1936 Nobel Prize in Physiology or Medicine β Dale and Loewi
What You Will Learn
This article explores how Otto Loewi, inspired by a dream, demonstrated that nerve impulses travel across the narrow gap (synapse) between neurons. It also examines the work of Henry Dale, who identified the chemical substance involved.
The Narrow Gap Between Neurons
In 1932, Sherrington and Adrian elucidated the principles of neuron firing, but one major mystery remained:
How do signals travel between neurons?
The electrical signal (action potential) within a neuron was already well-understood. The problem arose when the neuron needed to transmit the signal to the next. Neurons do not directly touch; they are separated by a very small space β the synaptic cleft. How does the signal cross this gap?
At the time, the scientific community was divided into two camps:
- Electrical Theory: The electrical current flows directly across the synaptic cleft. This was the simplest hypothesis.
- Chemical Theory: The first neuron releases a chemical substance at the synapse, and the next neuron receives it, initiating a new electrical signal.
These two sides were in fierce disagreement. A single experiment, conceived in a dream, decisively resolved this debate. It then took another 20 years to precisely identify the chemical substance.
The Zeitgeist β Europe on the Brink, Seoul's Golden Moment
1936 was a year when multiple potential flashpoints simultaneously ignited, leading toward war.
In July, the Spanish Civil War began with General Franco's coup in Spain. This conflict lasted three years and became a proxy war, with Nazi Germany and Fascist Italy supporting Franco, and the Soviet Union supporting the Republican government. This war, often called a dress rehearsal for World War II, saw the use of bombing, chemical warfare, and international brigades, foreshadowing many elements of the coming global conflict.
In August, the Berlin Olympics were held. Hitler intended this to be a political event to showcase the power of Nazi Germany. During the Olympics, Son Ki-jung won a gold medal in the marathon, but he competed under the Japanese flag, as he was a Korean athlete under Japanese rule. The subsequent "deletion of the Rising Sun flag" incident, in which the Japanese flag was erased from a photograph of his medal ceremony in the Joseon Ilbo newspaper, followed. This incident led to the newspaper being suspended.
In the Soviet Union, the Great Purge intensified. Stalin began the mass execution of political opponents and perceived threats. In these few years, a significant number of intellectuals, military officers, and scientists in the Soviet Union were executed or sent to the Gulag. Although the Soviet scientific community suffered great losses, those who survived continued to work and laid the foundation for Soviet physics and biology.
Loewi's homeland, Austria, was facing increasing pressure from the Nazis. Two years later, during the Anschluss (1938), Loewi, a Jew, was arrested by the Gestapo, his Nobel Prize money was confiscated, and he barely managed to escape to the United States. By this time, his research was already surrounded by dangerous shadows.
When viewed in conjunction with Korean history, 1936 was the year of Son Ki-jung's gold medal and the deletion of the Rising Sun flag. In Europe, the discovery that nerve signals are transmitted chemically across synapses won the Nobel Prize. In Korea, a Korean athlete's victory was tarnished by the forced display of a foreign flag, leading to an act of resistance. It was an era in which different kinds of "signal transmission" were occurring on two different levels.
The Story of the People β Inspired by a Dream
Loewi β The Frog Heart Experiment
Otto Loewi was born in 1873 in Frankfurt, Germany. He was Jewish. He spent many years as a professor of pharmacology at the University of Graz in Austria.
The origin of his pivotal experiment is rooted in a literal dream. Loewi himself confirmed this story on several occasions.
On the night of March 31, 1921, Loewi awoke suddenly from a dream with an experimental idea, which he quickly jotted down on a piece of paper. The next morning, he found that he couldn't decipher his own handwriting. The following night, he had the same dream again, and this time, he woke up completely and went to the laboratory. He started the experiment at 3 a.m. and completed it within a few hours.
The experiment was as follows: He prepared two frog hearts. One had an intact vagus nerve, and the other had the nerve removed. He placed the two hearts in separate containers of Ringer's solution, connecting the two solutions.
Now, he electrically stimulated the vagus nerve of the first heart. Stimulation of the vagus nerve is known to slow down the heart rate. As expected, the heart rate of the first heart slowed down. Surprisingly, the heart rate of the second heart β the one without the nerve β also slowed down a few seconds later.
The meaning of this result was clear: When the nerve of the first heart was stimulated, the nerve released a substance into the Ringer's solution, and this substance traveled to the second heart, slowing its heart rate. This was the first empirical evidence that nerves act on their targets chemically.
He named this unknown substance "Vagusstoff." He didn't know exactly what it was, but its existence was confirmed.
Dale β Identifying the Substance
Henry Dale was born in 1875 in London, England. He was a pharmacologist and worked at the National Institute for Medical Research in London.
Long before Loewi's 1921 experiment, Dale had been studying a chemical substance called acetylcholine. In 1914, he demonstrated that acetylcholine has potent physiological effects on various tissues β vasodilation, heart rate reduction, and muscle contraction.
After Loewi's 1921 experiment, the discoveries of the two researchers naturally came together. The physiological effects of acetylcholine, which Dale had identified, matched exactly the effects of Loewi's "Vagusstoff." Through 20 years of collaborative research, it was confirmed that Vagusstoff = acetylcholine.
Dale subsequently made crucial contributions to the identification of other neurotransmitters β norepinephrine and various amines. The "Dale's principle," which states that a neuron releases only one neurotransmitter (later partially modified), is also named after him.
Key Achievements β Serialized Synaptic Communication
Electrical β Chemical β Electrical
The two researchers established the multi-layered structure of signal transmission between neurons.
- An electrical signal (action potential) travels along the neuron A to the synapse.
- At the synapse, a chemical substance (acetylcholine, etc.) is released.
- The substance diffuses across the narrow synaptic cleft.
- It binds to receptors on neuron B.
- A new electrical signal is initiated in neuron B.
This electrical β chemical β electrical conversion occurs at every synapse.
The CS analogy applies perfectly here. This is similar to the serialization of network communication.
When two computers communicate over the Internet, what happens?
- Data in the memory of computer A exists in the form of bits/objects.
- To transmit, the data is serialized and converted into a byte stream.
- The byte stream travels across the network (cable, wireless).
- Computer B deserializes the data and restores it to an object.
Why is this multi-layered conversion necessary? Because the communication medium (network) cannot directly transmit the original data form. The object as it is cannot pass through the cable; the cable can only transmit bytes.
The synaptic cleft between neurons is the same. Electrical signals cannot directly cross the synaptic cleft. The cell membranes of the two neurons are insulators, and the ion concentration in the gap is regulated, limiting direct current flow. Therefore, it is converted into a chemical substance to cross this medium. On the other side, it is restored to an electrical signal.
However, this analogy breaks down here. In computer serialization, we design a protocol explicitly, and the original is restored accurately without any loss of information. However, in the chemical transmission of nerves, the signal is not simply transmitted; it is processed by a combination of various chemical substances and receptors, and its strength is amplified, reduced, or filtered. It is this chemical layer that creates most of the computational power of the nervous system. Today, it is said that the basic unit of brain computation is not a single neuron, but a single synapse.
Why Chemical?
The electrical theory seemed simpler, so why did evolution choose chemical transmission? The answer today is flexibility in information processing.
If the nervous system were purely electrical, the signals would simply be transmitted. However, chemical synapses are much more flexible:
- They can use different neurotransmitters to transmit various types of signals.
- They can adjust the number of receptors to achieve synaptic plasticity (long-term potentiation).
- They can filter, inhibit, or amplify signals with various modulatory substances.
This flexibility is what allows us to have a brain that can learn, remember, and experience emotions. A purely electrical nervous system would be limited to reflexes, while chemical synapses create a computational system that can be continuously reprogrammed.
Why It Matters
The Nobel Prize awarded to Dale and Loewi remains relevant today in three ways:
Pharmacology Level: All psychotropic drugs target chemical synapses. Antidepressants (serotonin reuptake inhibitors), antipsychotics (dopamine receptor blockers), benzodiazepines (GABA receptor modulators), ADHD medications β all these drugs adjust the balance of neurotransmitters at the synapse. The foundation of this pharmacology was laid by their discoveries.
Toxicology and Chemical Warfare Level: Nerve gases (sarin, VX), which target the acetylcholine system, block acetylcholinesterase (the degrading enzyme), causing continuous muscle contractions and death. Conversely, Alzheimer's drugs (donepezil, etc.) partially inhibit the same enzyme to enhance acetylcholine activity in the brain. The same target, but with drastically different purposes.
Neurosurgery and Anesthesiology Level: Neuromuscular blocking agents (used for muscle relaxation during surgery) are based on the principles of acetylcholine receptor regulation.
The lesson we can take away is: "Sometimes, the answer comes in a dream. But it is the act of putting that dream into practice that creates the discovery." Loewi had the idea in a dream, but if others had the same dream, they might have forgotten it the next morning. He went to the laboratory at 3 a.m. The execution is much more difficult and decisive than the idea. This principle is valid in software development and organizational management β there are many people with good ideas, but few who will execute them at 3 a.m.
Even as you read this sentence, countless synapses in your brain are releasing acetylcholine and other neurotransmitters. The chemical basis of this communication was revealed by a dream and a few hours of experimentation with frog hearts 100 years ago.
Summary of Chemical Synaptic Transmission: Loewi demonstrated through the frog heart experiment that nerves release a chemical substance when stimulated, and Dale identified that substance as acetylcholine. This discovery established the electrical β chemical β electrical model of synaptic communication, which became the foundation of 20th-century psychopharmacology and the treatment of neurological disorders.
β Experience it through coding: DevBench β Data Serialization and Network Transmission β Learn about CS concepts: DryBench β Protocol Layers and Form Conversion