In 1864, the German pharmacologist Oscar Liebrich presented a paper at a meeting in Giessen arguing that brain tissue was composed of a single giant molecule called "protagon." Any simpler lipids that chemists were isolating, Liebrich argued, were simply breakdown products of this primary, high-molecular-weight compound.

The protagon theory had quite an effect on Johann Ludwig Wilhelm Thudichum, a German-born physician and chemist who was working in London under contract to the medical officer of the Privy Council, John Simon. In an 1868 report to Simon, Thudichum wrote that he wanted to explore the theory further: "[Chemists] cannot form any conception of pathological processes of the brain matter before knowing [protagon's] chemical constitution of the whole." But when Thudichum started doing his own experiments on brain chemistry, he quickly became disenchanted with Liebrich's theory.

From 1865 to 1871, Thudichum carefully detailed the chemical constitution of the brain. He showed that the elemental composition of protagon was variable and that no carbon-carbon bonds were broken under differential solvent extraction, which indicated that protagon was actually a mechanical mixture of several fatty-like substances, all of which had slightly different solubilities.

Thudichum isolated, characterized, and often named various brain-derived compounds, including choline platinochloride, lecithin cadmium chloride, phrenosine, and kerasine (as seen above with Thudichum's handwritten labels). "Thudichum's ability to employ this procedure to separate compounds with similar, but slightly different, solubility properties marks him out as a genius of the lipid laboratory," says Theodore Sourkes, a biochemist at McGill University and the author of The Life and Work of J.L.W. Thudichum.

For decades, however, the scientific community largely rejected Thudichum's discoveries. Some accused him of "patent falsification"; others called him a "liar." Only in 1910—almost a decade after his death—was the protagon theory finally laid to rest when three labs in London, Edinburgh, and New York confirmed that protagon was nothing more than a mixture of simpler lipids.

How does it change a person who works strenuously to uncover the truth, presents a well-reasoned, well-evidenced, correct hypothesis, and have it so roundly rejected? He never gave up believing in his own theory, did he? What was his relationship with the greater world of biochemists after this?

We scientists are fond of the fiction that we are dispassionate, objective observers, but in fact we have these beliefs that once accepted create heretics of those who challenge them. Unfortuntely just because one challenges existing dogma doesn't mean the challenge is correct. I remember when I was in graduate school and the "central dogma" of molecular biology was challenged by the discovery of reverse transcriptase. Many simply refused to accept that the flow of information from DNA to RNA to protein was unidirectional. Never mind the data. I wonder what future scientists will see as our "protagon" or "phlogiston" for that matter.

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