August Krogh: Discoverer of the Capillary Motor Regulation Mechanism and Pioneer of Microcirculation Physiology (1920)

Nobel Information Card

• Award Year: 1920
• Field: Physiology or Medicine
• Award Rationale: For the discovery of the capillary motor regulation mechanism.
• Birth: 15 November 1874, Grenaa, Denmark
• Death: 13 September 1949, Copenhagen, Denmark
• Nationality: Danish
• Institution: University of Copenhagen

Life and Education

Schack August Steenberg Krogh was born on November 15, 1874, in the small town of Grenaa on the Jutland Peninsula in Denmark. His father, Viggo Krogh, was a shipbuilder, while his mother, Marie Drechmann, was the daughter of a brewer. Growing up in this coastal town with a strong maritime and craft tradition, Krogh developed an early fascination with nature and animals. The hours he spent by the sea instilled in him a habit of natural observation that would later influence his direction towards comparative physiology.

After completing his high school education in Aarhus, Krogh enrolled at the University of Copenhagen in 1893. Initially he intended to study physics and mathematics, but he was drawn to biology under the influence of zoology professor William Sørensen. In 1897 he joined the laboratory of Christian Bohr (father of the renowned physicist Niels Bohr), then professor of physiology at the university. This encounter fundamentally shaped Krogh's scientific career. Bohr was conducting significant research in respiratory physiology and trained Krogh in this field.

In 1903 Krogh received his doctorate from the University of Copenhagen with a thesis on the mechanism of cutaneous respiration in frogs. This work was an early example of the comparative-physiology approach and was the first evidence of the methodological rigor that would mark Krogh's entire career. In 1916 he was appointed professor of zoophysiology at the University of Copenhagen, a position he held until the end of his life.

The personal life of Krogh was intertwined with his scientific career. He married Marie Jorgensen in 1905. Marie was an accomplished scientist in her own right and actively participated in many of Krogh's research projects. They particularly collaborated on studies in the fields of metabolism and nutrition physiology. This scientific partnership is considered one of the most productive joint efforts in the history of science. The couple had four children.

Scientific Work

August Krogh's scientific career is characterized by an exceptionally broad range of physiological investigations. He conducted pioneering work in respiratory physiology, gas exchange, capillary circulation, comparative physiology, insect physiology, and metabolism. A distinctive feature of Krogh's approach was selecting the most suitable experimental organism for each physiological question he sought to investigate. This principle would later be formulated as the Krogh principle: for every biological problem there is an optimal organism on which it is most conveniently studied.

Krogh's early work focused on respiratory physiology. His mentor Christian Bohr argued that gas exchange in the lungs occurred via an active secretion mechanism. Krogh tested this hypothesis with painstaking experiments and ultimately proved his mentor wrong: gas exchange in the lungs is achieved by passive diffusion, not active secretion. This bold scientific conclusion was strong evidence of Krogh's intellectual independence and experimental rigor. Refuting his mentor's theory was not an easy decision, but Krogh considered following the data more important than personal loyalty.

By developing the concept of the diffusion constant, Krogh made it possible to model gas exchange in the lungs mathematically. He measured the diffusion rates of oxygen and carbon dioxide across the pulmonary membrane and showed that these values were sufficient to meet metabolic needs. This work laid the foundations of respiratory physiology.

From the 1910s onward, Krogh's research focus shifted gradually to capillary circulation. The trigger for this shift was his effort to understand how tissues meet their oxygen demand. If oxygen is transported by diffusion, then the distribution of oxygen within tissues depends directly on the structure and function of the capillary network. To investigate this question, Krogh used transparent tissues such as the frog mesentery, where the capillary network could be observed directly under the microscope.

The Discovery That Led to the Nobel Prize

The discovery for which Krogh was awarded the Nobel Prize was the demonstration that capillary circulation has an active regulatory mechanism. In the early 20th century the prevailing view was that capillary vessels were passive, elastic tubes and that blood flow was regulated solely by pressure changes in the arterioles. Capillaries themselves were thought to have no capacity to regulate blood flow.

By observing capillary networks directly under the microscope in frog muscle and mesentery, Krogh made a revolutionary discovery. He observed that in resting tissues the great majority of capillaries were closed or carried no blood flow. When the tissue was activated (for example when a muscle contracted), previously closed capillaries opened and blood flow increased dramatically. This observation proved that capillary blood flow is not a passive process but an actively regulated mechanism.

Krogh thoroughly examined the mechanism of capillary regulation. He showed that the opening and closing of capillaries was controlled by the contraction and relaxation of smooth muscle cells in the walls of capillaries or precapillary sphincters. An increase in tissue metabolism led to the release of local chemical factors (metabolites), which triggered the opening of capillaries. This mechanism ensured that tissues' increased oxygen needs were met precisely.

Krogh also revealed the quantitative aspect of capillary regulation. He showed that the number of active capillaries in a resting muscle is only a small fraction of the total number of capillaries. During muscle activity the number of active capillaries increases dramatically, shortening the diffusion distance and optimizing oxygen distribution. By modeling this process mathematically, Krogh developed the concept of the Krogh cylinder: each capillary supplies oxygen to a defined surrounding tissue volume, and as more capillaries open this volume shrinks and oxygenation improves.

Krogh's discovery of capillary regulation had far-reaching consequences in fields such as exercise physiology, shock pathophysiology, and tissue perfusion. How blood flow increases in muscles during exercise, why microcirculation breaks down in shock, and why tissue oxygenation can be insufficient in chronic disease all became intelligible in the light of Krogh's discovery.

The Prize and Its Aftermath

In 1920 the Nobel Prize in Physiology or Medicine was awarded to August Krogh for the discovery of the capillary motor regulation mechanism. Krogh received the prize in person at the ceremony in Stockholm. In his Nobel lecture he set out in detail the physiology of capillary circulation and his own experimental approach, and emphasized the importance of choosing the right experimental model in physiological research.

After the Nobel Prize, Krogh broadened his research. He carried out wide-ranging studies on insect physiology, including pioneering investigations of the insect respiratory system (the tracheal system), osmoregulation, and metabolism. His 1924 book Comparative Respiratory Physiology became the standard reference work in the field.

One of Krogh's significant contributions in the 1920s was developing the technique for tracing metabolic processes using heavy water (deuterium oxide). He pioneered the use of isotopic tracer techniques in physiological research. This approach would later form the basis for nuclear medicine and metabolic imaging.

In 1922, during a visit to Canada, Krogh learned of Frederick Banting and Charles Best's discovery of insulin. The fact that his wife Marie was a diabetic gave him a particular personal interest in the subject. On his return to Denmark he co-founded the Nordisk Insulinlaboratorium together with Hans Christian Hagedorn. This laboratory was the first European institution to produce insulin industrially and later became the foundation of the Novo Nordisk company. Today Novo Nordisk is one of the world's largest manufacturers of diabetes medications.

Krogh was deeply affected by the effects of World War II on Denmark. During the German occupation (1940-1945), research opportunities were limited. Krogh died on September 13, 1949, at the age of seventy-four in Copenhagen.

Legacy and Impact Today

The scientific legacy of August Krogh has left deep imprints in many subfields of physiology. The discovery of capillary motor regulation forms the foundation of microcirculation physiology. Today, microcirculation disorders play a central role in the pathophysiology of various clinical conditions such as diabetes, hypertension, sepsis, and chronic wounds.

The Krogh cylinder model remains widely used for mathematical analysis of tissue oxygenation. In tumor biology, Krogh's capillary diffusion model continues to serve as a fundamental reference for understanding angiogenesis and hypoxic regions. Anti-angiogenic strategies in cancer treatment rely on knowledge of capillary network regulation.

The Krogh principle is considered a fundamental methodological principle in comparative physiology and experimental biology fields. The principle of selecting an experimental organism according to the research question forms the basis of the concept of a model organism.

The role of Novo Nordisk's founding reflects Krogh's vision for converting scientific discoveries into industrial applications. Today, Novo Nordisk provides insulin and other diabetes treatments to millions of people worldwide.

Lesser-Known Facts

• Krogh experimentally refuted his mentor Christian Bohr's lung-secretion theory, demonstrating that scientific honesty must come before personal loyalty. This courage is regarded as an important example of scientific ethics.
• Krogh's wife Marie was an active partner in many of his investigations. They jointly carried out studies in metabolism and nutritional physiology.
• Krogh used part of his Nobel Prize money to help establish an insulin-production facility. This investment became the foundation of Novo Nordisk.
• The Krogh principle is a methodological precept widely known and still applied among biologists. It recommends choosing the most suitable model organism for each biological question.
• Krogh also did pioneering work in insect physiology. His research on the tracheal respiratory system and osmoregulatory mechanisms of insects helped lay the foundations of entomology.
• Christian Bohr was the father of the famous physicist Niels Bohr. As Krogh's mentor, he is indirectly linked to the story of two Nobel-winning families.
• Krogh was an exceptionally skilled instrument maker. He designed and built many of his experimental instruments with his own hands; this practical talent gave him a great advantage in developing his original experimental approaches.