small septal openings, encountered and was mixed with the air drawn from the lungs by the pulmonary vein (Fig. 3). The ensuing mixture was the vital spirit, which was conveyed to the whole body by the arterial system. The physiological significance of the vital spirit was to vitalize the organism. By contrast, the nourishing blood, which was called the natural spirit, originated in the liver by food concoction (digestion) and was transported to all tissues by the venous system. Thus, in Galen's view, the origin of the vascular system was placed in the liver, not the heart.
Galen mentioned a third type of spirit called the animal spirit or psychic pneuma. This special light and invisible substance originated in the rete mirabile (marvellous net), a hypothetical network of thin vessels located at the base of the brain, by further refinement of the vital spirit (Fig. 3). The resulting animal spirit permeated the brain ventricles and was responsible for performing sensory, motor, and psychic activities (Solmsen,1961). This anatomical and functional schema, codified by Galen in a complex conceptual system, lasted till Harvey's revolutionary discovery of blood circulation in 1628.
The origin of the Greek pneumatic physiology, that is, the conception that vascular channels were conduits for the passage of air or a mixture of blood and air, can be traced back to Diogenes of Apollonia. In a testimony reported by Aetius (DK 64 A 29), Diogenes maintains that sleep is produced when “the blood fills the vessels and pushes the air, which is contained inside them, toward the chest and downward in the belly.” In the same testimony, death is recognized to come when “all air retires from the vascular channels.” Thus, according to Diogenes, vessels contain blood mixed with air. In a more explicit testimony conveyed by Simplicius (DK 64 B 6), Diogenes is reported to believe that air inhaled by respiration “pervades the whole body through the vessels.” These statements are among the first documents in the pre-Socratic literature concerning the idea that blood vessels contain air.
As Diogenes attributed thinking and the senses to air, the question arises as to whether blood vessels are implicated in cognitive processes and other mind faculties. The Simplicius' testimony cited tells us that air mixed with blood and pervading the body through the blood channels produces thoughts (Kirk et al.,1983). In another testimony reported by Aetius, Diogenes claims that “the principal part of soul is located to the heat's cavity, which is filled with air” (DK 64 A 20). Thus, these passages would suggest a relationship between vascular physiology and thinking activity in humans. Diogenes does not explain how air would enter the bloodstream. He simply states that this happens through respiration. The first causal explanation concerning air presence in blood vessels was provided by Aristotle (384–322 BC), who mistakenly described anatomical passages connecting the lung with the heart's cavities (Historia Animalium I 17 496a 25; III 3 513a 35) (Peck,1965). He also claimed that it was possible to perceive clearly the entry of the breath into the heart of the large animals when their windpipe was inflated with air (Historia Animalium I 16 495b 15).
Which of the above views might have been the possible source transmitting an early pneumatic notion to Diogenes? One possibility was the theory of cutaneous breathing elaborated by Empedocles of Acragas (c. 495–435 BC) some years earlier. According to Empedocles, there are pores in the skin that are in connection with superficial blood vessels. Through these openings, air is sucked up by the vascular channels, if indeed that is how fragment DK 31 B 100 should be interpreted. Although Empedocles did not provide any description of blood vessels, let alone their connection with the heart, he is to be regarded as the real father of pneumatic physiology (Singer,1957), a conception that, according to Harris (1973), constituted “a tragical mistake in the history of Greek medicine, a mistake which more almost than any other prevented the discovery of the circulation.”
This article emphasizes Diogenes of Apollonia's pioneer contribution to the knowledge of vascular architecture in man. Diogenes provided indeed a very interesting and accurate description of the vascular system, which largely surpassed the standard of his time and has to be regarded as basically correct. We do not know if Diogenes was, like Empedocles, a medical doctor of some sort. We do not even know if Diogenes practiced dissections, human dissection in particular. Historians are inclined to believe that, save Herophilus and Erasistratus in Ptolemaic Alexandria, no Greek physicians or philosophers ever undertook dissection of human corpses (von Staden,1989). Diogenes' account we have presented here demonstrates, however, that his interest in vascular anatomy was far from being superficial and that he must have performed some kind of personal observations, not only in animals but perhaps occasionally also in man. He could have examined wounded persons who, under the most different circumstances, might have come to his observation. In addition, his notion of air circulation in blood vessels was remarkably influential and testifies once more to his profound participation in the development of leading concepts in ancient Greek science.
Supported by local funds from the Ministero dell'Istruzione, dell'Università e della Ricerca, Rome, to the Department of Medical and Morphological Research, Anatomy Section, University of Udine.