American Scientist

The Beautiful Brain: The Drawings of Santiago Ramón y Cajal. Edited by Eric A. Newman, Alfonso Araque, and Janet M. Dubinsky. Abrams, 2017. $40.

What makes a book thrilling to open? Sometimes it's because you're holding the latest title by a favorite author; other times it may be because the subject is one that especially intrigues you. If you're like me, occasionally all it takes is a transfixing title or dust jacket to set off a bookstore-aisle "you had me at 'hello'" moment.

But let's face it. Every once in a while, a book thrills because it's drop-dead gorgeous.

The Beautiful Brain, edited by neuroscientists Eric A. Newman, Alfonso Araque, and Janet M. Dubinsky explores the early years of microneurology, an enthralling topic. It's also a stunner, thanks to the research illustrations of its subject: Spanish neuroanatomist Santiago Ramón y Cajal (1852–1934) and his masterful microanatomical art.

Although he's credited as a founder of the field of neuroscience, Cajal isn't a household name. Perhaps he should be. Among his early accomplishments, he improved on Italian histologist Camillo Golgi's method of staining nerve tissue, which had for the first time made nerve cells stand out distinctly from neighboring cells. Cajal's method was more practical and its results more reliable, which paved the way for closer observation and study. His work confirmed that the brain is composed of nerve cells. (The term neuron came from German anatomist Heinrich Wilhelm Gottfried von Waldeyer-Hartz, a colleague and friend who promoted Cajal's work in Germany, then a hotbed of microanatomy studies.) In 1906, Cajal and Golgi (discoverer of the Golgi apparatus within cells) shared the Nobel Prize in Physiology or Medicine for their groundbreaking work.

Cajal continued to advance the field with his research into the behavior of neurons. As neurobiologist Larry W. Swanson explains in the book's opening essay, "Cajal provided the conceptual framework for thinking about the cellular wiring diagram of the brain and nervous system that is still in use today." This framework is built on two principles set forth by Cajal. The first, the Neuron Doctrine, Swanson notes, establishes that "the nerve cell (neuron) is the structural and functional unit of nervous system circuitry, and nerve cells interact with other nerve cells by way of contact or contiguity—they are not generally in direct continuity." The doctrine was at odds with Golgi's belief that nerve cells were physically connected in a weblike fashion; Cajal proposed that their positioning—and thus their signaling—is contiguous. (For more on this, see the sixth image below, which illustrates the calyces of Held synapses.) The second principle, the Theory of Dynamic Polarization, which Swanson explains is more typically described as functional polarity, holds that "during normal operation, information flows through a nerve cell, and thus through neural circuits, in one direction: from dendrites and cell body to axon. In other words, dendrites . . . act as the input side of nerve cells. And conversely, axons are the output side of nerve cells." (The seventh illustration below, showing cerebral cortex neurons, provides a detailed depiction of this information flow.) This theory also differed from Golgi's position: He believed that dendrites performed a nutritive role rather than a communicative one. Ultimately, Cajal's theories were proven correct, his thinking aided in part by an uncanny knack for meticulous observation. The very act of illustrating his observations may have played a role as well. Cajal, readers learn in the book's second essay, described drawing as "a language, an articulation of ideas which allowed thoughts to develop."

Beyond familiarizing readers with Cajal's research, The Beautiful Brain engages deeply with the artworks themselves. The book includes a gallery of 82 images, along with helpful accompanying text by editor Newman. (Several samples are included below.) In addition, an essay called "Drawing the Beautiful Brain," written by Lyndel King, the chief curator and director of Frederick R. Weisman Art Museum, and Eric Himmel, editor-in-chief of Abrams, pairs nicely with Swanson's research-focused essay. King and Himmel explore Cajal's background in art and the techniques he used when drawing his neurological illustrations. They go on to discuss his work from art-historical and curatorial perspectives, examining the relationship between thinking and drawing, analyzing Cajal's artistic style, and contextualizing his work within the larger frame of modernism.

The discussion of Cajal as a modernist is especially interesting because it's a label the artist himself would have very likely rejected—vehemently. He scorned modern art and was distressed to see realism fall out of favor during his lifetime. King and Himmel share a revealing passage from his memoir of old age, El mundo visto a los ochenta años [The World as Seen by an Eighty-Year-Old], in which he rails against art critics who lauded artists that spurned the "slavish copy of the natural . . . as if the strict copy of nature . . . was unable to communicate feelings an ideas." Indeed, Cajal performed prodigious feats of observation to produce data and diagrams that hewed precisely to what he saw; King and Himmel share an account of Cajal watching a leukocyte's movements through a microscope for 20 hours straight.

Nonetheless, considering his artistic gifts and the subjects of his compositions—microscopic life so novel as to be thrillingly wondrous and strange—it's little wonder that Cajal's illustrations caught the eye of Surrealists such as Salvador Dalí and Federico García Lorca. The Surrealists' debt to Cajal has received renewed attention in recent years; for example, King and Himmel share in the essay's notes that the University of Zaragoza, in Spain, mounted a 2015 exhibition examining Cajal's influence on the Surrealists. Fittingly, the essay closes with a 1927 drawing by Lorca that demonstrates a clear kinship with Cajal's works. Its delicate lines cascade down the page, concluding in tumbles of branching structures.

"Seeing the Beautiful Brain Today," the book's final essay, discusses how contemporary neuroscientific research is both fundamentally built on and has expanded dramatically beyond Cajal's discoveries. Neuroscientist Janet M. Dubinsky reminds readers that the aesthetic qualities of Cajal's work served a persuasive purpose. "The beauty of his plates," she notes, "helped convince other European neuroanatomists of the veracity of his conclusions, and it is clear from Cajal's writings that he understood the persuasive power of images."

Dubinsky posits that aesthetically pleasing images are not only easier to remember, but they also introduce an emotional element—an observation that chimes satisfyingly with Cajal's own belief in the emotional potential of realism. Greg Dunn, a neuroscientist who creates intricate paintings of neural microanatomy, has observed this phenomenon as well. As he explains in his essay "Etching the Neural Landscape," his fascination with neuroscience drives him to depict the brain's complexity, and when his perspective toggles from research to aesthetics, he witnesses a transformation as data becomes art: "Harnessing a viewer’s emotions is a key part of what makes art capable of such great impact." Further, he notes, "aesthetically compelling art invites further inquiry into its conceptual underpinning."

In the same vein, Dubinsky urges contemporary scientists to draw a lesson from the evidence before them in Cajal's drawings: "The composition and clarity of Cajal's presentations added an aesthetic sensibility and a subtle, emotional appeal to their scientific content. Today, neuroscientists with access to vastly more complex visualization tools than Cajal had, running laboratories with teams of scientists and substantially more resources, also need to create images . . . to share observations and make arguments." Highlighting her point, Dubinsky includes several striking digital images that demonstrate neuroscientific research. The one that opens her essay—a light-microscope image showing a dense array of vivid, fluorescing neurons—is especially fetching. It conveys structural information about information pathways, yet it would look right at home hanging on a gallery wall.

For all of his success in neuroscientific research, Cajal only entered the field at the urging of his father, a doctor eager to see his son take up the family business. Cajal saw himself first as an artist. Through his work in microanatomy, he was able to bring the two fields together, and his inspired drawings are simply beautiful. This is art of the highest scientific order, but make no mistake—as art, it stands on its own. Cajal's exquisite tracings of microscopic tissue structures do help the viewer envision their workings. At the same time, his drawings inspire wonder and spark curiosity—aesthetic and scientific.

Eight Neurological Portraits by Santiago Ramón y Cajal

Image commentaries by Eric A. Newman, from The Beautiful Brain.

The pyramidal neuron of the cerebral cortex

The cerebral cortex is the outermost layer of our brain. It receives and processes information from our sense organs, commands motor activity, and is responsible for higher brain functions. Pyramidal neurons, which are critical to the function of the cerebral cortex, were characterized in great detail by Cajal. The pyramidal neuron derives its name from its pyramid-shaped cell body, the large structure at the center of the cell. These neurons are found both in the neocortex, the evolutionarily advanced portion of the cerebral cortex that is involved in higher brain functions, and in the hippocampus, a more primitive portion of the cortex where many of our memories are first laid down. Like many neurons in the brain, the pyramidal neuron is axially symmetric around the large dendrite emerging from its cell body. This symmetry is beautifully conveyed in this drawing, where Cajal artfully varies the weight of the dendrites to give the viewer a sense of the three-dimensionality of the dendritic tree. Because of their large size, pyramidal neurons are among the few neurons in the brain that can be seen with the naked eye, without the benefit of a microscope. A single pyramidal neuron is illustrated in this iconic image.

Dendrites of pyramidal neurons of the rabbit cerebral cortex

One of Cajal's important discoveries was the dendritic spine. Cajal observed these spines, the fine hairs that profusely cover the dendrites of many neurons, using the Golgi method to stain the neurons. Many of Cajal's contemporaries believed that these spines were artifacts of the Golgi staining method and did not exist in living cells. To counter this argument, Cajal demonstrated that the spines were also seen when neurons were stained by an entirely different method. This drawing illustrates the multitude of spines on dendrites of pyramidal neurons stained by the Ehrlich methylene blue method, discovered by the famous microbiologist Paul Ehrlich. Results such as this convinced many scientists that dendritic spines were real. Cajal speculated that the dendritic spine was the input structure that received signals from other neurons. We now know that Cajal was correct and that spines receive synaptic inputs that control the electrical responses of neurons. The number and size of the spines present on dendrites can vary with the health of the brain. Spine size and numbers decrease as a result of many diseases associated with cognitive deficits, including Alzheimer's disease, Parkinson's disease, autism, Down syndrome, schizophrenia, and drug addiction.

Astrocytes in the hippocampus of the human brain

Cajal beautifully summarizes many of the properties of astrocytes in this drawing of the hippocampus of a man three hours after death. Holding center stage in the middle of the drawing is an astrocyte with its classical star-shaped appearance. Some of its appendages contact a neuron (the large, lightly shaded cell on its right). Other appendages contact a blood vessel (F) to its left. A second astrocyte (A) hugs a neuron, emphasizing the intimate relation between astrocytes and neurons in the brain. A third astrocyte (B) is caught in the act of dividing into two daughter cells. This is important because astrocytes, but few neurons, are able to divide in the adult brain. A fourth astrocyte (E) shows signs of degeneration.

Cells in the retina of the eye

Cajal summarizes in this drawing all of the important classes of cells in the retina, the light-sensitive tissue at the back of the eye. He emphasizes as well the many structural layers of the retina, which are labeled with capital letters at the right. In Cajal's time, it was known that light falling on the retina activated light-sensitive neurons (photoreceptors), located in layers B, C, and D. These cells convert light into electrical signals. As Cajal inferred, these signals are transmitted by contacts (synapses) to relay neurons in layer F (bipolar cells) and then to a third type of neuron in layer H (ganglion cells), which transmits the the visual information from the retina to the brain. Other neurons in layer F (horizontal cells and amacrine cells) contribute to the first steps in the processing of visual information even before the signals reach the brain. The cells at the right, labeled ñ and o, are glial cells, non-neuronal cells that assist neurons in the processing of visual signals. By placing them to the side, Cajal draws a clear distinction between the glial cells and the neurons. Cajal has turned one of the glial cells, the astrocyte (o), on its side so that we can see its shape better. As in a Cubist painting, he is showing us multiple views in a single image.

The labyrinth of the inner ear

Although Cajal was fascinated by vision and the structure of the retina, he also studied the other sensory organs of the body. Pictured here is the labyrinth of the inner ear, which contains the sensory structures for hearing and balance. A labyrinth is, of course, a maze, and sound waves travel through this maze as they are transformed into electrical signals. The drawing illustrates a slice through this maze. The organ of Corti, which converts sounds into electrical signals, is shown in a and b. The semicircular canals, the structures that detect rotation of the head, are shown in E and F, while the otolith organ, the structure that senses movement and tilting of the head, is shown in D. The neurons that transmit this information to the brain are indicated by A and B.

Calyces of Held in the nucleus of the trapezoid body

The calyces of Held are synapses made by axons carrying auditory information and contacting neurons in a brain stem structure called the trapezoid body. The calyces, named by Hans Held in 1883 for their resemblance to calyces of flowers (which envelop the base of flower petals), are the largest synapses in the brain. They are seen as stout black lines wrapped around the yellow cells. As was well-known to Cajal, these cells are part of the brain system that perceives sound. The large synapses, which transmit information quickly and reliably, help us to accurately localize the source of sounds. Cajal used the structure of this synapse to support his Neuron Doctrine of distinct neurons, stating, "One receives the impression that the chalice is something external to the cell, although very intimately applied to it."

Neurons in the cerebral cortex

The famous British neuroscientist Sir Charles Sherrington, who won the Nobel Prize in 1932, wrote of Cajal, "He solved at a single stroke the great question of the direction of nerve-currents in their travel through the brain and spinal cord. He showed, for instance, that each nerve path is always a line of one-way traffic only, and that the direction of traffic is at all times irreversibly the same." Cajal illustrates the direction of information flow in this drawing of different types of neurons in the cerebral cortex. Arrows in the drawing indicate the direction of information flow, including signals in axons originating in other brain areas (G), which then make contacts onto local neurons.

Injured Purkinje neurons of the cerebellum

Judging from this drawing, Cajal must have had a droll sense of humor. Pictured are damaged Purkinje neurons of the cerebellum. Cajal has chosen to focus on the cell bodies, which have a bloated, empty appearance. Large vacuoles (a) are present in several cells, a sure indication of degeneration. The most swollen of these cells (G) has the appearance of a penguin, swimming among the other neurons. Did Cajal actually see a penguin as he gazed into his microscope? Hard to tell, as Cajal typically drew from memory rather than tracing specific cells that he saw.