Review Article
The history of myelin
Section snippets
1543 Vesalius first mention of white matter
The renaissance physician Andreas Vesalius (1514–1564†), considered the father of modern anatomy, was the first to describe white matter and gray matter in the human brain in a monumental treatise known as ‘La Fabrica’ illustrated with many detailed anatomical drawings (Vesalius, 1543). Vesalius, born Andries van Wesel in Brussels, was encouraged early by his family to become physician, his grandfather being the Royal Physician of Emperor Maximilian. Vesalius became Professor at the University
1854 Virchow coins myelin
The word Myelin was coined by German pathologist Rudolf Ludwig Virchow (1821–1902†), author of the fame Neuroglia term (Kettenmann and Ransom, 2005). There was much confusion mid-19th century regarding the medullary substance, and Virchow expressed the need for a better terminology in Virchow's Archiv, the journal he founded (Virchow, 1854, page 571): “das Bedürfniss, sie mit einem Worte bezeichnen zu können, vorliegt, so schlage ich vor, um jede Verwechselung mit anderen schon bezeichneten,
1868 Charcot myelin droplets in multiple sclerosis
In 1868, the neurologist Jean-Martin Charcot (1825–1893†) used myelin (myéline) in what can be considered its first correct attribution. Charcot was an avid and respectful reader of German literature, until the 1870 French-German war dampened his enthusiasm (Guillain, 1955). Charcot established at the Parisian hospital Salpêtrière the clinical and histological criteria to diagnose multiple sclerosis in two articles. The histology article described demyelination in lesions (Charcot, 1868, Fig.
1872 Ranvier myelin is made by internode adipocyte
Ranvier, a sagacious observer particularly tracking staining artifacts, realized both sheaths of Schwann (1839) and Mauthner (1860) were not simple envelopes but contained a sheet of cytoplasm running from node to node. The question of whether there was cytoplasm in these sheaths was not trivial, because there was no specific stain for cytoplasm at the time. Ranvier hence boldly envisioned the axon enveloped by a muff of cytoplasm with finite boundary at the nodes. All cellular elements being
Myelin functions: myths and reality
By mid-19th century, the concept of axon had replaced myelin as the essential and active component of the nervous fiber. Myelin origin and function puzzled early investigators by appearing relatively late during development and not investing all fibers in adult. The following section, by no means exhaustive or comprehensive, presents the most remarkable theories.
1884 Thudichum biochemistry of myelin
It is beyond the scope of the present review to provide a detailed account of myelin chemical composition discovery. It was known by mid-19th century that in white matter the axons “consist of protein components very similar to muscular fibrin, the marrow sheath especially of fats from various kinds” (von Kölliker, 1863, page 105). Toward the end of the 19th century, Johann Ludwig Thudichum (1829–1901†), the founder of neurochemistry, partially characterized many lipids of myelin, including its
1939 Tasaki shows saltatory conduction
The real function of myelin of course is saltatory transmission of nerve impulse, leaping from one node of Ranvier to the next. It was first suggested in 1925 by Canadian born Ralph Stayner Lillie (1875–1952†), Professor of General Physiology at the University of Chicago (Lillie, 1925). Lillie experimented on an iron wire, considered a valid ‘passive’ nerve model. In a stroke of genius, he modeled the nodes by enclosing the iron wire in a glass insulant tube with periodic breaks, and noted that
1924 Schmidt birefringence
Myelin optic property of birefringence was discovered only in the second part of the 19th century because of the technical aspect of microscopes. Polarized light is generated by a pair of perpendicular filters, generating positive and negative birefringence. Gabriel Gustav Valentin (1810–1883†), German physiologist in Bern University, published the first study with polarized light (Valentin, 1861). When myelinated fibers were analyzed by Theodor Albrecht Klebs (1834–1913†), assistant of Virchow
1954 Geren myelin spirals from Schwann cell
The origin of such an exceptionally organized structure remained a mystery. The key person who solved it was Betty Ben Geren (1922–†), neuropathologist who graduated MD in 1945 at St. Louis Washington University followed by a pathology internship at Boston's Children's Hospital (Fig. 4). Geren received an American Cancer Society Research postdoctoral Fellowship to study with renowned F.O. Schmitt, and first addressed the question of whether myelin built by ‘crystallizing out’ droplets of
Conclusion
Myelin can be conceived as a gigantic 3-D puzzle in time and space. The best scientists across the world have studied this structure directly or incidentally since the 18th century. Each of them brought a piece to the puzzle. Myelin was first reported as white matter inside the brain during the Renaissance. At the dawn of neuroscience in early 19th century, myelin was considered the most important element of the nervous system. After the axon was discovered, myelin went overlooked for decades
List of abbreviations
- CNS
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central nervous system.
- MIT
-
Massachusetts Institute of Technology.
- PNS
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peripheral nervous system.
Declaration of interests
The author declares no conflict of interest and assumes all translations where not specified. Accessing original documents generated discrepancies with their formerly cited references.
Funding
This work was supported by NIH/NLM grant G13LM011465.
Acknowledgements
We thank Jeffrey Dupree (Virginia Commonwealth University) for stimulating discussions on the origin of g-ratio. We are grateful to Boris Zalc (Paris Pitié-Salpêtrière Institute) for interactions on history of myelin. We are indebted to the Classic papers Network Glia website for providing access to quality 19th century plates. We thank Douglas Fields (National Institutes of Health, Bethesda) for providing personal recollection of Dr. Tasaki. We are grateful to Betty Geren (Arkansas family
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