In the second half of the 19th century and the early 20th century, neuroscience and neurology emerged as established scientific fields. During this period, nerve cells (neurons) were identified and described, along with the anatomical structures of the brain and the central and peripheral nervous systems.
Researchers had already determined that neurons transmit electrical signals along their length, much like cables, but a key mystery remained: what happens at the nerve endings? How do neurons communicate with one another? Do they transmit electrical signals directly, or do they "talk" through the release of chemical substances?
The researcher who answered this question was German-Jewish scientist Otto Loewi, who credited an unconventional source of inspiration—a dream—with leading him to the breakthrough.
Otto Loewi was born in 1873 to a Jewish family in Frankfurt. At 18, he began studying medicine in Munich and later continued his studies at the University of Strasbourg (then part of Germany, now in France). At 20, he barely passed his medical qualification exams, as his interests leaned more toward philosophy and art. At 23, Loewi began practicing medicine in Frankfurt, but he quickly grew disillusioned with the limited resources available for treating infectious diseases and felt powerless. This experience led him to abandon clinical practice in favor of basic medical research.
Loewi first took a position as a research assistant at the University of Marburg, where he began working in pharmacology. In 1902, he completed a fellowship in London at Ernest Starling’s laboratory, where he met Henry Hallett Dale, a colleague who would later share both the research field and the Nobel Prize with him.
Loewi then moved to Austria, and after a brief period at the University of Vienna, he settled at the University of Graz in 1908. He would remain there for nearly three decades, becoming the last Jewish professor to receive a full professorship at the institution before World War II.
Focus: The autonomic nervous system
Loewi's research spanned a variety of topics, including metabolism and pancreatic function, but his primary focus was the autonomic nervous system. This network of nerves extends from the spinal cord and regulates or suppresses the activity of internal organs such as the heart, digestive system, sweat glands and more.
The evolutionary role of this system is to enable the "fight or flight" response, preparing the body for dangerous situations that require either fighting a predator or fleeing from it, and then returning the body to its normal state once the threat has passed.
The autonomic nervous system is divided into two distinct components. The first is the sympathetic system, which primes the body to respond to a threat – for example, by increasing the heart rate to supply more blood to the muscles. The second is the parasympathetic system, whose role is to restore the body to its baseline state, in part by slowing the heart rate back to its normal pace.
By the mid-19th century, it was understood that the vagus nerve, which extends from the skull and branches to various internal organs, forms part of the parasympathetic system and that its electrical stimulation slows the heart's activity.
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It was also known that stimulating certain other nerves that reach the heart increases its activity and that injecting a substance called adrenaline into a subject could mimic electrical stimulation, leading to an increased heart rate. However, the key question remained unanswered: is communication between nerve cells and the heart chemical or electrical?
An experiment inspired by a dream
In 1920, after 12 years at the University of Graz, Otto Loewi reportedly experienced a moment of inspiration that would forever change the field of neuroscience. During Easter, he had a dream that provided the idea for an experiment to definitively answer the question of how nerve cells communicate with organs.
He woke up feeling that the dream was extremely important and quickly jotted down its content. However, when he woke up in the morning, he was unable to read what he had written. Fortunately, the same dream repeated the following night, and when Loewi woke at 3 a.m., he immediately began one of the most brilliant experiments in the history of biology.
The experiment was remarkably simple. Loewi took two frog hearts and placed them in separate containers filled with a solution that allowed them to continue beating outside the body. One heart was taken with the vagus nerve still attached, while the other was without it. Loewi then electrically stimulated the vagus nerve, which slowed the heart rate of the first heart. Next, he took a small amount of the solution from the first heart's container and transferred it to the second heart, which lacked the nerve.
Remarkably, the second heart also slowed down. This demonstrated that a soluble chemical in the first heart's solution was responsible for slowing the heart rate, leading to the conclusion that communication between the vagus nerve and the heart – and, as later discovered, communication between most nerve cells – is chemical, not electrical.
Loewi suspected that the chemical responsible for this communication was acetylcholine, which had been discovered by Henry Dale in 1914. However, Loewi had only indirect evidence for this – he found that atropine, a substance that inhibits acetylcholine's effects by competing for the same receptors, reversed the heart's slowing.
In the absence of explicit proof, Loewi named the mysterious chemical Vagusstof, meaning "substance secreted by the vagus nerve." It was only later, through joint work with Dale, that Loewi confirmed it was indeed acetylcholine. For their discovery of the first neurotransmitter, Loewi and Dale were awarded the Nobel Prize in Physiology or Medicine in 1936.
Despite the recognition and acclaim Loewi received, his Jewish background and the political climate worked against him. After the annexation of Austria in 1938, the Gestapo arrested him. However, through the intervention of his colleagues, the Nazis allowed him to escape Austria in exchange for transferring his Nobel Prize money to the Third Reich.
Loewi fled to England, finding refuge with Dale, and later moved to the United States, joining New York University in 1940. He became a U.S. citizen in 1946 and passed away in 1961. His contributions to brain research were immense, and he is regarded as one of the founding fathers of the field.