A Hole in the Head Read online

  Many preliterate cultures and the early Egyptian, Mesopotamian, Indian, and Chinese civilizations attributed psychological functions to the viscera rather than the brain. In some of these cultures, such as the Egyptian and Indian, the heart was the center of all sensory, motor, and mental functions. In others, psychological functions were distributed among the viscera. For example, in Mesopotamian thought, the heart was the center of the intellect, the liver the center of emotions, the stomach of cunning, and the uterus of compassion. In the Chinese Yellow Emperor’s Classic mental functions are also distributed among the internal organs.1

  The Alcmaeon-Hippocratic-Alexandrian Encephalocentric View

  The explicit belief that the brain controlled sensation, cognition, and movement arose among the pre-Socratic philosopher-physicians of the fifth century BCE. The first of these was Alcmaeon of Croton (ca. 450 BCE) who is said to have been the first to dissect as an intellectual inquiry, to have described the optic nerves, and to have written:

  The seat of sensations is in the brain. This contains the governing faculty. All the senses are connected in some way with the brain; consequently they are incapable of action if the brain is disturbed or shifts its position, for this stops up the passages through which senses act. This power of the brain to synthesize sensations makes it also the seat of thought: the storing up of perceptions gives memory and belief, and when these are stabilized you get knowledge.2

  At about the same time we find the following famous paean to the importance of the brain in the Hippocratic treatise (ca. 425 BCE) On the Sacred Disease,

  It ought to be generally known that the source of our pleasure, merriment, laughter, and amusement, as of our grief, pain, anxiety, and tears, is none other than the brain. It is specially the organ which enables us to think, see, and hear, and to distinguish the ugly and the beautiful, the bad and the good, pleasant and unpleasant. . . . It is the brain too which is the seat of madness and delirium, of the fears and frights which assail us, often by night, but sometimes even by day; it is there where lies the cause of insomnia and sleep-walking, of thoughts that will not come, forgotten duties, and eccentricities.3

  The emphasis on the brain in sensation and thought was further developed by the Alexandrian anatomists Herophilus and Erasistratus (3rd C. BCE) who carried out the first systematic and detailed studies on the anatomy of the brain including of humans, probably some of them still alive.4 Herophilus and Erasistratus worked at The Museum in Alexandria founded by Ptolemy I (367–283 BCE), Alexander’s friend and general and the first Greek ruler of Egypt, who, as a young man, had been tutored, along with Alexander, by Aristotle.

  Aristotle’s Cardiocentric View

  The idea that the brain is central for sensation, movement, and mentation was a dominant tradition in Greek medicine from Alcmaeon through the Hippocratics and Alexandrians to Galen. However there was an opposing tradition in Greek philosophy, beginning with Aristotle, that held that the heart—not the brain—was the “command center” (hegemonikon) of the soul, the center of sensation, movement, and cognition.

  Aristotle (384–323) knew the arguments for the hegemony of the brain of Alcmaeon, the Hippocratic school, and others and argued against them in detail.5 In support of his cardiocentric view, Aristotle adduced several lines of evidence including (a) anatomical—the heart connects with all the sense organs but the brain does not (on dissection, blood vessels are indeed more prominent than nerves); the heart is centrally placed whereas the brain is peripherally located; (b) embryological—the heart develops before the brain; (c) comparative—all animals have a heart, but invertebrates, which do have sensation, have no brain; (d) observational—the heart, unlike the brain, is sensitive to touch; the heart but not the brain is affected by emotions; and (e) physiological—the heart provides blood needed for sensation but the brain is bloodless, without sensation; the heart is warm like higher life but the brain is cold; the heart but not the brain is essential for life.

  But there was an essential approach missing, namely, the clinical approach, the study of the brain-injured human. The champions of the hegemony of the brain, Alcmaeon, Hippocrates, Herophilus, and Erasistratus, were all practicing physicians. The evidence they had given in support of their opinions was strictly clinical. Since there is no evidence of systematic experiments on the brain and nervous system until Galen in the second century, the accidents of nature were the only sources of information about the functions of the brain. It is hard to conceive of Aristotle, in the course of his strictly zoological observations and dissections, coming across evidence strongly contradicting his view of the brain and heart.

  Although he came from a family of physicians and had been slated for a medical career, Aristotle at no time seemed interested in medicine or medical writing. Indeed, medicine appears to be one of the few things that this universal genius was not interested in. However, in the fourth century BCE, the study of the effects of damage to the human brain was the most likely way of getting a “more correct” view of the brain than Aristotle had.6

  The Tripartite Soul: Democritus and Plato

  Democritus (460–371 BCE) the pre-Socratic famous for his atomic theory and a friend of Hippocrates, took an intermediate position on the role of the brain and heart: he distributed the soul and mental function over three regions.7 The brain was the central organ of consciousness and thought, the heart the center of emotion, and the liver the site of lusts and appetites. Plato (428–347 BCE), following Democritus, put reason or intellect, the highest and immortal part of the soul, in the brain, which controls the rest of the body. In the Timaeus he wrote, “It is the divinest part of us and lords over all the rest.”8 Sensations were integrated in the heart, and the liver was responsible for lusts.

  The Stoics

  The Stoic philosophers adopted Aristotle’s cardiocentric view of all mental function. This school, founded by Zeno (344–262 BCE), became widely influential through the teachings of Chyrsippus (280–207 BCE). The Stoic school strongly objected to Plato’s separation of reason, emotion, and desire and argued for the unification of all aspects of the human mind and soul in one location.9 The location they chose was the heart. In addition to Aristotle’s arguments for the hegemony of the heart over the brain, the Stoic philosophers stressed the association of thought with speech and in turn with breath, which was considered a cardiac function. Here is their argument in a nutshell:

  Speech passes through the windpipe. If it were passing from the brain it would not pass through the windpipe. Speech passes from the same region as discourse. Discourse passes from the mind. Therefore the mind is not in the brain.10

  The Stoics developed an elaborate philosophy unifying ethics and politics with a view of the laws of the universe that provided a guide to human happiness. This system evolved over several hundred years, but only two aspects concern us here. First, it was by far the dominant philosophical school in Rome in Galen’s time. Indeed, Galen’s most famous patient was the Emperor Marcus Aurelius (121–180), a distinguished Stoic author in his own right. Second, it rejected the medical tradition from Alcmaeon and Hippocrates through the Alexandrians that sensation and thought were functions of the brain. Rather, it unified all mental functions in the heart.11

  Galen was a contentious and combative writer on many medical and philosophical subjects, but perhaps his major battle was with the Stoic cardiocentric view of mind. He not only wrote a long and detailed attack on it but also carried out what he considered a public experimental refutation of it, the subject of the following essay.12 This demonstration on a large pig became one of the most famous public physiology demonstrations of all time.

  GALEN AND THE SQUEALING PIG

  Galen, who lived in the Roman Empire in the second century, was the greatest experimental physiologist and anatomist of classical antiquity (figure 2.1). He was the most important figure in classical medical science and represents the peak of ancient Western anatomy, physiology, and medicine. His ideas were so pervasive that th
e medieval world saw the structure and function of the human body largely through his eyes.13 Today, his extensive writings (see box 2.1) provide a vivid account of the context, controversies, and achievements of the 600 years of classical biology and medicine. After a brief account of Galen’s life and his contributions to neuroscience, we consider his most famous experiment on the nervous system, namely, the effect of cutting the recurrent laryngeal nerves. This demonstration, carried out with a squealing pig as subject, was famous in its own time and for centuries later. Although there was a long tradition before Galen that the brain mediated sensation, cognition, and movement, the contrary view—that the heart subserved these functions—was dominant in Galen’s time. Galen’s findings on the recurrent laryngeals were viewed as strong experimental evidence for the primacy of the brain in behavior and thought.

  Life

  Galen was born of upper-class parents in 129 in Pergamon, a rich and ancient Greek city located on the site of the present-day Turkish city of Bergama, about 15 miles from the Ionian Sea. It was a traditional rival of Alexandria, and the rulers of Egypt had banned the export of papyrus to Pergamon in order to block the development of a rival library there. In response, the Pergamenians developed a new writing material made from animal skins called charta pergamena, which gives us the English parchment. In Galen’s time, both cities were part of the Roman Empire, then at its peak.14

  Pergamon was the site of one of the most famous Aesclepieia, named after the Greek god of medicine Aesclepius. It was a combination of a medical treatment center, a healing temple, a pilgrimage site, and a medical school. A common therapeutic technique was to induce sleep with drugs (“incubation”) and then to whisper in the sleeping patient’s ear that a particular treatment would be efficacious for his ills. The next day, when the patient was told the treatment plan by his doctor, he interpreted his dream as having foretold his doctor’s plans. The collection of buildings that made up the Pergamene Aesclepium, along with monuments left by rich patients in recognition of their cures, can still be visited today.15 Pergamon was also the site of a major gladiatorial school.

  Figure 2.1

  Portrait of Galen. From the Juliana Anicia Manuscript, written in 487 (Singer, 1957).

  Box 2.1

  Galen’s Writings

  Galen published voluminously on almost every branch of medical science and medical practice known in his time as well as on philosophy, rhetoric, and his own life story (Sarton, 1954). Most of Galen’s works are lost; in the 1820s the surviving Greek works were collected and translated into Latin by K. G. Kuhn. They make up 22 very large volumes. There are also some other works which survived only in Arabic. Much of Galen’s writings remain untranslated into English, and most of the English translations were published only in the last few decades.

  Galen discusses the circumstances surrounding his first public demonstration of the recurrent laryngeal nerves in On Prognosis. He gives an account of the recurrent laryngeal in On the Usefulness of Parts of the Body, but the most detailed account is in the later books of On Anatomical Procedures (or De Anat. Admin.; Galen’s works are most commonly denoted by abbreviations of their titles in Renaissance Latin).

  A brief history of On Anatomical Procedures gives the flavor of the adventures of the ancient texts that managed to survive. It was originally a two-chapter work written in 169. Soon after, Galen’s copies were lost in a fire and others were unavailable, so Galen eventually wrote a much expanded version in 177. Of this text, Books I–XI were published but Books XII–XV were destroyed, along with many of his other works, in another fire and had to be rewritten. Only one manuscript copy survived in Western Europe and it broke off in the middle of Book IX. It was first printed in 1525 by Aldus in Venice.

  In 1844 the remaining books of On Anatomical Procedures were discovered as an Arabic manuscript in Oxford’s Bodleian library. They had been translated from Greek into Syriac by the great Arab physician Hunain ibn Ishaq (809–873) and then into Arabic by him and his nephew. The Bodleian Arabic manuscript was translated into German in 1906 and then into English in 1962 by W. L. H. Duck-worth with the help of an anatomist and an Arabist.

  Galen’s father, an intellectually inclined architect, began to tutor his son in philosophy and mathematics at an early age. However, when Galen was 16 his father had a dream, supposedly sent by Aesclepius, that led Galen to begin the study of medicine. During his four years as a medical student in Pergamon, he published three medical texts, one on the uterus, one on the eye (now lost), and one on medical methodology. Over the next eight years he continued his medical studies at three other major medical centers including Alexandria, the leading center of medical research and teaching. In this period, he acted more as a postdoc than a medical student: carrying out research, writing on a variety of medical subjects, and maintaining his interest in philosophy. Finally, at the age of 28 he returned to Pergamon and was appointed physician to the gladiators, a rich source of clinical and anatomical material, as most combats ended in serious or fatal injury.16

  In 161, a war between Pergamon and its neighbors caused the gladiatorial “games” to be closed, so Galen set off for the Rome of Marcus Aurelius.17 In Rome at this time, there was an unusually close relationship between, on one hand, the ruling politicians and aristocrats and, on the other, the intelligentsia, particularly the philosophers and rhetoricians known as Sophists, but including other philosophers, physicians, and scientists. In this period, known as the “Second Sophistic,” the Empress Julia hosted a salon of philosophers and writers; Greek intellectuals married Roman aristocrats; and the rulers of the empire sponsored and attended scientific demonstrations and lectures.18

  In this unusual environment, Galen rapidly rose to the highest social and professional level of Roman society. Helped by curing several influential political figures, he built up a large and successful practice. One of his powerful patrons was Flavius Boethus, a former consul and later governor of Syria. Boethus encouraged him to compose his first major anatomical and physiological works. He also arranged for Galen to present a series of public anatomical demonstrations and lectures which were well attended by the intellectual and political elite. The most famous of these was Galen’s demonstration of the functions of the recurrent laryngeal nerves, discussed in detail below. During this period Galen also became involved in several acrimonious disputes with other leading physicians.19

  Perhaps because of these disputes, or because of an epidemic in Rome, Galen returned to Pergamon. Soon after, the co-emperors Marcus Aurelius and Lucius Verus recalled him to accompany their troops in the field. He talked his way out of this assignment by becoming personal physician to Marcus’s son Commodus. He continued to serve Commodus when he became emperor and treated the subsequent emperor Septimus Severus as well. Galen repeatedly boasted that as the result of his professional accomplishments he became well known to all the leading philosophers and writers of his time as well as all the emperors. He continued to treat patients, research, write, quarrel with other physicians, and be lionized in high society until his death in about 213.20

  Physiological System

  Galen believed that physiology and anatomy formed the critical bases of medical practice and he wrote extensively on both subjects. His physiological system totally dominated physiology and medicine until William Harvey in the sixteenth century and continued to be very influential until the nineteenth century.21

  In his system the fundamental principle of life was pneuma (akin to the chi of Chinese medicine and the vayu of Indian medicine.) It entered the body from the all-pervading world spirit during breathing and passed to the lungs and then via the pulmonary vein to the left ventricle where it mixed with the blood. The blood had been made in the liver from chyle brought from the intestines by the portal vein. The liver had also given the blood the lowest type of pneuma, natural spirits, which was believed to be innate in all living tissue. The blood with its natural spirits and nutritive material was now distributed throughout the b
ody by the veins in a tidal, or ebbing and flowing, motion. Some of the blood entered the right side of the heart, from which it had two possible routes. Most of it stayed in the right ventricle, from which its impurities were carried off by the pulmonary artery to the lungs and exhaled. A smaller portion of it trickled into the left ventricle through the holes that Galen thought existed in the interventricular septum. There it mixed with air, which had come in from the lungs via the pulmonary vein, and thereby became transformed into a higher type of pneuma, vital spirits. The vital spirits were distributed to the body and head via the blood in the arteries. Some blood carrying the vital spirits went to the base of the brain to the “rete mirabile” (a network of blood vessels at the base of the brain found only in the ox and some other animals, but not in humans—although it was described and drawn as a very prominent feature of the human brain until Vesalius). Both here and in the choroid plexi inside of the ventricles, vital spirits became transformed into the highest pneuma, animal or psychic spirits. The brain ventricles were an important storage site for this psychic pneuma; from there it was distributed throughout the brain and via the (hollow) nerves to the rest of the body. All this remained dogma for over 1,500 years.22

  Neuroscience Achievements

  Whatever the weaknesses, from our point of view, in some of Galen’s theoretical views, he made a number of major discoveries, particularly on the anatomy and physiology of the nervous system. He described in detail the course of nine, if not ten, of the cranial nerves (although he grouped them as seven pairs), as well as the sympathetic nerve trunks.23 He distinguished sensory and motor nerves for the first time and thought that this distinction derived from their source in the brain, a clear statement of Müller’s doctrine of specific nerve energies. Galen’s descriptions of the gross anatomy of the brain were very accurate, particularly with respect to the ventricles and the cerebral circulation, both important in his physiological system. Galen usually presented his dissections as if they were of the human, but, in fact, they were invariably of animals, usually the ox in the case of brain anatomy, the Barbary “ape” (the macaque M. sylvana) for cranial nerve anatomy, and pigs for vivisection. It was only very recently, when Galen’s descriptions were evaluated in terms of the actual species dissected, that their great accuracy was recognized.24