The leprous nodes have on section a smooth, white, glistening surface, if they are still sufficiently young. If one examines, microscopically, sections or teased preparations of fresh nodules, one sees little else but cells, with distinct nuclei, usually of the size of a white blood corpuscle, or rather larger. There are also a few larger so-called epithelioid cells, with larger nuclei, and among the cells, fragments of connective tissue and of blood vessels. With a higher power, one sees in the fluid of the preparation small straight rods, which are not destroyed by addition of potash. These are the lepra bacilli, and thus were they first discovered in the year 1871.
If one teases out preparations in osmic acid solution, or soaks a nodule in the solution some hours before teasing, the rods are coloured faint brown, and one finds them lying mostly in the cells ([Plate VI], Fig. 1). If one adds water to a fresh preparation, the bacilli move actively; even in the cells swollen up with water, one sees the bacilli moving; and this led us to regard them as movable, although we at the same time indicated a doubt whether the movement was not simply a molecular one; for the movements were equally vigorous in strong osmic acid solution as in water, and on the addition of glycerine or strong solution of albumen to the preparations, the movements ceased. All later observers, with the exception of Unna, regard the bacilli as motionless. We have no ambition to decide this question, because we know no absolutely trustworthy distinction between molecular movement and independent movement of the bacilli.
The older the nodules become, the more large multinuclear cells are found, and in nodules of the skin and cornea one always finds small flat cells with processes, and with oblong nuclei, which we recognise as the connective tissue and corneal cells ([Plate VI], Figs. 2 and 3).
The protoplasm of these cells is clear, while that of the round cells is more or less granular. The nuclei of the latter are also round, and usually very granular; the flat cells are much less stained by carmine than the round cells, and one sees the flat cells lying on connective tissue bundles. The nodules are richly supplied with blood vessels; in the nodules of the skin it cannot be determined whether the vessels are newly formed, or only those already present in the cutis. They are, however, always of embryonic type. One sees very plainly their formation from cells, and in the cornea, indeed, the vessels must be newly formed. Here the vessels penetrate into the cornea before the nodule forms, and round these vessels, penetrating into the cornea, there are always visible collections of cells which are apparently migrated white blood corpuscles ([Plate VI], Fig. 4).
One meets also in old nodules, among apparently only unproductive elements, blood vessels surrounded by young cells ([Plate VI], Fig. 5). This appears definitely to favour the view that the tumour cells are, at least for the most part, migrated blood corpuscles. These results have been obtained by examination of fresh nodules, and of those hardened in Müller’s fluid. As we have recently, while hardening the nodules in Fleming’s chromic and osmic acid mixture, and staining the sections with hæmatoxylin, been unable as yet to find any mitoses, and further, have found, by bacillary staining of an old section from a corneal node, an appearance like [Plate VI], Fig. 7, we must maintain provisionally that in the lepromata the new formations are, at least chiefly, formed by the immigration of white blood corpuscles. As the round cells infiltrate the connective tissue, the fibres are pressed asunder, and form a network closely resembling that of a lymph gland with nuclei in the angles ([Plate VI], Fig. 6).
When the nodule softens, which takes place almost always exactly in the middle, it attains a brownish tint, which is due to the transparent softened part. If one divides the softened nodule, the central part has a distinct brown colour, and the constituents of this part readily fall out. If this is examined under a microscope, one sees, almost exclusively, larger or smaller clumps of a brownish colour, and very granular. They are partly elastic, but partly brittle and fragile, so that by pressure on the cover glass they are easily broken up. One often sees clearly that the clumps lie in the cells, the nucleus and the cell substance being still evident ([Plate VII], Fig. 1). Sometimes only one lies in a cell, which then has the appearance of a signet ring, in whose circle the clump lies, but sometimes several lie in one cell. One finds similar clumps in all other organs affected with leprosy, as in the liver, the spleen ([Plate VII], Fig. 2), the nerves, lymphatic glands, the testicle and the eyes ([Plate VII], Fig. 3, which shows two clumps from the retina). In the nodes of the skin, but particularly in the testicles, one may find them so large that they may even be seen by the naked eye. Both in the small and the larger clumps there are usually vacuoles, not infrequently several. From the cornea we have often got preparations in which the corneal corpuscles are more or less completely filled with brown granules ([Plate VIII], Fig. 1). One sees here definitely the cell nucleus in the middle of the brown granular material.
We have described these elements as we first observed them in fresh and carmine-stained preparations, in which they stand out very definitely, as the brown masses do not take up the carmine stain. These brown elements, if one knows their characteristic appearance, may very well serve as diagnostic indications for leprous affections, for, according to our experience, one never fails to find them except in very young nodules. Since the discovery and easy recognition of the lepra bacillus, they have indeed lost their value as diagnostic signs, unless one is examining perfectly fresh preparations. Later investigation has proved that these brown clumps are nothing else but collections of lepra bacilli broken down into granules, and they have received from Neisser the well-chosen name of “globi,” as they usually appear in spherical form. Unna declares, in accordance with his view of the position of the lepra bacilli outside the tumour cells in the lymph spaces, that these “globi” are collections of bacilli in the lymph vessels, and that the vacuoles have arisen from the falling out of bacilli in the middle. In particular, Neisser, Touton, and we, ourselves, have opposed this view, in that we have all seen the bacilli definitely in the cells, and have figured them so. In view of the above description of the discovery of bacilli in fresh preparations and of these brown clumps, there can scarcely be any doubt of the position of the bacilli, and of the cellular nature of the brown clumps. Further, it may be noted that in the testicles the “globi” are chiefly in the lumen of the seminal canals, where no lymph vessels exist, and if Unna says of the “globi”[2] that “no one has certainly determined their cellular character,” he must have said this in ignorance of our earlier publications in Norwegian. The above description and the drawings were published by us in 1869 and 1870, in the Nordiskt Medicinsk Arkiv.
In connection with the vacuole, we have found in a testicle a “globus” with vacuoles, and in the vacuoles small granules which were recognised as remains of the nuclei ([Plate X], Fig. 2). We add to this the picture of a “globus,” or rather a developing “globus,” with two nuclei, from a skin nodule ([Plate VIII], Fig. 4). We have seen earlier, however, that the brown clump may lie in the cell without enclosing the nucleus, and also that the nucleus may lie in the middle of the brown mass. Now, if the vacuoles are transformed nuclei, as we believe, then it would be comprehensible that the vacuoles would be absent in many “globi,” and that in others which have developed from multinuclear cells, several vacuoles would be found. That appears, at least, the simplest explanation of their presence. But there are certain very small “globi” with vacuoles, such as are represented in [Plate VII], Fig. 2, c, and those small vacuoles can scarcely represent nuclei; small “globi” may however arise, as is evident at x and x1 of the same figure, from clumps of bacilli in the cells. The vacuoles of the larger “globi” of x and x1 may indeed possibly represent nuclei, but not the vacuoles in [Plate VII], Fig. 2, a-k, nor the vacuole in one of the small “globi” in x1. Possibly the vacuoles are also the result of a specific degeneration, either of the bacilli themselves, or of the cell protoplasm lying in the middle of the group of bacilli, but on this we would rather not express an opinion.
We have repeatedly demonstrated the position of the bacilli in the cells, and explained them in diagrams, but in many preparations it is impossible to distinguish where the bacilli lie. The best method of definitely noting their position, which we know, appears to be the fixing of small nodes or small pieces of organs in Fleming’s or Müller’s fluid, with subsequent dehydration and hardening in alcohol; sometimes one gets excellent preparations by simply hardening in absolute alcohol. If the preparations are stained with fuchsin, and counter-stained with methyl blue, or still better, stained with gentian violet, decolourised by Gram’s method, and counter-stained with Bismarck brown or with Bismarck brown and eosin, one will never fail to see the bacilli lying definitely in the cells ([Plate VI], Fig. 8). Even in such preparations there are many places where one cannot definitely distinguish the position of the bacilli; but as one always finds bacilli in the cells where the preparations are sufficiently clear, we may safely conclude that the bacilli lie everywhere in the cells. In the connective tissue spaces one often sees bacilli in and round the nuclei of the connective tissue cells ([Plate X], Fig. 8), and although the body of the cell is not visible, we may conclude that the bacilli lie in the cell body, and not free in the lymph spaces. We have found in many sections of the blood vessels in a testicle ([Plate X], Figs. 5 and 6), and in a liver ([Plate VIII], Fig. 6, and [Plate IX], Fig. 1), white blood corpuscles filled with bacilli, and in both cases only slight affection of the organ, and we also observed many bacilli in the endothelium of the vessels, as Touton and Unna have observed in skin nodules where we, we may remark in passing, have never seen them. From these observations we draw the conclusion that these two organs have been infected through the blood. As we do not know the manner and method of the primary infection of the organ, we must devote our attention to the search for discoveries like those described above, and to the localisation of the bacilli in general, in order to form an idea of the method of action of the bacilli.
As we have already noted, we found in the examination of an excised piece of a recent eruption, in a nodular case of leprosy, chiefly, round cells surrounding dilated vessels, and only after long search, a few bacilli. It thus appears not improbable that during the eruption a toxin (which is circulating in the blood), and only a few bacilli, escape from the vessels at various places, or, it may be, only the bacilli, which produce the toxin locally; that further, the toxin causes the emigration of white blood corpuscles, and that the escaped bacilli only after some time slowly increase in number and gradually fill the cells. From the presence of the bacilli in the endothelium of the vessels and in the connective tissue cells, one may speculate that the bacilli are passively forced into them by the blood or lymph pressure; we have certainly found, in the testicle referred to, bacilli free between the red blood corpuscles in the vessels ([Plate X], Fig. 7). Such a fresh eruption may remain stationary or slowly develop into a nodule, or it may apparently completely disappear, and only after several years again become apparent, it may be during a fresh eruption. We fancy that in these cases a few bacilli are deposited at the time of the first eruption, and that they have needed years to become so much increased that a permanent nodule has finally formed. That the vessels receive lasting injuries from the leprous infection, appears to us to be proved by the following observations. In an epidemic of measles in one of our institutions, we saw in anæsthetic patients the previous leprous spots, which had long disappeared from view, definitely reappear, the hyperæmia and turgescence being on these places general, so that the earlier spots stood out as well defined, red, and somewhat swollen areas. All this appears to point to the fact that the bacilli increase very, very slowly, and that possibly they also produce a toxin, usually only in small quantities, which causes no particular injury to the organism, since the patients, in spite of numerous nodules, with millions or milliards of bacilli, may remain in pretty good health for years. We may also conjecture that the toxin which is produced, usually only acts immediately around the bacilli, leading to dilatation of the vessels and favouring the migration of white blood corpuscles. Only occasionally does the production of toxin or the multiplication of the bacilli appear to become so vigorous that toxin and bacilli get into the blood and cause an eruption; possibly this is favoured by peculiar anatomical conditions, for it is very striking with what varied frequency eruptions appear in different patients. That the bacilli in the nodules are all of them dead, as has been assumed, we cannot admit, so long as the nodules still grow. It appears to us preferable to ascribe the character of the disease to the relative benignancy and slight viability of the bacilli, as Unna has already suggested. As we believe, as explained above, that the bacilli lie almost exclusively in the cells, the question arises whether the cells digest the bacilli, or not. As we often find cells with only one or two bacilli, and as we find in most cells balls or clumps of bacilli, we must admit that the bacilli multiply in the cells. In some cells the bacilli remain lying in separate collections, in others they fill the entire cell body, but they never penetrate into the nucleus. Finally, the bacilli break down into small granules, and this breaking down corresponds, according to our view, to a degeneration of the bacilli. Unna and Lütz have indeed stated that this granular appearance of the bacilli is constant, and is a mark of their structure, that they really consist of small rows of cocci, and Unna has therefore described them as coccothrix. This actual (!) structure of the bacilli, however, only becomes evident under the action of free iodine. But we have seen in our preparations, however they were treated, smooth and granular bacilli lying close to each other, and we cannot, therefore, corroborate the view of Unna and Lütz.