SOURCE: "The Dark Room," in Grand Street, Vol. 12, No. 3, Fall, 1993, pp. 223-40.

[In the following essay, Montgomery explores the impact of Ramón y Cajal's scientific research on the study of vision.]

1. Ayerbe, Spain—1860

Unlike the other boys at school, Santiago Ramón y Cajal had no fear of solitary confinement. The dark detention center, a basement room set below the town square, into which light slashed only through cracks in the room's single shuttered window, was a place for Cajal to think: a quiet room in which to concentrate on what outrages to commit tomorrow. Cajal was then eight or nine. His fellow delinquents, locked in the blackness of the school prison, felt the presence of evil spirits. But Cajal had been raised a rationalist by his physician father, Don Justo. When one day he saw a spectral image hanging on the ceiling of his cell, the ghostly form inspired not superstitious terror, but the first of Cajal's scientific discoveries.

Cajal's troubles with the schoolmaster and his father—indeed, with all the authorities of Ayerbe, the Aragonese town to which his family moved in 1860—had begun in the square outside the shuttered window of his detention cell. The new boy in town, Cajal had been mocked by the young ruffians of Ayerbe upon his first appearance in the square for his unvillagelike dress and his Castilian accent. Subsequent visits brought beatings and a rain of stones. In Valpalmas, where his family had spent the four previous years, Cajal had been a loner; when not following the rigorous course of studies demanded by his father, he had delighted in taking long rambles through the countryside, collecting young animals and bird eggs. It was in Ayerbe that Cajal became socialized, and the society he entered was the same band of boys who had assaulted and stoned him.

Cajal became the master craftsman of the armaments used by these vandals and thieves. He made slingshots of hemp and goatskin, helmets and cuirasses of cardboard and old tin, bows of every kind of wood available in the district, arrows of bamboo and broken shoemaker's awls. His athletic prowess, especially his skill in scaling the walls of private orchards from which he stole first fruits, combined with his genius for military artifice, soon made Cajal the gang's captain. He was listed in the village's "Index of Bad Companions" and was blamed for every mischief performed by the gang, for every penned rabbit shot at and every chicken killed; every arrow left behind pointed back to its maker.

The second source of Cajal's delinquency was art. "A smooth white wall exercised upon me an irresistible fascination," Cajal would write of his "graphomania" in his autobiography, Recollections of My Life (Recuerdos de mi vida). He felt impelled to apply a pencil to any blank surface he saw—whether smooth white wall or blank page—filling it especially with scenes of war from the age of swords and steeds and shining armor. Entirely self-taught, Cajal was a prodigiously gifted draftsman. But his father was irremediably opposed to this passion. Having lifted himself from poverty to a first-class degree in medicine and surgery, Don Justo was not about to see his firstborn waste his talents on such a precarious career as painting. His son would be a brilliant physician. That was the course laid out. When Don Justo came across his son's drawings and pencils, they were confiscated and his son whipped.

And so Cajal practiced his art in secret. He hid his drawings like illicit treasure. Escaping to the countryside, he would sketch the battles of the bullring and the bloody exploits of his name-saint, Santiago (St. James), the warrior apostle. Unable to buy paints, he extracted his own colors from wall scrapings and by soaking red and blue booklets of cigarette paper in water, then winding the wet papers into a stubby brush. In school, impossible as it was to draw on blank sheets of paper in open view, Cajal used the wide margins of the catechism as his canvas. Particularly popular were caricatures of the schoolmaster, passed from hand to hand around the class with much hilarity. Eventually the harassed teacher would intercept these lampoons and, since beatings did not seem to intimidate the artist, lock Cajal in the catacomb-like prison cell below the town square.

It was in this dark chamber that the boy's true vocation was announced. The visitation came in the form of an image drawn by no human hand. Looking one day at where a beam of light from a hole in the shuttered window hit the low ceiling, Cajal saw to his amazement the inverted forms of the people and beasts of burden filling the sunlit square outside. Their images hung and moved in luminous color. Cajal, already tutored in some of the elements of physics by his father, went to the window shutters and began to play with this projection. When he widened the hole in the shutter, he saw the contours and colors of the figures dissolve. Narrowing this aperture with a piece of saliva-moistened paper made the forms on the ceiling grow sharper, more vivid. Despite his ignorance of optics, Cajal was able to understand the basis of the phantom. If one's eye is placed at the hole in the shutter, the field of its vision expands in a cone whose apex is the eye. Rays of light reflected from each point in the scene outside converge at this peephole; move the eye from its aperture, and these rays cross and enter the room. A second, inverted cone projects inside. The scene this cone of light carries is visible if the room is darkened and the cone intersected by a ceiling or screen.

"Proud of my discovery," Cajal would write in his memoir, "I became daily more attached to the realm of shadows." Cajal, the covert artist, stood on a chair, held a sheet of paper before the lightbeam, and "amused myself by tracing on paper the bright and living images which appeared to console me, like a caress, in the solitude of my prison." The world outside was distanced, reduced to a representation. He watched the fights and play of his classmates projected on the blank page, thinking, "All these luminous shades are a faithful reproduction of reality and better than it is, since they are harmless."

Finally, one schoolday when Cajal's cell was filled with other troublemakers, he decided to reveal his discovery. But instead of being astonished, his fellow delinquents only laughed. It was a trick of the light, they said, of no importance whatever. Not for the last time, Cajal was struck by this absence of wonder at the phenomena of nature. "It is strange to see how the populace, which nourishes its imagination with tales of witches or saints, mysterious events and extraordinary occurrences, disdains the world around it as commonplace, monotonous and prosaic, without suspecting that at bottom it is all secret, mystery, and marvel."

Cajal, of course, would later learn that he was not the first to unlock the secrets of the dark room, generally known by its Italian name, "camera obscura." This "tremendous discovery," Cajal wrote, has been "wrongly ascribed to [Giambattista della] Porta, though its real discoverer was Leonardo da Vinci." But in fact the phenomenology of the dark room has been known since antiquity, and first received sustained investigation by the Islamic scholar Alhazen and his European followers in the Middle Ages. The camera obscura did not become a truly useful instrument, however, until the sixteenth century, when it was discovered that the placing of a convex lens at the aperture in the window shutter would greatly enhance the clarity and vividness of the projected image. This was first reported by Daniele Barbaro in 1569, but became generally known only through the second edition of Porta's best-selling compendium, Natural Magic, published in 1589. "In a small circle of paper," wrote Porta, "you shall see as it were the Epitome of the whole world."

Porta defined four uses for the dark room that foreshadow its development through our own time. The camera can be used to project eclipses of the sun and moon on a wall for safe viewing; this astronomical use seems to date back at least to Alhazen. (Cajal had been first introduced to the marvels of physics through his observation of the 1860 eclipse with his father, who had described the basic principles by which the moon shed its shadow across the earth's surface.) Second, the camera can be used as a place of entertainment, of spectacle. People will pay to enter the room to watch projections of painted scenes of demons, monsters, and fabulous battles—scenes painted on semitransparent paper and held before the camera's aperture. This use was to lead to the development of the magic lantern show and of course the cinema.

The camera's third use, wrote Porta, is as a draftsman's aid. A real scene will be projected on a flat surface in perfect perspective, where its form can be traced. The camera was used in this way by Dutch artists of the seventeenth century, notably Vermeer. By the end of that century the dark room had been shrunk down to a portable draftsman's box, and it was the discovery of how to chemically record the image projected into such a box that led to the invention of photography.

Photography would become one of Cajal's lifelong infatuations. Forbidden by his father to practice art, Cajal used the photographic camera as an alternate means of satisfying his mania for making images. He mastered the chemistry of synthesizing photographic emulsions; in 1912 he would publish one of the first books on the making of color photographs. Yet it was by following the thread of Porta's fourth use for the dark room that Cajal would find his greatest fulfillment: the camera obscura as a model for the structure and function of the eye.

In 1589, when Porta wrote, scholars still disagreed whether vision was the result of visual rays somehow sent out to objects by the eye or of light reflected back into this organ. For Porta, the dark room provided proof of this latter theory. Just as images from the outside world were projected into the camera obscura, so too were images projected into the eye. Yet Porta, standing on the murky threshold between Renaissance Neoplatonism and natural magic and the experimental natural philosophy of Galileo and Kepler, thought the light-sensitive element of the eye was its lens, whose crystalline transparence somehow made it suited for the faculty of sight. It was not until Kepler became acquainted with the dark room through his astronomical studies that the true isomorphism between eye and camera was identified: the aperture in the window shutter corresponded to the eye's pupil, the lens to the lens of the eye, and the room's projection screen to the retina lining the back of the eye's inner surface. "Thus vision is brought about," wrote Kepler in 1604, "by a picture of the thing seen being formed on the concave surface of the retina."

Santiago Ramón y Cajal would come to be generally considered the father of modern neuroscience. Nowhere was his revolutionary approach to the nervous system better displayed than in his study of the retina, that transparent sheet of neural tissue where light becomes transformed into the electrochemical language of the brain. It was in his analysis of the retina's exquisite cellular structure, wrote Cajal, that "I felt more profoundly than in any other subject of study the shuddering sensation of the unfathomable mystery of life." Yet Cajal's entry into the nervous system was in fact crucially conditioned by his occupation of the photographic dark room, and his revelations of the structure and function of retinal nerve cells were both guided and ultimately limited by his equation of eye and camera.

2. The Latticed Window

It was only in the summer of 1868, when Cajal was sixteen, that Don Justo realized that his son's passion for imagemaking might have some application in his training for medicine. That summer, Don Justo introduced his son to his beloved subject of human anatomy by climbing with him one moonlit night over a cemetery wall. There the two picked through a pile of exhumed bones for the most "perfect and least weathered crania, ribs, pelves, and femurs," which they took back for scrutiny in the family barn. Don Justo taught Cajal to overlook no detail in his observation of bone structure, and for Cajal's artistic leanings "osteology constituted one more subject for pictures." Within two months, to the amazement of his father, Cajal had formulated a detailed mental map of all the bones, muscles, arteries, and nerves of the human body.

That same year, in the city of Huesca, where Don Justo had sent his truant son for a solid dose of schooling and discipline, Cajal gained his first admittance to the photographic darkroom. A group of photographers known by a friend of his had set up a laboratory in the underground chambers of a ruined church. Here Cajal watched in wonder as the light-sensitive salts of silver were mixed into a colloidal film, which was then laid thinly over a plate of glass, and as albumen-covered paper for positive prints was sensitized. "All of these operations astonished me, but one of them, the development of the latent image by means of pyrogallic acid, positively stupefied me." The skin of the scene projected into the camera, the frozen forms of an instant of the past, gradually materialized within the developing bath, as if slowly surfacing from the depths of a dark lake. "The thing seemed simply absurd." Yet when Cajal questioned the practitioners of this magic on the "theory of the latent image," the laughter of his friends in the dark room of Ayerbe was audible again. The photographers had no knowledge of or interest in the mechanism behind this process; "the important thing to them was to take many portraits and to take in still more money."

It had been known since 1727 that certain compounds of silver blacken upon exposure to light. The first attempt to use a sheet of paper coated with silver nitrate to record a portable camera obscura image was made by Thomas Wedgwood, scion of the Wedgwood pottery family, around 1800. Wedgwood failed because his coatings of silver salts were insufficiently sensitive to the relatively weak camera image. Furthermore, he lacked a fixer: that is, he could lay a leaf directly on his coated paper under the sun and make a negative image, but any further exposure to sunlight spread a shadow of liberated silver across the white figure of the leaf. The whole paper turned black. Wedgwood had no way of stopping the light-recording process—of "fixing" his images.

The first fixed photograph was made by William Henry Fox Talbot in August 1835; it showed the view through a latticed window in his home at Lacock Abbey. "When first made," Talbot noted by the side of this paper negative, "the squares of glass about 200 in number could be counted, with help of a lens." In 1839 Daguerre announced his own method of fixing camera images on polished silver plates: a method dominant for the next two decades because of its greater rendering of detail, but ultimately without offspring, as Daguerre's negative images could not serve as a template for positive copies. Talbot was impelled to improve his process. The image of the latticed window had required a camera exposure of many minutes; it was only when the sun had visibly blackened the two hundred squares of light on the coated paper that Talbot ended the exposure. Such exposure times made portraiture impractical. But in 1840 Talbot discovered that a latent image could be formed on his photographic paper in a far shorter period of time and then developed into a visible image through the action of pyrogallic acid. This made possible such photographs as "The Open Door," published in his Pencil of Nature, in which the bright sun reflected from a stone stable is contrasted with the darkness of the room inside, at the far end of which is visible, through a half-open door, a dimly lit latticed window—a window that almost seems to refer back to the latticed glass in Talbot's 1835 composition.

The word "retina" derives from the Latin translation of a Greek term for the one-third-millimeter-thick sheet of transparent tissue lining the back of the eye: "netlike tunic." Two other Greek names for the retina compared it to a spiderweb and to glass; long before its light-sensing function was known, the retina itself was seen as a kind of latticed window. Its transparence fitted Greek theories that tied the retina to the conveyance of the "visual spirit" flowing from the brain to the eye's crystalline lens—the place where mind and image supposedly met.

Yet by the nineteenth century, scientists realized that if the retina contained the eye's true light-receptors, elements within the tissue must be colored so as to absorb light. In 1876 Franz Boll discovered that the purple rod cells lying within a frog's retina bleached yellow upon exposure to light. Descartes had described how the imaging function of the retina could be proved by placing the eyeball of an ox or dead person in the aperture of a dark room; remove the white sclera from the back half of the eye, and one could see projected there the inverted scene outside. In 1878 Willy Kuhne of the University of Heidelberg set out to prove that a living retina could record such a scene using visual purple as its photographic pigment. Kuhne secured the head of an albino rabbit in place before a barred window for a three-minute exposure. The rabbit was then decapitated and its retina removed. In a yellow image against the purple of this gossamer tissue were the window's six skylit panes. Kuhne fixed this "optogram" in alum and then drew a copy for all the world to see—a curious complement to the latticed window of Talbot's first photograph. The three-century-old analogy between eye and camera seemed deeper than ever.

That year, Santiago Ramón y Cajal coughed up blood. The young physician had already been stricken with malaria during military service in Cuba, and now he had contracted tuberculosis. Cajal had by then begun his investigations with a microscope and was studying anatomy in hopes of gaining an academic appointment, for Don Justo felt that his malaria-weakened son would be unable to maintain a medical practice. Now consumption had seized him. Cajal saw his death foretold in the artificially encouraging manner of his father's questions and his own emaciated frame.

But a long interval in the country, with his sister as nurse, served to restore Cajal's strength. In his autobiography, Cajal also credits photography with reviving his spirits and will to live, as it "obliged me to take continual exercise and, by offering me the daily solution of artistic problems, it flavored the monotony of my retreat. . . . " After his marriage, when Cajal was beginning his academic career, his passion for photography led him to begin manufacturing ultra rapid gelatin silver-bromide plates; these fast emulsions were then unavailable in Spain. Indeed, Cajal's photographs of bullfights, "and especially one of the president's box crowded with beautiful young ladies . . . created a furor." Cajal was compelled to manufacture these fast emulsions—whose standard formula he had improved—for general distribution, and might have begun a new Spanish industry if not for his preoccupation as director of Zaragoza's Anatomical Museum.

Cajal had become entranced with the invisible universe revealed by the microscope; he once peered through his lens for twenty consecutive hours in order to observe a white blood cell crawling out of a capillary. In 1880 he began publishing his findings; by 1884 he had the chair of Anatomy at Valencia. He specialized in histology, the study of the microstructure of tissues, publishing a book on the subject in 1885 filled with 203 woodcuts—the first Spanish histology text to contain original illustrations. Just as he had found the formula for ultrarapid gelatin silver-bromide emulsions in a foreign journal and subsequently improved it, Cajal was always searching for new techniques to visualize the cellular composition of the tissues he studied. At the time, the standard stains for nerve cells colored only the cell bodies and the thick beginnings of their fibers. The fiber's tangled terminations and interlinkings were impossible to see. Commencing his analysis of the nervous system, "that masterpiece of life," Cajal borrowed the superior microdissection technique that Max Schultze had pioneered in the retina. The nerve tissue was softened in solution, and then, with a needle, the cells' spidery fibers were teased apart. In Cajal's hands, the method enabled the isolation of the larger nerve cells in the body. But for the fine transparent cells of tissue such as the retina, Cajal thought, the method required the patience of a Benedictine monk. One did not merely have to count the angels dancing on the head of a pin; one also had to dissect them.

3. The Black Stain

Cajal's first vision of the black stain anticipated T. S. Eliot's line in "The Love Song of J. Alfred Prufrock": ".. . as if a magic lantern threw the nerves in patterns on a screen." The magic lantern was silver nitrate—the same salt of silver first used by Talbot as a photographic pigment. And this lantern first shined for Cajal in 1887, in the house of Luis Simarros, a psychiatrist and neurologist in Madrid.

Cajal was in Madrid to serve as a judge in the examinations for anatomy professorships. While in the capital he paid visits to the laboratories of fellow microscopists. Luis Simarros had just returned from Paris with samples of several novel methods for preparing neural tissue, among them the "black stain" (reazione negra) discovered in 1880 by the Italian histologist Camilo Golgi. Cajal had read a brief, dismissive note about Golgi's stain but had never before witnessed its workings. The procedure for black staining was relatively simple: bathe tiny slices of brain tissue in potassium bichromate, and then treat this tissue with a solution of silver nitrate crystals. Many samples failed to stain. But in those that did, a latent image of spectacular appearance developed: individual nerve cells were blackened from their cell bodies to their finest branching twigs. Under the microscope, the darkstained cells were framed against the surrounding tissue like wintry trees, stripped of leaves, standing black against the sky before dawn.

Finally Cajal had a method of penetrating the tangled thicket of the nervous system, of tracing ramifying fibers to their terminations. Within a year, Cajal had mastered and improved Golgi's black stain. Like Talbot increasing the sensitivity of his silver salt negatives, Cajal developed a method of double impregnation to maximize the chance of staining his cells. Just as importantly, still daunted by the crowded complexity of adult nervous tissue—"a forest so dense that . . . there are no spaces in it, so that the trunks, branches, and leaves touch everywhere"—Cajal reverted to the embryonic brains of birds and mammals. "Since the full-grown forest turns out to be impenetrable and indefinable, why not revert to the study of the young wood, in the nursery stage . . . ?" (Moreover, the insulating sheath of myelin that covers axonal fibers on adult nerves, which is not stained by the Golgi method, is largely absent in embryos and neonates.)

The pre-Cajal period in neuroanatomy had settled one important issue: all fibers ramified back to the bodies of nerve cells. But still unresolved was the nature of the relationships between these fibers. The dogma adhered to by Golgi and nearly all other researchers was that the fibers of the brain formed a unified whole, merging together in one vast and continuous plexus. For Cajal, this reticular theory was a "species of protoplasmic pantheism," precluding the specific nerve linkages required for reflex action and the doctrine of the association of ideas. According to the reticular hypothesis, nerve impulses could travel along no specific pathways, but instead fed into a "sort of unfathomable physiological sea, into which, on the one hand, were supposed to pour the streams arriving from the sense organs, and from which, on the other hand, the motor . . . conductors were supposed to spring like rivers originating in mountain lakes."

In a fever of graphically illustrated publications, Cajal showed instead that each nerve cell retained its individuality. Its branches did not merge with those of other trees of the neural forest, but instead communicated with them through intimate contact, across a narrow cleft that came to be called the synapse. Cajal's neuron theory underlies all modern attempts at a biological understanding of brain function. Synapses connect neurons along specific pathways, and the implications of this specificity of neural wiring were nowhere clearer than in the retina—for Cajal, "the oldest and most persistent of my laboratory loves."

Max Schultze had shown that we have in effect two retinas in each eye—one for day, and one for night. Night vision is mediated through the rod cells . . . and utilizes the visual purple studied by Kuhne; day and color vision works through the retina's cones . . . , which use three other related photopigments. Rod vision is color-blind and coarse, says Cajal, producing "an image with little detail, comparable roughly to an ordinary photograph out of focus." The cones, on the other hand, give "colored pictures, detailed and brilliant, like a photograph in colors on an autochrome plate."

Rods and cones occupy the retina's innermost layer. In order for their light-recording signals to be sent to the brain, they must pass their signal to bipolar cells, which in turn signal retinal ganglion cells, whose axonal fibers form the optic nerve connecting the eye and brain. Schultze had carried the cellular anatomy of the retina to its highest level before Cajal, but without the black stain he had been unable to trace the connections between rods, cones, and bipolar cells. He assumed, however, that they merged in a common plexus.

Cajal's first foray into the retina proved this view false. The cells of this outpost of the brain—for the retina is an outgrowth of the same embryonic tissue as the central nervous system—are independent and communicate through synaptic contacts. "This important point established," wrote Cajal, "I proposed a very simple question to myself. Since the impression received by the rod is different from that taken up by the cone, it is necessary from every point of view that each of these specific impressions should be conveyed through the retina by a specific channel." That is, the rod and cone signals must pass through separate classes of bipolar cells.

"Knowing what I was looking for, I began to explore eagerly and repeatedly the retina of fishes and mammals, . . . and finally, as the reward of my faith, there deigned to appear most clearly and brilliantly those two types of bipolar cells demanded by theory and guessed by reason." Cajal also found that in the fovea, the small cone-rich center of the retina that is the place of highest visual acuity (we read by flicking letters on a page across our foveas), bipolar cells synapse with single cones. This allows the foveal cones' fine-grained sensitivity to be transmitted individually to the brain.

Cajal spent the last years of his long life running the Madrid institute that had been constructed in his honor, extending his study of vision to the compound eye of insects. In 1906 he shared the Nobel Prize with his great adversary, Camillo Golgi, who, on the Stockholm stage, reportedly refused to speak to the Spaniard who had stolen his black stain. Golgi, though his grand vision of neural structure was utterly mistaken, felt the Nobel should have been his alone.

In his autobiography, Cajal laments his lack of progress in understanding the functional anatomy of the cerebral cortex, "enigma of enigmas." He predicted that "the supreme cunning" of the cortex "is so intricate that it defies and will continue to defy for many centuries the obstinate curiosity of investigators." And in a review published in 1933, a year before his death, Cajal revisited the retina, the place where his fascination with image-making and neuroanatomy had so happily converged. He had traced the pathways of day and night vision through the second layer of this transparent sheet and felt he understood well enough the vertical pathways leading from rods and cones through the optic nerve and brain. Yet two other classes of cells, whose fibers ran perpendicular to this direct pathway, continued to puzzle him. He had discovered and named these two cell types—"horizontal" and "amacrine." But their presence seemed a direct challenge to the specific retinal pathways he had delineated. For the horizontal cells seemed to pool together signals arriving from many contiguous cones—a design that seemed counterintuitive. It was as if the blackening of one silver crystal of fine-grained photographic film caused the blackening of neighboring crystals. Similarly, the amacrine cells contacted and apparently pooled signals from many contiguous bipolar cells. Cajal had hypothesized that these indirect connections might play a booster role in aiding neural transmission. But at the age of eightyone, with only a year to live, he admitted that this was only a poor guess. The amacrine cells, he said, were an "enigma," the horizontal cells a "paradox."

4. The Open Door

The beginning of an answer to Cajal's enigma came a few years after his death, in the late 1930s, when someone flicked on the light of H. Keffer Hartline's dark lab. Hartline, then at Johns Hopkins University, had pioneered methods for electrically recording the impulses transmitted by individual optic-nerve fibers. He worked in the dark, stimulating elements of the giant compound eye of the horseshoe crab with small spots of light. What happened when the overhead lights came on in his dark lab had happened many times before: the firing of the optic nerve fiber he had been stimulating with his penlight drastically diminished. But why should flooding the room with light decrease instead of increase this lightsensing fiber's firing pattern? "I have no idea how often I had noticed this [phenomenon] unthinkingly," Hartline later wrote, "without grasping its perversity."

Until the day the light went on, Hartline had assumed that the thousand elements of the horseshoe crab's retina, like the silver crystals of photographic film, functioned independently. If a single receptor "saw" light, it sent an impulse to the brain, no matter what neighboring receptors saw. But what Hartline discovered was that neighboring retinal cells in fact talk to each other. Investigations of the cat and frog retinas in the early 1950s, by Stephen Kuffler and Horace Barlow, indicated that the pathways of this communication were the horizontal and amacrine cells that had so bewildered Cajal. If retinal elements surrounding a light-detecting cell are themselves excited by light, they send inhibitory signals to this central cell, preventing it from firing. The retina is wired to respond not to regions of uniform darkness or light, but instead to areas of contrast, to the edges and contours of shadows and objects.

The eye is not a camera. A light square sitting on a black background looks brighter than the same square on a gray background. The eye, unlike a camera, does not record absolute luminosity. It looks at patches of the scene through a kind of latticed window, and compares the light radiating through one tiny pane of glass with that radiating through the immediately surrounding panes.

It is now known that the latticed window of the retina is remapped over twenty times in the brain. And here the dark room continues to serve as a model and machine, as a metaphor and theater of exploration. Beginning in the late 1950s, two of Stephen Kuffler's young colleagues, David Hubel and Torsten Wiesel, began projecting patterns of light on a screen of a dark room while recording from cells in the cerebral cortices of cats and monkeys facing the screen. They found that within the gridlike arrangements within the visual cortex lie cells that detect contrast across different dimensions of the image—form, color, motion, and depth. The more complex response properties of these cortical neurons are generated through their specific connections with lower-order cells; such cells are regularly arrayed within the cortex according to their function. The brain perceives the world through a series of grids whose functions are defined by their neuronal structure. These latticed windows are not transparent; they begin to transform the image projected into the camera obscura of the eye as soon as light strikes the retina.

Ultimately, however, the neurons of the visual system must perform an interpretive task not unlike that of the photographer in Michelangelo Antonioni's film Blow-Up, who secretly takes pictures of a couple cavorting in a deserted London park. Developing one of these photographs, the photographer then becomes puzzled by the troubled gaze of the woman over her companion's shoulder. In his darkroom, he blows up the image of the woman's face—an act akin to the magnification of detail that occurs when we point our eyes at an object and thus place this segment of the visual scene on our fovea—the cone-rich, high-resolution center of our retinas. Able to see where the woman's pupils are pointed, the photographer then goes back to the original photograph and blows up the segment of the surrounding bushes that the woman is foveating. But for a long time the photographer sees nothing in this sun-dappled patch of shrubbery. It is like the image of interbranching nerve cells Cajal encounters before the application of the black stain—"a forest so dense that . . . the trunks, branches, and leaves touch everywhere": there is no separation of figure and ground. Then suddenly, in a true gestalt shift, the scene in the park bushes resolves itself before the photographer's eyes. The latent image emerges from the undifferentiated mass of foliage, the fractured patches of shadow and flickers of reflection from sunlit leaves: the face of an assassin, aiming a sleek gray gun, waiting to kill the man the woman has lured to that deserted meadow. The human visual system evolved in conditions not unlike this leafy picture, in which prey and predators lay hidden in verdant underbrush. Such camouflaged objects do not simply exist in the raw image projected on the back of an eye or camera: they must be extracted. How such gestalt perceptions are pieced together remains unknown. Form recognition, the creative process by which disparate elements of a two-dimensional retinal image are reconstructed by the brain into the objects of the four-dimensional world, is perhaps the central problem of modern neuroscience.

The great neurosurgeon Wilder Penfield, who studied briefly at the Instituto Cajal in the 1920s, wrote of Cajal's first vision of the true structure of the nervous system: "Working alone, he was like a man who had lit a lantern in the dark, one who had a magic key. He opened the doors all along a dark street so others could see into the secret chambers where the brain meets the mind." No terminus to this street has yet been found. Each new discovery is a disclosure: a door opens to admit one. Beyond this threshold, at the dark room's far wall, stands a latticed window, palely lit.