CHAPTER 3

What the Neuropathologist Knew … and Didn’t Know

There are known knowns: there are things we know we know. We also know there are known unknowns: that is to say we know there are some things [we know] we do not know. But there are also unknown unknowns—the ones we don’t know we don’t know.

—DONALD RUMSFELD

The scientific enterprise of studying the postmortem neuroanatomy of an exceptional individual did not originate with Thomas Harvey. Studies of normative human neuroanatomy in the West date at least as far back as Vesalius in 1543,¹ and Harvey’s training in neuropathology would have ensured extensive expertise in the structure of diseased brains. However, there was a paucity of rigorous medical literature on the brains of geniuses and no personal hands-on experience with anatomizing virtuoso thinkers when Harvey began his study in 1955.

We can only imperfectly speculate on the extent of Harvey’s background knowledge of mankind’s study of the brain over the course of five millennia. Certainly, physicians since the time of Thomas Willis (1621–1675), who coined the term neurology, have been comfortable with the notion of the brain as the seat of the intellect. But it was not always so—there are few, if any, neuroscientific documents or incunabula preceding the ancient Egyptians, and they believed that the heart, not the brain, was the seat of thought and its weight the key to the afterlife. Although the brain was of minor importance in mummification and did not merit funereal storage in a canopic jar, the dire clinical implications of brain trauma may have been known to the Egyptians as early as 3000 BC (Third Dynasty). They were written down thirteen hundred years later in the Edwin Smith Surgical Papyrus, in which “we see the word ‘brain’ occurring for the first time in human speech, as far as it is known.”²

Another thirteen centuries would pass before we encountered evidence that the proposed source of sentience had passed from the heart to the brain. Hippocrates and his school (450–350 BC) posited the brain as the source of wisdom and understanding. Epilepsy was to be no longer regarded as a “sacred disease” of demonic possession but rather as an organic affliction of the brain.³

Incredibly, two more millennia elapse before we encounter the clinician-scientist who bridges the gap between neuroanatomy and neurologic disease. The aforementioned Thomas Willis proposed the cerebrum “as the center for memory, cognition, volition, and imagination.”⁴ In the seventeenth century, this was a bold assertion, running counter to the venerable belief (held by Leonardo da Vinci, no less!) that the brain’s hollow cavities, known as ventricles, were the loci of the higher regions of thought. Willis’s masterwork, Cerebri Anatome, graced with Christopher Wren’s engravings, was an incalculably important step down the road of cerebral localization, but even Willis (and his contemporaries) regarded the convolutions of the cerebral cortex as haphazard loops (much like intestines) with no specified areas of cognitive function. Thomas Harvey’s familiarity with Willis’s legacy aside, every time he dissected a brain on the autopsy table, he would observe and record the appearance of the circle of Willis (so named for the anastomosing circuit of collateral blood vessels at the brain’s base that Willis was the first to describe).

This whirlwind tour of five thousand years of neuroanatomy has remained curiously silent about the microscopic cellular anatomy (neurohistology) of the brain. Simply put, no microscope means no microanatomy, and so the initial forays into the study of the microscopic structure of the brain had to await the advent of the first microscopists, Anton van Leeuwenhoek and Robert Hooke, in the seventeenth century. Limited by primitive microscopes and rudimentary histologic stains, such as saffron and brandy, Leeuwenhoek searched in vain for the tiny neural canals for the conveyance of animal spirits that Galen had posited in the second century AD.⁵ It took another two centuries for the rudiments of neurohistology—the dendrite (1890), the axon (1896), and the neuron (1891)—to become part of the anatomical lexicon.⁶ Despite the adoption of this new detailed nomenclature, a major question about the structure of the nervous system remained. Was the nervous system an indivisible syncytium, or was it comprised of discrete units? The latter hypothesis was known as the neuron doctrine, and its most effective proponent was Ramón y Cajal, the son of a village surgeon in northeastern Spain. The countervailing hypotheses of neuroanatomy persisted even at the 1906 Nobel Prize lectures, when Cajal described the independent elements from which the nervous system is built, and Camillo Golgi, who shared the prize with Cajal, championed the fused neural net (syncytium) theory. We can distinguish the different types of neurons well into the hundreds, so it might be more accurate to call Cajal’s enduring scientific hypothesis the neurons doctrine rather than the monolithic neuron doctrine.

By the time Thomas Harvey was attending his preclinical histology courses at Yale in the late 1930s, the cellular elements of the brain were known to be divided into glia (astrocytes, oligodendroglia, and microglia) and neurons. As discussed in chapter 2, the synapse, the nearly infinitesimal gap (twenty to forty nanometers) that defines the anatomical limits of the neuron, was not visualized until 1954. My brief recap of neuroscientific discovery is to point out that as he embarked on his study of Einstein’s brain in 1955, Thomas Harvey was practicing a brave new science in which the basic unit of the nervous system—the neuron—was still being characterized. It cannot be overstressed that anatomizing Einstein’s brain was a foray into uncharted regions for Harvey, who was not a clinical or basic neuroscientist. His competence was in general anatomic pathology, although he had undergone additional training in the neuropathology labs of Harry Zimmerman at Yale and Frederick Lewey at Penn. (As part of Harvey’s immersion into the pathology of the nervous system, Lewey assigned Harvey the task of teaching neuroanatomy for two years.) Neuropathology was primarily concerned “with the various methods by which neurons undergo degeneration and death,” and “the pioneers of neuropathology were led on by the hope that the study of the diseased brain would lead to the interpretation of all disorders of action and conduct.”⁷ It was only by the early 1930s that “a few full-time neuropathologists emerged” in the United States.⁸ In and of itself, Harvey’s skillful familiarity with the brain tissue changes in neurologic disease would be useful but insufficient when confronted with the cerebral apparatus of a genius.

The limitations of a purely structural approach to the mysteries of the mind would not have escaped Harvey’s notice at Yale, where John Farquhar Fulton, the thirty-one-year-old Sterling Professor and Chair of Physiology, had written Physiology of the Nervous System—the first textbook devoted entirely to neurophysiology, particularly of the primate whose “greater encephalization … is more immediately applicable to the human being.”⁹ In 1941 Harvey’s medical school thesis, “A Developmental Analysis of the Rolling Behavior of Infants,” reflected the growing emphasis on neurologic function, rather than pure neuroanatomy, that was the zeitgeist of neuroscience at Yale during his undergraduate and graduate years.¹⁰ Under the tutelage of Arnold Gesell—psychologist, pediatrician, and founder of the Yale Clinic of Child Development—Harvey studied films of the rolling behavior of six infants and concluded that until one year of age neuromotor maturation is insufficient for infants’ control of rolling and allowing them to be safely left unguarded on a table. This thesis is the longest single-authored scientific paper that Harvey was to write; paradoxically, for the future pathologist of Einstein’s brain, there is no mention of neuroanatomy.

At this relatively late stage in Harvey’s professional training, we may well wonder whether the academic process had even begun to prepare the young Quaker pathologist for his rendezvous with destiny in the autopsy room of Princeton Hospital on April 18, 1955. In retrospect I can see two formidable challenges—one ahead and one behind—that Thomas Harvey would confront. The challenge ahead was the conceptual sea change of neuroscience from the painstakingly detailed but static neuroanatomy of the great cortical mapmakers and histologists, such as Oskar and Cécile Vogt, Brodmann, Campbell, and Cajal, to the dynamic neurophysiology that would irrevocably change our view of the brain in the mid-twentieth century.¹¹ The challenge in his rearview mirror was to see if past investigators had uncovered any defining characteristics of the brains of geniuses.

In New Haven, Philadelphia, and Princeton of the 1930s to the 1950s, it may have seemed possible to tackle the challenge posed by Einstein’s brain (for now we will leave Einstein’s mind alone) using the resources of neuroscience available to a lone investigator. (The biomedical ideal of the solitary genius was alive and well once upon a time—think Pasteur and rabies, Banting and insulin, and Fleming and penicillin.) At present the big problems of neuroscience require (actually, demand) the specialization and the fragmentation of expert knowledge systems. The late Vernon Mountcastle, who held the post of director of the Johns Hopkins’ Department of Physiology, dismissed the notion of a unitary neuroscience and listed no fewer than nineteen subdisciplines necessary to advance brain science—“neuroanatomy, neurophysiology, and biophysics; cellular and molecular neurobiology, genetic neurobiology, and neurochemistry; evolutionary and developmental neurobiology; experimental psychology and psychophysics; neuropsychology, the clinical neurological sciences, and neuropharmacology; classical cognitive science, cognitive neuroscience, and computational neuroscience; and some areas of epistemology, and philosophy.”¹² Mountcastle compiled his list two decades ago. In the interval, the neuroscience juggernaut has relentlessly added new subdisciplines such as hodology—the study of neural connectivity.

For now, we can leave Harvey blissfully unaware of the prospects for the ascendance of multidisciplinary neuroscience in the distant future, and, taking stock of his working knowledge of the nervous system, both normal and exceptional, we will return to the neuropathologist in his prime.

As already discussed, the neuron theory was dogma for Harvey. The well-connected but autonomous neuron was described and drawn in exquisite detail by Cajal and was posited in 1887 by Fridtjof Nansen (among others), who gave up his microscope for Arctic exploration and relief work with World War I refugees.¹³ (Coincidentally, both were Stockholm-bound—Cajal received his Nobel Prize in Physiology or Medicine in 1906, and the Norwegian explorer was to receive the Nobel Peace Prize sixteen years later.) Neurons aside, the identification of the other support cells (glia) that comprise the central nervous system (CNS) was enveloped in obscurity for these scientists, and Cajal spoke of an enigmatic “third element”—neither neuron nor astrocyte—when he examined microscope slides of the brain. The reliable identification of microglia (cells that clean up—phagocytose—dead brain tissue or infectious microorganisms) and oligodendroglia (cells that make electrical insulation—myelin—for axons) had to await del Río-Hortega’s and Wilder Penfield’s silver stains in 1919 and 1924.¹⁴ In effect, the characterization of glial cells—a glial doctrine, if you will—was a new technique when Harvey was learning the ropes of neurohistology. Notably, Harvey did not use the newfangled silver stains to differentiate Einstein’s glial cells in 1955. Thirty years would elapse before Marian Diamond would approach the riddle of Einstein’s glia.

The neuroanatomy taught to Harvey was conceived as a static arrangement of neurons and of commissures and fiber bundles made of axons and dendrites (elongated cell processes) connecting the neurons. The underlying physiology of the brain’s “wiring diagram” has been known to be electrical since the late eighteenth century, when Galvani observed a frog’s leg contract when a scalpel that had picked up an electric charge touched the sciatic nerve.¹⁵ However, the leap from descriptions of “animal electricity” to quantitative neurophysiology came with the first tracings of the action potential in 1939.¹⁶ The flow of current from neuron to neuron rested upon the ionic hypothesis, which characterized the brief and migratory depolarization of axonal membranes during which sodium channels would open and close, allowing a “brief intracellular sip of (positively charged) sodium ions from a salty extracellular sea.”¹⁷ This flow of current—the action potential—had to somehow traverse at least two kinds of anatomical gaps—the synapse from nerve to nerve and the neuromuscular junction from nerve to muscle. Two theories vied to explain transmission across the gaps—neurochemical transmitters at the synapse or electrical continuity via specialized junctional membranes between neurons. Or, more memorably, the competing “soups and sparks” hypotheses.

By the 1930s the chemical neurotransmitter hypothesis was beginning to prevail when future Nobelists Sir Henry Dale and Otto Loewi found the smoking gun for chemical neurotransmission with “the presence of acetylcholine at the nerve-skeletal muscle synapses.”¹⁸ The advent of microelectrodes gave a clearer picture of the spread of synaptic potentials and provided compelling evidence that acetylcholine “acts by increasing the permeability of the postsynaptic membrane to small ions.” These pioneering experiments on relatively simple and readily accessible preparations, such as the frog neuromuscular junction, led to the general acceptance of the soup hypothesis, also known as chemical synaptic neurotransmission, by the 1950s.¹⁹ As the events at the synapse became better understood, the door was opened for the hitherto unimaginable dynamic process of rewiring the nervous system. In 1949 the Canadian psychologist Donald Hebb wrote (his italics), “When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.”²⁰ The first glimmers of the as-yet-unseen synapse—measuring twenty billionths of a meter—as the arena of learning were detected while Harvey was plying the pathologist’s trade. Hebb postulated that the neuronal “growth process” was the development of “synaptic knobs.” (Hebb’s inspired hunch would prove correct in principle, and in 2000 Eric Kandel would receive the Nobel Prize for demonstrating the cellular changes underlying simple forms of learning, such as synaptic growth or pruning with sensitization or habituation of the gill withdrawal reflex in the sea slug Aplysia californica.²¹) Hebb’s postulate of a dynamic nervous system in which learning rerouted neural connections began to chip away at the prevailing representation of the nervous system as a hard-wired telephone switchboard.

Harvey’s exposure to and familiarity with new conceptions of neurophysiology were not reflected in his research agenda for Einstein’s brain. He was, first and foremost, a pathologist, and for a pathologist, anatomy is frequently biological destiny. Clinical generalizations aside, Harvey was very fortunate to learn about the brain at the Yale School of Medicine in the 1930s. Dean Milton Winternitz, himself a pathologist, “brought Yale from a second or third tier to the top ranks of American schools,” largely by following the Johns Hopkins system of recruiting full-time research-oriented faculty.²² Thomas Harvey would have learned his pathology from Winternitz and his neuropathology from Harry M. Zimmerman, who we previously encountered waiting in vain to get Harvey’s call to go to Princeton for Einstein’s postmortem (but that disappointment lies twenty years in the future). When Harvey Cushing, arguably the founder of American neurosurgery, left Harvard, he returned in 1937 to his alma mater in New Haven and brought his collection of two thousand brains and brain tumors—and the neuropathologist Louise Eisenhardt. These specimens catapulted Yale to the forefront of clinical neuroscience. “When Cushing found something of particular interest,” as the story goes, “he would hammer on the wall between his office and that of Harry (Zimmerman) inviting him to come and see, examine, and discuss the patient’s course.”²³ Such exposure to world-class neuropathology would not be lost on Harvey. Neurophysiology at Yale, led by the Sterling professor John Fulton, focused primarily on the frontal lobe and was ably abetted by such accomplished investigators as Margaret Kennard (child neurologist), Robert Yerkes (primatologist and psychometrist), and Karl Pribram (neurosurgeon), as well as de Barenne’s strychnine cortical stimulation research and Warren McCulloch’s attempts “to found a physiological theory of knowledge.”²⁴ Although the lessons imparted at Yale would not materialize in Harvey’s structural approach to Einstein’s brain two decades later, I believe that Harvey’s personal acquaintance with the leading lights of Yale’s ascendency in brain science in the 1930s and his lifelong investigation of Einstein’s brain were not mere happenstance.

With this compelling introduction to the study of the nervous system, Harvey could critically assess the advent of the modular nervous system heralded by Mountcastle’s discovery of the cortical column as an organizing principle of CNS anatomy. In 1957 Mountcastle found that “the basic unit of mature neocortex” was the minicolumn, a narrow chain of eighty to one hundred “neurons extending vertically” across layers two through six of the cerebral cortex. Many minicolumns linked by short-range horizontal connections would comprise a cortical column measuring three hundred to six hundred microns in diameter across species. With evolutionarily more complex brains, the cortical surface area would expand with increased numbers (but not sizes) of cortical columns. This high degree of columnar organization, which neuroanatomists at first met with disbelief, eventually became a tenet of cortical architectonics. It provided the foundation for the concept of receptive fields, in which a stimulus on the surface of the body would evoke an electrical discharge from the single neurons in columns in the sensory cortex.²⁵ Researchers could now use microelectrodes to impale a single cortical neuron and create a map linking a specific area of the body’s surface to a particular region of the cortex. This has become a dominant neuroscience technique going forward to the present day with the tour de force achievement of Hubel and Wiesel’s cartography of the functional microanatomy of cat and monkey visual systems.²⁶

Although Harvey had doubts as to whether the gross morphology (as opposed to the microanatomy) of Einstein’s brain would prove informative,²⁷ he would nevertheless have eagerly followed Wilder Penfield’s groundbreaking explorations of the cerebral cortex. In 1954 Penfield, a Canadian neurosurgeon and founder of the Montreal Neurological Institute, reviewed his data on 750 patients who underwent cortical mapping with bipolar electrodes applied to the surface of their brains.²⁸ The brain has no pain fibers, and accordingly, the surgery was performed with local anesthesia on a conscious patient who could tell Penfield when there was movement of the left hand as one-half to three volts were applied to the right motor cortex. Using electrical identification of functioning cortex, Penfield avoided or minimized the loss of normal brain tissue when extirpating a brain tumor. The amassed motor and sensory stimulation data culminated in the classic Penfield illustrations of the motor and sensory “homunculus,” which displayed the inordinately large portions of cortex subserving the astonishingly varied repertoire of motor and sensory functions of the face and hand (see Figure 3.1).²⁹ Just a few years before Einstein’s death, electrophysiological research employing intraoperative bipolar electrodes (for small circumscribed cortical regions) and microelectrodes (for individual neurons) had permitted hitherto “silent” neural tissue to speak to investigators. Was Thomas Harvey listening?

The reductionist approach that had served so well in elucidating the anatomy and physiology of individual neurons and small assemblages of neurons could not be extrapolated to the analysis of cognition in the 1950s. (A great leap forward in the interrogation and visualization of cortical function in living brains would not appear on the neuroscientific horizon until 1975, with the development of one of the earliest functional neuroimaging techniques, positron emission tomography.) The neurophysiological investigation of the embalmed brain of a dead genius was, of course, not an option, and Harvey was compelled to proceed as a cortical “archaeologist” who hoped to disinter living thought from dead neural tissue. To begin to reach even a rudimentary understanding of how Einstein navigated his world of ideas, Harvey needed to target the wellsprings of cognition—the association cortices.

The contemporary perspective on higher cortical functions holds multimodal association cortices in the frontal, temporal, and parietal lobes to be the essential regions for the highest levels of sensorimotor integration and cognition.³⁰ But this was not always the case. Sir William Gowers’s A Manual of Diseases of the Nervous System—the bible of nineteenth-century neurology—described “no motor or sensory symptoms” associated with disease of the posterior parietal lobes.³¹ If we fast-forward to Harvey’s era, we find that Macdonald Critchley, one of the most astute British clinicians of his time, concluded his magisterial The Parietal Lobes with the admonition that “to seek to establish a formula of normal parietal function is largely a vain and meaningless pursuit, however attractive.”³² Harvey’s active research agenda was winding down as the neuroscience community gained further insight into the role of the parietal lobe not as a mere cortical/homuncular map but as a critical gateway for accessing and integrating the information necessary for motor strategies that exploit extrapersonal space.³³

Figure 3.1. Wilder Penfield’s sensory (left) and motor (right) homunculi (little men) are superimposed on cross-sections of cerebral hemispheres. (The boomerang-shaped midline structures are the fluid-filled lateral ventricles.) Derived from decades of intraoperative electrical brain stimulation of conscious patients, the homunculi diagrams strikingly show the disproportionately larger cortical areas devoted to the sensorimotor functions of the hands and mouth. (Wilder Penfield and T. Rasmussen, The Cerebral Cortex of Man. New York: McMillan, 1955.)

The function of the most acknowledged seat of higher cognition, the frontal lobe, remained equally elusive to Harvey’s mentors. John Fulton studied the behavior of chimpanzees (“affectionate” Becky and “crotchety” Lucy) after the bilateral surgical removal of the frontal cortex at Yale in 1934.³⁴ Both animals began to fail learning tasks (the stick and platform test), and Fulton concluded that the frontal lobe lesions diminished the chimps’ learning capacity. He speculated that bilateral destruction of the frontal areas would cause greater intellectual loss in man, where they comprise 30 percent of the cortical surface (compared to 10 percent in the monkey).³⁵ Fulton also observed that the chimps no longer displayed frustrated behavior when they were not rewarded after failing a learning task. Postsurgically, Becky and Lucy seemed “devoid of emotional expression,” and this critical observation contributed to Egas Moniz and Almeida Lima’s decision to perform frontal lobotomies (leukotomies) on twenty patients with anxiety/obsessional states and psychoses.³⁶ The scientific evidence leading to the initial forays of psychosurgery to relieve psychopathology is fascinating in its own right but did not provide Harvey with firm grounding in the physiology of normal frontal lobes, let alone those of a genius!

This lesion-based approach to neurology had significant limitations in Fulton’s time, and they persist to the present day. My thorough grounding in the deficits that strokes, cerebral tumors, and multiple sclerosis create are invaluable when I evaluate and treat patients, but that expertise most emphatically does not elucidate the workings of the undamaged brain of a genius. A clinical neurologist knows that symptoms of frontal lobe damage include disinhibition, inappropriate jocularity, emotional lability, poor judgment, distractibility, apathy, indifference, psychomotor retardation, concrete thinking, impaired calculating ability, “forgetting to remember,” motor perseveration and impersistence, stimulus-bound behavior, motor programming deficits, poor word-list generation, poor abstraction and categorization, and diminished spontaneous movement.³⁷ However, a litany of such deficits does not comprise a true and comprehensive picture of frontal lobe function, and that same clinical neurologist must never forget “the fallacy of confusing localization of sign-producing lesions with localization of function.”³⁸ The brain remains an organ of immeasurable interconnectivity, and a lesion in one part of the brain may disinhibit functions in a separate but distantly connected area—the so-called release phenomena. Given the inability of lesion-based studies to delineate the normal function of parts of the brain and his training firmly rooted in neuroanatomy/neuropathology, where could Thomas Harvey turn?

From the time I was a neurology resident embarking on clinical research, I followed the venerable admonition to consult the German medical literature before claiming priority for a “new” discovery. And Harvey followed this time-tested medical adage when he “would say that Vogt’s study on Lenin’s brain was what inspired him to believe that Einstein’s was worth saving.”³⁹ Oskar and Cécile Vogt were neuropathology’s power couple for the first third of the twentieth century, and the Kaiser-Wilhelm-Institut für Hirnforschung was opened for them in the outskirts of Berlin in 1931. Beginning in 1925 their study of the brain of Vladimir Lenin (1870–1924), at the behest of the Soviet government, was arguably the most comprehensive study of a “genius” brain ever undertaken. The Communist leaders charged the Vogts with the task of performing a “cytoarchitectonic investigation [to] provide information on the material substrate of Lenin’s genius.”⁴⁰ And Professor Vogt did not disappoint them. A giant microtome sliced the formalin-fixed brain into as many as thirty thousand full coronal sections. In 1925 Vogt revealed his findings: “In the third cortical layer (of several brain areas) particularly in the deep portions, I found pyramidal neurons of extraordinary size and number never previously observed by myself … these anatomical findings allow us to identify a brain athlete and an association giant.”⁴¹ In 1928 Wilder Penfield, the savant of cortical histology, had occasion to visit the Vogts’ laboratory and examine microscope slides of Lenin’s brain. Penfield remained skeptical of Vogt’s claim that giant pyramidal cells were the structural underpinning of Lenin’s genius and wrote that a delay in brain tissue fixation could have brought about artifactual swelling of the neurons.⁴²

Did the Vogts’ study of Lenin’s brain further influence Harvey to scrutinize Einstein’s neurohistology rather than his gross cerebral anatomy? (Penfield’s technical concerns were not published until twenty-two years after Einstein’s death and would play no part in Harvey’s choices.) In this instance, the German medical literature may have been persuasive, for Harvey irrevocably chose the path of neurohistology when he instructed Marta Keller at the University of Pennsylvania to section twelve sets of two hundred microscope slides per set.

Outside the Vogts’ study of Lenin’s brain, we will never know how thoroughly Harvey was acquainted with the relatively small body of prior research on elite brains. The discussion of a few earlier reports will provide a picture of the field of elite brain research in its infancy. From today’s neuroscientific perspective, the basis of cognition, gifted or otherwise, is inextricably interlinked with the cortex (gray matter) and the connectome (white matter). But this was not always accepted as neurologic dogma: “Most mediaeval and later anatomists played down the role of the cortex and localized vital functions of the soul (‘mind’ in modern parlance) within such unlikely parts of the nervous system as the meninges (Schabtai-Donolo), pons (Lotze), ventricles (Gordon), nerve roots (Meyer), corpus callosum (Lancisi), cerebellum (Dorincourt), or the pineal (Descartes) and corpus striatum (Willis).”⁴³

In Postcards from the Brain Museum, Brian Burrell contended that Rudolf (and later Hermann) Wagner’s laborious measurement of the surface area of the brain of the German polymath Carl Friedrich Gauss (as in Gaussian distribution or the unit of magnetic flux density) in 1855 “kicked off the search for the anatomy of genius.”⁴⁴ Along with this birth announcement for the study of the anatomical trappings of genius, Burrell also wrote a requiem for the search for “something truly distinctive in the brains of great men, great women, depraved hoodlums, or murderers.”⁴⁵ After 154 years Gauss’s brain was removed from its sealed jar at the University of Göttingen to undergo MRI scanning. The world was indifferent. No one seized the opportunity to study the scans or “compare Gauss’s brain to Einstein’s” presumably because “Gauss’s intricately fissured brain is simply old news.”⁴⁶ In short, requiescat in pace C. F. Gauss and the materialist perspective on genius.

What Burrell didn’t know was that the brain in the sealed jar was not Gauss’s! The brain in the jar was part of a small collection of elite brains at Göttingen and had an extraordinary cortical anatomy consisting of a bridge of neural tissue connecting the pre- and postcentral gyrus of each hemisphere. This rare anatomical variation of a divided central sulcus of the right hemisphere and the more commonly encountered segmented central sulcus of the left hemisphere was rendered in exquisite detail in a lithograph of the brain of C. H. Fuchs (and not C. F. Gauss), which was published in Rudolf Wagner’s 1862 study.⁴⁷ Sometime after 1855 the brains of Fuchs, a physician and pathologist at Göttingen, and Gauss were inadvertently switched to wrongly labeled jars. The mix-up was discovered in 2013.⁴⁸

The foregoing tale of Wagner’s early foray into the neuroanatomy of genius does impart a positive lesson that by 1855 Wagner had gone well beyond the standard nineteenth-century brain metrics of size and weight and was examining the gyri and sulci with a critical eye. And this approach reaped dividends—Wagner’s detailed cortical observations enabled the brains of two specific individuals (Fuchs and Gauss) to be distinguished a century and a half later. In contrast, the so-called studies of Gauss that Burrell consigned to scientific oblivion were performed on the wrong brain and thus render his verdict inapplicable. Given the comedy of anatomical errors, the question of whether Gauss had exceptional neuroanatomy remains open, requiring further study. A comparison of the rediscovered brains of Einstein and Gauss, with the latter hiding in plain sight, might well invigorate the study of the brains of those with sublime intellect.⁴⁹

Was Wagner’s study of Gauss really the earliest probe into the anatomy of genius, as Burrell contends? The priority of a scientific discovery or technique can be very difficult to determine, and such for the pursuit of genius is no exception. It is known that nearly thirty years before Wagner’s study, the anatomist and physiologist François Magendie found the brain of Pierre-Simon Laplace (1749–1827), “the French Newton,” to be “remarkably small,” with a small amount of cerebrospinal fluid (CSF) in its ventricles. In this case the relatively small amount of fluid in the brain of a genius conformed nicely with Magendie’s theory that intelligence was inversely related to the volume of CSF. This evidence of scientific precedence was published a century after the fact by no less a student of human intellect than Karl Pearson, who regretted that “so few brains of great thinkers have been available for examination.”⁵⁰

The foregoing accounts of nineteenth- and early-twentieth-century investigators of elite neuroanatomy provide a glimpse of Harvey’s intellectual forebears, but if Harvey had a syllabus for anatomizing a genius, many of the citations remain blank for us in the present day.

Before closing the door on the scenes of Harvey’s scholarly preparation for the task of examining Einstein’s brain, we would do well to consider a well-known study that further characterizes the zeitgeist of eminent brain studies. In 1907 Edward Anthony Spitzka, editor of Gray’s Anatomy, published a 133-page article, “The Study of the Brains of Six Eminent Scientists and Scholars Belonging to the American Anthropometric Society, Together with a Description of the Skull of Professor E.D. Cope.”⁵¹ In addition to his own detailed anatomic examination of six brains in the American Anthropometric Society’s collection (Walt Whitman’s brain was unavailable and unsalvageable after being “dropped on the floor by a careless assistant”), Spitzka reviewed the literature of “notable individuals” (133 men and 4 women) ranging from Turgenev, topping out at 2,012 grams, to Ludwig II of Bavaria, “the Mad King.” He conceded that “it is difficult to give an exact expression of the inter-relation between brain-size and mental capacity.” Nevertheless, he subsequently launched into sheer insupportable speculation, invoking the mesial (midline) frontal lobe to cuneus/precuneus ratio as a “true somatic expression of naturally endowed superiority of the powers of conception of the concrete in the one brain [of Joseph Leidy], and of remarkable powers of thought in the abstract in the other brain [of Edward Cope].”⁵²

If Spitzka went off the rails of scientific induction with his conclusions about Leidy and Cope being “so differently endowed by nature,” he was prescient about the critical importance of “myelin-development” and the “intricate inter-connection of the many nerve cells by a multitude of association fibers.” Lacking axons and dendrites, “a brain made up of gray matter only would be as useless as a telephone system with all its inter-connecting wires destroyed.” In this case Spitzka got it right, and his views predate our present focus on the connectome of the human brain by roughly a century. Cerebral white matter can be organized into bundles of nerve fibers called commissures. The largest of these commissures is the corpus callosum, which is comprised of 250 million or so axons connecting both hemispheres of the brain. And Spitzka found that his notable men had “larger callosa,” serving to “distinguish the brain of the genius or talented man.” However, in 1907 conceptions of the functions of the corpus callosum were vague, and even decades later the astute neuropsychologist Karl Lashley “thought that the corpus callosum was merely a structural element that supported the two hemispheres.”⁵³ It was not until the 1960s that split-brain experimentation revealed the corpus callosum’s crucial role: “Severing the entire callosum blocks the interhemispheric transfer of perceptual, sensory, motor, gnostic, and other information in a dramatic way, allowing us to gain insights into hemispheric differences as well as the mechanisms through which the two hemispheres interact.”⁵⁴ Most astonishingly, following a simple neurosurgical procedure—callosal section for the treatment of epilepsy—“two minds, each with its own set of controls, could exist in one brain.”⁵⁵

Spitzka died suddenly in 1922 and did not live to see the experimental elucidation on the corpus callosum and the possible implications for his observations on the “larger callosa” of theeminent brains he measured. The revelations of split-brain research appended an interesting footnote to a century-old study with no expectations of further developments … until 2013, when a physicist in Shanghai discovered that Albert Einstein’s corpus callosum was significantly larger than those of age-matched and younger controls.⁵⁶

This chapter brings the curtain down on Thomas Harvey’s preparedness—real and imagined—to scientifically investigate the postmortem anatomy of Einstein’s brain. By the summer of 1955, Harvey had embalmed and photographed the brain, embedded 240 blocks of neural tissue, and cut twelve sets of microscope slides. Looking to the distant future, we have glimpsed the most recent (Einstein’s corpus callosum) in a series of startling neuroanatomical findings (with a little scientific perspective provided by Edward Spitzka and Michael Gazzaniga). But the question remains—What exactly have we learned from Einstein’s brain in the last six decades?