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Otto Warburg used light to unmask an invisible enzyme

Otto Warburg showed that carbon monoxide blocks cell breathing and that light lifts the block, and used this trick to read the chemical signature of the respiratory enzyme.

Otto Warburg
Otto Warburg · 1883–1970
Person
Otto Warburg
Lived
1883–1970
Field
Biochemistry
From
German

The story

By the mid-1920s Otto Warburg was convinced that cells breathe with the help of an iron-containing enzyme, which he called the Atmungsferment, or respiratory enzyme. The difficulty was that it exists in cells in vanishingly small amounts, far too little to isolate with the tools of the time. He needed a way to study it while it was still working inside living cells.

His starting point was carbon monoxide. Claude Bernard had shown long before that the gas binds to haemoglobin, and in 1926, working with yeast cells suspended in a glucose solution, Warburg found that it also blocks cell respiration. The strength of the block depended on the ratio of carbon monoxide to oxygen, which told him that the gas was competing with oxygen for iron in the enzyme.

Then came the decisive step. The chemists Mond and Langer had discovered in 1891 that compounds of carbon monoxide and iron can be split apart by light. Warburg found that by alternating light and darkness he could make respiration in the poisoned cells appear and disappear: in the light, carbon monoxide was knocked off the iron, freeing the enzyme to work again. His measurements showed that the effect obeyed Einstein's law of photochemical equivalence, with one iron and carbon monoxide pair split for each quantum of light absorbed.

By shining light of different colours but equal intensity on the cells and recording how much respiration recovered, Warburg mapped the absorption spectrum of the enzyme without ever purifying it. The pattern closely resembled that of carbon monoxide bound to haemoglobin, shifted slightly toward longer wavelengths, which identified the enzyme as a haem compound. Its very strong light absorption also showed that it was present in the cell only in minute concentrations. This work, carried out between 1927 and 1932, formed the core of the discovery honoured by his 1931 Nobel Prize.

The method was an elegant piece of experimental reasoning, in which an invisible molecule was identified by the way it responded to light. Warburg himself regarded the discovery of the respiratory enzyme as the most original of his career. Reading the chemistry of molecules inside living cells through their interaction with light later became one of the standard approaches of biochemistry.

Why it matters

Warburg's approach showed scientists how to study molecules inside living cells by their response to light, an idea that runs through modern spectroscopy and biochemistry.

About Otto Warburg

Biochemist who uncovered how cells breathe and discovered that tumours burn sugar by fermentation, the “Warburg effect”; Nobel laureate in 1931 who kept working in Nazi Berlin as a “Mischling.”

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Otto Warburg
1883–1970 · Biochemistry
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Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.

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