Although I cannot undertake here to give a detailed reply to the arguments of my critics, I may point out a fallacy that vitiates their reasoning. The study of the intimate structure of nervous tissue involves the treatment of that very delicate substance by numerous active reagents. It is extremely important not to forget the possibility of alterations which may be produced in the processes of preparation and which are extremely difficult to avoid. A glance at the figures given by my critics shows me that the neuronophags in their preparations had been subjected to violent treatment. When M. Léri speaks of “the nuclei which surround some of the nerve-cells,” and M. Sand of “cells without protoplasm,” it is clear that they had been observing cells destroyed by the processes of the laboratory. The illustrations in the memoir of M. Marinesco show that in his preparations, too, the neuronophags had been very greatly altered.
It is well known that nuclei do not exist free in tissues, and that when they appear devoid of protoplasm, there has been some defect in the technical methods of preparing them for examination. As a matter of fact, neuronophags do not consist of nuclei with at the most a pellicle of protoplasm; like other cells, they have protoplasmic bodies which, however, are frequently destroyed by the violent processes of histological preparation.
The arguments of my critics recall to me the words of a medical student, who, on being asked to describe the microbe of tuberculosis, said that it was a little red bacillus. The bacillus in question, like most bacilli, is colourless, but it is usual to stain it so that it may be visible under the microscope. The student, knowing it only in particular preparations, had a false idea of its appearance.
In well-made preparations, neuronophags are typical cells with abundant protoplasm. When they have been preserved by a process that does not dissolve their contents, they show granules like those found in nerve-cells.
To study neuronophagy, M. Manouélian,[13] in the laboratory of the Pasteur Institute in Paris, set himself to improve the technical methods of preparation. He succeeded in showing first that in the destruction of nerve-cells that occurs in cases of hydrophobia, the contents of these cells are absorbed by the surrounding neuronophags. “My observations on the cerebro-spinal ganglia of human cases of hydrophobia,” he wrote, “show clearly that the macrophags act as phagocytes of the nerve-cells.” “Most of the cells in the nerve-ganglia contain yellow, brown, and black pigmented granules, usually united in small masses. What becomes of these granulations on the destruction and disappearance of the nerve-cell? If, as M. Marinesco has it, there is no phagocytosis by the surrounding cells, but merely a mechanical interference, then the granules, on the destruction of the nerve-cells that contained them, should be found lying in the interstitial tissue. But this does not happen. The granules are ingested by cells which are true macrophags.”
By the aid of a very delicate mode of preparation, M. Manouélian has shown that in the case of senile brains the granules of the nerve-cells are absorbed by neuronophags. I have myself studied M. Manouélian’s preparations and can testify to the accuracy of his observations (Figs. [6] and [7]).
Doubt is no longer possible. In senile degeneration the nerve-cells are surrounded by neuronophags which absorb their contents and bring about more or less complete atrophy. It has been supposed that in order to devour their contents, the neuronophags must penetrate the nerve-cells, and such an event has rarely been seen. But it is well known, the phagocytosis of red blood corpuscles being a typical instance, that to absorb a cell a phagocyte does not necessarily engulf it bodily or penetrate it, but may gradually denude it of its contents merely by resting in contact with it.
There has been some discussion as to the condition of nerve-cells which are on the point of being devoured by neuronophags. It has been noticed that such cells may display a considerable amount of degeneration without being devoured, whilst, on the other hand, cells apparently normal have been found undergoing phagocytosis. As I cannot state definitely what are the conditions that induce the phagocytosis of nerve-cells, I shall not attempt a discussion of the problem.
Although the destruction of nerve-cells by neuronophags is a general occurrence in senile brains, one may conceive of cases where this does not occur. And so, in old people who have preserved their faculties, it may well be that the neuronophags have refrained from attacking the nerve-cells. But as such instances are rare, so also phagocytosis is usually found in senile brains, and I cannot accept M. Sand’s denial of its existence, based on his study of two cases.
