1944 Nobel Prize in Physiology or Medicine — Erlanger and Gasser: Multiple Signals in a Single Nerve

What You Will Learn in This Article

This article explores how two researchers used a vacuum tube oscilloscope to observe the sciatic nerve of frogs and cats, leading to the discovery that nerve impulses arrive as multiple peaks rather than a single waveform. It explains how this discovery laid the foundation for modern pain management (targeting opioids) and nerve conduction studies (EMG/NCS).

Beyond Common Sense — One Nerve Is Not a Single Channel

We often imagine nerves as “wires.” A stimulus from touching something on our fingertip travels along a single wire to the brain. While partially accurate, this is an oversimplification. In reality, a nerve is not a single wire but a cable composed of thousands of tiny fibers of varying thickness and speed.

Within this cable, multiple types of signals flow simultaneously. There are thick, fast-conducting fibers that transmit tactile sensations, intermediate-speed fibers that carry autonomic nerve signals, and thin, slow-conducting fibers that transmit pain. When you touch a hot pot, you quickly withdraw your hand (fast tactile/pain response), and only after a few seconds do you truly feel the pain (slow pain). This is because different types of signals within the same nerve arrive with a slight time difference.

Although this seems obvious now, it was unknown until the 1920s. The assumption that a single nerve is a single, uniform signal channel was a fundamental tenet of early 20th-century neurophysiology. To challenge this, a new tool capable of precisely measuring nerve activity in milliseconds was needed, and this tool emerged during the vacuum tube era. This is the story of Erlanger and Gasser.

The Zeitgeist — The Year Vacuum Tubes Changed Both War and Science

1944 was the year vacuum tube technology transformed the world.

On June 6th, the Normandy landings began. One of the key technologies that contributed to the success of this operation was radar. Between the English Channel, real-time information warfare unfolded between the German air defense system and Allied air support, and in this battle, the Allies' radar system was superior. In August, Paris was liberated, and in September, the Nazis began launching V-2 rockets against London. The V-2 was the first mass-produced weapon to use a vacuum tube-based circuit in its automatic guidance system.

These technologies, which decided the course of the war, all shared a common ancestor: the cathode-ray tube (CRT). This technology, which accelerates electrons in a vacuum tube and causes them to strike a fluorescent screen, became the display for radar, the time axis for oscilloscopes, and eventually the screen for televisions. And this technology provided a crucial tool for neurophysiology. The oscilloscope used by Erlanger and Gasser was precisely one of these devices.

There is an irony to the era. The same vacuum tube technology was used in one laboratory to create the guidance circuits for rockets that killed people, and in another laboratory, it became a tool for studying the subtle signals of nerves. The Nobel Committee, after a three-year hiatus, resumed awarding prizes, and the first cycle (1943-1945) recognized the neurological applications of this tool.

If we consider this in parallel with Korean history, 1944 was the year Yeo Un-hyung founded the Korean National United Front. While Korean intellectuals were organizing underground movements in preparation for the liberation, the Normandy landings and oscilloscope measurements were taking place simultaneously in Europe. It was an era in which various types of signals were quietly accumulating with a slight time difference.

Two Decades of Collaboration

Joseph Erlanger was an American physiologist trained at Johns Hopkins. He had been at Washington University in St. Louis since 1910 and had already established himself in the academic world through his work in cardiac electrophysiology. Herbert Spencer Gasser was Erlanger’s student. Their mentor-mentee relationship began when Gasser undertook postdoctoral training in Erlanger’s laboratory in St. Louis, and it evolved into more than 20 years of collaboration.

The pivotal moment for the two came in 1921 when Erlanger became interested in a new tool: the vacuum tube amplifier and cathode-ray oscilloscope developed by Western Electric. Why was this combination so crucial? Until then, nerve activity was measured using a galvanometer, which was too slow to capture the millisecond-scale action potential waveforms. The oscilloscope had an overwhelmingly faster response time, and for the first time, it was possible to visually observe the actual waveform of the action potential.

The two began by stimulating a sciatic nerve sample and recording the signal at another point. By measuring the time interval between nerve stimulation and signal arrival, they could calculate the conduction velocity, and by recording at multiple points, they could see the temporal evolution of the waveform. This was the basic experimental setup that they repeated for 20 years.

Multiple Bandwidths within a Single Cable

The first observations were unexpected. The response of the sciatic nerve that they recorded was not a single, smooth waveform but a complex waveform consisting of multiple peaks appearing with a slight time difference. A large peak appeared shortly after stimulation, followed by several smaller peaks, and then another peak appeared much later.

The two realized that each of these peaks represented a signal from a different group of fibers. The sciatic nerve was actually a cable made up of thousands of axons bundled together, and these axons varied in thickness and whether or not they were myelinated. Thick, myelinated axons conduct signals quickly, while thin, unmyelinated axons conduct them slowly. Even if the stimulus is transmitted simultaneously to the entire cable, at the point of arrival, the signals with different conduction velocities arrive in sequence.

The two organized these observations and classified the nerve fibers into three groups: A fibers (thick and myelinated, 30-120 m/s) carry tactile, motor, and proprioceptive sensations; B fibers (intermediate, 3-15 m/s) carry autonomic preganglionic signals; and C fibers (thin and unmyelinated, 0.5-2 m/s) carry pain and temperature. The A fibers are further subdivided into subgroups (Aα, Aβ, Aγ, Aδ). This classification is still found in modern neurology textbooks.

Now, the language of CS naturally permeates this. The sciatic nerve was a wire multiplexed cable. Multiple logical channels exist in parallel within a single physical cable, and each channel has its own bandwidth (conduction velocity). The stimulus is broadcast simultaneously to all channels, but the receiver separates the channels by arrival time for interpretation.

The oscilloscope, in this scenario, was a protocol analyzer. It captured the signals of the physical link with millisecond resolution, visualizing which channel’s signal arrived at what time. Today, network engineers do a similar kind of work with Wireshark to separate packet streams.

This analogy breaks down partially here. In a network, channel separation is typically a logical separation at the software level, but in the case of nerves, channel separation is a physical difference in the thickness of the cable (axon). In other words, the multiplexing of nerves is parallelization at the hardware level, not the software level. A key follow-up question is why this has been evolutionarily maintained — the separation of signals requiring extremely fast response times (reflexes, avoidance reactions) and relatively less urgent signals (dull pain) into different bandwidths to conserve processing resources.

The Dual Structure of Pain and Clinical Significance

The clinical impact of this discovery was particularly explosive in the area of pain.

When we touch something hot, we experience two types of pain: first sharp pain, with a clear, localized sensation, and then, a few seconds later, dull, diffuse pain. According to Erlanger and Gasser's classification, the first pain is carried by Aδ fibers (5-30 m/s, thin myelinated fibers), and the second pain is carried by C fibers (0.5-2 m/s, unmyelinated fibers). Our body communicates danger in two stages: a rapid avoidance command and a slow, long-term nociceptive signal.

This understanding clarified the targets of pain management drugs. Opioid analgesics inhibit the transmission of C fiber signals to the next neuron at the dorsal horn of the spinal cord. In other words, they block the C channel at the synapse between neurons. In contrast, local anesthetics such as lidocaine block the sodium channels in the nerve fibers themselves, stopping all A, B, and C channels. The difference in the spectrum of action of these two drugs could not be accurately explained without the classification by Erlanger and Gasser.

Another clinical application is nerve conduction study (NCS). Today, it is a common test performed in neurology clinics to identify the cause of numbness and paralysis in patients' arms and legs. They place a stimulation electrode and a recording electrode on the skin and measure the time it takes for the signal to arrive after stimulation. It is essentially replicating Erlanger and Gasser's sciatic nerve experiment in a non-invasive clinical setting. This test can differentiate between diabetic neuropathy, carpal tunnel syndrome, and spinal nerve root lesions.

Why This Matters

I believe that the lesson Erlanger and Gasser left us is that "understanding complex systems comes with the precision of tools."

It wasn't that neurophysiologists before the 1920s were lazy or foolish. They simply didn't have the tools (galvanometer) to see signals in milliseconds, so it was natural for them to view the nerve as a single, uniform channel. When a new tool, the oscilloscope, emerged, the frame shifted to multiple parallel channels of multiplexing. The tool created the concept.

This pattern repeats throughout the history of science. Optical microscope → discovery of cells. Electron microscope → discovery of organelles. Patch clamp → discovery of single ion channels. NMR → 3D map of the living brain. Each time, a leap in tools has led to a leap in understanding of the system. The things we still don't understand about the brain today are likely the things that we don't yet have the tools to see.

Another implication is that "complexity is the parallelization of simplicity." What appears to be complex about the sciatic nerve is actually the result of multiple simple units (channels) arranged in parallel. When we try to understand the complex functions of the cerebral cortex today, that complexity is likely also the result of relatively simple computational units being massively parallelized. The nerve of Erlanger and Gasser was the first empirical evidence of this.

The Nobel Committee's recognition of this discovery in 1944 was a precise direction for the resumption of the prize cycle (1943-1945). It was a new horizon created by tools and science, and a story of how that horizon actually took root in clinical practice, and it was a narrative completed by the quiet collaboration of two generations of scholars. That was the essence of that year's award.

1944 Erlanger and Gasser Summary: Using a vacuum tube oscilloscope, they observed the sciatic nerve and discovered that multiple groups of fibers with different thicknesses and speeds exist in parallel within a single nerve. This classification is the theoretical basis for modern nerve conduction studies and pain management drugs.

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