1920 Nobel Prize in Physiology or Medicine — August Krogh

What You Will Learn in This Article

You will understand why most of the capillaries in our muscles are usually closed and only open during exercise, and how this discovery is connected to the commercialization of insulin and even the Danish pharmaceutical industry.

The Discovery of Closed Pipes

The total length of capillaries in our body is about 100,000 km, which is two and a half times the circumference of the Earth. What would happen if all these capillaries opened at the same time? The blood in our body would not be enough to fill such a vast space, causing severe hypotension.

What Krogh discovered was that most of the capillaries in our body are closed at rest and only open in the tissues that need them. When a muscle is at rest, most of its capillaries are closed, and when it starts to exercise, they open one by one as needed. It is like the lights in an office that only turn on in the occupied spaces.

This regulation is highly precise and localized. It is not controlled by the brain in a centralized manner, but rather each tissue opens and closes the capillaries near it according to its own metabolic state. Today, we call this local metabolic regulation.

The Landscape of the Time — Quiet Copenhagen

Europe in 1920 was in the process of rebuilding. The Treaty of Versailles had been ratified (January 1920), the League of Nations was established, and the Allied nations were trying to establish a new order amidst the ruins.

Amidst this upheaval, Denmark was in a unique position. After losing Schleswig-Holstein in the 1864 war against Prussia and Austria, Denmark became a small country on the international stage. However, it focused on domestic cooperative movements and public education, becoming a quiet model society in Europe. Nikolaj Grundtvig's folk high school movement, agricultural cooperatives, and worker education — these were the infrastructures that created Denmark's knowledge society.

The fact that Krogh was able to continue his quiet experiments at the University of Copenhagen was due to this social stability. His laboratory functioned normally throughout World War I. While his colleagues in Paris, Berlin, and London were being drafted into the trenches and their experiments were being interrupted, Copenhagen quietly continued its progress.

When compared to Korean history, 1920 was the year when the Japanese colonial government's rule changed from military rule to cultural rule. In response to the March 1st Movement, the colonial government adopted a seemingly more lenient policy, but its actual control continued. The quiet progress of Denmark contrasts with the turbulent situation in Korea, which symbolizes the differences between nations in this era.

From a medical history perspective, 1920 was the year that microcirculation research became established as an academic field. Until then, circulatory research had focused on the heart and major blood vessels. Capillaries were difficult to observe, and it was extremely difficult to conduct experiments that involved manipulating individual capillaries. Krogh's Nobel Prize established this difficult field as an academic discipline.

The Story of the Man — The Artisan of Glass Tubes

Krogh was born in 1874 in Grena, Denmark. His father was a naval officer involved in shipbuilding, and young Krogh learned glassblowing as an amateur. This skill would become a key factor in his scientific career.

He studied zoology and physiology at the University of Copenhagen, and then conducted research under Christian Bohr — not the Einstein of light quanta, but his father. Bohr was a researcher of oxygen and blood interaction, and Krogh learned from him quantitative methods for measuring respiration and circulation.

Krogh's experimental style was extremely precise. He made the experimental tools he needed by blowing glass himself. The very small micromanometers, ultra-precise gas analyzers, and microchambers for muscle observation that he created allowed his experiments to be one or two orders of magnitude more precise than those of others at the time, as commercially available products did not exist.

One of the most famous of these is the Krogh spirometer. This device, which precisely measures human breathing, became the standard tool for respiratory physiology laboratories around the world for the next half-century. When his laboratory began commercially producing and selling this device, it contributed to the finances of the University of Copenhagen.

Another famous story is his collaboration with his wife, Marie Krogh. Marie obtained her medical degree after marrying him and conducted research together with him. The two were one of the first male-female research teams in the field of respiration and circulation. After Krogh's Nobel Prize, she continued her own research, contributing to various fields of clinical medicine.

Key Achievements — The On-Demand Pipe System

Sleeping Capillaries and Activation

Krogh's key observation came from a very simple experiment. He thinly sliced a frog muscle, placed it under a microscope, and observed the capillaries when the muscle was stimulated and when it was not. He discovered the following:

• Resting muscle: Blood does not flow through most of the capillaries; only a few are open.
• Active muscle: A dramatically larger number of capillaries open; the number increases in proportion to the activity.

Why is this observation surprising? Until then, the common understanding was that capillaries were always open, passive pipes. Krogh overturned this: capillaries are an actively regulated system that opens and closes as needed.

The CS analogy fits naturally here. This is on-demand autoscaling. In cloud systems, we don't keep the maximum capacity of servers running all the time. When traffic increases, we spin up new instances and shut them down when the traffic decreases. Capillary regulation works on exactly the same principle:

• Baseline: Only the minimum number of instances are open (energy saving).
• Load detection: Detects the accumulation of metabolic substances (CO₂, lactic acid, ADP, etc.) in the tissue.
• Scale out: The sphincter muscles of nearby capillaries relax, and new capillaries are activated.
• Scale in: After the metabolism normalizes, they close again.

However, this analogy breaks down here. Cloud autoscaling is determined by a central controller, but capillary regulation is a completely distributed, autonomous system. The sphincter muscles in front of each capillary respond to local signals from nearby tissues and decide independently. It is pure P2P coordination without a central control tower.

Krogh Cylinder Model

Krogh modeled this discovery mathematically. This model, called the Krogh cylinder model, places each capillary in the center of a cylindrical volume of tissue and calculates the diffusion of oxygen within that cylinder.

This model is the foundation of microcirculation theory still used today. Whether a tissue is oxygen-deficient, whether a tumor is hypoxic, or which muscle needs more capillaries — this model provides the framework for answering all these questions.

Krogh Principle: Choose the Right Animal

Krogh's second legacy is methodological. He said, "For every problem, there is an animal best suited to its study." This is the adage we now call the "Krogh principle."

Krogh himself put this principle into extreme practice. For respiratory research, he used frogs, fish, insects, cows, and humans — he chose the animal that was best suited for each problem. His laboratory was, in effect, a small zoo.

This principle became the basis for several discoveries that would later win the Nobel Prize. The giant axon of the squid (Hodgkin and Huxley, 1963), the genetics of fruit flies (Morgan, 1933), and the development of the nematode worm (Brenner, Horvitz, and Sulston, 2002) — all of these are examples of the Krogh principle in action.

Insulin and Novo Nordisk

Krogh's career has an interesting commercial side. In 1922, when Banting and Macleod discovered insulin (Nobel Prize in 1923), Krogh and his wife Marie went to Canada to learn the technique. This was partly because Marie herself was a diabetic.

They returned to Denmark and established the Nordisk Insulin Laboratory in 1923. This laboratory later became Novo Nordisk — today the world's largest insulin company. Krogh's Nobel Prize was for pure scientific research, but one of his legacies was the formation of the Danish pharmaceutical industry in the latter half of the 20th century.

Why It Matters

Krogh's Nobel Prize was the establishment of the understanding that "small tissues themselves regulate their own resources." Until then, the understanding of circulation was centered on the heart — the heart pumps, blood is distributed, and the tissues are passive recipients. After Krogh, circulation is understood as a system in which each tissue actively demands and receives resources according to its own needs.

The broader meaning is the establishment of the concept of a distributed autonomous system in physiology. The brain does not control everything; each part makes local decisions, and the sum of these local decisions leads to the overall optimum. This is the foundation of today's understanding of the integration of the nervous, immune, and metabolic systems.

There is a lesson for us. It is that "those who can make their own tools eventually see what others cannot." If Krogh had not known how to blow glass, his experiments would have been impossible. Today, we rely on commercial tools, but true innovation often comes from those who make their own tools. His legacy is a reminder of this principle.

Right now, as you read this sentence, the capillaries in the tissues that need it in your body are open, and the capillaries in the tissues that don't need it are closed, and this regulation is continuing. Krogh was the one who first showed this picture to the world.

Summary of On-Demand Capillary Regulation: In the baseline state, most capillaries are closed by sphincter muscles. Metabolic substances (CO₂, lactic acid, etc.) in the tissue act as local signals, relaxing the nearby sphincter muscles and opening the capillaries to supply oxygen. After the metabolism normalizes, they close again.

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