FIRST PROPOSITION.

The brain cell in health is a granular protoplasmic body, the chemical workshop of life. Figure 1 schematically represents a cortical pyramidal cell with its special apex dendrite (1), dividing and subdividing, with its receptive gemmules (2), protoplasmic buds, on the distal branches. Small dendrites (3) spring from the cell body. From the cell base arises on each side a large heavy dendrite (4), subdividing also into distal branches with gemmules (5), the protoplasmic buds. All ingoing sensory impressions to the brain, bringing in information from the external world, must eventually reach the gemmules (2 and 5) to pass along the dendrites (1) and (4) into the cell body. These impressions are now, after undergoing mental digestion and mental assimilation, enroute to the outer world to be externalized as an expression of the individual's judgment standard. But before these now outgoing impulses are externalized they must be refined in the chemical workshop of this cell body. The little granular bodies (6), known as Nissl's bodies, tigroid bodies, chromophylic bodies, etc., fill the entire cell body, surrounding the nucleus (7) with its nucleolus, and have much to do with this refining process in imparting a finished vigor and activity and delivering through the axon (8) the outgoing impulses to the exterior as a finished product. These chromatic bodies of Nissl accommodate themselves to the achromatic or non-stainable network (9) of the cell interior. The striations of this network come into the cell from the dendrites, enmesh the chromatic bodies and eventually unite at the cell base to pass out as the primitive fibrillae of the axon (8), the real impulse conductors to all peripheral nerve organs.

To further view the normal cell, Figure 2 shows an acrhystichochrome cell from the human motor cortex. In a stichochrome cell the chromatic or Nissl's bodies are spindle shaped. Figure 2 is a combination of an archychrome and stichochrome, hence the varied forms of Nissl's bodies seen in the cell body and extending into the dendrites.

Figure 3 shows a normal cell of the human spinal ganglion with its beautifully arranged chromatic bodies, at one time undescribed because of faulty technique, causing histologists to term the cell as

Figures 2, 3 and 4 by Ewing; Archives of Neurology, Vol. I, No. 3, 1908.

Figure 4 is a perfect Purkinye cell of the normal human cerebellar cortex with the chromatic bodies showing in uniformity to the nucleus and extending into the bifurcating apex dendrite.

This brief understanding of the normal cell is necessary before it is possible to grasp any cell pathology..

THE SECOND PROPOSITION.

The post-mortem changes in this cell and its branches resulting from alcoholic poisoning has long been studied. Clouston and Bevan Lewis recognized the cell damage twenty years as here illustrated in Fig. 5. This is an old reproduction of Bevan Lewis' but it presents a lesson. This patient went the usual course of alcoholism, alcoholic delirium and the final alcoholic insanity and death. The present day staining methods would show more explicit findings. The Scharlach R method for demonstrating fatty degeneration would have shown the disintegration of the cell interior beautifully in the accumulated fat products while Lewis could only describe the cell body as being "filled with minute, pale, yellow granules." Again the cell body is stripped clean of all the finest dendritic processes with a complete absence of all gemmular bodies as schematically illustrated in Fig. 1, much like a tree losing its foliage after a heavy frost.

Vas (1) experimentally produced chronic alcoholism, causing decided alterations in the ganglion cells known as Firediman's "homogenous swelling," or more classically designated as a central chromotolysis shown in Fig. 5, cut No. 2, eventually meaning a remaining damage of cell function, causing a toxic insanity, a post-alcoholic insanity if the acute cell destruction was not sufficient to produce death.

Dehio (2) induced acute fatal alcoholic poisoning. If the animal died in a few hours cell changes could not be demonstrated; if death occurred after eighteen to thirty-six hours Nissl's bodies (see (6) in Fig. 1) disappeared and were replaced by granular material and the non-stainable substance took on a light blue, diffuse stain. This change took place in the Purkinje cell, the cerebellar balancing cell, hence the staggering alcoholic gait. Imagine in Fig. 4, a normal Purkinje cell, that the beautifully arranged dark bodies in the network around the nucleus have been destroyed, then the picture observed by Dehio is seen.

FIG. 5, cut No. 2. Decided destruction of Nissl's bodies in cell center, but are present around the cell margin, though slightly so on the left margin, and at the right top, and seemed as if somewhat fused together: cell edema marked with the nucleus well out to the edge of the cell; nucleus is slightly vacuolated.

FIG. 5. Large pyramidal nerve cells of the frontal cortex, showing granular degeneration. Minute, pale, yellow granules fill the cell body, indicating degeneration. From a case of alcoholic insanity. (Bevan Lewis' now old method.)

Berkley's (3) studies of alcoholic poison ing showed definite atrophic changes in all the cortical cells. The varicose (see (4) in Fig. 1) enlargements of the dendrites were atrophied, the cell bodies were roughened and irregular and the little gemmules of the dendritic branches (see (2) and (3) in Fig. (1) were destroyed-gone. Nissl's bodies were damaged and indistinct, the unstainable or achromatic cell structures were unduly stainable and the nuclei were swelled and granular.

Stewart (4) experimentally duplicated the findings of Dehio, especially the changes found in the Purkinje cells already described.

Danas (5) twenty post-mortems on alcoholic wet brains revealed the brain cells in "various stages of degeneration." Nissl's bodies were "often unstained or had lost their true relations and seemed broken down." The cell outline was irregular and the nucleus was in the cell periphery or was outside of the cell. He thinks the cell degeneration is much like the cell degeneration caused by destroying the axon. Such a degeneration affects the cell body at first and not the nucleus till later. A cell so injured has remarkable power of recovery," which accounts for the recovery of many cases. Such a pathology is fairly well illustrated in Fig. 5, cut No. 2 and Fig. 14.

In alcoholic insanity Andersen (6) found advanced disorganization of the cortical cell. There was marked cell edema and Nissl's bodes were mostly invisible. Even the intranuclear network was thickened and damaged and pigmented debris was plentiful.

Ewing (7) contributes two cases of fatal alcoholism, ending in delirium tremens after six and twelve weeks of debauch. In both the lesions were identical. The cells of the cortex, medulla and cord were in "extreme chromatolysis. No normal cells were seen anywhere and in only a few were there any traces of the peripheral ring of the chromatic bodies," as shown in Fig. 5, cut 2 and Fig. 14 where the disintegrating process begins about the nucleus.'

Further Ewing says: "Alcoholism in the human subject is associated with lesions in the ganglion cells comparable with those found after experimental alcoholic poisoning in animals, nor can one hesitate to attribute in large measures the violent nervous symptoms observed in these cases, to the cellular lesions revealed by Nissl's stain NOTE-A letter from Dr. Berkley affirms his recorded findings, but owing to his giving up research work he has nothing bewer to add to his interesting findings here given.

and only faintly indicated by other technical methods."

With this accumulated pathological evidence of cell damage by alcohol it is selfevident in accentuating the absurdity of any few days treatment of any kind being curative. This cell pathology does point us to the necessity of a delicate therapeusis in the acute exacerbations to avoid further damage to the already badly damaged cell; it pictures to us how delirium can arise from the disarrangement of the cell chemistry and how a continued chemical disarrangement can terminate in interior molecular cell change, disabling cell function, as shown in the vicious hallucinations and delusions of the so-called toxic psychosis, and how the psychosis could progressively pass into the so-called alcoholic insanity and, later, into a true alcoholic dementia when the secondary cell atrophy follows.

How many alcoholics are further damaged by drastic narcotic poisoning and unnecessarily continued into insanity is the unanalyzed secret of the mad house; how many are killed "Johnny on the spot" by the same procedure is the secret of the dead; and what is equally as bad, how many are relieved from alcohol by making them morphine addicts is yet indefinite, but we do know the per cent is very large.

In 1906 I called attention to the pathology of morphinism. Fig. 6 here presented is a beautiful demonstration of what morphine does to the brain cell structure (9). There is a general destruction of the chromatic (Nissl's) bodies throughout the cell. Where they still remain they are distorted and "fused together." The nucleus is shrunken, has slipped to the margin of the cell. (eccentric) and has deeply stained rods" crowded into its edge, indicating a shrinking of the nucleus. The nucleus is also migrating to the nuclear margin and is vacuolated. It is true this is a death pic. ture but it is a safe conjecture that this is but an accentuation of the unseen pathol. ogy in the antemortem cell of morphinomania and the still less damaged cell of simple morphinism. It is in accord with the hypothesis advanced by Jennings (10) of Paris and myself (11) as to "How Morphinism Becomes Organic Disease." It is about like this:

Morphine over-stimulation does two things, namely, first, it provokes perversion of metabolism (1), and, second, a secondary exhaustion fatigue. Fatigued nerve cells means (2) katabolic insufficiency and formation of acid which further exhausts the ganglion cells by establishing a change of chemistry within the cells. Fatigue