Biomedicine and Health: The Brain and Nervous System

Introduction

The nervous system is just as much a concept as it is a natural object. The idea of a nervous system as the supreme bodily part is relatively modern. That the mind is a biological organ is an even more modern idea. Our apparently “instinctive” feeling that we think inside our heads is actually a point of view that we have learned. The concept of the nervous system as the central coordinating organ of the body, the source of motion, the headquarters of sensation, thought, and speech dates only to the seventeenth century. There have long been names for brain, spinal cord, and nerves. But other organs have been regarded as the seat of feeling, and the notion that organic harmony is brought about by the action of a particular part of the body has been expressed in many different ways.

Historical Background and Scientific Foundations

The Edwin Smith papyrus (named after the dealer who bought it in Luxor in 1862) dates from about 1600 BC and describes 48 cases of injuries, fractures, wounds, dislocations, and tumors. It seems to be a manual for doctors and contains directions such as: “Instructions concerning a gaping wound of the head, penetrating to the bone, smashing his skull, and rending open the brain of his skull.” The text then goes on to describe how such an injury might reveal “corrugations [like those] which form in molten copper,” presumably the cerebral folds and fissures, called sulci and gyri. Here the word “brain” meaning (as it later did in Greek) “marrow of the skull” is the first written use of a term to signify the content of the cranial cavity; presumably a word existed for thousands of years before (not least since animal brains must have been distinguished as edible).

The Egyptians extracted brains through the nose during mummification, and they also named and used the brains of animals for medicinal purposes. Exactly what they thought the brain did is unclear, but evidence from other papyri makes it obvious that the organ had a minor role in the body compared with the heart. This was also true of the other early cultures of the Mesopotamians and the Hebrews. Vestiges of the belief in the heart as the fount of the emotions are alive and well in popular culture.

The selection of the heart as the principle organ of the body and the seat of feeling and intellect was favored by many famous ancient Greek writers, although others chose the brain. One of the earliest Greek philosophers, Alcmaeon of Croton (c.572–c.490 BC), appears to have dissected animals and, according to ancient authors, claimed that the brain was the organ of sensation. The works associated with the Greek physician Hippocrates (c.460–375 BC) (but which are clearly from many different authors and sects), in general supported the brain theory. The author of a Hippocratic work on epilepsy, The Sacred Disease, deemed the cause of epileptic fits to be natural and to lie in the brain, “the most powerful organ of man's body.”

Favoritism for the brain was sustained by the philosopher Plato (c.428–348 BC) who declared it was the seat of the rational soul. Such an opinion, however, seems to have been a minority one. In general, the cardiac theory held sway and was supported by the most influential ancient writer on natural philosophy, Aristotle (384–322 BC), an accomplished dissector of animals, who regarded the heart as the center of thought and sensation; the brain, he believed, acted to cool the heart's actions.

In the Hellenistic period, Alexandria became the great center of ancient scholarship. Here human dissection was carried out by Herophilus of Chalcedon (born c.320 BC) and Erasistratus of Ceos (fl. c.250 BC). These anatomists first made the claim that medicine should be based on knowledge gained by observation of the hidden structure of the human frame. Nothing like this appears in the Hippocratic texts. For the first time the human brain was dissected and nerves distinguished from arteries and veins. Herophilus considered brain the organ of the soul and named a number of its parts. The confluence of the venous sinuses on the occipital bone he named the torcular (winepress); to this day it is called the torcula herophili.

It was, however, only in the works of Galen of Pergamum (AD 129–c.216), a Greek physician who practiced in Rome, that the idea of the brain, spinal cord, and nerves being continuous parts of a single organ was born. Galen, a great anatomist, recognized that there were separate sensory and motor nerves; he recognized seven of the 12 pairs of cranial nerves. He knew that some nerves were also involved in involuntary activities. The brain, he held, was the source of feeling and action, a position he defended philosophically and also by appeal to experiments. Wounding the brain of an animal, he wrote, deprived it of movement, while pressing the heart might have no effect.

Nonetheless, he considered the body had sensitive and nutritive souls in the heart and liver, which supervised vital and vegetative activities such as respiration and nutrition, respectively. In addition, each part of the body had innate faculties that allowed it to perform its proper function. The arteries, for example, possessed a faculty that enabled them to propel the blood forward—there was no need for a stimulus, such as a nervous impulse, to initiate, maintain, or change their actions. Galen had no concept of a nervous system in a modern sense.

The works of Galen formed the foundation of medicine in the Islamic civilization and then in Western Europe though the Middle Ages to the seventeenth century. Although the brain was generally considered the seat of consciousness, Aristotle's view that the heart was the source of vital activities such as nutrition, growth, and generation was given much respect. It was central to William Harvey's (1578–1657) view that the blood circulated around the body, a discovery he announced in 1628. Medieval clerics and physicians debated the seat of the soul and largely agreed that mental processes took place in the brain's ventricles or cavities. This, the so-called “cell doctrine” can be traced to the work of Herophilus.

The Renaissance

The Renaissance witnessed the flowering of the study of anatomy based on human dissection and the creation of modern naturalistic illustration. Nonetheless, Renaissance anatomists continued to emphasize the role of the ventricles, and the brain substance seems to have been of little interest. The cerebral folds and fissures, the sulci and gyri, which we now think of as having a regular pattern, were either not depicted or depicted differently from one illustrator to the next. A saggital (side view) section of the head drawn by Italian artist and engineer Leonardo da Vinci (1452–1519) is based on a description of the brain written by the Persian physician Avicenna (980–1037) and gives the ventricles particular prominence. Andreas Vesalius (1514–1564), the greatest anatomist of the age, recounts how he was taught the cell doctrine but, at the same time, he seems to cast doubt on it as he did with other teachings passed down from antiquity.

If anyone could be considered the architect of the modern idea of the nervous system it is the French mathematician, scientist, and philosopher René Descartes (1596–1650). Descartes's detailed ideas about how the body worked were basically Galenic and almost out of date even in his own time, but his overall concept of what sort of a thing the body was and how it moved was entirely new. Descartes's physiological ideas derived from his fundamental division of the universe into two sorts of stuff: matter and spirit or body and soul, a distinction known as Cartesian dualism.

Matter was particulate and extended (it had three dimensions) and was in motion. It could transmit this motion by contact to other particles of matter, but it could not initiate motion. Everything in the universe was made of matter in motion, a concept that allowed Descartes to argue that mathematics was the basic science of nature. What distinguished human beings from anything else in creation (for God had made the universe) was the possession of a soul. The soul was everything matter was not. Descartes viewed it as the thing in us that feels and perceives and is the source of our voluntary or willed actions. Animals, according to Descartes, do not have souls (since in Christian teaching they cannot have an afterlife) and are merely machines. That animals can feel (see, hear, smell) is an illusion.

What is important here for physiology is that Descartes was withdrawing from the body any ability of the parts to carry out physiological activity on the basis of their having sensory and purposive capacities. Galen's “natural faculties” were nonexistent, attributing to matter properties that rightly belonged to the soul. What drove the body's basic life processes and made interaction with the world possible was the mechanical action of the nervous system. The body was like a clock and did not need a soul to move it. Since the brain and nerves had long been known to have the capacity to transmit motion, it was not surprising Descartes chose them as the most important bodily organ. Descartes's mature views were published in his Treatise of Man, which was printed only after his death in 1662.

The nerves, wrote Descartes, were fine threads. When pressure was exerted at one end of them it was transmitted by the brain to other nerves and thence to a muscle to effect a mechanical action. Thus, he said, if you accidentally put your foot too near the fire, the flame pulls on the nerve like a bell rope which opens a pore in the brain, particles rush though this and along another nerve to a muscle which is inflated and yanks the foot away. (Later this action will be called a reflex.) In animals it is purely a mechanical phenomenon, without feeling. In humans, by some mysterious means known only to God, the soul is made aware of what is going on and registers pain. Described like this Descartes explanation seems crude indeed, but it offered powerful opportunities for analyzing more basic bodily activities in mechanical terms. Thus the heartbeat or respiration could be explained by what we now might call feedback mechanisms mediated through the nerves.

There were a couple of problems with Descartes's account. First, where was the human soul? This was both a philosophical problem and an anatomical one, the first of which Descartes never satisfactorily answered; his answer to the second was ignored. He could not answer the first question because by his own definition soul could not have a place, only matter had dimensions. Since, however, he needed a soul in the human brain, he chose the pineal gland. (Descartes had dissected many animals).

The second problem with Descartes's account was animal sensation. Theoretically his model was brilliant, but it required animals to be pieces of machinery, mere robots, whereas most people in the real world believed animals had feelings. From where did they arise? Not from mere matter, since that was an heretical view (the doctrine of materialism) and not from souls, since that put spiritual agencies back into a world supposedly explicable by mechanics and mathematics alone. In practice natural philosophers ignored the problem. They used Descartes's physiological model but treated the behavior of animals in a commonsense manner. Only in the nineteenth century when the brain was made the organ of the mind—of feeling and action—was this problem partially resolved (the problem of matter and consciousness—Cartesian dualism—has never quite gone away).

Descartes basic ideas dominated work on the nervous system for 150 years, until another revolution in thought changed its shape (the broadest of his concepts remained, however). From about 1650 onwards the nervous system became the focus of intense study by using anatomy, microscopy, animal experiment, and philosophical enquiry. By the end of the eighteenth century it was seen as the key organ for explaining life in all its manifestations in the animal kingdom.

If Descartes was the architect of the modern nervous system, its first great builder was Thomas Willis (1621–1675), an English physician who came from a family of staunch royalists. In between fighting as a soldier, Willis studied medicine at Oxford, a university devoted to the king. Here he met the aged William Harvey (1578–1657), whose views on anything but the circulation were well out of date. Yet, inspired by Harvey, with small group of young men, the “Oxford circle,” Willis plunged himself into the work of Descartes and the study of the new fashionable subject, chemistry. During Oliver Cromwell's (1599–1658) rule (1653–1658), Willis made a meager living as a country doctor but maintained his connections in Oxford where he became an intimate of the natural philosopher Robert Boyle (1627–1691), by this time the leading proponent of new experimental philosophy in England.

In the late 1650s Willis decided to study the nervous system. Fate played into his hands. Charles II was restored to the throne in 1660 and Willis, the royalist, was made professor of natural philosophy at Oxford. He dissected innumerable brains from human corpses, producing the most detailed account of its anatomy yet, and described what was later called the circle of Willis (the arterial circle at the base of the brain). He studied the distribution of nerves in viscera and muscles. He compared the brains of humans and animals. The exquisite drawings for Willis's The Anatomy of the Brain and Nerves were made by his friend, the architect of St Paul's Cathedral, Sir Christopher Wren (1632–1723).

Willis appears to have coined the word neurologie. His studies, by showing the extent of the nervous system, gave substance to Descartes's ideas. But Willis also conceptualized the system in new ways. First, and most important, he abandoned the cell doctrine. It was the cerebral substance, he declared, that was the seat of the faculties such as sensation and imagination. He rejected Descartes's positioning of the soul in the pineal gland. In addition, he claimed that different parts of the brain had different functions. The cerebellum, he wrote, controlled vascular and respiratory activity. Willis was a devout man and believed in the immortal soul. Yet, avoiding dangerous theological waters, he argued that the brains of animals carried out in less complicated form most of the functions found in humans, and these activities were based in sensation and motion. Animals, like humans, could perceive, remember, and imagine.

The neurological building designed by Descartes and whose main bricks were laid by Willis was investigated and its structure refined in numerous ways. The brain was examined microscopically, notably by Marcello Malpighi (1628–1694), a physician and professor at Bologna, who described the cortex as being composed of little glands. Vascular injection was used to map the brain's blood supply.

Interesting experimental work, which at the time was the source of much controversy, extended the reflex theory. In Edinburgh, the professor of medicine Robert Whytt (1714–1766) showed that decapitated frogs reacted to irritant stimuli and argued this action was mediated by nerves at the spinal cord level. In other words, the nervous system, below the level of consciousness, was involved in the body's fundamental reactions to the environment.

The Eighteenth Century

One of the most significant intellectual and practical interventions in eighteenth-century studies of the nervous system was the work of the Swiss biologist and professor, Albrecht von Haller (1708–1777), probably the most extensive experimentalist since Harvey. Based on his experimental researches, Haller published in 1755 A Treatise on the Sensible and Irritable parts of Animals, a work that was to shape ideas of life in general and the workings of the nervous system in particular. Haller claimed his experiments showed that nerves possessed one or other of two properties. On stimulation they either produced irritability (muscular motion), or they produced feeling—sometimes pain in humans or pain-like behavior in animals. (Haller was still worried about giving animals souls.)

The significance of his publication is twofold. First, Haller was creating the idea of a science of life based around biological properties; that is, qualities possessed by living things that were not reducible to mechanics or dynamics (the reductionism in favor since the scientific revolution). These properties were evoked by a method peculiar to this new science of life; animal experimentation. The second point about Haller's publication is that it was iterating a view, previously formulated in various ways, that the sensory motor division was fundamental to the nervous system. So respected was Haller that his authority sustained for a while a number of opinions that would come crashing down in the nineteenth century. These included the idea that the seat of the soul was in the brain (although in no particular place), and that the brain was the source of all nerves. In spite of his authority, forces were at work in the Enlightenment slowly overturning the sanctity of the soul.

Descartes considered that some ideas were inborn or innate and that we could arrive at first principles just by thinking. This position was shattered by the works of the English physician and philosopher John Locke (1632–1704) whose views were to underpin the Enlightenment's worship of experience. In his 1689 An Essay Concerning Human Understanding, written in 1689, Locke proposed that all our ideas, even the most complicated ones, are ultimately built from our sensations. This proposition gave a mental grounding to the philosophy of the Scientific Revolution that experience and experiment should be the basis of knowledge.

Throughout the eighteenth century philosophers continued to regard the mind as their subject, and theologians who identified mind with soul regarded the topic as off-limits to science. Nonetheless, philosophers such as David Hume (1711–1776) eschewed speculation about the soul and built up sophisticated psychologies of how the mind grew through association of ideas. Since ideas were agreed to arise from sensations and sensations were increasingly held to be based on the nervous property of sensibility, the way was laid open for a completely naturalistic theory uniting mind and body through the nervous system.

This was done, for example, by Scottish physician William Cullen (1710–1790) professor of medicine at Edinburgh and the most famous medical teacher of the age. Cullen, along with many other doctors, regarded the origins of most diseases to lie in the nervous system, and he coined the term “neuroses” to embrace these disorders. Nervous disorders and displaying “sensibility” became extremely fashionable in the Enlightenment. Jane Austen's Sense and Sensibility (1811) gently parodies this trend.

The nervous system was remodeled in the early nineteenth century within a complete upheaval in science. The fundamental change was the perception of the brain and spinal cord as a biological organ that had evolved during a massive time span and was adapted to the environment. Integral to this new view, the mind itself was studied as part of this biological system. The causes of this change lie in all those deep factors in the nineteenth century that produced a naturalistic account of human beings: industrialization, secularization, natural science, exploration, and so on.

Two important new anatomical perspectives on the nervous system were central to this remodeling. The first was the idea of segmentation, and the second, in some ways a special case of the first, was the concept of the cerebral localization of mental functions. In the eighteenth-century model the brain was the fount, anatomically and physiologically, of everything to do with the nervous system. Gradually the idea emerged in the nineteenth century that there was some fundamental nervous unit, increasingly identified with the reflex arc, which was the basic building block of all the higher functions. Increasingly too this hierarchy would be identified with evolutionary complexity.

The basic unit of the nervous system was seen at its simplest in the spinal cord and at its most complex in the cerebral cortex. The most primitive of animals were composed merely of these simple units (or low-level developments of them), whereas in the highest animals they had become so complex that only extremely technical scientific analysis could recognize them. As anthropology developed in the nineteenth century, tribal society was often described as being based on the activity of lower evolutionary levels of the nervous system. The idea of some fundamental unit that underlay complexity was crucial to the whole of biology in the nineteenth century. A prime example of this is modern cell theory, developed in the 1830s and 1840s. Modern embryology was created on a segmentation theory at the same time.

Phrenology

The first significant new ideas of nervous function were embodied in phrenology, which most consider a crazy pseudoscience in which “experts” feel the bumps on people's skulls to detect the development of their mental faculties. “Fowler's heads” or phrenological busts are still common in the antique trade, and reproductions of them abound. (The original phrenology head dates from around 1835 and was devised and marketed by L.N. Fowler & Co. of New York City.)

In its day, phrenology was a serious matter and an important channel for rethinking nervous anatomy and function. Phrenology was devised by a skilled Austrian anatomist, Franz Joseph Gall (1758–1828). Gall was one of the first thinkers to suggest that the nervous system was segmented. He argued that there were about 33 mental faculties, each of which had its own cerebral organ or location in the brain. The size of the organ was impressed on the skull, which thus could be palpated to determine its power.

Phrenology became very popular in radical and reforming circles; critics believed it insidiously promoted materialism and atheism. Phrenology was popularized in Britain by an Edinburgh lawyer George Combe (1788–1858). In America its disciple was Johann Gaspar Spurzheim (1776–1832), who lectured on phrenology in Boston, where a phrenological society was established. Phrenology's significance for neurological history is that it stressed that the brain was the organ of the mind (not the seat of the soul) and gave the first complete account of cerebral localization of function based on anatomy. That phrenology was eventually ridiculed should not allow its importance in promoting a new view of the nervous system to be overlooked. Gradually orthodox thinkers produced new models of the nervous system that incorporated the basic assumptions of phrenology. Its details, however, were increasingly ridiculed and a politically dangerous, reforming science was marginalized.

IN CONTEXT: THE CASE OF PHINEAS P. GAGE

In one celebrated nineteenth-century case of change in brain function, an injury to the brain's frontal lobes was associated with personality change. In 1848 Phineas P. Gage (1823–1860), an American railroad construction worker, was injured in an accidental explosion that blew a 3-foot (1-m) tamping iron right through his head. It entered under his left cheekbone and exited through the top of his skull, landing 30 yards away. Amazingly Phineas suffered no lasting physical symptoms. His personality, however, changed markedly: he become irreverent, profane, impatient, obstinate, and unrecognizable to his friends (there is reason to be skeptical of the degree of change, however). Gage's injury was widely taken to show that local brain injury could change personality. Spectacular though Gage's injury was, there is no doubt interest in it was generated by the nineteenth-century debate on cerebral localization that had simmered ever since phrenology burst on the scene.

One of the ways in which function was localized to parts of the brain was through clinical evidence. It had been recognized anecdotally since antiquity that damage to a part of the brain could produce local effects. Medical texts recorded post-mortems that showed pathological changes in the brain on the opposite side to an arm and a leg affected by sudden paralysis caused by a stroke.

The most significant claim for cerebral localization made on clinical grounds was put forward by the French physician and anthropologist Paul Broca (1824–1880). Broca had a patient who was nicknamed by the only word he could speak: “Tan.” After Tan's death in 1861 Broca determined at autopsy that there was a lesion of the cerebral hemisphere's left frontal lobe. This he said was the seat of speech production. Broca's claim was disputed, but eventually widely accepted and his speech center (the left inferior frontal gyrus) is now called Broca's area.

The nineteenth century also saw the creation of a new discipline: experimental physiology. Although investigators since antiquity had sometimes had recourse to experiments on animals, in the nineteenth century researchers, building on Haller's ideas, made vivisection the method for discovering something entirely new: biological properties and laws. Indeed the method and the objects discovered by it were irrevocably bound together. Given the general interest in the nature of mind and the increasing move to make it an object of biological study it is not surprising that a great deal of nineteenth century experimental physiology was directed towards the nervous system. In 1820s France, physiologist Marie-Jean-Pierre Flourens (1794–1867) experimented on the animal brain, his work largely being driven by his distaste for phrenology and his belief that mind and soul were one and the same undivided entity.

Flourens showed that a center in the brainstem coordinated the action of the respiratory muscles. He described how removing the cerebral hemispheres in a pigeon resulted in blindness and removing one hemisphere caused sight loss in the eye of the opposite side. He removed the cerebellums from dogs and showed that uncoordinated movement followed. The most famous French experimentalist of this era was François Magendie (1783–1855). In 1822 he selectively divided the spinal nerve roots of puppies, showing that the anterior roots were motor and the posterior roots were sensory. This was eventually seen as a crucial discovery. It concretized into a substantial anatomical entity the general feeling that the reflex and a sensory motor unit were important building blocks of the nervous system.

The reflex idea was raised from an experimental observation to a biological principle by the English physician Marshall Hall (1790–1857), who first used the term “reflex” in this sense. Reflexes for Hall were the fundamental action that governed most of the body's activities—they maintained the tone of the sphincters, governed swallowing, vomiting, and sneezing. Hall's writings were not entirely well received in Britain but were welcomed in Germany where, by the 1840s, distinct scientific disciplines had been established. Here Hall's ideas on the reflex were extended from the spinal cord to the brain, an extension Hall and others resisted because it threatened invasion of the soul's activities. In Germany, where so-called “romantic-biology” had encouraged the view that the mind was an intrinsic structure of organic beings, physiologist Johannes Müller (1801–1858) and neurologist Wilhelm Griesinger (1817–1868) freely extended reflexes to brain and mind. In Britain, physiologist Thomas Laycock (1812–1876), deeply read in German science, did likewise.

There was yet another route to making the mind a biological object and localizing function in the brain. In the early nineteenth century Hume's philosophy of the association of ideas was elaborated and employed by reformers as a political theory in which laws of human learning were described in such a way as to make social progress seem inevitable. The most important formulator of this concept was Scottish philosopher James Mill (1773–1836)—the father of British philosopher John Stuart Mill (1806–1873). Mill's account was based on sensation, but Scottish philosopher Alexander Bain (1818–1903) added to it the view that motor functions were also important in the way we learn about the world and construct our ideas.

These accounts, neurological theory, and the pre-Darwinian evolutionary debates that raged in early Victorian Britain were synthesized by English philosopher Herbert Spencer (1820–1903). Spencer, initially an enthusiastic disciple of phrenology, postulated that evolutionary development created increasingly complex levels of nervous organization based on sensorimotor units. The brain and the human mind represented the highest level of organization achieved.

Drawing on Spencer's speculative model, the English neurologist John Hughlings Jackson (1835–1911) constructed a picture of the brain in pathological conditions. Jackson studied epileptic seizures and observed that the convulsions often started in a specific area—such as the thumb—and then spread to involve the whole body. Drawing on reflex theory, associationism, and Spencerian evolutionism, Jackson suggested that motor and sensory function of the parts must be represented in specific areas of the cerebral cortex. Interestingly, Jackson's views were soon seen to have been confirmed by two workers who did not work in the associationist tradition at all.

German anatomist Gustav Theodor Fritsch (1837–1927) and author Julius Eduard Hitzig (1838–1907) were two young physicians in Berlin who conducted their experiments in Hitzig's bedroom. They exposed the cerebral cortex of a dog and claimed that according to the area electrically stimulated, specific movements of the opposite side of the body were elicited. Later the Scotsman David Ferrier (1843–1924), working very much within Jackson's model, confirmed the German work in a study of dogs and monkeys.

The cerebral cortex, once represented by random squiggles in Renaissance illustrations, was now symbolized by consistent maps showing the different functions of different areas. The division of labor model of the nervous system was supported in the late nineteenth century by the mapping of the two divisions of the autonomic nervous system: the sympathetic and the parasympathetic. These systems govern the activity of the viscera and blood vessels and other involuntary actions such as constriction and dilatation of the pupil.

The nineteenth-century mechanized, localized, reflex-based model of the nervous system was sustained and developed by a very important worker in the twentieth century, the Russian physiologist Ivan Pavlov (1849–1936). Trained in reductionist German physiology, Pavlov spent his working life at the military Medical Academy in St. Petersburg. In the first half of his career Pavlov studied the nervous pathways governing the salivary and gastric secretions of dogs, winning the 1904 Nobel Prize for physiology or medicine.

After about 1902 Pavlov brought his reflex-based concepts to the understanding of canine behavior and, as he conceived it, the human mind. Pavlov attempted to discover how new neural pathways were built up in dogs by studying the stimuli that provoked salivation. He described how auditory stimuli, such as the ringing of a bell, could become the basis of a learned reflex overlaying an innate one—the sight and smell of food. These new reflexes he called conditional (the Russian term usually being mistranslated as “conditioned”). From this work, Pavlov built up a picture of learning in general. Acclaimed though his laboratory studies were, outside Russia his model of the human mind was regarded as an oversimplification. However, communists (which Pavlov was not) were sympathetic to his mechanistic approach. Ironically, Pavlov's work also found fertile soil in the United States where American psychologist B.F. Skinner (1904–1990) created the behaviorist school of psychology.

The Rejection of Reductionism

Although he was highly praised by European and American physiologists, Pavlov was something of an oddity, a hangover from the nineteenth century. Where he continued to pursue a reductionist approach, breaking the brain and spinal cord into functional bits, researchers in other countries began to investigate the means by which the nervous system was integrated and acted as a whole. The most important of these workers was the English physiologist Charles Scott Sherrington (1857–1952).

Sherrington's studies were built on the work of the Spanish histologist Santiago Ramón y Cajal, whose microscopic researches supported the view that the nervous system was constructed from individual nerve cells (neurones) separated by a gap (the synapse) rather than being a continuous network (reticular theory). Although mainly studying a single reflex—the scratch reflex of the dog—Sherrington showed that even this required massive amounts of correlation and inhibition of the action of other muscles besides those directly involved. His classic text was appropriately named Integrative Action of the Nervous System (1906).

Nowhere was the rejection of mechanism and reductionism more pronounced than in Germany, once their high temple. Much of this rejection came through technical enquiries into the nature of language. Reductionists had regarded the neurological localization of language and speech as their greatest triumph. Their foremost spokesman was the neurologist Carl Wernicke (1848–1905) who regarded language as made up from various sensorimotor associations. This seemed to be proven by different sorts of clinical disturbance. For instance, after a stroke, comprehension might be lost, but speech preserved.

The Holistic Approach

Early and mid-twentieth-century neurologists gradually turned away from this approach, regarding these phenomena as basic facts that needed to be comprehended by a holistic understanding of brain function. The most vocal proponent of this view was the neurologist and psychiatrist Kurt Goldstein (1878–1965). During World War I, Goldstein headed an institute in Frankfurt for the study of soldiers with brain injuries and psychiatric disturbances, such as “shell shock.” Goldstein slowly came to the conclusion that, for instance, in patients whose injuries resulted in an inability to read, there was not damage to a specific center, rather the brain had lost its capacity to unify and give coherence to sensory stimuli.

After the war, Goldstein developed these insights into a full-blown theory of the brain's synthesizing power, its action in organizing isolated fragments of experience into a whole. This was a philosophy with important clinical consequences. Whereas mechanistic neurologists were only interested in those parts of a patient's history that indicated a specific loss of activity, Goldstein stressed the necessity of listening to the entire story. Goldstein, a Jew, was imprisoned and tortured by the Nazis in 1933; in 1935 he moved to the United States.

Goldstein's intellectual life was far from unusual. His move to holistic perspectives on the brain was shared with neurologists everywhere. The most famous neurological student of language in this period was the English neurologist Henry Head (1861–1940). In America, the Swiss psychiatrist Adolf Meyer (1866–1950) developed an extremely influential holistic approach to psychiatric patients that emphasized the importance of comprehending all the biological, psychological, and social factors implicated in a case. These holistic moves in neurology and psychiatry were far from isolated developments. They were part of a general cultural shift in Europe that embraced the arts, sciences, and social thought.

Substantively and conceptually, studies of the nervous system have benefited from work in other scientific disciplines and other broader intellectual and material changes. In the first half of the twentieth century, the new science of biochemistry enlightened the understanding of nervous transmission. In 1914 the English physiologist Henry Dale (1875–1968) and his colleagues isolated acetylcholine and suggested it was a neurotransmitter. In 1921, in Graz, Austria, pharmacologist Otto Loewi (1873–1961) demonstrated that a chemical transmitter controlled the heart rate of the frog. Later this substance was shown to be acetylcholine. Dale and Loewi jointly received the Nobel Prize for physiology or medicine in 1936. In danger from the Nazis like Goldstein, Loewi moved to the United States.

Conceptually, creators of models of the nervous system have borrowed from a variety of realms, notably the technological. In the eighteenth century, William Cullen considered that the nervous system bound the body together by sympathy, an idea that played a crucial role in the theories of social bonding employed by his friends the philosophers David Hume and Adam Smith (1723–1790). In the early twentieth century physiologists considered the nervous system as a sort of sophisticated telephone exchange. After World War II (1939–1945) modelers of the system drew on cybernetics. More recently, and not surprisingly, the computer seems to offer the best analogies for understanding the workings of the brain.

Before World War II neuroscience can scarcely be said to have existed as a recognizable subject area. Since the 1950s it has become a huge, massively-funded enterprise comprising a vast range of specialties. Despite the massive accumulation of facts about the nervous system, many of the fundamental theories previously discussed remain embedded in the core knowledge of its workings.

Modern Cultural Connections

Modern neuroscience, besides being enriched by the deployment of approaches from molecular biology, genetics, physiology, and biochemistry (to name but four), also embraces disciplines such as computer science, psychology, physics, and statistics. Imaging—notably magnetic resonance imaging (MRI)—is a major technique for mapping the central nervous system. Neuroscience today, although in many ways unprecedented in size and investigative power, shares two related features with the neurological studies that preceded it. First, it attempts to understand in great detail how the building blocks of the nervous system, such as reflexes, work. Second, by doing this, it strives to answer the big questions about the relations between physiological activity and the mind. What, in short, is the biological basis of consciousness? Today, as in the past, behavior is the key that links the small scale investigation with cosmic questions.

Fields within neuroscience overlap considerably but, broadly speaking, on the microscopic scale and below, molecular neuroscience investigates how neurons use and respond to molecular signals. Cellular neuroscience studies how neurons process signals physiologically and electrochemically. Geneticists and molecular biologists explore the birth, growth, and death of neurones. Neuroanatomists map neuronal networks, and neurophysiologists explore the ways that networks are related to behavior and their connections are modified by experience. Higher up, at the systems level, neuroscientists look at how circuits are formed and complex behaviors are produced through reflexes, sensory integration, motor coordination, learning, and memory.

How, for instance, do rats laboratory learn their way around a maze? In many labs, computers are used to create neural networks that simulate those in the brain. Higher still, cognitive neuroscience looks at questions close to human identity—questions of how mental functions are related to neural circuitry—the pathology of nervous diseases that produce behavioral change is an important dimension of this sort of investigation.

Psychology has always had a close, although not necessarily harmonious, relationship with neuroscience. Here science strays into philosophy, since although behaviorist psychologists may claim mental “laws” can be understood as complex combinations of simpler neurological activity, others deny that neuroscience can ever explicate the mind. As in the nineteenth century, vision and speech are at the core of many of the sciences that investigate the mind-body relationship. Psychiatry is an interesting borderland. Here, some investigators deem neurological defects to be the cause of mental illness, whereas others turn to irreducible social and cultural factors.

Likewise, the study of artificial intelligence to replicate brain function has its supporters, but many claim there are social dimensions to learning that can never be replicated. Using algorithms (a set of instructions that define a task) to mimic the brain has proved difficult and controversial. The brain's “wiring” or circuitry is not static but a constantly changing network of reception and transmission. Some Victorians found in brain research the potential for revealing the material basis of human nature and thought; for others it failed to address questions about the ineffable, spiritual nature of the mind. Today many believe the division still exists. In a way we can blame Descartes for it. He, after all, seated action in matter—in the nervous system—and thought in the soul, with the stipulation that neither could be reduced to the other.

Primary Source Connection

Canadian researcher Sandra F. Witelson maintains a large collection of human brains and corresponding cognitive data. While studying how the brain processes language, Dr. Whitelson's team has uncovered various other differences among the brains, from size and shape to neuron density.

Siobhan Roberts is a Toronto-based freelance writer and journalist. She primarily writes on issues in mathematics and is the author of King of Infinite Space a biography of mathematician Donald Coxeter.

SCIENTIST AT WORK; A HANDS-ON APPROACH TO STUDYING THE BRAIN, EVEN EINSTEIN'S

Standing in her vaultlike walk-in refrigerator, Sandra F. Witelson pries open a white plastic tub that looks like an ice cream container.

There, soaking in diluted formaldehyde, is a gleaming vanilla-colored brain: the curvy landscape of hills and valleys (the gyri and sulci) that channeled the thoughts of the late mathematician Donald Coxeter, known as the man who saved geometry from near extinction in the 20th century.

“His brain is amazingly plump,” Dr. Witelson says. She ought to know.

Here at McMaster University, where she is a neuroscientist with the Michael G. DeGroote School of Medicine, Dr. Witelson has a collection of 125 brains. They are all from Canadians: business people, professionals, homemakers, and blue- and white-collar workers.

By weighing her specimens, calculating their volumes and measuring their proportions, Dr. Witelson (pronounced WIT-il-son) investigates the relationship between brain structure and cognition, a focus of her research for three decades.

It was Dr. Witelson's 1999 study of Albert Einstein's brain that made headlines by revealing some remarkable features overlooked by other neuroscientists: the parietal lobe, the region responsible for visual thinking and spatial reasoning, was 15 percent larger than average, and it was structured as one distinct compartment, instead of the usual two compartments separated by the Sylvian fissure.

Dr. Witelson is continuing her analysis of Einstein's brain, but with a histological study, probing features of the cellular geography in the parietal lobe, like the packing density of his neurons.

These specimens of Einstein's brain came to Dr. Witelson via Thomas Harvey, the pathologist at the Princeton hospital where Einstein died in 1955. Shortly thereafter Dr. Harvey stole away with the great man's gray matter (and lost his job as a result).

Now 94, Dr. Harvey has received requests for Einstein's brain from many neuroscientists and turned most of them down. But hearing of Dr. Witelson's extensive brain bank, he sent her a handwritten note by fax in 1995 asking simply, “Do you want to study the brain of Albert Einstein?”

She sent a fax back: “Yes.”

Receiving her Ph.D. in neuropsychology from McGill University, in her hometown of Montreal (followed by a postdoctoral fellowship at the New York University School of Medicine), Dr. Witelson began her brain bank early in her career after winning a contract from the National Institutes of Health in 1977. The goal was to study why language capacity is lateralized—that is, represented in the left hemisphere for 90 to 95 percent of people.

Dr. Witelson's research team sought out donors with metastatic cancer in which the brain was unaffected—people who knew they faced death but were willing to undergo extensive testing while they were alive. So Dr. Witelson's brain bank not only is the world's largest collection of “cognitively normal” brains, but also includes a repository of personal data on each person.

Dr. Coxeter, the geometer, died in 2003 at 96. A brain that old is apt to have suffered considerable deterioration from loss of neural matter. But Dr. Coxeter, a lifelong vegetarian who rarely drank alcohol and did headstands every morning, remained intellectually active almost to the end of his life and had the brain of a much younger man. Like Einstein, he had a large parietal obe.

Dr. Witelson is known not only for her brain bank. She has also been in the forefront of controversial studies on the biological basis of intelligence, sex differences in the brain and sexual orientation.

While her N.I.H. study has yet to yield many answers on why language is lateralized, she said something unexpected “fell out” of the research: marked differences between male and female brains.

In 1995, after a 10-year study, Dr. Witelson published findings showing that on average the packing density of neurons was 12 percent greater in the adult female brain than in the adult male brain in the language region of the temporal lobe. A subsequent study of the frontal lobes, soon to be published, revealed similar sex differences.

On first interpretation, she said, this might lead to the conclusion that a woman's brain is more tightly packed with neurons simply to make up for the well-documented fact that the average female brain is 10 percent smaller than the male brain.

“But that's not correct,” she said, “because only some of the cortical layers show the difference.”

Layers 2 and 4, those important in processing the input of information, exhibited the differences in neuron capacity.

“Knowing that,” Dr. Witelson said, “one can ask the question of whether the processing of speech sounds could be related to the anatomy, and in fact that's what we're doing now.”

Sex differences also turned up in a number of other studies.

In 2005 Dr. Witelson and her colleagues reported that verbal ability was correlated with brain volume, but more strongly in women than in men. And they announced findings indicating that extremely premature birth affects the brain development of boys more adversely than girls.

Though she says the differences among female and male brains should not be discussed in terms of “better” and “worse,” they cannot be denied.

For that reason, her work was often cited by defenders of the former Harvard president Lawrence H. Summers after his suggestion that innate differences might help explain the gender gap on science faculties.

Interviewed on “The NewsHour With Jim Lehrer” on PBS in February 2005, Dr. Witelson said, “If we're going to try to understand the disparity between the number of women and men in different professions, and this would go for positions way beyond just academia, we have to put all the factors on the table.”

In a recent interview, she said, “It's clear societal influences are relevant, but that doesn't preclude the possibility that there are also contributing factors from nature.”

Dr. Witelson does not have a female genius in her brain bank. She is considering broadening the demographic, seeking exceptional individuals regardless of age or sex in a wide spectrum of fields: language, music, chess, even professional sports.

She has not met many of the people whose brains she studies. (Dr. Coxeter was an exception.) But the fact that she is handling the essence of their individualism sometimes gives her pause.

“I have to admit,” she said, “when I saw Einstein's brain, that was a pretty strong feeling. I realized this was the brain that had provided our current conception of the universe.

“I'm not a cardiologist or a nephrologist, so I don't hold hearts or kidneys, but I don't think I would get as touched by those organs. On the other hand, I have a bias towards brains.”

Siobhan Roberts

roberts, siobhan. “a hands-on a pproach to studying the brain, even einstein's.” the new york times (november 14, 2006).

See Also Biomedicine and Health: Dissection and Vivisection; Biomedicine and Health: Human Gross Anatomy.

bibliography

Books

Clarke, Edwin, and C.D. O'Malley. The Human Brain and Spinal Cord: A Historical Study Illustrated by Writings from Antiquity to the Twentieth Century. San Francisco: Norman Publishing, 1996.

Finger, Stanley. Origins of Neuroscience: A History of Explorations into Brain Function. New York: Oxford University Press, 1994.

Young, Robert M. Mind, Brain, and Adaptation in the Nineteenth Century: Cerebral Localization and Its Biological Context from Gall to Ferrier. Oxford: Oxford University Press, 1990.

Zimmer, Carl. Soul Made Flesh: The Discovery of the Brain, and How It Changed the World. London: Heinemann, 2004.

Periodicals

Roberts, Siobhan. “A Hands-On Approach to Studying the Brain, Even Einstein's.” The New York Times (November 14, 2006).

Christopher Lawrence