The history of myelin

Andreas Vesalius is attributed the discovery of white matter in the 16th century but van Leeuwenhoek is arguably the first to have observed myelinated fibers in 1717. A globular myelin theory followed, claiming all elements of the nervous system except for Fontana's primitive cylinder with outer sheath in 1781. Remak's axon revolution in 1836 relegated myelin to the unknown. Ehrenberg described nerve tubes with double borders in 1833, and Schwann with nuclei in 1839, but the medullary sheath acquired its name of myelin, coined by Virchow, only in 1854. Thanks to Schultze's osmium specific staining in 1865, myelin designates the structure known today. The origin of myelin though was baffling. Only after Ranvier discovered a periodic segmentation, which came to us as nodes of Ranvier, did he venture suggesting in 1872 that the nerve intemode was a fatty cell secreting myelin in cytoplasm. Ranvier's hypothesis was met with high skepticism, because nobody could see the cytoplasm, and the term Schwann cell very slowly emerged into the vocabulary with von Lenhossek in 1895. When Cajal finally admitted the concept of Schwann cell internode in 1912, he still firmly believed myelin was secreted by the axon. Del Rio-Hortega re-discovered oligodendrocytes in 1919 (after Robertson in 1899) and named them oligodendroglia in 1921, thereby antagonizing Cajal for discovering a second cell type in his invisible third element. Penfield had to come to del Rio-Hortega's rescue in 1924 for oligodendrocytes to be accepted. They jointly hypothesized myelin could be made by oligodendrocytes, considered the central equivalent of Schwann cells. Meanwhile myelin birefringence properties observed by Klebs in 1865 then Schmidt in 1924 confirmed its high fatty content, ascertained by biochemistry by Thudichum in 1884. The 20th century saw X-ray diffraction developed by Schmitt, who discovered in 1935 the crystal-like organization of this most peculiar structure, and devised the g-ratio concept in 1937. A revolution happened around the same time: saltatory conduction, the very reason for myelin existence, discovered by Tasaki in 1939 and confirmed by Huxley and Stampfli in 1949. After the second world war, widely available electron microscopes allowed Geren to finally discover the origin of myelin in 1954, exactly a century after Virchow coined 'myelin' in 1854. Geren had the genial insight that the Schwann cell wraps around the axon and generates a spiral of compacted membrane myelin. The central origin of myelin took a little longer due to the special configuration of oligodendrocyte distanced from the axon, but in 1962 the Bunges established the definitive proof that oligodendrocyte secretes myelin. The era of myelin biology had begun. In 1973 Norton devised a method to purify myelin which launched the modern molecular era. (C) 2016 Elsevier Inc. All rights reserved.