Nerve Endings: The Discovery of the SynapseBMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7536.308 (Published 02 February 2006) Cite this as: BMJ 2006;332:308
- Boleslav L Lichterman ()
The Spanish histologist Santiago Ramón y Cajal (1852-1934) wrote in his memoir: “Really, the garden of neurology offers the researcher captivating spectacles and incomparable artistic emotions. My aesthetic instincts find there full satisfaction. Like the entomologist catching beautiful butterflies, my attention pursued in the garden of gray matter, the delicately and gracefully shaped cells, the mysterious butterflies whose wing beats might some day reveal the secret of mental life.” Richard Rapport, a neurosurgeon from Seattle, found a copy of this book on a dusty shelf of a secondhand book shop, and it inspired him to tell a story aimed at a general audience about the life and work of this “constant gardener.”
W W Norton, £15.99/$23.95, pp 224
ISBN 0 393 06019 5
The son of a doctor's assistant in a remote Spanish village, Cajal had been interested in painting and photography from childhood and preferred Jules Verne's novels to academic routine. In 1877 he was appointed assistant professor of anatomy at the University of Zaragoza and managed to buy a microscope of his own, for an enormous sum, and a microtome. Cajal's laboratory occupied a table in the kitchen of his house.
By this time Camillo Golgi in Italy had already discovered the method for silver nitrate staining to expose neurones by their darkened outlines. Cajal further developed not only Golgi's staining technique but also his theory of neural conduction. While Golgi was convinced of the existence of a reticular network that connected nerve cells, Cajal argued that the nervous system is composed of units, without continuity of substance between cells. Rapport compares Golgi's view of the nervous system to “a kind of ant colony, made up of passages that routed information through an entirely connected labyrinth… Where Golgi had seen the tunnels of an anthill, Cajal saw the ants.” The terms we now use were coined later by other researchers—“dendrite” in 1889, “neurone” in 1891, “axon” in 1896, and “synapse” in 1897.
Rapport notes that “scientific theories are little more than intellectual models devised to define a strategy for collecting data about the physical world.” By the early 1890s the neurone theory had come to dominate among neurohistologists. According to this theory an electrical impulse is transmitted only in one direction: from the dendrite to the cell body and then further along the axon. Rapport notes, “It wasn't so much that the reticular theory had been wrong as that it was no longer a useful way to examine the problem.”
“If one wanted to explain the influence of Cajal's work on neurological science today, one would have to write the history of neurology in the last ninety years,” wrote Fernando Reinon-Suarez in 1981. Rapport has attempted it in one 14 page chapter. Electron microscopy permits us to visualise the synaptic cleft and to measure its width (2-3 nanometres). The number of contacts of a neurone might vary from 1000 to 80 000. Biochemistry has explained the transmission of electrical current (action potential) across the synapses. However, there are synapses called gap junctions where the cell membranes are so close to each other that electrical signals are transmitted directly from presynaptic to postsynaptic structures without any chemical involvement. Furthermore, some molecules travel from one cell to another through gap junctions without entering into extracellular space. So, it turns out that Golgi was also right.
Nevertheless, Rapport makes the strange claim that Cajal's identification of the gap “made the neuron theory law and eventually allowed… surgery of the brain.” The specialty of neurosurgery emerged with the concepts of intracranial pressure and cerebral localisation, which had nothing to do with neurone theory. Rapport's claim reminded me of discussions I had about a decade ago with Harold Hillman from the Unity Laboratory of Applied Neurobiology at the University of Surrey, during my fellowship at the Wellcome Institute for the History of Medicine in London. Dr Hillman summarised his concerns about the limitations in our understanding of neurones in a recent paper (Medical Hypotheses 2003;61: 190-3). What evidence is there that learning, memory, self consciousness, or the mind affect synapses? Does the chemical theory of transmission contain unproved and unprovable sub-hypotheses? Why are synapses regarded as necessary for the transmission of information, when electric conduction conveys information without crossing synapses? These are only three of 27 questions on neurobiology in Hillmann's article. Rapport's book addresses none of them.
Cajal and Golgi shared the 1906 Nobel prize for medicine. Rapport concludes that “for both of them in the end, who was right depended, at least in part, on a matter of intuition and manner… Looking down similar microscopes at the same tissues, they each saw a different nervous system.” Rapport explains the difference: “Whereas Cajal saw the world through the eyes of a passionate, liberal south Mediterranean, Golgi saw the same world with the colder eye of a conservative northerner.” However, such a geopolitical explanation is unconvincing.
In its clear and metaphorical language Nerve Endings echoes the passionate style of Cajal's memoirs. It has many other advantages: a historical context, carefully selected illustrations, a glossary, and an outline of basic neurophysiological processes (action and resting potentials, depolarisation, electrical gradients, and so on). It also has a bibliography—often missing in books at a general readership. It surely deserves a paperback edition.
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