On this page
Your NCERT chapter on neural control says a nerve impulse reaches a synapse and releases a neurotransmitter. For a long time nobody knew whether that step was electrical or chemical. In 1921 Otto Loewi answered it with two frog hearts and a pipette. This post walks through the experiment, the controls that made it convincing, and how to use it in a long answer.
Who was Otto Loewi?
Loewi was born in Frankfurt in 1873 and died in New York in 1961, according to his Nobel facts page. His Nobel biography describes a medical student who seldom went to lectures, then turned to pharmacology after seeing patients with tuberculosis and pneumonia die for lack of any treatment. He became professor of pharmacology at Graz in 1909.
He shared the 1936 Nobel Prize in Physiology or Medicine with Sir Henry Dale "for their discoveries relating to chemical transmission of nerve impulses". The two had first met in 1902 in Ernest Starling's laboratory in London.
What was the open question in 1921?
In his Nobel lecture, Loewi says that up to 1921 it was not known how stimulating a nerve changed the organ it supplied. Most physiologists thought the electrical wave passed straight from nerve to organ. A chemical route had been suggested, and others had looked for one, but there was no proof.
The heart was a good test case. Stimulating the vagus nerve slows it. Stimulating the sympathetic (accelerator) nerves speeds it up.
How did the two-heart experiment work?
The Nobel facts page summarises it: Loewi stimulated a frog heart electrically while it pumped a small amount of nutrient solution, then transferred the fluid to a second heart, which "operated in a similar way". In the lecture he puts the result like this: nerve stimulation released substances that passed into the heart fluid and, transferred into a test heart, made it react "in exactly the same way as the stimulation of the corresponding nerves".
Laid out as steps:
Donor heart. A frog heart, with its vagus nerve attached, beats while filled with salt solution.
Stimulate. The vagus is stimulated and the donor heart slows.
Collect. The solution from inside the donor heart is taken out.
Transfer. It is placed in a second heart that has had no nerve stimulation.
Observe. The second heart slows, as if its own vagus had been stimulated.
Doing the same with the accelerator nerve gave fluid that sped the test heart up. He published the result in Pflügers Archiv in 1921 under a title meaning "On the humoral transferability of the action of heart nerves".
How did he identify the chemical?
Loewi called the slowing agent "Vagusstoff" (vagus substance). His lecture lists the clues:
Its effect was blocked by atropine and it disappeared very quickly.
Of the known candidates (muscarine, pilocarpine, choline and acetylcholine), only acetylcholine had both properties.
Its rapid loss was caused by an esterase in the heart that breaks it down, and eserine blocked that esterase in tiny amounts.
Dale and Dudley then isolated acetylcholine directly from organs.
His conclusion: "there can be no more doubt that the vagus substance is Ac.Ch." For the accelerator nerve, he found the substance shared many properties with adrenaline, and that same year he reported direct evidence that it was adrenaline.
Eserine was the key tool. By stopping breakdown, it let the tiny, short-lived amounts of acetylcholine build up enough to detect.
How do you write this up in an exam?
A strong answer names the question, the method, the control and the conclusion:
Question: is nerve-to-organ transmission electrical or chemical?
Method: stimulate the vagus of a donor heart, move its fluid to an unstimulated heart.
Control logic: the test heart had no nerve stimulation, so any change came from the fluid.
Result: the test heart slowed; fluid from accelerator stimulation sped it up.
Conclusion: nerves act by releasing chemicals, later shown to be acetylcholine (vagus) and adrenaline-like substance (sympathetic).
Common mistakes: writing that Loewi recorded an electrical signal (he watched the heartbeat of a heart the nerve never touched), or mixing up which nerve slows the heart. For the idea of the junction itself, see our post on Charles Sherrington and the reflex. For the full chapter, see Neural control and coordination.
What happened to Loewi after the prize?
His biography records that when Germany annexed Austria in 1938, Loewi was forced to leave, but only after he had been made to instruct his Stockholm bank to transfer his Nobel Prize money to a Nazi-controlled bank. He worked in Brussels and Oxford, joined New York University's College of Medicine, arrived in the United States in 1940 and became an American citizen in 1946.
What can a student take from Loewi's way of working?
Design the decisive test. One transfer step separated two theories.
Use blockers as questions. Atropine and eserine told him what the substance was by how it behaved.
Leave open questions open. His lecture ends with cases atropine could not explain and says the reason "has so far escaped us".
Synaptic transmission is easier to follow when you can watch it happen. The Fermi Simulation Lab has interactive simulations for ideas that are easier to see than read.
Next step: draw Loewi's two hearts, label the donor and test heart, and write the one-line control logic beside them.
