David Hubel and Torsten Wiesel: The duo that deciphered the visual brain

One of the most exciting discoveries that happened in the field of Neuroscience is the unravelling of the mysteries of the visual brain. This edition brings out the story of the collaboration of David Hubel and Torsten Wiesel who deciphered the neurobiology of vision through their animal experiments and the implications this discovery had on further explorations in visual processing, neuroplasticity and modifying the clinical approach to many diseases like amblyopia [Figures 1 and 2].Figure 1: David Hubel and Torsten Weisel in their basement laboratory (credits: Canadian Medical Hall of Fame)Figure 2: Hubel and Wiesel mapping a receptive field in cat visual cortex using a crude projector and screen (credits: Harvard Medical Library in the Francis A. Countway Library of Medicine.)The mechanism by that the brain processed sensory data from our environment into cohesive visual images was largely unknown prior to the work of Hubel and Weisel, though some foundational insights were provided by the work of Ramón Y Cajal’s work on neuronal interconnections.[1] It was known that individual retinal receptors transmit numerous messages conveying information about small units of the visual field. Hubel and Wiesel went on to explain how the cerebral cortex reconstructs these messages to allow the brain to “see” the image. Dr. David Hunter Hubel was born on February 27, 1926, in Windsor, Ontario. He did Honors in Mathematics and Physics (1947, McGill University), and then applied to Medical School, where he was fascinated by Biochemistry and studies on the brain. Due to his interest in the studies of the brain, he mustered courage and arranged a meeting with the famous neurosurgeons Wilder Penfield and Herbert Jasper, who were famous for their work on epilepsy at the Montreal Neurological Institute, a part of the McGill University. Dr. Jasper promptly offered him a summer job in his Physiology laboratory. After receiving MD degree in 1951, Hubel continued his training at McGill, with an internship, a year of Neurology residency, and a fellowship in clinical electroencephalography with Dr. Jasper. In 1954, David moved to the United States for a second year of Neurology residency at Johns Hopkins Institute. He volunteered for the Army, and was assigned to the Walter Reed Army Institute of Research in Washington DC. In 1955, around the age of 30 years, David had his first opportunity to conduct his own research. Dr. Torsten Nils Wiesel was born in 1924 in Uppsala, Sweden. His family lived at the Beckomberga Hospital, a large mental hospital in Stockholm, where his father was the chief psychiatrist. Torsten graduated from the Karolinska Institute in Stockholm in 1954. He taught in the Karolinska Institute’s Department of Physiology and worked in the Child Psychiatry unit of the Karolinska Hospital. In 1955, he began to pursue his interest in visual physiology in association with Prof. Stefen Kuffler at Johns Hopkins University Medical School. Later in his career, he joined as the Vincent and Brooke Astor Professor Emeritus in Rockefeller University, New York. At Walter Reed, National Institutes of Health (NIH) in Bethesda, David had the opportunity to collaborate with Michelangelo Fuortes, a spinal cord neurophysiologist, who compared the flexor and extensor reflexes in decerebrate cats. For David, who had no prior experience in animal research, this provided a thorough grounding in electrophysiology. When David was pondering on his own research project, Mike suggested placing wires in the cortex of cats and recording from them while they were awake. That attempt failed, but the idea captured David’s imagination and he began developing techniques for brain recording from animals while awake. He first tried a tough tungsten microelectrode, and then developed an electrode advancer. The advancer required so many versions, and through the course of his experiments he learned to operate the lathe and made the new electrodes himself. David and Torsten first met when Torsten visited Walter Reed to learn how to make David’s tungsten electrodes. Torsten was then working in Prof. Stephen Kuffler’s laboratory in the Wilmer Institute at Johns Hopkins. David was planning to join the Physiology Department at Johns Hopkins at the invitation of Vernon Mountcastle, but it was not available at that point. To accommodate David at Johns Hopkins, Kuffler suggested that David spend time in his laboratory collaborating with Torsten. In 1958, David moved to the Wilmer Institute, which marked the beginning of a scientific partnership destined to last more than a quarter of a century. David and Torsten decided to take forward the investigations that Kuffler had done on the cat retina and the visual cortex. In 1959, when Kuffler moved from the Wilmer Institute at Johns Hopkins to Harvard Medical School, David and Torsten followed him to be among the first members of what eventually became the Department of Neurobiology at Harvard. As they began their collaboration, David and Torsten set up their laboratory at Havard and began to stimulate the cat’s retina by light and dark spots as Kuffler had conducted by using the projection ophthalmoscope. It turned out that they had great difficulty in activating the cortical visual neurons with spots of light. Here comes a serendipitous finding that changes their trajectory of experiments. For a single neuron, they were able to obtain only faint responses to spots of light in a part of the visual field; but when they changed the slide in the ophthalmoscope, there occurred a burst of activity which was produced by the line at the edge of the slide. They then realized that the neurons got excited by lines more than by spots. Subsequently, they discovered that different neurons preferred different orientations, and across a sample of neurons all orientations were represented. This was a preview of the observations in his landmark studies that was to describe the directionality and type of the stimulus that incited a response. In 1959, David and Torsten had their first publication in the Journal of Physiology titled “Receptive fields of single neurons in the cat’s striate cortex,” which reported the orientation selectivity of primary visual cortex.[2] In 1962 they published their ground breaking paper in that they differentiated the classes of visual neurons, described their columnar organization, demonstrated that neurons within a column preferred similar orientations and put forward the idea of ocular dominance.[3] Subsequent to the cat experiments, they switched to studying the monkey visual cortex and made detailed drawings on the sequence of visual processing in the cortex, the topographical mapping of the cortex and the color opponent organization in the lateral geniculate body. About three years later, they began to investigate the impact of congenital cataracts on the development of visual mechanisms in the brain. Initially they made several recordings from kittens at successive ages of their development. They noticed that shortly after the kitten’s eyes opened, many neurons in the primary visual cortex did show directional orientation like that of adults. Then they tested the effects of visual deprivation by sewing of one eye in new born kittens to simulate monocular deprivation, like unilateral cataracts in new born infants. After a few months they noticed that those kittens with monocular deprivation had reduced responses along with anatomical changes in the neurons of the lateral geniculate body and visual cortex receiving input from the deprived eye. But those neurons receiving input from the normal eye remained intact. Through a series of experiments, they concluded that the monocular deprivation was most severe when it was present before the eye opened, less severe if they were open for a few months and normal if the suturing was done in adulthood. They also paved way for the evolution of the concept of neuronal plasticity. The results of their experiments were published in a series of papers spanning over twenty-five years and made a quantum leap in the field of visual neurophysiology and their riveting insights channeled further explorations in remarkable ways. Through these innovative experiments, Hubel and Wiesel established two fundamental points about the developing visual system: one that the neuronal connections in the visual brain are largely existent before the eyes open and two, that the organization of these connections deteriorate if deprived of visual input during a critical period after birth, which was later elucidated to be four to eight weeks after eye opening. These novel experiments and their astounding results spawned a new field of research about the molecular mechanisms of visual plasticity and inspired generations of scientists. David and Torsten won the Nobel Prize for Physiology/Medicine in 1981, along with Roger Sperry, for his independent work on cerebral hemispheres [Figure 3].Figure 3: Torsten Wiesel, Roger Sperry, and David Hubel in Stockholm, 1981. (Credits: Harvard Medical Library in the Francis A. Countway Library of Medicine.)The collaboration of these two giants in the field of Neuroscience was also path breaking in many aspects. Hailed as one of the most successful and longest partnerships in the history of biological sciences, their respect for each other was immense as was their realization that they brought complementary abilities for a common good. They shared a common understanding of what they wanted to aim for, how to transform differences of opinion to pearls for intellectual stimulation and to nurture together their love for scientific discipline and innovative spirit. Over the long period of their bonding, they had realized that they had reached their studies on visual cortex at the right time, with the right techniques and had the responsibility to take it to a fruitful point of completion. The story of their combined work is summarized in the book, Brain, and Visual Perception (OUP USA; 1st edition, 2005). David spent the rest of his life at Harvard as the John Franklin Enders University Professor of Neurobiology and continued to work on many aspects including the functional correlates of the sub-modalities of vision like form, contrast, and color. Torsten moved to Rockefeller University, and worked on the connections within striate cortex. In addition to winning the Nobel Prize, David was elected to the leading societies of the world including the National Academy of Sciences, the American Academy of Arts and Sciences, the American Philosophical Society, and the Royal Society. He was honored by many honorary lectures, award, and honorary degrees. Torsten Wiesel is the member of the Royal Swedish Academy of Sciences, Serbian Academy of Sciences and Art. He has won numerous awards, presented numerous lectures, and bestowed with several honorary degrees. Hubel passed away at 87, in 2013. Torsten Wiesel, at 101 years of age, is still active as a mentor for young scientists and as a propounded of Human Rights. Hubel and Wiesel’s work was an epoch marking contribution, which had a great impact on our understanding of the visual brain. Their observations influenced the thought processes of many generations of scientists working in the field of Neurophysiology, Behavior Psychiatry etc., and had a huge impact on the clinical care in Neurology and Ophthalmology. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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