1922 Nobel Prize in Physiology or Medicine — Archibald Hill and Otto Meyerhof
What You Will Learn
How our bodies “borrow” oxygen to keep us going during a sprint, and why our muscles are sore the next day – the story of the two who first quantified this.
Muscles Borrow Oxygen to Run
Imagine a sprinter running 100 meters. In those 10 seconds, the oxygen taken in by the lungs is nowhere near enough to meet the muscle's energy demands. Yet, the runner keeps going.
How? Because the muscles briefly activate a “backup” pathway to create energy without oxygen. This backup pathway is called glycolysis, and the byproduct is lactic acid. Muscles briefly “borrow” oxygen (oxygen debt) and pay it back later with heavy breathing after the sprint.
This diagram is now a staple in exercise physiology textbooks, but before Hill and Meyerhof quantified it in 1922, people fundamentally didn’t know how muscles generated energy. Their Nobel Prize was for the first quantitative measurement of the body’s energy accounting.
A Glimpse of the Era — The Roaring Twenties Begin
1922 was effectively the start of the Roaring Twenties. Insulin was administered to humans for the first time (January), Stalin became the General Secretary of the Communist Party of the Soviet Union (April), and Mussolini’s March on Rome made him Prime Minister of Italy (October). And the Irish Free State was officially established (December).
From the perspective of medical history, this period marked the beginning of biochemistry establishing itself as a separate discipline. Until then, the study of cellular metabolism was awkwardly positioned between chemistry and physiology. Hill and Meyerhof’s research attracted people to the clear theme of “chemistry within living cells,” and over the next two decades, biochemistry established itself as an independent field.
There is another symbolic element of the era. Hill was British, and Meyerhof was German. Just four years earlier, the two countries were at war. The fact that scholars from these two countries shared the award symbolized the international academic community’s reintegration after the war. The Nobel Committee often intentionally used such joint awards to symbolize reconciliation.
In parallel with Korean history, 1922 was the year the Japanese colonial government revised the Joseon Education Ordinance. It nominally expanded opportunities for Koreans to attend higher education, but de facto discrimination was maintained. While biochemistry was establishing itself as a discipline in Europe, there was no university in Korea where one could learn biochemistry in their own language. This gap led to a half-century of delay in Korean science.
The Two Men — A Quantitative Physicist and an Experimental Biochemist
Archibald Hill (A.V. Hill, 1886-1977) studied mathematics and physics at Cambridge. Even after switching to physiology, his approach remained physical. His paper, “The Thermodynamics of Muscular Contraction,” embodies this approach.
His key experiments were remarkably precise. He stimulated frog muscles to contract and then measured the heat generated during the process with great precision. The ultra-precise thermocouple he created could measure the time difference between muscle stimulation and heat generation in milliseconds.
His experiments revealed:
- Heat generated during muscle contraction occurs in two phases – immediate (simultaneous with contraction) + delayed (after contraction)
- Delayed heat is related to oxygen consumption – no delayed heat without oxygen
- Heat is generated even in static contraction (isometric contraction) – muscles use energy even without visible movement
Otto Meyerhof (Otto Meyerhof, 1884-1951) had the opposite background to Hill. He studied medicine and chemistry at Heidelberg and was interested in the chemical reaction pathways within living cells.
His experiments involved stimulating frog muscles without oxygen and then analyzing what chemical substances accumulated within them. This approach revealed:
- When stimulated without oxygen, muscles accumulate lactic acid
- This lactic acid comes from glycogen (stored glucose)
- When oxygen is reintroduced, some of the lactic acid is converted back to glycogen – recycled
Meyerhof was Jewish. This fact cast a dark shadow over his career. In 1938, as the Nazis’ persecution of Jews intensified, he fled to France and then to the United States. He spent the rest of his life in Philadelphia, contributing to the development of American biochemistry. The cruelty of the 20th century, in which even a Nobel laureate had to be driven from his country because of his race, left a deep mark on his life.
Key Achievements — The Body’s Energy Accounting
Oxygen Debt: The Concept of Oxygen Debt
The concept of oxygen debt established by Hill is still a fundamental principle of exercise physiology today. The picture looks like this:
- Resting state – muscles metabolize normally with oxygen. ATP regeneration is balanced with oxygen supply.
- Start of intense exercise – ATP demand exceeds oxygen supply.
- Anaerobic metabolism is activated – ATP is produced through glycolysis, and lactic acid accumulates.
- End of exercise – heavy breathing. Excess oxygen processes the accumulated lactic acid and recovers the muscles.
The name itself, “oxygen debt,” is an accounting metaphor. Muscles briefly “borrow” oxygen and pay it back later. If they can’t pay it back (after prolonged intense exercise), it leads to severe fatigue and muscle soreness.
A CS analogy fits naturally here. This is a runtime energy profiler + backup process mode. In a normal state, the standard pipeline (aerobic metabolism) runs, but when the load surges, the system temporarily turns on a less efficient backup process (anaerobic glycolysis) to absorb the momentary load. Instead, byproducts (lactic acid) are queued up and the queue is cleared with spare resources (recovery oxygen).
However, this analogy breaks down here. Software backup processes can be turned on predictably at any time, but the muscle’s anaerobic mode is determined locally by individual cells. There is no coordination between neighboring cells, so some cells may already be overflowing with lactic acid while other cells are still in normal metabolism. The lack of coordination in a distributed system creates this imbalance.
Meyerhof Pathway: The Chemical Pathway to Lactic Acid
The chemical pathway revealed by Meyerhof is largely what we now call glycolysis. The steps he specifically identified:
- Glycogen → glucose-1-phosphate → glucose-6-phosphate
- Through several steps → pyruvate
- In the absence of oxygen, pyruvate → lactic acid
- In the presence of oxygen, pyruvate → mitochondria → complete oxidation → CO₂ + H₂O
This pathway came to be known as the Embden-Meyerhof pathway and became the first metabolic pathway in biochemistry textbooks. Today, this is the metabolic pathway that first-year medical students learn.
If we summarize it with a CS analogy, Meyerhof’s discovery is like reverse-engineering the way a compiler generates an optimized sequence of instructions. Having only known the input (glucose) and output (energy currency ATP), he revealed each of the precise instruction sequences (enzymatic reactions). This approach became the prototype for all subsequent metabolic pathway research.
The Integration of the Two: The Meeting of Power and Chemistry
It is symbolic that Hill (physical thermodynamics) and Meyerhof (chemical metabolic pathways) shared the award. This is because the two approaches were integrated into one picture:
- Hill’s delayed heat = Meyerhof’s oxygen-restoring metabolism
- Hill’s oxygen debt = Meyerhof’s lactic acid accumulation
- Hill’s immediate heat = Meyerhof’s energy release during glycolysis
This integration marked the beginning of a field called bioenergetics. Today, we deal with this big picture with concepts such as ATP, ADP, NAD⁺/NADH, and mitochondrial electron transport chains.
Why It Matters
The Nobel Prize awarded to Hill and Meyerhof was a recognition that “the chemistry of the living body can be understood quantitatively.” Before them, metabolism was a qualitative picture – this comes from that, and this is needed. After the two, metabolism becomes numerical – with how many millimoles, in how many seconds, with how many kilojoules.
The greater significance is the establishment of the concept of “energy accounting” itself. Today, when we talk about dieting, we say “calories in, calories out.” When athletes adjust their training intensity, they use this accounting. And when diagnosing metabolic diseases (diabetes, obesity, thyroid disorders), we use this accounting. All of this is built on the framework established by the two.
There is a lesson to be learned: “Try combining physics and chemistry in one experiment.” If Hill had only looked at thermodynamics, his experiment would have only shown the energy flow within a black box. If Meyerhof had only looked at chemistry, he would not have known how fast the reactions were. The integration of the two produced the real picture. The walls between disciplines are often imaginary walls.
While you are reading this sentence, the Hillian thermodynamics and Meyerhofian chemistry are working together in every muscle cell in your body.
Summary of Muscle’s Dual Metabolic Modes: When oxygen is sufficient, complete oxidation (glucose → CO₂ + H₂O) produces the maximum ATP. When oxygen is insufficient, anaerobic glycolysis (glucose → lactic acid) produces ATP rapidly but inefficiently. Accumulated lactic acid is processed by oxygen during recovery after exercise, which is the repayment of the oxygen debt.
→ Experience with coding: DevBench — Fallback Mode and Load Absorption → Learn about CS concepts: DryBench — Energy Profiling and Accounting