1938 Nobel Prize in Physiology or Medicine — Corneille Heymans

What You Will Learn

You will understand why our breathing rate is automatically adjusted based on activity level, and how a father-son team of scientists in Belgium discovered the two small sensors in our body responsible for this regulation.

Why Do We Automatically Breathe Faster When Climbing Stairs?

When you run up a flight of stairs, you start breathing faster within seconds. You didn’t consciously tell yourself, “Now I need to breathe faster.” Conversely, we continue to breathe even while we are asleep.

This automatic regulation of breathing has long been a mystery. What determines the rate of our breathing? Where is this regulatory mechanism located in our body?

Up until the early 20th century, the prevailing answer was that the respiratory center in the brainstem autonomously generates the rhythm of breathing. This answer was partially correct. There is indeed a respiratory center in the brainstem. However, how this center adjusts breathing intensity in response to activity remained unresolved.

The Heymans laboratory at the University of Ghent, Belgium, provided the missing piece of the puzzle. Their discovery revealed that chemical sensors located throughout the body detect real-time levels of oxygen, carbon dioxide, and pH in the blood and send signals to the brainstem to regulate breathing.

Critically, they found that a small tissue near the carotid sinus – what we now call the carotid body – was a major site of this detection.

The Zeitgeist — On the Cusp of European Collapse

In 1938, the world was in the year before the virtual certainty of World War II.

In March, Nazi Germany annexed Austria. Nazi troops marched into Austria without firing a single shot. Austrian Jewish scientists, including Loewi (the 1936 laureate), began mass emigration at this time.

In September, the Munich Agreement was signed. Britain and France agreed to allow Nazi Germany to annex Czechoslovakia in exchange for Hitler’s promise to make no further territorial demands. Hitler broke this promise within six months. In March of the following year, he fully annexed Czechoslovakia, and in September, he invaded Poland.

On the nights of November 9th and 10th, Kristallnacht took place. Jewish shops and synagogues throughout Nazi Germany were systematically destroyed. This was the direct prelude to the Holocaust.

During this period, Belgium, where Heymans worked, was nominally neutral. However, during the Nazi invasion of Western Europe in May 1940, Belgium was occupied within five days. Heymans’ Nobel Prize was awarded during this brief period of relative peace.

In the Far East that year, the Second Sino-Japanese War continued. After the Nanjing Massacre (December 1937), the Chinese Nationalist government retreated to Chongqing and continued to resist, while the Communist Party rebuilt in Yan'an.

When viewed in conjunction with Korean history, 1938 was the year that the National Mobilization Law was extended to Korea. This law provided the legal basis for the total mobilization of Korean labor and resources for the war effort. During this period, a system was created in Korea in which the country’s labor and resources were automatically redistributed according to the needs of the Empire of Japan. In Europe, the year saw the discovery of the automatic regulatory system within the body; in Korea, a system for the automatic mobilization of human society was being forcibly established.

Biographical Narrative — A Son Completes His Father’s Experiment

Corneille Heymans was born in Ghent, Belgium, in 1892. The most remarkable aspect of his story is that his father, Jean-François Heymans, was also a renowned pharmacologist. This is a case of a son continuing and completing the research begun by his father.

Jean-François, Corneille’s father, was a professor of pharmacology at the University of Ghent and had been interested in the connection between blood circulation and respiratory regulation since the 1920s. He had been approaching this problem through experiments involving connected dogs (cross-circulation).

Corneille’s crucial experiment was an extension of his father’s approach. He designed the experiment as follows:

He prepared two dogs. One would be the “donor dog,” and the other would be the “recipient dog.” The circulatory systems of the two dogs were partially connected, so that blood from the donor dog flowed into the recipient dog. Crucially, the recipient dog’s brain received blood only from the donor dog.

The donor dog was then subjected to various stimuli. The donor dog was made to breathe air with low oxygen content or to produce blood with high carbon dioxide levels. Then, the recipient dog’s brain was exposed to this altered blood from the donor.

The observations: When the blood chemistry of the donor changed, the recipient’s breathing immediately changed. If the oxygen level in the donor’s blood decreased, the recipient’s breathing became faster; if the carbon dioxide level increased, the recipient’s breathing became even more intense.

This experiment was decisive. It revealed how the brainstem detects blood chemistry — the answer was that the brainstem itself does not directly detect it, but rather that sensors in other parts of the body detect it and send signals to the brainstem.

Localization of the Crucial Site

In subsequent experiments, Heymans observed that if the carotid sinus and the area near the aortic arch were separated from the brainstem by severing the nerves connecting them, respiratory regulation was disrupted. These two sites were the chemical sensing centers.

This location is not accidental. The carotid artery is a major blood vessel that carries blood to the brain. The aortic arch is the major blood vessel that emerges from the heart. Both sites are ideal locations for monitoring real-time blood chemistry. Evolution had placed sensors in these crucial locations.

Key Contributions — Automatic Regulation Viewed Through the Lens of Sensor Interrupts

Real-Time Detection + Immediate Response

The system that Heymans elucidated is as follows:

1. The carotid body and aortic body chemoreceptors detect real-time levels of O2, CO2, and pH in the blood.
2. The detected results are transmitted to the respiratory center in the brainstem via the glossopharyngeal nerve and the vagus nerve.
3. The brainstem center sends commands to the diaphragm and intercostal muscles based on this information.
4. Breathing rate and depth are adjusted.

This entire process is completed within seconds. This is why we start breathing faster a few seconds after we begin climbing stairs.

A CS analogy is useful here. This is similar to a hardware sensor interrupt.

In a computer system, how does the CPU manage temperature? The CPU itself does not monitor the temperature. Instead, temperature sensors (located throughout the chip) detect the temperature in real time, and if a certain threshold is exceeded, they send an interrupt signal to the CPU. The CPU, upon receiving the interrupt, temporarily suspends its current task and executes a response, such as adjusting the fan speed or throttling the clock speed.

A three-step structure of sensor → interrupt → response. The respiratory regulation system that Heymans elucidated is precisely this structure.

• Sensor: Carotid body and aortic body
• Interrupt: Transmission of a nerve signal to the brainstem
• Response: Changes in respiratory muscle commands

Why is this structure useful? Because it eliminates the need for the CPU (brainstem) to expend resources on detection itself. If the brainstem had to actively monitor blood chemistry every moment, this would consume a significant amount of resources. By delegating this detection to dedicated sensor tissues and receiving only the results as a signal, the brainstem can focus on higher-level regulation. A distributed sensing, centralized decision-making architecture.

However, this analogy breaks down at this point. The sensor-interrupt system in computers is something we explicitly design, and the detection target of each sensor and the response rules are clear. However, the chemoreceptors in the body detect multiple substances simultaneously and create signals based on their relative strengths. A single carotid body cell responds to all three elements: O2, CO2, and pH. How this complex detection is integrated into a single signal remains, in part, a subject of research today.

Blood Pressure Regulation Follows the Same Framework

Heymans’ discovery was extended to blood pressure regulation, not just respiration. Near the carotid sinus, there are not only chemoreceptors but also baroreceptors that detect blood pressure in real time and send signals to the brainstem. These signals automatically adjust heart rate and blood vessel constriction.

The brief period of dizziness experienced when sitting down and standing up suddenly is due to the delay in this system. When posture changes, blood pressure in the brain temporarily drops, and it takes 1-2 seconds for the baroreceptors to detect this and adjust heart rate and blood vessel constriction. During this time, blood flow to the brain is temporarily reduced.

The reason why the elderly often experience dizziness is related to the slowing down of this automatic regulation system. As people age, this automatic regulation slows down.

Why Is It Important?

Heymans’ Nobel Prize remains relevant today at three levels.

Clinical Level: Sleep apnea, COPD, chronic heart failure, and high-altitude sickness are all related to normal/abnormal functioning of the chemoreceptor system. For example, in chronic hypoxia (high altitude, chronic lung disease), chemoreceptors recalibrate and may even perceive normal oxygen levels as a stimulus. This principle is reflected in various clinical treatment strategies.

Anesthesiology Level: The management of a patient’s breathing, heart rate, and blood pressure during anesthesia is based on an understanding of this chemoreceptor and baroreceptor system. How much a particular anesthetic agent inhibits this regulation is a fundamental concept in anesthesiology.

Space Medicine and Aviation Medicine Level: The prediction and regulation of this system are essential in high-altitude training, diving training, and spaceflight for dealing with low pressure and low oxygen.

The lesson it teaches us is: “To create a control system, separate detection, decision, and response.” If a single unit tries to do all three – detect, decide, and respond – that unit becomes a bottleneck. The body wisely solved this problem by delegating detection to distributed, specialized sensors, decision-making to the central brainstem, and response to multiple muscles. This principle is valid today in software architecture, organizational design, and even smart home systems.

Even as you read this sentence, your carotid bodies are detecting blood chemistry several times per second and sending signals to your brainstem. The system of real-time regulation was revealed in an experiment involving two connected dogs conducted 90 years ago in Ghent.

Chemoreceptors and Automatic Respiratory Regulation Summary: Heymans demonstrated through an experiment connecting two dogs in a circulatory system that chemoreceptors are located not in the brainstem but in other parts of the body (carotid body and aortic body), which detect real-time levels of O2, CO2, and pH in the blood. This discovery revealed the fundamental structure of the automatic respiratory and cardiovascular regulation system, and it is now the basis of anesthesiology, pulmonology, and sleep medicine.

→ Experience it with code: DevBench — Sensor Interrupts and Event Loops → Learn about CS concepts: DryBench — Distributed Sensing and Centralized Decision-Making Architecture