Hubel and Wiesel: Cutting the Lawn with Nail Scissors

Seeing is almost a miracle: light in the form of its smallest particles, photons, falls on the light-sensitive cells of the retina in the eye. As with a camera, this creates an image that is upside down. It is also pixelated, because each individual cell of the retina covers a small area of the visual field. When stimulated, it sends a nerve impulse along the visual pathway across the brain to the primary visual cortex. There, the signals are decoded pixel by pixel and assembled into an image of the outside world. But how exactly does information processing work?

Some things about the visual process were already known before Hubel and Wiesel entered the scene: In the retina, several receptor cells – the cones for color information, the rods for light-dark and movement – are connected to a ganglion cell via horizontal and bipolar cells. The Hungarian-born American neurologist Stephen Kuffler had already investigated how these cells respond to stimuli in 1950. Among other things, he discovered that they cover specific regions of the visual field: when a stimulus occurs here, the cell produces a whole salvo of electrical impulses.

The axons of the ganglion cells form the optic nerve of the respective eye. Both cross at the optic chiasm, exchanging around 50 percent of their fibers. They then reach the lateral geniculate nucleus of the thalamus (corpus geniculatum laterale, or CGL for short), the only switching station between the retina and the cortex. Irish scientist Gordon Morgan Holmes and English scientist Henry Head had already investigated the function of the CGL in 1908: its cells also respond to point-like light stimuli – just like the rods and cones of the retina.

The information travels further via the optic radiation directly to the primary visual cortex (V1), where processing begins. But “no one had any clear idea how to interpret this bucket-brigade-like handing on of information from one stage to the next,” David Hubel later wrote. The few scientists who had attempted to unlock the secrets of V1 in the 1950s had discovered nothing illuminating. In retrospect, Hubel was not surprised: the cells in V1 “...were far too selective to pay attention to something as coarse as diffuse light.”

Hubel met Torsten Wiesel in Kuffler's laboratory in 1958 – a Swede and a... Canadian? American? David Hubel was born in Ontario in 1926. That made him Canadian, which is why he had to serve in the Canadian training corps during the final phase of World War II. However, since his parents were American, he was drafted into the US Army in 1954 and served at Walter Reed Hospital. The Royal Society later stumbled upon this dual citizenship and did not know whether to accept him as a regular or foreign member.

Hubel was interested in science even as a child. This was reflected not only, but also, in his mixing of explosives. He studied physics and mathematics at McGill University in Montreal – not least so that he would have enough time to play the piano. More on a whim, he also applied to medical school – and was accepted. In the end, he decided to pursue medicine full-time. When he told his physics professor, the professor replied, “Well, I admire your courage – I wish I could say the same about your judgment.”

The physics professor was mistaken: at Walter Reed Hospital, Hubel began researching the primary visual cortex of cats. To this end, he developed the modern metal microelectrode, which enabled him to measure the activity of individual cells.

In his autobiography for the Nobel Foundation, Wiesel describes himself as a rather lazy, mischievous student who was more interested in sports than anything else. That did not prevent him from earning a doctorate in medicine at the Karolinska Institute in Stockholm and going to Kuffler in New York in 1955.

As unremarkable as Wiesel's biography may have been in his younger years, he stood out in his later years for his commitment to human rights. He was nominated several times for a position at the National Institutes of Health but was rejected by the official in charge. The official was a Republican, and Wiesel had signed too many full-page advertisements in the New York Times against President Bush. The fact that he was also involved in the fight against climate change probably did little to improve his chances.

Wiesel was already at Kuffler's laboratory when Hubel joined. And Hubel brought not only the microelectrode in his toolbox, but also a method for attaching it to a cat's head. This enabled them to pursue the first big question: if the cells of the CGL respond to point-like light stimuli in the same way as those of the retina, how do cells in the primary visual cortex respond?

The first successful derivation of a cell in V1 did not really start off promisingly. Although the microelectrode was stable, no matter what stimulus Hubel and Wiesel offered it, the cell remained silent. “We tried everything short of standing on our heads to get it to fire,” Hubel wrote. It took hours to find the retinal region that corresponded to it. But even that didn't help much: the cell responded occasionally, but mostly not. So it took quite a long time for the two researchers to recognize a pattern. And it was completely surprising: the cell only responded when the faint shadow of an edge of the slide was moved through a specific region. But that wasn't all: the line of the shadow also had to be at a certain angle, i.e., have a specific orientation. In every other case, the cell remained silent.

The rest is well-known history, as can be found in any basic work on the brain today: Hubel and Wiesel had stumbled upon what they later called a “complex cell” that responds specifically to orientation and movement. In this case, the cell only responded when the light bar was at the 11 o'clock position and moved to the upper right. Complex cells make up an estimated three-quarters of the neurons in V1 and actually form the second stage of cortical processing. The first stage consists of “simple cells” that only respond to lines at a very specific angle. These simple cells are arranged in columns one above the other – the basis of a complex architecture.

What the textbooks don't mention is the effort Hubel and Wiesel had to put in: they were able to examine 200 to 300 cells per experiment – for which they had to locate the receptive field and find the cell's preferred stimulus each time. Then they pushed the electrode a little deeper – they couldn't move it to the side because that would have destroyed the cortex tissue. Hubel later compared this Sisyphean task to cutting a lawn with nail scissors.

There is no question that David Hubel and Torsten Wiesel deserved the 1981 Nobel Prize in Physiology or Medicine “for their discoveries concerning information processing in the visual system.” The significance of their work can hardly be overestimated. Not only did it enable a detailed mapping of the visual cortex, it also provided the first insight into how the brain analyzes sensory information – with astonishing depth of detail. However, research continues. As Hubel said, “... we would be foolish to think that we had exhausted the list of possibilities.”