1970 Nobel Prize in Physiology or Medicine: Katz, Euler, and Axelrod – Release, Transmission, and Degradation of Neurotransmitters

What You Will Learn From This Article

If the 1963 Prize (Eccles, Hodgkin, and Huxley) elucidated signal transmission in neurons, the 1970 Prize completes the chemical lifecycle of the synapse. Learn how Katz discovered the mechanism of acetylcholine release, Euler identified adrenaline as a neurotransmitter, and Axelrod revealed its metabolic pathway. Also, understand how these discoveries are the theoretical foundation for today's emergency cardiac resuscitation and SSRI antidepressants.

Beyond Common Knowledge: What Happens to Signals After They Are Released?

Following the discovery of the 1963 Prize – that chemical neurotransmitters are released at the synapse – three unresolved questions remained.

• How is it released? The precise mechanism across the cell membrane.
• What substances are neurotransmitters? Is it only acetylcholine, or are there others?
• After release, how is the substance processed? Does it simply remain in the synapse?

Let's set the background first. Acetylcholine is a neurotransmitter secreted at the terminals of motor and parasympathetic nerves, carrying out several important functions in the body such as lowering blood pressure and contracting muscles. Acetylcholine itself was first isolated in 1914, and its function was elucidated by the German physiologist Loewi, who received the 1936 Nobel Prize in Physiology or Medicine for that work. Still, an open puzzle remained — where and how is acetylcholine actually released, and once its task is done, what happens to it afterward? Sir Bernard Katz set out to answer exactly this release mechanism.

In other words, the 1936 Nobel Prize to Loewi identified acetylcholine as a neurotransmitter, and the 1970 Prize elucidated the complete lifecycle (release, action, and degradation) of this substance.

In the language of computer science, this problem is about understanding the complete lifecycle of a message queue system. The entire process from when a message is issued by a publisher, enters the queue, and is processed by a subscriber, and then cleaned up. If signals are only transmitted and not cleared, the system will enter an infinite loop. Therefore, the cleanup phase is crucial.

The Zeitgeist: Korean Labor Issues and the Global Shift to the Left

1970 was the year when Korean labor issues and the global political shift to the left occurred simultaneously.

In Korean history, Jeon Tae-il, a 22-year-old worker, immolated himself on November 13th at the Cheonggyecheon Peace Market, demanding compliance with labor laws. "We are not machines" was his final cry. This event served as a crucial awakening for the Korean labor movement. In April, the Saemaul Movement began – the Park Chung-hee regime's rural modernization program.

In world history, Salvador Allende was inaugurated in November as the world's first democratically elected socialist president in Chile. Although he died three years later in the Pinochet coup, he became a symbol of left-wing politics in Latin America. In September, Anwar Sadat took office as president after Nasser's death in Egypt. In April, Apollo 13 faced a crisis – an oxygen tank exploded on the spacecraft en route to the moon, and the three astronauts made a dramatic return.

In this turbulent year, the Nobel Committee recognized the lifecycle of neurotransmitters. At a time when the question of how an individual's body responds to political power was particularly salient, the mechanism of how signaling molecules within the body are precisely managed was revealed.

The Three Laureates: London, Stockholm, and NIH

Sir Bernard Katz (1911-2003) was a British physiologist. He received his PhD from the University of London (1938), was a professor at the University of London (1952-1978), and was knighted by the British monarchy in 1969. He had a history of fleeing Nazi Germany to Britain because he was Jewish.

Ulf von Euler (1905-1983) was a Swedish physiologist. He received his PhD from the Karolinska Institute (1930) and served as a professor at the Karolinska Institute (1930-1971) for 41 years. He also served as the director of the Nobel Foundation from 1965 to 1975 – he was in charge of the operation of the Nobel Prize itself.

Julius Axelrod (1912-2004) was an American pharmacologist. He received his PhD from the University of Washington (1955), was a researcher at the National Heart Institute in Bethesda, USA (1950-1955), and served as the chief of the Pharmacology Department at the National Institute of Mental Health (1955-1984) for 30 years.

Axelrod's life story is one of the most moving of the entire award.

His trajectory contrasts sharply with that of most Nobel laureates. His father, a Polish Jewish immigrant, barely scraped a living together as a craftsman. Axelrod, who had aspired to medicine since childhood, managed to enroll at New York University, but his family's financial straits kept pushing back the timing of graduate school.

Put plainly — he came from a poor Polish immigrant family, barely made it into New York University, worked in industry for a long stretch, and only reentered academia after finishing his PhD in 1955 at the age of 43. It was an unusually late start for a Nobel laureate.

The Three Discoveries: Three Stages of the Synaptic Lifecycle

Katz's discovery: the mechanism of release. The precise mechanism by which acetylcholine is released into the synapse. His key observation was quantal release. At the nerve terminal, acetylcholine is released in individual vesicles, and each vesicle contains approximately a fixed number of acetylcholine molecules. When a stimulus arrives, multiple vesicles are released simultaneously.

This discovery is significant. Acetylcholine release is discrete rather than continuous – one vesicle at a time. This discreteness is the basis for the statistical properties of synaptic signal transmission (miniature end-plate potentials, or mEPPs). Katz also discovered that Ca2+ ions trigger the release.

Euler's discovery: adrenaline as a neurotransmitter. Euler's decisive measurement showed that the substance secreted by the axon terminals of sympathetic neurons is the same as the hormone secreted by the adrenal medulla. Once this identity was established, adrenaline extracted from the adrenal medulla was subsequently used far more widely as a drug for regulating various physiological functions.

Adrenaline (epinephrine) has long been known as a hormone secreted by the adrenal glands, but Euler demonstrated that it is also a neurotransmitter of the sympathetic nervous system. More precisely, noradrenaline (norepinephrine) is the neurotransmitter of the sympathetic nervous system, and the adrenal gland modifies it into adrenaline. This demonstrates a substance that performs two roles: as a hormone and as a neurotransmitter.

The clinical implication of this finding is significant. Adrenaline accelerates the heart and raises blood pressure, making it a mainstay in emergency medicine — but overuse invites side effects like stroke or myocardial infarction. This is precisely why, once adrenaline has been administered as a treatment, there must be an efficient pathway to break it down quickly so that it does not linger in the body.

Axelrod's discovery: the metabolic degradation pathway. Axelrod succeeded in isolating the very enzyme that could solve that problem — catechol-O-methyltransferase (COMT). This enzyme is used in tandem with experiments on the effects of psychotropic drugs that act on the brain, is deployed to suppress adverse reactions during animal testing of drug candidates and to confirm drug efficacy, and is also used in research on hypertension and schizophrenia.

COMT is an enzyme that chemically modifies and inactivates adrenaline. This enzyme is necessary for adrenaline to be cleared and not continue to act for an indefinite period. It is responsible for the cleanup stage of the lifecycle.

Axelrod's contribution does not stop there. Beyond medicine, he made important contributions to biochemistry and pharmacology as well, developing several drug candidates as a pharmacologist studying drug structure and action. In the course of his neurotransmitter research, he also invented a new method for detecting trace amounts of catecholamines. Catecholamines are the compound family in which catechol is attached to a monoamine — dopamine, norepinephrine, and epinephrine all belong to this group. The trace-detection technique he devised became a standard tool for later separation experiments and had a broad ripple effect on biochemical analysis and the extraction of new substances.

The method for detecting trace amounts of catecholamines was Axelrod's methodological contribution. It became a standard tool for subsequent neurotransmitter research.

Message Queue Lifecycle: A CS Framework

Now, let's organize the discoveries of the three individuals using the language of computer science.

A message queue system has a three-stage structure: publisher-queue-subscriber. Each message is issued by a publisher, enters the queue, and is processed by a subscriber. There are several detailed issues at each stage of this lifecycle.

• Publish: How are messages sent to the queue? Batch or individual, synchronous or asynchronous?
• Deliver: How are messages delivered from the queue to the subscriber? Issues such as ensuring order, handling duplicates, and setting timeouts.
• Cleanup: Cleaning up processed messages. If not cleaned up, the queue will accumulate indefinitely.

The synapse is exactly this type of message queue system.

• Publish = Katz's quantal release: Synaptic vesicles are released individually (discrete publishing, not batch). Ca2+ ions trigger the release.
• Deliver = Euler's list of neurotransmitters: The protocol of which substances actually bind to which receptors in the synapse.
• Cleanup = Axelrod's COMT degradation: The used neurotransmitter is broken down by the enzyme and removed from the synapse.

If any of these three stages are missing, the system will not work. If there is no publishing, there are no messages; if there is no delivery, messages are wasted; if there is no cleanup, the system will crash. The three individuals each elucidated one stage, completing the entire lifecycle.

Reuptake = Axelrod's other discovery. In addition to COMT degradation, another way to clear neurotransmitters is for the original neuron that released the substance to reabsorb it. Inhibiting this reuptake causes neurotransmitters to remain in the synapse for longer. Today, SSRI (selective serotonin reuptake inhibitor) antidepressants work on exactly this principle – inhibiting the reuptake of serotonin, prolonging its presence in the synapse.

Limitations of the analogy: Of course, the synapse is much more complex than a software message queue. Multiple neurotransmitters act simultaneously, receptor sensitivity changes over time, and the state of the cell itself influences signal processing. However, the fundamental lifecycle of "publish → deliver → cleanup" is exactly the same.

The Legacy Continues

The impact of these discoveries can be traced as follows. Acetylcholine has been continuously studied since Loewi's 1936 Nobel Prize, and Katz's work extended this line into a whole family of therapies for neurological disorders. In particular, acetylcholinesterase inhibitors are used to enhance cognitive function or treat behavioral abnormalities in patients with dementia, and approaches that modulate acetylcholine release via Ca²⁺ regulation are now being pursued in research on muscular dystrophy and other motor-control disorders.

This flow leads to the following today.

• Alzheimer's drugs: Donepezil, rivastigmine, etc., which inhibit acetylcholinesterase to maintain acetylcholine levels in the brain. Partially delays cognitive decline in Alzheimer's patients.
• Adrenaline in emergency cardiac resuscitation: Adrenaline injection is a standard emergency treatment for patients in cardiac arrest. This is the clinical culmination of Euler's discovery.
• SSRI antidepressants: Prozac, Zoloft, Lexapro, etc. Derived from Axelrod's discovery of the reuptake mechanism. Used by tens of millions worldwide today.
• Parkinson's disease treatment: The cause is a deficiency of dopamine, and L-DOPA and dopamine metabolism inhibitors (MAOI, COMT inhibitors) are standard treatments. Axelrod's discovery of COMT is the foundation.
• Emergency allergic response (EpiPen): Adrenaline auto-injector for anaphylaxis. Adrenaline causes strong vasoconstriction and increased heart rate.
• Attention-Deficit/Hyperactivity Disorder (ADHD) treatment: Methylphenidate (Ritalin), etc., which act by inhibiting dopamine and norepinephrine reuptake.

Why is it Important?

What the three scientists achieved is a demonstration of the principle that "a complete understanding of the lifecycle of a signal opens the door to clinical treatment."

Even if you know the signal itself, you cannot clinically apply it if you do not understand how to regulate it. It has long been known that adrenaline is a potent signal, but if you did not know why it acts briefly and how it is cleared, you could not design an accurate dosage and method of administration. Axelrod's understanding of the metabolic pathway provided this accuracy.

The discovery of reuptake created a particularly significant clinical impact. Not only antidepressants (SSRIs) but also many other psychiatric and neurological drugs utilize the principle of reuptake regulation. The idea that the drug works by slowing down the clearing of existing neurotransmitters rather than adding neurotransmitters is an approach that can only be achieved by understanding the fine regulation of natural systems.

Axelrod, who came from a poor Polish immigrant family, received his doctorate at the age of 43 and then followed the path to the Nobel Prize. It is said that his long experience working in industry and acquiring practical experimental skills was his strength. This is a case where an exception to the regular academic path created a new path to the Nobel Prize.

1970, Katz, Euler, and Axelrod Summary: Complete elucidation of the lifecycle of synaptic neurotransmitters. Katz elucidated the mechanism of acetylcholine quantum release (release), Euler identified adrenaline as a neurotransmitter (transmission), and Axelrod elucidated the COMT breakdown enzyme and reuptake mechanism (cleanup). This is the theoretical basis for today's SSRI antidepressants, emergency resuscitation, and Alzheimer's treatments.

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