MEDIA REVIEW - Nerve Endings: The Discovery of the Synapse by Richard Rapport

Zip-zip-zip-zip. An electrical signal jumps down a nerve axon. Pop! The signal reaches the end of the axon where tiny packets of chemicals burst open into a minute space between two cells. These chemicals, known as neurotransmitters, cause the next neuron in line to become active and send its own electrical signal, propagating the message forward towards its target. This is the current paradigm of neurotransmission – how neurons communicate with one another – and it forms the fundamental framework for the entire field of neuroscience.


However, this "neuron theory" (as it is known) was not the traditional model held by most scientists through much of history. In fact, the physical constitution and functional operation of the nervous system were fields left to philosophers into the 1800s. It was in this century, though, that the revolution of histology began to take place: the use of more precise microscopes as well as the development of dyes used to stain cells allowed scientists to view the tiny constituents of the body and wonder at their connected function.

It is in this scientific setting that the tale of the neuron unfolds. It is the chronicle of Camillo Golgi and Santiago Ramon y Cajal. These two men, though connected by their passion for the study of the nervous system, worked hundreds of miles apart and in completely different scientific worlds. However, the combination of their work led to groundbreaking contributions in the emerging field of neuroanatomy and truly shaped the future of the study of the brain.

The tale is related intricately and candidly by Richard Rapport, a neurosurgeon from Seattle, Washington, in his recent work Nerve Endings: The Discovery of the Synapse. Rapport paints a vivid picture of the history, often merging fact into his prose to create scenes that read like those plucked from a play rather than a textbook.

Rapport's history begins with the childhoods of Cajal and Golgi: Santiago Ramon y Cajal was the first son of Justo Ramon Casasus, a surgeon living in the small, remote Spanish village of Petilla. Cajal was a well-educated and docile child who metamorphosed into an adventurous, if not rebellious, youth with a passion for mischief as well as art. Rapport recounts a particularly lively tale of Cajal's construction and use of a workable cannon that was the demise of a neighbor's garden gate. However, in medical school Cajal found a love of anatomy and a use for his artistic proclivities by rendering on paper what he had dissected before him. Following a brief and dejected stint in the military, Cajal passed his doctoral examinations, became an assistant professor at the University of Zaragoza, and was introduced to the microscope, an event that changed his life.

Golgi's early life both mirrors and contrasts that of Cajal. The third son of an Italian physician, Golgi also grew up in a small village, though this one was set in the Alps. His early school record was impeccable, and he was accepted into the University of Pavia's medical school from which he graduated in 1865. Rapport notes, though, that Golgi was a more reticent youth, less engaged by life, and continually seeking approval and recognition. Like Cajal, however, Golgi's passions were also ignited by the study of the microscopic, and he pursued these at Pavia under noted scientists of the time.

Figure 1. Santiago Ramon y Cajal. Image Courtesy: La Universidad Complutense de Madrid.

Figure 1. Santiago Ramon y Cajal. Image Courtesy: La Universidad Complutense de Madrid.

The story progresses as the two men separately delve into the study of the constitution and composition of the nervous system. Golgi's early work continued at Pavia; however, financial woes eventually forced him to accept a position in medicine at a distant hospital. Refusing to give up his research in histology, Golgi converted his kitchen into a makeshift lab and began the hunt for a cellular stain that would allow him to better visualize nerve cells. A breakthrough came in late 1872 when Golgi discovered a procedure that stained only a fraction of the cells on a slide with a dark black outline. The significance of this method in permitting the detailed study of the structure of individual neurons, something no one had been capable of up to this point, cannot be overstated. Known as the black reaction, Golgi's new stain rapidly spread through the scientific world.

Oddly enough, Cajal also conducted his research in a kitchen setting. A determined and impassioned scientist, Cajal set about gathering, preparing, and staining tissue specimens for examination under the microscope. Unfortunately, Spain was behind the scientific times, and Cajal had little to no personal exposure to other researchers studying histology. However, this was not a deterrent to his learning and progress, and Cajal set about studying all the German and French histology texts he could obtain. After viewing slides prepared using Golgi's new silver staining technique in 1887, Cajal's passion for the study of the neuron sprouted new life. Cajal continued with groundbreaking work wherein he improves upon Golgi's stain and characterizes different areas of the nervous system, such as the retina. His efforts were directed at finding support for the existence of synapses, or small gaps between nerve cells.

For all their similarities, Cajal and Golgi were in fact men of two very different worlds. Golgi was a firm and adamant believer in the reticular theory of nervous system organization. This concept was founded on the belief in the physical interconnection of all elements of the nervous system into one enormous entity in which information flows in all directions. Initially this view was well accepted in science, but as histology and microscopy progressed evidence mounted against the reticularists.

Figure 2. Camillo Golgi. Image Courtesy: The Nobel Foundation.

Figure 2. Camillo Golgi. Image Courtesy: The Nobel Foundation.

In fact, Cajal's work was directed down this avenue of deducing the true structure of the nervous system. His careful examination of microscopic anatomy revealed single, unique cells, known as neurons, that exist independently of each other. The view propounded by Cajal was diametrically opposed to the reticulum of Golgi and was known as the neuron theory. Here the neuron is the fundamental unit of the nervous system and information flows in one direction through nerve cells. Over time neuronists began to outnumber the reticularists, and the interconnected network posited by Golgi began to wane in favor. However, Golgi never conceded the reticulum's existence.

Rapport's construction of these events in history makes use of numerous direct quotes from Cajal's autobiography which allows the reader to dip into the perception Cajal experienced himself. His characterization of his relationship to Golgi is nothing if not humorous: "what a cruel irony of fate to pair, like Siamese twins united by the shoulders, scientific adversaries of such contrasting character!" Despite the adversity of personality and scientific views between Cajal and Golgi, both men directly hold a distinction claimed by few; in 1906 both scientists shared the awarding of the Nobel Prize in Medicine for their significant contributions to the study and understanding of the nervous system.

Rapport finishes his book by examining the remaining years of life and research that existed for Cajal and Golgi after the Nobel Prize, a time when neither man truly allowed old age to slow him much.

This tale of neuroscience history is a fascinating story that exposes both the intricacies of research and the humanity of the scientists who conduct this work. Rapport's telling is engaging and entertaining, and his prose frequently surprises (".the flower gardens of gray matter, and the hidden islands and virginal forms waiting since creation to be found [by Cajal]," p. 142). Understandable by readers with or without a science background, Nerve Endings sheds light on the roots of neuroscience.

One of the founding fathers of JYI, Brian Su, became the youngest person to co-PI a grant from the NSF. The purpose of the grant was to fund the start-up costs for JYI.
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